tbuckley/cabot-search huggingface dataset:
Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10
Authors: WonJae Lee, Song Yi Ko, Hironari Akasaka, Melanie Weigert, Ernst Lengyel, Honami Naora
Journal: Cancer Cell (2025)

Disseminated cancer cells in the peritoneal fluid often colonize omental fat-associated lymphoid clusters but the mechanisms are unclear. Here, we identify that innate-like B cells accumulate in the omentum of mice and women with early-stage ovarian cancer concomitantly with the extrusion of chromatin fibers by neutrophils called neutrophil extracellular traps (NETs). Studies using genetically modified NET-deficient mice, pharmacologic inhibition of NETs, and adoptive B cell transfer show that NETs induce expression of the chemoattractant CXCL13 in the pre-metastatic omentum, stimulating recruitment of peritoneal innate-like B cells that in turn promote expansion of regulatory T cells and omental metastasis through producing interleukin (IL)-10. Ex vivo studies show that NETs elicit IL-10 production in innate-like B cells by inactivating SHP-1, a phosphatase that inhibits B cell activation pathways, and by generating reactive oxygen species. These findings reveal that NETs alter immune cell dynamics in the pre-metastatic omentum, rendering this niche conducive for colonization.
YTHDF2-mediated m6A modification of ONECUT2 promotes stemness and oxaliplatin resistance in gastric cancer through transcriptionally activating TFPI
Authors: Xingdi Fan, Fangyi Han, Haocheng Wang, Zhilin Shu, Bowen Qiu, Fanan Zeng, Hongzhen Chen, Ziying Wu, Yongwei Lin, Zhien Lan, Zhiwei Ye, Yao Ying, Tiansu Geng, Ziqian Xian, Xing Niu, Junming Wu, Ke Mo, Kehong Zheng, Yaping Ye, Chunhui Cui
Journal: Drug Resistance Updates (2025)
The interface in home non-invasive ventilation: is the nasal mask better?
Authors: Marta Amata, Giuseppe Arcoleo, Maria R. Bonsignore
Journal: European Respiratory Journal (2025)

<title>Extract</title> The choice of mask is a very important step in the management of sleep disordered breathing, in which most research is concerning patients with obstructive sleep apnoea (OSA). Compared to the very heavy, custom-made masks used in the early days of continuous positive airway pressure (CPAP) treatment for OSA [1], the technology regarding design and lightness of these masks has improved considerably. Optimal fit of the mask is essential to avoid leaks and improve acceptance of CPAP treatment, especially when auto-titrating machines are used in OSA patients [2]. A recent bench study analysed the response of three widely used CPAP devices to test their effectiveness in compensating for leaks, with variable results [3].
Reply to: Treat-and-repair: a simple but powerful term for a complex multimodal approach in patients with pulmonary arterial hypertension associated with congenital heart disease
Authors: Dunbar Ivy, Erika B. Rosenzweig, Steven H. Abman, Maurice Beghetti, Damien Bonnet, Johannes Menno Douwes, Alessandra Manes, Rolf M.F. Berger
Journal: European Respiratory Journal (2025)

<title>Extract</title> We want to thank K. Dimopoulos and A. Constantine for their remarks. We agree with the authors that pulmonary hypertension (PH) associated with complex congenital heart disease (CHD) is valuable in classifying PH in the 7th World Symposium on Pulmonary Hypertension (WSPH) proceedings. The members of the paediatric task force and the classification task force have extensive experience of CHD in adult patients and felt that re-introducing complex CHD into the classification is valuable.
Lowering blood pressure with continuous positive airway pressure: a work in progress
Authors: Naima Covassin
Journal: European Respiratory Journal (2025)

