tbuckley/cabot-search huggingface dataset:
Abstract 9102: Cytosolic and Nuclear LncRNA HBL1 Crosstalk to Orchestrate Human Cardiogenesis via Interactions With MicroRNA-1 and PRC2 Epigenetic Complex
Authors: Juli Liu, Sheng Liu, Yi Sheng, Jun Wan, Lei Yang
Journal: Circulation (2021)

Introduction: Compared to rodents, human embryos exhibit unique dynamics of cardiogenesis, suggesting the existence of novel human-specific genetic programs underlying early-stage human heart development. Due to lack of in vivo model, human-specific mechanisms underlying cardiogenesis remain elusive. Hypothesis: Human Heart Brake LncRNA 1 (HBL1) functions as a new layer of regulator controlling cardiogenic gene transcription via coordinating with microRNA-1 and PRC2 epigenetic complex. Methods: Human pluripotent stem cells (hPSCs) were utilized to model human cardiogenesis. CRISPR/Cas-9 was utilized to knockout HBL1 and coding genes, and disrupted microRNA-1 binding sites on HBL1. HBL1 interacting proteins were pulled down by Co-IP-MS. EMSA and RNA-IP tested HBL1 interactions with PRC2 subunits. ChIP-seq uncovered the impact of HBL1 on genome-wide PRC2 occupancy. Luciferase assay confirmed JARID2 is a target of microRNA-1. Results: HBL1 expresses in cytoplasm and nucleus of hPSCs. Gain-of-HBL1 represses, whereas loss-of-HBL1 increases cardiomyocyte differentiation from hPSCs. Cytosolic HBL1 modulates cardiac development from hPSCs by counteracting microRNA-1. In hPSCs, disruption of microRNA-1 binding sites on HBL1 phenocopies HBL1 deficiency. Nuclear HBL1 interacts with two PRC2 subunits, JARID2 and EED. Loss-of-JARID2 or EED phenocopies HBL1 deficiency to enhance cardiac differentiation from hPSCs. HBL1 deficiency disrupts genome-wide PRC2 occupancy and H3K27me3 deposition on essential cardiogenic genes, and consequently enhances their transcription in hPSCs. Both HBL1 and JARID2 are required for PRC2 deposition to determine the epigenetic state of critical cardiogenic genes in hPSCs. Furthermore, the cytosolic and nuclear fractions of HBL1 could crosstalk via a conserved “microRNA-1-JARID2” axis to modulate transcription of cardiogenic genes. Conclusions: Our findings delineate the indispensable role of human-specific HBL1 in early human cardiogenesis, and expand the mechanistic scope of lncRNA(s) that cytosolic and nuclear portions of HBL1 could coordinate to precisely control human cardiogenesis.
Grapes: Trivia Game Increases Sickle Cell Disease Knowledge in Patients and Providers and Mitigates Health Biases
Authors: Amy Ouyang, Manasa Gadiraju, Veda Gadiraju, Landon Power, Vinitha Gadiraju, Gloria Liu, Kristin P. Guilliams, Michael M. Binkley, Sherif M. Badawy, Melanie E. Fields
Journal: Blood (2021)
Abstract 14231: The Role of Altered Notch-Sox9-Hapln1 Signaling in the Pathogenesis of Bicuspid Aortic Valve
Authors: Zaniar Ghazizadeh, Ya Liu, Nelson Ugwu, Adebowale Adeniran, Arpita Neogi, Arya Mani
Journal: Circulation (2021)

Bicuspid aortic valve (BAV) is a common congenital valve disorder with a prevalence close to 1%. Genetic studies on familial forms of BAV had previously identified NOTCH1 receptor as key mediator in the disease pathogenesis. However, the role of different Notch ligands in valve development in health and disease has remained elusive. Here we sequenced a total of 158 individuals with BAV and identified a list of 12 genes significantly enriched in the patients. Among the identified genes, there were various mutations in NOTCH1 receptor and Notch ligands. To further dissect the role of various Notch ligands in valve development, we generated knock-out models of Jag1a, Jag2b, Dll4, and Dld in Zebrafish and explored their effect on the heart outflow tract. Interestingly, Jag1a and Jag2b had opposite effects on valve diameter. Using single cell RNA and bulk RNA seq, and chip sequencing techniques on murine knock-out models of the corresponding genes, we identified a novel Notch-Sox9-Hapln1 signaling pathway dysregulated in the genetic models of Notch mutation that could underlie the changes in endocardial cells. Finally, we observed alterations in this pathway in aortic valve specimens from patients with bicuspid versus tricuspid aortic valves. In conclusion, our study identifies an association between mutations in Notch ligands and BAV and highlights the role of Notch-Sox9-Hapln1 pathway in aortic valve development and implicates its altered function as a novel pathway for the pathogenesis of BAV.
