@article{kotlarz_mccord_wiecha_weed_cuffney_enders_strynar_knappe_reich_hoppin_2024, title={Measurement of Hydro-EVE and 6:2 FTS in Blood from Wilmington, North Carolina, Residents, 2017-2018}, volume={132}, ISSN={["1552-9924"]}, url={https://doi.org/10.1289/EHP14503}, DOI={10.1289/EHP14503}, number={2}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Kotlarz, Nadine and McCord, James and Wiecha, Nate and Weed, Rebecca A. and Cuffney, Michael and Enders, Jeffrey R. and Strynar, Mark and Knappe, Detlef R. U. and Reich, Brian J. and Hoppin, Jane A.}, year={2024}, month={Feb} }
 @article{weed_campbell_brown_may_sargent_sutton_burdette_rider_baker_enders_2024, title={Non-Targeted PFAS Suspect Screening and Quantification of Drinking Water Samples Collected through Community Engaged Research in North Carolina's Cape Fear River Basin}, volume={12}, ISSN={["2305-6304"]}, url={https://doi.org/10.3390/toxics12060403}, DOI={10.3390/toxics12060403}, abstractNote={A community engaged research (CER) approach was used to provide an exposure assessment of poly- and perfluorinated (PFAS) compounds in North Carolina residential drinking water. Working in concert with community partners, who acted as liaisons to local residents, samples were collected by North Carolina residents from three different locations along the Cape Fear River basin: upper, middle, and lower areas of the river. Residents collected either drinking water samples from their homes or recreational water samples from near their residence that were then submitted by the community partners for PFAS analysis. All samples were processed using weak anion exchange (WAX) solid phase extraction and analyzed using a non-targeted suspect screening approach as well as a quantitative approach that included a panel of 45 PFAS analytes, several of which are specific to chemical industries near the collection site locations. The non-targeted approach, which utilized a suspect screening list (obtained from EPA CompTox database) identified several PFAS compounds at a level two confidence rating (Schymanski scale); compounds identified included a fluorinated insecticide, a fluorinated herbicide, a PFAS used in polymer chemistry, and another that is used in battery production. Notably, at several locations, PFOA (39.8 ng/L) and PFOS (205.3 ng/L) were at levels that exceeded the mandatory EPA maximum contaminant level (MCL) of 4 ng/L. Additionally, several sites had detectable levels of PFAS that are unique to a local chemical manufacturer. These findings were communicated back to the community partners who then disseminated this information to the local residents to help empower and aid in making decisions for reducing their PFAS exposure.}, number={6}, journal={TOXICS}, author={Weed, Rebecca A. and Campbell, Grace and Brown, Lacey and May, Katlyn and Sargent, Dana and Sutton, Emily and Burdette, Kemp and Rider, Wayne and Baker, Erin S. and Enders, Jeffrey R.}, year={2024}, month={Jun} }
 @article{kotlarz_mccord_wiecha_weed_cuffney_enders_strynar_knappe_reich_hoppin_2024, title={Reanalysis of PFO5DoA Levels in Blood from Wilmington, North Carolina, Residents, 2017-2018}, volume={132}, ISSN={["1552-9924"]}, url={https://doi.org/10.1289/EHP13339}, DOI={10.1289/EHP13339}, abstractNote={,}, number={2}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Kotlarz, Nadine and McCord, James and Wiecha, Nate and Weed, Rebecca A. and Cuffney, Michael and Enders, Jeffrey R. and Strynar, Mark and Knappe, Detlef R. U. and Reich, Brian J. and Hoppin, Jane A.}, year={2024}, month={Feb} }
 @article{enders_weed_griffith_muddiman_2022, title={Development and validation of a high resolving power absolute quantitative per- and polyfluoroalkyl substances method incorporating Skyline data processing}, volume={36}, ISSN={["1097-0231"]}, url={https://doi.org/10.1002/rcm.9295}, DOI={10.1002/rcm.9295}, abstractNote={RationaleThe ability to perform absolute quantitation and non‐targeted analysis on a single mass spectrometry instrument would be advantageous to many researchers studying per‐ and polyfluoroalkyl substances (PFAS). High‐resolution accurate mass (HRAM) instrumentation (typically deployed for non‐targeted work) carries several advantages over traditional triple quadrupole workflows when performing absolute quantitation. Processing this data using a vendor‐neutral software would promote collaboration for these environmental studies.MethodsLC‐MS (Orbitrap Exploris 240) was