tbuckley/cabot-search huggingface dataset:
Risk of Incident Atrial Fibrillation in Women With a History of Hypertensive Disorders of Pregnancy: A Population-Based Retrospective Cohort Study
Authors: Amy Johnston, William Petrcich, Graeme N. Smith, Deshayne B. Fell, Peter Tanuseputro, Thais Coutinho, Jodi D. Edwards
Journal: Circulation (2025)

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality and are associated with acute cardiac events in the peripartum period, as well as cardiovascular disease later in life. Despite the robust association between hypertension and atrial fibrillation (AFib), comparatively little is known about HDP and its subtypes as sex-specific risk factors for AFib. METHODS: A population-based retrospective cohort study was conducted, including 771 521 nulliparous women discharged for obstetrical delivery of their first live or stillborn singleton infant between 2002 and 2017 in Ontario, Canada. Data were obtained from record-level, coded, and linked population-based administrative databases housed at ICES. Using competing risks Cox proportional hazards regression, we estimated crude and multivariable-adjusted cause-specific hazard ratios and 95% CIs for associations between history of any HDP (and its 6 subtypes), and AFib before death, as well as all-cause mortality without a previous AFib diagnosis. RESULTS: Approximately 8% of women were diagnosed with HDP during the 16-year exposure accrual period. The total person-time of follow-up was 7 380 304 person-years, during which there were 2483 (0.3%) incident AFib diagnoses and 2951 (0.4%) deaths. History of any HDP was associated with an increased cause-specific hazard ratios of incident AFib and death without a previous AFib diagnosis (adjusted cause-specific hazard ratios, 1.45 [95% CI, 1.28–1.64] and 1.31 [95% CI, 1.16–1.47], respectively). These associations were observed in relatively young women (median time to event, 7 years postpartum). Associations suggestive of a dose-response relationship were observed, with more severe HDP subtypes and prepregnancy chronic hypertension associated with a 1.5 to 2.2 times higher cause-specific rate of AFib, and a 1.4 to 2.1 times higher cause-specific rate of death compared with no hypertension in pregnancy. CONCLUSIONS: Women exposed to HDP in their first delivery have a significantly increased cause-specific hazard ratios of incident AFib compared to their unexposed counterparts, with higher rates observed in subjects exposed to more severe de novo HDP diagnoses as well as chronic hypertension in pregnancy. These findings underscore the need to consider HDP history in risk calculation/stratification for arrhythmic and nonarrhythmic cardiovascular diseases, improve surveillance of traditional and female-specific cardiovascular disease risk factors, and develop targeted prevention strategies to reduce the occurrence and burden of HDP.
Novel Therapeutic Approach Targeting CXCR3 to Treat Immunotherapy Myocarditis
Authors: Yuhsin Vivian Huang, Yin Sun, Harrison Chou, Noah Wagner, Maria Rosaria Vitale, Abraham L. Bayer, Bruce Xu, Daniel Lee, Zachary Lin, Corynn Branche, Sarah Waliany, Joel W. Neal, Heather A. Wakelee, Ronald M. Witteles, Patricia K. Nguyen, Edward E. Graves, Gerald J. Berry, Pilar Alcaide, Sean M. Wu, Han Zhu
Journal: Circulation Research (2025)

