tbuckley/cabot-search huggingface dataset:
Allogeneic Hematopoietic Stem Cell Transplantation for Elderly Acute Lymphoblastic Leukemia Patients: A Registry Study From the Société Francophone de Greffe de Moelle et Thérapie Cellulaire (<scp>SFGM</scp>‐<scp>TC</scp>)
Authors: Yves Chalandon, Raynier Devillier, Ariane Boumendil, Stephanie Nguyen, Claude‐Eric Bulabois, Patrice Ceballos, Eolia Brissot, Marie‐Thérèse Rubio, Hélène Labussière‐Wallet, Johan Maertens, Patrice Chevallier, Natacha Maillard, Xavier Poiré, Cristina Castilla‐Llorente, Yves Beguin, Jérôme Cornillon, Sébastien Maury, Tony Marchand, Etienne Daguindau, Jacques‐Olivier Bay, Pascal Turlure, Magalie Joris, Anne‐Lise Menard, Karin Bilger, Gaelle Guillerm, Sylvie François, Ali Bazarbachi, Sylvain Chantepie, Philippe Lewalle, Ambroise Marçais, Michael Loschi, Malek Benakli, Paul Chauvet, Edouard Forcade, Anne Huynh, Marie Robin, Stavroula Masouridi‐Levrat
Journal: American Journal of Hematology (2025)

ABSTRACT There are very limited data regarding the outcomes of elderly patients with acute lymphoblastic leukemia (ALL) who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). A total of 316 ALL patients aged ≥ 60 years who underwent alloHSCT between 2010 to 2022 were identified in the SFGM‐TC registry. The primary objective was to evaluate progression‐free survival (PFS), non‐relapse mortality (NRM), relapse incidence (RI), and graft‐versus‐host disease (GvHD)‐free relapse‐free survival (GRFS), as well as their risk factors. The median age was 63.8 years (range 60–75.8), 49.8% of patients had Philadelphia‐positive B‐ALL (Ph + ALL), and 70.9% were in first complete remission (CR1) at transplantation. The donor was an unrelated donor in 52.1%, a matched related donor (MRD) in 26.3%, and a haplo‐identical donor in 17.7%. Reduced‐intensity conditioning (RIC) was administered to 64.6% of patients, while total body irradiation (TBI) was used in 35.8%. The 3‐year overall survival (OS) was 46% (95% CI 40%–53%). The 3‐year PFS, NRM, RI, and GRFS were 41% (95% CI 35%–48%), 23% (95% CI 18%–28%), 36% (95% CI 31%–42%), and 30% (95% CI 25%–37%), respectively. Multivariable analyses confirmed poorer OS and PFS in patients with advanced disease, with an HR of 1.79 (95% CI 1.22–2.64), p = 0.0032. Additionally, the ALL subtype significantly impacted outcomes, with an HR of 1.99 (95% CI 1.42–2.79) for non‐Ph + ALL. This study suggests that alloHSCT is a viable option for elderly ALL patients, as age itself did not impact outcomes. However, advanced disease and non‐Ph + ALL were associated with significantly worse survival.
Neuronal CCL2 responds to hyperglycaemia and contributes to anxiety disorders in the context of diabetes
Authors: Kaijun Pan, Yanan Gao, Haichao Zong, Yongmei Zhang, Yingbei Qi, Hanlin Wang, Wengang Chen, Ting Zhou, Jinwen Zhao, Tao Yin, Haoran Guo, Min Wang, Hanmin Wang, Tao Pang, Yi Zang, Jia Li
Journal: Nature Metabolism (2025)
Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease
Authors: Michael E B FitzPatrick, Agne Antanaviciute, Melanie Dunstan, Karolina Künnapuu, Dominik Trzupek, Nicholas M Provine, Kyla Dooley, Jia-Yuan Zhang, Sophie L Irwin, Lucy C Garner, Jane I Pernes, Ricardo C Ferreira, Sarah C Sasson, Dominik Aschenbrenner, Devika Agarwal, Astor Rodrigues, Lucy Howarth, Oliver Brain, Darren Ruane, Elizabeth Soilleux, Sarah A Teichmann, Calliope A Dendrou, Alison Simmons, Holm H Uhlig, John A Todd, Paul Klenerman
Journal: Nature Immunology (2025)

