tbuckley/cabot-search huggingface dataset:
A Phase II Multi-Center Trial of Trabectedin in Combination with Olaparib in Patients with Advanced Unresectable or Metastatic Sarcoma
Authors: Brittany L. Siontis, John D. Rice, Scott M. Schuetze, Douglas Rottmann, Christina V. Angeles, Amanda K. Fox, Laura E. Zyczynski, Salim Hayek, Steven I. Robinson, Scott H. Okuno, Thanh P. Ho, Rashmi Chugh
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Soft tissue sarcoma (STS) are rare malignancies with poor prognosis and limited systemic treatment options. We conducted a phase II study to assess the efficacy and safety of trabectedin and olaparib in patients with advanced disease. Patients and Methods: Patients with STS who received ≥ 1 prior therapy were recruited into two cohorts. Cohort 1 included leiomyosarcoma and liposarcoma; Cohort 2 included other histologies. All patients received trabectedin (1.1 mg/m2 24-hour infusion every 21 days) and olaparib (150 mg BID continuously). The study was conducted using a Simon Minimax two-stage design with a primary endpoint of objective response rate per RECIST 1.1. Results: Twenty-nine patients enrolled (Cohort 1:16, Cohort 2:13); one patient in Cohort 2 was not evaluable. There were no confirmed objective responses in Cohort 1; best response was stable disease in 12 patients (75%) and progressive disease in 4 (25%). Two partial responses were observed in Cohort 2 (n=12). The most common adverse events were fatigue (75%), neutropenia (75%), anemia (68%), and thrombocytopenia (68%). Median progression free survival and overall survival for all patients was 3.5 (95% CI 3.3-8.2) and 13.2 months (95% CI 10.3-20.9), respectively. Next generation sequencing of 17 tumors revealed multiple abnormalities, most commonly in TP53, RB1, and ATRX. Conclusions: Trabectedin plus olaparib conferred high rates of toxicity and failed to demonstrate objective responses in leiomyosarcoma and liposarcoma. Preliminary evidence of clinical benefit in two patients in cohort 2 suggests potential value of either or both drugs in other sarcomas.
Pre-existing epigenetic state and differential NF-κB activation shape type 2 immune cell responses
Authors: Vincent Guichard, Felipe Batista Leão, Jingyao Zhao, Yingyu Zhang, Takamasa Ito, Simon Shirley, Thomas S Postler, Ruxiao Tian, Yuefeng Huang, Sankar Ghosh
Journal: Immunity (2025)
Genomic Profiling in Patients with Endometrial Cancer by Deep Sequencing of Vaginal Swabs and Plasma
Authors: Namsoo Kim, Yoo-Na Kim, Kyunglim Lee, Eunhyang Park, Yong Jae Lee, Eunha Baek, Seungki Min, Jihyang Park, Zisun Choi, Saeam Shin, Sang Wun Kim, Sunghoon Kim, Jong Rak Choi, Seung-Tae Lee, Jung-Yun Lee
Journal: Clinical Cancer Research (2025)

