David Michael Reif

Also known as: David M. Reif

predictive toxicology, data science, environmental health science, genetics, bioinformatics, NAMs, risk assessment, Artificial Intelligence / Machine Learning (AI / ML)

Works (163)

Updated: November 19th, 2024 18:50

2024 article

An in vitro and machine learning framework for quantifying serum albumin binding of per- and polyfluoroalkyl substances

Starnes, H. M., Green, A. J., Reif, D. M., & Belcher, S. M. (2024, October 3). TOXICOLOGICAL SCIENCES, Vol. 10.

By: H. Starnes n, A. Green n, D. Reif n & S. Belcher n

author keywords: binding affinity; bioaccumulation; computational toxicology; PFAS; protein binding
Sources: ORCID, Web Of Science, NC State University Libraries
Added: September 22, 2024

2024 journal article

Deep autoencoder-based behavioral pattern recognition outperforms standard statistical methods in high-dimensional zebrafish studies

PLOS COMPUTATIONAL BIOLOGY, 20(9).

By: A. Green n, L. Truong*, P. Thunga n, C. Leong*, M. Hancock n, R. Tanguay*, D. Reif n

Ed(s): S. Scarpino

Sources: ORCID, Web Of Science, NC State University Libraries
Added: September 15, 2024

2024 journal article

Investigating mouse hepatic lipidome dysregulation following exposure to emerging per- and polyfluoroalkyl substances (PFAS)

Chemosphere.

By: K. Kirkwood-Donelson, J. Chappel n, E. Tobin n, J. Dodds*, D. Reif*, J. DeWitt*, E. Baker n

TL;DR: Results provide valuable insight into the liver bioaccumulation and molecular mechanisms of GenX- and NBP2-induced hepatotoxicity and various specific fatty acyls were greatly impacted, indicating alteration of inflammation, oxidative stress, and cellular signaling processes due to emerging PFAS exposure. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (OpenAlex)
Source: ORCID
Added: March 15, 2024

2024 article

Streamlining Phenotype Classification and Highlighting Feature Candidates: A Screening Method for Non-Targeted Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS) Data

Chappel, J. R., Kirkwood-Donelson, K. I., Dodds, J. N., Fleming, J., Reif, D. M., & Baker, E. S. (2024, September 18). ANALYTICAL CHEMISTRY, Vol. 9.

By: J. Chappel n, K. Kirkwood-Donelson, J. Dodds*, J. Fleming n, D. Reif* & E. Baker*

Sources: Web Of Science, NC State University Libraries
Added: September 30, 2024

2024 article

The GeoTox Package: Open-source software for connecting spatiotemporal exposure to individual and population-level risk

Messier, K. P., Reif, D. M., & Marvel, S. W. (2024, September 24).

By: K. Messier, D. Reif* & S. Marvel

Source: ORCID
Added: October 1, 2024

2023 article

Aggregated Molecular Phenotype Scores: Enhancing Assessment and Visualization of Mass Spectrometry Imaging Data for Tissue-Based Diagnostics

Chappel, J. R., King, M. E., Fleming, J., Eberlin, L. S., Reif, D. M., & Baker, E. S. (2023, August 14). ANALYTICAL CHEMISTRY, Vol. 8.

By: J. Chappel n, M. King*, J. Fleming n, L. Eberlin*, D. Reif* & E. Baker*

TL;DR: Initial comparisons of cancerous human tissues to their normal or benign counterparts illustrated that AMP scores distinguished phenotypes with high accuracy, sensitivity, and specificity, leading to high diagnostic accuracy and interpretability. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: August 28, 2023

2023 article

Bayesian matrix completion for hypothesis testing

Jin, B., Dunson, D. B., Rager, J. E., Reif, D. M., Engel, S. M., & Herring, A. H. (2023, March 15). JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS, Vol. 3.

By: B. Jin*, D. Dunson*, J. Rager*, D. Reif n, S. Engel* & A. Herring*

author keywords: Bayesian hierarchical model; bioactivity profiles; chemical screening; heteroscedasticity; latent factor models; ToxCast; Tox21
TL;DR: This paper makes a novel attempt in toxicology to simultaneously model heteroscedastic errors and a nonparametric mean function, leading to a broader definition of activity whose need has been suggested by toxicologists. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: January 4, 2023

2023 article

Deep autoencoder-based behavioral pattern recognition outperforms standard statistical methods in high-dimensional zebrafish studies

Green, A. J., Truong, L., Thunga, P., Leong, C., Hancock, M., Tanguay, R. L., & Reif, D. M. (2023, September 17).

By: A. Green n, L. Truong, P. Thunga n, C. Leong, M. Hancock n, R. Tanguay, D. Reif n

TL;DR: It is demonstrated that a deep autoencoder using raw behavioral tracking data from zebrafish toxicity screens outperforms conventional statistical methods, resulting in a comprehensive evaluation of behavioral data. (via Semantic Scholar)
Source: ORCID
Added: September 18, 2023

2023 journal article

Estimation of the Half-Lives of Recently Detected Per- and Polyfluorinated Alkyl Ethers in an Exposed Community

ENVIRONMENTAL SCIENCE & TECHNOLOGY, 57(41), 15348–15355.

author keywords: exposure; PFAS; water; humans; environment; toxicokinetic modeling
TL;DR: These fluoroethers had biological half-Lives longer than published half-lives for PFHxA and PFHpA but shorter than those for PFOA andPFOS (800-1200 days). (via Semantic Scholar)
UN Sustainable Development Goal Categories
6. Clean Water and Sanitation (Web of Science; OpenAlex)
Sources: Web Of Science, NC State University Libraries, ORCID
Added: October 7, 2023

2023 article

From big data to big insights: statistical and bioinformatic approaches for exploring the lipidome

Chappel, J. R., Kirkwood-Donelson, K. I., Reif, D. M., & Baker, E. S. (2023, October 25). ANALYTICAL AND BIOANALYTICAL CHEMISTRY, Vol. 10.

By: J. Chappel n, K. Kirkwood-Donelson, D. Reif* & E. Baker*

author keywords: Lipidomics; Univariate; Multivariate; Pathway; Enrichment
TL;DR: A framework for guiding lipidomic data analysis to promote a greater assessment of lipidomic results, while understanding potential advantages and weaknesses along the way is provided. (via Semantic Scholar)
UN Sustainable Development Goal Categories
7. Affordable and Clean Energy (OpenAlex)
Sources: Web Of Science, NC State University Libraries
Added: November 20, 2023

2023 journal article

Guided optimization of ToxPi model weights using a Semi-Automated approach

COMPUTATIONAL TOXICOLOGY, 29.

By: J. Fleming n, J. House*, J. Chappel n, A. Motsinger-Reif* & D. Reif*

author keywords: Machine learning; Feature weighting; Exposure assessment; Chemical toxicity; Ordinal regression; Genetic algorithm
Sources: Web Of Science, NC State University Libraries
Added: January 16, 2024

2023 journal article

Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst

JOURNAL OF IMMUNOTOXICOLOGY, 20(1).

By: D. Phelps*, A. Palekar, H. Conley*, G. Ferrero, J. Driggers*, K. Linder*, S. Kullman n, D. Reif n ...

author keywords: Innate immunity; neutrophils; per- and polyfluoroalkyl substances (PFAS); reactive oxygen species; zebrafish
MeSH headings : Animals; Humans; Zebrafish; Neutrophils; Reactive Oxygen Species; Respiratory Burst; Fluorocarbons / toxicity; Alkanesulfonic Acids / toxicity; Environmental Pollutants
TL;DR: This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: ORCID, Web Of Science, NC State University Libraries
Added: February 15, 2023

2023 journal article

MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients

PHARMACEUTICALS, 16(5).

author keywords: precision medicine; colorectal cancer; pharmacogenomics; oxaliplatin; lncRNA's; antisense
TL;DR: An association between MKX-AS1 and MKX expression status that could be useful as a prognostic marker of response to OXAL and potential patient outcomes in CRC is suggested. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: May 19, 2023

2023 journal article

Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy

CELLS, 12(12).

By: G. Small*, F. Akhtari*, A. Green n, T. Havener*, M. Sikes n, J. Quintanhila, R. Gonzalez*, D. Reif* ...

author keywords: rituximab (Rituxan (R)); ofatumumab (Arzerra (R),& nbsp;Kesimpta (R)); obinutuzumab (Gazyva (R)); CD20 (MS4A1); MKL1 (MRTFA); TGFB1
TL;DR: Results suggest that the efficacy of anti-CD20 mAb therapy may be influenced by B cell developmental status as well as polymorphism in the MKL1 gene. (via Semantic Scholar)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: June 8, 2023

2023 journal article

RYK Gene Expression Associated with Drug Response Variation of Temozolomide and Clinical Outcomes in Glioma Patients

PHARMACEUTICALS, 16(5).

By: R. Gonzalez*, G. Small*, A. Green n, F. Akhtari*, T. Havener*, J. Quintanilha, A. Cipriani*, D. Reif* ...

author keywords: GWAS; chemotherapy; sensitivity; resistance; glioma; drug response; temozolomide; knockdown; overexpression; pharmacogenomics; gene expression; RYK
TL;DR: The findings suggest that RYK expression may serve as an important prognostic or predictor of TMZ response and survival for glioma patients and a combination of RyK expression and MGMT status could serve as a additional biomarker for improved survival. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: May 12, 2023

2023 journal article

Uncovering the common factors of chemical exposure and behavior: Evaluating behavioral effects across a testing battery using factor analysis

NEUROTOXICOLOGY, 99, 264–273.

By: W. Marinello n, S. Gillera n, L. Huang n, J. Rollman n, D. Reif n & H. Patisaul n

author keywords: EDCs; Endocrine disruptors; Neurodevelopment; Neurotoxicology; Organophosphate; Flame retardants; Vole; Behavior
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: December 18, 2023

2023 article

Utilizing Aggregated Molecular Phenotype (AMP) Scores to Visualize Simultaneous Molecular Changes in Mass Spectrometry Imaging Data

Chappel, J. R., King, M. E., Fleming, J., Eberlin, L. S., Reif, D. M., & Baker, E. S. (2023, June 5).

TL;DR: Initial comparisons of cancerous human tissues to normal or benign counterparts illustrated that AMP scores distinguished phenotypes with high accuracy, sensitivity, and specificity, leading to high diagnostic accuracy and interpretability of predictive models. (via Semantic Scholar)
Source: ORCID
Added: June 6, 2023

2022 journal article

Comparison of National Vulnerability Indices Used by the Centers for Disease Control and Prevention for the COVID-19 Response

Public Health Reports, 137(4), 803–812.

author keywords: COVID-19; vulnerability; social vulnerability index; GIS; geographic information systems
MeSH headings : COVID-19 / epidemiology; COVID-19 / prevention & control; Centers for Disease Control and Prevention, U.S.; Humans; Pandemics / prevention & control; Public Health; United States / epidemiology
TL;DR: The indices can empower local and state public health officials with additional information to focus resources and interventions on disproportionately affected populations to combat the ongoing pandemic and plan for future pandemics. (via Semantic Scholar)
UN Sustainable Development Goal Categories
2. Zero Hunger (Web of Science)
3. Good Health and Well-being (OpenAlex)
13. Climate Action (Web of Science)
14. Life Below Water (Web of Science)
15. Life on Land (Web of Science)
Sources: ORCID, Web Of Science, NC State University Libraries, Crossref
Added: May 6, 2022

2022 journal article

Demonstrating a systems approach for integrating disparate data streams to inform decisions on children's environmental health

BMC PUBLIC HEALTH, 22(1).

