tbuckley/cabot-search huggingface dataset:
Therapy-induced senescent glioblastoma cells sustain a procancer immune microenvironment by activating DDX58-mediated STAT1 signaling
Authors: Zhixing Wang, Yuxin Zhang, Fan Wu, Bojun Qiu, Yiyun Yin, Xinrun Wang, Ruoyu Huang, Xin Zhang, Zhiyan Sun, Wanjun Tang, Zefan Jing, Wei Han, Tao Jiang, Xiaozhong Peng
Journal: Neuro-Oncology (2025)

Abstract Background Depending on the context, therapy-induced cancer cell senescence promotes or inhibits tumor progression and recurrence, but the underlying mechanism and effects on the tumor immune microenvironment are poorly understood. Methods Here, we developed senescent glioblastoma cell models in vitro via drug treatment. The protumor function of senescent cells was demonstrated by coinjection of chemotherapy-induced senescent cells with tumorigenic GL261 cells in C57BL/6J male mice. In addition, conditioned medium coculture experiments were used to explore the functions of senescent glioblastoma cells in vitro. Mechanistically, through a CRISPR-Cas9-based screen, we revealed that the RNA-binding protein DDX58 was induced in senescent glioblastoma cells. By combining RNA sequencing and protein mass spectrometry analysis, we observed that STAT1 signaling was activated. Immunoprecipitation experiments were subsequently performed to identify the interaction between DDX58 and STAT1. Results We show that glioblastoma cells can enter a senescent state after chemotherapy. In vivo, senescent glioblastoma cells have a tumor-promoting function and reduce survival in male mice. Mechanistically, we found that the RNA-binding protein DDX58 plays an important role in therapy-induced senescent glioblastoma. Inhibition of DDX58 slowed therapy-induced senescence. The activation of DDX58 depends on the accumulation of mitochondrial double-stranded RNA (mtdsRNA) in the cytoplasm via the BAX protein. Moreover, DDX58 promotes the recruitment of tumor-associated macrophages (TAMs) and their M2-like polarization by activating the STAT1-mediated transcription of colony-stimulating factor 1 (CSF1). We also revealed that DDX58 regulates STAT1 at the post-translational level by inhibiting the ubiquitin E3 ligase TRIM21-mediated STAT1 ubiquitination. Compared with temozolomide (TMZ) treatment alone, treatment with fludarabine, which blocks STAT1 signaling, combined with TMZ can more effectively reduce the recruitment of TAMs and delay tumor growth in vivo. Moreover, knockdown of STAT1 enhances the therapeutic effect of TMZ in vivo and prolongs the survival of tumor-bearing male mice. Conclusion A critical mechanism for the protumor immune microenvironment mediated by therapy-induced senescent glioblastoma cells, the DDX58-STAT1-CSF1 axis, may be a potential therapeutic avenue for alleviating traditional therapy-induced glioblastoma cell senescence.
Macrophage‐Tased Dual‐Phase T Cell Immunomodulation to Combat Transplant Rejection
Authors: Wenyuan Wang, Tang Gao, Yihui Wang, Rui Wang, Mengrong He, Lufang Wang, Wuqi Zhou, Mengdan Ding, Yuan Song, Xiang Ji, Xueke Li, Yishu Song, Ye Zhu, Yiwei Zhang, Yuji Xie, Yan Chen, Qiaofeng Jin, Mingxing Xie, Li Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Transplant rejection remains a major challenge, driven primarily by the activation of alloreactive T cells. While enhancement of PD‐L1 checkpoint molecules has exhibited potential in inhibiting T cell activity, its efficacy is often hindered by limited specificity and inadequate efficiency. Herein, a novel dual‐phase immune modulation strategy is developed in which CTLA4‐Ig and PD‐L1 provide distinct, non‐redundant inhibitory signals during the initial activation phase and the post‐activation phase of T cells. PD‐L1 is stably expressed on macrophages (sPD‐L1 M) through lentiviral transduction, allowing them to leverage their chemotactic and antigen‐presenting functions to target and deliver PD‐L1 to transplant rejection sites. Notably, sPD‐L1 M exhibited adaptive targeting capabilities, increasing their migration to grafts in response to heightened rejection. In an allograft skin model, the combined intravenous administration of sPD‐L1 M and subcutaneous administration of CTLA4‐Ig demonstrated synergistic efficacy, significantly suppressing alloreactive T cell activation, enhancing the recruitment of regulatory T cells (Tregs), downregulating pro‐inflammatory cytokines, and prolonging allograft survival compared to either treatment alone. This study presents a promising strategy to effectively suppress T cell activity and prevent allogeneic immune responses without systemic immunosuppression.
Reply to Takefuji “Methodological limitations of linear parametric analysis in biological research: A critical review of NEO-Five personality traits and sleep characteristics study”
Authors: Ran Wang, Zexuan Mu, Xiao Li, Forrest Tin Wai Cheung, Ngan Yin Chan, Joey Wing Yan Chan, Yun Kwok Wing, Shirley Xin Li
Journal: Sleep Medicine Reviews (2025)
Complosome as a new intracellular regulatory network in both normal and malignant hematopoiesis
Authors: Mariusz Z Ratajczak, Adrian Konopko, Justyna Jarczak, Michalina Kazek, Janina Ratajczak, Magdalena Kucia
Journal: Leukemia (2025)

