tbuckley/cabot-search huggingface dataset:
Abstract LB-026: iDEP: integrated differential expression and pathway analysis of RNA-Seq data
Authors: Steven X. Ge
Journal: Cancer Research (2018)

Abstract Analysis and interpretation of RNA-Seq data remain a challenge for bench scientists. We aim to develop a user-friendly web application for exploratory data analysis (EDA), differential expression, and pathway analysis using summarized gene-level data from RNA-Seq, DNA microarray or other platforms. The key idea of iDEP (integrated Differential Expression and Pathway analysis) is to make many powerful R/Bioconductor packages easily accessible by wrapping them under a graphical interface, alongside annotation databases. For EDA, it performs hierarchical clustering, k-means clustering, and principal component analysis. iDEP detects differentially expressed genes using the limma and DESeq2 packages. For a group of co-expressed genes, it identifies enriched gene ontology (GO) terms as well as transcription factor binding motifs in promoters. Pathway analysis can be performed using packages like GAGE, GSEA, PGSEA, or ReactomePA. iDEP can also detect chromosomal gain or loss using the PREDA package. iDEP uses annotation of 163 metazoa and 45 plant genomes in Ensembl for ID mapping and GO functional categorization. Common gene IDs including microarray probe names can be automatically recognized. Pathway information was also compiled from databases like KEGG, Reactome, MSigDB, GSKB, GeneSetDB, and araPath. As an example, we analyzed an RNA-Seq dataset involving siRNA-mediated Hoxa1 knockdown in lung fibroblasts, and identified the downregulation of cell-cycle genes, in agreement with previous studies. Our analyses also reveal the possible roles of E2F1 and its target genes, including microRNAs, in blocking G1/S transition, and the upregulation of genes related to cytokines, lysosome, and neuronal parts. iDEP enables users to conduct in-depth bioinformatics analysis of transcriptomic data through a graphical interface. Freely available at http://gelab.org/idep/ Citation Format: Steven X. Ge. iDEP: integrated differential expression and pathway analysis of RNA-Seq data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-026.
Results of phase 1 clinical trial evaluating efficacy of 3rd party cord blood regulatory T cells for prevention of graft versus host disease.
Authors: Joshua Kellner, Eric Yvon, Joseph Khoury, Tuongvan Nguyen, Jennifer Ramos, Amanda Leigh Olson, Yago Nieto, Stefan O. Ciurea, Stefan Nierkens, Elena Delemarre, Jaap Jan Boelens, Richard E. Champlin, Borje Andersson, Simrit Parmar
Journal: Journal of Clinical Oncology (2018)

e15047 Background: Acute Graft-versus-Host Disease (aGVHD) is a life threatening complication of allogeneic hematopoietic stem cell transplantation generated by engagement of allo-reactive donor T cells (Allo-T cells) with host antigen presenting cells (APCs). Regulatory T cells (Tregs), a naturally occurring T cell subset, suppress Allo-T cells in adoptive therapy. We previously established clinically meaningful expansion of Tregs from cord blood (CB) which prevented GVHD in a xenogenic mouse model and improved with post-expansion fucosylation. We hypothesized that adoptive therapy with fucosylated Tregs would prevent GVHD at a lower ratio to infused allo-T cells. Methods: Selected CB CD25+ cells were activated with CD3/28 beads (1:1) and cultured in 1000 U/ml IL-2. Cells were harvested at Day 14 and fucosylated prior to patient infusion. Peripheral blood was drawn at baseline and Day -1 (before Treg), Day 0 (before transplant) and Day 1, 3, 7, 14, 21, 30, 60 and 90. Samples were examined for T, B, NK and DC cell reconstitution and for cytokine secreting subsets. Plasma was examined for inflammatory cytokines and biomarkers of GVHD. Results: Flow cytometry revealed increases in inflammatory T cell subsets in the first week with concurrent increases in Tregs through Day 21. Early increases in NK and DC subsets was also observed. Initially, inflammatory cytokines IL-2, IL-6 and IL-8 increased along with aGVHD biomarkers ST-2, Osteopontin and Follistatin before subsiding. Biomarkers associated with chronic GVHD were not present. Though all patients received propoer dose, patients receiving fucosylated CB Tregs exhibited fever in the first week lasting for 5-7 days and requiring steroids for control. Conclusions: CB Tregs at dose level 1.0 e6/kg was well-tolerated with no infusional toxicity or impact on engraftment. While current dose level did not prevent aGVHD regardless of fucosylation status of CB Tregs, chronic GVHD did not occur. High fevers observed in the fucosylated CB Treg recipients may be a result of expanding effector T cells and steroid treatment may have blunted Treg effect. Stage 2 of this clinical trial examining untreated CB Tregs at 1.0 e7/kg is currently underway. Clinical trial information: NCT02423915.
Abstract 18796: Characterization of Endothelial Colony-forming Cells Bioactivity in Young Adults Born Extremely Preterm Versus Term
Authors: Mariane Bertagnolli, Katryn Paquette, Megan Sutherland, Chanel Béland, Marie-Amélie Lukaszewski, Anik Cloutier, Bernard Thébaud, Thuy Mai Luu, Anne Monique Nuyt
Journal: Circulation (2015)

