tbuckley/cabot-search huggingface dataset:
Abstract 11922: Impact of Income Status on Prognosis of Acute Coronary Syndrome Patients During a Period of Financial Crisis - Insights From a Greek Prospective Multicenter Observational Study
Authors: George Andrikopoulos, Stylianos Tzeis, Dimitrios Terentes-Printzios, Christos Varounis, Charalampos Vlachopoulos, Ioannis Mantas, Sotirios Patsilinakos, Stylianos Lampropoulos, Christoforos Olympios, Athanasios Kartalis, Athanasios Manolis, Alexandros Gotsis, Filippos Triposkiadis, Themistoklis Tsaknakis, Ioannis Goudevenos, Ioannis Kaprinis, Athanasios Pras, Fotios Vasiliou, Emmanouil Skoumpourdis, Gerasimoula Sakka, Antonios Draganigos, Panos Vardas
Journal: Circulation (2015)

Introduction: The effect of income status on patient outcome merits investigation during periods of financial crisis. Hypothesis: We evaluated the impact of income status on out-of-hospital prognosis in a cohort of acute coronary syndrome (ACS) patients, included in a countrywide study during a period of financial crisis. Methods: The study is a secondary analysis of a prospective, multicenter, observational study - the PHAETHON study - enrolling consecutive ACS patients in 37 hospitals in Greece. Patients were classified as low- or high-income based on the reported net annual household income using as a cut-off point the relative poverty threshold for Greece of 12000 Euros. The outcome measure was survival free of the primary composite endpoint (cardiovascular death, myocardial infarction, stroke/transient ischemic attack, urgent revascularization and urgent hospitalization due to cardiovascular causes). Results: The study population included 794 patients. The administration rate of evidence-based medications was similar in the low- (n=455) and high-income (n=339) groups during hospitalization and upon discharge. In a median follow-up of 189 days (interquartile range: 180-212 days), low-income patients had 92% higher risk of the combined endpoint as compared to high-income patients [Hazard ratio (HR):1.92, 95%CI:1.25-2.94, p=0.003]. The effect of low-income status on the combined outcome remained significant after adjustment for age, gender and depression (HR:1.59, 95% CI:1.02-2.49; p=0.043). Conclusions: In a period of financial crisis, low income is a significant and independent predictor of poor out-of-hospital outcome in ACS patients. This association has profound implications and should be taken into consideration by public health policy makers.
High Homocysteine Levels Are Independently Related to Isolated Systolic Hypertension in Older Adults
Authors: KimSutton-Tyrrell, AndrewBostom, JacobSelhub, CharnitaZeigler-Johnson
Journal: Circulation (1997)

Background The association between homocysteine and isolated systolic hypertension in older adults was evaluated using a case-control design, and the relationship between homocysteine and clinical or subclinical atherosclerosis was explored. Methods and Results Cases were 179 adults ≥60 years with a systolic blood pressure of ≥160 mm Hg and diastolic blood pressure <90 mm Hg. One hundred seventy-one control subjects had the same criteria except systolic blood pressures were <160 mm Hg. All had normal creatinine levels. Homocysteine levels were performed on fasting blood samples that had been stored at −70°C. Atherosclerosis was defined as either a history of clinical disease, an internal carotid stenosis of ≥40% by duplex scan, or an ankle/arm pressure ratio of <0.9. The median homocysteine value was 11.5 μmol/L for cases and 9.9 for control subjects (P<.001). After control for potential confounders, homocysteine remained significantly associated with systolic hypertension (P=.019). For the hypertensive g...
Leukocyte-Targeted Myocardial Contrast Echocardiography Can Assess the Degree of Acute Allograft Rejection in a Rat Cardiac Transplantation Model
Authors: IsaoKondo, KojiOhmori, AkiraOshita, HirotoTakeuchi, JunjiYoshida, KaoriShinomiya, SachikoFuke, TakeoSuzuki, KatsufumiMizushige, MasakazuKohno
Journal: Circulation (2004)

