tbuckley/cabot-search huggingface dataset:
Sex differences in COPD in relation to smoking exposure: a population-based cohort study
Authors: Yunus Çolak, Børge G Nordestgaard, Peter Lange, Shoaib Afzal
Journal: Thorax (2025)

Background Sex discrepancies in the association between smoking and development and prognosis of chronic obstructive pulmonary disease (COPD) are controversial. We tested the hypothesis that females compared with males are more susceptible to the detrimental effects of smoking in relation to COPD. Methods We identified 47 231 males and 57 806 females from the Copenhagen General Population Study. Smoking amount was assessed with sex interaction against COPD-related outcomes, including the cross-sectional association with airway obstruction, chronic bronchitis and dyspnoea, assessed using logistic regression analyses, and longitudinal association with exacerbation and mortality, assessed using Cox proportional hazard regression adjusted for potential confounders. Results The increase in risk of airway obstruction (N=7367), chronic bronchitis (N=9206) and dyspnoea (N=8541) with higher smoking amount was greater in females compared with males. During 15 years’ follow-up (median 9.3 years), the increase in risk of exacerbation (events=2756), respiratory mortality (events=711) and all-cause mortality (events=10 658) with higher smoking was greater for females compared with males. Compared with never-smokers, adjusted HRs for exacerbation increased from 4.64 (95% CI 2.83 to 7.61) in females with 10 pack-years to 41.6 (95% CI 28.8 to 60.2) in females with ≥50 pack-years, and from 2.21 (95% CI 0.92 to 5.32) in males with 10 pack-years to 23.7 (95% CI 12.9 to 43.5) in males with ≥50 pack-years. Corresponding HR increases for respiratory mortality were 2.04 (95% CI 1.27 to 3.26) to 11.1 (95% CI 7.39 to 16.8) in females and 1.09 (95% CI 0.62 to 1.92) to 5.66 (95% CI 3.96 to 8.11) in males, and for all-cause mortality, HR increases were 1.50 (95% CI 1.34 to 1.67) to 3.53 (95% CI 3.11 to 4.00) in females and 1.62 (1.45–1.81) to 2.94 (2.69–3.21) in males, respectively. Conclusions Females seem more susceptible to the detrimental effects of smoking in development and prognosis of COPD compared with males.
Noninvasive early prediction of preeclampsia in pregnancy using retinal vascular features
Authors: Yuxuan Wu, Lixia Shen, Lanqin Zhao, Xiaohong Lin, Miaohong Xu, Zhenjun Tu, Yihong Huang, Lingyi Kong, Zhenzhe Lin, Duoru Lin, Lixue Liu, Xun Wang, Zizheng Cao, Xi Chen, Shengmei Zhou, Weiling Hu, Yunjian Huang, Shiyuan Chen, Meimei Dongye, Xulin Zhang, Dongni Wang, Danli Shi, Zilian Wang, Xiaohang Wu, Dongyu Wang, Haotian Lin
Journal: npj Digital Medicine (2025)

Preeclampsia (PE), a severe hypertensive disorder during pregnancy, significantly contributes to maternal and neonatal mortality. Existing prediction biomarkers are often invasive and expensive, hindering their widespread application. This study introduces PROMPT (Preeclampsia Risk factor + Ophthalmic data + Mean arterial pressure Prediction Test), an AI-driven model leveraging retinal photography for PE prediction, registered at ChiCTR (ChiCTR2100049850) in August 2021. Analyzing 1812 pregnancies before 14 gestational weeks, we extracted retinal parameters using a deep learning system. The PROMPT achieved an AUC of 0.87 (0.83-0.90) for PE prediction and 0.91 (0.85-0.97) for preterm PE prediction using machine learning, significantly outperforming the baseline model (p < 0.001). It also improved detection of severe adverse pregnancy outcomes from 35% to 41%. Economically, PROMPT was estimated to avert 1809 PE cases and saved over $50 million per 100,000 screenings. These results position PROMPT as a non-invasive and cost-effective tool for prenatal care, especially valuable in low- and middle-income countries.
Blood‐Brain Barrier‐Penetrating Nanocarriers Enable Microglial‐Specific Drug Delivery in Hypothalamic Neuroinflammation
Authors: Yoon Tae Goo, Vladislav Grigoriev, Tetiana Korzun, Kongbrailatpam Shitaljit Sharma, Prem Singh, Olena R. Taratula, Daniel L. Marks, Oleh Taratula
Journal: Advanced Healthcare Materials (2025)

