tbuckley/cabot-search huggingface dataset:
3D‐printed Engineered Trachea Functionalized by Diverse Extracellular Matrix Particles
Authors: Weikang Lin, Hai Tang, Runfeng Cao, Jiafei Chen, Long Wang, Yunlang She, Lei Zhang, Yi Chen, Ziyin Pan, Qingfeng Bai, Deping Zhao, Minglei Yang, Guofang Zhao, Weiyan Sun, Dong Xie, Chang Chen
Journal: Advanced Healthcare Materials (2025)

Abstract It remains a significant challenge to construct a tracheal substitute with both a native‐like structure and multiple essential physiological functions. In this study, a combination of 3D printing techniques and a modular strategy is employed to fabricate an engineered trachea, in which the decellularized extracellular matrix particles (DEPs) from diverse sources determined specific regenerative environments in different spatial regions. Costal cartilage‐derived DEPs are integrated within the cartilage rings of the engineered trachea. They effectively activated chondrocytes to secrete specific matrix proteins and develop into mature cartilage with a natural pattern of collagen deposition, which provided sufficient mechanical properties to maintain tracheal ventilation. Lung‐derived DEPsare strategically placed between the cartilage rings, and are able to accelerate endothelial cell migration to form a transmural vessel network. Additionally, lung‐derived DEPs exhibited a great capability to recruit macrophages and facilitate their polarization, which is beneficial for tissue regeneration. The engineered trachea underwent heterotopic vascularization and utilized for long‐segmental trachea replacement in a rabbit model, demonstrating a satisfactory physiological function. Through DEP functionalization, the tracheal substitute developed a native‐like complex structure with adequate mechanical supply, abundant blood perfusion, and favorable immune conditions, demonstrating significant clinical potential for patients requiring tracheal reconstruction.
4D printed Stimuli Responsive Scaffold with Tissue Expansion and Photothermal Tumor Ablation Property for Post‐Mastectomy Breast Reconstruction
Authors: Muran Zhou, Guo Zhang, Jinfei Hou, Lifeng Chen, Chao Luo, Shan Mou, Ke Guo, Rongrong Wang, Lingyun Xiong, Zhenxing Wang, Nengqiang Guo, Jiaming Sun
Journal: Advanced Healthcare Materials (2025)

Abstract Breast tissue engineering is a promising alternative to post‐mastectomy breast reconstruction. However, the high relapse rate (about 20%) of this malignant tumor negatively affects its long‐term prognosis. Moreover, the shortage of recipient site volume often hampers the reconstruction of large‐sized breast. Here, this work reports on the additive manufacturing of a novel breast tissue engineering scaffold with photothermal shape memory and tumor ablation properties to solve the aforementioned issues. Graphene nanosheets (GN) are used to functionalize the surface of 3D‐printed polyurethane scaffolds (GfPU) without compromising the biocompatibility of polyurethane. Subsequently, the GfPU scaffolds are remodeled into temporary shapes using established procedures. After exposure to an 808 nm laser, the GfPU scaffolds are heated to 47.1 °C, and they converted from a temporary shape to their original shape in a light intensity‐dependent manner. With an accurate structural design, the shape memory scaffold could act as a stimuli‐responsive tissue expander in vivo. Meanwhile, the laser‐irradiated GfPU could specifically ablate multiple breast cancer cell lines in vitro and suppress both tumor growth and tumor recurrence in vivo. This dual‐functional scaffold has the potential to be used in breast tissue engineering applications to optimize both the oncological and reconstructive effect.