Background— Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. Contrast ultrasound with microbubble targeting of leukocytes detects acute leukocyte infiltration. We examined whether leukocyte-targeted myocardial contrast echocardiography (MCE) could provide for the quantitative assessment of acute cardiac rejection. Methods and Results— Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts either untreated or treated with cyclosporin A (CsA) at a low dose (3 mg · kg−1 · d−1) or high dose (10 mg · kg−1 · d−1) from 3 days before transplantation were compared at posttransplantation day 3. Echocardiography-derived left ventricular wall thickening was comparable among the 4 groups. Myocardial blood flow assessed with MCE, relating pulsing intervals with signal intensity (SI), was slightly decreased only in untreated allografts. However, myocardial SI (in gray levels...
Nitric Oxide Spares Myocardial Oxygen Consumption Through Attenuation of Contractile Response to β-Adrenergic Stimulation in Patients With Idiopathic Dilated Cardiomyopathy
Authors: ToshiroShinke, HideyukiTakaoka, MotoshiTakeuchi, KatsuyaHata, HiroyaKawai, HideakiOkubo, YoichiKijima, TakeomiMurata, MitsuhiroYokoyama
Journal: Circulation (2000)

Background—The results of recent studies suggest that NO synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to β-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular (LV) contractile response to β-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. Methods and Results—We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (Emax, the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MVo2), and mechanical efficiency (measured as EW/MVo2) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4.8±0.3 μg · kg−1 · min−1 IV). Heart rate was kept constant wi...
A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma
Authors: Eugene J. Koay, Yeonju Lee, Vittorio Cristini, John S. Lowengrub, Ya'an Kang, F. Anthony San Lucas, Brian P. Hobbs, Rong Ye, Dalia Elganainy, Muayad Almahariq, Ahmed M. Amer, Deyali Chatterjee, Huaming Yan, Peter C. Park, Mayrim V. Rios Perez, Dali Li, Naveen Garg, Kim A. Reiss, Shun Yu, Anil Chauhan, Mohamed Zaid, Newsha Nikzad, Robert A. Wolff, Milind Javle, Gauri R. Varadhachary, Rachna T. Shroff, Prajnan Das, Jeffrey E. Lee, Mauro Ferrari, Anirban Maitra, Cullen M. Taniguchi, Michael P. Kim, Christopher H. Crane, Matthew H. Katz, Huamin Wang, Priya Bhosale, Eric P. Tamm, Jason B. Fleming
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with variable presentations and natural histories of disease. We hypothesized that different morphologic characteristics of PDAC tumors on diagnostic computed tomography (CT) scans would reflect their underlying biology. Experimental Design: We developed a quantitative method to categorize the PDAC morphology on pretherapy CT scans from multiple datasets of patients with resectable and metastatic disease and correlated these patterns with clinical/pathologic measurements. We modeled macroscopic lesion growth computationally to test the effects of stroma on morphologic patterns, hypothesizing that the balance of proliferation and local migration rates of the cancer cells would determine tumor morphology. Results: In localized and metastatic PDAC, quantifying the change in enhancement on CT scans at the interface between tumor and parenchyma (delta) demonstrated that patients with conspicuous (high-delta) tumors had significantly less stroma, higher likelihood of multiple common pathway mutations, more mesenchymal features, higher likelihood of early distant metastasis, and shorter survival times compared with those with inconspicuous (low-delta) tumors. Pathologic measurements of stromal and mesenchymal features of the tumors supported the mathematical model's underlying theory for PDAC growth. Conclusions: At baseline diagnosis, a visually striking and quantifiable CT imaging feature reflects the molecular and pathological heterogeneity of PDAC, and may be used to stratify patients into distinct subtypes. Moreover, growth patterns of PDAC may be described using physical principles, enabling new insights into diagnosis and treatment of this deadly disease.
Presentation and Disease Course of Childhood‐Onset Versus Adult‐Onset Takayasu Arteritis
Authors: Florence A. Aeschlimann, Lillian Barra, Roaa Alsolaimani, Susanne M. Benseler, Diane Hebert, Nader Khalidi, Ronald M. Laxer, Damien Noone, Christian Pagnoux, Marinka Twilt, Rae S. M. Yeung
Journal: Arthritis & Rheumatology (2018)

