tbuckley/cabot-search huggingface dataset:
Diversification and CXCR4-Dependent Establishment of the Bone Marrow B-1a Cell Pool Governs Atheroprotective IgM Production Linked to Human Coronary Atherosclerosis
Authors: Aditi Upadhye, Prasad Srikakulapu, Ayelet Gonen, Sabrina Hendrikx, Heather M. Perry, Anh Nguyen, Chantel McSkimming, Melissa A. Marshall, James C. Garmey, Angela M. Taylor, Timothy P. Bender, Sotirios Tsimikas, Nichol E. Holodick, Thomas L. Rothstein, Joseph L. Witztum, Coleen A. McNamara
Journal: Circulation Research (2019)

Rationale: B-1 cell-derived natural IgM antibodies against oxidation-specific epitopes on low-density lipoprotein are anti-inflammatory and atheroprotective. Bone marrow (BM) B-1a cells contribute abundantly to IgM production, yet the unique repertoire of IgM antibodies generated by BM B-1a and the factors maintaining the BM B-1a population remain unexplored. CXCR4 (C-X-C motif chemokine receptor 4) has been implicated in human cardiovascular disease and B-cell homeostasis, yet the role of B-1 cell CXCR4 in regulating atheroprotective IgM levels and human cardiovascular disease is unknown. Objective: To characterize the BM B-1a IgM repertoire and to determine whether CXCR4 regulates B-1 production of atheroprotective IgM in mice and humans. Methods and Results: Single-cell sequencing demonstrated that BM B-1a cells from aged ApoE −/− mice with established atherosclerosis express a unique repertoire of IgM antibodies containing increased nontemplate-encoded nucleotide additions and a greater frequency of unique heavy chain complementarity determining region 3 sequences compared with peritoneal cavity B-1a cells. Some complementarity determining region 3 sequences were common to both compartments suggesting B-1a migration between compartments. Indeed, mature peritoneal cavity B-1a cells migrated to BM in a CXCR4-dependent manner. Furthermore, BM IgM production and plasma IgM levels were reduced in ApoE −/− mice with B-cell–specific knockout of CXCR4, and overexpression of CXCR4 on B-1a cells increased BM localization and plasma IgM against oxidation specific epitopes, including IgM specific for malondialdehyde-modified LDL (low-density lipoprotein). Finally, in a 50-subject human cohort, we find that CXCR4 expression on circulating human B-1 cells positively associates with plasma levels of IgM antibodies specific for malondialdehyde-modified LDL and inversely associates with human coronary artery plaque burden and necrosis. Conclusions: These data provide the first report of a unique BM B-1a cell IgM repertoire and identifies CXCR4 expression as a critical factor selectively governing BM B-1a localization and production of IgM against oxidation specific epitopes. That CXCR4 expression on human B-1 cells was greater in humans with low coronary artery plaque burden suggests a potential targeted approach for immune modulation to limit atherosclerosis.
