tbuckley/cabot-search huggingface dataset:
Bioelectrically Reprogramming Hydrogels Rejuvenate Vascularized Bone Regeneration in Senescence
Authors: Tianli Wu, Mingxing Ren, Yuzhou Li, Qian Yang, Kai Xiang, Fengyi Liu, Sheng Yang
Journal: Advanced Healthcare Materials (2025)

Abstract Senescent bone tissue displays a pathological imbalance characterized by decreased angiogenesis, disrupted bioelectric signaling, ion dysregulation, and reduced stem cell differentiation. Once bone defects occur, this pathological imbalance makes them difficult to repair. An innovative synergistic therapeutic strategy is utilized to reverse these pathological imbalances via a conductive hydrogel doped with magnesium ion (Mg 2+ )‐modified black phosphorus (BP). The hydrogel reprograms electrical signals, restores Mg 2+ homeostasis, reconstructs physiological signals, and promotes blood vessel regeneration in senile bone defects. The conductive hydrogel synergistically restores both the chemical and bioelectric signals within the bone microenvironment. This hydrogel increases the expression of vascular endothelial growth factor (VEGF) and VEGF receptor‐2 (VEGFR2), activates the PI3K‐AKT‐eNOS pathway, and significantly increases the angiogenic ability of vascular endothelial cells in the aged state. In addition, the conductive hydrogel normalizes calcium ion (Ca 2+ ) influx, increases the accumulation of osteogenic transcription factors in the nucleus, and promotes the osteogenic differentiation of senescent stem cells. This innovative treatment strategy restores bone‐vascular coupling in areas of senile bone defects, achieves effective vascularized bone regeneration, and has good potential for the treatment of senile bone defects.
Cancer Research in the Age of Spatial Omics: Lessons from IMAXT
Authors: Dario Bressan, Nicholas Walton, Gregory J. Hannon, Mohammad Al Sa’d, Bruno Albuquerque, Hamid Raza Ali, Martina Alini, Samuel Aparicio, Heather Ashmore, Thomas Ashmore, Vinci Au, Shankar Balasubramanian, Caroline Baril, Giorgia Battistoni, Sean Beatty, Robby Becker, Bernd Bodenmiller, Alina Bollhagen, Carla Boquetale, Edward S. Boyden, Dario Bressan, Alejandra Bruna, Marcel Burger, Carlos Caldas, Maurizio Callari, Ian Gordon Cannell, Hannah Casbolt, Nick Chornay, Nikki Coutts, Ali Dariush, Lauren Deighton, Khanh N. Dinh, Natalie Duncan, Yaniv Eyal-Lubling, Ilaria Falciatori, Jean Fan, Atefeh Fatemi, Debarati Ghosh, Carlos González-Fernández, Eduardo A. González-Solares, Wendy Greenwood, Flaminia Grimaldi, Gregory J. Hannon, Owen Harris, Suvi Harris, Nicole Hemmer, Kui Hua, Melis Irfan, Cristina Jauset, Johanna A. Joyce, Tatjana Kovačević, Laura Kuett, Russell Kunes, Aybüke Küpcü Yoldaş, Daniel Lai, Emma Laks, Hsuan Lee, Max Lee, Giulia Lerda, Yangguang Li, Jack Lovell, Yangning Lu, John Marioni, Andrew McPherson, Neil Millar, Alireza Molaeinezhad, Claire M. Mulvey, Natasha Narayanan, João C.F. Nogueira, Fiona Nugent, Ciara H. O’Flanagan, Marta Paez Ribes, Isabella Pearsall, Sarah Pearsall, Brett Pryor, Fatime Qosaj, Clare Rebbeck, Andrew Roth, Oscar M. Rueda, Teresa Ruiz, Kirsty Sawicka, Leonardo A. Sepúlveda, Sohrab P. Shah, Abigail Shea, Anubhav Sinha, Austin Smith, Leigh Smith, Simon Tavaré, Ignacio Vázquez-García, Sara Lisa Vogl, Nicholas A. Walton, Spencer S. Watson, Joanna Weselak, Tristan Whitmarsh, Sophia A. Wild, Elena Williams, Jonas Windhager, Chenglong Xia, Chee Ying Sia, Chi Zhang, Ruihan Zhang, Pu Zheng, Xiaowei Zhuang
Journal: Cancer Discovery (2025)

