tbuckley/cabot-search huggingface dataset:
Abstract 16939: Metabolic and Electrophysiological Alterations Underlie Proarrhythmic Properties of Highly Reactive Isolevuglandins in Atrial Cardiomyocytes
Authors: Tuerdi Subati, Zhenjiang Yang, Isis L Christopher, Joseph C Van Amburg, Matthew B Murphy, Joshua M Stark, David Z Trykall, Joey V Barnett, Katherine Murray
Journal: Circulation (2020)

Background: Hypertension is one of the most common risk factors for atrial fibrillation (AF), although the precise cellular and molecular mechanism(s) by which hypertension leads to AF are not well understood. Isolevuglandins (IsoLGs) are highly reactive dicarbonyl products of lipid peroxidation responsible for a major component of oxidative stress-related injury. In a mouse model of hypertension, we recently demonstrated that IsoLGs are elevated in hypertensive mouse atria and that an IsoLG scavenger reduced both IsoLG burden and AF susceptibility. Hypothesis: In this study, we hypothesized that IsoLGs can promote AF by inducing proarrhythmic metabolic and electrophysiologic (EP) changes in atrial cardiomyocytes. Methods and Results: Using standard patch clamp methods, we found significant changes in action potential properties of isolated mouse atrial cardiomyocytes exposed to IsoLGs (1μM, n=15 cells), including elevation of resting membrane potential, shortening of APD and reduction of V max . Acute IsoLG treatment led to a reduction of intracellular ATP production in atrial HL-1 cardiomyocytes, as measured by using a luminescence assay. Employing TMRM and Mitotracker Green staining for confocal and high-throughput screening (HTS) live-cell imaging assays, we also found that IsoLGs decreased mitochondrial membrane potential (compared to control, TMRM fluorescence decreased by 23%, 28%, 36% and 42%, respectively, when exposed to 0.01, 0.1, 0.5 and 1μM concentrations of IsoLG) accompanied by increased apoptosis (Cell Event Caspase-3/7 Green Detection Reagent) in a concentration-dependent manner, suggesting a prolonged mitochondrial transition pore opening. Moreover, cell metabolism assays performed using Agilent’s Seahorse XF96 extracellular flux analyzer revealed that IsoLGs exert a concentration dependent decrease in basal oxygen consumption rate and ATP production in HL-1 atrial cardiomyocytes. Conclusion: Together, these findings indicate that IsoLGs promote proarrhythmic EP and mitochondrial effects in atrial cells and thus may provide a novel therapeutic target for AF.
AAV6-Mediated hACE2 Expression as a Versatile Model for SARS-CoV-2 Infection and synDNA Vaccine Efficacy
Authors: E. N. Gary, B. Warner, E. Parzych, B. Griffin, X. Z. Zhu, N. Tailor, M. Chan, R. Vandramelli, N. J. Tursi, M. Purwar, E. Reuschel, K. Liaw, A. Ali, S. K. Wootton, A. Patel, S. Ramos, T. Smith, D. B. Weiner, D. Kobasa
Journal: Molecular Therapy (2021)
Abstract P016: Association Between Life’S Simple 7 Score And Cognitive Status In Older Adults With Atrial Fibrillation
Authors: Eric Y Ding, Weijia Wang, Darleen Lessard, Jordy Mehawej, Tanya Mailhot, Benita Bamgbade, David D McManus, Jane Saczynski
Journal: Circulation (2021)