Results of a Non-Interventional Clinical Trial of Apograft — a Novel Technology for GvHD Prevention
Authors: Jerry Stein, Tsila Zuckerman, Yuval Baar, Hila Wildbaum, Tamar Katz, Michal Perl-Yaffe, Limor Horev-Azaria, Shai Yarkoni, Amotz Nechushtan, Galina Rodionov, Liron Gez, Michal Rosenzwaig, Anastasia Rodin, Yaron Pereg, John F DiPersio, Jacob M. Rowe, Isaac Yaniv
Journal: Blood (2017)
TCT-351 Diagnostic Performance of Post-Stenting 3-Dimensional Quantitative Coronary Angiography to Predict Underexpansion as Measured by Optical Coherence Tomography
Authors: Armando Vergara-Martel, Gabriel Tensol Rodrigues Pereira, Dean Jia, Elder Zago, Luis Dallan, Patricia Ely Pizzato, Abdul Jawwad Samdani, Vladislav Zimin, Anas Fares, Guilherme Attizzani, Hiram Bezerra
Journal: Journal of the American College of Cardiology (2019)
TCT-207 Frontiers in Machine Learning and ECG: Value of Enriching Data
Authors: Sameer Mehta, Francisco Fernandez, Carlos Villagran, Sebastian Niklitschek, Felipe Vera, Alejandra Frauenfelder, Mariana Ceschim, Daniel Vieira, Rodrigo Jacobucci, Anibal Munguia, Claudia Lopez, Maria Marin, Isabella Vallenilla, Carlos Peña, José Aguilar, Pedro Cruz
Journal: Journal of the American College of Cardiology (2019)
TCT-485 Does the Time of Day of Primary PCI Influence Infarct Size and Prognosis in Patients With Acute STEMI? Analysis From an Individual Patient Data Pooled Database of Randomized Trials
Authors: Shmuel Chen, Bjorn Redfors, Aaron Crowley, Ori Ben-Yehuda, Fotios Gkargkoulas, Ghazaleh Mehdipoor, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
TCT-301 Evaluating the Long-Term Prognosis of Coronary Artery Disease Patients With Biodegradable Polymer Drug-Eluting Stents Implantation After Risk Stratification With SYNTAX Revascularization Index: Results From a Secondary Analysis of the I-LOVE-IT 2 Trial
Authors: Miaohan Qiu, Liya Bian, Peng Fan, Weichao Zhao, Jing Li, Yi Li, Yaling Han
Journal: Journal of the American College of Cardiology (2019)
TCT-788 Integrative Approach Following Transradial Access for Coronary Angiography Yields Heparin Avoidance, Ultrafast Hemostasis and Absolute Radial Artery Patency
Authors: Gregory Sgueglia, Francesco Summaria, Gaetano Gioffrè, Fabrizio D’Errico, Maria Benedetta Giannico, Fabiana Piccioni, Achille Gaspardone
Journal: Journal of the American College of Cardiology (2019)
TCT-39 Long-Term Clinical and Echocardiographic Results After PFO Closure With Occlutech Figulla Flex II Device: a Single-Center Prospective Registry
Authors: Daniela Trabattoni, Giovanni Teruzzi, Franco Fabbiocchi, Giuseppe Calligaris, Piero Montorsi, Stefano Galli, Cristina Ferrari, Paolo Mario Ravagnani, Manuela Muratori, Antonio Bartorelli
Journal: Journal of the American College of Cardiology (2019)
Genetic Variants Predisposing Most Strongly to Type 1 Diabetes Diagnosed Under Age 7 Years Lie Near Candidate Genes That Function in the Immune System and in Pancreatic β-Cells
Authors: Jamie R.J. Inshaw, Antony J. Cutler, Daniel J.M. Crouch, Linda S. Wicker, John A. Todd
Journal: Diabetes Care (2019)

OBJECTIVE Immunohistological analyses of pancreata from patients with type 1 diabetes suggest distinct autoimmune islet β-cell pathology between those diagnosed at &amp;lt;7 years (&amp;lt;7 group) and those diagnosed at age ≥13 years (≥13 group), with both B- and T-lymphocyte islet inflammation common in children in the &amp;lt;7 group, whereas B cells are rare in the ≥13 group. Based on these observations, we sought to identify differences in genetic susceptibility between these prespecified age-at-diagnosis groups to inform on the etiology of the most aggressive form of type 1 diabetes that initiates in the first years of life. RESEARCH DESIGN AND METHODS Using multinomial logistic regression models, we tested if known type 1 diabetes loci (17 within the HLA and 55 non-HLA loci) had significantly stronger effect sizes in the &amp;lt;7 group compared with the ≥13 group, using genotype data from 27,071 individuals (18,485 control subjects and 3,121 case subjects diagnosed at &amp;lt;7 years, 3,757 at 7–13 years, and 1,708 at ≥13 years). RESULTS Six HLA haplotypes/classical alleles and six non-HLA regions, one of which functions specifically in β-cells (GLIS3) and the other five likely affecting key T-cell (IL2RA, IL10, IKZF3, and THEMIS), thymus (THEMIS), and B-cell development/functions (IKZF3 and IL10) or in both immune and β-cells (CTSH), showed evidence for stronger effects in the &amp;lt;7 group. CONCLUSIONS A subset of type 1 diabetes–associated variants are more prevalent in children diagnosed under the age of 7 years and are near candidate genes that act in both pancreatic β- and immune cells.