used for absolute quantitation of 45 PFAS using precursor (MS1) peak areas for quantitation, whereas isotope pattern matching and fragmentation (MS2) pattern matching were used for qualitative identification. In addition, a fluorinated chromatographic column achieved superior separation compared to the typical C18 columns typically used in PFAS analyses. This method was validated across eight different chemical classes using recommended guidelines found in EPA Method 537.1 and Skyline data processing software.ResultsThe validated limits of all 45 compounds, as well as metrics or accuracy and reproducibility, are reported. Most compounds achieved limits of quantitation in the range of 2‐50 ng/L. Four newly released Chemours‐specific compounds (PEPA, PFO3OA, PFO4DA, and PFO5DoA) were also validated. Aspects of data analysis specific to high resolving power absolute quantitation are reviewed as are the details of processing these data via Skyline.ConclusionsThis method shows the feasibility of performing reproducible absolute quantitation of PFAS on an HRAM platform and does so using an open‐source vendor‐neutral data processing software to facilitate sharing of data across labs and institutions.}, number={11}, journal={RAPID COMMUNICATIONS IN MASS SPECTROMETRY}, author={Enders, Jeffrey R. and Weed, Rebecca A. and Griffith, Emily H. and Muddiman, David C.}, year={2022}, month={Jun} }
 @article{weed_boatman_enders_2022, title={Recovery of per- and polyfluoroalkyl substances after solvent evaporation}, volume={10}, ISSN={["2050-7895"]}, url={https://doi.org/10.1039/D2EM00269H}, DOI={10.1039/D2EM00269H}, abstractNote={Presented data shows that vacuum evaporative concentration of PFAS standards can cause class-specific loss of material that can be mitigated via recovery steps.}, journal={ENVIRONMENTAL SCIENCE-PROCESSES & IMPACTS}, author={Weed, Rebecca A. and Boatman, Anna K. and Enders, Jeffrey R.}, year={2022}, month={Oct} }
 @article{zimmer_howell_ma_enders_lehman_corey_barycki_simpson_2021, title={Altered glucuronidation deregulates androgen dependent response profiles and signifies castration resistance in prostate cancer}, volume={12}, url={http://dx.doi.org/10.18632/oncotarget.28059}, DOI={10.18632/oncotarget.28059}, abstractNote={Glucuronidation controls androgen levels in the prostate and the dysregulation of enzymes in this pathway is associated with castration resistant prostate cancer. UDP-glucose dehydrogenase (UGDH) produces UDP-glucuronate, the essential precursor for glucuronidation, and its expression is elevated in prostate cancer. We compared protein and metabolite levels relevant to the glucuronidation pathway in five prostate cancer patient-derived xenograft models paired with their isogenic counterparts that were selected in vivo for castration resistant (CR) recurrence. All pairs showed changes in UGDH and associated enzymes and metabolites that were consistent with those we found in an isogenic androgen dependent (AD) and CR LNCaP prostate cancer model. Ectopic overexpression of UGDH in LNCaP AD cells blunted androgen-dependent gene expression, increased proteoglycan synthesis, significantly increased cell growth compared to controls, and eliminated dose responsive growth suppression with enzalutamide treatment. In contrast, the knockdown of UGDH diminished proteoglycans, suppressed androgen dependent growth irrespective of androgens, and restored androgen sensitivity in CR cells. Importantly, the knockdown of UGDH in both LNCaP AD and CR cells dramatically sensitized these cells to enzalutamide. These results support a role for UGDH in androgen responsiveness and a target for therapeutic strategies in advanced prostate cancer.}, number={19}, journal={Oncotarget}, publisher={Impact Journals, LLC}, author={Zimmer, Brenna M. and Howell, Michelle E. and Ma, Linlin and Enders, Jeffrey R. and Lehman, Danielle and Corey, Eva and Barycki, Joseph J. and Simpson, Melanie A.}, year={2021}, month={Sep}, pages={1886–1902} }
 @article{mora-navarro_garcia_sarker_ozpinar_enders_khan_branski_freytes_2022, title={Monitoring decellularization via absorbance spectroscopy during the derivation of extracellular matrix scaffolds}, volume={17}, ISSN={["1748-605X"]}, url={https://doi.org/10.1088/1748-605X/ac361f}, DOI={10.1088/1748-605X/ac361f}, abstractNote={Abstract