Summary: The Imaging and Molecular Annotation of Xenografts and Tumors Cancer Grand Challenges team was set up with the objective of developing the “next generation” of pathology and cancer research by using a combination of single-cell and spatial omics tools to produce 3D molecularly annotated maps of tumors. Its activities overlapped, and in some cases catalyzed, a spatial revolution in biology that saw new technologies being deployed to investigate the roles of tumor heterogeneity and of the tumor micro-environment. See related article by Stratton et al., p. 22 See related article by Bhattacharjee et al., p. 28 See related article by Goodwin et al., p. 34
Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs
Authors: Michael R. Stratton, Laura Humphreys, Ludmil B. Alexandrov, Allan Balmain, Paul Brennan, Peter J. Campbell, David H. Phillips
Journal: Cancer Discovery (2025)

Summary: The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases. See related article by Bressan et al., p. 16 See related article by Bhattacharjee et al., p. 28 See related article by Goodwin et al., p. 34
3D Bioprinted Head and Neck Squamous Cell Carcinoma (HNSCC) Model Using Tunicate Derived Nanocellulose (NC) Bioink
Authors: Alexya Azhakesan, Johann Kern, Ankit Mishra, Christine Selhuber‐Unkel, Annette Affolter, Paul Gatenholm, Nicole Rotter, Karen Bieback
Journal: Advanced Healthcare Materials (2025)

Abstract Head and neck squamous cell carcinoma (HNSCC) are invasive solid tumors accounting for high mortality. To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three ‐dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro. To establish long‐term HNSCC bioprinted constructs for personalized drug‐testing, this proof‐of‐principle study aims to compare two different innovative tunicate‐derived nanocellulose (NC) hydrogels against the widely used semi‐synthetic gelatin methacryloyl (GelMA). Cell lines of different tumor origin sites are printed in TEMPO and Carboxy‐NC, and GelMA in alginate (GelMAA). Both NC hydrogels show higher bioprintability than GelMAA. Carboxy‐NC supported long‐term HNSCC survival, proliferation, and maintenance of epithelial phenotype in 3D bioprinted constructs similar to GelMAA. The hydrogel microstructure revealed differences in pore size. Importantly, the established HNSCC bioprinted model allowed the testing of radiochemotherapy (RCT) both in cell lines and patient‐derived cultures. Compared to a spheroid model, the cytotoxic effects are less, better reflecting the response in patients. The proof‐of‐principle findings indicate that Carboxy‐NC is a viable alternative to gelatin‐based bioink with improved bioprintability allowing personalized drug‐testing. By adding other cell‐types of the TME, this model can be advanced to a heterotypic one.
Multiscale Mechanical Study of Proanthocyanidins for Recovering Residual Stress in Decellularized Blood Vessels
Authors: Yibo Han, Shuaiyuan Liu, Ben Omondi Ochieng, Yuanrui Gu, Lingwen Kong, Guixue Wang, Zhiyi Ye
Journal: Advanced Healthcare Materials (2025)

Abstract Decellularized artificial blood vessels prepared using physical and chemical methods often exhibit limitations, including poor mechanical performance, susceptibility to inflammation and calcification, and reduced patency. Cross‐linking techniques can enhance the stiffness, as well as anti‐inflammatory and anti‐calcification properties of decellularized vessels. However, conventional cross‐linking methods fail to effectively alleviate residual stress post‐decellularization, which significantly impacts the patency and vascular remodeling following the implantation of artificial vessels. This study enhances vascular residual stress through varied conditions of proanthocyanidin (PC) cross‐linking on decellularized vessels. Microstructural analysis and mechanical investigations across various scales of fresh, decellularized, and residual stress‐recovered vessels are performed using atomic force microscopy (AFM), scanning electron microscopy (SEM), and uniaxial tensile testing. Results demonstrate substantial alterations in the morphology of elastic and collagen fibers post‐decellularization, which remarkably resemble fresh vessels following residual stress recovery. Furthermore, both the micro‐ and macro‐mechanical characteristics of vessels post‐residual stress recovery, including Young's modulus, viscoelasticity, and adhesion, closely resemble those of fresh vessels. Finite element modeling (FEM) confirms the distribution of residual stress and its role in enhancing vascular mechanical integrity. This experimental investigation provides a theoretical foundation at both micro and macroscopic levels for the development of biomimetic blood vessels.
Oncolytic Virus Targeted Therapy for Glioma via Intravenous Delivery
Authors: Yechenxing He, Wei Li, Xiaowei Zhang, Zongqiang Cui
Journal: Advanced Healthcare Materials (2025)

