tbuckley/cabot-search huggingface dataset:
Abstract 445: Myristoylated Protein Kinase C Beta II Peptide Inhibitor Attenuates Hypoxia-Reoxygenation Injury in Human Umbilical Vein Endothelial Cells
Authors: Tameka Dean, Alexis Verwoert, Michael Lloyd, Gordon Heller, Rose Martorana, Claudine Andre, Chantel Thompson, Ahsal Major, Francis Jenney, Qian Chen, Robert Barsotti, Lindon Young
Journal: Circulation Research (2020)

Endothelial dysfunction as a result of ischemia/reperfusion (I/R) injury contributes to local organ damage in heart attack patients. In vascular cells, NADPH oxidase (NOX) and the mitochondrial electron transport chain are initiating sources of reactive oxygen species (ROS) during I/R injury. Protein kinase C beta II (PKCβII) is an attractive therapeutic target due to its phosphorylation of p66Shc to enhance mitochondrial-derived ROS production and p47 phox to promote ROS release from NOX. In previous studies, a cell-permeable myristoylated PKCβII peptide inhibitor (N-myr-SLNPEWNET; myr-PKCβII-) has been shown to improve post-reperfusion cardiac function and reduce infarct size in rat myocardial I/R injury. The decrease in myocardial I/R injury with myr-PKCβII- may in part be attributed to improved vascular endothelial function. Due to myr-PKCβII- peptide sequence being highly conserved among mammalian species, we hypothesize that myr-PKCβII- will confer protection by directly inhibiting ROS production from NOX and mitochondria in human umbilical endothelial cells (HUVECs) subjected to hypoxia/reoxygenation (H/R) mediated injury. HUVECs, cultured in gelatin-coated 96-well plates, were subjected to 24h hypoxia and 24h reoxygenation in a Billups-Rothenburg chamber with 1% O 2 , 5% CO 2 , and balance nitrogen. Myr-PKCβII- (20 μM) was administered at the beginning of the 24h reoxygenation period. Cell viability was assessed using tetrazolium-salt (WST-8) colorimetric assay with a microplate reader (450 nm) and normalized against the normoxia control group. Data were analyzed using Student-Newman-Keuls post-hoc analysis. At the 24h reoxygenation period, cell viability (%) was significantly reduced to 78±2% (n=5; p&lt;0.05) in the non-treated H/R group compared to normoxia controls (n=5). Myr-PKCβII- significantly improved HUVEC survival (95±4%; n=5) compared to non-treated H/R controls (n=5; p&lt;0.01) which were not significantly different from normoxia controls. The data suggest that PKCβII inhibition promotes cell survival possibly due to directly attenuating NOX and mitochondrial derived ROS in cells subjected to H/R conditions. Further studies are needed to determine cell survival potential under more severe H/R mediated injury.
Multiple Myeloma Course with Renal Insufficiency in Young Patient: Case Report
Authors: Hugo Henrique de Freitas Ferreira, Alessandra Suelen Jardim Silva, Lenilton Silva DA Silva Júnior, Gustavo Henrique de Medeiros Oliveira, Maria das Graças Pereira Araujo, Victor lima Soares, Frank Bahia, Taissa Moura Oliveira, Dany GKC Silva, Valéria SF Sales, Aldair Sousa Paiva, Geraldo Barroso Cavalcanti
Journal: Blood (2020)
Association of Circulating Tumor DNA from the Cerebrospinal Fluid with High-Risk CNS Involvement in Patients with Diffuse Large B-Cell Lymphoma
Authors: Xiaoxiao Wang, Yan Gao, Changguo Shan, Mingyao Lai, Haixia He, Bing Bai, Li-qin Ping, Qixiang Rong, Ruyu Ai, Lei Wen, Zhaoming Zhou, Ruoying Yu, Qiuxiang Ou, Xue Wu, Xiaoxia Wang, Yang Shao, Linbo Cai, Hui-qiang Huang
Journal: Blood (2020)
FDG-Avid Pulmonary Nodules and Tracheobronchial Mural Inflammation in IgG4-Related Disease
Authors: Meera K. Namireddy, Nikita Consul, Andrew C. Sher
Journal: Clinical Nuclear Medicine (2020)

We report the case of a 9-year-old girl who presented with acute fevers, cough, and epistaxis with nasal swelling, and found to have a nasal mass. On 18F-FDG PET/CT, she was found to have marked nodal and pulmonary parenchymal disease with diffuse and symmetrical mural FDG uptake within the trachea and bronchial tree. The differential diagnosis was broad, and she was diagnosed with IgG4-RD (IgG4-related disease) and improved on appropriate treatment. To our knowledge, there are only 2 other pediatric cases of IgG4-related pulmonary disease in the literature, and our case serves as a unique constellation of intrapulmonary IgG4-RD imaging findings.
