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Search Results (31,672)

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13 pages, 882 KiB  
Article
Predicting Biochemical and Physiological Parameters: Deep Learning from IgG Glycome Composition
by Ana Vujić, Marija Klasić, Gordan Lauc, Ozren Polašek, Vlatka Zoldoš and Aleksandar Vojta
Int. J. Mol. Sci. 2024, 25(18), 9988; https://doi.org/10.3390/ijms25189988 (registering DOI) - 16 Sep 2024
Abstract
In immunoglobulin G (IgG), N-glycosylation plays a pivotal role in structure and function. It is often altered in different diseases, suggesting that it could be a promising health biomarker. Studies indicate that IgG glycosylation not only associates with various diseases but also [...] Read more.
In immunoglobulin G (IgG), N-glycosylation plays a pivotal role in structure and function. It is often altered in different diseases, suggesting that it could be a promising health biomarker. Studies indicate that IgG glycosylation not only associates with various diseases but also has predictive capabilities. Additionally, changes in IgG glycosylation correlate with physiological and biochemical traits known to reflect overall health state. This study aimed to investigate the power of IgG glycans to predict physiological and biochemical parameters. We developed two models using IgG N-glycan data as an input: a regression model using elastic net and a machine learning model using deep learning. Data were obtained from the Korčula and Vis cohorts. The Korčula cohort data were used to train both models, while the Vis cohort was used exclusively for validation. Our results demonstrated that IgG glycome composition effectively predicts several biochemical and physiological parameters, especially those related to lipid and glucose metabolism and cardiovascular events. Both models performed similarly on the Korčula cohort; however, the deep learning model showed a higher potential for generalization when validated on the Vis cohort. This study reinforces the idea that IgG glycosylation reflects individuals’ health state and brings us one step closer to implementing glycan-based diagnostics in personalized medicine. Additionally, it shows that the predictive power of IgG glycans can be used for imputing missing covariate data in deep learning frameworks. Full article
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<p>Correlation between the glycan peaks in the glycomics data. The dataset shows high correlation between glycans, which necessitates appropriate predictive models that are immune or at least resistant to such correlated data. Both the elastic net and deep learning have that required property. Glycan composition of each peak within the human IgG glycome has been previously established [<a href="#B32-ijms-25-09988" class="html-bibr">32</a>]. A representative chromatogram of the human IgG glycome and a detailed characterization of the glycan composition for each peak can be found in Pučić et al. [<a href="#B32-ijms-25-09988" class="html-bibr">32</a>] and Krištić et al. [<a href="#B15-ijms-25-09988" class="html-bibr">15</a>].</p>
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<p>Relative RMSE (root mean square error) normalized to the mean of the dataset for prediction of selected biochemical and physiological parameters based on IgG glycosylation in the Korčula cohort. In addition to the relative area under each of the 24 glycan peaks, only sex was used as an input variable. It is predicted with 100% accuracy, which was used as a “positive control”. Other biochemical and physiological parameters can be predicted from an IgG glycosylation pattern with varying degrees of accuracy. A regression model (glmnet) and a machine learning approach (tensorflow) show a similar degree of predictive power.</p>
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<p>Validation of the model trained on the Korčula cohort in the Vis cohort shows that the model performs reasonably well with the data from an unrelated sampling event that encompasses a different population, time, and batch. Only the parameters measured in both cohorts are reported. Again, relative RMSE normalized to the mean of the dataset is shown as a metric of the success of prediction for selected biochemical and physiological parameters (lower RMSE means better prediction), based on IgG glycosylation as input. The machine learning approach (tensorflow) performs significantly better for most parameters than the regression model (glmnet). The machine learning approach has the additional advantage of being easily extensible.</p>
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11 pages, 458 KiB  
Article
Comparison of Superselective Renal Artery Embolization versus Retroperitoneal Laparoscopic Partial Nephrectomy in Ruptured Hemorrhagic Renal Angiomyolipoma: A Single-Center Study
by Zhaoyang Li, Lu Yang, Huitang Yang, Tonghe Zhang, Yandong Cai, Zhan Jiang, Guoju Fan, Kaiqiang Wang, Bo Chen, Hongwei Zhang, Hailong Hu and Yankui Li
Diseases 2024, 12(9), 218; https://doi.org/10.3390/diseases12090218 - 16 Sep 2024
Abstract
Purpose: To analyze the clinical efficacy of superselective renal artery embolization and retroperitoneal laparoscopic partial nephrectomy for the treatment of ruptured hemorrhagic renal angiomyolipoma and to provide a reference for the selection of treatment methods for ruptured hemorrhagic renal angiomyolipoma. Methods: A retrospective [...] Read more.
