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
conferenceObject PREDICTORS OF CORONARY ARTERY CALCIFICATION INCIDENCE IN SEVERE HYPERCHOLESTEROLEMIA(2023) MARTE, Ana; MINAME, Marcio Hiroshi; PARDI, Estevao Magalhaes; GANEM, Lucas; MIZUTA, Marjorie Hayashida; ROCHA, Viviane Zorzanelli; PEREIRA, Alexandre Costa; KRIEGER, Jose Eduardo; SANTOS, Raul- CardioBERTpt: Transformer-based Models for Cardiology Language Representation in Portuguese(2023) SCHNEIDER, Elisa Terumi Rubel; GUMIEL, Yohan Bonescki; SOUZA, Joao Vitor Andrioli de; MUKAI, Lilian Mie; OLIVEIRA, Lucas Emanuel Silva e; REBELO, Marina de Sa; GUTIERREZ, Marco Antonio; KRIEGER, Jose Eduardo; TEODORO, Douglas; MORO, Claudia; PARAISO, Emerson CabreraContextual word embeddings and the Transformers architecture have reached state-of-the-art results in many natural language processing (NLP) tasks and improved the adaptation of models for multiple domains. Despite the improvement in the reuse and construction of models, few resources are still developed for the Portuguese language, especially in the health domain. Furthermore, the clinical models available for the language are not representative enough for all medical specialties. This work explores deep contextual embedding models for the Portuguese language to support clinical NLP tasks. We transferred learned information from electronic health records of a Brazilian tertiary hospital specialized in cardiology diseases and pre-trained multiple clinical BERT-based models. We evaluated the performance of these models in named entity recognition experiments, fine-tuning them in two annotated corpora containing clinical narratives. Our pre-trained models outperformed previous multilingual and Portuguese BERT-based models for cardiology and multi-specialty environments, reaching the state-of-the-art for analyzed corpora, with 5.5% F1 score improvement in TempClinBr (all entities) and 1.7% in SemClinBr (Disorder entity) corpora. Hence, we demonstrate that data representativeness and a high volume of training data can improve the results for clinical tasks, aligned with results for other languages.
- Cardiovascular disease onset in old people with severe hypercholesterolemia(2023) COUTINHO, Elaine R.; MINAME, Marcio H.; ROCHA, Viviane Z.; BITTENCOURT, Marcio S.; JANNES, Cinthia E.; KRIEGER, Jose E.; PEREIRA, Alexandre C.; SANTOS, Raul D.Background and aims: Familial hypercholesterolemia (FH) variants are associated with higher atherosclerotic cardiovascular disease risk (ASCVD) even when compared with other forms of severe hypercholesterolemia, especially in young people. Lipid lowering therapies (LLT) may change hypercholesterolemia natural history. This study aimed at evaluating factors associated with occurrence of ASCVD in old severe hypercholesterolemics diagnosed or not with FH and undergoing LLT.Methods: Hypercholesterolemic individuals >= 60 years participating on a genetic cascade screening for FH were divided in 4 groups (2 x 2) according to the presence (variant+) or not (variant-) of FH genetic variants and previous ASCVD (ASCVD+ and ASCVD-). Biomarkers associated with new incident ASCVD events were tested using Cox models. Continuous data shown as medians (%25; %75).Results: From 4,111 genotyped individuals, 377 (9.1%) were elderly [age 66 (63; 71) years], 28.9% males, 42.7% variant+, 32.1% with previous ASCVD, LLT duration 9 (5; 16) years, and on treatment LDL-cholesterol 144 (109; 200) mg/dL. After 4.8 (7; 3) years of follow up there were 47 incident events (12.4%, 2.7% patient/year). The annualized event rates were 0.8% (95% CI 0.36%; 1.70%), 2.3% (95% CI 1.3%; 4.1%), 5.2% (95% CI 2.8%; 9.7%) and 6.3% (95% CI 4.0%; 10.0%) respectively for groups variant-/ASCVD-, variant+/ASCVD-, variant-/ ASCVD+ and, variant+/ASCVD+ (p log rank p < 0.001). Only presence of previous ASCVD was independently associated with incident ASCVD [hazard ratio 3.236 (95%CI 1.497-6.993, p = 0.003)]. No interaction was found for previous ASCVD and variants.Conclusions: In old severe hypercholesterolemic individuals undergoing long-term LLT previous ASCVD was associated with incident events while FH causing variants were not.