Abstract 234: Identification of a Novel Cardiomyocyte-enriched Long Noncoding Rna Counteracting Against Heart Failure Development
Authors: Michio Sato, Keishi Miyata, Tsuyoshi Kadomatsu, Koichi Node, Yuichi Oike
Journal: Circulation Research (2020)

Background: The number of patients with heart failure (HF) continues to increase as the elderly population grows, and mortality remains high, with about 50% of HF patients dying within 5 years of diagnosis. Therefore, defining molecular mechanisms underlying HF pathologies is urgently needed. Methods and Results: Using a gene trapping approach in mouse ES cells, we identified Caren (for car diomyocyte- en riched noncoding transcript), a novel cytoplasmic lncRNA abundantly expressed in cardiomyocytes. Caren expression in mice markedly decreased in heart failure (HF) induced by transverse aortic constriction (TAC), AngiotensinII loaded or aging. Caren ablation accelerated HF-related phenotypes, whereas Caren transgenic (Tg) mice in cardiomyocytes resisted TAC-induced HF. Furthermore, Caren overexpression in cardiomyocytes activated mitochondrial biogenesis and attenuated TAC-induced activation of Ataxia Telangiectasia Mutated (ATM) serine/threonine kinase, a regulator of the DNA damage response (DDR). Next, we generated Tg mice expressing Caren fragments (fragments A-E, from 5’ to 3’) respectively, by inserting that fragment into the corresponding endogenous Caren genomic locus. None of these Tg mice exhibited an anti-HF effect against TAC, suggesting that anti-HF effects of Caren may be more dependent on a structural motif displayed by the full-length lncRNA rather than on a specific Caren sequence. Consistently, restoration of expression of full-length Caren in TAC-induced failing cardiomyocytes slows HF progression in mice injected with AAV6- Caren . Mechanistically, Caren inhibited translation of mRNA encoding ‘ Caren Target Protein 1’ (CTP1), which activates the ATM-DDR pathway and reduces mitochondrial respiratory capacity in cardiomyocytes. CTP1 +/- mice resisted HF development, strongly suggesting that Caren protects against HF by suppressing CTP1 expression. Conclusion: This is the first study reporting that Caren , a novel cytoplasmic lncRNA , counteracts HF development and progression by inactivating the ATM-DDR pathway and activating mitochondrial bioenergetics, in part, by suppressing CTP1 translation in cardiomyocytes. Our findings could encourage development of RNA-based strategies to combat HF development.