               Extracellular matrix (ECM) is a complex structure composed of bioactive molecules representative of the local tissue microenvironment. Decellularized ECM biomaterials harness these biomolecules for regenerative medicine applications. One potential therapeutic application is the use of vocal fold (VF) specific ECM to restore the VFs after injury. ECM scaffolds are derived through a process of decellularization, which aims to remove unwanted immunogenic biomolecules (e.g. DNA) while preserving the composition of the ECM. The effectiveness of the decellularization is typically assessed at the end by quantifying ECM attributes such as final dsDNA content. However, batch-to-batch variability in ECM manufacturing remains a significant challenge for the standardization, cost-effectiveness, and scale-up process. The limited number of tools available for in-process control heavily restricts the uncovering of the correlations between decellularization process parameters and ECM attributes. In this study, we developed a technique applicable to both the classical batch method and semi-continuous decellularization systems to trace the decellularization of two laryngeal tissues in real-time. We hypothesize that monitoring the bioreactor’s effluent absorbance at 260 nm as a function of time will provide a representative DNA release profile from the tissue and thus allow for process optimization. The DNA release profiles were obtained for laryngeal tissues and were successfully used to optimize the derivation of VF lamina propria-ECM (auVF-ECM) hydrogels. This hydrogel had comparable rheological properties to commonly used biomaterials to treat VF injuries. Also, the auVF-ECM hydrogel promoted the down-regulation of CCR7 by THP-1 macrophages upon lipopolysaccharide stimulation in vitro suggesting some anti-inflammatory properties. The results show that absorbance profiles are a good representation of DNA removal during the decellularization process thus providing an important tool to optimize future protocols.}, number={1}, journal={BIOMEDICAL MATERIALS}, publisher={IOP Publishing}, author={Mora-Navarro, Camilo and Garcia, Mario E. and Sarker, Prottasha and Ozpinar, Emily W. and Enders, Jeffrey R. and Khan, Saad and Branski, Ryan C. and Freytes, Donald O.}, year={2022}, month={Jan} }
 @article{feng_strickland_enders_roslawski_mcintire_mcintire_2021, title={Ritalinic acid in urine: Impact of age and dose}, volume={27}, ISSN={["2352-5517"]}, DOI={10.1016/j.plabm.2021.e00258}, abstractNote={The objective of this work was to study the results of urine drug testing for ritalinic acid (RA), the major urinary metabolite of methylphenidate (MP) (e.g., Ritalin®). The impact of age from 4 to 65 years old and older on median levels of RA was investigated as well as potential variations in pH, specific gravity and creatinine content of the patient urine samples.Samples from patients who were 1) prescribed MP and found to be positive for RA, 2) prescribed MP but found to be negative for RA and 3) not prescribed MP but tested positive for RA were examined by liquid chromatography - mass spectrometry/mass spectrometry (LC-MS/MS) for RA concentration. The levels of RA were examined for median and average levels and further normalized and transformed to reveal a near gaussian distribution.Over 20,000 samples from patients who were prescribed MP were examined for this work. Analysis of these data for a subset of patients prescribed MP and testing positive for RA revealed statistically different median values of RA for school age patients of 6 years old through 17 years old from adult patients 18 through 64 years old. Another 6751 samples were positive for RA without a prescription but were not included in the overall assessment of these data.While not clear as to the reason, these data indicate that school age children under the age of 18 have much higher levels of RA than adult patients. These results can be used to estimate "normal" levels of RA in these chronically dosed populations.}, journal={PRACTICAL LABORATORY MEDICINE}, author={Feng, Sheng and Strickland, Erin and Enders, Jeffery and Roslawski, Michaela and McIntire, Timothy and McIntire, Gregory}, year={2021}, month={Nov} }
