tbuckley/cabot-search huggingface dataset:
A phase II study of abemaciclib for patients with retinoblastoma-positive, triple-negative metastatic breast cancer
Authors: Shom Goel, Bojana Jovanović, Xiangying Chu, Melissa Hughes, Timothy K. Erick, Douglas Russo, Molly DiLullo, Eileen Wrabel, Rinath Jeselsohn, Nancy U. Lin, Nabihah Tayob, Elizabeth Mittendorf, Stuart Schnitt, Sara M. Tolaney
Journal: Clinical Cancer Research (2025)

Abstract Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors can significantly extend survival when given in combination with endocrine therapy in hormone receptor-positive metastatic breast cancer patients. However, their activity has been relatively underexplored in patients with metastatic triple-negative breast cancer (mTNBC). Methods: We conducted a single-arm phase II study of abemaciclib monotherapy in patients with retinoblastoma-positive (Rb+) mTNBC. Patients were treated with abemaciclib 200 mg orally twice daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), disease control rate (DCR), and safety and tolerability. Results: A total of 27 patients were enrolled before the trial was closed early due to slow accrual. Patients had received a median of 2 lines of systemic therapy in the metastatic setting prior to enrollment. After a median follow-up of 28.5 months, the ORR was 0%, the CBR was 14.8%, and the DCR was 22.2%. The median PFS was 1.94 months (95% confidence interval (CI):1.84-11.47), and the median OS was 8.44 months (95% CI:4.57-15.57). Median PFS and OS did not differ significantly based on AR and PD-L1 status. Pre-treatment gene expression profiling of tumor tissue provided some hypothesis-generating insights into biological features associated with clinical benefit in this study. The most common treatment-related adverse events of grade 2 or higher were diarrhea (40.7%), neutropenia (40.7%), anemia (29.6%), and nausea (29.6%). Conclusions: Abemaciclib monotherapy did not show clinical activity in patients with pretreated Rb+ metastatic TNBC.
In situ Non-canonical Activation and Sensitization of cGAS-STING Pathway with Manganese Telluride Nanosheets
Authors: Hongbo Gao, Li Sun, Han Wang, Xiuru Ji, Qianwen Shen, Di Chen, Yuxin Jiao, Dalong Ni, Xiangpeng Zheng, Zhijun Bao
Journal: Biomaterials (2025)
Phase 1 clinical trial of B-Cell Maturation Antigen (BCMA) NEX-T® Chimeric Antigen Receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma
Authors: Gayathri Ravi, Shambavi Richard, Shaji Kumar, Shebli Atrash, Michaela Liedtke, Gurbakhash Kaur, Benjamin Derman, P. Leif Bergsagel, Sham Mailankody, Philip McCarthy, Alok Shrestha, Lisa M. Kelly, Thomas Ly, Sharmila Das, Jerill Thorpe, Alison Maier, Divya Varun, Garnet Navarro, Michael R. Burgess, Kristen Hege, Ashley K. Koegel, Luciano J. Costa
Journal: Leukemia (2025)
Cardiac imaging highlights from European Society of Cardiology 2024: the future is within our grasp!
Authors: Stefano Figliozzi, Erika Hutt, Alessia Gimelli, Wael A Jaber
Journal:  (2025)

