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  • Frontiers Media SA  (750)
  • 1
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    Image_4.tiff
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-3-9)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-9)
    Abstract: A recently developed treatment strategy for lung cancer that combines immune checkpoint inhibitors with chemotherapy has been applied as a standard treatment for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and it has improved the outcomes of chemotherapy. Maintenance treatment with anti-PD-1 antibody (aPD-1) enhances the effect of immunochemical combination therapy and improves therapeutic efficacy, which contributes toward a significant improvement in patient survival rates. The AXL receptor tyrosine kinase (AXL), which is expressed in tumor cells, plays an essential role in the resistance of cancers to chemotherapy and immunotherapy, and stimulates signaling associated with epithelial-mesenchymal transition (EMT) in metastatic cancer. AXL is thus an attractive target for controlling resistance to anti-tumor therapies. In this study, we examined the effect of AXL inhibitors on immune activation and tumor growth in TC1 and C3PQ mouse tumor models, in the context of clinical immunotherapy/chemotherapy and maintenance treatment, using an aPD-1 with/without pemetrexed. To determine the optimal timing for administration of SKI-G-801, an AXL inhibitor, we investigated its anti-tumor effects based on inclusion at the immunochemotherapy and maintenance therapy stages. We also performed flow cytometry-based immune profiling of myeloid cells and lymphoid cells at different points in the treatment schedule, to investigate the immune activation and anti-tumor effects of the AXL inhibitor. The addition of SKI-G-801 to the immune checkpoint inhibitor and chemotherapy stage, as well as the maintenance therapy stage, produced the best anti-tumor results, and significant tumor growth inhibition was observed in both the TC1 and C3PQ models. Both models also exhibited increased proportion of effector memory helper T cells and increased expression of CD86 + macrophages. Especially, regulatory T cells were significantly reduced in the TC1 tumor model and there was an increase in central memory cytotoxic T cell infiltration and an increased proportion of macrophages with high CD80 expression in the C3PQ tumor model. These results suggest increased infiltration of T cells, consistent with previous studies using AXL inhibitors. It is expected that the results from this study will serve as a stepping stone for clinical research to improve the existing standard of care.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.821391
    DOI: 10.3389/fonc.2022.821391.s001
    DOI: 10.3389/fonc.2022.821391.s002
    DOI: 10.3389/fonc.2022.821391.s003
    DOI: 10.3389/fonc.2022.821391.s004
    DOI: 10.3389/fonc.2022.821391.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 2
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2018
    In:  Frontiers in Immunology Vol. 9 ( 2018-4-11)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 9 ( 2018-4-11)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2018.00705
    DOI: 10.3389/fimmu.2018.00705.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2606827-8
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  • 3
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    Presentation_1.ZIP
    Frontiers Media SA ; 2023
    In:  Frontiers in Medicine Vol. 10 ( 2023-1-25)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 10 ( 2023-1-25)
    Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry. Materials and methods This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO 2 ) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model. Results Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38–3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60–4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p   & lt; 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality. Conclusion The GAP6 model adding nadir SpO 2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2023.1052129
    DOI: 10.3389/fmed.2023.1052129.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2775999-4
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  • 4
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    Influence of preparedness on caregiver burden, depression, and quality of life in caregivers of people with disabilities
    Frontiers Media SA ; 2023
    In:  Frontiers in Public Health Vol. 11 ( 2023-7-26)
    Details
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 11 ( 2023-7-26)
    Abstract: Caregiver preparedness is defined as the perceived preparation of caregivers to care for the physical and emotional needs of the patient. Purpose This study investigated caregiver preparedness and its influences on caregiver burden, depression, and quality of life (QoL) in caregivers of individuals with disabilities. Methods We conducted a multicenter cross-sectional survey study on caregivers caring for patients with disabilities. Sociodemographic characteristics were collected via questionnaires. The Preparedness for Caregiving Scale (PCS), Burden Interview (BI), Center for Epidemiologic Studies Depression Scale (CES-D), and EuroQol-Visual Analogue Scale (EQ-VAS) were administered. Results A total of 151 caregivers were enrolled. The mean age of caregivers was 53.7 ± 12.4 years, and 80.8% were female. The majority of participants were the main caregivers of patients with stroke, spinal cord injury, or traumatic brain injury. The mean PCS score was 2.1 ± 0.9, demonstrating significant relationships with BI (r = −0.512, p   & lt; 0.001), CES-D (r = −0.622, p   & lt; 0.001), and EQ-VAS (r = 0.441, p   & lt; 0.001). The CES-D was significantly associated with the PCS after controlling other variables. However, PCS did not show any correlation with the duration of caregiving or amount of time spent per day on caregiving. Discussion The clinical implications of this study are that higher caregiver preparedness is a predictor of less caregiver burden and depression, and better QoL. However, preparedness did not increase as the duration or time spent on caregiving was extended. Therefore, efforts to enhance the caregivers’ preparedness are required to reduce caregiver burden and improve health outcomes for both caregivers and patients.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    URL: Article
