tbuckley/cabot-search huggingface dataset:
Abstract 13924: NLRP3 Inflammasome Activation in Macrophages Drives Adverse Right Ventricular Remodeling and Dysfunction
Authors: Patricia D Lima, Ruaa Al-qazazi, Sasha Z Prisco, Francois Potus, Asish Das Gupta, Kuang-Hueih Chen, Lian Tian, Jeffrey Mewburn, Oliver Jones, Danchen Wu, Donald Maurice, Sebastien Bonnet, Steeve Provencher, Kurt W Prins, Stephen L Archer
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasculopathy that causes right ventricle failure (RVF) and death. This study evaluates the role of the pyrin domain-containing protein 3 (NLRP3) inflammasome activation within RV macrophages in RVF. Hypothesis: In PAH, the NLRP3 inflammasome is activated in macrophages infiltrating the RV and contributes to RVF. Methods: We compared inflammation in monocrotaline (MCT=25; PBS=21) rats, which have decompensated RV hypertrophy (RVH), and pulmonary artery banding (PAB=11; Sham=11) rats, which have compensated RVH. RV function was assessed by echocardiography and right heart catheterization. Macrophages’ abundance and polarization were evaluated by confocal microscopy and flow cytometry. NLRP3 inflammasome activation was assessed by western blot and in vitro strategies. On day 14 post-MCT injection, rats were treated daily with SC-144 (a GP130 antagonist) or MCC950 (an NLRP3 inhibitor). We assessed macrophage abundance and NLRP3 activity in PAH-RVF patients (n=12) and controls (n=9). Results: Macrophage abundance was significantly higher in MCT-RV compared to controls (p=0.023 microscopy; 0.004 flow cytometry), but it was insignificant between PAB and sham-RVs. While MCT-RV macrophages were inflammatory, lung macrophages carried an anti-inflammatory phenotype. NLRP3, cleaved caspase1 and IL1β were highest in MCT-RVs (p= 0.021, 0.008, 0.027). The macrophage-NLRP3 pathway was also upregulated in PAH-RVF patients. Cultured MCT monocytes revealed increased NLRP3:ASC interaction upon Nigericin stimulation, which MCC950 inhibited. In vivo , MCC950 reduced NLRP3 activation (p=0.012) and improved RV function. SC-144 significantly reduced RV macrophage count, STAT3 and NLRP3 activation (p= 0.0001, 0.042, 0.05), while improving RV function without regressing pulmonary vascular disease. Conclusion: The concept that PAH-RVF results, in part, from local RV inflammation rather than a passive consequence of elevated afterload is new. Blocking the inflammasome pathway reduces RV-macrophage accumulation and NLRP3 inflammasome activation. It also improves RV function, despite persistent pulmonary vascular remodeling offering a new therapeutic paradigm.
Abstract 10918: Use of Mobile Health Technology in the Assessment of Statin-Associated Muscle Symptoms (SAMS)
Authors: Luke G Silverman-Lloyd, Vasanth Sathiyakumar, Pauline Huynh, Blair Chang, Seth S Martin
Journal: Circulation (2021)

Background: Statins are the cornerstone pharmacotherapy for lowering LDL-C and reducing risk of ASCVD. However, statin initiation and adherence are limited by statin-associated muscle symptoms (SAMS), posing significant clinical and public health dilemmas. Mobile health (mHealth) tools offer novel ways to assess real-time symptom data and share them back with patients to facilitate shared decision-making. Objective: To assess the feasibility and usability of an automated, text-message-based SAMS symptom-tracking platform to longitudinally track SAMS in patients who previously experienced muscle symptoms while on statin therapy. Methods: We enrolled 19 patients from 2 clinics at a single health system (Johns Hopkins; Baltimore, MD) and recorded baseline demographics, statin history and indication, perceptions of SAMS, and technology use via an online survey. Quantitative SAMS scores were gathered via daily text messages, and qualitative symptom data were collected in weekly text messages. Monthly symptom reports were sent to select participants via email on study days 30, 60 and 90. Upon study completion, participants reported perceptions of the study, the mHealth platform, and study measures via an online exit survey. Results: A total of 18 patients (aged 59.3 [SD 14.5] years, 67% women) collected data, and 15 patients completed the 90-day study protocol. Overall response rate to text messages was 91.5% (92.2% for daily SAMS messages, 86.0% for weekly muscle symptom prompts). Patients reported a statin adherence of 70%. Nine patients reported intolerable muscle symptoms at least once during the study, and intolerable symptom scores represented 3% of all reported symptom scores. Patients reported overall satisfaction with the study and found the SAMS scores helpful. Conclusions: Patients with previously reported SAMS successfully engaged with a text-message-based symptom-tracking platform with high interactivity and acceptability. This study demonstrates the feasibility and usability of an automated mHealth platform for longitudinally tracking SAMS in patients on statin therapy, and may provide a means for improving shared decision making to tailor statin therapy and improve adherence.
