tbuckley/cabot-search huggingface dataset:
Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes
Authors: Rami S Komrokji, Luca Lanino, Somedeb Ball, Jan P Bewersdorf, Monia Marchetti, Giulia Maggioni, Erica Travaglino, Najla H Al Ali, Pierre Fenaux, Uwe Platzbecker, Valeria Santini, Maria Diez-Campelo, Avani Singh, Akriti G Jain, Luis E Aguirre, Sarah M Tinsley-Vance, Zaker I Schwabkey, Onyee Chan, Zhouer Xie, Andrew M Brunner, Andrew T Kuykendall, John M Bennett, Rena Buckstein, Rafael Bejar, Hetty E Carraway, Amy E DeZern, Elizabeth A Griffiths, Stephanie Halene, Robert P Hasserjian, Jeffrey Lancet, Alan F List, Sanam Loghavi, Olatoyosi Odenike, Eric Padron, Mrinal M Patnaik, Gail J Roboz, Maximilian Stahl, Mikkael A Sekeres, David P Steensma, Michael R Savona, Justin Taylor, Mina L Xu, Kendra Sweet, David A Sallman, Stephen D Nimer, Christopher S Hourigan, Andrew H Wei, Elisabetta Sauta, Saverio D'Amico, Gianluca Asti, Gastone Castellani, Mattia Delleani, Alessia Campagna, Uma M Borate, Guillermo Sanz, Fabio Efficace, Steven D Gore, Tae Kon Kim, Navel Daver, Guillermo Garcia-Manero, Maria Rozman, Alberto Orfao, Sa A Wang, M Kathryn Foucar, Ulrich Germing, Torsten Haferlach, Phillip Scheinberg, Yasushi Miyazaki, Marcelo Iastrebner, Austin Kulasekararaj, Thomas Cluzeau, Shahram Kordasti, Arjan A van de Loosdrecht, Lionel Ades, Amer M Zeidan, Matteo G Della Porta
Journal: The Lancet Haematology (2024)
Trimodal skin health programme for childhood impetigo control in remote Western Australia (SToP): a cluster randomised, stepped-wedge trial
Authors: Hannah M M Thomas, Stephanie L Enkel, Marianne Mullane, Tracy McRae, Timothy C Barnett, Jonathan R Carapetis, Raymond Christophers, Julianne Coffin, Rebecca Famlonga, John Jacky, Mark Jones, Julie Marsh, Kelli McIntosh, Vicki O'Donnell, Edward Pan, Glenn Pearson, Slade Sibosado, Bec Smith, Thomas Snelling, Andrew Steer, Steven Y C Tong, Roz Walker, Alexandra Whelan, Kristen White, Edie Wright, Asha C Bowen, Ingrid Amgarth-Duff, Lorraine Anderson, David Atkinson, Timothy Barnett, Tina Barrow, Liam Bedford, Asha Bowen, Cheryl Bridge, Jeffrey Cannon, Jonathan Carapetis, Raymond Christophers, Chicky Clements, Juli Coffin, Lucy Davidson, Rhona Dawson, Eloise Delaney, Rachael Donovan, Stephanie Enkel, Rebecca Famlonga, Eleasha Figredo, Abbey Ford, David Hendrickx, Christine Hoy, John Jacky, Mark Jones, Jessica Knight, Francene Leaversuch, Hannah Mann, Julie Marsh, Pippa May, Natasha McGinnis, Kelli McIntosh, Frieda McLoughlin, Janine McNamara, Tracy McRae, Katherine Middleton, Marianne Mullane, Rebekah Newton, Vicki O'Donnell, Edward Pan, Rebecca Pavlos, Glenn Pearson, Emma Pearson, Janessa Pickering, Rahaney Poelina, Clancy Read, Kalindu Rodrigo, Slade Sibosado, Bec Smith, Tom Snelling, Andrew Steer, Hannah Thomas, Steven Tong, Roz Walker, Alexandra Whelan, Kristen White, Bernadette Wong, Edie Wright
Journal: The Lancet Child & Adolescent Health (2024)
AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial
Authors: Jerry R. Mendell, Francesco Muntoni, Craig M. McDonald, Eugenio M. Mercuri, Emma Ciafaloni, Hirofumi Komaki, Carmen Leon-Astudillo, Andrés Nascimento, Crystal Proud, Ulrike Schara-Schmidt, Aravindhan Veerapandiyan, Craig M. Zaidman, Maitea Guridi, Alexander P. Murphy, Carol Reid, Christoph Wandel, Damon R. Asher, Eddie Darton, Stefanie Mason, Rachael A. Potter, Teji Singh, Wenfei Zhang, Paulo Fontoura, Jacob S. Elkins, Louise R. Rodino-Klapac
Journal: Nature Medicine (2024)

