tbuckley/cabot-search huggingface dataset:
Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria
Authors: Lixing Li, Xin Xu, Wentao Wang, Peiran Huang, Lei Yu, Zhenggang Ren, Jia Fan, Jian Zhou, Lan Zhang, Zheng Wang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Numerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has opened new avenues for HCC treatment. However, TACE combined with ICIs has not been investigated for patients with intermediate-stage HCC beyond the up-to-seven criteria. The study aims to evaluate the efficacy and safety of this treatment strategy for such patients. In this single-arm, prospective, phase II study, we enrolled eligible patients with HCC who were treated with TACE plus programmed cell death protein 1 (PD-1) inhibitors (sintilimab) from April 2021 to February 2023. The study's primary objectives were to assess progression-free survival (PFS) and safety. Secondary objectives included measuring the objective response rate (ORR) and disease control rate (DCR) as per both Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST (mRECIST) criteria, as well as overall survival (OS). Additionally, we conducted correlation analyses to identify predictors influencing the efficacy of tumor treatment. 20 patients participated in this study, with a median follow-up duration of 22.0 months. Median PFS was 8.4 months (95% CI: 4.7 to 19.7) according to both RECIST V.1.1 and mRECIST. The ORR was 30.0% (95% CI: 14.6% to 51.9%) per RECIST 1.1% and 60% (95% CI: 38.7% to 78.1%) per mRECIST. DCR was 95.0% (95% CI: 76.4% to 99.1%) according to both RECIST V.1.1 and mRECIST. Median OS was not yet reached. Notably, 20% (4/20) of patients underwent successful conversion to curative surgical resection. Treatment-related adverse events (TRAEs) mainly included elevated aspartate aminotransferase levels (19/20, 95.0%), elevated alanine aminotransferase levels (18/20, 90.0%), hypothyroidism (18/20, 90.0%), and reduced appetite (10/20, 50.0%). Among all participants, only one experienced grade 3 TRAE (myocarditis). We employed the Elastic Net regression model to analyze radiomic features from tumor and peritumoral areas to predict the efficacy of this treatment strategy. TACE plus PD-1 inhibitors demonstrated promising efficacy and an acceptable safety profile, suggesting it as a potential treatment option for patients with intermediate-stage HCC beyond up-to-seven criteria. Furthermore, our study indicates that specific image-based features may serve as predictors for patients likely to benefit from this treatment approach. NCT04842565.
Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines
Authors: Anton Lahusen, Nora Minhöfer, Kim-André Lohse, Christine Blechner, Jessica Lindenmayer, Tim Eiseler, Anton Wellstein, Alexander Kleger, Thomas Seufferlein, Sabine Windhorst, Yuan-Na Lin
Journal: Journal for ImmunoTherapy of Cancer (2025)

Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy. We used an unbiased screening approach of T cell resistant and sensitive murine KPC (KrasLSL-G12D/+; Trp53fl/fl; Ptf1aCre/+ ) PDAC cells in a three-dimensional co-culture platform with syngeneic antigen-educated T cells to identify potential cell-intrinsic drivers of T cell suppression in PDAC. Comparative transcriptomic analysis was performed to reveal promising candidates that mediate resistance to T cells. We investigated their contribution by shRNA-mediated knockdown and pharmacological inhibition in murine in vitro and in vivo studies, as well as in patient-derived organoids (PDOs). A combination of transcriptomic analyses, cytometric and immunohistochemistry techniques allowed us to validate the underlying T cell response phenotypes of PDAC cells. The action of TGM2 via interaction with tubulin and the impact of microtubule dynamics and vesicle trafficking were evaluated by protein analyses and live-cell imaging. Correlation analyses via TCGA data complemented the functional studies. We identified transglutaminase 2 (TGM2) as a mediator of T cell suppression in PDAC. We report that high levels of TGM2 expression in patients' tumors correlate with immunosuppressive signatures and poor overall survival. We found that TGM2 regulates vesicle trafficking by modulating microtubule network density and dynamics in pancreatic cancer cells, thus facilitating the secretion of immunosuppressive cytokines, which impair effector T cell functionality. In TGM2-expressing PDOs, pharmacological TGM2 inhibition or treatment with nocodazole increased T cell-mediated apoptosis. Also, pretreatment of TGM2high PDOs with sublethal doses of the spindle poisons paclitaxel or vincristine increased CD8+T cell activation and sensitized PDOs toward T cell-mediated cytotoxicity. These findings indicate that targeting microtubular function therapeutically may enhance antitumor T cell responses by impacting activity of immunosuppressive cytokines in the PDAC microenvironment.
Point-of-Care Testing to Combat Congenital Syphilis—The Time Is Now
Authors: Kristin M. Wall, Kimberly Workowski, Marisa Young, Irene A. Stafford
Journal: JAMA (2025)