Effect of seasonal allergen exposure on mucosal IL‐16 and CD4+ cells in patients with allergic rhinitis
Authors: T. Pullerits, A. Lindén, C. Malmhäll, J. Lötvall
Journal: Allergy (2001)

Background: CD4+ T cells constitute a major source of cytokines in allergic diseases such as allergic rhinitis. Interleukin (IL)‐16 selectively recruits CD4+ cells. Methods: We evaluated the effect of natural allergen exposure during a grass‐pollen season on IL‐16 expression and number of CD4+ cells in nasal mucosa. Patients with allergic rhinitis ( n =16) were treated with either a nasal glucocorticoid beclomethasone (BDP; 400 µg/day) or placebo, and gave nasal biopsies prior to and during the grass‐pollen season. The evaluated markers in allergic rhinitis patients were also compared to those in healthy control subjects ( n =5). Results: Prior to the pollen season, the expression of IL‐16, but not the number of CD4+ cells, was significantly higher in patients with allergic rhinitis than in healthy control subjects. The grass‐pollen season further increased IL‐16 expression and also increased the number of CD4+ cells in placebo‐treated, but not in BDP‐treated, allergic rhinitis patients. The pollen‐season‐induced change in IL‐16 expression and in CD4+ cells was significantly more pronounced in placebo‐ than in BDP‐treated patients. There was a significant correlation between the change in IL‐16 expression and the number of CD4+ cells. Conclusions: These data suggest that local upregulation of IL‐16 expression contributes to the inflammation observed in seasonal allergic rhinitis. Hypothetically, inhibition of IL‐16 expression can be one of several mechanisms by which nasal glucocorticoids achieve their anti‐inflammatory effect in allergic rhinitis.
Abstract 10955: The Effects of Acute and Chronic Selective Phosphodiesterase 1 Inhibition in Associated Smooth Muscle Cell-Specific Aging Features
Authors: Keivan Golshiri, Ehsan Ataei Ataabadi, René de Vries, Lei zhang, Suman Chalgeri, Amy Lin, Gretchen Snyder, Robert Davis, Jan H Danser, Anton Roks
Journal: Circulation (2021)

Introduction: Aging-related vascular smooth muscle cell (VSMC) remodeling plays an essential role in cardiovascular diseases. Reduced NO-cGMP pathway signalling is a major feature and pathogenic mechanism underlying VSMC dysfunction. Recently, we found that phosphodiesterase (PDE) 1, an enzyme that hydrolyzes and inactivates the cyclic nucleotides cAMP and cGMP, is a potential treatment target for restoring age-related deficits in VSMC signalling. We here tested the effects of PDE1 inhibition in SMC-specific Ercc1 DNA repair mutant mice, a model of isolated, accelerated SMC aging. Design and Method: SM22α Cre+ Ercc1 fl/- (SMC-KO) and SM22α Cre+ Ercc1 fl/+ littermate (SMC-LM) mice receive either vehicle or the PDE1 inhibitor lenrispodun (dose 40mg/kg/day) in drinking water for 8 weeks. Reactive hyperemia was measured in-vivo at the age of 14 and 25 weeks. Mice were sacrificed at 26 weeks. The endothelium-dependent (ED) and -independent (EI) relaxation of the thoracic aorta was assessed by wire myography. Moreover, we investigated the effect of PDE1 inhibition on the expression of selected PDEs involved in the vasculature by qPCR. Results: Reactive hyperemia was dramatically reduced in vehicle-treated SMC-KO vs. SMC-LM at the age of 25 weeks (P=0.0002) but was preserved in lenrispodun-treated SMC-KO mice. In vehicle-treated SMC-KO mice, the ED and EI relaxations were greatly diminished compared to SMC-LM (ED: 23.92±4.34 vs. 68.04±4.86, P&lt;0.0001; EI: 57.93±5.31 vs. 87.43±4.01, P=0.0004). Acute administration of lenrispodun in the organ bath improved both ED and EI responses (ED: 38.61±4.04, P=0.001; EI 69.99±4.29 P=0.01) while the relaxations remained unchanged after chronic lenrispodun treatment. In addition, lenrispodun upregulated PDE1a mRNA expression in SMC-KO, while no changes were observed in other PDEs. Conclusions: PDE1 inhibition may therapeutically be useful in restoring age-related vascular dysfunction by preserving microvascular function and potentiating NO-cGMP signaling. Yet, its chronic effects might be counteracted by the upregulation of PDE1a in vasculature. These results warrant further pharmacodynamic profiling of PDE enzyme regulation during chronic PDE1 inhibitor treatment.
