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Publications (80)
We assessed the role of patient-centered care on durable viral suppression (i.e., all viral load test results < 200 copies per ml during 2019) by conducting a retrospective cohort study of clients medically case managed by the Miami-Dade County Ryan White Program (RWP). Summary measures of patient-centered care practices of RWP-affiliated providers...
Background and Purpose: Pulmonary arterial hypertension (PAH) causes
debilitating harm to approximately 20,000 Americans who have a median survival
of 2.8 years and die due to right heart failure. PAH patients with occlusive
pulmonary artery vasculopathy have a grim survival prognosis. Current drugs
allow functional and hemodynamic improvements...
Heavy metals are toxic substances that have caused great ecological damage, can sorb with sediments, become mobile in surface waters and infiltrate the food chain. As a result, long-term exposures associated with ingestion and recreational exposures lead to environmental and human health-associated risks. The present work aims to monitor environmen...
Cerebral amyloid angiopathy (CAA) is a degenerative vasculopathy. We have previously shown that transcription regulating proteins- inhibitor of DNA binding protein 3 (ID3) and the nuclear respiratory factor 1 (NRF1) contribute to vascular dysregulation. In this study, we have identified sex specific ID3 and NRF1-mediated gene networks in CAA patien...
Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men in the world. Its prevention has been limited because of an incomplete understanding of how environmental exposures to chemicals contribute to the molecular pathogenesis of aggressive PCa. Environmental exposures to endocrine-disrupting chemicals (EDCs) may mimic hormon...
Purpose
The mechanisms contributing to recurrence of glioblastoma (GBM), an aggressive neuroepithelial brain tumor, remain unknown. We have recently shown that nuclear respiratory factor 1 (NRF1) is an oncogenic transcription factor and its transcriptional activity is associated with the progression and prognosis of GBM. Herein, we extend our effor...
Ovarian cancer is the most lethal gynecological cancer, accounting for thousands of cancer-related deaths in the United States every year. Though there has been progress towards understanding ovarian cancer pathogenesis, much is not yet understood about the molecular mechanisms that facilitate chemoresistance and metastasis. Our work has shown that...
Every year, biomedical data is increasing at an alarming rate and is being collected from many different sources, such as hospitals (clinical Big Data), laboratories (genomic and proteomic Big Data), and the internet (online Big Data). This article presents and evaluates a practical causal discovery algorithm that uses modern statistical, machine l...
Prostate cancer (PCa) is one of the leading malignant tumors in US men. The lack of understanding of the molecular pathology on the risk of food supply chain exposures of environmental phenol (EP) and paraben (PB) chemicals limits the prevention, diagnosis, and treatment options. This research aims to utilize a risk assessment approach to demonstra...
The small vessel disease, cerebral amyloid angiopathy (CAA), is characterized by amyloid beta protein in the vessel wall. Health complications arising from CAA include increased risk for stroke. Transcription factor nuclear respiratory factor 1 (NRF1) was reported to have a DNA binding motif in APOE4, a known risk factor for CAA. Exposure to amyloi...
Major findings from the study are:
NRF1 transcription factor mRNA expression and total transcription factor activity was lower in CAA cases compared to control. Lower NRF1 expression was also associated with APOE4 carriers and severe cases of CAA.
ID3 mRNA expression and total transcription activity was higher in CAA cases compared to control.
Es...
Using a machine learning method, this study aimed to identify unique causal networks of genes associated with bone, brain, and lung metastasis of breast cancer. Bayesian network analysis identified differentially expressed genes in primary breast cancer tissues, in bone, brain, and lung breast cancer metastatic tissues, and the clinicopathological...
Purpose:
Nuclear respiratory factor 1 (NRF1) drives estrogen-dependent breast tumorigenesis. Herein we examined the impact of NRF1 activity on the aggressiveness and disparate molecular signature of breast cancer in Black, White, Asian, and Hispanic women.
Methods:
NRF1 activity by transcription factor target enrichment analysis and causal NRF1-...
Despite tremendous progress in understanding the pathobiology of astrocytoma, major gaps remain in our knowledge of the molecular basis underlying the aggressiveness of high-grade astrocytoma (glioblastoma - GBM). Recently, we and others have shown nuclear respiratory factor 1 (NRF1) transcription factor being highly active in human cancers, but it...
