Journal of Translational Medicine最新文献

{"title":"GEM-CRAP: a fusion architecture for focal seizure detection.","authors":"Jianwei Shi, Yuanyuan Zhang, Ziang Song, Hang Xu, Yanfeng Yang, Lei Jin, Hengxin Dong, Zhaoying Li, Penghu Wei, Yongzhi Shan, Guoguang Zhao","doi":"10.1186/s12967-025-06414-5","DOIUrl":"https://doi.org/10.1186/s12967-025-06414-5","url":null,"abstract":"<p><strong>Background: </strong>Identification of seizures is essential for the treatment of epilepsy. Current machine-learning and deep-learning models often perform well on public datasets when classifying generalized seizures with prominent features. However, their performance was less effective in detecting brief, localized seizures. These seizure-like patterns can be masked by fixed brain rhythms.</p><p><strong>Methods: </strong>Our study proposes a supervised multilayer hybrid model called GEM-CRAP (gradient-enhanced modulation with CNN-RES, attention-like, and pre-policy networks), with three parallel feature extraction channels: a CNN-RES module, an amplitude-aware channel with attention-like mechanisms, and an LSTM-based pre-policy layer integrated into the recurrent neural network. The model was trained on the Xuanwu Hospital and HUP iEEG dataset, including intracranial, cortical, and stereotactic EEG data from 83 patients, covering over 8500 labeled electrode channels for hybrid classification (wakefulness and sleep). A post-SVM network was used for secondary training on channels with classification accuracy below 80%. We introduced an average channel deviation rate metric to assess seizure detection accuracy.</p><p><strong>Results: </strong>For public datasets, the model achieved over 97% accuracy for intracranial and cortical EEG sequences in patients, and over 95% for mixed sequences, with deviations below 5%. In the Xuanwu Hospital dataset, it maintained over 94% accuracy for wakefulness seizures and around 90% during sleep. SVM secondary training improved average channel accuracy by over 10%. Additionally, a strong positive correlation was found between channel accuracy distribution and the temporal distribution of seizure states.</p><p><strong>Conclusions: </strong>GEM-CRAP enhances focal epilepsy detection through adaptive adjustments and attention mechanisms, achieving higher precision and robustness in complex signal environments. Beyond improving seizure interval detection, it excels in identifying and analyzing specific epileptic waveforms, such as high-frequency oscillations. This advancement may pave the way for more precise epilepsy diagnostics and provide a suitable artificial intelligence algorithm for closed-loop neurostimulation.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"405"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tobacco smoke exposure is a driver of altered oxidative stress response and immunity in head and neck cancer.","authors":"Yang Li, Pedram Yadollahi, Fonma N Essien, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Abu Hena Mostafa Kamal, Nagireddy Putluri, Lama M Abdurrahman, Maria E Ruiz Echartea, Keenan J Ernste, Akshar J Trivedi, Jonathan Vazquez-Perez, William H Hudson, William K Decker, Rutulkumar Patel, Abdullah A Osman, Farrah Kheradmand, Stephen Y Lai, Jeffrey N Myers, Heath D Skinner, Cristian Coarfa, Kwangwon Lee, Antrix Jain, Anna Malovannaya, Mitchell J Frederick, Vlad C Sandulache","doi":"10.1186/s12967-025-06258-z","DOIUrl":"https://doi.org/10.1186/s12967-025-06258-z","url":null,"abstract":"<p><strong>Background: </strong>Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data show cigarette smoke to be a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming of the cellular reductive state.</p><p><strong>Methods: </strong>Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to analyze the impact of smoke exposure on HNSCC tumor biology and anti-tumor immunity.</p><p><strong>Results: </strong>Cigarette smoke persistently activated Nrf2 target genes essential for maintenance of the cellular reductive state and survival under conditions of increased oxidative stress in HNSCC regardless of human papillomavirus (HPV) association. In contrast to e-cigarette vapor, conventional cigarette smoke mobilizes cellular metabolism toward oxidative stress adaptation, resulting in development of cross-resistance to cisplatin. In parallel, smoke exposure modulates expression of PDL1 and the secretory phenotype of HNSCC cells resulting in an altered tumor immune microenvironment (TIME) in syngeneic mouse models and downregulated expression of antigen presentation and costimulatory genes in myeloid cells.