Clinical and Biological Effects of Combined CD27 and CD20 Antibody Therapy in Relapsed/Refractory B-Cell Lymphoma: The Riva Trial
Authors: Sean H Lim, Heng Sheng Sow, Christopher Wignall, Katy Mercer, Josh Caddy, Cherish Boxall, Kerensa Thorne, Joshua Northey, Louise Stanton, Zoë Konn, Keira Fines, Patrick G. Medd, Adam Coleman, Lorna Nunn, Robert Lown, Pamela McKay, Wendy Osborne, Kim Linton, Graham P. Collins, Andrew J Gentles, Matthew Rose-Zerilli, Gareth Griffiths
Journal: Blood (2021)
Abstract 12535: The Hemodynamic Response to Exercise in Patients With Obstructive Hypertrophic Cardiomyopathy and the Effect of Metoprolol
Authors: Anne M Dybro, Torsten Bloch B Rasmussen, Roni R Nielsen, Bertil T Ladefoged, Mads Andersen, Morten K Jensen, Steen H Poulsen
Journal: Circulation (2021)

Introduction: Patients with obstructive hypertrophic cardiomyopathy (HCM) frequently experience advanced heart failure symptoms at low levels of physical activity. The relationship between symptoms and loading conditions during exercise is incompletely understood. Whether standard treatment with beta-blockers affects exercise hemodynamics is unknown. Objectives: The aim of this study was to investigate the invasive hemodynamic response to exercise in moderately symptomatic patients with obstructive HCM, and how treatment with metoprolol affects this response. Method: This double-blinded, placebo-controlled, randomized crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥ II from May 2018 to September 2020. Patients received metoprolol or placebo for two consecutive two-week periods in random order. During each treatment period, patients underwent right-heart catheterization at rest and during exercise. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest. Results: There was no treatment effect on Δ PCWP between metoprolol and placebo treatment (21(9) mmHg versus 23(9) mmHg; p = 0.12). When comparing metoprolol to placebo treatment, there was no significant difference in PCWP at rest (15 (6) mmHg versus 13 (5) mmHg; p = 0.06) or at peak exercise (35 (12) mmHg versus 37 (10) mmHg; p = 0.38). At peak exercise, metoprolol treatment was associated with a higher stroke volume (101 (24) ml versus 92 (21) ml; p &lt; 0.01), a 25% lower heart rate (107 (19) beats/min versus 139 (23) beats/min; p &lt; 0.0001), and subsequently a lower cardiac output (10.8 (3.3) L/min versus 12.8 (3.2) L/min; p &lt; 0.0001). Conclusion: Exercise in patients with obstructive HCM is associated with a severe increase in left-sided filling pressures which are not affected by metoprolol treatment. Despite increased stroke volume during metoprolol treatment, cardiac output is reduced at peak exercise.
Born to survive: how cancer cells resist CAR T cell therapy
Authors: Jean Lemoine, Marco Ruella, Roch Houot
Journal: Journal of Hematology & Oncology (2021)

Abstract Although chimeric antigen receptor T cells demonstrated remarkable efficacy in patients with chemo-resistant hematologic malignancies, a significant portion still resist or relapse. This immune evasion may be due to CAR T cells dysfunction, a hostile tumor microenvironment, or resistant cancer cells. Here, we review the intrinsic resistance mechanisms of cancer cells to CAR T cell therapy and potential strategies to circumvent them.
