JOSE EDUARDO KRIEGER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
22 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 22
- 2D Image-Based Atrial Fibrillation Classification(2021) DIAS, Felipe M.; SAMESIMA, Nelson; RIBEIRO, Adele; MORENO, Ramon A.; PASTORE, Carlos A.; KRIEGER, Jose E.; GUTIERREZ, Marco A.Atrial fibrillation (AF) is a common arrhythmia (0.5% worldwide prevalence) associated with an increased risk of various cardiovascular disorders, including stroke. Automated routine AF detection by Electrocardiogram (ECG) is based on the analysis of one-dimensional ECG signals and requires dedicated software for each type of device, limiting its wide use, especially with the rapid incorporation of telemedicine into the healthcare system. Here, we implement a machine learning method for AF classification using the region of interest (ROI) corresponding to the long DII lead automatically extracted from DICOM 12-lead ECG images. We observed 94.3%, 98.9%, 99.1%, and 92.2% for sensitivity, specificity, AUC, and F1 score, respectively. These results indicate that the proposed methodology performs similar to one-dimensional ECG signals as input, but does not require a dedicated software facilitating the integration into clinical practice, as ECGs are typically stored in PACS as 2D images.
- Variant genotypes associated with reduced expression of RhCE antigens among Brazilian blood donors(2021) DEZAN, Marcia Regina; OLIVEIRA, Valeria B.; CONRADO, Marina C. A. V.; ROCHA, Mateus Cardoso da; LUZ, Fabio; GALLUCCI, Antonio; PEREIRA, Alexandre C.; KRIEGER, Jose E.; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla LuanaBackground The genetic diversity of the RHCE gene locus has been explored in diverse populations of different racial backgrounds. Data referring to the diversity of RHCE encoding weakened expression of C, c, E, and e in multiethnic populations is still incomplete. Methods Samples from Brazilian blood donors presenting reduced expression of C, c, E, or e on gel method were selected for the study. All exons and flanking introns of RHCE were genotyped though direct Sanger sequencing for the included donors. Results Sixty-six donors were included: 23 with weak C, 22 with weak c, 6 with weak E, 14 with weak e, and 1 with weak c and E. Among the samples with weak C, the following altered RH*C were encountered: RHCE*CeMA (n = 3), RHCE*Ce941C (n = 1), and RHCE*CeVA (n = 1). RHD*D-CE(4-7)-D was detected in six cases, RHCE*CE was presumably present in five cases, and seven cases were unexplained. Two altered alleles underlay the weak c phenotype: RHCE*ceJAL (n = 20) and RHCE*ce340T (n = 2), and two altered RHCE justified weak e: RHCE*ceMO (n = 6) and RHCE*ceJAL (n = 8). Three variant RHCE were associated with weak E: RHCE*cEJU (n = 4), RHCE*cE382C (n = 1), and RHCE*cEIV (n = 1). The RHCE*cE905A justified one case of weak c and E. Conclusion We describe the distribution of RHCE variants found in association with weak expression of C, c, E, and e in blood donors of multiethnic origin, which differs in comparison to that previously reported for people of African or Caucasian descent.
- Focal adhesion signaling: Vascular smooth muscle cell contractility beyond calcium mechanisms(2021) RIBEIRO-SILVA, J. C.; MIYAKAWA, A. A.; KRIEGER, J. E.Smooth muscle cell (SMC) contractility is essential to vessel tone maintenance and blood pressure regulation. In response to vasoconstrictors, calcium-dependent mechanisms promote the activation of the regulatory myosin light chain, leading to increased cytoskeleton tension that favors cell shortening. In contrast, SMC maintain an intrinsic level of a contractile force independent of vasoconstrictor stimulation and sustained SMC contraction beyond the timescale of calcium-dependent mechanisms suggesting the involvement of additional players in the contractile response. Focal adhesions (FAs) are conceivable candidates that may influence SMC contraction. They are required for actin-based traction employed by cells to sense and respond to environmental cues in a process termed mechanotransduction. Depletion of FA proteins impairs SMC contractility, producing arteries that are prone to dissection because of a lack of mechanical stability. Here, we discuss the role of calcium-independent FA signaling mechanisms in SMC contractility. We speculate that FA signaling contributes to the genesis of a variety of SMC phenotypes and discuss the potential implications for mechanical homeostasis in normal and diseased states. ©2021 The Author(s).