Hypoxia Impact on Red Blood Cell-Mediated Microvascular Occlusion and Adhesion in Sickle Cell Disease and Sickle Cell Trait
Authors: Yuncheng Man, Zoe Sekyonda, Karamoja Monchamp, Ran An, Erdem Kucukal, Chiara Federici, Lalitha V Nayak, Jane A. Little, Umut A. Gurkan
Journal: Blood (2021)
Abstract 12213: Exercise Induced Pulmonary Hypertension in Long Term Survivors of Congenital Diaphragmatic Hernia
Authors: Paul J Critser, Ming Hui Chen, Kimberlee Gauvreau, Jill M Zalieckas, Catherine A Sheils, Gary A Visner, Keri M Shafer, Jonathan Rhodes, Terry L Buchmiller, Mary P Mullen
Journal: Circulation (2021)

Introduction: Survivors of congenital diaphragmatic hernia (CDH) are at risk of pulmonary hypertension (PH) due to pulmonary hypoplasia and other pulmonary vascular abnormalities. Hypothesis: Exercise stress echocardiography (ESE) may detect PH, not apparent on echocardiography at rest, in children and young adults with repaired CDH. Methods: Single center retrospective cohort study of all CDH survivors who underwent ESE at Boston Children’s Hospital (January 2006 – June 2020). Severity of PH was assessed at baseline and after exercise. Patients were assigned to one of two categories based on right ventricular pressure: group 1: no or mild PH after exercise; and group 2: moderate or severe PH after exercise (right ventricular pressure ≥ 60 mmHg or ≥ ½ systemic blood pressure). Results: During the study period 84 CDH patients (70% male) underwent 173 ESE with a median age 8.1 (4.8 – 19.1) years at first ESE. Sixty-four patients were classified as group 1, 11 as group 2, and 9 were unable to be classified due to inconclusive ESE. Moderate to severe PH after exercise was found in 8 (10%) patients with no or mild PH at rest. Risk factors for PH after exercise included larger CDH defect size, patch repair, use of extracorporeal membrane oxygenation, and supplemental oxygen at discharge in univariate analysis (Table 1). Exercise and pulmonary function test parameters associated with a group 2 test included higher VE/VCO2 slope, lower peak oxygen saturation, and lower percent predicted FEV1 and FEV1/FVC ratio. Nine of 11 group 2 patients had a change in management based on ESE. PH was found in all 5 group 2 patients with cardiac catheterization after ESE, including 3 patients with no or mild PH on baseline ESE. Conclusions: Among long term CDH survivors, ESE identified 10% with moderate-severe exercise induced PH indicating ongoing pulmonary vascular abnormalities. Further studies are needed to optimally define screening and treatment for patients with repaired CDH.
Poem by a Woman With Glaucoma
Authors: Terri Kirby Erickson
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prediction of Early Death and Severe Infections during Novel Agent-Based Induction Therapy in Newly-Diagnosed Multiple Myeloma: An Intergroup Analysis from the German Speaking Myeloma Multicenter Group, the Dutch-Belgian Cooperative Trial Group for Hematology Oncology Foundation and the European Myeloma Network
Authors: Elias K Mai, Thomas Hielscher, Uta Bertsch, Hans Salwender, Sonja Zweegman, Markus Munder, Lucia Pantani, Peter Brossart, Meral Beksac, Igor Wolfgang Blau, Marc-Steffen Raab, Jan Dürig, Nicola Giesen, Britta Besemer, Roland Fenk, Peter Reimer, Bronno van der Holt, Mathias Haenel, Ivana v. Metzler, Ullrich Graeven, Mario Boccadoro, Christof Scheid, Meletios A. Dimopoulos, Katja Weisel, Michele Cavo, Pieter Sonneveld, Hartmut Goldschmidt
Journal: Blood (2021)
Abstract 10833: 30-Day Readmissions After Primary Percutaneous Coronary Intervention in Nonagenarians: A Nationwide Analysis from the United States
Authors: Mahmoud Ismayl, Akshay Machanahalli Balakrishna, Ryan Walters, Venkata Siva Kumar Pajjuru, Ahmed S Aboeata
Journal: Circulation (2021)