<title>Extract</title> Abundant evidence supports a role of obstructive sleep apnoea (OSA) in the pathophysiology of cardiovascular diseases (CVDs), including hypertension [1]. During sleep, patients with OSA experience repeated episodes of upper airway obstruction, which are associated with hypoxaemia, ventilatory changes and arousal that precipitate haemodynamic and autonomic responses leading to acute blood pressure (BP) surges. Recurrent exposure to apnoeas and hypopnoeas and related hypoxic perturbations are thought to induce chronic impairment in BP regulatory mechanisms, ultimately compromising BP control across the 24 h and predisposing to sustained hypertension. Accordingly, OSA and high BP frequently co-occur – hypertension affects about 50% of OSA patients and more than 30% of hypertensive patients have OSA [1]. OSA also confers more than a two-fold increased risk of incident hypertension [2, 3], and high BP partially accounts for the excess CVD and death risk observed in OSA [4, 5].
Dual‐Site Biomacromolecule Doped Poly(3, 4‐Ethylenedioxythiophene) for Bosting Both Anticoagulant and Electrochemical Performances (Adv. Healthcare Mater. 1/2025)
Authors: Xiangya Wang, Jianzhou Niu, Mohammed Kamal Hadi, Dongli Guo, Yuxia Zhang, Meimei Yu, Qi Zhou, Fen Ran
Journal: Advanced Healthcare Materials (2025)
Multi‐Chambered Core/Shell Supraparticles for Real‐Time, Full‐Time Diagnosis and Treatment Integration of Tumors (Adv. Healthcare Mater. 1/2025)
Authors: Degang Kong, Xiaotong Zheng, Kai Ding, Run Zhong, Zhao Zhang, Qingyi Wang, Chunxiu Dong, Zhiwen Zheng, Xiaohong Li, Jie Weng, Shaobing Zhou
Journal: Advanced Healthcare Materials (2025)
Human Chorionic Membrane‐derived Tunable Hydrogels for Vascular Tissue Engineering Strategies (Adv. Healthcare Mater. 1/2025)
Authors: Elisa A.G. Martins, Inês A. Deus, Maria C. Gomes, Ana S. Silva, João F. Mano, Catarina A. Custódio
Journal: Advanced Healthcare Materials (2025)
Nanoceria as a non-steroidal anti-inflammatory drug for endometriosis theranostics
Authors: Md Saidur Rahman, Kay Hadrick, Seock-Jin Chung, Ian Carley, Jung-Yoon Yoo, Shamsun Nahar, Tae Hoon Kim, Taeho Kim, Jae-Wook Jeong
Journal: Journal of Controlled Release (2025)
Ultrasound‐Controllable Release of Carbon Monoxide in Multifunctional Polymer Coating for Synergetic Treatment of Catheter‐Related Infections
Authors: Ziqing Liang, Rui Sun, Xu Zhang, Shifang Luan, Hong Xu, Rui Wang, Lingjie Song, Hengchong Shi, Lei Wang
Journal: Advanced Healthcare Materials (2025)

Medical catheters are susceptible to biological contamination and pathogen invasion, leading to infection and inflammatory complications. The development of antimicrobial coatings for medical devices has emerged as a promising strategy. However, limited biological functionality and the incompatibility between bactericidal properties and biosafety remain great challenges. Herein, a multifunctional polymer coating (CPB-Ac) is created, incorporating an ultrasonic-responsive carbon monoxide release unit (CORM-Ac) and antifouling unit to treat catheter-related complications. As-synthesized CPB-Ac polymer can be stably anchored to various medical devices with arbitrary shapes and compositions via facile UV treatment. Both in vivo and vitro experiments demonstrated that this multi-functional coating exhibits anti-fouling, anti-inflammatory, and broad-spectrum antibacterial activities as well as good biosafety. During the initial implantation phase, the antifouling units of CPB-Ac coating effectively inhibit the attachment of biological contaminants, significantly reducing the risk of thrombosis and bacterial infection. Once bacterial infection occurs, ultrasonic irradiation can activate CPB-Ac coating to release CO with a much higher amount of 55.3 µm than non-ultrasound controls, therefore rapidly eliminating bacteria and alleviating inflammatory response. It is believed that the work may provide an effective method for the development of next-generation intelligent medical coatings against catheter-related complications.
Large-Scale Plasma Proteomics Improves Prediction of Peripheral Artery Disease in Individuals With Type 2 Diabetes: A Prospective Cohort Study
Authors: Hancheng Yu, Jijuan Zhang, Frank Qian, Pang Yao, Kun Xu, Ping Wu, Rui Li, Zixin Qiu, Ruyi Li, Kai Zhu, Lin Li, Tingting Geng, Xuefeng Yu, Danpei Li, Yunfei Liao, An Pan, Gang Liu
Journal: Diabetes Care (2025)

