tbuckley/cabot-search huggingface dataset:
Noninvasive Determination of Coronary Blood Flow Velocity With Cardiovascular Magnetic Resonance in Patients After Stent Deployment
Authors: EikeNagel, ThomasThouet, ChristophKlein, SimonSchalla, AxelBornstedt, BernhardSchnackenburg, JürgenHug, ErnstWellnhofer, EckartFleck
Journal: Circulation (2003)

Background— In patients with coronary artery stents, no direct noninvasive coronary artery imaging is possible with magnetic resonance (MR). A well-established method for the assessment of the functional significance of a coronary lesion is the measurement of coronary flow reserve by invasive intracoronary Doppler. The purpose of the study was to determine coronary flow velocity reserve (CFVR) with MR after stent deployment. Methods and Results— Thirty-eight patients after successful PTCA and stent deployment were included. CFVR was measured perpendicular to the artery distal to the stent using phase-contrast velocity quantification at rest and during adenosine-stimulated hyperemia with a 1.5T MR tomograph (ACS NT, Philips). Measurements were repeated after 3 months and compared with invasive coronary angiography. In 18 patients, additional invasive Doppler flow measurements were obtained. CFVR could be determined in 29 of 38 (76%) of the patients. After 3 months, significant differences were obtained bet...
Predominant Distribution of Nifedipine-Insensitive, High Voltage–Activated Ca2+ Channels in the Terminal Mesenteric Artery of Guinea Pig
Authors: HiromitsuMorita, HelenCousins, HitoshiOnoue, YushiIto, RyujiInoue
Journal: Circulation Research (1999)

Abstract—We have found nifedipine-insensitive (NI), rapidly inactivating, voltage-dependent Ca2+ channels (current, NI-ICa) with unique biophysical and pharmacological properties in the terminal branches of guinea pig mesenteric artery, by using a whole-cell mode of the patch-clamp technique. The fraction of NI-ICa appeared to increase dramatically along the lower branches of mesenteric artery, amounting to almost 100% of global ICa in its periphery. With 5 mmol/L Ba2+ as the charge carrier, NI-ICa was activated with a threshold of −50 mV, peaked at −10 mV, and was half-activated and inactivated at −11 and −52 mV, respectively, generating a potential range of constant activation near the resting membrane potential. The NI-ICa was rundown resistant, was not subject to Ca2+-dependent inactivation, and exhibited the pore properties typical for high voltage–activated Ca2+ channels; Ba2+ is ≈2-fold more permeable than Ca2+, and Cd2+ is a better blocker than Ni2+ (IC50, 6 and 68 μmol/L, respectively). Relativel...
Abstract 2219: Expression of PCNA and MCM2 in ameloblastoma
Authors: Bhavana Mallipudi
Journal: Cancer Research (2018)

Abstract Background:-Ameloblastoma is an odontogenic neoplasm with the most frequent osseous destructive lesions of the jaws. Ameloblastoma deserves special attention, because of its biological behaviour exhibiting great infiltrative potential, high recurrence rate and capacity to metastasize. The increased proliferation rate in the odontogenic epithelium can be a result of perturbations in the cell cycle regulators and dictates the aggressive behavior of the tumors. Investigating proliferative rates in the epithelial lining of these lesions helps in assessing their biological behaviour. Various cell proliferation markers are used as diagnostic and prognostic tools in oral lesions. Assessing the expression of these markers helps in estimating the proliferative index of the tissues. Aim:- The aim of this study is to analyze the presence of, Proliferating cell nuclear antigen (PCNA) and the minichromosome maintenance-2 (MCM2) proteins, two well established markers of cell proliferation, in clinically diagnosed cases of ameloblastoma and correlate with aggressiveness and its types (Solid/multicystc{Follicular, plexiform} unicystic). Materials and method:-14 clinically diagnosed cases of ameloblastomas (10 Solid/multicystic cases{6 cases of Follicular, 4 cases of plexiform} and 4 cases of unicystic) are obtained from the archieves of the Department of Oral and Maxillofacial Pathology to study the expression of MCM2 and PCNA. The data was analysed by Kruskals ANOVA, Mann-Whitney U test and Post hoc analysis. Results and conclusion:- A Kruskal-Wallis ANOVA was used to detect if there was a significant difference in the expression of MCM2 and PCNA between the three variants of ameloblastoma. There was a significant difference between the three groups for mean percentage expression of MCM2 but there was uniformly higher expression of PCNA in all the three variants. Interestingly, further post hoc analysis revealed that the expression of MCM2 was significantly higher in the follicular variantas compared to the unicystic variant, suggesting that dual staining of MCM2 and PCNA may be a better marker for follicular variant. Keywords:-Ameloblastoma, MCM2, PCNA. Citation Format: Bhavana Mallipudi. Expression of PCNA and MCM2 in ameloblastoma [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 2219.
Abstract 3279: Comprehensive analysis of small nucleolar RNAs across in human cancers
Authors: Jing Gong, Yajuan Li, Chunjie Liu, Yu Xiang, An-yuan Guo, Chunru Lin, Leng Han
Journal: Cancer Research (2018)