The motive of this study is to investigate the molecular mechanisms of nrf1 and its target genes to furnish in the development of novel candidate gene networks which can be used to detect adverse responses elucidated by arsenic.
Cerebrovascular disease (CBVD) often leads to cognitive impairment and is
a prominent comorbidity of Alzheimer’s disease (AD) observed in 60%-90%
of patients. Single nucleotide polymorphism in the human ID3 gene has
been associated with atherosclerosis, however, its contribution to CBVD is
unknown. This study uses a machine learning-based analysis...
There is a growing convergence between molecular aspects of aging and cancer. Cellular senescence acts as a barrier through preventing the proliferation of cells under oncogenic stress. Therefore, we decided to examine the role of nuclear respiratory factor 1 (NRF1) transcription factor in human brain cancer and brain aging. In contrast to higher e...
There is a growing convergence between molecular aspects of aging and cancer. Cellular senescence acts as a barrier through preventing the proliferation of cells under oncogenic stress. Therefore, we decided to examine the role of nuclear respiratory factor 1 (NRF1) transcription factor in human brain cancer and brain aging. In contrast to higher e...
Objective:
To describe children's anxiety, depression, behaviors, and school performance at 2-13 months after sibling neonatal/pediatric intensive care unit (NICU/PICU) or emergency department (ED) death and compare these outcomes by child age, sex, race/ethnicity, whether the child saw their sibling in the NICU/PICU/ED, and attended the sibling's...
[This corrects the article on p. 251 in vol. 25, PMID: 30574470.].
Background:
The causal networks among genes that are commonly expressed in osteoblasts and during bone metastasis (BM) of breast cancer (BC) are not well understood. Here, we developed a machine learning method to obtain a plausible causal network of genes that are commonly expressed during BM and in osteoblasts in BC.
Methods:
We selected BC ge...
Nuclear respiratory factor 1 (NRF1) transcription factor has recently been shown to control breast cancer progression. However, mechanistic aspects by which NRF1 may contribute to susceptibility to different breast tumor subtypes are still not fully understood. Since transcriptional control of NRF1 seems to be dependent on epidermal growth factor r...
Purpose
As the elderly population increases, a growing number of patients have lower urinary tract symptom (LUTS)/benign prostatic hyperplasia (BPH). The aim of this study was to develop decision support formulas and nomograms for the prediction of bladder outlet obstruction (BOO) and for BOO-related surgical decision-making, and to validate them i...
Purpose
We aimed to externally validate the prediction model we developed for having bladder outlet obstruction (BOO) and requiring prostatic surgery using 2 independent data sets from tertiary referral centers, and also aimed to validate a mobile app for using this model through usability testing.
Methods
Formulas and nomograms predicting whether...
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine d...
Introduction: Estrogen is a driver in the growth and progression of gynecologic cancers (cervical, ovarian, and uterine). A number of estrogenically active chemicals are suspected to contribute in the development of gynecologic lesions, including an increased risk of estrogen-dependent cancer in women. Humans are exposed to estrogenic endocrine dis...
Objective:
Describe changes in mothers' and fathers' grief from 1 to 13 months after infant/child neonatal/pediatric intensive care unit death and identify factors related to their grief.
Methods:
Mothers (n = 130) and fathers (n = 52) of 140 children (newborn-18 years) completed the Hogan Grief Reaction Checklist at 1, 3, 6, and 13 months post-...
Most of the chronic diseases occur as a result of adverse effects at multiple points on behavioral, biochemical, genetic, and physiological systems, often from multiple exposures and across various life stages. There is also a tremendous interindividual variability in the health outcome in response to environmental and stochastic factors. This has...
We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Huma...
HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 c...
17β-Oestradiol (E2)-induced reactive oxygen species (ROS) have been implicated in regulating the growth of breast cancer cells. However, the underlying mechanism of this is not clear. Here we show how ROS through a novel redox signalling pathway involving nuclear respiratory factor-1 (NRF-1) and p27 contribute to E2-induced growth of MCF-7 breast c...
This cross-sectional study examined the physical and mental health, grief and role functioning of 136 grandparents in the first year after death of their young grandchild (newborn through 6 years). Grandparents were 36-77 years old; 73 % female; 24 % Hispanic, 38 % Black/African American, and 38 % White. Mean age of the 115 deceased grandchildren w...
