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1.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38513256

RESUMO

Recent studies have demonstrated regional differences in marine ecosystem C:N:P with implications for carbon and nutrient cycles. Due to strong co-variance, temperature and nutrient stress explain variability in C:N:P equally well. A reductionistic approach can link changes in individual environmental drivers with changes in biochemical traits and cell C:N:P. Thus, we quantified effects of temperature and nutrient stress on Synechococcus chemistry using laboratory chemostats, chemical analyses, and data-independent acquisition mass spectrometry proteomics. Nutrient supply accounted for most C:N:Pcell variability and induced tradeoffs between nutrient acquisition and ribosomal proteins. High temperature prompted heat-shock, whereas thermal effects via the "translation-compensation hypothesis" were only seen under P-stress. A Nonparametric Bayesian Local Clustering algorithm suggested that changes in lipopolysaccharides, peptidoglycans, and C-rich compatible solutes may also contribute to C:N:P regulation. Physiological responses match field-based trends in ecosystem stoichiometry and suggest a hierarchical environmental regulation of current and future ocean C:N:P.


Assuntos
Ecossistema , Synechococcus , Synechococcus/genética , Synechococcus/metabolismo , Proteoma/metabolismo , Teorema de Bayes , Temperatura , Nitrogênio/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-38530131

RESUMO

Mesenchymal stem cells (MSCs) are a promising therapy to potentially treat diabetes given their potent anti-inflammatory and immune-modulatory properties. While these regenerative cells have shown considerable promise in cell culture, their clinical translation has been challenging. In part, this can be attributed to these cells not reaching the pancreas to exert their regenerative effects following conventional intravenous (IV) injection, with the majority of cells being trapped in the lungs in the pulmonary first-pass effect. In the present study, we will therefore examine whether direct delivery of MSCs to the pancreas via an intra-arterial (IA) injection can improve their therapeutic efficacy. Using a mouse model, in which repetitive low doses of STZ induced a gentle, but progressive, hyperglycemia, we tested bone marrow-derived MSCs (BM-MSCs) which we have shown are enriched with pro-angiogenic and immunomodulatory factors. In cell culture studies, BM-MSCs were shown to preserve islet viability and function following exposure to proinflammatory cytokines (IFN-γ, IL-1ß, and TNF-α) through an increase in pAkt. When tested in our animal model, mice receiving IV BM-MSCs were not able to mitigate the effects of STZ, however those which received the same dose and batch of cells via IA injection were able to maintain basal and dynamic glycemic control, to similar levels as seen in healthy control animals, over 10 days. This study shows the importance of considering precision delivery approaches to ensure cell-based therapies reach their intended targets to enable them to exert their therapeutic effects.

3.
J Am Stat Assoc ; 118(541): 405-416, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37089274

RESUMO

The use of large datasets for targeted therapeutic interventions requires new ways to characterize the heterogeneity observed across subgroups of a specific population. In particular, models for partially exchangeable data are needed for inference on nested datasets, where the observations are assumed to be organized in different units and some sharing of information is required to learn distinctive features of the units. In this manuscript, we propose a nested common atoms model (CAM) that is particularly suited for the analysis of nested datasets where the distributions of the units are expected to differ only over a small fraction of the observations sampled from each unit. The proposed CAM allows a two-layered clustering at the distributional and observational level and is amenable to scalable posterior inference through the use of a computationally efficient nested slice sampler algorithm. We further discuss how to extend the proposed modeling framework to handle discrete measurements, and we conduct posterior inference on a real microbiome dataset from a diet swap study to investigate how the alterations in intestinal microbiota composition are associated with different eating habits. We further investigate the performance of our model in capturing true distributional structures in the population by means of a simulation study.

