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  • 1
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-1-23)
    Abstract: Fertility is an important issue for young women with breast cancer, but studies about physicians’ knowledge, attitudes, and practices toward fertility preservation (FP) are largely based on Western populations and do not reflect recent international guidelines for FP. In this international study, we aimed to assess the knowledge, attitudes, and practices of physicians from South Korea, other Asian countries, and Latin America toward FP in young women with breast cancer, and identify the related barriers. Methods The survey was conducted anonymously among physicians from South Korea, other Asian countries, and Latin America involved in breast cancer care between November 2020 and July 2021. Topics included knowledge, attitudes, and perceptions toward FP; practice behaviors; barriers; and participant demographics. We grouped related questions around two main themes—discussion with patients about FP, and consultation and referral to a reproductive endocrinologist. We analyzed the relationships between main questions and other survey items. Results A total of 151 physicians completed the survey. Most participants’ overall knowledge about FP was good. More than half of the participants answered that they discussed FP with their patients in most cases, but that personnel to facilitate discussions about FP and the provision of educational materials were limited. A major barrier was time constraints in the clinic (52.6%). Discussion, consultations, and referrals were more likely to be performed by surgeons who primarily treated patients with operable breast cancer (FP discussion odds ratio [OR]: 2.90; 95% confidence interval [CI] : 1.24–6.79; FP consultation and referral OR: 2.98; 95% CI: 1.14–7.74). Participants’ knowledge and attitudes about FP were significantly associated with discussion, consultations, and referrals. Conclusion Physicians from South Korea, other Asian countries, and Latin America are knowledgeable about FP and most perform practice behaviors toward FP well. Physicians’ knowledge and favorable attitudes are significantly related to discussion with patients, as well as consultation with and referral to reproductive endocrinologists. However, there are also barriers, such as limitations to human resources and materials, suggesting a need for a systematic approach to improve FP for young women with breast cancer.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-15)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-15)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 ( K18 ) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥10 5 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B ( SFTPB ) and secretoglobin family 1a member 1 ( Scgb1a1 ) promoters. After inoculation of 10 5 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.
    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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  • 3
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-2)
    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
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-7-1)
    Abstract: We aimed to compare the outcomes of adjuvant radiotherapy (ART) and surveillance in patients with grade 2 meningiomas (MNG2) who underwent surgical resection. Materials and Methods Data from four hospitals, in which patients aged ≥18 years underwent Simpson grade 1−4 surgical resection for newly diagnosed MNG2 between 1998 and 2018, were examined in this multicenter retrospective cohort study. Patients receiving ART with conventional fractionation were compared with those undergoing surveillance. Progression-free survival (PFS), progression/recurrence (P/R) were evaluated. Results This study included 518 patients, 158 of whom received ART. The median follow-up duration was 64.9 months. In the total cohort, ART was independently associated with significantly improved PFS (HR, 0.35; 95% CI, 0.23–0.55; P & lt;0.001) and P/R (HR, 0.30; 95% CI, 0.18–0.48; P & lt;0.001). In the propensity score-matched cohort (n=143 in each group), the 5-year PFS rates were 80.8% and 57.7% (P=0.004), and the 5-year P/R rates were 16.5% and 40.0% (P=0.002) in the ART and surveillance groups, respectively. After gross total resection, the 5-year PFS (85.0% vs. 64.7%; P=0.020) and P/R rates (15.2% vs. 32.0%; P=0.035) were significantly better in the ART group than in the surveillance group. A model for P/R was developed using recursive partitioning analysis with surgical extent, tumor size, and Ki-67 index. ART reduced the risk of P/R in the low- (P=0.069), intermediate- (P=0.044), and high-risk groups (P & lt;0.001). Local control was also significantly enhanced by ART among all the risk groups (all P & lt;0.05). Conclusions ART significantly improved PFS and P/R in patients with MNG2, irrespective of the surgical extent, and can be recommended after gross total resection. A prognostic model may guide decision-making for the use of ART.