Introduction: The American Heart Association’s Life’s Simple 7 (LS7) score is a well-validated metric of cardiovascular health shown to be associated with cognitive status in numerous cardiac cohorts. However, little is known regarding this relationship in older adults with atrial fibrillation (AF). We aim to characterize LS7 scores in this population and examine its relationship with cognitive status. Hypothesis: We hypothesize that LS7 score is associated with cognitive status in older adults with AF. Methods: The Systematic Assessment of Geriatric Elements in AF (SAGE-AF) study is a longitudinal cohort of patients over 65 years of age who are diagnosed with AF from Massachusetts and Georgia. The LS7 components are collected through self-reported data from the baseline visit as well as medical records. Cognitive status is operationalized using the Montreal Cognitive Assessment (MoCA). Descriptive statistics were calculated and univariate logistic regression using tertiles of LS7 as exposure was used to assess the relationship between LS7 score and cognitive status. Results: A total of 1241 participants were included in study sample. Average age of the population was 76, 49% were female, and most of the sample were White (89%). Mean LS7 score was 7.92 (SD 2.05), and the tertile thresholds were 0-6, 7-9, and 10-14 (n = 302, 671, 268). Those in the lowest and middle tertiles of LS7 score were more likely than those in the highest to be cognitively impaired (lowest - OR 1.86, 95% CI 1.33 - 2.61; middle - OR 1.52, 95% CI 1.14 - 2.03) Conclusions: Most older adults with AF had LS7 scores of between 7-9 out of 14, and those with more favorable cardiovascular health were less likely to be cognitively impaired.
Long-term Clinical Follow-up of Patients after Percutaneous Transvenous Mitral Commissurotomy: Single-center Experience over 20 Years
Authors: Asano Ryuta, Takayama Morimasa, Watanabe Yusuke, Takamisawa Itaru, Inoue Kanki, Seki Atsushi, Aikawa Masaru, Tanizaki Kohei, Tobaru Tetsuya, Iguchi Nobuo, Watanabe Hiroyuki, Nagayama Masatoshi, Umemura Jun, Sumiyoshi Tetsuya
Journal: Circulation (2009)
Salmonella flagella confer anti-tumor immunological effect via activating Flagellin/TLR5 signalling within tumor microenvironment
Authors: Jianxiang Chen, Yiting Qiao, Guo Chen, Cunjie Chang, Heng Dong, Bo Tang, Xiawei Cheng, Xiufeng Liu, Zichun Hua
Journal: Acta Pharmaceutica Sinica B (2021)

mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models, but the detailed mechanism remains unsolved. In this report, the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts. Since flagella are key inducers of the host immune response during bacterial infection, flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy. The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects, even when more bacteria were administered to offset the difference in invasion efficiency. Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5 (TLR5) signalling pathway. Indeed, we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma. Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy, thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.
Adenocarcinoma arising from a long-standing solitary rectal ulcer syndrome
Authors: Thomas Lambin, Pierre Lafeuille, Jérôme Rivory, Florian Rostain, Martin Fabritius, Eddy Cotte, Mathieu Pioche
Journal: Endoscopy (2021)

Solitary rectal ulcer syndrome (SRUS) is a rare chronic disease characterized by a combination of clinical symptoms, endoscopic appearance, and histology findings, with periods of remission and relapse [1] [2]. It most commonly affects young adults [3]. Patients usually pass mucus and blood while defecating, but can also complain about tenesmus, straining on defecation, incontinence, or a sensation of incomplete evacuation [4]. SRUS is a benign condition, but some rare cases of associated adenocarcinomas have been described [5].
Mass SARS-CoV-2 serological screening, a population-based study in the Principality of Andorra
Authors: Cristina Royo-Cebrecos, David Vilanova, Joel López, Vanesa Arroyo, Marc Pons, Guillem Francisco, Mireia G. Carrasco, Josep M. Piqué, Sergi Sanz, Carlota Dobaño, Alberto L. García-Basteiro
Journal: The Lancet Regional Health - Europe (2021)

Andorra is a small country located in the Pyrenees attracting millions of visitors for tourism, mostly associated with skiing, and nature-related activities. As its neighbouring countries, Spain and France, it has been heavily affected by the COVID-19 pandemic. We estimated SARS-CoV-2 seroprevalence in the entire country by universal serological testing under a lockdown environment.A total of 77,543 inhabitants of Andorra were invited to participate in the study. From 4-28 May, 2020, two cross sectional serological surveys were conducted using a rapid serological test (nCOV IgG/IgM) on a finger prick blood sample in 59 drive-through or walk-through checkpoints, all over Andorra. We calculated seroprevalence of antibodies against SARS-CoV-2 and analysed the main sociodemographic factors associated with being seropositive.70,494 inhabitants (90.9% of the population) participated in at least one survey. Overall seroprevalence was 11.0%. The most affected age groups were those over 90 years old (15.2%) and 80-89 (13.8%), followed by adults 50-59 (13.6%) and adolescents 10-19 (13.7%). Most seropositive participants, 6,061 (95.1%), were asymptomatic before the surveys. The multivariable analysis showed that the odds of being seropositive was higher among seasonal workers (OR 2.41; 95% CI 1.07-5.45) or in the population living in La Massana region, a popular ski-related area (OR 2.66; 95% CI 2.44-2.89). A higher seroprevalence was observed in those familiar nuclei with greater numbers of cohabitants: 18% in families with 6 household members or more; 13% in medium size families (3/4/5 people) and 12% in small size (1 to 2 people) nuclei.The prevalence of antibodies against SARS-CoV-2 in the population of Andorra was high during the first wave of the pandemic. Seasonal workers and inhabitants based in La Massana presented a higher seroprevalence. Mass antibody screening allows to identify infection hotspots and should contribute to the design of tailored interventions to prevent SARS-CoV-2 transmission in Andorra.Andorran Ministry of Health, Andorran Health Services.
Abstract 15079: Equitable Access to MHealth Through a Smartphone Loaner Program in Patients With Acute Myocardial Infarction
Authors: William E Yang, Erin Spaulding, Lochan Shah, George Hung, Dominique Vervoort, Jie Ding, Francoise A Marvel, Seth S Martin
Journal: Circulation (2020)