By: E. Hubal*, N. DeLuca*, A. Mullikin*, R. Slover*, J. Little* & D. Reif n

author keywords: Chemical exposure; ANOVA; ToxPi; Children's health; Environmental health; Systems approach; Multivariate analysis; Data-driven
MeSH headings : Child; Child Health; Child, Preschool; Environmental Health; Humans; Lead; Public Health; Systems Analysis
TL;DR: This analysis demonstrated how systems science principles can be used to synthesize holistic insights for decision making using publicly available data and computational tools, focusing on a children’s environmental health example. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: March 7, 2022

2022 journal article

Systematic developmental toxicity assessment of a structurally diverse library of PFAS in zebrafish

JOURNAL OF HAZARDOUS MATERIALS, 431.

author keywords: PFAS; Developmental toxicity; Structure-activity relationship; Abnormal behavior; Zebrafish
MeSH headings : Animals; Fluorocarbons / analysis; Larva; Teratogens; Zebrafish
TL;DR: The results illustrate the power of a multi-dimensional in vivo platform to assess the developmental (neuro)toxicity of diverse PFAS and in the acceleration of PFAS safety research. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries, ORCID
Added: March 8, 2022

2022 article

TCDD alters essential transcriptional regulators of osteogenic differentiation in multipotent mesenchymal stem cells

Watson, A. L. T. D., Carmona Baez, A., Jima, D., Reif, D., Ding, J., Roberts, R., & Kullman, S. W. (2022, November 12). TOXICOLOGICAL SCIENCES, Vol. 11.

author keywords: mesenchymal stem cell; AhR; cell differentiation
MeSH headings : Humans; Osteogenesis / genetics; Polychlorinated Dibenzodioxins / toxicity; Cell Differentiation; Fibroblast Growth Factors / metabolism; Mesenchymal Stem Cells / metabolism; Cells, Cultured; Osteoblasts
TL;DR: A global transcriptomic landscape during early, intermediate, and apical stages of osteogenic differentiation in vitro in response to TCDD is established to identify novel pathways and transcription factors that may facilitate a better understanding of the osteoblast differentiation process, perturbation by exogenous agents, and potential intervention strategies targeting those specific pathways. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: ORCID, Web Of Science, NC State University Libraries
Added: November 12, 2022

2022 article

The Ahr2-Dependent wfikkn1 Gene Influences Zebrafish Transcriptome, Proteome, and Behavior

Shankar, P., Garcia, G. R., LaDu, J. K., Sullivan, C. M., Dunham, C. L., Goodale, B. C., … Tanguay, R. L. (2022, April 4). TOXICOLOGICAL SCIENCES, Vol. 4.

By: P. Shankar*, G. Garcia*, J. LaDu*, C. Sullivan*, C. Dunham*, B. Goodale*, K. Waters*, S. Stanisheuski* ...

author keywords: aryl hydrocarbon receptor (AHR); zebrafish; TCDD; wfikkn1; transcriptomics; behavior
MeSH headings : Animals; Embryo, Nonmammalian; Polychlorinated Dibenzodioxins / toxicity; Polycyclic Aromatic Hydrocarbons / toxicity; Proteome / genetics; Proteome / metabolism; Receptors, Aryl Hydrocarbon / genetics; Receptors, Aryl Hydrocarbon / metabolism; Transcriptome; Zebrafish / genetics; Zebrafish / metabolism; Zebrafish Proteins / genetics; Zebrafish Proteins / metabolism
TL;DR: Functional enrichment demonstrated wfikkn1 was involved in skeletal muscle development and played a role in neurological pathways after TCDD exposure, and was likely a necessary functional member of the AHR signaling cascade. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: May 2, 2022

2022 article

ToxPi*GIS Toolkit: creating, viewing, and sharing integrative visualizations for geospatial data using ArcGIS

Fleming, J., Marvel, S. W., Supak, S., Motsinger-Reif, A. A., & Reif, D. M. (2022, April 26). JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY, Vol. 4.

By: J. Fleming n, S. Marvel n, S. Supak n, A. Motsinger-Reif* & D. Reif n

author keywords: Visual analytics; Geographic information systems; Data integration
MeSH headings : Humans; Geographic Information Systems; COVID-19
TL;DR: The integration of ToxPi profiles with ArcGIS provides new avenues for geospatial analysis, visualization, and public sharing of multi-factor data that can support decisions that help address issues such as disease prevention, environmental health, natural disaster prevention, chemical risk, and many others. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: May 10, 2022

2022 journal article

Utilizing Pine Needles to Temporally and Spatially Profile Per- and Polyfluoroalkyl Substances (PFAS)

ENVIRONMENTAL SCIENCE & TECHNOLOGY, 56(6), 3441–3451.

By: K. Kirkwood n, J. Fleming n, H. Nguyen n, D. Reif n, E. Baker n & S. Belcher n

author keywords: Biomonitoring; contamination; per- and polyfluoroalkyl substances; fluoroethers; ion mobility; mass spectrometry; PFAS
MeSH headings : Alkanesulfonic Acids / analysis; Chromatography, Liquid; Fluorocarbons / analysis; United States; United States Environmental Protection Agency
UN Sustainable Development Goal Categories
15. Life on Land (OpenAlex)
Sources: Web Of Science, NC State University Libraries, ORCID
Added: February 18, 2022

2022 journal article

Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure

TOXICS, 10(12).

author keywords: gene-environment interaction; chemical risk-assessment; zebrafish behavior; toxicity screening
TL;DR: It is demonstrated how standing genetic variation in a heterogeneous population such as the authors' can be leveraged to test for potential GxE by showing evidence that heritable genetics are directly affecting gene expression and behavioral susceptibility of individuals to PFHxA exposure. (via Semantic Scholar)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: December 10, 2022

2022 journal article

Wildfires and extracellular vesicles: Exosomal MicroRNAs as mediators of cross-tissue cardiopulmonary responses to biomass smoke

ENVIRONMENT INTERNATIONAL, 167.

author keywords: Exosomes; Extracellular vesicles; Environmental exposures; Mixtures; Systems biology; Wildfires
MeSH headings : Animals; Biomass; Extracellular Vesicles / metabolism; Female; Hypoxia; Mice; MicroRNAs; Soil; Wildfires
TL;DR: A potential mechanism through which wildfire exposures induce cardiopulmonary responses is posited, highlighting the role of circulating plasma EVs in intercellular and systems-level communication between tissues. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: October 3, 2022

2021 journal article

Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification

Frontiers in Toxicology, 3.

By: P. Thunga n, L. Truong*, R. Tanguay* & D. Reif n

TL;DR: It is found that combining information from behavioral and mortality assessments captures early signals of potential chemical hazards, obviating the need to evaluate a comprehensive suite of morphological endpoints in initial screens for toxicity. (via Semantic Scholar)
Source: ORCID
Added: June 22, 2021

2021 journal article

Development of a Pandemic Awareness STEM Outreach Curriculum: Utilizing a Computational Thinking Taxonomy Framework

EDUCATION SCIENCES, 11(3).

By: P. Gilchrist n, A. Alexander n, A. Green n, F. Sanders*, A. Hooker* & D. Reif n

author keywords: science learning; STEM competencies; informal learning; computational thinking; education; curriculum development; data science; teaching; problem solving
TL;DR: This paper documents the theory and design approach used by researchers and practitioners to create a Pandemic Awareness STEM Curriculum and future implications for teaching and learning computational thinking practices through engaging with data science. (via Semantic Scholar)
UN Sustainable Development Goal Categories
4. Quality Education (Web of Science)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: March 9, 2021

2021 article

Extending the lymphoblastoid cell line model for drug combination pharmacogenomics

Green, A. J., Anchang, B., Akhtari, F. S., Reif, D. M., & Motsinger-Reif, A. (2021, May 28). PHARMACOGENOMICS, Vol. 5.

author keywords: combination treatment; drug response; LCLs; omics; synergism
MeSH headings : Antineoplastic Combined Chemotherapy Protocols / administration & dosage; Antineoplastic Combined Chemotherapy Protocols / therapeutic use; Cell Line, Tumor / drug effects; Humans; Lymphocytes / drug effects; Pharmacogenomic Testing / methods
UN Sustainable Development Goal Categories
Sources: ORCID, Web Of Science, NC State University Libraries
Added: May 29, 2021

2021 journal article

High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs

PLOS GENETICS, 17(8).

Ed(s): F. Vazquez

MeSH headings : Antineoplastic Agents / pharmacology; Biomarkers, Pharmacological / analysis; Cell Line, Tumor; Genome-Wide Association Study / methods; High-Throughput Screening Assays / methods; Humans; NAD(P)H Dehydrogenase (Quinone) / drug effects; NAD(P)H Dehydrogenase (Quinone) / genetics; NAD(P)H Dehydrogenase (Quinone) / metabolism
TL;DR: The NAD(P)H quinone dehydrogenase 1 (NQO1) gene was found to be associated with the dose-response of arsenic trioxide, erlotinib, tramet inib, and a combination treatment of paclitaxel + epirubicin. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: August 27, 2021

2021 journal article

Leveraging high-throughput screening data, deep neural networks, and conditional generative adversarial networks to advance predictive toxicology

PLOS COMPUTATIONAL BIOLOGY, 17(7).

Ed(s): V. Hatzimanikatis

MeSH headings : Animals; Computational Biology; Embryo, Nonmammalian / drug effects; High-Throughput Screening Assays; Models, Chemical; Neural Networks, Computer; Toxicity Tests; Toxicology; Zebrafish
TL;DR: E embryonic zebrafish were used to examine a suite of morphological and mortality endpoints at six concentrations from over 1,000 unique chemicals found in the ToxCast library, and Go-ZT significantly outperformed the cGAN, support vector machine, random forest and multilayer perceptron models in cross-validation, and when tested against an external test dataset. (via Semantic Scholar)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: July 5, 2021

2021 journal article

Multiomic Big Data Analysis Challenges: Increasing Confidence in the Interpretation of Artificial Intelligence Assessments

ANALYTICAL CHEMISTRY, 93(22), 7763–7773.

By: M. Odenkirk n, D. Reif n & E. Baker n

MeSH headings : Artificial Intelligence; Big Data; Data Analysis
TL;DR: The present and future capabilities of AI techniques in multiomic studies are discussed while introducing analytical checks and balances to validate the computational conclusions. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: July 19, 2021

2021 personal communication

The COVID-19 Pandemic Vulnerability Index (PVI) Dashboard: Monitoring County-Level Vulnerability Using Visualization, Statistical Modeling, and Machine Learning

Marvel, S. W., House, J. S., Wheeler, M., Song, K., Zhou, Y.-H., Wright, F. A., … Reif, D. M. (2021, January).

