tbuckley/cabot-search huggingface dataset:
Clinical usefulness of digital twin guided virtual amiodarone test in patients with atrial fibrillation ablation
Authors: Taehyun Hwang, Byounghyun Lim, Oh-Seok Kwon, Moon-Hyun Kim, Daehoon Kim, Je-Wook Park, Hee Tae Yu, Tae-Hoon Kim, Jae-Sun Uhm, Boyoung Joung, Moon-Hyoung Lee, Chun Hwang, Hui-Nam Pak
Journal: npj Digital Medicine (2024)

It would be clinically valuable if the efficacy of antiarrhythmic drugs could be simulated in advance. We developed a digital twin to predict amiodarone efficacy in high-risk atrial fibrillation (AF) patients post-ablation. Virtual left atrium models were created from computed tomography and electroanatomical maps to simulate AF and evaluate its response to varying amiodarone concentrations. As the amiodarone concentration increased in the virtual setting, action potential duration lengthened, peak upstroke velocities decreased, and virtual AF termination became more frequent. Patients were classified into effective (those with virtually terminated AF at therapeutic doses) and ineffective groups. The one-year clinical outcomes after AF ablation showed significantly better results in the effective group compared to the ineffective group, with AF recurrence rates of 20.8% vs. 45.1% (log-rank p = 0.031, adjusted hazard ratio, 0.37 [0.14-0.98]; p = 0.046). This study highlights the potential of a digital twin-guided approach in predicting amiodarone's effectiveness and improving personalized AF management. Clinical Trial Registration Name: The Evaluation for Prognostic Factors After Catheter Ablation of Atrial Fibrillation: Cohort Study, Registration number: NCT02138695. The date of registration: 2014-05. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695.
Progress on Carbon Dots with Intrinsic Bioactivities for Multimodal Theranostics
Authors: Hao Zhang, Hao Liu, Xiaohui Liu, Aiguo Song, Hui Jiang, Xuemei Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Carbon dots (CDs) with intrinsic bioactivities are candidates for bioimaging and disease therapy due to their diverse bioactivities, high biocompatibility, and multiple functionalities in multimodal theranostics. It is a multidisciplinary research hotspot that includes biology, physics, materials science, and chemistry. This progress report discusses the CDs with intrinsic bioactivities and their applications in multimodal theranostics. The relationship between the synthesis and structure of CDs is summarized and analyzed from a material and chemical perspective. The bioactivities of CDs including anti‐tumor, antibacterial, anti‐inflammatory etc. are discussed from biological points of view. Subsequently, the optical and electronic properties of CDs that can be applied in the biomedical field are summarized from a physical perspective. Based on the functional review of CDs, their applications in the biomedical field are reviewed, including optical diagnosis and treatment, biological activity, etc. Unlike previous reviews, this review combines multiple disciplines to gain a more comprehensive understanding of the mechanisms, functions, and applications of CDs with intrinsic bioactivities.
Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells
Authors: Xiang‐Yu Wang, Yi Yan, Xiao‐Ru Guo, An Lu, Lin‐Xia Jiang, Yuan‐Jun Zhu, Yu‐Jie Shi, Xiao‐Yan Liu, Jian‐Cheng Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Insufficient activation of stimulator of interferon genes (STING) signaling pathway in tumor‐associated dendritic cells limits the efficiency of tumor immunotherapy. Herein, the “three‐in‐one” IAHA‐LaP/siPTPN6 NPs containing lanthanum ions (La 3+ ), cGAMP, and PTPN6 siRNA are developed for triple amplification of the STING pathway. In vitro results demonstrate that La 3+ significantly promotes cGAMP‐mediated activation of the STING pathway by enhancing the phosphorylation of STING, TBK1, IRF3, and NF‐ κ B p65. Moreover, the IAHA‐LaP/siPTPN6 NPs further significantly enhance the phosphorylation of STING and NF‐ κ B p65 and augment K63‐linked ubiquitination of STING protein via siPTPN6‐mediated downregulation of SHP‐1 protein. Furthermore, NPs improve the secretion of IFN β (2.4‐fold), IL‐6 (1.5‐fold), and TNF‐ α (1.4‐fold), thereby promoting DCs maturation compared to the mixture of La 3+ and cGAMP. In vivo results show that the IAHA‐LaP/siPTPN6 NPs remarkably inhibit primary tumor growth by increasing the percentage of mature DCs in tumor‐draining lymph nodes, polarizing M2/M1 phenotype in TME, and promoting the infiltration of CD8 + T cells into tumors. Moreover, these NPs dramatically prevent the growth of distal tumor by inducing systemic anti‐tumor immunity and generating a long‐term anti‐tumor memory for protection against tumor recurrence in mice bearing bilateral B16F10. These IAHA‐LaP/siPTPN6 NPs may offer a promising platform for robust anti‐tumor immune responses.
Inflammation‐Targeted Biomimetic Nano‐Decoys via Inhibiting the Infiltration of Immune Cells and Effectively Delivering Glucocorticoids for Enhanced Multiple Sclerosis Treatment
Authors: Yiling Yang, Yuzhen Zhao, Huixian Liu, Xinyun Wu, Mingming Guo, Li Xie, Guangsheng Wang, Jinjin Shi, Wenyan Yu, Gang Dong
Journal: Advanced Healthcare Materials (2024)

