tbuckley/cabot-search huggingface dataset:
Associations and Diagnostic Accuracy of Ultrasound Features in Knee Osteoarthritis: Cross‐sectional Results from a Large Community‐based Cohort
Authors: Katherine A. Yates, Carolina Alvarez, Todd A. Schwartz, Serena Savage‐Guin, Jordan B. Renner, Catherine J. Bakewell, Minna J. Kohler, Janice Lin, Jonathan Samuels, Tessa Walker, Yvonne M. Golightly, Amanda E. Nelson
Journal: Arthritis & Rheumatology (2025)

To determine 1) associations among ultrasound (US) features of knee osteoarthritis (KOA), radiographic KOA (rKOA), and patient-reported symptoms, and 2) diagnostic accuracy of US definitions for rKOA, in a community-based cohort. Participants enrolled in the Johnston County Health Study (JoCoHS, 2019-24, n=902) provided demographics, comorbidities, clinical features and symptoms, along with imaging with standardized acquisition and scoring protocols. Logistic regression models provided odds ratios adjusted for age, sex, race, ethnicity, body mass index (BMI), education level, comorbidities, and knee injury for associations among US features and KOA outcomes. Diagnostic accuracy was assessed using standard metrics with rKOA as the gold standard. Complete imaging data were available for 861 participants (1711 knees), 34% men, 25% Black, 10% Hispanic, mean age 55 years and mean BMI 33 kg/m2. Half of knees were symptomatic, 1/3 had rKOA, and 1 in 5 had symptomatic rKOA. US-identified osteophytes, effusion, meniscal extrusion, cartilage damage, calcium crystals, and popliteal cysts were associated with KOA outcomes. A US definition including both mild osteophytes and mild cartilage damage gave an area under the receiver operating characteristic curve (AUC) of 0.76 for diagnosing rKOA (validated in an external cohort). We identified common US features in participants with and without KOA, along with significant associations between US features and rKOA, symptomatic rKOA, and symptoms. US-based diagnosis of rKOA shows promise for general use. US is a valuable and accessible modality for assessment of knee OA features in clinical and research settings, including those with limited resources.
Plasma proteomic profiles predict individual future osteoarthritis risk
Authors: Zijian Kang, Jianzheng Zhang, Wenxin Liu, Chen Zhu, Ying Zhu, Ping Li, Kai Li, Qiang Tong, Sheng‐Ming Dai
Journal: Arthritis & Rheumatology (2025)

Osteoarthritis (OA) is a widespread degenerative joint disease that causes a considerable socioeconomic burden. Despite progress in genetic and environmental insights, early diagnosis is still limited by the lack of evident symptoms during the initial phases and accurate biomarkers. This study aims to identify plasma proteins associated with future risk of OA and develop a predictive model. We conducted a large-scale proteomic analysis of 45,307 participants from the UK Biobank, excluding those with baseline OA. Plasma samples were assayed using the Olink Explore Proximity Extension Assay targeting 1,463 unique proteins. Clinical variables and OA outcomes were extracted and linked to electronic health records. A predictive model was constructed using the LightGBM machine learning method, and the SHapley Additive exPlanations (SHAP) were applied to evaluate the importance of variables. We identified a panel of proteins significantly associated with the risk of developing OA. Notably, after adjusting for multiple confounders, Collagen Type IX Alpha 1 Chain (COL9A1) and Cartilage Acidic Protein 1 (CRTAC1) were the most significant predictors of incident OA, with hazard ratios (HR) of 1.54 (95% confidence interval [CI]:1.48-1.61) and 1.65 (95% CI:1.54-1.78), respectively. SHAP analysis allowed a profound interpretation of the contribution of each protein and clinical variable to the model, revealing the multifactorial nature of OA risk prediction. The temporal trajectories of plasma proteins indicated that the levels of COL9A1 and CRTAC1 began to deviate from normal for more than a decade before OA onset, suggesting their potential use in early detection strategies. The predictive model, developed using the LightGBM algorithm, integrated proteins with clinical covariates and demonstrated an area under the curve (AUC) of 0.729 for 5-year OA prediction, 0.721 for 10-year prediction, and 0.723 for all incident OA. The predictive accuracy of the model was further enhanced for hip and knee OA, achieving AUCs of 0.820 and 0.803 for 5-year predictions. Our study identified the role of plasma proteomics in predicting future OA risk, which could contribute to preemptive measures. The innovative model, which integrates proteomic biomarkers with clinical data, offers a potential tool for risk assessment, potentially optimizing OA management strategies and enhancing prevention efforts.
Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies
Authors: Dandan Guo, Songhua Cai, Lvdan Deng, Wangting Xu, Sentao Fu, Yaling Lin, Tong Jiang, Qing Li, Zhijun Shen, Jian Zhang, Peng Luo, Bufu Tang, Ling Wang
Journal: MedComm (2025)

