tbuckley/cabot-search huggingface dataset:
Abstract 13471: Additional Prognostic Value of Vasodilator Stress Cardiovascular Magnetic Resonance in Patients With Inconclusive Stress Test to Detect Coronary Artery Disease
Authors: Theo Pezel, Guillaume Bonnet, Francesca Sanguineti, Marine Kinnel, Anouk Asselin, Thomas Hovasse, Philippe Garot, Solenn Toupin, Marie Claude Morice, Stephane Champagne, Thierry Unterseeh, Yves Louvard, Jerome Garot
Journal: Circulation (2020)

Introduction: Non-invasive testing for ischemia to diagnose coronary artery disease(CAD) are frequently inconclusive(25%). Hypothesis: To assess the prognostic value of stress CMR in patients with a first inconclusive stress test. Methods: Between 2008 and 2018, consecutive patients with inconclusive stress test, defined by stress echocardiography or nuclear testing with uncertain conclusion, prospectively referred for stress CMR with dipyridamole were followed for major adverse cardiovascular events(MACE): cardiac death or myocardial infarction. An unsupervised clustering analysis was performed. Results: Of 1502 patients (62±12yrs, 59%men), 1397 completed the follow-up (median 5.5±2.3yrs). Three clusters were identified: Cluster 1 (n=524) had the highest prevalence of previous PCI, the highest presence of a myocardial scar defined, the lowest LVEF (35±7%) and the highest LV dilatation. Cluster 2 (n=406) had the highest previous CABG prevalence, preserved LVEF, absence of LV dilatation, and presence of myocardial scar. This cluster comprised predominantly male patients, with the highest rate of hypertension. Cluster 3 (n=572) had the lowest rate of previous PCI/CABG, the lowest rate of myocardial scar, predominantly female, the highest atrial fibrillation rate and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p=0.02). Inducible ischemia was associated with MACE occurrence in each cluster (C1, HR 2.28; 95%CI[1.31-3.99]; p=0.0028; C2, HR 3.37; 95%CI[1.97-5.75]; p&lt;0.0001; C3, HR 2.73; 95%CI[1.67-4.46]; p&lt;0.0001). In multivariable analysis, inducible ischemia predicted MACE in each cluster (p&lt;0.001 for all). Conclusions: Cluster analysis identified 3 different phenotypes with distinct clinical and prognostic profiles. Within these clusters, stress CMR has an additional prognostic value to predict MACE..
Abstract 15019: Differential Effects of Omega-3 Fatty Acid Combinations on the Inhibition of Oxidation Of Human Low-density Lipoproteins <i>in vitro</i>
Authors: Samuel Sherratt, James J Ferguson, Deepak L Bhatt, Preston Mason
Journal: Circulation (2020)

Background: Omega-3 fatty acids (O3FAs) reduce levels of triglyceride but may also have additional atheroprotective benefits. Randomized trials have suggested potential clinical outcome differences among O3FAs formulations. Oxidative modification of low-density lipoproteins (LDL) contributes to endothelial dysfunction, inflammation, and other aspects of atherogenesis. Individual O3FAs have been shown to inhibit LDL oxidation to varying degrees, but the antioxidant effects of combining O3FAs is unknown. Objective: To compare the dose- and time-dependent antioxidant effects of eicosapentaenoic acid (EPA, 20:5) alone and in combination with either docosapentaenoic acid (DPA, 22:5) or docosahexaenoic acid (DHA, 22:6) in human LDL in vitro . Methods: Human LDL was isolated from healthy subjects and adjusted to a final ApoB concentration of 100 μg/mL in physiologic buffer (PBS) before being incubated with O3FAs at 37°C. The EPA levels in the combinations were fixed at either 2.0, 3.0, or 4.5 μM, while the DPA or DHA levels were set at 0, 0.5, 1.0, and 2.0 μM. Oxidation was initiated by copper sulfate (10 μM) and measured over time by formation of malondialdehyde (MDA), a lipid oxidation product. Results: When combined with EPA, both DPA and DHA increased inhibition of oxidation in a dose- and time-dependent manner, with DPA showing a greater effect and more prolonged inhibition. At high levels of EPA (4.5 μM), DPA showed significantly greater antioxidant activity than equimolar DHA; these differences were more apparent with time. After 8 hours, adding 1.0 μM DPA reduced MDA formation by 61% versus vehicle (3.10 ± 0.42 vs. 7.98 ± 0.56, p &lt;0.001), while adding 1.0 μM DHA only reduced MDA formation by 20% (6.40 ± 1.23, p &lt;0.05). When 2 μM DPA or DHA were added, after 10 hours only DPA still had a significant degree of inhibition versus vehicle (37%; 6.65 ± 0.95 vs. 8.21 ± 0.53, p &lt;0.05). Similar trends were observed in combinations containing 2.0 and 3.0 μM EPA. Conclusion: Adding DPA or DHA to EPA provide dose-dependent incremental antioxidant effects, with DPA providing a larger degree and a longer duration of inhibition. These observations highlight potential differences among O3FAs (and their combinations) in novel mechanisms of atheroprotection.
Abstract 15079: Utility of RR Interval and Systolic Blood Pressure Relation Derived From 24-Hour Ambulatory Blood Pressure Monitoring in Detecting Autonomic Failure
Authors: Hamza Lodhi, Poghni Peri-Okonny, Kevin Schesing, Debbie Arbique, Angela Price, Steven Vernino, Lauren Phillips, Jere Mitchell, Scott Smith, Yuichiro Yano, Sandeep Das, Tao Wang, Wanpen Vongpatanasin
Journal: Circulation (2018)

