tbuckley/cabot-search huggingface dataset:
Lymphatic Endothelial Branched-Chain Amino Acid Catabolic Defects Undermine Cardiac Lymphatic Integrity and Drive HFpEF
Authors: Xiong Guo, Chong Huang, Ling Zhang, Guangyu Hu, Yunhui Du, Xiyao Chen, Fangfang Sun, Tongzheng Li, Zhe Cui, Congye Li, Yongzhen Guo, Wenjun Yan, Yunlong Xia, Shan Wang, Hui Liu, Zhiyuan Liu, Zhen Lin, Xinyi Wang, Zhengyang Wang, Fuyang Zhang, Ling Tao
Journal: Circulation (2025)

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, but effective treatments are lacking. Cardiac lymphatics play a crucial role in maintaining heart health by draining fluids and immune cells. However, their involvement in HFpEF remains largely unexplored. METHODS: We examined cardiac lymphatic alterations in mice with HFpEF with comorbid obesity and hypertension, and in heart tissues from patients with HFpEF. Using genetically engineered mouse models and various cellular and molecular techniques, we investigated the role of cardiac lymphatics in HFpEF and the underlying mechanisms. RESULTS: In mice with HFpEF, cardiac lymphatics displayed substantial structural and functional anomalies, including decreased lymphatic endothelial cell (LEC) density, vessel fragmentation, reduced branch connections, and impaired capacity to drain fluids and immune cells. LEC numbers and marker expression levels were also decreased in heart tissues from patients with HFpEF. Stimulating lymphangiogenesis with an adeno-associated virus expressing an engineered variant of vascular endothelial growth factor C (VEGFC C156S ) that selectively activates vascular endothelial growth factor receptor 3 (VEGFR3) in LECs restored cardiac lymphatic integrity and substantially alleviated HFpEF. Through discovery-driven approaches, defective branched-chain amino acid (BCAA) catabolism was identified as a predominant metabolic signature in HFpEF cardiac LECs. Overexpression of branched-chain ketoacid dehydrogenase kinase (encoded by the Bckdk gene), which inactivates branched-chain ketoacid dehydrogenase (the rate-limiting enzyme in BCAA catabolism), resulted in spontaneous lymphangiogenic defects in LECs. In mice, inducible Bckdk gene deletion in LECs to enhance their BCAA catabolism preserved cardiac lymphatic integrity and protected against HFpEF. BCAA catabolic defects caused ligand-independent phosphorylation of VEGFR3 in the cytoplasm by Src kinase, leading to lysosomal degradation of VEGFR3 instead of its trafficking to the cell membrane. Reduced VEGFR3 availability on the cell surface impeded downstream Akt (protein kinase B) activation, hindered glucose uptake and utilization, and inhibited lymphangiogenesis in LECs with BCAA catabolic defects. CONCLUSIONS: Our study provides evidence that cardiac lymphatic disruption, driven by impaired BCAA catabolism in LECs, is a key factor contributing to HFpEF. These findings unravel the crucial role of BCAA catabolism in modulating lymphatic biology, and suggest that preserving cardiac lymphatic integrity may present a novel therapeutic strategy for HFpEF.
A Randomized Controlled Trial of Thoracentesis in Acute Heart Failure
Authors: Signe Glargaard, Jakob Hartvig Thomsen, Christian Tuxen, Matias Greve Lindholm, Christian Axel Bang, Morten Schou, Kasper Iversen, Rasmus Vedby Rasmussen, Brian Bridal Løgstrup, Søren Vraa, Nis Stride, Ekim Seven, Anders Barasa, Marlene Tofterup, Dan Eik Høfsten, Kasper Rossing, Lars Køber, Finn Gustafsson, Jens Jakob Thune
Journal: Circulation (2025)