Abstract Recent studies demonstrated that small nucleolar RNAs (snoRNAs) play important roles in tumorigenesis. We systematically investigated the expression landscape and clinical relevance of snoRNAs in &amp;gt;10,000 samples across 31 cancer types. We observed overall elevated expression of snoRNAs and their ribonucleoproteins in multiple cancer types. We showed complex regulation of snoRNA expression by their host genes, copy number variation, and DNA methylation. Unsupervised clustering revealed that the snoRNA expression subtype is highly concordant with other molecular/clinical subtypes. We further identified 46 clinically relevant snoRNAs and experimentally demonstrated functional roles of SNORD46 in promoting cell proliferation, migration, and invasion. We developed a user-friendly data portal, SNORic, to benefit the research community. Our study highlights the significant roles of snoRNAs in the development and implementation of biomarkers or therapeutic targets for cancer and provides a valuable resource for cancer research. Citation Format: Jing Gong, Yajuan Li, Chunjie Liu, Yu Xiang, An-yuan Guo, Chunru Lin, Leng Han. Comprehensive analysis of small nucleolar RNAs across in human cancers [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 3279.
Abstract 238: Interaction analysis between germline susceptibility loci and somatic alterations in lung cancer
Authors: Yuzhuo Wang, Cheng Wang, Meng Zhu, Guangfu Jin, Hongbing Shen
Journal: Cancer Research (2018)

Abstract Emerging evidence indicates that germline variations may interact with somatic events in carcinogenesis. However, the germline-somatic interaction in lung cancer remains largely unknown. In the present study, we investigated whether lung cancer driver genes (CDGs) were more likely to locate within cancer susceptibility regions. Additional pathway enrichment analysis was performed to identify common pathways underlying CDGs and cancer susceptibility genes (CSGs). Next, we analyzed the associations between lung cancer risk SNPs and somatic alterations, including mutations and copy number alterations, in the level of genes, pathways, and overall burden of alterations. Enrichment analysis showed that lung CDGs are more likely to locate within cancer susceptibility regions (P = 8.40×10-3). Both of lung CSGs and CDGs showed significant enrichment in pathways such as cell cycle and p53 signaling pathway. Gene-based analysis showed that rs36600 (22q12.2) was associated with somatic mutations within ARID1A (OR = 2.45, 95%CI: 1.47-4.08, P = 5.78×10-4). Pathway-based analysis identified rs2395185 and rs3817963 at 6p22.1 were associated with somatic truncation mutations in cell cycle pathway (OR = 1.56, P = 3.61×10-4 for rs2395185; OR = 1.58, P = 4.15×10-4 for rs3817963), and rs3817963 was also associated with somatic truncation mutations in MAPK signaling pathway (OR = 1.54, P = 8.58×10-4). Further analysis associated rs2395185 at 6p22.1 (HLA class II genes) with increased APOBEC3A expression (P = 9.50×10-3) and elevated APOBEC mutagenesis (P = 3.58×10-3). These results provide evidence for the germline-somatic interactions on lung tumorigenesis. This can help to uncover the molecular mechanisms by which risk SNPs influence lung cancer risk. Citation Format: Yuzhuo Wang, Cheng Wang, Meng Zhu, Guangfu Jin, Hongbing Shen. Interaction analysis between germline susceptibility loci and somatic alterations in lung cancer [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 238.
Abstract 14126: Safety and Efficacy of Anti-thrombotic Therapy After PCI in Octogenarians With Atrial Fibrillation: A Multi-center Study
Authors: Hisao Otsuki, Junichi Yamaguchi, Hiroyuki Arashi, Kentaro Jujo, Kazuho Kamishima, Masashi Nakao, Kensuke Shimazaki, Takehiro Hata, Yasuhiro Kkuchi, Hiroshi Ogawa, Nobuhisa Hagiwara
Journal: Circulation (2015)