4.
Stat Med ; 42(12): 1931-1945, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-36914221

RESUMO

The analysis of large-scale datasets, especially in biomedical contexts, frequently involves a principled screening of multiple hypotheses. The celebrated two-group model jointly models the distribution of the test statistics with mixtures of two competing densities, the null and the alternative distributions. We investigate the use of weighted densities and, in particular, non-local densities as working alternative distributions, to enforce separation from the null and thus refine the screening procedure. We show how these weighted alternatives improve various operating characteristics, such as the Bayesian false discovery rate, of the resulting tests for a fixed mixture proportion with respect to a local, unweighted likelihood approach. Parametric and nonparametric model specifications are proposed, along with efficient samplers for posterior inference. By means of a simulation study, we exhibit how our model compares with both well-established and state-of-the-art alternatives in terms of various operating characteristics. Finally, to illustrate the versatility of our method, we conduct three differential expression analyses with publicly-available datasets from genomic studies of heterogeneous nature.


Assuntos
Genômica , Humanos , Funções Verossimilhança , Teorema de Bayes , Simulação por Computador
5.
J Digit Imaging ; 36(3): 1049-1059, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36854923

RESUMO

Deep learning (DL) has been proposed to automate image segmentation and provide accuracy, consistency, and efficiency. Accurate segmentation of lipomatous tumors (LTs) is critical for correct tumor radiomics analysis and localization. The major challenge of this task is data heterogeneity, including tumor morphological characteristics and multicenter scanning protocols. To mitigate the issue, we aimed to develop a DL-based Super Learner (SL) ensemble framework with different data correction and normalization methods. Pathologically proven LTs on pre-operative T1-weighted/proton-density MR images of 185 patients were manually segmented. The LTs were categorized by tumor locations as distal upper limb (DUL), distal lower limb (DLL), proximal upper limb (PUL), proximal lower limb (PLL), or Trunk (T) and grouped by 80%/9%/11% for training, validation and testing. Six configurations of correction/normalization were applied to data for fivefold-cross-validation trainings, resulting in 30 base learners (BLs). A SL was obtained from the BLs by optimizing SL weights. The performance was evaluated by dice-similarity-coefficient (DSC), sensitivity, specificity, and Hausdorff distance (HD95). For predictions of the BLs, the average DSC, sensitivity, and specificity from the testing data were 0.72 [Formula: see text] 0.16, 0.73 [Formula: see text] 0.168, and 0.99 [Formula: see text] 0.012, respectively, while for SL predictions were 0.80 [Formula: see text] 0.184, 0.78 [Formula: see text] 0.193, and 1.00 [Formula: see text] 0.010. The average HD95 of the BLs were 11.5 (DUL), 23.2 (DLL), 25.9 (PUL), 32.1 (PLL), and 47.9 (T) mm, whereas of SL were 1.7, 8.4, 15.9, 2.2, and 36.6 mm, respectively. The proposed method could improve the segmentation accuracy and mitigate the performance instability and data heterogeneity aiding the differential diagnosis of LTs in real clinical situations.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Inteligência Artificial
6.
Biometrics ; 79(2): 1370-1382, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35191539

RESUMO

Recent advancements in miniaturized fluorescence microscopy have made it possible to investigate neuronal responses to external stimuli in awake behaving animals through the analysis of intracellular calcium signals. An ongoing challenge is deconvolving the temporal signals to extract the spike trains from the noisy calcium signals' time series. In this article, we propose a nested Bayesian finite mixture specification that allows the estimation of spiking activity and, simultaneously, reconstructing the distributions of the calcium transient spikes' amplitudes under different experimental conditions. The proposed model leverages two nested layers of random discrete mixture priors to borrow information between experiments and discover similarities in the distributional patterns of neuronal responses to different stimuli. Furthermore, the spikes' intensity values are also clustered within and between experimental conditions to determine the existence of common (recurring) response amplitudes. Simulation studies and the analysis of a dataset from the Allen Brain Observatory show the effectiveness of the method in clustering and detecting neuronal activities.