Introduction: Mobile health (mHealth) is expanding as a healthcare delivery tool but depends on patients’ existing ownership of technology, which could create inequity. We faced this challenge in developing and implementing the “Corrie” mHealth program for Apple iOS and watchOS to aid patients in post-myocardial infarction recovery. Considering that cardiologists commonly loan equipment to patients (e.g. Holter monitors), we created an iPhone loaner program to expand access to Corrie. Here, we explore sociodemographics and readmission outcomes associated with loaner use. Methods: In the Myocardial infarction COmbined-device Recovery Enhancement (MiCORE) study, we prospectively enrolled acute myocardial infarction patients at four hospitals. Patients who owned a compatible iPhone used Corrie on their own phone (“non-iShare”) while others used a loaner iPhone (“iShare”). Loaned phones were returned 30 days after discharge. We used logistic regression models to evaluate sociodemographic differences in iShare versus non-iShare patients. We also explored readmission outcomes in the two groups. Results: Of the 200 patients in MiCORE, 46% (n=92) were in the iShare group. Compared to non-iShare patients, iShare patients were younger (mean age 57.4±11 years [range 30-81] vs 60.8±11 [32-89]; p=0.04). After adjusting for age, iShare patients were more likely to be women (36% vs 23%, p=0.03), insured by Medicaid (20% vs 4%, p&lt;0.01), and less likely to have commercial insurance (47% vs 61%, p&lt;0.01). More iShare patients were black (25% vs 14%), unmarried (49% vs. 35%) and unemployed/disabled (29% vs 16%) relative to non-iShare patients, albeit not reaching statistical significance (p&gt;0.05). Among patients asked about income (53%, n=106), iShare patients had a lower mean annual income ($56,000 vs. $97,000, p&lt;0.01) and a higher percentage of annual income &lt;$30,000 (35% vs 11%, p&lt;0.01). Readmissions were infrequent and similar in iShare and non-iShare patients, including 30-day all-cause readmission (10% vs 4%, p=0.09) and cardiac readmission (4% vs 2%, p=0.66). Conclusions: These results suggest the potential for a smartphone loaning program to facilitate equitable mHealth access for underserved patients including those with a lower income.
Screening for Colorectal Cancer
Authors: Jill Jin
Journal: JAMA (2016)

US Preventive Services Task Force; Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Susan J. Curry, PhD; Karina W. Davidson, PhD, MASc; John W. Epling Jr, MD, MSEd; Francisco A. R. García, MD, MPH; Matthew W. Gillman, MD, SM; Diane M. Harper, MD, MPH, MS; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Douglas K. Owens, MD, MS; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH; Albert L. Siu, MD, MPH
Abstract P166: Plasma Acylcarnitines During Pregnancy And Neonatal Anthropometry: A Prospective And Longitudinal Study
Authors: Yiqing Song, Chen Lyu, Ming Li, Mohammad Rahman, Yeyi Zhu, Stefanie Hinkle, Liwei Chen, Susanna D Mitro, Lingjun Li, Natalie Weir, Michael Y Tsai, Cuilin Zhang
Journal: Circulation (2021)

As surrogate readouts reflecting tissue acyl-CoA pools, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight (BW), BW z-score, the sum of skinfolds (SS), body length, and head circumference. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10-14, 15-26, 23-31 and 33-39 among 321 pregnant women from the NICHD Fetal Growth Studies-Singletons and performed latent-class trajectory approach to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal outcomes using weighted generalized linear models adjusting for maternal age, race, education, parity, gestational age of blood collection, and pre-pregnancy BMI. Women showed changes in plasma levels of all acylcartinines across gestation and had at least two significantly distinct group-based trajectories for 32% of acylcartinines. Longitudinally, women with increased C12 levels across gestation (5.7%) had significantly smaller BW (-475 g; 95% CI, -942, -6.79), BW z-score (-0.39, 95% CI, -0.71, -0.06), and length (-1.38, 95% CI, -2.49, -0.27) than those with persistently stable C12 levels during pregnancy (all FDR&lt;0.05). Women with persistently higher levels of C10 (6.1%) or C10:1 (87.4%) had greater sum of skinfolds (4.91, 95%, 0.85, 8.98) than those with lower levels during pregnancy (P&lt;0.05). In conclusion, this study identified that gestational trajectories of C10, C10:1, and C12 acylcarnitine levels were significantly associated with neonatal anthropometry. Further studies are needed to replicate and assess clinical utility of these findings.
Abstract P031: Endothelial Microparticles In Pediatric Obesity
Authors: Subin Jang, Elise F Palzer, Kyle D Rudser, Claudia K Fox, Robert P Hebbel, Donald R Dengel, Liming Milbauer, Aaron S Kelly, Justin R Ryder
Journal: Circulation (2021)

