tbuckley/cabot-search huggingface dataset:
Abstract IA019: Addressing genomic heterogeneity in glioblastoma personalized vaccine design
Authors: Elaine R Mardis, Elizabeth A.R. Garfinkle, Tanner Johanns, Katherine E. Miller, Gavin P Dunn
Journal: Cancer Research (2025)

Abstract Glioblastoma is a highly lethal brain cancer that is known for extensive intratumoral genomic heterogeneity. This characteristic makes it difficult to comprehensively identify a set of tumor-unique neoantigens suitable for developing a personalized vaccine for each patient. Our collaborative work has helped to refine this therapeutic approach, encompassing three FDA-IND clinical trials, with increasing refinement. In practice, we utilize multi-region sampling of the resected GBM from each patient to gain an appreciation of region-specific and -shared small variants (SNVs and indels) and their respective neoantigenic properties using pVACseq. A combination of region-specific and -shared neoantigens is advanced for vaccine design, which is administered post-resection in newly diagnosed GBM patients. In cases where, due to progression, post-vaccine tissues are available for study, we perform extensive immunogenomic profiling to evaluate changes in the tumor immune microenvironment and in T cell clonality. We will present results from our most recent trial, including data from nine patients enrolled onto the trial and immunogenomic comparisons of a short-term and long-term responder. Citation Format: Elaine R Mardis, Elizabeth A.R. Garfinkle, Tanner Johanns, Katherine E. Miller, Gavin P Dunn. Addressing genomic heterogeneity in glioblastoma personalized vaccine design [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA019.
Abstract IA018: The evolutionary origins of cancer lethality
Authors: Paul C Boutros
Journal: Cancer Research (2025)

Abstract Cancer is fundamentally a disease of evolution. But why do some cancers evolve into lethal entities while others rarely if ever evolve the capacity to metastasize and become lethal? We will explore how each of the cancer genome, transcriptome, proteome, gene-regulation and microenvironment are dysregulated in ways that explain variable clinical outcomes. Taken together, these converge on an evolutionary understanding of when the capacity to become lethal emerges, and how to predict that. We will conclude by briefly discussing the underlying genetic and lifestyle factors that influence the emergence of lethality, and that may give some indications of improved prevention and mitigation strategies. Citation Format: Paul C Boutros. The evolutionary origins of cancer lethality [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA018.
Reply: Downstaging of hepatocellular carcinoma before liver transplantation
Authors: Edison Xu, Neil Mehta
Journal: Hepatology (2025)

1Department of Medicine, University of California, San Francisco, San Francisco, CA 2Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA Abbreviations: AFP, alpha-fetoprotein; DS, downstaging; HCC, hepatocellular carcinoma; LRT, local regional therapy; LT, liver transplantation; MERITS-LT, Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation; TACE, trans-arterial chemoembolization; TARE, trans-arterial radioembolization; UNOS, United Network for Organ Sharing; Y90, Yttrium-90. Correspondence Neil Mehta, University of California, San Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA 94143-0538. Email: [email protected]
Erratum: MiR-199a-5p is negatively associated with malignancies and regulates glycolysis and lactate production by targeting hexokinase 2 in liver cancer
Authors: Weijie Guo, Zhaoping Qiu, Zhichao Wang, Qifeng Wang, Ning Tan, Taoyang Chen, Zhiao Chen, Shenglin Huang, Jianren Gu, Jinjun Li, Ming Yao, Yingjun Zhao, Xianghuo He
Journal: Hepatology (2025)
A prospective multicenter validation of RETREAT for post-transplantation hepatocellular carcinoma recurrence prediction
Authors: P. Jonathan Li, Parissa Tabrizian, Darine Daher, Felipe Gaviria, Veeral Ajmera, Eleazar E. Montalvan-Sanchez, Julio A. Gutierrez, Kali Zhou, Fanny Delebecque, Nicole Garcia, Bethany Barrick, Christopher Wong, Lauren Nephew, John Holden, Shravan Dave, Gabriel T. Schnickel, Nicole E. Rich, Sander S. Florman, Gonzalo Sapisochin, Francis Yao, Amit G. Singal, Neil Mehta
Journal: Hepatology (2025)