MeSH headings : COVID-19 / epidemiology; Data Visualization; Health Status Indicators; Humans; Machine Learning; Models, Statistical; Vulnerable Populations
Sources: Web Of Science, NC State University Libraries, ORCID
Added: March 22, 2021

2021 article

ToxPi*GIS Toolkit: Creating, viewing, and sharing integrative visualizations for geospatial data using ArcGIS

Fleming, J., Marvel, S. W., Motsinger-Reif, A. A., & Reif, D. M. (2021, October 11). (Vol. 10). Vol. 10.

TL;DR: An actively developed suite of software for creating, viewing, sharing, and analyzing interactive ToxPi figures in ArcGIS, and a collection of Python routines for useful data manipulation and preprocessing for both novice and advanced users looking for additional customizability are proposed. (via Semantic Scholar)
Source: ORCID
Added: October 13, 2021

2021 review

Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions

[Review of ]. TOXICS, 9(4).

By: D. Wallis n, L. Truong*, J. La Du*, R. Tanguay* & D. Reif n

author keywords: endocrine-disrupting chemical (EDC); gene-environment interaction (GxE); differential susceptibility
TL;DR: It is proposed that EDCs causing such differential responses may be identified by looking for a signal of population variability after exposure, and called for further, deeper analysis of the EDCs, particularly the thyroid disruptors, to identify if these chemicals participate in GxE leading to differences in susceptibility. (via Semantic Scholar)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: April 7, 2021

2021 article

Utilizing Pine Needles to Temporally and Spatially Profile Per- and Polyfluoroalkyl Substances

Kirkwood, K. I., Fleming, J., Nguyen, H., Reif, D. M., Baker, E. S., & Belcher, S. M. (2021, August 26). (Vol. 8). Vol. 8.

TL;DR: Over 70 PFAS were detected in the pine needles from this study, providing information from the last six decades related to PFAS exposure, contamination, and reduction. (via Semantic Scholar)
UN Sustainable Development Goal Categories
15. Life on Land (OpenAlex)
Source: ORCID
Added: August 27, 2021

2020 article

Bayesian Matrix Completion for Hypothesis Testing

(2020, September 17).

David Reif

Source: ORCID
Added: September 24, 2020

2020 journal article

Children’s Environmental Health: A Systems Approach for Anticipating Impacts from Chemicals

International Journal of Environmental Research and Public Health, 17(22), 8337.

By: E. Hubal*, D. Reif n, R. Slover*, A. Mullikin* & J. Little*

author keywords: systems approach; children’ s environmental health
TL;DR: A systems approach is considered to address the complexity of children’s environmental health and the role of exposure to chemicals during early life, in the context of nonchemical stressors, on health outcomes by advancing the tools for integrating more complex information. (via Semantic Scholar)
Source: ORCID
Added: November 13, 2020

2020 journal article

HGBEnviroScreen: Enabling Community Action through Data Integration in the Houston–Galveston–Brazoria Region

International Journal of Environmental Research and Public Health, 17(4), 1130.

By: S. Bhandari*, P. Lewis*, E. Craft*, S. Marvel n, D. Reif n & W. Chiu*

author keywords: environmental justice; geographic information systems; vulnerable populations; community; public health; data; screening; enviroscreen
MeSH headings : Accidents, Occupational; Community Participation; Disasters; Environmental Exposure; Floods; Humans; Public Health; Risk Assessment; Risk Factors; Vulnerable Populations
TL;DR: HGBEnviroScreen is not only helping identify communities of greatest overall vulnerability but is also providing insights into which domains would most benefit from improved planning, policy, and action in order to reduce future vulnerability. (via Semantic Scholar)
Source: ORCID
Added: February 15, 2020

2020 journal article

In vivo assessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

Journal of Immunotoxicology, 17(1), 94–104.

author keywords: Chemical screen; high throughput; phagocyte; reactive oxygen species (ROS); polycyclic aromatic hydrocarbons (PAH); endocrine disrupting compounds (EDC); lead
MeSH headings : Animals; Animals, Genetically Modified; Benzo(a)pyrene / adverse effects; Blood Cell Count; Cytotoxicity Tests, Immunologic / methods; Embryo, Nonmammalian; Estradiol / adverse effects; Feasibility Studies; High-Throughput Screening Assays / methods; Immunity, Innate / drug effects; Macrophages / drug effects; Macrophages / immunology; Methoxychlor / adverse effects; Neutrophils / drug effects; Neutrophils / immunology; Organometallic Compounds / adverse effects; Phenanthrenes / adverse effects; Reactive Oxygen Species / analysis; Reactive Oxygen Species / metabolism; Respiratory Burst / drug effects; Respiratory Burst / immunology; Zebrafish
TL;DR: The utility of zebrafish larvae as a vertebrate model for identifying compounds that impact innate immune function at non-teratogenic levels is demonstrated and validates measuring ROS production and phagocyte numbers as metrics for monitoring how xenobiotic exposure alters the innate immune system. (via Semantic Scholar)
UN Sustainable Development Goal Categories
14. Life Below Water (OpenAlex)
Source: ORCID
Added: May 15, 2020

2020 journal article

Structural-based connectivity and omic phenotype evaluations (SCOPE): a cheminformatics toolbox for investigating lipidomic changes in complex systems

ANALYST, 145(22), 7197–7209.

By: M. Odenkirk n, P. Zin n, J. Ash n, D. Reif n, D. Fourches n & E. Baker n

MeSH headings : Cheminformatics; Lipidomics; Lipids; Mass Spectrometry; Phenotype
TL;DR: A Structural-based Connectivity and Omic Phenotype Evaluations (SCOPE) cheminformatics toolbox to aid in these evaluations of lipid species and their respective biological roles is developed. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: November 24, 2020

2020 article

The COVID-19 Pandemic Vulnerability Index (PVI) Dashboard: monitoring county level vulnerability

Marvel, S. W., House, J. S., Wheeler, M., Song, K., Zhou, Y., Wright, F. A., … Reif, D. M. (2020, August 13). MedRxiv, Vol. 8.

TL;DR: The Pandemic Vulnerability Index (PVI) presents a visual synthesis of county-level vulnerability indicators that can be compared in a regional, state, or nationwide context to enable more effective and coordinated action to combat the pandemic. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (OpenAlex)
Source: ORCID
Added: August 21, 2020

2020 journal article

The multi-dimensional embryonic zebrafish platform predicts flame retardant bioactivity

REPRODUCTIVE TOXICOLOGY, 96, 359–369.

author keywords: Developmental toxicity; Flame retardants; Benchmark dose; Lowest effect concentration; Neurotoxicity; Classification model
MeSH headings : Animals; Embryo, Nonmammalian; Embryonic Development / drug effects; Flame Retardants / toxicity; Models, Animal; Neurotoxicity Syndromes; Risk Assessment; Structure-Activity Relationship; Teratogens / chemistry; Teratogens / toxicity; Zebrafish
TL;DR: Developmental zebrafish were sufficiently sensitive at detecting FRC structure-bioactivity impacts that this work illustrates the power of a multi-dimensional in vivo platform to expand the ability to predict the hazard potential of new compounds based on structural relatedness, ultimately leading to reliable toxicity predictions based on chemical structure. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: November 30, 2020

2019 journal article

Associations between access to healthcare, environmental quality, and end-stage renal disease survival time: Proportional-hazards models of over 1,000,000 people over 14 years

PLOS ONE, 14(3).

Contributors: M. Kosnik n, D. Reif n, D. Lobdell*, T. Astell-Burt*, X. Feng*, J. Hader*, J. Hoppin n

Ed(s): W. Cheungpasitporn

MeSH headings : Adolescent; Adult; Aged; Air Pollution / adverse effects; Female; Health Services Accessibility; Humans; Kidney Failure, Chronic / epidemiology; Male; Middle Aged; Prevalence; Proportional Hazards Models; Risk Factors; Socioeconomic Factors; United States / epidemiology; Water Quality; Young Adult
TL;DR: The results demonstrate the importance of considering multiple factors when studying ESRD survival and future efforts should consider additional components of the broader environment. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: April 9, 2019

2019 journal article

Concentration-response evaluation of ToxCast compounds for multivariate activity patterns of neural network function

ARCHIVES OF TOXICOLOGY, 94(2), 469–484.

author keywords: Neurotoxicity; Screening; ToxCast
MeSH headings : Animals; Cell Culture Techniques / instrumentation; Cell Culture Techniques / methods; Databases, Chemical; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical / methods; Machine Learning; Microelectrodes; Nerve Net / drug effects; Neural Networks, Computer; Neurons / drug effects; Neurotoxicity Syndromes / pathology; Rats, Long-Evans; Toxicity Tests / methods
TL;DR: It is demonstrated that multivariate MEA activity patterns can efficiently screen for diverse chemical activities relevant to neurotoxicity, and that response patterns may have predictive value related to chemical structural features. (via Semantic Scholar)
UN Sustainable Development Goal Categories
15. Life on Land (OpenAlex)
Sources: Web Of Science, NC State University Libraries
Added: March 30, 2020

2019 journal article

Determination of chemical-disease risk values to prioritize connections between environmental factors, genetic variants, and human diseases

Toxicology and Applied Pharmacology, 379, 114674.

By: M. Kosnik n & D. Reif n

Contributors: M. Kosnik n & D. Reif n

author keywords: Data integration; Risk assessment; New approach methodologies; Gene-environment interactions
MeSH headings : Animals; Databases, Factual; Datasets as Topic; Environmental Exposure / adverse effects; Environmental Exposure / statistics & numerical data; Gene-Environment Interaction; Genetic Predisposition to Disease / etiology; Genetic Predisposition to Disease / genetics; Genetic Variation; High-Throughput Screening Assays; Humans; Information Storage and Retrieval; Risk Assessment / methods; Toxicology / methods
TL;DR: This work presents an approach that systematically links multiple data sources to relate chemical risk values to diseases and gene-disease variants and develops a new value that estimates the risk of these associations toward differential population responses. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: ORCID
Added: July 17, 2019

2019 journal article

Inappropriate Citation of Vaccine Article

The Journal of Infectious Diseases, 222(8), 1413–1414.

MeSH headings : Humans; Smallpox; Vaccination; Vaccines / adverse effects
UN Sustainable Development Goal Categories
Source: ORCID
Added: June 19, 2019

2019 journal article

Integration of curated and high-throughput screening data to elucidate environmental influences on disease pathways

Computational Toxicology, 12, 100094.

Contributors: M. Kosnik n, A. Planchart n, S. Marvel n, D. Reif n & C. Mattingly n

Sources: ORCID, Crossref, NC State University Libraries
Added: August 30, 2019

2019 journal article

Multivariate modeling of engineered nanomaterial features associated with developmental toxicity

NanoImpact, 16.