BACKGROUND: Immune checkpoint inhibitors (ICIs) are successful in treating many cancers but may cause immune-related adverse events. ICI-mediated myocarditis has a high fatality rate with severe cardiovascular consequences. Targeted therapies for ICI myocarditis are currently limited. METHODS: We used a genetic mouse model of PD1 deletion ( MRL/Pdcd1 −/− ) along with a novel drug-treated ICI myocarditis mouse model to recapitulate the disease phenotype. We performed single-cell RNA-sequencing, single-cell T-cell receptor sequencing, and cellular indexing of transcriptomes and epitopes on immune cells isolated from MRL and MRL/Pdcd1 −/− mice at serial time points. We assessed the impact of macrophage deletion in MRL/Pdcd1 −/− mice, then inhibited CXCR3 (C-X-C motif chemokine receptor 3) in ICI-treated mice to assess the therapeutic effect on myocarditis phenotype. Furthermore, we delineated the functional and mechanistic effects of CXCR3 blockade on T-cell and macrophage interactions. We then correlated the results in human single-cell multiomics data from blood and heart biopsy data from patients with ICI myocarditis. RESULTS: Single-cell multiomics demonstrated expansion of CXCL (C-X-C motif chemokine ligand) 9/10+CCR2+ macrophages and CXCR3hi (C-X-C motif chemokine receptor 3 high-expressing) CD8+ (cluster of differentiation) effector T lymphocytes in the hearts of MRL/Pdcd1 −/− mice correlating with onset of myocarditis development. Both depletion of CXCL9/10+CCR2+ (C-C motif chemokine receptor) macrophages and CXCR3 blockade, respectively, led to decreased CXCR3hi CD8+ T-cell infiltration into the heart and significantly improved survival. Transwell migration assays demonstrated that the selective blockade of CXCR3 and its ligand, CXCL10, reduced CXCR3+CD8+ T-cell migration toward macrophages, implicating this interaction in T-cell cardiotropism toward cardiac macrophages. Furthermore, cardiomyocyte apoptosis was induced by CXCR3hi CD8+ T cells. Cardiac biopsies from patients with confirmed ICI myocarditis demonstrated infiltrating CXCR3+ T cells and CXCL9+/CXCL10+ macrophages. Both mouse cardiac immune cells and patient peripheral blood immune cells revealed expanded TCR s (T-cell receptors) correlating with CXCR3hi CD8+ T cells in ICI myocarditis samples. CONCLUSIONS: These findings bring forth the CXCR3-CXCL9/10 axis as an attractive therapeutic target for ICI myocarditis treatment, and more broadly as a druggable pathway in cardiac inflammation.
SMC Abca1 and Abcg1 Deficiency Enhances Urinary Bladder Distension but Not Atherosclerosis
Authors: Benedek Halmos, Anouk M. La Rose, Daisey Methorst, Anouk G. Groenen, Dalibor Nakládal, Venetia Bazioti, Mirjam H. Koster, Niels J. Kloosterhuis, Azuwerus van Buiten, Elisabeth M. Schouten, Nicolette C.A. Huijkman, Miriam Langelaar-Makkinje, Laura Bongiovanni, Simon M. De Neck, Alain de Bruin, Hendrik Buikema, Leo E. Deelman, Marius C. van den Heuvel, Folkert Kuipers, Igle Jan de Jong, Judith C. Sluimer, Helle F. Jørgensen, Robert H. Henning, Marit Westerterp
Journal: Circulation Research (2025)

BACKGROUND: Smooth muscle cells (SMCs) regulate blood flow distribution via vasoconstriction mediated by α-ARs (α-adrenergic receptors). Plasma membrane cholesterol accumulation affects α 1 -AR signaling and promotes loss of SMC contractile markers in vitro. ABCA1 and ABCG1 (ATP-binding cassette transporter A1 and G1) mediate cholesterol efflux to HDL (high-density lipoprotein). ABCA1/ABCG1 show high expression in medial and low expression in intimal SMCs of atherosclerotic plaques. The role of ABCA1 and ABCG1 in SMC-mediated vasoconstriction and atherogenesis remains poorly understood. METHODS: We generated mice with SMC-specific Abca1/Abcg1 deficiency on the low-density lipoprotein receptor–deficient ( Ldlr − / − ) background by crossbreeding Abca1 fl/fl Abcg1 fl/fl Ldlr −/− mice with Myh11Cre ERT2 transgenic mice. To induce SMC cholesterol accumulation and atherogenesis, we fed Myh11Cre ERT2 Abca1 fl/fl Abcg1 fl/fl Ldlr −/− , Myh11Cre ERT2 Abca1 fl/fl Ldlr −/− , Myh11Cre ERT2 Abcg1 fl/fl Ldlr −/− , and Myh11Cre ERT2 Ldlr −/− mice Western-type diet for 16 weeks. RESULTS: Combined SMC-Abca1/Abcg1 deficiency increased vasoconstriction in aortic rings induced by the α 1 -AR agonist phenylephrine. Unexpectedly, SMC - Abca1/Abcg1 deficiency induced urinary bladder distension by &gt;20-fold. This was reversed by the α 1 -AR antagonist tamsulosin, indicating its dependence on bladder neck SMC constriction. Moreover, SMC - Abca1/Abcg1 deficiency decreased contractile markers and increased macrophage and fibroblast markers in bladder SMCs, indicating SMC transdifferentiation. This was accompanied by free cholesterol accumulation and increased endoplasmic reticulum stress. SMC - Abca1/Abcg1 deficiency did not induce thoracic aorta SMC transdifferentiation, presumably due to increased cholesteryl ester accumulation and no endoplasmic reticulum stress in thoracic aorta SMCs. Surprisingly, SMC - Abca1/Abcg1 deficiency did not affect atherosclerotic lesion size or composition in the aortic root or brachiocephalic artery. CONCLUSIONS: We uncover a new role of SMC cholesterol efflux pathways in suppressing α 1 -AR–mediated vasoconstriction and bladder SMC transdifferentiation, decreasing urinary bladder distension. Our data may provide a mechanistic link for the association between urinary bladder distension and diabetes in humans, particularly because diabetes is associated with decreased cholesterol efflux. SMC - Abca1/Abcg1 deficiency did not affect atherosclerotic lesion size or plaque composition, presumably due to low expression of Abca1/Abcg1 in intimal SMCs.
Protecting mother and baby: Learnings from an Ebola vaccination campaign on the evolving landscape of vaccines and pregnancy
Authors: Rebecca F. Grais, Kathleen M. Neuzil, Helen Rees, Cristiana M. Toscano
Journal: PLoS Medicine (2025)