Assuntos
Encéfalo , Cálcio , Animais , Teorema de Bayes , Simulação por Computador , Análise por Conglomerados
7.
Neuron ; 110(1): 21-35, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34784504

RESUMO

In basic neuroscience research, data are often clustered or collected with repeated measures, hence correlated. The most widely used methods such as t test and ANOVA do not take data dependence into account and thus are often misused. This Primer introduces linear and generalized mixed-effects models that consider data dependence and provides clear instruction on how to recognize when they are needed and how to apply them. The appropriate use of mixed-effects models will help researchers improve their experimental design and will lead to data analyses with greater validity and higher reproducibility of the experimental findings.


Assuntos
Neurociências , Projetos de Pesquisa , Análise de Variância , Modelos Lineares , Modelos Estatísticos , Reprodutibilidade dos Testes
8.
Biometrics ; 78(1): 313-323, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33058149

RESUMO

Electroencephalography (EEG) is a noninvasive neuroimaging modality that captures electrical brain activity many times per second. We seek to estimate power spectra from EEG data that ware gathered for 557 adolescent twin pairs through the Minnesota Twin Family Study (MTFS). Typically, spectral analysis methods treat time series from each subject separately, and independent spectral densities are fit to each time series. Since the EEG data were collected on twins, it is reasonable to assume that the time series have similar underlying characteristics, so borrowing information across subjects can significantly improve estimation. We propose a Nested Bernstein Dirichlet prior model to estimate the power spectrum of the EEG signal for each subject by smoothing periodograms within and across subjects while requiring minimal user input to tuning parameters. Furthermore, we leverage the MTFS twin study design to estimate the heritability of EEG power spectra with the hopes of establishing new endophenotypes. Through simulation studies designed to mimic the MTFS, we show our method out-performs a set of other popular methods.


Assuntos
Eletroencefalografia , Gêmeos , Adolescente , Teorema de Bayes , Humanos , Gêmeos/genética
9.
Anaesthesiol Intensive Ther ; 53(3): 223-231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34284554

RESUMO

INTRODUCTION: Although humans are capable of enduring critically low levels of oxygen, many hypoxaemic patients die despite aggressive therapies. Mimicking the physiological hyperventilation necessary to survive extreme hypoxic conditions could minimize the derangements caused by acute hypoxic-hypoxia. The objective of this study was to measure the haemodynamic-biochemical response to artificially induced hyperventilation in hypoxic rats. MATERIAL AND METHODS: Twenty-four deeply anaesthetized and mechanically ventilated rats were allocated to 3 groups: control (n = 5, FiO2 = 1); hypoxic spontaneously hyperventilating (n = 10, FiO2 = 0.08); and hypoxic artificially induced hyperventilation (n = 9, targeting PaCO2 = 10 mm Hg, FiO2 = 0.08). We compared the spontaneously and artificially hyperventilating groups. P-values < 0.01 were considered statistically significant. Mean arterial pressure (MAP) and serum chemistry were measured for 180 minutes. RESULTS: The control group remained stable throughout the experiment. The hypoxic groups developed profound hypotension after the decrease in FiO2. However, the artificially induced hyperventilated rats recovered their MAP to levels higher than the spontaneously hyperventilating group (117.1 ± 17.2 vs. 68.1 ± 16.0, P = 0.0048). In regard to the biochemical derangements, even though the serum lactate and PaO2 were not different among the hypoxic groups, the artificially hyperventilated group achieved significantly higher SaO2 (94.3 ± 3.6 vs. 58.6 ± 9.6, P = 0.005), pH (7.87 ± 0.04 vs. 7.50 ± 0.13, P = 0.005), and CaO2 (17.7 ± 2.6 vs. 10.2 ± 1.3, P = 0.005) at 180 minutes. CONCLUSIONS: Artificially induced hyperventilation led to the correction of arterial oxygen content, severe serum chemistry, and haemodynamic derangements. These findings may represent a novel rescue manoeuvre and serve as a bridge to a permanent form of support, but should be further studied before being translated to the clinical setting.


