tbuckley/cabot-search huggingface dataset:
Abstract 9149: The Novel Wnt-Pathway Inhibitor Podocan is Not Associated with All-Cause Mortality or Cardiovascular Outcome in Patients Admitted with Suspected Acute Coronary Syndrome
Authors: Thomas Andersen, Dennis W Nilsen, Heidi Grundt, Harry Staines, Thor Ueland, Pal Aukrust, Frederic P Kontny
Journal: Circulation (2021)

Introduction: Podocan, a novel extracellular matrix glycoprotein, is a smooth muscle cell regulator and abundantly expressed in human atheroma. The association of Podocan with cardiovascular outcome remains unclear. The aim of this study was to assess the predictive value of Podocan concerning adverse outcome in patients admitted with acute chest pain suspected to be acute coronary syndrome (ACS). Methods: Plasma Podocan was measured with an enzyme immune assay in samples taken upon hospital admission from patients with suspected ACS who were enrolled in the Risk markers in Acute Coronary Syndrome (RACS) study (NCT00521976). RACS was a Norwegian single center study including patients from November 2002 to September 2003. The primary outcome was a composite of all-cause mortality, myocardial infarction, or stroke within 7 years. Additional analyzes included these individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. Associations between quartiles of Podocan and the primary outcome, its individual components, and cardiac death were assessed in both univariate analyzes and in stepwise multivariable Cox regression analyzes fitted with significant clinical variables, past medical history, medication, TnT, BNP, and eGFR before Podocan was introduced. Results: Samples were available from 815 patients (mean age: 69.6 years, male: 61.3%, elevated TnT: 53.0%). Mean Podocan level was 1.03 ng/mL (CI 0.93-1.13). Podocan was neither associated with the primary composite endpoint within 7 years in univariate analyzes (X 2 analyzes (p=0.426), AUROC 0.518 (p=0.374), Kaplan Meier analyzes (log-rank test p=0.594), and Cox regression (p=0.595)), nor in multivariable Cox regression analyzes (p=0.744). Similar results were found by analyzes of the individual components of the primary outcome and of cardiac death for all time points, as well as in subgroup analyzes of patients with elevated TnT (p&gt;0.05 for all). Conclusions: This first report in the literature on Podocan in acute chest pain did not reveal any significant predictive value of this novel wnt-pathway inhibitor concerning the combination of all-cause death, MI, or stroke, its individual components or cardiac death in patients admitted with suspected ACS, irrespective of TnT status.
Cutaneous manifestations of paediatric multisystem inflammatory syndrome temporally associated with <scp>SARS</scp> ‐ <scp>CoV</scp> ‐2: a single‐centre experience
Authors: Kate Dear, Cristina Psomadakis, Samiullah Dost, Nikolina Lalagianni, Jaimie Oldham, Ai Hew, Julia Kenny, Shelley Riphagen, Danielle Greenblatt, Carsten Flohr, Wedad Abdelrahman
Journal: British Journal of Dermatology (2021)

Paediatric inflammatory multisystem syndrome associated with severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) infection (PIMS-TS) is defined as 'a child presenting with persistent fever, inflammation and evidence of single or multi-organ dysfunction with additional features which include a rash'.1 The World Health Organisation's (WHO) definition further includes a 'rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs'.2 Previously reported mucocutaneous manifestations (MCM) in PIMS-TS have been vague. This study aimed to delineate the MCM of children presenting with PIMS-TS in more detail.
Abstract P345: A MRI Displacement-based Deep-learning Semantic Segmentation Tool For Left-ventricular Longitudinal Strain Analysis In Cardiotoxicity
Authors: Julia Kar, Michael V Cohen, Teja Poorsala, Samuel A McQuiston, Cheri Revere, Angela Judice-Yates, Christopher M Malozzi
Journal: Circulation Research (2021)

