tbuckley/cabot-search huggingface dataset:
Correction: DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming
Authors: Ilaria Gritti, Jinkai Wan, Vajira Weeresekara, Joel M. Vaz, Giuseppe Tarantino, Tenna Holgersen Bryde, Vindhya Vijay, Ashwin V. Kammula, Prabhat Kattel, Songli Zhu, Phuong Vu, Marina Chan, Meng-Ju Wu, John D. Gordan, Krushna C. Patra, Vanessa S. Silveira, Robert T. Manguso, Marc N. Wein, Christopher J. Ott, Jun Qi, David Liu, Kei Sakamoto, Taranjit S. Gujral, Nabeel Bardeesy
Journal: Cancer Discovery (2025)
Loss of p53 Induces Tolerance to Viral Mimicry as a Mechanism of Immune Evasion in Early Tumorigenesis
Authors: Takahiko Murayama, Israel Cañadas
Journal: Cancer Discovery (2025)

Summary: Ishak and colleagues report that the loss of p53 disrupts constitutive heterochromatin, enabling the transcription of immunogenic repetitive elements. Unlike acute viral mimicry activation, a chronic viral mimicry response mediated by p53 loss during cancer initiation induces tolerance to cytosolic nucleic acids, ultimately diminishing cellular immunogenicity as a strategy for immune evasion. See related article by Ishak et al., p. 793
Don’t Lose Your Nerve: Adrenergic Signaling and Bone Marrow Regeneration after Transplantation
Authors: Ravi Bhatia
Journal: Cancer Discovery (2025)

Summary: In this issue, Nishino, Hu, Kishtagari, and colleagues report that patients who receive nonselective β-blockers after allogeneic hematopoietic cell transplant exhibit delayed platelet engraftment and reduced survival. See related article by Nishino et al., p. 748
Insights on Future Directions in Cancer Research from the 2025 AACR NextGen Stars
Authors: Edmond M. Chan, Yash Chhabra, Karen O. Dixon, Adam D. Durbin, Anniina Färkkilä, Anand D. Jeyasekharan, Zuzana Keckesova, John R. Prensner, Elvin Wagenblast, Stephanie Z. Xie, Di Zhao
Journal: Cancer Discovery (2025)
Engineering the Future of Restorative Clinical Peripheral Nerve Surgery
Authors: Justin C. Burrell, Zarina S. Ali, Eric L. Zager, Joseph M. Rosen, Mykhailo M. Tatarchuk, D. Kacy Cullen
Journal: Advanced Healthcare Materials (2025)

Abstract Peripheral nerve injury is a significant clinical challenge, often leading to permanent functional deficits. Standard interventions, such as autologous nerve grafts or distal nerve transfers, require sacrificing healthy nerve tissue and typically result in limited motor or sensory recovery. Nerve regeneration is complex and influenced by several factors: 1) the regenerative capacity of proximal neurons, 2) the ability of axons and support cells to bridge the injury, 3) the capacity of Schwann cells to maintain a supportive environment, and 4) the readiness of target muscles or sensory organs for reinnervation. Emerging bioengineering solutions, including biomaterials, drug delivery systems, fusogens, electrical stimulation devices, and tissue‐engineered products, aim to address these challenges. Effective translation of these therapies requires a deep understanding of the physiology and pathology of nerve injury. This article proposes a comprehensive framework for developing restorative strategies that address all four major physiological responses in nerve repair. By implementing this framework, we envision a paradigm shift that could potentially enable full functional recovery for patients, where current approaches offer minimal hope.
Endothelial insulin-like growth factor-1 signaling regulates vascular barrier function and atherogenesis
Authors: Michael Drozd, Alexander-Francisco Bruns, Nadira Y Yuldasheva, Azhar Maqbool, Hema Viswambharan, Anna Skromna, Natallia Makava, Chew W Cheng, Piruthivi Sukumar, Lauren Eades, Andrew M N Walker, Kathryn J Griffin, Stacey Galloway, Nicole T Watt, Natalie Haywood, Victoria Palin, Nele Warmke, Helen Imrie, Katherine Bridge, David J Beech, Stephen B Wheatcroft, Mark T Kearney, Richard M Cubbon
Journal: Cardiovascular Research (2025)