Abstract Hypothalamic inflammation plays a pivotal role in appetite dysregulation across various pathological conditions, including cancer cachexia. However, delivering anti‐inflammatory agents to microglia, key mediators of hypothalamic inflammation, remains challenging due to the unsurmountable blood‐brain barrier (BBB). To overcome this challenge, dual peptide‐functionalized polymeric nanocarriers capable of both BBB penetration and microglial targeting are engineered for systemic delivery of IRAK4 inhibitors to treat hypothalamic inflammation. After intravenous administration, the nanocarriers demonstrated efficient brain and hypothalamic accumulation in both acute (lipopolysaccharide‐induced) and chronic (pancreatic cancer cachexia) neuroinflammation mouse models. Their microglial targeting capability is confirmed through hypothalamic immunohistochemistry and flow cytometry analysis using a BBB‐microglia co‐culture model. Systemic administration of IRAK4 inhibitor‐loaded nanocarriers effectively attenuated hypothalamic inflammation in both animal models, as evidenced by marked reductions in pro‐inflammatory cytokine expression. Treated animals displayed significantly increased food intake and improved body weight compared to the saline‐treated group. In the cancer cachexia model, the treatment preserved muscle mass, reducing cachexia‐induced gastrocnemius muscle loss by 50% relative to controls. These findings highlight the potential of this nanocarrier system as a promising therapeutic strategy for conditions characterized by hypothalamic dysfunction, particularly cancer cachexia, where neuroinflammation plays a crucial role in disease progression.
Development of Akkermansia Muciniphila Membrane‐Coated Mesoporous Silica Nanoparticles with a Cerium Oxide Core for Inflammatory Bowel Disease Treatment
Authors: Nianhua Zhang, Xu Zhang, Jiulong Li, Baoyi Li, Shuai Wang, Xiao Liu, Huan Meng, Motao Zhu
Journal: Advanced Healthcare Materials (2025)

Abstract While convenient for patient compliance, the efficacy of oral treatments for inflammatory bowel disease (IBD) is often compromised by the dynamic and harsh chemical environment of the gastrointestinal tract, presenting challenges for effective therapeutic management. The pathological complexity of IBD frequently involves multiple factors such as oxidative stress, immune dysregulation, gut microbiome abnormality, and inadequate drug bioavailability, among others. To address these challenges, this project develops an oral nanomedicine platform based on mesoporous silica nanoparticles with a cerium oxide core, further coated with an outer membrane (OM) derived from Akkermansia muciniphila ( Akk ), a beneficial bacteria naturally present in the human gut. This novel nanocomplex, termed “OM‐CeMeso,” is evaluated for its enhanced stability, reactive oxygen species (ROS) scavenging capacity, and ability to restore microbiota homeostasis. This project demonstrates that the silica‐based nanomaterials’ acid‐resistant yet base‐degradable properties significantly improved stability in a murine IBD model. The incorporation of cerium oxide nanoparticles (CeO 2 NPs) added further benefits by enhancing ROS scavenging. Notably, the Akk‐ derived OM coat also increases the diversity and abundance of beneficial gut microbiota. These complementary and integrated functions lead to significant symptom alleviation in murine IBD models while avoiding any unwanted toxicity.
Recent Developments in the Optical Control of Adrenergic Signaling
Authors: Shuang Shi, Yangzhi Cao, Maikel Wijtmans, Henry F. Vischer, Rob Leurs
Journal: Medicinal Research Reviews (2025)

ABSTRACT Adrenoceptors (ARs) play a vital role in various physiological processes and are key therapeutic targets. The advent of optical control techniques, including optogenetics and photopharmacology, offers the potential to modulate AR signaling with precise temporal and spatial resolution. In this review, we summarize the latest advancements in the optical control of AR signaling, encompassing optogenetics, photocaged compounds, and photoswitchable compounds. We also discuss the limitations of current tools and provide an outlook on the next generation of optogenetic and photopharmacological tools. These emerging optical technologies not only enhance our understanding of AR signaling but also pave the way for potential therapeutic developments.
Editorial Expression of Concern: Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: Pathological significance in early- and late-onset breast carcinoma
Authors: Satyabrata Sinha, Ratnesh K Singh, Neyaz Alam, Anup Roy, Susanta Roychoudhury, Chinmay Kumar Panda
Journal: Molecular Cancer (2025)
Development of Itaconate Polymers Microparticles for Intracellular Regulation of Pro‐Inflammatory Macrophage Activation
Authors: Kaitlyn E. Woodworth, Zachary S.C.S. Froom, Natasha D. Osborne, Christian N. Rempe, Brenden Wheeler, Kyle Medd, Neal I. Callaghan, Huikang Qian, Abhinav P. Acharya, Carlie Charron, Locke Davenport Huyer
Journal: Advanced Healthcare Materials (2025)