Global longitudinal strain (GLS) computed in the left-ventricle (LV) is an established metric for detecting cardiotoxicity in breast cancer patients treated with antineoplastic agents. The purpose of this study was to develop a novel, MRI-based, deep-learning semantic segmentation tool that automates the phase-unwrapping for LV displacement computation in GLS. Strain analysis via phase-unwrapping was conducted on 30 breast cancer patients and 30 healthy females acquired with the Displacement Encoding with Stimulated Echoes (DENSE) sequence. A ResNet-50 deep convolutional neural network (DCNN) architecture for automated phase-unwrapping, a previously validated ResNet-50 DCNN for chamber quantification and the Radial Point Interpolation Method were used for GLS computation (Figure 1). The DCNN's performance was measured with F1 and Dice scores, and validated in comparison to the robust transport of intensity equation (RTIE) and quality guided phase-unwrapping (QGPU) conventional algorithms. The three techniques were compared by intraclass correlation coefficient with Cronbach’s alpha (C-alpha) index. Classification accuracy with the DCNN was F1 score of 0.92 and Dice score of 0.89. The GLS results from RTIE, QGPU and DCNN were -16.0 ± 2%, -16.1 ± 3% and -15.9 ± 3% (C-alpha = 0.89) for patients and -18.9 ± 3%, -19.0 ± 4% and -18.9 ± 3% (C-alpha = 0.92) for healthy subjects. Comparable validation results from the three techniques show the feasibility of a DCNN-based approach to LV displacement and GLS analysis. The dissimilarities between patients and healthy subjects demonstrate that DCNN-based GLS computation may detect LV abnormalities related to cardiotoxicity.
Abstract 13914: Low-Density Lipoprotein Delivery of Microbial Small RNAs Drives Atherosclerosis Through Macrophage Toll-Like Receptor 8
Authors: Ryan M Allen, Danielle L Michell, Ashley Cavnar, Wanying Zhu, Neil Makhijani, Danielle M Contreras, Chase Raby, Elizabeth M Semler, Carlisle DeJulius, Mark Castleberry, Youmin Zhang, Marisol Ramirez, SHilin Zhao, Craig Duvall, Amanda C Doran, Quanhu Sheng, Macrae F Linton, Kasey C Vickers
Journal: Circulation (2021)

Low-density lipoproteins (LDL) are a causal factor for atherosclerosis, a key pathological process in cardiovascular disease. Within atherosclerotic lesions, macrophages present a spectrum of phenotypes that mediate both disease pathogenesis and resolution. Inflammatory macrophage phenotypes are pro-atherogenic, but the natural factors that promote polarization remain to be identified. Here, we demonstrate that microbial small RNAs (msRNA) are enriched on LDL and drive pro-inflammatory macrophage polarization and cytokine secretion via activation of toll-like receptor 8 (TLR8). Removal of msRNA cargo during LDL reconstitution yields particles that are taken up by macrophages but fail to stimulate inflammatory activation. Using loss-of-function and gain-of-function studies, we demonstrate that TLR8 is both necessary and sufficient for LDL-induced activation of NF-kappa-B, a central regulator of inflammatory macrophage polarization. TLR8 recognition of msRNA was found to be antagonized by non-targeting locked-nucleic acids (nt-LNA). Pre-treatment of macrophages with a nt-LNA was found to prevent LDL-induced macrophage polarization in vitro , and re-organize lesion macrophage phenotypes in vivo , as determined by single-cell RNA sequencing. Critically, we demonstrate that nt-LNA treatment reduced plaque burden in 4-week and 10-week atherosclerosis progression studies in Apoe -/- mice fed a western diet. Moreover, in a regression model using male and female Ldlr -/- mice with advanced lesions, nt-LNA treatment in combination with dietary intervention promoted lesion regression relative to mice receiving only dietary intervention. These results identify LDL-msRNA as stimuli for atherosclerosis-associated inflammation and support alternative functions of LDL beyond cholesterol transport.
Abstract 10225: Vasopressor Use and 60-Day Outcomes Among Covid-19 Patients in the Intensive Care Unit
Authors: Mina M Kerlos, Ahmad Gill, Max Ruge, Jeanne M Du-Fay-de-Lavallaz, Joanne Gomez, Annabelle Santos Volgman, Kim A Williams, Anupama Rao, Karolina Marinescu, Tisha Marie Suboc
Journal: Circulation (2021)

Introduction: Vasopressor use has been associated with higher mortality rates in patients with COVID-19, the association between the maximum number of concurrent vasopressors with mortality has not yet been studied. Methods: A retrospective cohort study was conducted on patients admitted with COVID-19 to the intensive care unit (ICU) at Rush University System for Health in Illinois between March and October 2020. Multivariable logistic regression, adjusted for age, BMI, history of CAD and diabetes, was used to determine if an increasing number of vasopressors is associated with higher 60-day mortality. Results: A total of 637 patients met the inclusion criteria. Composite 60-day mortality was 28.6%. Of the 637 patients who met inclusion criteria, 338 (53.1%) required the support of at least one vasopressor. When compared to patients with no vasopressor requirement, those who required 1 (adjusted OR [aOR] 3.27, p&lt;0.01), 2 (aOR 4.71, p&lt;0.01), 3 (aOR 26.2, p&lt;0.01), and 4 or 5 (aOR 106.38, p&lt;0.01) vasopressor(s) were at increased risk of 60-day mortality (Figure 1). Additionally, the incidence of mechanical ventilation, venous thromboembolism, ventricular arrhythmia, and new renal replacement therapy increased with additional vasopressor requirement (p &lt; 0.001 for each outcome; Table 1). There was no statistical difference in the incidence of MACE between the groups (p = 0.139). Conclusion: In this cohort, each additional vasopressor added was associated with escalating 60-day mortality. Identifying these high-risk patients can help determine prognostic outcomes and guide decision-making. .
Abstract 10386: Supervised Machine Learning for Relating Echocardiographic Parameters to Invasive Pressure Measurements in Pediatric Diastolic Function Assessment
Authors: Minh B Nguyen, Andreea Dragulescu, Rajiv Chaturvedi, Chun-po S Fan, olivier villemain, Mark K Friedberg, Luc L Mertens
Journal: Circulation (2021)