The purpose of the present study was to clarify the safety and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in octogenarians with atrial fibrillation (AF) undergoing PCI. Method and Result: We examined consecutive 360 AF patients registered at 8 medical centers who took DAPT or OAC + DAPT at the time of PCI. Octogenarians (n=77) were compared with those of younger patients (n=283). In octogenarians, acute coronary syndrome (octogenarians vs. younger patients = 54.6% vs. 37.4%) was more common and diabetes (32.5% vs. 45.6%) and usage of drug-eluting stent (58.4% vs. 73.1%) were less common (P&lt;0.01, respectively). There was a significant difference in CHADS2 score (2.9±1.0 vs. 2.2±1.3, P&lt;0.01) and no statistical difference HAS-BLED score (2.4±0.7 vs. 2.2±0.8). At 1-year, major adverse cerebro-cardiovascular events (MACCE) was significantly higher in octogenarians than in younger patients (16.9% vs. 3.9% P&lt;0.01) and bleeding complications (defined as TIMI minor plus major) were similar (7.8% vs. 5.6% P=0.48). In octogenarians, there was a trend in lower cumulative incidence of MACCE in OAC+DAPT patients (n=44) compared to DAPT patients (n=33; 13.6% vs. 21.2% p=0.06), however, there was an excess risk of bleeding complications (13.6% vs. 0%, p=0.008). Conclusion: Octogenarians with AF undergoing PCI showed poor prognosis and were at high risk of bleeding, especially in patients who took OAC + DAPT. “Tailor-made” treatment strategies should be considered in this high-risk subset.
Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model
Authors: Giuseppe Locatelli, Delphine Theodorou, Arek Kendirli, Marta Joana Costa Jordão, Ori Staszewski, Kshiti Phulphagar, Ludovico Cantuti-Castelvetri, Athanasios Dagkalis, Alain Bessis, Mikael Simons, Felix Meissner, Marco Prinz, Martin Kerschensteiner
Journal: Nature Neuroscience (2018)
New Three-Dimensional Echocardiographic System Using Digital Radiofrequency Data—Visualization and Quantitative Analysis of Aortic Valve Dynamics With High Resolution
Authors: MichaelHandke, CosimaJahnke, GudrunHeinrichs, JörgSchlegel, ClemensVos, DanielSchmitt, ChristophBode, AnnetteGeibel
Journal: Circulation (2003)

Background— Common 3D systems have only limited spatial and temporal resolution (frame rate of 25 Hz). Thin structures such as cardiac valves are not imaged exactly; rapid movement patterns cannot be precisely recorded. The objective of the present project was to achieve radiofrequency (RF) data transmission to the 3D workstation to improve image resolution. Methods and Results— A commercially available echocardiographic system (5-MHz transesophageal echocardiography probe) with an integrated raw data interface enables transmission of RF data (up to 40 megabytes per second). A 3D data set may contain up to 3 gigabytes, so that all of the high-resolution ultrasound information of the 2D image is available. Frame rates of up to 168 Hz result in temporal resolution 6 times that of standard 3D systems. The applicability of the system and the image quality were tested in 10 patients. The structure of the aortic valve and the dynamic changes were depicted by volume rendering. The changes in the orifice areas we...
Abstract 1187: Comparison of intra-tumor heterogeneity and clonal evolution across lung cancer subtypes by multi-region whole genome sequencing
Authors: Tongwu Zhang, Joshua Sampson, Pier Alberto Bertazzi, Angela Pesatori, Dario Consonni, Bin Zhu, Belynda Hicks, Xing Hua, Jianxin Shi, Kevin Brown, Stephen Chanock, Maria Teresa Landi
Journal: Cancer Research (2018)