Contributors: K. To n, L. Truong*, S. Edwards*, R. Tanguay* & D. Reif n

author keywords: Engineered nanomaterials; Predictive modeling; Feature analysis; Developmental toxicity; Zebrafish
TL;DR: This work analyzes ENM physico-chemical measurements that have not previously been studied within a developmental toxicity framework using an embryonic zebrafish model and finds that concentration, surface area, shape, and polydispersity can accurately capture the developmental toxicity profile of ENMs with consideration to whole-organism effects. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: ORCID
Added: December 4, 2019

2019 journal article

Population-based toxicity screening in human induced pluripotent stem cell-derived cardiomyocytes

Toxicology and Applied Pharmacology, 381.

author keywords: iPSC; In vitro; Alternative methods; Cardiotoxicity; High-content screening; Environmental chemicals
MeSH headings : Calcium / metabolism; Cardiotoxicity; Cells, Cultured; Drug Evaluation, Preclinical / methods; Female; Genotype; Humans; Induced Pluripotent Stem Cells / cytology; Male; Myocytes, Cardiac / drug effects; Myocytes, Cardiac / metabolism; Phenotype; Racial Groups; Toxicity Tests / methods
TL;DR: This study shows the feasibility of using an organotypic population-based human in vitro model to quantitatively assess chemicals for which little cardiotoxicity information is available, and shows reproducible inter-individual variability in both baseline and chemical-induced effects on iPSC-derived cardiomyocytes. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: ORCID
Added: August 30, 2019

2019 journal article

Sex-specific effects of perinatal FireMaster® 550 (FM 550) exposure on socioemotional behavior in prairie voles

Neurotoxicology and Teratology, 79, 106840.

author keywords: Social; Anxiety; Brain; Neurodevelopment; Neural; Endocrine disruptors; Endocrine disrupting chemicals; Flame retardants
MeSH headings : Animals; Anxiety / chemically induced; Arvicolinae; Behavior, Animal / drug effects; Exploratory Behavior / drug effects; Female; Flame Retardants / toxicity; Male; Organophosphates / toxicity; Polybrominated Biphenyls / toxicity; Pregnancy; Prenatal Exposure Delayed Effects / chemically induced; Prenatal Exposure Delayed Effects / psychology; Sex Characteristics; Social Behavior
TL;DR: The utility of the prairie vole for investigating the impact of chemical exposures on social behavior is demonstrated and the hypothesis that developmental FR exposure impacts the social brain is supported. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Source: ORCID
Added: December 4, 2019

2019 journal article

Synergistic Chemotherapy Drug Response Is a Genetic Trait in Lymphoblastoid Cell Lines

FRONTIERS IN GENETICS, 10.

author keywords: synergy; heritability; chemotherapy; lymphoblastoid cell lines; linkage mapping
TL;DR: It is demonstrated that synergy occurs and can be quantified in LCLs across a range of clinically important drug combinations, which supports the premise of expanding the use of the LCL model to perform association mapping for combination therapies. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: December 2, 2019

2019 journal article

Systematic determination of the relationship between nanoparticle core diameter and toxicity for a series of structurally analogous gold nanoparticles in zebrafish

Nanotoxicology, 4, 1—15.

author keywords: Size-dependency; gold nanoparticles; zebrafish; uptake; ligands
MeSH headings : Animals; Gold / toxicity; Metal Nanoparticles / toxicity; Particle Size; Zebrafish
TL;DR: The results indicate that larger NPs may be the most toxic on a per particle basis and highlight the importance of using particle number and surface area, in addition to mass, when evaluating the size-dependent bioactivity of NPs. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2018 journal article

Characterizing the effects of missing data and evaluating imputation methods for chemical prioritization applications using ToxPi

BIODATA MINING, 11(1).

By: K. To n, R. Fry* & D. Reif n

Contributors: K. To n, R. Fry* & D. Reif n

author keywords: Chemical prioritization; ToxPi; ToxCast; Missing data; Imputation; Multiple imputation; Simulation
TL;DR: Simulation studies around high-throughput screening data generated by the ToxCast and Tox21 programs on chemicals highlighted by the Agency for Toxic Substances and Disease Registry’s Substance Priority List (SPL) can augment confidence in the robustness of decisions regarding the health and ecological effects of environmental chemicals. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2018 journal article

Confirmation of high-throughput screening data and novel mechanistic insights into VDR-xenobiotic interactions by orthogonal assays

Scientific Reports, 8(1).

By: D. Mahapatra n, J. Franzosa*, K. Roell n, M. Kuenemann n, K. Houck*, D. Reif n, D. Fourches n, S. Kullman n

Contributors: D. Mahapatra n, J. Franzosa*, K. Roell n, M. Kuenemann n, K. Houck*, D. Reif n, D. Fourches n, S. Kullman n

MeSH headings : Drug Evaluation, Preclinical; Genes, Reporter; High-Throughput Screening Assays; Humans; Luciferases / analysis; Luciferases / genetics; Protein Binding; Receptors, Calcitriol / agonists; Receptors, Calcitriol / antagonists & inhibitors; Two-Hybrid System Techniques; Xenobiotics / metabolism
TL;DR: Data emphasizes the molecular complexity of ligand-mediated interactions with VDR and suggest that VDR transactivation may be a target site of action for diverse xenobiotics. (via Semantic Scholar)
Sources: ORCID, NC State University Libraries, Crossref, NC State University Libraries
Added: August 6, 2018

2018 journal article

Elucidating Gene-by-Environment Interactions Associated with Differential Susceptibility to Chemical Exposure.

Environmental Health Perspectives, 6(6).

By: M. Balik-Meisner n, L. Truong*, E. Scholl n, D. La*, R. Tanguay* & D. Reif n

Contributors: M. Balik-Meisner n, L. Truong*, E. Scholl n, J. La Du*, R. Tanguay* & D. Reif n

MeSH headings : Animals; Embryo, Nonmammalian / drug effects; Embryonic Development / drug effects; Female; Gene-Environment Interaction; Genetic Variation; Genome-Wide Association Study; High-Throughput Screening Assays / methods; Ivermectin / analogs & derivatives; Ivermectin / toxicity; Male; Phenotype; Zebrafish / embryology; Zebrafish / genetics
TL;DR: The results for Abamectin in zebrafish demonstrate that GxE associated with naturally occurring, population genetic variation play a significant role in mediating individual response to chemical exposure. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2018 journal article

Neonatal mice exposed to a high-fat diet in utero influence the behaviour of their nursing dam

Proceedings of the Royal Society B: Biological Sciences, 285(1891), 20181237.

By: M. Baptissart n, H. Lamb n, K. To n, C. Bradish n, J. Tehrani n, D. Reif n, M. Cowley n

Contributors: M. Baptissart n, H. Lamb n, K. To n, C. Bradish n, J. Tehrani n, D. Reif n, M. Cowley n

MeSH headings : Animals; Animals, Newborn / physiology; Diet, High-Fat; Female; Maternal Behavior / physiology; Maternal Exposure; Mice / physiology; Mice, Inbred C57BL; Pregnancy
TL;DR: In utero exposure to HF diet programmes physiological changes in the offspring which influence the maternal behaviours of their dam after birth are suggested. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: NC State University Libraries, ORCID, NC State University Libraries
Added: December 10, 2018

2018 journal article

Population genetic diversity in zebrafish lines

MAMMALIAN GENOME, 29(1-2), 90–100.

Contributors: M. Balik-Meisner n, L. Truong*, E. Scholl n, R. Tanguay* & D. Reif n

MeSH headings : Animals; Gene Frequency; Genetic Variation; Genetics, Population; Genome / genetics; Polymorphism, Single Nucleotide / genetics; Zebrafish / genetics
TL;DR: T5D is established as a model that is representative of diversity levels within laboratory zebrafish lines and demonstrated that experimental design and analysis can exert major effects when characterizing genetic diversity in heterogeneous populations. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2018 journal article

ToxPi Graphical User Interface 2.0: Dynamic exploration, visualization, and sharing of integrated data models.

BMC Bioinformatics, 3(1).

Contributors: S. Marvel n, K. To n, F. Grimm*, F. Wright n, I. Rusyn* & D. Reif n

author keywords: Visual analytics; Software; systems biology; Risk assessment; Data integration; Graphical user interface
MeSH headings : Cluster Analysis; Information Dissemination; Information Storage and Retrieval; Models, Theoretical; Software; User-Computer Interface
TL;DR: A new graphical user interface for ToxPi (Toxicological Prioritization Index) is detailed, that provides interactive visualization, analysis, reporting, and portability and introduces several features, from flexible data import formats to similarity-based clustering. (via Semantic Scholar)
Sources: ORCID, NC State University Libraries, NC State University Libraries
Added: August 6, 2018

2017 journal article

A New Statistical Approach to Characterize Chemical-Elicited Behavioral Effects in High-Throughput Studies Using Zebrafish

PLOS ONE, 12(1).

Contributors: G. Zhang n, L. Truong*, R. Tanguay* & D. Reif n

Ed(s): S. Neuhauss

MeSH headings : Animals; Biometry / methods; High-Throughput Screening Assays / methods; Models, Statistical; Zebrafish
TL;DR: A novel, robust statistical approach to characterize chemical-elicited effects in behavioral data from high-throughput screening of all 1,060 Toxicity Forecaster chemicals across 5 concentrations at 120 hours post-fertilization (hpf) achieves a significant reduction in coefficient of variation compared to many traditional statistical modeling methods. (via Semantic Scholar)
Sources: ORCID, Web Of Science
Added: August 6, 2018

2017 journal article

An introduction to terminology and methodology of chemical synergy-perspectives from across disciplines

Frontiers in Pharmacology, 8(APR).

Contributors: K. Roell n, D. Reif n & A. Motsinger-Reif n

author keywords: synergy; mixtures; non-additive; interactions; drug combinations
TL;DR: The various terminology surrounding the idea of synergy is discussed, providing a comprehensive list of terms defined across numerous disciplines, including the two most prominent reference models for describing additive interactions: Loewe Additivity and Bliss Independence. (via Semantic Scholar)
Sources: ORCID, NC State University Libraries
Added: May 14, 2019

2017 review

An introduction to terminology and methodology of chemical synergy-perspectives from across disciplines

[Review of ]. Frontiers in Pharmacology, 8.

By: K. Roell, D. Reif & A. Motsinger-Reif

Source: NC State University Libraries
Added: August 6, 2018

2017 journal article

Incorporating ToxCast and Tox21 datasets to rank biological activity of chemicals at Superfund sites in North Carolina

ENVIRONMENT INTERNATIONAL, 101, 19–26.

By: S. Tilley*, D. Reif n & R. Fry*

Contributors: S. Tilley*, D. Reif n & R. Fry*

author keywords: North Carolina; Risk assessment; Superfund; Tox21; ToxCast; ToxPi
MeSH headings : Databases, Factual; Environmental Pollutants / toxicity; Hazardous Waste / economics; Hazardous Waste / legislation & jurisprudence; Humans; North Carolina; Public Health; Risk Assessment; United States; United States Environmental Protection Agency; Waste Management / standards
TL;DR: This study provides a novel methodology for creating state or regional databases of biological activity of contaminants at Superfund sites and identifies residual pesticides and organic solvents to be some of the most highly-ranking predicted bioactive chemicals. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2017 article

Integrating Morphological and Behavioral Phenotypes in Developing Zebrafish

The Rights and Wrongs of Zebrafish: Behavioral Phenotyping of Zebrafish, pp. 259–272.