OBJECTIVE Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction. RESEARCH DESIGN AND METHODS This cohort study included 1,859 individuals with T2D from the UK Biobank. Multivariable-adjusted Cox regression models were used to explore associations between 2,920 plasma proteins and incident PAD. Proteins were further selected as predictors using least absolute shrinkage and selection operator (LASSO) penalty. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, continuous/categorical net reclassification improvement, and integrated discrimination improvement. RESULTS Over a median follow-up of 13.2 years, 157 incident PAD cases occurred. We observed 463 proteins associated with PAD risk, primarily involved in pathways related to signal transduction, inflammatory response, plasma membrane, protein binding, and cytokine-cytokine receptor interactions. Ranking by P values, the top five proteins associated with increased PAD risk included EDA2R, ADM, NPPB, CD302, and NPC2, while BCAN, UMOD, PLB1, CA6, and KLK3 were the top five proteins inversely associated with PAD risk. Incorporating 45 LASSO-selected proteins or a weighted protein risk score significantly enhanced PAD prediction beyond clinical variables alone, reaching a maximum C-index of 0.835. CONCLUSIONS This study identified plasma proteins associated with PAD risk in individuals with T2D. Adding proteomic data into the clinical model significantly improved PAD prediction.
Development of Neural Cells and Spontaneous Neural Activities in Engineered Brain‐Like Constructs for Transplantation (Adv. Healthcare Mater. 1/2025)
Authors: Ke Gai, Mengliu Yang, Wei Chen, Chenyujun Hu, Xiao Luo, Austin Smith, Caizhe Xu, Hefeng Zhang, Xiang Li, Wei Shi, Wei Sun, Feng Lin, Yu Song
Journal: Advanced Healthcare Materials (2025)
Taming the flame: SerpinB1 suppression of pyroptosis in pathological cardiac hypertrophy
Authors: Beatrijs Bartelds, Daphne Merkus
Journal: Cardiovascular Research (2025)

Journal Article Accepted manuscript Taming the flame: SerpinB1 suppression of pyroptosis in pathological cardiac hypertrophy Get access Beatrijs Bartelds, MD PhD, Beatrijs Bartelds, MD PhD Dept op Pediatrics, pediatric cardiology, Erasmus MC- Sophia Children's Hospital, Rotterdam, The Netherlands Email: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Daphne Merkus, PhD Daphne Merkus, PhD Dept of Cardiology, Erasmus MC, Rotterdam, The NetherlandsWalter Brendel Center of Experimental Medicine, University Clinic Munich, LMU Munich, Munich, GermanyGerman Center for Cardiovascular Research (DZHK), Munich Heart Alliance (MHA), Partner Site MunichInterfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich, Munich, Germany https://orcid.org/0000-0002-4852-831X Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, cvae262, https://doi.org/10.1093/cvr/cvae262 Published: 02 January 2025 Article history Received: 18 October 2024 Accepted: 02 January 2025 Published: 02 January 2025
Cellular and Molecular Mechanisms Leading to Air Travel-Induced Thrombosis
Authors: Julie Tourn, Lydie Crescence, Laurie Bruzzese, Laurence Panicot-Dubois, Christophe Dubois
Journal: Circulation Research (2025)

Venous thromboembolism, characterized by deep vein thrombosis and pulmonary embolism, is the third cardiovascular disease in the world. Deep vein thrombosis occurs when a blood clot forms in areas of impaired blood flow, and it is significantly affected by environmental factors. Local hypoxia, caused by venous stasis, plays a critical role in deep vein thrombosis under normal conditions, and this effect is intensified when the P o 2 decreases, such as during air travel or high-altitude exposure. The lower oxygen levels and reduced pressure at high altitudes further contribute to deep vein thrombosis development. These conditions increase the pro-coagulant activity of neutrophils, platelets, and red blood cells, which interact on the surface of activated endothelial cells, promoting clot formation. Understanding the mechanisms involved in thrombus formation when P o 2 is reduced, with or without pressure reduction, is crucial for preventing the development of venous thromboembolisms in such conditions and identifying innovative therapeutic targets. This literature review explores the mechanisms involved in thrombus formation related to high-altitude conditions and discusses the pro-coagulant consequences induced by environmental disturbances.
Discovery of Titin and Its Role in Heart Function and Disease
Authors: Henk L. Granzier, Siegfried Labeit
Journal: Circulation Research (2025)