Background: Abnormal pattern of BP and heart rate variability are often observed in patients with autonomic failure (ATF) during 24-hour ambulatory BP monitoring (ABPM). Whether ATF patients displa...
A Visual Circuit Related to the Nucleus Reuniens for the Spatial-Memory-Promoting Effects of Light Treatment
Authors: Xiaodan Huang, Pengcheng Huang, Lu Huang, Zhengfang Hu, Xianwei Liu, Jiawei Shen, Yue Xi, Yan Yang, Yunwei Fu, Qian Tao, Song Lin, Anding Xu, Fuqiang Xu, Tian Xue, Kwok-Fai So, Haohong Li, Chaoran Ren
Journal: Neuron (2020)
Abstract 13810: TT-00920, a Clinical Stage Novel Phosphodiesterase 9 Inhibitor, Protects Against Heart Failure in a Rat Model of Myocardial Infarction
Authors: Zejuan Sheng, Xiaoyan Qiang, Guoyu Li, Huimin Wang, Wenxin Dong, Frank Wu
Journal: Circulation (2020)

Introduction: Phosphodiesterase 9 (PDE9) controls natriuretic-peptide-stimulated cyclic guanosine monophosphate in cardiac myocytes and is stongly upregulated in human heart failure, suggesting its potential as a promising therapeutic target in heart failure. Here we investigated the potential effects of TT-00920, a clinical stage novel and highly selective PDE9 inhibitor, on heart failure in a rat model of myocardial infarction. Methods: Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation in male Sprague Dawley rats. After 4-week treatment of vehicle, LCZ696, TT-00920, or TT-00920/Valsartan by oral gavage, efficacy was assessed by echocardiography and cardiac histopathology. Results: TT-00920 had remarkably improved cardiac function, protected against cardiac remodeling and fibrosis in a dose-dependent manner. TT-00920/Valsartan combination showed superior beneficial efficacy when compared to TT-00920 or LCZ696 single agent.Figure 1. TT-00920 improved cardiac function and ventricular remodeling.Figure 2. TT-00920 attenuated cardiac fibrosis in peri-infarct zone. Conclusions: TT-00920 reversed LAD-induced left ventricular dysfunction and remodeling, supporting its potential as a novel therapeutic agent for heart failure. The superior efficacy of TT-00920/Valsartan combination suggests that TT-00920 and renin-angiotensin-aldosterone system inhibitors may have additive therapeutic effects in heart failure.TT-00920 is currently being evaluated in Phase 1 clinical study for safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers (NCT04364789).
Increased adaptive immune responses and proper feedback regulation protect against clinical dengue
Authors: Etienne Simon-Lorière, Veasna Duong, Ahmed Tawfik, Sivlin Ung, Sowath Ly, Isabelle Casadémont, Matthieu Prot, Noémie Courtejoie, Kevin Bleakley, Philippe Buchy, Arnaud Tarantola, Philippe Dussart, Tineke Cantaert, Anavaj Sakuntabhai
Journal: Science Translational Medicine (2017)

Dengue is the most prevalent arthropod-borne viral disease. Clinical symptoms of dengue virus (DENV) infection range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on t v 'health. We used an integrated approach of transcriptional profiling and immunological analysis comparing a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune responses were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T and B cell activation pathways were differentially regulated, independent of viral load or previous DENV infection. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals as demonstrated by increased activation of T cell apoptosis-related pathways and Fc$\gamma$RIIB signaling associated with decreased anti-DENV specific antibody concentrations. Taken together, our data illustrate that symptom-free DENV infection in children is determined by increased activation of the adaptive immune compartment and proper control mechanisms leading to elimination of viral infection without excessive immune activation, having implications for novel vaccine development strategies.
Abstract 13479: Association of Plasma Branched Chain Amino Acid With Biomarkers of Inflammation and Lipid Metabolism in Women
Authors: Rikuta Hamaya, Samia Mora, Patrick R Lawler, Nancy R Cook, Paul M Ridker, Julie E Buring, I-min M Lee, Joann E Manson, Deirdre K Tobias
Journal: Circulation (2020)