- Automated radiographic bone suppression with deep convolutional neural networks(2021) CARDENAS, Diego Armando Cardona; FERREIRA JUNIOR, Jose Raniery; MORENO, Ramon Alfredo; REBELO, Marina de Fatima de Sa; KRIEGER, Jose Eduardo; GUTIERREZ, Marco AntonioDual-energy subtraction (DES) is a technique that separates soft tissue from bones in a chest radiograph (CR). As DES requires specialized equipment, we propose an automatic method based on convolutional neural networks (CNNs) to generate virtual soft tissue images. A dataset comprising 35 pairs of CR and its soft-tissue version split in training (28 image pairs) and testing (7 image pairs) sets were used with data augmentation. We tested two types of images: the lung region's cropped image and the segmented lung image. The ribs suppression was treated as a local problem, so each image was divided into 784 patches. The U-Net architecture was used to perform bone suppression. We tested two types of loss functions: mean squared error (L-mse) and L-sm, which combines L-mse with the structural similarity index measure (SSIM). Due to the patches overlapping, it was necessary to interpolate the gray levels on the reconstructed image from the predicted patches. Evaluations were based on SSIM and root mean square error (RMSE) over the reconstructed lung area. The combination that presented the best results used the loss L-sm and the segmented lung image as input to the U-Net (SSIM of 0.858 and RMSE of 0.033). We observed that the U-Net has poor performance when trained with cropped images containing all information from the chest cavity and how the loss using local information can improve CR rib bone suppression. Our results suggest that it is possible removing the rib bones accurately in CR using CNN and a patch-based approach.y
- Novel Chest Radiographic Biomarkers for COVID-19 Using Radiomic Features Associated with Diagnostics and Outcomes(2021) FERREIRA JUNIOR, Jose Raniery; CARDENAS, Diego Armando Cardona; MORENO, Ramon Alfredo; REBELO, Marina de Fatima de Sa; KRIEGER, Jose Eduardo; GUTIERREZ, Marco AntonioCOVID-19 is a highly contagious disease that can cause severe pneumonia. Patients with pneumonia undergo chest X-rays (XR) to assess infiltrates that identify the infection. However, the radiographic characteristics of COVID-19 are similar to the other acute respiratory syndromes, hindering the imaging diagnosis. In this work, we proposed identifying quantitative/radiomic biomarkers for COVID-19 to support XR assessment of acute respiratory diseases. This retrospective study used different cohorts of 227 patients diagnosed with pneumonia; 49 of them had COVID-19. Automatically segmented images were characterized by 558 quantitative features, including gray-level histogram and matrices of co-occurrence, run-length, size zone, dependence, and neighboring gray-tone difference. Higher-order features were also calculated after applying square and wavelet transforms. Mann-Whitney U test assessed the diagnostic performance of the features, and the log-rank test assessed the prognostic value to predict Kaplan-Meier curves of overall and deterioration-free survival. Statistical analysis identified 51 independently validated radiomic features associated with COVID-19. Most of them were wavelet-transformed features; the highest performance was the small dependence matrix feature of ""low gray-level emphasis"" (area under the curve of 0.87, sensitivity of 0.85, p<0.001). Six features presented short-term prognostic value to predict overall and deterioration-free survival. The features of histogram ""mean absolute deviation"" and size zone matrix ""non-uniformity"" yielded the highest differences on Kaplan-Meier curves with a hazard ratio of 3.20 (p<0.05). The radiomic markers showed potential as quantitative measures correlated with the etiologic agent of acute infectious diseases and to stratify short-term risk of COVID-19 patients.
- High stretch induces endothelial dysfunction accompanied by oxidative stress and actin remodeling in human saphenous vein endothelial cells(2021) GIRAO-SILVA, T.; FONSECA-ALANIZ, M. H.; RIBEIRO-SILVA, J. C.; LEE, J.; PATIL, N. P.; DALLAN, L. A.; BAKER, A. B.; HARMSEN, M. C.; KRIEGER, J. E.; MIYAKAWA, A. A.The rate of the remodeling of the arterialized saphenous vein conduit limits the outcomes of coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested the hypothesis that high stretch (HS) induces human saphenous vein endothelial cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed that in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin and VCAM1) and THP-1 cell adhesion. HS decreases F-actin in hSVECs, but not in human arterial endothelial cells, and is accompanied by G-actin and cofilin's nuclear shuttling and increased reactive oxidative species (ROS). Pre-treatment with the broad-acting antioxidant N-acetylcysteine (NAC) supported this observation and diminished stretch-induced actin remodeling and inflammatory adhesive molecule expression. Altogether, we provide evidence that increased oxidative stress and actin cytoskeleton remodeling play a role in HS-induced saphenous vein endothelial cell dysfunction, which may contribute to predisposing saphenous vein graft to failure.
