@article {1562916, title = {Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells}, journal = {J Hazard Mater}, volume = {463}, year = {2024}, month = {2024 Feb 05}, pages = {132906}, abstract = {

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood. Here, we identified F2RL2, TRIM16L, and PANX2 as novel targets of Nuclear factor erythroid 2-related factor 2 (NRF2)-the master transcriptional factor for the oxidative stress response-that are commonly upregulated with both Pb and As in human neural progenitor cells (NPCs). Using a ChIP (Chromatin immunoprecipitation)-qPCR assay, we showed that NRF2 directly binds to the promoter region of F2RL2, TRIM16L, and PANX2 to regulate expression of these genes. We demonstrated that F2RL2, PANX2, and TRIM16L have differential effects on cell death, proliferation, and differentiation of NPCs in both the presence and absence of metal exposures, highlighting their roles in regulating NPC function. Furthermore, the analyses of the transcriptomic data on NPCs derived from autism spectrum disorder (ASD) patients revealed that dysregulation of F2RL2, TRIM16L, and PANX2 was associated with ASD genetic backgrounds and ASD risk genes. Our findings revealed that Pb and As induce a shared NRF2-dependent transcriptional response in NPCs and identified novel genes regulating NPC function. While further in vivo studies are warranted, this study provides a novel mechanism linking metal exposures to NPC function and identifies potential genes of interest in the context of neurodevelopment.

}, keywords = {Arsenic, Arsenic Poisoning, Autism Spectrum Disorder, Child, Connexins, Humans, Lead, Neural Stem Cells, NF-E2-Related Factor 2}, issn = {1873-3336}, doi = {10.1016/j.jhazmat.2023.132906}, author = {Park, Hae-Ryung and Azzara, David and Cohen, Ethan D and Boomhower, Steven R and Diwadkar, Avantika R and Himes, Blanca E and O{\textquoteright}Reilly, Michael A and Lu, Quan} } @article {1562911, title = {Mechanistic Insights into the Selectivity for Arsenic over Phosphate Adsorption by Fe-Cross-Linked Chitosan Using DFT}, journal = {J Phys Chem B}, volume = {128}, year = {2024}, month = {2024 Feb 22}, pages = {1689-1699}, abstract = {

Fe-cross-linked chitosan exhibits the potential for selectively adsorbing arsenic (As) over competing species, such as phosphate, for water remediation. However, the effective binding mechanisms, bond nature, and controlling factor(s) of the selectivity are poorly understood. This study employs ab initio calculations to examine the competitive binding of As(V), P(V), and As(III) to neat chitosan and Fe-chitosan. Neat chitosan fails to selectively bind As oxyanions, as all three oxyanions bind similarly via weak hydrogen bonds with preferences of P(V) = As(V) > As(III). Conversely, Fe-chitosan selectively binds As(V) over As(III) and P(V) with binding energies of -1.9, -1, and -1.8 eV for As(V), As(III), and P(V), respectively. The preferences are due to varying Fe-oxyanion donor-acceptor characteristics, forming covalent bonds with distinct strengths (Fe-O bond ICOHP values: - 4.9 eV/bond for As(V), - 4.7 eV/bond for P(V), and -3.5 eV/bond for As(III)). Differences in p between As(V)/P(V) and As(III) preclude any preference for As(III) under typical environmental pH conditions. Furthermore, our calculations suggest that the binding selectivity of Fe-chitosan exhibits a pH dependence. These findings enhance our understanding of the Fe-oxyanion interaction crucial for preferential oxyanion binding using Fe-chitosan and provide a lens for further exploration into alternative transition-metal-chitosan combinations and coordination chemistries for applications in selective separations.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.3c06838}, author = {Nwokonkwo, Obinna and Muhich, Christopher} } @article {1568301, title = {Quantified retrospective biomonitoring of fetal and infant elemental exposure using LA-ICP-MS analysis of deciduous dentin in three contrasting human cohorts}, journal = {J Expo Sci Environ Epidemiol}, year = {2024}, month = {2024 Feb 12}, abstract = {

BACKGROUND: Spatial elemental analysis of deciduous tooth dentin combined with odontochronological estimates can provide an early life (in utero to ~2 years of age) history of inorganic element exposure and status.

OBJECTIVE: To demonstrate the importance of data normalization to a certified reference material to enable between-study comparisons, using populations with assumed contrasting elemental exposures.

METHODS: We used laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) of dentin to derive a history of elemental composition from three distinct cohort studies: a present day rural cohort, (the New Hampshire Birth Cohort Study (NHBCS; N = 154)), an historical cohort from an urban area (1958-1970), (the St. Louis Baby Tooth Study (SLBT; N = 78)), and a present-day Nigerian cohort established to study maternal HIV transmission (Dental caries and its association with Oral Microbiomes and HIV in young children-Nigeria (DOMHaIN; N = 31)).

RESULTS: We report Li, Al, Mn, Cu, Zn, Sr, Ba and Pb concentrations ({\textmu}g/g) and qualitatively examine As, Cd and Hg across all three cohorts. Rates of detection were highest, both overall and for each cohort individually, for Zn, Sr, Ba and Li. Zinc was detected in 100\% of samples and was stably present in teeth at a concentration range of 64 - 86 {\textmu}g/g. Mercury, As and Cd detection rates were the lowest, and had high variability within individual ablated spots. We found the highest concentrations of Pb in the pre- and postnatal dentin of the SLBT cohort, consistent with the prevalent use of Pb as an additive to gasoline prior to 1975. The characteristic decline in Mn after the second trimester was observed in all cohorts.

IMPACT: Spatially resolved elemental analysis of deciduous teeth combined with methods for estimating crown formation times can be used to reconstruct an early-life history of elemental exposure inaccessible via other biomarkers. Quantification of data into absolute values using an external standard reference material has not been conducted since 2012, preventing comparison between studies, a common and highly informative component of epidemiology. We demonstrate, with three contrasting populations, that absolute quantification produces data with the lowest variability, compares well with available data and recommends that future tooth biomarker studies report data in this way.

}, issn = {1559-064X}, doi = {10.1038/s41370-024-00652-3}, author = {Punshon, T and Bauer, Julia A and Karagas, Margaret R and Coker, Modupe O and Weisskopf, Marc G and Mangano, Joseph J and Bidlack, Felicitas B and Barr, Matthew N and Jackson, Brian P} } @article {1516481, title = {Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity}, journal = {Extracellular Vesicle}, volume = {2}, year = {2023}, month = {2023/12/01/}, pages = {100027}, abstract = {Exposure to environmental heavy metals such as cadmium (Cd) is often linked to neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs){\textendash}an important class of extracellular vesicles (EVs) whose biogenesis occurs at the plasma membrane{\textendash}protect against Cd-induced neurotoxicity. Cd increased the production of EVs, including ARMMs, in a human neural progenitor cell line, ReNcell CX (ReN) cells. ReN cells that lack ARMMs production as a result of CRISPR-mediated ARRDC1 knockout were more susceptible to Cd toxicity as evidenced by increased LDH production as well as elevated level of oxidative stress markers. Importantly, adding ARMMs back to the ARRDC1-knockout ReN cells significantly reduced Cd-induced toxicity. Consistent with this finding, proteomics data showed that anti-oxidative stress proteins are enriched in ARMMs secreted from ReN cells. Together our study reveals a novel protective role of ARMMs in Cd neurotoxicity and suggests that ARMMs may be used therapeutically to reduce neurotoxicity caused by exposure to Cd and potentially other metal toxicants.}, keywords = {Extracellular Vesicles, Heavy metals, Neurotoxicity, proteomics}, isbn = {2773-0417}, url = {https://www.sciencedirect.com/science/article/pii/S2773041723000069}, author = {Chen, Zunwei and Qiao, Zhi and Wirth, Charlotte R. and Park, Hae-Ryung and Lu, Quan} } @article {1420283, title = {On Statistical Inference with High-Dimensional Sparse CCA}, journal = {Inf inference}, volume = {12}, year = {2023}, note = {

Link\ to our R package, which implements our method.