Assuntos
Hiperventilação , Hipóxia , Animais , Gasometria , Hemodinâmica , Humanos , Hipóxia/terapia , Oxigênio , Ratos
10.
Front Cell Dev Biol ; 9: 650490, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055779

RESUMO

Human platelet lysate (hPL) is considered a valid substitute to fetal bovine serum (FBS) in the expansion of mesenchymal stromal cells (MSC), and it is commonly produced starting from intermediate side products of whole blood donations. Through freeze-thaw cycles, hPL is highly enriched in chemokines, growth factors, and adhesion and immunologic molecules. Cell therapy protocols, using hPL instead of FBS for the expansion of cells, are approved by regulatory authorities without concerns, and its administration in patients is considered safe. However, published data are fairly difficult to compare, since the production of hPL is highly variable. This study proposes to optimize and standardize the hPL productive process by using instruments, technologies, and quality/safety standards required for blood bank activities and products. The quality and improved selection of the starting material (i.e., the whole blood), together with the improvement of the production process, guarantee a product characterized by higher content and quality of growth factors as well as a reduction in batch-to-batch variability. By increasing the number of freeze/thaw cycles from one (hPL1c) to four (hPL4c), we obtained a favorable effect on the release of growth factors from platelet α granules. Those changes have directly translated into biological effects leading to a decreasing doubling time (DT) of MSC expansion at 7 days (49.41 ± 2.62 vs. 40.61 ± 1.11 h, p < 0.001). Furthermore, mass spectrometry (MS)-based evaluation has shown that the proliferative effects of hPL4c are also combined with a lower batch-to-batch variability (10-15 vs. 21-31%) at the proteomic level. In conclusion, we have considered lot-to-lot hPL variability, and by the strict application of blood bank standards, we have obtained a standardized, reproducible, safe, cheap, and ready-to-use product.

11.
Biometrics ; 77(2): 622-633, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32535900

RESUMO

The simultaneous testing of multiple hypotheses is common to the analysis of high-dimensional data sets. The two-group model, first proposed by Efron, identifies significant comparisons by allocating observations to a mixture of an empirical null and an alternative distribution. In the Bayesian nonparametrics literature, many approaches have suggested using mixtures of Dirichlet Processes in the two-group model framework. Here, we investigate employing mixtures of two-parameter Poisson-Dirichlet Processes instead, and show how they provide a more flexible and effective tool for large-scale hypothesis testing. Our model further employs nonlocal prior densities to allow separation between the two mixture components. We obtain a closed-form expression for the exchangeable partition probability function of the two-group model, which leads to a straightforward Markov Chain Monte Carlo implementation. We compare the performance of our method for large-scale inference in a simulation study and illustrate its use on both a prostate cancer data set and a case-control microbiome study of the gastrointestinal tracts in children from underdeveloped countries who have been recently diagnosed with moderate-to-severe diarrhea.


Assuntos
Microbiota , Teorema de Bayes , Criança , Simulação por Computador , Humanos , Cadeias de Markov , Método de Monte Carlo
12.
Econom Stat ; 15: 117-135, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33163735

