880 results on '"Baccarelli, P."'
Search Results
2. Multi-resolution Twinned Residual Auto-Encoders (MR-TRAE)—A Novel DL Model for Image Multi-resolution
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Momenzadeh, Alireza, Baccarelli, Enzo, Scarpiniti, Michele, and Sarv Ahrabi, Sima
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- 2024
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3. Endocrine-disrupting chemical concentrations in follicular fluid and follicular reproductive hormone levels
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Hoffmann-Dishon, Nathalie, Barnett-Itzhaki, Zohar, Zalko, Daniel, Hemi, Rina, Farzam, Nahid, Hauser, Russ, Racowsky, Catherine, Baccarelli, Andrea A., and Machtinger, Ronit
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- 2024
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4. Psychosocial Stress and MicroRNA Expression Profiles in Myometrial Tissue of Women Undergoing Surgical Treatment for Uterine Fibroids
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Dye, Christian K., Wu, Haotian, VanNoy, Brianna, Calluori, Stephanie, Marfori, Cherie Q., Baccarelli, Andrea A., and Zota, Ami R.
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- 2024
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5. Climate change and health: understanding mechanisms will inform mitigation and prevention strategies
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Prada, Diddier, Baccarelli, Andrea A., Kupsco, Allison, and Parks, Robbie M.
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- 2024
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6. Intermediate and long-term exposure to air pollution and temperature and the extracellular microRNA profile of participants in the normative aging study (NAS)
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Danesh Yazdi, Mahdieh, Nassan, Feiby L, Kosheleva, Anna, Wang, Cuicui, Xu, Zongli, Di, Qian, Requia, Weeberb J, Comfort, Nicole T, Wu, Haotian, Laurent, Louise C, DeHoff, Peter, Vokonas, Pantel, Baccarelli, Andrea A, and Schwartz, Joel D
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Environmental Sciences ,Pollution and Contamination ,Aging ,Genetics ,Biotechnology ,Climate-Related Exposures and Conditions ,Aetiology ,2.2 Factors relating to the physical environment ,Good Health and Well Being ,Humans ,Air Pollutants ,Nitrogen Dioxide ,Temperature ,Particulate Matter ,Air Pollution ,MicroRNAs ,Environmental Exposure ,Ozone ,Particulate matter ,Nitrogen dioxide ,Ambient temperature ,microRNA ,Air pollution ,Chemical Sciences ,Biological Sciences ,Toxicology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
BackgroundThe molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.ObjectivesTo assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.MethodsOur study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM2.5, O3, NO2, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis.ResultsWe found 151 significant associations between levels of PM2.5, O3, NO2, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O3, long-term exposure to PM2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionOur results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted.
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- 2023
7. Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging
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Dye, Christian K., Wu, Haotian, Jackson, Gabriela L., Kidane, Altaye, Nkambule, Rejoice, Lukhele, Nomthandazo G., Malinga, Bongiwe Prudence, Chekenyere, Rhinos, El-Sadr, Wafaa M., Baccarelli, Andrea A., and Harris, Tiffany G.
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- 2024
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8. Establishing non-fasting reference values for plasma lipids levels based on age, sex, and puberty stage in a French-Canadian pediatric population
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Bouhour, Sophie, Plantefève, Rosalie, Gillet, Virginie, Abolghasemi, Armita, Bouchouirab, Fatima Zahra, Baccarelli, Andrea A., Takser, Larissa, and Çaku, Artuela
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- 2024
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9. Accelerated biological aging elevates the risk of cardiometabolic multimorbidity and mortality
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Jiang, Meijie, Tian, Sifan, Liu, Shuzhen, Wang, Yuting, Guo, Xinbiao, Huang, Tao, Lin, Xihong, Belsky, Daniel W., Baccarelli, Andrea A., and Gao, Xu
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- 2024
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10. Author Correction: Accelerated biological aging elevates the risk of cardiometabolic multimorbidity and mortality
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Jiang, Meijie, Tian, Sifan, Liu, Shuzhen, Wang, Yuting, Guo, Xinbiao, Huang, Tao, Lin, Xihong, Belsky, Daniel W., Baccarelli, Andrea A., and Gao, Xu
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- 2024
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11. Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.
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Do, Whitney, Sun, Dianjianyi, Meeks, Karlijn, Dugué, Pierre-Antoine, Demerath, Ellen, Guan, Weihua, Li, Shengxu, Chen, Wei, Milne, Roger, Adeyemo, Abedowale, Agyemang, Charles, Nassir, Rami, Manson, JoAnn, Hou, Lifang, Horvath, Steve, Assimes, Themistocles, Bhatti, Parveen, Jordahl, Kristina, Baccarelli, Andrea, Smith, Alicia, Staimez, Lisa, Stein, Aryeh, Whitsel, Eric, Narayan, K, Conneely, Karen, and Shadyab, Aladdin
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BMI ,DNA methylation ,adiposity ,epigenome-wide association study ,epigenomics ,metabolic disease ,obesity ,prediction ,Humans ,Female ,Body Mass Index ,Epigenome ,Epigenesis ,Genetic ,Obesity ,Cholesterol ,HDL ,Genome-Wide Association Study ,DNA Methylation ,Epigenomics ,Triglycerides ,CpG Islands - Abstract
This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Womens Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p
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- 2023
12. Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants
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Danesh Yazdi, Mahdieh, Nassan, Feiby L, Kosheleva, Anna, Wang, Cuicui, Xu, Zongli, Di, Qian, Requia, Weeberb J, Comfort, Nicole T, Wu, Haotian, Laurent, Louise C, DeHoff, Peter, Vokonas, Pantel, Baccarelli, Andrea A, and Schwartz, Joel D
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Genetics ,Aging ,Climate-Related Exposures and Conditions ,Biotechnology ,Good Health and Well Being ,Humans ,Air Pollutants ,Air Pollution ,Environmental Exposure ,MicroRNAs ,Nitrogen Dioxide ,Ozone ,Particulate Matter ,Temperature ,Air pollution ,microRNA ,Particulate matter ,Nitrogen dioxide ,Ambient temperature ,Environmental Sciences - Abstract
BackgroundWhile the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.MethodsWe examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM2.5, NO2, O3, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses.ResultsWe found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionsAir pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.