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease caused by pathogenic variants in the DMD gene that result in the absence of functional dystrophin, beginning at birth and leading to progressive impaired motor function, loss of ambulation and life-threatening cardiorespiratory complications. Delandistrogene moxeparvovec, an adeno-associated rh74-viral vector-based gene therapy, addresses absent functional dystrophin in DMD. Here the phase 3 EMBARK study aimed to assess the efficacy and safety of delandistrogene moxeparvovec in patients with DMD. Ambulatory males with DMD, ≥4 years to <8 years of age, were randomized and stratified by age group and North Star Ambulatory Assessment (NSAA) score to single-administration intravenous delandistrogene moxeparvovec (1.33 × 10
Novel H-2D<sup>b</sup>-restricted CD8 epitope derived from mouse MAGE-type antigen P1A mediates antitumor immunity in C57BL/6 mice
Authors: James McAuliffe, Silvia Panetti, Emily Steffke, Amanda Wicki, Vinnycius Pereira-Almeida, Laurine Noblecourt, Yushu Hu, Shi Yu William Guo, Julie Lesenfants, Ramiro Andrei Ramirez-Valdez, Vineethkrishna Chandrasekar, Maryam Ahmad, Vincent Stroobant, Nathalie Vigneron, Benoit J Van den Eynde, Carol Sze Ki Leung
Journal: Journal for ImmunoTherapy of Cancer (2024)

Melanoma antigen gene (MAGE)-type antigens are promising targets for cancer immunotherapy as they are expressed in cancer cells but not in normal tissues, except for male germline cells. The mouse P1A antigen shares this MAGE-type expression pattern and has been used as a target antigen in preclinical tumor models aiming to induce antitumor CD8
Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer
Authors: Shigeo Koido, Junichi Taguchi, Masamori Shimabuku, Shin Kan, Tuuse Bito, Takeyuki Misawa, Zensho Ito, Kan Uchiyama, Masayuki Saruta, Shintaro Tsukinaga, Machi Suka, Hiroyuki Yanagisawa, Nobuhiro Sato, Toshifumi Ohkusa, Shigetaka Shimodaira, Haruo Sugiyama
Journal: Journal for ImmunoTherapy of Cancer (2024)

We aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms' tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes, and WT1-specific immune responses of patients with unresectable advanced pancreatic ductal adenocarcinoma (UR-PDAC) who received this treatment.
Effects of tenofovir disoproxil fumarate on intrahepatic viral burden and liver immune microenvironment in patients with chronic hepatitis B
Authors: David Z Pan, Cameron M Soulette, Abhishek Aggarwal, Dong Han, Nicholas van Buuren, Peiwen Wu, Becket Feierbach, Jaw-Town Lin, Cheng-Hao Tseng, Chi-Yi Chen, Bryan Downie, Hongmei Mo, Lauri Diehl, Li Li, Simon P Fletcher, Scott Balsitis, Ricardo Ramirez, Vithika Suri, Yao-Chun Hsu
Journal: Gut (2024)

The impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear.
Undiagnosed Diabetes in Heart Failure With Preserved Ejection Fraction
Authors: John W Ostrominski, Mats C Højbjerg Lassen, Brian L Claggett, Akshay S Desai, Marc A Pfeffer, Bertram Pitt, Carolyn S P Lam, John J V McMurray, Scott D Solomon, Muthiah Vaduganathan
Journal: JACC Heart Failure (2024)
Cardiac Resynchronization Therapy in Ischemic Versus Nonischemic Cardiomyopathy
Authors: Saurabh Sudesh, William T Abraham, John G F Cleland, Anne B Curtis, Daniel J Friedman, Michael R Gold, Valentina Kutyifa, Cecilia Linde, Anthony S Tang, Antonio Olivas-Martinez, Lurdes Y T Inoue, Gillian D Sanders, Sana M Al-Khatib
Journal: JACC Heart Failure (2024)
Right Ventricular Systolic Strain Reference Ranges Across Contemporary Vendor-Neutral Echocardiography Software in Healthy Patients
Authors: Elio Haroun, Ankit Agrawal, Joseph El Dahdah, Tiffany Dong, Aro Daniela Arockiam, Muhammad Majid, Sharmeen Sorathia, Richard A. Grimm, L. Leonardo Rodriguez, Zoran B. Popovic, Brian P. Griffin, Tom Kai Ming Wang
Journal: JACC. Cardiovascular imaging (2024)
Sleep-sensitive dopamine receptor expression in male mice underlies attention deficits after a critical period of early adversity
Authors: Yuichi Makino, Nathaniel W. Hodgson, Emma Doenier, Anna Victoria Serbin, Koya Osada, Pietro Artoni, Matthew Dickey, Breanna Sullivan, Amelia Potter-Dickey, Jelena Komanchuk, Bikram Sekhon, Nicole Letourneau, Neal D. Ryan, Jeanette Trauth, Judy L. Cameron, Takao K. Hensch
Journal: Science Translational Medicine (2024)