Introduction: Endothelial activation represents one of the earliest signs of the atherosclerotic process. Microparticles (MPs) in plasma, particularly endothelial MPs (EMPs) are reproducible biomarkers of endothelial dysfunction with a simple blood draw. The goal of this study was to examine the association of obesity with MPs, EMPs (CD31+/CD41– and/or CD 144+/CD31–), and activated EMPs (CD106+). Hypothesis: We hypothesized that higher body mass index (BMI), body fat percent (BF%), and visceral adipose tissue (VAT) would be associated with higher levels of MPs, EMPs, and activated EMPs. Methods: This was a cross-sectional study of 280 children and adolescents ages 8-18 years old. Whole venous blood was collected and processed for platelet free-plasma (PFP) collection less than 3 hours after being drawn. PFP samples were prepared using serial centrifugations and then frozen as 100 μl aliquots at -80 ° C. MPs were measured using flow cytometry with size ranging from 0.3 to 1.0 μm. EMPs were defined as MP with CD31+/CD41– and/or CD 144+/CD31–. Active EMP was identified as EMP with CD 106+. BF% and VAT were measured using dual X-ray absorptiometry. Linear (total MPs and EMPs) and logistic (activated EMPs) regression models were used to examine the associations with adiposity group, BF%, and VAT, adjusting for Tanner stage, sex, and race. Results: The mean age of the cohort was 12.7 years, consisting of 147 females and BMI distribution: 112 normal-weight, 77 overweight/obesity, 91 severe obesity. Youth with overweight/obesity and severe obesity had higher numbers of total MPs (28,690 per μL PFP/g [-2,315, 59,695], p=0.07 and 52,744 per μL PFP/g [22,163, 83,324], p&lt;0.001, respectively) and total EMPs (350 per μL PFP/g [81, 618], p=0.011 and 278 per μL PFP/g [13, 543], p=0.040, respectively) compared to peers with normal weight. In the entire cohort, higher BF% was associated with higher MPs (1,646 per μL PFP per percent [509, 2,783], p=0.005) and EMPs (11 per μL PFP per percent [2, 21], p=0.023), and higher VAT was associated with higher MPs (34 per μL PFP/g [11, 57], p=0.004) but not EMPs. Logistic regression analysis showed higher odds of active EMPs (odds ratio, 1.72 [1.0, 2.97], p=0.0502) in those with a BMI &gt;85 th percentile compared to youth with a BMI &lt;85 th percentile. In the entire cohort, BF% (odds ratio, 1.02 [1.00, 1.04], p=0.108) and VAT (odds ratio, 1.00 [1.00, 1.00], p=0.472) were not significantly associated with active EMPs. Conclusions: Higher levels of endothelial cell damage and activation were associated with obesity and excess adiposity in youth. The potential role of MPs and EMPs as useful biomarkers of cardiovascular disease risk merits further study.
Abstract 15609: Risk of Aortic Valve Disease and Aortopathy in Patients With Bicuspid Aortic Valve Referred to a Central County Hospital in Denmark
Authors: Kristina Procida, Riina Oksjoki, Sandra Wulffeld, Dorthe Guldbrand Nielsen, Soren Schmiegelow, Anh T Ngo, Michelle Schmiegelow, Niels E Bruun
Journal: Circulation (2020)