Abstract Aims Progressive deposition of cholesterol in the arterial wall characterizes atherosclerosis, which underpins most cases of myocardial infarction and stroke. Insulin-like growth factor-1 (IGF-1) is a hormone that regulates systemic growth and metabolism and possesses anti-atherosclerotic properties. We asked whether endothelial-restricted augmentation of IGF-1 signaling is sufficient to suppress atherogenesis. Methods and Results We generated mice with endothelial-restricted over-expression of human wildtype IGF-1R (hIGFREO/ApoE-/-) or a signaling defective K1003R mutant human IGF-1R (mIGFREO/ApoE-/-) and compared them to their respective ApoE-/- littermates. hIGFREO/ApoE-/- had less atherosclerosis, circulating leukocytes, arterial cholesterol uptake, and vascular leakage in multiple organs, whereas mIGFREO/ApoE-/- did not exhibit these phenomena. Overexpressing wildtype IGF-1R in human umbilical vein endothelial cells (HUVEC) altered the localization of tight junction proteins and reduced paracellular leakage across their monolayers, whilst overexpression of K1003R IGF-1R did not have these effects. Moreover, only overexpression of wildtype IGF-1R reduced HUVEC internalization of cholesterol-rich low density lipoprotein particles and increased their association of these particles with clathrin, but not caveolin-1, implicating it in vesicular uptake of lipoproteins. Endothelial overexpression of wildtype versus K1003R IGF-1R also reduced expression of YAP/TAZ target genes and nuclear localization of TAZ, which may be relevant to its impact on vascular barrier and atherogenesis. Conclusions Endothelial IGF-1 signaling modulates both para- and trans-cellular vascular barrier function. Beyond reducing atherosclerosis, this could have relevance to many diseases associated with abnormal vascular permeability.
Neutrophil Membrane‐Encapsulated Polymerized Salicylic Acid Nanoparticles Effectively Alleviating Rheumatoid Arthritis by Facilitating Sustained Release of Salicylic Acid into the Articular Cavity from Chondrocytes
Authors: Luying Yang, Feng Cao, Jiayu Lu, Simo Wu, Le Wang, Jianzhen She, Boling He, Xiaoying Xu, Fan Shi, Ye Gao, Zhou Ye, Baolin Guo, Liang Kong, Ronghua Jin, Bolei Cai
Journal: Advanced Healthcare Materials (2025)

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily instigates chronic inflammation in multiple joints. Salicylic acid (SA) is a classic anti‐inflammatory agent for the treatment of RA. To enhance the therapeutic effect of SA, an innovative therapeutic approach for RA is developed by encapsulating polymerized‐SA (PSA) nanoparticles within neutrophil membranes. The study demonstrated that neutrophil membranes endowed PSAs with the ability to selectively target inflammatory joints in RA mice, where they specifically accumulated within the inflammatory chondrocytes. The internalized PSAs underwent gradual degradation into SA within chondrocytes, facilitating sustained release into the articular cavity and effectively alleviating RA symptoms. By attenuating the expression of inflammatory mediators within the joint cavity and suppressing neutrophil extracellular traps (NETs) in the synovium, neutrophil membrane encapsulated polymerized salicylic acid nanoparticles (N‐PSAs) effectively restore long‐term intra‐articular homeostasis in RA mice, thereby establishing a conducive microenvironment for cartilage repair. In summary, the articular chondrocytes represent an optimal reservoir for therapeutic agents targeting joint disorders. By conferring PSA with the capability to specifically target inflammatory chondrocytes, the neutrophil membrane‐coated drug‐polymerized nanoparticles offer a promising therapeutic strategy for the management of rheumatoid arthritis (RA) and serve as a valuable reference for treating other inflammatory joint disorders.
Molecular Modeling Studies of Hapten Design and Antibody Recognition for Sensitive Detection of Vitamin K3 by Strip Biosensor
Authors: Jialin Hu, Xinxin Xu, Liqiang Liu, Aihua Qu, Hua Kuang, Chuanlai Xu
Journal: Advanced Healthcare Materials (2025)