Purpose: To analyze the clinical efficacy of superselective renal artery embolization and retroperitoneal laparoscopic partial nephrectomy for the treatment of ruptured hemorrhagic renal angiomyolipoma and to provide a reference for the selection of treatment methods for ruptured hemorrhagic renal angiomyolipoma. Methods: A retrospective analysis was conducted on the clinical data of 24 patients who were diagnosed with ruptured hemorrhagic renal angiomyolipoma at the Second Hospital of Tianjin Medical University between January 2019 and December 2021. Among them, 10 patients were treated with superselective arterial embolization (SAE), and 14 patients were treated with retroperitoneal laparoscopic part nephrectomy (RLPN). The differences between the two treatment methods in terms of hospital stay, hospital costs, anesthesia method, operation time, intraoperative blood loss, postoperative bed rest time, antibiotic dosage, postoperative complication rate, tumor diameter changes, creatinine value changes, hemoglobin value changes, tumor recurrence rate, and reoperation rate were compared. Results: All patients completed the treatment and were discharged. There were no significant differences in length of hospital stay, hospital costs, creatinine change values, or postoperative complication rates between the two groups (p > 0.05). However, there were statistically significant differences (p < 0.05) in surgical time (85.50 ± 19.94 min vs. 141.07 ± 76.33 min), intraoperative blood loss (21.50 ± 14.72 mL vs. 153.57 ± 97.00 mL), postoperative bed rest time (22.7 ± 1.56 h vs. 41.21 ± 3.57 h), preoperative hemoglobin levels (94.7 ± 23.62 g/L vs. 113.79 ± 17.83 g/L), and hemoglobin changes (−6.60 ±10.36 g/L vs. −15.21 ± 8.79 g/L) between the two groups. Both groups of patients had an average follow-up period of 22 months, and patients in the SAE group had a mean reduction of 3.33 cm in tumor diameter within the follow-up period compared with the pre-embolization period (p < 0.05). None of the patients in the SAE group experienced rebleeding, and there was no tumor recurrence in either group. Conclusion: SAE and RLPN are effective treatments for ruptured renal angiomyolipoma with good outcomes. Furthermore, compared to RLPN, SAE offers advantages such as simplicity of operation, minimal trauma, shorter surgical time, minimal impact on hemoglobin levels, shorter bed rest time, faster postoperative recovery, and maximal preservation of renal units. Full article
15 pages, 841 KiB  
Article
PREVENT Equation: The Black Sheep among Cardiovascular Risk Scores? A Comparative Agreement Analysis of Nine Prediction Models in High-Risk Lithuanian Women
by Petras Navickas, Laura Lukavičiūtė, Sigita Glaveckaitė, Arvydas Baranauskas, Agnė Šatrauskienė, Jolita Badarienė and Aleksandras Laucevičius
Medicina 2024, 60(9), 1511; https://doi.org/10.3390/medicina60091511 - 16 Sep 2024
Abstract
Background and Objectives: In the context of female cardiovascular risk categorization, we aimed to assess the inter-model agreement between nine risk prediction models (RPM): the novel Predicting Risk of cardiovascular disease EVENTs (PREVENT) equation, assessing cardiovascular risk using SIGN, the Australian CVD risk [...] Read more.
Background and Objectives: In the context of female cardiovascular risk categorization, we aimed to assess the inter-model agreement between nine risk prediction models (RPM): the novel Predicting Risk of cardiovascular disease EVENTs (PREVENT) equation, assessing cardiovascular risk using SIGN, the Australian CVD risk score, the Framingham Risk Score for Hard Coronary Heart Disease (FRS-hCHD), the Multi-Ethnic Study of Atherosclerosis risk score, the Pooled Cohort Equation (PCE), the QRISK3 cardiovascular risk calculator, the Reynolds Risk Score, and Systematic Coronary Risk Evaluation-2 (SCORE2). Materials and Methods: A cross-sectional study was conducted on 6527 40–65-year-old women with diagnosed metabolic syndrome from a single tertiary university hospital in Lithuania. Cardiovascular risk was calculated using the nine RPMs, and the results were categorized into high-, intermediate-, and low-risk groups. Inter-model agreement was quantified using Cohen’s Kappa coefficients. Results: The study uncovered a significant diversity in risk categorization, with agreement on risk category by all models in only 1.98% of cases. The SCORE2 model primarily classified subjects as high-risk (68.15%), whereas the FRS-hCHD designated the majority as low-risk (94.42%). The range of Cohen’s Kappa coefficients (−0.09–0.64) reflects the spectrum of agreement between models. Notably, the PREVENT model demonstrated significant agreement with QRISK3 (κ = 0.55) and PCE (κ = 0.52) but was completely at odds with the SCORE2 (κ = −0.09). Conclusions: Cardiovascular RPM selection plays a pivotal role in influencing clinical decisions and managing patient care. The PREVENT model revealed balanced results, steering clear of the extremes seen in both SCORE2 and FRS-hCHD. The highest concordance was observed between the PREVENT model and both PCE and QRISK3 RPMs. Conversely, the SCORE2 model demonstrated consistently low or negative agreement with other models, highlighting its unique approach to risk categorization. These findings accentuate the need for additional research to assess the predictive accuracy of these models specifically among the Lithuanian female population. Full article
(This article belongs to the Special Issue Current Advances in Cardiovascular Disease Research)
15 pages, 660 KiB  
Systematic Review
Objectively Measured Physical Activity and Sedentary Behaviour on Cardiovascular Risk and Health-Related Quality of Life in Adults: A Systematic Review
by Beatriz Santos, Diogo Monteiro, Fernanda M. Silva, Gonçalo Flores, Teresa Bento and Pedro Duarte-Mendes
Healthcare 2024, 12(18), 1866; https://doi.org/10.3390/healthcare12181866 - 16 Sep 2024
Abstract
Background: This systematic review analysed the association between objectively measured physical activity and sedentary behaviour with cardiovascular risk and HRQoL in adults without previous CVD. Additionally, we analysed the impact of the intensity of the physical activity in this association. Methods: The search [...] Read more.