Abstract Glioma, the deadly primary intracranial tumor, poses challenges in clinical treatment due to its infiltrative growth and resistance to radiation. Oncolytic virus therapy holds potential for the treatment of malignant gliomas, but its application is impeded by the requirement for intracranial injections due to the presence of blood‐brain barrier (BBB). In this study, to overcome this limitation, the study develops a nanocapsule encapsulating the recombinant oncolytic virus EV‐A71‐miR124T, enabling the treatment of glioma through intravenous administration. It is demonstrated that the nanocapsule can cross the BBB and selectively release oncolytic virus at the tumor site, resulting in targeted and specific killing of glioma cells. In mice with implanted intracranial orthotopic gliomas, intravenous administration of the nanocapsule suppresses tumor growth and significantly extends survival time. Consequently, the study establishes an effective treatment method for malignant gliomas using an oncolytic virus nanocapsule through intravenous administration. These findings provide a new strategy for oncolytic virus therapy in glioma treatment and offer perspectives for targeted therapies of other brain tumors and diseases.
Author Correction: Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial
Authors: Sant-Rayn Pasricha, Ernest Moya, Ricardo Ataíde, Glory Mzembe, Rebecca Harding, Martin N. Mwangi, Truwah Zinenani, Khic-Houy Prang, Justina Kaunda, Owen P. L. Mtambo, Maclean Vokhiwa, Gomezgani Mhango, Elisabeth Mamani-Mategula, Katherine Fielding, Ayşe Demir, Naomi Von Dinklage, Hans Verhoef, Alistair RD McLean, Lucinda Manda-Taylor, Sabine Braat, Kamija S. Phiri
Journal: Nature Medicine (2025)
CD93 blockade promotes effector T-cell infiltration and facilitates adoptive cell therapy in solid tumors
Authors: Yi Sun, Elliott Yee, Yuki Fujiwara, Kaitlyn Dickinson, Yujie Guo, Zhiwei Sun, Junyi Hu, Eduardo Davila, Richard D Schulick, Yuwen Zhu
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Adaptive cellular therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has been successful in the treatment of hemopoietic malignancies. However, poor trafficking of administered effector T cells to the tumor poses a great hurdle for this otherwise powerful therapeutic approach in solid cancers. Our previous study revealed that targeting CD93 normalizes tumor vascular functions to improve immune checkpoint blockade therapy. The objective of this study is to evaluate whether CD93 blockade improves ACT in solid cancers. Methods Monoclonal antibodies (mAbs) against CD93 or IGFBP7 were administered in implanted mouse melanoma models to assess the effect of CD93 blockade on ACT. Different sources of effector T cells were used, including pre-activated CD8+OT-1, pmel-1 transgenic T cells, and CAR-T cells. Rip-OVA and Rip-TAG-OVA transgenic mice were used to evaluate the selective impact of CD93 blockade on effector T-cell infiltration in tumors. For mechanistic studies, vascular maturation was determined by immunofluorescent staining and flow cytometry was performed to examine tumor-infiltrating T lymphocytes. Neutralizing mAbs against adhesion molecules ICAM1 and VCAM1 were infused to assess their involvement. Results Blockade of the CD93 pathway increases the expression of adhesion molecules on tumor vasculature to improve effector T-cell infiltration and function. T-cell transfer and CD93 blockade synergistically improve tumor vascular maturation, as well as inhibit tumor progression. Anti-CD93 selectively promotes effector T-cell infiltration in a tumorous setting where the CD93 pathway is upregulated. In a solid mouse tumor model, blockade of the CD93 pathway improves CAR-T therapy. Conclusions CD93 blockade normalizes tumor vasculature leading to improved effector T-cell infiltration and function in solid cancers. Our study advocates the application of CD93 blockade for ACT in solid cancers.
ZNFX1 functions as a master regulator of epigenetically induced pathogen mimicry and inflammasome signaling in cancer
Authors: Lora Stojanovic, Rachel Abbotts, Kaushelendra Tripathi, Collin M. Coon, Saranya Rajendran, Elnaz Abbasi Farid, Galen Hostetter, Joseph W. Guarnieri, Douglas C. Wallace, Sheng Liu, Jun Wan, Gennaro Calendo, Rebecca Marker, Zahra Gohari, Mohammed M.A. Inayatullah, Vijay K. Tiwari, Tanjina Kader, Sandro Santagata, Ronny Drapkin, Stefan Kommoss, Jacobus Pfisterer, Gottfried E. Konecny, Ryan Coopergard, Jean-Pierre J. Issa, Boris J.N. Winterhoff, Michael J. Topper, George E. Sandusky, Kathy D. Miller, Stephen B. Baylin, Kenneth P. Nephew, Feyruz V. Rassool
Journal: Cancer Research (2025)