Systolic Blood Pressure and Cardiovascular Mortality in U.S. Adults Aged 80+ Taking Antihypertensive Medications
Authors: Huanhuan Yang, Chenxi Huang, Mitsuaki Sawano, Jeph Herrin, Guochong Chen, Zhihui Li, Erica S Spatz, Harlan M Krumholz, Yuan Lu
Journal: Journal of the American College of Cardiology (2025)
A special short-wing petal faba genome and genetic dissection of floral and yield-related traits accelerate breeding and improvement of faba bean
Authors: Rong Liu, Chaoqin Hu, Dan Gao, Mengwei Li, Xingxing Yuan, Liyang Chen, Qin Shu, Zonghe Wang, Xin Yang, Zhengming Dai, Haitian Yu, Feng Yang, Aiqing Zheng, Meiyuan Lv, Vanika Garg, Chengzhi Jiao, Hongyan Zhang, Wanwei Hou, Changcai Teng, Xianli Zhou, Chengzhang Du, Chao Xiang, Dongxu Xu, Yongsheng Tang, Annapurna Chitikineni, Yinmei Duan, Fouad Maalouf, Shiv Kumar Agrawal, Libin Wei, Na Zhao, Rutwik Barmukh, Xiang Li, Dong Wang, Hanfeng Ding, Yujiao Liu, Xin Chen, Rajeev K. Varshney, Yuhua He, Xuxiao Zong, Tao Yang
Journal: Genome biology (2025)

A comprehensive study of the genome and genetics of superior germplasms is fundamental for crop improvement. As a widely adapted protein crop with high yield potential, the improvement in breeding and development of the seeds industry of faba bean have been greatly hindered by its giant genome size and high outcrossing rate. To fully explore the genomic diversity and genetic basis of important agronomic traits, we first generate a de novo genome assembly and perform annotation of a special short-wing petal faba bean germplasm (VF8137) exhibiting a low outcrossing rate. Comparative genome and pan-genome analyses reveal the genome evolution characteristics and unique pan-genes among the three different faba bean genomes. In addition, the genome diversity of 558 accessions of faba bean germplasm reveals three distinct genetic groups and remarkable genetic differences between the southern and northern germplasms. Genome-wide association analysis identifies several candidate genes associated with adaptation- and yield-related traits. We also identify one candidate gene related to short-wing petals by combining quantitative trait locus mapping and bulked segregant analysis. We further elucidate its function through multiple lines of evidence from functional annotation, sequence variation, expression differences, and protein structure variation. Our study provides new insights into the genome evolution of Leguminosae and the genomic diversity of faba bean. It offers valuable genomic and genetic resources for breeding and improvement of faba bean.
Visualization of P2X7 Receptors in Living Human Gliomas: an 18F-GSK1482160 PET Imaging and Neuropatholopy Study
Authors: Weiyan Zhou, Qi Yue, Yifan Yuan, Qi Huang, Kun He, Tao Hua, Junbin Han, Yingfang He, Yihui Guan, Liang Chen, Fang Xie, Ying Mao
Journal: Clinical Cancer Research (2025)

Abstract Purpose: PET imaging targeting the purinergic receptor subtype 7 (P2X7R) is of high interest for assessing glioma microenvironment. No reports were published regarding the P2X7R imaging in gliomas. Therefore, we compared the uptake characteristics of 18F-GSK1482160, a novel P2X7R ligand, to conventional 11C-MET PET and contrast-enhanced MRI in patients with gliomas. Experimental Design: Thirteen glioma patients (8 grade II, 5 grade III/IV) at initial diagnosis were consecutively included and underwent 18F-GSK1482160 PET, 11C-MET PET and MRI. The semi-quantitative analyses were performed in both 18F-GSK1482160 and 11C-MET PET images. Dynamic 18F-GSK1482160 PET analysis (n=8) generated parametric maps of binding potential (BPND) for the lesions. The tumor tissue was quantitatively assessed for P2X7R expression and infiltration of glioma associated microglia/macrophages (GAMs). Results: The multilinear reference tissue model (MRTM) was sufficient for quantifying 18F-GSK1482160. The SUVRmean for duration of 50-70min correlated best to mean BPND in the dynamic scan analysis. A strong linear relationship between the uptakes of 18F-GSK1482160 and 11C-MET was observed. The two tracers showed distinct spatial distribution by metabolic volume comparison, but were both associated with tumor grade and lesion contrast-enhancement status. IDH-wildtype gilomas tended to have higher tracer uptake for both tracers without reaching the level of significance. P2X7R in gliomas was expressed predominately by GAMs, and its expression exhibited positive correlation with uptake of 18F-GSK1482160 (r=0.7783, p=0.0029) in the tumors. Conclusions: The first-in-man study of P2X7R-PET demonstrated PET with 18F-GSK1482160 and 11C-MET provides complementary information characterizing tumor heterogeneity and the cellular composition of the microenvironment in untreated gliomas.