Early life stress (ELS) yields cognitive impairments of unknown molecular and physiological origin. We found that fragmented maternal care of mice during a neonatal critical period from postnatal days P2-9 elevated dopamine receptor D2R and suppressed D4R expression, specifically within the anterior cingulate cortex (ACC) in only the male offspring. This was associated with poor performance on a two-choice visual attention task, which was acutely rescued in adulthood by local or systemic pharmacological rebalancing of D2R/D4R activity. Furthermore, ELS male mice demonstrated heightened hypothalamic orexin and persistently disrupted sleep. Given that acute sleep deprivation in normally reared male mice mimicked the ACC dopamine receptor subtype modulation and disrupted attention of ELS mice, sleep loss likely underlies cognitive deficits in ELS mice. Likewise, sleep impairment mediated the attention deficits associated with early adversity in human children, as demonstrated by path analysis on data collected with multiple questionnaires for a large child cohort. A deeper understanding of the sex-specific cognitive consequences of ELS thus has the potential to reveal therapeutic strategies for overcoming them.
Development of an orthotopic medulloblastoma zebrafish model for rapid drug testing
Authors: Niek van Bree, Ann-Sophie Oppelt, Susanne Lindström, Leilei Zhou, Lola Boutin, Beth Coyle, Fredrik J Swartling, John Inge Johnsen, Lars Bräutigam, Margareta Wilhelm
Journal: Neuro-Oncology (2024)

Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current preclinical in vivo model systems for MB have increased our understanding of molecular mechanisms regulating MB development. However, they may not be suitable for large-scale studies. The aim of this study was to investigate if a zebrafish-based xenograft model can recapitulate MB growth and enable rapid drug testing.
Advances and applications of RNA vaccines in tumor treatment
Authors: Ruohan Yang, Jiuwei Cui
Journal: Molecular Cancer (2024)

Compared to other types of tumor vaccines, RNA vaccines have emerged as promising alternatives to conventional vaccine therapy due to their high efficiency, rapid development capability, and potential for low-cost manufacturing and safe drug delivery. RNA vaccines mainly include mRNA, circular RNA (circRNA), and Self-amplifying mRNA(SAM). Different RNA vaccine platforms for different tumors have shown encouraging results in animal and human models. This review comprehensively describes the advances and applications of RNA vaccines in antitumor therapy. Future directions for extending this promising vaccine platform to a wide range of therapeutic uses are also discussed.
Decreased mitochondrial creatine kinase 2 impairs skeletal muscle mitochondrial function independently of insulin in type 2 diabetes
Authors: David Rizo-Roca, Dimitrius Santiago P. S. F. Guimarães, Logan A. Pendergrast, Nicolas Di Leo, Alexander V. Chibalin, Salwan Maqdasy, Mikael Rydén, Erik Näslund, Juleen R. Zierath, Anna Krook
Journal: Science Translational Medicine (2024)

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 ( CKMT2 ). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog β-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing Ckmt2 using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet–fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of Ckmt2 improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes.
An altered natural killer cell immunophenotype characterizes clinically severe pediatric RSV infection
Authors: Roisin B. Reilly, Saïsha K. Ramdour, Mary E. Fuhlbrigge, Luciana P. Tavares, Steven J. Staffa, Jocelyn M. Booth, Nandini Krishnamoorthy, Bruce D. Levy, Melody G. Duvall
Journal: Science Translational Medicine (2024)

Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV
Physical activity, metabolites, and breast cancer associations
Authors: Eleanor L Watts, Steven C Moore, Leila Abar, Hyokyoung G Hong, Pedro F Saint-Maurice, Caitlin O’Connell, Charles E Matthews, Erikka Loftfield
Journal: JNCI Journal of the National Cancer Institute (2024)