Abstract Excessive infiltration of neutrophil and inflammatory cytokines accumulation as well as the inadequate delivery of drugs to the targeted site are key pathological cascades in multiple sclerosis (MS). Herein, inflammation‐targeting biomimetic nano‐decoys (TFMN) is developed that inhibit the infiltration of immune cells and effectively deliver glucocorticoids to lesions for enhanced MS treatment. Nano‐decoys encapsulated with the glucocorticoid methylprednisolone (MPS) are prepared by coating neutrophil membrane (NM) on nanoparticles formed by the self‐assembly of tannic acid and poloxamer188/pluronic68. Benefiting from the natural inflammation‐targeting ability of activated neutrophil membranes, TFMN can target the lesion site and prevent neutrophils infiltration by adsorbing and neutralizing elevated neutrophil‐related cytokines, subsequently modulating the inflammatory microenvironment in experimental autoimmune encephalomyelitis mice. TFMN exhibits a strong antioxidant capacity and scavenged excessive reactive oxygen species to enhance neuronal protection. Furthermore, at the inflammation site, perforin, discharged by cytotoxic T‐lymphocytes, triggered the controlled release of MPS within the TFMN through perforin‐formed pores in the NM. Simultaneously, this mechanism protected neurons from perforin‐induced toxicity. The MPS liberated at the targeted site achieves optimal drug accumulation, thereby enhancing therapeutic efficacy. In conclusion, the innovative system shows potential for integrating various therapeutic agents, offering a novel strategy for CNS disorders.
A Multiple Targeting Genome Editing System for Remodulation of Circulating Malignant Cells to Eliminate Cancer Immunosuppression and Restore Immune Responses
Authors: Xiao‐He Ren, Tao Guo, Ma‐Fei Xu, Yun Huang, Xin‐Ru Liao, Li‐Jin Qi, Si‐Xue Cheng
Journal: Advanced Healthcare Materials (2024)

Abstract Cancer immunotherapy, which aims to eliminate cancer immunosuppression and reactivate anticancer immunity, holds great promise in oncology treatments. However, it is challenging to accurately study the efficacy of immunotherapy based on human‐derived cells through animal experiments due to xenogeneic immune rejection. Herein, a personalized and precise strategy to evaluate the effectiveness of immunotherapy using the blood samples of cancer patients is presented. Through the utilization of multiple cancer‐targeting delivery system decorated with the epidermal growth factor receptor (EGFR)‐specific aptamer CL4 and the AXL‐specific aptamer GL21.T to achieve superior efficiency in delivering the genome editing plasmid for MUC1 knockout, effective modulation on the behavior of circulating malignant cells (CMCs) is realized. After genome editing, both mucin 1 (MUC1) and programmed death‐ligand 1 (PD‐L1) are significantly downregulated in CMCs. The elimination of immunosuppression results in markedly enhanced secretion of pro‐inflammatory anticancer cytokines encompassing interleukins 2, 12, and 15 and interferon‐γ by immune cells. The study not only provides a strategy to overcome immunosuppression but also yields critical insights for personalized immunotherapy approaches.
Enhancing Cytoplasmic Expression of Exogenous mRNA Through Dynamic Mechanical Stimulation
Authors: Jiawen Chen, Aneri Patel, Mohammad Mir, Maria R. Hudock, Meghan R. Pinezich, Brandon Guenthart, Matthew Bacchetta, Gordana Vunjak‐Novakovic, Jinho Kim
Journal: Advanced Healthcare Materials (2024)

