tbuckley/cabot-search huggingface dataset:
Modulating the Secretome of Fat to Treat Heart Failure
Authors: Lorien G. Salyer, Yajing Wang, Xinliang Ma, Anna Foryst-Ludwig, Ulrich Kintscher, Saravanakkumar Chennappan, Maria I. Kontaridis, Timothy A. McKinsey
Journal: Circulation Research (2025)

Heart failure afflicts &gt;6 million individuals in the United States alone and is associated with significant mortality (≈40% within 5 years of diagnosis) and cost (estimated to exceed $70 billion in the United States by 2030). Obesity is a major risk factor for the development of heart failure. The contribution of excess adipose tissue to heart failure pathogenesis is multifactorial. For example, adipose tissue–driven inflammation contributes to the development of other cardiometabolic comorbidities, such as hypertension, leading to left ventricular pressure overload and adverse remodeling of the heart. Adipose tissue also functions as an endocrine organ, and altered secretion of proteins, lipid mediators, metabolites, and small extracellular vesicles (collectively referred to as the secretome) from dysfunctional fat can lead to cardiac inflammation and oxidative stress, which drive changes in structure and function of the heart. In this review, we begin with an overview of current therapies for obesity and what is known about how they influence the heart. Then we focus on mechanisms by which fat communicates with the heart via secreted factors and highlight druggable nodes in this circuit that could be exploited to develop next-generation therapies for heart failure.
Emerging Technologies and Future Directions in Interorgan Crosstalk Cardiometabolic Research
Authors: Hosung Bae, Christy M. Nguyen, Jorge Ruiz-Orera, Nicholas L. Mills, Michael P. Snyder, Cholsoon Jang, Svati H. Shah, Norbert Hübner, Marcus Seldin
Journal: Circulation Research (2025)

The heart does not work in isolation, with cardiac health and disease occurring through complex interactions between the heart with multiple organs. Furthermore, the integration of organ-specific lipid metabolism, blood pressure, insulin sensitivity, and inflammation involves a complex network of signaling pathways between many organs. Dysregulation in these communications is now recognized as a key contributor to many manifestations of cardiovascular disease. Mechanistic characterization of specific molecules mediating interorgan signaling has been pivotal in advancing our understanding of cardiovascular disease. The discovery of insulin, glucagon, and other hormones in the early 20th century illustrated the importance of communication between organs in maintaining physiological homeostasis. For example, elegant studies evaluating insulin signaling and its role in regulating glucose metabolism have shed light on its broader impact on cardiovascular health, hypertension, atherosclerosis, and other cardiovascular disease risks. Recent technological advances have revolutionized our understanding of interorgan signaling. Global approaches such as proteomics and metabolomics applications to blood have enabled the simultaneous profiling of thousands of circulating factors, revealing previously unknown signaling molecules and pathways. These large-scale studies have identified biomarkers linked to early stages of heart disease and offered new therapeutic targets. By understanding how specific cells in the heart interact with cells in other organs, such as the kidney or liver, researchers can identify key pathways that, when disrupted, lead to cardiovascular pathology. The ability to capture a more holistic view of the cardiovascular system positions interorgan signaling at the forefront of cardiovascular research. As we continue to refine our tools for mapping these complex networks, the insights gained hold the potential to not only improve early diagnosis but also to develop more targeted and effective treatments for cardiovascular disease. In this review, we discuss current approaches used to enhance our understanding of organ crosstalk with a specific emphasis on cardiac and cardiovascular physiology.
