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"Miranda, Nicole"
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Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank
2022
Background
Genetic and lifestyle factors have considerable effects on obesity and related diseases, yet their effects in a clinical cohort are unknown. This study in a patient biobank examined associations of a BMI polygenic risk score (PRS), and its interactions with lifestyle risk factors, with clinically measured BMI and clinical phenotypes.
Methods
The Mass General Brigham (MGB) Biobank is a hospital-based cohort with electronic health record, genetic, and lifestyle data. A PRS for obesity was generated using 97 genetic variants for BMI. An obesity lifestyle risk index using survey responses to obesogenic lifestyle risk factors (alcohol, education, exercise, sleep, smoking, and shift work) was used to dichotomize the cohort into high and low obesogenic index based on the population median. Height and weight were measured at a clinical visit. Multivariable linear cross-sectional associations of the PRS with BMI and interactions with the obesity lifestyle risk index were conducted. In phenome-wide association analyses (PheWAS), similar logistic models were conducted for 675 disease outcomes derived from billing codes.
Results
Thirty-three thousand five hundred eleven patients were analyzed (53.1% female; age 60.0 years; BMI 28.3 kg/m
2
), of which 17,040 completed the lifestyle survey (57.5% female; age: 60.2; BMI: 28.1 (6.2) kg/m
2
). Each standard deviation increment in the PRS was associated with 0.83 kg/m
2
unit increase in BMI (95% confidence interval (CI) =0.76, 0.90). There was an interaction between the obesity PRS and obesity lifestyle risk index on BMI. The difference in BMI between those with a high and low obesogenic index was 3.18 kg/m
2
in patients in the highest decile of PRS, whereas that difference was only 1.55 kg/m
2
in patients in the lowest decile of PRS. In PheWAS, the obesity PRS was associated with 40 diseases spanning endocrine/metabolic, circulatory, and 8 other disease groups. No interactions were evident between the PRS and the index on disease outcomes.
Conclusions
In this hospital-based clinical biobank, obesity risk conferred by common genetic variants was associated with elevated BMI and this risk was attenuated by a healthier patient lifestyle. Continued consideration of the role of lifestyle in the context of genetic predisposition in healthcare settings is necessary to quantify the extent to which modifiable lifestyle risk factors may moderate genetic predisposition and inform clinical action to achieve personalized medicine.
Journal Article
Spatiotemporal variations of hydrochemical characteristics of irrigation water: a case study of the Lower Rio Grande Valley, USA
by
De La Garza, Miranda Nicole
,
Ren, Jianhong
,
Ancona, Veronica
in
agriculture
,
chemical indices
,
crops
2023
Hydrochemical characteristics of irrigation water and their spatiotemporal variations can provide critical information for ensuring healthy crop growth and determining the best water management practices. The Lower Rio Grande Valley (LRGV) is heavily dependent upon ditch irrigation to deliver water from the Rio Grande River to support its staple crop production. To date, no studies have been conducted to quantify the water quality and its variations along the distribution system. This research measured water quality parameters at seven sites in LRGV irrigation water in 2021. Chemical indices including salinity hazard (SH), sodium adsorption ratio (SAR), sodium percentage (Na%), residual sodium carbonate (RSC), magnesium hazard (MH), Kelly's Ratio (KR), and permeability index (PI) were calculated. Classification diagrams were prepared. Results revealed the locations that had doubtful water for irrigation use and more problematic water quality index levels. June and August had the highest index levels, which may have been attributable to the large rainfall events in May and July. The SH, Na%, KR, and MH indices exceeded recommended levels. ANOVA analyses showed significant temporal variations in SAR, RSC, MH, KR, and PI. These findings indicate the importance of incorporating water quality spatiotemporal variation information in routine irrigation planning and management.
Journal Article
Ensemble of global climate simulations for temperature in historical, 1.5 °C and 2.0 °C scenarios from HadAM4
by
Sparrow, Sarah N.
,
Watson, Peter A. G.
,
Miranda, Nicole D.
in
704/106
,
704/106/694/2739
,
704/172
2024
Large ensembles of global temperature are provided for three climate scenarios: historical (2006–16), 1.5 °C and 2.0 °C above pre-industrial levels. Each scenario has 700 members (70 simulations per year for ten years) of 6-hourly mean temperatures at a resolution of 0.833° ´ 0.556° (longitude ´ latitude) over the land surface. The data was generated using the climate
prediction
.net (CPDN) climate simulation environment, to run HadAM4 Atmosphere-only General Circulation Model (AGCM) from the UK Met Office Hadley Centre. Biases in simulated temperature were identified and corrected using quantile mapping with reference temperature data from ERA5. The data is stored within the UK Natural and Environmental Research Council Centre for Environmental Data Analysis repository as NetCDF V4 files.
