tbuckley/cabot-search huggingface dataset:
Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease
Authors: Laurent Peyrin-Biroulet, J. Casey Chapman, Jean-Frederic Colombel, Flavio Caprioli, Geert D’Haens, Marc Ferrante, Stefan Schreiber, Raja Atreya, Silvio Danese, James O. Lindsay, Peter Bossuyt, Britta Siegmund, Peter M. Irving, Remo Panaccione, Qian Cao, Ezequiel Neimark, Kori Wallace, Toni Anschutz, Kristina Kligys, W. Rachel Duan, Valerie Pivorunas, Xiu Huang, Sofie Berg, Lei Shu, Marla Dubinsky
Journal: New England Journal of Medicine (2024)

The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown.
Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A
Authors: Lynn Malec, Flora Peyvandi, Anthony K.C. Chan, Christoph Königs, Bulent Zulfikar, Huixing Yuan, Mindy Simpson, Maria Teresa Álvarez Román, Manuel Carcao, Janice M. Staber, Amy L. Dunn, Sheng-Chieh Chou, Roseline d’Oiron, Manuela Albisetti, Marek Demissie, Elena Santagostino, Abhimanyu Yarramaneni, Nancy Wong, Lydia Abad-Franch, Sriya Gunawardena, Karin Fijnvandraat
Journal: New England Journal of Medicine (2024)

Once-weekly efanesoctocog alfa provides high sustained factor VIII activity with superior bleeding prevention as compared with prestudy factor VIII prophylaxis in previously treated patients 12 years of age or older with severe hemophilia A. Data on outcomes of efanesoctocog alfa treatment in children younger than 12 years of age with severe hemophilia A are limited.
Sotorasib for Vascular Malformations Associated with <i>KRAS</i> G12C Mutation
Authors: Antoine Fraissenon, Charles Bayard, Gabriel Morin, Sandro Benichi, Clément Hoguin, Sanela Protic, Lola Zerbib, Sophia Ladraa, Marina Firpion, Thomas Blauwblomme, Olivier Naggara, Michael Duruisseaux, Marion Delous, Clothilde Boitel, Pierre-Paul Bringuier, Léa Payen, Christophe Legendre, Sophie Kaltenbach, Estelle Balducci, Patrick Villarese, Vahid Asnafi, Annouk Bisdorff, Laurent Guibaud, Guillaume Canaud
Journal: New England Journal of Medicine (2024)

gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such
Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras
Authors: Yan Xie, Taeyoung Choi, Ziyad Al-Aly
Journal: New England Journal of Medicine (2024)