Contributors: G. Zhang n, L. Truong*, R. Tanguay* & D. Reif n

TL;DR: It is concluded that appropriate design and analysis of integrated morphological and behavioral studies using zebrafish can elucidate new chemical bioactivity pathways, identify compounds eliciting a broad range of effects, and paint a more comprehensive picture of development than either class of phenotype alone. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2017 journal article

Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish

TOXICOLOGY AND APPLIED PHARMACOLOGY, 329, 148–157.

By: A. Knecht*, L. Truong*, S. Marvel n, D. Reif n, A. Garcia*, C. Lu*, M. Simbnich, J. Teeguarden*, R. Tanguay*

Contributors: A. Knecht*, L. Truong*, S. Marvel n, D. Reif n, A. Garcia*, C. Lu*, M. Simonich*, J. Teeguarden*, R. Tanguay*

author keywords: Zebrafish Benzo[a]pyrene; Transgenerational; Neurobehavioral; Developmental toxicity; Physiological deficits; Aryl hydrocarbon receptor
MeSH headings : Animals; Animals, Genetically Modified; Behavior, Animal / drug effects; Benzo(a)pyrene / toxicity; DNA Methylation / drug effects; DNA Modification Methylases / metabolism; Dose-Response Relationship, Drug; Epigenesis, Genetic / drug effects; Genotype; Heart Rate / drug effects; Heredity; Inheritance Patterns / drug effects; Learning / drug effects; Mitochondria / drug effects; Mitochondria / metabolism; Motor Activity / drug effects; Neurotoxicity Syndromes / genetics; Neurotoxicity Syndromes / metabolism; Neurotoxicity Syndromes / physiopathology; Phenotype; Repressor Proteins / agonists; Repressor Proteins / deficiency; Repressor Proteins / genetics; Respiration / drug effects; Risk Assessment; Social Behavior; Time Factors; Water Pollutants, Chemical / toxicity; Zebrafish / genetics; Zebrafish / growth & development; Zebrafish / metabolism; Zebrafish Proteins / agonists; Zebrafish Proteins / deficiency; Zebrafish Proteins / genetics
TL;DR: Exposure to benzo[a]pyrene during development resulted in transgenerational inheritance of neurobehavioral and physiological deficiencies, and indirect evidence suggested the potential for an AHR2‐dependent epigenetic route. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2017 journal article

Use of high-throughput in vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups.

ALTEX, 35(1), 51–64.

By: W. Chiu*, K. Guyton, M. Martin, D. Reif & I. Rusyn

Contributors: W. Chiu*, K. Guyton, M. Martin, D. Reif & I. Rusyn

author keywords: carcinogenicity; high throughput screening; in vitro; mechanisms
MeSH headings : Animals; Biological Assay; Carcinogenicity Tests; Carcinogens / toxicity; High-Throughput Screening Assays / methods; Humans; International Agencies; Publications; United States; United States Environmental Protection Agency
TL;DR: ToxCast HTS data were useful both in evaluating specific mechanistic hypotheses and in contributing to the overall evaluation of mechanistic evidence, however, additional HTS assays are needed to provide more comprehensive coverage of the 10 key characteristics of carcinogens that form the basis of current IARC mechanistic evaluations. (via Semantic Scholar)
Sources: ORCID, NC State University Libraries, NC State University Libraries
Added: August 6, 2018

2016 journal article

A chemical-biological similarity-based grouping of complex substances as a prototype approach for evaluating chemical alternatives

GREEN CHEMISTRY, 18(16), 4407–4419.

By: F. Grimm*, Y. Iwata*, O. Sirenko*, G. Chappell*, F. Wright n, D. Reif n, J. Braisted*, D. Gerhold* ...

Contributors: F. Grimm*, Y. Iwata*, O. Sirenko*, G. Chappell*, F. Wright n, D. Reif n, J. Braisted*, D. Gerhold* ...

TL;DR: An experimental and computational approach to categorizing UVCBs according to chemical and biological similarities is presented. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 journal article

A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

TOXICOLOGY AND APPLIED PHARMACOLOGY, 314, 109–117.

Contributors: G. Zhang n, K. Roell n, L. Truong*, R. Tanguay* & D. Reif n

author keywords: Zebrafish; High-dimensional; Bayesian; Developmental cascade; ToxRefDB; Risk assessment; Multiple endpoints; Multivariate; Scoring
MeSH headings : Animals; Models, Theoretical; Multivariate Analysis; Phenotype; Zebrafish / embryology
TL;DR: The results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints, and wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. (via Semantic Scholar)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: August 6, 2018

2016 journal article

Advancing Exposure Science through Chemical Data Curation and Integration in the Comparative Toxicogenomics Database

Environmental Health Perspectives, 124(10), 1592–1599.

By: C. Grondin n, A. Davis n, T. Wiegers n, B. King*, J. Wiegers n, D. Reif n, J. Hoppin n, C. Mattingly n

Contributors: C. Grondin n, A. Davis n, T. Wiegers n, B. King*, J. Wiegers n, D. Reif n, J. Hoppin n, C. Mattingly n

TL;DR: Curation and integration of exposure data within the CTD provides researchers with new opportunities to correlate exposures with human health outcomes, to identify underlying potential molecular mechanisms, and to improve understanding about the exposome. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018

2016 journal article

Advancing Exposure Science through Chemical Data Curation and Integration in the Comparative Toxicogenomics Database.

Environmental Health Perspectives, 10. http://europepmc.org/abstract/med/27170236

By: C. Grondin, A. Davis, T. Wiegers, B. King, J. Wiegers, D. Reif, J. Hoppin, C. Mattingly

Source: ORCID
Added: May 14, 2019

2016 journal article

Advancing toxicology research using in vivo high throughput toxicology with small fish models

ALTEX, 33(4), 435–452.

By: A. Planchart n, C. Mattingly, D. Allen, P. Ceger, W. Casey, D. Hinton, J. Kanungo, S. Kullman ...

Contributors: A. Planchart n, C. Mattingly, D. Allen, P. Ceger, W. Casey, D. Hinton, J. Kanungo, S. Kullman ...

author keywords: aquatic models; 21st century toxicology; alternatives
TL;DR: The recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies are summarized, as well as many of the advances in the field of toxicology that resulted from usingSmall freshwater fish species, including advances in developmental toxicology, cardiovascular toxicologists, neurotoxicology, and immunotoxicology are reviewed. (via Semantic Scholar)
Sources: ORCID, NC State University Libraries, Crossref, NC State University Libraries
Added: August 6, 2018

2016 journal article

Aggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure

REPRODUCTIVE TOXICOLOGY, 62, 92–99.

Contributors: G. Zhang n, S. Marvel n, L. Truong*, R. Tanguay* & D. Reif n

author keywords: Developmental neurotoxicology; Chemical biology; Morphology; Zebrafish; High throughput screening; ToxCast; Multiplexed assays
MeSH headings : Animals; Embryo, Nonmammalian; Entropy; Flame Retardants / toxicity; High-Throughput Screening Assays; Models, Theoretical; Phenotype; Teratogens / toxicity; Zebrafish / embryology
TL;DR: An information-theoretic method named Aggregate Entropy (AggE) is proposed and applied to scoring multiplexed, phenotypic endpoints measured in developing zebrafish across a broad concentration-response profile for a diverse set of 1060 chemicals, identifying chemicals with significant morphological effects. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 journal article

Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space.

Toxicological Sciences : an Official Journal of the Society of Toxicology, 10(2), 409–409.

By: R. Judson*, K. Houck*, M. Martin*, A. Richard*, T. Knudsen*, I. Shah*, S. Little*, J. Wambaugh* ...

Contributors: R. Judson*, K. Houck*, M. Martin*, A. Richard*, T. Knudsen*, I. Shah*, S. Little*, J. Wambaugh* ...

TL;DR: Responses of 1060 chemicals including pharmaceuticals, natural products, pesticidals, consumer, and industrial chemicals across a battery of 815 in vitro assay endpoints from 7 high-throughput assay technology platforms were analyzed to suggest that activity can be broadly divided into specific biomolecular interactions at concentrations below which overt cytotoxicity-associated activity is observed. (via Semantic Scholar)
UN Sustainable Development Goal Categories
2. Zero Hunger (OpenAlex)
Source: ORCID
Added: May 14, 2019

2016 journal article

Decoupling of a neutron interferometer from temperature gradients

Review of Scientific Instruments, 87(12), 123507.

By: P. Saggu*, T. Mineeva*, M. Arif*, D. Cory*, R. Haun*, B. Heacock n, M. Huber*, K. Li* ...

TL;DR: The vacuum chamber is found to have no depreciable effect on the performance of the interferometer (contrast) while improving system stability, thereby showing that it is feasible to replace large temperature isolation and control systems with a compact vacuum enclosure for perfect crystal neutron interferometry. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018

2016 journal article

Editor's Highlight: Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space.

Toxicological Sciences : an Official Journal of the Society of Toxicology, 8(2), 323–339.

By: R. Judson*, K. Houck*, M. Martin*, A. Richard*, T. Knudsen*, I. Shah*, S. Little*, J. Wambaugh* ...

Contributors: R. Judson*, K. Houck*, M. Martin*, A. Richard*, T. Knudsen*, I. Shah*, S. Little*, J. Wambaugh* ...

author keywords: In vitro; high-throughput screening; oxidative stress; cytotoxicity; cell stress
MeSH headings : Biological Assay / methods; Humans; In Vitro Techniques; Stress, Physiological; Toxicity Tests / methods
TL;DR: Responses of 1060 chemicals including pharmaceuticals, natural products, pesticidals, consumer, and industrial chemicals across a battery of in vitro assay endpoints from 7 high-throughput assay technology platforms were analyzed to suggest that activity can be broadly divided into specific biomolecular interactions against one or more targets at concentrations below which overt cytotoxicity-associated activity is observed. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2016 journal article

Eigenvector metabolite analysis reveals dietary effects on the association among metabolite correlation patterns, gene expression, and phenotypes

METABOLOMICS, 12(11).

Contributors: C. Scott Chialvo*, R. Che n, D. Reif n, A. Motsinger-Reif n & L. Reed*

author keywords: Eigenvector metabolite analysis; Linkage analyses; Environment; Enrichment analyses
TL;DR: Eigenvector Metabolite Analysis provides a simple method to identify correlations between metabolites, gene expression, and phenotypes, which can allow us to partition multivariate datasets into meaningful biological modules and identify under-studied metabolites and unannotated gene transcripts that may be central to important biological processes. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 journal article

Evolutionary and Functional Diversification of the Vitamin D Receptor-Lithocholic Acid Partnership

PLOS ONE, 11(12).