Background: This systematic review analysed the association between objectively measured physical activity and sedentary behaviour with cardiovascular risk and HRQoL in adults without previous CVD. Additionally, we analysed the impact of the intensity of the physical activity in this association. Methods: The search was carried out in three electronic databases with access until February 2023 to find studies with an observational design. For quality assessment, we used The National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: We identified 5819 references, but only five studies were included. One study shows a positive association between physical activity and HRQoL, while sedentary behaviour was negatively related to HRQoL. Another study showed an association between high-intensity physical activity with a better physical component of HRQoL and low-intensity physical activity with a better mental component of HRQoL. Three studies concluded that higher levels of physical activity are associated with lower levels of cardiovascular risk and higher levels of sedentary behaviour are associated with higher levels of cardiovascular risk. Conclusion: Our findings suggested that people who spend more time being active and spend less time being sedentary appear to have lower cardiovascular risk and higher HRQoL. Full article
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<p>Search strategy and studies selection flow chart.</p>
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12 pages, 617 KiB  
Article
Baseline Predictors of Adverse Outcomes for Transthyretin Amyloidosis Cardiomyopathy Patients Treated and Untreated with Tafamidis: A Canadian Referral Center Experience
by Karan Shahi, Robert J. H. Miller, Steven Dykstra, Yuanchao Feng, Jonathan G. Howlett, Victor Jimenez-Zepeda, Jan Veenhuyzen, James A. White and Nowell M. Fine
J. Clin. Med. 2024, 13(18), 5490; https://doi.org/10.3390/jcm13185490 - 16 Sep 2024
Abstract
Background: Tafamidis is a costly therapy that improves outcomes for patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM), although significant knowledge gaps exist for predicting longer-term response to treatment. The purpose of this study was to examine baseline predictors of adverse outcomes and their association [...] Read more.
Background: Tafamidis is a costly therapy that improves outcomes for patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM), although significant knowledge gaps exist for predicting longer-term response to treatment. The purpose of this study was to examine baseline predictors of adverse outcomes and their association with tafamidis treatment in comparison with those untreated in a clinical cohort from a Canadian ATTR-CM referral center. Methods: Patients with a confirmed diagnosis of ATTR-CM were included. Multivariable modeling was used to identify baseline variables associated with the primary outcome of all-cause mortality and secondary outcomes of cardiovascular mortality or hospitalization. Cox proportional hazard and competing risk analyses were used, with tafamidis modeled as a time-varying covariate. Results: In total, 139 ATTR-CM patients were included, with a median age of 80.9 years [74.3–86.6 years], from 2011 to 2022. The mean follow-up was 2.9 ± 1.8 years. Eighty (55%) patients were treated with tafamidis. All-cause mortality and cardiovascular mortality alone were associated with the following baseline variables: age, clinical frailty scale, systolic blood pressure, renal function, and right ventricular size and function (all p < 0.05), with no identified interactions with tafamidis treatment. Only baseline renal function was associated with cardiovascular hospitalization (p < 0.05). Conclusion: Important baseline variables associated with adverse ATTR-CM disease outcomes included renal function, systolic blood pressure, frailty, and right ventricular size and function. The risk factors were independent of treatment with tafamidis. These findings may help improve risk stratification for determining eligibility for ATTR-CM therapies. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)
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<p>Kaplan–Meier survival curves for all-cause mortality (<b>A</b>), cardiovascular mortality (<b>B</b>), and hospitalization (<b>C</b>) stratified by tafamidis therapy.</p>
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<p>Kaplan–Meier survival curves for all-cause mortality (<b>A</b>), cardiovascular mortality (<b>B</b>), and hospitalization (<b>C</b>) stratified by tafamidis therapy.</p>
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12 pages, 1878 KiB  
Article
Comparative Temporal Analysis of Morbidity and Early Mortality in Heart Transplantation with Extracorporeal Membrane Oxygenation Support: Exploring Trends over Time
by Raquel López-Vilella, Manuel Pérez Guillén, Borja Guerrero Cervera, Ricardo Gimeno Costa, Iratxe Zarragoikoetxea Jauregui, Francisca Pérez Esteban, Paula Carmona, Tomás Heredia Cambra, Mónica Talavera Peregrina, Azucena Pajares Moncho, Carlos Domínguez-Massa, Víctor Donoso Trenado, Luis Martínez Dolz, Pilar Argente, Álvaro Castellanos, Juan Martínez León, Salvador Torregrosa Puerta and Luis Almenar Bonet
Biomedicines 2024, 12(9), 2109; https://doi.org/10.3390/biomedicines12092109 - 16 Sep 2024
Abstract
Background/Objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare [...] Read more.
Background/Objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare the presumed differences between various eras over a 17-year timeline. Methods: This is a prospective, observational study on consecutive patients stabilized with VA-ECMO and transplanted with VA-ECMO from July 2007 to December 2023 at a reference center (98 patients). Objective variables were mortality and morbidity from renal failure, venous thromboembolic disease (VTD), primary graft dysfunction (PGD), the need for tracheostomy, severe myopathy, reoperation, post-transplant ECMO, vascular complications, and sepsis/infection. Results: The percentage of patients who reached transplantation without the need for mechanical ventilation has increased over the periods studied. No significant differences were found between the study periods in 30-day mortality (p = 0.822), hospital discharge (p = 0.972), one-year mortality (p = 0.706), or five-year mortality (p = 0.797). Survival rates in these periods were 84%, 75%, 64%, and 61%, respectively. Comorbidities were very frequent, with an average of 3.33 comorbidities per patient. The most frequent were vascular complications (58%), the need for post-transplant ECMO (57%), and myopathy (55%). The development of myopathy and the need for post-transplant ECMO were higher in recent periods (p = 0.004 and p = 0.0001, respectively). Conclusions: VA-ECMO support as a bridge to HT allows hospital discharge for 3 out of 4 transplanted patients. This survival rate has not changed over the years. The comorbidities associated with this device are frequent and significant. Full article
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<p>Study flowchart. Abbreviations: HLT: heart–lung transplantation; HKT: heart–kidney transplantation; and HT: heart transplantation.</p>
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<p>Venoarterial ECMO cannulation.</p>
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<p>Survival at thirty days, one year, and five years.</p>
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<p>Overall prevalence of complications in patients pre-transplant (complications per patient). The histogram shows the percentage of patients presenting each number of complications.</p>
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<p>Association between complications and duration of pre-transplant ECMO support. Statistically significant associations are shown in green, trends in yellow, and associations without statistical significance in blue (Pearson correlation). Abbreviations: DVT: deep vein thrombosis; ECMO: extracorporeal membrane oxygenation; EP: pulmonary embolism; PC: Pearson correlation; PGD: primary graft dysfunction.</p>
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11 pages, 565 KiB  
Article
Lifestyle Habits and Risk of Cardiovascular Mortality in Menopausal Women with Cardiovascular Risk Factors: A Retrospective Cohort Study
by Adriana Lopez-Pineda, Cristina Soriano-Maldonado, Vicente Arrarte, Francisco Sanchez-Ferrer, Vicente Bertomeu-Gonzalez, Juan Miguel Ruiz-Nodar, Jose A. Quesada and Alberto Cordero
J. Cardiovasc. Dev. Dis. 2024, 11(9), 287; https://doi.org/10.3390/jcdd11090287 - 16 Sep 2024
Abstract
Current cardiovascular prevention guidelines emphasise considering sex, gender, and gender identity in risk assessment. This study evaluated the impact of lifestyle habits and chronic diseases on cardiovascular mortality risk in women over 50 with high vascular risk and developed a predictive model for [...] Read more.