Evolving Trends in Adult Heart Transplant With the 2018 Heart Allocation Policy Change
Authors: Arman Kilic, Michael A. Mathier, Gavin W. Hickey, Ibrahim Sultan, Victor O. Morell, Suresh R. Mulukutla, Mary E. Keebler
Journal: JAMA Cardiology (2020)

The US heart allocation policy was changed on October 18, 2018. The association of this change with recipient and donor selection and outcomes remains to be elucidated.To evaluate changes in patient characteristics, wait list outcomes, and posttransplant outcomes after the recent allocation policy change in heart transplant.In this cohort study, all 15 631 adults undergoing heart transplants, excluding multiorgan transplants, in the US as identified by the United Network for Organ Sharing multicenter, national registry were reviewed. Patients were stratified according to prepolicy change (October 1, 2015, to October 1, 2018) and postpolicy change (October 18, 2018 or after). Follow-up data were available through March 31, 2020.Heart transplants after the policy change.Competing risk regression for wait list outcomes was performed. Posttransplant survival was compared using the Kaplan-Meier method, and risk adjustment was performed using multivariable Cox proportional hazards regression analysis.In this cohort study, of the 15 631 patients undergoing transplant, 10 671 (mean [SD] age, 53.1 [12.7] years; 7823 [73.3%] male) were wait listed before and 4960 (mean [SD] age, 52.7 [13.0] years; 3610 [72.8%] male) were wait listed after the policy change. Competing risk regression demonstrated reduced likelihood of mortality or deterioration (subhazard ratio [SHR], 0.60; 95% CI, 0.52-0.69; P < .001), increased likelihood of transplant (SHR, 1.38; 95% CI, 1.32-1.45; P < .001), and reduced likelihood of recovery (SHR, 0.54; 95% CI, 0.40-0.73; P < .001) for wait listed patients after the policy change. A total of 6078 patients underwent transplant before and 2801 after the policy change. Notable changes after the policy change included higher frequency of bridging with temporary mechanical circulatory support and lower frequency of bridging with durable left ventricular assist devices. Posttransplant survival was reduced after the policy change (1-year: 92.1% vs 87.5%; log-rank P < .001), a finding that persisted after risk adjustment (HR, 1.29; 95% CI, 1.07-1.55; P = .008).Substantial changes have occurred in adult heart transplant in the US after the policy change in October 2018. Wait list outcomes have improved, although posttransplant survival has decreased. These data confirm findings from earlier preliminary analyses and demonstrate that these trends have persisted to 1-year follow-up, underscoring the importance of continued reevaluation of the new heart allocation policy.
The STIMULUS Program: Clinical Trials Evaluating Sabatolimab (MBG453) Combination Therapy in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) or Acute Myeloid Leukemia (AML)
Authors: Amer M. Zeidan, Jordi Esteve, Aristoteles Giagounidis, Hee-Je Kim, Yasushi Miyazaki, Uwe Platzbecker, Andre C. Schuh, Mikkael A. Sekeres, Jörg Westermann, Zhijian Xiao, Kamel Malek, Jeffrey Scott, Julie Niolat, Severine Peyrard, Fei Ma, Flavia Kiertsman, Mario Stegert, Sabine Hertle, Pierre Fenaux, Valeria Santini
Journal: Blood (2020)
Hypoxic conditioning: a novel therapeutic solution for load-compromised individuals to achieve similar exercise benefits by doing less mechanical work!
Authors: Olivier Girard, Ivana Matic Girard, Peter Peeling
Journal: British Journal of Sports Medicine (2020)

Identifying an intervention whereby mechanical loading during aerobic exercise remains low, while metabolic solicitation is elevated, provides an endless challenge for health professionals working with load-compromised individuals. There are many situations where injured athletes (eg, awaiting surgical procedures or within rehabilitative settings) or patients suffering from chronic musculoskeletal disorders (eg, osteoarthritis or osteoporosis) experience difficulties maintaining or regaining fitness via appropriate levels of physical activity. In such individuals, a progressive return to weight-bearing activity can be painful because of excessive plantar and joint loads imposed by ground reaction forces.