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- 2023
13. Extracellular Vesicle-Encapsulated microRNAs as Novel Biomarkers of Lung Health.
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Eckhardt, Christina M, Gambazza, Simone, Bloomquist, Tessa R, De Hoff, Peter, Vuppala, Aishwarya, Vokonas, Pantel S, Litonjua, Augusto A, Sparrow, David, Parvez, Faruque, Laurent, Louise C, Schwartz, Joel, Baccarelli, Andrea A, and Wu, Haotian
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Genetics ,Lung ,Clinical Research ,Prevention ,Biotechnology ,Respiratory ,Good Health and Well Being ,Humans ,MicroRNAs ,Lung Injury ,Longitudinal Studies ,Prospective Studies ,Biomarkers ,Extracellular Vesicles ,extracellular vesicles ,microRNAs ,lung function ,spirometry ,Medical and Health Sciences ,Respiratory System - Abstract
Rationale: Early detection of respiratory diseases is critical to facilitate delivery of disease-modifying interventions. Extracellular vesicle-enriched microRNAs (EV-miRNAs) may represent reliable markers of early lung injury. Objectives: Evaluate associations of plasma EV-miRNAs with lung function. Methods: The prospective NAS (Normative Aging Study) collected plasma EV-miRNA measurements from 1996-2015 and spirometry every 3-5 years through 2019. Associations of EV-miRNAs with baseline lung function were modeled using linear regression. To complement the individual miRNA approach, unsupervised machine learning was used to identify clusters of participants with distinct EV-miRNA profiles. Associations of EV-miRNA profiles with multivariate latent longitudinal lung function trajectories were modeled using log binomial regression. Biological functions of significant EV-miRNAs were explored using pathway analyses. Results were replicated in an independent sample of NAS participants and in the HEALS (Health Effects of Arsenic Longitudinal Study). Measurements and Main Results: In the main cohort of 656 participants, 51 plasma EV-miRNAs were associated with baseline lung function (false discovery rate-adjusted P value
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- 2023
14. To promote healthy aging, focus on the environment
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Belsky, Daniel W. and Baccarelli, Andrea A.
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- 2023
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15. Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging
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Christian K. Dye, Haotian Wu, Gabriela L. Jackson, Altaye Kidane, Rejoice Nkambule, Nomthandazo G. Lukhele, Bongiwe Prudence Malinga, Rhinos Chekenyere, Wafaa M. El-Sadr, Andrea A. Baccarelli, and Tiffany G. Harris
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Epigenetics ,Epigenetic aging ,Biological aging ,HIV ,Epigenetic age acceleration ,DunedinPACE ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background People living with HIV (PLHIV) on effective antiretroviral therapy are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases. In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether epigenetic aging (i.e., the residual between regressing epigenetic age on chronological age) was associated with HIV-related parameters, and whether lifestyle factors modified these relationships. We calculated epigenetic aging focusing on the Horvath, Hannum, PhenoAge and GrimAge epigenetic clocks, and a pace of biological aging biomarker (DunedinPACE) among 44 OPLHIV in Eswatini. Results Age at HIV diagnosis was associated with Hannum epigenetic age acceleration (EAA) (β-coefficient [95% Confidence Interval]; 0.53 [0.05, 1.00], p = 0.03) and longer duration since HIV diagnosis was associated with slower Hannum EAA (− 0.53 [− 1.00, − 0.05], p = 0.03). The average daily dietary intake of fruits and vegetables was associated with DunedinPACE (0.12 [0.03, 0.22], p = 0.01). The associations of Hannum EAA with the age at HIV diagnosis and duration of time since HIV diagnosis were attenuated when the average daily intake of fruits and vegetables or physical activity were included in our models. Diet and self-perceived quality of life measures modified the relationship between CD4+ T cell counts at participant enrollment and Hannum EAA. Conclusions Epigenetic age is more advanced in OPLHIV in Eswatini in those diagnosed with HIV at an older age and slowed in those who have lived for a longer time with diagnosed HIV. Lifestyle and quality of life factors may differentially affect epigenetic aging in OPLHIV. To our knowledge, this is the first study to assess epigenetic aging in OPLHIV in Eswatini and one of the few in sub-Saharan Africa.
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- 2024
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16. Establishing non-fasting reference values for plasma lipids levels based on age, sex, and puberty stage in a French-Canadian pediatric population
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Sophie Bouhour, Rosalie Plantefève, Virginie Gillet, Armita Abolghasemi, Fatima Zahra Bouchouirab, Andrea A. Baccarelli, Larissa Takser, and Artuela Çaku
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Non-fasting state ,Reference intervals ,Pediatric ,French-Canadian ,Lipid profile ,Dyslipidemia ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background Dyslipidemias, including familial hypercholesterolemia (FH), are a significant risk factor for cardiovascular diseases. FH is a genetic disorder resulting in elevated levels of low-density lipoprotein cholesterol (LDL-C) and an increased probability of early cardiovascular disorders. Heterozygous familial hypercholesterolemia (HeFH) is the most common form, affecting approximately 1 in 250 individuals worldwide, with a higher prevalence among the French-Canadian population. Childhood is a critical period for screening risk factors, but the recommendation for non-fasting screening remains controversial due to a lack of specific reference values for this state. This study aims to establish reference values for lipid levels in non-fasting children from Sherbrooke, Quebec, Canada, that will be specific for sex, age, and pubertal stages. Methods Blood samples and corresponding anthropometric data were collected from 356 healthy children aged from 6 to 13. They were categorized either into two age groups: Cohort 6–8 and Cohort 9–13, or into pubertal stages. Reference values, specifically the 2.5th, 5th, 10th, 50th, 90th, 95th, and 97.5th percentiles were determined using the CLSI C28-A3 guidelines. Results Lipid profiles did not significantly differ between sexes, except for higher levels of high-density lipoprotein (HDL-C) in boys within Cohort 6–8. HDL-C levels significantly increased, while LDL-C and non-HDL-C levels significantly decreased in both sexes with age. Non-fasting age- and pubertal stages-specific reference values were established. Conclusion This study established reference intervals for lipid markers in non-fasting state within the pediatric French-Canadian population. These findings could be used in dyslipidemia screening in daily practice.
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- 2024
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17. A Resonant-Cavity Antenna With High-Gain and Wide Bandwidth With an All-Dielectric 3D-Printed Superstrate
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Cristina Ponti, Silvio Ceccuzzi, Paolo Baccarelli, and Giuseppe Schettini
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3D printing ,additive manufacturing ,electromagnetic-band gap (EBG) ,high gain ,resonant-cavity antenna (RCA) ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
The 3D-printing of dielectric superstrates of Resonant Cavity Antennas has advantages of fast prototyping and flexibility in the realization of customized layouts. In this work, the low dielectric permittivity of test filaments is experimentally measured for their use in superstrates of Resonant Cavity Antennas. A suitable combination of thickness, side extension and permittivity of the superstrate can enhance the antenna gain of the primary source over a broad frequency interval. With non-periodic and perforated layouts, instead, the radiative properties can be improved in terms of reductions of the Side-Lobe Level. The use of an all-dielectric superstrate in the design of an RCA is presented, demonstrating the possibility of obtaining a broadband gain enhancement with a single dielectric layer of low permittivity.
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- 2024
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18. AFAFed -- Protocol analysis
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Baccarelli, Enzo, Scarpiniti, Michele, Momenzadeh, Alireza, and Ahrabi, Sima Sarv
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Computer Science - Machine Learning ,Computer Science - Distributed, Parallel, and Cluster Computing - Abstract
In this paper, we design, analyze the convergence properties and address the implementation aspects of AFAFed. This is a novel Asynchronous Fair Adaptive Federated learning framework for stream-oriented IoT application environments, which are featured by time-varying operating conditions, heterogeneous resource-limited devices (i.e., coworkers), non-i.i.d. local training data and unreliable communication links. The key new of AFAFed is the synergic co-design of: (i) two sets of adaptively tuned tolerance thresholds and fairness coefficients at the coworkers and central server, respectively; and, (ii) a distributed adaptive mechanism, which allows each coworker to adaptively tune own communication rate. The convergence properties of AFAFed under (possibly) non-convex loss functions is guaranteed by a set of new analytical bounds, which formally unveil the impact on the resulting AFAFed convergence rate of a number of Federated Learning (FL) parameters, like, first and second moments of the per-coworker number of consecutive model updates, data skewness, communication packet-loss probability, and maximum/minimum values of the (adaptively tuned) mixing coefficient used for model aggregation.