Objective To compare the clinical features, efficacy and safety of treatment regimens, and outcomes of childhood‐ and adult‐onset Takayasu arteritis ( TAK ). Methods The study was designed as a retrospective cohort study comparing patients with childhood‐onset TAK (from 1986 onward) to patients with adult‐onset TAK (from 1988 onward) who were followed up until 2014 or 2015 at 4 centers in Ontario, Canada. Demographic, clinical, laboratory, and angiographic features, treatment regimens, and outcomes were recorded throughout the course of the disease. Disease activity and damage scores were completed retrospectively. Results Twenty‐nine children and 48 adults (median age at diagnosis 12.1 years and 31.2 years, respectively) were included. A lower predominance of females was observed among the childhood‐onset TAK cohort (76% versus 100% of patients with adult‐onset TAK ; P &lt; 0.01), and children had a shorter delay to diagnosis (median 6.0 months versus 12.2 months for adults; P = 0.03). The distribution of vascular involvement was also different, with children having significantly more aortic and renal artery involvement and a higher frequency of arterial hypertension. Relapses in the first year after diagnosis were common both in children (39%) and in adults (28%). Two children, but no adults, died. Conclusion Childhood‐onset TAK has a lower female predominance and a higher frequency of aortic and renal involvement compared to adult‐onset TAK . Relapses and disease burden were high in both groups, corroborating the need for careful monitoring of disease activity and aggressive therapeutic management.
ADAMTS-7 Mediates Vascular Smooth Muscle Cell Migration and Neointima Formation in Balloon-Injured Rat Arteries
Authors: LiWang, JingangZheng, XueBai, BoLiu, Chuan-juLiu, QingboXu, YiZhu, NanpingWang, WeiKong, XianWang
Journal: Circulation Research (2009)

The migration of vascular smooth muscle cells (VSMCs) plays an essential role during the development of atherosclerosis and restenosis. Extensive studies have implicated the importance of extracellular matrix (ECM)-degrading proteinases in VSMC migration. A recently described family of proteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), is capable of degrading vascular ECM proteins. Here, we sought to determine whether ADAMTS-7 is involved in VSMC migration and neointima formation in response to vascular injury. ADAMTS-7 protein accumulated preferentially in neointima of the carotid artery wall after balloon injury. In primary VSMCs, ADAMTS-7 level was enhanced by the proinflammatory cytokine tumor necrosis factor α and growth factor platelet-derived growth factor-BB. ADAMTS-7 overexpression greatly accelerated and small interfering RNA knockdown markedly retarded VSMC migration/invasion in vitro. In addition, luminal delivery of ADAMTS-7 adenovirus to carotid arteries ex...
Benefits of Off-Pump Coronary Artery Bypass Grafting in High-Risk Patients
Authors: AkiraMarui, HitoshiOkabayashi, TatsuhikoKomiya, ShiroTanaka, YutakaFurukawa, ToruKita, TakeshiKimura, RyuzoSakata
Journal: Circulation (2012)

Background—The benefits of off-pump coronary artery bypass graft (OPCAB) compared with conventional on-pump coronary artery bypass graft (CCAB) remain controversial. Thus, it is important to investigate which patient subgroups may benefit the most from OPCAB rather than CCAB. Methods and Results—Among the patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto Registry (a registry of first-time percutaneous coronary intervention and coronary artery bypass graft patients in Japan), 2468 patients undergoing coronary artery bypass graft were entered into the study (mean age, 67±9 years). Predicted risk of operative mortality (PROM) of each patient was calculated by logistic EuroSCORE. Patients were divided into tertile based on their PROM. Mortality rates and the incidences of cardiovascular events were compared between CCAB and OPCAB within each PROM tertile using propensity score analysis. A total of 1377 patients received CCAB whereas 1091 received OPCAB. Adjusted 30-day mortality...
Oxidant Signaling in Vascular Cell Growth, Death, and Survival
Authors: KaikobadIrani
Journal: Circulation Research (2000)

Abstract—Reactive oxygen species (ROS) have been traditionally regarded as toxic byproducts of aerobic metabolism. However, ROS can also act as intracellular signaling molecules in vascular cells. ROS can mediate phenotypes in vascular endothelial and smooth muscle cells that may be considered both physiological and pathophysiological. Among these are growth, apoptosis, and survival. The specific response elicited by reactive oxygen intermediaries is determined by their specific intracellular target(s). This, in turn, is dependent on the species of oxidant(s) produced, the source and therefore subcellular localization of the oxidant(s), the kinetics of production, and the quantities produced. A fuller understanding of how ROS regulate mitogenesis and apoptosis in vascular smooth muscle and endothelial cells will permit the development of novel strategies to modify or prevent vascular diseases in which these phenotypes predominate.
Abstract 4120: A novel HDAC-targeted probe for triple-negative breast tumor imaging
Authors: Chu Tang, Yang Du, Jie Tian
Journal: Cancer Research (2018)

