tbuckley/cabot-search huggingface dataset:
Lamin C is required to establish genome organization after mitosis
Authors: Xianrong Wong, Victoria E. Hoskins, Ashley J. Melendez-Perez, Jennifer C. Harr, Molly Gordon, Karen L. Reddy
Journal: Genome biology (2021)

Abstract Background The dynamic 3D organization of the genome is central to gene regulation and development. The nuclear lamina influences genome organization through the tethering of lamina-associated domains (LADs) to the nuclear periphery. Evidence suggests that lamins A and C are the predominant lamins involved in the peripheral association of LADs, potentially serving different roles. Results Here, we examine chromosome architecture in mouse cells in which lamin A or lamin C are downregulated. We find that lamin C, and not lamin A, is required for the 3D organization of LADs and overall chromosome organization. Striking differences in localization are present as cells exit mitosis and persist through early G1 and are linked to differential phosphorylation. Whereas lamin A associates with the nascent nuclear envelope (NE) during telophase, lamin C remains in the interior, surrounding globular LAD aggregates enriched on euchromatic regions. Lamin C association with the NE is delayed until several hours into G1 and correlates temporally and spatially with the post-mitotic NE association of LADs. Post-mitotic LAD association with the NE, and global 3D genome organization, is perturbed only in cells depleted of lamin C, and not lamin A. Conclusions Lamin C regulates LAD dynamics during exit from mitosis and is a key regulator of genome organization in mammalian cells. This reveals an unexpectedly central role for lamin C in genome organization, including inter-chromosomal LAD-LAD segregation and LAD scaffolding at the NE, raising intriguing questions about the individual and overlapping roles of lamin A/C in cellular function and disease.
Abstract 13876: Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Macaque Model
Authors: Manish K Gupta, Maryam Rabbani, Jay Rappaport
Journal: Circulation (2021)

Background: Recent reports suggest the presence of the SARS-CoV-2 virus in the myocardium of patients who died from the COVID-19 disease. Cardiovascular injury in COVID-19 patients is an established extra-pulmonary manifestation of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection which may lead to induction of arrhythmia, acute heartfailure, thickening of ventricular wall, reduced ejection fraction and thromboembolism. Non-human primates (NHP) provide a useful model to study cardiovascular changes due to their homology to the ACE2 receptor in humans. Aim: The aim of this study is to characterize the pathological changes in the heart of SARS-CoV-2 infected NHPs. Methods: In the present study, SARS-CoV-2 infected primates via aerosol route (n=4), multi-routes (i.e., oral, nasal, intratracheal and conjunctival) (n=4), and a control group (n=5) were included. Heart tissue samples were collected and the left ventricular tissue was analyzed by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to CD3, CD68 andSARS-CoV-2 nucleocapsid protein. Results: Several pathological findings were observed in the heart, including cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells as well as hypertrophy. Collagen specific staining showed development of cardiac fibrosis in the interstitial as well as in the perivascularregion in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. Additionally, SARS-CoV-2 nucleocapsid protein staining detected the presence of virus particles in the myocardium. Conclusion: COVID19 infection is characterized by exaggerated inflammatory immune response in the heart which possibly contributes to myocardial remodeling and subsequent fibrosis. These findings suggest progression of disease which could lead to development of severe complications including heart failure.
Abstract 9447: Hospital-level Disparities in Management and Outcomes of Cardiac Arrest Complicating Acute Myocardial Infarction
Authors: Venkata Siva Kumar S Pajjuru, Sri Patlolla, Pranathi R Sundaragiri, Saraschandra Vallabhajosyula
Journal: Circulation (2021)

