tbuckley/cabot-search huggingface dataset:
FUNDC1 alleviates doxorubicin-induced cardiotoxicity by restoring mitochondrial-endoplasmic reticulum contacts and blocked autophagic flux
Authors: Weibin He, Zhongchan Sun, Guang Tong, Lin Zeng, Wenlong He, Xiaopan Chen, Cien Zhen, Pengyuan Chen, Ning Tan, Pengcheng He
Journal: Theranostics (2024)

Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a tethering protein of MERCs. We aim to investigate the effect of DOX on MERCs in cardiomyocytes and explore whether it is involved in the dysregulated autophagy in DIC.
Modularized supramolecular assemblies for hypoxia-activatable fluorescent visualization and image-guided theranostics
Authors: Wen Liu, Bincheng Wang, Bei Guo, Junbin Zhu, Zejun Xu, Jiayue Xu, Zhen Wang, Guodong Sun, Wei Wang, Yi Zhang, Wei Xue
Journal: Theranostics (2024)

: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution.
External validation of the myocardial-ischaemic-injury-index machine learning algorithm for the early diagnosis of myocardial infarction: a multicentre cohort study
Authors: Pedro Lopez-Ayala, Jasper Boeddinghaus, Thomas Nestelberger, Luca Koechlin, Tobias Zimmermann, Paolo Bima, Jonas Glaeser, Carlos C Spagnuolo, Arnaud Champetier, Oscar Miro, Francisco Javier Martin-Sanchez, Dagmar I Keller, Michael Christ, Karin Wildi, Tobias Breidthardt, Ivo Strebel, Christian Mueller
Journal: The Lancet Digital Health (2024)

The myocardial-ischaemic-injury-index (MI
Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada
Authors: Elisa Cohen, Michael A Tsoukas, Laurent Legault, Michael Vallis, Julia E Von Oettingen, Emilie Palisaitis, Madison Odabassian, Jean-François Yale, Natasha Garfield, Nikita Gouchie-Provencher, Joanna Rutkowski, Adnan Jafar, Milad Ghanbari, Ahmad Haidar
Journal: The Lancet Digital Health (2024)

In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements.
Low Natriuretic Peptide Levels and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Toru Kondo, Ross Campbell, Pardeep S. Jhund, Inder S. Anand, Peter E. Carson, Carolyn S.P. Lam, Sanjiv J. Shah, Muthiah Vaduganathan, Faiez Zannad, Michael R. Zile, Scott D. Solomon, John J.V. McMurray
Journal: JACC Heart Failure (2024)

Although some patients with heart failure (HF) with mildly reduced/preserved ejection fraction have low natriuretic peptide levels, there are no large-scale systematic studies of how common these individuals are or what happens to them. The purpose of this study was to examine the proportion of patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction) trial with an N-terminal pro–B-type natriuretic peptide (NT-proBNP) level <125 pg/mL, their clinical characteristics, and outcomes. I- PRESERVE enrolled patients with symptomatic HF and a LVEF ≥45% but who did not have NT-proBNP or body mass index inclusion/exclusion criteria. Baseline NT-proBNP was measured after enrollment but not reported to investigators. The primary outcome in this analysis was the composite of cardiovascular death or HF hospitalization. Overall, 808 of 3,480 patients (23.2%) had NT-proBNP <125 pg/mL. Patients with a low NT-proBNP were younger (68.6 years vs 72.6 years; P < 0.001), were less often men (36.1% vs 40.9%; P = 0.015), and had a higher body mass index (48.4% vs 38.7% obese; P < 0.001) than those with a higher NT-proBNP level. Patients with a low NT-proBNP had less atrial fibrillation (8.5% vs 35.1%; P < 0.001), myocardial infarction, diabetes, chronic obstructive pulmonary disease, and anemia but better kidney function. Patients with a lower NT-proBNP level had less marked echocardiographic abnormalities and were less likely to experience cardiovascular death or HF hospitalization; adjusted HR: 0.35 (95% CI: 0.27-0.46; P < 0.001). However, health status was similarly impaired in patients with lower and higher NT-proBNP levels (median Minnesota Living with Heart Failure Questionnaire 43 vs 43; P = 0.95). Almost one-quarter of patients with HF with mildly reduced/preserved ejection fraction had a low NT-proBNP level. Although these patients have a favorable prognosis, compared to those with a high NT-proBNP level, they have similarly impaired health status which should be a target for treatment. (Irbesartan in Heart Failure With Preserved Systolic Function [I- PRESERVE]; NCT00095238)
Transfer of cardiomyocyte-derived extracellular vesicles to neighboring cardiac cells requires tunneling nanotubes during heart development
Authors: Ting Chen, Ditte Gry Ellman, Shu Fang, Sara Thornby Bak, Mikkel Ørnfeldt Nørgård, Per Svenningsen, Ditte Caroline Andersen
Journal: Theranostics (2024)