Abstract The European Society of Cardiology has held its annual Congress in London, UK, from 30 August to 2 September 2024. With a total of 31 800 participants, 5400 faculty and presenters, and many National Cardiac Societies and industry partners, the Congress has taken an enormous step forward to present and discuss the latest advances in cardiovascular medicine. The sizable intercontinental reach was proved by the fact that 5 of the 10 top countries, in terms of submission of abstracts, were from outside Europe: China, the USA, Japan, Korea, and Australia. This brought a great impetus for international collaboration and exchange of views, learning from different perspectives. Specifically, the field of cardiovascular imaging has been in the spotlight, remarking its growing, central, and transversal role in modern cardiovascular medicine. In this communication, we offer a summary of some notable advances in research, either in terms of novelty or clinical applicability, within the realm of four imaging modalities: echocardiography, cardiovascular magnetic resonance, computed tomography, and nuclear imaging.
New potent HBV replication inhibitors for the management of chronic hepatitis B are needed
Authors: Timothy M Block, Ju-Tao Guo, Fabien Zoulim, Charles M Rice, Chloe L Thio, William M Schneider, Harvey J Alter, Ira M Jacobson, Robert G Gish, Peter D Block, Mark Sulkowski, Jordan J Feld, Chari A Cohen
Journal: Nature Reviews Gastroenterology & Hepatology (2025)
Author Correction: A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens
Authors: Christopher L. Yankaskas, Keyata N. Thompson, Colin D. Paul, Michele I. Vitolo, Panagiotis Mistriotis, Ankit Mahendra, Vivek K. Bajpai, Daniel J. Shea, Kristen M. Manto, Andreas C. Chai, Navin Varadarajan, Aikaterini Kontrogianni-Konstantopoulos, Stuart S. Martin, Konstantinos Konstantopoulos
Journal: Nature Biomedical Engineering (2025)
Author Correction: Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTENmRNA
Authors: Mohammad Ariful Islam, Yingjie Xu, Wei Tao, Jessalyn M. Ubellacker, Michael Lim, Daniel Aum, Gha Young Lee, Kun Zhou, Harshal Zope, Mikyung Yu, Wuji Cao, James Trevor Oswald, Meshkat Dinarvand, Morteza Mahmoudi, Robert Langer, Philip W. Kantoff, Omid C. Farokhzad, Bruce R. Zetter, Jinjun Shi
Journal: Nature Biomedical Engineering (2025)
Correspondence on ‘Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration’ by Fan et al
Authors: Kohei Nishitani, Yu Kobori, Hiroyuki Yoshitomi, Akinori Murakami, Koichi Murata, Takayuki Fujii, Yugo 侑吾 Morita, Takashi Sono, Shuichi Matsuda
Journal: Annals of the Rheumatic Diseases (2025)
An inversion polymorphism under balancing selection, involving giant mobile elements, in an invasive fungal pathogen
Authors: Fanny E Hartmann, Ricardo C Rodríguez de la Vega, Arthur Demené, Thomas Badet, Jean-Philippe Vernadet, Quentin Rougemont, Amandine Labat, Alodie Snirc, Lea Stauber, Daniel Croll, Simone Prospero, Cyril Dutech, Tatiana Giraud
Journal: Molecular Biology and Evolution (2025)

Recombination suppression can evolve in sex or mating-type chromosomes, or in autosomal supergenes, with different haplotypes being maintained by balancing selection. In the invasive chestnut blight fungus Cryphonectria parasitica, a genomic region was suggested to lack recombination and to be partially physically linked to the mating-type (MAT) locus based on segregation analyses. Using hundreds of available C. parasitica genomes and generating new high-quality genome assemblies, we show that a ca. 1.2 Mb genomic region proximal to the mating-type locus lacks recombination, with the segregation of two highly differentiated haplotypes in balanced proportions in invasive populations. High-quality genome assemblies further revealed an inversion in one of the haplotypes in the invaded range. The two haplotypes were estimated to have diverged 1.5 million years ago, and each harboured specific genes, some of which likely belonging to Starships. These are large trasnposable elements, mobilized by tyrosine recombinases, able to move accessory genes, and involved in adaptation in multiple fungi. The MAT-proximal region carried genes upregulated under virus infection or vegetative incompatibility reaction. In the native range, the MAT-proximal region also appeared to have a different evolutionary history than the rest of the genome. In all continents, the MAT-Proximal region was enriched in non-synonymous substitutions, in gene presence/absence polymorphism, in tyrosine recombinases and in transposable elements. This study thus sheds light on a case of a large non-recombining region partially linked to a mating compatibility locus, likely maintained by balancing selection on differentiated haplotypes, possibly involved in adaptation in a devastating tree pathogen.
Kidney Fibrosis In Vitro and In Vivo Models: Path Toward Physiologically Relevant Humanized Models
Authors: Gabriele Addario, Lorenzo Moroni, Carlos Mota
Journal: Advanced Healthcare Materials (2025)