Abstract Introduction: Endometrial cancer is a common gynecologic malignancy lacks effective non-invasive screening tools, as traditional approaches rely on invasive biopsies. In this large prospective study, we evaluated a novel approach combining vaginal swab DNA and plasma-based circulating tumor DNA (ctDNA) for genomic profiling to provide a comprehensive framework for diagnosis, prognosis, and disease monitoring. Materials and Methods: Adult patients with diverse stages of endometrial cancer, pre-neoplastic disease, and benign endometrial conditions were prospectively recruited over two years. Paired vaginal swab DNA and plasma-based ctDNA were collected pre-operatively, and additional plasma samples were obtained multiple time points post-operatively. Deep next-generation sequencing targeting 101 genes was performed, achieving an average depth exceeding 40,000x. Results: A total of 191 patients contributed 388 samples. Vaginal swab DNA demonstrated 77.7% sensitivity and 96.6% specificity. PTEN mutations were associated with favorable prognosis (hazard ratio: 0.27; 95% CI: 0.092-0.77) and TP53 mutations were associated with poor prognosis (hazard ratio: 3.7; 95% CI: 1.4-10). A novel classification system based on the mutational profile of PTEN/TP53 identified distinct prognostic groups. Plasma-based ctDNA was significantly associated with stage, lymphovascular invasion, and prognosis (p &amp;lt; 0.01 for all). Patients with pre-operative positive plasma-based ctDNA results exhibited poorer outcomes (p &amp;lt; 0.01), whereas post-operative positive ctDNA enabled early detection of recurrence. Discussion: These two non-invasive methods have distinct, complementary roles in the management of endometrial cancer. Vaginal swab DNA and novel PTEN/TP53-based classification have distinct prognostic advantages over existing frameworks. Plasma-based ctDNA provides dynamic insights into recurrence risk and disease progression.
DNGR-1 regulates proliferation and migration of bone marrow dendritic cell progenitors
Authors: Ana Cardoso, Michael D. Buck, Bruno Frederico, Probir Chakravarty, Oliver Schulz, Kok Haw Jonathan Lim, Cécile Piot, Mariana Pereira da Costa, Evangelos Giampazolias, Francesca Gasparrini, Neil Rogers, Caetano Reis e Sousa
Journal: The Journal of Experimental Medicine (2025)

Conventional dendritic cells (cDCs) are sentinel cells that play a crucial role in both innate and adaptive immune responses. cDCs originate from a progenitor (pre-cDC) in the bone marrow (BM) that travels via the blood to seed peripheral tissues before locally differentiating into functional cDC1 and cDC2 cells, as part of a process known as cDCpoiesis. How cDCpoiesis is regulated and whether this affects the output of cDCs is poorly understood. In this study, we show that DNGR-1, an innate immune receptor expressed by cDC progenitors and type 1 cDCs, can regulate cDCpoiesis in mice. In a competitive chimera setting, cDC progenitors lacking DNGR-1 exhibit increased proliferation and tissue migratory potential. Compared with their WT counterparts, DNGR-1–deficient cDC progenitor cells display superior colonization of peripheral tissues but an altered distribution. These findings suggest that cDCpoiesis can be regulated in part by precursor cell-intrinsic processes driven by signals from innate immune receptors such as DNGR-1 that may respond to alterations in the BM milieu.
Human papillomavirus integration induces oncogenic host gene fusions in oropharyngeal cancers
Authors: Nusrat Khan, Keiko Akagi, Shiming Jiang, Joe Dan. Dunn, Bo Jiang, Weihong Xiao, Madison P. O'Hara, Li Shen, Qi Wang, Vakul Mohanty, Jing Wang, Sara Goodwin, Jamie L. Hutchins, Kevin R. Coombes, Jagannadha K. Sastry, David E. Symer, Maura L. Gillison
Journal: Cancer Discovery (2025)

Abstract HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host fusion genes, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites. Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of E6 and E7, thereby increasing oncoprotein abundance. We conclude that expression of HPV16 oncoproteins and host gene fusions generated from HPV integration sites can be sufficient for cancer development.
Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer
Authors: Harveer Dev, Mark Linch, Krishna Narahari, Toby Milne-Clark, Melissa Cheung, Anne Warren, Alopa Malaviya, Vincent Gnanapragasam, Tatiana Hernandez, Nicholas Bullock, Andrea Machin, Alimu Dayimu, Tamsin Robb, Elizabeth Cromwell, Alex Freeman, Elizabeth A. Harrington, Niedzika Camacho, Silvia Glont, Massimo Squatrito, Asaf Rotem, Luiza Moore, Robert Hanson, Marc Dodd, Shubha Anand, Howard Kynaston, Greg Shaw, Nimish Shah, Simon Pacey
Journal: Clinical Cancer Research (2025)