https://github.com/nilanjanalaha/de.bias.CCA

}, abstract = {
We consider asymptotically exact inference on the leading canonical correlation directions and strengths between two high dimensional vectors under sparsity restrictions. In this regard, our main contribution is the development of a loss function, based on which, one can operationalize a one-step bias-correction on reasonable initial estimators. Our analytic results in this regard are adaptive over suitable structural restrictions of the high dimensional nuisance parameters, which, in this set-up, correspond to the covariance matrices of the variables of interest. We further supplement the theoretical guarantees behind our procedures with extensive numerical studies.
}, url = {https://arxiv.org/abs/2109.11997v1}, author = {Nilanjana Laha and Huey, Nathan and Brent Coull and Rajarshi Mukherjee} } @article {doi:10.1021/acs.jpca.3c03826, title = {Functionalized Ferrocene Enables Selective Electrosorption of Arsenic Oxyanions over Phosphate-A DFT Examination of the Effects of Substitutional Moieties, pH, and Oxidation State}, journal = {The Journal of Physical Chemistry A}, year = {2023}, note = {PMID: 37682592}, month = {9/8/2023}, pages = {null}, doi = {10.1021/acs.jpca.3c03826}, url = {https://doi.org/10.1021/acs.jpca.3c03826}, author = {Nwokonkwo, Obinna and Pelletier, Vivienne and Broud, Michael and Muhich, Christopher} } @article {1493131, title = {Understanding the Effect of Single Atom Cationic Defect Sites in an Al2O3 (012) Surface on Altering Selenate and Sulfate Adsorption: An Ab Initio Study}, journal = {J. Phys. Chem. C}, volume = {127}, year = {2023}, note = {NIHMSID:\ 1908488}, pages = {6925-6937}, abstract = {Adsorption is a promising under-the-sink selenate remediation technique for distributed water systems. Recently it was shown that adsorption induced water network rearrangement control adsorption energetics on the α-Al2O3\ (012) surface. Here, we aim to elucidate the relative importance of the water network effects and surface cation identity on controlling selenate and sulfate adsorption energy using density functional theory calculations. Density functional theory (DFT) calculations predicted the adsorption energies of selenate and sulfate on nine transition metal cations (Sc{\textendash}Cu) and two alkali metal cations (Ga and In) in the α-Al2O3\ (012) surface under simulated acidic and neutral pH conditions. We find that the water network effects had a larger impact on the adsorption energy than the cationic identity. However, cation identity secondarily controlled adsorption. Most cations decreased the adsorption energy, weakening the overall performance, the larger Sc and In cations enabled inner-sphere adsorption in acidic conditions because they relaxed outward from the surface, providing more space for adsorption. Additionally, only Ti induced Se selectivity over S by reducing the adsorbing selenate to selenite but not reducing the sulfate. Overall, this study indicates that tuning water network structure will likely have a larger impact than tuning cation{\textendash}selenate interactions for increasing adsorbate effectiveness.}, url = {https://doi.org/10.1021/acs.jpcc.3c00098}, author = {Gupta, Srishti and Chismar, Adam and Muhich, Christopher} } @article {1470511, title = {The Utility of Machine Learning Models for Predicting Chemical Contaminants in Drinking Water: Promise, Challenges, and Opportunities}, journal = {Curr Environ Health Rep}, volume = {10}, year = {2023}, month = {2022 Dec 17}, pages = {45-60}, abstract = {

PURPOSE OF REVIEW: This review aims to better understand the utility of machine learning algorithms for predicting spatial patterns of contaminants in the United States (U.S.) drinking water.

RECENT FINDINGS: We found 27 U.S. drinking water studies in the past ten years that used machine learning algorithms to predict water quality. Most studies (42\%) developed random forest classification models for groundwater. Continuous models show low predictive power, suggesting that larger datasets and additional predictors are needed. Categorical/classification models for arsenic and nitrate that predict exceedances of pollution thresholds are most common in the literature because of good national scale data coverage and priority as environmental health concerns. Most groundwater data used to develop models were obtained from the United States Geological Survey (USGS) National Water Information System (NWIS). Predictors were similar across contaminants but challenges are posed by the lack of a standard methodology for imputation, pre-processing, and differing availability of data across regions. We reviewed 27 articles that focused on seven drinking water contaminants. Good performance metrics were reported for binary models that classified chemical concentrations above a threshold value by finding significant predictors. Classification models are especially useful for assisting in the design of sampling efforts by identifying high-risk areas. Only a few studies have developed continuous models and obtaining good predictive performance for such models is still challenging. Improving continuous models is important for potential future use in epidemiological studies to supplement data gaps in exposure assessments for drinking water contaminants. While significant progress has been made over the past decade, methodological advances are still needed for selecting appropriate model performance metrics and accounting for spatial autocorrelations in data. Finally, improved infrastructure for code and data sharing would spearhead more rapid advances in machine-learning models for drinking water quality.

}, issn = {2196-5412}, doi = {10.1007/s40572-022-00389-x}, author = {Hu, Xindi C and Dai, Mona and Sun, Jennifer M and Sunderland, Elsie M} } @article {1568326, title = {Differences in set-based tests for sparse alternatives when testing sets of outcomes compared to sets of explanatory factors in genetic association studies}, journal = {Biostatistics}, volume = {25}, year = {2023}, month = {2023 Dec 15}, pages = {171-187}, abstract = {

Set-based association tests are widely popular in genetic association settings for their ability to aggregate weak signals and reduce multiple testing burdens. In particular, a class of set-based tests including the Higher Criticism, Berk-Jones, and other statistics have recently been popularized for reaching a so-called detection boundary when signals are rare and weak. Such tests have been applied in two subtly different settings: (a) associating a genetic variant set with a single phenotype and (b) associating a single genetic variant with a phenotype set. A significant issue in practice is the choice of test, especially when deciding between innovated and generalized type methods for detection boundary tests. Conflicting guidance is present in the literature. This work describes how correlation structures generate marked differences in relative operating characteristics for settings (a) and (b). The implications for study design are significant. We also develop novel power bounds that facilitate the aforementioned calculations and allow for analysis of individual testing settings. In more concrete terms, our investigation is motivated by translational expression quantitative trait loci (eQTL) studies in lung cancer. These studies involve both testing for groups of variants associated with a single gene expression (multiple explanatory factors) and testing whether a single variant is associated with a group of gene expressions (multiple outcomes). Results are supported by a collection of simulation studies and illustrated through lung cancer eQTL examples.

}, keywords = {Computer Simulation, Genetic Association Studies, Genome-Wide Association Study, Humans, Lung Neoplasms, Models, Genetic, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci}, issn = {1468-4357}, doi = {10.1093/biostatistics/kxac036}, author = {Sun, Ryan and Shi, Andy and Lin, Xihong} } @article {1562936, title = {MAD Water: Integrating Modular, Adaptive, and Decentralized Approaches for Water Security in the Climate Change Era}, journal = {WIREs Water}, volume = {10}, year = {2023}, month = {2023 Nov-Dec}, abstract = {

Centralized water infrastructure has, over the last century, brought safe and reliable drinking water to much of the world. But climate change, combined with aging and underfunding, is increasingly testing the limits of-and reversing gains made by-these large-scale water systems. To address these growing strains and gaps, we must assess and advance alternatives to centralized water provision and sanitation. The water literature is rife with examples of systems that are neither centralized nor networked, but still meet water needs of local communities in important ways, including: informal and hybrid water systems, decentralized water provision, community-based water management, small drinking water systems, point-of-use treatment, small-scale water vendors, and packaged water. Our work builds on these literatures by proposing a convergence approach that can integrate and explore the benefits and challenges of modular, adaptive, and decentralized ("MAD") water provision and sanitation, often foregrounding important advances in engineering technology. We further provide frameworks to evaluate justice, economic feasibility, governance, human health, and environmental sustainability as key parameters of MAD water system performance.

}, issn = {2049-1948}, doi = {10.1002/wat2.1680}, author = {Wutich, Amber and Thomson, Patrick and Jepson, Wendy and Stoler, Justin and Cooperman, Alicia D and Doss-Gollin, James and Jantrania, Anish and Mayer, Alex and Nelson-Nu{\~n}ez, Jami and Walker, W Shane and Westerhoff, Paul} } @article {1562931, title = {Membrane Functionalization Approaches toward Per- and Polyfluoroalkyl Substances and Selected Metal Ion Separations}, journal = {ACS Appl Mater Interfaces}, volume = {15}, year = {2023}, month = {2023 Sep 20}, pages = {44224-44237}, abstract = {

Adsorption and ion exchange technologies are two of the most widely used approaches to separate pollutants from water; however, their intrinsic diffusion limitations continue to be a challenge. Pore functionalized membranes are a promising technology that can help overcome these challenges, but the extents of their competitive benefits and broad applicability have not been systematically evaluated. Herein, three types of adsorptive/ion exchange (IX) polymers containing strong/weak acid, strong base, and iron-chitosan complex groups were synthesized in the pores and partially on the surface of microfiltration (MF) membranes and tested for the removal of organic and inorganic cations and anions from water, including arsenic, per- and polyfluoroalkyl substances (PFAS), and calcium (hardness). When directly compared with beads (0.5-6 mm) and crushed resins (0.05 mm), adsorptive/IX pore-functionalized membranes demonstrated an increased relative sorption capacity, up to 2 orders of magnitude faster kinetics and the ability to regenerate up to 70-100\% of their capacity while concentrating the initial solution concentration up to 12 times. The simple and versatile synthesis approach used to functionalize membranes, notably independent of the polymer type of the MF membrane, utilized pores throughout the entire cross section of the membrane to immobilize the polymers that contain the functional groups. Utilizing the pore volume of commercial membranes (6-112 mL/m), the scientific weight capacity of the polymer (3.1-11.5 mequiv/g), and the synthesis conditions (e.g., monomer concentration), the theoretical adsorption/IX capacities per area of the membranes were calculated to be as high as 550 mequiv/m, substantially higher than the 175 mequiv/m value needed to compete with commercially available IX resins. This work therefore shows that pore functionalized membranes are a promising path to tackle water contamination challenges, lowering separation diffusion limitations.