Abstract The immune–epithelial–stromal interactions underpinning intestinal damage in celiac disease (CD) are incompletely understood. To address this, we performed single-cell transcriptomics (RNA sequencing; 86,442 immune, parenchymal and epithelial cells; 35 participants) and spatial transcriptomics (20 participants) on CD intestinal biopsy samples. Here we show that in CD, epithelial populations shifted toward a progenitor state, with interferon-driven transcriptional responses, and perturbation of secretory and enteroendocrine populations. Mucosal T cells showed numeric and functional changes in regulatory and follicular helper-like CD4 + T cells, intraepithelial lymphocytes, CD8 + and γδ T cell subsets, with skewed T cell antigen receptor repertoires. Mucosal changes remained detectable despite treatment, representing a persistent immune–epithelial ‘scar’. Spatial transcriptomics defined transcriptional niches beyond those captured in conventional histological scores, including CD-specific lymphoid aggregates containing T cell–B cell interactions. Receptor–ligand spatial analyses integrated with disease susceptibility gene expression defined networks of altered chemokine and morphogen signaling, and provide potential therapeutic targets for CD prevention and treatment.
PRESCOTT: a population aware, epistatic, and structural model accurately predicts missense effects
Authors: Mustafa Tekpinar, Laurent David, Thomas Henry, Alessandra Carbone
Journal: Genome biology (2025)

Abstract Predicting the functional impact of point mutations is a critical challenge in genomics. PRESCOTT reconstructs complete mutational landscapes, identifies mutation-sensitive regions, and categorizes missense variants as benign, pathogenic, or variants of uncertain significance. Leveraging protein sequences, structural models, and population-specific allele frequencies, PRESCOTT surpasses existing methods in classifying ClinVar variants, the ACMG dataset, and over 1800 proteins from the Human Protein Dataset. Its online server facilitates mutation effect predictions for any protein and variant, and includes a database of over 19,000 human proteins, ready for population-specific analyses. Open access to residue-specific scores offers transparency and valuable insights for genomic medicine.
Polygraph: a software framework for the systematic assessment of synthetic regulatory DNA elements
Authors: Avantika Lal, Laura Gunsalus, Anay Gupta, Tommaso Biancalani, Gokcen Eraslan
Journal: Genome biology (2025)

The design of regulatory elements is pivotal in gene and cell therapy, where DNA sequences are engineered to drive elevated and cell-type specific expression. However, the systematic assessment of synthetic DNA sequences without robust metrics and easy-to-use software remains challenging. Here, we introduce Polygraph, a Python framework that evaluates synthetic DNA elements, based on features like diversity, motif and k-mer composition, similarity to endogenous sequences, and screening with predictive and foundational models. Polygraph is the first instrument for assessing synthetic regulatory sequences, enabling faster progress in therapeutic interventions and improving our understanding of gene regulatory mechanisms.
TET3 regulates hematopoietic stem cell homeostasis during embryonic and adult hematopoiesis
Authors: Harmony C. Ketchum, Claudia Morganti, Chie Yanase, Blake Ebert, Keisuke Ito, Meelad M. Dawlaty
Journal: HemaSphere (2025)

ABSTRACT The ten‐eleven translocation family of enzymes (TET1/2/3) promotes DNA demethylation and is essential for hematopoiesis. While the roles of TET1 and TET2 are well‐studied in hematopoiesis, the requirement of TET3 in embryonic and adult hematopoiesis is less investigated. In this study, by characterizing embryonic and adult hematopoiesis in Tie2 +/cre ; Tet3 f/f mice, we have established a requirement for TET3 in regulating hematopoietic stem cells (HSCs; CD150 + CD48 – ). We found that loss of TET3 in the fetal liver and adult bone marrow causes a reduction in the percent of long‐term HSCs (LT‐HSCs; CD150 + CD48 – CD34 – ). This was accompanied by reduced colony forming capacity of TET3‐deficient HSCs in vitro and reduced contribution of HSCs after a competitive bone marrow transplantation in vivo. TET3 deficiency increased DNA methylation at several cell cycle regulator genes leading to their down regulation. This is consistent with, and likely underpins, the reduced number of quiescent HSCs in TET3‐deficient bone marrow. These findings uncover a new role for TET3 in HSC homeostasis during embryonic and adult hematopoiesis.
Advancing Cellular‐Specific Delivery: Machine Learning Insights into Lipid Nanoparticles Design and Cellular Tropism
Authors: Belal I. Hanafy, Michael J. Munson, Ramesh Soundararajan, Sara Pereira, Audrey Gallud, Sajib Md Sanaullah, Gianluca Carlesso, Mariarosa Mazza
Journal: Advanced Healthcare Materials (2025)