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- 2022
19. Epigenetics of early-life adversity in youth: cross-sectional and longitudinal associations
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Sumner, Jennifer A, Gambazza, Simone, Gao, Xu, Baccarelli, Andrea A, Uddin, Monica, and McLaughlin, Katie A
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Biological Sciences ,Genetics ,Pediatric ,Violence Research ,Mental Health ,Human Genome ,Clinical Research ,Behavioral and Social Science ,Pediatric Research Initiative ,2.3 Psychological ,social and economic factors ,Aetiology ,Good Health and Well Being ,Adolescent ,Adverse Childhood Experiences ,Child ,Cross-Sectional Studies ,DNA Methylation ,Epigenesis ,Genetic ,Epigenomics ,Humans ,Threat ,Deprivation ,Abuse ,Neglect ,DNA methylation ,Clinical Sciences ,Paediatrics and Reproductive Medicine - Abstract
BackgroundAltered DNA methylation (DNAm) may be one pathway through which early-life adversity (ELA) contributes to adverse mental and physical health outcomes. This study investigated whether the presence versus absence of ELA experiences reflecting the dimensions of threat and deprivation were associated with epigenome-wide DNAm cross-sectionally and longitudinally in a community-based sample of children and adolescents.MethodsIn 113 youths aged 8-16 years with wide variability in ELA, we examined associations of abuse (physical, sexual, emotional; indicating threat-related experiences) and neglect (emotional, physical; indicating deprivation-related experiences) with DNAm assessed with the Illumina EPIC BeadChip array, with DNA derived from saliva. In cross-sectional epigenome-wide analyses, we investigated associations of lifetime abuse and neglect with DNAm at baseline. In longitudinal epigenome-wide analyses, we examined whether experiencing abuse and neglect over an approximately 2-year follow-up were each associated with change in DNAm from baseline to follow-up.ResultsIn cross-sectional analyses adjusting for lifetime experience of neglect, lifetime experience of abuse was associated with DNAm for four cytosine-phosphodiester-guanine (CpG) sites (cg20241299: coefficient = 0.023, SE = 0.004; cg08671764: coefficient = 0.018, SE = 0.003; cg27152686: coefficient = - 0.069, SE = 0.012; cg24241897: coefficient = - 0.003, SE = 0.001; FDR
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- 2022
20. Correction to: Endocrine-disrupting chemical concentrations in follicular fluid and follicular reproductive hormone levels
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Hoffmann-Dishon, Nathalie, Barnett-Itzhaki, Zohar, Zalko, Daniel, Hemi, Rina, Farzam, Nahid, Hauser, Russ, Racowsky, Catherine, Baccarelli, Andrea A., and Machtinger, Ronit
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- 2024
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21. Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study
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Comfort, Nicole, Wu, Haotian, De Hoff, Peter, Vuppala, Aishwarya, Vokonas, Pantel S, Spiro, Avron, Weisskopf, Marc, Coull, Brent A, Laurent, Louise C, Baccarelli, Andrea A, and Schwartz, Joel
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Mental Health ,Dementia ,Neurosciences ,Aging ,Biotechnology ,Alzheimer's Disease ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Brain Disorders ,Neurodegenerative ,Infectious Diseases ,Acquired Cognitive Impairment ,Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Aged ,Cognition ,Cognitive Dysfunction ,Cross-Sectional Studies ,Fatty Acids ,Humans ,Male ,MicroRNAs ,Prospective Studies ,Veterans ,plasma ,extracellular RNA ,RNA-seq ,microRNA ,cognitive decline ,cognitive impairment ,Biochemistry and Cell Biology ,Physiology ,Oncology and Carcinogenesis ,Developmental Biology - Abstract
BackgroundAging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.MethodsThis study includes data from up to 530 NAS participants (median age: 71.0 years) collected from 1996 to 2013, with a total of 1,331 person-visits (equal to 2,471 years of follow up). Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Plasma miRNAs were profiled using small RNA sequencing. Associations of expression of 381 miRNAs with current cognitive function and rate of change in cognitive function were assessed using linear regression (N = 457) and linear mixed models (N = 530), respectively.ResultsIn adjusted models, levels of 2 plasma miRNAs were associated with higher MMSE scores (p < 0.05). Expression of 33 plasma miRNAs was associated with rate of change in MMSE scores over time (p < 0.05). Enriched KEGG pathways for miRNAs associated with concurrent MMSE and MMSE trajectory included Hippo signaling and extracellular matrix-receptor interactions. Gene targets of miRNAs associated with MMSE trajectory were additionally associated with prion diseases and fatty acid biosynthesis.ConclusionsCirculating miRNAs were associated with both cross-sectional cognitive function and rate of change in cognitive function among cognitively normal men. Further research is needed to elucidate the potential functions of these miRNAs in the CNS and investigate relationships with other neurological outcomes.
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- 2022
22. Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease
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Uddin, MD Mesbah, Nguyen, Ngoc Quynh H, Yu, Bing, Brody, Jennifer A, Pampana, Akhil, Nakao, Tetsushi, Fornage, Myriam, Bressler, Jan, Sotoodehnia, Nona, Weinstock, Joshua S, Honigberg, Michael C, Nachun, Daniel, Bhattacharya, Romit, Griffin, Gabriel K, Chander, Varuna, Gibbs, Richard A, Rotter, Jerome I, Liu, Chunyu, Baccarelli, Andrea A, Chasman, Daniel I, Whitsel, Eric A, Kiel, Douglas P, Murabito, Joanne M, Boerwinkle, Eric, Ebert, Benjamin L, Jaiswal, Siddhartha, Floyd, James S, Bick, Alexander G, Ballantyne, Christie M, Psaty, Bruce M, Natarajan, Pradeep, and Conneely, Karen N
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Cardiovascular ,Stem Cell Research - Nonembryonic - Non-Human ,Aging ,Heart Disease - Coronary Heart Disease ,Atherosclerosis ,Human Genome ,Hematology ,Stem Cell Research ,Heart Disease ,2.1 Biological and endogenous factors ,Aetiology ,Cancer ,Good Health and Well Being ,Clonal Hematopoiesis ,Coronary Artery Disease ,DNA Methylation ,Hematopoiesis ,Hematopoietic Stem Cells ,Humans - Abstract
Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.
