Biomedical Journal最新文献

{"title":"The legacy and future of recurrent neural networks in personalized medicine: A reflection on the 2024 Nobel Physics Prize","authors":"Emily Wittrup ,&nbsp;Alan Kay ,&nbsp;Jett Rosen ,&nbsp;Kuan-Fu Chen ,&nbsp;Kayvan Najarian","doi":"10.1016/j.bj.2025.100933","DOIUrl":"10.1016/j.bj.2025.100933","url":null,"abstract":"<div><div>The 2024 Nobel Physics Prize was awarded to Geoffrey Hinton and John Hopfield for their pioneering contributions to neural networks and artificial intelligence (AI), marking a significant milestone in AI’s development, particularly in the potential integrations into personalized medicine. This article surveys the profound influence of Hopfield’s and Hinton’s foundational work, tracing the development of recurrent neural networks (RNNs) from early associative memory models to advanced deep learning architectures. We delve into how contemporary RNN architectures are transforming personalized medicine by improving diagnostic accuracy, facilitating image analysis, generating radiology reports, and estimating individual treatment effects. Despite advancements, current challenges such as model interpretability, generalizability, and ethical considerations in AI application demand further exploration. This article posits that future RNN development will blend rigorous algorithmic insights with powerful generative capabilities to advance both medical applications and theoretical understanding. We conclude with a reflection on the future trajectory of RNNs in AI, underscoring a need for balancing computational efficiency with transparency and adaptability in healthcare environments.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100933"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762121","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":"Dynamic regulation of RNA m6A methylation in the ribonucleoprotein complexes in apicomplexan and kinetoplastid parasites","authors":"Kaitlin Klotz,&nbsp;Carli Camporeale,&nbsp;Kausik Chakrabarti","doi":"10.1016/j.bj.2025.100903","DOIUrl":"10.1016/j.bj.2025.100903","url":null,"abstract":"<div><div>m⁶A, or N⁶-methyladenosine, is the most abundant modification of mRNA transcripts. These modifications are known to influence mRNA transcript stability, transcription, translation, alternative splicing and decay, with undoubtedly more functions to be discovered. In this review, we explored the roles of m⁶A modifications in two groups of protozoan parasites: the apicomplexans, which include <em>Plasmodium</em> and <em>Toxoplasma</em> species, and kinetoplastids, which include <em>Trypanosoma</em> and <em>Leishmania</em> species. We also compared the key players of m⁶A epitranscriptomic machinery in creating, interpreting, and removing m⁶A modifications between these parasitic protists as well as a discussion of how m⁶A modifications facilitate parasite survival through features specific to apicomplexans and kinetoplastids. Beyond parasite epitranscriptomes, this review compares m⁶A dynamics in host and vector species (humans, flies and mosquitoes), highlighting coevolutionary adaptations. Strikingly, both the parasites and their vectors lack canonical m⁶A demethylases, implying a largely irreversible, streamlined m⁶A landscape fine-tuned for synchronized gene regulation. Overall, a mechanistic understanding is emerging of how m⁶A-modified RNAs and their binding proteins orchestrate RNA processing, translation, and turnover in parasitic protists, revealing an evolutionarily tuned epitranscriptomic system.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100903"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941112","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":"ShinySC: An R/Shiny-based desktop application for seamless analysis of scRNA-Seq data","authors":"Po-Jung Huang ,&nbsp;Fang-Yu Tsai ,&nbsp;Yi-Ju Wu ,&nbsp;Yi-Chen Weng ,&nbsp;Chi-Ching Lee ,&nbsp;Sin-Hong Shih ,&nbsp;Shih Sheng Jiang","doi":"10.1016/j.bj.2025.100885","DOIUrl":"10.1016/j.bj.2025.100885","url":null,"abstract":"<div><h3>Background</h3><div>Single-cell RNA sequencing (scRNA-seq) enables detailed profiling of cellular heterogeneity, but complex workflows and diverse data formats limit accessibility for clinicians and researchers without programming expertise.