Abstract Hematopoietic cells and lymphocytes arise from a common stem cell for both lineages. This explains why similar signaling networks regulate the development and biological functions of these cells. One crucial regulatory mechanism involves interactions with soluble mediators of innate immunity, including activated elements of the complement cascade (ComC). For many years, ComC proteins were thought to be synthesized only in the liver and released into blood to be activated by one of the three proteolytic cascades. The regulatory effects of activated components of ComC on hematopoietic stem progenitor cells (HSPCs) and mature hematopoietic cells have been well demonstrated in the past. However, recent data indicate that complement proteins are also expressed in several cell types, including lymphocytes and innate immune cells. This intracellular complement network has been named the “complosome.” Recent evidence from our group shows that the complosome is also expressed in HSPCs and plays an important yet underappreciated role in the expansion, trafficking, and metabolism of these cells. We propose that the complosome, like its role in lymphocytes, is necessary for the optimal function of mitochondria in hematopoietic cells, including HSPCs. This opens a new area for investigation and potential pharmacological intervention into the complosome network in normal and malignant hematopoiesis.
A scoping review on the role of virtual walking intervention in enhancing wellness
Authors: Yushen Dai, Jiaying Li, Yan Li, Frances Kam Yuet Wong, Mengqi Li, Chen Li, Ye Jia, Yueying Wang, Janelle Yorke
Journal: npj Digital Medicine (2025)

Virtual walking has the potential to be an adjunct to traditional physical therapy. This scoping review aims to synthesize evidence on the characteristics, effectiveness, feasibility, and neurological mechanism of virtual walking interventions on health-related outcomes. Articles in English were retrieved from twelve databases (January 2014-October 2024). Thirteen interventional studies were included, focusing on three types of virtual walking: passive observing moving (71.4%), arm swing locomotion (21.5%), and foot tracking locomotion (7.1%). Most studies (84.6%) involved individuals with spinal cord injuries, while the remaining studies focused on lower back pain (7.7%) and lower limb pain (7.7%). Over 70% of studies lasted 11-20 min, 1-5 weekly sessions for 10-14 days. Statistically significant findings included pain reduction (84.6%), improved physical function (mobility and muscle strength), and reduced depression. Mild adverse effects (fatigue and dizziness) were transient. Neurological evidence indicates somatosensory cortex activation during virtual walking, possibly linked to neuropathic pain.
Tracking Endothelial Extracellular Vesicles in a Mouse Model of Atherosclerosis
Authors: Mandy Kunze Guo, Corey A. Scipione, Leandro C. D. Breda, Kamalben Prajapati, Sneha Raju, Steven R. Botts, Majed Abdul-Samad, Sarvatit Patel, Garry Yu, Andrew C. Dudley, Jason E. Fish, Kathryn L. Howe
Journal: Circulation Research (2025)
Comparative benchmarking of the DeepSeek large language model on medical tasks and clinical reasoning
Authors: Mickael Tordjman, Zelong Liu, Murat Yuce, Valentin Fauveau, Yunhao Mei, Jerome Hadjadj, Ian Bolger, Haidara Almansour, Carolyn Horst, Ashwin Singh Parihar, Amine Geahchan, Anis Meribout, Nader Yatim, Nicole Ng, Phillip Robson, Alexander Zhou, Sara Lewis, Mingqian Huang, Timothy Deyer, Bachir Taouli, Hao-Chih Lee, Zahi A Fayad, Xueyan Mei
Journal: Nature Medicine (2025)
Emerging artificial intelligence-driven precision therapies in tumor drug resistance: recent advances, opportunities, and challenges
Authors: Yuan Mao, Dangang Shangguan, Qi Huang, Ling Xiao, Dongsheng Cao, Hui Zhou, Yi-Kun Wang
Journal: Molecular Cancer (2025)