BACKGROUND: TAP-IT (Thoracentesis to Alleviate Cardiac Pleural Effusion–Interventional Trial) investigated the effect of therapeutic thoracentesis in addition to standard medical therapy in patients with acute heart failure and sizeable pleural effusion. METHODS: This multicenter, unblinded, randomized controlled trial, conducted between August 31, 2021, and March 22, 2024, included patients with acute heart failure, left ventricular ejection fraction ≤45%, and non-negligible pleural effusion. Patients with very large effusions (more than two-thirds of the hemithorax) were excluded. Participants were randomly assigned 1:1 to upfront ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard medical therapy or standard medical therapy alone. The primary outcome was days alive out of the hospital over the following 90 days; key secondary outcomes included length of admission and 90-day all-cause mortality. All outcomes were analyzed according to the intention-to-treat principle. RESULTS: A total of 135 patients (median age, 81 years [25th; 75th percentile, 75; 83]; 33% female; median left ventricular ejection fraction, 25% [25th; 75th percentile, 20%; 35%]) were randomized to either thoracentesis (n=68) or standard medical therapy (n=67). The thoracentesis group had a median of 84 days (77; 86) alive out of the hospital over the following 90 days compared with 82 days (73; 86) in the control group ( P =0.42). The mortality rate was 13% in both groups, with no difference in survival probability ( P =0.90). There were no differences in the duration of the index admission (control group median, 5 days [3; 8]; thoracentesis group median, 5 days [3; 7; P =0.69]). Major complications occurred in 1% of thoracenteses performed during the study period. CONCLUSIONS: For patients with acute heart failure and pleural effusion, a strategy of upfront routine thoracentesis in addition to standard medical therapy did not increase days alive out of the hospital for 90 days, all-cause mortality, or duration of index admission. The current findings lay the groundwork for future research to confirm the results. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05017753.
Current and future therapies for small cell lung carcinoma
Authors: Xiaoqian Zhai, Zhengkun Zhang, Yuxin Chen, Yanmou Wu, Cheng Zhen, Yu Liu, Yiyun Lin, Chong Chen
Journal: Journal of Hematology & Oncology (2025)

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation and high metastatic potential. It is characterized by universal inactivation of and RB1, overexpression of the MYC family and dysregulation of multiple oncogenic signaling pathways. Among different patients, SCLCs are similar at the genetic level but exhibit significant heterogeneity at the molecular level. The classification of SCLC has evolved from a simple neuroendocrine (NE)/non-neuroendocrine (non-NE) classification system to a transcription factor-based molecular subtype system; lineage plasticity adds further complexity and poses challenges for therapeutic development. While SCLC is initially sensitive to platinum-based chemotherapy, resistance develops rapidly, leading to a dismal prognosis. Various antibodies, including PD-1/PD-L1 inhibitors and antibody‒drug conjugates, have been introduced into clinical practice or are being evaluated in clinical trials. However, their therapeutic benefits for SCLC patients remain limited. This review summarizes SCLC carcinogenic mechanisms, tumor heterogeneity, and the immune microenvironment of SCLC, with a focus on recent advances in metastasis and resistance mechanisms. Additionally, the corresponding clinical progress in tackling these challenges is discussed.
Furuncular Myiasis in the skin of colour
Authors: Neerja Saraswat, Durga Madhab Tripathy, Rajesh W Adhau, Anirudh Tripathy, Anil Balki
Journal: British Journal of Dermatology (2025)

This case highlights an underreported zoonosis in our dermatology clinic. The diagnosis of furuncular myiasis was made based on typical clinical findings and with a characteristic history in the skin of colour.
Reply to ‘The disruption of circadian rhythm as a potential mechanism of nocturia-like symptoms — a paediatric urology perspective’
Authors: Qi-Xiang Song, Sylvia Suadicani, Hiromitsu Negoro, Hai-Hong Jiang, Rita Jabr, Christopher Fry, Wei Xue, Margot S. Damaser
Journal: Nature Reviews Urology (2025)
Correction: Proteomic screening identifies PF4/Cxcl4 as a critical driver of myelofibrosis
Authors: Daniele Capitanio, Francesca R. Calledda, Vittorio Abbonante, Daniele Cattaneo, Manuela Moriggi, Niccolò Bartalucci, Cristina Bucelli, Delfina Tosi, Umberto Gianelli, Alessandro Maria Vannucchi, Alessandra Iurlo, Cecilia Gelfi, Alessandra Balduini, Alessandro Malara
Journal: Leukemia (2025)
Mechanisms of experience-dependent place-cell referencing in hippocampal area CA1
Authors: Fish Kunxun Qian, Yiding Li, Jeffrey C. Magee
Journal: Nature Neuroscience (2025)

