tbuckley/cabot-search huggingface dataset:
Rationale and Design of SCOT-HEART 2 Trial
Authors: Michael McDermott, Mohammed N Meah, Phyo Khaing, Kang-Ling Wang, Jennifer Ramsay, Gillian Scott, Hannah Rickman, Tom Burt, Ian McGowan, Timothy Fairbairn, Marise Bucukoglu, Russell Bull, Adam Timmis, Edwin J R van Beek, Giles Roditi, Philip D Adamson, Steff Lewis, John Norrie, Brian McKinstry, Bruce Guthrie, Lewis Ritchie, Nicholas L Mills, Marc R Dweck, Michelle C Williams, David E Newby
Journal: JACC. Cardiovascular imaging (2024)

Coronary artery disease continues to be the leading cause of death globally. Identifying patients who are at risk of coronary artery disease remains a public health priority. At present, the focus of cardiovascular disease prevention relies heavily on probabilistic risk scoring despite no randomized controlled trials demonstrating their efficacy. The concept of using imaging to guide preventative therapy is not new, but has previously focused on indirect measures such as carotid intima-media thickening or coronary artery calcification. In recent trials, patients found to have coronary artery disease on computed tomography (CT) coronary angiography were more likely to be started on preventative therapy and had lower rates of cardiac events. This led to the design of the SCOT-HEART 2 (Scottish Computed Tomography of the Heart 2) trial, which aims to determine whether screening with the use of CT coronary angiography is more clinically effective than cardiovascular risk scoring to guide the use of primary preventative therapies and reduce the risk of myocardial infarction.
Prognostic Value of Left Ventricular 18F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis
Authors: Olivier F Clerc, Yesh Datar, Sarah A M Cuddy, Giada Bianchi, Alexandra Taylor, Dominik C Benz, Matthew Robertson, Marie Foley Kijewski, Michael Jerosch-Herold, Raymond Y Kwong, Frederick L Ruberg, Ronglih Liao, Marcelo F Di Carli, Rodney H Falk, Sharmila Dorbala
Journal: JACC. Cardiovascular imaging (2024)
Heart Failure Drug Development Over the Eras
Authors: Vanessa Blumer, James L Januzzi, JoAnn Lindenfeld, Scott D Solomon, Mitchell A Psotka, Peter E Carson, Michael R Bristow, William T Abraham, Charu Gandotra, Benjamin R Saville, Christopher O'Connor, Mona Fiuzat
Journal: JACC Heart Failure (2024)

Over the past decade, the field of heart failure (HF) has witnessed remarkable progress in drug development, resulting in the approval of numerous groundbreaking drugs by the U.S. Food and Drug Administration. To address some of these challenges, the U.S. Food and Drug Administration has issued guidance documents that have been critical in contemporary HF drug development; however, there are still many challenges in need of investigation. This paper leverages efforts of the Heart Failure Collaboratory and the scientific community to discuss the critical need for innovative trial designs, important concepts in clinical trials in the modern era, and the utilization of big data to accelerate HF drug development. At this inflection point in HF drug development, it is imperative that, as a global scientific community, we foster increased collaboration among researchers, clinicians, patients, and regulatory bodies. Only through such unified efforts can we navigate the complexities of HF, accelerate the development process, and ultimately deliver effective therapies that transform patient outcomes.
Machine Learning in Hypertrophic Cardiomyopathy
Authors: Kankan Zhao, Yanjie Zhu, Xiuyu Chen, Shujuan Yang, Weipeng Yan, Kai Yang, Yanyan Song, Chen Cui, Xi Xu, Qingyong Zhu, Zhuo-Xu Cui, Gang Yin, Huaibin Cheng, Minjie Lu, Dong Liang, Ke Shi, Lei Zhao, Hui Liu, Jiayin Zhang, Liang Chen, Sanjay K Prasad, Shihua Zhao, Hairong Zheng
Journal: JACC. Cardiovascular imaging (2024)
Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis
Authors: Mohammad Saeid Rezaee-Zavareh, Yee Hui Yeo, Tielong Wang, Zhiyong Guo, Parissa Tabrizian, Stephen C. Ward, Fatma Barakat, Tarek I. Hassanein, Shravan Dave, Veeral Ajmera, Sherrie Bhoori, Vincenzo Mazzaferro, David M.H. Chascsa, Margaret C. Liu, Elizabeth S. Aby, John R. Lake, Miguel Sogbe, Bruno Sangro, Maen Abdelrahim, Abdullah Esmail, Andreas Schmiderer, Yasmina Chouik, Mark Rudolph, Davendra Sohal, Heloise Giudicelli, Manon Allaire, Mehmet Akce, Jessica Guadagno, Clara Y. Tow, Hatef Massoumi, Paolo De Simone, Elise Kang, Robyn D. Gartrell, Mercedes Martinez, Ricardo Paz-Fumagalli, Beau B. Toskich, Nguyen H. Tran, Gabriela Azevedo Solino, Dra Mariana Poltronieri Pacheco, Richard S. Kalman, Vatche G. Agopian, Neil Mehta, Neehar D. Parikh, Amit G. Singal, Ju Dong Yang
Journal: Journal of Hepatology (2024)
An open-label, randomized controlled trial to assess a ketogenic diet in critically ill patients with sepsis
Authors: Tim Rahmel, David Effinger, Thilo Bracht, Leonore Griep, Björn Koos, Barbara Sitek, Max Hübner, Simon Hirschberger, Jale Basten, Nina Timmesfeld, Michael Adamzik, Simone Kreth
Journal: Science Translational Medicine (2024)