Itaconate (IA) is an endogenous metabolite and a potent regulator of the innate immune system. It's use in immunomodulatory therapies has faced limitations due to challenges in controlled delivery and requirements of high extracellular concentrations for internalization of the highly polar small molecule to achieve its intracellular therapeutic activity. Microparticle (MP)-based delivery strategies are a promising approach for intracellular delivery of small molecule metabolites through macrophage phagocytosis and subsequent intracellular polymer degradation-based delivery. Toward the goal of intracellular delivery of IA, degradable polyester polymer- (poly(dodecyl itaconate)) based IA polymer microparticles (IA-MPs) are generated using an emulsion method, forming micron-scale (≈1.5 µm) degradable microspheres. IA-MPs are characterized with respect to their material properties and IA release kinetics to inform particle fabrication. Treatment of murine bone marrow-derived macrophages with an optimized particle concentration of 0.1 mg million-1 cells enables phagocytosis-mediated internalization and low levels of cytotoxicity. Flow cytometry demonstrates IA-MP-specific regulation of IA-sensitive inflammatory targets. Metabolic analyses demonstrate that IA-MP internalization inhibits oxidative metabolism and induced glycolytic reliance, consistent with the established mechanism of IA-associated inhibition of succinate dehydrogenase. This development of IA-based polymer microparticles provides a basis for additional innovative metabolite-based microparticle drug delivery systems for the treatment of inflammatory disease.
Beyond fluorodeoxyglucose: Molecular imaging of cancer in precision medicine
Authors: Malik E. Juweid, Soud F. Al‐Qasem, Fadlo R. Khuri, Andrea Gallamini, Philipp Lohmann, Hans‐Joachim Ziellenbach, Felix M. Mottaghy
Journal: CA A Cancer Journal for Clinicians (2025)

Cancer molecular imaging is the noninvasive visualization of a process unique to or altered in neoplasia, such as proliferation, glucose metabolism, and receptor expression, which is relevant to patient management. Several molecular imaging modalities are now available, including magnetic resonance, optical, and nuclear imaging. Nuclear imaging, particularly using fluorine-18-fluorodeoxyglucose positron emission tomography, is widely used in the staging and response assessment of multiple cancer types. However, at this writing, new nuclear medicine probes, especially positron emission tomography tracers, are increasingly used or are being investigated for cancer evaluation. This review focuses on these probes, their biologic targets, and the applications or potential applications for their use in the assessment of various neoplasms, including both probes available for commercial use-such as somatostatin receptor ligands in neuroendocrine tumors, prostate-specific membrane antigen ligands in prostate cancer, norepinephrine analogs in neural crest tumors like neuroblastoma, and estrogen analogs in breast cancer-and others in clinical development, such as fibroblast-activating protein inhibitors, C-X-C chemokine receptor type 4 ligands, and monoclonal antibodies targeting receptor tyrosine kinases, CD4-positive or CD8-positive tumor-infiltrating lymphocytes, tumor-associated macrophages, and cancer stem cell biomarkers. These developments represent a major step toward the integration of molecular imaging as a powerful tool in precision medicine, with an expectedly significant impact on patient management and outcome.
O-GlcNAcylation-mediated endothelial metabolic memory contributes to cardiac damage via small extracellular vesicles
Authors: Mingge Ding, Rui Shi, Yanyan Du, Pan Chang, Tian Gao, Dema De, Yunan Chen, Man Li, Jun Li, Ke Li, Shuli Cheng, Xiaoming Gu, Juan Li, Shumiao Zhang, Na Feng, Jianzheng Liu, Min Jia, Rong Fan, Jianming Pei, Chao Gao, Feng Fu
Journal: Cell Metabolism (2025)
Ultrasound‐Guided Functionalized Extracellular Vesicles for Visualized, Controlled, and Efficient Renal Delivery for Enhanced Kidney Repair
Authors: Yuhao Chen, Chunjia Sheng, Tuo Xiao, Bo Jiang, Xieguanxuan Xu, Shaoyuan Cui, Wanjun Shen, Xumin Zheng, Xinru Guo, Xiangmei Chen, Chuyue Zhang, Guangyan Cai
Journal: Advanced Healthcare Materials (2025)

