<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Morshead, Mackenzie L</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Carrell, Steven J</style></author><author><style face="normal" font="default" size="100%">Scott, Richard</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Tanguay, Robyn L</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Chemical structure drives developmental toxicity of alkyl-substituted naphthalenes in zebrafish.</style></title><secondary-title><style face="normal" font="default" size="100%">Environ Int</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Environ Int</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Docking Simulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Naphthalenes</style></keyword><keyword><style  face="normal" font="default" size="100%">Polycyclic Aromatic Hydrocarbons</style></keyword><keyword><style  face="normal" font="default" size="100%">Toxicity Tests</style></keyword><keyword><style  face="normal" font="default" size="100%">Water Pollutants, Chemical</style></keyword><keyword><style  face="normal" font="default" size="100%">Zebrafish</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2025 Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">204</style></volume><pages><style face="normal" font="default" size="100%">109837</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Naphthalene and its alkyl-substituted derivatives are among the most abundant polycyclic aromatic hydrocarbons (PAHs) in environmental and human exposure studies, yet their developmental toxicity and mode of action remain poorly understood due to challenges in testing semi-volatile compounds. This study developed a vial based, high throughput method to effectively assess the activity of naphthalenes and a set of 24 alkyl-substituted naphthalenes. Early life stage zebrafish were exposed to a concentration series of each chemical (0-50&amp;nbsp;µM) in rotating sealed glass vials to minimize volatilization. Benchmark concentration (BMC) values were calculated for morphological endpoints and lowest effect levels were determined for behavioral effects. The data were assessed for evidence of a narcotic mode of action using body burden measurements for select chemicals and logK modeling. Targeted transcriptomics at a single concentration and timepoint as well as in silico molecular docking were conducted to generate mode of action hypotheses. The vial method enabled detection of highly variable developmental toxicity not previously observed using standard 96-well plate exposures. LogK and body burden were poor predictors of toxicity, suggesting a non-narcotic mode of action. Transcriptomic analysis revealed evidence for the disruption of glucocorticoid signaling pathways. Molecular docking identified potential protein targets (e.g., CYP1A2, NT5E, FOLR1) that may mediate observed effects. This study demonstrates the importance of appropriate exposure methods for semi-volatile compounds, reveals structure-dependent toxicity among alkyl-substituted naphthalenes, and provides a foundation for further mechanistic studies and improved risk assessment of alkyl-substituted PAHs.&lt;/p&gt;
</style></abstract></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Morshead, Mackenzie L</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Simonich, Michael T</style></author><author><style face="normal" font="default" size="100%">Moran, Jessica E</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Tanguay, Robyn L</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Developmental toxicity of alkylated PAHs and substituted phenanthrenes: Structural nuances drive diverse toxicity and AHR activation.</style></title><secondary-title><style face="normal" font="default" size="100%">Chemosphere</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Chemosphere</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 Dec 10</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">370</style></volume><pages><style face="normal" font="default" size="100%">143894</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Polycyclic aromatic hydrocarbons (PAHs) are a diverse class of chemicals that occur in complex mixtures including parent and substituted PAHs. To understand the hazard posed by complex environmental PAH mixtures, we must first understand the structural drivers of activity and mode of action of individual PAHs. Understanding the toxicity of alkylated PAHs is important as they often occur in higher abundance in environmental matrices and can be more biologically active than their parent compounds. 