Objective: To assess 30-day readmission rates and mortality at readmission in nonagenarians following primary percutaneous coronary intervention (pPCI) for ST elevation myocardial infarction (STEMI). Background: There is limited contemporary data exploring the 30-day readmission rates and mortality in nonagenarians (age greater than 90 years) with STEMI following pPCI when compared to no pPCI. Methods: We utilized the National Readmissions Database (NRD) from 2010 to 2018 to identify nonagenarians hospitalized with STEMI. We divided the total cohort into two groups based on pPCI status. We analyzed 30-day readmission rates, mortality at the time of readmission, and causes of readmissions in both study cohorts. Results: Between 2010-2018, an estimated 37,363 STEMI hospitalizations were identified in nonagenarians, of which 12,062 (32.3%) included pPCI and 25,301 (67.7%) had no pPCI. Compared to pPCI cohort, no pPCI had more women (69.8% vs 36.7%), higher elixhauser comorbidity index (13% vs 8%), palliative care consultation (12.6% vs 3.4%), and nursing home placement (48% vs 33.3%) (all p&lt;0.01). Overall, 30-day readmission rates were higher in pPCI cohort compared with no pPCI (22.1% vs 16.2%; p&lt;0.01). However, the in-hospital mortality rates at 30-day readmission were significantly lower in pPCI cohort compared with no pPCI (7.0% vs 14.3%; p&lt;0.01). Heart failure is the most common cause of 30-day readmissions in both cohorts, followed by acute myocardial infarction (MI) and gastrointestinal hemorrhage. Recurrent MI rates were significantly lower in pPCI cohort compared with no pPCI (12.3% vs 18.4%; p&lt;0.01). Conclusion: In nonagenarians with STEMI, pPCI during index hospitalization is associated with slightly higher 30-day readmissions but significantly lower mortality at the time of readmission. Given the remarkable mortality benefit with pPCI, further research is necessary to risk stratify and optimize readmission rates following STEMI in nonagenarians.
Topographic Analysis of Low-Grade Myeloid Neoplasms By Multiparametric in Situ Imaging of Human Bone Marrow Core Biopsy Tissues
Authors: Sanjay Patel, Viktor Svekolkin, Arina Varlamova, Ilia Galkin, Itzel Valencia, Aida Akaeva, Sofia Smirnova, Pavel Ovcharov, Margarita Polyakova, Dmitrii Tabakov, Ekaterina Postovalova, Eleonora Koltakova, Sarah Gunn, Alexander Bagaev, Julia T Geyer
Journal: Blood (2021)
Multicenter Analysis of Treatment and Outcomes for Patient with <i>TP53</i> Mutated AML in the Era of Novel Therapies; Significant Impact of Allogeneic Stem Cell Transplantation on Survival
Authors: Talha Badar, Mark R. Litzow, Rory M. Shallis, Jan Philipp Bewersdorf, Antoine Saliba, Guilherme sacchi De Camargo Correia, Maximilian Stahl, Aaron D Goldberg, Ehab L. Atallah, James M. Foran
Journal: Blood (2021)
Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs
Authors: Cassandra Miller, Julie Rousseau, Caterina F. Ramogida, Anna Celler, Arman Rahmim, Carlos F. Uribe
Journal: Theranostics (2021)

Theranostics is an emerging paradigm that combines imaging and therapy in order to personalize patient treatment. In nuclear medicine, this is achieved by using radiopharmaceuticals that target identical molecular targets for both imaging (using emitted gamma rays) and radiopharmaceutical therapy (using emitted beta, alpha or Auger-electron particles) for the treatment of various diseases, such as cancer. If the therapeutic radiopharmaceutical cannot be imaged quantitatively, a "theranostic pair" imaging surrogate can be used to predict the absorbed radiation doses from the therapeutic radiopharmaceutical. However, theranostic dosimetry assumes that the pharmacokinetics and biodistributions of both radiopharmaceuticals in the pair are identical or very similar, an assumption that still requires further validation for many theranostic pairs. In this review, we consider both same-element and different-element theranostic pairs and attempt to determine if factors exist which may cause inaccurate dose extrapolations in theranostic dosimetry, either intrinsic (e.g. chemical differences) or extrinsic (e.g. injecting different amounts of each radiopharmaceutical) to the radiopharmaceuticals. We discuss the basis behind theranostic dosimetry and present common theranostic pairs and their therapeutic applications in oncology. We investigate general factors that could create alterations in the behavior of the radiopharmaceuticals or the quantitative accuracy of imaging them. Finally, we attempt to determine if there is evidence showing some specific pairs as suitable for theranostic dosimetry. We show that there are a variety of intrinsic and extrinsic factors which can significantly alter the behavior among pairs of radiopharmaceuticals, even if they belong to the same chemical element. More research is needed to determine the impact of these factors on theranostic dosimetry estimates and on patient outcomes, and how to correctly account for them.