This Viewpoint highlights the importance of point-of-care tests to detect syphilis, leading to timely treatment of syphilis and reducing complications including congenital syphilis.
Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment
Authors: Qibo Huang, Bai Hu, Ping Zhang, Ye Yuan, Shiwei Yue, Xiaoping Chen, Junnan Liang, Zhouping Tang, Bixiang Zhang
Journal: Molecular Cancer (2025)

The study of the multifaceted interactions between neuroscience and cancer is an emerging field with significant implications for understanding tumor biology and the innovation in therapeutic approaches. Increasing evidence suggests that neurological functions are connected with tumorigenesis. In particular, the peripheral and central nervous systems, synapse, neurotransmitters, and neurotrophins affect tumor progression and metastasis through various regulatory approaches and the tumor immune microenvironment. In this review, we summarized the neurological functions that affect tumorigenesis and metastasis, which are controlled by the central and peripheral nervous systems. We also explored the roles of neurotransmitters and neurotrophins in cancer progression. Moreover, we examined the interplay between the nervous system and the tumor immune microenvironment. We have also identified drugs that target the nervous system for cancer treatment. In this review we present the work supporting that therapeutic agent targeting the nervous system could have significant potential to improve cancer therapy.
Efficacy and Safety of CDK4/6 Inhibitors: A Focus on HR+/HER2− Early Breast Cancer
Authors: Eva Valentina Klocker, Daniel Egle, Rupert Bartsch, Gabriel Rinnerthaler, Michael Gnant
Journal: Drugs (2025)

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2−) metastatic breast cancer, and are now also established agents in the treatment of high-risk and intermediate-risk HR+ early breast cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression have been successfully evaluated in the metastatic setting, and are considered a standard of care. Mechanism of action of and resistance mechanisms against CDK4/6i in addition to endocrine resistance represent an important research topic, important for the treatment of HR+ breast cancer. Clinically, CDK4/6i are efficient substances that are usually well tolerated. However, side effects differing between the substances have been reported, and might lead to treatment discontinuation, including in the early disease setting. In the adjuvant setting, the addition of palbociclib to standard endocrine treatment has not improved outcomes, whereas large randomized phase III trials have demonstrated significant disease-free survival benefit for the addition of ribociclib (NATALEE trial) and abemaciclib (monarchE trial). Patient selection, treatment duration, endocrine backbone therapy, and other study details differ between these pivotal trials. This review focuses on both the scientific background as well as all available clinical data of CDK4/6i, with particular emphasis on their use in early breast cancer.
Meta-analyses of mouse and human prostate single-cell transcriptomes reveal widespread epithelial plasticity in tissue regression, regeneration, and cancer
Authors: Luis Aparicio, Laura Crowley, John R. Christin, Caroline J. Laplaca, Hanina Hibshoosh, Raul Rabadan, Michael M. Shen
Journal: Genome Medicine (2025)

Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate. We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner. Using random matrix theory to denoise datasets, we have established reference cell type classifications for the normal mouse and human prostate and have used optimal transport to compare the cross-species transcriptomic similarities of epithelial cell populations. In addition, we have integrated analyses of single-cell transcriptomic states with copy number variants to elucidate transcriptional programs in epithelial cells during human prostate cancer progression. Our analyses demonstrate transcriptomic similarities between epithelial cell states in the normal prostate, in the regressed prostate after androgen-deprivation, and in primary prostate tumors. During regression in the mouse prostate, all epithelial cells shift their expression profiles toward a proximal periurethral (PrU) state, demonstrating an androgen-dependent plasticity that is restored to normal during androgen restoration and gland regeneration. In the human prostate, we find substantial rewiring of transcriptional programs across epithelial cell types in benign prostate hyperplasia and treatment-naïve prostate cancer. Notably, we detect copy number variants predominantly within luminal acinar cells in prostate tumors, suggesting a bias in their cell type of origin, as well as a larger field of transcriptomic alterations in non-tumor cells. Finally, we observe that luminal acinar tumor cells in treatment-naïve prostate cancer display heterogeneous androgen receptor (AR) signaling activity, including a split between AR-positive and AR-low profiles with similarity to PrU-like states. Taken together, our analyses of cellular heterogeneity and plasticity provide important translational insights into the origin and treatment response of prostate cancer. In particular, the identification of AR-low tumor populations suggests that castration-resistance and predisposition to neuroendocrine differentiation may be pre-existing properties in treatment-naïve primary tumors that are selected for by androgen-deprivation therapies.
The CD123 antibody–drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia
Authors: Ben Watts, Christopher M. Smith, Kathryn Evans, Andrew J. Gifford, Sara M. A. Mohamed, Stephen W. Erickson, Eric J. Earley, Steven Neuhauser, Timothy M. Stearns, Vivek M. Philip, Jeffrey H. Chuang, Patrick A. Zweidler‐McKay, Sribalaji Lakshmikanthan, Emily L. Jocoy, Carol J. Bult, Beverly A. Teicher, Malcolm A. Smith, Richard B. Lock
Journal: HemaSphere (2025)

Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin-3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123-targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient-derived xenograft (PDX) models (n = 39). PVEK administered once weekly for 3 weeks resulted in a median event-free survival (EFS) of 57.2 days across all PDXs. CD123 mRNA and protein expression was significantly higher in B-lineage (n = 65) compared with T-lineage (n = 25) ALL PDXs (p < 0.0001), and mice engrafted with B-lineage PDXs achieved significantly longer EFS than those engrafted with T-lineage PDXs (p < 0.0001). PVEK treatment also resulted in significant clearance of human leukemia cells in hematolymphoid organs in mice engrafted with B-ALL PDXs. Notably, our results showed no direct correlation between CD123 expression and mouse EFS, indicating that CD123 is necessary but not sufficient for in vivo PVEK activity. Importantly, a PDX with very high CD123 cell surface expression but resistant to in vivo PVEK treatment, failed to internalize the G4723A antibody while remaining sensitive to the PVEK payload, DGN549, suggesting a novel mechanism of resistance. In conclusion, PVEK was highly effective against a large panel of B-ALL PDXs supporting its clinical translation for B-lineage pediatric ALL.
Publisher Correction: TIGIT and PD-L1 co-blockade promotes clonal expansion of multipotent, non-exhausted antitumor T cells by facilitating co-stimulation
Authors: Katherine Nutsch, Karl L. Banta, Thomas D. Wu, Charles W. Tran, Stephanie Mittman, Ellen Duong, Barzin Y. Nabet, Yan Qu, Katherine Williams, Sören Müller, Namrata S. Patil, Eugene Y. Chiang, Ira Mellman
Journal: Nature Cancer (2025)
Therapeutic Errors Associated With Antithrombotic Medications Reported to United States Poison Centers
Authors: Emma N. Cravo, Hannah L. Hays, Jaahnavi Badeti, Henry A. Spiller, Natalie I. Rine, Motao Zhu, Gary A. Smith
Journal: American Journal of Hematology (2025)