104 alkylated PAHs were screened from 11 different parent compounds with emphasis on substituted phenanthrenes and their structurally dependent toxicity differences. Using a high-throughput early life stage zebrafish assay, embryos were exposed to concentrations between 0.1 and 100&amp;nbsp;μM and assessed for morphological and behavioral outcomes. The aryl hydrocarbon receptor (AHR) is often implicated in the toxicity of PAHs and the induction of cytochrome P4501A (cyp1a) is an excellent biomarker of Ahr activation. Embryos were evaluated for cyp1a induction using a fluorescence reporter line. Alkyl and polar phenanthrene derivatives were further assessed for spatial cyp1a expression and Ahr dependence of morphological effects. In the alkyl PAH screen 35 (33.7%) elicited a morphological or behavioral response and of those 23 (65%) also induced cyp1a. 31 (29.8%) of the chemicals only induced cyp1a. Toxicity varied substantially in response to substitution location, the amount of ring substitutions and alkyl chain length. Cyp1a induction varied by parent compound group and was a poor indicator of morphological or behavioral outcomes. Polar phenanthrenes were more biologically active than alkylated phenanthrene derivatives and their toxicity was not dependent upon the Ahr2, Ahr1a or Ahr1b when tested individually, despite cyp1a induction by 50% of polar phenanthrenes. Our results demonstrated that induction of cyp1a did not always correlate with PAH toxicity or Ahr dependence and that the type and location of phenanthrene substitution determined potency.&lt;/p&gt;
</style></abstract></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Gosline, Sara J C</style></author><author><style face="normal" font="default" size="100%">Kim, Doo Nam</style></author><author><style face="normal" font="default" size="100%">Pande, Paritosh</style></author><author><style face="normal" font="default" size="100%">Thomas, Dennis G</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Peter D Hoffman</style></author><author><style face="normal" font="default" size="100%">Michael L Barton</style></author><author><style face="normal" font="default" size="100%">Loftus, Joseph</style></author><author><style face="normal" font="default" size="100%">Moran, Addy</style></author><author><style face="normal" font="default" size="100%">Hampton, Shawn</style></author><author><style face="normal" font="default" size="100%">Dowson, Scott</style></author><author><style face="normal" font="default" size="100%">Franklin, Lyndsey</style></author><author><style face="normal" font="default" size="100%">David J Degnan</style></author><author><style face="normal" font="default" size="100%">Anderson, Lindsey</style></author><author><style face="normal" font="default" size="100%">Thessen, Anne</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Katrina M Waters</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The Superfund Research Program Analytics Portal: linking environmental chemical exposure to biological phenotypes.</style></title><secondary-title><style face="normal" font="default" size="100%">Sci Data</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Sci Data</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Environmental Exposure</style></keyword><keyword><style  face="normal" font="default" size="100%">Hazardous Substances</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Northwestern United States</style></keyword><keyword><style  face="normal" font="default" size="100%">Polycyclic Aromatic Hydrocarbons</style></keyword><keyword><style  face="normal" font="default" size="100%">Zebrafish</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2023 Mar 21</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">10</style></volume><pages><style face="normal" font="default" size="100%">151</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The OSU/PNNL Superfund Research Program (SRP) represents a longstanding collaboration to quantify Polycyclic Aromatic Hydrocarbons (PAHs) at various superfund sites in the Pacific Northwest and assess their potential impact on human health. To link the chemical measurements to biological activity, we describe the use of the zebrafish as a high-throughput developmental toxicity model that provides quantitative measurements of the exposure to chemicals. Toward this end, we have linked over 150 PAHs found at Superfund sites to the effect of these same chemicals in zebrafish, creating a rich dataset that links environmental exposure to biological response. To quantify this response, we have implemented a dose-response modelling pipeline to calculate benchmark dose parameters which enable potency comparison across over 500 chemicals and 12 of the phenotypes measured in zebrafish. We provide a rich dataset for download and analysis as well as a web portal that provides public access to this dataset via an interactive web site designed to support exploration and re-use of these data by the scientific community at http://srp.pnnl.gov .&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rivera, Brianna N</style></author><author><style face="normal" font="default" size="100%">Christine C Ghetu</style></author><author><style face="normal" font="default" size="100%">Yvonne Chang</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxics</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxics</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2022</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2022 Oct 29</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">10</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;There is a growing need to establish alternative approaches for mixture safety assessment of polycyclic aromatic hydrocarbons (PAHs). Due to limitations with current component-based approaches, and the lack of established methods for using whole mixtures, a promising alternative is