</div></div><div><h3>Results</h3><div>We introduce <strong>ShinySC</strong>, an R/Shiny-based desktop application designed to streamline comprehensive scRNA-seq analysis through an intuitive graphical interface. ShinySC supports various input formats, including 10x Genomics, Seurat, Scanpy, BD Rhapsody, and CellView. The tool integrates essential analytical procedures such as quality control, normalization, dimensionality reduction, clustering, marker gene identification, batch correction, differential expression analysis, and trajectory inference. Notably, ShinySC implements multiple automatic cell-type annotation methods—reference-based (SingleR), marker-based (ScType, scCATCH), and GPT-based (GPTCelltype)—with features for side-by-side comparison and manual label refinement. Benchmarking indicates robust performance for datasets containing up to 200,000 cells on standard desktop systems with 64 GB RAM, with analysis duration dependent on specific tasks and annotation methods. Demonstrative analyses of PBMC and interferon-stimulated datasets confirm ShinySC's efficacy in accurately annotating cell types and capturing condition-specific transcriptional dynamics.</div></div><div><h3>Conclusions</h3><div>ShinySC provides a unified, user-friendly, and scalable platform for scRNA-seq analysis explicitly tailored for non-programming users. It surpasses existing limitations by accommodating multiple data formats, employing versatile annotation strategies, and generating high-quality, publication-ready figures. Available freely across Windows, macOS, and Linux platforms, ShinySC enhances the accessibility and reproducibility of single-cell transcriptomic research.</div></div><div><h3>Availability</h3><div><span><span>http://tardis.cgu.edu.tw/ShinySC</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100885"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558931","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":"Associations with lip cant and facial midline correction following bimaxillary surgery in class III asymmetry: A CBCT-based analysis","authors":"Chih-Ling Lin ,&nbsp;Yun-Fang Chen ,&nbsp;Ying-An Chen ,&nbsp;Chuan-Fong Yao ,&nbsp;Tong Xi ,&nbsp;Yu-Fang Liao ,&nbsp;Yu-Ray Chen","doi":"10.1016/j.bj.2025.100877","DOIUrl":"10.1016/j.bj.2025.100877","url":null,"abstract":"<div><h3>Background</h3><div>This study evaluated the outcomes of bimaxillary surgery for class III asymmetry and lip cant, and identified factors associated with lip cant and facial midline correction.</div></div><div><h3>Materials and methods</h3><div>Fifty adult patients (22 females, 28 males; mean age: 24.8 ± 5.1 years) with class III asymmetry and lip cant who underwent bimaxillary surgery were prospectively and consecutively analyzed. Cone-beam computed tomography scans obtained preoperatively and at postoperative follow-up were superimposed to assess surgical jaw movements in six degrees of freedom and their effects on lip cant and facial midline symmetry.</div></div><div><h3>Results</h3><div>Significant reductions were observed in lip cant (1.6 ± 1.6 mm), lower lip deviation (2.4 ± 1.7 mm), chin deviation (5.8 ± 4.2 mm), and facial midline deviation (9.7 ± 7.2 mm). Multiple linear regression analysis identified mandibular roll correction (β = 0.456, <em>p</em> &lt; 0.01) and pre-treatment lip cant severity (β = 0.394, <em>p</em> &lt; 0.01) as significant factors of lip cant reduction. Additionally, chin shift (β = 0.495, <em>p</em> &lt; 0.01) and mandibular shift (β = 0.461, <em>p</em> &lt; 0.01) were significant factors of facial midline correction.</div></div><div><h3>Conclusion</h3><div>Bimaxillary surgery significantly improved lip cant and facial midline deviation in patients with class III asymmetry and lip cant. Mandibular roll correction and pre-treatment lip cant severity were key factors associated with lip cant correction, while chin and mandibular shift correction were associated with facial midline improvement.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100877"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293273","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":"Influence of acupuncture twisting parameters on analgesic effects mediated by mast cells in AA rat models","authors":"Yi Yu ,&nbsp;Yi-Xuan Wang ,&nbsp;Xuan Qiao ,&nbsp;Ying-Chen Li ,&nbsp;Yu-Hang Liu ,&nbsp;Zouqin Huang ,&nbsp;Wei Yao","doi":"10.1016/j.bj.2025.100876","DOIUrl":"10.1016/j.bj.2025.100876","url":null,"abstract":"<div><div>Acupuncture has been recognized for its potential effectiveness in pain relief without the side effects commonly associated with pharmaceutical treatments. This study investigates the effects of various acupuncture twisting parameters on analgesia using an