tbuckley/cabot-search huggingface dataset:
Maximizing oral intake tolerance in malignant gastric outlet obstruction – a Markov decision tree analysis comparing duodenal stenting, endoscopic ultrasound-guided gastroenterostomy and surgical gastrojejunostomy based on a meta-analysis of randomized controlled trials
Authors: Koy Min Chue, Benjamin Robert Douglass, Lester Ong Wei Lin, Jeremy Tan Tian Hui, Jonathan Guo Xiang Teh, Martin Putera, Clarence Kah Wai Kwan, Wai Keong Wong, Baldwin Yeung Po Man
Journal: International Journal of Surgery (2025)

Introduction: Malignant gastric outlet obstruction (GOO) has a significant impact on quality of life. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has shown promising results. Traditional isolated outcome measures do not sufficiently address critical considerations for end-of-life patients like oral intake tolerance. This study aimed to determine via a probabilistic approach, the optimal management strategy for GOO patients that maximizes their oral intake tolerance. Methods: A Markov decision model was developed, with input variables based on a systematic review and meta-analysis of randomized controlled trials (RCT) comparing duodenal stenting (DS), EUS-GE and surgical gastrojejunostomy (GJ). A prospective cohort study with a comparator group was also included for EUS-GE model given the scarcity of RCTs. Model assumption was a patient with malignant GOO, with equal probabilities of being allocated to 1 of 3 treatment options. Each data point was evaluated using pooled probabilities from the meta-analysis of clinical outcomes. Primary outcome was successful oral intake tolerance at various time points of 1–6 months post-intervention. Results: Fifteen studies were included into the Markov model. Based on 10 000 simulations in each arm, at a survival of 1-month, DS and EUS-GE had the highest likelihood of oral intake (81.2% and 80.4%) compared to GJ (75.5%). However, at a survival of 6-month, EUS-GE and GJ were better at palliating GOO, with likelihood of oral intake at 23.8% and 25.2%, compared to 21.3% for DS. Conclusion: For patients with a prognosis of more than 1-month, a surgical GJ, or EUS-GE if technical expertise is available, is preferred for GOO palliation.
AKR1D1 suppresses liver cancer progression by promoting bile acid metabolism-mediated NK cell cytotoxicity
Authors: Haoran Wei, Caixia Suo, Xuemei Gu, Shengqi Shen, Kashuai Lin, Chuxu Zhu, Kai Yan, Zhenhua Bian, Liang Chen, Tong Zhang, Ronghui Yan, Zhiyi Yang, Yingxuan Yu, Zhikun Li, Rui Liu, Junming He, Qiwei He, Xiuying Zhong, Weidong Jia, Chun-Ming Wong, Zhongjun Dong, Jie Cao, Linchong Sun, Huafeng Zhang, Ping Gao
Journal: Cell Metabolism (2025)
Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations
Authors: Sjoerd J D Tjalsma, Niels J Rinzema, Marjon J A M Verstegen, Michelle J Robers, Andrea Nieto-Aliseda, Richard A Gremmen, Amin Allahyar, Mauro J Muraro, Peter H L Krijger, Wouter de Laat
Journal: Cell Genomics (2025)

Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also most sensitive to perturbations of other regulatory proteins and to BET inhibitor JQ1, this being more a consequence of their distinct enhancer features than distance. Our work predicts that lengthening of intervening sequences can help limit the expression of target genes to specialized cells with optimal trans-factor environments.
Effects of CPAP on Neuroimaging Biomarkers and Cognition in Adult OSA: A Randomized Controlled Trial
Authors: Huajun Xu, Yupu Liu, Chenyang Li, Xinyi Li, Li Shen, Hui Wang, Feng Liu, Juanjuan Zou, Yunyan Xia, Weijun Huang, Yuenan Liu, Zhenfei Gao, Yiqun Fu, Fan Wang, Shujian Huang, Zhiyuan Song, Fan Song, Yiqing Gao, Yu Peng, Jianyin Zou, Huaming Zhu, Suru Liu, Linpeng Li, Xiaoyue Zhu, Yuanping Xiong, Yuli Hu, Jiaxin Yang, Yuehua Li, Feng Gao, Qihao Guo, Hengye Huang, Weituo Zhang, Jiping Li, Yanqing Chen, Pin Dong, Jun Yang, Jingrong Lv, Peihua Wang, Yiyuan Sun, Biyun Qian, Kristine Yaffe, Jian Guan, Hongliang Yi, Yue Leng, Shankai Yin
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Obstructive sleep apnea (OSA) is associated with cognitive impairment. The effects of continuous positive airway pressure (CPAP) on neuroimaging biomarkers and cognitive performance among middle-aged patients with OSA and normal cognition remain unclear. To investigate the effects of CPAP therapy over 12 months on neuroimaging biomarkers and cognitive performance. In this multicenter, randomized clinical trial, we randomly assigned 148 participants with normal cognition and an apnea-hypopnea index ≥15/hour into two groups: patients receiving CPAP with best supportive care (BSC); and patients receiving BSC alone. The primary endpoint was MoCA score at 6 months after enrollment. The secondary endpoints were intranetwork functional connectivity (FC) of default mode network (DMN) and cortical thickness assessed by functional and structural magnetic resonance imaging, other neuroimaging biomarkers and neurobehavioral tests. Between 2017 and 2021, 148 patients were recruited from 5 hospitals. Linear mixed models showed that there was no significant difference in MoCA scores at 6 months between the CPAP and BSC groups (difference, -0.04, 95% confidence interval (CI), -0.72 to 0.65, P=0.91). However, there were significant differences in the FC of DMN (difference, -13.73, 95% CI, -23.40 to -4.06, P=0.01) and cortical thickness (difference, -0.06 mm, 95% CI, -0.10 to -0.01mm, P=0.02) between CPAP and BSC groups at 6 months after treatment. No serious adverse events occurred. CPAP improved cortical thickness and FC of DMN, suggesting that patients with OSA may recover from brain atrophic processes following CPAP treatment. However, no improvement in MoCA was found. Clinical trial registration available at www. gov, ID: NCT02886156.
Lenalidomide combined with R-CHOP (R2-CHOP) in the treatment of newly diagnosed double-expressor diffuse large B-cell lymphoma: a prospective phase II clinical trial
Authors: Yizhen Liu, Qunling Zhang, Fangfang Lv, Xiaojian Liu, Dongmei Ji, Zuguang Xia, Jia Jin, Rong Tao, Wenhao Zhang, Xiaoqiu Li, Shengjian Zhang, Zezhou Wang, Jiachen Wang, Xiaonan Hong, Junning Cao
Journal: Blood Cancer Journal (2025)
An inherited predisposition allele promotes gastric cancer via enhancing deubiquitination-mediated activation of epithelial-to-mesenchymal transition signaling
Authors: Bolin Tao, Zhenning Wang, Xuanyi Wang, Aixia Song, Jiaxian Liu, Jianan Wang, Qin Zhang, Zhaolin Chen, Zixian Wang, Wenjie Xu, Menghong Sun, Yanong Wang, Ping Zhang, Tao Xu, Gong-Hong Wei, Fei Xavier Chen, Mengyun Wang
Journal: Journal of Clinical Investigation (2025)

Genome-wide human genetic studies have identified inherited cis-regulatory loci variants that predispose to cancers. However, the mechanisms by which these germline variants influence cancer progression, particularly through gene expression and proteostasis control, remain unclear. By analyzing genomic data from a gastric cancer (GC) case-control study (2,117 individuals), focusing on the ubiquitin-specific protease (USP) family, we identify the single nucleotide polymorphism (SNP) rs72856331 (G>A) in the promoter region of the proto-oncogene USP47 as a putative susceptibility allele for GC (OR = 0.78, P = 0.015). Mechanistically, the risk allele G is associated with enhanced USP47 expression, mediated by altered recruitment of the transcription factor GLI3 and changes in the epigenetic status at promoter. CRISPR/Cas9-mediated single-nucleotide conversion into risk allele G results in increased GLI3 binding and subsequent USP47 upregulation. The depletion of GLI3 results in a reduction of cancer-related phenotypes, similar to those observed following USP47 knockdown. Furthermore, we identify Snai1 as a deubiquitination target of USP47, explaining USP47-dependent activation of epithelial-mesenchymal transition pathway and tumor progression. Our findings identify an important genetic predisposition that implicates the perturbation of transcription and proteostasis programs in GC, offering insights into prevention and therapeutic strategies for genetically stratified patients.
Novel Protein‐Rich Bioactive Bioink Stimulates Cellular Proliferation and Response in 3D Bioprinted Volumetric Constructs
Authors: Suihong Liu, David Kilian, Anne Bernhardt, Katharina Wirsig, Max von Witzleben, Sarah Duin, Anja Lode, Qingxi Hu, Michael Gelinsky
Journal: Advanced Healthcare Materials (2025)