to use sufficiently similar mixtures; although, an established framework is lacking. In this study, several approaches are explored to form sufficiently similar mixtures. Multiple data streams including environmental concentrations and empirically and predicted toxicity data for cancer and non-cancer endpoints were used to prioritize chemical components for mixture formations. Air samplers were analyzed for unsubstituted and alkylated PAHs. A synthetic mixture of identified PAHs was created (Creosote-Fire Mix). Existing toxicity values and chemical concentrations were incorporated to identify hazardous components in the Creosote-Fire Mix. Sufficiently similar mixtures of the Creosote-Fire Mix were formed based on (1) relative abundance; (2) toxicity values; and (3) a combination approach incorporating toxicity and abundance. Hazard characterization of these mixtures was performed using high-throughput screening in primary normal human bronchial epithelium (NHBE) and zebrafish. Differences in chemical composition and potency were observed between mixture formation approaches. The toxicity-based approach (Tox Mix) was the most potent mixture in both models. The combination approach (Weighted-Tox Mix) was determined to be the ideal approach due its ability to prioritize chemicals with high exposure and hazard potential.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mitra Geier</style></author><author><style face="normal" font="default" size="100%">Chlebowski, Anna C</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Staci M Simonich</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons.</style></title><secondary-title><style face="normal" font="default" size="100%">Arch Toxicol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Arch. Toxicol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Cytochrome P-450 CYP1A1</style></keyword><keyword><style  face="normal" font="default" size="100%">Embryo, Nonmammalian</style></keyword><keyword><style  face="normal" font="default" size="100%">Larva</style></keyword><keyword><style  face="normal" font="default" size="100%">Polycyclic Aromatic Hydrocarbons</style></keyword><keyword><style  face="normal" font="default" size="100%">Toxicity Tests</style></keyword><keyword><style  face="normal" font="default" size="100%">Zebrafish</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">92</style></volume><pages><style face="normal" font="default" size="100%">571-586</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that occur in complex mixtures. Several PAHs are known or suspected mutagens and/or carcinogens, but developmental toxicity data is lacking for PAHs, particularly their oxygenated and nitrated derivatives. Such data are necessary to understand and predict the toxicity of environmental mixtures. 123 PAHs were assessed for morphological and neurobehavioral effects for a range of concentrations between 0.1 and 50&amp;nbsp;µM, using a high throughput early-life stage zebrafish assay, including 33 parent, 22 nitrated, 17 oxygenated, 19 hydroxylated, 14 methylated, 16 heterocyclic, and 2 aminated PAHs. Additionally, each PAH was evaluated for AHR activation, by assessing CYP1A protein expression using whole animal immunohistochemistry (IHC). Responses to PAHs varied in a structurally dependent manner. High-molecular weight PAHs were significantly more developmentally toxic than the low-molecular weight PAHs, and CYP1A expression was detected in five distinct tissues, including vasculature, liver, skin, neuromasts and yolk.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mitra Geier</style></author><author><style face="normal" font="default" size="100%">D James Minick</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Susan C Tilton</style></author><author><style face="normal" font="default" size="100%">Pande, Paritosh</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">JG Teeguarden</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Appl Pharmacol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol. Appl. Pharmacol.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Apr 06</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Superfund sites often consist of complex mixtures of polycyclic aromatic hydrocarbons (PAHs). It is widely recognized that PAHs pose risks to human and environmental health, but the risks posed by exposure to PAH mixtures are unclear. We constructed an environmentally relevant PAH mixture with the top 10 most prevalent PAHs (SM10) from a Superfund site derived from environmental passive sampling data. Using the zebrafish model, we measured body burden at 48 hours post fertilization (hpf) and evaluated the developmental and neurotoxicity of SM10 and the 10 individual constituents at 24 hours post fertilization (hpf) and 5 days post fertilization (dpf). Zebrafish embryos were exposed from 6 to 120 hpf to (1) the SM10 mixture, (2) a variety of individual PAHs: pyrene, fluoranthene, retene, benzo[a]anthracene, chrysene, naphthalene, acenaphthene, phenanthrene, fluorene, and 2-methylnaphthalene. We demonstrated that SM10 and only 3 of the individual PAHs were developmentally toxic. Subsequently, we constructed and exposed developing zebrafish to two sub-mixtures: SM3 (comprised of 3 