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- 2022
23. How Healthcare Systems Negatively Impact Environmental Health? The Need for Institutional Commitment to Reduce the Ecological Footprint of Medical Services
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Prisco Piscitelli, Stela Karaj, Alessandro Miani, Tassos C. Kyriakides, Enrico Greco, Elena Colicino, Antonio Bray, Fernando Simón, Vasilis Vasiliou, and Andrea A. Baccarelli
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n/a ,Internal medicine ,RC31-1245 - Abstract
The global healthcare industry plays a crucial role in preserving human health and well-being [...]
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- 2023
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24. Gomoku: analysis of the game and of the player Wine
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Piazzo, Lorenzo, Scarpiniti, Michele, and Baccarelli, Enzo
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Computer Science - Artificial Intelligence - Abstract
Gomoku, also known as five in a row, is a classical board game, ideally suited for quickly testing novel Artificial Intelligence (AI) techniques. With the aim of facilitating a developer willing to write a new Gomoku player, in this report we present an analysis of the main game concepts and strategies, which is wider and deeper than existing ones. Moreover, after discussing the general structure of an artificial player, we present and analyse a strong Gomoku player, named Wine, the code of which is freely available on the Internet and which is an excelent example of how a modern player is organised., Comment: 32 pages, 1 figure
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- 2021
25. Long-term exposure to ambient fine particulate components and leukocyte epigenome-wide DNA Methylation in older men: the Normative Aging Study
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Wang, Cuicui, Amini, Heresh, Xu, Zongli, Peralta, Adjani A., Yazdi, Mahdieh Danesh, Qiu, Xinye, Wei, Yaguang, Just, Allan, Heiss, Jonathan, Hou, Lifang, Zheng, Yinan, Coull, Brent A., Kosheleva, Anna, Baccarelli, Andrea A., and Schwartz, Joel D.
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- 2023
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26. A precision environmental health approach to prevention of human disease
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Baccarelli, Andrea, Dolinoy, Dana C., and Walker, Cheryl Lyn
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- 2023
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27. The effect of high polycyclic aromatic hydrocarbon exposure on biological aging indicators
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Campisi, Manuela, Mastrangelo, Giuseppe, Mielżyńska-Švach, Danuta, Hoxha, Mirjam, Bollati, Valentina, Baccarelli, Andrea A., Carta, Angela, Porru, Stefano, and Pavanello, Sofia
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- 2023
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28. Tétano em equino
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João Vitor Fraianella Teixeira de Godoy, Camila Alves Sobral, Tainá Rodrigues de Oliveira Zamian, Fernanda Meireles dos Reis, Gabriela Barbosa de Almeida, Paula Cristina Guimarães, Paulo Roberto Griska, Danielle Baccarelli da Silva, and Michele Andrade de Barros
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Soro antitetânico ,tetanoespasmina ,tetanolisina ,toxi-infecção ,Veterinary medicine ,SF600-1100 - Abstract
O tétano é causado pelas toxinas sintetizadas pelo Clostridium tetani, bactéria Gram-positiva, esporulada e anaeróbica obrigatória. A espécie equina possui uma alta exposição e sensibilidade ao patógeno. Sendo assim, as medidas profiláticas como vacinação, antissepsia de feridas com água oxigenada e soro antitetânico em feridas cirúrgicas são necessárias Os sinais clínicos apresentados são a principal ferramenta diagnóstica, pois na maioria das vezes os sinais são patognomônicos, sendo eles posição de cavalete, andar rígido, cauda em bandeira, protusão de 3ª pálpebra, sensibilidade a estímulos sonoros e luminosos, dispneia e disfagia. A toxi-infecção ocorre a partir de feridas pré-existentes ou decorrente de lesões gastrointestinais. O objetivo deste estudo é relatar um caso de tétano em uma égua de 10 anos, SRD, abordando características diagnósticas e terapêuticas. O tratamento clínico se demonstrou eficaz, com resultados satisfatórios após aplicação intratecal e intravenosa de soro antitetânico, somados com antibioticoterapia e medicações que promovem relaxamento
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- 2024
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29. Longitudinal associations between early-life fluoride exposures and cardiometabolic outcomes in school-aged children
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Sandra India Aldana, Elena Colicino, Alejandra Cantoral Preciado, Maricruz Tolentino, Andrea A. Baccarelli, Robert O. Wright, Martha María Téllez Rojo, and Damaskini Valvi
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Fluoride ,Endocrine-disrupting chemicals ,Cardiometabolic health ,Obesity ,Children ,Environmental sciences ,GE1-350 - Abstract
Background/Aim: Fluoride is a natural mineral present in food, water, and dental products, constituting ubiquitous long-term exposure in early childhood and across the lifespan. Experimental evidence shows fluoride-induced lipid disturbances with potential implications for cardiometabolic health. However, epidemiological studies are scarce. For the first time, we evaluated associations between repeated fluoride measures and cardiometabolic outcomes in children. Methods: We studied ∼ 500 Mexican children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with measurements on urinary fluoride at age 4, and dietary fluoride at ages 4, 6, and 8 years approximately. We used covariate-adjusted linear mixed-effects and linear regression models to assess fluoride associations with multiple cardiometabolic outcomes (ages 4–8): lipids (total cholesterol, HDL, LDL, and triglycerides), glucose, HbA1c, adipokines (leptin and adiponectin), body fat, and age- and sex-specific z-scores of body mass index (zBMI), waist circumference, and blood pressure. Results: Dietary fluoride intake at age 4 was associated with annual increases in triglycerides [β per-fluoride-doubling = 2.02 (95 % CI: 0.37, 3.69)], cholesterol [β = 1.46 (95 % CI: 0.52, 2.39)], HDL [β = 0.39 (95 % CI: 0.02, 0.76)], LDL [β = 0.87 (95 % CI: 0.02, 1.71)], and HbA1c [β = 0.76 (95 % CI: 0.28, 1.24)], and decreased leptin [β = -3.58 (95 % CI: −6.34, −0.75)] between the ages 4 and 8. In cross-sectional analyses at age 8, higher tertiles of fluoride exposure were associated with increases in zBMI, triglycerides, glucose, and leptin (p-tertile trend
