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  • 1
    Online Resource
    Online Resource
    Antenatal Glucocorticoid Administration Promotes Cardiac Structure and Energy Metabolism Maturation in Preterm Fetuses
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 17 ( 2022-09-05), p. 10186-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 17 ( 2022-09-05), p. 10186-
    Abstract: Although the rate of preterm birth has increased in recent decades, a number of preterm infants have escaped death due to improvements in perinatal and neonatal care. Antenatal glucocorticoid (GC) therapy has significantly contributed to progression in lung maturation; however, its potential effects on other organs remain controversial. Furthermore, the effects of antenatal GC therapy on the fetal heart show both pros and cons. Translational research in animal models indicates that constant fetal exposure to antenatal GC administration is sufficient for lung maturation. We have established a premature fetal rat model to investigate immature cardiopulmonary functions in the lungs and heart, including the effects of antenatal GC administration. In this review, we explain the mechanisms of antenatal GC actions on the heart in the fetus compared to those in the neonate. Antenatal GCs may contribute to premature heart maturation by accelerating cardiomyocyte proliferation, angiogenesis, energy production, and sarcoplasmic reticulum function. Additionally, this review specifically focuses on fetal heart growth with antenatal GC administration in experimental animal models. Moreover, knowledge regarding antenatal GC administration in experimental animal models can be coupled with that from developmental biology, with the potential for the generation of functional cells and tissues that could be used for regenerative medical purposes in the future.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231710186
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 2
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    The Association between Total Genotype Score and Athletic Performance in Weightlifters
    MDPI AG ; 2022
    In:  Genes Vol. 13, No. 11 ( 2022-11-10), p. 2091-
    Details
    In: Genes, MDPI AG, Vol. 13, No. 11 ( 2022-11-10), p. 2091-
    Abstract: This study aimed to investigate the relationship between power-oriented genetic polymorphisms and weightlifting status, create a total genotype score (TGS), and validate the association between TGS models and power-oriented athletes. First, 192 weightlifters and 416 controls were studied, and 12 polymorphisms that have previously been associated with strength, power status, and phenotype were genotyped using the TaqMan SNP genotyping assay. We calculated the TGS for the 12 polymorphisms using a PWM (power-oriented whole model) and for 6 of them using a WRM (weightlifting-related model) based on a case–control study. Second, the TGS of the WRM was compared for 177 strength and power athletes and 416 controls. There was no significant difference in the PWM score between weightlifters and the controls. Weightlifters and elite weightlifters had higher WRM scores than the controls. However, the WRM score had no association with weightlifting performance. There was no significant difference in the WRM between power-oriented athletes and the controls. Our study was able to create a TGS model for weightlifters based on case–control results. However, the TGS model could not be applied to other power-oriented athletes.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes13112091
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527218-4
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  • 3
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    Clinical Utility of Comprehensive Genomic Profiling in Patients with Unresectable Hepatocellular Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-24), p. 719-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-24), p. 719-
    Abstract: This study aimed to investigate the clinical usefulness of comprehensive genomic profiling (CGP) in patients with unresectable hepatocellular carcinoma who received multiple systemic therapies in real-world practice. In this study, all nine patients had gene alterations, and seven were candidates eligible for clinical trials based on the results of CGP. The median number of alterations per patient was four, and the blood sample was used in five patients with extrahepatic metastasis. We revealed the genomic information of the patients who received multiple systemic therapies and reported the utility of blood samples in patients with extrahepatic metastasis. Furthermore, the genomic status in patients treated with multiple molecular-targeted agents, including checkpoint inhibitors, would contribute to developing newer systemic agents. The molecular mechanism of hepatocellular carcinoma (HCC) is partially demonstrated. Moreover, in the patients receiving multiple molecular-targeted therapies, the gene alternations are still unknown. Six molecular-targeted therapies of unresectable HCC (uHCC) and comprehensive genomic profiling (CGP) have been approved in clinical practice. Hence, the utility of CGP in patients with uHCC treated with multiple molecular-targeted agents is investigated. The data of the patients with uHCC who received CGP tests were collected, retrospectively, between February 2021 and May 2022. Gene alterations detected by foundation testing, excluding variants of unknown significance, were reported in all nine patients. The samples for CGP were derived from liver tumor biopsy (n = 2), surgical specimens of bone metastases (n = 2), and blood (n = 5). The median number of systemic therapies was four. Seven patients were candidates eligible for clinical trials. One patient with a high tumor mutation burden (TMB) could receive pembrolizumab after CGP. This study presented genomic alternations after receiving multiple molecular-targeted therapies. However, further investigation needs to be conducted to develop personalized therapies and invent newer agents for treating HCC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030719
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Clinical Features and Outcomes of Japanese Patients with Giant Cell Arteritis: A Comparison with Takayasu Arteritis