Ferroptosis is a distinct form of iron-dependent programmed cell death characterized primarily by intracellular iron accumulation and lipid peroxidation. Multiple cellular processes, including amino acid metabolism, iron metabolism, lipid metabolism, various signaling pathways, and autophagy, have been demonstrated to influence the induction and progression of ferroptosis. Recent investigations have elucidated that ferroptosis plays a crucial role in the pathogenesis of various pulmonary disorders, including lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma. Ferroptosis is increasingly recognized as a promising novel strategy for cancer treatment. Various immune cells within the tumor microenvironment, including CD8+ T cells, macrophages, regulatory T cells, natural killer cells, and dendritic cells, have been shown to induce ferroptosis in tumor cells and modulate the process through the regulation of iron and lipid metabolism pathways. Conversely, ferroptosis can reciprocally alter the metabolic environment, leading to the activation or inhibition of immune cell functions, thereby modulating immune responses. This paper reviews the molecular mechanism of ferroptosis and describes the tumor immune microenvironment, discusses the connection between ferroptosis and the tumor microenvironment in lung cancer and pulmonary diseases, and discusses the development prospect of their interaction in the treatment of lung cancer and pulmonary diseases.
Associations of fire smoke and other pollutants with incident rheumatoid arthritis and rheumatoid arthritis‐associated interstitial lung disease: comment on the article by Kronzer VL et al
Authors: Gang Wang, Zhichun Liu
Journal: Arthritis & Rheumatology (2025)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Associations of fire smoke and other pollutants with incident rheumatoid arthritis and rheumatoid arthritis associated interstitial lung disease: reply
Authors: Vanessa L. Kronzer, Yangyuna Yang, Punyasha Roul, James L. Crooks, Cynthia S. Crowson, John M. Davis, Jeffrey A. Sparks, Jeffrey R. Pierce, Katelyn O'Dell, Brian C. Sauer, Grant W. Cannon, Joshua F. Baker, Ted R. Mikuls, Bryant R. England
Journal: Arthritis & Rheumatology (2025)
Harnessing Nanohybridized Niclosamide for Precision Mpox Therapeutics
Authors: N. Sanoj Rejinold, Geun‐woo Jin, Jin‐Ho Choy
Journal: Advanced Healthcare Materials (2025)