</p><p><strong>Conclusion: </strong>The cigarette smoke exposome is a potent activator of the Nrf2 pathway and appears to be the primary trigger for a tripartite phenotype of aggressive HNSCC consisting of: (1) reduced chemotherapy sensitivity, (2) enhanced metastatic potential and (3) suppressed anti-tumor immunity.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"403"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics guiding personalized first-line immunotherapy response in lung and bladder tumors.","authors":"Jenifer Brea-Iglesias, María Gallardo-Gómez, Ana Oitabén, Martin E Lázaro-Quintela, Luis León, Joao M Alves, Manuel Pino-González, Laura Juaneda-Magdalena, Carme García-Benito, Ihab Abdulkader, Laura Muinelo, Jesús M Paramio, Mónica Martínez-Fernández","doi":"10.1186/s12967-025-06323-7","DOIUrl":"https://doi.org/10.1186/s12967-025-06323-7","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, particularly in advanced non-small cell lung cancer (NSCLC) and muscle-invasive bladder cancer (MIBC). However, identifying reliable predictive biomarkers for ICI response remains a significant challenge. In this study, we analyzed real-world cohorts of advanced NSCLC and MIBC patients treated with ICI as first-line therapy.</p><p><strong>Methods: </strong>Tumor samples underwent Whole Genome Sequencing (WGS) to identify specific somatic variants and assess tumor mutational burden (TMB). Additionally, mutational signature extraction and pathway enrichment analyses were performed to uncover the underlying mechanisms of ICI response. We also characterized HLA-I haplotypes and investigated LINE-1 retrotransposition.</p><p><strong>Results: </strong>Distinct mutation patterns were identified in patients who responded to treatment, suggesting potential biomarkers for predicting ICI effectiveness. In NSCLC, tumor mutational burden (TMB) did not differ significantly between responders and non-responders, while in MIBC, higher TMB was linked to better responses. Specific mutational signatures and HLA haplotypes were associated with ICI response in both cancers. Pathway analysis showed that NSCLC responders had active inflammatory and immune pathways, while pathways enriched in non-responders related to FGFR3 and neural crest differentiation, associated to resistance mechanisms. In MIBC, responders had alterations in DNA repair, leading to more neoantigens and a stronger ICI response. Importantly, for the first time, we found that LINE-1 activation was positively linked to ICI response, especially in MIBC.</p><p><strong>Conclusion: </strong>These findings reveal promising biomarkers and mechanistic insights, offering a new perspective on predicting ICI response and opening up exciting possibilities for more personalized immunotherapy strategies in NSCLC and MIBC.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"404"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human neural stem cell-derived exosomes activate PINK1/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke.","authors":"Mengke Zhao, Jiayi Wang, Shuaiyu Zhu, Shensen Zhang, Chao Han, Chengcheng Tan, Yubing Huang, Zhaokai Sun, Liang Wang, Jing Liu","doi":"10.1186/s12967-025-06283-y","DOIUrl":"https://doi.org/10.1186/s12967-025-06283-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary therapeutic promise of exosomes derived from human neural stem cells (hNSCs) in the management of central nervous system (CNS) diseases. Nonetheless, the precise mechanisms by which these exosomes target mitochondria to ameliorate the effects of IS remain only partially elucidated. This study investigates the protective effects of hNSC derived exosomes (hNSC-Exos) on neuronal damage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Using a rat model of middle cerebral artery occlusion (MCAO) in vivo and OS-induced HT22 cells in vitro. Firstly, our research group independently isolated human neural stem cells (hNSCs) and subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored to blood flow perfusion to simulate ischemia-reperfusion injury, and hNSC-Exos were injected through stereotaxic injection into the brain. Subsequently, the protective effects of hNSC-Exos on MCAO rats were evaluated, including histological studies, behavioral assessments. In vivo, H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; was used in HT22 cells to simulate the OS environment in MCAO, and then its protective effects on HT22 were evaluated by co-culturing with hNSC-Exos, including immunofluorescence staining, western blotting (WB), quantitative real time PCR (qRT-PCR). In the process of exploring specific mechanisms, we utilized RNA sequencing (RNA-seq) to detect the potential induction of mitophagy in OS-induced HT22 cells. Afterwards, we employed a series of mitochondrial function assessments and autophagy related detection techniques, including