Introduction: Diagnosing diastolic dysfunction (DD) non-invasively in children is challenging as no validated pediatric diagnostic algorithm is available. The aim of this study is to use machine learning (ML) to identify a model that integrates echocardiographic measurements to predict invasive hemodynamic markers of DD in children. Methods: We enrolled children with Kawasaki disease, heart transplant, aortic stenosis, and coarctation of the aorta undergoing left heart catheterization. We obtained simultaneous invasive and echo DD measurements. We applied random forest (RF) algorithms to develop separate models for each cath marker (time constant of isovolumic relaxation (Tau), LVEDP, and -dP/dt max) and used demographics, diagnosis, and echo features as inputs. Model approximation was done using a regression tree with the top ranked features of each RF model to improve model interpretability (Figure 1). Spearman correlations were also assessed. Results: 59 children were included. Spearman correlations were low. However, the RF models' adjusted R 2 values in predicting Tau, LVEDP, and -dP/dt max are 0.62, 0.51, and 0.83, respectively. A representative ML-generated tree for LVEDP is shown in Figure 2. The most important features were propagation velocity (Vp) for Tau; E/Vp ratio for LVEDP; and systolic global longitudinal strain rate for -dP/dt max. Model approximation showed that a Vp &lt; 42 cm/s predicted a Tau &gt; 39 ms, and an E/Vp &gt; 2.4 predicted an LVEDP &gt; 13 mmHg. Conclusions: Predicting invasively measured diastolic parameters with echo data may be improved using ML algorithms. Model approximation may help better interpret the complex interactions in ML models.
心エコーが診断,経過観察に有用で,手術適応となった肺血栓塞栓症の一例
Authors: 岩崎正道, 金秀植, 望月泰秀, 上田亮介, 岡本浩, 松尾洋介, 高僑裕子, 宝田明, 横山光宏, 杉本貴樹
Journal: Circulation (2008)
Welsh GPs are awarded 3% pay rise
Authors: Adele Waters
Journal: BMJ (2021)

Cytosolic retinoic acid receptor in carcinoma, chronic pancreatitis, and normal pancreatic tissue were examined using sucrose density gradient centrifugation, isoelectric focussing on agarose gel and saturation analysis. Thirteen patients were studied. Cytosolic retinoic acid binding protein (cRABP) was detected in all the samples with chronic pancreatitis and pancreatic carcinoma, but not in the normal tissue. Using sucrose gradient centrifugation, the highest concentrations of cRABP were found in pancreatic carcinoma tissues, ranging from 5.5-23.9 pmol/mg protein. These concentrations were markedly different than in chronic pancreatitis tissue (0.7-2.7 pmol/mg protein). Saturation analysis of cRABP showed a mean dissociation constant of 21.5 nM and maximum binding sites of 5.2 pmol/mg protein. Cytosolic retinoic acid binding protein was separated at an isoelectric point of 4.5 on agarose gel. The presence of cRABP suggest that retinoic acid may have a role to play in the function of the pancreas.
Abstract 6916: The Right Ventricle in Adolescent Athletes: Standing up for the Smaller Side
Authors: Sanjay Sivalokanathan, Daniel X Augustine, Anushka Sharma, James Willis, keith pearce, Michael Papadakis, Sanjay Sharma, Aneil Malhotra
Journal: Circulation (2021)