Contributions of Noncardiac Organ–Heart Immune Crosstalk and Somatic Mosaicism to Heart Failure: Current Knowledge and Perspectives
Authors: Marinos Kallikourdis, Jesse D. Cochran, Kenneth Walsh, Gianluigi Condorelli
Journal: Circulation Research (2025)

Heart failure is the final outcome of most cardiovascular diseases and shares risk factors with other cardiovascular pathologies. Among these, inflammation plays a central role in disease progression and myocardial remodeling. Over the past 2 decades, numerous studies have explored immune-related mechanisms in cardiovascular disease, highlighting the importance of immune cross-talk between the heart and extra-cardiac organs, including bone marrow, spleen, liver, gut, and adipose tissue. This review examines how immune interactions among these organs contribute to heart failure pathogenesis, with a focus on clonal hematopoiesis, an age-related alteration of hematopoietic stem cells that fosters pathological bone marrow–heart communication. Additionally, we explore recent advances in the understanding of clonal hematopoiesis and its role in heart failure, emphasizing its implications for prognosis and potential therapeutic interventions. By integrating insights from immunology, metabolism, and aging, we provide a comprehensive perspective on the immunologic determinants of heart failure, paving the way for precision medicine approaches aimed at mitigating cardiovascular risk.
Galectin-1 modulates glycolysis via a GM1-galactose-dependent pathway to promote hyperthermia resistance in hepatocellular carcinoma
Authors: Tu Nguyen, Yonghwan Shin, Aravinth Ruppa, Abigail S. Krall, Janet Pham, Po-Chun Chen, Hannah Mirmohammadi, Pedram Keshavarz, Richard S. Finn, Vatche G. Agopian, Samuel W. French, Heather R. Christofk, David S. K. Lu, Steven S. Raman, Jason Chiang
Journal: Hepatology (2025)

Background and Aims: Thermal ablation is the standard of care treatment modality with curative intent for early-stage non-resectable hepatocellular carcinoma (HCC), but a durable response is limited—with up to 40% of HCC patients eventually experiencing local recurrence on post-treatment surveillance. While thermal ablation has been established to cause immediate cell death in the center of the thermal ablation zone, its metabolic impact in the peri-ablational region remains unclear. We aimed to elucidate the metabolic mechanism by which Galectin-1 (Gal-1) promotes thermal-ablation-induced hyperthermia resistance in HCC and demonstrate the therapeutic potential of inhibiting Gal-1 in combination with thermal ablation in vivo. Approach and Results: Proteomic analysis was performed using an untargeted approach on pre-ablation formalin-fixed paraffin-embedded (FFPE) biopsy specimens of thermal ablation responders (n=32) and nonresponders (n=23). Gal-1 was found to be overexpressed in thermal ablation nonresponders compared to responders. Moreover, HCC with Gal-1 overexpression demonstrated reduced sensitivity to hyperthermia in vitro and increased utilization of glycolysis and downstream TCA cycle under hyperthermia-induced stress. Gal-1-overexpressing HCC enhanced its metabolic utilization through Gal-1-facilitated GM1-ganglioside breakdown, producing galactose to increase the metabolic influxes into glycolysis and consequently the downstream TCA cycle. In vivo studies showed that inhibiting Gal-1 in combination with thermal ablation significantly reduced tumor size compared to either monotherapy thermal ablation or Gal-1 inhibition alone. Conclusions: Gal-1 can mediate hyperthermia resistance in HCC and can potentially be modulated as a therapeutic target to reduce rapid progression after thermal ablation.