Abstract DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling. Loss of ZNFX1 in ovarian cancer cells promoted proliferation and spheroid formation in vitro and tumor growth in vivo. In patient ovarian cancer databases, expression of ZNFX1 was elevated in advanced stage disease, and ZNFX1 expression alone significantly correlated with an increase in overall survival in a phase 3 trial for therapy-resistant ovarian cancer patients receiving bevacizumab in combination with chemotherapy. RNA-sequencing revealed an association between inflammasome signaling through ZNFX1 and abnormal vasculogenesis. Together, this study identified that ZNFX1 as a tumor suppressor that controls PMR signaling through mitochondria and may serve as a biomarker to facilitate personalized therapy in ovarian cancer patients.
Corneal first aid lens: Collagen-based hydrogels loading aFGF as contact lens for treating corneal injuries
Authors: Anqi Ye, Hao Mei, Zheng Zhang, Fuqiang Song, Linyuan Jiang, Ting Huang, Ping Li, Siting Du, Yanzhen Feng, Tianyao Jiang, Fenzan Wu, Li Cheng, Jia Qu, Jian Xiao
Journal: Journal of Controlled Release (2025)
Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency
Authors: Shuhong Sun, Chao Wang, Junyan Hu, Pei Zhao, Xi Wang, William E. Balch
Journal: Cell Reports Medicine (2025)

Highlights•HTS discovers nutraceutical compounds MPTC and PEITC that restore function in AATD•MPTC and PEITC regulate cellular redoxstasis to restore function in AATD through PDIA4•GP-SCV machine learning captures residue-by-residue responses of AAT to MPTC/PEITC•GP-SCV provides an atomic-resolution description of nutraceutical regulation in AATDSummaryAlpha-1 antitrypsin (AAT) deficiency (AATD) is a monogenic disease caused by misfolding of AAT variants resulting in gain-of-toxic aggregation in the liver and loss of monomer activity in the lung leading to chronic obstructive pulmonary disease (COPD). Using high-throughput screening, we discovered a bioactive natural product, phenethyl isothiocyanate (PEITC), highly enriched in cruciferous vegetables, including watercress and broccoli, which improves the level of monomer secretion and neutrophil elastase (NE) inhibitory activity of AAT-Z through the endoplasmic reticulum (ER) redox sensor protein disulfide isomerase (PDI) A4 (PDIA4). The intracellular polymer burden of AAT-Z can be managed by combination treatment of PEITC and an autophagy activator. Using Gaussian process (GP)-based spatial covariance (SCV) (GP-SCV) machine learning to map on a residue-by-residue basis at atomic resolution all variants in the worldwide AATD clinical population, we reveal a global rescue of monomer secretion and NE inhibitory activity for most variants triggering disease. We present a proof of concept that GP-SCV mapping of restoration of AAT variant function serves as a standard model to discover natural products such as the anti-oxidant PEITC that could potentially impact the redox/inflammatory environment of the ER to provide a nutraceutical approach to help minimize disease in AATD patients.Graphical abstract
Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface
Authors: Ellen G Avery, Lea-Maxie Haag, Victoria McParland, Sarah M Kedziora, Gabriel J Zigra, Daniela S Valdes, Marieluise Kirchner, Oliver Popp, Sabrina Geisberger, Olivia Nonn, Tine V Karlsen, Gabriele N’Diaye, Alex Yarritu, Hendrik Bartolomaeus, Theda U P Bartolomaeus, Nurana A Tagiyeva, Moritz I Wimmer, Nadine Haase, Yiming D Zhang, Andreas Wilhelm, Gerald Grütz, Olav Tenstad, Nicola Wilck, Sofia K Forslund, Robert Klopfleisch, Anja A Kühl, Raja Atreya, Stefan Kempa, Philipp Mertins, Britta Siegmund, Helge Wiig, Dominik N Müller
Journal: Cardiovascular Research (2025)