 @article{enders_grace m. o'neill_whitten_muddiman_2021, title={Understanding the electrospray ionization response factors of per- and poly-fluoroalkyl substances (PFAS)}, volume={7}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-021-03545-8}, abstractNote={Per- and polyfluoroalkyl substances (PFAS) are used extensively in commercial products. Their unusual solubility properties make them an ideal class of compounds for various applications. However, these same properties have led to significant contamination and bioaccumulation given their persistence in the environment. Development of analytical techniques to detect and quantify these compounds must take into account the potential for these properties to perturb these measurements, specifically the potential to bias the electrospray ionization (ESI) process. Direct injection ESI analysis of 23 different PFAS species revealed that hydrophobicity and PFAS class can predict the ESI overall response factors. In this study, a method for predicting the behavior of individual PFAS compounds, including relative retention order in chromatography, is presented which is simply based on the number of fluorine atoms in the molecule as well as the class of the compound (e.g., perfluroalkylcarboxylic acids) vs. computational estimations (e.g., non-polar surface area and logP).}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Enders, Jeffrey R. and Grace M. O'Neill and Whitten, Jerry L. and Muddiman, David C.}, year={2021}, month={Jul} }
 @article{natalia gonzalez_mills_maugeri_olaya_laguera_enders_sherman_rodriguez_pierce_jose cazzulo_et al._2021, title={Design, synthesis, and evaluation of substrate - analogue inhibitors of Trypanosoma cruzi ribose 5-phosphate isomerase type B}, volume={32}, ISSN={["1464-3405"]}, url={http://dx.doi.org/10.1016/j.bmcl.2020.127723}, DOI={10.1016/j.bmcl.2020.127723}, abstractNote={Ribose 5-phosphate isomerase type B (RPI-B) is a key enzyme of the pentose phosphate pathway that catalyzes the isomerization of ribose 5-phosphate (R5P) and ribulose 5-phosphate (Ru5P). Trypanosoma cruzi RPI-B (TcRPI-B) appears to be a suitable drug-target mainly due to: (i) its essentiality (as previously shown in other trypanosomatids), (ii) it does not present a homologue in mammalian genomes sequenced thus far, and (iii) it participates in the production of NADPH and nucleotide/nucleic acid synthesis that are critical for parasite cell survival. In this survey, we report on the competitive inhibition of TcRPI-B by a substrate - analogue inhibitor, Compound B (Ki = 5.5 ± 0.1 μM), by the Dixon method. This compound has an iodoacetamide moiety that is susceptible to nucleophilic attack, particularly by the cysteine thiol group. Compound B was conceived to specifically target Cys-69, an important active site residue. By incubating TcRPI-B with Compound B, a trypsin digestion LC-MS/MS analysis revealed the identification of Compound B covalently bound to Cys-69. This inhibitor also exhibited notable in vitro trypanocidal activity against T. cruzi infective life-stages co-cultured in NIH-3T3 murine host cells (IC50 = 17.40 ± 1.055 μM). The study of Compound B served as a proof-of-concept so that next generation inhibitors can potentially be developed with a focus on using a prodrug group in replacement of the iodoacetamide moiety, thus representing an attractive starting point for the future treatment of Chagas' disease.}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, publisher={Elsevier BV}, author={Natalia Gonzalez, Soledad and Mills, Jonathan J. and Maugeri, Dante and Olaya, Christopher and Laguera, Breana L. and Enders, Jeffrey R. and Sherman, Julian and Rodriguez, Ana and Pierce, Joshua G. and Jose Cazzulo, Juan and et al.}, year={2021}, month={Jan} }
 @article{badileanu_mora-navarro_martins_garcia_sze_ozpinar_gaffney_enders_branski_freytes_2020, title={Fast Automated Approach for the Derivation of Acellular Extracellular Matrix Scaffolds from Porcine Soft Tissues.}, volume={6}, url={https://doi.org/10.1021/acsbiomaterials.0c00265}, DOI={10.1021/acsbiomaterials.0c00265}, abstractNote={Decellularized extracellular matrix (ECM) scaffolds derived from tissues and organs are complex biomaterials used in clinical and research applications. A number of decellularization protocols have been described for ECM biomaterials derivation, each adapted to a particular tissue and use, restricting comparisons among materials. One of the major sources of variability in ECM products comes from the tissue source and animal age. Although this variability could be minimized using established tissue sources, other sources arise from the decellularization process itself. Overall, current protocols require manual work and are poorly standardized with regard to the choice of reagents, the order by which