Abstract Niclosamide, initially developed as an anthelmintic, has recently emerged as a potential antiviral, showing efficacy against diverse viral threats, including Mpox. As the global health landscape faces recurrent Mpox outbreaks, repurposing niclosamide through advanced material strategies offers promising therapeutic avenues. This article explores the antiviral mechanisms of niclosamide, focusing on how innovative nano‐hybrid formulations enhance its bioavailability and pharmacological performance. By leveraging nanohybridization, niclosamide's limitations—such as poor solubility and bioavailability—are addressed, enabling targeted delivery and sustained release. Early preclinical studies reveal that niclosamide disrupts Mpox replication and entry processes, suggesting its utility as a therapeutic option against poxvirus infections. Looking forward, further in vitro, animal models, and clinical investigations are essential to optimize its application and dosing for Mpox. With continued development in advanced materials, nanohybrid niclosamide could become a critical tool in managing Mpox and related viral threats, offering an accessible, cost‐effective option for outbreak preparedness.
Shikonin‐Cu(II) Supramolecular Polymers Exhibit Antitumor Activity via Necrosis and Cuproptosis
Authors: Hongyang Zhang, Rui‐Hong Gong, Yu−Shan Lin, Tao Wang, Dou Luo, Jiahua Li, Li‐Sha Shen, Wai‐Yeung Wong, Sibao Chen, Guo‐Qing Chen
Journal: Advanced Healthcare Materials (2025)

Supramolecular polymers driven by the metal-ligand coordination possess reversible bonds, making them promising candidates for integrating the therapeutic functions of metal ions and small-molecule drugs, and subsequently releasing these components within cells after endocytosis. In this study, a kind of supramolecular polymer, SHICU, is developed, composed of Shikonin ligand and Cu(II) ion. Upon reduction by intracellular glutathione (GSH), SHICU dissociates to release Shikonin, Cu(II), and SHICU fragments. The released Shikonin and Cu(II) exhibit a synergistic antitumor effect through the reactive oxygen species (ROS)-dependent necrosis. Meanwhile, the released SHICU that remains structural integrity induces a distinct antitumor mechanism by triggering cuproptosis in tumor cells. This dual functionality, combining ROS-dependent necrosis and cuproptosis, highlights the potential of SHICU in advancing antitumor therapies, while the integration of supramolecular polymers with the emerging cell death mechanism of cuproptosis facilitates the development of innovative cancer drugs.
Active Iron‐Drug Nanocomplexes Improve Photodynamic and Photothermal Cancer Therapy by Mitigating Tumor Hypoxia and Counteracting Tumor Heat Resistance
Authors: Yuying Yin, Ka Hong Wong, Liewei Wen, Meiwan Chen
Journal: Advanced Healthcare Materials (2025)

Abstract Photodynamic therapy (PDT) and photothermal therapy (PTT) offer the advantages of precise temporal and spatial selectivity in cancer treatment, minimizing damage to normal cells while effectively eliminating tumor cells. However, the therapeutic efficacy of phototherapy is always hindered by challenges such as hypoxia and tumor heat resistance. Herein, a pH‐responsive metal‐drug nanocomplex (denoted as PAFH) comprising hypericin (HYP), apigenin (APG), polyvinylpyrrolidone (PVP), and Fe 3+ is developed to enhance the therapeutic efficacy of PDT and PTT. The PAFH nanocomplex exhibits photothermal properties under 808 nm laser irradiation, which can disassociate in response to the acidic tumor microenvironment and the temperature increase induced by PTT, thereby eventually triggering the on‐site release of APG and HYP. The released APG inhibits the synthesis of heat shock protein HSP‐90, facilitating the PAFH‐mediated PTT to kill tumor cells at mild temperature. Additionally, APG alleviates hypoxia and then regulates the expression of hypoxia‐inducible factor HIF‐1𝛼, increasing cellular oxygen levels to produce singlet oxygen for enhanced HYP‐mediated PDT and inhibiting tumor metastasis. Ultimately, this sophisticated nanosystem represents an advanced strategy to promote PDT and PTT by mitigating tumor hypoxia and counteracting tumor heat resistance, significantly improving therapeutic efficacy for precise cancer therapy.
Sepsis: the evolution of molecular pathogenesis concepts and clinical management
Authors: Zhongxue Feng, Lijun Wang, Jing Yang, Tingting Li, Xuelian Liao, Yan Kang, Fei Xiao, Wei Zhang
Journal: MedComm (2025)