    DOI: 10.3389/fpubh.2023.1153588
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711781-9
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  • 5
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    Genetic Determinants of Visit-to-Visit Lipid Variability: Genome-Wide Association Study in Statin-Naïve Korean Population
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-1-31)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-1-31)
    Abstract: There is a growing evidence that fluctuation in lipid profiles is important in cardiovascular outcomes. We aimed to identify single nucleotide polymorphism (SNP) variants associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) variability in statin-naïve Korean subjects and evaluate their associations with coronary atherosclerosis. Methods In statin-naïve subjects from Gene-Environment of Interaction and phenotype cohort, we performed genome-wide association studies of lipid variability; the discovery (first) and replication (second) sets included 4,287 and 1,086 subjects, respectively. Coronary artery calcium (CAC) score and degree of coronary artery stenosis were used as outcome measures. Cholesterol variability was determined by standard deviation and average successive variability, and significant coronary atherosclerosis was defined as CAC score ≥400 or coronary stenosis ≥70%. Results Mean HDL-C and LDL-C level were 54 ± 12 and 123 ± 30 mg/dL in the first set and 53 ± 12 and 126 ± 29 mg/dL in the second set. APOA5 rs662799 and APOA5 rs2266788 were associated with LDL-C variability and PXDNL rs80056520, ALDH2 rs671, HECTD4 rs2074356, and CETP rs2303790 were SNPs associated for HDL-C variability. APOA5 rs662799 passed Bonferroni correction with p -value of 1.789 × 10 −9 . Among the SNPs associated with cholesterol variability, rs80056520 and rs2266788 variants were associated with CACS ≥400 and coronary stenosis ≥70% and rs662799 variant was associated with coronary stenosis ≥70%. Conclusion Two SNPs associated with LDL-C variability ( APOA5 rs662799 and rs2266788) and one SNP associated with HDL-C variability ( PXDNL rs80056520) were significantly associated with advanced coronary artery stenosis. Combining GWAS results with imaging parameters, our study may provide a deeper understanding of underlying pathogenic basis of the link between lipid variability and coronary atherosclerosis.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2022.811657
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 6
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    DataSheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-3-18)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-3-18)
    Abstract: TNF-α plays a crucial role in cancer initiation and progression by enhancing cancer cell proliferation, survival, and migration. Even though the known functional role of AWP1 (zinc finger AN1 type-6, ZFAND6) is as a key mediator of TNF-α signaling, its potential role in the TNF-α-dependent responses of cancer cells remains unclear. In our current study, we found that an AWP1 knockdown using short hairpin RNAs increases the migratory potential of non-aggressive MCF-7 breast cancer cells with no significant alteration of their proliferation in response to TNF-α. A CRISPR/Cas9-mediated AWP1 knockout in MCF-7 cells led to mesenchymal cell type morphological changes and an accelerated motility. TNF-α administration further increased this migratory capacity of these AWP1-depleted cells through the activation of NF-κB accompanied by increased epithelial-mesenchymal transition-related gene expression. In particular, an AWP1 depletion augmented the expression of Nox1, reactive oxygen species (ROS) generating enzymes, and ROS levels and subsequently promoted the migratory potential of MCF-7 cells mediated by TNF-α. These TNF-α-mediated increases in the chemotactic migration of AWP1 knockout cells were completely abrogated by an NF-κB inhibitor and a ROS scavenger. Our results suggest that a loss-of-function of AWP1 alters the TNF-α response of non-aggressive breast cancer cells by potentiating ROS-dependent NF-κB activation.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.631469
    DOI: 10.3389/fonc.2021.631469.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 7
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    Predictors of consciousness improvement in patients with hypoglycemic encephalopathy
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-8-16)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-8-16)