3D extrusion bioprinting, a promising and widely adopted technology in the emerging field of biofabrication, has gained considerable attention for its ability to fabricate hierarchically structured, native-mimicking tissue substitutes with precisely defined cell distributions. Despite notable advancements, the limited availability of suitably bioactive bioinks remains a major challenge, hindering the construction of volumetric tissue substitutes effectively mimicking biological functionality. Therefore, this work proposes a protein-rich, low-cost, bioactive bioink: abundantly available eggwhite powder (EWP) is leveraged to functionalize an alginate-methylcellulose (AlgMC) hydrogel matrix and enhance cellular response. The developed EWP-supplemented bioinks not only maintain favorable printability and high shape fidelity but also exhibit remarkable bioactivity. Notably, incorporating EWP into AlgMC-based bioinks enhances shear-thinning features, thereby improving the viability of encapsulated cells within the bioprinted constructs. The versatility and biofunctionality of EWP in bioprinted constructs are demonstrated using three distinct cell types, encompassing sources such as a stem cell line, human soft skin, and stiff bone tissues. Furthermore, the promising and wide applicability of the EWP-supplemented bioink for biofabrication is demonstrated exemplarily in core-shell and multi-channel bioprinting strategies as a proof-of-concept for functional tissue construction. These findings underscore the significant and versatile potential of this novel bioink in biofabrication and biomedical applications.
3D Printed Bioactive Mechanical‐Adaptive Polyetheretherketone Implants with Non‐Invasive Tracking for Immunomodulatory Osseointegration
Authors: Hongyun Ma, Jin Tong, Xiaochen Su, Liang Liu, Jingqi Liang, Jianbo Sun, Jun Lu, Yingang Zhang, Bo Lei, Hongmou Zhao
Journal: Advanced Healthcare Materials (2025)

Abstract Polyether‐ether‐ketone (PEEK) has become a much‐attracted biomedical implant material in orthopedic surgery, serving as a more biocompatible alternative to conventional metals. However, the inherent bioinert and mismatched mechanical surface of PEEK have limited their optimized bone fixation and repair. In this work, a PEEK implant is printed and a bioactive mechanical‐adaptive surface via in situ chemical linking of photoluminescent elastomeric poly(citrate‐silicon) (PCS) polymer (PEEK‐PCS) is subsequently constructed, which could be used for real‐time bioimaging and enhanced osseointegration. The PEEK‐PCS surface exhibits viscoelastic properties, enabling it to conform to complex tissue geometries and effectively alleviate surface stress. Furthermore, PEEK‐PCS modulates the inflammatory response by promoting macrophage M2 phenotypic polarization and reducing the expression of inflammatory factors. Additionally, PEEK‐PCS promotes the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), significantly enhancing the osseointegration and osteogenesis ability of PEEK implants. Notably, PEEK‐PCS demonstrates excellent autofluorescence properties both in vitro and in vivo, along with remarkable fluorescence stability over 14 d in vivo, suggesting real‐time tracking potential of bioimaging. Compared to traditional coated implants, PEEK‐PCS provides distinct advantages in surface adhesion, mechanical compatibility, real‐time bioimaging, and osseointegration, representing a promising solution for implant‐related bone repair.
The Phase‐Transited Lysozyme Coating Modified Small Intestinal Submucosa Membrane Loaded with Calcium and Zinc Ions for Enhanced Bone Regeneration
Authors: Yilin Yang, Tianyi Tong, Xin Li, Hong Zheng, Shiyu Yao, Jiayin Deng, Qi Zhang, Zihao Liu, Xin Huang, Hongjie Li, Yuzhu Mu, Shiqing Ma
Journal: Advanced Healthcare Materials (2025)

Bone defects caused by severe trauma, tumors, infections and diseases remain a global challenge due to limited natural regeneration capacity of bone tissue in large-scale or complex injuries. Guided bone regeneration (GBR) has emerged as a pivotal technique in addressing these issues, relying on barrier membranes to facilitate osteoprogenitor cell infiltration. Current clinical GBR membranes function solely as physical barriers, lacking antibacterial and osteoinductive properties, which underscores the need for advanced alternatives. This study focuses on resorbable GBR membranes made from small intestinal submucosa (SIS), known for biocompatibility and tissue regeneration but hindered by low mechanical strength and rapid degradation. In addition, SIS lacks both antibacterial properties and strong osteogenic capabilities. Enhancements involve crosslinking treatment and dual incorporation of calcium (Ca2+) and zinc (Zn2+), which address the physical property shortcomings and synergistically boost osteoinductivity by activating osteogenic signaling pathways. Additionally, phase-transited lysozyme (PTL) nanofilm technique enables efficient ion loading and controlled release, while offering antibacterial properties. In this study, a multifunctional SIS membrane is constructed by PTL-ions layers, providing a potential solution to the challenge of clinical bone defects.
Clusterzyme‐Enabled Oxidative Stress Alleviation and Microglial Polarization Modulation for Efficient Ischemic Stroke Treatment
Authors: Lin Zhu, Weijie Zhong, Xuchen Meng, Xin Lv, Tanjun Deng, Zixian Mei, Xinru Liu, Fanying Meng, Yayuan Tian, Lan Hu, Huijing Xiang, Yu Chen, Yi Li
Journal: Advanced Healthcare Materials (2025)