Background: There is limited contemporary data exploring the impact of hospital characteristics on the outcomes of AMI-CA patients. Methods: We used the National Inpatient Sample database (2000-2017), to identify adult admissions with a primary diagnosis of AMI and concomitant CA. Inter-hospital transfers were excluded and hospitals were classified based on location and teaching status (rural, urban nonteaching and urban-teaching), and bed size (small, medium and large) as specified by the Agency for Healthcare Research and Quality Results: Among 494,083 AMI-CA admissions, 9.3% received care at rural hospitals, 43.4% at urban non-teaching hospitals, and 47.3% at urban teaching hospitals. Compared to urban non-teaching and teaching hospitals, AMI-CA admissions at rural hospitals received lower rates of coronary angiography (36.5% vs 57.7% vs 69.1%), PCI (28.1% vs 42.6% vs 52.1%), CABG (3.4%, 7.6% vs. 10.1%), MCS (10.1% vs 17.8% vs 22.6%), and invasive mechanical ventilation (42.9%, 49.7% vs. 48.7%) (all p &lt;0.001). Admissions to urban teaching hospitals had higher rates of acute organ failure, concomitant cardiogenic shock and higher rates of cardiac and non-cardiac procedures. When hospitals were stratified by bed-size, 9.8% of AMI-CA admissions were admitted to small hospitals, 26.0% to medium-sized, and 64.2% to large hospitals. Compared to medium and large hospitals, AMI-CA admissions at small hospitals had lower rates of coronary angiography (48.9% vs 56.8% vs 64.7%), PCI (37.5% vs 42.5% vs 48.4%), CABG (5.3%, 6.8% vs. 9.5%), MCS (14.3% vs 17.3% vs 21%), and invasive mechanical ventilation (48.3%, 50.1% vs. 48%) (all p &lt;0.001). In-hospital mortality was higher in urban non-teaching (adjusted odds ratio [aOR] 1.17 [95% confidence interval {CI} 1.14-1.20]; p&lt;0.001) and urban teaching hospitals (aOR 1.36 [95% CI 1.32-1.39]; p&lt;0.001) compared to rural hospitals. Compared to small hospitals, medium (aOR 1.11 [95% CI 1.08-1.14]; p&lt;0.001) and large hospitals (aOR 1.22 [95% CI 1.19-1.25]; p&lt;0.001) were associated with higher in-hospital mortality. Conclusions: AMI-CA admissions to large and urban hospitals had higher in-hospital mortality compared to small and rural hospitals potentially due to greater acuity.
Abstract 12399: Don’t Burst My Blood: Ticagrelor Induced Thrombotic Thrombocytopenic Purpura
Authors: John L Medamana, Saif Laljee, Nicholas Kiefer, Shelly Brejt
Journal: Circulation (2021)

Background: Dual antiplatelet therapy, a fundamental component of the treatment of acute coronary syndromes (ACS), increases bleeding risk. Patients with thrombocytopenia and ACS are difficult to manage as thrombocytopenia increases the risk both of bleeding and ischemic events. Case: A 47 year old male with a medical history most significant for coronary artery disease (requiring multiple stents) and stroke who presented with chest pain and was found to have a NSTEMI. Notably, the patient stopped his ticagrelor six weeks prior to presentation. The initial CBC demonstrated clumped platelets. The patient was loaded with aspirin and ticagrelor, placed on a heparin drip and admitted. Decision Making: Exam on the morning after presentation demonstrated jaundice as well as petechiae on the patient’s extremities. He then exhibited altered mental status concerning for a seizure. Repeat labs demonstrated new severe thrombocytopenia, confirmed on a dedicated platelet count, anemia and indirect hyperbilirubinemia. A peripheral smear did not demonstrate schistocytes; however, the PLASMIC score indicated a high risk of thrombotic thrombocytopenic purpura (TTP) and he was started on plasmapheresis and steroids. His ADAMTS13 activity level returned low, confirming TTP. Common causes of TTP were excluded and Ticagrelor was deemed responsible. With continued plasmapheresis and steroids, his platelets normalized. A diagnostic left heart catheterization demonstrated patent prior stents as well as a 90% mid circumflex lesion. The patient was discharged on aspirin and rivaroxaban per the COMPASS trial, and was advised to avoid further P2Y12 inhibitors. Conclusion: This case demonstrated ticagrelor induced TTP, which has been infrequently reported in the literature. The patient was likely previously sensitized to ticagrelor and then developed TTP when he was loaded on presentation. It also demonstrates the importance of not ignoring clumped platelets and obtaining a true platelet count prior to starting triple therapy. In normal circumstances, his circumflex lesion would likely have been intervened upon; however, the patient’s intolerance of P2Y12 inhibitors limited management options during this presentation and will likely limit future interventions.
A Phase 3, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination with Azacitidine in Previously Untreated Patients with <i>TP53</i>-Mutant Acute Myeloid Leukemia
Authors: Naval Daver, Paresh Vyas, Mark Chao, Guan Xing, Camille Renard, Giri Ramsingh, David A. Sallman, Andrew H. Wei
Journal: Blood (2021)
Abstract 12561: Dietary and Lifestyle Behaviors Among Women of Reproductive Age by Disability Status
Authors: Jacqueline Litvak, Cheryl R Stein, Andrea L Deierlein
Journal: Circulation (2021)