Patients with sepsis experience metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutrition. A ketogenic diet (KD) may offer an immunologically advantageous alternative, although clinical evidence is limited. We conducted a single-center, open-label, randomized controlled trial to assess whether a KD could induce stable ketosis in critically ill patients with sepsis. Secondary outcomes included assessment of feasibility and safety of KD, as well as explorative analysis of clinical and immunological characteristics. Forty critically ill adults were randomized to either a ketogenic or standard high-carbohydrate diet. Stable ketosis was achieved in all KD patients, with significant increases in β-hydroxybutyrate levels compared with controls [mean difference 1.4 milimoles per liter; 95% confidence interval (CI): 1.0 to 1.8;
Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation
Authors: Wenliang Zhu, Wan Du, Arun Prabhu Rameshbabu, Ariel Miura Armstrong, Stewart Silver, Yehree Kim, Wei Wei, Yilai Shu, Xuezhong Liu, Morag A. Lewis, Karen P. Steel, Zheng-Yi Chen
Journal: Science Translational Medicine (2024)

Mutations in microRNA-96 ( MIR96 ) cause autosomal dominant deafness-50 (DFNA50), a form of delayed-onset hearing loss. Genome editing has shown efficacy in hearing recovery through intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications, which has not been done. Here, we developed a genome editing therapy for the MIR96 mutation 14C&gt;A by screening different CRISPR systems and optimizing Cas9 expression and the sgRNA scaffold for efficient and specific mutation editing. AAV delivery of the KKH variant of Staphylococcus aureus Cas9 (SaCas9-KKH) and sgRNA to the cochleae of presymptomatic (3-week-old) and symptomatic (6-week-old) adult Mir96 14C&gt;A/+ mutant mice improved hearing long term, with efficacy increased by injection at a younger age. Adult inner ear delivery resulted in transient Cas9 expression without evidence of AAV genomic integration, indicating the good safety profile of our in vivo genome editing strategy. We developed a dual-AAV system, including an AAV-sgmiR96-master carrying sgRNAs against all known human MIR96 mutations. Because mouse and human MIR96 sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lay the foundation for the development of treatment for patients with DFNA50 caused by MIR96 mutations.
Hemodynamic evaluation of biomaterial-based surgery for Tetralogy of Fallot using a biorobotic heart, in silico, and ovine models
Authors: Manisha Singh, François Roubertie, Caglar Ozturk, Paul Borchiellini, Adeline Rames, Jean Bonnemain, Samuel Dutra Gollob, Sophie X. Wang, Jérôme Naulin, Dounia El Hamrani, Nathalie Dugot-Senant, Isalyne Gosselin, Célia Grenet, Nicolas L’Heureux, Ellen T. Roche, Fabien Kawecki
Journal: Science Translational Medicine (2024)