Abstract Hippocampal CA1 place cells (PCs) encode both space- and goal-referenced information to support a cognitive map. The mechanism of this referencing and the role of experience remain poorly understood. Here we longitudinally recorded PC activity while head-fixed mice performed a spatial learning task on a treadmill. In a familiar environment, the CA1 representation consisted of PCs that were referenced to either specific spatial locations or a reward goal in approximately equal proportions; however, the CA1 representation became predominately goal-referenced upon exposure to a novel environment, as space-referenced PCs adaptively switched reference frames. Intracellular membrane potential recordings revealed that individual CA1 neurons simultaneously received both space- and goal-referenced synaptic inputs, and the ratio of these inputs was correlated with individual PC referencing. Furthermore, behavioral timescale synaptic plasticity shaped PC referencing. Together, these results suggest that experience-dependent adjustment of synaptic input shapes PC referencing to support a flexible cognitive map.
Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial
Authors: Frank J. Lowery, Stephanie L. Goff, Billel Gasmi, Maria R. Parkhurst, Nivedita M. Ratnam, Hyunmi K. Halas, Thomas E. Shelton, Michelle M. Langhan, Aarushi Bhasin, Aaron J. Dinerman, Victoria Dulemba, Ian S. Goldlust, Alexandra M. Gustafson, Abraham A. Hakim, Kyle J. Hitscherich, Lisa M. Kenney, Lior Levy, Juliette G. Rault-Wang, Alakesh Bera, Satyajit Ray, Courtney D. Seavey, Chuong D. Hoang, Jonathan M. Hernandez, Jared J. Gartner, Sivasish Sindiri, Todd D. Prickett, Lori S. McIntyre, Sri Krishna, Paul F. Robbins, Nicholas D. Klemen, Mei Li M. Kwong, James C. Yang, Steven A. Rosenberg
Journal: Nature Medicine (2025)
An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma
Authors: Sandeep S. Raj, Teng Fei, Shalev Fried, Andrew Ip, Joshua A. Fein, Lori A. Leslie, Ana Alarcon Tomas, Doris Leithner, Jonathan U. Peled, Magdalena Corona, Parastoo B. Dahi, Ivetta Danylesko, Zachary Epstein-Peterson, Tyler Funnell, Sergio A. Giralt, Elad Jacoby, Meirav Kedmi, Ivan Landego, Richard J. Lin, Allison Parascondola, Lauren Pascual, Natali Orozco, Jae H. Park, M. Lia Palomba, Gilles Salles, Amethyst Saldia, Heiko Schöder, Inbal Sdayoor, Gunjan L. Shah, Michael Scordo, Noga Shem-Tov, Avichai Shimoni, John Slingerland, Ronit Yerushalmi, Arnon Nagler, Benjamin D. Greenbaum, Andrew J. Vickers, Hyung C. Suh, Abraham Avigdor, Miguel-Angel Perales, Marcel R. M. van den Brink, Roni Shouval
Journal: Nature Medicine (2025)

Disease progression is a substantial challenge in patients with non-Hodgkin lymphoma (NHL) undergoing chimeric antigen receptor T cell (CAR-T) therapy. Here we present InflaMix (INFLAmmation MIXture Model), an unsupervised quantitative model integrating 14 pre-CAR-T infusion laboratory and cytokine measures capturing inflammation and end-organ function. Developed using a cohort of 149 patients with NHL, InflaMix revealed an inflammatory signature associated with a high risk of CAR-T treatment failure, including increased hazard of death or relapse (hazard ratio, 2.98; 95% confidence interval, 1.60–4.91; P < 0.001). Three independent cohorts comprising 688 patients with NHL from diverse treatment centers were used to validate our approach. InflaMix consistently and reproducibly identified patients with a higher likelihood of disease relapse and mortality, and it provided supplementary predictive value beyond established prognostic markers, including tumor burden. Moreover, InflaMix exhibited robust performance in cases with missing data, maintaining accuracy when considering only six readily available laboratory measures. These findings show that InflaMix is a valuable tool for point-of-care clinical decision-making in patients with NHL undergoing CAR-T therapy. A preinfusion circulatory inflammation biomarker-based signature predicts the likelihood of treatment failure in patients with non-Hodgkin lymphoma who were treated with CAR-T cell therapy, with an inflammatory cluster assignment being prognostic of clinical response and survival outcomes.
Spatially resolved transcriptomic analysis of the adult human prostate
Authors: Junyi Hu, Fei Liu, Jing Zhang, Lei Yin, Wanli Cao, Weidong Xu, Yifan Chang, Ye Wang, Jian Wang, Yaxin Hou, Lilong Liu, Sujun Chen, Guanghui Zhu, Junhui Jiang, Zixian Wang, Gong-Hong Wei, Housheng Hansen He, Di Gu, Ke Chen, Shancheng Ren
Journal: Nature Genetics (2025)
Quantitative characterization of tissue states using multiomics and ecological spatial analysis
Authors: Daisy Yi Ding, Zeyu Tang, Bokai Zhu, Hongyu Ren, Alex K. Shalek, Robert Tibshirani, Garry P. Nolan
Journal: Nature Genetics (2025)