Abstract Chronic kidney disease (CKD) affects over 10% of the global population and is a leading cause of mortality. Kidney fibrosis, a key endpoint of CKD, disrupts nephron tubule anatomy and filtration function, and disease pathomechanisms are not fully understood. Kidney fibrosis is currently investigated with in vivo models, that gradually support the identification of possible mechanisms of fibrosis, but with limited translational research, as they do not fully recapitulate human kidney physiology, metabolism, and molecular pathways. In vitro 2D cell culture models are currently used, as a starting point in disease modeling and pharmacology, however, they lack the 3D kidney architecture complexity and functions. The failure of several therapies and drugs in clinical trials highlights the urgent need for advanced 3D in vitro models. This review discusses the urinary system's anatomy, associated diseases, and diagnostic methods, including biomarker analysis and tissue biopsy. It evaluates 2D and in vivo models, highlighting their limitations. The review explores the state‐of‐the‐art 3D‐humanized in vitro models, such as 3D cell aggregates, on‐chip models, biofabrication techniques, and hybrid models, which aim to mimic kidney morphogenesis and functions. These advanced models hold promise for translating new therapies and drugs for kidney fibrosis into clinics.
Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention
Authors: Rodrigo Fonseca, Yuan Xiao Zhu, Laura A. Bruins, Joseph Ahmann, Cecilia de Bonolo Campos, Esteban Braggio, Xianfeng Chen, Mariano Arribas, Susie Darvish, Seth Welsh, Erin Meermeier, Kiran K. Mangalaparthi, Richard K. Kandasamy, Greg Ahmann, J. Erin Wiedmeier-Nutor, Akhilesh Pandey, Marta Chesi, P. Leif Bergsagel, Rafael Fonseca
Journal: Blood Cancer Journal (2025)

Abstract Investigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members. Notably, the re-introduction of BIM into resistant cells restored VTX sensitivity and synergized with MCL-1 inhibitors. Upstream signaling pathways, including growth factor receptor tyrosine kinase (RTK) and phosphoinositide-3-kinase (PI3K) were implicated in this dysregulation. Simultaneous inhibition of MCL-1, BCL-XL, and upstream PI3K, RTK (FGF, EGF, and IGF1) mediated signaling enhanced VTX sensitivity. Post-translational modifications of MCL-1, particularly its stabilization via acetylation and phosphorylation, were investigated, although their inhibition only marginally increased VTX sensitivity. Lastly, the inhibition of AURKA and mitochondrial respiration also improved VTX sensitivity in some resistant HMCLs. Our findings suggest that combining VTX with MCL-1 and BCL-XL inhibitors or PIK3/RTK inhibitors holds potential for overcoming resistance. The study illustrates the importance of understanding molecular determinants of resistance to develop tailored therapeutic strategies.
Assessment of priorities, quality, and inclusivity of digital therapeutics trials in China
Authors: Ziming Wang, Xinxin Xia, Weijia Lu, Yuguo Ye, Jin Xu
Journal: npj Digital Medicine (2025)

Abstract Digital therapeutics (DTx) are software-driven solutions for prevention, treatment, and management of medical conditions. Despite a pro-DTx momentum in China, global DTx trial assessments overlooked the country. We identified 756 DTx trials in China and analyzed their characteristics and quality parameters. Over 70% were funded by governments, hospitals, and universities, with tertiary hospitals in eastern China leading most trials. 44.8% used automated DTx, with 39.2% DTx-guided. Most trials focused on management (52.5%) and treatment (38.1%), with few on prevention (9.4%). Mental, behavioral, or neurodevelopmental disorders represented the leading condition category of focus. Recent declines in median sample size, median duration, and mean number of sites were noted. Only 18% of trials were at low overall risk of bias. While recognizing the rapid development of DTx trials in China, we call for better trial design and methodological rigor, prioritization of preventive and primary care, wider condition category scope, and higher inclusivity.
A Potential 3‐in‐1 Combined AntiSARS‐CoV‐2 Therapy Using Pulmonary MIL‐100(Fe) Formulation
Authors: Beatrice Fodor, Inés Álvarez‐Miguel, Catalina Biglione, Guillermo G. López, África González‐Fernández, Fabrice Salles, Tania Hidalgo, Patricia Horcajada
Journal: Advanced Healthcare Materials (2025)

The emergence and rapid propagation of infectious diseases, including the COVID-19 pandemic, has evidenced the vulnerabilities in global health surveillance, the ease of transmission, and the imperative need for effective treatments. In this context, nanomedicines based on metal-organic frameworks (MOFs) have garnered great relevance as promising drug delivery platforms in a large range of complex diseases (e.g., cancer, and infections). However, most research has focused on sensing with scarce examples in antiviral therapies. Hence, here a pioneer combined 3-in-1 effect anti-COVID pulmonary multitherapy based on the mesoporous iron(III) carboxylate MIL-100(Fe) nanoparticles is proposed, with the proven intrinsic MOF effect, associated with favipiravir drug into their porosity and heparin on their external surface. A significant antiviral effect against a real scenario of COVID-19 infection is demonstrated (≈70% inhibition), ensuring a suitable cellular viability. Further, a convenient pulmonary formulation is prepared based on mannitol-based microspheres, testing its safety and biodistribution in healthy mice. No significant side effects are observed, reaching successfully the deep lungs, emphasizing a reduced immunological response compared to their controls. Therefore, these promising results open new horizons for future (pre)clinical trials targeting challenging infectious/pulmonary pathologies, enhancing the feasibility of designing customized therapeutic MOF platforms.
Glepaglutide‐Loaded Foam for the Induction of Mucosal Healing in the Treatment of Inflammatory Bowel Disease
Authors: Wunan Zhang, William Van den Bossche, Hafsa Yagoubi, Espoir K Kambale, Khadija Wahni, Tanya Saxena, Léo Guilbaud, Tom G. Moreels, Joris Messens, Ana Beloqui
Journal: Advanced Healthcare Materials (2025)