Abstract Lipid nanoparticles (LNPs) have gained significant attention as effective nucleic acid delivery vehicles. Despite their success, LNPs are predominantly liver‐targeted which limits their broader application. To expand the therapeutic potential of LNPs, this work implements a data‐driven approach that combines design of experiments (DoE), high throughput screening (HTS), and machine learning (ML) to tailor LNP formulations for preferential immune cell targeting. This methodology involves the generation of 180 LNP formulations, with varying lipid molar ratios and lipid chemistries, to explore a diverse design space. This work aims to identify LNP properties that enhance immune cell specificity while reducing hepatic uptake. The in vitro screening of these LNPs provided a rich dataset for ML analysis, leading to the identification of promising candidates with improved immune cellular selectivity profiles. These findings are validated in vivo where it is demonstrated that selected LNPs achieved preferential spleen expression with a successful redirection of LNP tropism beyond hepatic cells. This workflow highlights the importance of tailoring LNP compositions for the development of LNPs with selective cellular tropism.
Carrier‐Free Self‐Assembled Nanoparticles for Triple‐Amplified Tumor Chemodynamic Therapy and Cuproptosis Induction
Authors: Jiamin Cheng, Siyu Chen, Meijuan Geng, Xuan Wei, Siyu Meng, Liyang Gong, Keying Chen, Ziyan Wang, Yi Liu, Xiner Li, Ao Li, Xiaojiao Li, Liangliang Dai
Journal: Advanced Healthcare Materials (2025)

Abstract Chemodynamic therapy (CDT) holds great promise in cancer treatment, whereas its efficacy is severely compromised by the low concentration of endogenous hydrogen peroxide(H 2 O 2 ), insufficient exogenous catalytic ions, and the presence of high levels of cellular glutathione (GSH). Herein, a dissociable, tumor cell membrane‐camouflaged carrier‐free nanoparticle is developed through the molecular interaction of copper ions (Cu 2+ ), dequalinium (DQ), and β‐Lapachone (β‐Lap). Upon homotypic tumor targeting, the system releases Cu 2+ (exogenous catalytic ions), β‐Lap (H 2 O 2 donor), and DQ (GSH scavenger), achieving triple amplification of CDT efficacy. Concurrently, the intracellular accumulation of Cu 2+ induces cuproptosis, thereby synergistically augmenting CDT efficacy and strikingly restraining tumor growth. Overall, the integration of Cu 2+ supplementation, H 2 O 2 self‐supplying, and GSH depletion offers a promising avenue for improving cancer treatment outcomes and paves a new way for multimodal cancer therapy.
Construction of Cells‐Membrane‐Cells Living Complexes for Cartilage Repair by Enhancing the Structural Stability of Fibrous Membranes
Authors: Yanru Hu, Lihui Meng, Wenchao Li, Zilin Zhou, Shuojie Cui, Meng Wang, Zebin Chen, Qingzhi Wu
Journal: Advanced Healthcare Materials (2025)

Abstract 3D cartilage tissue engineering scaffolds with stable structures are crucial for promoting cartilage tissue growth and repair. However, limited research attention is given to the effects of 3D cells‐membrane‐cells sandwich‐like living complexes with enhanced structural stability for cartilage repair. In this study, silk fibroin/graphene oxide@kartogenin (SF/GO@KGN) fibrous membranes with improved structural stability are developed through the regulation of the crystallinity, and living complexes are constructed for cartilage repair using rat bone marrow stromal cells (rBMSCs) and the SF/GO@KGN fibrous membranes. Results show that the physicochemical properties of the SF/GO@KGN fibrous membranes, including morphology, tensile strength, swelling ratio, degradation, and KGN release rate are greatly influenced by the crystallinity of the fibrous membranes. The enhanced structural stability of the fibrous membranes promotes the adhesion, proliferation, and chondrogenic differentiation of rBMSCs on the surface of the fibrous membranes, as well as the deposition of the cartilage's extracellular matrix (ECM). Animal experiments demonstrate that sandwich‐like cells‐membrane‐cells living complexes with high structural stability significantly promote early cartilage formation and ECM deposition. This study not only provides a facile and effective strategy for cartilage regeneration and repair but also provides new insights for designing and preparing other tissue engineering scaffolds.
Encapsulation of Small Extracellular Vesicles into Selectively Disassemblable Shells of PEGylated Metal‐Phenolic Networks
Authors: Chenyu Wang, Ailifeire Fulati, Kenta Kimura, Xianglan Li, Joseph J. Richardson, Mitsuru Naito, Kanjiro Miyata, Takanori Ichiki, Hirotaka Ejima
Journal: Advanced Healthcare Materials (2025)