The objective of this study was to investigate the characteristics and trends of therapeutic errors in non-healthcare facility settings associated with antithrombotic medications reported to United States Poison Centers by analyzing data from the National Poison Data System from 2000 to 2021. There were 57 288 reported therapeutic error-related exposures involving antithrombotic medications as the primary substance. The rate of therapeutic errors increased by 590.9% during this 22-year period. Although most (90.1%) therapeutic errors were clinically inconsequential and did not receive treatment at a healthcare facility, 2.3% were medically admitted, and 2.1% experienced a serious medical outcome, including 16 fatalities. Three-fourths (74.9%) of therapeutic errors were among > 59-year-olds, and females represented 58.0% of exposures. Warfarin was the most commonly involved antithrombotic medication (37.5%), followed by direct oral anticoagulants (DOACs, 28.7%) and clopidogrel (23.3%). Therapeutic errors involving warfarin were more likely to be associated with a medical admission (odds ratio [OR] = 2.23; 95% confidence interval [CI]: 1.99-2.49) or a serious medical outcome (OR = 2.99; 95% CI: 2.65-3.37), and DOACs were less likely to be associated with a medical admission (OR = 0.53, 95% CI: 0.46-0.61) or a serious medical outcome (OR = 0.45; 95% CI: 0.38-0.53) than therapeutic errors involving other antithrombotic medications. The rate of therapeutic errors involving warfarin significantly increased by 187.0% during 2000-2011, followed by a 57.6% significant decrease during 2011-2021. The rate of therapeutic errors involving DOACs increased significantly by 1118.2% during 2011-2021. The scenario "inadvertently took/given medication twice" accounted for 56.3% of all therapeutic errors. Increased risk reduction efforts are needed to prevent antithrombotic-related therapeutic errors.
Myt1 kinase: An Emerging Cell Cycle Regulator for Cancer Therapeutics
Authors: Fengchao Lang, Karambir Kaur, Javeria Zaheer, Diego Luis. Ribeiro, Chunzhang Yang
Journal: Clinical Cancer Research (2025)

Abstract Cell cycle checkpoints are stringent quality control mechanisms that regulate cell cycle progression and division. Cancer cells often develop a dependency on the G2/M cell cycle checkpoint to facilitate DNA repair and resolve intrinsic or therapy-induced DNA damage. This dependency leads to therapy resistance, continuous cell division, and disease progression. Targeting G2/M checkpoints has been heavily pursued over the past two decades and has progressed into clinical studies. Recent genome-scale functional genomic studies have revealed that Myt1 kinase, an essential but previously overlooked molecule for the G2/M checkpoint, is a promising target for multiple types of cancers. In this work, we summarize the latest discoveries in molecular targeting of Myt1 kinase and discuss the challenges and limitations in expanding its clinical application.
Challenges and opportunities for digital twins in precision medicine from a complex systems perspective
Authors: Manlio De Domenico, Luca Allegri, Guido Caldarelli, Valeria d’Andrea, Barbara Di Camillo, Luis M. Rocha, Jordan Rozum, Riccardo Sbarbati, Francesco Zambelli
Journal: npj Digital Medicine (2025)

Digital twins (DTs) in precision medicine are increasingly viable, propelled by extensive data collection and advancements in artificial intelligence (AI), alongside traditional biomedical methodologies. We argue that including mechanistic simulations that produce behavior based on explicitly defined biological hypotheses and multiscale mechanisms is beneficial. It enables the exploration of diverse therapeutic strategies and supports dynamic clinical decision-making through insights from network science, quantitative biology, and digital medicine.
Misdiagnosis of borderline personality disorder in transgender and gender nonbinary populations
Authors: Olivia Opal Mounet, Lauren Mizock, Allen Cornelius, Ruben Hopwood
Journal: International Journal of Transgender Health (2025)

Background Transgender and nonbinary (TNB) individuals have faced problems with clinical bias in the mental health world. TNB individuals appear to be assigned pathologizing diagnoses like personality disorders at disproportionate rates from their cisgender counterparts, which can result from transphobia and lack of trans-affirmative training.
A Paper‐Based Sensor for the Detection of Gastroesophageal Reflux Disease Utilizing a Cleavable Fluorescent Polymer
Authors: Zejian He, Jun Wu, Zhen He, Jia Chen, Weipin Fang, Yifan Zhang, Xinyi Shen, Yangjing Ren, Yulong Chen, Jianguo He, Donghai Yan, Pin Chen, Mi Zhou
Journal: Advanced Healthcare Materials (2025)