To ascertain the association of cystourethroscopic findings of bladder neck elevation with urodynamic bladder outlet obstruction (BOO) in patients with lower urinary tract symptoms and benign prostatic hyperplasia (LUTS-BPH).
Study subjects were 646 consecutive men aged >40 years diagnosed with LUTS-BPH at Seoul National University Hospital from De...
To identify the factors affecting the surgical decisions of experienced physicians when treating patients with lower urinary tract symptoms that are suggestive of benign prostatic hyperplasia (LUTS/BPH).
Patients with LUTS/BPH treated by two physicians between October 2004 and August 2013 were included in this study. The causal Bayesian network (CB...
Purpose
To identify non-invasive clinical parameters to predict urodynamic bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH) using causal Bayesian networks (CBN).
Subjects and Methods
From October 2004 to August 2013, 1,381 eligible BPH patients with complete data were selected for analysis. The following clinica...
The molecular mechanism unraveling why a particular type of pediatric brain tumor (pBT) behaves so differently from child to child or genetic/epigenetic changes in the mitochondrial genome vary from tumor to tumor is not clearly understood. Despite the identification of mitochondrial DNA (mtDNA) mutations in different types of pBT, the contribution...
Objective
To establish a cystoscopic grading system for trabeculation of neurogenic bladders.
Materials and Methods
A total of 140 neurogenic bladder patients who had undergone both fluoroscopic urodynamic study and cystoscopic examination were retrospectively reviewed. Cystoscopic images were categorized into 4 grades according to the formation o...
Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antig...
According to a survey from the HIV Cost and Services Utilization Study (HCSUS), approximately 53% of HIV-infected patients reported drinking alcohol and 8% were classified as heavy drinkers. The role of alcohol as a risk factor for HIV infection has been widely studied and recent research has found a significant association between heavy alcohol co...
Despite that mutations in mitochondrial DNA (mtDNA) have been associated with major epilepsy syndromes, the role of mtDNA instability and mitochondrial dysfunction in epileptogenesis has not been comprehensively examined. In the present study, we investigated the role of mtDNA copy number, oxidative damage, and mtDNA variants as independent or comb...
Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the...
In this article we introduce modern statistical machine learning and bioinformatics approaches that have been used in learning statistical relationships from big data in medicine and behavioral science that typically include clinical, genomic (and proteomic) and environmental variables. Every year, data collected from biomedical and behavioral scie...
Autophagy is an important catabolic process for the clearance of damaged or superfluous proteins and organelles. The role of ethanol in the regulation of autophagy remains controversial, with some studies showing induction of autophagy by ethanol while others show inhibition. Nevertheless, the view that maintenance of adequate levels of autophagy p...
Patients can experience urinary retention (UR) after Holmium laser enucleation of the prostate (HoLEP) that requires bladder distension during the procedure. The aim of this retrospective study is to identify factors affecting the UR after HoLEP.
336 patients, which underwent HoLEP for a symptomatic benign prostatic hyperplasia between July 2008 an...
Discernment analyses in survey data are being developed to help researchers better understand intentions of surveyed subjects. These models can aid in successful decision-making by allowing calculation of the likelihood of a particular outcome based on subject’s known characteristics. The most frequently used discernment analysis in epidemiological...
Faulty autophagy has been linked to various diseases including neurodegenerative disorders, diabetes, and cancer. Increasing evidence support the notion that activation of autophagy protects against ethanol-induced steatosis and liver injury. Herein, we investigated the role of zinc in autophagy in human hepatoma cells VL-17A exposed or not to etha...
HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in H...
In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene...
To establish a grading system for bladder trabeculation.
A total of 228 patients who underwent videourodynamic studies were retrospectively reviewed. All fluoroscopic images included were gathered and were classified into 4 grades of trabeculation according to maximum depth and portion of bladder surface occupied: 0 (none), 1 (mild, depth <5 mm and...
In recent years, scientists and health professionals have become overwhelmed by the amount of genomic data available for epidemiological studies and patient care. In April 1996, the genome sequence of the yeast Saccharomyces cerevisiae was completed. By December 1999, the first plant's complete genome sequence from Arabidopsis thaliana was publishe...
This paper describes a Bayesian method for combining an arbitrary mixture of
observational and experimental data in order to learn causal Bayesian networks.
