tbuckley/cabot-search huggingface dataset:
Abstract 16017: Anatomically-Guided Deep Learning (DL) Approach to Late Gadolinium Enhanced (LGE)-CMR Left Ventricle (LV) Segmentation Enables Efficient and Accurate Clinical Analyses
Authors: Haley G Abramson, Dan M Popescu, Rebecca Yu, Changxin Lai, Julie K Shade, Katherine C Wu, Mauro Maggioni, Natalia A Trayanova
Journal: Circulation (2020)

Rationale: LV segmentation is crucial to analyzing heart pathologies. DL applications for LGE-CMR image segmentation offer automation and reliability over costly feature learning and manual input. However, existing DL algorithms suffer from poor quality and quantity of training data, lack of clinical relevance in evaluation methods, and low generalizability. Objective: We propose a neural network approach to LV segmentation with superior performance and ensured anatomical fidelity on various imaging protocols and patient populations, with direct clinical evaluation via LV volume calculation and ventricular arrhythmia (VA) risk assessment. Methods: We train a multistage network for LV segmentation on 4,000 LGE-CMR (PROSe-ICD study) and cine (MICCAI 2009 and 2017 datasets) short-axis images, where cine scans augment the data via a cine-to-LGE style transfer. At testing, images enter a network that crops and refines the region-of-interest (fig. 1A), which is fed into a network for differentiation of viable and hyper-enhanced myocardium (fig. 1B). An autoencoder network takes the union of these images, encodes them to a densely populated, reduced space, finds the nearest neighbor, and decodes them to anatomically correct segmented scans (fig. 1C). To assess VA risk, we fit a Cox regression model to survival data with image features (ex. LV volume) from manual or predicted segmentations. Results: Our segmented LGE-CMR scans (0.81 Dice score) surpass an inter-observer Dice score of 0.76, upholding anatomical guidelines across ambiguous regions such as apex and base (fig. 1D). Differences in calculated LV volumes (accuracy 98.4%, precision 78.9%) and C-indices of Cox regression models that stratify VA risk using automatic versus manual segmentations (0.62 vs. 0.60) show no statistical significance. Conclusion: We developed a DL LV segmentation algorithm tailored to clinical application, ensuring relevant predictions and outperforming inter-observed Dice scores.
Abstract 15577: Mst 4, a Novel Stripak Associated Kinase is Upregulated in Human Cardiomyopathy and Regulates Cardiomyocyte Hypertrophy, Contractility and Apoptosis
Authors: Matthias Eden, Marius Leye, Christin Tannert, Norbert Frey
Journal: Circulation (2020)

Heart failure is one of the major causes of death worldwide. Its pathophysiology is complex and involves alterations in calcium cycling and hypertrophic signaling, as well as subsequent loss of cardiomyocytes due to apoptosis, cardiac fibrosis and progressive contractile dysfunction. The Striatin-interacting phosphatase and kinase (STRIPAK) complex is a mammalian multiprotein complex that consists of phosphatases, kinases and various adaptor proteins. Yet, the STRIPAK complex has so far not been studied in cardiomyocytes. Now we show in cardiomyocytes that the STRIPAK associated kinase MST4 directly interacts with a recently described novel cardiac STRIPAK protein, Myoscape/STRIP2. Multi tissue immunoblot experiments showed that Mst4 abundance is also highly enriched in heart and skeletal muscle. Immunoblot analyses in human biopsy samples form patients with dilated (DCM n=10) or ischemic cardiomyopathy (ICM n=10) revealed that MST4 is strongly upregulated in DCM (12-fold p&lt;0.001) and ICM (9.6 fold p&lt;0.05) vs. controls. Conversely, upon biomechanical stretch we observed a significant downregulation of MST4 in vitro by 30% (p&lt;0.05) as well as in vivo (-45%, n=6; P&lt;0.001) in a murine model for pressure overload (experimental aortic constriction, (TAC) vs. Sham) under Moreover, we also observed downregulation of MST4 in a porcine myocardial infarction model (-48% vs. porcine controls; n=5 p&lt;0.05). Adenoviral overexpression of MST4 in NRVCM results in significant cellular hypertrophy (485μm2 vs 421μm2; p&lt;0.001) compared to LacZ. Overexpression of MST4 also increases cellular and sarcomeric fractional shortening in adult rat cardiac myocytes vs. LacZ (p&lt;0.05). Finally, MST4 overexpression also protects from cardiac apoptosis as shown by 90% reduced PARP cleavage as well as significantly reduced expression of Caspase 3 and 7 (n=3; p&lt;0.05). Taken together we show that MST 4 is a cardiac enriched Kinase that regulates cardiomyocyte hypertrophy, contractility and apoptosis and may thus be a target for future therapeutic intervention
Joachim Robert Kalden: one of the founders of autoimmunity research and immunotherapy
Authors: Gerd R Burmester, Bernhard Manger, Georg Schett, Hendrik Schulze-Koops
Journal: Annals of the Rheumatic Diseases (2021)