Abstract Aims The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health. Variation in bacterial load and composition along the GI tract may influence the mucosal microenvironment and thus be reflected its interstitial fluid (IF). Characterization of the segment-specific microenvironment is challenging and largely unexplored because of lack of available tools. Methods and results Here, we developed methods, namely tissue centrifugation and elution, to collect IF from the mucosa of different intestinal segments. These methods were first validated in rats and mice, and the tissue elution method was subsequently translated for use in humans. These new methods allowed us to quantify microbiota-derived metabolites, mucosa-derived cytokines, and proteins at their site-of-action. Quantification of short-chain fatty acids showed enrichment in the colonic IF. Metabolite and cytokine analyses revealed differential abundances within segments, often significantly increased compared to plasma, and proteomics revealed that proteins annotated to the extracellular phase were site-specifically identifiable in IF. Lipopolysaccharide injections in rats showed significantly higher ileal IL-1β levels in IF compared to the systemic circulation, suggesting the potential of local as well as systemic effect. Conclusion Collection of IF from defined segments and the direct measurement of mediators at the site-of-action in rodents and humans bypasses the limitations of indirect analysis of faecal samples or serum, providing direct insight into this understudied compartment.
Lifetime risk and projected burden of dementia
Authors: Michael Fang, Jiaqi Hu, Jordan Weiss, David S Knopman, Marilyn Albert, B Gwen Windham, Keenan A Walker, A Richey Sharrett, Rebecca F Gottesman, Pamela L Lutsey, Thomas Mosley, Elizabeth Selvin, Josef Coresh
Journal: Nature Medicine (2025)
Leading Causes of Death Among Asian American Compared With Pacific Islander Individuals
Authors: Jacqueline B. Vo, Jazmyn L. Bess, Kekoa Taparra, Paloma R. Mitra, Amy Berrington de González, Neal D. Freedman, Meredith S. Shiels, Jaimie Z. Shing
Journal: JAMA Internal Medicine (2025)

This cross-sectional study compares the disaggregated mortality rates and leading causes of death among Asian American and Pacific Islander individuals.
Research on Noncigarette Tobacco Products and Public Health
Authors: Wilson M. Compton
Journal: JAMA Network Open (2025)

Erfan Tasdighi, MD; Zhiqi Yao, MD, ScM; Kunal K. Jha, MD; Zeina A. Dardari, MS; Ngozi Osuji, MD, MPH; Tanuja Rajan, MD, MPH; Ellen Boakye, MD, MPH; Carlos J. Rodriguez, MD, MPH; Kunihiro Matsushita, MD; Eleanor M. Simonsick, PhD; João A. C. Lima, MD, MBA; Rachel Widome, PhD; Debbie Cohen, MD; Lawrence J. Appel, MD, MPH; Amit Khera, MD; Michael E. Hall, MD; Suzanne Judd, PhD; Shelley A. Cole, PhD; Vasan S. Ramachandran, MD; Emelia J. Benjamin, MD, ScM; Aruni Bhatnagar, PhD; Andrew P. DeFilippis, MD, MSc; Michael J. Blaha, MD, MPH
Queries on Sudden Infant Death Syndrome—Reply
Authors: Scott P. Oltman, Elizabeth E. Rogers, Laura L. Jelliffe-Pawlowski
Journal: JAMA Pediatrics (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Pediatrician Perspectives on Incorporating Discussion of Police Encounters Into Anticipatory Guidance for Black Youth and Their Caregivers
Authors: Jeffrey M. Eugene, Maria Nelson, Rebecca Neergaard, Emma Edmondson, Sarah Capponi, M. Christina Herrera, Judy A. Shea, Katherine Yun, Nicole Jaffe, Julie Premo, George Dalembert
Journal: JAMA Pediatrics (2025)

This study explores the barriers and facilitators to pediatricians discussing safely navigating police interactions with Black youth and their caregivers.