CTIM-33. PHASE II TRIAL OF VACCINE IMMUNOTHERAPY IN PRIMARY GLIOBLASTOMA: ADJUNCTIVE AUTOLOGOUS DENDRITIC CELLS PULSED WITH LYSATE FROM IRRADIATED SELF-RENEWING AUTOLOGOUS TUMOR CELLS (AV-GBM-1)
Authors: Daniela A Bota, David E Piccioni, Christopher M Duma, Renato V LaRocca, Santosh Kesari, Mehrdad Abedi, Jose A Carrillo, Robert D Aiken, Frank Hsu, Xiao-Tang Kong, Thomas H Taylor, Candace Hsieh, Gabriel Nistor, Robert Dillman
Journal: Neuro-Oncology (2021)

Abstract In primary glioblastoma (GBM), overall survival (OS) is poor despite standard aggressive therapy. Adjunctive AV-GBM-1 vaccine immunotherapy may improve OS. In this multi-institutional phase II trial, key eligibility criteria for intent-to-treat (ITT) enrollment were: (1) primary GBM, (2) age &amp;lt; 70 years when GBM was resected, (3) successful GBM cell culture, (4) successful monocyte collection by leukapheresis, (5) KPS &amp;gt; 70 post-surgery, and (6) plan to treat with concurrent RT/TMZ. Dendritic cells (DC) were differentiated from monocytes by culturing in IL-4 and granulocyte-macrophage colony stimulating factor (GM-CSF). AV-GBM-1 consisted of autologous DC incubated with autologous tumor antigens contained in the lysate of irradiated cultured GBM cells. After recovery from RT/TMZ, doses were admixed with 500 mcg GM-CSF; up to 8 doses were injected subcutaneously over 6 months. Patients were not excluded by apparent progression or pseudo-progression post RT/TMZ. OS and progression-free-survival (PFS) were calculated from ITT enrollment. The success rate was 97% for both GBM cell cultures and collection of monocytes; 60/60 vaccines were successfully manufactured. Median age was 59 years. 57 patients received 392 injections. After two weekly injections there were significant increases in plasma lipocalin-2 and angiopoietin-1, and decreases in thrombospondin-5, angiotensinogen, and beta-fibroblast growth factor. The most common adverse events attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). With follow up from 15.2 to 32 months, median PFS and OS were 10.3 (8.5,11.6 95% CI) and 16.0 (13.0,21.3 95% CI) months respectively. OS was better in the 25 patients who had methylguanine-methyltransferase (MGMT) methylation and/or isocitrate dehydrogenase (IDH) mutation. Age was not independently correlated with survival. From date of first injection, OS was not increased in 14 patients who were treated with alternating electrical tumor-treating fields. CONCLUSION: feasibility, safety, and PFS were encouraging. A phase III trial is in development. Clinicaltrials.gov NCT03400917.