Observational data are passively observed. Experimental data, such as that
produced by randomized controlled trials, result from the experimenter
manipulating one or more variables (typically r...
Glioblastoma Multiforme (GBM) is the most common and aggressive type of human brain tumor. Although considerable efforts to delineate the underlying pathophysiological pathways have been made during the last decades, only very limited progress on treatment have been achieved because molecular pathways that drive the aggressive nature of GBM are lar...
To learn about the progression of a complex disease, it is necessary to understand the physiology and function of many genes operating together in distinct interactions as a system. In order to significantly advance our understanding of the function of a system, we need to learn the causal relationships among its modeled genes. To this end, it is d...
Background: Haiti has the highest number of HIV-infected persons in the Caribbean region. For people living with HIV/AIDS, high levels of adherence to ARV treatment is critical to maintaining health and reducing transmission risk. Methods: This study was conducted to examine factors influencing ARV drug adherence among a sample of HIV+ adult patien...
Previous studies have demonstrated that alcohol use disorders (AUDs) are regulated by multiple mechanisms such as neurotransmitters and enzymes. The neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) may contribute to alcohol effects and serotonin receptors, including 5-HT3, play an important role in AUDs. Recent studies have also implicated h...
This paper describes a Bayesian method for learning causal Bayesian networks through networks that contain latent variables from an arbitrary mixture of observational and experimental data. The paper presents Bayesian methods (including a new method) for learning the causal structure and parameters of the underlying causal process that is generatin...
Despite the extensive research in the field of vascular proliferative disease, the complex interaction of genes with environmental factors with respect to its impact on this disease is not yet fully understood. To date, results from the literature show no direct studies of vascular gene-environment interactions. Vascular lesions consist of actively...
The exponential growth of molecular biology data led to an intense focus on the study of interactions among DNA, RNA, protein
biosynthesis, and environment. Using advanced genomics revolution tools, large datasets generated by the gene expression profiling
experiments and next generation sequences technologies enable us to link molecular states and...
The cardiovascular system is an important target of estrogenic compounds. Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that estrogenic environmental compounds may contribute to the pathology of vascular lesion formation.
Real-time quantitative PCR was used to moni...
Using microarray experiments, we can model causal relationships of genes measured through mRNA expression levels. To this end, it is desirable to compare experiments of the system under complete interventions of some genes, such as by knock out of some genes, with experiments of the system under no interventions. However, it is expensive and diffic...
The main topic of this paper is evaluating a system that uses the expected value of experimentation for discovering causal pathways in gene expression data. By experimentation we mean both interventions (e.g., a gene knock-out experiment) and observations (e.g., passively observing the expression level of a “wild-type” gene). We introduce a system...
The main topic of this paper is modeling the expected value of experimentation (EVE) for discovering causal pathways in gene expression data. By experimentation we mean both interventions (e.g., a gene knockout experiment) and observations (e.g., passively observing the expression level of a “wild-type” gene). We introduce a system called GEEVE (ca...
The main topic of this paper is modeling the expected value of experimentation (EVE) for discovering causal pathways in gene expression data. By experimentation we mean both interventions (e.g., a gene knockout experiment) and observations (e.g., passively observing the expression level of a “wild-type” gene). We introduce a system called GEEVE (ca...
This paper reports the methods and evaluation of a computer-based system that recommends microarray experimental design for biologists - causal discovery in Gene Expression data using Expected Value of Experimentation (GEEVE). The GEEVE system uses causal Bayesian networks and generates a decision tree for recommendations. To evaluate the GEEVE sys...
This paper reports the methods and results of a computer-based algorithm that takes as input the expression levels of a set of genes as given by DNA microarray data, and then searches for causal pathways that represent how the genes regulate each other. The algorithm uses local heuristic search and a Bayesian scoring metric. We applied the algorith...
This paper reports the methods and results of a computer-based search for causal relationships in the gene-regulation pathway of galactose metabolism in the yeast Saccharomyces cerevisiae. The search uses recently published data from cDNA microarray experiments. A Bayesian method was applied to learn causal networks from a mixture of observational...
Instrumental Variable (IV) estimation is a powerful strategy for estimating causal influence, even in the presence of confounding. Standard IV estimation requires that the relationships between variables is linear. Here we relax the linearity requirement by constructing a piecewise linear IV estimator. Simulation studies show that when the causal i...