Abstract Purpose: Due to lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2), there was no specific imaging probes can be applied to detect triple-negative breast cancers (TNBCs). Currently, several lines of evidences support that overexpression of histone deacetylases (HDACs) has been associated with TNBC. Here, we sought to develop HDAC-targeted probe for TNBC imaging. Experimental Design: The pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was chosen as the targeting ligand, and was labeled with a near-infrared dye IRDye800CW for the development of HDAC-targeted probe IRDye800CW-SAHA. Subsequently, HDAC binding affinity and specificity of probe IRDye800CW-SelSA to TNBC MDA-MB-231 cells was evaluated by HDAC inhibition assay, flow cytometry and confocal laser microscope experiments. Moreover, the in vivo fluorescence molecular imaging (FMI) was performed to monitor the biodistribution and tumor targeting effects of the probe in MDA-MB-231 tumor xenografts. Results: The fluorescence probe IRDye800CW-SAHA was successfully developed, and conjugating IRDye800CW to SAHA did not alter the HDAC binding affinity. The cellular uptake and the fluorescence intensity of probe on MDA-MB-231 cells were significantly higher compared to normal MCF-10A cells (P &amp;lt; 0.05). Meanwhile, the cellular uptake of probe can be effectively blocked by co-incubation with SAHA. The in vivo imaging results showed that IRDye800CW-SelSA was able to target tumor rapidly, and the tumor to normal tissue (T/N) fluorescence intensity ratio reached the peak around 12 h (T/N = 3.4). Conclusions: Our study demonstrated that IRDye800CW-SAHA is an efficient probe for the targeted imaging of TNBC and may possess clinical translation in the future. CT and YD contributed equally to this work Citation Format: Chu Tang, Yang Du, Jie Tian. A novel HDAC-targeted probe for triple-negative breast tumor imaging [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 4120.
Abstract 3676: CMS classification of colorectal adenomas
Authors: Malgorzata A. Komor, Linda J. Bosch, Gergana Bounova, Anne S. Bolijn, Pien Delis-van Diemen, Christian Rausch, Youri Hoogstrate, Andrew Stubbs, Mark de Jong, Guido Jenster, Nicole C. an Grieken, Beatriz Carvalho, Lodewyk Wessels, Connie R. Jimenez, Remond J. Fijneman, Gerrit A. Meijer, NGS-ProToCol Consortium
Journal: Cancer Research (2018)

Abstract Background Consensus molecular subtyping (CMS) is an RNA-expression-based classification of colorectal cancers (CRC). Genomic alterations, resulting in specific RNA-expression patterns, accumulate during CRC pathogenesis, including the premalignant adenoma stage. Aim This study aimed to investigate whether differentiation of colorectal neoplasia into CMS classes can already be recognized at the adenoma stage, and whether specific CMS classes could be associated with DNA copy number aberrations that mark adenomas at high-risk of progressing to CRC. Materials and Methods RNA-sequencing was performed on 62 advanced adenomas and 59 CRCs. DNA copy number analysis in adenomas was performed by low-coverage DNA-sequencing (n=30) or array-Comparative Genomic Hybridization (n=32). Microsatellite instability (MSI) status was determined by PCR methods. Adenomas and CRCs were classified into CMS subtypes together with CRCs (n=556) from The Cancer Genome Atlas, using the Random Forest CMS classifier. Results The majority of the adenomas were classified as CMS3 (n=45; 72%), the 'metabolic subtype', recognized as least common among CRCs. No adenomas were classified as the 'mesenchymal' CMS4 subtype. One adenoma was classified as the 'MSI immune' CMS1 (2%), and 8 adenomas as the 'canonical' CMS2 (13%) type. The remaining 8 (13%) could not be classified. The CMS3 class was enriched with adenomas at low-risk of progression. Conclusion Most adenomas were successfully classified. The lack of CMS4 adenomas is consistent with the fact that adenomas lack invasion-associated stroma. Adenomas showing cancer-associated chromosomal instability (CIN) or MSI (24%) were mostly classified as CMS2 and CMS1, respectively. The CMS3 subtype appeared to be the predominant adenoma signature. Citation Format: Malgorzata A. Komor, Linda J. Bosch, Gergana Bounova, Anne S. Bolijn, Pien Delis-van Diemen, Christian Rausch, Youri Hoogstrate, Andrew Stubbs, Mark de Jong, Guido Jenster, Nicole C. an Grieken, Beatriz Carvalho, Lodewyk Wessels, Connie R. Jimenez, Remond J. Fijneman, Gerrit A. Meijer, NGS-ProToCol Consortium. CMS classification of colorectal adenomas [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 3676.
Danger Signaling in Atherosclerosis
Authors: SebastianZimmer, AlenaGrebe, EickeLatz
Journal: Circulation Research (2015)