Current cardiovascular prevention guidelines emphasise considering sex, gender, and gender identity in risk assessment. This study evaluated the impact of lifestyle habits and chronic diseases on cardiovascular mortality risk in women over 50 with high vascular risk and developed a predictive model for menopausal women with cardiovascular risk factors. A retrospective cohort study used data from the 2011 Spanish National Health Survey and the national death register, focusing on menopausal and postmenopausal women without prior cardiovascular events but with at least one major risk factor. Participants were followed for up to 10 years, assessing mortality from circulatory system diseases and other causes. Exposure variables included socio-demographics, lifestyle habits, health status, self-perceived health, health service use, and pharmacological treatments. Of the 21,007 respondents, 3057 women met the inclusion criteria. The 10-year cumulative incidence of mortality from circulatory causes was 5.9%, and from other causes, 12.7%. Independent predictors of cardiovascular mortality were never consuming legumes, poor self-perceived health, diabetes treatment, lack of physical activity, and older age. Lipid-lowering treatment was protective. The model demonstrated good fit and predictive capacity (C-index = 0.773). This study highlights the significant influence of physical activity, legume consumption, self-perceived health, and specific treatments on cardiovascular mortality risk in menopausal women. Full article
(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)
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<p>Flow chart of the study.</p>
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13 pages, 281 KiB  
Perspective
Polypills in the Management of Cardiovascular Risk—A Perspective
by Erlon Oliveira de Abreu-Silva, Martin Siepmann and Timo Siepmann
J. Clin. Med. 2024, 13(18), 5487; https://doi.org/10.3390/jcm13185487 - 16 Sep 2024
Viewed by 66
Abstract
Cardiovascular disease and cardiovascular risk factors are global healthcare problems, given their high prevalence and the recognized low rates of adequate control despite the abundant body of evidence on different therapeutic options. The World Heart Federation has scrutinized the reasons for poor control [...] Read more.
Cardiovascular disease and cardiovascular risk factors are global healthcare problems, given their high prevalence and the recognized low rates of adequate control despite the abundant body of evidence on different therapeutic options. The World Heart Federation has scrutinized the reasons for poor control of cardiovascular risk factors. Among these reasons, patients’ poor adherence to treatment regimens as well as limited rates of evidence-based therapy prescription from healthcare providers play a substantial role in the challenge of cardiovascular risk management. Polypills are fixed-dose combinations including two or more active drugs, from different pharmacological classes, combined in a single dosage form. Polypills were designed to simplify the clinical management of pharmacotherapy and increase adherence to treatment. From this perspective, we discuss the current literature on the use of polypills in the primary and secondary prevention of cardiovascular disease as well as future challenges and the potentials of this treatment strategy. Full article
(This article belongs to the Section Pharmacology)
24 pages, 1007 KiB  
Review
Cardiovascular and Metabolic Benefits of Extra Virgin Olive Oil Phenolic Compounds: Mechanistic Insights from In Vivo Studies
by Gabriele Serreli, Anna Boronat, Rafael De la Torre, Josè Rodriguez-Moratò and Monica Deiana
Cells 2024, 13(18), 1555; https://doi.org/10.3390/cells13181555 - 16 Sep 2024
Viewed by 86
Abstract
Extra virgin olive oil (EVOO) represents a significant source of monounsaturated fatty acids (MUFA) and vitamin E, but it is also considered a functional food, due to the content of peculiar bioactive molecules, such as phenolic compounds, being able to modulate various processes [...] Read more.
Extra virgin olive oil (EVOO) represents a significant source of monounsaturated fatty acids (MUFA) and vitamin E, but it is also considered a functional food, due to the content of peculiar bioactive molecules, such as phenolic compounds, being able to modulate various processes related to aging and the most common metabolic and degenerative diseases. A lot of experimental research has focused on some of these components, but in most cases, the studies were performed in vitro testing compounds at non-physiological concentrations and achieving results that cannot easily be translated in vivo. Recent clinical studies demonstrated that in vivo these compounds are able to regulate physiological functions and prevent several pathological events including metabolic and cardiovascular diseases (CVDs), which represent the main causes of death worldwide. This review aims to sum up the major evidence on the beneficial effects of EVOO phenolic compounds in vivo on these pathologies, describing and evaluating the efficacy in relation to the mechanisms of diseases of the whole phenolic fraction and some of its specific components. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms on Plant Polyphenols)
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<p>Chemical structures of main phenylethanoids and secoiridoids present in EVOO.</p>
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<p>Main mechanisms involved in the protective effects of EVOO phenolic compounds against cardiovascular and metabolic diseases.</p>
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16 pages, 1211 KiB  
Article
Patterns of Lipid Abnormalities in Obesity: A Comparative Analysis in Normoglycemic and Prediabetic Obese Individuals
by Yazeed Alshuweishi, Abdulmalik A. Almufarrih, Arwa Abudawood, Dalal Alfayez, Abdullah Y. Alkhowaiter, Hamood AlSudais and Abdulaziz M. Almuqrin
J. Pers. Med. 2024, 14(9), 980; https://doi.org/10.3390/jpm14090980 (registering DOI) - 15 Sep 2024
Viewed by 235
Abstract
Abstract: Background: Obesity is a growing global health concern, often accompanied by dyslipidemia, contributing to cardiovascular risk. Understanding the patterns of dyslipidemia in different glycemic states is crucial for targeted interventions. This study compares dyslipidemia patterns in normoglycemic and prediabetic obesity to [...] Read more.