Introduction: We previously observed that circulating branched-chain amino acids (BCAAs) were associated with a higher risk of cardiovascular disease (CVD). However, the relationships of BCAAs with other cardiometabolic pathways other than type 2 diabetes (T2D) are unclear, including inflammation, dyslipidemia, and impaired glucose metabolism. Hypothesis: We hypothesized plasma BCAAs are correlated with cardiometabolic dysfunction in women, independent of shared risk factors. Methods: We conducted a cross-sectional analysis of 19,472 participants (mean age=54.9 years, SD=7.2) in the Women’s Health Study without a history of T2D, CVD, or cancer at baseline blood collection. We used multivariable linear regression models comparing quartiles of BCAAs (sum of fasting isoleucine, leucine and valine concentrations via NMR spectroscopy) with biomarkers of inflammation, lipids, and glucose metabolism, adjusting for age, body mass index, smoking, diet, and other CVD risk factors. Results: Women in the highest vs. lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (hsCRP; adjusted mean: 2.7 vs. 2.0 mg/L), fibrinogen (390 vs. 384 mg/dL), GlycA (420 vs. 384 μmol/L), and soluble intercellular cell adhesion molecule-1 (sICAM-1; 350 vs. 341 ng/mL) (p&lt;0.001 for linear trends across quartiles). Similarly for lipids, women with higher BCAAs had lower HDL-c (48.8 vs. 54.7 mg/dL), and higher LDL-c (142 vs. 135 mg/dL) and triglycerides (142 vs. 114 mg/dL) (p&lt;0.001). BCAAs were positively associated with insulin resistance (lipoprotein insulin resistance [LPIR] score [54.8 vs. 40.0]) and HbA1c (5.2 vs. 5.1%). BCAAs remained associated with GlycA and hsCRP, but not fibrinogen or sICAM-1, when we further adjusted for LPIR and HbA1c, and remained associated with lipids after additional adjustment for HbA1c. Conclusions: Circulating BCAAs are concurrently associated with biomarkers of inflammation, dyslipidemia and impaired glucose metabolism indicative of an overall poorer cardiometabolic health profile. BCAAs remained positively associated with some of these pathways when adjusted for impaired glucose metabolism, suggesting elevated BCAAs may be an independent CVD risk factor in women.
Neurologic manifestations associated with COVID-19: a multicentre registry
Authors: Elodie Meppiel, Nathan Peiffer-Smadja, Alexandra Maury, Imen Bekri, Cécile Delorme, Virginie Desestret, Lucas Gorza, Geoffroy Hautecloque-Raysz, Sophie Landre, Annie Lannuzel, Solène Moulin, Peggy Perrin, Paul Petitgas, François SellaI, Adrien Wang, Pierre Tattevin, Thomas de Broucker, Sophie Abgrall, Fanny Alby-Laurent, Thibault Allou, Joséphine Amevigbe, Hanifa Amarguellay, Nabil Alloussi, Guillaume Baille, Mathilde Barbaz, Imen Bekri, Lamia Bencherif, Samia Bensaadi, Guillaume Beraud, Alexandra Bizot, Laure Bottin, Fabrice Bruneel, Jean-Philippe Camdessanche, Jeanne Chauffier, Jean-Philippe Csajaghy, Chloé De Broucker, Thomas De Broucker, Luc Defebvre, Cécile Delorme, Elodie Dembloque, Nathalie Derache, Olivier Dereeper, Céline Derollez, Cécile Descotes-Genon, Virginie Desestret, Mathilde Devaux, Lydie Dubuc, Gilles Edan, Andréa Fickl, Thibault Fraisse, Michel Gugenheim, Karolina Hankiewicz, Yves Hansmann, Geoffroy Hautecloque-Raysz, Carole Henry, Stéphanie Jobard, Fanny Jouan, Arnaud Kwiatkowski, Thibault Lalu, Sophie Landre, Annie Lannuzel, Johan Leguilloux, Camille Lejeune, Clémence Liegeois, Sophie Mahy, Jonathan Marey, Alexandra Maury, Elodie Meppiel, Laure Michel, Rita Mitri, Chloé Moulin, Solène Moulin, Nathan Peiffer-Smadja, Asma Omarjee, Canan Ozsancak, Peggy Perrin, Paul Petitgas, Fernando Pico, Marie Poupard, Valérie Rabier, Camille Rizzato, Caroline Roos, Julien Saison, Naomi Sayre, Nicolas Sedillot, François Sellal, Jérôme Servan, Caroline Storey, Laurent Suchet, Paul Tarteret, Pierre Tattevin, Mathilde Thiebaut, Claudia Vaduva, David Varlan, Adrien Wang, Virginie Zarrouk
Journal: Clinical Microbiology and Infection (2020)
Abstract 16156: Association of Electronic Nicotine Delivery Systems (ENDS) Usage and EVALI-like Symptoms
Authors: joy L hart, Thomas J Payne, Allison Groom, Hy Tran, kandi L walker, Anshula Kesh, Rose M Robertson, Thanh-Huyen T Vu
Journal: Circulation (2020)