    MDPI AG ; 2023
    In:  Journal of Personalized Medicine Vol. 13, No. 3 ( 2023-02-22), p. 387-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 3 ( 2023-02-22), p. 387-
    Abstract: Background: Giant cell arteritis (GCA) and Takayasu arteritis (TA) are distinct types of large-vessel vasculitis; however, the clinical features of the diseases have some similarities. Limited data are available regarding Japanese patients with GCA and TA. The present study aimed to compare the clinical features and outcomes of Japanese patients with GCA and TA and the effects of large vessel involvement (LVI). Methods: We performed a retrospective cohort study of the patients with GCA (n = 15) and TA (n = 30) who visited our department from April 2012 to June 2022. Signs and symptoms attributed to the disease, treatment, clinical outcomes, and mortality were recorded using a standardized database. Results: The median age of onset was significantly higher in the GCA group at 24 years (range, 16–72 years) in the TA group and 77 years (range, 57–89 years) in the GCA group (p 〈 0.001). There were no significant differences in survival rates or the cumulative rates of cardiovascular events between the GCA and TA groups. However, relapse-free survival rates were significantly higher in patients with GCA than in patients with TA. Seven of the 15 patients with GCA had large vessel involvement, which did not affect the survival rates. Prednisolone (PSL) doses were significantly decreased after induction therapy in both groups, and the rates of achieving steroid tapering (PSL 〈 5.0 mg/day) were significantly higher in patients with GCA compared with those in patients with TA. Conclusions: Our study demonstrated no significant difference in the survival rates of Japanese patients with GCA and TA. The relapse-free survival rates were significantly higher in the GCA group than in the TA group. LVI may not be associated with disease relapse or survival rate in Japanese patients with GCA.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm13030387
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
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  • 5
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    Online Resource
    Evaluation of the Effects of Microgravity on Activated Primary Human Hepatic Stellate Cells
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 13 ( 2022-07-04), p. 7429-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 13 ( 2022-07-04), p. 7429-
    Abstract: In recent years, research has been conducted to develop new medical treatments by simulating environments existing in space, such as zero-gravity. In this study, we evaluated the cell proliferation and gene expression of activated primary human hepatic stellate cells (HHSteCs) under simulated microgravity (SMG). Under SMG, cell proliferation was slower than in 1 G, and the evaluation of gene expression changes on day 1 of SMG by serial analysis of gene expression revealed the presence of Sirtuin, EIF2 signaling, hippo signaling, and epithelial adherence junction signaling. Moreover, reactive oxygen species were upregulated under SMG, and when N-acetyl-cystein was added, no difference in proliferation between SMG and 1 G was observed, suggesting that the oxidative stress generated by mitochondrial dysfunction caused a decrease in proliferation. Upstream regulators such as smad3, NFkB, and FN were activated, and cell-permeable inhibitors such as Ly294002 and U0126 were inhibited. Immunohistochemistry performed to evaluate cytoskeletal changes showed that more β-actin was localized in the cortical layer under SMG.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23137429
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 6
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    Online Resource
    Differences in Demographic and Radiographic Characteristics between Patients with Visible and Invisible T1 Slopes on Lateral Cervical Radiographic Images
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 2 ( 2022-01-14), p. 411-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 2 ( 2022-01-14), p. 411-
    Abstract: Introduction: The T1 slope is important for cervical surgical planning, and it may be invisible on radiographic images. The prevalence of T1 invisible cases and the differences in demographic and radiographic characteristics between patients whose T1 slopes are visible or invisible remains unexplored. Methods: This pilot study aimed to evaluate the differences in these characteristics between outpatients whose T1 slopes were visible or invisible on radiographic images. Patients (n = 60) who underwent cervical radiography, whose T1 slope was confirmed clearly, were divided into the visible (V) group and invisible (I) group. The following radiographic parameters were measured: (1) C2-7 sagittal vertical axis (SVA), (2) C2-7 angle in neutral, flexion, and extension positions. Results: Based on the T1 slope visibility, 46.7% of patients were included in group I. The I group had significantly larger C2-7 SVA than the V group for males (p 〈 0.05). The C2-7 SVA tended to be larger in the I group, without significant difference for females (p = 0.362). Discussion: The mean C2-7 angle in neutral and flexion positions was not significantly different between the V and I groups for either sex. The mean C2-7 angle in the extension position was greater in the V group. The T1 slope was invisible in males with high C2-7 SVA.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11020411
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 7
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    Online Resource
    Circulating Syndecan-1 Levels Are Associated with Chronological Coagulofibrinolytic Responses and the Development of Disseminated Intravascular Coagulation (DIC) after Trauma: A Retrospective Observational Study
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 13 ( 2023-06-29), p. 4386-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 13 ( 2023-06-29), p. 4386-