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) can affect many organ systems. However, temporal changes during the coronavirus disease 2019 (Covid-19) pandemic, including the evolution of SARS-CoV-2, may have affected the risk and burden of PASC. Whether the risk and burden of PASC have changed over the course of the pandemic is unclear.
Case Series of Patients with Marburg Virus Disease, Equatorial Guinea, 2023
Authors: Luca Fontana, Cándido O. Ondo Avomo, Ladislao E. Ngomo Mikue, Domitila Ñ. Fuga Eyemam, Micaela A. Nguere, Ilda E. Mometolo, Rosalia N. Bibang Nzang, Damaso M. Nguema Maye, Ruggero Giuliani, Frédérique Jacquerioz, Hans-Joerg Lang, Richard Kojan, Antoine Chaillon, Stephanie Ngai, Olivier le Polain de Waroux, Anna Silenzi, Michele Di Marco, María E. Negrón, John D. Klena, Mary J. Choi, Oren Mayer, Florine E.M. Scholte, Stephen R. Welch, Emily Zielinski-Gutierrez, Janet Diaz
Journal: New England Journal of Medicine (2024)
Sudan Virus Disease among Health Care Workers, Uganda, 2022
Authors: Abdullah Wailagala, Paul W. Blair, Kenneth Kobba, Kayiira Mubaraka, Hellen Aanyu-Tumukahebwa, Daniel Kiiza, Musoke T. Sekikongo, John D. Klena, Peter Waitt, Rony R. Bahatungire, Henry S. Kyobe, Diana Atwine, Alex Adaku, Bodo Bongomin, Bruce Kirenga, Amy Boore, Danielle V. Clark, David Kaggwa, Melissa Gregory, Wilberforce Kabweru, Willy Kayondo, Stacy K. Mbabazi, Hannah Kibuuka, Ivan Kimuli, Sophie Mulei, Michael Mutegeki, Batibwe Emmanuel, Henry Mwebesa, Prossy Naluyima, Stephen Okello, Alex Tumusiime, Joel Montgomery, Vamsi Vasireddy, Charles Olaro, Misaki Wayengera, Mohammed Lamorde
Journal: New England Journal of Medicine (2024)
Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial
Authors: Alexios Matikas, Volker Möbus, Richard Greil, Anne Andersson, Günther G. Steger, Michael Untch, Tommy Fornander, Per Malmström, Sabine Schmatloch, Hemming Johansson, Mats Hellström, Yvonne Brandberg, Michael Gnant, Sibylle Loibl, Theodoros Foukakis, Jonas Bergh, Niklas Lohman, Martin Söderberg, Per Malmström, Zakaria Einbeigi, Per Karlsson, Barbro Linderholm, Stig Holmberg, Lotta Dabrosin, Elham Hedayati, Kenneth Villman, Sam Rotstein, Birgitta Wallberg, Tommy Fornander, Henrik Lindman, Johan Ahlgren, Per Edlund, Lena Carlsson, Nils-Olof Bengtsson, Eva Karlsson, Sabine Schmatloch, Matthias Kögel, Andreas Kohls, Eva-Maria Grischke, Gerold Baake, Gerald Hoffmann, Maria Dietrich, Volker Möbus, Ralf Adrion, Volker Heyl, Benjamin Schnappauf, Thomas Göhler, Gabriele Ziemendorff, Ingo Thalmann, Claudia Schumacher, Erich Weiss, Oliver Tomé, Wolfgang Bauer, Angelika Ober, Andeas Schneeweiss, HG Höffkes, Helmut Forstbauer, Erich-Franz Solomayer, Doris Augustin, Holger Schultz, Barmak Adhami, Michael Niedermeier, Hans Ulrich Ulmer, Andrea Hocke, Manfred Kusche, Reinhard Hackenberg, Andreas Rossmann, Tilmann Lantzsch, Jürgen Schulze‐Tollert, Christoph Lerchenmüller, Ekkehart Ladda, Elke Wierick, Hans Werner Tessen, Gerd Raudies, Alexandra Sallmann, Berhardt Martin, Christoph Uleer, Kristina Maria Lübbe, Ricardo Felberbaum, Wolfgang Wiest, Marc Sütterlin, Christoph Thomssen, Uwe-Jochen Göhring, Hans Tesch, Axel Gatzweiler, Wolfgang Janni, Marcus Schmidt, Andeas Werner, Lelia Bauer, Agustinus Tulusan, Tjong-Won Park, Michael Berghorn, Thomas Noesselt, Stephan Henschen, Herbert Stöger, Christian Marth, Angelika Pichler, Michael Fridrik, Volker Ömer, Alois Lang, Richard Greil, Harald Weiß, Johannes Andel, Josef Thaler, Arik Galid, Paul Sevelda, Christian Singer, Günther Steger, Elisabeth Melbinger‐Zeinitzer, Jörg Keckstein, Felix Keil, Christoph Tinchon, Ernst Kubista, Michael Stierer, Hans Jörg Neumann, Thomas Bauernhofer, Gertraud Tschurtschenthaler, Hellmut Samonigg
Journal: Journal of Clinical Oncology (2024)

JCO
Post-Transplant Cyclophosphamide–Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors
Authors: Brian C. Shaffer, Mahasweta Gooptu, Todd E. DeFor, Martin Maiers, Javier Bolaños-Meade, Ramzi Abboud, Adrienne D. Briggs, Farhad Khimani, Dipenkumar Modi, Richard Newcomb, Elizabeth J. Shpall, Caitrin Bupp, Stephen R. Spellman, Heather E. Stefanski, Bronwen E. Shaw, Jeffery J. Auletta, Steven M. Devine, Antonio M. Jimenez Jimenez, Monzr M. Al Malki
Journal: Journal of Clinical Oncology (2024)