measuring mitochondrial membrane potential, reactive oxygen species (ROS) levels, transmission electron microscopy (TEM) imaging, monodansylcadaverine (MDC) staining, and mCherry-GFP-LC3B staining. In addition, we further investigated the regulatory pathway of hNSC-Exos by using autophagy inhibitor mdivi-1 and knocking out PTEN induced kinase 1 (PINK1) in HT22 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Administration of hNSC-Exos significantly ameliorated brain tissue damage and enhanced behavioral outcomes in MCAO rats. This treatment led to a reduction in brain tissue apoptosis and facilitated the normalization of impaired neurogenesis and neuroplasticity. Notably, the application of hNSC-Exos in vitro resulted in an upregulation of mitophagy in HT22 cells, thereby remedying mitochondrial dysfunction. We demonstrate that hNSC-Exos activate mitophagy via the PINK1/Parkin pathway, improving mitochondrial function and reducing neuronal apoptosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings suggest that hNSC-Exos alleviate OS-induced neuronal damage by regulating the PINK1/Parkin pathway. These reveals a novel role of stem cell-derived mitochondrial therapy in promoting neuroprotection and suggest their potential as a thera","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"402"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL12/CXCR4 axis mediates CD8 ⁺ T cell overactivation in the progression of viral myocarditis.","authors":"Li Zhang, Keyu Liu, Xiuyun Duan, Shan Zhou, Hailin Jia, Yingnan You, Bo Han","doi":"10.1186/s12967-025-06394-6","DOIUrl":"https://doi.org/10.1186/s12967-025-06394-6","url":null,"abstract":"<p><strong>Background: </strong>Myocarditis is a common inflammatory heart disease in children and young adults, with fulminant myocarditis (FM) being the most severe form due to its rapid onset and high mortality rate. However, the precise pathological immune subsets and molecular change in myocarditis, particularly FM, remain unknown.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing of pediatric peripheral blood mononuclear cells during the acute and recovery phases of FM. A viral myocarditis (MC) mouse model was established using CVB3. Deletion and adoptive transfer of CD8⁺T cells, as well as blockade of CXCR4, were conducted in vivo. CD8⁺T cells were sorted and cultivated in vitro, then stimulated with CXCL12 and CXCR4 antagonists to investigate the mechanism of CD8⁺T cell overactivation.</p><p><strong>Results: </strong>CD8⁺T cells show significant activation, amplification, enhanced cytotoxicity, and increased chemotactic ability in FM. Deletion of CD8⁺T cells alleviates myocardial injury and improves cardiac function in MC mice, while adoptive transfer of CD8⁺T cells from MC mice aggravates myocardial inflammation and injury. The transcriptomic analysis reveals elevated CXCR4 expression in CD8⁺T cells in acute FM. In vitro experiments demonstrate that the CXCL12/CXCR4 axis drives the overactivation and cytotoxicity of CD8⁺T cells. In vivo treatment with a CXCR4 antagonist effectively reduces CD8⁺T cell accumulation in the heart, alleviates myocardial inflammation, and improves cardiac function in MC mice.</p><p><strong>Conclusions: </strong>These findings provide deeper insights into the immune landscape of pediatric FM, uncovering a novel role of the CXCL12/CXCR4 axis in driving CD8⁺T cell responses in myocarditis. Furthermore, they highlight the CXCL12/CXCR4 axis as a promising therapeutic target for myocarditis treatment.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"399"},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epicardial fat thickness is increased in menopausal patients in comparison with premenopausal patients with similar excess weight: a cross-sectional study.","authors":"Elena Gangitano, Giuseppe Barbaro, Lucio Gnessi, Gianluca Iacobellis, Carla Lubrano","doi":"10.1186/s12967-025-06335-3","DOIUrl":"https://doi.org/10.1186/s12967-025-06335-3","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of excess weight and ageing is notably high in contemporary Western societies. The effectiveness of body mass index (BMI) and waist circumference as tools for identifying excess weight and ectopic fat deposition, both associated with an increased cardiovascular risk, is questionable.</p><p><strong>Methods: </strong>Our objective is to compare women affected by overweight and obesity during fertile years and menopausal time and identify easily accessible clinical parameters associated with ectopic fat deposition, providing valuable insights into cardiovascular risk. Over 1300 female patients with excess weight referred to the CASCO Centre (High Specialization Centre for the Care of Obesity) at Umberto I Polyclinic in Rome, Italy, were included. Each participant underwent a DXA scan and a cardiac ultrasound, and blood tests to verify menopausal status and evaluate metabolic profile and hepatic steatosis through indirect measurements.