Abstract: Background: Obesity is a growing global health concern, often accompanied by dyslipidemia, contributing to cardiovascular risk. Understanding the patterns of dyslipidemia in different glycemic states is crucial for targeted interventions. This study compares dyslipidemia patterns in normoglycemic and prediabetic obesity to improve clinical management strategies. Methods: The study analyzed the complete lipid profiles of 138 subjects, comparing the medians, prevalence, diagnostic performance, and risk assessment of each lipid parameter across 54 non-obese (NO), 44 normoglycemic obese (NG-OB), and 40 pre-diabetic obese (PreDM-OB) groups. Results: Elevated total cholesterol (TC) and low-density lipoprotein (LDL) were the most prevalent forms of dyslipidemia observed in obesity (45.35% and 43.53%, respectively). Stratification by glycemic status revealed that triglyceride (TG) levels were elevated in both the NG-OB and PreDM-OB groups, with a more marked increase in the latter group (73.07 mg/dL vs. 97.87 mg/dL vs. 121.8 mg/dL, respectively). Elevated LDL showed better diagnostic performance and higher odds ratios (OR) in the NG-OB group (AUC = 0.660, p = 0.006; OR = 2.78, p = 0.022). Conversely, low high-density lipoprotein (HDL) was more common and exhibited significant diagnostic performance, with higher OR values in the PreDM-OB group (AUC = 0.687, p = 0.002; OR = 3.69, p = 0.018). Importantly, all lipid ratios were elevated in obesity, with TC/HDL showing the highest predictive ability for prediabetes (AUC = 0.7491, p < 0.001). Conclusions: These findings revealed unique and common lipid abnormalities in normoglycemic and prediabetic obesity. Future research should explore the effects of targeted lipid management on obesity-associated complications. Full article
(This article belongs to the Topic Metabolic Syndrome, Biomarkers and Lifestyles)
17 pages, 5163 KiB  
Article
Fermented Fish Collagen Attenuates Melanogenesis via Decreasing UV-Induced Oxidative Stress
by Kyung-A Byun, So Young Lee, Seyeon Oh, Sosorburam Batsukh, Jong-Won Jang, Bae-Jin Lee, Kyoung-min Rheu, Sichao Li, Min-Seok Jeong, Kuk Hui Son and Kyunghee Byun
Mar. Drugs 2024, 22(9), 421; https://doi.org/10.3390/md22090421 - 15 Sep 2024
Viewed by 261
Abstract
Excessive melanogenesis leads to hyperpigmentation-related cosmetic problems. UV exposure increases oxidative stress, which promotes melanogenesis-related signal pathways such as the PKA, microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2) pathways. Glycine is a source of endogenous antioxidants, including [...] Read more.
Excessive melanogenesis leads to hyperpigmentation-related cosmetic problems. UV exposure increases oxidative stress, which promotes melanogenesis-related signal pathways such as the PKA, microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2) pathways. Glycine is a source of endogenous antioxidants, including glutathione. Fermented fish collagen (FC) contains glycine; thus, we evaluated the effect of FC on decreasing melanogenesis via decreasing oxidative stress. The glycine receptor (GlyR) and glycine transporter-1 (GlyT1) levels were decreased in UV-irradiated keratinocytes; however, the expression levels of these proteins increased upon treatment with FC. The FC decreased oxidative stress, as indicated by the decreasing expression of NOX1/2/4, increased expression of GSH/GSSG, increased SOD activity, and decreased 8-OHdG expression in UV-irradiated keratinocytes. Administration of conditioned media from FC-treated keratinocytes to melanocytes led to decreased p38, PKC, MITF, TRP1, and TRP2 expression. These changes induced by the FC were also observed in UV-irradiated animal skin. FC treatment increased the expression of GlyR and GlyT, which was accompanied by decreased oxidative stress in the UV-irradiated skin. Moreover, the FC negatively regulated the melanogenesis signaling pathways, leading to decreased melanin content in the UV-irradiated skin. In conclusion, FC decreased UV-induced oxidative stress and melanogenesis in melanocytes and animal skin. FC could be used in the treatment of UV-induced hyperpigmentation problems. Full article
(This article belongs to the Special Issue Marine Cosmeceuticals)
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<p>Regulation of GlyR and GlyT expression and oxidative stress by FC and glycine in UV-exposed keratinocytes. (<b>A</b>) Schematic diagram of the treatment of UV-exposed keratinocytes with FC and glycine. (<b>B</b>) Protein expression of GlyR and GlyT in UV-exposed keratinocytes following FC and glycine treatment. (<b>C</b>) Protein expression of NOX1/2/4 in UV-exposed keratinocytes following FC and glycine treatment. (<b>D</b>) The increased level of GSH/GSSG ratio in UV-exposed keratinocytes following FC and glycine treatment. (<b>E</b>) The SOD activity in UV-exposed keratinocytes following FC and glycine treatment. (<b>F</b>) The increased level of 8-OHdG in UV-exposed keratinocytes following FC and glycine treatment. Data are presented as the mean ± SD of three independent experiments. ***, <span class="html-italic">p</span> &lt; 0.001, first bar vs. second bar; <span>$</span><span>$</span>, <span class="html-italic">p</span> &lt; 0.01, vs. second bar; #, <span class="html-italic">p</span> &lt; 0.05, vs. third bar (Mann–Whitney U test). FC, fermented fish collagen; GlyR, glycine receptor; GlyT, glycine transporter; GSH, glutathione; GSSG, oxidized glutathione; NOX, nicotinamide adenine dinucleotide phosphate oxidase; PBS, phosphate-buffered saline; SD, standard deviation; SOD, superoxide dismutase; UV, ultraviolet; 8-OHdG, 8-hydroxy-2-deoxyguanosine.</p>