Abstract Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID‐19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid‐based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP‐mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA, and increase the transfection efficiency of mRNA. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to mitochondrial membrane potential and Golgi apparatus integrity. Thus, this work presents a user‐friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, this work can be potentially utilized in both research and clinical fields to facilitate LNP‐based delivery by enabling more effective release of LNP‐encapsulated cargos from endosomes.
Progress in Designing Therapeutic Antimicrobial Hydrogels Targeting Implant‐associated Infections: Paving the Way for a Sustainable Platform Applied to Biomedical Devices
Authors: Caroline Dini, Maria Helena Rossy Borges, Samuel Santana Malheiros, Rodolfo Debone Piazza, Jeroen J.J.P. van den Beucken, Erica Dorigatti de Avila, João Gabriel S. Souza, Valentim A. R. Barão
Journal: Advanced Healthcare Materials (2024)

Implantable biomedical devices have found widespread use in restoring lost functions or structures within the human body, but they face a significant challenge from microbial-related infections, which often lead to implant failure. In this context, antimicrobial hydrogels emerge as a promising strategy for treating implant-associated infections owing to their tunable physicochemical properties. However, the literature lacks a comprehensive analysis of antimicrobial hydrogels, encompassing their development, mechanisms, and effect on implant-associated infections, mainly in light of existing in vitro, in vivo, and clinical evidence. Thus, this review addresses the strategies employed by existing studies to tailor hydrogel properties to meet the specific needs of each application. Furthermore, this comprehensive review critically appraises the development of antimicrobial hydrogels, with a particular focus on solving infections related to metallic orthopedic or dental implants. Then, preclinical and clinical studies centering on providing quantitative microbiological results associated with the application of antimicrobial hydrogels are systematically summarized. Overall, antimicrobial hydrogels benefit from the tunable properties of polymers and hold promise as an effective strategy for the local treatment of implant-associated infections. However, future clinical investigations, grounded on robust evidence from in vitro and preclinical studies, are required to explore and validate new antimicrobial hydrogels for clinical use.
Early Diagnosis of Liver Injury and Real‐Time Evaluation of Photothermal Therapy Efficacy with a Viscosity‐Responsive NIR‐II Smart Molecule
Authors: Qi Zan, Li Fan, Wenjing Lu, Yuewei Zhang, Yunong Huang, Xue Yu, Yahong Han, Ruiping Zhang, Chuan Dong, Shaomin Shuang
Journal: Advanced Healthcare Materials (2024)

Abstract The early diagnosis of liver injury and in situ real‐time monitoring of tumor therapy efficacy are important for the enhancement of personalized precision therapy but remain challenging due to the lack of reliable in vivo visualization tools with integrated diagnostic, therapeutic, and efficacy monitoring functions. Herein, a smart second near‐infrared window (NIR‐II) molecule ( BITX‐OH ) is rationally designed for diagnosis and therapy by vinyl‐bridging hydroxyl diphenyl xanthine unit and benzo[cd]indolium skeleton. BITX‐OH exhibits high selectivity and sensitivity toward viscosity, exhibiting a significant enhancement (1167‐fold) in NIR‐II fluorescence at 962 nm. With the assistance of BITX‐OH and NIR‐II fluorescence imaging, early diagnosis and therapeutic evaluation of non‐alcoholic fatty liver (NAFL), as well as in‐site real‐time monitoring of hepatic fibrosis (HF) in live mice have been successfully achieved, which is at least several hours earlier than the typical clinical test. Notably, BITX‐OH displays excellent photothermal conversion efficiency when exposed to an 808 nm laser, which can induce tumor ablation and increase viscosity, thereby enhancing NIR‐II fluorescence for the real‐time evaluation of photothermal therapy (PTT). This viscosity‐based “self‐monitoring” strategy provides a convenient and reliable platform for timely obtaining therapeutic feedback to avoid over‐ or under‐treatment, thus enabling personalized precision therapy.
Netrin1‐Enriched Exosomes From Genetically Modified ADSCs as a Novel Treatment for Diabetic Limb Ischemia
Authors: Yihong Jiang, Jiateng Hu, Chaoyi Cui, Zhaoxi Peng, Sen Yang, Jiahao Lei, Bo Li, Xinrui Yang, Jinbao Qin, Minyi Yin, Xiaobing Liu, Kaichuang Ye, Zhijue Xu, Xing Zhang, Xinwu Lu
Journal: Advanced Healthcare Materials (2024)