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- 2024
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30. Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
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Liu, Yun, Eliot, Melissa N, Papandonatos, George D, Kelsey, Karl T, Fore, Ruby, Langevin, Scott, Buckley, Jessie, Chen, Aimin, Lanphear, Bruce P, Cecil, Kim M, Yolton, Kimberly, Hivert, Marie-France, Sagiv, Sharon K, Baccarelli, Andrea A, Oken, Emily, and Braun, Joseph M
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Biomedical and Clinical Sciences ,Health Sciences ,Pediatric ,Clinical Research ,Genetics ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,Aetiology ,Good Health and Well Being ,Adolescent ,Alkanesulfonic Acids ,Child ,DNA Methylation ,Environmental Pollutants ,Epigenome ,Female ,Fluorocarbons ,Humans ,Infant ,Newborn ,Longitudinal Studies ,Pregnancy ,Environmental Sciences ,Medical and Health Sciences ,Toxicology ,Biomedical and clinical sciences ,Environmental sciences ,Health sciences - Abstract
BackgroundDNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.ObjectivesWe examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio).MethodsWe quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations.ResultsAfter adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q
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- 2022
31. Mid-life epigenetic age, neuroimaging brain age, and cognitive function: coronary artery risk development in young adults (CARDIA) study
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Zheng, Yinan, Habes, Mohamad, Gonzales, Mitzi, Pomponio, Raymond, Nasrallah, Ilya, Khan, Sadiya, Vaughan, Douglas E, Davatzikos, Christos, Seshadri, Sudha, Launer, Lenore, Sorond, Farzaneh, Sedaghat, Sanaz, Wainwright, Derek, Baccarelli, Andrea, Sidney, Stephen, Bryan, Nick, Greenland, Philip, Lloyd-Jones, Donald, Yaffe, Kristine, and Hou, Lifang
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Dementia ,Genetics ,Clinical Research ,Aging ,Neurosciences ,Neurodegenerative ,Prevention ,Brain Disorders ,Behavioral and Social Science ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Acquired Cognitive Impairment ,Alzheimer's Disease ,Underpinning research ,Detection ,screening and diagnosis ,1.1 Normal biological development and functioning ,4.1 Discovery and preclinical testing of markers and technologies ,Neurological ,Mental health ,Good Health and Well Being ,Biomarkers ,Brain ,Cognition ,Cognitive Dysfunction ,Cohort Studies ,Coronary Vessels ,Epigenesis ,Genetic ,Humans ,Longitudinal Studies ,Neuroimaging ,cognitive function ,epigenetic age ,brain age ,DNA methylation ,magnetic resonance ,magnetic resonance imaging ,Biochemistry and Cell Biology ,Physiology ,Oncology and Carcinogenesis ,Developmental Biology - Abstract
The proportion of aging populations affected by dementia is increasing. There is an urgent need to identify biological aging markers in mid-life before symptoms of age-related dementia present for early intervention to delay the cognitive decline and the onset of dementia. In this cohort study involving 1,676 healthy participants (mean age 40) with up to 15 years of follow up, we evaluated the associations between cognitive function and two classes of novel biological aging markers: blood-based epigenetic aging and neuroimaging-based brain aging. Both accelerated epigenetic aging and brain aging were prospectively associated with worse cognitive outcomes. Specifically, every year faster epigenetic or brain aging was on average associated with 0.19-0.28 higher (worse) Stroop score, 0.04-0.05 lower (worse) RAVLT score, and 0.23-0.45 lower (worse) DSST (all false-discovery-rate-adjusted p
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- 2022
32. Associations of Childhood and Perinatal Blood Metals with Children’s Gut Microbiomes in a Canadian Gestation Cohort
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Shen, Yike, Laue, Hannah E, Shrubsole, Martha J, Wu, Haotian, Bloomquist, Tessa R, Larouche, Annie, Zhao, Kankan, Gao, Feng, Boivin, Amélie, Prada, Diddier, Hunting, Darel J, Gillet, Virginie, Takser, Larissa, and Baccarelli, Andrea A
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Environmental Sciences ,Genetics ,Pediatric ,2.2 Factors relating to the physical environment ,Aetiology ,Canada ,Child ,Cohort Studies ,Female ,Gastrointestinal Microbiome ,Humans ,Metals ,Pregnancy ,RNA ,Ribosomal ,16S ,Medical and Health Sciences ,Toxicology ,Biomedical and clinical sciences ,Environmental sciences ,Health sciences - Abstract
BackgroundThe gut microbiome is important in modulating health in childhood. Metal exposures affect multiple health outcomes, but their ability to modify bacterial communities in children is poorly understood.ObjectivesWe assessed the associations of childhood and perinatal blood metal levels with childhood gut microbiome diversity, structure, species, gene family-inferred species, and potential pathway alterations.MethodsWe assessed the gut microbiome using 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing in stools collected from 6- to 7-year-old children participating in the GESTation and Environment (GESTE) cohort study. We assessed blood metal concentrations [cadmium (Cd), manganese (Mn), mercury (Hg), lead (Pb), selenium (Se)] at two time points, namely, perinatal exposures at delivery (N=70) and childhood exposures at the 6- to 7-y follow-up (N=68). We used multiple covariate-adjusted statistical models to determine microbiome associations with continuous blood metal levels, including linear regression (Shannon and Pielou alpha diversity indexes), permutational multivariate analysis of variance (adonis; beta diversity distance matrices), and multivariable association model (MaAsLin2; phylum, family, species, gene family-inferred species, and pathways).ResultsChildren's blood Mn and Se significantly associated with microbiome phylum [e.g., Verrucomicrobiota (coef=-0.305, q=0.031; coef=0.262, q=0.084, respectively)] and children's blood Mn significantly associated with family [e.g., Eggerthellaceae (coef=-0.228, q=0.052)]-level differences. Higher relative abundance of potential pathogens (e.g., Flavonifractor plautii), beneficial species (e.g., Bifidobacterium longum, Faecalibacterium prausnitzii), and both potentially pathogenic and beneficial species (e.g., Bacteriodes vulgatus, Eubacterium rectale) inferred from gene families were associated with higher childhood or perinatal blood Cd, Hg, and Pb (q
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- 2022
33. Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.
