{"title":"Deep Learning Significantly Boosts CRT Response Prediction Using Synthetic Longitudinal Strain Data: Training on Synthetic Data and Testing on Real Patients.","authors":"Ying-Feng Chang, Kun-Chi Yen, Chun-Li Wang, Sin-You Chen, Jenhui Chen, Pao-Hsien Chu, Chao-Sung Lai","doi":"10.1016/j.bj.2024.100803","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100803","url":null,"abstract":"<p><strong>Background: </strong>Recently, as a relatively novel technology, artificial intelligence (especially in the deep learning fields) has received more and more attention from researchers and has successfully been applied to many biomedical domains. Nonetheless, just a few research works use deep learning skills to predict the cardiac resynchronization therapy (CRT)-response of heart failure patients.</p><p><strong>Objective: </strong>We try to use the deep learning-based technique to construct a model which is used to predict the CRT response of patients with high prediction accuracy, precision, and sensitivity.</p><p><strong>Methods: </strong>Using two-dimensional echocardiographic strain traces from 131 patients, we pre-processed the data and synthesized 2,000 model inputs through the synthetic minority oversampling technique (SMOTE). These inputs trained and optimized deep neural networks (DNN) and one-dimensional convolution neural networks (1D-CNN). Visualization of prediction results was performed using t-distributed stochastic neighbor embedding (t-SNE), and model performance was evaluated using accuracy, precision, sensitivity, F1 score, and specificity. Variable importance was assessed using Shapley additive explanations (SHAP) analysis.</p><p><strong>Results: </strong>Both the optimal DNN and 1D-CNN models demonstrated exceptional predictive performance, with prediction accuracy, precision, and sensitivity all around 90%. Furthermore, the area under the receiver operating characteristic curve (AUROC) of the optimal 1D-CNN and DNN models achieved 0.8734 and 0.9217, respectively. Crucially, the most significant input variables for both models align well with clinical experience, further corroborating their robustness and applicability in real-world settings.</p><p><strong>Conclusions: </strong>We believe that both the DL models could be an auxiliary to help in treatment response prediction for doctors because of the excellent prediction performance and the convenience of obtaining input data to predict the CRT response of patients clinically.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100803"},"PeriodicalIF":4.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ching-Yi Hsieh, Ying-Chieh Lai, Kuan-Ying Lu, Gigin Lin
{"title":"Advancements, Challenges, and Future Prospects in Clinical Hyperpolarized Magnetic Resonance Imaging: A Comprehensive Review.","authors":"Ching-Yi Hsieh, Ying-Chieh Lai, Kuan-Ying Lu, Gigin Lin","doi":"10.1016/j.bj.2024.100802","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100802","url":null,"abstract":"<p><p>Hyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2-13C]pyruvate and [1-13C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100802"},"PeriodicalIF":4.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Communicating across distances – Biological functions of extracellular vesicles","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2024.100792","DOIUrl":"10.1016/j.bj.2024.100792","url":null,"abstract":"<div><div>This issue of the <em>Biomedical Journal</em> features a special section on extracellular vesicles (EVs), covering their role in neurological diseases, viral infections, trogocytosis, allogeneic organ rejection and tolerance, as well as EV biodistribution. Two articles explore the mechanisms of Parkinson's disease, focusing on white matter and exosomes. This journal issue also examines polyomavirus-induced damage in renal transplant grafts, proposes a miRNA signature as a diagnostic biomarker for Kawasaki disease, discusses neural gating and associated brain wave alterations, and further clarifies the relationship between gut microbiota and immune checkpoint inhibitors. Additionally, the importance of therapeutic drug monitoring is reaffirmed.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 5","pages":"Article 100792"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Ratio of Remaining to Expected Small Bowel Length Predicts Enteral Autonomy in Pediatric Patients with Short Bowel Syndrome.","authors":"Chia-Wei Chang, Pai-Jui Yeh, Hung-Hsian Lai, Mi-Chi Chen, Yung-Ching Ming, Jing-Yao Lai, Ming-Wei Lai","doi":"10.1016/j.bj.2024.100791","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100791","url":null,"abstract":"<p><strong>Background: </strong>Pediatric patients with short bowel syndrome (SBS) often require long-term parenteral nutrition and intravenous fluid support (PN) until enteral autonomy (EA). However, long-term PN accounts for many complications. We aimed to investigate the outcome and predictors of EA in these patients.</p><p><strong>Material and methods: </strong>This retrospective observational study was conducted in Children's Medical Center, Chang Gung Memorial Hospital, a tertiary hospital in Northern Taiwan. Twenty-four patients afflicted with short bowel syndrome between 2002 and 2021 were included. Demographics, operation results, follow-up status, complications, and outcomes were reviewed.