By: E. Kollitz n, G. Zhang n, M. Hawkins n, G. Whitfield*, D. Reif n & S. Kullman n

Contributors: E. Kollitz n, G. Zhang n, M. Hawkins n, G. Whitfield*, D. Reif n & S. Kullman n

Ed(s): C. Zhang n

MeSH headings : Animals; Biological Evolution; Hep G2 Cells; Humans; Lithocholic Acid / metabolism; Receptors, Calcitriol / metabolism; Vertebrates
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 journal article

From the Cover: Embryonic Exposure to TCDD Impacts Osteogenesis of the Axial Skeleton in Japanese medaka,Oryzias latipes

Toxicological Sciences, 155(2), 485–496.

Contributors: A. Watson, A. Planchart n, C. Mattingly n, C. Winkler*, D. Reif n & S. Kullman n

author keywords: receptor, aryl hydrocarbon; gene expression/regulation, bone; transgenic models; methods, developmental/teratology; reproductive and developmental toxicology
MeSH headings : Animals; Calcification, Physiologic / drug effects; Down-Regulation / drug effects; Microscopy, Confocal; Musculoskeletal Diseases / metabolism; Oryzias / embryology; Osteogenesis / drug effects; Polychlorinated Dibenzodioxins / toxicity; Real-Time Polymerase Chain Reaction; Skeleton / drug effects; Skeleton / metabolism; Trans-Activators / drug effects
TL;DR: It is suggested that TCDD exposure inhibits axial bone formation through dysregulation of osteoblast differentiation. (via Semantic Scholar)
UN Sustainable Development Goal Categories
14. Life Below Water (OpenAlex)
Sources: ORCID, Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018

2016 journal article

Lifetime substance use as a predictor of postpartum mental health

Archives of Women's Mental Health, 20(1), 189–199.

author keywords: Postpartum mental health; Alcohol use; Drug use; Screening
MeSH headings : Adult; Alcohol Drinking / epidemiology; Alcohol Drinking / psychology; Anxiety / epidemiology; Anxiety / psychology; Canada / epidemiology; Depression, Postpartum / diagnosis; Depression, Postpartum / epidemiology; Depression, Postpartum / psychology; Female; Humans; Interviews as Topic; Mood Disorders / epidemiology; Mood Disorders / psychology; Pregnancy; Risk Factors; Stress Disorders, Post-Traumatic / epidemiology; Stress Disorders, Post-Traumatic / psychology; Substance-Related Disorders / epidemiology; Substance-Related Disorders / psychology; Surveys and Questionnaires; Urban Population; Women's Health; Young Adult
UN Sustainable Development Goal Categories
5. Gender Equality (Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018

2016 review

Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast (TM) High-Throughput Data

[Review of ]. ENVIRONMENTAL HEALTH PERSPECTIVES, 124(8), 1141–1154.

MeSH headings : Databases, Factual; Diabetes Mellitus / chemically induced; Diabetes Mellitus / epidemiology; Environment; Environmental Exposure / statistics & numerical data; Environmental Pollutants / standards; Environmental Pollutants / toxicity; High-Throughput Screening Assays; Humans; Obesity / chemically induced; Obesity / epidemiology; Outcome Assessment, Health Care; Risk Assessment; United States; United States Environmental Protection Agency
TL;DR: The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2015 journal article

Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid.

The Lancet. Oncology, 8.

By: D. Loomis*, K. Guyton*, Y. Grosse*, G. El*, V. Bouvard*, L. Benbrahim-Tallaa*, N. Guha*, H. Mattock*, K. Straif*, France

TL;DR: This poster presents a poster presenting a poster presented at the 2015 European Congress of Oncology on how to select patients suitable for radiotherapy with a history of prior cancer treatment. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2015 book

Computational Methods Used in Systems Biology

In Systems Biology in Toxicology and Environmental Health (pp. 85–115).

By: M. Meisner & D. Reif*

Contributors: M. Meisner & D. Reif*

TL;DR: Progress in computational methods research has resulted in a trend toward standardization, where coalescence of statistical methods into powerful software packages handle early stages of analysis in a generally accepted manner. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2015 journal article

Data-driven asthma endotypes defined from blood biomarker and gene expression data

PLoS ONE, 10(2).

By: B. George*, D. Reif*, J. Gallagher*, C. Williams-DeVane*, B. Heidenfelder*, E. Hudgens*, W. Jones*, L. Neas*, E. Cohen Hubal*, S. Edwards*

Contributors: B. George*, D. Reif*, J. Gallagher*, C. Williams-DeVane*, B. Heidenfelder*, E. Hudgens*, W. Jones*, L. Neas*, E. Cohen Hubal*, S. Edwards*

MeSH headings : Adaptive Immunity; Anti-Asthmatic Agents / therapeutic use; Asthma / blood; Asthma / classification; Asthma / genetics; Asthma / immunology; Biomarkers / blood; Decision Trees; Eosinophilia / complications; Humans; Immunity, Innate; Medical Informatics / methods; Metabolic Syndrome / complications; Transcriptome
TL;DR: This study describes four distinct asthma endotypes identified via a purely data-driven method, specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotype. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2015 book

Embracing complexity: Searching for gene-gene and gene environment interactions in genetic epidemiology

In Genomics and Proteomics: Principles, Technologies, and Applications (pp. 19–58).

By: A. Motsinger & D. Reif

Contributors: A. Motsinger & D. Reif

TL;DR: Mango (Mangifera indica L.) is an important tropical fruit crop that is thought to be an allotetraploid species with an estimated genome size of 439 mega base pairs. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2015 journal article

Food for Thought...: Toxicity testing in the 21st century beyond environmental chemicals

Altex, 32(3), 171–181.

By: C. Rovida*, S. Asakura*, M. Daneshian*, H. Hofman-Huether*, M. Leist*, L. Meunier*, D. Reif n, A. Rossi* ...

Contributors: C. Rovida*, S. Asakura*, M. Daneshian*, H. Hofman-Huether*, M. Leist*, L. Meunier*, D. Reif n, A. Rossi* ...

author keywords: food ingredients; drugs; Tox21c; safety assessment
MeSH headings : Animal Testing Alternatives / methods; Animals; Drug Approval; Drug Evaluation / methods; Drug Industry; Humans; In Vitro Techniques; Risk Assessment; Safety / standards; Toxicity Tests / methods; United States; United States Environmental Protection Agency
TL;DR: The question is whether the latest paradigm shift proposed by the Tox21c report for chemicals may provide a useful tool to improve the risk assessment approach also for drugs and food ingredients. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2015 journal article

High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes

ARCHIVES OF TOXICOLOGY, 90(6), 1459–1470.

By: D. Reif n, L. Truong*, D. Mandrell*, S. Marvel n, G. Zhang n & R. Tanguay*

Contributors: D. Reif n, L. Truong*, D. Mandrell*, S. Marvel n, G. Zhang n & R. Tanguay*

author keywords: Developmental neurotoxicology; Alternative testing; Chemical biology; Behavior; Zebrafish; High-throughput screening; Bioinformatics; Data integration; ToxCast; Bioactivity
MeSH headings : Animals; Behavior, Animal / drug effects; Dose-Response Relationship, Drug; Embryo, Nonmammalian / abnormalities; Embryo, Nonmammalian / drug effects; Embryo, Nonmammalian / physiopathology; Hazardous Substances / toxicity; High-Throughput Screening Assays; Predictive Value of Tests; Teratogens / toxicity; Zebrafish / abnormalities; Zebrafish / embryology
TL;DR: This high-throughput screening system using a vertebrate organism can provide rapid characterization of chemical-elicited behavioral responses at an early developmental stage that are predictive of observable adverse effects later in life. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2015 journal article

Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study

TOXICOLOGICAL SCIENCES, 148(2), 341–354.

Contributors: M. Rebuli n, L. Camacho*, M. Adonay n, D. Reif n, D. Aylor n & H. Patisaul n

author keywords: bisphenol A; CLARITY; behavior; anxiety; exploratory activity; endocrine disruption; EDC; sexually dimorphic; brain; BPA; plastic
MeSH headings : Age Factors; Animals; Anxiety / chemically induced; Anxiety / psychology; Behavior, Animal / drug effects; Benzhydryl Compounds / toxicity; Dose-Response Relationship, Drug; Endocrine Disruptors / toxicity; Exploratory Behavior / drug effects; Female; Gestational Age; Lactation; Male; Maternal Exposure / adverse effects; Motor Activity / drug effects; Neurotoxicity Syndromes / etiology; Neurotoxicity Syndromes / psychology; Phenols / toxicity; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Risk Assessment; Sex Factors
TL;DR: No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exp exposed groups were identified for some endpoints. (via Semantic Scholar)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: August 6, 2018

2015 journal article

Molecular Cloning, Functional Characterization, and Evolutionary Analysis of Vitamin D Receptors Isolated from Basal Vertebrates

PLOS ONE, 10(4).

By: E. Kollitz n, G. Zhang n, M. Hawkins n, G. Whitfield*, D. Reif n & S. Kullman n

Contributors: E. Kollitz n, G. Zhang n, M. Hawkins n, G. Whitfield*, D. Reif n & S. Kullman n

MeSH headings : Animals; Base Sequence; Cloning, Molecular; Computational Biology; Electrophoretic Mobility Shift Assay; Evolution, Molecular; Fishes / genetics; Likelihood Functions; Models, Genetic; Molecular Sequence Data; Petromyzon / genetics; Phylogeny; Protein Binding; Protein Interaction Mapping; Receptors, Calcitriol / genetics; Sequence Analysis, DNA; Skates, Fish / genetics; Species Specificity; Two-Hybrid System Techniques
TL;DR: This study compares molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs and suggests that 1, 25D3 acts as a partial agonist in basal species. (via Semantic Scholar)
UN Sustainable Development Goal Categories
14. Life Below Water (OpenAlex)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: August 6, 2018

2015 journal article

Using toxcast™ data to reconstruct dynamic cell state trajectories and estimate toxicological points of departure

Environmental Health Perspectives, 124(7), 910–919.

By: I. Shah*, R. Setzer*, J. Jack n, K. Houck*, R. Judson*, T. Knudsen*, J. Liu*, M. Martin* ...

Contributors: I. Shah*, R. Woodrow Setzer*, J. Jack n, K. Houck*, R. Judson*, T. Knudsen*, J. Liu*, M. Martin* ...

MeSH headings : Environmental Pollutants / toxicity; High-Throughput Screening Assays; Membrane Potential, Mitochondrial; Risk Assessment; Toxicity Tests / methods
TL;DR: These findings show the utility of HCI data for reconstructing cell state trajectories and provide insight into the adaptation and resilience of in vitro cellular systems based on tipping points. (via Semantic Scholar)
Sources: ORCID, NC State University Libraries, NC State University Libraries
Added: August 6, 2018

2014 journal article

Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing

Reproductive Toxicology, 55, 3–10.

Contributors: N. Ducharme*, D. Reif n, J. Gustafsson* & M. Bondesson*

author keywords: Meta-analysis; Toxicity; Teratogen; Zebrafish; Human exposure
MeSH headings : Animal Testing Alternatives; Animals; Embryo, Nonmammalian / drug effects; Larva / drug effects; Lethal Dose 50; Mice; Rabbits; Rats; Toxicity Tests / methods; Zebrafish / embryology
TL;DR: Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos are considered high priority chemicals for testing in higher vertebrates. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2014 journal article

Erratum to Incorporating human dosimetry and exposure into High-throughput in Vitro Toxicity Screening [Toxicological sciences 137, 2, (2014), 499]

Toxicological Sciences, 137(2).