of the developmentally toxicity PAHs) and SM7 (7 non-developmentally toxic PAHs). We found that the SM3 toxicity profile was similar to SM10, and SM7 unexpectedly elicited developmental toxicity unlike that seen with its individual components. The results demonstrated that the overall developmental toxicity in the mixtures could be explained using the general concentration addition model. To determine if exposures activated the AHR pathway, spatial expression of CYP1A was evaluated in the 10 individual PAHs and the 3 mixtures at 5 dpf. Results showed activation of AHR in the liver and vasculature for the mixtures and some individual PAHs. Embryos exposed to SM10 during development and raised in chemical-free water into adulthood exhibited decreased learning and responses to startle stimulus indicating that developmental SM10 exposures affect neurobehavior. Collectively, these results exemplify the utility of zebrafish to investigate the developmental and neurotoxicity of complex mixtures.&lt;/p&gt;
</style></abstract></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Knecht, Andrea L</style></author><author><style face="normal" font="default" size="100%">Goodale, Britton C</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Simonich, Michael T</style></author><author><style face="normal" font="default" size="100%">Swanson, Annika J</style></author><author><style face="normal" font="default" size="100%">Matzke, Melissa M</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Katrina M Waters</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Comparative developmental toxicity of environmentally relevant oxygenated PAHs.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Appl Pharmacol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol. Appl. Pharmacol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Abnormalities, Drug-Induced</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Biological Markers</style></keyword><keyword><style  face="normal" font="default" size="100%">Embryo, Nonmammalian</style></keyword><keyword><style  face="normal" font="default" size="100%">Environmental Pollutants</style></keyword><keyword><style  face="normal" font="default" size="100%">Extracellular Space</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation, Developmental</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunohistochemistry</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitochondria</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxidation-Reduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxidative Stress</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxygen Consumption</style></keyword><keyword><style  face="normal" font="default" size="100%">Polycyclic Hydrocarbons, Aromatic</style></keyword><keyword><style  face="normal" font="default" size="100%">Real-Time Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA</style></keyword><keyword><style  face="normal" font="default" size="100%">Teratogens</style></keyword><keyword><style  face="normal" font="default" size="100%">Zebrafish</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">11/2013</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">271</style></volume><pages><style face="normal" font="default" size="100%">266-75</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are byproducts of combustion and photo-oxidation of parent PAHs. OPAHs are widely present in the environment and pose an unknown hazard to human health. The developing zebrafish was used to evaluate a structurally diverse set of 38 OPAHs for malformation induction, gene expression changes and mitochondrial function. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to a dilution series of 38 different OPAHs and evaluated for 22 developmental endpoints. AHR activation was determined via CYP1A immunohistochemistry. Phenanthrenequinone (9,10-PHEQ), 1,9-benz-10-anthrone (BEZO), xanthone (XAN), benz(a)anthracene-7,12-dione (7,12-B[a]AQ), and 9,10-anthraquinone (9,10-ANTQ) were evaluated for transcriptional responses at 48hpf, prior to the onset of malformations. qRT-PCR was conducted for a number of oxidative stress genes, including the glutathione transferase(gst), glutathione peroxidase(gpx), and superoxide dismutase(sod) families. Bioenergetics was assayed to measure in vivo oxidative stress and mitochondrial function in 26hpf embryos exposed to OPAHs. Hierarchical clustering of the structure-activity outcomes indicated that the most toxic of the OPAHs contained adjacent diones on 6-carbon moieties or terminal, para-diones on multi-ring structures. 5-carbon moieties with adjacent diones were among the least toxic OPAHs while the toxicity of multi-ring structures with more centralized para-diones varied considerably. 9,10-PHEQ, BEZO, 7,12-B[a]AQ, and XAN exposures increased expression of several oxidative stress related genes and decreased oxygen consumption rate (OCR), a measurement of mitochondrial respiration. Comprehensive in vivo characterization of 38 structurally diverse OPAHs indicated differential AHR dependency and a prominent role for oxidative stress in the toxicity mechanisms.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/23684558?dopt=Abstract</style></custom1></record></records></xml>