Born in Marburg in 1937, Joachim (Jochen) R Kalden studied medicine in Freiburg, Marburg and Tubingen. He developed his passion for immunology early on: ‘The immunological histamine release in the diagnosis of drug allergic conditions’, was the title of his doctoral thesis in 1966, and it was the first testimony to his occupation with immunology, his later great professional love. Always at the forefront of research, he developed this passion with his characteristic great curiosity and visionary power over many decades. As a postdoctoral fellow in the Department of Therapeutics at the University of Edinburgh, he was deeply involved in the scientific basis of immunopathogenesis of autoimmune diseases with a then very novel idea: autoantibodies were responsible for the development of myasthenia gravis, an autoimmune disease of the neuromuscular endplate. He was dedicated to find new methods to detect such autoantibodies to open diagnostic and, more importantly, therapeutic opportunities. This was the temptation that drove him throughout his life: to develop methods based on an understanding of the pathophysiology of autoimmune diseases that could be used to precisely intervene into their disease processes. This concept is the basis of modern therapy of inflammatory rheumatic diseases and the concept to induce remission, which is intensively connected with Joachim R Kalden as a worldwide appreciated, extremely active protagonist.

Joachim R Kalden received his clinical training in Hannover, Germany, as an assistant in the Division of Clinical Immunology at the Department of Internal Medicine at the Hannover Medical School, which had just been founded and had set itself the goal of promoting innovative approaches in teaching and research. His mentor, Helmut Deicher, had discovered the anti-DNA antibodies in parallel to Maxime Seligmann, Paris, when he was a …
Abstract MP60: Blood Pressure Variability And Risk Of Heart Failure In Postmenopausal Women. Results From The Women's Health Initiative.
Authors: Bernhard Haring, Rebecca Hunt, JoAnn Manson, Michael J Lamonte, Liviu Klein, Matthew A Allison, Robert A Wild, Robert B Wallace, Aladdin Shadyab, Khadijah Breathett, Charles B Eaton, Sylvia W Wassertheil-smoller, Daichi Shimbo
Journal: Circulation (2021)

Introduction: Little is known about the relationships between visit-to-visit BPV and HF sub-phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). The aim of this analysis was to investigate the relationship of visit-to-visit systolic and diastolic BPV and risk of HF subtypes HFrEF and HFpEF in a large cohort of postmenopausal women. Hypothesis: We hypothesized that greater systolic and diastolic BPV would be associated with a higher risk for HFrEF and HFpEF. Methods: This study consisted of 23,918 postmenopausal women aged 50-79 enrolled in the Women’s Health Initiative Hormone Therapy Trials. Blood pressure (BP) was measured at baseline (1993-1998) and then annually through 2005 by trained clinical staff. Variability was defined as the standard deviation of the mean BP across visits (SDm). The outcome was first HF hospitalization, which was adjudicated by physician review of medical records. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for HF endpoints with adjustments for demographic, medical history, lifestyle factors, antihypertensive medication use, mean systolic and diastolic BPs, and time-varying coronary events interim to HF hospitalization. Results: During a mean follow-up of 15.8 years, 913 incident cases of HFpEF and 421 cases of HFrEF were identified. In fully adjusted models, women in the highest quartile of SDm for systolic blood pressure were at higher risk of HFpEF [HR (95% CI): 1.61, 95% confidence interval: 1.12, 2.31)], but not HFrEF [1.18 (0.70,1.96)] compared to women in the lowest quartile of SDm. Higher SDm for diastolic blood pressure was not related to HFpEF [1.19 (0.85,1.65)] or HFrEF [1.56 (0.89,2.74)]. Conclusions: Greater systolic BPV was associated with a higher risk of HFpEF independent of mean blood pressure and coronary events interim to HF hospitalization. These findings suggest that control of BPV may be a relevant target for the prevention of HFpEF in postmenopausal women.
춘계학술대회 : 구연 ; 전골수세포와 간엽줄기세포에서 기능성 간세포로의 분화
Authors: 배시현, 윤승규, 양연주, 장우임, 남순우, 최종영, 한남익, 안병민, 최상욱, 이창돈, 선희식, 김부성
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 골수에 존재하는 조혈모 줄기세포(hematopoietic stem cell)와 간엽 줄기세포(mesenchymal stem cell)는 자가재생(selfrenewal) 능력을 가지면서 다양한 종류의 세포로 분화 가능성을 지니는 성체줄기세포 (adult stem cell)로 알려져 있다. 본 연구에서는 전골수(whole bone marrow) 세포와 간엽줄기(mesenchymal stem) 세포를 배양조건에 따라 기능성 간세포로 분화 가능성을
Abstract P187: Analysis Of Online Information On Lifestyle Modification For Post-Myocardial Infarction Patients
Authors: Jooyoung Moon, Hanna Moon
Journal: Circulation (2021)