The dynamically evolving cell states and ecosystem from benign nevi to melanoma
Authors: Xin Li, Xiyuan Zhang, Shuang Zhao, Shiyao Pei, Jie Sun, Liang Dong, Xu Pan, Wenhua Wang, Hao Liu, Yaoxuan Huang, Teng Liu, Jinhai Deng, Chunlan Hu, Chao Lv, Juan Su, Mingzhu Yin, Xiang Chen
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Approximately 30% of non-chronically sun-damaged melanomas originate from nevi, yet the dynamic changes and crucial mechanisms driving the transition from benign nevi to melanoma remain elusive. Experimental Design: Here, we performed single-cell transcriptome sequencing on multiple paired tissue sites from 5 patients diagnosed with melanoma arising in congenital melanocytic nevi (CMN), identifying four distinct states of melanocyte subpopulations during the progression from nevi to melanoma, characterized by dynamic changes in their functions and regulatory pathways. Results: In the nevi state, interferon regulatory factor 1 (IRF1) was specifically upregulated in melanocytes, fibroblasts, and endothelial cells (ECs), potentially activating immune surveillance in the microenvironment. Conversely, the critical inhibitory checkpoint HLA-E for NK cells exhibited high expression in a cluster of malignant melanocytes and fibroblasts enriched in melanoma. This interaction with ligands expressed in NK cells could potentially serve as a key factor leading to immune evasion. In malignant melanoma samples, we detected high expression of Midkine (MDK) in melanocytes. It is a pivotal factor that facilitates melanoma invasion and malignant transformation, potentially through interaction with ECs to stimulate angiogenesis. The targets identified in our study are crucial factors in detecting the malignant transformation of nevi. Ultimately, we developed a malignant progression model capable of predicting patient prognosis and malignant progression status using bulk RNA sequencing (RNA-seq) data. Conclusions: Our study provides a high-resolution atlas of the malignant transformation of melanoma from nevi and highlights potential targets for further investigation.
PGV001, a multi-peptide personalized neoantigen vaccine platform: Phase I study in patients with solid and hematological malignancies in the adjuvant setting
Authors: Mansi Saxena, Thomas U. Marron, Julia Kodysh, John P. Finnigan, Sayali Onkar, Anna Kaminska, Kevin Tuballes, Ruiwei Guo, Rachel Lubong. Sabado, Marcia Meseck, Timothy J. O'Donnell, Robert P. Sebra, Samir Parekh, Matthew D. Galsky, Ana Blasquez, Gustavo Gimenez, Mesude Bicak, Cansu Cimen Bozkus, Daniela Delbeau-Zagelbaum, Denise Rodriguez, Ana Acuna-Villaorduna, Krzysztof J. Misiukiewicz, Marshall R. Posner, Brett A. Miles, Hanna Y. Irie, Amy Tiersten, Deborah B. Doroshow, Andrea Wolf, John Mandeli, Rachel Brody, Andres M. Salazar, Sacha Gnjatic, Jeff Hammerbacher, Eric Schadt, Philip Friedlander, Alexander Rubinsteyn, Nina Bhardwaj
Journal: Cancer Discovery (2025)

Abstract Immunotherapies like immune checkpoint inhibitors (ICIs) have changed the standard of care for cancer patients, often leading to durable responses. However, many patients remain or become refractory to ICIs owing to factors such as a lack of primed neoantigen-reactive T cells. We developed a peptide-based vaccination platform that utilizes fully personalized genome vaccines (PGV) and targets neoantigens predicted by our OpenVax computational pipeline. Here we report results from PGV001 study (NCT02721043) targeting up to 10 neoantigens, administered in the adjuvant setting to patients with both solid and hematological malignancies who have high risk of recurrence. Our data indicates that PGV001 is feasible and safe, with 13 out of 14 enrolled patients receiving the vaccine and 11 completing the treatment. 100% of vaccinated patients developed targeted T cell and B cell responses highlighting the capacity of OpenVax to predict immunogenic neoantigens and the potential of PGV001 for safely inducing targeted immunity.