Abstract Purpose: The purpose was to investigate combined PARP and androgen inhibition in primary prostate cancer and understand the biological mechanisms underlying clinical efficacy, especially in the absence of mutations in homologous recombination (HR) repair pathways. Patients and Methods: The primary objective was to measure PARP inhibition, and the secondary objectives were to assess safety and feasibility. Participants received olaparib for 2 weeks before prostatectomy and were randomly assigned or not assigned (1:1) to degarelix. We analyzed diagnostic biopsy and radical prostatectomy samples for PARylated protein expression using IHC. Exploratory analyses included tumor gene sequencing, mutation analysis, and RNA sequencing (RNA-seq) using both bulk and single-cell RNA-seq performed on pretreatment and posttreatment tissues. Results: PARylated protein expression was significantly reduced in both cohorts, with no drug-related delays in radical prostatectomy. The gene set enrichment analysis identified distinct treatment response signatures related to olaparib in both cohorts and showed downregulation of androgen response genes after olaparib + degarelix treatment. Transcript profiling revealed an upregulation of the p53 hallmark, which was more pronounced with the combination treatment. Canonical cell-cycle progression hallmarks, including E2F targets and the G2–M checkpoint, were suppressed across all cases, correlating with a HR-deficient transcriptional signature. Single-nuclear RNA-seq indicated a greater increase in inflammatory response pathway activity within tumor epithelia after combination treatment. Conclusions: Transcriptomic analysis identified common hallmark alterations reflecting the combined impact of PARP inhibitor and androgen blockade on cell-cycle progression. We observed a shared phenotypic response to combination therapy across prostate cancers without known HR repair gene alterations. This suggests alternative mechanisms rather than antiandrogen-induced HR deficiency.
Publisher Correction: GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice
Authors: Robert M Gutgesell, Ahmed Khalil, Arkadiusz Liskiewicz, Gandhari Maity-Kumar, Aaron Novikoff, Gerald Grandl, Daniela Liskiewicz, Callum Coupland, Ezgi Karaoglu, Seun Akindehin, Russell Castelino, Fabiola Curion, Xue Liu, Cristina Garcia-Caceres, Alberto Cebrian-Serrano, Jonathan D Douros, Patrick J Knerr, Brian Finan, Richard D DiMarchi, Kyle W Sloop, Ricardo J Samms, Fabian J Theis, Matthias H Tschöp, Timo D Müller
Journal: Nature Metabolism (2025)
Efficacy and safety of varenicline and bupropion, in combination and alone, for alcohol use disorder: a randomized, double-blind, placebo-controlled multicentre trial
Authors: Bo Söderpalm, Helga Lidö, Johan Franck, Anders Håkansson, Daniel Lindqvist, Markus Heilig, Joar Guterstam, Markus Samuelson, Barbro Askerup, Cecilia Wallmark-Nilsson, Andrea de Bejczy
Journal: The Lancet Regional Health - Europe (2025)
Acid-activated mitochondria-targeting nanoprodrug for reactive oxygen species (ROS)-tolerant cancer therapy via antioxidant defense inhibition
Authors: Zihao Teng, Chen Liu, Xiangfu Du, Yuchen Guo, Zhenkun Huang, Ingya Gu, Iaohui Chen, Menghan Xiao, Shipeng Chen, Xiao-Bin Hao, Jingbo Qin, Shuaidong Huo
Journal: Journal of Controlled Release (2025)
Microbial metabolites as engines of behavioral variation across animals
Authors: Eric Siaw Ntiri, Adam Chun Nin Wong
Journal: Gut Microbes (2025)