Mesenchymal stem cell-derived extracellular vesicles (EVs) hold great promise for the treatment of acute kidney injury (AKI). However, their efficacy is limited by inefficient delivery. Current studies largely focus on increasing the proportion of EVs reaching renal cells, with less emphasis on enhancing the uptake capacity of damaged cells. In AKI, tubular cells exhibit reduced EV uptake owing to cisplatin damage. This study aims to engineer ultrasound-guided microbubble-functionalized EVs (MB-EVs) via an RGD-integrin connection for visualized, controlled, and efficient renal delivery. Following percutaneous intrarenal injection, MB-EVs demonstrate clear ultrasound imaging enabling precise localization for visualization, while ultrasound triggers the microbubble-mediated release of EVs. During the delivery process, multiple endocytic pathways are involved, with F-actin as a central regulatory hub. Although F-actin is disrupted by cisplatin, MB-EVs restore F-actin, promoting the endocytic pathways and improving EV uptake in renal cells. In terms of efficacy, MB-EVs achieve a more pronounced recovery of renal function, morphological structure, apoptosis, and mitochondrial morphology than EVs alone. Moreover, miR-24-3p carried by EVs restores CPT1A-mediated fatty acid oxidation, thereby promoting favorable renal recovery. In conclusion, the engineered ultrasound-guided EVs enable visualized, controlled, and efficient renal delivery, achieving superior therapeutic outcomes and offering new hope for AKI treatment.
Genomic and Immune Profiling of Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Therapy Versus Upfront Surgery Identifies Novel Immunogenic Cell Death‐Based Signatures for Predicting Clinical Outcomes
Authors: Peidong Song, Wenze Tian, Yujia Zheng, Sukai Xu, Zihao Hu, Xing Jin, Xuejuan Zhu, Lijie Tan, Donglai Chen, Yongbing Chen
Journal: MedComm (2025)

It remains undetermined regarding the impact of neoadjuvant therapy on immunogenic cell death (ICD) and subsequent tumor microenvironment (TME) remodeling in esophageal squamous cell carcinoma (ESCC). And it is of paramount significance to identify beneficiaries from neoadjuvant therapy in treatment-naïve ESCC. In this study, 88 ESCC samples undergoing neoadjuvant therapy plus surgery (NA+S) or surgery alone (SA) were subjected to bulk-RNA sequencing. A five-gene RINscore incorporating ICD-related signature genes with TME-based hub genes was established to predict clinical outcomes and pharmacological responses, in which SLAMF7 and IL1R1 were selected out as co-expressed genes. The regulatory mechanism of the repressive co-transcription factor BATF of SLAMF7 and IL1R1 was further demonstrated. Our data demonstrated that NA+S led to high abundance in kinds of T helper cells, nature killer T cells and M1-like macrophages with increased CD8+T cells infiltration compared with SA. ICD phenotypes were further characterized in treatment-naïve ESCC to determine their differences in TME and potential benefits from NA. Our findings not only offered novel insights into the distinct TME and ICD profiles of ESCC undergoing different therapeutic modes, but also provided the RINscore, which may aid oncologists in determining individualized (neo)adjuvant immunotherapy regimen.
Mandibular Implants: A Metamaterial‐Based Approach to Reducing Stress Shielding
Authors: Jorn‐Ids Heins, Bram B.J. Merema, Joep Kraeima, Max J.H. Witjes, Anastasiia O. Krushynska
Journal: Advanced Healthcare Materials (2025)