A phase I dose escalation and cohort expansion study of CB307, a trispecific Humabody® against PSMA, CD137, and albumin in patients with PSMA-positive solid tumors
Authors: Johann S. de Bono, Anja Williams, Ignacio Melero, Anuradha Jayaram, Jessica E. Hawley, Bernard Doger de Speville, Irene Moreno, Daniel Castellano, Òscar Reig, Daan G. Knapen, Georgia Anguera, Julia Martinez, Eelke Gort, Maja de Jonge, Jose Luis Alonso-Romero, Valentina Boni, Jose Luis Perez-Gracia, Alejandro Falcon, Derk Jan de Groot, Andrew J. Pierce, Andrew J. Leishman, Peter Lloyd, Phillip D. Bartlett, Philip Bland-Ward, Albert Chau, Minjung Song, Kevin Duffy, Kenji Hashimoto, Elisabeth de Vries
Journal: Clinical Cancer Research (2025)

Abstract Background:CB307 is a tri-specific variable heavy-chain antibody fragment against PSMA, CD137, and human serum albumin. It is designed to mitigate hepatotoxicity by activating T cells only in the PSMA-positive tumors and to increase drug half-life by albumin binding. This Phase I study investigated the safety and tolerability of CB307 as monotherapy or with pembrolizumab.Methods: Patients who were heavily pretreated with PSMA-positive solid tumors were enrolled in the dose-escalation phase of CB307 monotherapy. Additional safety and efficacy of CB307 were assessed in CB307 monotherapy expansion cohort and in combination with pembrolizumab.Results:CB307 was administered in 75 patients. CB307 was given Q1W as monotherapy (N = 50) or in combination with pembrolizumab (N = 25). Two dose-limiting toxicities (DLTs, grade 3 transient transaminitis) were observed. A total of three grade 3 transaminitis events (one in the monotherapy cohort and two in the combination cohort) were observed, and none involved bilirubin elevation. Durable RECIST responses were observed in two patients with mCRPC enrolled in 800 mg CB307 monotherapy and in one patient in the combination cohort (overall response rate: 11.1% and 7.1%, respectively). A disease control rate (DCR) of 50% was observed in patients enrolled in the 800 mg CB307 monotherapy cohort and 42.9% in the combination cohort. In a post-hoc analysis, the response was numerically better in patients who had not received chemotherapy in the 6 months prior to starting CB307 (ORR = 20%, DCR 60% vs. ORR 0%, DCR 37.5%). CB307 induces cytotoxic cell expansion in tumors and PD-L1 expression.