</p><p><strong>Results: </strong>Among the 24 patients, 14 were males (58%). The median age at bowel resection was 3 days (IQR, 1.3 to 28.8 days). The most common etiologies were total/subtotal intestinal aganglionosis (TIA) (N=6) and malrotation with midgut volvulus (N=6). The median length of the residual small intestine was 25cm (IQR, 7.8 to 71.3cm). Ten (41.7%) had preserved ileocecal valve, and 14 (58.3%) had colon-in-continuity. Intestinal failure-associated liver disease (IFALD) occurred in 14 patients (58.3%), but none had advanced disease. Seven (29.2%) patients achieved enteral autonomy after 10.1±7.3 months. Five patients (21%) expired due to sepsis. Logistic regression and Kaplan-Meier analysis showed the predictors of enteral autonomy were remaining-to-expected small bowel length ratio > 25% and the absence of IFALD.</p><p><strong>Conclusions: </strong>In this pediatric short bowel syndrome study, enteral autonomy was achieved in 29% after a mean PN duration of 10 months. The remaining-to-expected small bowel length ratio at bowel resection was the most critical predictor of enteral autonomy.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100791"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytidine Deaminase Enhances Liver Cancer Invasion by Modulating Epithelial-Mesenchymal Transition via NFκB Signaling.","authors":"Chia-Jung Liao, Yang-Hsiang Lin, Huei-Tzu Chien, Yi-Wen Wang, Tzu-Kang Lin, Chau-Ting Yeh, Kwang-Huei Lin","doi":"10.1016/j.bj.2024.100789","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100789","url":null,"abstract":"<p><strong>Background: </strong>Cancer metastasis is the leading cause of cancer-related deaths, underscoring the importance of understanding its underlying mechanisms. Hepatocellular carcinoma (HCC), a highly malignant type of cancer, was selected as our research model.</p><p><strong>Material and methods: </strong>We aimed to develop high-metastatic cell lines using in vitro and in vivo selection strategies and identify critical metastasis-related genes through microarray analyses by comparing them with parental cells.</p><p><strong>Results: </strong>Our results showed that the high-metastatic cell lines exhibited significantly stronger invasion abilities than parental cells. Microarray analyses identified cytidine deaminase (CDA), a gene associated with systemic chemotherapy resistance, as one of the overexpressed genes in the high-metastatic cells. Data analysis from The Cancer Genome Atlas Program revealed that while CDA is downregulated in HCC, patients with high CDA expression tend to have poorer prognoses. Cell models confirmed that CDA overexpression enhances cell migration and invasion, whereas CDA knockdown inhibits these abilities. Investigating the key molecules involved in the epithelial-mesenchymal transition (EMT), we found that CDA overexpression increases the expression of fascin, N-cadherin, β-catenin, and snail while decreasing E-cadherin expression. Conversely, CDA knockdown produced opposite results. Additionally, we discovered that CDA regulates NF-κB signaling, which controls the expression of N-cadherin, thereby promoting the invasion capability of HCC cells.</p><p><strong>Conclusions: </strong>We isolated highly metastatic cells and identified potential HCC metastasis-related genes. CDA promotes cell invasion by regulating EMT through the NF-κB pathway. Future studies are warranted to explore the potential of CDA as a biomarker for prognosis and therapeutic decision-making.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100789"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang-Hsiang Lin, Chau-Ting Yeh, Cheng-Yi Chen, Kwang-Huei Lin
{"title":"Pseudogene: Relevant or Irrelevant?","authors":"Yang-Hsiang Lin, Chau-Ting Yeh, Cheng-Yi Chen, Kwang-Huei Lin","doi":"10.1016/j.bj.2024.100790","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100790","url":null,"abstract":"<p><p>With the advancement of high-throughput technologies, the pivotal role of non-coding RNA (ncRNA) as a master regulator of various biological functions has become increasingly apparent. Historically considered non-functional and labeled as \"junk DNA,\" pseudogenes can be transcribed into RNA, indicating a potential role similar to ncRNAs. Recent research suggests that some pseudogenes can encode functional peptides or proteins. A growing body of evidence has revealed that pseudogenes and their derived functional molecules are involved in various biological processes and can serve as prognostic markers in cancers. This review comprehensively summarizes and discusses the current understanding of the functional roles of pseudogenes and their derived molecules in biological functions.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100790"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean M. Kanellopoulos, Frédéric Rieux-Laucat, David M. Ojcius
{"title":"Biological functions of extracellular vesicles from mammalian cells","authors":"Jean M. Kanellopoulos, Frédéric Rieux-Laucat, David M. Ojcius","doi":"10.1016/j.bj.2024.100788","DOIUrl":"10.1016/j.bj.2024.100788","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) are enclosed by a phospholipid bilayer and can be secreted by most types of cells. EVs deliver cargo from the secreting cell into the cytoplasm of recipient cells, influencing the function of the recipient cells. EVs are attracting increasing attention from a broad range of clinicians and scientists due to their ability to promote or inhibit various physiological pathways or pathological conditions. This special issue of <em>Biomedical Journal</em> contains articles describing the biogenesis and biodistribution of EVs and their role in the intercellular transfer of various molecules or viruses to target cells, in rejecting allogeneic transplants and maintaining immune tolerance of the allogeneic fetus, and in modulating innate and adaptive immunity. Characterization of the role of EVs in various pathological conditions and our ability to engineer modified EVs may lead to discovery of novel biomarkers and development of therapeutic strategies for treatment of disease.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 5","pages":"Article 100788"},"PeriodicalIF":4.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S231941702400091X/pdfft?md5=a66d3b73e737d5696a9075543f2fd341&pid=1-s2.0-S231941702400091X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Dima, Gian Luca Salvagno, Giuseppe Lippi