    Abstract: Background: The purpose of this study was to evaluate the association between endotheliopathy represented by high levels of circulating syndecan-1 (SDC-1) and coagulofibrinolytic responses due to trauma, which can lead to disseminated intravascular coagulation (DIC). Methods: We retrospectively evaluated 48 eligible trauma patients immediately admitted to our hospital and assessed SDC-1 and coagulofibrinolytic parameters for 7 days after admission. We compared the longitudinal changes of coagulofibrinolytic parameters and SDC-1 levels between two groups (high and low SDC-1) according to median SDC-1 value on admission. Results: The median circulating SDC-1 level was 99.6 (61.1–214.3) ng/mL on admission, and levels remained high until 7 days after admission. Coagulofibrinolytic responses assessed by biomarkers immediately after trauma were correlated with SDC-1 elevation (thrombin–antithrombin complex, TAT: r = 0.352, p = 0.001; antithrombin, AT: r = −0.301, p 〈 0.001; plasmin-α2-plasmin inhibitor complex, PIC: r = 0.503, p = 0.035; tissue plasminogen activator, tPA: r = 0.630, p 〈 0.001). Sustained SDC-1 elevation was associated with intense and prolonged coagulation activation, impairment of anticoagulation, and fibrinolytic activation followed by inhibition of fibrinolysis, which are the primary responses associated with development of DIC in the acute phase of trauma. Elevation of circulating SDC-1 level was also associated with consumption coagulopathy and the need for transfusion, which revealed a significant association between high SDC-1 levels and the development of DIC after trauma (area under the curve, AUC = 0.845, cut-off value = 130.38 ng/mL, p = 0.001). Conclusions: High circulating levels of syndecan-1 were associated with intense and prolonged coagulation activation, impairment of anticoagulation, fibrinolytic activation, and consumption coagulopathy after trauma. Endotheliopathy represented by SDC-1 elevation was associated with trauma induced coagulopathy, which can lead to the development of DIC.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12134386
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 8
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    Online Resource
    Serum Levels of T Cell Immunoglobulin and Mucin-Domain Containing Molecule 3 in Patients with Systemic Lupus Erythematosus
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 11 ( 2020-11-05), p. 3563-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 11 ( 2020-11-05), p. 3563-
    Abstract: Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p 〈 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9113563
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 9
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    Efficacy and Safety of a Novel Mouthpiece for Esophagogastroduodenoscopy: A Multi-Center, Randomized Study
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 3 ( 2021-03-17), p. 538-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 3 ( 2021-03-17), p. 538-
    Abstract: This randomized trial aimed to compare the safety and efficacy of the GAGLESS mouthpiece for esophagogastroduodenoscopy (EGD) with that of the conventional mouthpiece. In all, 90 participants were divided into the GAGLESS mouthpiece and conventional mouthpiece groups. The primary endpoint was the severity of pain using the visual analog scale (VAS), and secondary endpoints were examination time, past history of endoscopy, success of the procedure, systolic (SBP) and diastolic (DBP) blood pressure, oxygen saturation, pulse rate before and after EGD, and adverse events. Endoscopy was completed in all cases, and no complications were observed. VAS, when passing the scope through the pharynx, was 2.5 ± 2.4 and 2.0 ± 1.9 cm (p = 0.24) in the conventional and GAGLESS groups, respectively, and that, throughout the examination, was 2.5 ± 2.4 and 1.7 ± 1.5 cm (p = 0.06), respectively. The difference in blood pressure between the GAGLESS and conventional groups was not significant for SBP (p = 0.08) and significant for DBP (p = 0.03). The post-EGD difference in DBP was significantly lower in the GAGLESS group than in the conventional group. The results indicate that GAGLESS mouthpieces had a lower VAS during endoscopy than the conventional mouthpieces, and the changes in blood pressure were smaller with the GAGLESS mouthpiece.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11030538
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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  • 10
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    Delirium Prediction Using Machine Learning Interpretation Method and Its Incorporation into a Clinical Workflow
    MDPI AG ; 2023
    In:  Applied Sciences Vol. 13, No. 3 ( 2023-01-25), p. 1564-
    Details
    In: Applied Sciences, MDPI AG, Vol. 13, No. 3 ( 2023-01-25), p. 1564-
    Abstract: Delirium in hospitalized patients is a worldwide problem, causing a burden on healthcare professionals and impacting patient prognosis. A machine learning interpretation method (ML interpretation method) presents the results of machine learning predictions and promotes guided decisions. This study focuses on visualizing the predictors of delirium using a ML interpretation method and implementing the analysis results in clinical practice. Retrospective data of 55,389 patients hospitalized in a single acute care center in Japan between December 2017 and February 2022 were collected. Patients were categorized into three analysis populations, according to inclusion and exclusion criteria, to develop delirium prediction models. The predictors were then visualized using Shapley additive explanation (SHAP) and fed back to clinical practice. The machine learning-based prediction of delirium in each population exhibited excellent predictive performance. SHAP was used to visualize the body mass index and albumin levels as critical contributors to delirium prediction. In addition, the cutoff value for age, which was previously unknown, was visualized, and the risk threshold for age was raised. By using the SHAP method, we demonstrated that data-driven decision support is possible using electronic medical record data.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app13031564
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704225-X
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