Introduction: Athletic training often results in changes that may mimic features of pathological cardiomyopathies. These changes are influenced by age, ethnicity and sporting discipline. Studies detailing the physiological adaptation to exercise on the right ventricle (RV) of adolescent athletes are fewer compared to the left ventricle, with even fewer describing the impact of ethnicity on the RV. One such potential physiological overlap with pathological change is arrhythmogenic right ventricular dysplasia (ARVD). An erroneous interpretation may have profound consequences ranging from false reassurance in a vulnerable athlete to unfair disqualification in a healthy individual. Therefore, it is important for the clinician to distinguish physiology from pathology. Results: ECG and echocardiographic data of 3000 academy male footballers were analysed, aged between 13 and 18 years old (mean age 16.4 ± 0.5 years), who underwent mandatory cardiac screening. Ethnicity was categorised as white (n=1000), black (n=1000) and mixed-race (n=1000). Overlap between ECG changes expected in ARVD and the adolescent athlete was observed. ARVD major criteria for TWI was seen in (n=63) 6.3% of the cohort. This was more prevalent in black footballers (n= 37; 3.7%) when compared to mixed race footballers (n=20; 2%) or white footballers (n=6; 0.6%), p&lt;0.05. In up to 67% of the overall cohort, RV values exceeded those for normal adult reference ranges. Overall, 0.2% of the cohort would fulfil diagnosis for ‘definite’ ARVD and 2.2% would fulfil diagnosis for ‘borderline’ ARVD. This was seen more frequently in black footballers (n=99, 9.9%) than mixed race footballers (n=39, 3.9%) or white footballer (n=6; 0.6%), P = 0.0005. Among athletes meeting definite or borderline ARVD criteria, no cardiomyopathy was identified. Conclusion: This is the largest study to our knowledge that reports RV dimension data among adolescent footballers of different ethnicities. Right heart sizes in excess of standard adult ranges occurred in as many as one in 5 athletes. It is not unusual to observe values that would overlap with criteria for ARVD. As with LV parameters, variations in terms of ethnicity should be accounted for when performing routine cardiac assessments of adolescent athletes.
Usability and Performance Testing of Pointcheck™: A Noninvasive Neutropenia Screening Device for Chemotherapy Outpatients
Authors: Ganimete Lamaj, Alberto Pablo-Trinidad, Ian Butterworth, Nolan Bell, Ryan Benasutti, Antonio Verdone, Aurelien Bourquard, Alvaro Sanchez-Ferro, Carlos Castro-Gonzalez, Antonia Rodriguez Izquierdo, Tycho Baumann, Elizabeth Pottier, Joaquín Martínez-López, John Mark Sloan
Journal: Blood (2021)
Abstract 10776: Market-Level Variation in Utilization of Percutaneous Ventricular Assist Devices Utilization in the United States
Authors: Thorarinn Arni A Bjarnason, Mary Sarrazin, Yubo Gao, Saket Girotra
Journal: Circulation (2021)

Introduction: Percutaneous ventricular assist devices (PVAD) have begun to replace intra-aortic balloon pumps (IABP) for hemodynamic support during high-risk percutaneous coronary intervention (PCI) procedures even though data on effectiveness of PVAD compared to IABP for hard clinical endpoints remains limited. We examined variation in utilization of PVADs during PCI across U.S. markets and identify factors associated with PVAD utilization. Methods: Using 2013-2017 MEDPAR data, we identified all patients aged 65 years or older who underwent PCI with placement of either a PVAD or an IABP on the same date as the PCI procedure. The primary outcome was 30-day mortality. We used hospital referral region (HRR) to define regional healthcare markets with geographic contiguity. We examined variation in utilization of PVADs across HRRs and examined patient- and market-level characteristics across HRR quartiles of PVAD utilization. Using multilevel models, we examined the association of market-level factors with utilization of PVADs and whether higher utilization of PVADs was associated with lower risk of 30-day mortality at a market-level. Results: A total of 52,755 patients underwent inpatient PCI with either an IABP (36,260 [68.7%]) or PVAD (16,495 [31.3%]). There was a significant increase in the proportion of PCI procedures with PVAD (17% in 2013 to 46% in 2017), with a corresponding decrease in IABP (83% to 54%; P&lt;.0001 for both). There was large variation in PVAD utilization across markets (0% to 84%), which persisted even after adjustment for differences in patient characteristics (adjusted median OR of 2.19; 95% CI: 2.03-2.35). Markets in the highest quartile of PVAD utilization were larger with a higher number of hospitals and had more market-level competition compared to markets in the lowest quartile of PVAD utilization. Greater utilization of PVAD at the market-level was not associated with lower risk-adjusted 30-day mortality. Conclusions: Utilization of PVADs for PCI in the U.S. continues to increase with marked variation in PVAD use across U.S. healthcare markets. Although patient- and market-level factors were associated with use of PVADs at the market-level, greater market utilization of PVADs was not associated with lower 30-day mortality.
Anti‐PD‐L1 DNAzyme Loaded Photothermal Mn<sup>2+</sup>/Fe<sup>3+</sup> Hybrid Metal‐Phenolic Networks for Cyclically Amplified Tumor Ferroptosis‐Immunotherapy
Authors: Peng Liu, Xinyi Shi, Ying Peng, Jianming Hu, Jinsong Ding, Wenhu Zhou
Journal: Advanced Healthcare Materials (2021)