The effects of usual physical activity on physiology and disease prevention are not fully understood. We examined the associations between physical activity, metabolites, and breast cancer risk.
A multispecific antibody against SARS-CoV-2 prevents immune escape in vitro and confers prophylactic protection in vivo
Authors: John Misasi, Ronnie R. Wei, Lingshu Wang, Amarendra Pegu, Chih-Jen Wei, Olamide K. Oloniniyi, Tongqing Zhou, Juan I. Moliva, Bingchun Zhao, Misook Choe, Eun Sung Yang, Yi Zhang, Marika Boruszczak, Man Chen, Kwanyee Leung, Juan Li, Zhi-Yong Yang, Hanne Andersen, Kevin Carlton, Sucheta Godbole, Darcy R. Harris, Amy R. Henry, Vera B. Ivleva, Q. Paula Lei, Cuiping Liu, Lindsay Longobardi, Jonah S. Merriam, Danielle Nase, Adam S. Olia, Laurent Pessaint, Maciel Porto, Wei Shi, Shannon M. Wallace, Jeremy J. Wolff, Daniel C. Douek, Mehul S. Suthar, Jason G. Gall, Richard A. Koup, Peter D. Kwong, John R. Mascola, Gary J. Nabel, Nancy J. Sullivan
Journal: Science Translational Medicine (2024)

Despite effective countermeasures, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists worldwide because of its ability to diversify and evade human immunity. This evasion stems from amino acid substitutions, particularly in the receptor binding domain (RBD) of the spike protein that confers resistance to vaccine-induced antibodies and antibody therapeutics. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different RBD sites into multispecific antibodies. Here, we describe multispecific antibodies, including a trivalent trispecific antibody that potently neutralized diverse SARS-CoV-2 variants and prevented virus escape more effectively than single antibodies or mixtures of the parental antibodies. Despite being generated before the appearance of Omicron, this trispecific antibody neutralized all major Omicron variants through BA.4/BA.5 at nanomolar concentrations. Negative stain electron microscopy suggested that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated binding across more than one spike protein. Moreover, a tetravalent trispecific antibody containing the same variable regions as the trivalent trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2, and BA.5 challenge, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. These results demonstrated that multispecific antibodies have the potential to provide broad SARS-CoV-2 coverage, decrease the likelihood of escape, simplify treatment, and provide a strategy for antibody therapies that could help eliminate pandemic spread for this and other pathogens.
A proinflammatory stem cell niche drives myelofibrosis through a targetable galectin-1 axis
Authors: Rong Li, Michela Colombo, Guanlin Wang, Antonio Rodriguez-Romera, Camelia Benlabiod, Natalie J. Jooss, Jennifer O’Sullivan, Charlotte K. Brierley, Sally-Ann Clark, Juan M. Pérez Sáez, Pedro Aragón Fernández, Erwin M. Schoof, Bo Porse, Yiran Meng, Abdullah O. Khan, Sean Wen, Pengwei Dong, Wenjiang Zhou, Nikolaos Sousos, Lauren Murphy, Matthew Clarke, Aude-Anais Olijnik, Zoë C. Wong, Christina Simoglou Karali, Korsuk Sirinukunwattana, Hosuk Ryou, Ruggiero Norfo, Qian Cheng, Joana Carrelha, Zemin Ren, Supat Thongjuea, Vijay A. Rathinam, Anandi Krishnan, Daniel Royston, Gabriel A. Rabinovich, Adam J. Mead, Bethan Psaila
Journal: Science Translational Medicine (2024)

Myeloproliferative neoplasms are stem cell-driven cancers associated with a large burden of morbidity and mortality. Most patients present with early-stage disease, but a substantial proportion progress to myelofibrosis or secondary leukemia, advanced cancers with a poor prognosis and high symptom burden. Currently, it remains difficult to predict progression, and therapies that reliably prevent or reverse fibrosis are lacking. A major bottleneck to the discovery of disease-modifying therapies has been an incomplete understanding of the interplay between perturbed cellular and molecular states. Several cell types have individually been implicated, but a comprehensive analysis of myelofibrotic bone marrow is lacking. We therefore mapped the cross-talk between bone marrow cell types in myelofibrotic bone marrow. We found that inflammation and fibrosis are orchestrated by a "quartet" of immune and stromal cell lineages, with basophils and mast cells creating a TNF signaling hub, communicating with megakaryocytes, mesenchymal stromal cells, and proinflammatory fibroblasts. We identified the β-galactoside-binding protein galectin-1 as a biomarker of progression to myelofibrosis and poor survival in multiple patient cohorts and as a promising therapeutic target, with reduced myeloproliferation and fibrosis in vitro and in vivo and improved survival after galectin-1 inhibition. In human bone marrow organoids, TNF increased galectin-1 expression, suggesting a feedback loop wherein the proinflammatory myeloproliferative neoplasm clone creates a self-reinforcing niche, fueling progression to advanced disease. This study provides a resource for studying hematopoietic cell-niche interactions, with relevance for cancer-associated inflammation and disorders of tissue fibrosis.
Choroid Plexus Pathophysiology
Authors: Ya'el Courtney, Alexandra Hochstetler, Maria K. Lehtinen
Journal: Annual Review of Pathology Mechanisms of Disease (2024)