Whether one burns fat, and not the type of fat one eats, is the important thing in type 2 diabetes
Authors: George Henderson
Journal: BMJ (2019)

Brown and colleagues investigated the effects of omega-3, omega-6, and total dietary polyunsaturated fat on the prevention and treatment of type 2 diabetes.1

Type 2 diabetes is a disease of fat accumulation in the liver and pancreas and of excessive free fatty acid flux from insulin resistant adipose tissue.2 This state saturates mitochondrial β-oxidation of fatty acids …
TCT-834 Coronary Plaque Vulnerability in Statin Treated Patients With Elevated LDL-C and hs-CRP: Optical Coherence Tomography Study
Authors: Surbhi Chamaria, Yuliya Vengrenyuk, Naotaka Okamoto, Nitin Barman, Samit Bhatheja, Vishal Kapur, Choudhury Hasan, Asaad Khan, Usman Baber, Samin Sharma, Jagat Narula, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2019)
TCT-659 Intravascular Ultrasound Analysis of Calcified Neoatherosclerosis Causing In-Stent Restenosis and Its Clinical Implication: From IRIS DES and DEB Registry
Authors: Sang-Cheol Cho, Yeongjin Jeong, Junghoon Lee, Yujin Yang, KyungJin Choe, Ju Hyeon Kim, Junho Hyun, Sangwoo Park, Hanbit Park, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Seung-Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2019)
Allele-specific NKX2-5 binding underlies multiple genetic associations with human electrocardiographic traits
Authors: Paola Benaglio, Agnieszka D’Antonio-Chronowska, Wubin Ma, Feng Yang, William W. Young Greenwald, Margaret K. R. Donovan, Christopher DeBoever, He Li, Frauke Drees, Sanghamitra Singhal, Hiroko Matsui, Jessica van Setten, Nona Sotoodehnia, Kyle J. Gaulton, Erin N. Smith, Matteo D’Antonio, Michael G. Rosenfeld, Kelly A. Frazer
Journal: Nature Genetics (2019)
MicroRNAs act as decoy molecules to restore granulocytic maturation of differentiation-arrested BCR/ABL+ myeloid progenitors
Authors: Anna Eiring, Paolo Neviani, George Calin, Denis Roy, Carlo Croce, Danilo Perrotti
Journal: Cancer Research (2008)

1494  Altered microRNA (miR) expression contributes to aberrant post-transcriptional regulation of gene expression in different type of cancers; however, their role in the pathogenesis and progression of chronic myelogenous leukemia (CML) from chronic phase (CP) to blast crisis (BC) is still largely unknown. Microarray analysis revealed that a discrete number of miRs are significantly upregulated (6.7% of the total 505 miRs present on the chip; 34 miRs) or downregulated (2.8%; 14 miRs) in an imatinib-sensitive manner in CML-BCCD34+ compared to CML-CPCD34+ progenitors and in BCR/ABL+ hematopoietic cell lines compared to untransformed cells. Among them, we investigated miR-223, miR-15a/16-1 and miR-328, a microRNA with no currently known function, because of their importance in myelopoiesis, potential role as tumor suppressors and sequence homology with the 5’ UTR of CEBPA mRNA, respectively. In BCR/ABL cell lines and primary CD34+ patient-derived myeloid cells, Northern blot and/or TaqMan RT-PCR analyses revealed that miR-223, miR-328, miR-15a/16-1 expression was markedly suppressed (50-75% inhibition) in a imatinib-sensitive manner by BCR/ABL kinase activity. Interestingly, sequence analysis of miR-223 and miR-328 revealed homology with the hnRNP E2-binding site contained in the CEBPA uORF/spacer mRNA. Accordingly, REMSA and UV-crosslinking showed that miR-223 and to a greater extent miR-328 bind recombinant and endogenous hnRNP E2 protein and compete for its binding to the CEBPA uORF/spacer region, which is required for hnRNP E2-mediated translational inhibition of CEBPA in CML-BCCD34+ progenitors, suggesting that miR-223 and miR-328 may act as decoy molecules that interfere with hnRNP E2 translation-inhibitory activity. Indeed, ectopic miR-223 expression restored G-CSF-driven C/EBPα-dependent granulocytic maturation of differentiation-arrested 32D-BCR/ABL cells, whereas it did not have any effect on cytokine-independent growth and clonogenic potential. Consistent with its ability to bind hnRNP E2, miR-328 also rescued C/EBPα expression and differentiation of cytokine-independent 32D-BCR/ABL myeloid precursors and primary CD34+ CML-BC progenitors. By contrast, BCR/ABL-dependent colony formation was markedly reduced by miR-15a/16-1 overexpression (65-75% inhibition, P
TCT-376 Randomized Trial of Conventional Transseptal Needle Versus Radiofrequency Energy Needle Puncture for Left Atrial Access During Cryoballoon Ablation (CRYO-LATS Study)
Authors: Jason Andrade, Jean Champagne, Marc Deyell, Vidal Essebag, Carlos Morillo, John Sapp, Patricia Theoret-Patrick, George Wells, Atul Verma
Journal: Journal of the American College of Cardiology (2019)
Reply
Authors: Mohammad Bilal Siddiqui, Mohammad Shadab Siddiqui
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. Aberrant lipid metabolism, central to atherosclerosis, is mechanistically influenced by insulin resistance and nonalcoholic fatty liver disease (NAFLD), which favors production and secretion of large very low‐density lipoprotein (VLDL) particles from the liver.1 These large VLDL particles are slowly metabolized in the periphery, leading to formation of atherogenic small dense low‐density lipoprotein (sdLDL) particles.2 Thus, biological elevation of sdLDL is often seen in patients with underlying NAFLD and diabetes, and attempting to match the study cohort with regard to these covariates would ignore the biology that leads to formation of sdLDL. With progression to cirrhosis, synthetic hepatic failure results in artificial “normalization” of lipids and lipoproteins.2 Following liver transplant (LT), restoration of hepatic function, immunosuppression, and development of cardiometabolic conditions promote production of atherogenic lipoproteins3 and lead to accelerated atherosclerosis.4 Thus, the results would be difficult to interpret in patients with cirrhosis with an artificially normal lipoprotein profile. In the present study, we included established atherosclerosis risk factors, such as sex, age, insulin, and resistance. Covariates, such as intensive care unit status, ventilator status, pre‐LT hospitalization, and so on, may be important peri‐LT; however, their utility years after LT is unknown and likely mechanistically less relevant. The study from Van Wagner et al.5 emphasized outcomes within 30 days of LT, which is significantly different from our study design where time from LT to end of follow up was 111 months. Additionally, we have incorporated several covariates included by Sastre et al.6 but were unable to include all because of sample size and number of observed events. The diagnostic threshold for sdLDL was chosen based on published cardiac literature,7 as our sample size of 130 patients with 20 cardiovascular disease (CVD) events is not large enough to perform adequate biomarker validation studies. Determination of LT‐specific size would require a large sample size with training and validation cohorts with adequate sample size to detect differences. In the absence of any significant literature linking lipoproteins to CVD events after LT, our study provides foundational data for sample size calculation to construct larger prospective trials to better investigate the relationship between lipoproteins and CVD.