The spatial organization of cells in tissues underlies biological function, and recent advances in spatial profiling technologies have enhanced our ability to analyze such arrangements to study biological processes and disease progression. We propose MESA (multiomics and ecological spatial analysis), a framework drawing inspiration from ecological concepts to delineate functional and spatial shifts across tissue states. MESA introduces metrics to systematically quantify spatial diversity and identify hot spots, linking spatial patterns to phenotypic outcomes, including disease progression. Furthermore, MESA integrates spatial and single-cell multiomics data to facilitate an in-depth, molecular understanding of cellular neighborhoods and their spatial interactions within tissue microenvironments. Applying MESA to diverse datasets demonstrates additional insights it brings over prior methods, including newly identified spatial structures and key cell populations linked to disease states. Available as a Python package, MESA offers a versatile framework for quantitative decoding of tissue architectures in spatial omics across health and disease. Multiomics and ecological spatial analysis (MESA) calculates ecodiversity-inspired metrics in spatially resolved omics integrated with single-cell data, enabling the quantitative comparison of tissue states across a range of conditions.
Reply to: Short‐term risk of cardiovascular events in people newly diagnosed with gout: comment on the article by Cipolletta et al.
Authors: Edoardo Cipolletta, Laila J. Tata, Abhishek Abhishek
Journal: Arthritis & Rheumatology (2025)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Short‐Term Risk of Cardiovascular Events in People Newly Diagnosed With Gout: Comment on the article by Cipolletta E et al
Authors: Teng‐Fei Li, Rui‐Jun Bai
Journal: Arthritis & Rheumatology (2025)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
All-stage targeted therapy for invasive cryptococcosis through interaction between the secretory protein Cig1 and hemin
Authors: Liting Cheng, Zhongyi Ma, Xinlin Yang, Xue Wang, Yuqiong Wang, Xinlong Liu, Zhongjie Tang, Dingxi Jang, Guojian Liao, Tongbao Liu, Shuang Wu, Chong Li
Journal: Asian Journal of Pharmaceutical Sciences (2025)
Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification
Authors: Mingyao Huang, Quansong Ji, Huiyan Huang, Xiaoqian Wang, Lin Wang
Journal: Gut Microbes (2025)

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota – such as fecal microbiota transplantation, dietary interventions, and probiotics – as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.
PANCREATIC NEUROENDOCRINE NEOPLASMS (pNENs): GENETIC AND ENVIRONMENTAL BIOMARKERS FOR RISK OF OCCURRENCE AND PROGNOSIS
Authors: Matteo Tacelli, Manuel Gentiluomo, Paolo Biamonte, Justo Castano, Maja Cigrovski Berković, Mauro Cives, Sanja Kapitanović, Ilaria Marinoni, Sonja Marinovic, Ilias Nikas, Lenka Nosáková, Sergio Pedraza-Arevalo, Eleonora Pellè, Aurel Perren, Jonathan Strosberg, Daniele Campa, Gabriele Capurso
Journal: Seminars in Cancer Biology (2025)
Correction to: Prenatal Lipopolysaccharides Exposure Induces Transgenerational Inheritance of Hypertension
Authors: Nian Cao, Cong Lan, Caiyu Chen, Zaicheng Xu, Hao Luo, Shuo Zheng, Xue Gong, Hongmei Ren, Zhuxin Li, Shuang Qu, Cheng Yu, Jining Yang, Pedro A. Jose, Yundai Chen, Gengze Wu, Cuimei Hu, Junyi Yu, Chunyu Zeng
Journal: Circulation (2025)
Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
Authors: Amanda Ke Hornsby, Richard C Brown, Thomas W Tilston, Harry A Smith, Alfonso Moreno-Cabañas, Bradley Arms-Williams, Anna L Hopkins, Katie D Taylor, Simran Kr Rogaly, Lois Hm Wells, Jamie J Walker, Jeffrey S Davies, Yuxiang Sun, Jeffrey M Zigman, James A Betts, Timothy Wells
Journal: Journal of Clinical Investigation (2025)