By: D. Rotroff, B. Wetmore, D. Dix, S. Ferguson, H. Clewell, K. Houck, E. LeCluyse, M. Andersen ...

Contributors: D. Rotroff, B. Wetmore, D. Dix, S. Ferguson, H. Clewell, K. Houck, E. LeCluyse, M. Andersen ...

Source: ORCID
Added: May 14, 2019

2014 journal article

Hierarchical Dose-Response Modeling for High-Throughput Toxicity Screening of Environmental Chemicals

BIOMETRICS, 70(1), 237–246.

Contributors: A. Wilson n, D. Reif n & B. Reich n

author keywords: Bayesian; Computational toxicology; Dose-response; MCMC; Monotonicity; Semiparametric; ToxCast
MeSH headings : Algorithms; Bayes Theorem; Computer Simulation; Dose-Response Relationship, Drug; Environmental Pollutants / toxicity; Estrogen Receptor alpha / metabolism; Humans; Markov Chains; Models, Statistical; Monte Carlo Method; PPAR gamma / metabolism; Toxicity Tests / methods; United States; United States Environmental Protection Agency
TL;DR: This work proposes a semiparametric Bayesian model that borrows strength across chemicals and assays and demonstrates that the hierarchical method provides more accurate estimates of the probability of response, efficacy, and potency than separate curve estimation in a simulation study. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: ORCID, Web Of Science, NC State University Libraries
Added: August 6, 2018

2014 journal article

Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms

Nature Biotechnology, 32(6), 583–591.

By: N. Kleinstreuer*, J. Yang*, E. Berg*, T. Knudsen*, A. Richard*, M. Martin*, D. Reif*, R. Judson* ...

Contributors: N. Kleinstreuer*, J. Yang*, E. Berg*, T. Knudsen*, A. Richard*, M. Martin*, D. Reif*, R. Judson* ...

MeSH headings : Animal Testing Alternatives / methods; Animals; Computer Simulation; High-Throughput Screening Assays / methods; Humans; Mice; Models, Biological; Phenotype; Rats; Small Molecule Libraries; Toxicity Tests / methods; United States; United States Environmental Protection Agency
TL;DR: The results demonstrate that assaying complex biological pathways in primary human cells can identify potential chemical targets, toxicological liabilities and mechanisms useful for elucidating adverse outcome pathways. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2014 journal article

Predictive endocrine testing in the 21st century using in vitro assays of estrogen receptor signaling responses

Environmental Science and Technology, 48(15), 8706–8716.

By: D. Rotroff*, M. Martin*, D. Dix*, D. Filer*, K. Houck*, T. Knudsen*, N. Sipes*, D. Reif* ...

Contributors: D. Rotroff*, M. Martin*, D. Dix*, D. Filer*, K. Houck*, T. Knudsen*, N. Sipes*, D. Reif* ...

MeSH headings : Algorithms; Animals; Biological Assay; Endocrine Disruptors / analysis; Estrogen Antagonists / analysis; Estrogen Receptor alpha / agonists; Estrogen Receptor alpha / antagonists & inhibitors; Estrogen Receptor beta / agonists; Estrogen Receptor beta / antagonists & inhibitors; Estrogens / analysis; High-Throughput Screening Assays; Humans; MCF-7 Cells; Models, Chemical; Pesticides; Signal Transduction
TL;DR: A novel method for combining in vitro concentration response data from multiple assays and, when applied to a large set of ER data, accurately predicted estrogenic responses and demonstrated its utility for chemical prioritization is provided. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2014 journal article

Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway

Scientific Reports, 4.

By: R. Huang*, S. Sakamuru*, M. Martin*, D. Reif*, R. Judson*, K. Houck*, W. Casey*, J. Hsieh* ...

Contributors: R. Huang*, S. Sakamuru*, M. Martin*, D. Reif*, R. Judson*, K. Houck*, W. Casey*, J. Hsieh* ...

MeSH headings : Cell Line; Estrogen Receptor alpha / agonists; Estrogen Receptor alpha / antagonists & inhibitors; Genes, Reporter / drug effects; HEK293 Cells; High-Throughput Screening Assays / methods; Humans; Ligands; Protein Binding / drug effects; Signal Transduction / drug effects; Small Molecule Libraries / pharmacology; Structure-Activity Relationship
TL;DR: The results demonstrate the feasibility of qHTS to identify environmental chemicals with the potential to interact with the ERα signaling pathway and the two different assay formats improve the confidence in correctly identifying these chemicals. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2014 journal article

Test driving ToxCast: endocrine profiling for 1858 chemicals included in phase II

CURRENT OPINION IN PHARMACOLOGY, 19, 145–152.

By: D. Filer*, H. Patisaul n, T. Schug*, D. Reif n & K. Thayer*

Contributors: D. Filer*, H. Patisaul n, T. Schug*, D. Reif n & K. Thayer*

MeSH headings : Animals; Databases, Factual; Endocrine Disruptors / toxicity; High-Throughput Screening Assays; Humans; Models, Theoretical; Risk Assessment; United States; United States Environmental Protection Agency
TL;DR: Results from this exercise suggest the spectrum of environmental chemicals with potential endocrine activity is much broader than indicated, and that some aspects of endocrine disruption are not fully covered in ToxCast. (via Semantic Scholar)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: August 6, 2018

2014 journal article

ToxiFly: Can fruit flies be used to identify toxicity pathways for airborne chemicals?

Neurotoxicology and Teratology, 43, 89.

By: P. Bushnell*, R. Tatum-Gibbs*, J. McKee*, P. Evansky*, M. Higuchi*, M. MLin*, W. Oshiro*, R. Judson* ...

Sources: Crossref, NC State University Libraries
Added: February 21, 2020

2013 journal article

A Computational Model Predicting Disruption of Blood Vessel Development

PLoS Comput Biol, 9(4), e1002996.

By: N. Kleinstreuer*, D. Dix*, M. Rountree*, N. Baker*, N. Sipes*, D. Reif*, R. Spencer*, T. Knudsen*

Contributors: N. Kleinstreuer*, D. Dix*, M. Rountree*, N. Baker*, N. Sipes*, D. Reif*, R. Spencer*, T. Knudsen*

Ed(s): S. Peirce

MeSH headings : Algorithms; Animals; Blood Vessels / embryology; Chemokines / metabolism; Chemotaxis; Computer Simulation; Endothelial Cells / cytology; Endothelium, Vascular / pathology; Humans; Inflammation; Models, Theoretical; Neovascularization, Physiologic; Phenotype; Signal Transduction; Software; Vascular Endothelial Growth Factor A / metabolism
TL;DR: The model was shown to recapitulate stereotypical capillary plexus formation and structural emergence of non-coded cellular behaviors, such as a heterologous bridging phenomenon linking endothelial tip cells together during formation of polygonal endothelial cords, which support the utility of cell agent-based models for simulating a morphogenetic series of events and for the first time demonstrate the applicability of these models for predictive toxicology. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2013 journal article

Comparing metabolomic and pathologic biomarkers alone and in combination for discriminating Alzheimer's disease from normal cognitive aging

Acta Neuropathologica Communications, 2(1), 28.

By: A. Motsinger-Reif n, H. Zhu*, M. Kling*, W. Matson*, S. Sharma*, O. Fiehn*, D. Reif n, D. Appleby* ...

Contributors: A. Motsinger-Reif n, H. Zhu*, M. Kling*, W. Matson*, S. Sharma*, O. Fiehn*, D. Reif n, D. Appleby* ...

author keywords: Alzheimer's disease; Dementias; Metabolomics; Cerebrospinal fluid biomarkers; Stepwise logistic regression
MeSH headings : Aged; Aging / cerebrospinal fluid; Aging / drug effects; Aging / pathology; Alzheimer Disease / cerebrospinal fluid; Alzheimer Disease / diagnosis; Alzheimer Disease / drug therapy; Alzheimer Disease / pathology; Amyloid beta-Peptides / cerebrospinal fluid; Area Under Curve; Biomarkers / cerebrospinal fluid; Chromatography, Liquid; Cognition; Diagnosis, Differential; Female; Gas Chromatography-Mass Spectrometry; Humans; Logistic Models; Male; Metabolomics / methods; Neuropsychological Tests; tau Proteins / cerebrospinal fluid
TL;DR: Several CSF small-molecule metabolites that discriminated especially well between clinically diagnosed AD and control groups appear to be suitable for further confirmatory and validation studies, and show the potential to provide predictive performance for AD. (via Semantic Scholar)
UN Sustainable Development Goal Categories
10. Reduced Inequalities (OpenAlex)
Source: ORCID
Added: May 14, 2019

2013 journal article

Decision tree-based method for integrating gene expression, demographic, and clinical data to determine disease endotypes.

BMC Systems Biology, 7, 119.

By: C. Williams-DeVane*, D. Reif*, E. Cohen Hubal*, P. Bushel*, E. Hudgens*, J. Gallagher*, S. Edwards*

Contributors: C. Williams-DeVane*, D. Reif*, E. Cohen Hubal*, P. Bushel*, E. Hudgens*, J. Gallagher*, S. Edwards*

author keywords: Asthma; Endotypes; Gene Expression; Integrated analysis
MeSH headings : Adolescent; Asthma / blood; Asthma / genetics; Child; Cluster Analysis; Computational Biology / methods; Decision Trees; Demography; Gene Expression Profiling; Genome-Wide Association Study; Humans
TL;DR: A multi-step decision tree-based method is described for defining endotypes based on gene expression, clinical covariates, and disease indicators using childhood asthma as a case study and it gives the best segregation of asthmatics and non-asthmatics. (via Semantic Scholar)
UN Sustainable Development Goal Categories
16. Peace, Justice and Strong Institutions (OpenAlex)
Source: ORCID
Added: May 14, 2019

2013 journal article

Dosimetric anchoring of in vivo and in vitro studies for perfluorooctanoate and perfluorooctanesulfonate.

Toxicological Sciences, 136(2), 308–327.

author keywords: perfluorooctanoate; perfluorooctanoic acid; perfluorooctanesulfonate; perfluorooctanesulfonic acid; compartment model; saturable resorption model; pharmacokinetics; statistical analysis; Bayesian analysis; ToxCast; in vitro-in vivo extrapolation
MeSH headings : Alkanesulfonic Acids / pharmacokinetics; Alkanesulfonic Acids / toxicity; Animals; Caprylates / pharmacokinetics; Caprylates / toxicity; Dose-Response Relationship, Drug; Female; Fluorocarbons / pharmacokinetics; Fluorocarbons / toxicity; In Vitro Techniques; Macaca fascicularis; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Sprague-Dawley
TL;DR: In vitro assay results for PFOA and PFOS from EPA's ToxCast project were examined and it was found that most in vitro bioactivity occurs at concentrations lower than the predicted concentrations for the in vivo LOELs and higher than the expected concentrations forthe in vivo NOELs, for a variety of nonimmunological effects. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2013 journal article

High-throughput models for exposure-based chemical prioritization in the ExpoCast project.