Journal Article
Overcoming the incumbency and barriers to sustainable cooling
by
Fahr, Patrick
,
Miranda, Nicole D
,
Jani, Anant
in
adaptation
,
Adaptive systems
,
Air conditioners
2022
This article examines cooling in the built environment, an area of rapidly rising energy demand and greenhouse gas emissions. Specifically, the status quo of cooling is assessed and proposals are made for how to advance towards sustainable cooling through five levers of change: social interactions, technology innovations, business models, governance and infrastructure design. Achieving sustainable cooling requires navigating the opportunities and barriers presented by the incumbent technology that currently dominates the way in which cooling is provided—the vapour-compression refrigerant technology (or air-conditioners). Air-conditioners remain the go-to solution for growing cooling demand, with other alternatives often overlooked. This incumbent technology has contributed to five barriers hindering the transition to sustainable cooling: (1) building policies based exclusively on energy efficiency; (2) a focus on temperature rather than other thermal comfort variables; (3) building-centric design of cooling systems instead of occupant-centric design; (4) businesses guided by product-only sales; and (5) lack of innovation beyond the standard operational phase of the incumbent technology. Opportunities and priority actions are identified for policymakers, cooling professionals, technicians and citizens to promote a transition towards sustainable cooling.
Journal Article
BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer
by
Matta, Bruna Palma
,
Barros Moreira, Fábio Carvalho
,
Boroni, Mariana
in
Biopsy
,
Brazil - epidemiology
,
BRCA1
2024
Background Approximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high‐grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss‐of‐function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression‐free survival and overall survival. Methods The study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2. Results A total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression‐free survival. Conclusion Frequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non‐functional or non‐functional somatic variants, while eight 14.2% presented likely non‐functional or non‐functional somatic variants in BRCA1 or BRCA2.
Journal Article
Preparation of Novel Electrospun Organic–Inorganic Hybrid Nanofibers Based on Polycaprolactone, Glycine Betaine, and Calcium Carbonate (P/G/CaCO3-EPnF)
by
Ibáñez, Andrés
,
Neira-Carrillo, Andrónico
,
Cabrera-Barjas, Gustavo
in
Analysis
,
Calcium carbonate
,
Contact angle
2023
Biomedicine requires materials able to respond to specific needs without affecting the organism. Organic–inorganic fibrillar polymeric matrices possess unique properties that may fulfill these needs. In the present study, different topology-controlled poly(ε-caprolactone)-based fibrillar matrices containing glycine betaine at varying concentrations (0.5, 1, and 2% w/v) were prepared via electrospinning. The matrices were used as substrates in calcium carbonate crystallization assays with gas diffusion to obtain a single organic–inorganic hybrid material. The resulting matrices and crystalline material were characterized using spectroscopic, microscopic, and thermogravimetric analyses. The incorporation of glycine betaine into a poly(ε-caprolactone) mesh modified the diameter of the fibers, without affecting the thermal behavior of the matrices. However, the chemical and morphological characteristics of the matrices did influence in vitro inorganic mineralization. The thermogravimetric analysis of the matrices, performed after the mineralization tests, demonstrated the existence of a new organic–inorganic hybrid material with unique properties, which is discussed in the present study.
Journal Article
Synergistic Effect of Composite Nickel Phosphide Nanoparticles and Carbon Fiber on the Enhancement of Salivary Enzyme-Free Glucose Sensing
by
Bollo, Soledad
,
Ruíz-León, Domingo
,
Neira-Carrillo, Andrónico
in
Biosensing Techniques - methods
,
Carbon
,
Carbon - chemistry
2022
An electrospinning method was used for the preparation of an in situ composite based on Ni2P nanoparticles and carbon fiber (FC). The material was tested for the first time against direct glucose oxidation reaction. The Ni2P nanoparticles were distributed homogeneously throughout the carbon fibers with a composition determined by thermogravimetric analysis (TGA) of 40 wt% Ni2P and 60 wt% carbon fiber without impurities in the sample. The electrochemical measurement results indicate that the GCE/FC/Ni2P in situ sensor exhibits excellent catalytic activity compared to the GCE/Ni2P and GCE/FC/Ni2P ex situ electrodes. The GCE/FC/Ni2P in situ sensor presents a sensitivity of 1050 µAmM−1cm−2 in the range of 5–208 µM and a detection limit of 0.25 µM. The sensor was applied for glucose detection in artificial saliva, with a low interference observed from normally coexisting electroactive species. In conclusion, our sensor represents a novel and analytical competitive alternative for the development of non-enzymatic glucose sensors in the future.