Abstract Computer‐aided molecular design techniques are used to analyze vitamin K3 (VK3) and VK3‐hapten. Based on VK3‐hapten, a specific monoclonal antibody (mAb) against VK3 is prepared with a sensitivity (IC 50 ) of 0.49 ng mL −1 . The recombinant technology is used to investigate the molecular docking mechanism of mAb recognition of VK3. Then, a model of the mAb is established, and the amino acid distributions of the complementarity determining region regions of the mAb are determined. Hydrogen bonding and hydrophobic interactions of specific amino acids of the mAb are further confirmed by the recognition mechanism of the antibody with VK3. Based on these results, a gold immunochromatographic assay (GICA) is developed to detect VK3. The recovery of VK3 in the sample is 99.50%–101.12%, showing a better agreement with the results of the high‐performance liquid chromatography. In addition, the calculated limit of detection of VK3 in milk powder, vitamin tablets, and mixed animal feed is 1.16, 1.18, and 10.06 µg kg −1 , respectively. The concentrations of VK3 in vitamin tablets and mixed animal feed as determined with the GICA strips are 5.82 mg/tablet and 1.47 mg kg −1 , respectively. These results confirmed that the developed GICA strips have great potential for detecting VK3 in actual samples.
Symptom burden in myeloproliferative neoplasms: clinical correlates, dynamics, and survival impact—a study of 784 patients from the Quebec MPN research group
Authors: Alisa Poullet, Lambert Busque, Shireen Sirhan, Robert Delage, Ghislain Cournoyer, Ines Chamakhi, Danielle Talbot, Luigina Mollica, Daniele Marceau, Vincent Ethier, Pierre Desjardins, Harold J Olney, Michaël Harnois, Natasha Szuber
Journal: Blood Cancer Journal (2025)
DeepGuide: a novel wavelength-specific navigation system for membrane visualization in surgery
Authors: Zehong Chen, Xuejie Li, Zongheng Zheng, Jianpei Liu, Jiafeng Fang, Jianglong Huang, Tufeng Chen, Hongbo Wei
Journal: International Journal of Surgery (2025)

Background: Membrane anatomy (MA) has become pivotal in modern surgery, enabling surgeons to operate within avascular natural planes to minimize concomitant injury. However, intraoperative identification of membranous structures remains challenging. Poor membrane visualization compromises both radical resection and functional preservation, underscoring the need for innovative solutions. Methods: In this study, we develop a innovative tool, DeepGuide, to help surgeon make membrane visualization during surgery. Moreover, we design a single-arm prospective study to validated its effectiveness. A total of 60 patients undergoing laparoscopic radical resection for gastrointestinal tumors at The Third Affiliated Hospital of Sun Yat-sen University were enrolled. Primary outcomes included signal-to-background ratio (SBR), mesenteric integrity, absorbance of membrane specimens, and immunofluorescence staining of collagen components. Results: DeepGuide significantly improved mesenteric integrity rates from 75% (conventional laparoscopy) to 98%. SBR under DeepGuide (2.30 ± 0.15) surpassed conventional lighting (1.32 ± 0.16). Absorbance analysis revealed reduced light absorption at 385 nm. Immunofluorescence confirmed collagen I/III enrichment in mesenteric submucosa, aligning with 385 nm-excited autofluorescence properties. Conclusion: DeepGuide revolutionizes intraoperative membrane visualization without requiring contrast agents. It enhances surgical precision and supports MA principles. These findings highlight DeepGuide’s potential to redefine standards in oncologic surgery.
Global, regional, and national burden of brain and central nervous system cancer: a systematic analysis of incidence, deaths, and DALYS with predictions to 2040
Authors: Qi Zhang, Honghao Yu, Jue Zhong, Weiting Cheng, Yiwei Qi
Journal: International Journal of Surgery (2025)

Background: Brain and central nervous system (CNS) cancers present significant health challenges globally, characterized by increasing incidence and mortality rates. This study utilizes data from the Global Burden of Disease (GBD) 2021 to analyze trends and project future burdens. Methods: We calculated age-standardized rates (ASRs) of incidence, mortality, and disability-adjusted life years (DALYs) for brain and CNS cancers from 1990 to 2021. Trends were analyzed using estimated annual percentage change, and future projections were made with an Autoregressive Integrated Moving Average (ARIMA) model. Correlations between the socio-demographic index (SDI) and ASR were also examined. Results: The study revealed a 106% increase in incidence and a 63.67% rise in deaths over the study period. The ARIMA model predicts declines in incidence, mortality, and DALYs by 2040. Higher incidence rates were observed in high SDI regions, while greater mortality occurred in low SDI areas, indicating significant disparities. Conclusion: These findings underscore the need for targeted interventions and sustained healthcare investments to manage the global burden of brain and CNS cancers effectively. The projected declines suggest potential effectiveness of current public health strategies but highlight the importance of addressing socio-demographic disparities.
Toxicological insights and safety considerations of vorasidenib in grade 2 astrocytoma and oligodendroglioma—research letter
Authors: Gabriel Vinícius Rolim Silva, M. Aktaruzzaman, Umberto Laino Fulco, Taha Alqahtani, Magdi E A Zaki, Jonas Ivan Nobre Oliveira
Journal: International Journal of Surgery (2025)