RESUMO

There is a strong interest in the neuroscience community to measure brain connectivity and develop methods that can differentiate connectivity across patient groups and across different experimental stimuli. The development of such statistical tools is critical to understand the dynamics of functional relationships among brain structures supporting memory encoding and retrieval. However, the challenge comes from the need to incorporate within-condition similarity with between-conditions heterogeneity in modeling connectivity, as well as how to provide a natural way to conduct trial- and condition-level inference on effective connectivity. A Bayesian hierarchical vector autoregressive (BH-VAR) model is proposed to characterize brain connectivity and infer differences in connectivity across conditions. Within-condition connectivity similarity and between-conditions connectivity heterogeneity are accounted for by the priors on trial-specific models. In addition to the fully Bayesian framework, an alternative two-stage computation approach is also proposed which still allows straightforward uncertainty quantification of between-trial conditions via MCMC posterior sampling, but provides a fast approximate procedure for the estimation of trial-specific VAR parameters. A novel aspect of the approach is the use of a frequency-specific measure, partial directed coherence (PDC), to characterize effective connectivity under the Bayesian framework. More specifically, PDC allows inferring directionality and explaining the extent to which the present oscillatory activity at a certain frequency in a sender channel influences the future oscillatory activity in a specific receiver channel relative to all possible receivers in the brain network. The proposed model is applied to a large electrophysiological dataset collected as rats performed a complex sequence memory task. This unique dataset includes local field potentials (LFPs) activity recorded from an array of electrodes across hippocampal region CA1 while animals were presented with multiple trials from two main conditions. The proposed modeling approach provided novel insights into hippocampal connectivity during memory performance. Specifically, it separated CA1 into two functional units, a lateral and a medial segment, each showing stronger functional connectivity to itself than to the other. This approach also revealed that information primarily flowed in a lateral-to-medial direction across trials (within-condition), and suggested this effect was stronger on one trial condition than the other (between-conditions effect). Collectively, these results indicate that the proposed model is a promising approach to quantify the variation of functional connectivity, both within- and between-conditions, and thus should have broad applications in neuroscience research.

13.
Materials (Basel) ; 13(10)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413993

RESUMO

One of the main hurdles to improving scaffolds for regenerative medicine is the development of non-invasive methods to monitor cell proliferation within three-dimensional environments. Recently, an electrical impedance-based approach has been identified as promising for three-dimensional proliferation assays. A low-cost impedance-based solution, easily integrable with multi-well plates, is here presented. Sensors were developed using biocompatible carbon-based ink on foldable polyimide substrates by means of a novel aerosol jet printing technique. The setup was tested to monitor the proliferation of human mesenchymal stromal cells into previously validated gelatin-chitosan hybrid hydrogel scaffolds. Reliability of the methodology was assessed comparing variations of the electrical impedance parameters with the outcomes of enzymatic proliferation assay. Results obtained showed a magnitude increase and a phase angle decrease at 4 kHz (maximum of 2.5 kΩ and -9 degrees) and an exponential increase of the modeled resistance and capacitance components due to the cell proliferation (maximum of 1.5 kΩ and 200 nF). A statistically significant relationship with enzymatic assay outcomes could be detected for both phase angle and electric model parameters. Overall, these findings support the potentiality of this non-invasive approach for continuous monitoring of scaffold-based cultures, being also promising in the perspective of optimizing the scaffold-culture system.

14.
J Womens Health (Larchmt) ; 29(6): 837-846, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32466701

RESUMO

Background: Three national career development programs (CDPs)-Early and Mid-Career Programs sponsored by the Association of American Medical Colleges and the Hedwig van Ameringen Executive Leadership in Academic Medicine sponsored by Drexel University-seek to expand gender diversity in faculty and institutional leadership of academic medical centers. Over 20 years of success and continued need are evident in the sustained interest and investment of individuals and institutions. However, their impact on promotion in academic rank remains unknown. The purpose of the study is to compare promotion rates of women CDP participants and other faculty of similar institutional environment and initial career stage. Methods: The study examined retrospective cohorts of 2,719 CDP participants, 12,865 nonparticipant women, and 26,810 men, from the same institutions, with the same degrees, and first years of appointment in rank. Rates of promotion to Associate and Full Professor ranks in respective cohorts of Assistant and of Associate Professors were compared using Kaplan-Meier survival curves and log-rank tests, and logistic regression adjusting for other predictors of academic success. Results: In adjusted analyses, participants were more likely than men and non-participant women to be promoted to Associate Professor and as likely as men and more likely than non-participant women to be promoted to Full Professor within 10 years. Within 5 years, CDP participants were more likely than nonparticipant women to be promoted to Associate Professor and as likely as to be promoted to Full Professor; in the same interval, participants were promoted to both higher ranks at the same rates as men. For both intervals, nonparticipant women were significantly less likely than men to be promoted to either rank. Conclusions: The higher rates of promotion for women participating in national CDPs support the effectiveness of these programs in building capacity for academic medicine.