This Perspective article from Rebecca Grais and colleagues places a recently published study in PLOS Medicine in the context of the evolving landscape of vaccines and pregnancy.
Early-life protein-bound skin ceramides help predict the development of atopic dermatitis
Authors: Chia-Lun Chang, Evgeny Berdyshev, Elasma Milanzi, Caroline J Lodge, Diego J Lopez, Irina Bronova, Jennifer J Koplin, Rachel L Peters, Mimi L K Tang, Shyamali C Dharmage, Michael J Abramson, Jennie Hui, George Varigos, Kirsten P Perrett, Arun Sasi, Jennifer L Perret, John C Su, Paul D Robinson, Donald Y M Leung, Adrian J Lowe
Journal: Journal of Allergy and Clinical Immunology (2025)

Skin lipids are crucial components of the skin barrier. Individuals with atopic dermatitis (AD or eczema) have a different skin lipid profile from those without. However, whether altered skin lipids precede and predict the subsequent risk of AD remained unclear, especially for different AD phenotypes. We sought to examine the relationship between skin lipids and subsequent AD and AD phenotypes in infants. Skin lipids from the forearms of 133 infants with family history of allergic disease were sampled using tape strips at age 6 weeks. Lipids were quantified using liquid chromatography-tandem mass spectrometry. AD by age 1 year was diagnosed using modified UK Working Party Criteria. Allergic sensitization was assessed using skin prick tests. Associations and predictive discrimination were estimated using univariable logistic regression. Potential causation was explored using multivariable logistic regression. Reduced levels of 6 protein-bound ω-hydroxyl sphingosine (POS) ceramides with C30 and C32 fatty acids at 6 weeks were associated with increased risk of AD by age 1 year. In univariate models, a number of POS ceramides predicted subsequent AD, such as PO30:0-C20S (area under the curve, 0.65; 95% CI, 0.55-0.75). After confounders were adjusted, only PO30:0-C20S was associated with AD (adjusted odds ratio, 0.62; 95% CI, 0.39-0.96 per 1-SD increase), and a trend for AD without sensitization (adjusted odds ratio, 0.57; 95% CI, 0.31-1.05) but not AD with sensitization (adjusted odds ratio, 0.76; 95% CI, 0.39-1.47). Reduced levels of POS ceramides are associated with the development of nonatopic AD, suggesting that these lipids may play a role in the pathogenesis of AD and may be useful predictive biomarkers. Interventions that increase POS ceramides may reduce the incidence of AD.
A tale of too many trees: a conundrum for phylogenetic regression
Authors: Richard Adams, Jenniffer Roa Lozano, Mataya Duncan, Jack Green, Raquel Assis, Michael DeGiorgio
Journal: Molecular Biology and Evolution (2025)