Vorasidenib, a dual inhibitor of isocitrate dehydrogenase 1 and 2 (IDH1/2), has shown promise as a therapeutic agent following its recent FDA approval for the treatment of grade 2 astrocytomas and oligodendrogliomas harboring IDH mutations in patients 12 years of age and older following surgery. While Vorasidenib offers significant potential in targeting altered metabolic pathways in low-grade gliomas, its comprehensive toxicologic and safety profile has not been adequately explored. This research letter addresses this critical gap by presenting an in silico analysis of the potential toxicologic effects of Vorasidenib. Using computational tools – ADMETlab 3.0, FAF-Drugs 4.1, DeepPK, vNN-ADMET, Pred-hERG 5.0, ADVERPred, PreADMET, and ADMET-AI – and databases such as ChEMBL, PubChem, and ChemSpider, we evaluated the key physicochemical properties and predicted ADMET profiles of Vorasidenib, along with a comparative analysis of two other drugs, namely Ivosidenib and Enasidenib. Our results suggest potential risks associated with drug-induced liver injury (DILI) and hepatotoxicity, with structural properties indicative of hepatocellular damage during and after treatment. The low clearance rates associated with the low maximum recommended dose suggest that Vorasidenib may accumulate in the bloodstream over time, increasing the likelihood of toxic reactions. In addition, the predictive models indicate concerns for neurotoxicity, nephrotoxicity and cardiotoxicity, including potential blockade of hERG channels leading to QT interval prolongation and cardiac arrhythmias. Importantly, the analysis also indicates risks of genotoxicity and carcinogenicity, raising concerns about promoting additional tumor formation in patients already prone to malignancies. These results emphasize the need for further preclinical and clinical studies to validate the safety of Vorasidenib. A comprehensive understanding of the toxicologic profile is critical to ensure that the therapeutic benefit for patients with IDH1/2-mutated low-grade gliomas is not compromised by potential adverse effects. Careful monitoring of patients and tailored therapeutic strategies are essential to optimize clinical outcomes and guide physicians in the safe use of Vorasidenib in clinical practice.
Right ventricular dysfunction following tetralogy of Fallot correction: anatomical determinants and therapeutic strategies
Authors: Qiang Fan, Yabo Wang, Qi An, Yunfei Ling
Journal: International Journal of Surgery (2025)

Right ventricular dysfunction following surgical correction of tetralogy of Fallot (TOF) remains a major determinant of long-term morbidity and mortality in survivors. Despite advancements in surgical techniques, residual anatomical abnormalities – including pulmonary regurgitation, right ventricular outflow tract obstruction, abnormal coronary artery anatomy, scar formation, and tricuspid regurgitation – synergistically drive ventricular remodeling and functional decline. This review synthesizes evidence on the pathophysiological interplay of these anatomical substrates. Key imaging modalities, such as 3D late gadolinium enhancement cardiac magnetic resonance, and artificial intelligence tools enhance risk stratification for ventricular arrhythmias. We propose a hierarchical management framework prioritizing hemodynamic stabilization, electrophysiological substrate modification and individualized strategies for concomitant lesions considerations. This work aims to bridge anatomical insights with therapeutic innovations, offering a roadmap for improving longevity and quality of life in repaired TOF patients.
Junction Plakoglobin – A Dual-Role Player in Cancer Biology
Authors: Wei Ding, Jiaao Sun, Shiyan Song, Yuying Cui, Feng Chen, Qihang Yuan, Wei Shang
Journal: International Journal of Surgery (2025)

Junction plakoglobin (JUP) is a critical cell adhesion molecule implicated in mediating cell-cell adhesion. Cancer, characterized by the loss of normal cellular regulation, results in unchecked proliferation and the breakdown of cell-cell junctions, facilitating malignant cell invasion into surrounding tissues. Recent studies have highlighted the involvement of JUP in the transduction of various intercellular signaling pathways, underscoring its significant role in tumor initiation, progression, and prognosis. In contrast to its homolog β-catenin, the interplay between JUP and cancer remains underexplored. To clarify JUP’s role and underlying mechanisms in cancer progression, this review examines recent advancements, focusing on JUP’s regulation of key cancer-related signaling pathways, such as Wnt/β-catenin, p53, and cadherin-mediated pathways. The review also investigates JUP’s relevance across various cancer types, including those of the reproductive, digestive, and urinary systems. Mechanistically, JUP exhibits context-dependent actions in different cancers, demonstrating dual roles in tumorigenesis. Lastly, the potential of JUP as a target for early diagnosis, effective treatment, and prognostic prediction in cancer is evaluated. In conclusion, targeting JUP offers a promising avenue for cancer therapy, providing valuable insights for future research.
Author Correction: An activity-regulated transcriptional program directly drives synaptogenesis
Authors: Callista Yee, Yutong Xiao, Hongwen Chen, Anay R Reddy, Bing Xu, Taylor N Medwig-Kinney, Wan Zhang, Alan P Boyle, Wendy A Herbst, Yang Kevin Xiang, David Q Matus, Kang Shen
Journal: Nature Neuroscience (2025)
Effects of bacteriophages on gut microbiome functionality
Authors: Elena Kurilovich, Naama Geva-Zatorsky
Journal: Gut Microbes (2025)