Background: The RETREAT score is a simple risk stratification tool for post-liver transplantation (LT) hepatocellular carcinoma (HCC) recurrence that has been validated in retrospective cohort studies. A prospective, multicenter study is needed to further demonstrate accuracy especially given evolving clinical demographics and HCC transplant practice. Aim: To validate and compare the RETREAT score to other post-LT HCC recurrence risk scores in a contemporary, prospective cohort of patients Approach: We prospectively enrolled post-LT HCC patients from 8 centers between 2018 and 2022. The primary outcome was post-LT recurrence-free survival (RFS). Secondary outcomes included post-LT and post-recurrence survival. Model performance, determined using concordance index, Akaike information criterion, integrated Brier score, and calibration, was compared to that of other established risk scores. Results: We included 1166 post-LT HCC patients of which 78 (6.7%) had post-LT HCC recurrence after a median follow up time of 2.2 years (IQR 1.2 – 3.2). Median RETREAT score was 4 (IQR 3 – 5) in patients with post-LT HCC recurrence and 1 (IQR 1 – 2) in patients without. Those with a RETREAT score of 0, 3, and 5+ had a 99.4%, 84.1%, and 55.6% RFS, respectively, at 3 years post-LT. The RETREAT score was also able to stratify post-LT overall and post-recurrence survival. The RETREAT score’s concordance index was 0.81 (95% CI: 0.77 – 0.85) and outperformed the MORAL and RELAPSE scores across multiple metrics. Conclusion: The RETREAT score retains high accuracy for predicting post-LT HCC recurrence, further supporting RETREAT guided post-LT HCC surveillance and care.
AI-driven synthetic data generation for accelerating hepatology research: A study of the United Network for Organ Sharing (UNOS) database
Authors: Joseph C. Ahn, Yung-Kyun Noh, Mingzhao Hu, Xiaotong Shen, Douglas A. Simonetto, Patrick S. Kamath, Rohit Loomba, Vijay H. Shah
Journal: Hepatology (2025)

Background and Aims: Clinical hepatology research often faces limited data availability, underrepresentation of minority groups, and complex data-sharing regulations. Synthetic data—artificially generated patient records designed to mirror real-world distributions— offers a potential solution. We hypothesized that diffusion models, a state-of-the-art generative technique, could produce synthetic liver transplant waitlist data from the United Network for Organ Sharing (UNOS) database that maintains statistical fidelity, replicates clinical correlations and survival patterns, and ensures robust privacy protection. Methods: Diffusion models were used to generate synthetic patient cohorts mirroring the UNOS liver transplant waitlist database between years 2019 and 2023. Statistical fidelity was assessed using Maximum Mean Discrepancy (MMD) and Wasserstein distance, correlation analysis, and variable-level metrics. Clinical utility was evaluated by comparing transplant-free survival via Kaplan-Meier curves and the MELD score performance. Privacy was quantified using the Distance to Closest Record (DCR) and attribute disclosure risk assessments. Results: The synthetic dataset was nearly indistinguishable from the original dataset (MMD=0.002, standardized Wasserstein distance&lt;1.0), preserving clinically relevant correlations and survival patterns as evidenced by similar median survival times (110 vs. 101 days) and 5-year survival rates (22.2% vs. 22.8%). MELD-based 90-day mortality prediction was maintained (original AUC=0.839 vs. synthetic AUC=0.844). Privacy metrics indicated no identifiable patient matches, and mean DCR values ensured that synthetic individuals were not direct replicas of real patients. Conclusion: AI-generated synthetic data derived from diffusion models can faithfully replicate complex hepatology datasets, maintain key clinical signals, and ensure strong privacy safeguards. This approach can help address data scarcity, enhance model generalizability, foster multi-institutional collaboration, and accelerate progress in hepatology research.
Letter to the Editor: Downstaging of hepatocellular carcinoma before liver transplantation: More details, more significance
Authors: Pusen Wang, Lin Zhong
Journal: Hepatology (2025)

Department of Liver Surgery and Organ Transplantation Center, Shenzhen Third People's Hospital, Second Affiliated Hospital, Southern University of Science and Technology Correspondence Pusen Wang, Department of Liver Surgery and Organ Transplantation Center, Shenzhen Third People's Hospital, Second Affiliated Hospital, Southern University of Science and Technology. Email: [email protected]
Reprogramming of Thyroid Cancer Metabolism: from Mechanism to Therapeutic Strategy
Authors: Yuxuan Wan, Guoqing Li, Gaoyuan Cui, Saili Duan, Shi Chang
Journal: Molecular Cancer (2025)