Introduction: Among subtypes of endothelial progenitor cells, endothelial colony-forming cells (ECFC) display high proliferative and angiogenic capacity in vitro and are considered biomarkers of angiogenic/regenerative capacity. Cord blood ECFC from preterm born (PT) infants have impaired bioactivity, especially in those who develop prematurity-related complications such as bronchopulmonary dysplasia. Whether ECFC dysfunction persists in PT beyond the neonatal period is not known. Objective: Our aim was to assess ECFC bioactivity (in vitro growth, angiogenic capacity) in extremely PT vs. term (T) born young adults. Methods: ECFC were obtained from peripheral blood from 19 young adults (21-28 years old) born extremely PT (&lt;29 weeks gestation) and 19 T (≥37 weeks, paired by gender, age and socioeconomic status). Mononuclear cells (PBMC) were separated by density gradient and plated (5x10(6) cells/flask) to allow ECFC colony formation. ECFC were cultured to assess cell phenotype (CD45-/CD34+/CD31+/KDR+), in vitro proliferation rate by modified thymidine analogue EdU incorporation, and tubular formation in Matrigel. Results: ECFC colonies were obtained from 9 PT (48%) and 12 T (63%). The frequency distribution of the number of days to first colony formation was significantly different in PT vs. T, with higher frequency of late (&gt; 15 days) and absence of any colony formation in PT (p=0.033). In PT, days to form 1st ECFC colony inversely correlated with ECFC proliferation rate (r=-0.85, p&lt;0.001), and angiogenic capacity shown as number of tubes (r=-0.72, p=0.037) and branches (r=-0.68, p=0.043) formed in Matrigel, whereas in T these correlations were not significant with similar ECFC function at any time of colony formation. In PT, tubular formation negatively correlated with neonatal length of hospital stay (r=-0.72, p=0.03), a proxy of prematurity-related complications. Conclusions: Time to first ECFC colony formation, proliferation rate and in vitro tubular formation are significantly altered in PT vs. T young adults. Overall data suggests that extremely PT born young adults display impaired ECFC bioactivity, which may contribute to the development of cardiovascular diseases associated with impaired angiogenesis in this population.
Abstract 20405: Potential Value of an Aspirin-Dose Trial for Secondary Prevention of Coronary Artery Disease: Informing PCORI and Future Trial Design
Authors: Gillian D Sanders, Anirban Basu, Evan Myers, David Meltzer
Journal: Circulation (2016)

Objective: Despite established benefits of aspirin (ASA) in reducing risk for MI, stroke, and fatal coronary events among persons with preexisting atherosclerotic cardiovascular disease, uncertainty exists on the optimal dosage. PCORI recently funded a pragmatic RCT (ADAPTABLE) to answer this question. PCORI sought to explore how value-of-information (VOI) methods might be used to inform RCT design and funding decisions, using the ADAPATABLE trial as an example. Methods: We developed two independent models of cardiovascular events and mortality among target patients using a probabilistic minimal and a maximal lifetime model. Each model calculated the potential VOI for comparative effectiveness research comparing two daily doses of ASA (81mg vs 325mg). Each month, patients in the model were at risk for MI, stroke, major bleed, minor side effects, and death from other causes. Model parameters were based on literature reviews and data analyses. The minimal model expressed value in life years and carried out ...
Abstract 9576: Predictors of Silent Cerebral Events Detected on Magnetic Resonance Imaging in Patients After Atrial Fibrillation Ablation
Authors: ThomasDeneke, KarinNentwich, PatrickMüller, MarkusRoos, JoachimKrug, AndreasMügge, AtillaSzöllösi, RainerSchmitt, AnjaSchade
Journal: Circulation (2014)