The gut microbiome, composed of bacteria, fungi, and viruses, plays a crucial role in maintaining the delicate balance of human health. Emerging evidence suggests that microbiome disruptions can have far-reaching implications, ranging from the development of inflammatory diseases and cancer to metabolic disorders. Bacteriophages, or "phages", are viruses that specifically infect bacterial cells, and their interactions with the gut microbiome are receiving increased attention. Despite the recently revived interest in the gut phageome, it is still considered the "dark matter" of the gut, with more than 80% of viral genomes remaining uncharacterized. Today, research is focused on understanding the mechanisms by which phages influence the gut microbiota and their potential applications. Bacteriophages may regulate the relative abundance of bacterial communities, affect bacterial functions in various ways, and modulate mammalian host immunity. This review explores how phages can regulate bacterial functionality, particularly in gut commensals and pathogens, emphasizing their role in gut health and disease.
Clonal Evolution of<i> PPM1D</i> Mutations in the Spectrum of Myeloid Disorders
Authors: David Fandrei, Jean Pegliasco, Florence Pasquier, Nathalie Ibrahim, Maria Kfoury, Céline Berthon, Mael Heiblig, Delphine Lebon, Ambroise Marçais, Mathieu Meunier, Ahmad Al Jijakli, Emilie Lemasle, Sylvain Chantepie, Cecile Pautas, Pierre-Yves Dumas, Celia Salanoubat, Diana Carp, Romain Loyaux, Cyril Quivoron, Arnaud Pages, Bastien Job, Remy Jelin, Gerome Jules-Clement, Iléana Antony-Debré, Aline Renneville, Sophie Cotteret, Raphael Itzykson, Herve Dombret, Nicolas Duployez, Nathalie Droin, Alexandra Leary, Christophe Marzac, Elsa Bernard, Jean-Baptiste Micol
Journal: Clinical Cancer Research (2025)

PPM1D, a central regulator of the DNA damage response, is commonly mutated in therapy-related clonal hematopoiesis (CH), acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). PPM1D mutations have been shown to expand under selective pressure of DNA-damaging chemotherapy. However, whether PPM1D mutations promote the development of hematologic malignancies remains unclear. We characterized the clinical and genomic profiles of 112 PPM1D-mutated patients across the spectrum of myeloid disorders using a combination of bulk and single-cell analyses on diagnostic and longitudinal samples. Among all patients, 78% had a history of primary cancer, with DNMT3A and TP53 being the most frequent co-mutated genes. In ten patients with high-grade serous ovarian cancer, longitudinal analysis showed variable dynamics of PPM1D-mutant clones, with 81% of clones expanding during exposure to alkylating agents. Clonal hierarchy estimation revealed that 44% of PPM1D-mutated acute myeloid leukemia (AML) patients had a PPM1D mutation in the founder clone, with rare TP53 co-mutations. Both TP53 wildtype and mutated AML patients had poor overall survival. Single cell DNA and surface protein analysis in seven patients confirmed that PPM1D mutations can arise in the founding clone, and were associated with expression of leukemic markers. PPM1D mutated CH clones can spontaneously regress after treatment discontinuation, however they can also be found in the dominant clone in AML/MDS.
A streaming brain-to-voice neuroprosthesis to restore naturalistic communication
Authors: Kaylo T Littlejohn, Cheol Jun Cho, Jessie R Liu, Alexander B Silva, Bohan Yu, Vanessa R Anderson, Cady M Kurtz-Miott, Samantha Brosler, Anshul P Kashyap, Irina P Hallinan, Adit Shah, Adelyn Tu-Chan, Karunesh Ganguly, David A Moses, Edward F Chang, Gopala K Anumanchipalli
Journal: Nature Neuroscience (2025)