Abstract Small extracellular vesicles (sEVs) are cell‐derived particles used for intercellular communication in living organisms that have gained great interest from researchers for their use as drug carriers and diagnostic agents. However, the isolation and storage of sEVs lead to issues including lipid membrane disruption, protein denaturation, and nucleic acid degradation. Herein, a surface functionalization strategy is reported for encapsulating single sEV into selectively disassemblable protective shells composed of metal‐phenolic networks (MPNs) post‐modified with poly(ethylene glycol) (PEG). Disassemblable MPN shells can be rapidly deposited on sEVs in a one‐step manner and post‐modified with PEG. These coatings enhance the colloidal stability of sEVs and protect them against harsh storage conditions, while the non‐covalent and selectively disassemblable nature of the MPN shell allows recovery after storage without compromising their surface integrity and functionality. It is demonstrated that various triggers, such as pH adjustment, competitive chelation, and redox reactions, can be used to disassemble the MPN shell, thereby offering widely adoptable strategies depending on the target applications. This approach potentially overcomes conventional challenges associated with sEV processing and storage and may contribute to reducing cold‐chain requirements and transportation costs of future sEVs‐based therapeutics and diagnostics.
Pericyte‐Assisted Vascular Lumen Organization in a Novel Dynamic Human Blood‐Brain Barrier‐on‐Chip Model
Authors: Vita Guarino, Elisabetta Perrone, Elisa De Luca, Alberto Rainer, Maura Cesaria, Alessandra Zizzari, Monica Bianco, Giuseppe Gigli, Lorenzo Moroni, Valentina Arima
Journal: Advanced Healthcare Materials (2025)

Abstract Organ‐on‐Chip (OoC) technology provides a powerful platform for neurovascular research, enabling the precise replication of the blood‐brain barrier (BBB) microenvironment, including its 3D architecture and the influence of dynamic blood flow. This study introduces a novel microfluidic device designed to investigate the morphological and structural adaptations of human brain endothelial cells (ECs) within narrow, square‐shaped microchannels that closely mimic the microvessels of the brain's microcirculation. The endothelial microchannels are layered above a microchamber filled with Matrigel and abluminal vascular cells, enhancing cell‐cell interactions across the BBB interface. The system integrates co‐culture with pericytes and astrocytes while subjecting brain ECs to physiologically relevant pulsatile flow. The findings reveal that the morphology and cytoskeletal organization of brain ECs are distinctly influenced by pulsatile flow depending on the presence of pericytes and astrocytes. Specifically, in the absence of perivascular support, brain ECs exhibit a stretched morphology with prominent actin stress fibers, while co‐culture with pericytes and astrocytes promotes endothelial rearrangement, leading to lumen formation and enhanced barrier properties. This study highlights the essential role of perivascular cells in modulating endothelial responses under microvascular confinement and physiologically relevant flow. These insights advance in vitro models of the neurovascular unit and BBB mechanobiology.
Manipulating ICG <i>J</i>‐Aggregation and Disaggregation for Imaging‐Guided Cancer Therapy with Self‐Reporting Efficiency
Authors: Zhicong Chao, Kun Wu, Jiahui Sun, Mengchen Wang, Huangxian Ju, Ying Liu
Journal: Advanced Healthcare Materials (2025)

Abstract Integrating imaging guided therapy and therapeutic effect self‐reporting would highly benefit clinic applications. J ‐type aggregates of organic dyes with corresponding photothermal effect have made them popular agents for photoacoustic (PA) imaging and photothermal therapy (PTT). However, approaches to manipulate the disaggregation of J ‐aggregate with corresponding organic dye fluorescence recovery have rarely been reported, which limits the full exploration of J ‐aggregate in therapeutic applications. Herein, indocyanine green (ICG) J ‐aggregate is designed in a micelle structure ( J ‐ICG‐Micelle) by co‐assembling ICG with DSPE‐Pep‐PEG, which contains peptide KADEVDAC that recognized and cleaved by caspase‐3. Taking advantages of the red‐shifted absorbance of J ‐ICG‐Micelle, it achieves PA imaging navigated delivery process with an indication of tumor accumulation time and position to perform PTT. Corresponding cell apoptosis and caspase‐3 generation cleaves peptide KADEVDAC and results in fluorescence recovery of ICG, which self‐reports therapeutic effect in real time, and the intensity for fluorescence recovery demonstrates similar tendency as H&amp;E staining at tumor sections. The as‐presented J ‐ICG‐Micelle would have a promising contribution to precise cancer therapy.
Dosage Optimization of Pediatric Oncology Products: Our Patients Deserve Better
Authors: Kristin M. Wessel, Nicole Drezner, Stacy S. Shord, Mirat Shah, Marc R. Theoret, Martha Donoghue
Journal: Clinical Cancer Research (2025)