Background: With continual advancement of treatment modalities, uncomplicated myocardial infarction (MI) patients are being discharged after only one to two days of hospitalization. Though patient education routinely takes place prior to discharge, patients often rely on online information for further guidance. This study aimed to analyze the content and variability of information regarding lifestyle modification for post-MI patients on the internet. Methods: The lay terms 'lifestyle changes after heart attack' were queried using the Google search engine. The first 100 websites were reviewed by two independent investigators. Websites were categorized as either professional or informational depending on the target audience, with the former written for healthcare professionals and the latter for average consumers. Websites that were personal, non-accessible, required payments for access, or included videos were excluded. Statistical analyses were performed using the chi-squared test and Fisher's exact test with significance level set at p&lt;0.05. Results: A total of 86 websites (49 professional, 37 informational) met our inclusion criteria. The most frequently addressed changes were exercise (86.0%), nutrition (82.6%), smoking cessation (74.4%), mental health (50.0%), weight loss (38.4%), risk factor control (36.0%), adherence to cardiac rehabilitation (30.2%), compliance to prescribed medications (26.7%), alcohol abstinence (20.9%), and compliance to follow-up visits (11.6%). Smoking cessation was addressed significantly more often on informational websites (p=0.025), while alcohol abstinence was addressed significantly more often on professional websites (p=0.003). Conclusions: This study demonstrates the variability in information that post-MI patients will encounter on the internet. As it is difficult for patients to determine the credibility of different websites, it is crucial that online resources provide a full range of necessary information for their readers.
Abstract 12541: Left Atrial Cardiomyopathy and Associations With Left Atrial Structure and Function
Authors: Christopher Madison, Colby Ayers, Ambarish Pandey, David McNamara
Journal: Circulation (2020)

Introduction: Abnormally negative P-wave terminal force in lead V1 (aPTFV1 &lt;-5000μV*ms) is an electrocardiographic marker of left atrial (LA) myopathy and is associated with an increased risk of stroke, independent of atrial fibrillation. Whether the LA myopathy associated with aPTFV1 is associated with LA structural/mechanical dysfunction is unknown. Hypothesis: aPTFV1 is positively correlated with markers of LA mechanical dysfunction including LA end diastolic volume (LAEDV), systolic volume (LAESV), and ejection fraction (LA EF). Methods: Dallas Heart Study participants free of atrial fibrillation with concomitant cardiac MRI (CMR) and ECG were included. Participants were categorized as aPTFV1, defined as &lt;-5000μV*ms, or normal PTFV1 (nPTFV1). Demographics, established cardiovascular risk factors, and CMR markers of LA and LV structure/function were compared. Multivariable forward step-wise logistic regression models tested the association of aPTFV1 with the univariate variables (p&lt;0.1 for entry/exit). Results: Among 1,880 participants, 214 had an aPTFV1. Participants with aPTFV1 were more likely to be older, black, and have traditional atherosclerotic risk factors including hypertension, diabetes, smoking, and prior stroke (Table 1). aPTFV1 was associated with larger LAEDV and LAESV, and lower LA EF. Multivariable regression models demonstrated increased LV mass, but no markers of LA structural or mechanical dysfunction were associated with an aPTFV1. Modeling explained little of the variability in PTFV1 (cumulative R 2 = 0.03). Conclusions: In a large, multi-ethnic cohort, important differences in traditional cardiovascular risk exist between aPTFV1 and nPTFV1; however, cardiac MRI-derived LA structure/function explain very little of the variability in PTFV1. These data suggest the LA cardiomyopathy associated with aPTFV1 may be a manifestation of electrical rather than structural/mechanical dysfunction.
Abstract 15343: Increasing Left Ventricular Mass is Associated With Greater Microvascular Obstruction During ST-elevation Myocardial Infarction
Authors: Nicole L Bonfig, Chase R Soukup, Ross F Garberich, Sarah J Davidson, Rose M Peterson, Christian W Schmidt, Jay H TRAVERSE
Journal: Circulation (2020)