Abstract Thyroid cancer as one of the most prevalent malignancies of endocrine system, has raised public concern and more research on its mechanism and treatment. And metabolism-based therapies have advanced rapidly, for the exclusive metabolic profiling of thyroid cancer. In thyroid cancer cells, plenty of metabolic pathways are reprogrammed to accommodate tumor microenvironment. In this review, we initiatively summarize recent progress in the full-scale thyroid cancer metabolic rewiring and the interconnection of various metabolites. We also discuss the efficacy and prospect of metabolic targeted detection as well as therapy. Comprehending metabolic mechanism and characteristics of thyroid cancer roundly will be highly beneficial to managing individual patients.
Specialized Cancer Care for Adolescent and Young Adult Acute Lymphoblastic Leukemia: Barriers and Opportunities
Authors: Lori Muffly, Theresa H.M. Keegan, Heather Z. Mui, Elysia M. Alvarez, Rachel Siden, Laura M. Holdsworth, Helen M. Parsons
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Research has demonstrated that survival of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) is superior following treatment at specialized cancer centers (SCCs), such as NCI-designated Cancer Centers or Children’s Oncology Group sites. However, a minority of newly diagnosed AYAs with ALL receive care at SCCs. We conducted a qualitative study to better understand provider and policy expert perspectives on this discrepancy and to identify barriers and potential solutions to improving access to SCCs for AYAs with ALL. Methods: We performed in-depth, semistructured interviews with pediatric and adult hematology/oncology clinicians and policy experts across the United States. Interviews were recorded, transcribed, and uploaded into NVivo for analysis. We used the Expanded Chronic Care Model as a conceptual framework for analysis and interpretation. Results: We interviewed 16 clinicians and policy experts (56% health policy experts, 75% male, 75% White) from 8 states. Thematic analysis identified organizational infrastructure, institutional expertise, and ALL clinician specialization as potential contributors to improved outcomes at SCCs. Barriers to receiving care at SCCs included incompatible health insurance, transportation/lodging costs, patient preference, limited health literacy, and variable provider knowledge. Suggested solutions for improving access and outcomes included developing AYA-focused legislative policies, strengthening ALL clinical guidelines, expanding health care delivery models and partnerships, educating and empowering patient advocacy groups, and enhancing self-advocacy and care management skills. Conclusions: This study highlights barriers associated with low rates of treatment at SCCs and identifies opportunities for intervention to improve access and outcomes for AYAs with ALL.
Mohs micrographic surgery reduces the risk of reconstruction with positive margins, repeat surgeries, and time to definitive reconstruction compared to conventional excision of hand and foot melanomas: a retrospective cohort study
Authors: Daniela Frankel, Karla Valdes-Morales, Mara D Trifoi, Stephanie K Lin, Annika M Deitermann, Manisha Banala, Esther Zhang, Nicole Easo, Marissa Lubeck, Dylan Haynes, Daniel Lewis, Shannon T Nugent, Jeremy R Etzkorn, Neha N Jariwala, Junqian Zhang, Joanna L Walker, H William Higgins, Joseph F Sobanko, Cerrene N Giordano, Parnaz Daneshpajouhnejad, Mitul Modi, Ines C Lin, Benjamin Chang, Jason Wink, Giorgos Karakousis, John Miura, Christopher J Miller
Journal: Journal of the American Academy of Dermatology (2025)
Correspondence to “The Bronchodilator and Anti‐Inflammatory Effect of Long‐Acting Muscarinic Antagonists in Asthma: An <scp>EAACI</scp> Position Paper”
Authors: Umberto Semenzato, Daniele Previtero, Ylenia Padrin, Simonetta Baraldo, Mariaenrica Tinè
Journal: Allergy (2025)

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Intestinal Ultrasound Findings and Their Prognostic Value in Early Crohn’s Disease – a Copenhagen IBD Cohort Study
Authors: Gorm Roager Madsen, Mohamed Attauabi, Johan F.K.F. Ilvemark, Klaus Theede, Jacob Tveiten Bjerrum, Flemming Bendtsen, Jakob Benedict Seidelin, Rune Wilkens, Trine Boysen, Johan Burisch
Journal: Clinical Gastroenterology and Hepatology (2025)
Differential Impact of Hospitalization on Cystatin C– and Creatinine-Based Estimated GFR
Authors: Ian E. McCoy, Alan S. Go, Jesse Y. Hsu, Xiaoming Zhang, Anthony N. Muiru, Vallabh O. Shah, Matthew Weir, Hernan Rincon-Choles, Debbie L. Cohen, Amanda Anderson, Bernard Jaar, James Sondheimer, Panduranga S. Rao, Anand Srivastava, Laura Dember, Jiang He, Jing Chen, Chi-yuan Hsu
Journal: Journal of the American Society of Nephrology (2025)