</p><p><strong>Results: </strong>775 patients were in the pre-menopausal phase and 617 in the post-menopausal phase. The two cohorts did not differ in BMI, total body fat and lean mass, or waist circumference. However, the post-menopausal group showed an increased visceral fat deposition, evaluated by waist-to-hip ratio and epicardial fat thickness (EFT), and a worse metabolic profile.</p><p><strong>Conclusion: </strong>Menopause is associated with a worsening of the metabolic features observed in obesity, with an increase in visceral fat deposition. Of note, these alterations are more pronounced despite similar BMI and waist circumference.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"401"},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression analysis in circulating tumour cells to determine resistance to CDK4/6 inhibitors plus endocrine therapy in HR + /HER2- metastatic breast cancer patients.","authors":"Miriam González-Conde, Celso Yáñez, Carmen Abuín, Corinna Keup, Ramón Lago-Lestón, Maribel Aybar, Lucía Pedrouzo, Patricia Palacios, Teresa Curiel, Juan Cueva, Carmela Rodríguez, Marta Carmona, Alexandra Cortegoso, Tomás García-Caballero, Laura Muinelo-Romay, Sabine Kasimir-Bauer, Rafael López-López, Clotilde Costa","doi":"10.1186/s12967-025-06374-w","DOIUrl":"https://doi.org/10.1186/s12967-025-06374-w","url":null,"abstract":"<p><strong>Background: </strong>Metastatic breast cancer (BC) is the main cause of cancer-related mortality in women worldwide. HR + /HER2- BC patients are treated with endocrine therapy (ET), but therapeutic resistance is common. The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with ET was approved for metastatic BC patients and extended the median progression-free survival to 24 months. This therapy is not always effective, and in every patient, resistance ultimately occurs, but the underlying resistance mechanisms remain unclear. To address this gap, we explored circulating tumour cells (CTCs) as biomarkers to assess treatment response and resistance in metastatic HR + /HER2- BC patients receiving CDK4/6i plus ET.</p><p><strong>Methods: </strong>In total, 53 HR + /HER2- metastatic BC patients who received a CDK4/6i plus ET as first-line treatment were analysed, including samples from internal and external validation cohorts. CTCs were isolated using the negative enrichment approach RosetteSep (STEMCELL Technologies) or positive immunomagnetic selection targeting EpCAM, EGFR, and HER2 (AdnaTest EMT-2/StemCell Select™, QIAGEN). RNA was extracted from CTCs and PBMCs for nCounter analysis (Pancancer pathways panel) in a discovery phase. Subsequent validation was performed by RT-qPCR.</p><p><strong>Results: </strong>CTC gene expression analysis revealed that non responder patients (those who experienced disease progression before 180 days) exhibited elevated PRKCB (p-value: 0.011), MAPK3 (p-value: 0.006) and STAT3 (p-value: 0.008) expression, while responders showed increased CDK6 (p-value: 0.011) and CCND1 (p-value: 0.035) expression at baseline. CTC transcriptional characterization revealed a gene expression signature (STAT3^highPRKCB^highCDK6^low) that accurately classified HR + /HER2- metastatic BC patients who responded to CDK4/6i plus ET, regardless of the CTC isolation method (AUC > 0.8). CTC characterization at progression also identified biomarkers linked to therapy resistance, including the epigenetic regulators EZH2 and HDAC6 and the cell cycle regulator CDC7, which could guide the selection of subsequent therapy lines. The expression of the CDK4 and STAT3 genes in CTCs was associated with progression-free survival and overall survival, respectively. Likewise, the presence of ≥ one CTC after one cycle of therapy predicts a worse prognosis.</p><p><strong>Conclusions: </strong>CTC gene expression provides information about treatment outcomes in HR + /HER2- metastatic BC patients receiving CDK4/6i plus ET and could guide personalized strategies and improve prognosis.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"400"},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer's disease.","authors":"Ke Ye, Xinyu Han, Mengjie Tian, Lulu Liu, Xu Gao, Qing Xia, Dayong Wang","doi":"10.1186/s12967-025-06324-6","DOIUrl":"10.1186/s12967-025-06324-6","url":null,"abstract":"<p><strong>Background: </strong>RNA modification plays a critical role in Alzheimer's disease (AD) by modulating the expression and function of AD-related genes, thereby affecting AD occurrence and progression. Programmed cell death is closely related to neuronal death and associated with neuronal loss and cognitive function changes in AD. However, the mechanism of their joint action on AD remains unknown and requires further exploration.