Randomized Phase Ib Clinical Trial of DB-020 Intratympanic Injections to Reduce High-Dose Cisplatin Ototoxicity
Authors: Benedict J. Panizza, Stephen John O'Leary, Christopher David Hart, Chandra Sai Diwakarla, Catherine Barnett, Pablo Lapuerta, John Lee, Shane Raines, Tera Quigley, Heather M. Wolff, John Keilty, Rahul Ladwa, Sandro V. Porceddu, Margaret McGrath, Nagashree Seetharamu, Tsien Fua, Danny Rischin
Journal: Journal of Clinical Oncology (2025)

PURPOSE This study evaluated DB-020, a formulation of thiosulfate for intratympanic (IT) injection, in patients receiving high-dose cisplatin chemotherapy. METHODS This randomized phase Ib clinical trial enrolled patients older than 18 years from five centers in Australia and the United States scheduled for at least three cycles of cisplatin and total cumulative exposure of ≥280 mg/m 2 . Patients received IT DB-020 (at a dose level of either 12% or 25%) in one ear and placebo in the other, once every 3 or 4 weeks, within 3 hours before receiving cisplatin. The primary end points were safety and tolerability, and the secondary end points included ototoxicity measured by air conduction audiometry. Ototoxicity was defined by American Speech-Language-Hearing Association criteria. RESULTS Twenty-two patients with a median age of 55.1 years were randomly assigned and received a mean total cumulative cisplatin dose of 255 mg/m 2 . Mean number of cisplatin cycles was 2.3. Twenty patients had both baseline and follow-up audiometry. Ear pain of short duration was common after IT injection. There were no persistent tympanic perforations and no serious adverse events in the category of ear and labyrinth disorders. A progressive reduction in patient numbers was observed at each cycle due to patients ceasing cisplatin treatment. DB-020 treatment did not affect plasma thiosulfate concentrations. Ototoxicity after cisplatin administration was significantly more common in placebo-treated ears than in DB-020–treated ears (DB-020 v placebo, P = .0027). The incidence of ototoxicity (250-8,000 Hz) was 85.0% in placebo-treated ears, and 54.5% and 22.2% in ears treated with DB-020 12% and DB-020 25%, respectively. CONCLUSION DB-020 IT injections were tolerated by patients and showed meaningful reductions in cisplatin ototoxicity.
ESMO-Magnitude of Clinical Benefit Scale version 2.0 (ESMO-MCBS v2.0)
Authors: N I Cherny, S F Oosting, U Dafni, N J Latino, M Galotti, P Zygoura, G Dimopoulou, T Amaral, J Barriuso, A Calles, B Kiesewetter, C Gomez-Roca, B Gyawali, M Piccart, A Passaro, F Roitberg, N Tarazona, D Trapani, G Curigliano, R Wester, G Zarkavelis, C Zielinski, E G E de Vries
Journal: Annals of Oncology (2025)
Safety of nOPV2 administered during a supplementary immunisation activity in Uganda, 2022: data triangulation from a prospective cohort event monitoring programme and vaccine safety surveillance reports
Authors: Ashley T Longley, Fred Nsubuga, Zunera Gilani, Farrell A Tobolowsky, Annet Kisakye, Sharon A Greene, Immaculate Ampeire, Vincent Fred Ssennono, Samuel Ofori Gyasi, Ismail Ntale, Philip Bammeke, Brock Stewart, Helen Byomire Ndagije, Daniel J Kyabayinze, Jane F Gidudu
Journal: The Lancet Global Health (2025)
Deterioration of health outcomes in Gaza: 19 months of protracted conflict
Authors: Laura Paris, Ghada Al-Jadba, Wafaa Zeidan, Paul Spiegel, Zoheir Elkhatib, Rami Habash, Sanaa Al Najjar, Haya Khammash, Shatha Albeik, Tamer Shaer, Mohannad Ramadan, Seita Akihiro