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<p>Regulation of p38, PKC, MITF, TRP1, TRP2, and TYR activity by FC and glycine in melanocytes. (<b>A</b>) Schematic diagram demonstrating melanocytes affected by conditioned media obtained from cultures of keratinocyte with UV-induced pigmentation for the evaluation of FC and glycine. (<b>B</b>) Protein expression of GlyR and GlyT in melanocytes treated with CM from UV-exposed keratinocytes with or without FC and glycine treatments. (<b>C</b>,<b>D</b>) Quantitative assessment of Western blot data presented in (<b>B</b>). (<b>E</b>) Protein expression of pp38, p38, PKC, MITF, TRP1, and TRP2 in melanocytes treated with CM from UV-exposed keratinocytes with or without FC and glycine treatments. (<b>F</b>–<b>J</b>) Quantitative assessment of Western blot data presented in (<b>E</b>). (<b>K</b>) Tyrosinase activity in melanocytes treated with CM from UV-exposed keratinocytes with or without FC and glycine treatments. Data are presented as the mean ± SD of three independent experiments. ***, <span class="html-italic">p</span> &lt; 0.001, first bar vs. second bar; <span>$</span><span>$</span>, <span class="html-italic">p</span> &lt; 0.01, vs. second bar; #, <span class="html-italic">p</span> &lt; 0.05; ##, <span class="html-italic">p</span> &lt; 0.01, vs. third bar (Mann–Whitney U test). CM, conditioned media; FC, fermented fish collagen; GlyR, glycine receptor; GlyT, glycine transporter; MITF, microphthalmia-associated transcription factor; PBS, phosphate-buffered saline; PKC, protein kinase C; pp38, phosphorylated p38; SD, standard deviation; TRP1, tyrosinase-related protein-1; TRP2, tyrosinase-related protein-2; UV, ultraviolet.</p>
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<p>Regulation of p38, PKC, MITF, TRP1, TRP2, and TYR activity by FC and glycine in melanocytes. (<b>A</b>) Schematic diagram demonstrating melanocytes affected by conditioned media obtained from cultures of keratinocyte with UV-induced pigmentation for the evaluation of FC and glycine. (<b>B</b>) Protein expression of GlyR and GlyT in melanocytes treated with CM from UV-exposed keratinocytes with or without FC and glycine treatments. (<b>C</b>,<b>D</b>) Quantitative assessment of Western blot data presented in (<b>B</b>). (<b>E</b>) Protein expression of pp38, p38, PKC, MITF, TRP1, and TRP2 in melanocytes treated with CM from UV-exposed keratinocytes with or without FC and glycine treatments. (<b>F</b>–<b>J</b>) Quantitative assessment of Western blot data presented in (<b>E</b>). (<b>K</b>) Tyrosinase activity in melanocytes treated with CM from UV-exposed keratinocytes with or without FC and glycine treatments. Data are presented as the mean ± SD of three independent experiments. ***, <span class="html-italic">p</span> &lt; 0.001, first bar vs. second bar; <span>$</span><span>$</span>, <span class="html-italic">p</span> &lt; 0.01, vs. second bar; #, <span class="html-italic">p</span> &lt; 0.05; ##, <span class="html-italic">p</span> &lt; 0.01, vs. third bar (Mann–Whitney U test). CM, conditioned media; FC, fermented fish collagen; GlyR, glycine receptor; GlyT, glycine transporter; MITF, microphthalmia-associated transcription factor; PBS, phosphate-buffered saline; PKC, protein kinase C; pp38, phosphorylated p38; SD, standard deviation; TRP1, tyrosinase-related protein-1; TRP2, tyrosinase-related protein-2; UV, ultraviolet.</p>
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<p>Regulation of GlyR and GlyT expression and oxidative stress by FC in UV-exposed animal skin. (<b>A</b>) Schematic diagram of the treatment of UV-exposed animal skin with FC. (<b>B</b>) Protein expression of GlyR and GlyT in UV-exposed animal skin following FC treatment was measured using Western blot. (<b>C</b>) Protein expression of NOXs in UV-exposed animal skin following FC treatment. (<b>D</b>) The increased level of GSH/GSSG ratio in UV-exposed animal skin following FC treatment. (<b>E</b>) The SOD activity in UV-exposed animal skin following FC treatment. (<b>F</b>) The increased level of 8-OHdG in UV-exposed animal skin following FC treatment. Data are presented as the mean ± SD of three independent experiments. ***, <span class="html-italic">p</span> &lt; 0.001, first bar vs. second bar; <span>$</span><span>$</span>, <span class="html-italic">p</span> &lt; 0.01, vs. second bar; ##, <span class="html-italic">p</span> &lt; 0.01, vs. fourth bar (Mann–Whitney U test). FC, fermented fish collagen; GlyR, glycine receptor; GlyT, glycine transporter; GSH, glutathione; GSSG, oxidized glutathione; NOX, nicotinamide adenine dinucleotide phosphate oxidase; SD, standard deviation; SOD, superoxide dismutase; UV, ultraviolet; 8-OHdG, 8-hydroxy-2-deoxyguanosine.</p>
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<p>Regulation of melanogenesis upon treatment with different concentrations of FC in UV-exposed animal skin. (<b>A</b>) Protein expression of pp38, p38, PKC, MITF, TRP1, and TRP2 in UV-exposed animal skin following FC treatment. (<b>B</b>) Tyrosinase activity in UV-exposed animal skin following FC treatment. (<b>C</b>,<b>E</b>) Melanin content was determined using Fontana–Masson staining in UV-exposed animal skin with or without FC treatments. Scale bar = 100 µm. The blue dotted boxes are magnified images of the Fontana–Masson image. (<b>D</b>,<b>F</b>) Skin lightness in UV-irradiated animal skin with or without FC treatments. Scale bar = 500 µm. Data are presented as the mean ± SD of three independent experiments. ***, <span class="html-italic">p</span> &lt; 0.001, first bar vs. second bar; <span>$</span><span>$</span>, <span class="html-italic">p</span> &lt; 0.01, vs. second bar; ##, <span class="html-italic">p</span> &lt; 0.01, vs. fourth bar (Mann–Whitney U test). A.U., arbitrary unit; FC, fermented fish collagen; L*, lightness; MITF, microphthalmia-associated transcription factor; PKC, protein kinase C; pp38, phosphorylated p38; SD, standard deviation; TRP1, tyrosinase-related protein-1; TRP2, tyrosinase-related protein-2; UV, ultraviolet.</p>