}, issn = {1944-8252}, doi = {10.1021/acsami.3c08478}, author = {L{\'e}niz-Pizarro, Francisco and Rudel, Holly E and Briot, Nicolas J and Zimmerman, Julie B and Bhattacharyya, Dibakar} } @article {1568341, title = {On statistical inference with high-dimensional sparse CCA}, journal = {Inf inference}, volume = {12}, year = {2023}, month = {2023 Dec}, pages = {iaad040}, abstract = {

We consider asymptotically exact inference on the leading canonical correlation directions and strengths between two high-dimensional vectors under sparsity restrictions. In this regard, our main contribution is developing a novel representation of the Canonical Correlation Analysis problem, based on which one can operationalize a one-step bias correction on reasonable initial estimators. Our analytic results in this regard are adaptive over suitable structural restrictions of the high-dimensional nuisance parameters, which, in this set-up, correspond to the covariance matrices of the variables of interest. We further supplement the theoretical guarantees behind our procedures with extensive numerical studies.

}, issn = {2049-8764}, doi = {10.1093/imaiai/iaad040}, author = {Laha, Nilanjana and Huey, Nathan and Coull, Brent and Mukherjee, Rajarshi} } @article {1529006, title = {Bias Amplification and Variance Inflation in Distributed Lag Models Using Low-Spatial-Resolution Data}, journal = {Am J Epidemiol}, volume = {192}, year = {2023}, month = {2023 Apr 06}, pages = {644-657}, abstract = {

Distributed lag models (DLMs) are often used to estimate lagged associations and identify critical exposure windows. In a simulation study of prenatal nitrogen dioxide (NO2) exposure and birth weight, we demonstrate that bias amplification and variance inflation can manifest under certain combinations of DLM estimation approaches and time-trend adjustment methods when using low-spatial-resolution exposures with extended lags. Our simulations showed that when using high-spatial-resolution exposure data, any time-trend adjustment method produced low bias and nominal coverage for the distributed lag estimator. When using either low- or no-spatial-resolution exposures, bias due to time trends was amplified for all adjustment methods. Variance inflation was higher in low- or no-spatial-resolution DLMs when using a long-term spline to adjust for seasonality and long-term trends due to concurvity between a distributed lag function and secular function of time. NO2-birth weight analyses in a Massachusetts-based cohort showed that associations were negative for exposures experienced in gestational weeks 15-30 when using high-spatial-resolution DLMs; however, associations were null and positive for DLMs with low- and no-spatial-resolution exposures, respectively, which is likely due to bias amplification. DLM analyses should jointly consider the spatial resolution of exposure data and the parameterizations of the time trend adjustment and lag constraints.

}, keywords = {Air Pollutants, Air Pollution, Birth Weight, Female, Humans, Nitrogen Dioxide, Particulate Matter, Pregnancy}, issn = {1476-6256}, doi = {10.1093/aje/kwac220}, url = {https://academic.oup.com/aje/article-abstract/192/4/644/6958521?redirectedFrom=fulltext}, author = {Leung, Michael and Rowland, Sebastian T and Coull, Brent A and Modest, Anna M and Hacker, Michele R and Schwartz, Joel and Kioumourtzoglou, Marianthi-Anna and Weisskopf, Marc G and Wilson, Ander} } @article {1476601, title = {Displaying and delivering viral membrane antigens via WW domain-activated extracellular vesicles}, journal = {Sci Adv}, volume = {9}, year = {2023}, month = {2023 Jan 27}, pages = {eade2708}, abstract = {

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle-based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain-activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral membrane proteins displayed on WAEVs elicits production of virus-specific neutralizing antibodies and, in the case of influenza antigens, protects mice from the lethal viral infection. WAEVs thus represent a versatile platform for presenting and delivering membrane antigens as vaccines against influenza, HIV, and potentially many other viral pathogens.

}, keywords = {Animals, Antigens, Antigens, Viral, Extracellular Vesicles, HIV Infections, Humans, Influenza Vaccines, Influenza, Human, Mice, Proline, WW Domains}, issn = {2375-2548}, doi = {10.1126/sciadv.ade2708}, author = {Choi, Sengjin and Yang, Zhiping and Wang, Qiyu and Qiao, Zhi and Sun, Maoyun and Wiggins, Joshua and Xiang, Shi-Hua and Lu, Quan} } @article {1535896, title = {Early-life participation in cognitively stimulating activities and risk of depression and anxiety in late life}, journal = {Psychol Med}, year = {2023}, month = {2023 Sep 14}, pages = {1-9}, abstract = {

BACKGROUND: Early-life stressful experiences are associated with increased risk of adverse psychological outcomes in later life. However, much less is known about associations between early-life positive experiences, such as participation in cognitively stimulating activities, and late-life mental health. We investigated whether greater engagement in cognitively stimulating activities in early life is associated with lower risk of depression and anxiety in late life.

METHODS: We surveyed former participants of the St. Louis Baby Tooth study, between 22 June 2021 and 25 March 2022 to collect information on participants{\textquoteright} current depression/anxiety symptoms and their early-life activities ( = 2187 responded). A composite activity score was created to represent the early-life activity level by averaging the frequency of self-reported participation in common cognitively stimulating activities in participants{\textquoteright} early life (age 6, 12, 18), each rated on a 1 (least frequent) to 5 (most frequent) point scale. Depression/anxiety symptoms were measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7). We used logistic regressions to estimate odds ratios (OR) and 95\% confidence intervals (CI) of outcome risk associated with frequency of early-life activity.

RESULTS: Each one-point increase in the early-life composite cognitive activity score was associated with an OR of 0.54 (95\% CI 0.38-0.77) for late-life depression and an OR of 0.94 (95\% CI 0.61-1.43) for late-life anxiety, adjusting for age, sex, race, parental education, childhood family structure, and socioeconomic status.

CONCLUSIONS: More frequent participation in cognitively stimulating activities during early life was associated with reduced risk of late-life depression.

}, issn = {1469-8978}, doi = {10.1017/S0033291723002702}, author = {Qiu, Xinye and Robert, Andrea L and McAlaine, Kaleigh and Quan, Luwei and Mangano, Joseph and Weisskopf, Marc G} } @article {1525996, title = {Elucidating the Role of Capping Agents in Facet-Dependent Adsorption Performance of Hematite Nanostructures}, journal = {ACS Appl Mater Interfaces}, volume = {15}, year = {2023}, month = {2023 Jul 26}, pages = {34829-34837}, abstract = {

Organic capping agents are a ubiquitous and crucial part of preparing reproducible and homogeneous batches of nanomaterials, particularly nanocrystals with well-defined facets. Despite studies reporting surface ligands (e.g., capping agents) having a non-negligible role in catalytic behavior, their impact is less understood in contaminant adsorption, an important consideration given their potential to obfuscate facet-dependent trends in performance. To ascribe observed behaviors to the facet or the ligand, this report evaluates the impact of poly(-vinyl-2-pyrrolidone) (PVP), a commonly utilized capping agent, on the adsorption performance of nanohematite particles of varying prevailing facet in the removal of selenite (Se(IV)) as a model system. The PVP capping agent reduces the available surface area for contaminant binding, thus resulting in a reduction in overall Se(IV) adsorbed. However, accounting for the effects of surface area, {012}-faceted nanohematite demonstrates a significantly higher sorption capacity for Se(IV) compared with that of {001}-faceted nanohematite. Notably, chemical treatment is minimally effective in removing strongly bound PVP, indicating that complete removal of surface ligands remains challenging.

}, issn = {1944-8252}, doi = {10.1021/acsami.3c05104}, author = {Rudel, Holly E and Zimmerman, Julie B} } @article {1535921, title = {FAVOR: functional annotation of variants online resource and annotator for variation across the human genome}, journal = {Nucleic Acids Res}, volume = {51}, year = {2023}, note = {doi: 10.1093/nar/gkac966. PMID: 36350676; PMCID: PMC9825437.}, month = {2023 Jan 06}, pages = {D1300-D1311}, abstract = {

Large biobank-scale whole genome sequencing (WGS) studies are rapidly identifying a multitude of coding and non-coding variants. They provide an unprecedented resource for illuminating the genetic basis of human diseases. Variant functional annotations play a critical role in WGS analysis, result interpretation, and prioritization of disease- or trait-associated causal variants. Existing functional annotation databases have limited scope to perform online queries and functionally annotate the genotype data of large biobank-scale WGS studies. We develop the Functional Annotation of Variants Online Resources (FAVOR) to meet these pressing needs. FAVOR provides a comprehensive multi-faceted variant functional annotation online portal that summarizes\ and visualizes findings of all possible nine billion single nucleotide variants (SNVs) across the genome. It allows for rapid variant-, gene-\ and region-level queries of variant functional annotations. FAVOR integrates variant functional information from multiple sources to describe the functional characteristics of variants and facilitates prioritizing plausible causal variants influencing human phenotypes. Furthermore, we provide a scalable annotation tool, FAVORannotator, to functionally annotate large-scale WGS studies and efficiently store the genotype and their variant functional annotation data in a single file using the annotated Genomic Data Structure (aGDS) format, making downstream analysis more convenient. FAVOR and FAVORannotator are available at https://favor.genohub.org.