Abstract Ischemic stroke (IS) presents a significant challenge to global health, as conventional reperfusion strategies aimed at restoring cerebral circulation paradoxically exacerbate neurological damage. This injury primarily results from the excessive production of reactive oxygen species (ROS) and the initiation of a widespread neuroinflammatory response. In this study, mercaptosuccinic acid (MSA)‐coated bimetallic clusterzymes, containing an optimized ratio of Au 7 Ag 1 nanoclusters (NCs), are developed for the targeted treatment of IS reperfusion injury. The ultrafine particle size of bimetallic nanoclusters facilitates the penetration across the blood‐brain barrier (BBB) and enhances catalytic capacity and enzymatic activity through synergistic effects. Comprehensive in vitro and in vivo studies demonstrate that Au 7 Ag 1 NCs provide neuroprotection by efficiently scavenging ROS and modulating microglial polarization, alleviating oxidative stress‐induced injury. Furthermore, Au 7 Ag 1 NCs play a crucial role in reducing brain tissue damage following reperfusion and promoting long‐term neurological function recovery. Notably, RNA sequencing reveals that Au 7 Ag 1 NCs impact key molecular pathways linked to apoptosis and inflammation. In summary, this study demonstrates the potential of Au 7 Ag 1 NCs as a novel therapeutic approach for IS reperfusion injury and highlights a promising pathway for nanomedicine‐based interventions targeting ischemic cerebral disorders.
Skin‐Tailored Adhesive Bio‐Electrode with Tunable Poisson's Ratio for Stable Electrophysiological Communication
Authors: Hyun Seok Kang, Sumin Kim, Hyunggwi Song, Yung Lee, Junho Jang, Won Gi Chung, Chang‐Yeon Gu, Junmo Kim, Taek‐Soo Kim, Seunghwa Ryu, Jang‐Ung Park, Byeong‐Soo Bae
Journal: Advanced Healthcare Materials (2025)

Abstract Stretchable electrodes are crucial healthcare device components for electrophysiology signal sensing. Compared to conventional rigid gel electrodes, stretchable electrodes are advantageous for long‐term monitoring with superior skin conformality. However, current devices often show limited compliance and adhesive reliability, especially during human motion. Here, a skin‐tailored adhesive bio‐electrode (STABL) is fabricated using a substrate designed to comply with the deformation behavior of wrist skin. The substrate patch possesses a negative Poisson's ratio (PR) through an auxetic structured glass fabric reinforcement embedded in a soft, adhesive elastomer film. Based on the direct measurement of wrist skin deformation behavior, the chemical composition and geometry of the substrate patch are optimized to match the negative PR of the skin. Using this tailored substrate, STABL is fabricated with EGaIn liquid metal conductors and exhibits superior stability in electrophysiology communication during repetitive wrist motion compared to conventional pristine PDMS substrates. This result highlights the potential of skin‐tailored auxetic substrates and liquid metal electrodes for reliable, long‐term wearable bioelectronics applications.
Hollow‐Structured Nanorobot with Excellent Magnetic Propulsion for Catalytic Pollutant Degradation, Anti‐Bacterial and Biofilm Removal
Authors: Jing Wang, Guangjin Yu, Qunling Fang, Yunqi Xu, Jie Zhang, Ailing Hui, Shouhu Xuan, Ken Cham‐Fai Leung
Journal: Advanced Healthcare Materials (2025)