Abstract Both lung squamous cell carcinoma (LUSC) and lung cancer with neuroendocrine features (LUNE; i.e., small cell carcinoma (SCLC), large cell carcinoma (LCNEC) and other subtypes) are associated with tobacco smoking and have a very poor prognosis. We sought to characterize their clonal architecture and illustrate how the evolutionary patterns differ across these lung cancer subtypes. We performed multi-region whole genome sequencing of 83 samples from 36 LUSC and 67 samples from 23 LUNE patients that had been resected before systemic therapy. Among somatic copy number alterations, we observed genome doubling intra-tumor heterogeneity (ITH) and massive genomic instability in both subtypes. For somatic nucleotide variants (SNVs), the total mutation burden was higher in LUSC (16.7 average number of mutations/Mb) than LUNE (12.7/Mb), but for SNVs ITH was higher in LUNE. Among driver genes, TP53, CDKN2A, CR1, and NRK in LUSC and TP53, KRAS, KMT2D, and RB1 in LUNE were frequently mutated and were always clonal. Evidence of positive selection was found for TP53, PTEN, KMT2D and KEAP1 in LUSC, and for TP53 and KRAS in LUNE. As expected, the dominant mutation signatures in LUSC clones included signatures 4, 1, and 5, while APOBEC signatures (2 and 13) were predominantly found in sub-clones. In contrast, no evidence of APOBEC signatures were found in LUNE. Among structural variants, LUNE had more events (339.25 average number of events/tumor) than LUSC (206.7/tumor), with considerable ITH in both subtypes, particularly in LUNE. In LUNE, the dominant mechanism responsible for SVs included fork stalling and template switching within the microhomology-mediated break-induced repair (MMBIR). We found recurrent fusion events with hotspots including those previously identified near TTC28/CHEK2 (42% LUSC and 35% LUNE) and LRP1B (42% LUSC). Additional hotspots were found in chromosome bands 20p12.1 (22% LUSC), 1p31.1 (19% LUSC) and 12p11.22 (22% LUNE). We found &amp;gt;10-fold higher transposon insertions (LINE1) in LUSC (71.9 average number of events/tumor) than LUNE (6.3/tumor). Our findings improve our evolutionary understanding of these lung cancer subtypes and warrant further investigations on the mechanisms involved in clonal genomic instability. Citation Format: Tongwu Zhang, Joshua Sampson, Pier Alberto Bertazzi, Angela Pesatori, Dario Consonni, Bin Zhu, Belynda Hicks, Xing Hua, Jianxin Shi, Kevin Brown, Stephen Chanock, Maria Teresa Landi. Comparison of intra-tumor heterogeneity and clonal evolution across lung cancer subtypes by multi-region whole genome sequencing [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 1187.
Abstract 4201: Dp44mT, an iron chelator, suppresses cell growth and invasion by inducing N-myc downstream-regulated gene 1 and inhibiting Wnt/β-catenin signaling in human glioma cells
Authors: Peng Luo, Ye Zhang, Yang Jiang, Ying Xu, Zhitao Jing
Journal: Cancer Research (2018)

Abstract The iron-chelating agent di-2-pyridylketone 4, 4-dimethyl-3-thiosemicarbazone (Dp44mT) can inhibit cell growth and invasion in some human cancers. However, the precise molecular mechanisms involved remain obscure in the context of glioma. Recent evidence suggests that N-myc downstream-regulated gene (NDRG)1 has an oncogenic role function. In the present study, we investigated whether Dp44mT regulates the NDRG1 expression and thereby inhibits glioma cell growth and invasion. We found that Dp44mT inhibited glioma proliferation and invasion in vitro, and reduced average tumor size and wet weight in a xenograft model. Dp44mT overexpression increased NDRG1 expression; NDRG1 silencing stimulated cell growth and invasion and triggered epithelial-to-mesenchymal transition (EMT). We also found that Dp44mT exerts its anti-tumor activity via inhibition of Wnt/β-catenin signaling. Taken together, these findings suggest that the iron chelator Dp44mT inhibits glioma development and progression both in vitro and in vivo by inducing the expression of NDRG1 and suppressing Wnt/β-catenin signaling. Thus, targeting NDRG1 with Dp44mT can be an effective treatment for glioma. Citation Format: Peng Luo, Ye Zhang, Yang Jiang, Ying Xu, Zhitao Jing. Dp44mT, an iron chelator, suppresses cell growth and invasion by inducing N-myc downstream-regulated gene 1 and inhibiting Wnt/β-catenin signaling in human glioma cells [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 4201.
Twelve-Month Outcomes After Transplant of Hepatitis C–Infected Kidneys Into Uninfected Recipients
Authors: Peter P. Reese, Peter L. Abt, Emily A. Blumberg, Vivianna M. Van Deerlin, Roy D. Bloom, Vishnu S. Potluri, Matthew Levine, Paige Porrett, Deirdre Sawinski, Susanna M. Nazarian, Ali Naji, Richard Hasz, Lawrence Suplee, Jennifer Trofe-Clark, Anna Sicilia, Maureen McCauley, Caren Gentile, Jennifer Smith, Bijan A. Niknam, Melissa Bleicher, K. Rajender Reddy, David S. Goldberg
Journal: Annals of Internal Medicine (2018)