The microbiome, especially that present in the gut, has emerged as a key modulator of animal behavior. However, the extent of its influence across species and behavioral repertoires, as well as the underlying mechanisms, remains poorly understood. Increasing evidence suggests that microbial metabolites play an important role in driving behavioral variation. In this review, we synthesize findings from vertebrates to invertebrates, spanning both model and non-model organisms, to define key groups of microbial-derived metabolites involved in modulating seven distinct behaviors: nutrition, olfaction, circadian rhythms, reproduction, locomotion, aggression, and social interactions. We discuss how these microbial metabolites interact with host chemosensory systems, neurotransmitter signaling, and epigenetic modifications to shape behavior. Additionally, we highlight critical gaps in mechanistic understanding, including the need to map additional host receptors and signaling pathways, as well as the untapped potential of microbial biosynthetic gene clusters as sources for novel bioactive compounds. Advancing these areas will enhance understanding of the microbiome's role in behavioral modulation and open new avenues for microbiome-based interventions for behavioral disorders.
3D Bioprinting of Prevascularized Bone Organoids for Rapid In Situ Cranial Bone Reconstruction
Authors: Jing Duan, Yongcong Fang, Yueming Tian, Ziyu Wang, Bin Yang, Zhuo Xiong
Journal: Advanced Healthcare Materials (2025)

Abstract Despite rapid advances in the field of bone tissue engineering, cranial bone defects of critical size remain difficult to repair due to the limited self‐regeneration capacity of the bone. Developmental engineering with mesenchymal stem cells (MSCs) aggregates has shown promise for enhanced bone regeneration; however, these MSCs aggregates require extended in vitro osteogenic induction time and lack sufficient vascularization to enable rapid in situ osteogenesis. To address these issues, a novel strategy is introduced for the large‐scale generation of prevascularized bone organoids with self‐organized vascularization and enhanced osteogenic properties by combining MSCs, human umbilical vein endothelial cells, and osteogenic microparticles. The osteogenic differentiation effects across different microparticles were systematically evaluated and identified graphene oxide as the most effective, which primarily promoted osteogenesis through the focal adhesion and PI3K/Akt pathway. Further, the prevascularized bone organoid‐laden hydrogels can be 3D printed into complex tissue constructs with high cell density and osteogenic capacity. In vivo experiments confirmed that this approach promoted rapid vascularized bone tissue formation, achieving effective in situ regeneration and repair of cranial bone defects. This innovative developmental engineering strategy provides a promising, scalable, and effective approach to bone regeneration, advancing developmental tissue engineering for therapeutic applications.
Grancalcin Hydrogel Microneedle Patches Alleviate Sepsis via Modulation of Calcium Signaling to Augment Immune Cell Phagocytosis
Authors: Peng Xiang, Mingyang Zhao, Yue He, Min Wang, Ping Yin, Tian Su
Journal: Advanced Healthcare Materials (2025)

Abstract Disorders in Ca 2+ signaling contribute to many metabolic manifestations of sepsis and are one of the driving forces underlying multiorgan failur e. Herein, a compensatory elevation in calcium‐binding protein grancalcin (GCA) levels in monocytes and macrophages of patients and mice with sepsis is observed. Gca deletion in myeloid cells displays increased inflammation and organ damage in cecal ligation and puncture‐induced sepsis. Mechanistically, GCA enhances the phagocytic function of immune cells by regulating intracellular calcium signaling. A GCA@Acrylate‐PEG‐NHS/weakly temperature‐sensitive gelatin methacrylate (GelMA) microneedle patch (GCA@NHS/GelMA‐MNPs) is designed. In vivo experiments demonstrate that this patch establishes a sustained drug release mechanism, boosts the phagocytic capacity of immune cells, and improves sepsis outcomes by restoring Ca 2+ signaling homeostasis. These findings suggest that GCA‐loaded hydrogel microneedle patches can be a promising new treatment for sepsis.
Supramolecular Porous Materials for Biomedical Applications
Authors: Xin Liu, Yevhen Fatieiev, Niveen M. Khashab
Journal: Advanced Healthcare Materials (2025)