Abstract Glucagon‐like peptide 2 (GLP‐2) stimulates intestinal growth, repairs mucosa, and enhances epithelial integrity but has a short half‐life (7 min). Glepaglutide (GL), a GLP‐2 analog with an extended half‐life (50 h), is currently undergoing clinical trials for patients with short bowel syndrome. GL requires subcutaneous injection, which poses challenges for potential patient compliance. To address this challenge, GL was loaded into a rectal foam formulation using CO 2 as a permeation enhancer to combine both the local and systemic effects of the GLP‐2 analog. In a dextran sodium sulfate (DSS)‐induced colitis model, the GL‐loaded foam (GLF) significantly mitigated the severity of colitis. GLF facilitated mucosal healing, as evidenced by colonoscopy images, increased plasma markers of mucosal healing, and increased crypt depth. To evaluate GL absorption in the colon, fluorescein dextran 4K (FD 4K) was employed. The foam formulation improved macromolecule absorption in the colon, with fast recovery of enhanced permeation that dissipated after 4 h. This study highlights GLF as a promising formulation for GL administration, balancing systemic and local anti‐inflammatory effects.
Macrophage Membrane‐Camouflaged Nanozymes for Combating the Oxidative Stress‐Microvascular Perfusion Negative Feedback in Ischemia‐Reperfusion Induced Acute Kidney Injury
Authors: Fan Xia, Shanshan Xiang, Yihe Qiu, Haiya Lou, Shuaifei Wang, Yupeng Liu, Fangying Yu, Shiyan Li
Journal: Advanced Healthcare Materials (2025)

Abstract Oxidative stress plays a critical role in the pathogenesis of ischemia‐reperfusion injury (IRI)‐induced acute kidney injury (AKI), driving necrosis of proximal tubule cells, inflammation, and capillary rarefaction. Inadequate perfusion resulting from capillary rarefaction can, in turn, induce chronic tissue hypoxia and exacerbate ischemic acute tubular necrosis, leading to an “oxidative stress‐microvascular perfusion” negative feedback that further aggravate kidney damage. In this study, a macrophage membrane‐camouflaged manganese‐based antioxidant nanozyme (MB@LM) is developed for targeted delivery and oxidative stress relief in AKI therapy. By inheriting macrophage surface proteins, MB@LM selectively targets damaged renal tissues that overexpress adhesion molecules like intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1), facilitating enhanced accumulation at the injury site. The manganese‐based nanozyme core provides antioxidant enzyme‐mimicking activities, effectively reducing oxidative stress and inhibiting apoptosis. In IRI‐induced AKI mouse model, MB@LM treatment significantly reduces renal damage, restores renal microvascular perfusion as assessed by ultrasound imaging, and alleviated inflammation, demonstrating remarkable therapeutic efficacy. Overall, MB@LM represents a promising targeted therapy for AKI, offering precise delivery, potent antioxidant protection, and anti‐inflammatory effects to support renal recovery and improve outcomes for AKI.
GDH1-dependent α-ketoglutarate promotes HBV transcription by modulating histone methylations on the cccDNA minichromosome
Authors: Sheng-Tao Cheng, Wei-Xian Chen, Hai-Jun Deng, Xin He, Hui Zhang, Ming Tan, Hai-Bo Yu, Zhen-Zhen Zhang, Ji-Hua Ren, Min-Li Yang, Da-Peng Zhang, Zhi-Hong Li, Juan Chen
Journal: Clinical and Molecular Hepatology (2025)