All aspects of the pathogenesis of atherosclerosis are critically influenced by the inflammatory response in vascular plaques. Research in the field of innate immunity from the past 2 decades has uncovered many novel mechanisms elucidating how immune cells sense microbes, tissue damage, and metabolic derangements. Here, we summarize which triggers of innate immunity appear during atherogenesis and by which pathways they can contribute to inflammation in atherosclerotic plaques. The increased understanding gained from studies assessing how immune activation is associated with the pathogenesis of atherosclerosis has provided many novel targets for potential therapeutic intervention. Excitingly, the concept that inflammation may be the core of cardiovascular disease is currently being clinically evaluated and will probably encourage further studies in this area.
Abstract 1490: Molecular function of the read-through transcript PRR5-ARHGAP8
Authors: Jasmeen K. Sethi, Oscar G. Wong, Esther S. Wong, Annie N. Cheung
Journal: Cancer Research (2018)

Abstract Background: Ovarian carcinoma is one of the most fatal malignancies in females. From the analysis of RNA-seq we have previously conducted to study the transcriptome of ovarian carcinoma upon knockdown of transcription factor hepatic nuclear factor 1β (HNF-1β), PRR5-ARHGAP8 was identified as the only read-through transcript not targeted for the nonsense-mediated decay pathway. Read-through transcription refers to the splicing of the intergenic region from two adjacent genes resulting in a chimeric transcript comprising of one or more exons from both genes. Although several of such transcripts are found in the transcriptome, their significance remains an enigma. Our aim was to ascertain the differential expression of the read-through transcript PRR5-ARHGAP8 in ovarian cancers and to determine its molecular functions. Materials &amp; Methods: The deregulation of PRR5-ARHGAP8 was validated by RT-qPCR in several ovarian carcinoma cell lines. The expression of this fusion transcript and the individual genes were studied in immortalised human ovarian surface epithelial (HOSE) cell lines, ovarian carcinoma cell lines, and matched tumour and non-tumour pairs from frozen patient samples. Overexpression of this transcript was achieved by transient transfection in HEK293T cells to study its effect on proliferation using MTT assays. RNA and protein lysates were also obtained at several time points to evaluate the pathways affected by RT-qPCR and western blot, respectively. Results: There was an approximate 3- to 9-fold upregulation of PRR5-ARHGAP8 transcript with a decrease in the expression of PRR5 and ARHGAP8 transcripts in OVMANA, OVISE and KK ovarian carcinoma cell lines upon the knockdown of HNF-1β. Moreover, higher transcript levels of PRR5, ARHGAP8 and PRR5-ARHGAP8 were observed in ovarian carcinoma cell lines compared to HOSE cell lines and in ovarian cancer samples compared to the non-tumour counterparts. Overexpression of PRR5-ARHGAP8 in HEK293T cells resulted in the decrease of phosphorylated Akt protein expression and a reduction of cell viability. RT-qPCR analysis showed a decrease in E-cadherin and an increase in vimentin expression upon PRR5-ARHGAP8 overexpression. Discussion: The present data suggests PRR5-ARHGAP8 is highly abundant in ovarian carcinomas and may mediate its effects on proliferation via the MAPK pathway and on migration by regulating the epithelial to mesenchymal transition. Overall, this study provides novel insights into the biological relevance of read-through transcription in carcinogenesis. Citation Format: Jasmeen K. Sethi, Oscar G. Wong, Esther S. Wong, Annie N. Cheung. Molecular function of the read-through transcript PRR5-ARHGAP8 [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 1490.