they are added, and exposure times. The combination of these factors adds variability affecting the uniformity of the final product between batches. Furthermore, each protocol needs to be optimized for each tissue and tissue source making tissue-to-tissue comparisons difficult. Automation and standardization of ECM scaffold development constitute a significant improvement to current biomanufacturing techniques but remains poorly explored. This study aimed to develop a biofabrication method for fast and automated derivation of raw material for ECM hydrogel production while preserving ECM composition and controlling lot-to-lot variability. The main result was a closed semibatch bioreactor system with automated dosing of decellularization reagents capable of deriving ECM material from pretreated soft tissues. The ECM was further processed into hydrogels to demonstrate gelation and cytocompatibility. This work presents a versatile, scalable, and automated platform for the rapid production of ECM scaffolds.}, number={7}, journal={ACS biomaterials science & engineering}, publisher={American Chemical Society (ACS)}, author={Badileanu, Andreea and Mora-Navarro, Camilo and Martins, Ana M. Gracioso and Garcia, Mario E. and Sze, Daphne and Ozpinar, Emily W. and Gaffney, Lewis and Enders, Jeffrey R. and Branski, Ryan C. and Freytes, Donald O.}, year={2020}, month={Jun}, pages={4200–4213} }
 @article{mora-navarro_badileanu_martins_ozpinar_gaffney_huntress_harrell_enders_peng_branski_et al._2020, title={Porcine Vocal Fold Lamina Propria-Derived Biomaterials Modulate TGF-β1-Mediated Fibroblast Activation in Vitro.}, volume={6}, url={https://doi.org/10.1021/acsbiomaterials.9b01837}, DOI={10.1021/acsbiomaterials.9b01837}, abstractNote={The vocal fold lamina propria (VFLP), one of the outermost layers of the vocal fold (VF), is composed of tissue-specific extracellular matrix (ECM) proteins and is highly susceptible to injury. Various biomaterials have been clinically tested to treat voice disorders (e.g., hydrogels, fat, and hyaluronic acid), but satisfactory recovery of the VF functionality remains elusive. Fibrosis or scar formation in the VF is a major challenge, and the development and refinement of novel therapeutics that promote the healing and normal function of the VF are needed. Injectable hydrogels derived from native tissues have been previously reported with major advantages over synthetic hydrogels, including constructive tissue remodeling and reduced scar tissue formation. This study aims to characterize the composition of a decellularized porcine VFLP-ECM scaffold and the cytocompatibility and potential antifibrotic properties of a hydrogel derived from VFLP-ECM. In addition, we isolated potential matrix-bound vesicles (MBVs) and macromolecules from the VFLP-ECM that also downregulated smooth muscle actin ACTA2 under transforming growth factor-beta 1 (TGF-β1) stimulation. The results provide evidence of the unique protein composition of the VFLP-ECM and the potential link between the components of the VFLP-ECM and the inhibition of TGF-β1 signaling observed in vitro when transformed into injectable forms.}, number={3}, journal={ACS biomaterials science & engineering}, publisher={American Chemical Society (ACS)}, author={Mora-Navarro, Camilo and Badileanu, Andreea and Martins, Ana M. Gracioso and Ozpinar, Emily W. and Gaffney, Lewis and Huntress, Ian and Harrell, Erin and Enders, Jeffrey R. and Peng, Xinxia and Branski, Ryan C. and et al.}, year={2020}, month={Feb}, pages={1690–1703} }
 @article{feng_enders_cummings_strickland_mcintire_mcintire_2020, title={A Dilute and Shoot LC-MS/MS Method for Antipsychotics in Urine}, volume={44}, ISSN={["1945-2403"]}, DOI={10.1093/jat/bkz098}, abstractNote={Abstract
               Adherence to prescribed antipsychotics is an ongoing problem. Traditionally, estimates of adherence have been made from patient interviews, pill counting and blood testing. A number of methods for the analysis of antipsychotics in blood have been reported for both therapeutic drug monitoring and postmortem testing for toxicity. This report details a dilute and shoot method for the analysis of 19 different antipsychotics and metabolites. The method takes advantage of earlier reports demonstrating unique, prevalent urine metabolites for aripiprazole, brexpiprazole, haloperidol and lurasidone to enhance sensitivity for these analytes. With a fast analysis time and minimal sample preparation, this method can be used for quantitation of antipsychotics in urine. Finally, this method has been used to test samples for over a year with the results summarized in this report. While further improvements are certainly possible, this method is selective and sensitive for this group of important compounds.}, number={4}, journal={JOURNAL OF ANALYTICAL TOXICOLOGY}, author={Feng, Sheng and Enders, Jeffrey R. and Cummings, Oneka T. and Strickland, Erin C. and McIntire, Timothy and McIntire, Gregory}, year={2020}, month={May}, pages={331–338} }