Background: Cystatin C has entered mainstream clinical care as a measure of kidney function, joining serum creatinine which has been used for almost a century. But many physicians notice that eGFRCr and eGFRCys values can differ considerably. Hospitalization with critical illness is known to acutely decrease eGFRdiff (eGFRCys – eGFRCr). However, whether this effect occurs in all-cause hospitalizations and persists after hospitalization is unknown. Methods: Among 5,599 adult participants in the Chronic Renal Insufficiency Cohort (CRIC) study with serum creatinine and cystatin C measurements, we estimated the association of six categories of total days of hospitalization between annual study visits (never hospitalized, hospitalized &lt;7 days, 7-&lt;14 days, 14-&lt;28 days, 28-&lt;42 days, and ≥ 42 days) and changes in eGFRCr, eGFRCys, and eGFRdiff between those study visits. Results: Compared to no hospitalization between study visits, increasing days of hospitalization were associated with decreases in eGFRCys (e.g., -3.30 [95% CI -5.48, -1.13] ml/min/1.73m 2 for ≥ 42 days of hospitalization, test for trend p&lt;0.001), while eGFRCr remained relatively stable (e.g., -1.12 [-2.77, 0.53] ml/min/1.73m 2 for ≥ 42 days of hospitalization, test for trend p=0.21). The differential effect resulted in eGFRdiff becoming progressively more negative with more total days of hospitalization (test for trend p&lt;0.001). Conclusions: Prolonged or repeated hospitalization was associated with larger decreases in eGFRCys compared to eGFRCr on measurements months after hospital discharge.
Long-term safety and efficacy of delgocitinib cream for up to 52 weeks in adults with Chronic Hand Eczema: results of the phase 3 open-label extension DELTA 3 trial following the DELTA 1 and 2 trials
Authors: Melinda Gooderham, Sonja Molin, Robert Bissonnette, Margitta Worm, Marie-Noëlle Crépy, Luca Stingeni, Richard B Warren, Sibylle Schliemann, Marie-Louise Schuttelaar, Silvia Ferrucci, Esther Serra-Baldrich, Jonathan I Silverberg, Cherry Lou Balita-Crisostomo, Marie Louise Oesterdal, Ursula Plohberger, Tove Agner
Journal: Journal of the American Academy of Dermatology (2025)

There are no topical treatments that have been specifically developed and approved for moderate to severe Chronic Hand Eczema (CHE). To evaluate the long-term safety and efficacy of delgocitinib cream 20 mg/g as needed for 36 weeks in adults with CHE. In phase 3 open-label DELTA 3 (NCT04949841), patients who completed the 16-week(W) treatment period in DELTA 1 and 2 were treated on an as-needed basis with twice-daily delgocitinib for 36 weeks (n=801). Patients with Investigator's Global Assessment for CHE (IGA-CHE)≥2 received treatment until IGA-CHE≤1 was achieved. Primary endpoint was number of treatment-emergent adverse events (AEs). Key secondary endpoints were IGA-CHE 0/1 and ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) scores. Delgocitinib was well tolerated (n=801; R=231.1; PYO=535.7), with most frequent AEs being COVID-19 and nasopharyngitis. DELTA 3 baseline IGA-CHE 0/1 (24.6%), HECSI-75/HECSI-90 (51.8%/31.8%) were maintained to W36 (30.0% and 58.6%/36.6%, respectively) among delgocitinib-treated patients in the parent trials. Among those previously treated with cream vehicle, corresponding response rates improved from DELTA 3 baseline (9.1% and 23.7%/12.0%, respectively) to W36 (29.5% and 51.5%/35.7%). Open-label trial. Delgocitinib cream treatment was well-tolerated and efficacious in maintaining disease control in CHE patients up to 52 weeks.
Activin A activation of Smad3 mitigates innate inflammation in mouse models of psoriasis and sepsis
Authors: Thierry Gauthier, Yun-Ji Lim, Wenwen Jin, Na Liu, Liliana C. Patiño, Weiwei Chen, James Warren, Daniel Martin, Robert J. Morell, Gabriela S. Dveksler, Gloria H. Su, WanJun Chen
Journal: Journal of Clinical Investigation (2025)