Introduction: Comprehensive studies regarding clinical symptoms related to electronic nicotine delivery systems (ENDS) usage are sparse. Methods: The sample included 1,432 current ENDS users, ages 18-64, drawn from a national online survey conducted in 2016. A quota sampling method was used for key demographic characteristics such as age, gender, and race/ethnicity. ENDS use included types of devices, flavors, and knowledge of e-liquid used. Outcomes included any E-cigarette or Vaping use-Associated Lung Injury (EVALI)-like symptoms (e.g., cough, shortness of breath, nausea) and any clinical symptoms (see Table footnotes). Results: Of the sample, 50% were female, 23% non-Hispanic (NH) White, 23% NH Black, 54% Hispanic, 18% aged 18-24, 17% LGBTQ, 41% with &lt;$50K income, 55% 1+ any symptoms, and 33% 1+ any EVALI-like symptoms. Cough and nausea were most prevalent among EVALI-like symptoms (27% and 7.3%, respectively). The proportion of having any EVALI-like symptoms was higher in the following groups: younger, Hispanic, current smokers, and current other product users. With multiple adjustments (see Table footnotes), those who used refillable devices, varied nicotine content, flavored products or made their own e-liquids were more likely to have clinical symptoms than their counterparts. For example, the odds (95% CI) of having 1+ EVALI-like symptoms in those who used refillable devices with e-liquid pour or with e-liquid cartridge replacement were 1.70 (1.13, 2.56) and 1.95 (1.27, 2.99), respectively, compared to the non-refillable group (see Table). It should be noted that those who used non-refillable devices were also more likely not to know the nicotine content in their e-liquid. However, their use pattern seemed stable: They tended to use only one brand, one type of device, and non-flavored e-liquid (results not tabulated). Conclusions: ENDS use was significantly associated with the odds of having clinical symptoms, including EVALI-like symptoms.
Abstract 13698: Prospective Comparison of Lipid Responses in Plant-based, Mediterranean, Paleolithic an Dash Diets
Authors: Sophie Talreja, Deepak Talreja
Journal: Circulation (2020)

Introduction: Cardiovascular disease (CVD) is the leading cause of death in the United States for middle-aged men and women despite the fact that prevention and control of CVD is achievable by modifying risk factors through lifestyle changes and diet therapy. We examined the impact of four diet programs (plant-based (Vegan), Mediterranean, Paleolithic (Paleo) and DASH diets) on the CV risk factor profile of adults in the Hampton Roads area of Virginia. Hypothesis: Among the Diets studies, there will be a variable response with regards to impact on lipids. Methods: Nondiabetic adults (ages 35-85) with one or more risk factors for CVD were invited to participate in 1 of the 4 diet arms. Participants underwent a comprehensive nutrition education program prior to a 60-day diet intervention in which they kept a daily food log and met weekly with a multi-disciplinary study team. An initial health screen was performed to assess weight, blood pressure (BP), fasting glucose (FPG), A1C, lipids and lipoprotein particles, and repeated after 60 days on the diet and at 6-months follow-up. Results: 279 subjects completed the 60-day dietary intervention (58 Vegan, 80 Mediterranean, 76 Paleo, 65 DASH), and 199 returned for 6-month follow-up. At baseline, mean FPG, TG and HDL-C were within the normal range, whereas LDL-P and BP were elevated. After 60 days on the respective diets, subjects lost an average of 9 lbs which was associated with improvements in BP across all groups. Subjects on the Vegan and Paleo diets lost the most weight (~6.5%) and showed the greatest improvement in lipid risk factors (11-14% decrease in LDL-P; 10-20% decrease in VLDL and TG). Conclusion: All four diets promoted weight loss and improved BP but had variable effects on lipid risk factors.
Abstract 14476: A Randomized, Double-blind Comparison Study of Royal Jelly to Improve Endothelial Function in Healthy Volunteers
Authors: Koichiro Fujisue, Kenichi Tsujita
Journal: Circulation (2020)