Assuntos
Centros Médicos Acadêmicos/organização & administração , Mobilidade Ocupacional , Docentes de Medicina/estatística & dados numéricos , Médicas/estatística & dados numéricos , Desenvolvimento de Pessoal , Feminino , Humanos , Liderança , Masculino , Estudos Retrospectivos , Fatores Sexuais , Estados Unidos
15.
Int J Mol Sci ; 21(8)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331251

RESUMO

Atherosclerosis represents one of the main risk factors for the development of cardiovascular diseases. Their etiologies have been studied in recent years in order to better define therapeutic targets for intervention and to identify diagnostic methods. Two different subtypes of macrophages, M1 and M2, have been described in physiological conditions. They can also be found in the atherosclerotic process, where they both have opposite roles in disease progression. Perivascular brown adipose tissue is also involved in inflammation and endothelial damage. In this work, we provide insights into the protective role of melatonin in the atherosclerotic process by morphological and 18F-FDG-PET/CT analyses. In particular, we examined the effects of melatonin on pathways that are linked to atherosclerosis development. We showed that melatonin, by suppressing M1 activity, reduced inflammation and directed macrophage polarization toward the M2 macrophage subtype. Moreover, melatonin preserved the activity of perivascular brown adipose tissue. In addition, 18F-FDG uptake is very high in mice treated with melatonin, confirming that other factors may alter 18F-FDG distribution. In conclusion, we showed that melatonin affects inflammatory pathways that have been linked to atherosclerosis, assessed the relationships of the 18F-FDG PET/CT parameters with macrophage markers and the production of their cytokines, which that have been defined by morphological evaluations.


Assuntos
Apolipoproteínas E/deficiência , Fluordesoxiglucose F18 , Melatonina/metabolismo , Imagem Molecular , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tecido Adiposo Marrom/metabolismo , Animais , Aortite/etiologia , Aortite/metabolismo , Aortite/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/etiologia , Aterosclerose/metabolismo , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Imunofluorescência , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Imagem Molecular/métodos , Compostos Radiofarmacêuticos
16.
Skeletal Radiol ; 49(6): 1005-1014, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31965239

RESUMO

OBJECTIVES: The objectives of the study are (1) to distinguish lipoma (L) from atypical lipomatous tumor (ALT) using MRI qualitative features, (2) to assess the value of contrast enhancement, and (3) to evaluate the reproducibility and confidence level of radiological readings. MATERIALS AND METHODS: Patients with pathologically proven L or ALT, who underwent MRI within 3 months from surgical excision were included in this retrospective multicenter international study. Two radiologists independently reviewed MRI centrally. Impressions were recorded as L or ALT. A third radiologist was consulted for discordant readings. The two radiologists re-read all non-contrast sequences; impression was recorded; then post-contrast images were reviewed and any changes were recorded. RESULTS: A total of 246 patients (135 females; median age, 59 years) were included. ALT was histopathologically confirmed in 70/246 patients. In multivariable analysis, in addition to the lesion size, deep location, proximal lower limb lesions, demonstrating incomplete fat suppression, or increased architectural complexity were the independent predictive features of ALT; but not the contrast enhancement. Post-contrast MRI changed the impression in a total of 5 studies (3 for R1 and 4 for R2; 2 studies are common); all of them were incorrectly changed from Ls to ALTs. Overall, inter-reader kappa agreement was 0.42 (95% CI 0.39-0.56). Discordance between the two readers was statistically significant for both pathologically proven L (p < 0.001) and ALT (p = 0.003). CONCLUSION: Most qualitative MR imaging features can help distinguish ALTs from BLs. However, contrast enhancement may be limited and occasionally misleading. Substantial discordance on MRI readings exists between radiologists with a relatively high false positive and negative rates.


Assuntos
Lipoma/diagnóstico por imagem , Lipossarcoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Feminino , Humanos , Lipoma/patologia , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
17.
Psychophysiology ; 56(4): e13309, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30556253

RESUMO

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue-induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food-related cues than to erotic images are more susceptible to cue-induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue-induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.