Tetralogy of Fallot is a congenital heart disease affecting newborns and involves stenosis of the right ventricular outflow tract (RVOT). Surgical correction often widens the RVOT with a transannular enlargement patch, but this causes issues including pulmonary valve insufficiency and progressive right ventricle failure. A monocusp valve can prevent pulmonary regurgitation; however, valve failure resulting from factors including leaflet design, morphology, and immune response can occur, ultimately resulting in pulmonary insufficiency. A multimodal platform to quantitatively evaluate the effect of shape, size, and material on clinical outcomes could optimize monocusp design. This study introduces a benchtop soft biorobotic heart model, a computational fluid model of the RVOT, and a monocusp valve made from an entirely biological cell-assembled extracellular matrix (CAM) to tackle the multifaceted issue of monocusp failure. The hydrodynamic and mechanical performance of RVOT repair strategies was assessed in biorobotic and computational platforms. The monocusp valve design was validated in vivo in ovine models through echocardiography, cardiac magnetic resonance, and catheterization. These models supported assessment of surgical feasibility, handling, suturability, and hemodynamic and mechanical monocusp capabilities. The CAM-based monocusp offered a competent pulmonary valve with regurgitation of 4.6 ± 0.9% and a transvalvular pressure gradient of 4.3 ± 1.4 millimeters of mercury after 7 days of implantation in sheep. The biorobotic heart model, in silico analysis, and in vivo RVOT modeling allowed iteration in monocusp design not now feasible in a clinical environment and will support future surgical testing of biomaterials for complex congenital heart malformations.
Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system
Authors: Carolina Rosselot, Yansui Li, Peng Wang, Alexandra Alvarsson, Kara Beliard, Geming Lu, Randy Kang, Rosemary Li, Hongtao Liu, Virginia Gillespie, Nikolaos Tzavaras, Kunal Kumar, Robert J. DeVita, Andrew F. Stewart, Sarah A. Stanley, Adolfo Garcia-Ocaña
Journal: Science Translational Medicine (2024)

Five hundred thirty-seven million people globally suffer from diabetes. Insulin-producing β cells are reduced in number in most people with diabetes, but most individuals still have some residual β cells. However, none of the many diabetes drugs in common use increases human β cell numbers. Recently, small molecules that inhibit dual tyrosine-regulated kinase 1A (DYRK1A) have been shown to induce immunohistochemical markers of human β cell replication, and this is enhanced by drugs that stimulate the glucagon-like peptide 1 (GLP1) receptor (GLP1R) on β cells. However, it remains to be demonstrated whether these immunohistochemical findings translate into an actual increase in human β cell numbers in vivo. It is also unknown whether DYRK1A inhibitors together with GLP1R agonists (GLP1RAs) affect human β cell survival. Here, using an optimized immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO
Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities
Authors: Brian J. Mog, Nikita Marcou, Sarah R. DiNapoli, Alexander H. Pearlman, Tushar D. Nichakawade, Michael S. Hwang, Jacqueline Douglass, Emily Han-Chung Hsiue, Stephanie Glavaris, Katharine M. Wright, Maximilian F. Konig, Suman Paul, Nicolas Wyhs, Jiaxin Ge, Michelle S. Miller, P. Azurmendi, Evangeline Watson, Drew M. Pardoll, Sandra B. Gabelli, Chetan Bettegowda, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Shibin Zhou
Journal: Science Translational Medicine (2024)