Introduction: Silent cerebral events (SCE) have been identified on magnetic resonance imaging (MRI) in asymptomatic patients after atrial fibrillation (AF) ablation. Silent cerebral lesions represent irreversible cerebral damage, comparative analysis using a consistent MRI definition is missing and factors influencing the risk of SCE are poorly understood. Methods: 351 Patients undergoing AF ablation underwent post-ablation cerebral MRI. SCE were identified based on a sensitive definition using a 1.5Tesla MRI including DWI and ADC-map (but not including FLAIR). AF ablation was performed either using irrigated single-tip radiofrequency (RF) ablation (group 1, N=73), phased RF pulmonary vein isolation (PVI) (group 2, N=129), endoscopically-guided laser balloon (group 3, N=41), cryo-balloon PVI (group4, N=34) and irrigated RF multipolar catheters (nMARQ) (group 5, N=73). Differences in regard to SCE rates were analyzed. Results: In group 1 22%, in group 2 37%, in group 41%, in group 4 21% and in group 5 27% ...
PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection
Authors: Loghman Salimzadeh, Nina Le Bert, Charles-A. Dutertre, Upkar S. Gill, Evan W. Newell, Christian Frey, Magdeleine Hung, Nikolai Novikov, Simon Fletcher, Patrick T.F. Kennedy, Antonio Bertoletti
Journal: Journal of Clinical Investigation (2018)

Chronic HBV (CHB) infection suppresses virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a dual-staining method that utilizes hepatitis B virus (HBV) surface antigens (HBsAg) labeled with fluorochromes as "baits" for specific ex vivo detection of HBsAg-specific B cells and analysis of their quantity, function, and phenotype. We studied healthy vaccinated subjects (n = 18) and patients with resolved (n = 21), acute (n = 11), or chronic (n = 96) HBV infection and observed that frequencies of circulating HBsAg-specific B cells were independent of HBV infection status. In contrast, the presence of serum HBsAg affected function and phenotype of HBsAg-specific B cells that were unable to mature in vitro into Ab-secreting cells and displayed an increased expression of markers linked to hyperactivation (CD21lo) and exhaustion (PD-1). Importantly, B cell alterations were not limited to HBsAg-specific B cells, but affected the global B cell population. HBsAg-specific B cell maturation could be partially restored by a method involving the combination of the cytokines IL-2 and IL-21 and CD40L-expressing feeder cells and was further boosted by the addition of anti–PD-1 Abs. In conclusion, HBV infection has a marked impact on global and HBV-specific humoral immunity, yet HBsAg-specific B cells are amenable to a partial rescue by B cell–maturing cytokines and PD-1 blockade.
Quality of Life and Functional Outcomes 12 Months After Out-of-Hospital Cardiac Arrest
Authors: KarenSmith, EmilyAndrew, MarijanaLijovic, ZiadNehme, StephenBernard
Journal: Circulation (2015)

Background—Out-of-hospital cardiac arrest (OHCA) is a significant global health problem. There has been considerable investment in improving the emergency medical response to OHCA, with associated improvements in survival. However, concern remains that survivors have a poor quality of life. This study describes the quality of life of OHCA survivors at 1-year postarrest in Victoria, Australia. Methods and Results—Adult OHCA patients who arrested between 2010 and 2012 were identified from the Victorian Ambulance Cardiac Arrest Registry. Paramedics attended 15 113 OHCA patients of which 46.3% received an attempted resuscitation. Nine hundred and twenty-seven (13.2%) survived to hospital discharge of which 76 (8.2%) died within 12 months. Interviews were conducted with 697 (80.7%) patients or proxies, who were followed-up via telephone interview, including the Glasgow Outcome Scale–Extended, the 12-item short form health survey, and the EuroQol. The majority (55.6%) of respondents had a good recovery via the ...
Abstract 18471: A Teachable Moment: Clinically Stable Emergency Department Patients and Their Companions are Willing to Learn Compression-only Cardiopulmonary Resuscitation
Authors: Munish Goyal, Tanya Dall, Valerie Tainsh, Jaime Konieczny, Olga E Garcia, David Carlberg
Journal: Circulation (2015)