Drug resistance is one of the main reasons for cancer treatment failure, leading to a rapid recurrence/disease progression of the cancer. Recently, artificial intelligence (AI) has empowered physicians to use its powerful data processing and pattern recognition capabilities to extract and mine valuable drug resistance information from large amounts of clinical or omics data, to study drug resistance mechanisms, to evaluate and predict drug resistance, and to develop innovative therapeutic strategies to reduce drug resistance. In this review, we proposed a feasible workflow for incorporating AI into tumor drug resistance research, highlighted current AI-driven tumor drug resistance applications, and discussed the opportunities and challenges encountered in the process. Based on a comprehensive literature analysis, we systematically summarized the role of AI in tumor drug resistance research, including drug development, resistance mechanism elucidation, drug sensitivity prediction, combination therapy optimization, resistance phenotype identification, and clinical biomarker discovery. With the continuous advancement of AI technology and rigorous validation of clinical data, AI models are expected to fuel the development of precision oncology by improving efficacy, guiding therapeutic decisions, and optimizing patient prognosis. In summary, by leveraging clinical and omics data, AI models are expected to pioneer new therapy strategies to mitigate tumor drug resistance, improve efficacy and patient survival, and provide novel perspectives and tools for oncology treatment.
P2X7 receptor promotes the growth and metastasis of gastric cancer by activating P13/AKT/GSK-3 beta signaling (experimental research)
Authors: Wen-Jun Zhang, Hong-Liang Luo, Ji-Peng Liu, Yong-Sheng Xu, Wen-Long Wang, Chao Huang
Journal: International Journal of Surgery (2025)

Objective: This study investigated the role of P2X7 receptor (P2X7R) in the proliferation and metastasis of gastric cancer (GC). Methods: The functional role and possible mechanism of P2X7R in the progression of GC were investigated through in vitro and in vivo experiments. Results: The results showed that ATP and its analogue BzATP increased calcium current in AGS and HGC-27 cells, while P2X7R antagonists A438079 and AZD9056 decreased the ATP-induced calcium influx. Activation of P2X7R increased the glycogen accumulation in GC cells, enhanced the stress ability of actin fibers and cell morphology changes, and promoted the proliferation, migration and invasion of GC cells. Conversely, the application of A438079, AZD9056 or siP2X7R inhibited the proliferation, migration and invasion of GC cells. Moreover, activation of P2X7R increased the expression levels of EMT/metastasis related genes MMP-2, MMP-9, N-cadherin, Zeb1, Vimentin and Snail, hut decreased the E-cadherin expression. While A438069, AZD9056, LY294002 or siP2X7R reversed the expression of the above genes. Activation of P2X7R activated P13/AKT/GSK-3beta signaling to promote the proliferation, migration and invasion of GC. Additionally, in vivo experiments showed that ATP activated P2X7R to induce the growth of tumors. Conclusions: Our conclusion is that activation of P2X7R promotes the proliferation, metastasis and EMT of GC cells by activating P13/AKT/GSK-3beta signaling, and indicates that P2X7R may become a new potential target for GC treatment.
Clinical performance of a machine learning-based model for detecting lymph node metastasis in papillary thyroid carcinoma: A multicenter study
Authors: Wei Liu, Jiaojiao Zheng, Jing Han, Weifeng Qu, Qiao Wu, Zhou Yuan, Gaolei Jia, Xiaolong Wang, Linxiong Ye, Jiaqi Zhang, Shisheng Zhang, Xuanye Cao, Ying Liu, Zhilong Ai
Journal: International Journal of Surgery (2025)

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with a generally favorable prognosis, but lymph node metastasis (LNM) complicates treatment and increases recurrence risk. Current preoperative methods like neck ultrasound often miss LNM, leading to unnecessary surgeries. This study developed a non-invasive, artificial intelligence (AI)-driven predictive model for LNM using gene expression data from 157 PTC patients and validated it with qRT-PCR across 807 participants from multiple centers. The model focused on three key genes – RPS4Y1, PKHD1L1, and CRABP1 – chosen for their predictive strength. A random forest algorithm achieved high accuracy, with an AUROC of 0.992 in training and 0.911–0.953 in external validation. RPS4Y1 emerged as a standout predictor, showing the strongest distinction between metastatic and non-metastatic cases. The study also identified immune-related pathways, such as TGF-β signaling and cancer-associated fibroblast activation, as critical in metastasis. This gene expression-based model offers a non-invasive, cost-effective solution for predicting LNM, providing valuable insights to guide surgical decisions and reduce unnecessary procedures, ultimately improving patient outcomes.
Acute Pain Service for Postoperative Pain in Adults
Authors: Lu Chen, Xixia Feng, Ling Ye, Jiaqi Yang, Ruihao Zhou, Yong Qiu, Guo Chen, Tao Zhu
Journal: International Journal of Surgery (2025)