Two types of engineered T cells have been successfully used to treat patients with cancer, one with an antigen recognition domain derived from antibodies [chimeric antigen receptors (CARs)] and the other derived from T cell receptors (TCRs). CARs use high-affinity antigen-binding domains and costimulatory domains to induce T cell activation but can only react against target cells with relatively high amounts of antigen. TCRs have a much lower affinity for their antigens but can react against target cells displaying only a few antigen molecules. Here, we describe a new type of receptor, called a Co-STAR (for costimulatory synthetic TCR and antigen receptor), that combines aspects of both CARs and TCRs. In Co-STARs, the antigen-recognizing components of TCRs are replaced by high-affinity antibody fragments, and costimulation is provided by two modules that drive NF-κB signaling (MyD88 and CD40). Using a TCR-mimic antibody fragment that targets a recurrent p53 neoantigen presented in a common human leukocyte antigen (HLA) allele, we demonstrate that T cells equipped with Co-STARs can kill cancer cells bearing low densities of antigen better than T cells engineered with conventional CARs and patient-derived TCRs in vitro. In mouse models, we show that Co-STARs mediate more robust T cell expansion and more durable tumor regressions than TCRs similarly modified with MyD88 and CD40 costimulation. Our data suggest that Co-STARs may have utility for other peptide-HLA antigens in cancer and other targets where antigen density may limit the efficacy of engineered T cells.
RBCs Regulate Platelet Function and Hemostasis under Shear Conditions through Biophysical and Biochemical Means
Authors: Debbie Jiang, Katie L Houck, Lydia Murdiyarso, Harrison Higgins, Nicole M Rhoads, Sophia K Romero, Rosemary Kozar, Angelo Nascimbene, Terry B Gernsheimer, Zyrina Alura C Sanchez, Anand Ramasubramanian, Reheman Adili, Jing-fei Dong
Journal: Blood (2024)
Enhanced Procoagulant Activity of Select Hemophilia B Causing Factor IX Variants with Emicizumab
Authors: Kyumin Lee, Julia Q. Chau, Yani B. Suber, Anna R. Sternberg, Allyson M. Pishko, Lindsey A. George, Vijay G. Bhoj, Bhavya S. Doshi, Benjamin J. Samelson-Jones
Journal: Blood (2024)
Itaconate is a metabolic regulator of bone formation in homeostasis and arthritis
Authors: Markus Kieler, Leona Sophia Prammer, Gerwin Heller, Melanie Hofmann, Simon Sperger, Dominik Hanetseder, Birgit Niederreiter, Andrea Komljenovic, Kristaps Klavins, Thomas Köcher, Julia Stefanie Brunner, Irena Stanic, Laura Oberbichler, Ana Korosec, Andrea Vogel, Martina Kerndl, Dominika Hromadová, Laszlo Musiejovsky, Alexander Hajto, Anja Dobrijevic, Tina Piwonka, Arvand Haschemi, Anne Miller, Philippe Georgel, Darja Marolt Presen, Johannes Grillari, Silvia Hayer, Jean-Philippe Auger, Gerhard Krönke, Omar Sharif, Daniel Aletaha, Gernot Schabbauer, Stephan Blüml
Journal: Annals of the Rheumatic Diseases (2024)

Bone remodelling is a highly dynamic process dependent on the precise coordination of osteoblasts and haematopoietic-cell derived osteoclasts. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis.
Deep Learning for Strain Field Customization in Bioreactor with Dielectric Elastomer Actuator Array
Authors: Jue Wang, Dhirodaatto Sarkar, Atulya Mohan, Mina Lee, Zeyu Ma, Alex Chortos
Journal: Cyborg and Bionic Systems (2024)

In the field of biomechanics, customizing complex strain fields according to specific requirements poses an important challenge for bioreactor technology, primarily due to the intricate coupling and nonlinear actuation of actuator arrays, which complicates the precise control of strain fields. This paper introduces a bioreactor designed with a 9 × 9 array of independently controllable dielectric elastomer actuators (DEAs), addressing this challenge. We employ image regression-based machine learning for both replicating target strain fields through inverse control and rapidly predicting feasible strain fields generated by the bioreactor in response to control inputs via forward control. To generate training data, a finite element analysis (FEA) simulation model was developed. In the FEA, the device was prestretched, followed by the random assignment of voltages to each pixel, yielding 10,000 distinct output strain field images for the training set. For inverse control, a multilayer perceptron (MLP) is utilized to predict control inputs from images, whereas, for forward control, MLP maps control inputs to low-resolution images, which are then upscaled to high-resolution outputs through a super-resolution generative adversarial network (SRGAN). Demonstrations include inputting biomechanically significant strain fields, where the method successfully replicated the intended fields. Additionally, by using various tumor-stroma interfaces as inputs, the bioreactor demonstrated its ability to customize strain fields accordingly, showcasing its potential as an advanced testbed for tumor biomechanics research.
Health-related quality of life and symptoms of chronic myeloid leukemia patients after discontinuation of tyrosine kinase inhibitors: results from the EURO-SKI Trial
Authors: Fabio Efficace, Francois-Xavier Mahon, Johan Richter, Alfonso Piciocchi, Marta Cipriani, Franck E Nicolini, Jiri Mayer, Daniela Zackova, Jeroen J W M Janssen, Panayiotis Panayiotidis, Hanne Vestergaard, Perttu Koskenvesa, Antonio Almeida, Henrik Hjorth-Hansen, Joaquin Martinez-Lopez, Ulla Olsson-Strömberg, Andreas Hochhaus, Marc G Berger, Gabriel Etienne, Hana Klamova, Edgar Faber, Philippe Rousselot, Markus Pfirrmann, Susanne Saussele
Journal: Leukemia (2024)
Sustained 3-Year Improvement of Glucose Control With Hybrid Closed Loop in Children With Type 1 Diabetes While Going Through Puberty
Authors: Élise Bismuth, Nadia Tubiana-Rufi, Corey A. Rynders, Fabienne Dalla-Vale, Elisabeth Bonnemaison, Régis Coutant, Anne Farret, Amélie Poidvin, Natacha Bouhours-Nouet, Caroline Storey, Aurélie Donzeau, Mark D. DeBoer, Marc D. Breton, Orianne Villard, Éric Renard
Journal: Diabetes Care (2024)