Journal: The Lancet (2025)
Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series
Authors: Neil A Shneider, Matthew B Harms, Vlad A Korobeynikov, Olivia M Rifai, Benjamin N Hoover, Elizabeth A Harrington, Sonya Aziz-Zaman, Jessica Singleton, Arish Jamil, Vikram R Madan, Ikjae Lee, Jinsy A Andrews, Richard M Smiley, Mahabub M Alam, Lauren E Black, Minwook Shin, Jonathan K Watts, David Walk, Daniel Newman, Robert M Pascuzzi, Markus Weber, Christoph Neuwirth, Sandrine Da Cruz, Armand Soriano, Roger Lane, Scott Henry, Joel Mathews, Paymaan Jafar-Nejad, Dan Norris, Frank Rigo, Robert H Brown, Stephan Miller, Rebecca Crean, C Frank Bennett
Journal: The Lancet (2025)
Prospective analysis of endoscopic impedance planimetry pyloric measurements and its association with clinical outcomes with gastric peroral endoscopic myotomy
Authors: Aimen Farooq, BahaAldeen Bani Fawwaz, Yiyang Zhang, Muhammad Khalid Hasan, Arooj Mian, Hafiz Muzaffar Akbar Khan, Tony S Brar, Sanmeet Singh, Artur Viana, Maham Hayat, Yasi Xiao, Waleed Aljohani, Abdullah Abbasi, Saurabh Chandan, Sagar Pathak, Kambiz Kadkhodayan, Mustafa A Arain, Natalie Cosgrove, Deepanshu Jain, Irteza Inayat, Dennis Yang
Journal: Endoscopy (2025)

Background and Aims: Functional luminal imaging probe (FLIP) assesses pyloric sphincter physiology. We aimed to prospectively use FLIP to evaluate the association between pyloric measurements and clinical outcomes of gastric peroral endoscopic myotomy (G-POEM) in patients with refractory gastroparesis. Methods: Single-center prospective trial of patients who underwent G-POEM between January 2022 and March 2024. FLIP was performed pre-G-POEM, immediately post-G-POEM and at follow-up (median 6 months). Clinical response was defined as an improvement of ≥ 1 point on the Gastroparesis Cardinal Symptom Index (GCSI). Receiver operating characteristic curve was constructed to evaluate the relationship between FLIP measurements and response to G-POEM. Results: Clinical response was achieved in 64 out of 90 (71.1%) at a median of 6-months. Pre-G-POEM FLIP mean distensibility index (DI) was significantly lower among responders vs. non-responders (7.1±2.8 vs. 9.2±3.1 mm2/mm Hg; p=0.002). Mean DI increased significantly in both groups immediately after G-POEM, but this remained persistently elevated only among responders (10.4±4.4 mm2/mm Hg; p=0.02), while returning towards baseline among non-responders (9.7±4.7 mm2/mm Hg; p=0.69) at 6-month follow-up. Pre-G-POEM DI with an area under the curve of 0.72 yielded a specificity of 80.8% and sensitivity of 60.6% at a cut-off point of 7.35 mm2/mm Hg. Conclusion: Sustained improvement in pyloric FLIP measurements was seen in patients who endorsed a clinical response to G-POEM. Patients who responded to G-POEM had a lower baseline DI when compared to non-responders. Additional studies optimizing and standardizing FLIP protocols in patients undergoing G-POEM are needed.
The multifaceted biomimetic titanium implant promotes bone integration with sequential antibacterial and immune modulation properties
Authors: Long Chen, Zili Guo, Guowei Duan, Guodong Zhao, Xinyao Liu, Zian Wang, Yuan Liu, Lingling Bai, Hong Xu, Yan Peng, Lei Qiang, Dongbiao Chang, Jun Sheng, Tong Sun, Jie Weng
Journal: Bioactive Materials (2025)