 @inproceedings{feng_enders_cummings_strickland_mcintire_mcintire_2019, title={A Dilute-and-Shoot LC-MS/MS Method for Antipsychotics in Urine}, author={Feng, Sheng and Enders, Jeffrey and Cummings, Oneka T. and Strickland, Erin C. and McIntire, Timothy and McIntire, Gregory}, year={2019}, month={Oct} }
 @inproceedings{enders_cone_fisher_2019, title={A Proteomic Investigation of Changes in the Collagen Types Present in the Anterior Cruciate Ligament During Post-natal Growth}, author={Enders, Jeffrey R. and Cone, Stephanie G. and Fisher, Matthew B.}, year={2019}, month={Jun} }
 @article{strickland_enders_mcintire_2019, title={Determination of the Relative Prevalence of Lurasidone Metabolites in Urine Using Untargeted HRMS}, volume={17}, url={http://www.spectroscopyonline.com/determination-relative-prevalence-lurasidone-metabolites-urine-using-untargeted-hrms-0}, number={2}, journal={Current Trends in Mass Spectrometry}, author={Strickland, E.S. and Enders, J.R. and McIntire, G.L.}, year={2019}, month={May}, pages={8–15} }
 @article{yeyeodu_martin_reaves_enders_costantini_fleming_2019, title={Experimental data demonstrating the effects of silver nanoparticles on basement membrane gene and protein expression in cultured colon, mammary and bronchial epithelia}, volume={26}, ISSN={["2352-3409"]}, DOI={10.1016/j.dib.2019.104464}, abstractNote={This data article is related to the research article entitled "Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression and TGF-beta secretion", available in the journal Nanomedicine: Nanotechnology, Biology, and Medicine [1]. This Data in Brief consists of data that describe changes in the expression of basement membrane (BM)-associated genes and proteins in three non-transformed epithelial cell lines following acute (6 h) and chronic (24 h plus 7-day chase) exposure to silver nanoparticles (AgNPs). Human BEAS2B (lung), MCF10AI (breast), and CCD-18Co (colon) cultured epithelia were analyzed for protein expression by LC-MS/MS and for gene expression by pathway-focused QRT-PCR arrays of 168 focal adhesion, integrin, and extracellular matrix (ECM) genes known to be localized to the plasma membrane, the BM/ECM, or secreted into the extracellular space. Ingenuity pathway analysis (IPA) of combined gene and protein expression datasets was then used to predict canonical pathways affected by AgNP exposure.}, journal={DATA IN BRIEF}, author={Yeyeodu, Susan T. and Martin, Megan E. and Reaves, Denise K. and Enders, Jeffrey R. and Costantini, Lindsey M. and Fleming, Jodie M.}, year={2019}, month={Oct} }
 @article{martin_reaves_jeffcoat_enders_costantini_yeyeodu_botta_kavanagh_fleming_2019, title={Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression, and TGF-β1 secretion}, volume={21}, ISSN={1549-9634}, url={http://dx.doi.org/10.1016/j.nano.2019.102070}, DOI={10.1016/j.nano.2019.102070}, abstractNote={Silver nanoparticles (AgNPs) are widely used in consumer and pharmaceutical products due to their antipathogenic properties. However, safety concerns have been raised due to their bioactive properties. While reports have demonstrated AgNPs can embed within the extracellular matrix, their effects on basement membrane (BM) production, integrin engagement, and tissue-integrity are not well-defined. This study analyzed the effects of AgNPs on BM production, composition and integrin/focal adhesion interactions in representative lung, esophageal, breast and colorectal epithelia models. A multidisciplinary approach including focused proteomics, QPCR arrays, pathway analyses, and immune-based, structural and functional assays was used to identify molecular and physiological changes in cell adhesions and the BM induced by acute and chronic AgNP exposure. Dysregulated targets included CD44 and transforming growth factor-beta, two proteins frequently altered during pathogenesis. Results indicate AgNP exposure interferes with BM and cell adhesion dynamics, and provide insight into the mechanisms of AgNP-induced disruption of epithelial physiology.}, journal={Nanomedicine: Nanotechnology, Biology and Medicine}, publisher={Elsevier BV}, author={Martin, Megan E. and Reaves, Denise K. and Jeffcoat, Breanna and Enders, Jeffrey R and Costantini, Lindsey M. and Yeyeodu, Susan T. and Botta, Diane and Kavanagh, Terrance J. and Fleming, Jodie M.}, year={2019}, month={Oct}, pages={102070} }