Microbiota-produced immune regulatory bile acid metabolites control central nervous system autoimmunity
Authors: Martina Antonini Cencicchio, Federico Montini, Vittoria Palmieri, Luca Massimino, Marta Lo Conte, Annamaria Finardi, Alessandra Mandelli, Francesco Asnicar, Radmila Pavlovic, Denise Drago, Federica Ungaro, Annapaola Andolfo, Nicola Segata, Vittorio Martinelli, Roberto Furlan, Marika Falcone
Journal: Cell Reports Medicine (2025)
<i>LCORL</i> and <i>STC2</i> Variants Increase Body Size and Growth Rate in Cattle and Other Animals
Authors: Fengting Bai, Yudong Cai, Min Qi, Chen Liang, Linqian Pan, Yayi Liu, Yanshuai Feng, Xuesha Cao, Qimeng Yang, Gang Ren, Shaohua Jiao, Siqi Gao, Meixuan Lu, Xihong Wang, Rasmus Heller, Johannes A Lenstra, Yu Jiang
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstracts Natural variants can significantly improve growth traits in livestock and serve as safe targets for gene editing, thus being applied in animal molecular designed breeding. However, such safe and large-effect mutations are severely lacking. Using ancestral recombination graphs, we investigated recent selection signatures in beef cattle breeds, pinpointing sweep-driving variants in the LCORL and STC2 loci with notable effects on body size and growth rate. The ACT-to-A frameshift mutation in LCORL occurs mainly in central-European cattle, and stimulates growth. Remarkably, convergent truncating mutations were also found in commercial breeds of sheep, goats, pigs, horses, dogs, rabbits, and chickens. In STC2 gene, we identified a missense mutation (A60P) located within the conserved region across vertebrates. We validated the two natural mutations in gene-edited mouse models, where both variants in homozygous carriers significantly increase the average weight by 11%. Our findings provide insights into a seemingly recurring gene target of body size enhancing truncating mutations across domesticated species, and offer valuable targets for gene editing-based breeding in animals.
Harnessing the Foundation Model for Exploration of Single-cell Expression Atlases in Plants
Authors: Guangshuo Cao, Haoyu Chao, Wenqi Zheng, Yangming Lan, Kaiyan Lu, Yueyi Wang, Ming Chen, He Zhang, Dijun Chen
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract Single-cell RNA sequencing (scRNA-seq) provides unprecedented insights into plant cellular diversity by enabling high-resolution analyses of gene expression at the single-cell level. However, the complexity of scRNA-seq data, including challenges in batch integration, cell type annotation, and gene regulatory network (GRN) inference, demands advanced computational approaches. To address these challenges, we developed scPlantLLM, a Transformer model trained on millions of plant single-cell data points. Using a sequential pretraining strategy incorporating masked language modeling and cell type annotation tasks, scPlantLLM generates robust and interpretable single-cell data embeddings. When applied to Arabidopsis thaliana datasets, scPlantLLM excels in clustering, cell type annotation, and batch integration, achieving an accuracy of up to 0.91 in zero-shot learning scenarios. Furthermore, the model demonstrates an ability to identify biologically meaningful GRNs and subtle cellular subtypes, showcasing its potential to advance plant biology research. Compared to traditional methods, scPlantLLM outperforms in key metrics such as adjusted rand index (ARI), normalized mutual information (NMI) and silhouette score (SIL), highlighting its superior clustering accuracy and biological relevance. scPlantLLM represents a foundational model for exploring plant single-cell expression atlases, offering unprecedented capabilities to resolve cellular heterogeneity and regulatory dynamics across diverse plant systems. The code used in this study is available at https://github.com/compbioNJU/scPlantLLM.
The proto-oncogenic miR-106a-363 cluster enhances adverse risk acute myeloid leukemia through mitochondrial activation
Authors: Nadine Sperb, Irina A. Maksakova, Leo Escano, Libin Abraham, Liam MacPhee, Ariene Cabantog, Dexter Kim, Mansen Yu, Kathrin Krowiorz, Junbum Im, Sarah Grasedieck, Nicole Pochert, Christoph Ruess, Reinhild Rösler, Stephane Flibotte, Tobias Maetzig, Enrico Calzia, Lars Palmqvist, Sebastian Wiese, Linda Fogelstrand, Michael R. Gold, Arefeh Rouhi, Florian Kuchenbauer
Journal: Leukemia (2025)
Belly Dancer’s Dyskinesia Following Acute Corpus Callosum Infarction
Authors: Juntao Yin, Yuqing Wei, Lixin Guo
Journal: JAMA Neurology (2025)

This case report describes a patient with spontaneous, arrhythmic, spasmodic contractions of the abdominal muscles whose imaging confirmed involvement of the genu, body, and splenium of the corpus callosum.
