Deep learning is widely applicable to phenotyping embryonic development and disease

Genome editing simplifies the generation of new animal models for congenital disorders. However, the detailed and unbiased phenotypic assessment of altered embryonic development remains a challenge. Here, we explore how deep learning (U-Net) can automate segmentation tasks in various imaging modalities, and we quantify phenotypes of altered renal, neural and craniofacial development in Xenopus embryos in comparison with normal variability. We demonstrate the utility of this approach in embryos with polycystic kidneys (pkd1 and pkd2) and craniofacial dysmorphia (six1). We highlight how in toto light-sheet microscopy facilitates accurate reconstruction of brain and craniofacial structures within X. tropicalis embryos upon dyrk1a and six1 loss of function or treatment with retinoic acid inhibitors. These tools increase the sensitivity and throughput of evaluating developmental malformations caused by chemical or genetic disruption. Furthermore, we provide a library of pre-trained networks and detailed instructions for applying deep learning to the reader's own datasets. We demonstrate the versatility, precision and scalability of deep neural network phenotyping on embryonic disease models. By combining light-sheet microscopy and deep learning, we provide a framework for higher-throughput characterization of embryonic model organisms. This article has an associated 'The people behind the papers' interview

RE: Kalp cerrahisi sonrasi AF gelişme riski

[No abstract available

Increased epicardial adipose tissue thickness is correlated with ascending aortic diameter

PubMed: 22343433Epicardial adipose tissue (EAT), localized beneath the visceral pericardium, is a metabolically active endocrine and paracrine organ with possible interactions within the heart. Recent studies identified possible roles of uric acid (UA)-induced oxidative stress and increased inflammatory status in the pathogenesis of ascending aortic dilatation. The aim of this study was to investigate whether EAT is an independent factor for ascending aortic dilatation. The patients were evaluated by a complete transthoracic echocardiographic examination including measurements of EAT and aortic dimensions. Serum levels of UA and C-reactive protein and EAT thicknesses were compared in 38 patients with dilated ascending aorta (DAA) (the diameter ? 37 mm) vs. 107 subjects with normal aortic diameter (AD) of < 37 mm. EAT thickness was significantly higher in DAA group compared to normal AD group (8.3 ± 2.7 vs. 5.4 ± 2.2 mm, p < 0.001) as well as age (53 ± 10 vs. 48 ± 9 years, p = 0.004), the presence of hypertension (54% vs. 30%, p = 0.009) and UA levels (6.0 ± 1.4 vs. 5.2 ± 1.1 mg/dL, p < 0.001). There was a strong correlation between EAT thickness and ascending aortic diameter (r = 0.521, p < 0.001). In multiple logistic regression analysis, EAT thickness (OR: 1.429, p = 0.006), body mass index (OR: 1.169, p = 0.014) and UA levels (OR: 1.727, p = 0.023) were independently correlated to ascending aortic dilatation. We therefore propose that increased EAT thickness is an independent predictor of ascending aortic dilation. © 2012 Tohoku University Medical Press