Ikaros Family Zinc Finger 1 Mutation Is a Poor Prognosis Factor of Adult B Cell Acute Lymphoblastic Leukemia
Authors: Shanhao Tang, Hongjie Shen, Xinliang Mao, Haiping Dai, Xiaming Zhu, Shengli Xue, Zixuan Ding, Jing Lu, Depei Wu, XiaoWen Tang
Journal: Blood (2017)
Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma: 5-Year Follow-up and Correlative Analysis from a Multi-Center Phase II Study
Authors: Jia Ruan, Peter Martin, Paul J Christos, Leandro Cerchietti, Bijal D. Shah, Stephen J. Schuster, Wayne Tam, Amelyn Rodriguez, David Hyman, Maria Nieves Calvo Vidal, Lidia Roman Gonzalez, Sonali M. Smith, Jakub Svoboda, Richard R. Furman, Morton Coleman, John P. Leonard
Journal: Blood (2017)
TCT-705 Thrombocytopenia and Outcomes After Transcatheter Aortic Valve Implantation
Authors: Shinya Ito, Kyohei Yamaji, Tomohiro Kawaguchi, Tomohiko Taniguchi, Akihiro Isotani, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2019)
TCT-576 Clinical Outcome of Fractional Flow Reserve (FFR) and Its Associated Alternate Indices During Practical Routine Clinical Procedures (PRESSUREwire Registry)
Authors: Colin Berry, Stephan Achenbach, Gautam Kumar, Erick Schampaert, Nobuhiro Tanaka, Tarn Teraphongphom, Gregory Ginn, Zhen Zhang, Samer Somi, Giovanni Amoroso, Paul Knaapen, Joshua Krasnow, Guus Brueren
Journal: Journal of the American College of Cardiology (2019)
TCT-109 Inaccuracy of FFR in Clinical Practice: A High-Volume Single-Center Experience
Authors: Ankita Gore, Mitsuaki Matsumura, Hussein Rahim, Erin Flattery, Michael Brener, Fotios Gkargkoulas, Evan Shlofmitz, Ajay Jayant Kirtane, Dimitri Karmpaliotis, Jeffrey W. Moses, Ori Ben-Yehuda, Gregg Stone, Martin Leon, Gary Mintz, Allen Jeremias, Akiko Maehara, Ziad Ali
Journal: Journal of the American College of Cardiology (2019)
TCT-784 Comparison of Simultaneous Radial Artery With Upper Extremity Venous Access and Femoral Artery With Femoral Vein Access in Patients Undergoing Bilateral Heart Catheterization: A Systemic Review and Meta-Analysis
Authors: Ahmed Alabbady, Nath Limpruttidham, Tanawan Riangwiwat, Hadi Mahmaljy, Gregory Yost
Journal: Journal of the American College of Cardiology (2019)
TCT-55 Incidence, Predictors, and Clinical Implications of Stent Optimization on Intravascular Ultrasound After New-Generation Drug-Eluting Stent Implantation for Diffuse Long Coronary Stenotic Lesions
Authors: Daehoon Kim, Sung-Jin Hong, Byeong-Keuk Kim, Dong-Ho Shin, Chul-Min Ahn, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Myeong-Ki Hong, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2019)
TCT-436 Transcatheter Versus Surgical Mitral Valve Repair in Patients With Prior CABG: A Nationwide Analysis
Authors: Aaqib Malik, Syed Zaid, Srikanth Yandrapalli, Suchith Shetty, Senada Malik, Wilbert Aronow, Cenap Undemir, Hasan Ahmad, Gilbert Tang
Journal: Journal of the American College of Cardiology (2019)
TCT-605 Sympathetic Renal Denervation in Patients With Refractory Arterial Hypertension: 2-Year Follow-Up
Authors: Zaur Shugushev, Daniil Maximkin, Chepurnoy Alexandr, Alexandr Faibushevich, Olga Safonova, Aslan Mambetov
Journal: Journal of the American College of Cardiology (2019)
TCT-421 Predicting 2 Years All-Cause Mortality After Contemporary PCI: Revising and Updating the Logistic Clinical SYNTAX Score in the GLOBAL LEADERS Study
Authors: Ply Chichareon, David van Klaveren, Rodrigo Modolo, Norihiro Kogame, Kuniaki Takahashi, Mariusz Tomaniak, Robert-Jan Van Geuns, Adel Aminian, Scot Garg, Paul Ong, Manel Sabate, Christian Hamm, Peter Juni, Marco Valgimigli, Stephan Windecker, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2019)
TCT-221 Initial Report of Safety and Feasibility of Robotic-Assisted Chronic Total Occlusion Coronary Intervention
Authors: Taishi Hirai, Kathleen Kearney, Akash Kataruka, Kensey Gosch, Hunter Brandt, William Nicholson, Adam Salisbury, J. Aaron Grantham
Journal: Journal of the American College of Cardiology (2019)