Clonal Hematopoiesis Driven By MDM4 Amplification Defines a Canonical Route Towards Secondary MDS/AML in Fanconi Anemia Patients
Authors: Marie Sebert, Stéphanie Gachet, Thierry Leblanc, Alix Rousseau, Olivier Bluteau, Rathana KIM, Raouf Benabelali, Flore Sicre de Fontbrune, Loïc Maillard, Carèle Fedronie, Nadia Vasquez, Yves Bertrand, Jean-Hugues Dalle, Francois Sigaux, Sylvie Chevret, Gerard Socie, Hugues de Thé, Christophe Antoniewski, Dominique Bluteau, Regis Peffault De Latour, Jean Soulier
Journal: Blood (2021)
Real-World Outcomes with Immunosuppressive Therapy for Aplastic Anemia in Patients Treated at the University of Michigan
Authors: Daniel H. Foley, Charles E. Foucar, Kristen M. Pettit, Patrick W. Burke, Lydia L. Benitez, Anthony J. Perissinotti, Bernard L. Marini, Dale L. Bixby
Journal: Blood (2021)
Specificity of CD8-Targeted Fusosomes in Human PBMCs Using Single Cell RNA and T Cell Receptor Sequencing
Authors: Hina Iftikhar, Nikolas Balanis, Chamith Fonseka, Christopher Bandoro, Patricia Cruite, Samantha Davis, Shirisha Amatya, Zach Frye, Lauren Pepper, Michael Laska, Terry J. Fry, Jagesh V Shah, Saurabh Paliwal, Christina Chaivorapol
Journal: Blood (2021)
<i>The Outcome of Treatment-Free Remission after First-Line Nilotinib or Dasatinib in Chronic Phase Chronic Myeloid Leukemia Patients Is Different</i>
Authors: Franck E. Nicolini, Vincent Alcazer, Stephanie Dulucq, Sandrine Hayette, Jean-Michel Cayuela, Stephane Morisset, Christophe Bouvier, Francois-Xavier Mahon, Gabriel Etienne, Delphine Rea
Journal: Blood (2021)
Single Agent CD117-Targeted Antibody Drug Conjugate in Combination with Lymphodepleting Antibodies Enables Allogenic Hematopoietic Stem Cell Transplantation in Mice without Chemotherapy or Radiation
Authors: Leanne Lanieri, Tahirih Lamothe, Prashant Bhattarai, Rahul Palchaudhuri, Lisa Olson
Journal: Blood (2021)
Long Term Outcome Patterns and Risk Factors for Early Mortality and Disease Progression in ALK-Positive Anaplastic Large Cell Lymphoma
Authors: Luis Malpica-Castillo, Lei Feng, Jie Xu, Ranjit Nair, Alexandra Elias, Preetesh Jain, Dai Chihara, Raphael Steiner, Luis Fayad, Felipe Samaniego, Sairah Ahmed, Nathan H. Fowler, Loretta Nastoupil, Samer A. Srour, Yago Nieto, Chitra Hosing, Roberto N. Miranda, Francisco Vega, Chelsea C. Pinnix, Jillian R. Gunther, Penny Fang, Susan Wu, Bouthaina S. Dabaja, Jeffrey Medeiros, Michael Wang, Sattva S. Neelapu, Christopher R. Flowers, Swaminathan Padmanabhan Iyer
Journal: Blood (2021)
Patient Satisfaction Questionnaire After Transcatheter Aortic Valve Replacement
Authors: Shikhar Agarwal, Imran Baig, Amir Eslami, Tanawan Riangwiwat
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Health-related quality of life (HRQoL) is a multi-dimensional concept that includes domains related to physical, mental, emotional, and social functioning. Kansas City Cardiomyopathy Questionnaire (KCCQ) is typically utilized to assess the HRQoL after TAVR
The Importance of Maintaining the Momentum of Telemedicine after COVID-19
Authors: Aisha Siraj, Negar Salehi, Saima Karim
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Telemedicine has been in existence for years with little traction for global mainstream medicine. COVID19 has exposed the importance of providing continued care for patients while minimizing the risk of exposure during pandemics. There has been robust growth in the use of telemedicine since the pandemic began rendering care possible while providing safety to patients and healthcare workers. Various digital applications are available to facilitate telehealth. Even in the absence of a pandemic, telemedicine allows the care of patients who may live in remote areas, or those who have issues with transportation or comorbidities prohibiting ambulation. This study is based on a questionnaire of providers who have been exposed to telemedicine during COVID19. A survey was shared in social media forums involving groups of physicians, and nurse practitioners who were willing to take the survey. Telemedicine is one of the best approaches to handling situations like pandemics or disease surges. In these circumstances, a virtual visit is beneficial for social distancing if a laptop, smartphone, or tablet is available, along with an internet or cellular coverage. Based on this survey conducted for healthcare workers from a variety of specialties, there was a considerable impetus for the continued benefit from telemedicine as an alternative to in-person visits for selected patients. Ongoing improvements in quality of applications/tools, education, and the cost are essential to maintain the benefits of telemedicine. There is also an ongoing necessity for vast improvements in healthcare policies and reimbursements.
A Novel WNT5A-Mimicking Peptide Affects Leukemia Cell Survival in the Bone Marrow Microenvironment
Authors: Fernanda Marconi Roversi, Maura Lima Pereira Bueno, Rafael Gonçalves Barbosa Gomes, Guilherme Rossi Assis-Mendonça, Paulo Latuf Filho, Adriana Silva Santos Duarte, Sara T Olalla Saad
Journal: Blood (2021)