This review examines the giant elastic protein titin and its critical roles in heart function, both in health and disease, as discovered since its identification nearly 50 years ago. Encoded by the TTN (titin gene), titin has emerged as a major disease locus for cardiac disorders. Functionally, titin acts as a third myofilament type, connecting sarcomeric Z-disks and M-bands, and regulating myocardial passive stiffness and stretch sensing. Its I-band segment, which includes the N2B element and the PEVK (proline, glutamate, valine, and lysine-rich regions), serves as a viscoelastic spring, adjusting sarcomere length and force in response to cardiac stretch. The review details how alternative splicing of titin pre-mRNA produces different isoforms that greatly impact passive tension and cardiac function, under physiological and pathological conditions. Key posttranslational modifications, especially phosphorylation, play crucial roles in adjusting titin’s stiffness, allowing for rapid adaptation to changing hemodynamic demands. Abnormal titin modifications and dysregulation of isoforms are linked to cardiac diseases such as heart failure with preserved ejection fraction, where increased stiffness impairs diastolic function. In addition, the review discusses the importance of the A-band region of titin in setting thick filament length and enhancing Ca² + sensitivity, contributing to the Frank-Starling Mechanism of the heart. TTN truncating variants are frequently associated with dilated cardiomyopathy, and the review outlines potential disease mechanisms, including haploinsufficiency, sarcomere disarray, and altered thick filament regulation. Variants in TTN have also been linked to conditions such as peripartum cardiomyopathy and chemotherapy-induced cardiomyopathy. Therapeutic avenues are explored, including targeting splicing factors such as RBM20 (RNA binding motif protein 20) to adjust isoform ratios or using engineered heart tissues to study disease mechanisms. Advances in genetic engineering, including CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), offer promise for modifying TTN to treat titin-related cardiomyopathies. This comprehensive review highlights titin’s structural, mechanical, and signaling roles in heart function and the impact of TTN mutations on cardiac diseases.
Nutritional Support in the ICU
Authors: Jean Reignier, Todd W Rice, Yaseen M Arabi, Michael Casaer
Journal: BMJ (2025)

Abstract Critical illness is a complex condition that can have a devastating impact on health and quality of life. Nutritional support is a crucial component of critical care that aims to maintain or restore nutritional status and muscle function. A one-size-fits-all approach to the components of nutritional support has not proven beneficial. Recent randomized controlled trials challenge the conventional strategy and support the safety and potential benefits of below-usual calorie and protein intakes at the early, acute phase of critical illness. Further research is needed to define optimal nutritional support throughout the intensive care unit stay. Individualized nutritional strategies relying on risk assessment tools or biomarkers deserve further investigation in rigorously designed, large, multicenter, randomized, controlled trials. Importantly, although nutritional support is crucial, it might not be sufficient to enhance the recovery of critically ill patients. Thus, achieving the greatest efficacy may require individualized nutritional support combined with early, prolonged physical rehabilitation within a multimodal, holistic care program throughout the patient's recovery journey.
Implementing a closed loop clinical decision support system for sustainable preoperative care
Authors: José Luis Gracia Martínez, Bernadette Pfang, Miguel Ángel Morales Coca, Cristina Caramés Sánchez, Marta del Olmo Rodríguez, Marco Antonio Villegas García, Jorge Short Apellaniz, Javier Arcos Campillo, Juan Antonio Álvaro de la Parra, Florencia Manzano Lorefice, Luis Enrique Muñoz Alameda
Journal: npj Digital Medicine (2025)

Unnecessary preoperative testing poses a risk to patient safety, causes surgical delays, and increases healthcare costs. We describe the effects of implementing a fully EHR-integrated closed-loop clinical decision support system (CDSS) for placing automatic preprocedural test orders at two teaching hospitals in Madrid, Spain. Interrupted time series analysis was performed to evaluate changes in rates of preoperative testing after CDSS implementation, which took place from September 2019 to December 2019. We included 228,671 surgical procedures during a 69-month period from January 1st, 2018, to October 1st, 2023, of which 78,388 were from the preintervention period and 150,283 from the postimplementation period. We observed a significant reduction (p < 0.001) of 83% (−83.4% to −83.1%) for chest X-ray orders, 54% (−54.7% to −54.2%) for ECG orders, 50% for blood type testing (−50.5% to −50.1%), and 29% (−29.5% to −29.0%) for preoperative blood test order sets, leading to overall cost-savings of €1,013,666. No increase in postoperative adverse events or same-day cancellations was observed. Our results demonstrate that an EHR-embedded closed-loop CDSS can reduce avoidable preoperative testing without increasing surgical cancelations, postoperative adverse events, or early re-interventions, thus improving the quality of care and healthcare expenditure.
Incidence and Risk Factors of Diagnosed Young-Adult-Onset Type 2 Diabetes in the U.S.: The National Health Interview Survey 2016–2022
Authors: Lan Xu, Jinjun Ran, Hui Shao, Meng Chen, Hao Tang, Yongxuan Li, Yaqing Xu, Yue Huang, Feng Tao, Zhenxiu Liu, Victor W. Zhong
Journal: Diabetes Care (2025)