</p><p><strong>Methods: </strong>We used the MSBB RNA-seq dataset to analyze the correlation between RNA modification, programmed cell death, and AD. We used combined studies of RNA modification and programmed cell death to distinguish subgroups of patients, and the results highlight the strong correlation between RNA modification-related programmed cell death and AD. A weighted gene co-expression network was constructed, and the pivotal roles of programmed cell death genes in key modules were identified. Finally, by combining unsupervised consensus clustering, gene co-expression networks, and machine learning algorithms, an RNA modification-related programmed cell death network was constructed, and the pivotal roles of programmed cell death genes in key modules were identified. An RNA modification-related programmed cell death risk score was calculated to predict the occurrence of AD.</p><p><strong>Results: </strong>RPCD-related genes classified patients into subgroups with distinct clinical characteristics. Nineteen key genes were identified and an RPCD risk score was constructed based on the key genes. This score can be used for the diagnosis of AD and the assessment of disease progression in patients. The diagnostic efficacy of the RPCD risk score and the key genes was validated in the ROSMAP, GEO, and ADNI datasets.</p><p><strong>Conclusion: </strong>This study uncovered that RNA modification-related PCD is of significance for AD progression and early prediction, providing insights from a new perspective for the study of disease mechanisms in AD.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"396"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety comparison of CAR-T and blinatumomab immunotherapy as bridge-to-transplant strategies in relapsed/refractory B cell acute lymphoblastic leukemia.","authors":"Wenyue Cao, Ningwen Li, Gaoxiang Wang, Hao Xu, Yang Yang, Jue Wang, Jinhuan Xu, Yun Li, Yicheng Zhang, Yang Cao, Na Wang","doi":"10.1186/s12967-025-06399-1","DOIUrl":"10.1186/s12967-025-06399-1","url":null,"abstract":"<p><strong>Background: </strong>Despite recent advances, B cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge. Hematopoietic stem cell transplantation (HSCT) provides a potential cure but is hindered by various limitations. Emerging immunotherapies, including chimeric antigen receptor T cell (CAR-T) therapy and blinatumomab, have shown potential as bridging strategies to HSCT in relapsed/refractory (R/R) patients.</p><p><strong>Methods: </strong>This retrospective study was conducted at Tongji Hospital from March 2017 to March 2023 and involved 36 R/R B-ALL patients who underwent HSCT. Prior to transplantation, 27 patients received CD19/CD22 CAR-T therapy, while 9 received blinatumomab. The outcomes assessed included overall survival (OS), progression-free survival (PFS), graft-versus-host disease-free and relapse-free survival (GRFS), and non-relapse mortality (NRM), with comparisons between treatment groups. Hematopoietic reconstitution and transplant-related complications were also evaluated.</p><p><strong>Results: </strong>The median follow-up time was 28.07 months (range: 2.29-92.21 months). The 2-year OS, PFS, GRFS, and NRM rates of the entire cohort were 76.54%, 54.97%, 40.12%, and 9.93%, respectively. In the CAR-T and blinatumomab treatment groups before transplantation, the 2-year OS rates were 73.89% and 88.89% (P = 0.862), the PFS rates were 59.03% and 44.44% (P = 0.501), the GRFS rates were 47.86% and 13.89% (P = 0.083), and the NRM rates were 8.52% and 11.11% (P = 0.713), respectively. The safety profiles were similar, with no significant differences observed in hematopoietic reconstitution, infection, incidence of grade II-IV acute graft-versus-host disease (GVHD), or chronic GVHD incidence between the CAR-T and blinatumomab groups.</p><p><strong>Conclusion: </strong>CAR-T and blinatumomab therapies demonstrate comparable safety and efficacy as bridging treatments to HSCT in patients with R/R B-ALL. Further studies are needed to optimize these treatment strategies.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"391"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing innovative machine learning techniques to combat drug resistance in solid tumors.","authors":"Hao Zhang, Wendy Mao","doi":"10.1186/s12967-025-06390-w","DOIUrl":"10.1186/s12967-025-06390-w","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"398"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}