To evaluate the impact of prolonged hybrid closed loop (HCL) use in children with type 1 diabetes (T1D) on glucose control and BMI throughout pubertal progression.
Calcitonin Gene-Related Peptide Inhibition and Development of Acne and Rosacea
Authors: Christopher J. Thang, Jenny Lai, David Garate, George Golovko, Michael G. Wilkerson, Elizabeth W. Loder, John S. Barbieri
Journal: JAMA Dermatology (2024)

This cohort study investigates whether calcitonin gene-related peptide inhibition is associated with reduced rates of developing acne or rosacea in patients who experience migraines.
Risks of Placental Abruption and Preterm Delivery in Patients Undergoing Assisted Reproduction
Authors: Jennifer T. Zhang, Rachel Lee, Mark V. Sauer, Cande V. Ananth
Journal: JAMA Network Open (2024)

Importance Patients using assisted reproductive technology (ART) may need additional counseling about the increased risks of placental abruption and preterm delivery. Further investigation into the potential additive risk of ART and placental abruption is needed. Objective To ascertain the risk of placental abruption in patients who conceived with ART and to evaluate if placental abruption and ART conception are associated with an increased risk of preterm delivery (&amp;amp;lt;37 weeks’ gestation) over and above the risks conferred by each factor alone. Design, Setting, and Participants This cross-sectional study used data from the National Inpatient Sample, which includes data from all-payer hospital inpatient discharges from 48 states across the US. Participants included women aged 15 to 54 years who delivered from 2000 through 2019. Data were analyzed from January 17 to April 18, 2024. Exposures Pregnancies conceived with ART. Main Outcomes and Measures Risks of placental abruption and preterm delivery in ART conception compared with spontaneous conceptions. Associations were expressed as odds ratios (ORs) and 95% CIs derived from weighted logistic regression models before and after adjusting for confounders. The relative excess risk due to interaction (RERI) of the risk of preterm delivery based on ART conception and placental abruption was also assessed. Results Of 78 901 058 deliveries, the mean (SD) maternal age was 27.9 (6.0) years, and 9 212 117 patients (11.7%) were Black individuals, 14 878 539 (18.9%) were Hispanic individuals, 34 899 594 (44.2%) were White individuals, and 19 910 807 (25.2%) were individuals of other races and ethnicities. Of the total hospital deliveries, 98.2% were singleton pregnancies, 68.8% were vaginal deliveries, and 52.1% were covered by private insurance. The risks of placental abruption among spontaneous and ART conceptions were 11 and 17 per 1000 hospital discharges, respectively. After adjusting for confounders, the adjusted OR (AOR) of placental abruption was 1.42 (95% CI, 1.34-1.51) in ART pregnancies compared with spontaneous conceptions, with increased odds in White women (AOR, 1.42; 95% CI, 1.31-1.53) compared with Black women (AOR, 1.16; 95% CI, 0.93-1.44). The odds of preterm delivery were significantly higher in pregnancies conceived by ART compared with spontaneous conceptions (AOR, 1.46; 95% CI, 1.42-1.51). The risk of preterm delivery increased when patients had both ART conception and placental abruption (RERI, 2.0; 95% CI, 0.5-3.5). Conclusions and Relevance In this cross-sectional study, patients who conceived using ART and developed placental abruption had a greater risk of preterm delivery compared with spontaneous conception without placental abruption. These findings have implications for counseling patients who seek infertility treatment and obstetrical management of ART pregnancies.
Feedback and Financial Incentives for Reducing Cell Phone Use While Driving
Authors: M. Kit Delgado, Jeffrey P. Ebert, Ruiying A. Xiong, Flaura K. Winston, Catherine C. McDonald, Roy M. Rosin, Kevin G. Volpp, Ian J. Barnett, Dylan S. Small, Douglas J. Wiebe, Dina Abdel-Rahman, Jessica E. Hemmons, Rafi Finegold, Benjamin Kotrc, Emma Radford, William J. Fisher, Kristen L. Gaba, William C. Everett, Scott D. Halpern
Journal: JAMA Network Open (2024)

Handheld phone use while driving is a major factor in vehicle crashes. Scalable interventions are needed to encourage drivers not to use their phones.