Introduction: The development of microvascular obstruction (MVO) in the setting of ST-Elevation Myocardial Infarction (STEMI) is a powerful predictor of reduced left-ventricular (LV) function, adverse LV remodeling and increased mortality. Although MVO is associated with increasing infarct size and ischemic duration, additional causes of MVO have not been clearly identified. Although MVO may arise from intravascular obstruction from embolization of thrombus, it may also arise from compression of the microvasculature due to increased myocardial edema and extravascular compressive forces. Hypothesis: Because left-ventricular hypertrophy (LVH) is associated with increased extravascular compressive forces, we hypothesized that patients with greater LV mass may be more susceptible to the development of MVO during STEMI. Methods: We measured MVO in 385 patients (59.4 + 12.3 years; 77% male) admitted to our Institution with STEMI who underwent cardiac MRI for measurement of LV function and infarct size following successful primary PCI. A total of 219 patients (57%) had MVO on cardiac MRI measured 1-3 days following PCI of which 172 patients had paired measurements of LV mass. Results: Patients with MVO (13.7 + 13.9 grams) had significantly greater infarct size (54 vs. 31 g; p &lt; 0.001) and LV mass (151 vs 140 g; p&lt;0.01) but reduced LVEF (43.1 vs. 47.8%) despite having similar ischemic times. Among patients with MVO, there was a linear increase in MVO with increasing LV mass (Figure). Conclusions: MVO increases with increasing LV mass and may contribute to the known adverse effects of LVH in STEMI.
A phase 2 study of isatuximab monotherapy in patients with multiple myeloma who are refractory to daratumumab
Authors: Joseph Mikhael, Karim Belhadj-Merzoug, Cyrille Hulin, Laure Vincent, Philippe Moreau, Cristina Gasparetto, Ludek Pour, Ivan Spicka, Ravi Vij, Jeffrey Zonder, Djordje Atanackovic, Nashat Gabrail, Thomas G. Martin, Aurore Perrot, Samira Bensfia, Qilong Weng, Claire Brillac, Dorothée Semiond, Sandrine Macé, Kathryn P. Corzo, Xavier Leleu
Journal: Blood Cancer Journal (2021)
Spinal Cord Injury Repair: NSCs Migration Promoted and Drug Delivered Exosomes‐Collagen Scaffold via a Bio‐Specific Peptide for One‐Step Spinal Cord Injury Repair (Adv. Healthcare Mater. 8/2021)
Authors: Lulu Zhang, Caixia Fan, Wangping Hao, Yan Zhuang, Xiru Liu, Yannan Zhao, Bing Chen, Zhifeng Xiao, Yanyan Chen, Jianwu Dai
Journal: Advanced Healthcare Materials (2021)

To achieve one-step spinal cord injury (SCI) repairs, in article number 2001896 and Yanyan Chen, Jianwu Dai, and co-workers, a scaffold-retained paclitaxel-loaded exosome from mesenchymal stem cells (MExos) is established. Benefiting from the synergistic effects of endogenous NSCs recruitment and NSCs differentiation into neurons induced by MExos and paclitaxel respectively in the injured site, this multifunctional scaffold shows a superior performance for motor functional recovery after complete SCI in rats.
Abstract 13104: The Concomitant Inflammation Affect the Ratio of N-terminal Pro B-type Natriuretic Peptide to B-type Natriuretic Peptide in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Tsutomu Kawai, Takahisa Yamada, Tetsuya Watanabe, Shunsuke Tamaki, Shungo Hikoso, Daisaku D Nakatani, Masamichi Yano, Hayashi Takaharu, Akito Nakagawa, Yusuke Nakagawa, Yoshio Yasumura, Masatake Fukunami, Yasushi Sakata
Journal: Circulation (2020)