Introduction: Patients with bicuspid aortic valve (BAV) are at increased risk of developing severe aortic valve disease and aortopathy at an early age. We therefore performed a retrospective study to describe all patients diagnosed with BAV in an entire region of Denmark. Methods: We included patients≥18 years old with BAV, who had a transthoracic echocardiography (TTE) at our hospital before May 2020, and through electronic health records and our echocardiography database, we achieved baseline data. Results: A total of 545 patients with BAV (74.1% men) were identified. At the time of BAV diagnosis the median age was 54 years (IQR 42-62), and the causes for referral to TTE were primarily chest discomfort (21.1%), dyspnea (17.6%), or a newly discovered murmur (40.0%). Upon diagnosis 19.3% of the patients had an aortic valve area (AVA)&lt;1,0 cm 2 , 2.4% had severe aortic regurgitation and the majority (84.0%) had normal left ventricular ejection fraction. The ascending aorta was dilated in 51.9% of the patients while aortic coarctation was found in 5.1% of all patients. According to Sievers BAV classification 24.4% (N=133) had Type 0, 58.7% (N=320) had Type 1 left/right(L/R) fusion, 10.6% (N=58) had Type 1 right/noncoronary (R/N) fusion, 2.6% (N=14) had Type 1 left/noncoronary (L/N) fusion and 2.2% (N=12) had Type 2. Coexisting diabetes mellitus (10.1%), ischemic heart disease (13.2%) and chronic obstructive pulmonary disease (10.1%) was low, whereas hypertension was frequent (47.9%). The majority had sinus rhythm (75.6%) and normal eGFR (84.4%). Surgery was performed in 37.3% (N=203) of all patients and primarily due to aortic valve stenosis (N=172, 84.7%). Surgery was performed in a higher frequency of patients with Sievers Type 1 L/N fusion (N=9, 4.4%; 64.3% of all Type 1 L/N) and Type 2 (N=10, 4.9%, 83.3% of all Type 2) and lowest in patients with Sievers Type 0 (N=35, 17.2%; 26.3% of all Type 0). However, likelihood of surgery was only significantly different between patients with BAV Type 2 and Type 1 L/R (OR 14.21 (2.83-71.35). Conclusion: In this cohort of patients with BAV a higher fraction of patients with BAV type 1 L/N and BAV type 2 required valve replacement compared with particularly BAV type 0 suggesting important differences according to BAV subtype.
Abstract 13420: The LDL/apolipoprotein B Ratio Which is an Index for LDL Particle Size is a Strong Predictor for Neointimal Characteristics and In-stent Restenosis After Everolimus-eluting Stent Implantation
Authors: Naotaka Akutsu, Riku Arai, Daisuke Fukamachi, Yasuo Okumura
Journal: Circulation (2020)

Introduction: The smaller size of LDL particle has suggested the development of endothelial dysfunction, atherosclerosis and in-stent restenosis (ISR), but little is known regarding the impact of LDL particle size on neointimal formation leading to ISR. Hypothesis: The LDL-C/Apolipoprotein B (Apo B) ratio &amp;lt; 1.2 has been reported to indirectly represent a high proportion of sdLDL. It was hypothesized that in-stent neointimal proliferation in LDL/ApoB &amp;lt; 1.2 patients may be excessive and unstable. Methods: In 135 patients, we investigated the relationship between the LDL particle size and neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during follow-up angiography after stent implantation. Results: ISR was identified in 35 patients, who had a significantly lower LDL/ApoB ratio (0.99±0.25 vs. 1.17±0.25; p &amp;lt; 0.01) and higher proportion of yellow grade 2 and 3 by CAS than non-ISR group (n=100). Among the non-ISR group, LDL/ApoB &amp;lt; 1.2 group (n=59) had a significantly larger neointimal volume by OCT, and higher proportion of yellow grade 2 and 3 by CAS compared with LDL/ApoB &amp;gt; 1.2 group (n=41) (Figure). Conclusions: Smaller size of LDL strongly associated with the neointimal proliferation, the neointimal instability and ISR evidenced by multimodalities, suggesting that smaller ratio of LDL/ApoB could be a surrogate marker for the neointimal characteristics after stent implantation.
Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2
Authors: Thomas Thiele, Lena Ulm, Silva Holtfreter, Linda Schönborn, Sven Olaf Kuhn, Christian Scheer, Theodore E. Warkentin, Barbara M. Bröker, Karsten Becker, Konstanze Aurich, Kathleen Selleng, Nils-Olaf Hübner, Andreas Greinacher
Journal: Blood (2021)
Re: Jens-Uwe Stolzenburg, Sigrun Holze, Petra Neuhaus, et al. Robotic-assisted Versus Laparoscopic Surgery: Outcomes from the First Multicentre, Randomised, Patient-blinded Controlled Trial in Radical Prostatectomy (LAP-01). Eur Urol 2021;79:750–9
Authors: Riccardo Bertolo, Pierluigi Bove
Journal: European Urology (2021)