Introduction: In the United States (U.S.), 18% of women age 18-44 years report at least one physical, sensory, or cognitive disability. Compared to the general population, women with disabilities are more likely to have multiple comorbidities and experience adverse pregnancy outcomes. Diet and physical activity are important and modifiable lifestyle behaviors for women’s preconception and long-term health, as well as the health of their offspring. This study examined diet quality, physical activity, and related lifestyle factors among women of reproductive age by disability status and disability type. Hypothesis: Diet quality, physical activity, and other lifestyle factors will differ across disability status. Methods: Data were from the U.S. National Health and Nutrition Examination Survey 2013-2018 (n=3,409). Disability status was determined by the Washington Group on Disability Statistics questions regarding difficulty hearing, seeing, concentrating, walking, dressing, or running errands alone. Diet quality was evaluated using the Healthy Eating Index (HEI) 2015, with higher scores indicating better diet quality. Self-reported physical activity, food security, and fast food and ready-to-eat food consumption were also assessed. Chi-square tests and generalized linear regression evaluated differences across disability status and disability type. Results: Compared to women with no disabilities, women with any self-reported disabilities had lower HEI-2015 scores (46.8 and 50.5, respectively; p&lt;0.05), were more likely to report low/very low food security (48% and 18%, respectively; p&lt;0.05), and were less likely to report meeting physical activity recommendations of ≥150 minutes/week of moderate/vigorous activities (27% and 43%, respectively; p&lt;0.05). Differences were also observed by disability type, such that women with self-reported vision difficulty consume more fast food meals in one week compared to women with no disabilities. Conclusions: Women of reproductive age with disabilities report lower diet quality, food security, and physical activity. Future research should focus on identifying and improving modifiable lifestyle behaviors among this population to reduce disparities in maternal and child health outcomes.
Abstract 9433: The Combination of the Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as a Novel Predictor of Cardiac Death in Acute Decompensated Heart Failure Patients With Preserved Left Ventricular Ejection Fraction: A Multicenter Study
Authors: Shunsuke Tamaki, Yoshiyuki Nagai, Ryu Shutta, Daisaku Masuda, Ryosuke Murai, Shohei Yoshima, Makoto Abe, Koji Sako, Shizuya Yamashita, Masahiro Seo, Takahisa Yamada, Akito Nakagawa, Yoshio Yasumura, Yusuke Nakagawa, Masamichi Yano, Takaharu Hayashi, Shungo Hikoso, Yohei Sotomi, Yasushi Sakata
Journal: Circulation (2021)

Background: Inflammation plays a central role in the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory markers which have been shown to predict post-discharge outcome in patients with HF. However, there is no information available on the combined usefulness of NLR and PLR in patients with HFpEF who are admitted with acute decompensated heart failure (ADHF). Methods: Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF), which is a prospective multicenter observational registry for ADHF patients with LVEF ≥50% in Osaka area. We studied 1011 patients who survived to discharge. NLR and PLR were measured at the time of admission. The NLR was calculated as the ratio of the neutrophil count to the lymphocyte count, and the PLR was calculated as the ratio of the platelet count to the lymphocyte count. The endpoint was cardiac death (CD). Results: During a follow-up period of 539±423 days, 81 patients had CD. Both NLR and PLR were significantly higher in the patients with than without CD. The optimal cut-off values of NLR and PLR were 4.5 and 193 on receiver operating characteristic curve analysis, respectively. At multivariate Cox analysis, higher NLR (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.49-4.22, p=0.0006) or higher PLR (HR 1.91, 95% CI 1.15-3.19, p=0.0130) were independently associated with CD. Moreover, the combination of higher NLR and higher PNR was the strongest predictor of CD (HR 2.84, 95% CI 1.56-5.17, p=0.0007). There was significant difference in the rate of CD among the three groups stratified by NLR and PLR values. Conclusions: In this multicenter study, the combination of NLR and PLR was shown to be a useful marker for the prediction of post-discharge outcome in patients with HFpEF admitted for ADHF.
Abstract 13292: Sex Differences in Clinical Outcomes and Quality of Life in Patients With Non-Obstructive CAD (a FAME 2 Substudy)
Authors: Sonia Shah, Takeshi Nishi, Yuhei Kobayashi, Emanuele Barbato, Pim Tonino, Peter Juni, Nico H.J. Pijls, Bernard De Bruyne, William Fearon
Journal: Circulation (2018)