}, keywords = {Genetic Variation, Genome, Human, Genomics, Genotype, Humans, Molecular Sequence Annotation, Software}, issn = {1362-4962}, doi = {10.1093/nar/gkac966}, author = {Zhou, Hufeng and Arapoglou, Theodore and Li, Xihao and Li, Zilin and Zheng, Xiuwen and Moore, Jill and Asok, Abhijith and Kumar, Sushant and Blue, Elizabeth E and Buyske, Steven and Cox, Nancy and Felsenfeld, Adam and Gerstein, Mark and Kenny, Eimear and Li, Bingshan and Matise, Tara and Philippakis, Anthony and Rehm, Heidi L and Sofia, Heidi J and Snyder, Grace and NHGRI~Genome~Sequencing~Program~Variant~Functional~Annotation~Working Group and Weng, Zhiping and Neale, Benjamin and Sunyaev, Shamil R and Lin, Xihong} } @article {1516476, title = {Mechanistic Study of Arsenate Adsorption onto Different Amorphous Grades of Titanium (Hydr)Oxides Impregnated into a Point-of-Use Activated Carbon Block}, journal = {ACS ES\&T EngineeringACS ES\&T Engineering}, volume = {3}, year = {2023}, note = {

doi: 10.1021/acsestengg.3c00012; NIHMSID:\ 1908485

}, month = {2023/07/14}, pages = {989 - 1000}, publisher = {American Chemical Society}, abstract = {Millions of households still rely on drinking water from private wells or municipal systems with arsenic levels approaching or exceeding regulatory limits. Arsenic is a potent carcinogen, and there is no safe level of it in drinking water. Point-of-use (POU) treatment systems are a promising option to mitigate arsenic exposure. However, the most commonly used POU technology, an activated carbon block filter, is ineffective at removing arsenic. Our study aimed to explore the potential of impregnating carbon blocks with amorphous titanium (hydr)oxide (THO) to improve arsenic removal without introducing titanium (Ti) into the treated water. Four synthesis methods achieved 8{\textendash}16 wt \% Ti-loading within the carbon block with a 58{\textendash}97\% amorphous THO content. The THO-modified carbon block could adsorb both oxidation states of arsenic (arsenate and arsenite) in batch or column tests. Modified carbon block with higher Ti and amorphous content always led to better arsenate removal, achieving arsenic loadings up to 31 mg As/mg Ti after 70,000 bed volumes in continuous-flow tests. Impregnating carbon block with amorphous THO consistently outperformed impregnation using crystalline TiO2. The best-performing system (TTIP-EtOH carbon block) was an amorphous THO derived using titanium isopropoxide, ethanol, and acetic acid via the sol{\textendash}gel technique, aged at 80 {\textdegree}C for 18 h and dried overnight at 60 {\textdegree}C. Comparable pore-size distribution and surface area of the impregnated carbon blocks suggested that chemical properties play a more crucial role than physical and textural properties in removing arsenate via the amorphous Ti-impregnated carbon block. Freundlich isotherms indicated energetically favorable adsorption for amorphous chemically synthesized adsorbents. The mass transport coefficients for the amorphous TTIP-EtOH carbon block were fitted using a pore-surface diffusion model, resulting in Dsurface = 3.1 {\texttimes} 10{\textendash}12 and Dpore = 3.2 {\texttimes} 10{\textendash}6 cm2/s. Impregnating the carbon block with THO enabled effective arsenic removal from water without adversely affecting the pressure drop across the unit or the carbon block{\textquoteright}s ability to remove polar organic chemical pollutants efficiently.Millions of households still rely on drinking water from private wells or municipal systems with arsenic levels approaching or exceeding regulatory limits. Arsenic is a potent carcinogen, and there is no safe level of it in drinking water. Point-of-use (POU) treatment systems are a promising option to mitigate arsenic exposure. However, the most commonly used POU technology, an activated carbon block filter, is ineffective at removing arsenic. Our study aimed to explore the potential of impregnating carbon blocks with amorphous titanium (hydr)oxide (THO) to improve arsenic removal without introducing titanium (Ti) into the treated water. Four synthesis methods achieved 8{\textendash}16 wt \% Ti-loading within the carbon block with a 58{\textendash}97\% amorphous THO content. The THO-modified carbon block could adsorb both oxidation states of arsenic (arsenate and arsenite) in batch or column tests. Modified carbon block with higher Ti and amorphous content always led to better arsenate removal, achieving arsenic loadings up to 31 mg As/mg Ti after 70,000 bed volumes in continuous-flow tests. Impregnating carbon block with amorphous THO consistently outperformed impregnation using crystalline TiO2. The best-performing system (TTIP-EtOH carbon block) was an amorphous THO derived using titanium isopropoxide, ethanol, and acetic acid via the sol{\textendash}gel technique, aged at 80 {\textdegree}C for 18 h and dried overnight at 60 {\textdegree}C. Comparable pore-size distribution and surface area of the impregnated carbon blocks suggested that chemical properties play a more crucial role than physical and textural properties in removing arsenate via the amorphous Ti-impregnated carbon block. Freundlich isotherms indicated energetically favorable adsorption for amorphous chemically synthesized adsorbents. The mass transport coefficients for the amorphous TTIP-EtOH carbon block were fitted using a pore-surface diffusion model, resulting in Dsurface = 3.1 {\texttimes} 10{\textendash}12 and Dpore = 3.2 {\texttimes} 10{\textendash}6 cm2/s. Impregnating the carbon block with THO enabled effective arsenic removal from water without adversely affecting the pressure drop across the unit or the carbon block{\textquoteright}s ability to remove polar organic chemical pollutants efficiently.}, url = {https://doi.org/10.1021/acsestengg.3c00012}, author = {Farsad, Alireza and Niimi, Ken and Ersan, Mahmut Selim and Gonzalez-Rodriguez, Jose Ricardo and Hristovski, Kiril D. and Westerhoff, Paul} } @article {1525986, title = {The Minus Approach Can Redefine the Standard of Practice of Drinking Water Treatment}, journal = {Environ Sci Technol}, volume = {57}, year = {2023}, month = {2023 May 09}, pages = {7150-7161}, abstract = {

Chlorine-based disinfection for drinking water treatment (DWT) was one of the 20th century{\textquoteright}s great public health achievements, as it substantially reduced the risk of acute microbial waterborne disease. However, today{\textquoteright}s chlorinated drinking water is not unambiguously safe; trace levels of regulated and unregulated disinfection byproducts (DBPs), and other known, unknown, and emerging contaminants (KUECs), present chronic risks that make them essential removal targets. Because conventional chemical-based DWT processes do little to remove DBPs or KUECs, alternative approaches are needed to minimize risks by removing DBP precursors and KUECs that are ubiquitous in water supplies. We present the "Minus Approach" as a toolbox of practices and technologies to mitigate KUECs and DBPs without compromising microbiological safety. The Minus Approach reduces problem-causing chemical addition treatment (i.e., the conventional "Plus Approach") by producing biologically stable water containing pathogens at levels having negligible human health risk and substantially lower concentrations of KUECs and DBPs. Aside from ozonation, the Minus Approach avoids primary chemical-based coagulants, disinfectants, and advanced oxidation processes. The Minus Approach focuses on bank filtration, biofiltration, adsorption, and membranes to biologically and physically remove DBP precursors, KUECs, and pathogens; consequently, water purveyors can use ultraviolet light at key locations in conjunction with smaller dosages of secondary chemical disinfectants to minimize microbial regrowth in distribution systems. We describe how the Minus Approach contrasts with the conventional Plus Approach, integrates with artificial intelligence, and can ultimately improve the sustainability performance of water treatment. Finally, we consider barriers to adoption of the Minus Approach.

}, keywords = {Artificial Intelligence, Disinfectants, Disinfection, Drinking Water, Halogenation, Humans, Water Pollutants, Chemical, Water Purification}, issn = {1520-5851}, doi = {10.1021/acs.est.2c09389}, author = {Reid, Elliot and Igou, Thomas and Zhao, Yangying and Crittenden, John and Huang, Ching-Hua and Westerhoff, Paul and Rittmann, Bruce and Drewes, J{\"o}rg E and Chen, Yongsheng} } @article {1568336, title = {Multiple exposure distributed lag models with variable selection}, journal = {Biostatistics}, volume = {25}, year = {2023}, pages = {1}, author = {Joseph Antonelli and Ander Wilson and Brent A Coull} } @article {1525936, title = {Sociodemographic Disparities in Mercury Exposure from United States Coal-Fired Power Plants}, journal = {Environ Sci Technol Lett}, volume = {10}, year = {2023}, month = {2023 Jul 11}, pages = {589-595}, abstract = {

Hazardous air pollutants emitted by United States (U.S) coal-fired power plants have been controlled by the Mercury and Air Toxics Standards (MATS) since 2012. Sociodemographic disparities in traditional air pollutant exposures from U.S. power plants are known to occur but have not been evaluated for mercury (Hg), a neurotoxicant that bioaccumulates in food webs. Atmospheric Hg deposition from domestic power plants decreased by 91\% across the contiguous U.S. from 6.4 Mg in 2010 to 0.55 Mg in 2020. Prior to MATS, populations living within 5 km of power plants ( = 507) included greater proportions of frequent fish consumers, individuals with low annual income and less than a high school education, and limited English-proficiency households compared to the US general population. These results reinforce a lack of distributional justice in plant siting found in prior work. Significantly greater proportions of low-income individuals lived within 5 km of active facilities in 2020 ( = 277) compared to plants that retired after 2010, suggesting that socioeconomic status may have played a role in retirement. Despite large deposition declines, an end-member scenario for remaining exposures from the largest active power plants for individuals consuming self-caught fish suggests they could still exceed the U.S. Environmental Protection Agency reference dose for methylmercury.