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12 pages, 1679 KiB  
Article
Omega-3 Fatty Acids Modify Drp1 Expression and Activate the PINK1-Dependent Mitophagy Pathway in the Kidney and Heart of Adenine-Induced Uremic Rats
by Dong Ho Choi, Su Mi Lee, Bin Na Park, Mi Hwa Lee, Dong Eun Yang, Young Ki Son, Seong Eun Kim and Won Suk An
Biomedicines 2024, 12(9), 2107; https://doi.org/10.3390/biomedicines12092107 - 15 Sep 2024
Viewed by 206
Abstract
Mitochondrial homeostasis is controlled by biogenesis, dynamics, and mitophagy. Mitochondrial dysfunction plays a central role in cardiovascular and renal disease and omega-3 fatty acids (FAs) are beneficial for cardiovascular disease. We investigated whether omega-3 fatty acids (FAs) regulate mitochondrial biogenesis, dynamics, and mitophagy [...] Read more.
Mitochondrial homeostasis is controlled by biogenesis, dynamics, and mitophagy. Mitochondrial dysfunction plays a central role in cardiovascular and renal disease and omega-3 fatty acids (FAs) are beneficial for cardiovascular disease. We investigated whether omega-3 fatty acids (FAs) regulate mitochondrial biogenesis, dynamics, and mitophagy in the kidney and heart of adenine-induced uremic rats. Eighteen male Sprague Dawley rats were divided into normal control, adenine control, and adenine with omega-3 FA groups. Using Western blot analysis, the kidney and heart expression of mitochondrial homeostasis-related molecules, including peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), dynamin-related protein 1 (Drp1), and phosphatase and tensin homolog-induced putative kinase 1 (PINK1) were investigated. Compared to normal, serum creatinine and heart weight/body weight in adenine control were increased and slightly improved in the omega-3 FA group. Compared to the normal controls, the expression of PGC-1α and PINK1 in the kidney and heart of the adenine group was downregulated, which was reversed after omega-3 FA supplementation. Drp1 was upregulated in the kidney but downregulated in the heart in the adenine group. Drp1 expression in the heart recovered in the omega-3 FA group. Mitochondrial DNA (mtDNA) was decreased in the kidney and heart of the adenine control group but the mtDNA of the heart was recovered in the omega-3 FA group. Drp1, which is related to mitochondrial fission, may function oppositely in the uremic kidney and heart. Omega-3 FAs may be beneficial for mitochondrial homeostasis by activating mitochondrial biogenesis and PINK1-dependent mitophagy in the kidney and heart of uremic rats. Full article
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<p>Changes in the expression of factors related to mitochondrial biogenesis including PGC-1α, SIRT1/3, and Nrf2 in the kidney (<b>A</b>) and heart (<b>B</b>). * <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from the control group). <sup>a</sup> <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from the adenine group).</p>
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<p>Changes in the expression of factors related to mitochondrial fusion and fission including OPA1, Drp1, and Mfn1/2 in the kidney (<b>A</b>) and heart (<b>B</b>). * <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from normal control group). <sup>a</sup> <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from the adenine group).</p>
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<p>Changes in the expression of factors related to mitochondrial mitophagy including PINK1, BNIP3, and NIX in the kidney (<b>A</b>) and heart (<b>B</b>). * <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from the control group). <sup>a</sup> <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from the adenine group).</p>
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<p>Relative mitochondrial DNA (mtDNA) content in the kidney (<b>A</b>) and heart (<b>B</b>). * <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from the control group). <sup>a</sup> <span class="html-italic">p</span> value &lt; 0.05 (mean values are significantly different from the adenine group).</p>
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15 pages, 479 KiB  
Article
Impact of Newly Diagnosed Left Bundle Branch Block on Long-Term Outcomes in Patients with STEMI
by Larisa Anghel, Cristian Stătescu, Radu Andy Sascău, Bogdan-Sorin Tudurachi, Andreea Tudurachi, Laura-Cătălina Benchea, Cristina Prisacariu and Rodica Radu
J. Clin. Med. 2024, 13(18), 5479; https://doi.org/10.3390/jcm13185479 - 15 Sep 2024
Viewed by 178
Abstract
Background/Objectives: This study assessed the long-term prognostic implications of newly developed left bundle branch block (LBBB) in patients with ST-elevation myocardial infarction (STEMI) and a single coronary lesion, following primary percutaneous coronary intervention (PCI). Methods: Among 3526 patients admitted with acute myocardial [...] Read more.