- Familial hypercholesterolemia and cardiovascular disease in older individuals(2021) COUTINHO, Elaine R.; MINAME, Marcio H.; ROCHA, Viviane Z.; BITTENCOURT, Marcio S.; JANNES, Cinthia E.; TADA, Mauricio T.; LIMA, Isabella R.; SALGADO FILHO, Wilson; CHACRA, Ana P.; PEREIRA, Alexandre C.; KRIEGER, Jose E.; SANTOS, Raul D.Background and aims: Familial hypercholestemlemia (FH) is characterized by high LDL-cholesterol (LDL-C) and early atherosclerotic cardiovascular disease (ASCVD). With a lipid lowering therapy (LLT), most individuals with FH may have a longer ASCVD-free survival. However, there is scant data about older individuals with FH. Methods: We compared characteristics of genetically defined FH older individuals with age-matched non-FH counterparts. Results: From 4111 genotyped individuals, 462 older than 60 years were included (198 positive and 264 negative for FH variants). There were no differences regarding median age [%25; 75%] 66.0 (62.0; 71.0) and 66.0 (62.2; 71.0) years, p = 0.68 for FH and non-FH, respectively. In both groups, there was a higher frequency of females, however, there were more males in the FH group 37.4% vs. 24.2%, p = 0.002. No differences were seen between FH and non-FH in LLT use: 88.5% vs. 91.5%, p = 0.29. Despite a longer LLT duration in FH patients (with 11.0 (7.0; 20.0) vs. 7.0 (3.0; 13.0) years, p < 0.001), treatment was started late in both groups: at 54.0 (47.0; 61.0) and 59.0 (52.0; 64.0) years, p < 0.001, in FH and non-FH, respectively. FH had greater frequencies of previous and early ASCVD (40.9% vs. 27.3%, p = 0.002, and 22.2% vs. 9.0%, p < 0.001). In FH, male sex [HR (95%C01 2.67 (1.50-4.73), p = 0.001, and LLT onset age 0.96 (0.93-0.99), p = 0.009, were independently associated with ASCVD. Conclusions: Among hypercholesterolemic older individuals participating in a cascade screening program, the genetic diagnosis of FH was associated with higher ASCVD rates, emphasizing the relevance of a monogenic defect as the cause of long-lasting hypercholesterolemia and ASCVD risk, particularly in men.
- Metabolomic Evaluation of Chronic Periodontal Disease in Older Adults(2021) RODRIGUES, Wellington F.; MIGUEL, Camila B.; AGOSTINHO, Ferdinando; V, Gabriela da Silva; LAZO-CHICA, Javier E.; SCAPIN, Sandra M. Naressi; NAPIMOGA, Marcelo H.; TRINDADE-DA-SILVA, Carlos A.; KRIEGER, Jose E.; PEREIRA, Alexandre da Costa; OLIVEIRA, Carlo J. Freire; SOARES, Siomar de Castro; UEIRA-VIEIRA, Carlos; KLEINJAN, AlexPeriodontal disease is an infectious inflammatory disease related to the destruction of supporting tissues of the teeth, leading to a functional loss of the teeth. Inflammatory molecules present in the exudate are catalyzed and form different metabolites that can be identified and quantified. Thus, we evaluated the inflammatory exudate present in crevicular fluid to identify metabolic biological markers for diagnosing chronic periodontal disease in older adults. Research participants were selected from long-term institutions in Brazil. Participants were individuals aged 65 years or older, healthy, or with chronic periodontal disease. Gas chromatography/mass spectrometry was used to evaluate potential biomarkers in 120 crevicular fluid samples. We identified 969 metabolites in the individuals. Of these, 15 metabolites showed a variable importance with projection score>1 and were associated with periodontal disease. Further analysis showed that among the 15 metabolites, two (5-aminovaleric acid and serine, 3TMS derivative) were found at higher concentrations in the crevicular fluid, indicating their potential diagnostic power for periodontal disease in older adults. Our findings indicated that some metabolites are present at high concentrations in the crevicular fluid in older adults with periodontal disease and can be used as biomarkers of periodontal disease.
- Dynamic Crosstalk between Vascular Smooth Muscle Cells and the Aged Extracellular Matrix(2021) RIBEIRO-SILVA, Joao Carlos; NOLASCO, Patricia; KRIEGER, Jose Eduardo; MIYAKAWA, Ayumi AureaVascular aging is accompanied by the fragmentation of elastic fibers and collagen deposition, leading to reduced distensibility and increased vascular stiffness. A rigid artery facilitates elastin to degradation by MMPs, exposing vascular cells to greater mechanical stress and triggering signaling mechanisms that only exacerbate aging, creating a self-sustaining inflammatory environment that also promotes vascular calcification. In this review, we highlight the role of crosstalk between smooth muscle cells and the vascular extracellular matrix (ECM) and how aging promotes smooth muscle cell phenotypes that ultimately lead to mechanical impairment of aging arteries. Understanding the underlying mechanisms and the role of associated changes in ECM during aging may contribute to new approaches to prevent or delay arterial aging and the onset of cardiovascular diseases.
- Study of CNN Capacity Applied to Left Ventricle Segmentation in Cardiac MRI(2021) TOLEDO, M. A. F.; LIMA, D. M.; KRIEGER, J. E.; GUTIERREZ, M. A.CNN (Convolutional Neural Network) models have been successfully used for segmentation of the left ventricle (LV) in cardiac MRI (Magnetic Resonance Imaging), providing clinical measurements. In practice, two questions arise with deployment of CNNs: (1) when is it better to use a shallow model instead of a deeper one? (2) how the size of a dataset might change the network performance? We propose a framework to answer them, by experimenting with deep and shallow versions of three U-Net families, trained from scratch in six subsets varying from 100 to 10,000 images, different network sizes, learning rates and regularization values. 1620 models were evaluated using five-fold cross-validation by loss and DICE. The results indicate that: sample size affects performance more than architecture or hyper-parameters; in small samples the performance is more sensitive to hyper-parameters than architecture; the performance difference between shallow and deeper networks is not the same across families. © 2021, The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd.
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