    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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  • 5
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-4-14)
    Abstract: For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND 50 ≥ 20 was comparable among the four immunoassays (Cohen’s kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND 50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson’s R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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  • 6
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-8)
    Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in carcinogenesis. We previously reported that Nrf2 deficiency enhances the anti-tumorigenic effect of 17β-estradiol (E2) in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated cancer (CAC). Herein, we aimed to determine a possible explanation for our recent work and investigated the immune microenvironment represented by programmed death-ligand 1 (PD-L1) expression. One week after the AOM injection, mice were administered with DSS in drinking water for seven days; daily E2 injections were intraperitoneally administered during this period. The mice were sacrificed 16 weeks after AOM injection and analyzed for PD-L1 expression in the distal colon tissues using Western blotting and immunohistochemistry (IHC). Based on Western blotting results, PD-L1 expression was reduced in Nrf2 knockout (KO) female and E2-treated male mice when compared with their wild-type counterparts, following AOM/DSS treatment; this supports the association of PD-L1 expression with tumor progression. Additionally, this finding was in good agreement with the IHC results for PD-L1. Furthermore, we observed that PD-L1 is predominantly expressed in stromal cells rather than on epithelial cells in the colon. Western blotting revealed that PD-L1 expression in the colon positively correlates with expressions of inducible nitric oxide synthase (iNOS) (male, P = 0.002; female, P  & lt; 0.001) and cyclooxygenase-2 (COX-2) (male, P & lt; 0.001; female, P & lt; 0.001). Collectively, our findings indicate that estrogen ameliorates the immune microenvironment represented by PD-L1 expression and enhances its effect in the absence of Nrf2.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 7
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-11-19)
    Abstract: Tubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-β) is well known for epithelial–mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-β superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-β, inhibiting fibrotic progression in many organs. However, soluble rhBMP-7 is hardly available for therapeutics due to its limited pharmacodynamic profile and rapid clearance in clinical settings. In this study, we have developed a novel therapeutic approach with protein transduction domain (PTD) fused BMP-7 in micelle (mPTD-BMP-7) for long-range signaling in vivo . Contrary to rhBMP-7 targeting its cognate receptors, the nano-sized mPTD-BMP-7 is transduced into cells through an endosomal pathway and secreted to the exosome having active BMP-7. Further, transduced mPTD-BMP-7 successfully activates SMAD1/5/8 and inhibits the TGF-β–mediated epithelial–mesenchymal transition process in vitro and in an in vivo unilateral ureter obstruction model. To determine the clinical relevance of our strategy, we also developed an intra-arterial administration of mPTD-BMP-7 through renal artery in pigs. Interestingly, mPTD-BMP-7 through renal artery intervention effectively delivered into Bowman’s space and inhibits unilateral ureter obstruction–induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-β–mediated renal fibrosis and other organs as well as a clinically available approach for kidney.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 12 ( 2022-1-13)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 12 ( 2022-1-13)
    Abstract: Drought and salinity are major important factors that restrain growth and productivity of rice. In plants, many really interesting new gene (RING) finger proteins have been reported to enhance drought and salt tolerance. However, their mode of action and interacting substrates are largely unknown. Here, we identified a new small RING-H2 type E3 ligase OsRF1 , which is involved in the ABA and stress responses of rice. OsRF1 transcripts were highly induced by ABA, salt, or drought treatment. Upregulation of OsRF1 in transgenic rice conferred drought and salt tolerance and increased endogenous ABA levels. Consistent with this, faster transcriptional activation of key ABA biosynthetic genes, ZEP, NCED3 , and ABA4 , was observed in OsRF1 -OE plants compared with wild type in response to drought stress. Yeast two-hybrid assay, BiFC, and co-immunoprecipitation analysis identified clade A PP2C proteins as direct interacting partners with OsRF1. In vitro ubiquitination assay indicated that OsRF1 exhibited E3 ligase activity, and that it targeted OsPP2C09 protein for ubiquitination and degradation. Cell-free degradation assay further showed that the OsPP2C09 protein is more rapidly degraded by ABA in the OsRF1 -OE rice than in the wild type. The combined results suggested that OsRF1 is a positive player of stress responses by modulating protein stability of clade A PP2C proteins, negative regulators of ABA signaling.
    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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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2018
    In:  Frontiers in Molecular Neuroscience Vol. 11 ( 2018-8-14)
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 11 ( 2018-8-14)
    Type of Medium: Online Resource
    ISSN: 1662-5099
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2452967-9
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  • 10
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-10-4)
    Abstract: Influenza vaccination reduces cardiovascular events in patients with cardiovascular disease (CVD). Identifying the factors that affect influenza vaccination uptake can help improve the prognosis in patients with CVD. This study aimed to evaluate the secular trends of influenza vaccination uptake and factors associated with lack of vaccination in individuals with CVD. Materials and methods We analyzed the annual trends and factors associated with influenza vaccination among 3,264 patients with CVD, included from the Korea National Health and Nutrition Examination Survey which reflect the health and nutritional status of the nationwide population of Korea conducted between 2007/2008 and 2018/2019. We used a stratified, multistage sampling method. Results The influenza vaccination rate was greater in patients with CVD (53–74%) than in those without CVD (28–40%). Multivariable logistic regression analysis showed that age & lt;50 years [odds ratio (OR), 16.22; 95% confidence interval (CI), 7.72–34.07], 50–64 years (OR, 6.71; 95% CI, 4.37–10.28), male sex (OR, 1.45; 95% CI, 1.14–1.65), and asthma (OR, 0.45; 95% CI, 0.22–0.92) were independently associated with a lack of influenza vaccination. Among patients aged & lt;65 years, smoking (OR, 2.30; 95% CI, 1.31–4.04), college graduation status (OR, 1.81; 95% CI, 1.16–2.82), and hypertension (OR, 0.70; 95% CI, 0.51–0.95) were independently associated with influenza vaccination. For individuals aged 65years, there was no significant determinant of lack of vaccination. Conclusion In patients with CVD, a continuous increase in the secular trend of influenza vaccination was demonstrated in Korea. Young age, male sex, and non-asthma status were independently associated with lack of influenza vaccination uptake.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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