B cell receptor silencing reveals origin and dependencies of high-grade B cell lymphomas with MYC and BCL2 rearrangements
Authors: Gabriele Varano, Silvia Lonardi, Paola Sindaco, Ilaria Pietrini, Gaia Morello, Piera Balzarini, Filippo Vit, Hadas Neuman, Giorgio Bertolazzi, Silvia Brambillasca, Nicara C. Parr, Marco Chiarini, Silvia Bellesi, Elena Maiolo, Sabrina Giampaolo, Federica Mainoldi, Viveka Selvarasa, Hiroshi Arima, Vilma Pellegrini, Chiara Pagani, Mattia Bugatti, Cecilia Ranise, Tommaso M. Taddei, Takashi Sonoki, Hajdica Thanasi, Elena Morlacchi, Daniel Segura-Garzon, Emma Albertini, Rosa Daffini, Anojan Sivacegaram, Henry Yang, Ying Li, Valeria Cancila, Giada Cicio, Michela Robusto, Brian Leuzzi, Adrian Andronache, Paolo Trifiro, Mirko Riboni, Simone P. Minardi, Raoul JP. Bonnal, Cristina Lopez. Gonzalez, Euplio Visco, Pasquale Capaccio, Sara Torretta, Lorenzo Pignataro, Camillo Almici, Mario Varasi, Luigi M. Larocca, Reiner Siebert, Brunangelo Falini, Andrés J.M. Ferreri, Alessandra Tucci, Daniele Lorenzini, Antonello D. Cabras, Giancarlo Pruneri, Arianna Di Napoli, Marco Ungari, Marco Pizzi, Stefan Hohaus, Ciro Mercurio, Joo Y. Song, Wing C. Chan, Luisa Lorenzi, Riccardo Bomben, Maurilio Ponzoni, Ramit Mehr, Claudio Tripodo, Fabio Facchetti, Stefano Casola
Journal: Blood Cancer Discovery (2025)

Abstract The B cell receptor (BCR) is critical for mature B cell lymphomas, serving as a therapeutic target. We show that high-grade B cell lymphomas with MYC and BCL2 rearrangements (HGBCL-DH-BCL2) predominantly exhibit immunoglobulin heavy (IGH) chain silencing, leading to BCR shutdown. IGH-silenced HGBCL-DH-BCL2 (IGHUND) differ from IGH+ counterparts in germinal center-zone programs, MYC expression, and immune infiltrate. While IGH+ HGBCL-DH-BCL2 favor IGM/IG-Kappa expression, IGHUND counterparts complete IGH isotype switching and IG-Lambda rearrangements. IGHUND lymphomas retain productive IGHV rearrangements and require IGH for optimal fitness. BCR silencing, caused by accelerated IGH turnover and reduced IGH expression, precedes HGBCL-DH-BCL2 onset, inducing RAG1/2-dependent IG light chain editing and facilitating t(8;22)/IGL::MYC translocations. IGHUND HGBCL-DH-BCL2 models exhibit reduced sensitivity to the CD79B-targeting antibody-drug conjugate Polatuzumab-vedotin. Collectively, HGBCL-DH-BCL2 commonly arises from isotype-switched t(14;18)+ germinal center B cells, which edit IG light chains, fueling intra-clonal diversification, BCR extinction, and t(8;22) while maintaining IGH dependence, with clinical implications.
Detection of cancers three years prior to diagnosis using plasma cell-free DNA
Authors: Yuxuan Wang, Corinne E. Joshu, Samuel D. Curtis, Christopher Douville, Vernon A. Burk, Meng Ru, Maria Popoli, Janine Ptak, Lisa Dobbyn, Natalie Silliman, Josef Coresh, Eric Boerwinkle, Anna Prizment, Chetan Bettegowda, Kenneth W. Kinzler, Nickolas Papadopoulos, Elizabeth A. Platz, Bert Vogelstein
Journal: Cancer Discovery (2025)

Abstract To explore how early can cancers be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six participants, the same mutations detected by the MCED test could be identified, but at 8.6 to 79-fold lower mutant allele fractions. These results demonstrate that it is possible to detect circulating tumor DNA more than three years prior to clinical diagnosis, and provide benchmark sensitivities required for this purpose.