OBJECTIVE To estimate the incidence and identify risk factors for diagnosed type 2 diabetes (T2D) among young U.S. adults. RESEARCH DESIGN AND METHODS We analyzed 142,884 adults aged 18–79 years with self-reported diabetes type from the cross-sectional National Health Interview Survey in 2016–2022, representing the noninstitutionalized U.S. civilian population. Incidence of diagnosed T2D was calculated for three age groups: young-adult onset (18–44 years), middle-age onset (45–64 years), and older-adult onset (65–79 years); the latter two groups were included to highlight the distinct risk factor profile of young-adult-onset T2D. Multivariable logistic regressions were used to identify risk factors for young-adult-onset T2D. RESULTS The estimated incidence of diagnosed young-adult-onset T2D was 3.0 per 1000 adults (95% CI 2.6–3.5). Minority groups, socioeconomically disadvantaged individuals, and people with cardiometabolic diseases or psychological conditions had a higher incidence of diagnosed young-adult-onset T2D compared with their counterparts. Lipid-lowering medication use (adjusted odds ratio [aOR] 13.15, 95% CI 8.85–19.55), antihypertensive medication use (aOR 11.89, 95% CI 7.97–17.73), and obesity (BMI ≥30 vs. &amp;lt;25 kg/m2, aOR 10.89, 95% CI 6.69–17.7) were the strongest risk factors for young-adult-onset T2D; these risk factors, along with hypertension, hyperlipidemia, and coronary heart disease, were more strongly associated with young-adult-onset T2D compared with later-onset T2D, with up to 4.5 times higher aORs. CONCLUSIONS This study quantified the incidence of diagnosed young-adult-onset T2D in U.S. adults and identified its distinct risk factor profile. Targeted prevention strategies for young-adult-onset T2D are needed for minority and socioeconomically disadvantaged people and those with cardiometabolic diseases.
Functional differences between rodent and human PD-1 linked to evolutionary divergence
Authors: Takeya Masubuchi, Lin Chen, Nimi Marcel, George A. Wen, Christine Caron, Jibin Zhang, Yunlong Zhao, Gerald P. Morris, Xu Chen, Stephen M. Hedrick, Li-Fan Lu, Chuan Wu, Zhengting Zou, Jack D. Bui, Enfu Hui
Journal: Science Immunology (2025)

Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2. In a mouse melanoma model with adoptively transferred T cells, humanization of a PD-1 intracellular domain disrupted the antitumor activity of CD8
NEK7 phosphorylation amplifies NLRP3 inflammasome activation downstream of potassium efflux and gasdermin D
Authors: Jie Xu, Lingzhi Zhang, Yanhui Duan, Fangyuan Sun, Nouha Odeh, Yuan He, Gabriel Núñez
Journal: Science Immunology (2025)

The NLRP3 inflammasome plays a critical role in innate immunity and inflammatory diseases. NIMA-related kinase 7 (NEK7) is essential for inflammasome activation, and its interaction with NLRP3 is enhanced by K + efflux. However, the mechanism by which K + efflux promotes this interaction remains unknown. Here, we show that NEK7 is rapidly phosphorylated at threonine-190/191 by JNK1 downstream of K + efflux and gasdermin D (GSDMD) after NLRP3 activation. NEK7 phosphorylation enhances the binding between NEK7 and NLRP3, which further promotes inflammasome assembly and activation. Mutant mice and macrophages in which Thr 190 and Thr 191 of Nek7 were replaced by valine exhibited impaired NEK7 phosphorylation, NLRP3 inflammasome activation, and IL-1β secretion. Thus, NEK7 phosphorylation is an important event that acts downstream of K + efflux and GSDMD to further enhance NLRP3 inflammasome activation.
Suppression of thrombospondin-1–mediated inflammaging prolongs hematopoietic health span
Authors: Pradeep Ramalingam, Michael C. Gutkin, Michael G. Poulos, Agatha Winiarski, Arianna Smith, Cody Carter, Chelsea Doughty, Taylor Tillery, David Redmond, Ana G. Freire, Jason M. Butler
Journal: Science Immunology (2025)

Chronic low-grade inflammation observed in older adults, termed inflammaging, is a common feature underlying a multitude of aging-associated maladies including a decline in hematopoietic activity. However, whether suppression of inflammaging can preserve hematopoietic health span remains unclear, in part because of a lack of tools to measure inflammaging within hematopoietic stem cells (HSCs). Here, we identify thrombospondin-1 (Thbs1) as an essential regulator of inflammaging within HSCs. We describe a transcriptomics-based approach for measuring inflammaging within stem cells and demonstrate that deletion of Thbs1 is sufficient to prevent HSC inflammaging. Our results demonstrate that suppression of HSC inflammaging prevents aging-associated defects in hematopoietic activity including loss of HSC self-renewal, myeloid-biased HSC differentiation, and anemia. Our findings indicate that suppression of HSC inflammaging may also prolong overall systemic health span.