acute adjuvant-induced arthritis (AA) rat model, focusing on the roles of mast cell activation, histamine (HIS) release, and local neural pathways. Utilizing robot-assisted acupuncture, we varied rotation angles (60°–360°) and frequencies (0.5–2.5 Hz) to evaluate their influence on pain modulation. The pain threshold recovery ratio (PTRR) was used to quantify the analgesic effect. The optimal combination of a 180° rotation angle and 1.0 Hz frequency resulted in the strongest analgesic effect, as indicated by increased PTRR and elevated mast cell degranulation rates (MCdR). Additionally, local HIS injections replicated the analgesic effects of acupuncture, whereas administration of an H1 receptor antagonist and lidocaine reduced these effects, highlighting the essential roles of HIS and local nerve conduction in acupuncture-induced analgesia. This study demonstrates the existence of optimal acupuncture parameters for achieving maximal analgesic effects in rat models, and elucidates the critical role of mast cell-mediated neural pathways, thus providing insights into optimizing acupunctire's clinical application in pain management.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100876"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246247","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":"Defining epitranscriptomic hallmarks at the host-parasite interface and their roles in virulence and disease progression in Theileria annulata-infected leukocytes","authors":"Malak Haidar ,&nbsp;Tobias Mourier ,&nbsp;Rahul Salunke ,&nbsp;Abhinav Kaushik ,&nbsp;Fathia Ben-Rached ,&nbsp;Sara Mfarrej ,&nbsp;Arnab Pain","doi":"10.1016/j.bj.2025.100828","DOIUrl":"10.1016/j.bj.2025.100828","url":null,"abstract":"<div><div><em>Theileria</em> parasites are known to induce the transformation of host bovine leukocytes, involved in rapid proliferation, evasion from apoptotic mechanisms, and increased dissemination. In this study, we reveal the involvement of m⁶A RNA modification in <em>T. annulata</em> infection-induced transformation of bovine leukocytes. We conducted m⁶A sequencing and bioinformatics analysis to map the mRNA methylation patterns of <em>T. annulata</em>-infected host leukocytes. We observe specific mRNA modifications for <em>T. annulata</em>-infected leukocytes and a strong correlation between the proliferation rate of the infected Leukocytes with m⁶A modifications We observe that the increased amounts of m⁶A seem to impact some cell cycle dynamics, potentially via modifications of E2F4 mRNA. Moreover, we further identify HIF-1α as a possible driver of these m⁶A RNA modifications that have clear relevance to cellular proliferation dynamics. Overall, our results provide insights into the role of m6A mRNA methylation in the molecular crosstalk between <em>Theileria</em> and their host leukocytes, emphasizing the critical role of mRNA methylation in host-parasite interaction.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100828"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969465","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":"PAI-1 is a common driver of aging and diverse diseases","authors":"Alireza Khoddam ,&nbsp;Toshio Miyata ,&nbsp;Douglas Vaughan","doi":"10.1016/j.bj.2025.100892","DOIUrl":"10.1016/j.bj.2025.100892","url":null,"abstract":"<div><div>Plasminogen activator inhibitor-1 (PAI-1) is a key driver of aging and contributes to diverse pathologies. This review examines PAI-1's multifaceted contributions to aging. At the cellular level, PAI-1 amplifies senescence, exhausts stem cell niches, and disrupts metabolism. These cellular alterations translate into physiological decline: PAI-1 drives cardiovascular aging by promoting vascular senescence and arterial stiffening, contributes to cognitive decline by impairing amyloid-beta clearance, fuels cancer progression through angiogenesis and immune suppression, and exacerbates muscle atrophy by hindering regeneration. A rare loss-of-function <em>SERPINE1</em> mutation extends lifespan, illustrating how lifelong PAI-1 reduction can positively impact the human healthspan. Looking forward, targeting PAI-1 with inhibitors could mitigate senescence, restore stem cell function, improve metabolic profile, enhance physiological health, and promise a longer healthspan.