Introduction: Patients with non-obstructive CAD have an increased risk of cardiovascular events compared with the general population. Recent studies have suggested that women with non-obstructive C...
Impact of COVID-19 on Hemodialysis Patients: The Quebec Renal Network (QRN) COVID-19 Study
Authors: Marie-Chantal Fortin, Marie-Françoise A. Malo, Aliya O. Affdal, Fabián A. Ballesteros Gallego, Annie-Claire Nadeau-Fredette, William Beaubien-Souligny, Rita Suri
Journal: Journal of the American Society of Nephrology (2021)

Background: Hemodialysis patients had to face numerous challenges during the COVID-19 pandemic. They are at increased risk of severe complications of COVID-19 and continued to visit hospitals thrice weekly, increasing their risk of being infected. The objective of this study was to document the impact of the COVID-19 on patient's experience in hemodialysis in Quebec. Methods: Between November 2020 and May 2021, we conducted semi-structured interviews with 20 patients who were undergoing dialysis treatments in six hemodialysis units in Montreal. Interviews were transcribed and analyzed using thematic content analysis. Results: Patients were satisfied by the measures implemented within their units in order to prevent COVID-19 outbreaks, such as making masks mandatory, restricting access to the dialysis ward, and even limiting the number of accompanying persons allowed. Participants reported that following the public health guidelines (social distancing, wearing a mask and washing hands) was easy and important in order to ensure their own and their family members' safety. Because of this, participants were more likely to refuse to see their family resulting in feeling of isolation. This was particularly relevant for Indigenous patients who were having their hemodialysis treatment away from their home and family. This sub-group experienced particular issues due to the prolonged remoteness from their loved ones, change in their hemodialysis center and with the measures put in place by the hotel they were residing at. Even though their usual routine outside of dialysis might have changed due to the pandemic, hemodialysis treatments allowed patients to keep a certain normality in their lives. Positive consequences were mentioned such as frequent contact through telemedicine and the existing solidarity between patients during the pandemics. Conclusions: Patients undergoing hemodialysis faced particular challenges due to the COVID-19 pandemic. Nonetheless, they showed great resilience in their capacity to adapt to the new reality of their hemodialysis treatments.
Evaluating the Carg Chemotherapy Toxicity Calculator Among Older Adults Newly Diagnosed with Hematologic Malignancy
Authors: Ashley E. Rosko, Sarah A Wall, Ying Huang, Alice S. Mims, Jennifer A. Woyach, Erin Stevens, Allesia Funderburg, Kaitlyn Dvorak, Christin Burd, Carolyn Presley, Michelle Naughton
Journal: Blood (2021)
Persistent SARS-CoV-2 infection with repeated clinical recurrence in a patient with common variable immunodeficiency
Authors: Marta Dafne Cabañero-Navalon, Victor Garcia-Bustos, Paula Ruiz-Rodriguez, Iñaki Comas, Mireia Coscollá, Llúcia Martinez-Priego, José Todolí, Pedro Moral Moral
Journal: Clinical Microbiology and Infection (2021)
Arming of iPSC-Derived NK Cells Expressing a Novel CD64 Fusion Receptor with Therapeutic Antibodies Represents a Novel Off-the-Shelf, Antigen-Targeting Strategy for Cancer
Authors: Kate Dixon, Kristin Snyder, Melissa Khaw, Robert Hullsiek, Zachary Davis, Tom Lee, Hui-yi Chu, Paul Rogers, Ryan Bjordahl, Martin Hosking, Soheila Shirinbak, Jeffrey S. Miller, Bahram Valamehr, Jianming Wu, Bruce Walcheck
Journal: Blood (2021)
Safety of Autologous Hematopoietic Stem Cell Transplantation in Patients over 75 Years Old. Single Center Experience Serving a Minority Population
Authors: Kateryna Fedorov, Tanim Jain, Jennat Mustafa, Amanda Lombardo, Fariha Khatun, Felisha Joseph, Kailyn Gillick, Anjali Naik, Richard Elkind, Michelly Abreu, Karen Fehn, Alyssa De Castro, Kith Pradhan, Donika Binakaj, Randin Nelson, Monika Paroder, Joan Uehlinger, Carlo Palesi, Kira Gritsman, R. Alejandro Sica, Noah Kornblum, Aditi Shastri, Ioannis Mantzaris, Lizamarie Bachier-Rodriguez, Amit Verma, Ira Braunschweig, Mendel Goldfinger
Journal: Blood (2021)
Ex Vivo Production of Large Numbers of Genetically Modified NK Cells from Cord Blood or Mobilized Peripheral Blood CD34 + Cells Using Notch Ligand Delta-like 4 Culture System
Authors: Akshay Joshi, Isabelle Andre, Pierre Gaudeaux, Ranjita Devi Moirangthem, Tayebeh Shabi Soheili, Marina Cavazzana, Chantal Lagresle-Peyrou
Journal: Blood (2021)
Evaluation of Global Coagulation Tests for Monitoring Bleeding Phenotypes and Response to Treatments in FVII Deficiency
Authors: Elena G Arias-Salgado, María Isabel Rivas Pollmar, Elena Monzón Manzano, Paula Acuña, María Teresa Alvarez Román, Mónica Martín, Sara García Barcenilla, Tamara Cebanu, Nuria Díaz Blazquez, Miguel Canales, Nora V. Butta, Víctor Jiménez-Yuste
Journal: Blood (2021)
Kynurenine Pathway Activation and Deviation in Fibrosing Chronic Graft-Versus-Host Disease
Authors: Orsatti Laura, Thomas Stiehl, Katharina Dischinger, Roberto Speziale, Pamela Di Pasquale, Edith Monteagudo, Carsten Mueller-Tidow, Aleksandar Radujkovic, Peter Dreger, Thomas Luft
Journal: Blood (2021)
Abstract PO-081: Studying MYC's contribution to replication stress at the nuclear pore
Authors: Gabriel M. Cohn, Colin J. Daniel, Daniel F. Liefwalker, Rosalie C. Sears
Journal: Cancer Research (2021)