Abstract Just exactly which tree(s) should we assume when testing evolutionary hypotheses? This question has plagued comparative biologists for decades. Though all phylogenetic comparative methods require input trees, we seldom know with certainty whether even a perfectly estimated tree (if this is possible in practice) is appropriate for our studied traits. Yet, we also know that phylogenetic conflict is ubiquitous in modern comparative biology, and we are still learning about its dangers when testing evolutionary hypotheses. Here we investigate the consequences of tree-trait mismatch for phylogenetic regression in the presence of gene tree-species tree conflict. Our simulation experiments reveal excessively high false positive rates for mismatched models with both small and large trees, simple and complex traits, and known and estimated phylogenies. In some cases, we find evidence of a directionality of error: assuming a species tree for traits that evolved according to a gene tree sometimes fares worse than the opposite. We also explored the impacts of tree choice using an expansive, cross-species gene expression dataset as an arguably “best-case” scenario in which one may have a better chance of matching tree with trait. Offering a potential path forward, we found promise in the application of a robust estimator as a potential, albeit imperfect, solution to some issues raised by tree mismatch. Collectively, our results emphasize the importance of careful study design for comparative methods, highlighting the need to fully appreciate the role of accurate and thoughtful phylogenetic modeling.
A BPTF-specific PROTAC degrader enhances NK cell-based cancer immunotherapy
Authors: Yunjia Li, Lin Bai, Hao Liang, Peidong Yan, Hao Chen, Zhuoxian Cao, Yiqing Shen, Zhongyv Wang, Mei Huang, Bin He, Quan Hao, Yide Mei, Haiming Wei, Chen Ding, Jing Jin, Yi Wang
Journal: Molecular Therapy (2025)

Natural killer (NK) cell-based immunotherapy shows promise in cancer treatment, but its efficacy remains limited, necessitating the development of novel strategies. In this study, we demonstrate that the epigenetic factor BPTF (bromodomain PHD-finger containing transcription factor) hinders hepatocellular carcinoma (HCC) recognition by NK cells through its PHD finger's interpretation of H3K4me3. We have generated a small-molecule proteolysis-targeting chimera (PROTAC) that selectively degrades human and murine BPTF. The degradation of BPTF using PROTACs directly enhances the abundance of natural cytotoxicity receptor (NCR) ligands on HCC cells, facilitating their recognition by NK cells and thereby augmenting NK cell cytotoxicity against HCC both in vitro and in vivo. Through multidisciplinary techniques, our findings establish targeting BPTF with PROTACs as a promising approach to overcome immune evasion of HCC from NK cells and provide a new strategy to enhance NK cell-based cancer immunotherapy.
Necklace‐Structured PVA Sponges for Fast Bleeding Control in the Punctured Femoral Artery Hemorrhage
Authors: Weihang Wu, Hongjian Huang, Zhicheng Huang, Qinghui Wang, Zongxuan Huang, Hongwen Zhang, Dongsheng Chen, Wen Wang, Hu Zhao, Haiqing Liu, Baodong Zheng, Yu Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Uncontrollable hemorrhage from deep, narrow wounds poses a critical threat to life, as locating the bleeding arteries in such areas is challenging. Rapid bleeding control remains a significant challenge in pre‐hospital care. Herein, an injectable hemostatic device filled with disc‐like PVA sponges is developed for this objective. The pristine PVA sponge is strung as a necklace‐structured sponge loaded in a foldable injector. With a novel retraction mechanism, this self‐designed injector precisely deploys hemostatic sponges to deep bleeding sites, surpassing the XStat TM injector in design innovation. The PVA sponges' high porosity and unique porous structure allowed it for rapid shape recovery (&lt;30 s) and good compressive strength. In the punctured wound, the swollen PVA sponges exert high compression to close the bleeding artery, resulting in fast‐bleeding control. In the pig groin femoral artery injury model, the PVA sponge treatment resulted in a 100% survival rate during a 2‐h hemostasis period, compared to a 33.3% survival rate in the cotton gauze control group. In addition, it can be easily taken out by a simple pulling. The easily applicable and removable necklace‐structured PVA sponge is a highly promising hemostat for punctured wounds.
Protein phosphatase 6 regulates metabolic dysfunction-associated steatohepatitis via the mTORC1 pathway
Authors: Zhengshuai Liu, Shuang Wei, Yang Jiang, Weitong Su, Fengguang Ma, Genxiang Cai, Yuxiao Liu, Xiaoyang Sun, Ling Lu, Wenguang Fu, Yong Xu, Ruijing Huang, Jian Li, Xu Lin, Aoyuan Cui, Mengwei Zang, Aimin Xu, Yu Li
Journal: Journal of Hepatology (2025)
Abstract 12552: Is Primary Angioplasty the Best Reperfusion Strategy in Very Old Patients With Myocardial Infarction? A Systematic Overview of Randomized Control Trials
Authors: Monica Masotti, Amadeo Betriu, Magda Heras, Hector Bueno, Angel Cequier, Joaquin Alonso, Rosana Hernandez, Eulogio Garcia, Carlos Macaya, Jose Luis Lopez-Sendon
Journal: Circulation (2010)