Backgrounds: Although B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP ) are interrelated parameters in assessment heart failure severity and prognosis, the ratio of NT-proBNP to BNP (NT-proBNP/BNP) are affected by various clinical factors, such as renal function. However, little is known about the influence of inflammation on NT-proBNP/BNP in patients with heart failure and preserved ejection fraction (HFpEF). Methods and Results: Patients data were extracted from PURSUIT-HFpEF registry, which is a multicenter prospective observational study including patients hospitalized for acute heart failure with left ventricular ejection fraction of &gt;50%. Of 871 patients, data of BNP and NT-proBNP was available in 654 patients. The median baseline concentration of BNP was 474 pg/ml (299-720), NT-proBNP was 3310 pg/ml (1740-6840), and NT-proBNP/BNP was 7.6 (5.0-11.8). In multivariable linear regression analyses, older age [odds ratio (OR); 1.05, 95% confidence interval (CI); 1.02-1.09, p=0.001], higher creatinine [OR; 2.63, 95% CI; 1.66-4.16, p&lt;0.001], and higher C-reactive protein (CRP) [OR; 1.17, 95% CI; 1.06-1.28, p&lt;0.001] were significantly associated with a higher NT-proBNP/BNP (&gt;median value of 7.6). However, other factors expected to affect NT-proBNP/BNP, such as atrial fibrillation and body mass index, were not associated with a higher NT-proBNP/BNP in this study. Patients in the highest CRP quartile had significantly higher NT-proBNP/BNP than those with other quartiles. Conclusion: In HFpEF patients, concomitant inflammation was associated with high NT-proBNP/BNP, which indicated that we need a careful interpretation on these two natriuretic peptides of patients with HFpEF and inflammatory status, such as infection.
Abstract 16136: Underutilization of Appropriate Testing for Transthyretin Amyloidosis Despite Suspicious Clinical &amp; Echocardiographic Findings
Authors: Katelyn Young, Kinjal Banerjee, Maulin Patel, Sangeeta Prabhakar Bhat, Colin Reynolds, Christopher M Haggerty, Brendan Carry
Journal: Circulation (2020)

Introduction: Both hereditary (hATTR) and wild-type (wtATTR) transthyretin amyloidosis are under-recognized causes of cardiomyopathy (CM) and heart failure. Certain findings on Transthoracic Echocardiography (TTE) and cardiac Magnetic Resonance Imaging (cMRI) are suggestive but not diagnostic of ATTR. Although biopsy historically has been the gold standard for diagnosis, patients can be diagnosed with the highly sensitive and specific technetium-99m pyrophosphate scan (Tc-99m PYP). Genetic testing is recommended to confirm hATTR in patients diagnosed with ATTR cardiac amyloidosis. Despite growing awareness of this condition, many cases remain undiagnosed. This study evaluated if patients with TTEs concerning for infiltrative CM received appropriate diagnostic testing for ATTR-CM. Methods: Our echocardiography registry was queried from January 2011 to March 2020 for patients with our echo lab’s embedded infiltrative CM code. Data on demographics, comorbidities, TTE variables, cMRI results, PYP scans, genetic testing and biopsy results were retrieved from electronic medical records. Thorough manual chart review excluded other causes of CM. Data was expressed as mean ± SD and n (%). Results: We retrieved 510 patients (mean age 64 ± 16 years; 43% female) with TTEs suspicious for infiltrative CM revealing a mean interventricular septal diameter (IVSd) of 1.6 ± 0.3 cm. Only 67 (13%) patients underwent cMRI with 11 (16%) suggestive of cardiac amyloidosis. Of the patients with suspicious TTEs, 16 (3.1%) had PYP scans and 24 (4.7%) had tissue biopsy, with positive results in 7 (44%) and 11 (46%), respectively. Genetic testing in 31 (6%) patients revealed known hATTR mutations in 2 (6.5%) patients. Cardiac amyloidosis was diagnosed in 23 (4.5%) with 11 ATTR (2 hATTR), 5 amyloid light chain, and 7 unknown subtype. Conclusion: Despite clinical and TTE findings suspicious for ATTR-CM, many patients did not undergo appropriate confirmatory testing (see Figure 1).
Multiplexed detection and differentiation of bacterial enzymes and bacteria by color-encoded sensor hydrogels
Authors: Zhiyuan Jia, Mareike Müller, Tony Le Gall, Martijn Riool, Max Müller, Sebastian A.J. Zaat, Tristan Montier, Holger Schönherr
Journal: Bioactive Materials (2021)

We report on the fabrication and characterization of color-encoded chitosan hydrogels for the rapid, sensitive and specific detection of bacterial enzymes as well as the selective detection of a set of tested bacteria through characteristic enzyme reactions. These patterned sensor hydrogels are functionalized with three different colorimetric enzyme substrates affording the multiplexed detection and differentiation of α-glucosidase, β-galactosidase and β-glucuronidase. The limits of detection of the hydrogels for an observation time of 60 min using a conventional microplate reader correspond to concentrations of 0.2, 3.4 and 4.5 nM of these enzymes, respectively. Based on their different enzyme expression patterns,