Abstract Diabetic limb ischemia (DLI) is a frequent complication of diabetes and the leading cause of non‐traumatic amputation. Traditional treatments like stent placement and bypass surgery may not suit all patients. Exosome transplantation has emerged as a promising therapy. Netrin1, a protective cardiovascular factor, has an unclear role in DLI. This study investigates the role of Netrin1 in DLI patients and evaluates the therapeutic potential of exosomes derived from Netrin1‐overexpressing adipose‐derived stem cells (N‐ADSCs). The expression of Netrin1 is significantly decreased in both endothelial cells and serum of DLI patients, highlighting its potential as a biomarker or therapeutic target. In vitro, Netrin1‐enriched exosomes (N‐Exos) promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, tube formation, and increased resistance to apoptosis under high glucose conditions. These protective effects are mediated through PI3K/AKT/eNOS and MEK/ERK pathways, and N‐Exos further facilitated macrophage polarization from M1 to M2. In vivo, N‐Exos demonstrates superior therapeutic effects over ADSC exosomes (Exos), including enhanced angiogenesis, improved collateral artery remodeling, reduced inflammation, and muscle protection. Collectively, these findings identify Netrin1 as a critical factor in DLI and underscore its significance in disease progression and therapeutic strategies. N‐Exos offers a promising non‐cellular therapeutic approach for the treatment of DLI.
Pitaya‐Inspired Metal‐Organic Framework Nanozyme for Multimodal Imaging‐Guided Synergistic Cuproptosis, Nanocatalytic Therapy, and Photothermal Therapy
Authors: Quer Yue, Qingbin Zeng, Qianni Guo, Xiuchao Zhao, Yaping Yuan, Yuqi Yang, Weiping Jiang, Xin Zhou
Journal: Advanced Healthcare Materials (2024)

Abstract Nature often provides invaluable insights into technological innovation and the construction of nanomaterials. Inspired by the pitaya fruit's strategy of wrapping seeds within its pulp to enhance seed survival, a unique nanocomposite based on metal‐organic framework (MOF)‐encapsulated CuS nanoparticles (NPs) is developed. This design effectively addresses the challenge of short retention time afforded by CuS NPs for therapeutic and imaging purposes. The MOF acts as the “pitaya pulp” protecting the internal CuS NPs (“pitaya seeds”), thereby increasing their retention time in vivo. This system exhibits triple‐enzyme‐mimicking activities and is proposed for application in photoacoustic and magnetic resonance imaging‐guided therapies, including chemodynamic therapy, photothermal therapy, and cuproptosis‐related therapy. The exceptional enzyme‐mimicking activities of superoxide dismutase, catalase, and peroxidase not only produce oxygen to alleviate hypoxia but also generate a reactive oxygen species (ROS) storm for effective tumor destruction. By combining these multienzymatic properties, superior photothermal performance, and Cu‐induced cuproptosis, nanozyme‐treated mice exhibited an 84% inhibition of tumor growth—approximately double the effect observed in mice treated with CuS NPs alone. This study presents a smart strategy for integrating imaging with therapeutic modalities, achieving exceptional outcomes for precise imaging‐guided tumor therapy.
CAR-NK cells for gastrointestinal cancer immunotherapy: from bench to bedside
Authors: Xingwang Zhu, Jieyun Xue, Hongzhou Jiang, Dongwei Xue
Journal: Molecular Cancer (2024)

Gastrointestinal (GI) cancers represent a significant health burden worldwide. Their incidence continues to increase, and their management remains a clinical challenge. Chimeric antigen receptor (CAR) natural killer (NK) cells have emerged as a promising alternative to CAR-T cells for immunotherapy of GI cancers. Notably, CAR-NK cells offer several advantages, including reduced risk of graft-versus-host disease, lower cytokine release syndrome, and the ability to target cancer cells through both CAR-dependent and natural cytotoxic mechanisms. This review comprehensively discusses the development and applications of CAR-NK cells in the treatment of GI cancers. We explored various sources of NK cells, CAR design strategies, and the current state of CAR-NK cell therapy for GI cancers, highlighting recent preclinical and clinical trials. Additionally, we addressed existing challenges and propose potential strategies to enhance the efficacy and safety of CAR-NK cell therapy. Our findings highlight the potential of CAR-NK cells to revolutionize GI cancer treatment and pave the way for future clinical applications.
Conduction Disturbances and Outcome After Surgical Aortic Valve Replacement in Patients With Bicuspid and Tricuspid Aortic Stenosis
Authors: Johan O. Wedin, Viktor Näslund, Sergey Rodin, Oscar E. Simonson, Frank A. Flachskampf, Stefan K. James, Elisabeth Ståhle, Karl-Henrik Grinnemo
Journal: Circulation (2024)