Hypoxic conditioning (HC) is defined as an exposure to systemic and/or local hypoxia—that is, a reduced (or insufficient) oxygen (O2) supply to tissues caused by decreases in O2 saturation of arterial blood—at rest (passive) or combined with exercise (active) training.1 Contrasting results have been observed regarding HC studies that prescribed exercise at a set work rate in hypoxia, and then compared this with exercising at the same absolute intensity under normal O2 conditions, for instance, with either greater (ie, reduction in triglycerides, muscle growth) or similar (ie, body mass) cardiometabolic adaptations in overweight individuals or those with obesity.2 Compared with normal O2 conditions, Haufe …
Abstract 10999: Outcomes Associated With Under-Dosing of Rivaroxaban for Management of Non-Valvular Atrial Fibrillation in Real World Clinical Setting From the XAPASS (Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients With Atrial Fibrillation)
Authors: Takanori Ikeda, Satoshi Ogawa, Takanari Kitazono, Jyoji Nakagawara, Kazuo Minematsu, Susumu Miyamoto, Yuji Murakawa, Sanghun Iwashiro, Makiko Takeichi, Yutaka Okayama, Toshiyuki Sunaya, Yohei Ohashi, Satoshi Yamanaka
Journal: Circulation (2018)

Background and Objective: Recent real-world studies demonstrate that prescription of under-dosed Factor Xa inhibitor rivaroxaban is seen in the clinical management of non-valvular atrial fibrillati...
Myeloablative Fractionated Busulfan with Fludarabine in Older Patients: Long Term Outcomes of Prospective Phase II Clinical Trial
Authors: Rohtesh S. Mehta, Roland Bassett, Julianne Chen, Benigno C. Valdez, Jitesh Kawedia, Amin M. Alousi, Gheath Alatrash, Qaiser Bashir, Stefan Ciurea, Chitra Hosing, Jin S. Im, Partow Kebriaei, Amanda L. Olson, Betul Oran, Muzaffar H. Qazilbash, Samer A. Srour, Elizabeth J. Shpall, Borje S. Andersson, Richard E. Champlin, Uday R. Popat
Journal: Blood (2020)
SAT0596 RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS AMONG PATIENTS WITH RHEUMATOID ARTHRITIS AND A LOW-INTERMEDIATE Á PRIORI RISK OF CORONARY ARTERY DISEASE AFTER INITIAL CT-BASED DIAGNOSIS AND TREATMENT A REGISTRY-BASED FOLLOW-UP STUDY USING DATA FROM THE WESTERN DENMARK HEART REGISTRY
Authors: Annette de Thurah, Ina Trolle Andersen, Andreas Bugge Tinggaard, Anders Hammerich Riis, Josephine Therkildsen, Hans Erik Bøtker, Morten Böttcher, Ellen-Margrethe Hauge
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a known risk factor for developing coronary artery disease (CAD). The influence of RA on the prognosis after initial diagnosis and treatment of CAD is however largely unknown. <h3>Objectives:</h3> To examined the risk of major cardiovascular events among RA and non-RA patients with chest pain referred to cardiac computed tomography (CCT). <h3>Methods:</h3> This was a follow-up study, using data from the Western Denmark Heart Registry[1]. Information on RA diagnosis and co-variates were identified through nationwide administrative registers. The primary outcome was a combined outcome including<i>,</i> myocardial infarction, ischemic or uspecified stroke, coronary artery bypass grafting, percutaneus coronary intervention, <i>and all-cause mortality. In the studied region, RA-f</i>lares are controlled through escalation of disease modifying drugs and intra-articular or intramuscular glucocorticoid injections (GCI). Hence, the number of times a patient had received GCIs 3 years prior to the CCT were used as a surrogate marker of<i> disease activity.</i> Analyses were performed for overall RA and the serological subtypes: 'seropositive RA'(ICD-10: M05) and 'other RA'(ICD-10: M06). Median time until events or censoring was 3.5 years (min/max: 0.0: 9.2). Cox proportional hazard models were used to examine the association between RA/non-RA patients and outcomes<i>.