Extracellular vesicles (EVs) are thought to mediate intercellular communication during development and disease. Yet, biological insight to intercellular EV transfer remains elusive, also in the heart, and is technically challenging to demonstrate. Here, we aimed to investigate biological transfer of cardiomyocyte-derived EVs in the neonatal heart.
Single cell analyses reveal the PD-1 blockade response-related immune features in hepatocellular carcinoma
Authors: Yao Li, Fengwei Li, Lei Xu, Xiaodong Shi, Hui Xue, Jianwei Liu, Shilei Bai, Yeye Wu, Zhao Yang, Feng Xue, Yong Xia, Hui Dong, Feng Shen, Kui Wang
Journal: Theranostics (2024)

Immunotherapy has demonstrated its potential to improve the prognosis of patients with hepatocellular carcinoma (HCC); however, patients' responses to immunotherapy vary a lot. A comparative analysis of the tumor microenvironment (TME) in responders and non-responders is expected to unveil the mechanisms responsible for the immunotherapy resistance and provide potential treatment targets.
Overcoming colonialism in pathogen genomics
Authors: Senjuti Saha, Yogesh Hooda, Gathsaurie Neelika Malavige, Muhammad Imran Nisar
Journal: The Lancet Digital Health (2024)

Historical legacies of colonialism affect the distribution and control of scientific knowledge today, including within the pathogen genomics field, which remains dominated by high-income countries (HICs). We discuss the imperatives for decolonising pathogen genomics, including the need for more equitable representation, collaboration, and capacity-strengthening, and the shared responsibilities that both low-income and middle-income countries (LMICs) and HICs have in this endeavour. By highlighting examples from LMICs, we illuminate the pathways and challenges that researchers in LMICs face in the bid to gain autonomy in this crucial domain. Recognising the inherent value of local expertise and resources, we argue for a more inclusive, globally collaborative approach to pathogen genomics. Such an approach not only fosters scientific growth and innovation, but also strengthens global health security by equipping all nations with the tools needed to respond to health crises.
Obesity, Challenges, and Weight-Loss Strategies for Patients With Ventricular Assist Devices
Authors: Adrian daSilva-deAbreu, Jo E. Rodgers, Jessica Seltz, Stacy A. Mandras, Carl J. Lavie, Juan Francisco Loro-Ferrer, Hector O. Ventura, Philip R. Schauer, Amanda R. Vest
Journal: JACC Heart Failure (2024)
The efficacy of automated feedback after internet-based depression screening (DISCOVER): an observer-masked, three-armed, randomised controlled trial in Germany
Authors: Sebastian Kohlmann, Franziska Sikorski, Hans-Helmut König, Marion Schütt, Antonia Zapf, Bernd Löwe
Journal: The Lancet Digital Health (2024)

Despite the availability of effective treatments, most depressive disorders remain undetected and untreated. Internet-based depression screening combined with automated feedback of screening results could reach people with depression and lead to evidence-based care. We aimed to test the efficacy of two versions of automated feedback after internet-based screening on depression severity compared with no feedback.
Towards effective CAIX-targeted radionuclide and checkpoint inhibition combination therapy for advanced clear cell renal cell carcinoma
Authors: Simone C Kleinendorst, Egbert Oosterwijk, Janneke Molkenboer-Kuenen, Cathelijne Frielink, Gerben M Franssen, Daan F Boreel, Giulia Tamborino, Manon Gloudemans, Merel Hendrikx, Dennis Kroon, Jopp Hillen, Johan Bussink, Stijn Muselaers, Peter Mulders, Mark W Konijnenberg, Michael P Wheatcroft, Kwame Twumasi-Boateng, Sandra Heskamp
Journal: Theranostics (2024)

Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) is a systemic radiation treatment, ideally suited for precision irradiation of metastasized cancer. Therefore, the aim of this study is to explore the potential of combined TRT, targeting carbonic anhydrase IX (CAIX) which is overexpressed in ccRCC, using [
Prolonged Cadmium Exposure and Osteoclastogenesis: A Mechanistic Mouse and <i>in Vitro</i> Study
Authors: Zhiyuan Liu, Jinzhi Wu, Zhe Dong, Yanshuai Wang, Gang Wang, Chengjie Chen, Huihui Wang, Yang Yang, Yongxin Sun, Maowei Yang, Jingqi Fu, Jiliang Li, Qiang Zhang, Yuanyuan Xu, Jingbo Pi
Journal: Environmental Health Perspectives (2024)

Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear.
Pachydermodactyly: mimic of arthritis in a young man
Authors: Cassandra Michelle Skinner-Taylor, Pablo Gamez-Siller, Brenda Cantu-Garza, Hector Guerra, Héctor Teodoro Rios-Bazaldua, Dionicio Angel Galarza-Delgado, Jesus Alberto Cardenas-de la Garza
Journal: The Lancet Rheumatology (2024)
Brain responses to intermittent fasting and the healthy living diet in older adults
Authors: Dimitrios Kapogiannis, Apostolos Manolopoulos, Roger Mullins, Konstantinos Avgerinos, Francheska Delgado-Peraza, Maja Mustapic, Carlos Nogueras-Ortiz, Pamela J. Yao, Krishna A. Pucha, Janet Brooks, Qinghua Chen, Shalaila S. Haas, Ruiyang Ge, Lisa M. Hartnell, Mark R. Cookson, Josephine M. Egan, Sophia Frangou, Mark P. Mattson
Journal: Cell Metabolism (2024)
An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation
Authors: Hang Zhou, Zhongyuan He, Youde Cao, Lei Chu, Bing Liang, Kexiao Yu, Zhongliang Deng
Journal: Theranostics (2024)

The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis.
Profiling the SARS-CoV-2-specific T-cell response
Authors: Daryl Geers, Lennert Gommers, Ngoc H Tan, Susanne Bogers, Debbie van Baarle, Alba Grifoni, Alessandro Sette, Annemarie Boerma, Frederique Visscher, Mathilde Richard, Mathis Funk, Luca M Zaeck, P Hugo M van der Kuy, Bart L Haagmans, Marion PG Koopmans, Corine H GeurtsvanKessel, Rory D de Vries
Journal: The Lancet Infectious Diseases (2024)
Collateral-based selection for endovascular treatment of acute ischaemic stroke in the late window (MR CLEAN-LATE): 2-year follow-up of a phase 3, multicentre, open-label, randomised controlled trial in the Netherlands
Authors: Ilse Huijberts, Florentina M E Pinckaers, Susanne G H Olthuis, Sander M J van Kuijk, Alida A Postma, Hieronymus D Boogaarts, Yvo B W E M Roos, Charles B L M Majoie, Aad van der Lugt, Diederik W J Dippel, Wim H van Zwam, Robert J van Oostenbrugge
Journal: The Lancet Neurology (2024)
Epidemiology and management of gestational diabetes
Authors: Arianne Sweeting, Wesley Hannah, Helena Backman, Patrick Catalano, Maisa Feghali, Willliam H Herman, Marie-France Hivert, Jincy Immanuel, Claire Meek, Maria Lucia Oppermann, Christopher J Nolan, Uma Ram, Maria Inês Schmidt, David Simmons, Tawanda Chivese, Katrien Benhalima
Journal: The Lancet (2024)
Pathophysiology from preconception, during pregnancy, and beyond
Authors: Marie-France Hivert, Helena Backman, Katrien Benhalima, Patrick Catalano, Gernot Desoye, Jincy Immanuel, Christopher J D McKinlay, Claire L Meek, Christopher J Nolan, Uma Ram, Arianne Sweeting, David Simmons, Alicia Jawerbaum
Journal: The Lancet (2024)
A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation
Authors: Jiayang Chen, Mary E. Lambo, Xia Ge, Joshua T. Dearborn, Yating Liu, Katherine B. McCullough, Raylynn G. Swift, Dora R. Tabachnick, Lucy Tian, Kevin Noguchi, Joel R. Garbow, John N. Constantino, Harrison W. Gabel, Keith B. Hengen, Susan E. Maloney, Joseph D. Dougherty
Journal: Neuron (2024)
<b>International Union of Basic and Clinical Pharmacology CXIV: Orexin Receptor Function, Nomenclature and Pharmacology</b>
Authors: Jyrki P. Kukkonen, Laura H. Jacobson, Daniel Hoyer, Maiju K. Rinne, Stephanie L. Borgland
Journal: Pharmacological Reviews (2024)