}, issn = {2328-8930}, doi = {10.1021/acs.estlett.3c00216}, url = {https://pubmed.ncbi.nlm.nih.gov/37455865/}, author = {Dai, Mona Q and Geyman, Benjamin M and Hu, Xindi C and Thackray, Colin P and Sunderland, Elsie M} } @article {1545051, title = {Sous Vide-Inspired Impregnation of Amorphous Titanium (Hydr)Oxide into Carbon Block Point-of-Use Filters for Arsenic Removal from Water}, journal = {Environmental Science \& TechnologyEnvironmental Science \& Technology}, volume = {57}, year = {2023}, note = {doi: 10.1021/acs.est.3c06586}, month = {2023/11/10}, pages = {20410-20420}, publisher = {American Chemical Society}, isbn = {0013-936X}, url = {https://doi.org/10.1021/acs.est.3c06586}, author = {Farsad, Alireza and Marcos-Hernandez, Mariana and Sinha, Shahnawaz and Westerhoff, Paul} } @article {1544361, title = {On Support Recovery with Sparse CCA: Information Theoretic and Computational Limits}, journal = {IEEE Trans Inf Theory}, volume = {69}, year = {2023}, note = {PMC10569110; PMID\ 37842015; DOI:\ 10.1109/tit.2022.3214201}, month = {2023 Mar}, pages = {1695-1738}, abstract = {

In this paper, we consider asymptotically exact support recovery in the context of high dimensional and sparse Canonical Correlation Analysis (CCA). Our main results describe four regimes of interest based on information theoretic and computational considerations. In regimes of "low" sparsity we describe a simple, general, and computationally easy method for support recovery, whereas in a regime of "high" sparsity, it turns out that support recovery is information theoretically impossible. For the sake of information theoretic lower bounds, our results also demonstrate a non-trivial requirement on the "minimal" size of the nonzero elements of the canonical vectors that is required for asymptotically consistent support recovery. Subsequently, the regime of "moderate" sparsity is further divided into two subregimes. In the lower of the two sparsity regimes, we show that polynomial time support recovery is possible by using a sharp analysis of a co-ordinate thresholding [1] type method. In contrast, in the higher end of the moderate sparsity regime, appealing to the "Low Degree Polynomial" Conjecture [2], we provide evidence that polynomial time support recovery methods are inconsistent. Finally, we carry out numerical experiments to compare the efficacy of various methods discussed.

}, issn = {0018-9448}, doi = {10.1109/tit.2022.3214201}, url = {https://ieeexplore.ieee.org/document/9920972}, author = {Laha, Nilanjana and Mukherjee, Rajarshi} } @article {1535911, title = {Surface water H-bonding network is key controller of selenate adsorption on [012] α-alumina: An Ab-initio study}, journal = {J Colloid Interface Sci}, volume = {617}, year = {2022}, month = {2022 Jul}, pages = {136-146}, abstract = {

Selenate adsorption onto metal oxide surfaces is a cost-effective method to remove the toxin from drinking water systems. However, the low selectivity of metal oxides requires frequent sorbent replacement. The design of selective adsorbents is stymied because the surface factors controlling selenate adsorption remain unknown. We calculate adsorption energies of selenate on the (012) α-AlO surface using density functional theory to unravel the physics that controls adsorption. Our model is validated against experiment by correctly predicting selenate removal efficiency as a function pH. We find that the selenate adsorption energy on the anhydrous α-AlO surface is surprisingly anti-correlated with the fully solvated adsorption energy; therefore, the direct interaction between adsorbate and sorbent is eliminated as the controlling mechanism. Rather, the change in number of surface hydrogen bonds after adsorption is the factor most correlated with the adsorption energy (R~>~0.8); and is thus determined to be the factor controlling selenate adsorption. We find that pH affects adsorption by controlling the number of surface protons available for H-bonding to selenate. This work demonstrates that adsorption prediction should not be made based on gas phase sorption energies and suggests that surface engineering which increases surface protonation may be an effective strategy for increasing selenate sorption.

}, keywords = {Adsorption, Aluminum Oxide, Hydrogen-Ion Concentration, Oxides, Protons, Selenic Acid, Water}, issn = {1095-7103}, doi = {10.1016/j.jcis.2022.02.128}, author = {Gupta, Srishti and Anh Nguyen, Ngan and Muhich, Christopher L} } @article {1528996, title = {Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study}, journal = {Aging (Albany NY)}, volume = {14}, year = {2022}, month = {2022 Sep 06}, pages = {6859-6886}, abstract = {

BACKGROUND: Aging-related cognitive decline is an early symptom of Alzheimer{\textquoteright}s disease and other dementias, and on its own can have substantial consequences on an individual{\textquoteright}s ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.

METHODS: This study includes data from up to 530 NAS participants (median age: 71.0 years) collected from 1996 to 2013, with a total of 1,331 person-visits (equal to 2,471 years of follow up). Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Plasma miRNAs were profiled using small RNA sequencing. Associations of expression of 381 miRNAs with current cognitive function and rate of change in cognitive function were assessed using linear regression ( = 457) and linear mixed models ( = 530), respectively.

RESULTS: In adjusted models, levels of 2 plasma miRNAs were associated with higher MMSE scores ( \< 0.05). Expression of 33 plasma miRNAs was associated with rate of change in MMSE scores over time ( \< 0.05). Enriched KEGG pathways for miRNAs associated with concurrent MMSE and MMSE trajectory included Hippo signaling and extracellular matrix-receptor interactions. Gene targets of miRNAs associated with MMSE trajectory were additionally associated with prion diseases and fatty acid biosynthesis.

CONCLUSIONS: Circulating miRNAs were associated with both cross-sectional cognitive function and rate of change in cognitive function among cognitively normal men. Further research is needed to elucidate the potential functions of these miRNAs in the CNS and investigate relationships with other neurological outcomes.

}, keywords = {Aged, Aging, Cognition, Cognitive Dysfunction, Cross-Sectional Studies, Fatty Acids, Humans, Male, MicroRNAs, Prospective Studies, Veterans}, issn = {1945-4589}, doi = {10.18632/aging.204268}, author = {Comfort, Nicole and Wu, Haotian and De Hoff, Peter and Vuppala, Aishwarya and Vokonas, Pantel S and Spiro, Avron and Weisskopf, Marc and Coull, Brent A and Laurent, Louise C and Baccarelli, Andrea A and Schwartz, Joel} } @article {1535916, title = {Large-Scale Hypothesis Testing for Causal Mediation Effects with Applications in Genome-wide Epigenetic Studies}, journal = {J Am Stat Assoc}, volume = {117}, year = {2022}, note = {doi: 10.1080/01621459.2021.1914634. PMID: 35989709; PMCID: PMC9385159.}, month = {2022}, pages = {67-81}, abstract = {

In genome-wide epigenetic studies, it is of great scientific interest to assess whether the effect of an exposure on a clinical outcome is mediated through DNA methylations. However, statistical inference for causal mediation effects is challenged by the fact that one needs to test a large number of composite null hypotheses across the whole epigenome. Two popular tests, the Wald-type Sobel{\textquoteright}s test and the joint significant test using the traditional null distribution are underpowered and thus can miss important scientific discoveries. In this paper, we show that the null distribution of Sobel{\textquoteright}s test is not the standard normal distribution and the null distribution of the joint significant test is not uniform under the composite null of no mediation effect, especially in finite samples and under the singular point null case that the exposure has no effect on the mediator and the mediator has no effect on the outcome. Our results explain why these two tests are underpowered, and more importantly motivate us to develop a more powerful Divide-Aggregate Composite-null Test (DACT) for the composite null hypothesis of no mediation effect by leveraging epigenome-wide data. We adopted Efron{\textquoteright}s empirical null framework for assessing statistical significance of the DACT test. We showed analytically that the proposed DACT method had improved power, and could well control type I error rate. Our extensive simulation studies showed that, in finite samples, the DACT method properly controlled the type I error rate and outperformed Sobel{\textquoteright}s test and the joint significance test for detecting mediation effects. We applied the DACT method to the US Department of Veterans Affairs Normative Aging Study, an ongoing prospective cohort study which included men who were aged 21 to 80 years at entry. We identified multiple DNA methylation CpG sites that might mediate the effect of smoking on lung function with effect sizes ranging from -0.18 to -0.79 and false discovery rate controlled at level 0.05, including the CpG sites in the genes AHRR and F2RL3. Our sensitivity analysis found small residual correlations (less than 0.01) of the error terms between the outcome and mediator regressions, suggesting that our results are robust to unmeasured confounding factors.