Background/Objectives: This study assessed the long-term prognostic implications of newly developed left bundle branch block (LBBB) in patients with ST-elevation myocardial infarction (STEMI) and a single coronary lesion, following primary percutaneous coronary intervention (PCI). Methods: Among 3526 patients admitted with acute myocardial infarction between January 2011 and December 2013, 42 were identified with STEMI, a single coronary lesion, and newly diagnosed LBBB. A control group of 42 randomly selected STEMI patients without LBBB was also included. All participants were prospectively evaluated with a median follow-up duration of 9.4 years. Demographic, clinical, and laboratory data were analyzed to assess the impact of LBBB on long-term outcomes. Results: The baseline characteristics were similar between the groups. The STEMI with new LBBB group had significantly higher rates of new myocardial infarction, revascularization, and mortality, highlighting the severe prognostic implications and elevated risk for adverse outcomes compared to STEMI without LBBB. The multivariate Cox regression analysis demonstrated that the presence of LBBB (HR: 2.15, 95% CI: 1.28–3.62, p = 0.003), lower LVEF (HR: 1.45, 95% CI: 1.22–1.72, p < 0.001), and longer pain-to-admission time (HR: 1.32, 95% CI: 1.09–1.61, p = 0.008) were significant independent predictors of adverse outcomes. Conclusions: Newly acquired LBBB in STEMI patients is associated with poorer long-term outcomes. Early identification and management of factors such as reduced LVEF and timely hospital admission, specifically in patients with new-onset LBBB, can improve prognosis. Full article
(This article belongs to the Special Issue Clinical Management of Patients with Heart Failure)
15 pages, 480 KiB  
Review
The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19
by Jingwen Li, Xiangrui Kong, Tingting Liu, Meiyan Xian and Jianshe Wei
Int. J. Mol. Sci. 2024, 25(18), 9960; https://doi.org/10.3390/ijms25189960 (registering DOI) - 15 Sep 2024
Viewed by 210
Abstract
Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a [...] Read more.
Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a critical role in the cardiovascular system but also plays an important role in the protection, development, and inflammation regulation of the nervous system. The COVID-19 pandemic further highlights the importance of ACE2 in the nervous system. SARS-CoV-2 enters host cells by binding to ACE2, which may directly or indirectly affect the nervous system, leading to a range of neurological symptoms. This review aims to explore the function of ACE2 in the nervous system as well as its potential impact and therapeutic potential in various neurological diseases, providing a new perspective for the treatment of neurological disorders. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 3.0)
13 pages, 1096 KiB  
Article
Fibrosis-4 Score Is Associated with Mortality in Hemodialysis Patients with Chronic Viral Hepatitis: A Retrospective Study
by Hao-Hsuan Liu, Chieh-Li Yen, Wen-Juei Jeng, Cheng-Chieh Hung, Ching-Chung Hsiao, Ya-Chung Tian and Kuan-Hsing Chen
Diagnostics 2024, 14(18), 2048; https://doi.org/10.3390/diagnostics14182048 - 15 Sep 2024
Viewed by 186
Abstract
BACKGROUND: Chronic hepatitis B and C infections are major causes of morbidity and mortality in end-stage kidney disease (ESKD) patients on hemodialysis (HD). The Fibrosis-4 (FIB-4) score is a non-invasive method to evaluate chronic liver disease. However, it is unclear whether there is [...] Read more.
BACKGROUND: Chronic hepatitis B and C infections are major causes of morbidity and mortality in end-stage kidney disease (ESKD) patients on hemodialysis (HD). The Fibrosis-4 (FIB-4) score is a non-invasive method to evaluate chronic liver disease. However, it is unclear whether there is a connection between the FIB-4 score and major adverse cardiovascular events (MACEs) and mortality in patients on HD. This study investigates the relationship between FIB-4 scores, MACEs, and mortality in HD patients. METHODS: A 5-year retrospective study included 198 HD patients with chronic hepatitis B and C from Chang Gung Memorial Hospital. FIB-4 scores were categorized into high (>2.071), middle (1.030~2.071), and low (<1.030) tertiles for cross-sectional analyses. MACEs and mortality were tracked longitudinally. RESULTS: Patients with high FIB-4 scores had lower hemoglobin and albumin levels. Cox multivariate analysis showed that high FIB-4 scores (aHR: 1.589) and diabetes mellitus (aHR: 5.688) were significant factors for all-cause mortality. The optimal FIB-4 score for 5-year mortality was 2.942. FIB-4 scores were not significant for predicting 5-year MACEs. CONCLUSIONS: High FIB-4 scores are associated with increased 5-year all-cause mortality risk in HD patients with chronic hepatitis virus infection. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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<p>Flowchart of included patients in this study.</p>
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<p>ROC curve and AUC of the FIB-4 score for identifying 5-year mortality. ROC curve: receiver operating characteristic curve; AUC: area under the curve; FIB-4 score: Fibrosis-4 score.</p>
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<p>Kaplan–Meier plot with the diagnostic point of the FIB-4 score (2.942) for identifying 5-year mortality. Group 1: FIB-4 score ≥ 2.942; Group 2: FIB-4 score &lt; 2.942.</p>
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