The orexin system consists of the peptide transmitters orexin-A and -B and the G protein-coupled orexin receptors OX
An Acellular, Self‐Healed Trilayer Cryogel for Osteochondral Regeneration in Rabbits
Authors: Tsai‐Yu Chen, Niann‐Tzyy Dai, Tsung‐Kai Wen, Shan‐hui Hsu
Journal: Advanced Healthcare Materials (2024)

Osteochondral regeneration remains formidable challenges despite significant advances in microsurgery. Herein, an acellular trilayer cryogel (TC) with injectability, tunable pore sizes (80-200 µm), and appropriate compressive modulus (10.8 kPa) is manufactured from self-healable hydrogel under different gelling times through Schiff reaction between chitosan and difunctionalized polyurethane (DFPU). Bioactive molecules (Y27632 and dexamethasone) are respectively loaded in the top and bottom layers to form the Y27632/dexamethasone-loaded trilayer cryogel (Y/DEX-TC). Mesenchymal stem cells (MSCs) seeded in Y/DEX-TC proliferated ≈350% in vitro and underwent chondrogenesis or osteogenesis in response to the respective release of Y or DEX in 14 days. Acupuncture is administered to animals in an attempt to modulate the innate regulatory system and mobilize endogenous MSCs for osteochondral defect regeneration. In vivo rabbit experiments using Y/DEX-TC combined with acupuncture successfully regulate SDF-1 and TGF-β1 levels, which possibly cause MSC migration toward Y/DEX-TC. The synergistic effect of cryogel and acupuncture on immunomodulation is verified with a ≈7.3-fold enhancement of the M2-/M1-macrophage population ratio by treatment of Y/DEX-TC combining acupuncture, significantly greater than ≈1.5-fold increase by acupuncture or ≈2.2-fold increase by Y/DEX-TC alone. This novel strategy using acellular drug-loaded cryogel and accessible acupuncture shows promise in treating osteochondral defects of joint damage.
Suicidal Ideation, Suicide Attempts, and Suicide Deaths in Adolescents and Young Adults With Type 1 Diabetes: A Systematic Review and Meta-analysis
Authors: Olivier Renaud-Charest, Alexander Stoljar Gold, Elise Mok, Jessica Kichler, Meranda Nakhla, Patricia Li
Journal: Diabetes Care (2024)

BACKGROUND Evidence is lacking on the risk of suicide-related behaviors (suicidal ideation, suicide attempt, suicide death) in youth with type 1 diabetes (T1D). PURPOSE We aimed to 1) determine the prevalence of suicidal ideation, suicide attempts, and suicide deaths in adolescents and young adults (AYA) with T1D aged 10–24 years; 2) compare suicide-related behavior prevalence in youth with and without T1D; and 3) identify factors associated with suicide-related behaviors. DATA SOURCES A systematic search was conducted in MEDLINE, Embase, and PsycInfo up to 3 September 2023. STUDY SELECTION We included observational studies where investigators reported the prevalence of suicide-related behaviors among AYA aged 10–24 years with T1D. DATA EXTRACTION We collected data on study characteristics, data on prevalence of suicide-related behaviors, and data on associated factors. DATA SYNTHESIS We included 31 studies. In AYA with versus without T1D, pooled prevalence of suicidal ideation was 15.4% (95% CI 10.0–21.7; n = 18 studies) vs. 11.5% (0.4–33.3; n = 4), respectively, and suicide attempts 3.5% (1.3–6.7; n = 8) vs. 2.0% (0.0–6.4; n = 5). Prevalence of suicide deaths ranged from 0.04% to 4.4% among youth with T1D. Difficulties with T1D self-management were frequently reported to be associated with higher rates of suicide-related behaviors. However, findings on the association of glycemic levels and suicide-related behaviors were inconsistent. LIMITATIONS There was a considerable level of heterogeneity in meta-analysis of both suicidal ideation and suicide attempts. CONCLUSIONS Suicidal ideation and suicide attempts are prevalent in AYA with T1D. Current evidence does not suggest that these rates are higher among AYA with T1D than rates among those without.
RUVBL1/2 Blockade Targets YTHDF1 Activity to Suppress m6A-Dependent Oncogenic Translation and Colorectal Tumorigenesis
Authors: Danyu Chen, Fenfen Ji, Qiming Zhou, Henley Cheung, Yasi Pan, Harry Cheuk-Hay. Lau, Cong Liang, Zhenjie Yang, Pingmei Huang, Qinyao Wei, Alvin Ho-Kwan. Cheung, Wei Kang, Huarong Chen, Jun Yu, Chi Chun. Wong
Journal: Cancer Research (2024)