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Solomon, Olivia, Huen, Karen, Yousefi, Paul, Küpers, Leanne K, González, Juan R, Suderman, Matthew, Reese, Sarah E, Page, Christian M, Gruzieva, Olena, Rzehak, Peter, Gao, Lu, Bakulski, Kelly M, Novoloaca, Alexei, Allard, Catherine, Pappa, Irene, Llambrich, Maria, Vives, Marta, Jima, Dereje D, Kvist, Tuomas, Baccarelli, Andrea, White, Cory, Rezwan, Faisal I, Sharp, Gemma C, Tindula, Gwen, Bergström, Anna, Grote, Veit, Dou, John F, Isaevska, Elena, Magnus, Maria C, Corpeleijn, Eva, Perron, Patrice, Jaddoe, Vincent WV, Nohr, Ellen A, Maitre, Lea, Foraster, Maria, Hoyo, Cathrine, Håberg, Siri E, Lahti, Jari, DeMeo, Dawn L, Zhang, Hongmei, Karmaus, Wilfried, Kull, Inger, Koletzko, Berthold, Feinberg, Jason I, Gagliardi, Luigi, Bouchard, Luigi, Ramlau-Hansen, Cecilia Høst, Tiemeier, Henning, Santorelli, Gillian, Maguire, Rachel L, Czamara, Darina, Litonjua, Augusto A, Langhendries, Jean-Paul, Plusquin, Michelle, Lepeule, Johanna, Binder, Elisabeth B, Verduci, Elvira, Dwyer, Terence, Carracedo, Ángel, Ferre, Natalia, Eskenazi, Brenda, Kogevinas, Manolis, Nawrot, Tim S, Munthe-Kaas, Monica C, Herceg, Zdenko, Relton, Caroline, Melén, Erik, Gruszfeld, Dariusz, Breton, Carrie, Fallin, MD, Ghantous, Akram, Nystad, Wenche, Heude, Barbara, Snieder, Harold, Hivert, Marie-France, Felix, Janine F, Sørensen, Thorkild IA, Bustamante, Mariona, Murphy, Susan K, Raikkönen, Katri, Oken, Emily, Holloway, John W, Arshad, Syed Hasan, London, Stephanie J, and Holland, Nina
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Humans ,DNA Methylation ,Epigenesis ,Genetic ,Pregnancy ,Sex Characteristics ,Adolescent ,Child ,Infant ,Newborn ,Female ,Male ,Epigenomics ,Epigenome ,Children ,Cord blood ,DNA methylation ,EWAS ,Sex ,Digestive Diseases ,Human Genome ,Genetics ,Prevention ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Toxicology - Abstract
BackgroundAmong children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.MethodsWe performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268).ResultsIn newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p
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- 2022
34. Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study
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Wang, Cuicui, Cardenas, Andres, Hutchinson, John N, Just, Allan, Heiss, Jonathan, Hou, Lifang, Zheng, Yinan, Coull, Brent A, Kosheleva, Anna, Koutrakis, Petros, Baccarelli, Andrea A, and Schwartz, Joel D
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Genetics ,Human Genome ,Aging ,Good Health and Well Being ,Aged ,Air Pollutants ,DNA Methylation ,Epigenome ,Humans ,Leukocytes ,Male ,Particulate Matter ,PM2.5 ,PM2.5 elments ,DNA methylation ,Epigenome-wide association study ,Distributed-lag ,Pathway analyses ,PM(2.5) ,PM(2.5) elements ,Environmental Sciences - Abstract
BackgroundSeveral epigenome-wide association studies (EWAS) of ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) have been reported. However, EWAS of PM2.5 elements (PEs), reflecting different emission sources, are very limited.ObjectivesWe performed EWAS of short- and intermediate-term exposure to PM2.5 and 13 PEs. We hypothesized that significant changes in DNAm may vary by PM2.5 mass and its elements.MethodsWe repeatedly collected blood samples in the Normative Aging Study and measured leukocyte DNA methylation (DNAm) with the Illumina HumanMethylation450K BeadChip. We collected daily PM2.5 and 13 PEs at a fixed central site. To estimate the associations between each PE and DNAm at individual cytosine-phosphate-guanine (CpG) sites, we incorporated a distributed-lag (0-27 d) term in the setting of median regression with subject-specific intercept and examined cumulative lag associations. We also accounted for selection bias due to loss to follow-up and mortality prior to enrollment. Significantly differentially methylated probes (DMPs) were identified using Bonferroni correction for multiple testing. We further conducted regional and pathway analyses to identify significantly differentially methylated regions (DMRs) and pathways.ResultsWe included 695 men with 1,266 visits between 1999 and 2013. The subjects had a mean age of 75 years. The significant DMPs, DMRs, and pathways varied by to PM2.5 total mass and PEs. For example, PM2.5 total mass was associated with 2,717 DMPs and 10,470 DMRs whereas Pb was associated with 3,173 DMPs and 637 DMRs. The identified pathways by PM2.5 mass were mostly involved in mood disorders, neuroplasticity, immunity, and inflammation, whereas the pathways associated with motor vehicles (BC, Cu, Pb, and Zn) were related with cardiovascular disease and cancer (e.g., "PPARs signaling").ConclusionsPM2.5 and PE were associated with methylation changes at multiple probes and along multiple pathways, in ways that varied by particle components.
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- 2022
35. Long-term exposure to ambient fine particulate components and leukocyte epigenome-wide DNA Methylation in older men: the Normative Aging Study
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Cuicui Wang, Heresh Amini, Zongli Xu, Adjani A. Peralta, Mahdieh Danesh Yazdi, Xinye Qiu, Yaguang Wei, Allan Just, Jonathan Heiss, Lifang Hou, Yinan Zheng, Brent A. Coull, Anna Kosheleva, Andrea A. Baccarelli, and Joel D. Schwartz
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PM2.5 components ,Sources ,DNA methylation ,Epigenome-wide association study ,Pathway analyses ,Industrial medicine. Industrial hygiene ,RC963-969 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources.
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- 2023
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36. Early Environment and Telomeres: a Long-Term Toxic Relationship
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Herrera-Moreno, José Francisco, Prada, Diddier, and Baccarelli, Andrea A.
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- 2023
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37. Molecular mechanisms of environmental exposures and human disease
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Wu, Haotian, Eckhardt, Christina M., and Baccarelli, Andrea A.
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- 2023
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38. Association of cardiovascular health and epigenetic age acceleration
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Pottinger, Tess D, Khan, Sadiya S, Zheng, Yinan, Zhang, Wei, Tindle, Hilary A, Allison, Matthew, Wells, Gretchen, Shadyab, Aladdin H, Nassir, Rami, Martin, Lisa Warsinger, Manson, JoAnn E, Lloyd-Jones, Donald M, Greenland, Philip, Baccarelli, Andrea A, Whitsel, Eric A, and Hou, Lifang
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Aging ,Genetics ,Cardiovascular ,Good Health and Well Being ,Acceleration ,Aged ,American Heart Association ,Cardiovascular Diseases ,Cohort Studies ,CpG Islands ,Cross-Sectional Studies ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Health Status ,Humans ,Longevity ,Middle Aged ,Postmenopause ,United States ,Women's Health ,Cardiovascular health ,Epigenetic age acceleration ,Women's health initiative ,DNA methylation ,Simple seven ,Women’s health initiative ,Clinical Sciences ,Paediatrics and Reproductive Medicine - Abstract
BackgroundCardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the "Life's Simple 7" ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age.Methods and resultsWe performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women's Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p
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- 2021
39. Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals
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Bozack, Anne K, Rifas-Shiman, Sheryl L, Coull, Brent A, Baccarelli, Andrea A, Wright, Robert O, Amarasiriwardena, Chitra, Gold, Diane R, Oken, Emily, Hivert, Marie-France, and Cardenas, Andres
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Biological Sciences ,Genetics ,Human Genome ,Perinatal Period - Conditions Originating in Perinatal Period ,Pediatric ,Clinical Research ,2.2 Factors relating to the physical environment ,Aetiology ,2.1 Biological and endogenous factors ,Reproductive health and childbirth ,Adult ,DNA Methylation ,Epigenome ,Female ,Fetal Blood ,Humans ,Infant ,Infant ,Newborn ,Pregnancy ,Prenatal Diagnosis ,Prenatal Exposure Delayed Effects ,DNA methylation ,EWAS ,Manganese ,Metals ,Prenatal exposure ,Clinical Sciences ,Paediatrics and Reproductive Medicine - Abstract
BackgroundPrenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6-10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR
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- 2021
40. Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci
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Breeze, Charles E, Batorsky, Anna, Lee, Mi Kyeong, Szeto, Mindy D, Xu, Xiaoguang, McCartney, Daniel L, Jiang, Rong, Patki, Amit, Kramer, Holly J, Eales, James M, Raffield, Laura, Lange, Leslie, Lange, Ethan, Durda, Peter, Liu, Yongmei, Tracy, Russ P, Van Den Berg, David, Evans, Kathryn L, Kraus, William E, Shah, Svati, Tiwari, Hermant K, Hou, Lifang, Whitsel, Eric A, Jiang, Xiao, Charchar, Fadi J, Baccarelli, Andrea A, Rich, Stephen S, Morris, Andrew P, Irvin, Marguerite R, Arnett, Donna K, Hauser, Elizabeth R, Rotter, Jerome I, Correa, Adolfo, Hayward, Caroline, Horvath, Steve, Marioni, Riccardo E, Tomaszewski, Maciej, Beck, Stephan, Berndt, Sonja I, London, Stephanie J, Mychaleckyj, Josyf C, and Franceschini, Nora
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Biological Sciences ,Genetics ,Kidney Disease ,Human Genome ,Renal and urogenital ,CpG Islands ,DNA Methylation ,Epigenesis ,Genetic ,Epigenomics ,Gene Expression Regulation ,Genetic Variation ,Genetics ,Population ,Genome-Wide Association Study ,Glomerular Filtration Rate ,Humans ,Kidney ,Kidney Function Tests ,Phenotype ,Quantitative Trait Loci ,Quantitative Trait ,Heritable ,Racial Groups ,Epigenetic ,Kidney function ,Gene regulation ,Kidney development ,DNA methylation ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,TOPMed MESA Multi-Omics Working Group ,Clinical Sciences - Abstract
BackgroundDNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach.MethodsThe study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses.ResultsWe identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development.ConclusionsWe uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
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- 2021
41. Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood
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Smith, Anna R, Lin, Pi-I D, Rifas-Shiman, Sheryl L, Rahman, Mohammad L, Gold, Diane R, Baccarelli, Andrea A, Henn, Birgit Claus, Amarasiriwardena, Chitra, Wright, Robert O, Coull, Brent, Hivert, Marie-France, Oken, Emily, and Cardenas, Andres
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Prevention ,Clinical Research ,Reproductive health and childbirth ,Bayes Theorem ,Child ,DNA Copy Number Variations ,DNA ,Mitochondrial ,Female ,Fetal Blood ,Humans ,Metals ,Heavy ,Mitochondria ,Pregnancy ,Telomere ,Environmental Sciences ,Medical and Health Sciences ,Toxicology - Abstract
BackgroundMetal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants.ObjectivesWe evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress.MethodsWe measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn (n=898) and TL (n=893) in second-trimester maternal blood and mtDNAcn (n=419) and TL (n=408) in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions.ResultsA 2-fold increase in maternal magnesium was associated with lower maternal [β=-0.07, 95% confidence interval (CI): -0.10, -0.01] and cord blood (β=-0.08, 95% CI: -0.20, -0.01) mtDNAcn. Lead was associated with higher maternal mtDNAcn (β=0.04, 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL (β=0.30, 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn (β=0.04, 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium.DiscussionMaternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294.
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- 2021
42. Residential PM2.5 exposure and the nasal methylome in children
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Sordillo, Joanne E, Cardenas, Andres, Qi, Cancan, Rifas-Shiman, Sheryl L, Coull, Brent, Luttmann-Gibson, Heike, Schwartz, Joel, Kloog, Itai, Hivert, Marie-France, DeMeo, Dawn L, Baccarelli, Andrea A, Xu, Cheng-Jian, Gehring, Ulrike, Vonk, Judith M, Koppelman, Gerard, Oken, Emily, and Gold, Diane R
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Biological Sciences ,Genetics ,Climate-Related Exposures and Conditions ,Pediatric ,Lung ,Human Genome ,Clinical Research ,Adolescent ,Air Pollution ,Child ,DNA Methylation ,Epigenome ,Humans ,Netherlands ,Particulate Matter ,Environmental Sciences - Abstract
RationalePM2.5-induced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known.ObjectivesWe aimed to study associations of fine particulate matter PM2.5 exposure with DNA methylation in nasal cells.MethodsWe conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM2.5 at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA).ResultsIn adjusted analyses, we found 362 CpGs associated with 1-year PM2.5 (FDR
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- 2021
43. Recombinant human chorionic gonadotropin and gonadotropin-releasing hormone agonist differently affect the profile of extracellular vesicle microRNAs in human follicular fluid
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Machtinger, R., Racowsky, C., Baccarelli, A. A., Bollati, V., Orvieto, R., Hauser, R., and Barnett-Itzhaki, Z.
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- 2023
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44. How much BiGAN and CycleGAN-learned hidden features are effective for COVID-19 detection from CT images? A comparative study
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Sarv Ahrabi, Sima, Momenzadeh, Alireza, Baccarelli, Enzo, Scarpiniti, Michele, and Piazzo, Lorenzo
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- 2023
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45. A precision environmental health approach to prevention of human disease
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Andrea Baccarelli, Dana C. Dolinoy, and Cheryl Lyn Walker
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Science - Abstract
Abstract Human health is determined by the interaction of our environment with the genome, epigenome, and microbiome, which shape the transcriptomic, proteomic, and metabolomic landscape of cells and tissues. Precision environmental health is an emerging field leveraging environmental and system-level (‘omic) data to understand underlying environmental causes of disease, identify biomarkers of exposure and response, and develop new prevention and intervention strategies. In this article we provide real-life illustrations of the utility of precision environmental health approaches, identify current challenges in the field, and outline new opportunities to promote health through a precision environmental health framework.
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- 2023
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46. Why should we add early exits to neural networks?
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Scardapane, Simone, Scarpiniti, Michele, Baccarelli, Enzo, and Uncini, Aurelio
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Computer Science - Neural and Evolutionary Computing ,Computer Science - Machine Learning ,Statistics - Machine Learning - Abstract
Deep neural networks are generally designed as a stack of differentiable layers, in which a prediction is obtained only after running the full stack. Recently, some contributions have proposed techniques to endow the networks with early exits, allowing to obtain predictions at intermediate points of the stack. These multi-output networks have a number of advantages, including: (i) significant reductions of the inference time, (ii) reduced tendency to overfitting and vanishing gradients, and (iii) capability of being distributed over multi-tier computation platforms. In addition, they connect to the wider themes of biological plausibility and layered cognitive reasoning. In this paper, we provide a comprehensive introduction to this family of neural networks, by describing in a unified fashion the way these architectures can be designed, trained, and actually deployed in time-constrained scenarios. We also describe in-depth their application scenarios in 5G and Fog computing environments, as long as some of the open research questions connected to them., Comment: Published in Cognitive Computation
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- 2020
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47. DNA methylation architecture of the ACE2 gene in nasal cells of children.
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Cardenas, Andres, Rifas-Shiman, Sheryl L, Sordillo, Joanne E, DeMeo, Dawn L, Baccarelli, Andrea A, Hivert, Marie-France, Gold, Diane R, and Oken, Emily
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Nasal Mucosa ,Humans ,Severity of Illness Index ,Risk Factors ,DNA Methylation ,Adolescent ,Child ,Female ,Male ,COVID-19 ,Angiotensin-Converting Enzyme 2 ,SARS-CoV-2 - Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity.1,2 The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean = 12.71%) and 3 sites greater DNAm (mean = 1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference = 3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference = 1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference = 7.86%) and females (mean absolute difference = 8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences. Findings need to be confirmed among adults and patients with risk factors for COVID-19 severity.