Abstract 11283: Prevalence of Metabolic Syndrome and Associated Risk Factors in Women Living with HIV
Authors: Claudia Arrais, Nilviane Pires, Luana M Azoubel, Cindy Lima, Allan Kardec K Barros
Journal: Circulation (2021)

Introduction: The presence of Metabolic Syndrome (MetS) increases the risk of developing cardiovascular diseases and diabetes. People living with HIV (PLHIV) using antiretrovirals (ART) have a higher cardiometabolic risk and, consequently, a higher risk of presenting MetS. Thus, the present study evaluated the prevalence of MetS in PLHIV women. Methods: This is a cross-sectional study, carried out with 123 PLHIV women who use ART, aged 21 to 55 years, from a city in the Northeast of Brazil. Were evaluated clinical variables such as age, body mass index (BMI), waist circumference (WC) and neck circumference (NC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), HDL-cholesterol (HDL), triglycerides (TG) and fasting blood glucose (FBG), for the classification of MetS, the criterion of the International Diabetes Federation (IDF) was used. The present study is approved by the research ethics committee, according to the opinion no CAEE: 2.781.461. Results: The prevalence of MetS was 39% (n = 48) in the sample evaluated, the group with MetS had the highest mean / median of the variables age (42.8 years; p = 0.012), BMI (29 kg/m 2 ; p &lt;0.001), NC (35 cm; p &lt;0.001), SBP (130 mmHg; p &lt;0.001), DBP (89 mmHg; p &lt;0.001), CT (186 mg/dL; p &lt;0.001) and TG (157 mg/dL; p &lt;0.001) compared to the group without MetS, moreover 58.15% (n = 82) of the individuals in the group with MetS were overweight. Conclusions: There was a high prevalence of MetS in the sample evaluated, in addition to risk factors. Patients on ART can demonstrate metabolic changes such as dyslipidemia, atherosclerosis, among others, so it is essential to prevent and control the presence of risk factors in order to avoid the development of chronic and consequently cardiovascular diseases.
Smoking Cessation Prevalence and Inequalities in the United States: 2014-2019
Authors: Adam M Leventhal, Hongying Dai, Stephen T Higgins
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Smoking is a leading cause of premature death and health inequities in the United States. Methods We estimated cross-sectional prevalence of smoking cessation indicators among US adult recent smokers (n = 43 602) overall and by sociodemographic subgroups in the Current Population Survey Tobacco Use Supplement 2014-2015 and 2018-2019 timepoints. Respondents reported past-year quit smoking interest, attempts, sustained (successful) cessation for 6 or more months and use of e-cigarettes or behavioral or pharmacological cessation treatments to quit smoking. Results Past-year quit smoking attempts declined slightly from 2014-2015 (52.9%) to 2018-2019 (51.3%) overall. Quit interest (pooled = 77.1%) and sustained cessation (pooled = 7.5%) did not change across timepoints. Among smokers making past-year quit attempts, 34.4% reported using cessation treatments in 2018-2019, and using e-cigarettes to quit smoking declined from 2014-2015 (33.3%) to 2018-2019 (25.0%). Several non-White (vs White) racial and ethnic groups had higher prevalence of quit interest and attempts but lower prevalence of sustained cessation or using e-cigarettes or treatments to quit. Income, education, employment, and metropolitan residence were positively associated with sustained cessation. Sociodemographic inequalities in sustained cessation and most other outcomes did not change across timepoints. Conclusions Although about half of US adult smokers made past-year quit attempts from 2014 to 2019, only 7.5% reported sustained cessation, and most who made quit attempts did not report using cessation treatments. Sociodemographic inequalities in cessation were pervasive and not entirely correspondent with sociodemographic variation in motivation to quit. Smoking cessation prevalence and inequalities did not improve from 2014 to 2019. Encouraging quit attempts and equitable access to smoking cessation aids are public health priorities.