Abstract Genomic instability is a hallmark of cancer which promotes oncogenic mutations in pancreatic ductal adenocarcinoma (PDAC), leading to more aggressive tumors with greater potential for drug resistance. Deregulation of the master transcription factor, MYC, is found in virtually all PDAC tumors and promotes genomic alterations by increasing replication stress, augmenting DNA repair pathways, and promoting cell survival. To resolve replication stress, stalled forks are trafficked to the nuclear pores where the necessary machinery accumulates. Activated MYC is spatially reorganized to the nuclear pores as well, a mechanism that is exacerbated in cancer. Whether MYC activity at the nuclear pores contributes to resolving replication stress in PDAC remains to be known. To investigate this mechanism, we are creating genomic and proteomic tools to determine MYC’s function at the nuclear pores during replication stress induced by olaparib treatment in PDAC cells. We found that olaparib significantly increases MYC accumulation at the nuclear pore in low-passage cell lines we established from PDAC patient tumors. Furthermore, we showed that MYC interacts with the nuclear pore resident SUMO protease, SENP1, which plays a key role in resolving stalled forks. Our preliminary data suggest a role for MYC resolving replication stress at nuclear pores, and could indicate MYC activity as a therapeutic target in olaparib-resistant PDAC. Citation Format: Gabriel M. Cohn, Colin J. Daniel, Daniel F. Liefwalker, Rosalie C. Sears. Studying MYC's contribution to replication stress at the nuclear pore [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-081.
MYC/BCL2/BCL6 triple hit and TP53 deletion in a case of high-grade B cell lymphoma receiving CAR T cell immunotherapy
Authors: Jiachen Wang, Zhen Shang, Jue Wang, Jinhuan Xu, Weigang Li, Yuqi Guan, Li Yang, Wei Zhang, Kefeng Shen, Meilan Zhang, Jin Wang, Liting Chen, Qinlu Li, Cheng He, Na Wang, Liang Huang, Yi Xiao, Min Xiao, Jianfeng Zhou
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immunotherapy has become one of the most effective treatments for refractory/relapsed (r/r) B cell lymphoma.[1][1] In particular, chimeric antigen receptor (CAR) T cell immunotherapy has recently been found to be a highly effective treatment for r/r diffuse large B cell lymphoma (DLBCL).[2][2] High
Late vs Early Response and Depth of Response Are Associated with Improved Outcomes in Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) Treated with Ixazomib-Lenalidomide-Dexamethasone (IRd) or Placebo-Lenalidomide-Dexamethasone (pbo-Rd) in the Phase 3 TOURMALINE-MM2 Trial
Authors: Paul G. Richardson, Thierry Facon, Christopher P. Venner, Nizar J. Bahlis, Fritz Offner, Darrell White, Lionel Karlin, Lotfi Benboubker, Sophie Rigaudeau, Eric Voog, Sung-Soo Yoon, Kenshi Suzuki, Hirohiko Shibayama, Xiaoquan Zhang, Arun Kumar, Philip Twumasi-Ankrah, Richard Labotka, Robert M. Rifkin, Sagar Lonial, Shaji Kumar, S. Vincent Rajkumar, Philippe Moreau
Journal: Blood (2021)