</i> <h3>Results:</h3> Among 42,257 patients, referred between 2008 and 2016, we identified 358 (0.8%) with RA. An increased risk was seen in RA compared to non-RA (adjusted hazard ratio (HR) 1.35 (95% CI: 0.93; 1;96)). An additional risk was found among patients who had received flare treatment more than once prior to CCT (adjusted HR 1.80 (95% CI: 1.08; 3.00)), and in patients with sero-positive RA (adjusted HR: 1.42 (95% CI: 0.93; 2.16)). <h3>Conclusion:</h3> In patients with low-intermediate a priori risk of CAD, we found an association between RA and the combined primary outcome, supporting that RA per se, but in particular sero-positive and active RA, increase the risk of cardiovascular events even after initial CAD diagnosis and treatment. <h3>References</h3> [1] Nielsen LH, et al. The Western Denmark cardiac Computed Tomography Registry: a review and validation study. Clinical epidemiology2014, Dec31; 53-64 <h3>Disclosure of Interests:</h3> None declared
Elevated Expression of Mir-130a in t(8,21) AML Reinforces the Aberrant Molecular Program of AML1-ETO
Authors: Gabriela Krivdova, Veronique Voisin, Sajid Marhon, Schoof E Erwin, Martino Gabra, Jessica L. McLeod, Leonardo Salmena, Mark D. Minden, Eric R. Lechman,, John E. Dick
Journal: Blood (2020)
Multicenter Validation of a Personalized Model to Predict Hypomethylating Agent Response in Myelodysplastic Syndromes (MDS)
Authors: Nathan Radakovich, David A. Sallman, Rena J. Buckstein, Andrew M. Brunner, Sudipto Mukherjee, Rami Komrokji, Najla Al Ali, Jacob Shreve, Yazan Rouphail, Cassandra M Kerr, Yihong Guan, Teodora Kuzmanovic, Metis Hasipek, Babal K. Jha, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Aziz Nazha
Journal: Blood (2020)
Multi-Omic Based Antigen Discovery for the Immunotherapy of Pediatric Acute T Cell Lymphoblastic Leukemia
Authors: Nikhil Hebbar, Chunxu Qu, Hong Wang, Ying Shao, Phuong Nguyen, Abdullah Freiwan, Rebecca Epperly, Yuxin Li, Ji-Hoon Cho, Timothy Shaw, Junmin Peng, John Easton, Stephen Gottschalk, Charles G Mullighan, Mireya Paulina Velasquez
Journal: Blood (2020)
Impact of HLA Evolutionary Divergence on Clinical Features of Patients with Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria
Authors: Simona Pagliuca, Carmelo Gurnari, Diego Chowell, Chirag Krishna, Bhumika J. Patel, Hassan Awada, Cassandra M Kerr, Sunisa Kongkiatkamon, Ashwin Kishtagari, Thomas Laframboise, Yogenthiran Saunthararajah, Babal K. Jha, Valeria Visconte, Timothy Chan, Jaroslaw Maciejewski
Journal: Blood (2020)
Longitudinal Molecular Profiling in Patients with <i>IDH1</i>-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib
Authors: Sung Choe, Hongfang Wang, Gail J. Roboz, Courtney D. DiNardo, Eytan M. Stein, Alice S. Mims, Gabrielle T. Prince, Justin M. Watts, Bin Fan, Parham Nejad, Vickie Zhang, Hua Liu, Eyal C. Attar, Bin Wu, Richard M. Stone
Journal: Blood (2020)
Simoultaneous Home Palliative Care in Onco-Hematological Patients: An Italian Single Institution Experience
Authors: Anna Ines Gregorini, Francesca Gaia Rossi, Sara Lodi Rizzini, Valeria Ferla, Giorgia Saporiti, Loredana Pettine, Mariarita Sciumè, Fabio Serpenti, Veronica Mattiello, Maria Chiara Barbanti, Giorgio Maggioni, Luca Baldini, Roberto Scarani, Massimo Pizzuto, Francesco Onida
Journal: Blood (2020)
Higher Hemoglobin Levels Achieved with Voxelotor Are Associated with Lower Vaso-occlusive Crisis Incidence: 72-Week Analysis from the HOPE Study
Authors: Elliott Vichinsky, Victor R. Gordeuk, Paul Telfer, Adlette Inati, Margaret Tonda, Sarah Gray, Irene Agodoa, Kenneth I. Ataga
Journal: Blood (2020)
Comparison of Conventional Xrays with CT Based Approaches for Detection of Lytic Lesions in Multiple Myeloma