- Artificial Intelligence-Driven Screening System for Rapid Image-Based Classification of 12-Lead ECG Exams: A Promising Solution for Emergency Room Prioritization(2023) DIAS, Felipe Meneguitti; RIBEIRO, Estela; MORENO, Ramon Alfredo; RIBEIRO, Adele Helena; SAMESIMA, Nelson; PASTORE, Carlos Alberto; KRIEGER, Jose Eduardo; GUTIERREZ, Marco AntonioThe electrocardiogram (ECG) serves as a valuable diagnostic tool, providing crucial information about life-threatening cardiac conditions such as atrial fibrillation and myocardial infarction. A prompt and efficient assessment of ECG exams in environments such as Emergency Rooms (ERs) can significantly enhance the chances of survival for high-risk patients. Despite the presence of numerous works on ECG classification, most of these studies have concentrated on one-dimensional ECG signals, which are commonly found in publicly available ECG datasets. Nevertheless, the practical relevance of such methods is limited in hospital settings, where ECG exams are usually stored as images. In this study, we have developed an artificial intelligence-driven screening system specifically designed to analyze 12-lead ECG images. Our proposed method has been trained on an extensive dataset comprising 99,746 12-lead ECG exams collected from the ambulatory section of a tertiary hospital. The primary goal was to precisely classify the exams into three classes: Normal (N), Atrial Fibrillation (AFib), and Other (O). The evaluation of our approach yielded AUROC scores of 93.2%, 99.2%, and 93.1% for N, AFib, and O, respectively. To further validate our approach, we conducted evaluations using the 2018 China Physiological Signal Challenge (CPSC) database. In this evaluation, we achieved AUROC scores of 91.8%, 97.5%, and 70.4% for the classes N, AFib, and O, respectively. Additionally, we assessed our method using 1,074 exams acquired in the ER and obtained AUROC values of 98.3%, 98.0%, and 97.7% for the classes N, AFib, and O, respectively. Furthermore, we developed and deployed a system with a trained model within the ER of a tertiary hospital for research purposes. This system automatically retrieves newly captured ECG chart images from the Picture Archiving and Communication System (PACS) within the ER. These images undergo necessary preprocessing steps and serve as input for our proposed classification method. This comprehensive approach established an efficient and versatile end-to-end framework for ECG classification. The results of our study highlight the potential of leveraging artificial intelligence in the screening of ECG exams, offering a promising solution for the rapid assessment and prioritization of patients in the ER.
- Additional improvement in regional myocardial ischemia after intracardiac injection of bone marrow cells during CABG surgery(2023) GOWDAK, Luis Henrique Wolff; SCHETTERT, Isolmar Tadeu; ROCHITTE, Carlos Eduardo; CARVALHO, Leonardo P. de; VIEIRA, Marcelo Luiz Campos; DALLAN, Luis Alberto Oliveira; OLIVEIRA, Sergio Almeida de; CESAR, Luiz Antonio Machado; BRITO, Jose Oscar Reis; GUARITA-SOUZA, Luiz Cesar; CARVALHO, Antonio Carlos Campos de; KRIEGER, Jose EduardoBackground: Post-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD).Objective: We evaluated whether autologous bone marrow-derived cells (BMC) contribute to additional reduction in regional stress-induced myocardial ischemia (SIMI) in patients undergoing incomplete coronary artery bypass graft surgery (CABG).Methods: In a double-blind, randomized, placebo-controlled trial, we enrolled 143 patients (82% men, 58 & PLUSMN; 11 years) with stable CAD and not candidates for complete CABG. They received 100 million BMC (n = 77) or placebo (n = 66) injected into ischemic non-revascularized segments during CABG. The primary outcome was improvement on SIMI quantified as the area at risk in injected segments assessed by cardiovascular magnetic resonance (CMR) 1, 6, and 12 months after CABG.Results: The reduction in global SIMI after CABG was comparable (p = 0.491) in both groups indicating sustained beneficial effects of the surgical procedure over 12 month period. In contrast, we observed additional improvement in regional SIMI in BMC treated group (p = 0.047). Baseline regional SIMI values were comparable [18.5 (16.2-21.0) vs. 18.5 (16.5-20.7)] and reached the lowest values at 1 month [9.74 (8.25; 11.49) vs. 12.69 (10.84; 14.85)] for BMC and placebo groups, respectively. The ischemia's improvement from baseline represented a 50% difference in regional SIMI in favor of the BMC transplanted group at 30 days. We found no differences in clinical and LVEF% between groups during the 12 month follow-up period. The 1 month rate of major adverse cerebral and cardiovascular events (MACCE) (p = 0.34) and all-cause mortality (p = 0.08) did not differ between groups 1 month post intervention.Conclusion: We provided evidence that BMC leads to additional reduction in regional SIMI in chronic ischemic patients when injected in segments not subjected to direct surgical revascularization. This adjuvant therapy deserves further assessment in patients with advanced CAD especially in those with microcirculation dysfunction.