Abstract 13215: Clinical Features Do Not Identify Risk of Progression From Isolated Post-Capillary Pulmonary Hypertension to Combined Pre- and Post-Capillary Pulmonary Hypertension
Authors: Gautam Babu, Jeffrey S Annis, Matthew S Freiberg, Anna R Hemnes, Evan L Brittain
Journal: Circulation (2021)

Introduction: Pulmonary hypertension (PH) is a common sequelae of left heart failure and is designated as either isolated post-capillary pulmonary hypertension (Ipc-PH) or combined pre- and post-capillary pulmonary hypertension (Cpc-PH). Clinical features associated with progression from Ipc-PH to Cpc-PH have not been described. Hypothesis: We hypothesized that clinical features do not distinguish patients who progress from Ipc-PH to Cpc-PH. Methods: We extracted hemodynamic and clinical data from patients referred for right heart catheterization (RHC) at least two times within 5 years. Ipc-PH was defined as mean pulmonary pressure ≥ 25 mmHg, wedge &gt; 15 mmHg and pulmonary vascular resistance (PVR) &lt; 3 WU. Progression to Cpc-PH required an increase in PVR to &gt; 3 WU at the subsequent RHC. Comparisons made using the Mann-Whitney U and paired T-tests, and logistic regression adjusted for age and sex. Results: We identified 157 patients with Ipc-PH at baseline who underwent a repeat RHC after a median of 0.7 years (IQR 0.2, 2.1). The prevalence of Cpc-PH at the second RHC was 31% (49/157). The most common indication for repeat RHC referral was persistent heart failure symptoms (n = 107). Table 1 displays characteristics at the baseline RHC. BMI was lower and HDL higher among those who progressed. No other demographic, clinical, or laboratory features distinguished those who progressed either in univariate comparisons or after adjustment for age and sex. Of note, cardiac index was not significantly changed between baseline and repeat RHC (2.57 vs. 2.30 L/min/m2, p = 0.27) in those who progressed to Cpc-PH, indicating the increase in PVR was not driven by reduced right ventricular function. Conclusions: Clinical features alone cannot clearly distinguish patients at risk for progression from Ipc-PH to Cpc-PH. These findings support the need for molecular and genetic studies to identify risk factors for progression of pulmonary vascular disease in patients with heart failure.
Racial and socioeconomic differences in acral lentiginous melanoma outcomes: A Surveillance, Epidemiology, and End Results analysis
Authors: Neel S Raval, Wesley T Hodges, Pearl O Ugwu-Dike, Fellipe Godoy, George Ansstas, Lynn A Cornelius, Amy C Musiek, Maryam M Asgari, Yevgeniy R Semenov
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 11885: An App That Brings Guidelines to the Point-of-Care: A Pathway for Anticoagulation in Prosthetic Heart Valves
Authors: Tikal Kansara, Yair Saperstein, Joongheum Park, Ashish Kumar, Monil Majmundar, Samarthkumar J Thakkar, Savi Mushiyev, Aravind Kokkirala, Craig Basman
Journal: Circulation (2021)

Introduction: AHA/ACC guidelines are updated regularly, but their clinical implementation at bedside or in the clinic is cumbersome, complicated, and difficult. Apps may fill this gap by bringing medical guidelines to the physician at the bedside. We built the AHA/ACC guidelines as an interactive app that makes the guidelines accessible at the point-of care. This app, in turn, saves time, increases efficiency, and improves the quality of care. Method: While reviewing the AHA/ACC guidelines, we realized that several unique flowcharts can be created each with endpoints being the recommendation for a specific patient characteristic. We used Google App Script and build a spreadsheet-based branching-tree questionnaire with data entry points (e.g., segmented buttons, text data field, or multiple-item selectors) for data inputs. Our data inputs were based on the most recent AHA/ACC guidelines. A unique trigger was set to each data entry item, allowing branching of questions and the users being exposed to a specific subset of questions at each selection. On completion of the clinical module, the app script packages the contents into multiple CSV files (dashboard, pages, contents of each page, and references), and sends the files to Google Firebase, which is Google’s real-time database. In the end, the final recommendation presented is the specific section of the AHA/ACC guideline pertaining to the characteristics of the patient as entered by the user. Qualitative feedback found our app to be “more usable” than the traditional review of guidelines on the website or a paper printout. A subset of the questions for “anticoagulation in prosthetic heart valve patients” is shown in Figure 1. This example represents one of the many modules designed on the same principle. Conclusion: Our interactive app based on AHA/ACC guideline can both save time and improve the quality of care. The app is called “AvoMD”, and we made it available for free on app stores to help clinicians in their practice.
Aptamer-mediated doxorubicin delivery reduces HCC burden in 3D organoids model
Authors: Kevin Zhou, Xiaoqi Huo, Romario Nguyen, Sarah Da Won Bae, Shuanglin Han, Zhiqiang Zhang, Wei Duan, Lawrence Yuen, Vincent Lam, Jacob George, Liang Qiao
Journal: Journal of Controlled Release (2021)