Increased serum resistin levels in patients with coronary slow-flow phenomenon

PubMed: 23400345Background. Slow coronary flow (SCF) is an angiographic finding characterized by delayed opacification of the epicardial coronary arteries without obstructive coronary disease. Resistin, an adipocytokine, plays a major role besides low-grade inflammation in atherosclerotic vascular processes and may be of importance in other coronary pathologies such as SCF. Methods. The present study was cross-sectional and observational, consisting of 70 individuals who underwent coronary angiography and had angiographically normal coronary arteries of varying coronary flow rates. The study included 50 patients with isolated SCF and 20 control participants with normal coronary flow (NCF). Results. There were no statistically significant differences between the SCF and NCF groups with respect to age, gender, presence of hypertension or diabetes mellitus, and smoking habit, except for increased creatinine levels (p=0.014). The serum resistin level was significantly higher in the SCF group than in the NCF group (8.4±7.2 vs. 5.4±2.6 ng/ml, p=0.014). Ln-transformed resistin levels correlated positively with left anterior descending (LAD) coronary artery TIMI frame count (TFC) (r=0.408, p<0.001) as well as with glucose (r=0.340, p=0.004), creatinine (r=0.248, p=0.044), and C-reactive protein (CRP; r=0.283, p=0.023) levels, and negatively with LAD coronary flow velocity (r=-0.314, p=0.009). When multivariate analyses were performed, in linear regression analysis, ln-resistin was associated with a longer TFC [beta (standardized regression coefficient): 0.404, p=0.001] and lower coronary flow velocity (beta: -0.280, p=0.035); in logistic regression analysis, ln-resistin was an independent predictor of the presence of SCF (OR: 6.692, 65%CI: 1.117-40.1, p=0.037). Conclusion. We demonstrated, for the first time, a significant increase in serum resistin levels in patients with SCF compared to subjects with NCF. We believe that further studies are needed to clarify the role of resistin in patients with SCF. © Urban & Vogel 2013

Increased epicardial adipose tissue in patients with isolated coronary artery ectasia

PubMed: 22504235Background Epicardial adipose tissue (EAT), localized beneath the visceral pericardium, is a metabolically active endocrine and paracrine organ with possible interactions within the heart. Coronary artery ectasia (CAE) is a clinical entity characterized with localized or diffuse dilatation, of the coronary arteries, with a diameter of greater than 1.5 times that of adjacent segments. Although the etiopathogenesis is not clearly understood, some studies have revealed that CAE may be a form of atherosclerosis that has greater inflammatory properties than atherosclerosis. The goal of this study was to investigate whether EAT and the level of C-reactive protein (CRP) are increased in patients with isolated CAE compared to normal subjects. Methods Thirty-three patients with isolated CAE (mean age: 57±9 years) and 32 age- and gender-matched control participants with NCA, but without CAE (mean age: 56±10 years), were included in the study. The relationship between EAT thickness, CRP levels and the presence of CAE was investigated. Results Epicardial adipose tissue thickness was significantly higher in CAE group compared to NCA group (7.2±3.2 vs. 4.7±2.1 mm, p<0.001). Body mass index (BMI, p=0.013), CRP (p=0.047), and the percentage of isolated CAE (p=0.012) were significantly higher in patients with an increased EAT thickness. While CRP correlated with increased EAT, it was not related to CAE. However, CRP levels were higher in patients with diffuse coronary ectatic involvement than the focal lesions (0.58±0.32 vs. 0.31±0.11 mg/dL, p=0.046). When we performed multiple logistic regression analysis, only increased EAT thickness was related to CAE independent of CRP and BMI (OR: 1.442, 95%CI: 1.066-1.951, p=0.018). Conclusion This is the first study, displaying a significantly higher EAT-thickness in patients with isolated CAE. We believe that further studies are needed to clarify the role of adipose tissue in patients with isolated CAE. © 2012 The Japanese Society of Internal Medicine

Alanin aminotransferaz düzeyleri ve monosit sayısı primer perkutan koroner girişim ile başarılı TIMI-3 koroner akım sağlanan ST yükselmeli miyokard infarktüsünde 30 Günlük sonuçları bağımsız olarak öngörür