Phosphorylation of Smad3 is a critical mediator of TGF-β signaling, which plays an important role in regulating innate immune responses. However, whether Smad3 activation can be regulated in innate immune cells in TGF-β-independent contexts remains poorly understood. Here, we show that Smad3 is activated through the phosphorylation of its C-terminal residues (pSmad3C) in murine and human macrophages in response to bacterial and viral ligands, which is mediated by Activin A in a TGF-β independent manner. Specifically, infectious ligands, such as LPS, induced secretion of Activin A through the transcription factor STAT5 in macrophages, and Activin A signaling in turn activated pSmad3C. This Activin A-Smad3 axis controlled the mitochondrial ATP production and ATP conversion into adenosine by CD73 in macrophages, enforcing an anti-inflammatory mechanism. Consequently, mice with a deletion of Activin A receptor 1b specifically in macrophages (Acvr1bf/f-Lyz2cre) succumbed more to sepsis due to uncontrolled inflammation and exhibited exacerbated skin disease in a mouse model of imiquimod-induced psoriasis. Thus, we have revealed a previously unrecognized natural brake to inflammation in macrophages that occurs through the activation of Smad3 in an Activin A-dependent manner.
Proteostasis and metabolic dysfunction characterize a subset of storage-induced senescent erythrocytes targeted for post-transfusion clearance
Authors: Sandy Peltier, Mickaël Marin, Monika Dzieciatkowska, Michaël Dussiot, Micaela Kalani Roy, Johanna Bruce, Louise Leblanc, Youcef Hadjou, Sonia Georgeault, Aurélie Fricot, Camille Roussel, Daniel Stephenson, Madeleine Casimir, Abdoulaye Sissoko, François Paye, Safi Dokmak, Papa Alioune Ndour, Philippe Roingeard, Emilie-Fleur Gautier, Steven L. Spitalnik, Olivier Hermine, Pierre A. Buffet, Angelo D’Alessandro, Pascal Amireault
Journal: Journal of Clinical Investigation (2025)

Although refrigerated storage slows the metabolism of volunteer donor RBCs, which is essential in transfusion medicine, cellular aging still occurs throughout this in vitro process. Storage-induced microerythrocytes (SMEs) are morphologically-altered senescent RBCs that accumulate during storage and are cleared from circulation following transfusion. However, the molecular and cellular alterations that trigger clearance of this RBC subset remain to be identified. Using a staining protocol that sorts long-stored SMEs (i.e., CFSEhigh) and morphologically-normal RBCs (CFSElow), these in vitro aged cells were characterized. Metabolomics analysis identified depletion of energy, lipid-repair, and antioxidant metabolites in CFSEhigh RBCs. By redox proteomics, irreversible protein oxidation primarily affected CFSEhigh RBCs. By proteomics, 96 proteins, mostly in the proteostasis family, had relocated to CFSEhigh RBC membranes. CFSEhigh RBCs exhibited decreased proteasome activity and deformability; increased phosphatidylserine exposure, osmotic fragility, and endothelial cell adherence; and were cleared from the circulation during human spleen perfusion ex vivo. Conversely, molecular, cellular, and circulatory properties of long-stored CFSElow RBCs resembled those of short-stored RBCs. CFSEhigh RBCs are morphologically and metabolically altered, have irreversibly oxidized and membrane-relocated proteins, and exhibit decreased proteasome activity. In vitro aging during storage selectively alters metabolism and proteostasis in these storage-induced senescent RBCs targeted for clearance.
Clinical Utility of <sup>18</sup>Fluorine‐Fibroblast Activation Protein Inhibitor‐04 Positron Emission Tomography/Computed Tomography in the Evaluation of Pancreatic Ductal Adenocarcinoma: Comparison With <sup>18</sup>Fluorine‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Authors: Lili Lin, Guangfa Wang, Yafei Zhang, Guolin Wang, Kui Zhao, Xinhui Su
Journal: MedComm (2025)

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is highly susceptible to metastasis, making early detection of metastases and associated risk factors crucial for effective management. This study aimed to assess the performance of 18 fluorine ( 18 F)‐ fibroblast activation protein inhibitor‐04 ( 18 F‐FAPI‐04) positron emission tomography/computed tomography (PET/CT) in detecting metastasis and predicting pathological characteristics and risk factors in 67 PDAC patients. Comparisons were made with 18 F‐fluorodeoxyglucose ( 18 F‐FDG) PET/CT. Lesion identifications and radiotracer uptakes were evaluated through visual inspection and semiquantitative analysis using the maximum standardized uptake value (SUVmax). We analyzed the risk factors for metastasis and observed that 18 F‐FAPI‐04 identified more positive lesions and showed significantly higher SUVmax values than 18 F‐FDG in both primary tumors and metastases, leading to upstaging in several cases. In primary tumors, 18 F‐FAPI‐04 was associated with higher levels of poorly differentiated PDAC, compared to those with moderately differentiated tumors. Notably, the SUVmax of 18F‐FAPI‐04 in primary tumors demonstrated a significant correlation with pathological differentiation and served as an independent prognostic factor for peritoneal metastasis, rather than lymph node or liver metastasis. Our findings suggested that 18 F‐FAPI‐04 PET/CT offers superior tumor detectability and improved node‐metastasis (NM) staging in PDAC patients, positioning it as a more effective tool than 18 F‐FDG PET/CT.