Biomechanical complications, such as stress shielding, bone resorption, and reconstruction failure, are prevalently associated with solid titanium mandible reconstruction plates. This study evaluates the potential of metamaterial designs with porous gyroid microarchitectures, to enhance biomechanical stimulation and mitigate these complications. A novel metamaterial reconstruction plate is compared with solid titanium plates, both patient-specifically designed and fabricated from Ti6Al4 V alloy. Stress shielding is assessed through photoelasticity experiments and validated with finite element analysis (FEA). Transparent mandible models are loaded incrementally (0-1000 N) to analyze stress distributions in the implants, screws, and mandible segments. The metamaterial plate reduces stress concentrations in the distant mandibular regions from the defect, while increasing stress around the screws near the defect, favoring local mechanical stimulation. FEA confirms improved load distribution (p = 0.003). However, the metamaterial plate exhibited a lower load-bearing capacity, failing at 775 N, while the solid plate withstood 1800 N without failure. Yet, the metamaterial design effectively reduced stress shielding, thereby enhancing biomechanical function near critical mandibular regions. Hence, despite their reduced load-bearing capacity, they can, potentially, preserve bone integrity and prevent implant failure that should be validated in future (pre-)clinical studies.
Dynamic-covalent hybrid hydrogels with cartilaginous immune microenvironment temporally regulating meniscus regeneration
Authors: Zhanyu Chang, Xinyue Ran, Yaru Chu, Bohui Li, Zhenlin Fan, Genke Li, Dan Li, Wenjie Ren, Yujie Hua, Guangdong Zhou
Journal: Bioactive Materials (2025)
A multifunctional hydrogel loaded with magnesium-doped bioactive glass-induced vesicle clusters enhances diabetic wound healing by promoting intracellular delivery of extracellular vesicles
Authors: Zetao Wang, Zhipeng Sun, Shuangli Zhu, Zhihao Qin, Xiaohong Yin, Yilin Ding, Huichang Gao, Xiaodong Cao
Journal: Bioactive Materials (2025)
MHC class II-mediated spontaneous rejection of breast carcinomas expressing model neoantigens
Authors: James William Jenkins, Alvaro Peña, Sarah A Castro, Michael J Hansen, Virginia P Van Keulen, Sean T Foster, Pablo E Rios-Cruz, Joshua Yakubov, Destin T Hinson, Samuel M Olivier, Kevin D Pavelko, Sara J Felts, Aaron J Johnson, Larry R Pease
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Cancers persist despite expression of immunogenic neoantigens and ongoing antitumor immune responses. While some occult tumors likely are cleared by effective antitumor immune responses, the targeted antigens are not easily identifiable as those tumors spontaneously disappear. Methods We used mouse models with a defined antigenic protein mimicking tumor-specific neoantigens to address the nature of these spontaneous anti-tumor immune responses. Results BALB/c ( H-2 d ) mice challenged with BALB/c breast tumors expressing the rat-erbB2 oncoprotein succumb to their tumors despite ongoing immune responses targeting tumor-specific model antigens. Meanwhile, congenic BALB.B ( H-2 b ) and H-2 d /H-2 b F1 hybrid mice spontaneously eliminate genetically matched tumors in a major histocompatibility complex (MHC)-II dependent manner. Adoptive transfer and immune cell depletion strategies revealed CD4+ T cells and CD20+ B cells are crucial mediators of the protective response in H-2 b mice. Furthermore, passive transfer of immune serum from mice rejecting their tumors confers resistance in tumor antigen-tolerant animals with an inversely proportional relationship between tumor outgrowth and the amount of rat-erbB2 specific antibody present in tumor-bearing mice. Introduction of the rat-erb2 ectodomain into other H-2 b tumor models also promotes their spontaneous tumor rejection. Notably, the tumor microenvironments differ in rat-erbB2+ tumor-bearing BALB.B and BALB/c mice at the time of fate decision in the models reflecting the differences between effective and ineffective tumor immune responses. Conclusions We find that the effective antitumor immunity targeting neoantigens in these breast cancer models is determined by MHC-II-restricted presentation of optimal cancer-associated antigens. These responses are dependent on CD4+ T cells, B cells, and antigen-specific antibodies.
Characteristics of second primary malignancies following bispecific antibodies therapy
Authors: Xiaojie Liang, Baiwei Luo, Bingyu Lin, Dan Liu, Jia Guo, Weixiang Lu, Shengyu Tian, Zihong Cai, Xinyu Zhou, Zhihao Jin, Tong Li, Keren Chen, Hongsheng Zhou, Liang Wang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background The risk of secondary primary malignancies (SPMs) associated with bispecific antibody (BsAb)—a promising alternative to chimeric antigen receptor (CAR)-T therapy—remains insufficiently explored. Methods Using large-scale, real-world data from the US Food and Drug Administration’s Adverse Event Reporting System, we identified the relative frequency and characteristics of SPMs following BsAbs therapy and conducted a comprehensive comparison of treatment-related SPM profiles between BsAbs and CAR-T therapies. Results We identified 108 cases among 10,280 BsAb-treated patients. The incidence risk of SPMs was stable over the past 8 years, accounting for 1–2% of all adverse events, with a case fatality rate of 29.63% among the SPM cases. Myeloid leukemias and non-Hodgkin’s lymphoma were more frequent in blinatumomab recipients, while solid malignancies predominated in those treated with teclistamab. Time-to-onset (TTO) was significantly shorter in BsAb recipients compared with non-recipients, with weight and treatment duration influencing TTO, while no significant differences in TTO were observed across different BsAb products, ages, and genders. Our findings highlight the first year of BsAbs as a critical window for early detection and intervention. Although the overall risk of SPMs was lower with BsAbs than with CAR-T, the outcomes of SPMs were comparable in both groups. TTO and SPM patterns were statistically similar between the two therapies. Conclusion Our study provides the first detailed characterization of SPMs post-BsAb, underscoring the need for continued pharmacovigilance and individualized risk management to mitigate SPM risks in patients undergoing BsAb therapy.