Aim: To investigate the relationship of various hematological and biochemical parameters besides the cardiac enzymes with 30-day outcomes in patients with successfully restored coronary TIMI-3 flow by primary percutaneous coronary intervention (p-PCI). Materials and methods: Two hundred patients with ST elevation myocardial infarction (STEMI), with no history of prior myocardial infarction (MI), who underwent p-PCI and had TIMI-3 flow, were enrolled, consecutively. The primary endpoint of the study was defined as the composite of death, fatal and non-fatal MI, target vessel revascularization and cerebrovascular event. Results: Only ALT concentration (OR: 1.010, 95% CI: 1.003-1.018, P = 0.008), monocyte count (OR: 1.002, 95% CI: 1.001 - 1.004, P = 0.005), hypertension (OR: 3.010, 95% CI: 1.081 - 8.384, p = 0.035) and lower LVEF (OR: 0.926, 95% CI: 0.875 - 0.981, P = 0.008) were independent predictors of primary endpoint in multivariate logistic regression analysis. Conclusion: We found that elevated liver enzymes as determined by serum Alanine aminotransferase levels and monocyte count as well as hypertension and lower LVEF independently predicted 30-day outcomes in patients with successfully restored coronary flow by p-PCI. These parameters may provide new aspects, to identify the pathophysiology and prognosis of acute vascular events, which in turn may facilitate discovery of new treatment modalities. © 2012 Düzce Medical Journal

Relationship of fragmented QRS with prognostic markers and in-hospital MACE in patients undergoing CABG

PubMed: 22185330Background. Fragmented QRS complex (fQRS) is associated with increased morbidity and mortality, sudden cardiac death and recurrent cardiovascular events. However, its prognostic role has not been studied comprehensively in patients undergoing coronary artery bypass graft (CABG) surgery. In this study, we investigated the relationship between the presence of fQRS, and the prognostic markers and in-hospital major adverse cardiovascular events (MACE). Methods. Two hundred and forty two eligible patients who underwent CABG surgery at our institution were enrolled consecutively. In analysis of fragmentations on electrocardiograms, presence of fQRS was defined as various RSR? patterns (? 1 R? or notching of S wave or R wave) with or without Q waves without a typical bundle-branch block in two contiguous leads corresponding to a major coronary artery territory. MACE was defined as cardiac death, recurrent myocardial infarction, heart failure, cerebrovascular event, sustained ventricular tachycardia or fibrillation. Results. Patients with fragmented QRS had older age (64 ± 10 vs. 61 ± 9 years, p = 0.03), prolonged QRS time (99 ± 11 vs. 87 ± 11 ms, p < 0.001), higher rate of Q wave on ECG (29% vs. 12%, p = 0.001), higher European system for cardiac operative risk evaluation (EUROSCORE) (4.0 ± 1.9 vs. 2.6 ± 1.6, p < 0.001) and lower left ventricular ejection fraction (LVEF)% (43 ± 12 vs. 60 ± 12, p < 0.001) in comparison to patients with non-fragmented QRS. In addition, the patients with fQRS had longer cross-clamp time (67 ± 23 vs. 55 ± 20 minutes, p = 0.001) and extracorporeal circulation (105 ± 31 vs. 91 ± 30 minutes, p = 0.003), increased inotropic usage (p < 0.001) and prolonged cardiac surgery intensive care unit (53 ± 25 vs. 35 ± 12 hours, p < 0.001) and in-hospital stay after CABG. Conclusion. FQRS may have additional value in the assessment of cardiac function and in prediction of intra- and post-operative hemodynamic instability and adverse cardiovascular events. Fragmentations on admission ECG may be useful for identifying patients with higher risk who will need additional support after CABG surgery. © 2012 Informa Healthcare

Relationship of fragmented QRS complexes with inadequate coronary collaterals in patients with chronic total occlusion