Nowadays, gastroesophageal reflux disease (GERD) has emerged as one of the major hazards to the health of the upper gastrointestinal tract, and there is an urgent need for a low-cost, user-friendly, and non-invasive detection method. Herein, a paper-based sensor (CP sensor) for the non-invasive screening of GERD is proposed. The sensor is structured as a specially shaped cellulose paper strip embedded with fluorescent colloids, which are self-assembled from a cleavable synthetic fluorescent polymer (P4). Benefiting from the introduction of amide bonds and the unique assembled structure of the nanocolloids, the pepsin in the sample solution will hydrolyze the water-soluble branches in the micellar shell during detection, resulting in a corresponding output of the fluorescent signal. This responsiveness, which can be observed by the naked eye, is so sensitive with a minimum detectable concentration for pepsin as low as 0.3 ng·mL-1. Clinical trials have further demonstrates that the designed paper sensor is capable of providing improved accuracy in the early diagnosis of GERD.
BileMet: A new frontier in distinguishing malignant from benign biliary conditions
Authors: Binbin Li
Journal: Hepatology (2025)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA Abbreviation: BTC, biliary tract cancer. Correspondence Binbin Li, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905. Email: [email protected]
ABE-Mediated Cardiac Gene Silencing via Single AAVs Requires DNA Accessibility
Authors: Zhanzhao Liu, Luzi Yang, Yuhan Yang, Jiting Li, Zhan Chen, Congting Guo, Qianhao Guo, Qiuxuan Li, Dongyu Zhao, Xiaomin Hu, Fei Gao, Yuxuan Guo
Journal: Circulation Research (2025)
Single-cell microbiota phenotyping reveals distinct disease and therapy-associated signatures in Crohn’s disease
Authors: Lisa Budzinski, Gi-Ung Kang, René Riedel, Toni Sempert, Leonie Lietz, René Maier, Janine Büttner, Bettina Bochow, Marcell T. Tordai, Aayushi Shah, Amro Abbas, Tanisha Momtaz, Jannike L. Krause, Robin Kempkens, Katrin Lehman, Gitta A. Heinz, Anne E. Benken, Stefanie Bartsch, Kathleen Necke, Ute Hoffmann, Mir-Farzin Mashreghi, Robert Biesen, Tilmann Kallinich, Tobias Alexander, Bosse Jessen, Carl Weidinger, Britta Siegmund, Andreas Radbruch, Anja Schirbel, Benjamin Moser, Hyun-Dong Chang
Journal: Gut Microbes (2025)

IgA-coated fractions of the intestinal microbiota of Crohn's disease (CD) patients have been shown to contain taxa that hallmark the compositional dysbiosis in CD microbiomes. However, the correlation between other cellular properties of intestinal bacteria and disease has not been explored further, especially for features that are not directly driven by the host immune-system, e.g. the expression of surface sugars by bacteria. By sorting and sequencing IgA-coated and lectin-stained fractions from CD patients microbiota and healthy controls, we found that lectin-stained bacteria were distinct from IgA-coated bacteria, but still displayed specific differences between CD and healthy controls. To exploit the discriminatory potential of both, immunoglobulin coated bacteria and the altered surface sugar expression of bacteria in CD, we developed a multiplexed single cell-based analysis approach for intestinal microbiota. By multi-parameter microbiota flow cytometry (mMFC) we characterized the intestinal microbiota of 55 CD patients and 44 healthy controls for 11-parameters in total, comprising host-immunoglobulin coating and the presence of distinct surface sugar moieties. The data were analyzed by machine-learning to assess disease-specific marker patterns in the microbiota phenotype. mMFC captured detailed characteristics of CD microbiota and identified patterns to classify CD patients. In addition, we identified phenotypic signatures in the CD microbiota which not only reflected remission after 6 weeks of anti-TNF treatment, but were also able to predict remission before the start of an adalimumab treatment course in a pilot study. We here present the proof-of-concept demonstrating that multi-parameter single-cell bacterial phenotyping by mMFC could be a novel tool with high translational potential to expand current microbiome investigations by phenotyping of bacteria to identify disease- and therapy-associated cellular alterations and to reveal novel target properties of bacteria for functional assays and therapeutic approaches.