Abstract The N6-methyladenosine (m6A) RNA-binding protein YTHDF1 is frequently overexpressed in colorectal cancer and drives chemotherapeutic resistance. To systematically identify druggable targets in colorectal cancer with high expression of YTHDF1, this study used a CRISPR/Cas9 screening strategy that revealed RUVBL1 and RUVBL2 as putative targets. RUVBL1/2 were overexpressed in primary colorectal cancer samples and represented independent predictors of poor patient prognosis. Functionally, loss of RUVBL1/2 preferentially impaired the growth of YTHDF1-high colorectal cancer cells, patient-derived primary colorectal cancer organoids, and subcutaneous xenografts. Mechanistically, YTHFD1 and RUVBL1/2 formed a positive feedforward circuit to accelerate oncogenic translation. YTHDF1 bound to m6A-modified RUVBL1/2 mRNA to promote translation initiation and protein expression. Coimmunoprecipitation and mass spectrometry identified that RUVBL1/2 reciprocally interacted with YTHDF1 at 40S translation initiation complexes. Consequently, RUVBL1/2 depletion stalled YTHDF1-driven oncogenic translation and nascent protein biosynthesis, leading to proliferative arrest and apoptosis. Ribosome sequencing revealed that RUVBL1/2 loss impaired the activation of MAPK, RAS, and PI3K-AKT signaling induced by YTHDF1. Finally, the blockade of RUVBL1/2 by the pharmacological inhibitor CB6644 or vesicle-like nanoparticle-encapsulated siRNAs preferentially arrested the growth of YTHDF1-expressing colorectal cancer in vitro and in vivo. Our findings show that RUVBL1/2 are potential prognostic markers and druggable targets that regulate protein translation in YTHDF1-high colorectal cancer. Significance: RUVBL1/2 inhibition is a therapeutic strategy to abrogate YTHDF1-driven oncogenic translation and overcome m6A dysregulation in colorectal cancer.
PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT
Authors: Wenchao Zhang, Wei Li, Chi Yin, Chengyao Feng, Binfeng Liu, Haodong Xu, Xin Jin, Chao Tu, Zhihong Li
Journal: Cancer Research (2024)

Abstract Chemoresistance is one of the major causes of poor prognosis in osteosarcoma. Alternative therapeutic strategies for osteosarcoma are limited, indicating that increasing sensitivity to currently used chemotherapies could be an effective approach to improve patient outcomes. Using a kinome-wide CRISPR screen, we identified PRKDC as a critical determinant of doxorubicin (DOX) sensitivity in osteosarcoma. The analysis of clinical samples demonstrated that PRKDC was hyperactivated in osteosarcoma, and functional experiments showed that the loss of PRKDC significantly increased sensitivity of osteosarcoma to DOX. Mechanistically, PRKDC recruited and bound GDE2 to enhance the stability of protein GNAS. The elevated GNAS protein levels subsequently activated AKT phosphorylation and conferred resistance to DOX. The PRKDC inhibitor AZD7648 and DOX synergized and strongly suppressed the growth of osteosarcoma in mouse xenograft models and human organoids. In conclusion, the PRKDC-GDE2-GNAS-AKT regulatory axis suppresses DOX sensitivity and comprises targetable candidates for improving the efficacy of chemotherapy in osteosarcoma. Significance: Targeting PRKDC suppresses AKT activation and increases sensitivity to doxorubicin in osteosarcoma, which provides a therapeutic strategy for overcoming chemoresistance.
Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis
Authors: Sydney J. Conner, Hannah B. Borges, Justinne R. Guarin, Thomas J. Gerton, Anna Yui, Kenneth J. Salhany, Diamond N. Mensah, Grace A. Hamilton, Giang H. Le, Katherine C. Lew, Crystal Zhang, Madeleine J. Oudin
Journal: Cancer Research (2024)

Abstract Obesity is associated with increased incidence and metastasis of triple-negative breast cancer, an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet (HFD)–driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or HFD, assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to an increased abundance of the proinvasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and collagen VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from the lungs and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, these data suggest that changes in the breast, lungs, and liver ECM underlie some of the effects of obesity on triple-negative breast cancer incidence and metastasis. Significance: Organ-specific extracellular matrix changes in the primary tumor and metastatic microenvironment are mechanisms by which obesity contributes to breast cancer progression.