This review examines the crucial roles of the choroid plexus (ChP) in central nervous system (CNS) pathology, emphasizing its involvement in disease mechanisms and therapeutic potential. Structural changes in the human ChP have been reported across various diseases in case reports and descriptive work, but studies have yet to pin down the physiological relevance of these changes. We highlight primary pathologies of the ChP, as well as their significance in neurologic disorders, including stroke, hydrocephalus, infectious diseases, and neurodegeneration. Synthesizing recent research, this review positions the ChP as a critical player in CNS homeostasis and pathology, advocating for enhanced focus on its mechanisms to unlock new diagnostic and treatment strategies and ultimately improve patient outcomes in CNS diseases. Whether acting as a principal driver of disease, a gateway for pathogens into the CNS, or an orchestrator of neuroimmune processes, the ChP holds tremendous promise as a therapeutic target to attenuate a multitude of CNS conditions.
Precision preclinical modeling to advance cancer treatment
Authors: David H Gutmann, Jesse S Boehm, Elinor K Karlsson, Eric Padron, Mukund Seshadri, Deeann Wallis, Joshua C Snyder
Journal: JNCI Journal of the National Cancer Institute (2024)

A new era of cancer management is underway in which treatments are being developed for the entire continuum of the disease process. The availability of genetically engineered and naturally occurring preclinical models serve as instructive platforms for evaluating therapeutic mechanisms. However, a major clinical challenge is that the entire malignancy process occurs across multiple scales including genetic mutations, malignant changes in cell behavior, dysregulated tumor microenvironments, and systemic adaptations in the host. A multi-disciplinary group of investigators coalesced at the National Cancer Institute Oncology Models Forum (NCI-OMF) with the overall goal to provide updates on the use of precision preclinical models of cancer. The benefits and limitations of preclinical models were discussed in order to identify strategies for maximizing opportunities in modeling that could inform future cancer prevention and treatment approaches. Our shared perspective is that the continuum of single cell, multi-cell, organoid, and in situ models are remarkable resources for the clinical challenges ahead. We provide a roadmap for parsing already available models and include preliminary recommendations for the application of next generation preclinical modeling in cancer intervention.
May the force be with you: Targeting mechanical forces in keloids
Authors: Steven O’Reilly
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript May the force be with you: Targeting mechanical forces in keloids Get access Steven O'Reilly Steven O'Reilly Department of Biosciences, Durham University, South Road, Durham, UK Email:stevenoreilly@hotmail.com https://orcid.org/0000-0001-7483-740X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae388, https://doi.org/10.1093/bjd/ljae388 Published: 09 October 2024 Article history Received: 25 September 2024 Revision received: 25 September 2024 Accepted: 08 October 2024 Published: 09 October 2024
Prevalence of cancer survivors diagnosed during adolescence and young adulthood in the United States
Authors: Lindsey L Page, Theresa P Devasia, Angela Mariotto, Lisa Gallicchio, Michelle A Mollica, Emily Tonorezos
Journal: JNCI Journal of the National Cancer Institute (2024)

Adolescent and young adult (AYA) cancer incidence rates are rising, and survivors are at risk for numerous cancer- and treatment-related consequences. Despite growing attention to this population, prevalence estimates are lacking.
Interleukin 11 therapy causes acute left ventricular dysfunction
Authors: Mark Sweeney, Katie O’Fee, Chelsie Villanueva-Hayes, Ekhlas Rahman, Michael Lee, Chung Nga Tam, Eneko Pascual-Navarro, Henrike Maatz, Eric L Lindberg, Konstantinos Vanezis, Chrishan J Ramachandra, Ivan Andrew, Emma R Jennings, Wei-Wen Lim, Anissa A Widjaja, David Carling, Derek J Hausenloy, Norbert Hübner, Paul J R Barton, Stuart A Cook
Journal: Cardiovascular Research (2024)

Interleukin 11 (IL11) was initially thought important for platelet production, which led to recombinant IL11 being developed as a drug to treat thrombocytopenia. IL11 was later found to be redundant for haematopoiesis and its use in patients is associated with unexplained and severe cardiac side effects. Here we aim to identify, for the first time, direct cardiomyocyte toxicities associated with IL11, which was previously believed cardioprotective.