Abstract Supramolecular porous materials have been used to tackle some major challenges in modern biomedical science, including disease therapy and diagnosis. Their inherent dynamicity, stimuli‐responsiveness, and tunable architectures enable precise control over molecular recognition, cargo encapsulation, and release kinetics. This perspective explores their potential in diagnostics and therapeutics, highlighting adaptability to physiological stimuli and precise control over structure via bottom‐up assembly. A visionary framework is proposed for programmable self‐assembly, where supramolecular building blocks form porous architectures with customized channels and responsive behavior, facilitating applications in tissue engineering, biosensing, soft robotics, and cargo recognition. Addressing challenges related to building block design, assembly conditions, and scalability will be crucial for translating these materials from bench to bedside. This perspective underscores the transformative potential of supramolecular porous materials in advancing personalized medicine and smart diagnostics.
Synthesis of Phosphorescent Carbon Dot Composite with Redshift Emission by Annealing Treatment for Bioimaging
Authors: Mengyao Chen, Yuqi Zhang, Jiajia Ren, Lin Chen, Yingying Wei, Jinglei Du, Yongzhen Yang, Xuguang Liu, Shiping Yu
Journal: Advanced Healthcare Materials (2025)

Abstract Room‐temperature phosphorescent carbon dots (RTP CDs) are promising afterglow materials applied in bioimaging owing to their long‐lived emission and biocompatibility. Achieving RTP CDs with long emission wavelengths in aqueous environments remains challenging because of the influence of surface and carbon core states of CDs on luminescence. Herein, thermally annealed solid CDs encapsulated with SiO 2 are developed in this work to obtain yellow‐green RTP CD composites (A‐CDs@SiO 2 ) with redshifted emission wavelengths. After thermal annealing, the carbonization degree of CDs increases, resulting in a redshift of their optimal phosphorescence emission wavelength from 500 to 525 nm, and the phosphorescence lifetime of CDs reaches 926.97 ms. Additionally, the optimal phosphorescence emission wavelength of A‐CDs@SiO 2 is 513 nm. SiO 2 encapsulation restricted the movement of luminescent centers, thereby extending the phosphorescence lifetime of CDs in aqueous solution to 1263.40 ms. Biological imaging experiments confirmed that the obtained A‐CDs@SiO 2 exhibited significant phosphorescence signals in mice with a phosphorescence intensity of 1.490 × 10 5 p/(s cm 2 sr), and the phosphorescence signals can still be collected after re‐excitation within 1 h. Therefore, as a bioluminescent afterglow probe, A‐CDs@SiO 2 demonstrates great potential in bioimaging.
Modeling Idiopathic Inflammatory Myopathy in the Bioinspired Muscle Tissue on Chip
Authors: Xu Zhang, Mengqian Zhao, Pengwei Deng, Haitao Liu, Hongjing Li, Xiaoqing Zhang, Daqing Wang, Jianhua Qin
Journal: Advanced Healthcare Materials (2025)

Abstract Idiopathic inflammatory myopathy (IIM) is an autoimmune disease that characterized by non‐purulent inflammation of the skeletal muscle. However, due to the limitation of study model that can recapitulate the complex pathological process of IIM, the pathogenesis of IIM is still not fully clear. This manuscript develops a vascularized muscle tissue model on a chip that allows to model the immunity mediated pathological changes in IIM. This vascularized muscle model is constructed by layer‐by‐layer assembly, which could coculture of endothelial cells, myoblasts, and monocytes in a perfusable 3D system. The vascularized muscle model exhibits good biofunctions, including muscle cells alignment and fusion, myofibers generation, force production and expression of muscular biomarkers (myosin heavy chains 1, myosin heavy chains 7, actinin alpha 2, myogenin, and Desmin). Exposure to perfusion of activated monocytes, this work observes the functional changes of muscle tissue, which referred to myofibers atrophy, inflammatory response, and downregulated expression of muscle mature marker, consistent with clinical features of IIM. This work provides a unique platform for modelling IIM and paves a promising avenue for myopathies study and drug testing.
Chondrogenic Potential of Cryopreserved Aortic Allografts: Guiding Perichondrial Regeneration in Tracheal Repair
Authors: Wan‐Ting Hung, Kuan‐Chuan Tsou, Huan‐Chieh Cho, Pei‐Shan Wu, Miao‐Hsia Lin, Sy‐Chi Chen, Hsien‐Chi Liao, Chao‐Wen Lu, Chi‐Fang Li, Wei‐Ching Su, Chih‐Hsuan Huang, Wen‐Ming Hsu, Yu‐Ten Ju, Ching‐Fu Tu, Sung‐Jan Lin, Hsao‐Hsun Hsu, Jin‐Shing Chen, Tai‐Horng Young
Journal: Advanced Healthcare Materials (2025)