Hepatitis B virus (HBV) hijacks host cell metabolism, especially host glutamine metabolism, to support its replication. Glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme crucial for glutamine metabolism, can interact with histone demethylases to regulate gene expression through histone methylation. However, the mechanisms underlying GDH1-mediated glutamine metabolism reprogramming and the roles of key metabolites during HBV infection remain unclear. Transcriptomic and metabolomic analyses of HBV-infected cell were performed. Both HBV-infected cells and humanized liver chimeric mice were used to elucidate the effect of glutamine metabolism on HBV. HBV infection leads to the abnormal activation of glutamine metabolism, including upregulation of key enzymes and metabolites involved in glutamine metabolism. The viral core protein (HBc) mediates the translocation of GDH1 into the nucleus, where GDH1 activates covalently closed circular DNA (cccDNA) transcription by converting glutamate to α-ketoglutarate (αKG). Mechanistically, the promoting effect of GDH1-derived αKG on cccDNA transcription is independent of its conventional role. Rather, αKG directly interacts with the lysine-specific demethylase KDM4A and enhances KDM4A demethylase activity to regulate αKG-dependent histone demethylation, controlling cccDNA transcription. Our findings highlight the importance of glutamine metabolism in HBV transcription and suggest that glutamine deprivation is a potential strategy for silencing cccDNA transcription.
FIB-4plus Score: A novel machine learning-based tool for screening high-risk varices in compensated cirrhosis (CHESS2004): An international multicenter study
Authors: Bingtian Dong, Ruiling He, Shenghong Ju, Yuping Chen, Ivica Grgurevic, Jianzhong Ma, Ying Guo, Huizhen Fan, Qiang Yan, Chuan Liu, Huixiong Xu, Anita Madir, Kristian Podrug, Jia Wang, Linxue Qian, Zhengzi Geng, Shanghao Liu, Tao Ren, Guo Zhang, Kun Wang, Meiqin Su, Fei Chen, Sumei Ma, Liting Zhang, Zhaowei Tong, Yonghe Zhou, Xin Li, Fanbin He, Hui Huan, Wenjuan Wang, Yunxiao Liang, Juan Tang, Fang Ai, Tingyu Wang, Liyun Zheng, Zhongwei Zhao, Jiansong Ji, Wei Liu, Jiaojiao Xu, Bo Liu, Xuemei Wang, Yao Zhang, Qiong Yan, Hui Liu, Xiaomei Chen, Shuhua Zhang, Yihua Wang, Yang Liu, Li Yin, Yanni Liu, Yanqing Huang, Li Bian, Ping An, Xin Zhang, Shaoting Zhang, Jinhua Shao, Xiangman Zhang, Wei Rao, Chaoxue Zhang, Christoph Frank Dietrich, Won Kim, Xiaolong Qi
Journal: Clinical and Molecular Hepatology (2025)

A large percentage of patients undergoing esophagogastroduodenoscopy (EGD) screening do not have esophageal varices (EV) or have only small EV. We evaluated a large, international, multicenter cohort to develop a novel score, termed FIB-4plus, by combining the fibrosis-4 (FIB-4) score, liver stiffness measurement (LSM), and spleen stiffness measurement (SSM) to identify high-risk EV (HRV) in compensated cirrhosis. This international cohort study involved patients with compensated cirrhosis from 17 Chinese hospitals and one Croatian institution (NCT04546360). Two-dimensional shear wave elastography-derived LSM and SSM values, and components of the FIB-4 score (i.e., age, aspartate aminotransferase, alanine aminotransferase, and platelet count [PLT]) were combined using machine learning algorithms (logistic regression [LR] and extreme gradient boosting [XGBoost]) to develop the LR-FIB-4plus and XGBoost-FIB-4plus models, respectively. Shapley Additive exPlanations method was used to interpret the model predictions. We analyzed data from 502 patients with compensated cirrhosis who underwent EGD screening. The XGBoost-FIB-4plus score demonstrated superior predictive performance for HRV, with an area under the receiver operating characteristic curve (AUROC) of 0.927 (95% CI: 0.897-0.957) in the training cohort (n=268), and 0.919 (95% CI: 0.843-0.995) and 0.902 (95% CI: 0.820-0.984) in the first (n=118) and second (n=82) external validation cohorts, respectively. Additionally, the XGBoost-FIB-4plus score exhibited high AUROC values for predicting EV across all cohorts. The FIB-4plus score outperformed the individual parameters (LSM, SSM, PLT, and FIB-4). The FIB-4plus score effectively predicted EV and HRV in patients with compensated cirrhosis, providing clinicians with a valuable tool for optimizing patient management and outcomes.