BACKGROUND: This study aimed to compare the incidence and prognostic implications of new-onset conduction disturbances after surgical aortic valve replacement (SAVR) in patients with bicuspid aortic valve (BAV) aortic stenosis (AS) versus patients with tricuspid aortic valve (TAV) AS (ie, BAV-AS and TAV-AS, respectively). Additionally, the study included stratification of BAV patients according to subtype. METHODS: In this cohort study, the incidence of postoperative third-degree atrioventricular (AV) block with subsequent permanent pacemaker requirement and new-onset left bundle-branch block (LBBB) was investigated in 1147 consecutive patients without preoperative conduction disorder who underwent isolated SAVR (with or without ascending aortic surgery) between January 1, 2005, and December 31, 2022. The groups were stratified by aortic valve morphology (BAV, n=589; TAV, n=558). The outcomes of interests were new-onset third-degree AV block or new-onset LBBB during the index hospitalization. The impact of new-onset postoperative conduction disturbances on survival was investigated in BAV-AS and TAV-AS patients during a median follow-up of 8.2 years. BAV morphology was further categorized according to the Sievers and Schmidtke classification system (possible in 307 BAV-AS patients) to explore association between BAV subtypes and new-onset conduction disturbances after SAVR. RESULTS: The overall incidence of third-degree AV block and new-onset LBBB after SAVR was 4.5% and 7.8%, respectively. BAV-AS patients had a higher incidence of both new-onset third-degree AV block (6.5% versus 2.5%; P =0.001) and new-onset LBBB (9.7% versus 5.7%; P =0.013) compared with TAV-AS patients. New-onset LBBB was associated with an increased all-cause mortality during follow-up (adjusted hazard ratio, 1.60 [95% CI, 1.12–2.30]; P =0.011), whereas new-onset third-degree AV block was not associated with worse prognosis. Subgroup analysis of the BAV cohort revealed that BAV-AS patients with fusion of the right- and non-coronary cusps had the highest risk of new-onset third-degree AV block (adjusted odds ratio [aOR], 8.33 [95% CI, 3.31–20.97]; P &lt;0.001, with TAV as reference group) and new-onset LBBB (aOR, 4.03 [95% CI, 1.84–8.82]; P &lt;0.001, with TAV as reference group), whereas no significant association was observed for the other BAV subtypes. CONCLUSIONS: New-onset LBBB after SAVR is associated with increased all-cause mortality during follow-up, and is more frequent complication in BAV AS patients compared with TAV-AS patients. BAV-AS patients with fusion of the right- and non-coronary cusps have an increased risk for conduction disturbances after SAVR. This should be taken into consideration when managing these patients.
Effectiveness and cost-effectiveness of online recorded recovery narratives in improving quality of life for people with psychosis experience (NEON Trial): a pragmatic randomised controlled trial
Authors: Mike Slade, Stefan Rennick-Egglestone, Clare Robinson, Chris Newby, Rachel A Elliott, Yasmin Ali, Caroline Yeo, Tony Glover, Sean P Gavan, Luke Paterson, Kristian Pollock, Stefan Priebe, Graham Thornicroft, Jeroen Keppens, Melanie Smuk, Donna Franklin, Rianna Walcott, Julian Harrison, Dan Robotham, Simon Bradstreet, Steve Gillard, Pim Cuijpers, Marianne Farkas, Dror Ben-Zeev, Julie Repper, Yasuhiro Kotera, James Roe, Joy Llewellyn-Beardsley, Fiona Ng
Journal: The Lancet Regional Health - Europe (2024)
Targeting Senescence with Radioactive 223Ra/Ba SAzymes Enables Senolytics-Unlocked One‐Two Punch Strategy to Boost Anti-tumor Immunotherapy
Authors: Jiajia Zhang, Shenghong Zhang, Chao Cheng, Chunyan Zhu, Taixia Wang, Linglin Tang, Jingjing Lou, Xian Li, Hai Wang, Fan Hu, Ming Sun, Kun Zhang, Fei Yu
Journal: Biomaterials (2024)