Environmental Science and Technology, 47(15), 8479–8488.

By: J. Wambaugh*, R. Setzer*, D. Reif*, S. Gangwal*, J. Mitchell-Blackwood*, J. Arnot*, O. Joliet, A. Frame* ...

Contributors: J. Wambaugh*, R. Setzer*, D. Reif*, S. Gangwal*, J. Mitchell-Blackwood*, J. Arnot*, O. Joliet, A. Frame* ...

MeSH headings : Environmental Exposure; Environmental Pollutants / classification; Models, Theoretical
TL;DR: An analysis was conducted that predicts human exposure potential for chemicals and estimates uncertainty in these predictions by comparison to biomonitoring data, and a framework for high-throughput exposure assessment is proposed. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2013 journal article

Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies.

Reproductive Toxicology, 41, 98–108.

author keywords: Developmental toxicity; Zebrafish; ToxPi; Teratogen; Meta-analysis
MeSH headings : 1-Octanol / chemistry; Animals; Embryo, Nonmammalian / abnormalities; Embryo, Nonmammalian / drug effects; Teratogens / chemistry; Teratogens / toxicity; Toxicity Tests; Water / chemistry; Zebrafish
TL;DR: It was found that the physical properties of chemicals did not fully predict lethality or developmental outcomes, and individual outcomes such as pericardial edema and yolk sac edema were more reliable indicators of developmental toxicity. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2013 journal article

Multidimensional in vivo hazard assessment using zebrafish.

Toxicological Sciences, 137(1), 212–233.

By: L. Truong*, D. Reif n, M. St*, M. Geier*, H. Truong* & R. Tanguay*

Contributors: L. Truong*, D. Reif n, L. Mary*, M. Geier*, H. Truong* & R. Tanguay*

MeSH headings : Animals; Cluster Analysis; Computational Biology; Dose-Response Relationship, Drug; Embryo, Nonmammalian / drug effects; Embryo, Nonmammalian / metabolism; Embryo, Nonmammalian / pathology; Embryonic Development / drug effects; Environmental Pollutants / toxicity; High-Throughput Screening Assays; Humans; Motor Activity / drug effects; Notochord / drug effects; Notochord / pathology; Reproducibility of Results; Risk Assessment; Toxicity Tests / methods; Zebrafish / embryology
TL;DR: An experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors is described and it is demonstrated that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2013 journal article

Perspectives on validation of high-throughput assays supporting 21st century toxicity testing.

Altex, 30(1), 51–66. http://europepmc.org/abstract/med/23338806

By: R. Judson, R. Kavlock, M. Martin, D. Reif, K. Houck, T. Knudsen, A. Richard, R. Tice ...

Contributors: R. Judson, R. Kavlock, M. Martin, D. Reif, K. Houck, T. Knudsen, A. Richard, R. Tice ...

Source: ORCID
Added: May 14, 2019

2013 journal article

Profiling 976 ToxCast Chemicals across 331 Enzymatic and Receptor Signaling Assays

Chem. Res. Toxicol., 26(6), 878–895.

Contributors: N. Sipes*, M. Martin*, P. Kothiya*, D. Reif*, R. Judson*, A. Richard*, K. Houck*, D. Dix*, R. Kavlock*, T. Knudsen*

MeSH headings : Animals; Enzymes / metabolism; Guinea Pigs; High-Throughput Screening Assays; Humans; Membrane Transport Proteins / metabolism; Organic Chemicals / toxicity; Rats; Receptors, G-Protein-Coupled / antagonists & inhibitors; Receptors, G-Protein-Coupled / metabolism; Signal Transduction / drug effects
TL;DR: Analyzes 976 chemicals in Phases I and II of the U.S. EPA’s ToxCast project across 331 cell-free enzymatic and ligand-binding high-throughput screening (HTS) assays to find novel findings for previously unreported chemical–target combinations clustered with known chemical– target interactions. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2013 journal article

Real-time growth kinetics measuring hormone mimicry for ToxCast chemicals in T-47D human ductal carcinoma cells.

Chemical Research in Toxicology, 26(7), 1097–1107.

By: D. Rotroff*, D. Dix*, K. Houck*, R. Kavlock*, T. Knudsen*, M. Martin*, D. Reif*, A. Richard* ...

Contributors: D. Rotroff*, D. Dix*, K. Houck*, R. Kavlock*, T. Knudsen*, M. Martin*, D. Reif*, A. Richard* ...

MeSH headings : Breast Neoplasms / metabolism; Breast Neoplasms / pathology; Carcinoma, Ductal, Breast / metabolism; Carcinoma, Ductal, Breast / pathology; Cell Line, Tumor; Cell Proliferation / drug effects; Environmental Pollutants / toxicity; Female; High-Throughput Screening Assays; Hormones / metabolism; Humans; Kinetics; Molecular Mimicry; Receptors, Estrogen / metabolism; Time Factors; Toxicity Tests
TL;DR: This cell-based assay rapidly detects chemical effects on T-47D growth and shows potential, in combination with other HTS assays, to detect environmentally relevant chemicals with potential estrogenic activity. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2013 article

ToxCast: Predicting Toxicity Potential Through High-Throughput Bioactivity Profiling

Houck, K. A., Richard, A. M., Judson, R. S., Martin, M. T., Reif, D. M., & Shah, I. (2013, February). High-Throughput Screening Methods in Toxicity Testing, Vol. 2, p. 1–31.

Source: ORCID
Added: May 14, 2019

2012 conference paper

A comparison of GE optimized neural networks and decision trees

Proceedings of the fourteenth international conference on Genetic and evolutionary computation conference companion - GECCO Companion '12, 611–614.

By: K. Hoover, R. Marceau n, T. Harris n, D. Reif n & A. Motsinger-Reif n

Contributors: K. Hoover, D. Reif n, R. Marceau n, T. Harris n & A. Motsinger-Reif n

TL;DR: Grammatical evolution of decision trees (GEDT) is shown to be not as effective as GENN at detecting disease causing polymorphisms especially in more difficult to detect models, but this power trade off may be worth it for interpretability. (via Semantic Scholar)
UN Sustainable Development Goal Categories
16. Peace, Justice and Strong Institutions (OpenAlex)
Source: ORCID
Added: May 14, 2019

2012 journal article

A comparison of internal model validation methods for multifactor dimensionality reduction in the case of genetic heterogeneity

BMC Research Notes, 5(1), 623.

By: J. Gory n, H. Sweeney n, D. Reif n & A. Motsinger-Reif n

Contributors: J. Gory n, H. Sweeney n, D. Reif n & A. Motsinger-Reif n

MeSH headings : Algorithms; Computer Simulation; Epistasis, Genetic; Genetic Heterogeneity; Humans; Models, Genetic; Multifactor Dimensionality Reduction / standards; Research Design; Validation Studies as Topic
TL;DR: Results show that the cross-validation approach greatly outperformed the three-way split approach in detecting heterogeneity and emphasize the challenge of detecting heterogeneity models and the need for further methods development. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2012 journal article

Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System.

International Journal of Molecular Sciences, 13(2), 1805–1831.

By: R. Judson*, M. Martin*, P. Egeghy*, S. Gangwal*, D. Reif*, P. Kothiya*, M. Wolf*, T. Cathey* ...

Contributors: R. Judson*, M. Martin*, P. Egeghy*, S. Gangwal*, D. Reif*, P. Kothiya*, M. Wolf*, T. Cathey* ...

author keywords: computational toxicology; database; hazard; exposure; high-throughput screening; ACToR; ToxCastDB; ExpoCastDB; ToxRefDB; DSSTox
MeSH headings : Algorithms; Computational Biology / methods; Databases, Factual / standards; Databases, Factual / supply & distribution; Ecotoxicology / methods; Ecotoxicology / organization & administration; Environmental Pollutants / toxicity; Humans; Software; United States; United States Environmental Protection Agency / organization & administration
TL;DR: The organization of the ACToR data repository is described and selected examples of use cases are provided, including links to underlying biological information related to genes and pathways. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2012 journal article

In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.

Toxicological Sciences, 131(1), 40–55.

By: N. Kleinstreuer*, D. Dix*, K. Houck*, R. Kavlock*, T. Knudsen*, M. Martin*, K. Paul*, D. Reif* ...

Contributors: N. Kleinstreuer*, D. Dix*, K. Houck*, R. Kavlock*, T. Knudsen*, M. Martin*, K. Paul*, D. Reif* ...

author keywords: cancer hallmarks; carcinogenesis; predictive toxicology; in vitro and alternatives; bioinformatics
MeSH headings : Animals; Biomarkers, Tumor / analysis; Biomarkers, Tumor / genetics; Carcinogenicity Tests; Carcinogens / chemistry; Carcinogens / toxicity; Databases, Factual; Endpoint Determination; High-Throughput Screening Assays; In Vitro Techniques; Mice; Neoplasms / chemically induced; Neoplasms / genetics; Predictive Value of Tests; Rats; Species Specificity; Thyroid Neoplasms / chemically induced; Thyroid Neoplasms / genetics
TL;DR: A model was developed in which genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption, which represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2012 journal article

Incorporating biological, chemical, and toxicological knowledge into predictive models of toxicity.

Toxicological Sciences, 130(2), 440–441.

By: D. Dix*, K. Houck*, R. Judson*, N. Kleinstreuer*, T. Knudsen*, M. Martin*, D. Reif*, A. Richard* ...

Contributors: D. Dix*, K. Houck*, R. Judson*, N. Kleinstreuer*, T. Knudsen*, M. Martin*, D. Reif*, A. Richard* ...

MeSH headings : Animals; Hazardous Substances / toxicity
TL;DR: An evaluation of statistical models for classifying in vivo toxicity endpoints from ToxRefDB using ToxCast in vitro bioactivity data and chemical structure descriptors concluded that the current Tox cast phase I assays and chemicals have limited applicability for predicting in vivo chemical hazards. (via Semantic Scholar)
Source: ORCID
Added: May 14, 2019

2012 journal article

Incorporating exposure information into the toxicological prioritization index decision support framework

Science of The Total Environment, 435-436, 316–325.

By: S. Gangwal*, D. Reif*, S. Mosher*, P. Egeghy*, J. Wambaugh*, R. Judson*, E. Hubal*

Contributors: S. Gangwal*, D. Reif*, S. Mosher*, P. Egeghy*, J. Wambaugh*, R. Judson*, E. Hubal*

author keywords: ExpoCast; Exposure assessment; ToxCast; Exposure metrics; Exposure prioritization; Pesticides
MeSH headings : Adolescent; Adult; Child; Child, Preschool; Decision Support Techniques; Environmental Exposure; Fruit / chemistry; Hazardous Substances / analysis; Humans; Infant; Male; Middle Aged; Models, Biological; Nutrition Surveys / statistics & numerical data; Pesticide Residues / adverse effects; Pesticide Residues / analysis; Risk Assessment / methods; Vegetables / chemistry; Young Adult
TL;DR: The goal of this analysis is to