Authors: Radhika Bansal, Sagar Rakshit, Katrina Glazebrook, Prashant Kapoor, Francis K. Buadi, Martha Q. Lacy, Morie A. Gertz, Angela Dispenzieri, David Dingli, Yi L. Hwa, Amie Fonder, Miriam A. Hobbs, Suzanne R. Hayman, John A. Lust, Nelson Leung, Ronald S. Go, Yi Lin, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma M Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: Blood (2020)
Abstract PO-026: GLUER: integrative analysis of multi-omics data at single-cell resolution
Authors: Tao Peng, Kamyar Esmaeili Pourfarhangi, Kai Tan
Journal: Cancer Research (2020)

Abstract Single-cell omics assays such as RNA-Seq, ATAC-Seq and methylome sequencing have been developed to identify cell types and/or states in heterogeneous tissues. However, it is challenging to integrate these different types of single-cell omics data. Moreover, the advent of spatially resolved single-cell imaging data represent another challenge for integrative analysis with omics data. Here, we present a new algorithm, inteGrative anaLysis of mUlti-omics at single-cEll Resolution (GLUER), for integration of single-cell multi-omics data as well as imaging data. We tested GLUER using multiple datasets generated using multiomics data generated on the same single cells, which was taken as the ground truth. Our results demonstrate that GLUER has significantly improved performance in terms of the accuracy of matching cells with different data modalities, which in turn enhances downstream analyses such as clustering and trajectory inference. GLUER provides a principled analytical framework for studying the heterogeneity of cell populations using multi-omics and imaging data. Citation Format: Tao Peng, Kamyar Esmaeili Pourfarhangi, Kai Tan. GLUER: integrative analysis of multi-omics data at single-cell resolution [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-026.
Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles
Authors: Wei Tong, Hui Hui, Wenting Shang, Yingqian Zhang, Feng Tian, Qiang Ma, Xin Yang, Jie Tian, Yundai Chen
Journal: Theranostics (2020)

Inflammation is a pivotal driver of atherosclerotic plaque progression and rupture and is a target for identifying vulnerable plaques. However, challenges arise with the current in vivo imaging modalities for differentiating vulnerable atherosclerotic plaques from stable plaques due to their low specificity and sensitivity. Herein, we aimed to develop a novel multimodal imaging platform that specifically targets and identifies high-risk plaques in vivo by detecting active myeloperoxidase (MPO), a potential inflammatory marker of vulnerable atherosclerotic plaque. Methods: A novel multimodal imaging agent, 5-HT-Fe3O4-Cy7 nanoparticles (5HFeC NPs), used for active MPO targeting, was designed by conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with 5-hydroxytryptamine and cyanine 7 N-hydroxysuccinimide ester. The specificity and sensitivity of 5HFeC NPs were evaluated using magnetic particle imaging (MPI), fluorescence imaging (FLI), and computed tomographic angiography (CTA) in an ApoE-/- atherosclerosis mouse model. Treatment with 4-ABAH, an MPO inhibitor, was used to assess the monitoring ability of 5HFeC NPs. Results: 5HFeC NPs can sensitively differentiate and accurately localize vulnerable atherosclerotic plaques in ApoE-/- mice via MPI/FLI/CTA. High MPI and FLI signals were observed in atherosclerotic plaques within the abdominal aorta, which were histologically confirmed by multiple high-risk features of macrophage infiltration, neovascularization, and microcalcification. Inhibition of active MPO reduced accumulation of 5HFeC NPs in the abdominal aorta. Accumulation of 5HFeC NPs in plaques enabled quantitative evaluation of the severity of inflammation and monitoring of MPO activity. Conclusions: This multimodal MPI approach revealed that active MPO-targeted nanoparticles might serve as a method for detecting vulnerable atherosclerotic plaques and monitoring MPO activity.