Abstract Ferroptosis can activate immune response via inducing tumor cells immunogenic cell death (ICD), and antitumor immunity in turn boosts the efficacy of ferroptosis by excreting interferon gamma (IFN‐ γ ), which shows a promising combo for synergistically amplified tumor treatment. However, their combination is strictly limited by the complexity of tumor microenvironment, including poor ferroptosis response and immunosuppressive factors in tumor. Herein, a metal‐phenolic networks (MPNs) nanoplatform with all‐active components is constructed to favor the ferroptosis‐immunotherapy cyclical synergism. The photothermal MPNs are assembled via coordination between tannic acid (TA) and metal‐ion complex of Fe 3+ /Mn 2+ , through which a PD‐L1 inhibiting DNAzyme (DZ) is loaded to regulate the immunosuppressive PD‐1/PD‐L1 pathway. After intracellular delivery, each component of MPNs exerts their respective functions: Fe 2+ is in situ generated from Fe 3+ by TA reduction to trigger ferroptosis, while DZ is activated by Mn 2+ to effectively silence PD‐L1. With external laser irradiation, photothermal therapy is initiated to synergize with ferroptosis for enhanced ICD, which induces strong antitumor immunes. Combined with DZ‐mediated PD‐L1 suppression, a cyclically amplified tumor ferroptosis‐immunotherapy is achieved, resulting in obliteration of both primary and distant tumor. This work provides a smart, simple, yet robust nanomedicine‐based combination for self‐amplified tumor treatment.
TMOD-09. CREATION OF A P53-INDEPENDENT IN VITRO AND IN VIVO MODEL SYSTEM FOR THE STUDY OF H3.1K27M DIPG
Authors: Joseph Lagas, Lihua Yang, Oren Becher, Joshua Rubin
Journal: Neuro-Oncology (2021)

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating pediatric high-grade glioma that occurs in the brainstem with a median survival of less than 1 year. A greater understanding of the early tumorigenic events is essential for the development of effective therapeutics. DIPG is characterized by founder mutations in histone H3, either H3.1K27M or H3.3K27M. These mutations cause global hypomethylation, resulting in aberrant gene expression. It is unknown how this mechanism contributes to tumorigenesis. Interestingly, H3.1K27M DIPG show an increased incidence in females, whereas H3.3K27M DIPG shows no sex difference. This illustrates that the tumorigenic potential of H3.1K27M may be different between the sexes. Few models of DIPG incorporate the study of H3.1K27M despite the fact that it represents a unique opportunity to obtain valuable information on the tumorigenesis of DIPG through the study of the sex difference. Thus, we have created an in vitro and in vivo model system for H3.1K27M DIPG utilizing the RCAS mouse model system. This system utilizes RCAS vectors and a RCAS-ntva transgenic mouse line to deliver specific mutations to nestin expressing cells in the brainstem, including oligodendrocyte progenitor cells (OPCs), the predicted cell of origin. Delivering H3.1K27M, ACVR1 R206H, and PDGFaa at postnatal day 7 produces DIPG-like tumors in vivo, confirmed by H and E staining, between 60 – 110 days post injection. Additionally, confirmed through immunofluorescence staining, we can isolate a pure population of OPCs via immunopanning and infect them with RCAS vectors in vitro to produce stable expression of H3.1K27M. Introduction of H3.1K27M alone into male and female OPC cultures provides an opportunity to compare the early tumorigenic effects of H3.1K27M between the sexes in vitro. These results demonstrate that we have created an in vitro and in vivo H3.1K27M DIPG model system for the study of sex differences and tumorigenesis in DIPG.
Racial and Ethnic Differences in Clonal Hematopoiesis, Tumor Markers, and Clinical Outcomes of Patients with Multiple Myeloma
Authors: Nancy Gillis, Lauren C Peres, Christelle M Colin-Leitzinger, Mingxiang Teng, Raghunandan Reddy Alugubelli, Gabriel De Avila, Dongliang Du, Erin M Siegel, Jamie Teer, Oliver Hampton, Melissa Alsina, Jason Brayer, Brandon J. Blue, Ariosto Siqueira Silva, Rachid Baz, Taiga Nishihori, Kenneth H. Shain
Journal: Blood (2021)