Abstract The mortality rate of sepsis is approximately 22.5%, accounting for 19.7% of the total global mortality. Since Lewis Thomas proposed in 1972 that “it is our response that makes the disease (sepsis)” rather than the invading microorganisms, numerous drugs have been developed to suppress the “overwhelming” inflammatory response, but none of them has achieved the desired effect. Continued failure has led investigators to question whether deaths in septic patients are indeed caused by uncontrolled inflammation. Here, we review the history of clinical trials based on evolving concepts of sepsis pathogenesis over the past half century, summarize the factors that led to the failure of these historical drugs and the prerequisites for the success of future drugs, and propose the basic principles of preclinical research to ensure successful clinical translation. The strategy of targeting inflammatory factors are like attempting to eliminate invaders by suppressing the host's armed forces, which is logically untenable. Sepsis may not be that complex; rather, sepsis may be the result of a failure to fight microbes when the force of an invading pathogen overwhelms our defenses. Thus, strengthening the body's defense forces instead of suppressing them may be the correct strategy to overcome sepsis.
Single‐Cell Liquid‐Core Microcapsules for Biomedical Applications
Authors: Manuel Pires‐Santos, Mariana Carreira, Bruno P. Morais, Francisca G. Perfeito, Mariana B. Oliveira, Cátia F. Monteiro, Sara Nadine, João F. Mano
Journal: Advanced Healthcare Materials (2025)

Abstract More recently, single‐cell encapsulation emerged as a promising field in biomedicine due to its potential applications, in cell analysis and therapy. Traditional techniques involve embedding cells in crosslinked polymers to create continuous microgels, suitable mainly for adherent cells, or encapsulating them in droplets for only short‐term analysis, due to their instability. In this study, we developed a method for encapsulating single cells in liquid‐core microcapsules to address these limitations. The liquid encapsulation system is generated in an all aqueous environment through polymeric electrostatic interactions. Additionally, we design an innovative and low cost sorting system utilizing magnetic nanoparticles (MNPs) to efficiently select single‐cell encapsulated units for further analysis and applications. This system is tested with both suspension and adherent cell types, demonstrating cytocompatibility and no abnormal effects on cell behavior. The MNP‐based sorting achieved nearly 80% purity of the single‐cell population. Overall, this technology provides a highly efficient method for single‐cell applications, such as cell screening, by enabling precise short to medium‐term analysis, real time monitoring, and high resolution imaging of cellular behavior. Furthermore, the semipermeable membrane unlocks new potential for advancing cell therapy by offering protection for encapsulated cells while ensuring the efficient diffusion of therapeutic factors, paving the way for innovative therapeutic strategies.
Five‐Year Real‐World Safety of Inotuzumab Ozogamicin Before Hematopoietic Stem Cell Transplantation in B‐Cell Precursor Acute Lymphoblastic Leukemia
Authors: Marcos de Lima, Partow Kebriaei, Francesco Lanza, Christina Cho, Gizelle Popradi, Manmeet Kaur, Mei‐Jie Zhang, Fan Zhang, Richa Shah, Erik Vandendries, Kofi Asomaning, Stephanie Dorman, Matthias Stelljes, David I. Marks, Wael Saber
Journal: American Journal of Hematology (2025)
Immunoregulatory Neuro‐Vascularized Osseointegration Driven by Different Nano‐Morphological CaTiO<sub>3</sub> Bioactive Coatings on Porous Titanium Alloy Scaffolds
Authors: Dongmei Yu, Zhen Tang, Shusen Bao, Shuo Guo, Changchen Chen, Qi Wu, Mo Wang, Zenghui Zheng, Pengfei Cao, Bin Xu, Hao Wu, Ning Wang, Hai Huang, Chaozong Liu, Xiaokang Li, Zheng Guo
Journal: Advanced Healthcare Materials (2025)

