RESUMO
Bronchopulmonary dysplasia (BPD) is the most common lung disease of extreme prematurity, yet mechanisms that associate with or identify neonates with increased susceptibility for BPD are largely unknown. Combining artificial intelligence with gene expression data is a novel approach that may assist in better understanding mechanisms underpinning chronic lung disease and in stratifying patients at greater risk for BPD. The objective of this study is to develop an early peripheral blood transcriptomic signature that can predict preterm neonates at risk for developing BPD. Secondary analysis of whole blood microarray data from 97 very low birth weight neonates on day of life 5 was performed. BPD was defined as positive pressure ventilation or oxygen requirement at 28 days of age. Participants were randomly assigned to a training (70%) and testing cohort (30%). Four gene-centric machine learning models were built, and their discriminatory abilities were compared with gestational age or birth weight. This study adheres to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement. Neonates with BPD (n = 62 subjects) exhibited a lower median gestational age (26.0 wk vs. 30.0 wk, P < 0.01) and birth weight (800 g vs. 1,280 g, P < 0.01) compared with non-BPD neonates. From an initial pool (33,252 genes/patient), 4,523 genes exhibited a false discovery rate (FDR) <1%. The area under the receiver operating characteristic curve (AUC) for predicting BPD utilizing gestational age or birth weight was 87.8% and 87.2%, respectively. The machine learning models, using a combination of five genes, revealed AUCs ranging between 85.8% and 96.1%. Pathways integral to T cell development and differentiation were associated with BPD. A derived five-gene whole blood signature can accurately predict BPD in the first week of life.
Assuntos
Displasia Broncopulmonar , Recém-Nascido , Humanos , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/genética , Peso ao Nascer , Transcriptoma/genética , Inteligência Artificial , Recém-Nascido Prematuro , Idade GestacionalRESUMO
Colombia has great potential to produce clean energy through the use of residual biomass from the agricultural sector, such as residues obtained from the life cycle of rice production. This document presents a mixed approach methodology study to examine the combustion of rice husks as a possible energy alternative in the Tolima department of Colombia. First, the physicochemical characteristics of the rice husk were analyzed to characterize the raw material. Next, System Advisor Model (SAM) software was used to model a bioenergy plant to obtain biochar, bio-oil, and biogas from the combustion of rice husks and generate performance matrices, such as thermal efficiency, heat rate, and capacity factor. Then, the project was evaluated for financial feasibility using a mathematical model of net present value (NPV) with a planning horizon of 5 years. Finally, a subset of the local population was surveyed to assess perspectives on the project in the region. The results of the rice husk physicochemical analysis were the following: nitrogen content (0.74%), organic carbon (38.04%), silica (18.39%), humidity determination (7.68%), ash (19.4%), presence of carbonates (< 0.01%), and pH (6.41). These properties are adequate for the combustion process. The SAM simulation showed that the heat transferred in the boiler was 3180 kW, maintaining an efficiency between 50 and 52% throughout the 12 months of the year, meaning that the rice husk can generate electricity and thermal energy. The financial analysis showed that the internal rate of return (IRR) was 6% higher than the opportunity interest rate (OIR), demonstrating economic feasibility of the project. The design and creation of a rice husk processing plant is socially and environmentally viable and has the potential to contribute to the economic development of the Tolima community and reduce greenhouse gases. Likewise, this activity has the potential to promote energy security for consumers and environmental sustainability while at the same time being economically competitive.
Assuntos
Oryza , Oryza/química , Colômbia , Biocombustíveis/análise , Biomassa , Agricultura/métodos , Carvão Vegetal/químicaRESUMO
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of extreme prematurity. Despite more than 50 years of research, current treatments are ineffective, and clinicians are largely unable to accurately predict which neonates the condition will develop in. A deeper understanding of the molecular mechanisms underlying the characteristic arrest in lung development are warranted. Integrating high-fidelity technology from precision medicine approaches may fill this gap and provide the tools necessary to identify biomarkers and targetable pathways. In this review, we describe insights garnered from current studies using omics for BPD prediction and stratification. We conclude by describing novel programs that will integrate multi-omics in efforts to better understand and treat the pathogenesis of BPD. [Pediatr Ann. 2022;51(10):e396-e404.].
Assuntos
Displasia Broncopulmonar , Doenças do Prematuro , Big Data , Biomarcadores , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Humanos , Recém-Nascido , Medicina de PrecisãoRESUMO
Vasoinhibin belongs to a family of angiogenesis inhibitors generated when the fourth α-helix (H4) of the hormone prolactin (PRL) is removed by specific proteolytic cleavage. The antiangiogenic properties are absent in uncleaved PRL, indicating that conformational changes create a new bioactive domain. However, the solution structure of vasoinhibin and the location of its bioactive domain are unknown. Molecular dynamic simulation (MD) showed that the loss of H4 exposes the hydrophobic nucleus of PRL and leads to the compression of the molecule into a three-helix bundle that buries the hydrophobic nucleus again. Compression occurs by the movement of loop 1 (L1) and its interaction with α-helix 1 (H1) generating a new L1 conformation with electrostatic and hydrophobic surfaces distinct from those of PRL, that may correspond to a bioactive domain. Consistent with this model, a recombinant protein containing the first 79 amino acids comprising H1 and L1 of human PRL inhibited the proliferation and migration of endothelial cells and upregulated the vasoinhibin target genes, IL1A and ICAM1. This bioactivity was comparable to that of a conventional vasoinhibin having the 123 residues encompassing H1, L1, Η2, L2, and Η3 of human PRL. These findings extend the vasoinhibin family to smaller proteins and provide important structural information, which will aid in antiangiogenic drug development.