conferenceObject RAPID PROGRESSION OF CORONARY ATHEROSCLEROSIS IN A PATIENT WITH AUTOSSOMAL RECESSIVE HYPERCHOLESTEROLEMIA(2023) MIZUTA, Marjorie Hayashida; AMORIM, Matheus; ROCHA, Viviane Zorzanelli; MINAME, Marcio Hiroshi; JANNES, Cinthia Elim; PEREIRA, Alexandre Costa; KRIEGER, Jose Eduardo; SANTOS, Raul; CHACRA, Ana Paula Marte- Wearable potentiometric biosensor for analysis of urea in sweat(2023) IBANEZ-REDIN, Gisela; CAGNANI, Giovana Rosso; GOMES, Nathalia O.; RAYMUNDO-PEREIRA, Paulo A.; MACHADO, Sergio A. S.; GUTIERREZ, Marco Antonio; KRIEGER, Jose Eduardo; OLIVEIRA, Osvaldo N.Herein, we introduce wearable potentiometric biosensors on screen-printed carbon electrodes (SPCEs) for onbody and on-site monitoring of urea in sweat. The biosensor architecture was judiciously designed to detect urea at different pHs and incorporate a pH sensor, thus containing polyaniline ink, urease bioink and a polyvinylchloride membrane. Urea detection could be performed in the wide range from 5 to 200 mM at pH 7.0, encompassing urea levels in human sweat. The biosensor response was fast (incubation time 5 min), with no interference from other substances in sweat. Reliable urea detection could be done in undiluted human sweat with a skin-worn flexible device using the pH correction strategy afforded by the pH sensor. The performance of the epidermal biosensor was not affected by severe bending strains. The feasibility of mass production was demonstrated by fabricating epidermal flexible biosensors using slot-die coating with a roll-to-roll technique.
conferenceObject CRP3 ABSENCE IMPAIRS FOCAL ADHESION SIGNALING AND AORTIC SMOOTH MUSCLE CELL CONTRACTION(2023) RIBEIRO-SILVA, J.; FONSECA-ALANIZ, M. H.; KRIEGER, J. E.; MIYAKAWA, A. A.- Integrated systems biology approach identifies gene targets for endothelial dysfunction(2023) PINHEIRO-DE-SOUSA, Iguaracy; FONSECA-ALANIZ, Miriam Helena; GIUDICE, Girolamo; VALADAO, Iuri Cordeiro; MODESTIA, Silvestre Massimo; MATTIOLI, Sarah Viana; ROSA JUNIOR, Ricardo; ZALMAS, Lykourgos-Panagiotis; FANG, Yun; PETSALAKI, Evangelia; KRIEGER, Jose EduardoEndothelial dysfunction (ED) is critical in the development and progression of cardiovascular (CV) disorders, yet effective therapeutic targets for ED remain elusive due to limited understanding of its underlying molecular mechanisms. To address this gap, we employed a systems biology approach to identify potential targets for ED. Our study combined multi omics data integration, with siRNA screening, high content imaging and network analysis to prioritise key ED genes and identify a pro- and anti-ED network. We found 26 genes that, upon silencing, exacerbated the ED phenotypes tested, and network propagation identified a pro-ED network enriched in functions associated with inflammatory responses. Conversely, 31 genes ameliorated ED phenotypes, pointing to potential ED targets, and the respective anti-ED network was enriched in hypoxia, angiogenesis and cancer-related processes. An independent screen with 17 drugs found general agreement with the trends from our siRNA screen and further highlighted DUSP1, IL6 and CCL2 as potential candidates for targeting ED. Overall, our results demonstrate the potential of integrated system biology approaches in discovering disease-specific candidate drug targets for endothelial dysfunction. imageMulti-omics data integration, genetic and pharmacological perturbations, and network analysis on endothelial cells are combined to identify endothelial dysfunction network signatures and prioritise candidate therapeutic targets.Multi-omics data integration of endothelial cells treated with mimics of major cardiovascular disease factors identified 81 putative endothelial dysfunction (ED) genes.Upon siRNA-mediated gene knockdown, 83% of ED gene candidates affected at least one ED phenotype (26 exacerbating and 31 ameliorating the ED phenotypes).The analyses reveal emergent properties of disease networks, distinguishing between adaptation and rewiring for survival and those associated with deregulation that can be targeted for ED treatment.An orthogonal drug screen on treated endothelial cells provided additional support for DUSP1, IL6 and CCL2 as putative targets for ED. Multi-omics data integration, genetic and pharmacological perturbations, and network analysis on endothelial cells are combined to identify endothelial dysfunction network signatures and prioritise candidate therapeutic targets.image
- LDLR gene's promoter region hypermethylation in patients with familial hypercholesterolemia(2023) ZORZO, R. A.; SUEN, V. M. M.; SANTOS, J. E.; SILVA-JR, W. A.; SUAZO, V. K.; HONORATO, A. L. S. C.; SANTOS, R. D.; JANNES, C. E.; PEREIRA, A.; KRIEGER, J. E.; LIBERATORE, R. D. R.Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in the LDLR, APOB, and PCSK9 genes were not found in 20-40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis of APOB and PCSK9 was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. As the LDLR gene has two CpG islands, we analyzed each island separately. The analysis of LDLR-island1 showed PR = 0.982 (CI 0.33-2.95; chi(2) = 0.001; p = 0.973), also suggesting no relationship between methylation and the FH phenotype. Analysis of LDLR-island2 showed a PR of 4.12 (CI 1.43-11.88; chi(2) = 13,921; p = 0.00019), indicating a possible association between methylation on this island and the FH phenotype.
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