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.RESULTSIncluded were 10,025 HCT recipients (7,272 recipients of MUD with CNI, 1,681 MUD with PTCy, 613 MMUD with CNI, and 459 MMUD with PTCy) who underwent HCT for acute leukemia (70.9%) or myelodysplastic syndromes (29.2%). Median patient age was 60.7 years (range, 18.0-82.7) and median follow-up was 36.6 (range, 3.0-77.8) months. When compared with MUD HCT with PTCy, MMUD HCT with PTCy had similar OS (hazard ratio [HR], 0.96 [95% CI, 0.823 to 1.11];
Lymphoma Classifications, How to Develop a Future Unified Taxonomy
Authors: Elias Campo, Daan Dierickx, Stefan Dirnhofer, Kieron Dunleavy, Philippe Gaulard, Robert P. Hasserjian, Elaine S. Jaffe, Won Seog Kim, Rebecca L. King, Megan S. Lim, German Ott, Miguel A. Piris, Gilles Salles, Reiner Siebert
Journal: Journal of Clinical Oncology (2024)
Internal world models in humans, animals, and AI
Authors: Ilka Diester, Marlene Bartos, Joschka Bödecker, Adam Kortylewski, Christian Leibold, Johannes Letzkus, Mathew M Nour, Monika Schönauer, Andrew Straw, Abhinav Valada, Andreas Vlachos, Thomas Brox
Journal: Neuron (2024)
Chondroitin sulfate proteoglycan 4 (CSPG4) increases invasion of recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma by modifying TGFβ signaling
Authors: Allison R K Macaulay, Jianbo Yang, Matthew A Price, Colleen L Forster, Megan J Riddle, Christen L Ebens, Frank W Albert, Alessio Giubellino, James B McCarthy, Jakub Tolar
Journal: British Journal of Dermatology (2024)

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin-blistering disorder often progressing to metastatic cutaneous squamous cell carcinoma (cSCC) at chronic wound sites. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell-surface proteoglycan that is an oncoantigen in multiple malignancies, where it modulates oncogenic signaling, drives epithelial-to-mesenchymal transition (EMT), and enables cell motility.
Preventing chemotherapy-induced peripheral neuropathy with acupuncture, a multinational parallel randomized controlled trials project (PACT).
Authors: Weidong Lu, Anita Giobbie-Hurder, Anna Tanasijevic, Sylvia Baedorf Kassis, Ellie Diederich, Aliya Sahraoui, Sung Hwan Park, Young Ju Jeong, Im Hee Shin, Chang Yao, Xiping Zhang, Hyun Jung Jung, Na-Rang Lee, Yao Yao, Chao Bao, Ting Bao, EunMee Yang, Robert Knoerl, Barbara E Bierer, Jennifer A. Ligibel
Journal: Journal of Clinical Oncology (2024)

TPS12156 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant challenge for patients (pts) with breast cancer treated with taxanes and platinum compounds. CIPN severely affects quality of life, leading to paresthesia and pain, and often results in dose modifications and discontinuation of treatment. Although preliminary trials suggest the effectiveness of acupuncture in managing existing symptoms of CIPN, the use of acupuncture to prevent CIPN is not well studied. Prior studies provide inconclusive results, underscoring the need for more rigorous investigation. We designed an international study, PACT, to evaluate the impact of acupuncture on the prevention of CIPN in breast cancer pts who undergo adjuvant or neoadjuvant taxane-based chemotherapy. Methods: PACT is a coordinated multi-national study consisting of three parallel randomized trials in USA, China, and South Korea, using the same inclusion/exclusion criteria, randomization, interventions, and validated measures. PACT is designed to evaluate the effectiveness of acupuncture in preventing CIPN in pts undergoing taxane-based chemotherapy for early-stage breast cancer. Participants include pts with newly diagnosed stage I-III breast cancer without preexisting neuropathy, scheduled for adjuvant or neoadjuvant taxane-based chemotherapy. Target enrollment is 140 pts from three sites: Dana-Farber Cancer Institute (USA) (n=100), Jiangsu Province Hospital of Chinese Medicine (China) (n = 20) and the Daegu Catholic University Medical Center (South Korea) (n=20), randomized (1:1) to the acupuncture arm or a control. The acupuncture arm receives a standardized protocol of 1-2 sessions per week for 12 weeks (total of 14 sessions). The control arm receives relaxation exercises with nature scenery videos for 14 sessions. The follow-up period for both arms is 12 weeks. Main measures include The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, QLQ-30 and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) CIPN items. The primary outcome measure is the change in CIPN severity, assessed using the EORTC QLQ-CIPN20 sensory subscale, between baseline and week 12, with secondary outcomes including occurrence of CIPN and maximum CIPN scores, pain, sleep quality, and overall quality of life. A planned pooled analysis of individual patient data will be performed. The ethics review committee of each site has approved the study. Today, 89 (64%) of the planned 140 participants have been enrolled. Clinical trial information: NCT05528263 , ChiCTR2200066714, KCT0008470.
Dapagliflozin Effects on Cardiac Deformation in Heart Failure and Secondary Clinical Outcome
Authors: Maria Concetta Pastore, Andrea Stefanini, Giulia Elena Mandoli, Pietro Piu, Enrico Emilio Diviggiano, Maria Alma Iuliano, Leonardo Carli, Andrea Marchese, Luca Martini, Alessio Pecere, Luna Cavigli, Elisa Giacomin, Antonio Pagliaro, Francesca Maria Righini, Carlotta Sorini Dini, Hatem Soliman Aboumarie, Marta Focardi, Flavio D’Ascenzi, Serafina Valente, Matteo Cameli
Journal: JACC. Cardiovascular imaging (2024)

Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66)
Seroprevalence of Chagas Cardiomyopathy Among Hospitalized Latin American Immigrants Within a Washington, DC, Hospital
Authors: Ajay Kerai, Ritika Gadodia, Tsion Aberra, Omar Shakhtour, Jiling Chou, Ingy Mahana, Puja Patel, Diego Medvedofsky, Rachel Marcus
Journal: JACC Heart Failure (2024)
Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming
Authors: Tian Y. Du, Steven R. Hall, Felicity Chung, Sergey Kurdyukov, Edouard Crittenden, Karishma Patel, Charlotte A. Dawson, Adam P. Westhorpe, Keirah E. Bartlett, Sean A. Rasmussen, Cesar L. Moreno, Christopher E. Denes, Laura-Oana Albulescu, Amy E. Marriott, Joel P. Mackay, Mark C. Wilkinson, José María Gutiérrez, Nicholas R. Casewell, G. Gregory Neely
Journal: Science Translational Medicine (2024)

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including
Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression
Authors: Constanca Figueiredo, Chen Chen-Wacker, Jawad Salman, Marco Carvalho-Oliveira, Thierry Siemeni Monthé, Klaus Höffler, Tamina Rother, Karolin Hacker, Emilio Valdivia, Olena Pogozhykh, Sabine Hammer, Wiebke Sommer, Yuliia Yuzefovych, Nadine Wenzel, Axel Haverich, Gregor Warnecke, Rainer Blasczyk
Journal: Science Translational Medicine (2024)

Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. Minipig donor lungs with unmodified SLA expression (control group,
Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae after acute COVID-19
Authors: Chaofan Li, Wei Qian, Xiaoqin Wei, Harish Narasimhan, Yue Wu, Mohd Arish, In Su Cheon, Jinyi Tang, Gislane de Almeida Santos, Ying Li, Kamyar Sharifi, Ryan Kern, Robert Vassallo, Jie Sun
Journal: Science Translational Medicine (2024)

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target.
Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models
Authors: Shangyou Zheng, Chonghui Hu, Qing Lin, Tingting Li, Guolin Li, Qing Tian, Xiang Zhang, Tianhao Huang, Yuancheng Ye, Rihua He, Changhao Chen, Yu Zhou, Rufu Chen
Journal: Science Translational Medicine (2024)

Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles (EVs) were involved in PNI in dorsal root ganglion coculture and mouse sciatic nerve models. Next, we demonstrated that CAFs promoted PNI through extracellular vesicle transmission of PNI-associated transcript (PIAT). Mechanistically, PIAT specifically bound to YBX1 and blocked the YBX1-Nedd4l interaction to inhibit YBX1 ubiquitination and degradation. Furthermore, PIAT enhanced the binding of YBX1 and PNI-associated mRNAs in a 5-methylcytosine (m5C)-dependent manner. Mutation of m5C recognition motifs in YBX1 or m5C sites in downstream target genes reversed PIAT-mediated PNI. Consistent with these findings, analyses using a KPC mouse model demonstrated that the PIAT/YBX1 axis enhanced PNI through m5C modification. Clinical data suggested that the PIAT expression in the serum EVs of patients with pancreatic cancer was associated with the degree of neural invasion and prognosis. Our study revealed the important role of the PIAT/YBX1 signaling axis in the tumor microenvironment (TME) in promoting tumor cell PNI and provided a new target for precise interference with CAFs and RNA methylation in the TME to suppress PNI in pancreatic cancer.
Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction
Authors: Deborah M. Eaton, Benjamin W. Lee, Matthew A. Caporizzo, Amit Iyengar, Christina Y. Chen, Keita Uchida, Guillaume Marcellin, Yoann Lannay, Alexia Vite, Kenneth C. Bedi, Claire F. Brady, Julia N. Smolyak, Danika Meldrum, Jessica Dominic, Noah Weingarten, Mrinal Patel, Andrew Belec, Khaled Hached, Pavan Atluri, Siem Van Der Laan, Benjamin L. Prosser, Kenneth B. Margulies
Journal: Science Translational Medicine (2024)

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.