Introduction: Bystander CPR is uncommonly performed in out of hospital cardiac arrest patients transported to our Emergency Department (ED). ED visits are brief and complex, but represent a valuable opportunity to teach CPR to members of our community. Our objective was to determine what percentage of ED patients and their companions are willing to learn compression-only CPR. Hypothesis: The majority of ED patients and their companions are willing to learn compression-only CPR. Methods: A convenience sample of clinically stable adults age 18-70 from two urban, academic EDs with socioeconomically diverse patient populations was recruited. Patients in hallways and non-english speakers were excluded. Subjects were asked to complete a pre-video survey to assess baseline knowledge and willingness to perform CPR, watch a 60-second previously validated CPR instructional video, and then complete a post-training CPR survey. Consenting patients were asked if they thought their ED visit was related to their heart. All study subjects were categorized as: 1. patient or companion, and 2. cardiovascular or non-cardiovascular complaint. Subjects who did not consent were asked to share reasons for not participating. Data were entered into a REDCap database. Results: Between 1/1/15 to 6/7/15, 281 patients and their companions were approached about study participation. Mean age was 47, 66% female, 68% African American, and 69% had a college education. 73 believed their visit was related to their heart. 70% were patients, and the remainder were their companions. Overall, 229 (82%) were willing to learn compression-only CPR. 51 of 52 shared reasons for not participating. Reasons included: not feeling well (29%), already CPR trained (16%), and not interested (16%). Patients who thought their ED visit was related to their heart and their companions were equally likely to participate than those who did not (80% vs 83%). Conclusion: In two diverse, academic EDs, 82% of medically stable adult patients and their companions were willing to learn compression-only CPR.
Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma
Authors: Raj K. Gopal, Kirsten Kübler, Sarah E. Calvo, Paz Polak, Dimitri Livitz, Daniel Rosebrock, Peter M. Sadow, Braidie Campbell, Samuel E. Donovan, Salma Amin, Benjamin J. Gigliotti, Zenon Grabarek, Julian M. Hess, Chip Stewart, Lior Z. Braunstein, Peter F. Arndt, Scott Mordecai, Angela R. Shih, Frances Chaves, Tiannan Zhan, Carrie C. Lubitz, Jiwoong Kim, A. John Iafrate, Lori Wirth, Sareh Parangi, Ignaty Leshchiner, Gilbert H. Daniels, Vamsi K. Mootha, Dora Dias-Santagata, Gad Getz, David G. McFadden
Journal: Cancer Cell (2018)
Abstract 19170: Lesion Morphological Classification by Optical Coherence Tomography to Predict Therapeutic Efficacy After Balloon Pulmonary Angioplasty
Authors: Taku Inohara, Takashi Kawakami, Masaharu Kataoka, Keiichi Fukuda
Journal: Circulation (2015)

Introduction: Conventionally, angiographic classification has been used for chronic thromboembolic pulmonary hypertension (CTEPH). However, a classification based on lesion morphology is needed in the era of balloon pulmonary angioplasty (BPA). We sought to propose a classification of CTEPH based on lesion morphology detected by optical coherence tomography (OCT) and to evaluate its association with physiological stenosis assessed with a pressure wire and therapeutic efficacy in BPA. Methods: We analyzed 43 lesions in 17 patients who were treated with BPA under OCT and pressure-wire guidance from November 2012 to March 2015. OCT findings were classified into the following 4 categories: 1) mono-hole, 2) septum, 3) multi-hole with thin wall, and 4) multi-hole with thick wall. Results: Angiographic findings did not match the specific morphologic classification based on OCT findings. At the pre-BPA assessment, the pressure ratio of the septum type was significantly higher than that of the mono-hole and multi-hole with thick wall types (p = 0.026 and 0.047, respectively). Under the OCT-based classification, more than 50% of the septum and multi-hole with thin wall types could accomplish &gt;0.8 of the mean pressure ratio assessed by a pressure wire, and these proportions were significantly higher than those of the other 2 types: mono-hole and multi-hole with thick wall (p = 0.044). Based on angiographic classification, accomplishment of this criterion was not significantly different among angiographic types. Conclusions: OCT-based morphologic lesion classifications in CTEPH were useful to predict whether the lesion stenosis could improve to the acceptable level mediated by BPA.
The Conduction System in Acute Myocardial Infarction Complicated by Heart Block
Authors: Richardsutton, Michaeldavies
Journal: Circulation (1968)

Detailed histological examination of the conduction system in 29 cases of acute myocardial infarction complicated by heart block has been carried out. In 24 cases posterior infarction was present and occlusion had occurred in the artery from which the blood supply to the A-V node was ultimately derived. In these cases major structural damage to the conduction system was rare, but when present, involved the bundle branches. A-V block in posterior infarction is therefore usually due to hypoxia or other reversible factors rather than structural damage to the conduction system. These findings are consistent with the high incidence of transient heart block in survivors. In five cases anterior infarction alone was present. The blood supply of the A-V node was not compromised, but massive infarction had caused major damage to both bundle branches. Since major structural damage to the conduction system is uncommon in myocardial infarction, only a minority of survivors will have permanent heart block. In those cas...
Inhibition of Experimental Abdominal Aortic Aneurysm in the Rat by Use of Decoy Oligodeoxynucleotides Suppressing Activity of Nuclear Factor κB and ets Transcription Factors
Authors: HidekiNakashima, MotokuniAoki, TakashiMiyake, TomioKawasaki, MasahiroIwai, NobuoJo, MasakoOishi, KazusaburoKataoka, ShigetsuguOhgi, ToshioOgihara, YasufumiKaneda, RyuichiMorishita
Journal: Circulation (2004)