Abstract Despite survival gains for many pediatric cancers since the 1970s, cancer remains the leading cause of death by disease for children and adolescents in the United States. Survivors of pediatric cancer often experience acute and long-term toxicities resulting in diminished quality of life and reduced life expectancy. Thus, development of new therapies that offer a better balance between efficacy and safety remains an urgent unmet need. Dose-finding trials for pediatric oncology products have traditionally focused on identifying the maximum tolerated dose based on evaluation of acute, dose-limiting toxicities. However, oncology drug development has largely shifted from cytotoxic chemotherapies to targeted therapies such as kinase inhibitors, monoclonal antibodies, antibody-drug conjugates, and cellular products, which often have different dose-response relationships for efficacy and safety and are sometimes administered on a chronic basis. These differences between cytotoxic chemotherapies and newer targeted therapies necessitate adoption of new, tailored approaches to identify the recommended dosage for oncology products in pediatric patients. The FDA Oncology Center of Excellence’s Project Optimus is working to help develop such approaches, and an FDA Guidance containing recommendations for optimizing the dosage of oncology products was finalized in 2024. Some members of the pediatric oncology community have expressed concerns regarding the potential impact of ongoing dosage optimization efforts on development of new treatments for pediatric cancers. Herein, we clarify FDA’s perspectives on dosage optimization in pediatric oncology and affirm our commitment to collaborating with stakeholders to expedite development of more effective, better tolerated drugs and biologics for pediatric patients with cancer.
Advances in cancer immunotherapy: historical perspectives, current developments, and future directions
Authors: Meiyin Zhang, Chaojun Liu, Jing Tu, Min Tang, Milad Ashrafizadeh, Noushin Nabavi, Gautam Sethi, Peiqing Zhao, Shijian Liu
Journal: Molecular Cancer (2025)

Cancer immunotherapy, encompassing both experimental and standard-of-care therapies, has emerged as a promising approach to harnessing the immune system for tumor suppression. Experimental strategies, including novel immunotherapies and preclinical models, are actively being explored, while established treatments, such as immune checkpoint inhibitors (ICIs), are widely implemented in clinical settings. This comprehensive review examines the historical evolution, underlying mechanisms, and diverse strategies of cancer immunotherapy, highlighting both its clinical applications and ongoing preclinical advancements. The review delves into the essential components of anticancer immunity, including dendritic cell activation, T cell priming, and immune surveillance, while addressing the challenges posed by immune evasion mechanisms. Key immunotherapeutic strategies, such as cancer vaccines, oncolytic viruses, adoptive cell transfer, and ICIs, are discussed in detail. Additionally, the role of nanotechnology, cytokines, chemokines, and adjuvants in enhancing the precision and efficacy of immunotherapies were explored. Combination therapies, particularly those integrating immunotherapy with radiotherapy or chemotherapy, exhibit synergistic potential but necessitate careful management to reduce side effects. Emerging factors influencing immunotherapy outcomes, including tumor heterogeneity, gut microbiota composition, and genomic and epigenetic modifications, are also examined. Furthermore, the molecular mechanisms underlying immune evasion and therapeutic resistance are analyzed, with a focus on the contributions of noncoding RNAs and epigenetic alterations, along with innovative intervention strategies. This review emphasizes recent preclinical and clinical advancements, with particular attention to biomarker-driven approaches aimed at optimizing patient prognosis. Challenges such as immunotherapy-related toxicity, limited efficacy in solid tumors, and production constraints are highlighted as critical areas for future research. Advancements in personalized therapies and novel delivery systems are proposed as avenues to enhance treatment effectiveness and accessibility. By incorporating insights from multiple disciplines, this review aims to deepen the understanding and application of cancer immunotherapy, ultimately fostering more effective and widely accessible therapeutic solutions.
Myelodysplastic neoplasms with ring sideroblasts without SF3B1 mutations in adults: enrichment of germline variants in congenital sideroblastic anemia genes
Authors: Sandra Novoa-Jáuregui, Sandra Huber, Maria Gabarrós-Subirà, Tzu Hua Chen-Liang, Sara Torres-Esquius, Salvador Carrillo-Tornel, Marta Santiago, Teresa Bernal Del Castillo, Iván Martín-Castillo, Francisca Maria Hernandez, Mónica Del Rey, Alessandro Liquori, Mar Tormo, Jose Cervera, Francesc Bosch, David Valcárcel, Claudia Haferlach, María Díez-Campelo, María Julia Montoro, Torsten Haferlach, Andrés Jerez
Journal: Leukemia (2025)