Abstract Native tracheal cartilage exhibits limited regenerative capacity, making the search for suitable biomaterials for tracheal repair a persistent challenge. In this study, a non‐decellularized cryopreserved aortic allograft (CAo) is investigated as a scaffold for tracheal cartilage regeneration. Originally used to reconstruct infected aortas, CAo retains key features of a large artery—abundant elastic fibers and smooth muscle cells—and demonstrates favorable in vitro biocompatibility with chondrocytes. A trachea–CAo patch construct maintains tensile properties comparable to native trachea and tolerates normal expiratory forces. In a rabbit patch‐defect model, CAo elicits only a mild‐to‐moderate immune response that gradually subsides. Within one month of implantation, robust neocartilage formation is observed, along with angiogenesis and epithelial regeneration. Over the next 12 months, the original aortic scaffold progressively degrades, while newly formed cartilage—originating from recipient perichondrial chondroprogenitor cells—replaces it. Proteomic analyses show that CAo is enriched in cytoskeletal, adhesion, cell migration, and extracellular matrix (ECM)–related proteins, with fibroblast growth factor 2 emerging as a critical mediator of chemotaxis and chondrogenic differentiation. These findings indicate that CAo serves as both a structural and biological scaffold, activating tracheal cartilage regeneration through synergistic biocompatibility, growth factor signaling, and ECM support.
Mucosal unadjuvanted booster vaccines elicit local IgA responses by conversion of pre-existing immunity in mice
Authors: Dong-Il Kwon, Tianyang Mao, Benjamin Israelow, Keyla Santos Guedes de Sá, Huiping Dong, Akiko Iwasaki
Journal: Nature Immunology (2025)

Abstract Mucosal delivery of vaccine boosters induces robust local protective immune responses even without any adjuvants. Yet, the mechanisms by which antigen alone induces mucosal immunity in the respiratory tract remain unclear. Here we show that an intranasal booster with an unadjuvanted recombinant SARS-CoV-2 spike protein, after intramuscular immunization with 1 μg of mRNA–LNP vaccine encoding the full-length SARS-CoV-2 spike protein (Pfizer/BioNTech BNT162b2), elicits protective mucosal immunity by retooling the lymph node-resident immune cells. On intranasal boosting, peripheral lymph node-primed B cells rapidly migrated to the lung through CXCR3–CXCL9 and CXCR3–CXCL10 signaling and differentiated into antigen-specific IgA-secreting plasma cells. Memory CD4 + T cells in the lung served as a natural adjuvant for developing mucosal IgA by inducing the expression of chemokines CXCL9 and CXCL10 for memory B cell recruitment. Furthermore, CD40 and TGFβ signaling had important roles in mucosal IgA development. Repeated mucosal boosting with an unadjuvanted protein amplified anamnestic IgA responses in both the upper and the lower respiratory tracts. These findings help explain why nasal boosters do not require an adjuvant to induce robust mucosal immunity at the respiratory mucosa and can be used to design safe and effective vaccines against respiratory pathogens.
CHD1 loss reprograms SREBP2-driven cholesterol synthesis to fuel androgen-responsive growth and castration resistance in SPOP-mutated prostate tumors
Authors: Feiyu Chen, Haoyan Li, Yin Wang, Ximing Tang, Kevin Lin, Qidong Li, Chenling Meng, Wei Shi, Javier Leo, Xin Liang, Jie Zhang, Vivien Van, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Maria G Raso, Ana Aparicio, Yue Lu, Daniel E Frigo, Boyi Gan, Di Zhao
Journal: Nature Cancer (2025)