Background— Two phenomena, inflammation and matrix degradation, contribute to the progression of abdominal aortic aneurysm (AAA). Importantly, the inflammation is regulated by the transcription factor nuclear factor (NF)–κB, whereas the destruction and degradation of elastin fibers by matrix metalloproteinases (MMP) are regulated by ets. Thus, we developed a novel strategy to treat AAA by simultaneous inhibition of both NF-κB and ets by using chimeric decoy oligodeoxynucleotides (ODN). Methods and Results— AAA was induced in rats by transient aortic perfusion with elastase, whereas transfection of decoy ODN was performed by wrapping a delivery sheet containing decoy ODN around the aorta. Gel-mobility shift assay at 7 days after treatment demonstrated that both NF-κB and ets binding activity were simultaneously inhibited by chimeric decoy ODN. Transfection of chimeric decoy ODN resulted in significant inhibition of the progression of AAA such as aneurysmal dilation at 4 weeks after treatment as compared wi...
Abstract 20600: Visualization of Flow and Movement of Lymphatic Valves in Biological Pumps Made From Engineered Heart Tissue
Authors: HaykSimonyan, NeeravPatel, NarineMuselimyan, LutherSwift, NarineSarvazyan
Journal: Circulation (2014)

Introduction: At present, the arsenal of approaches to treat lymphedema is very limited and new therapies to improve lymph drainage are critically needed. We aim to address this need using newly available tools of tissue engineering. Specifically, we propose to create a regularly contracting layer of cardiomyocytes around thoracic duct and other major lymphatic vessels creating tissue engineered lymph heart. Methods: Tissue engineered cardiac fibers were made of rat neonatal cardiac myocytes mixed with fibrin hydrogel and seeded in rectangular agarose molds. The fibers ranged from 100 to 200 micron diameter and 1-2 cm in length and were amendable to surgical manipulation. Lymphatic system was visualized using tissue injection of indocyanine green dye and infrared sensitive CCD-camera. Movement of lymphatic valves was observed using Zeiss LSM 510 confocal imaging system using fluorescent membrane dyes. Results: Excised segments of rat and rabbit thoracic duct with and without valves were wrapped with engin...
Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system
Authors: Carlota Oleaga, Anne Riu, Sandra Rothemund, Andrea Lavado, Christopher W. McAleer, Christopher J. Long, Keisha Persaud, Narasimhan Sriram Narasimhan, My Tran, Jeffry Roles, Carlos A. Carmona-Moran, Trevor Sasserath, Daniel H. Elbrecht, Lee Kumanchik, L. Richard Bridges, Candace Martin, Mark T. Schnepper, Gail Ekman, Max Jackson, Ying I. Wang, Reine Note, Jessica Langer, Silvia Teissier, James J. Hickman
Journal: Biomaterials (2018)
TRPV2 Is a Component of Osmotically Sensitive Cation Channels in Murine Aortic Myocytes
Authors: KatsuhikoMuraki, YukoIwata, YukiKatanosaka, TomohiroIto, SusumuOhya, MunekazuShigekawa, YujiImaizumi
Journal: Circulation Research (2003)

Changes in membrane tension resulting from membrane stretch represent one of the key elements in blood flow regulation in vascular smooth muscle. However, the molecular mechanisms involved in the regulation of membrane stretch remain unclear. In this study, we provide evidence that a vanilloid receptor (TRPV) homologue, TRPV2 is expressed in vascular smooth muscle cells, and demonstrate that it can be activated by membrane stretch. Cell swelling caused by hypotonic solutions activated a nonselective cation channel current (NSCC) and elevated intracellular Ca2+ ([Ca2+]i) in freshly isolated cells from mouse aorta. Both of these signals were blocked by ruthenium red, an effective blocker of TRPVs. The absence of external Ca2+ abolished this increase in [Ca2+]i caused by the hypotonic stimulation and reduced the activation of NSCC. Significant immunoreactivity to mouse TRPV2 protein was detected in single mouse aortic myocytes. Moreover, the expression of TRPV2 was found in mesenteric and basilar arterial my...