Background: Organs from hepatitis C virus (HCV)–infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk. Objective: To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients. Design: Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897) Setting: Single center. Participants: 20 HCV-negative transplant candidates. Intervention: Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir–grazoprevir on posttransplant day 3. Measurements: The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores at enrollment and after transplant, and 2) posttransplant renal function, which was compared in a 1:5 matched sample with recipients of HCV-negative kidneys. Results: The mean age of THINKER participants was 56.3 years (SD, 6.7), 70% were male, and 40% were black. All 20 participants achieved HCV cure. Hepatic and renal complications were transient or were successfully managed. Mean PCS and MCS quality-of-life scores decreased at 4 weeks; PCS scores then increased above pretransplant values, whereas MCS scores returned to baseline values. Estimated GFRs were similar between THINKER participants and matched recipients of HCV-negative kidneys at 6 months (median, 67.5 vs. 66.2 mL/min/1.73 m2; 95% CI for between-group difference, −4.2 to 7.5 mL/min/1.73 m2) and 12 months (median, 72.8 vs. 67.2 mL/min/1.73 m2; CI for between-group difference, −7.2 to 9.8 mL/min/1.73 m2). Limitation: Small trial. Conclusion: Twenty HCV-negative recipients of HCV-infected kidneys experienced HCV cure, good quality of life, and excellent renal function. Kidneys from HCV-infected donors may be a valuable transplant resource. Primary Funding Source: Merck.
Abstract 16792: Deletion of Angiotensin II Type 1a Receptor in Perivascular Adipose Tissue Attenuates Abdominal Aortic Aneurysm in Apolipoprotein E-/- Mice
Authors: Tomoki Sakaue, Jun Suzuki, Chika Suehiro, Teruyoshi Uetani, Jun Aono, Takafumi Okura, Jitsuo Higaki, Shuntaro Ikeda
Journal: Circulation (2016)

Introduction: Perivascular adipose tissue (PVAT) exhibits features characteristic of active local inflammation, which contributes to the development of atherosclerotic disease as a complication of ...
Noninvasive Arrhythmia Risk Stratification in Idiopathic Dilated Cardiomyopathy
Authors: WolframGrimm, MichaelChrist, JenniferBach, Hans-HelgeMüller, BernhardMaisch
Journal: Circulation (2003)

Background— Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator therapy is a completely unsolved issue in idiopathic dilated cardiomyopathy (IDC). Methods and Results— Arrhythmia risk stratification was performed prospectively in 343 patients with IDC, including analysis of left ventricular (LV) ejection fraction and size by echocardiography, signal-averaged ECG, arrhythmias on Holter ECG, QTc dispersion, heart rate variability, baroreflex sensitivity, and microvolt T-wave alternans. During 52±21 months of follow-up, major arrhythmic events, defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death, occurred in 46 patients (13%). On multivariate analysis, LV ejection fraction was the only significant arrhythmia risk predictor in patients with sinus rhythm, with a relative risk of 2.3 per 10% decrease of ejection fraction (95% CI, 1.5 to 3.3; P=0.0001). Nonsustained ventricular tachycardia on Holter was associated with a trend towa...
Chronic Orthostatic Intolerance
Authors: RaffaelloFurlan, GirisJacob, MarieSnell, DavidRobertson, AlbertoPorta, PaulHarris, RogelioMosqueda-Garcia
Journal: Circulation (1998)

Background—Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). Methods and Results—In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75° tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index α, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, M...