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- 2021
48. Blood DNA methylation biomarkers of cumulative lead exposure in adults.
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Colicino, Elena, Just, Allan, Kioumourtzoglou, Marianthi-Anna, Vokonas, Pantel, Cardenas, Andres, Sparrow, David, Weisskopf, Marc, Nie, Linda H, Hu, Howard, Schwartz, Joel D, Wright, Robert O, and Baccarelli, Andrea A
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DNA methylation ,Epidemiology ,Exposure Modeling ,Metals ,Methods ,Personal exposure ,Chemical Sciences ,Environmental Sciences ,Medical and Health Sciences - Abstract
BackgroundLead is a ubiquitous toxicant following three compartment kinetics with the longest half-life found in bones. Patella and tibia lead levels-validated measures of cumulative exposure-require specialized X-ray-fluorescence-spectroscopy available only in a few centers worldwide. We developed minimally invasive biomarkers reflecting individual cumulative lead exposure using blood DNA methylation profiles-obtainable via Illumina 450K or IlluminaEPIC bead-chip assays.MethodsWe developed and tested two methylation-based biomarkers from 348 Normative Aging Study (NAS) elderly men. We selected methylation sites with strong associations with bone lead levels via robust regressions analysis and constructed the biomarkers using elastic nets. Results were validated in a NAS subset, reporting specificity, and sensitivity.FindingsParticipants were 73 years old on average (standard deviation, SD = 6), with moderate lead levels of (mean ± SD patella: 27 ± 18 µg/g; tibia:21 ± 13 µg/g). Methylation-based biomarkers for lead in patella and tibia included 59 and 138 DNA methylation sites, respectively. Estimated lead levels were significantly correlated with actual measured values, (r = 0.62 patella, r = 0.59 tibia) and had low mean square error (MSE) (MSE = 0.68 patella, MSE = 0.53 tibia). Means and distributions of the estimated and actual lead levels were not significantly different across patella and tibia bones (p > 0.05). Methylation-based biomarkers discriminated participants highly exposed (>median) to lead with a specificity of 74 and 73% for patella and tibia lead levels, respectively, with 70% sensitivity.InterpretationDNA methylation-based lead biomarkers are novel tools that can be used to reconstruct decades' worth of individual cumulative lead exposure using only blood DNA methylation profiles and may help identify the consequences of cumulative exposure.
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- 2021
49. The effect of high polycyclic aromatic hydrocarbon exposure on biological aging indicators
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Manuela Campisi, Giuseppe Mastrangelo, Danuta Mielżyńska-Švach, Mirjam Hoxha, Valentina Bollati, Andrea A. Baccarelli, Angela Carta, Stefano Porru, and Sofia Pavanello
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Biological aging ,DNA alterations ,DNA methylation age ,Mitochondrial DNA copy number ,Occupational exposure ,Polycyclic aromatic hydrocarbons ,Industrial medicine. Industrial hygiene ,RC963-969 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Aging represents a serious health and socioeconomic concern for our society. However, not all people age in the same way and air pollution has been shown to largely impact this process. We explored whether polycyclic aromatic hydrocarbons (PAHs), excellent fossil and wood burning tracers, accelerate biological aging detected by lymphocytes DNA methylation age (DNAmAge) and telomere length (TL), early nuclear DNA (nDNA) hallmarks of non-mitotic and mitotic cellular aging, and mitochondrial DNA copy number (mtDNAcn). Methods The study population consisted of 49 male noncurrent-smoking coke-oven workers and 44 matched controls. Occupational and environmental sources of PAH exposures were evaluated by structured questionnaire and internal dose (urinary 1-pyrenol). We estimated Occup_PAHs, the product of 1-pyrenol and years of employment as coke-oven workers, and Environ_PAHs, from multiple items (diet, indoor and outdoor). Biological aging was determined by DNAmAge, via pyrosequencing, and by TL and mtDNAcn, via quantitative polymerase chain reaction. Genomic instability markers in lymphocytes as target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)–DNA adduct], genetic instability (micronuclei), gene-specific (p53, IL6 and HIC1) and global (Alu and LINE-1 repeats) DNA methylation, and genetic polymorphisms (GSTM1) were also evaluated in the latent variable nDNA_changes. Structural equation modelling (SEM) analysis evaluated these multifaceted relationships. Results In univariate analysis, biological aging was higher in coke-oven workers than controls as detected by higher percentage of subjects with biological age older than chronological age (AgeAcc ≥ 0, p = 0.007) and TL (p = 0.038), mtDNAcn was instead similar. Genomic instability, i.e., genotoxic and epigenetic alterations (LINE-1, p53 and Alu) and latent variable nDNA_changes were higher in workers (p
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- 2023
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50. Psychological stress and epigenetic aging in older men: The VA normative aging study
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Jamaji C. Nwanaji-Enwerem, Andres Cardenas, Xu Gao, Cuicui Wang, Pantel Vokonas, Avron Spiro, Anwar D. Osborne, Anna Kosheleva, Lifang Hou, Andrea A. Baccarelli, and Joel Schwartz
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Perceived stress ,DNA methylation ,DNAm age ,Trauma ,Epigenetic clock ,Biological age ,Medicine - Abstract
Psychological stress remains an important risk factor for morbidity and mortality throughout the life course. However, there have been counterintuitive findings reported in previous studies of older persons that examine the relationships of perceived psychological stress with DNA methylation-based markers of aging, which also serve as predictors of morbidity and mortality (epigenetic age/clocks). We aimed to replicate and expand findings from existing work by examining relationships of self-reported stress with nine epigenetic clocks: Hannum, Horvath, Intrinsic, Extrinsic, SkinBloodClock, PhenoAge, GrimAge, DNAm Telomere Length, and Pace of Aging. We analyzed data from 607 male participants (mean age 73.2 years) of the VA Normative Aging Study with one to two study visits from 1999 to 2007 (observations = 956). Stress was assessed via the 14-item Perceived Stress Scale (PSS). Epigenetic age was calculated from DNA methylation measured in leukocytes with the HumanMethylation450 BeadChip. In linear mixed effects models adjusted for demographic/lifestyle/health factors, a standard deviation (sd) increase in PSS was associated with Horvath (β = −0.35-years, 95%CI: −0.61, −0.09, P = 0.008) and Intrinsic (β = −0.40-years, 95%CI: −0.67, −0.13, P = 0.004) epigenetic age deceleration. However, in models limited to participants with the highest levels of stress (≥75th-percentile), Horvath (β = 2.29-years, 95%CI: 0.16, 4.41, P = 0.04) and Intrinsic (β = 2.06-years, 95%CI: −0.17, 4.28, P = 0.07) age acceleration associations were observed. Our results reinforce the complexity of psychological stress and epigenetic aging relationships and lay a foundation for future studies that explore longitudinal relationships with other adult stress metrics and factors that can influence stress such as resilience measures.
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- 2023
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