Abstract 6207: Trends in breast cancer incidence-based mortality among US women aged 20-49 by molecular subtypes and race
Authors: Yueshiu Lyu, Suleepon Uttamapinan, Adetunji T. Toriola
Journal: Cancer Research (2025)

Abstract Background: Breast cancer incidence is rising in women aged 20-49 years, yet data on trends in mortality for this age group are limited. Mortality varies by several factors, underscoring the need for comprehensive analyses. We, therefore, investigated trends in breast cancer incidence-based mortality (IBM) by race and molecular subtypes. Methods: We performed a population-based study of women aged 20-49 years diagnosed with breast cancer between 2010 and 2020 using SEER 17-registry data. We applied IBM method to evaluate mortality trends by molecular subtype and race/ethnicity. We used Joinpoint regression models to identify changes in IBM trends, using annual percent changes (APC). Additionally, we evaluated breast cancer survival rates by race/ethnicity. Results: We analyzed data on 11,661 breast cancer deaths among women aged 20-49 years. Overall, IBM declined from 9.70/100,000 in 2010 to 1.47/100,000 in 2020. The declines occurred in all subtypes and racial/ethnic groups, with some differences in the points of inflexion. IBM for luminal A decreased consistently from 2010, with more marked decline from 2017 (APC, -32.88; 95%CI, -55.17 to -21.30). TNBC followed a similar pattern, with marked decline in 2018 (APC, -32.82; 95%CI, -41.47 to -17.79). Non-Hispanic Black (NHB) women had the highest IBM in 2010 (16.56/100,000) and 2020 (3.41/100,000) compared with Non-Hispanic White (NHW) women (9.18/100,000 in 2010 and 1.16/100,000 in 2020). Declines in IBM in NHB women become pronounced from 2016 (APC, -24.15; 95% CI -34.36 to -17.92), narrowing the gap with other racial groups. Significant declines in IBM for non-Hispanic Asian/Pacific Islander (API) women started earlier from 2013, compared to 2017 for NHW, non-Hispanic American Indian/Alaska Native, and Hispanic women. Survival analyses showed that NHB women had the worst survival outcomes, while NHW and non-Hispanic API had the best. Conclusion: IBM among US women aged 20-49 years with breast cancer declined significantly from 2010 to 2020, with variations by molecular subtype and race/ethnicity. The rapid decline in IBM after 2016-2018 likely reflects advancements in breast cancer management, particularly in novel treatments. Although NHB women still have the highest IBM, the differences have narrowed in recent years. Efforts should continue to focus on further enhancing access to early screening for high-risk women and effective treatment to fully mitigate racial disparities in mortality. Citation Format: Yueshiu Lyu, Suleepon Uttamapinan, Adetunji T. Toriola. Trends in breast cancer incidence-based mortality among US women aged 20-49 by molecular subtypes and race [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6207.
The Central Role of Pin1 in Age-Related Cancer Signaling Pathways
Authors: George Xie, Sho Okuda, Jing-Yan Gao, Timothy Wu, Jessica Jeong, Kun Ping Lu, Xiao Zhen Zhou
Journal: Seminars in Cancer Biology (2025)

The prolyl-isomerase Pin1 is a unique enzyme that catalyzes cis-trans isomerization of phosphorylated Ser/Thr-Pro motifs. These motifs are present in many proteins, where isomerization of the typically rigid prolyl-peptide bond can lead to conformational changes, and subsequently regulate activity, stability, or localization. The specificity of Pin1 for phosphorylated motifs allows it to serve as a master regulator of proteins after phosphorylation, adding an additional layer of regulation to intricately control cellular signaling. As such, Pin1 plays an expansive role in numerous cancer and age-related signaling pathways, and is recognized as a major driver of cancer and promising therapeutic target. In this review, we discuss the role of Pin1 in regulation of age-related cancer signaling pathways, and we highlight the early development and current landscape of Pin1 inhibitors, and the prospect of Pin1 inhibition for cancer therapy.
Dermatology Images: frequent cutaneous findings in neurofibromatosis type 1
Authors: Jeremy Orloff, Dina Poplausky, Jade N Young, Hannah Verma, Shaan Lalvani, Kaya L Curtis, Patricia Cabral, Jonathan Ungar, Shari R Lipner, Susan Shin, Justine Fenner, Gurcharanjeet Kaur, Rebecca Brown, Nicholas Gulati
Journal: Journal of the American Academy of Dermatology (2025)
Red blood cell membrane-derived phototherapeutic nanodiscs: A new platform for enhanced phototherapy
Authors: Deli Zhuge, Li Li, Xueying Sun, Hui Liang, Chenjie Jin, Ailing Lu, Wenli Gao, Yutong Zhong, Wenlu Li, Sihao Chen, Fang Wang, Linzhi Yan, Weiyang Meng, Xiaoji Lin, Xufei Zhang, Yong Liu, Yuanfeng Li, Yingzheng Zhao, Xiang Zhang, Mengchun Chen, Yijie Chen
Journal: Journal of Controlled Release (2025)