Background: Overall, primary percutaneous coronary intervention (PCI) is the preferred therapy in STEMI. However, in older patients -the fastest growing population group- individual randomized cont...
Can SAFE score be utilized as a universal hepatocellular carcinoma prediction score? Editorial on “High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease”
Authors: Michael Kwan-Lung Ko, Loey Lung-Yi Mak
Journal: Clinical and Molecular Hepatology (2025)

Can SAFE score be utilized as a universal hepatocellular carcinoma prediction score? Editorial on "High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease"
Y4 RNA fragment mitigates myocardial ischemia-reperfusion injury in heart transplantation through SNRNP200-mediated enhancement of IL-10 pre-mRNA splicing
Authors: Chuanghong Lu, Zhongyuan Meng, Senhu Tang, Heng Wei, Yaoshi Hu, Dexin Chen, Dezhao Liu, Hong Wen, Kun Dong, Na Na, Feng Huang, Zhiyu Zeng
Journal: Molecular Therapy (2025)
Polyphenol‐Modified Mg−Zn Layered Hydroxide‐Contained Microneedle Patch Enhance Mucosal Repair by Remolding Diabetic Oral Microenvironment
Authors: Haibo Liu, Zhongyi Sun, Mengting Yin, Jing Ru, Xiaohao Liu, Ziyan Chen, Yating Liu, Wang Sun, Longpo Zheng, Xinyu Zhao, Feng Chen
Journal: Advanced Healthcare Materials (2025)

Abstract Diabetic oral ulcers pose a significant challenge in healing due to persistent inflammation. Despite local therapeutic interventions remaining the primary mode of treatment, the dynamic nature of the oral cavity, characterized by continuous muscular activity and salivary secretion, poses barriers to sustained drug retention and thereby limits therapeutic efficacy. To address this issue, an approach has been devised that aims to facilitate transdermal delivery of bioactive components to promote the healing of diabetic oral ulcers. A multifunctional soluble microneedle (MN) patch is prepared using γ‐polyglutamic acid (γ‐PGA), which is loaded with quercetin (Qu)‐modified Mg−Zn layered hydroxide salt (LHS) nanosheets (LHSQ) with anti‐inflammatory, antimicrobial and pro‐angiogenic bioactivities to combat the diabetic oral ulcers. These findings demonstrate that the LHSQ‐loaded MN (LHSQ‐MN) patches are capable of effectively penetrating the oral mucosa. In a rat model of diabetic oral ulcers, the application of LHSQ‐MN patches is found to facilitate the establishment of regeneration sites, regulate the inflammatory microenvironment of damaged tissues, exhibit potent antibacterial effects, expedite the reconstitution of the mucosal epithelium, and accelerate ulcer healing through the promotion of angiogenesis. These outcomes highlight the potential of LHSQ‐MN patches as a promising therapeutic strategy for the management of oral ulcers in diabetic patients.
Dasatinib-Resistant Universal CAR-T cells Proliferate in the Presence of Host Immune Cells and Exhibit Antitumor Activity
Authors: Yuhang Cheng, Jiayuan Zhang, Wei Mu, Shanwei Ye, Jiali Cheng, Li Zhu, Gaoxiang Wang, Yang Cao, Dengju Li, Guang Hu, Liang Huang, Jue Wang, Jianfeng Zhou
Journal: Molecular Therapy (2025)