}, issn = {0162-1459}, doi = {10.1080/01621459.2021.1914634}, author = {Liu, Zhonghua and Shen, Jincheng and Barfield, Richard and Schwartz, Joel and Baccarelli, Andrea A and Lin, Xihong} } @article {1471101, title = {Lithium occurrence in drinking water sources of the United States}, journal = {Chemosphere}, volume = {305}, year = {2022}, month = {2022 Oct}, pages = {135458}, abstract = {

Lithium (Li) is listed in the fifth Unregulated Contaminant Monitoring Rule (UCMR 5) because insufficient exposure data exists for lithium in drinking water. To help fill this data gap, lithium occurrence in source waters across the United States was assessed in 21 drinking water utilities. From the 369 samples collected from drinking water treatment plants (DWTPs), lithium ranged from 0.9 to 161\ μg/L (median\ =\ 13.9\ μg/L) in groundwater, and from \<0.5 to 130\ μg/L (median\ =\ 3.9\ μg/L) in surface water. Lithium in 56\% of the groundwater and 13\% of the surface water samples were above non-regulatory Health-Based Screening Level (HBSL) of 10\ μg/L. Sodium and lithium concentrations were strongly correlated: Kendall{\textquoteright}s τ\ \>\ 0.6 (p\ \<\ 0.001). As sodium is regularly monitored, this result shows that sodium can serve as an indicator to identify water sources at higher risk for elevated lithium. Lithium concentrations in the paired samples collected in source water and treated drinking water were almost identical showing lithium was not removed by conventional drinking water treatment processes. Additional sampling in wastewater effluents detected lithium at 0.8-98.2\ μg/L (median\ =\ 9.9\ μg/L), which suggests more research on impacts of lithium in direct and indirect potable reuse may be warranted, as the median was close to the HBSL. For comparison with the study samples collected from DWTPs, lithium concentrations from the national water quality portal (WQP) database were also investigated. Over 35,000 measurements were collected from waters that could potentially be used as drinking water sources (Cl\ \<\ 250\ mg/L). Data from WQP had comparable median lithium concentrations: 18 and 20\ μg/L for surface water and groundwater, respectively. Overall, this study provides a comprehensive occurrence potential for lithium in US drinking water sources and can inform the data collection effort in UCMR 5.

}, keywords = {Drinking Water, Environmental Monitoring, Groundwater, Lithium, Sodium, United States, Water Pollutants, Chemical}, issn = {1879-1298}, doi = {10.1016/j.chemosphere.2022.135458}, author = {Sharma, Naushita and Westerhoff, Paul and Zeng, Chao} } @article {1535906, title = {A multi-dimensional integrative scoring framework for predicting functional variants in the human genome}, journal = {Am J Hum Genet}, volume = {109}, year = {2022}, month = {2022 Mar 03}, pages = {446-456}, abstract = {

Attempts to identify and prioritize functional DNA elements in coding and non-coding regions, particularly through use of in silico functional annotation data, continue to increase in popularity. However, specific functional roles can vary widely from one variant to another, making it challenging to summarize different aspects of variant function with a one-dimensional rating. Here we propose multi-dimensional annotation-class integrative estimation (MACIE), an unsupervised multivariate mixed-model framework capable of integrating annotations of diverse origin to assess multi-dimensional functional roles for both coding and non-coding variants. Unlike existing one-dimensional scoring methods, MACIE views variant functionality as a composite attribute encompassing multiple characteristics and estimates the joint posterior functional probabilities of each genomic position. This estimate offers more comprehensive and interpretable information in the presence of multiple aspects of functionality. Applied to a variety of independent coding and non-coding datasets, MACIE demonstrates powerful and robust performance in discriminating between functional and non-functional variants. We also show an application of MACIE to fine-mapping and heritability enrichment analysis by using the lipids GWAS summary statistics data from the European Network for Genetic and Genomic Epidemiology Consortium.

}, keywords = {Genome, Human, Genome-Wide Association Study, Genomics, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Probability}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2022.01.017}, author = {Li, Xihao and Yung, Godwin and Zhou, Hufeng and Sun, Ryan and Li, Zilin and Hou, Kangcheng and Zhang, Martin Jinye and Liu, Yaowu and Arapoglou, Theodore and Wang, Chen and Ionita-Laza, Iuliana and Lin, Xihong} } @article {1420027, title = {Portable X-ray Fluorescence as a Rapid Determination Tool to Detect Parts per Million Levels of Ni, Zn, As, Se, and Pb in Human Toenails: A South India Case Study}, journal = {Environ Sci Technol}, volume = {55}, year = {2021}, note = {

PMID:\ 34529917; PMCID: PMC8582015,\ doi:\ 10.1021/acs.est.1c00937

}, month = {2021 10 05}, pages = {13113-13121}, abstract = {Chronic exposure to inorganic pollutants adversely affects human health. Inductively coupled plasma mass spectrometry (ICP-MS) is the most common method used for trace metal(loid) analysis of human biomarkers. However, it leads to sample destruction, generation of secondary waste, and significant recurring costs. Portable X-ray fluorescence (XRF) instruments can rapidly and nondestructively determine low concentrations of metal(loid)s. In this work, we evaluated the applicability of portable XRF as a rapid method for analyzing trace metal(loid)s in toenail samples from three populations (n = 97) near the city of Chennai, India. A Passing-Bablok regression analysis of results from both methods revealed that there was no proportional bias among the two methods for nickel (measurement range \~{}25 to 420 mg/kg), zinc (10 to 890 mg/kg), and lead (0.29 to 4.47 mg/kg). There was a small absolute bias between the two methods. There was a strong proportional bias (slope = 0.253, 95\% CI: 0.027, 0.614) between the two methods for arsenic (below detection to 3.8 mg/kg) and for selenium when the concentrations were lower than 2 mg/kg. Limits of agreement between the two methods using Bland-Altman analysis were derived for nickel, zinc, and lead. Overall, a suitably calibrated and evaluated portable XRF shows promise in making high-throughput assessments at population scales.}, keywords = {Humans, India, Lead, Nails, Spectrometry, X-Ray Emission, X-Rays, Zinc}, issn = {1520-5851}, doi = {10.1021/acs.est.1c00937}, url = {https://pubs.acs.org/doi/10.1021/acs.est.1c00937}, author = {Bhatia, Mayuri and Specht, Aaron J and Ramya, Vallabhuni and Sulaiman, Dahy and Konda, Manasa and Balcom, Prentiss and Sunderland, Elsie M and Qureshi, Asif} } @article {1428014, title = {Neighboring Pd single atoms surpass isolated single atoms for selective hydrodehalogenation catalysis.}, journal = {Nat Commun}, volume = {30}, year = {2021}, note = {doi: 10.1038/s41467-021-25526-2. PMID: 34462434; PMCID: PMC8405729.}, pages = {5179}, abstract = {

Single atom catalysts have been found to exhibit superior selectivity over nanoparticulate catalysts for catalytic reactions such as hydrogenation due to their single-site nature. However, improved selectively is often accompanied by loss of activity and slow kinetics. Here we demonstrate that neighboring Pd single atom catalysts retain the high selectivity merit of sparsely isolated single atom catalysts, while the cooperative interactions between neighboring atoms greatly enhance the activity for hydrogenation of carbon-halogen bonds. Experimental results and computational calculations suggest that neighboring Pd atoms work in synergy to lower the energy of key meta-stable reactions steps, i.e., initial water desorption and final hydrogenated product desorption. The placement of neighboring Pd atoms also contribute to nearly exclusive hydrogenation of carbon-chlorine bond without altering any other bonds in organohalogens. The promising hydrogenation performance achieved by neighboring single atoms sheds light on a new approach for manipulating the activity and selectivity of single atom catalysts that are increasingly studied in multiple applications.