Journal Article
Genes Controlled by DNA Methylation Are Involved in Wilms Tumor Progression
by
Guerra, João Victor da Silva
,
Faria, Paulo
,
Montalvão de Azevedo, Rafaela
in
Bayesian analysis
,
cancer progression
,
Chemotherapy
2019
To identify underlying mechanisms involved with metastasis formation in Wilms tumors (WTs), we performed comprehensive DNA methylation and gene expression analyses of matched normal kidney (NK), WT blastemal component, and metastatic tissues (MT) from patients treated under SIOP 2001 protocol. A linear Bayesian framework model identified 497 differentially methylated positions (DMPs) between groups that discriminated NK from WT, but MT samples were divided in two groups. Accordingly, methylation variance grouped NK and three MT samples tightly together and all WT with four MT samples that showed high variability. WT were hypomethylated compared to NK, and MT had a hypermethylated pattern compared to both groups. The methylation patterns were in agreement with methylases and demethylases expression. Methylation data pointed to the existence of two groups of metastases. While hierarchical clustering analysis based on the expression of all 2569 differentially expressed genes (DEGs) discriminated WT and MT from all NK samples, the hierarchical clustering based on the expression of 44 genes with a differentially methylated region (DMR) located in their promoter region revealed two groups: one containing all NKs and three MTs and one containing all WT and four MTs. Methylation changes might be controlling expression of genes associated with WT progression. The 44 genes are candidates to be further explored as a signature for metastasis formation in WT.
Journal Article
Electrospun Poly(acrylic acid-co-4-styrene sulfonate) as Potential Drug-Eluting Scaffolds for Targeted Chemotherapeutic Delivery Systems on Gastric (AGS) and Breast (MDA-Mb-231) Cancer Cell Lines
by
Palacio, Daniel A.
,
Neira-Carrillo, Andrónico
,
Urbano, Bruno F.
in
Acrylic acid
,
Antineoplastic drugs
,
Assaying
2022
Potential drug-eluting scaffolds of electrospun poly(acrylic acid-co-styrene sulfonate) P(AA-co-SS) in clonogenic assays using tumorigenic gastric and ovarian cancer cells were tested in vitro. Electrospun polymer nanofiber (EPnF) meshes of PAA and PSSNa homo- and P(AA-co-SS) copolymer composed of 30:70, 50:50, 70:30 acrylic acid (AA) and sodium 4-styrene sulfonate (SSNa) units were performed by electrospinning (ES). The synthesis, structural and morphological characterization of all EPnF meshes were analyzed by optical and electron microscopy (SEM-EDS), infrared spectroscopy (FTIR), contact angle, and X-ray diffraction (XRD) measurements. This study shows that different ratio of AA and SSNa of monomers in P(AA-co-SS) EPnF play a crucial role in clonogenic in vitro assays. We found that 50:50 P(AA-co-SS) EPnF mesh loaded with antineoplastic drugs can be an excellent suppressor of growth-independent anchored capacities in vitro assays and a good subcutaneous drug delivery system for chemotherapeutic medication in vivo model for surgical resection procedures in cancer research.
Journal Article
Electrocrystallization of Calcium Oxalate Mediated by Electrospun Polymer Fiber Using Poly(acrylic acid-co-4-styrene sulfonate)
by
Yazdani-Pedram, Mehrdad
,
Cataldo, Dania
,
Neira-Carrillo, Andrónico
in
Acrylic acid
,
Calcium
,
Copolymers
2025
Calcium oxalate (CaOx) crystals play a central role in urolithiasis, a pathological crystallization process that remains difficult to prevent. In this study, electrospun polymeric fiber (EPF) meshes of poly(acrylic acid-co-styrene sulfonate) P(AA-co-SS) were fabricated by electrospinning (ES) under controlled positive (+) or negative (−) voltages. The influence of PAA and PSS homopolymers, as well as P(AA-co-SS) copolymers with varying compositions, was evaluated as anionic scaffolds in in vitro CaOx electrocrystallization (EC) experiments. The structural and morphological features of the EPF meshes were characterized by scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Our results demonstrate that specific EPF meshes can effectively guide CaOx crystal growth, promoting the selective stabilization of either calcium oxalate monohydrate (COM) or calcium oxalate dihydrate (COD) phases. These findings highlight the potential of tailored EPF meshes as anionic scaffolds for modulating pathological CaOx crystallization.
Journal Article