Background: Postoperative pain significantly impacts patients’ quality of life and recovery. Although acute pain services (APS) have been implemented in many hospitals worldwide, no study has directly compared the efficacy of different APS subtypes in managing acute postoperative pain. Objective: This network meta-analysis aimed to evaluate the effectiveness of various APS models in alleviating postoperative pain in adults undergoing surgery. Methods: Four English-language databases (PubMed, Web of Science, Embase, and Cochrane Library) and three Chinese-language databases (CNKI, WANFANG, and SinoMed) were searched to identify randomized controlled trials (RCTs) that compared the efficacy of different pain management models for postoperative pain in adult patients. Statistical analyses were conducted using R version 4.4.2 and Stata version 18. Results: A total of 38 studies were included in this network meta-analysis. All APS subtypes demonstrated superior pain relief compared to the traditional ward doctor-nurse model. These included nurse-based anesthesiologist specialist-supervised APS (NBASS-APS; SMD: − 1.99, 99%CI: − 2.55, − 1.43), nurse-based anesthesiologist-supervised APS (NBAS-APS; SMD: − 1.44, 99%CI: − 2.18, − 0.70), pain management multidisciplinary team (PMDT; SMD: − 1.31, 99%CI: − 1.74, − 0.87), and conventional APS (C-APS; SMD: − 0.83, 99%CI: − 1.43, − 0.24). Surface under the cumulative ranking (SUCRA) analysis identified NBASS-APS as having the highest probability of achieving optimal pain relief (98.0%), followed by NBAS-APS (65.9%), PMDT (58.0%), C-APS (28.1%), and the traditional model (0.1%). Conclusion: APS models are significantly more effective than the traditional ward doctor-nurse model in relieving postoperative pain, with NBASS-APS emerging as the most promising approach, followed by NBAS-APS, PMDT, and C-APS.
Peripheral nerve blocks for hip fracture surgeries: a bibliometric and visual analysis
Authors: Chunyang Zhang, Jie Su, Jun Yao, Miao Wang, Cheng Xu, Aizhong Wang
Journal: International Journal of Surgery (2025)

Background: Hip fractures – encompassing femoral neck and intertrochanteric injuries – are widely recognized as having high morbidity, mortality, and financial burden, particularly among older adults. Despite the growing adoption of peripheral nerve block (PNB) for postoperative pain management, there is a lack of comprehensive bibliometric analyses that elucidate global research trends, collaborations, and advancements in PNB for hip fracture surgeries. Methods: We employed the Web of Science Core Collection to identify 377 English-language original research articles (2004–2024) on PNB in hip fracture procedures. We then utilized VOSviewer and CiteSpace to map publication dynamics, detect prolific contributors, and reveal keyword clusters. Results: Our analysis showed that the yearly publication rate rose by 31.81%, with the United States, China, and the United Kingdom leading in output and collaboration. Key techniques included the fascia iliaca, quadratus lumborum, triple nerve, and pericapsular nerve group blocks, each with unique advantages and limitations. The PENG block and adapted fascia iliaca approaches were frequently cited, highlighting their promise for improving analgesia and preserving postoperative mobility. However, high-end ultrasound equipment costs and knowledge gaps in resource-limited settings remain barriers to broader clinical implementation. Conclusion: These findings indicate a rapid expansion of PNB research in hip fracture care, reflecting its potential to enhance perioperative recovery and reduce complications. Nonetheless, questions persist regarding long-term outcomes, mortality, and cost-effectiveness – particularly in older, high-risk patients. Addressing these challenges through interdisciplinary research, expanded database inclusion, and standardized guidelines could strengthen the role of PNB in hip fracture management worldwide, ultimately improving patient outcomes and advancing the field of perioperative pain control.
Artificial neural network model enhancing the accuracy of clinical evaluation for high-risk population of lymph node metastasis in non-intestinal type early gastric cancer: a multicenter real-world study in China
Authors: Jiamei Guo, Kecheng Zhang, Gang Ji, Wei Wang, Gang Li, Zhiqiang Liu, Zuli Yang, Zaisheng Ye, Yantao Tian, Tao Zhang, Xiangyu Wang, Kun Yang, Tong Zhou, Qi You, Yong Li, Peng Ren, Rupeng Zhang, Jingyu Deng
Journal: International Journal of Surgery (2025)