The universal chimeric antigen receptor T-cell (UCAR-T) immunotherapy derived from healthy donors holds great promise in pan-cancer treatment. However, UCAR-T cell therapy faces a challenge in the rapid elimination of allogeneic cells by the host immune system. To address this, we introduced a T316I mutation in the leukocyte-specific protein tyrosine kinase (LCK) locus in CAR-T cells using the cytosine base editor (CBE) system. Concurrently, we disrupted endogenous T-cell receptor alpha chain (TRAC) and beta-2 microglobulin (B2M) with the CRISPR-Cas9 system, along with dasatinib to overcome host immune rejection, an Src family kinase (SFK) inhibitor. The resulting LCK mutated UCAR-T (KM UCAR-T) cells exhibited normal phenotypes in activation, proliferation, differentiation, and tumor cytotoxicity in vitro. Moreover, KM UCAR-T cells demonstrated sustained expansion in mixed lymphocyte reactions (MLR) when incubated with T-cells or peripheral blood mononuclear cells (PBMCs) from HLA-mismatched donors upon dasatinib treatment. Additionally, we illustrated that KM UCAR-T cells displayed anti-tumor activity in a xenograft murine model and verified the expansion and cytotoxicity of KM UCAR-T over traditional UCAR-T in the presence of allogeneic PBMCs when treated with dasatinib in vivo. These findings offer a novel strategy for UCAR-T cells to resist host immune rejection and achieve sustained expansion.
Robust 3D‐Printable, Injectable, and Adhesive Hydrogels with Stepwise‐Triggered Dual Reversible/Irreversible Covalent Linkages for Wound Healing
Authors: Fucheng Li, Xiaoying Zhang, Tingting Cui, Fukun He, Lingyu Lu, Cai‐Feng Wang, Su Chen
Journal: Advanced Healthcare Materials (2025)

Abstract The development of 3D‐printable and injectable biocompatible hydrogels with robust mechanical and adhesive properties useful for biomedical applications remains a great challenge. Herein, stepwise‐triggered dual reversible/irreversible covalent linkages are engineered between two functionalized polymers, glycidyl methacrylate‐modified polyvinyl alcohol (PVA‐GMA) and oxidized sodium alginate tailed with 3‐aminophenylboronic acid (OSA‐PBA), allowing the availability of PVA‐GMA/OSA‐PBA (PGOP) hydrogels with versatile properties and functions. The PGOP hydrogels have excellent injectability, processability, mechanical strength (39.5 ± 2.3 kPa), self‐healing, elasticity and toughness (80% compressive strain at 84.5 kPa stress), bioadhesion (34.2 ± 2.7 kPa adhesive strength to fresh pig skin, vs 7.3–15.38 kPa for commercial fibrin glue adhesives), degradability, antibacterial property, and biocompatibility (265% cell survival with fibroblasts co‐culture for 5 d). With these merits, PGOP pregel and hydrogels can be applied as 3D‐printing glue and construct materials to produce diverse 3D hierarchical architectures with high shape fidelity, good mechanical properties, and active materials‐laden capacity. The mouse liver hemorrhage model and the full‐thickness skin defect model demonstrate that PGOP hydrogels have excellent hemostatic ability and accelerated wound healing capacity. Therefore, this work provides 3D‐printable and injectable glue and hydrogel adhesives with favorable mechanical strength useful for various biomedical applications such as tissue engineering and wound healing.
A critical role for Phocaeicola vulgatus in negatively impacting metformin response in diabetes
Authors: Manyun Chen, Yilei Peng, Yuhui Hu, Zhiqiang Kang, Ting Chen, Yulong Zhang, Xiaoping Chen, Qing Li, Zuyi Yuan, Yue Wu, Heng Xu, Gan Zhou, Tao Liu, Honghao Zhou, Chunsu Yuan, Weihua Huang, Wei Zhang
Journal: Acta Pharmaceutica Sinica B (2025)