{"title":"Effects of recombinant SARS-CoV-2 spike protein variants on red blood cells parameters and red blood cell distribution width","authors":"Francesco Dima, Gian Luca Salvagno, Giuseppe Lippi","doi":"10.1016/j.bj.2024.100787","DOIUrl":"10.1016/j.bj.2024.100787","url":null,"abstract":"<div><div>We planned a series of experiments to investigate the possible role of spike protein of different SARS-CoV-2 variants in influencing erythrocyte biology. The values of erythrocyte count, hemoglobin, and mean corpuscular hemoglobin (MHC) did not vary across all samples challenged with both concentrations of the four different SARS-CoV-2 recombinant spike proteins. A significant increase in mean corpuscular volume (MCV) was observed with the recombinant SARS-CoV-2 Alpha and Delta spike proteins at both 2 and 20 ng/mL final concentrations. Red blood cell distribution width (RDW) values increased significantly in samples treated with 20 ng/mL of all SARS-CoV-2 recombinant spike proteins and reached the highest values in samples treated with Omicron recombinant spike protein. Blood smear revision evidenced hemagglutination and rouleaux in samples to which recombinant SARS-CoV-2 spike proteins were added, especially in those with Alpha and Delta variants.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 6","pages":"Article 100787"},"PeriodicalIF":4.1,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancements in Chondrocyte 3-Dimensional Embedded Culture: Implications for Tissue Engineering and Regenerative Medicine.","authors":"Yu-Ying Chu, Atsuhiko Hikita, Yukiyo Asawa, Kazuto Hoshi","doi":"10.1016/j.bj.2024.100786","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100786","url":null,"abstract":"<p><p>Cartilage repair necessitates regenerative medicine because of the unreliable healing mechanism of cartilage. To yield a sufficient number of cells for transplantation, chondrocytes must be expanded in culture. However, in 2D culture, chondrocytes tend to lose their distinctive phenotypes and functionalities after serial passage, thereby limiting their efficacy for tissue engineering purposes. The mechanism of dedifferentiation in 2D culture can be attributed to various factors, including abnormal nuclear strength, stress-induced mitochondrial impairment, chromatin remodeling, ERK-1/2 and the p38/mitogen-activated protein kinase (MAPK) signaling pathway. These mechanisms collectively contribute to the loss of chondrocyte phenotype and reduced production of cartilage-specific extracellular matrix (ECM) components. Chondrocyte 3D culture methods have emerged as promising solutions to prevent dedifferentiation. Techniques, such as scaffold-based culture and scaffold-free approaches, provide chondrocytes with a more physiologically relevant environment, promoting their differentiation and matrix synthesis. These methods have been used in cartilage tissue engineering to create engineered cartilage constructs for transplantation and joint repair. However, chondrocyte 3D culture still has limitations, such as low viability and proliferation rate, and also difficulties in passage under 3D condition. These indicate challenges of obtaining a sufficient number of chondrocytes for large-scale tissue production. To address these issues, ongoing studies of many research groups have been focusing on refining culture conditions, optimizing scaffold materials, and exploring novel cell sources such as stem cells to enhance the quality and quantity of engineered cartilage tissues. Although obstacles remain, continuous endeavors to enhance culture techniques and overcome limitations offer a promising outlook for the advancement of more efficient strategies for cartilage regeneration.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100786"},"PeriodicalIF":4.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extracellular vesicles in fetal-maternal immune tolerance","authors":"William J. Burlingham","doi":"10.1016/j.bj.2024.100785","DOIUrl":"10.1016/j.bj.2024.100785","url":null,"abstract":"<div><p>Two key problems of allo-tolerance during fetal-maternal co-existence are: 1) it's focus must be local, allowing the mother's continued peripheral immune competence to resist pathogens ubiquitously, and 2) it must propagate itself, i.e. continuously recruit new re-enforcements of the local tolerant state. Both are solved by the exosomal pathway of Tregs & Bregs. While the fetal-maternal accomodations of pregnancy terminate at the time of partrurition, geography, climate and the endemic pathogens of the <u>environment</u> surrounding the mother-baby pair would then define the short and long-term effects of their immunologic interaction.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 5","pages":"Article 100785"},"PeriodicalIF":4.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S231941702400088X/pdfft?md5=6f157fefa6eb4b07b939d1c3f2880ec8&pid=1-s2.0-S231941702400088X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}