Abstract Up to now, how to implement the optimal regenerative repair of large load‐bearing bone defects using artificial bone prosthesis remains to be an enormous challenge in clinical practice. Titanium‐based alloys, especially Ti6Al4V, are applied as artificial bone grafts due to their favorable mechanical property and biocompatibility, assisted by personalized customization of 3D‐printing to completely match with the bone defect. However, their bioinert peculiarity restricts osteointegration at the interface between bone and titanium‐based implants and bone growth into porous titanium‐based scaffolds, for lack of bone regeneration with the aid of blood vessels and neural networks. Of note, ample blood delivery and integral innervation are pivotal to the survival of artificially tissue‐engineered bones. Herein, the functionalized surface of 3D printed titanium alloy scaffolds driven immunoregulatory neuro‐vascularized osseointegration is delved. Bone‐like micro/nano morphology and chemical composition of calcium‐rich formula are scrutinized to accelerate the process of bone defect repair, including inflammatory response, angiogenesis, neurogenesis, and osseointegration. Micro/nano‐topographic calcium titanate (CaTiO 3 ) coating, especially 10%H 2 O 2 ‐Ca, driven immunoregulatory neuro‐vascularized osseointegration is validated and its underlying mechanism is attributed to the signaling pathway of TNF‐α /oxidative phosphorylation, providing an effective tactic of the bone tissue‐engineered scaffold with surface functionalization‐driven immunoregulatory neuro‐vascularized osseointegration for clinical large segmental bone defects.
Easily Injectable, Organic Solvent‐Free Self‐Assembled Hydrogel Platform for Endoscope Mediated Gastrointestinal Polypectomy
Authors: Muzammil Kuddushi, Hitasha Vithalani, Hemant Singh, Harshil Dave, Abhinav Jain, Ankit Pal, Sunny Kumar, Zeel Bhatia, Sriram Seshadri, Mukesh Dhanka
Journal: Advanced Healthcare Materials (2025)

Abstract Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (ESR) are used to eliminate tiny, flat lesions in the gastrointestinal tract (GIT). A substantial submucosal cushion is required for effective dissection. Commonly used saline and hypertonic dextrose injections disperse quickly and do not offer significant elevation, whereas polymers such as gelatin and alginate are challenging to inject. In this study, a novel amphiphilic polyglycerol stearate‐based hydrogel (PGSH) platform is demonstrated which could be administered via an endoscopic catheter to help create a stable submucosal elevation. PGSH is easy to inject across different needle gauges, shear‐thinning, and forms a long‐lasting submucosal cushion during ESD. This hydrogel can encapsulate hydrophilic drugs such as streptomycin, allowing controlled enzymatic and nonenzymatic release. Ex‐vivo experiments on goat's GIT demonstrate that PGSH is smoothly injectable without clogging the catheter's needle, achieving the necessary submucosal elevation. Furthermore, ex‐vivo blood studies demonstrate immediate clotting behavior while maintaining hemocompatibility. In‐vivo, investigations in mice show that the hydrogel forms a biocompatible cushion of suitable height with a nontoxic organ profile that does not overexpress inflammatory cytokines. ESD studies in the porcine model suggest that PGSH has the potential to significantly improve treatment outcomes in the early endoscopic removal of gastrointestinal polyps.
Hypoxia‐Induced O‐GlcNAcylation of GATA3 Leads to Excessive Testosterone Production in Preeclamptic Placentas
Authors: Juan Liu, Yun Yang, Hongyu Wu, Feihong Dang, Xin Yu, Feiyang Wang, Yongqing Wang, Yangyu Zhao, Xiaoming Shi, Wei Qin, Yanling Zhang, Yu‐Xia Li, Chu Wang, Xuan Shao, Yan‐Ling Wang
Journal: MedComm (2025)