A Cluster Randomized Trial to Screen for Abusive Head Trauma in the Pediatric Intensive Care Unit—How to Manage Site-Specific Evidence of Racial/Ethnic Disparity
Authors: Liza-Marie Johnson, Jennifer Zabrowski, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2019)

"A Cluster Randomized Trial to Screen for Abusive Head Trauma in the Pediatric Intensive Care Unit—How to Manage Site-Specific Evidence of Racial/Ethnic Disparity." The American Journal of Bioethics, 19(10), pp. 108–109
Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study
Authors: Johan Staaf, Dominik Glodzik, Ana Bosch, Johan Vallon-Christersson, Christel Reuterswärd, Jari Häkkinen, Andrea Degasperi, Tauanne Dias Amarante, Lao H. Saal, Cecilia Hegardt, Hilary Stobart, Anna Ehinger, Christer Larsson, Lisa Rydén, Niklas Loman, Martin Malmberg, Anders Kvist, Hans Ehrencrona, Helen R. Davies, Åke Borg, Serena Nik-Zainal
Journal: Nature Medicine (2019)
Review of Thomas H. Murray, <i>Good Sport: Why Our Games Matter and How Doping Undermines Them</i>
Authors: Craig Klugman
Journal: The American Journal of Bioethics (2019)

"Review of Thomas H. Murray, Good Sport: Why Our Games Matter and How Doping Undermines Them." The American Journal of Bioethics, 19(10), pp. W1–W2
Innovative intelligent insole system reduces diabetic foot ulcer recurrence at plantar sites: a prospective, randomised, proof-of-concept study
Authors: Caroline A Abbott, Katie E Chatwin, Philip Foden, Ahmad N Hasan, Chandbi Sange, Satyan M Rajbhandari, Prabhav N Reddy, Loretta Vileikyte, Frank L Bowling, Andrew J M Boulton, Neil D Reeves
Journal: The Lancet Digital Health (2019)

Prevention of diabetic foot ulcer recurrence in high risk patients, using current standard of care methods, remains a challenge. We hypothesised that an innovative intelligent insole system would be effective in reducing diabetic foot ulcer recurrence in such patients.In this prospective, randomised, proof-of-concept study, patients with diabetes, and with peripheral neuropathy and a recent history of plantar foot ulceration were recruited from two multidisciplinary outpatient diabetic foot clinics in the UK, and were randomly assigned to either intervention or control. All patients received an insole system, which measured plantar pressure continuously during daily life. The intervention group received audiovisual alerts via a smartwatch linked to the insole system and offloading instructions when aberrant pressures were detected; the control group did not receive any alerts. The primary outcome was plantar foot ulcer occurrence within 18 months. This trial is registered with ISRCTN, ISRCTN05585501, and is closed to accrual and complete.Between March 18, 2014, and Dec 20, 2016, 90 patients were recruited and consented to the study, and 58 completed the study. At follow-up, ten ulcers from 8638 person-days were recorded in the control group and four ulcers from 11 835 person-days in the intervention group: a 71% reduction in ulcer incidence in the intervention group compared with the control group (incidence rate ratio 0·29, 95% CI, 0·09-0·93; p=0·037). The number of patients who ulcerated was similar between groups (six of 26 [control group] vs four of 32 [intervention group]; p=0·29); however, individual plantar sites ulcerated more often in the control group (ten of 416) than in the intervention group (four of 512; p=0·047). In an exploratory analysis of good compliers (n=40), ulcer incidence was reduced by 86% in the intervention group versus control group (incidence rate ratio 0·14, 95% CI 0·03-0·63; p=0·011). In the exploratory analysis, plantar callus severity (change from baseline to 6 months) was greater in re-ulcerating patients (6·5, IQR 4·0-8·3) than non-re-ulcerating patients (2·0, 0·0-4·8; p=0·040).To our knowledge, this study is the first to show that continuous plantar pressure monitoring and dynamic offloading guidance, provided by an innovative intelligent insole system, can lead to a reduction in diabetic foot ulcer site recurrence.Diabetes UK and Orpyx Medical Technologies.