}, author = {Chu C and Huang D and Gupta S and Weon S and Niu J and Stavitski E and Muhich C and Kim JH} } @article {1402082, title = {Survey of Industrial Perceptions for the Use of Nanomaterials for In-Home Drinking Water Purification Devices}, journal = {NanoImpact}, volume = {22}, year = {2021}, note = {

PMID:\ \ 35559977;\ PMCID: PMC9106971;\  doi: 10.1016/j.impact.2021.100320

}, pages = {1-6}, abstract = {

As businesses, specifically technology developers and industrial suppliers, strive to meet growing demand for higher\ quality drinking water, the use of engineered nanomaterials in commercial point-of-use (POU) in-home water purification devices are becoming an increasingly important option. Anecdotally, some businesses appear wary of developing and marketing nanomaterial-enabled devices because of concerns that they will face onerous regulation and consumer pushback. However, little of substance is known about business perceptions of and attitudes toward the use of engineered nanomaterials in POU water purification devices, or how these compare with consumer perceptions. To address this knowledge-gap, we administered a 14-question survey among 65 participants from US-based industrial companies focused on drinking water purification. Our results indicate that the dominant concerns for businesses are costs and public perceptions associated with nanomaterial-enabled POU devices for drinking water purification. Cost-specific barriers include competition from more conventional technologies, and tensions between operational versus capital costs. 57\% of respondents were concerned or very concerned that public perceptions will influence the long-term viability of nanomaterial-enabled POU devices for drinking water purification. 49\% of respondents stated that government regulation of nanomaterials would be the preferred approach to ensure public safety, followed by the certification of POU devices (28\%). When asked about specific nanomaterials and their potential use in POU devices for drinking water purification, respondents ranked carbon nanotubes as the nanomaterial with highest concern for environmental health and safety, followed by silver, titanium dioxide, zinc oxide, and copper. Respondents ranked nanoclays as the nanomaterial with highest likelihood for public acceptance, followed by silica,\ cerium\ oxide, titanium dioxide, and aluminum oxide

}, url = {https://doi.org/10.1016/j.impact.2021.100320}, author = {Kidd, J and Westerhoff, P and Maynard, A} } @article {1390706, title = {Evolving Science and Practice of Risk Assessment}, journal = {Risk Anal}, volume = {41}, year = {2021}, note = {

PMID:\ 33295028;\ PMCID:\ PMC8257268\ (available on\ ); DOI:\ 10.1111/risa.13647

}, month = {2020 Dec 08}, pages = {571-583}, abstract = {Managing public health risks from environmental contaminants has historically relied on a risk assessment process defined by the regulatory context in which these risks are assessed. Risk assessment guidance follows a straightforward, chemical-by-chemical approach to inform regulatory decisions around the question "what is the risk-based concentration protective of human and ecological health outcomes?" Here we briefly summarize regulatory risk assessment in the context of innovative risk assessment approaches based on an evolving understanding of the underlying scientific disciplines that support risk analysis more broadly. We discuss scientific versus regulatory tensions in the application of these approaches for future risk assessments, and challenges in translating our improved understanding of the underlying scientific complexity to the regulatory landscape to better inform decision making that extends beyond conventional regulatory mandates.
PMID:\ 33295028;\ PMCID:\ PMC8257268\ (available on\ ); DOI:\ 10.1111/risa.13647}, issn = {1539-6924}, doi = {10.1111/risa.13647}, url = {https://pubmed.ncbi.nlm.nih.gov/33295028/}, author = {von Stackelberg, Katherine and Williams, Pamela R D} } @article {1535946, title = {Selective adsorption of arsenic over phosphate by transition metal cross-linked chitosan}, journal = {Chem Eng J}, volume = {412}, year = {2021}, month = {2021 May 15}, abstract = {

The ability of transition metal chitosan complexes (TMCs) of varying valence and charge to selectively adsorb As(III) and As(V) over their strongest adsorptive competitor, phosphate is examined. Fe(III)-chitosan, Al(III)-chitosan, Ni(II)-chitosan, Cu(II)-chitosan, and Zn(II)-chitosan are synthesized, characterized via Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy (ATR-FTIR) and X-ray Diffractometry (XRD), and their selective sorption capabilities towards As(III) and As(V) in the presence of phosphate are evaluated. It was found that the stability of the metal-chitosan complexes varied, with Al(III)- and Zn(II)-chitosan forming very unstable complexes resulting in precipitation of gibbsite, and Wulfingite and Zincite, respectively. Cu(II)-, Ni(II)-, and Fe(III)-chitosan formed a mixture of monodentate and bidentate complexes. The TMCs which formed the bidentate complex (Cu(II)-, Ni(II)-, and Fe(III)-) showed greater adsorption capability for As(V) in the presence of phosphate. Using the binary separation factor , it can be shown that only Fe(III)-chitosan is selective for As(V) and As(III) over phosphate. Density Functional Theory (DFT) modeling and extended X-ray adsorption fine structure (EXAFS) determined that Fe(III)-chitosan and Ni(II)-chitosan adsorbed As(V) and As(III) via inner-sphere complexation, while Cu(II)-chitosan formed mainly outer-sphere complexes with As(V) and As(III). These differences in complexation likely result in the observed differences in selective adsorption capability towards As(V) and As(III) over phosphate. It is hypothesized that the greater affinity of Fe(III)- and Ni(II)-chitosan towards As(V) and As(III) compared to Cu(II)-chitosan is due to their forming less-stable, more reactive chitosan complexes as predicted by the Irving Williams Series.

}, issn = {1385-8947}, doi = {10.1016/j.cej.2021.128582}, author = {Pincus, Lauren N and Petrovi{\'c}, Predrag V and Gonzalez, Isabel S and Stavitski, Eli and Fishman, Zachary S and Anastas, Paul T and Zimmerman, Julie B} } @article {1529001, title = {Early pregnancy essential and non-essential metal mixtures and gestational glucose concentrations in the 2nd trimester: Results from project viva}, journal = {Environ Int}, volume = {155}, year = {2021}, month = {2021 Oct}, pages = {106690}, abstract = {

Metals are involved in glucose metabolism, and some may alter glycemic regulation. However, joint effects of essential and non-essential metals on glucose concentrations during pregnancy are unclear. This study explored the joint associations of pregnancy exposures to essential (copper, magnesium, manganese, selenium, zinc) and non-essential (arsenic, barium, cadmium, cesium, lead, mercury) metals with gestational glucose concentrations using 1,311 women enrolled 1999-2002 in Project Viva, a Boston, MA-area pregnancy cohort. The study measured erythrocyte metal concentrations from 1 trimester blood samples and used glucose concentrations measured 1\ h after non-fasting 50-gram glucose challenge tests (GCT) from clinical gestational diabetes screening at 26-28\ weeks gestation. Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation were applied to model the associations of metal mixtures-including their interactions-with glucose concentrations post-GCT. We tested for reproducibility of BKMR results using generalized additive models. The BKMR model showed an inverse U-shaped association for barium and a linear inverse association for mercury. Specifically, estimated mean glucose concentrations were highest around 75th percentile of barium concentrations [2.1 (95\% confidence interval: -0.2, 4.4) mg/dL higher comparing to the 25th percentile], and each interquartile range increase of erythrocyte mercury was associated with 1.9\ mg/dL lower mean glucose concentrations (95\% credible interval: -4.2, 0.4). Quantile g-computation showed joint associations of all metals, essential-metals, and non-essential metals on gestational glucose concentrations were all null, however, we observed evidences of interaction for barium and lead. Overall, we found early pregnancy barium and mercury erythrocytic concentrations were associated with altered post-load glucose concentrations in later pregnancy, with potential interactions between barium and lead.

}, keywords = {Bayes Theorem, Diabetes, Gestational, Female, Glucose, Humans, Pregnancy, Pregnancy Trimester, Second, Reproducibility of Results}, issn = {1873-6750}, doi = {10.1016/j.envint.2021.106690}, author = {Zheng, Yinnan and Lin, Pi-I Debby and Williams, Paige L and Weisskopf, Marc G and Cardenas, Andres and Rifas-Shiman, Sheryl L and Wright, Robert O and Amarasiriwardena, Chitra and Claus Henn, Birgit and Hivert, Marie-France and Oken, Emily and James-Todd, Tamarra} } @article {1421728, title = {Roles and Knowledge Gaps of Point-of-Use Technologies for Mitigating Health Risks from Disinfection Byproducts in Tap Water: A Critical Review}, journal = {Water Res}, volume = {200}, year = {2021}, note = { }, month = {2021 Jul 15}, pages = {117-265}, abstract = {Due to rising concerns about water pollution and affordability, there is a rapidly-growing public acceptance and global market for a variety of point-of-use (POU) devices for domestic uses. However, the efficiencies and mechanisms of POU technologies for removing regulated and emerging disinfection byproducts (DBPs) are still not systematically known. To facilitate the development of this field, we summarized performance trends of four common technologies (i.e., boiling, adsorption, membrane filtration, and advanced oxidation) on mitigating preformed DBPs and identified knowledge gaps. The following highest priority knowledge gaps include: 1) data on DBP levels at the tap or cup in domestic applications; 2) certainty regarding the controls of DBPs by heating processes as DBPs may form and transform simultaneously; 3) standards to evaluate the performance of carbon-based materials on varying types of DBPs; 4) long-term information on the membrane performance in removing DBPs; 5) knowledge of DBPs{\textquoteright} susceptibility toward advanced redox processes; 6) tools to monitor/predict the toxicity and diversity of DBPs formed in waters with varying precursors and when implementing different treatment technologies; and 7) social acceptance and regulatory frameworks of incorporating POU as a potential supplement to current centralized-treatment focused DBP control strategies. We conclude by identifying research needs necessary to assure POU systems protect the public against regulated and emerging DBPs.}, keywords = {Adsorption, Disinfectants, Disinfection, Halogenation, Water, Water Pollutants, Chemical, Water Purification}, issn = {1879-2448}, doi = {10.1016/j.watres.2021.117265}, url = {https://www.sciencedirect.com/science/article/abs/pii/S0043135421004632?via\%3Dihub}, author = {Chen, Baiyang and Jiang, Jingyi and Yang, Xin and Zhang, Xiangru and Paul Westerhoff} } @article {1471106, title = {Unified Metallic Catalyst Aging Strategy and Implications for Water Treatment}, journal = {Environ Sci Technol}, year = {2021}, month = {2021 Jul 26}, abstract = {

Heterogeneous catalysis holds great promise for oxidizing or reducing a range of pollutants in water. A well-recognized, but understudied, barrier to implement catalytic treatment centers around fouling or aging over time of the catalyst surfaces. To better understand how to study catalyst fouling or aging, we selected a representative bimetallic catalyst (Pd-In supported on AlO), which holds promise to reduce nitrate to innocuous nitrogen gas byproducts upon hydrogen addition, and six model solutions (deionized water, sodium hypochlorite, sodium borohydride, acetic acid, sodium sulfide, and tap water). Our novel aging experimental apparatus permitted single passage of each model solution, separately, through a small packed-bed reactor containing replicate bimetallic catalyst "beds" that could be sacrificed weekly for off-line characterization to quantify impacts of fouling or aging. The composition of the model solutions led to the following gradual changes in surface composition, morphology, or catalytic reactivity: (i) formation of passivating species, (ii) decreased catalytic sites due to metal leaching under acid conditions or sulfide poisoning, (iii) dissolution and/or transformation of indium, (iv) formation of new catalytic sites by the introduction of an additional metallic element, and (v) oxidative etching. The model solution water chemistry captured a wide range of conditions likely to be encountered in potable or industrial water treatment. Aging-induced changes altered catalytic activity and provided insights into potential strategies to improve long-term catalyst operations for water treatment.