ABSTRACT The maintenance of endocrine homeostasis in the placenta is crucial for ensuring successful pregnancy. An abnormally elevated production of placental testosterone (T 0 ) has been documented in patients with early‐onset preeclamptic (E‐PE). However, the underlying mechanisms remain unclear. In this study, we found that E‐PE placentas exhibited significantly increased expressions of 3β‐HSD1 (3β‐Hydroxysteroid Dehydrogenase 1) and 17β‐HSD3 (17β‐Hydroxysteroid Dehydrogenase 3), the rate‐limiting enzymes for T 0 synthesis. This was strongly correlated with an elevated level of O‐linked N‐acetylglucosaminylation (O‐GlcNAcylation) of GATA3 (GATA binding protein 3). In human trophoblast cells, O‐linked‐N‐acetylglucosamine (O‐GlcNAc) modification of GATA3 on Thr 322 stabilized the protein and enhanced the transcriptional regulation of 3β‐HSD1 and 17β‐HSD3, thereby increasing T 0 production. Hypoxia, a well‐established pathological factor in PE, significantly enhanced the O‐GlcNAcylation of GATA3 in human trophoblast cells. Our findings suggest that hypoxia‐induced overactive O‐GlcNAcylation of GATA3 contributes to the exacerbated T 0 production in E‐PE placentas. These findings provide a new perspective on the pathogenesis of E‐PE from the standpoint of posttranslational regulation and may illuminate novel therapeutic strategies for adverse pregnancy outcomes such as E‐PE.
Synchronously Delivering Melittin and Evoking Ferroptosis via Tumor Microenvironment‐Triggered Self‐Destructive Metal–Organic Frameworks to Boost Cancer Immunotherapy
Authors: Dongsheng Zhang, Tingting Wang, Xun Zhang, Yuting Xu, Jiang Ming, Xiaoxiao Wang, Zhenfeng Liu, Jingchao Li, Xinhui Su
Journal: Advanced Healthcare Materials (2025)

Abstract The primary goal of treating malignant tumors is to efficiently eliminate the primary tumor and prevent metastasis and recurrence. Unfortunately, the immunosuppressive tumor microenvironment (TME) is a significant obstacle to effective oncotherapy. Herein, a therapeutic strategy based on melittin (MLT) encapsulated in hyaluronic acid‐modified metal–organic frameworks (MOFs) is pioneered, focusing on the safe delivery and TME‐responsive release of MLT to reshaping the immunosuppressive TME and simultaneously activating the immune system to eradicate cancerous cells. Iron‐based MOFs respond to glutathione and pH, degrade within a moderately acidic TME, and achieve tumor‐specific release of MLT. Additionally, the iron‐mediated Fenton reaction produces reactive oxygen species that augment oxidative stress, ultimately leading to tumor‐specific ferroptosis, whereas MLT‐induced membrane disruption promotes immunogenic cell death to activate the immune system. In combination with the immune checkpoint inhibitor anti‐PD‐L1, this nanodrug elicits potent antitumor immune responses, facilitating the infiltration of effector T cells and enhancing systemic antitumor T cell immunity to suppress both primary and distant tumors. This study demonstrates the tremendous potential of nanoscale self‐destructive MOFs for the targeted transport and controlled release of MLT and reveals the promoting effect of combined MLT and ferroptosis delivery on cancer immunotherapy.
FDG-PET/CT Findings in Hemophagocytic Lymphohistiocytosis
Authors: Debra Ann Dawson, Duncan E.K. Sutherland
Journal: Clinical Nuclear Medicine (2025)

A 44-year-old man was admitted to the hospital with fever, pancytopenia, and a new rash. FDG-PET was ordered in light of nonspecific clinical, imaging, and biopsy findings. Findings included diffuse FDG uptake throughout the subcutaneous fat overlying fat stranding/haziness on CT. FDG uptake was associated with scattered subsolid/ground-glass lesions in the lungs. Splenomegaly and increased FDG uptake throughout the bone marrow were seen. Diagnostic considerations included infectious versus lymphomatous processes, and possible sites for biopsy were identified. Biopsy of a highly FDG-avid lung lesion led to a diagnosis of hemophagocytic lymphohistiocytosis secondary to peripheral T-cell lymphoma, not otherwise specified.