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100892"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673894","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":"Significance of PAI-1 on the development of skin cancer: Optimal targets for cancer therapies","authors":"Taku Fujimura","doi":"10.1016/j.bj.2025.100850","DOIUrl":"10.1016/j.bj.2025.100850","url":null,"abstract":"<div><div>Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor that plays a critical role in cancer progression, particularly in skin cancers. PAI-1 is widely recognized for its role in inhibiting fibrinolysis; however, emerging evidence suggests that it also contributes to tumor progression through multiple mechanisms, including tumor angiogenesis, immunomodulation, and stromal cell regulation. In the tumor microenvironment (TME), PAI-1 influences tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), promoting an immunosuppressive environment that supports cancer growth and therapy resistance. Furthermore, PAI-1 has been implicated in the regulation of programmed death-ligand 1 (PD-L1) expression via the JAK/STAT signaling pathway, thereby influencing immune evasion in various skin cancers. The significance of PAI-1 as a therapeutic target has been demonstrated in melanoma and other cutaneous malignancies, where inhibition of PAI-1 has shown promise in overcoming resistance to immune checkpoint inhibitors. Additionally, clinical trials evaluating PAI-1 inhibitors, such as TM5614, highlight its potential as an adjunctive therapy for melanoma and cutaneous angiosarcoma. This review comprehensively explores PAI-1's role in skin cancer progression, its influence on tumor-stromal interactions, and its potential as a therapeutic target.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100850"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669051","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":"PAI-1, hematopoietic stem cell, and chronic myeloid leukemia","authors":"Naoto Takahashi ,&nbsp;Hideo Harigae","doi":"10.1016/j.bj.2025.100854","DOIUrl":"10.1016/j.bj.2025.100854","url":null,"abstract":"<div><div>The new treatment goal for chronic myeloid leukemia (CML) is treatment-free remission, which requires the achievement and maintenance of a deep molecular response (DMR) using a tyrosine kinase inhibitor (TKI). However, only a limited number of patients achieve or maintain DMR. TM5614, a PAI1 inhibitor, can bring quiescent hematopoietic stem cells from the bone marrow niche into the cell cycle. Thus, the combination of TM5614 and TKI may eradicate CML cells. Currently, a phase III clinical trial is confirming the efficacy of TM5614 and TKI combination therapy.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100854"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959192","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":"Plasminogen activator Inhibitor-1 in systemic sclerosis: A nexus of fibrosis, vasculopathy, and senescence","authors":"Takuya Takahashi,&nbsp;Takehiro Takahashi,&nbsp;Yoshihide Asano","doi":"10.1016/j.bj.2025.100906","DOIUrl":"10.1016/j.bj.2025.100906","url":null,"abstract":"<div><div>Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system, has emerged as a multifaceted contributor to the pathogenesis of systemic sclerosis (SSc). Beyond its classical role in inhibiting plasminogen activation, PAI-1 is implicated in the dysregulation of vascular remodeling, promotion of fibrosis, modulation of immune responses, and the maintenance of cellular senescence—all of which are hallmarks of SSc. Notably, elevated PAI-1 expression has been observed in both patient-derived tissues and experimental models of the disease. Mice deficient in the urokinase-type plasminogen activator receptor (uPAR), which functions with its ligand urokinase-type plasminogen activator (uPA) in the plasminogen activation system, exhibit impaired fibrinolysis and spontaneously develop vasculopathy and fibrosis, closely mirroring human SSc. These findings underscore the pathogenic relevance of the uPA–uPAR–PAI-1 axis in disease progression. Moreover, recent studies suggest that pharmacological inhibition of PAI-1 may not only ameliorate fibrosis and vascular abnormalities but also promote the clearance of senescent cells, thereby interrupting the vicious cycle of chronic inflammation and maladaptive tissue remodeling in SSc. This review highlights the emerging roles of PAI-1 in SSc pathophysiology and explores its potential as a novel therapeutic target for disease modification.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 1","pages":"Article 100906"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871262","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}