 @article{yoon_phillips_enders_balbuena-venancio_billings_norini_karsten_clewell_2018, title={Alginate-encapsulated primary human hepatocyte culture system to increase the accuracy of the predicted in vivo half-life of low clearance compounds}, volume={33}, ISSN={1347-4367}, url={http://dx.doi.org/10.1016/j.dmpk.2017.11.232}, DOI={10.1016/j.dmpk.2017.11.232}, number={1}, journal={Drug Metabolism and Pharmacokinetics}, publisher={Elsevier BV}, author={Yoon, Miyoung and Phillips, Martin B. and Enders, Jeffrey R. and Balbuena-Venancio, Pergentino and Billings, David and Norini, Rachel and Karsten, Ruby and Clewell, Harvey J., III}, year={2018}, month={Jan}, pages={S69–S70} }
 @article{enders_smith_feng_strickland_mcintire_2018, title={Analytical Considerations When Developing an LC-MS/MS Method for Over 30 Analytes}, volume={2}, DOI={10.1373/jalm.2017.024174}, abstractNote={Abstract
               
                  Background
                  While validation of analytical (LC-MS/MS) methods has been documented in any number of articles and reference texts, the optimal design and subsequent validation of a method for over 30 analytes presents special challenges. Conventional approaches to calibration curves, controls, and run time are not tenable in such methods. This report details the practical aspects of designing and implementing such a method in accordance with College of American Pathologists validation criteria.
               
               
                  Methods
                  Conventional criteria were followed in the design and validation of a method for 34 analytes and 15 internal standards by LC-MS/MS. These criteria are laid out in a standard operating procedure, which is followed without exception and is consistent with College of American Pathologists criteria.
               
               
                  Results
                  The method presented herein provides quality results and accurate medication monitoring. The method was optimized to negate interferences (both from within the method and from potential concomitant compounds), increase throughput, and provide reproducible quality quantification over relevant analyte concentrations ranges.
               
               
                  Conclusions
                  The method was designed primarily with quality and accurate medication monitoring in mind. The method achieves these goals by use of novel approaches to calibration curves and controls that both improve performance and minimize risk (financial and operational). As automation and LC-MS/MS equipment continue to improve, it is expected that more methods like this one will be developed.
               }, number={4}, journal={The Journal of Applied Laboratory Medicine}, author={Enders, J.R. and Smith, J.P. and Feng, S. and Strickland, E.C. and McIntire, G.}, year={2018}, month={Jan}, pages={543–554} }
 @inproceedings{enders_2018, title={Investigation of a targeted protein panel of diagnostic and prognostic value to ALS in biological fluids}, author={Enders, Jeffrey}, year={2018}, month={Jun} }
 @article{bereman_beri_enders_nash_2018, title={Machine Learning Reveals Protein Signatures in CSF and Plasma Fluids of Clinical Value for ALS}, volume={8}, ISSN={["2045-2322"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85056076502&partnerID=MN8TOARS}, DOI={10.1038/s41598-018-34642-x}, abstractNote={AbstractWe use shotgun proteomics to identify biomarkers of diagnostic and prognostic value in individuals diagnosed with amyotrophic lateral sclerosis. Matched cerebrospinal and plasma fluids were subjected to abundant protein depletion and analyzed by nano-flow liquid chromatography high resolution tandem mass spectrometry. Label free quantitation was used to identify differential proteins between individuals with ALS (n = 33) and healthy controls (n = 30) in both fluids. In CSF, 118 (p-value < 0.05) and 27 proteins (q-value < 0.05) were identified as significantly altered between ALS and controls. In