Abstract Chemical pollution, pathogenic bacteria, and bacterial biofilms pose significant threats to public health. Although various nanoplatforms with both catalytic and antibacterial activities have been developed, creating a remotely controllable nanorobot with precise targeting and propulsion capabilities remains a challenge. This study presents the fabrication of a hollow‐structured Fe 3 O 4 @AgAu@polydopamine (PDA) nanosphere, which demonstrated controllable catalytic activity and superior magnetically enhanced antibacterial and biofilm removal properties. The AgAu bimetallic nanorods are assembled between the Fe 3 O 4 core and the biocompatible PDA, resulting in a magnetic nanorobot with high photothermal conversion efficiency (54%) and excellent catalytic activity. Importantly, due to the efficient propulsion behavior originating from the magnetic Fe 3 O 4 , organic pollutants such as 4‐nitrophenol and methylene blue can be accurately degraded by the catalytic Fe 3 O 4 @AgAu@PDA magnetic nanorobots in a simulated wastewater pool. By incorporating the zinc phthalocyanine (ZnPc) photosensitizer, the Fe 3 O 4 @AgAu@PDA‐ZnPc nanosphere exhibits a synergistic “photothermal‐photodynamic‐Ag + ” antibacterial effect against Escherichia coli and Staphylococcus aureus . Remarkably, the antibacterial rate can be enhanced to 99.99% by applying magnetic propulsion via a rotating magnetic field (RMF). Furthermore, this unique magnetic propulsion endows the nanorobot with effective biofilm removal capabilities in both flat surfaces and tubular structures, highlighting its advantages over traditional antibacterial agents in dynamic removal applications.
Bimetallic MnZnS<sub>X</sub> Nanotheranostics for Self‐Activatable Chemo‐Immunotherapy of Hepatocellular Carcinoma via H₂S‐Triggered Arsenic Prodrug Activation and Binary cGAS‐STING Pathway Modulation
Authors: WeiYi Cheng, Xuqi Peng, Li He, WeiYe Ren, JingQuan Chen, XiaoQian Tang, Dandan Bao, Gang Liu, Lai Jiang, Ji‐Gang Piao
Journal: Advanced Healthcare Materials (2025)

Arsenic trioxide (As2O3) has long been utilized in traditional Chinese medicine due to its therapeutic properties. While it exhibits potent anticancer activity, its clinical application is hindered by systemic toxicity and limited tissue specificity. In this study, an advanced therapeutic approach is developed using arsenic prodrug-loaded bimetallic sulfide MnZnSX nanorods (As-MnZnSX NRs) to enhance both the efficacy and safety of As2O3 in hepatocellular carcinoma treatment. These nanorods are engineered to release Mn2+ and H2S within the tumor microenvironment, facilitating binary-cooperative activation of the cGAS-STING pathway. This dual activation mechanism enhances immune responses while converting the arsenic prodrug into its cytotoxic form, AsIII. The results demonstrate that Mn2+ amplifies the cGAS-STING pathway by inducing TBK1 phosphorylation and IRF3 activation, leading to dendritic cell maturation and improved tumor antigen cross-presentation. Simultaneously, H2S promotes prodrug conversion and enhances immune activation, collectively driving binary stimulation of the cGAS-STING pathway. This strategy significantly augments the antitumor efficacy of As2O3 by integrating immune modulation with targeted cytotoxic effects. Furthermore, MnZnSX nanorods enable in vivo MRI, allowing real-time monitoring of treatment progression. This study represents a substantial advancement in liver cancer therapy by integrating chemoimmunotherapy with diagnostic imaging, thereby improving therapeutic precision while minimizing systemic toxicity.
Inducing Cuproptosis with Copper Ion‐Loaded Aloe Emodin Self‐Assembled Nanoparticles for Enhanced Tumor Photodynamic Immunotherapy
Authors: Zhen Yu, Lei Cao, Yue Shen, Jieqi Chen, Huizhen Li, Chengmin Li, Ji‐Ye Yin, Yueqin Li, Yingcai Meng, Xiangping Li
Journal: Advanced Healthcare Materials (2025)

Immunotherapy has fundamentally transformed the clinical treatment landscape for non-small cell lung cancer (NSCLC). While its effectiveness is ultimately limited by patient heterogeneity and immunosuppressive tumor microenvironment. Photodynamic therapy (PDT), as an emerging antitumor immunotherapy, has shown its unique therapeutic advantages. However, previous studies often overlooked the potential toxicity of photosensitizers (PS), making the discovery of safe and effective PS a pressing clinical need. In this study, Aloe Emodin (AE), a medicinal plant natural compound, was loaded with copper ions (Cu), and self-assembled into nanoparticles (NPs) under the modification of PEG2k-DSPE-FA. NPs can target, accumulate, and reside within tumor sites, responsively releasing copper ions and AE, thus dual-functioning by inducing tumor cell death via cuproptosis and enhancing PDT effects. The LLC tumor-bearing mouse model demonstrated that NPs induce the maturation of dendritic cells (DCs) in vivo, promote lymphocyte infiltration, transform "cold tumors" into "hot tumors" and significantly enhance the efficacy of immune checkpoint blockade (ICB). This study provides experimental evidence of AE as a clinically promising PDT agent and offers a novel perspective for the synergistic treatment of clinical NSCLC.