Assuntos
Sinais (Psicologia) , Literatura Erótica , Potenciais Evocados/fisiologia , Comportamento Alimentar/fisiologia , Alimentos , Sobrepeso/fisiopatologia , Adulto , Idoso , Suscetibilidade a Doenças , Eletroencefalografia , Endofenótipos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Adulto Jovem
18.
Biometrics ; 75(1): 183-192, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30125947

RESUMO

In this article, we develop a Bayesian hierarchical mixture regression model for studying the association between a multivariate response, measured as counts on a set of features, and a set of covariates. We have available RNA-Seq and DNA methylation data measured on breast cancer patients at different stages of the disease. We account for the heterogeneity and over-dispersion of count data (here, RNA-Seq data) by considering a mixture of negative binomial distributions and incorporate the covariates (here, methylation data) into the model via a linear modeling construction on the mean components. Our modeling construction includes several innovative characteristics. First, it employs selection techniques that allow the identification of a small subset of features that best discriminate the samples while simultaneously selecting a set of covariates associated to each feature. Second, it incorporates known dependencies into the feature selection process via the use of Markov random field (MRF) priors. On simulated data, we show how incorporating existing information via the prior model can improve the accuracy of feature selection. In the analysis of RNA-Seq and DNA methylation data on breast cancer, we incorporate knowledge on relationships among genes via a gene-gene network, which we extract from the KEGG database. Our data analysis identifies genes which are discriminatory of cancer stages and simultaneously selects significant associations between those genes and DNA methylation sites. A biological interpretation of our findings reveals several biomarkers that can help understanding the effect of DNA methylation on gene expression transcription across cancer stages.


Assuntos
Teorema de Bayes , Distribuição Binomial , Neoplasias da Mama/genética , Redes Reguladoras de Genes , Modelos Estatísticos , Análise de Regressão , Sequência de Bases , Biomarcadores Tumorais , Metilação de DNA , Interpretação Estatística de Dados , Feminino , Humanos
20.
Echocardiography ; 35(10): 1512-1518, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30005128

RESUMO

BACKGROUND: Previous studies have not evaluated the prevalence and specific risk factors for the development of left ventricular (LV) thrombus in patients with severely reduced left ventricular dysfunction due to chemotherapy-related cardiomyopathy. We sought to evaluate the prevalence and potential markers of LV thrombus in this patient population. METHODS: From January 2009 to December 2013, patients with chemotherapy-related severe LV dysfunction (LV ejection fraction [LVEF] ≤ 30%) identified from MD Anderson Cancer Center database were reviewed. Patient characteristics and echocardiographic parameters were analyzed to determine potential risk factors for LV thrombus. RESULTS: A total of 121 patients met inclusion criteria (age 54.8 ± 15.2 years; female 63.6%; LVEF 26.3 ± 4%). LV thrombus was present in 9 patients (7.4%). Patients with LV thrombus have significantly lower LVEF compared to those without (18.7 ± 3.8% vs 26.9 ± 3.4%, P < .0001). Prevalence of LV thrombus increased as LVEF decreased and was the highest in patients with LVEF < 20%. By univariate analysis, decreased LVEF, particularly LVEF < 20% (OR 36.30, 95% CI 7.35-179.25, P < .0001) and restrictive LV filling pattern (OR 18.13, 95% CI 4.17-78.89, P = .0001) were associated with presence of LV thrombus. CONCLUSION: In patients with severely reduced LV systolic function due to chemotherapy-induced cardiomyopathy, LV thrombus was found in 7.4% of subjects. Severely decreased LVEF (<20%) and restrictive LV filling pattern were associated with the presence of LV thrombus.


Assuntos
Antineoplásicos/efeitos adversos , Ecocardiografia/métodos , Cardiopatias/induzido quimicamente , Trombose/diagnóstico por imagem , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Feminino , Cardiopatias/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/complicações
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