Statin Use and Risk of Hepatocellular Carcinoma and Liver Fibrosis in Chronic Liver Disease
Authors: Jonggi Choi, Vy H. Nguyen, Eric Przybyszewski, Jiunn Song, Allison Carroll, Megan Michta, Erik Almazan, Tracey G. Simon, Raymond T. Chung
Journal: JAMA Internal Medicine (2025)

Importance Statins may lower the risk of hepatocellular carcinoma (HCC) by mitigating liver fibrosis progression. Objective To evaluate the association between statin use and the risk of HCC and hepatic decompensation, with an emphasis on liver fibrosis progression, among adult patients with chronic liver disease (CLD). Design, Setting, and Participants This cohort study used data from the Research Patient Data Registry from 2000 to 2023 on patients 40 years or older with CLD and a baseline Fibrosis-4 (FIB-4) score of 1.3 or higher. Participants were grouped into statin users and nonusers. Data analysis was conducted from August 5, 2024, to January 3, 2025. Exposures Statin use. Main Outcomes and Measures Outcomes included 10-year cumulative incidence of HCC and hepatic decompensation as well as transitions in liver fibrosis risk categories based on FIB-4 scores. Statin use was defined as exposure to a cumulative defined daily dose (cDDD) of 30 or more. Fibrosis progression was assessed through FIB-4 group transitions (low, intermediate, and high) over time. Outcomes were analyzed using adjusted subhazard ratio (aSHR) and trends in serial FIB-4 scores. Results The analysis included 16 501 participants (mean [SD] age, 59.7 [11.0] years; 6750 females [40.9%] and 9751 males [59.1%]) with CLD, including 3610 statin users and 12 891 nonusers. Statin users exhibited a significantly lower 10-year cumulative incidence of HCC (3.8% vs 8.0.%; risk difference, −4.2%; 95% CI, −5.3 to −3.1%) and hepatic decompensation (10.6% vs 19.5%; risk difference, −9.0%; 95% CI, −10.6 to −7.3) compared with nonusers. The aSHR was 0.67 (95% CI, 0.59 to 0.76) for HCC and 0.78 (95% CI, 0.67 to 0.91) for hepatic decompensation. Exposure to lipophilic statins and duration of statin use (≥600 cDDDs) were associated with further reductions in HCC and hepatic decompensation risks. Among 7038 patients with serial FIB-4 data, patients with intermediate baseline FIB-4 scores, 14.7% (95% CI, 13.0% to 16.6%) of statin users transitioned to the high group compared with 20.0% (95% CI, 18.6% to 21.5%) of nonusers. For patients with high baseline FIB-4 scores, 31.8% (95% CI, 28.0% to 35.9%) of statin users transitioned to the intermediate group and 7.0% (95% CI, 5.2% to 9.6%) transitioned to the low-risk group, compared to 18.8% (95% CI, 17.2% to 20.6%) and 4.3% (95% CI, 3.5% to 5.2%) of nonusers, respectively ( P &amp;amp;lt; .001). Conclusions and Relevance This cohort study found that statin use was associated with a reduced risk of HCC and hepatic decompensation in patients with CLD, as well as improved FIB-4 group transitions over time. These findings provide support for the potential role of statins in prevention of HCC and liver disease progression.
Mailed Fecal Immunochemical Tests and Patient Navigation to Increase Colon Cancer Screening in Rural Populations
Authors: Michael Dougherty
Journal: JAMA Network Open (2025)

Gloria D. Coronado, PhD; Amanda F. Petrik, PhD; Michael C. Leo, PhD; Jennifer Coury, MALS; Robert Durr, MPH; Brittany Badicke, MPH; Jamie H. Thompson, MPH; Anna C. Edelmann, MScN; Melinda M. Davis, PhD
Financial Incentives to Promote Sustained Improvements in Child Health
Authors: Davene R. Wright, Faisal S. Malik, Seema K. Shah
Journal: JAMA Pediatrics (2025)

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