PubMed: 22498998BACKGROUND: Fragmented QRS (fQRS) complexes are defined as various RSR? patterns (?1 R? or notching of S wave or R wave) in two contiguous leads corresponding to a major coronary artery territory. In previous studies, fQRS has been associated with increased morbidity and mortality, sudden cardiac death and recurrent cardiovascular events (CVEs). The causative relationship between fQRS and cardiac fibrosis has been shown in prior studies. The association between inadequate (poor) coronary collaterals and presence of fQRS has not comprehensively been studied in patients with chronic total occlusion (CTO) until now. We tested the hypothesis that the presence of fQRS is associated with inadequate coronary collateral growth. METHODS: This study had a cross-sectional observational design. The study population consisted of patients who underwent coronary angiography with the suspicion of coronary artery disease at our institution in an outpatient manner. Patients who had CTO in at least one major epicardial coronary artery were included. Coronary angiograms of 148 eligible patients from our database were analyzed again. Ninety-three patients had good and 55 had poor collateral development according to the Cohen-Rentrop method. RESULTS: Patients with poor collateral development had higher plasma glucose (130±54 vs. 116±33mg/dl, P=0.047) and an older age (65±10 vs. 61±10years, P=0.042) in comparison to patients with good collateral growth. The presence and number of fQRS were higher in the poor collateral group than the good collateral group (64 vs. 32%, P<0.001 and 2.3±2.4 vs. 1.2±2.0, P=0.002, respectively). Left ventricular ejection fraction was significantly lower in the poor collateral group than the good collateral group (45±11 vs. 51±13, P=0.014). There was a significant correlation between number of fQRSs and the echocardiographic wall-motion abnormality score (r=0.662, P<0.001). In multivariate analysis, only the presence of fQRS was independently related to poor collateral development (odds ratio, 3.559; 95% confidence interval, 1.708-7.415, P=0.001). CONCLUSION: We found that fQRS was independently related to inadequate coronary collaterals in patients with CTO. fQRS, which may be derived from the effects of myocardial ischemia or scar on myocardial electricity at the cellular level, can represent inadequate coronary collateral development in patients with CTO. © 2012 Italian Federation of Cardiology

Increased carotid and brachial intima-media thickness is related to diffuse coronary involvement rather than focal lesions

PubMed: 22584246We evaluated whether an increased carotid intima-media thickness (cIMT) and brachial artery IMT (bIMT) are related to diffuse coronary involvement rather than focal lesions. Patients (n = 88) with at least 1 significant lesion of the main epicardial coronary arteries (?50%) were included in the present study. We used a novel score based on length and mean narrowing of all lesions in order to predict diffuse coronary involvement. Both cIMT and bIMT were higher in patients with long coronary lesion than focal lesion (P <.001). The patients with long coronary lesion had a higher rate of total coronary involvement than patients with focal lesion (P <.001). The cIMT had a higher correlation with total atherosclerotic burden in the coronary vasculature (r =.495, P <.001) and the longest lesion length (r =.489, P <.001) than cardiovascular risk factor score (r =.453, P <.001 and r =.324, P =.012, respectively). These findings may be valuable for clarifying the prognostic value of IMT measurements. © The Author(s) 2012

Relationship of fragmented QRS with prognostic markers and long-term major adverse cardiac events in patients undergoing coronary artery bypass graft surgery

PubMed: 25545656Background: Fragmented QRS (fQRS) complex is associated with increased sudden cardiac death, recurrent cardiovascular events, morbidity and mortality. However, the prognostic role of fQRS has not been comprehensively studied in patients undergoing coronary artery bypass graft (CABG) surgery. In this study, we planned to investigate the relationship of fQRS with prognostic markers and long-term major adverse cardiovascular events (MACEs) following isolated CABG surgery. Methods: Two hundred and thirteen patients who underwent CABG surgery at our institution were enrolled consecutively. MACE was defined as cardiac death, recurrent myocardial infarction, decompensated heart failure and re-hospitalization. The patients were followed up for a mean duration of 26±10 months for MACE. Results: Patients with fQRS had a higher rate of Q wave on ECG (30 vs. 10%, P100 ms) (OR 3.898, 95% CI 1.463-10.39, P=0.007) were the only independent predictors of long-term MACE in multivariate logistic regression analysis. However, QRS duration had a better association with MACE than the presence of fQRS. Conclusion: fQRS and prolonged QRS duration may have an additional value in predicting cardiac status and long-term prognosis. Fragmentations on admission ECG and prolonged QRS duration may be useful for identifying patients with higher long-term risk who will need more intense treatment and close follow-up after CABG surgery. © 2015 Wolters Kluwer Health, Inc. All rights reserved