}, issn = {1520-5851}, doi = {10.1021/acs.est.1c02364}, author = {Lee, Chung-Seop and Guo, Sujin and Rho, Hojung and Levi, Juliana and Garcia-Segura, Sergi and Wong, Michael S and Gardea-Torresdey, Jorge and Westerhoff, Paul} } @article {1411648, title = {Utilizing the broad electromagnetic spectrum and unique nanoscale properties for chemical-free water treatment}, journal = {Current Opinion in Chemical Engineering}, volume = {33}, year = {2021}, note = {PMID:\ 34804780; PMCID: PMC8597955}, abstract = {Clean water is critical for drinking, industrial processes, and aquatic organisms. Existing water treatment and infrastructure are chemically intensive and based on nearly century-old technologies that fail to meet modern large and decentralized communities. The next-generation of water processes can transition from outdated technologies by utilizing nanomaterials to harness energy from across the electromagnetic spectrum, enabling electrified and solar-based technologies. The last decade was marked by tremendous improvements in nanomaterial design, synthesis, characterization, and assessment of material properties. Realizing the benefits of these advances requires placing greater attention on embedding nanomaterials onto and into surfaces within reactors and applying external energy sources. This will allow nanomaterial-based processes to replace Victorian-aged, chemical intensive water treatment technologies.}, url = {https://www.sciencedirect.com/science/article/pii/S2211339821000411}, author = {Paul Westerhoff and Pedro JJ Alvarez and Jaehong Kim and Qilin Li and Alessandro Alabastri and Naomi J Halas and Dino Villagran and Julie Zimmerman and Michael S Wong} } @article {1525991, title = {Exploring the Mechanisms of Selectivity for Environmentally Significant Oxo-Anion Removal during Water Treatment: A Review of Common Competing Oxo-Anions and Tools for Quantifying Selective Adsorption}, journal = {Environ Sci Technol}, volume = {54}, year = {2020}, month = {2020 Aug 18}, pages = {9769-9790}, abstract = {

Development of novel adsorbents often neglects the competitive adsorption between co-occurring oxo-anions, overestimating realistic pollutant removal potentials, and overlooking the need to improve selectivity of materials. This critical review focuses on adsorptive competition between commonly co-occurring oxo-anions in water and mechanistic approaches for the design and development of selective adsorbents. Six "target" oxo-anion pollutants (arsenate, arsenite, selenate, selenite, chromate, and perchlorate) were selected for study. Five "competing" co-occurring oxo-anions (phosphate, sulfate, bicarbonate, silicate, and nitrate) were selected due to their potential to compete with target oxo-anions for sorption sites resulting in decreased removal of the target oxo-anions. First, a comprehensive review of competition between target and competitor oxo-anions to sorb on commonly used, nonselective, metal (hydr)oxide materials is presented, and the strength of competition between each target and competitive oxo-anion pair is classified. This is followed by a critical discussion of the different equations and models used to quantify selectivity. Next, four mechanisms that have been successfully utilized in the development of selective adsorbents are reviewed: variation in surface complexation, Lewis acid/base hardness, steric hindrance, and electrostatic interactions. For each mechanism, the oxo-anions, both target and competitors, are ranked in terms of adsorptive attraction and technologies that exploit this mechanism are reviewed. Third, given the significant effort to evaluate these systems empirically, the potential to use computational quantum techniques, such as density functional theory (DFT), for modeling and prediction is explored. Finally, areas within the field of selective adsorption requiring further research are detailed with guidance on priorities for screening and defining selective adsorbents.

}, keywords = {Adsorption, Anions, Kinetics, Phosphates, Water, Water Pollutants, Chemical, Water Purification}, issn = {1520-5851}, doi = {10.1021/acs.est.0c01666}, author = {Pincus, Lauren N and Rudel, Holly E and Petrovi{\'c}, Predrag V and Gupta, Srishti and Westerhoff, Paul and Muhich, Christopher L and Zimmerman, Julie B} } @article {1535901, title = {Identification of novel loci associated with infant cognitive ability}, journal = {Mol Psychiatry}, volume = {25}, year = {2020}, month = {2020 Nov}, pages = {3010-3019}, abstract = {

It is believed that genetic factors play a large role in the development of many cognitive and neurological processes; however, epidemiological evidence for the genetic basis of childhood neurodevelopment is very limited. Identification of the genetic polymorphisms associated with early-stage neurodevelopment will help elucidate biological mechanisms involved in neuro-behavior and provide a better understanding of the developing brain. To search for such variants, we performed a genome-wide association study (GWAS) for infant mental and motor ability at two years of age with mothers and children recruited from cohorts in Bangladesh and Mexico. Infant ability was assessed using mental and motor composite scores calculated with country-specific versions of the Bayley Scales of Infant Development. A missense variant (rs1055153) located in the gene WWTR1 reached genome-wide significance in association with mental composite score (meta-analysis effect size of minor allele β = -6.04; 95\% CI: -8.13 to -3.94; P = 1.56{\texttimes}10). Infants carrying the minor allele reported substantially lower cognitive scores in both cohorts, and this variant is predicted to be in the top 0.3\% of most deleterious substitutions in the human genome. Fine mapping and region-based association testing provided additional suggestive evidence that both WWTR1 and a second gene, LRP1B, were associated with infant cognitive ability. Comparisons with recently conducted GWAS in intelligence and educational attainment indicate that our phenotypes do not possess a high genetic correlation with either adolescent or adult cognitive traits, suggesting that infant neurological assessments should be treated as an independent outcome of interest. Additional functional studies and replication efforts in other cohorts may help uncover new biological pathways and genetic architectures that are crucial to the developing brain.

}, keywords = {Adult, Alleles, Bangladesh, Child, Preschool, Cognition, Cohort Studies, Female, Genetic Loci, Genome, Human, Genome-Wide Association Study, Humans, Male, mexico, Mothers, Motor Skills, Phenotype}, issn = {1476-5578}, doi = {10.1038/s41380-018-0205-3}, author = {Sun, Ryan and Wang, Zhaoxi and Claus Henn, Birgit and Su, Li and Lu, Quan and Lin, Xihong and Wright, Robert O and Bellinger, David C and Kile, Molly and Mazumdar, Maitreyi and Tellez-Rojo, Martha Maria and Schnaas, Lourdes and Christiani, David C} } @article {1390705, title = {Toward Informed Design of Nanomaterials: A Mechanistic Analysis of Structure-Property-Function Relationships for Faceted Nanoscale Metal Oxides}, journal = {ACS Nano}, year = {2020}, note = {

PMID: 33237735; PMCID: PMC8144246

}, month = {2020 Nov 25}, abstract = {Nanoscale metal oxides (NMOs) have found wide-scale applicability in a variety of environmental fields, particularly catalysis, gas sensing, and sorption. Facet engineering, or controlled exposure of a particular crystal plane, has been established as an advantageous approach to enabling enhanced functionality of NMOs. However, the underlying mechanisms that give rise to this improved performance are often not systematically examined, leading to an insufficient understanding of NMO facet reactivity. This critical review details the unique electronic and structural characteristics of commonly studied NMO facets and further correlates these characteristics to the principal mechanisms that govern performance in various catalytic, gas sensing, and contaminant removal applications. General trends of facet-dependent behavior are established for each of the NMO compositions, and selected case studies for extensions of facet-dependent behavior, such as mixed metals, mixed-metal oxides, and mixed facets, are discussed. Key conclusions about facet reactivity, confounding variables that tend to obfuscate them, and opportunities to deepen structure-property-function understanding are detailed to encourage rational, informed design of NMOs for the intended application.}, issn = {1936-086X}, doi = {10.1021/acsnano.0c08356}, author = {Rudel, Holly E and Lane, Mary Kate M and Muhich, Christopher L and Zimmerman, Julie B} }