Backgrounds: Royal jelly is a creamy substance secreted by honeybees. It has been reported that royal jelly has benefits on dyslipidemia and metabolic syndrome. However, the effects of royal jelly on atherogenesis remains unknown. We prospectively evaluated the effects of royal jelly on endothelial function, which can reflect early atherogenesis, in healthy volunteers. Methods: This was a single center, double-blind, 1:1 randomized placebo-controlled study. One-hundred healthy volunteers were randomly assigned to receive royal jelly 690 mg daily (equivalent 2040 mg of fresh royal jelly) or placebo from October 2018 and December 2019. Royal jelly or placebo were administered for 28 days. Endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and blood chemistries were compared between baseline and 28 days after enrollment. Primary endpoint was the change of RH-PAT index. Secondary endpoint was the change of liver function and lipid profiles. Results: The mean (SD) age of the participants was 35.0 (9.3) and 36.1 (9.1) years, and male was 45% and 50% in the placebo and the royal jelly group, respectively. The relative change of RH-PAT index was significantly higher in the royal jelly group compared with placebo control (21.4 ± 53.1% vs. 0.05 ± 40.9%, P = 0.037). The relative change of alanine aminotransferase and γ-glutamyl transpeptidase were significantly lower in the royal jelly group than the placebo group (alanine aminotransferase: –6.06 ± 22.2% vs. 11.6 ± 46.5%, P = 0.02; γ-glutamyl transpeptidase: -3.45 ± 17.8% vs. 4.62 ± 19.4%, P = 0.045). Lipid profiles were not significantly different between two study groups. Conclusions: Royal jelly improved endothelial function assessed by RH-PAT and liver function in healthy volunteer. It can be expected that royal jelly has anti-atherogenic property through improving endothelial function.
Isolation and characterization of exosomes for cancer research
Authors: Le Zhu, Hao-Ting Sun, Shun Wang, Sheng-Lin Huang, Yan Zheng, Chao-Qun Wang, Bei-Yuan Hu, Wei Qin, Tian-Tian Zou, Yan Fu, Xiao-Tian Shen, Wen-Wei Zhu, Yan Geng, Lu Lu, Hu-liang Jia, Lun-Xiu Qin, Qiong-Zhu Dong
Journal: Journal of Hematology & Oncology (2020)

Abstract Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.
Abstract 17082: Recurrent Multisite Spontaneous Coronary Artery Dissections in a Patient Using Prescription Amphetamine
Authors: Likhitesh Jaikumar, Mehul Patel, Mandar Jagtap, Dakshin Gangadharamurthy, Theodore Richards, Linnea LeBaron, John Prather, Anju Priyadarshini
Journal: Circulation (2020)

Introduction: Spontaneous Coronary Artery Dissection (SCAD) is an uncommon condition. In patients taking prescription amphetamine or with methamphetamine abuse, SCAD has been reported in some case reports. We describe a case of a young female patient who had recurrent SCAD on prescription amphetamine with multisite involvement. Case presentation: A 48-year-old woman with history of active tobacco use, hypertension presented with substernal chest pain radiating to both arms. Her home medications included prescription amphetamine (Amphetamine, Dextroamphetamine) for reported history of ADHD (Attention Deficit Hyperactivity Disorder, diagnosed in childhood). The patient’s electrocardiogram showed ST elevations in V2,V3 and V4 and with reciprocal changes in leads II, III and aVF. On emergent cardiac catheterization we noted dominant left system with 99% occlusion with thrombus of mid LAD with radiolucent lumens and contrast dye extravasation into the arterial wall suggesting type 1 SCAD. Otherwise we noted normal RCA, LCx and OM branches. An IVUS was not used during the procedure. This lesion was revascularized with a drug eluding stent with containment of the dissection and achievement of TIMI 3 flow. We noted that the patient presented similarly two separate times in the past 2 years and cardiac catheterizations at that time revealed type 2B SCAD involving OM3, which appeared angiographically normal on current angiogram and 90% distal LAD occlusion from type 1 SCAD. The patient was treated with aspirin and ticagrelor and discharged 2 days post procedure in stable condition. Conclusions: Spontaneous Coronary Artery Dissection (SCAD) has been reported in patients with prescription amphetamine and methamphetamine use, but it is imperative to rule out alternative etiologies and amphetamine related SCAD should be a diagnosis of exclusion. We opted to intervene on the mid LAD dissection and the distal dissections were treated medically.