    Abstract: Hypoglycemic encephalopathy (HE) can cause long-lasting mental changes, disability, and even death. We aimed to investigate prognostic factors for HE and to determine when the treatment of HE becomes futile. Methods We retrospectively evaluated the data of patients admitted for prolonged HE at Dongguk University Ilsan Hospital between December 2005 and July 2021. We assessed the Glasgow Outcome Scale (GOS) to assess functional outcome. Results Forty-four patients were enrolled in the study. Thirty-two of these showed the improvement on GOS after treatment. Patients with improved consciousness had a shorter duration of hypoglycemia (1.6±1.4 vs. 7.8±15.0 hours, p = 0.04) and a lower incidence of brain lesions than those without improvements in consciousness (76.0% vs. 25.0%, p & lt; 0.01). Patients whose lesions were detected in initial MRIs were 1.3 times less likely to recover consciousness after HE (odds ratios, 1.28; 95% CI, 1.09-1.52; p & lt; 0.01). None of the patients recovered consciousness after 320 h. Maximum time spent to recover was 194 in patients without brain lesions and 319 in those with lesions. Conclusions Hypoglycemic brain injury detected in initial MRIs predicted poorer HE prognosis. Nevertheless, treatment should be provided for at least for 14 days after admission.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    DOI: 10.3389/fendo.2022.956367
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 8
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    Corrigendum: Genetic Determinants of Visit-to-Visit Lipid Variability: Genome-Wide Association Study in Statin-Naïve Korean Population
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-3-1)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-1)
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2022.869777
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 9
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    DataSheet2.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-9-12)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-9-12)
    Abstract: Despite recent advancements in our understanding of genetic etiology and its molecular and physiological consequences, it is not yet clear what genetic features determine the inheritance pattern of a disease. To address this issue, we conducted whole exome sequencing analysis to characterize genetic variants in 1,180 Korean patients with neurological symptoms. The diagnostic yield for definitive pathogenic variant findings was 50.8%, after including 33 cases (5.9%) additionally diagnosed by reanalysis. Of diagnosed patients, 33.4% carried inherited variants. At the genetic level, autosomal recessive-inherited genes were characterized by enrichments in metabolic process, muscle organization and metal ion homeostasis pathways. Transcriptome and interactome profiling analyses revealed less brain-centered expression and fewer protein-protein interactions for recessive genes. The majority of autosomal recessive genes were more tolerant of variation, and functional prediction scores of recessively-inherited variants tended to be lower than those of dominantly-inherited variants. Additionally, we were able to predict the rates of carriers for recessive variants. Our results showed that genes responsible for neurodevelopmental disorders harbor different molecular mechanisms and expression patterns according to their inheritance patterns. Also, calculated frequency rates for recessive variants could be utilized to pre-screen rare neurodevelopmental disorder carriers.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fgene.2022.990015
    DOI: 10.3389/fgene.2022.990015.s001
    DOI: 10.3389/fgene.2022.990015.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 10
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Aging Neuroscience Vol. 12 ( 2021-1-26)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 12 ( 2021-1-26)
    Abstract: Background: Mild cognitive impairment (MCI) is a condition with diverse causes and clinical outcomes that can be categorized into subtypes. [ 18 F]THK5351 has been known to detect reactive astrogliosis as well as tau which is accompanied by neurodegenerative changes. Here, we identified heterogeneous groups of MCI patients using TH K retention patterns and a graph theory approach, allowing for the comparison of risk of progression to dementia in these MCI subgroups. Methods: Ninety-seven participants including 60 MCI patients and individuals with normal cognition (NC, n = 37) were included and undertook 3T MRI, [ 18 F]THK5351 PET, and detailed neuropsychological tests. [ 18 F]Flutemetamol PET was also performed in 62 participants. We calculated similarities between MCI patients using their regional standardized uptake value ratio of THK retention in 75 ROIs, and clustered subjects with similar retention patterns using the Louvain method based on the modularity of the graph. The clusters of patients identified were compared with an age-matched control group using a general linear model. Dementia conversion was evaluated after a median follow-up duration of 34.6 months. Results: MCI patients were categorized into four groups according to their THK retention patterns: (1) limbic type; (2) diffuse type; (3) sparse type; and (4) AD type (retention pattern as in AD). Subjects of the limbic type were characterized by older age, small hippocampal volumes, and reduced verbal memory and frontal/executive functions. Patients of the diffuse type had relatively large vascular burden, reduced memory capacity and some frontal/executive functions. Co-morbidity and mortality were more frequent in this subgroup. Subjects of the sparse type were younger and declined only in terms of visual memory and attention. No individuals in this subgroup converted to dementia. Patients in the AD type group exhibited the poorest cognitive function. They also had the smallest hippocampal volumes and the highest risk of progression to dementia (90.9%). Conclusion: Using cluster analyses with [ 18 F]THK5351 retention patterns, it is possible to identify clinically-distinct subgroups of MCI patients and those at greater risk of progression to dementia.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    URL: Article
    DOI: 10.3389/fnagi.2020.615467
    DOI: 10.3389/fnagi.2020.615467.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2558898-9
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