Background: Recent years have witnessed a proliferation of studies aimed at developing clinical models capable of predicting lymph node metastasis (LNM) in early gastric cancer (EGC), yet tools for prediction grounded in the Lauren classification remain scarce. Methods: Data of 6468 patients diagnosed with EGC from fifteen Chinese high-volume cancer centers between January 2005 and December 2015 were retrospectively analyzed. Utilizing multivariate logistic regression analysis and the multilayer perceptron (MLP) prediction algorithm, a nomogram and an artificial neural network (ANN) model were developed and validated, respectively, for predicting the likelihood of LNM in non-intestinal EGC cases. The models’ performances were evaluated and a comparative analysis of their parameters was undertaken. Subsequently, in-depth risk stratification analyses were performed around the two models. Results: Non-intestinal type EGC demonstrated an elevated LNM rate and inferior prognosis compared to the intestinal type. Both nomogram and ANN model were developed and performed well in discrimination, calibration and clinical utility. Notably, the ANN model surpassed the nomogram in specificity (95.8% vs. 71.3%, P &lt; 0.001), positive predictive value (PPV) (62.0% vs. 36.2%, P &lt; 0.001) and overall accuracy (82.7% vs. 70.5%, P &lt; 0.001). Patients with different risk strata derived from the nomogram, ANN model, and their combined application exhibited significantly different outcomes. The extent of lymph node dissection significantly influenced prognoses in high-risk patients identified by the combined model, whereas the anatomical location of metastatic lymph nodes did not. Conclusion: The ANN model established in this study can screen the patients at high risk of LNM in non-intestinal type EGC more accurately. Considering the high extragastric LNM rate observed in the high-risk stratum, radical gastrectomy combined with D2 lymph node dissection is strongly recommended.
Single-cell transcriptomics reveals the interaction between fibroblasts and activated immune cells
Authors: Fengxu Chi, Weidong Sun, Cong Zhang, Xiangwen Yu, Cen Huang, Xiangchen Ding, Hanman Chang, Jun Gao, Shi Yan, Anlong Zhu, Yanwei Xing, Xiufeng Jiang, an Yan, Niansheng Ren, Linfeng Yu, Xuhui Bao, Yuekun Zhu
Journal: International Journal of Surgery (2025)

Background: Slow transit constipation (STC) is an intestinal disease characterized by colonic dyskinesia which involves multiple factors such as neuroendocrine, substance metabolism, gut microbiota, ion channels, and aquaporin. Increasing evidence indicates that modulation of immune signaling, activation of immune cells, and secretion of cytokines impact oxidative stress, disruption of the intestinal mucosal barrier and the subsequent intestinal dysfunction in STC. However, the landscape of the immune microenvironment (IME) and the disease-specific cell type in STC patients is unclear, and the detailed mechanism of how immune cells affect stromal cells during chronic inflammation is still lacking. Materials and methods: We performed single-cell RNA sequencing (scRNA-seq) on 6 STC cases and 6 control cases to elucidate the IME in STC patients. By identifying differentially expressed genes and pathways between groups, tracking cell differentiation trajectories, and constructing an integrated analysis of intercellular communication, we aimed to elucidate the potential mechanisms of specific immune cell types. Results: We identified STC-specific XCL2 + CD8 + T cells, which exhibit extensive intercellular communication with other immune cells and intestinal stromal cells. B cells and myeloid cells could promote the immune function of XCL2 + CD8 + T cells by CD137 co-stimulatory molecules. Afterwards, the activated XCL2 + CD8 + T cells enhanced the secretion of pro-inflammatory cytokines of fibroblasts through IFNG and TNFSF14 signaling pathways. Additionally, fibroblasts exert immune regulation on XCL2 + CD8 + T cells through the NECTIN signaling pathway. Conclusion: These results suggested that STC-specific XCL2 + CD8 + T cells might influence the homeostasis of the IME and further disrupt intestinal function.
A commentary on “The efficacy of diltiazem, glyceryl trinitrate, nifedipine, minoxidil, and lidocaine for the medical management of anal fissure: a systematic review and network meta-analysis of randomized controlled trials”
Authors: Peng Li, Lijuan Zhu, Xiutian Guo, Wenqi Jin, Jie Hu, Yan Chen, Jingen Lu
Journal: International Journal of Surgery (2025)