The physiological impact of ultradian temporal feeding patterns remains a major unanswered question in nutritional science. We have employed automated and nasogastric feeding to address this question in male rodents and human volunteers. While grazing and meal-feeding reduced food intake in parallel (compared to ad libitum-fed rodents), body length and tibial epiphysial plate width were maintained in meal-fed rodents via the action of ghrelin and its receptor, GHS-R. Grazing and meal-feeding initially suppressed elevated pre-prandial ghrelin levels in rats, followed by either a sustained elevation in ghrelin in grazing rats or pre-prandial ghrelin surges in meal-fed rats. Episodic growth hormone (GH) secretion was largely unaffected in grazing rats, but meal-feeding tripled GH secretion, with burst height augmented and two additional bursts of GH per day. Continuous nasogastric infusion of enteral feed in humans failed to suppress circulating ghrelin, producing continuously elevated circulating GH with minimal rhythmicity. In contrast, bolus enteral infusion elicited post-prandial ghrelin troughs accompanied by reduced circulating GH, with enhanced ultradian rhythmicity. Taken together, our data imply that the contemporary shift from regular meals to snacking behaviour may be detrimental to optimal skeletal growth outcomes by sustaining circulating GH at levels associated with undernourishment and diminishing GH pulsatility.
Cxcr3 promotes protection from colorectal cancer liver metastasis by driving NK cell infiltration and plasticity
Authors: Eleonora Russo, Chiara D'Aquino, Chiara Di Censo, Mattia Laffranchi, Luana Tomaipitinca, Valerio Licursi, Stefano Garofalo, Johann Promeuschel, Giovanna Peruzzi, Francesca Sozio, Anna Kaffke, Cecilia Garlanda, Ulf Panzer, Cristina Limatola, Christian A J Vosshenrich, Silvano Sozzani, Giuseppe Sciumè, Angela Santoni, Giovanni Bernardini
Journal: Journal of Clinical Investigation (2025)

The anti-metastatic activity of NK cells is well established in several cancer types, but the mechanisms underlying NK cell metastasis infiltration and acquisition of anti-tumor characteristics remain unclear. Herein, we investigated the cellular and molecular factors required to facilitate the generation of an ILC1-like CD49a+NK cell population within the liver metastasis (LM) environment of colorectal cancer (CRC). We show that CD49a+NK cells had the highest cytotoxic capacity among metastasis-infiltrating NK cells in the MC38 mouse model. Furthermore, the chemokine receptor CXCR3 promoted CD49a+NK cell accumulation and persistence in metastasis where NK cells co-localize with macrophages in CXCL9 and CXCL10 rich areas. By mining a published scRNA-seq dataset of a cohort of treatment-naïve CRC patients, we confirmed the accumulation of CXCR3+NK cells in metastatic samples. Conditional deletion of Cxcr3 in NKp46+ cells and antibody-mediated depletion of metastasis-associated macrophages impaired CD49a+NK cell development, indicating that CXCR3 and macrophages contribute to efficient NK cell localization and polarization in LM. Conversely, CXCR3neg NK cells maintained a CD49a- phenotype in metastasis with reduced parenchymal infiltration and tumor killing capacity. Furthermore, CD49a+NK cell accumulation was impaired in an independent SL4-induced CRC metastasis model, which fails to accumulate CXCL9+ macrophages. Together, our results highlight a role for CXCR3/ligand axis in promoting macrophage-dependent NK cell accumulation and functional sustenance in CRC LM.
Site-specific analysis of extranodal involvement in large B-cell lymphoma reveals distinct efficacy with chimeric antigen receptor T-cell therapy
Authors: Gloria Iacoboni, Kai Rejeski, Víctor Navarro, Tom van Meerten, Alex Rampotas, Ana África Martín-López, Mariana Bastos, Ana Benzaquén, Juan Luis Reguera-Ortega, Cecilia Carpio, Claire Roddie, Lucia López-Corral, Javier Delgado-Serrano, Maria Landwehr, Sophia Stock, Pablo Silva de Tena, Pau Abrisqueta, Janneke de Boer, Alejandro Martin Garcia-Sancho, Rafael Hernani, Mi Kwon, Marion Subklewe, Maeve O’Reilly, Pere Barba
Journal: Leukemia (2025)