plasma, 20 (p-value < 0.05) and 0 (q-value < 0.05) proteins were identified as significantly altered between ALS and controls. Proteins involved in complement activation, acute phase response and retinoid signaling pathways were significantly enriched in the CSF from ALS patients. Subsequently various machine learning methods were evaluated for disease classification using a repeated Monte Carlo cross-validation approach. A linear discriminant analysis model achieved a median area under the receiver operating characteristic curve of 0.94 with an interquartile range of 0.88–1.0. Three proteins composed a prognostic model (p = 5e-4) that explained 49% of the variation in the ALS-FRS scores. Finally we investigated the specificity of two promising proteins from our discovery data set, chitinase-3 like 1 protein and alpha-1-antichymotrypsin, using targeted proteomics in a separate set of CSF samples derived from individuals diagnosed with ALS (n = 11) and other neurological diseases (n = 15). These results demonstrate the potential of a panel of targeted proteins for objective measurements of clinical value in ALS.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Bereman, Michael S. and Beri, Joshua and Enders, Jeffrey R. and Nash, Tara}, year={2018}, month={Nov} }
 @misc{l_ayodele_oneka_jeffrey_2018, title={NORMALIZING MEASURED DRUG CONCENTRATIONS IN ORAL FLUIDS AND TESTING FOR POTENTIAL NON-COMPLIANCE WITH DRUG TREATMENT REGIMEN}, url={https://www.lens.org/109-358-919-977-271}, number={US 2018/0045744 A1}, author={L, MCINTIRE GREGORY and AYODELE, MORRIS and ONEKA, CUMMINGS and JEFFREY, ENDERS}, year={2018}, month={Feb} }
 @book{mcintire_morris_cummings_enders_2018, title={Normalizing measured drug concentrations in oral fluids and testing for potential non-compliance with drug treatment regimen}, number={2018/20180045744 A1.}, author={McIntire, G.L. and Morris, A.A. and Cummings, O.T. and Enders, J.R.}, year={2018} }
 @article{phillips_balbuena-venancio_enders_norini_shim_burgunder_rao_billings_pedersen_macdonald_et al._2018, title={Xenobiotic Metabolism in Alginate-Encapsulated Primary Human Hepatocytes over Long Timeframes}, volume={4}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053864396&partnerID=MN8TOARS}, DOI={10.1089/aivt.2017.0029}, abstractNote={Introduction: Application of in vitro-to-in vivo extrapolation to chemical safety assessment has gained significant attention in the past few years. Accurate prediction of hepatic metabolic clearance from in vitro data is critical in this regard as it determines compound pharmacokinetics and exposure at sites of action. To estimate hepatic metabolic clearance, intrinsic clearance (CLint) is typically measured using in vitro systems such as primary hepatocytes or subcellular fractions derived from liver tissues. However, currently available in vitro systems used in these studies often lack long-term metabolic competence, making it challenging to estimate CLint for poorly metabolized and slowly cleared chemicals. Materials and Methods: To address this challenge, we developed a three-dimensional (3D) primary human hepatocyte cell culture system using alginate hydrogels (“alginate bead culture”) with extended viability and metabolic competence. Results: Alginate bead culture generates comparable estimates of metabolism to other in vitro and in vivo systems. In addition, expression of several xenobiotic metabolizing enzymes over long timeframes in beads is comparable to freshly isolated hepatocytes in suspension culture. Discussion: We compare CLint estimated from traditional suspension versus alginate bead culture for two chemicals (S-warfarin and coumarin) and show that alginate bead culture holds promise to increase confidence in estimates of CLint for slowly cleared chemicals. Conclusions: In addition to providing an improved in vitro tool to estimate metabolic clearance for a broad range of chemicals, this simple 3D hepatocyte culture can be adapted to a continuous flow-based bioreactor system allowing repeated exposure experiments over long periods in vitro, tackling an important challenge in in vitro-based chemical safety assessment.}, number={3}, journal={Applied In Vitro Toxicology}, author={Phillips, M.B. and Balbuena-Venancio, P. and Enders, J.R. and Norini, R.L. and Shim, Y.-S. and Burgunder, E. and Rao, L. and Billings, D. and Pedersen, J. and MacDonald, J.M. and et al.}, year={2018}, pages={238–247} }
 @inproceedings{enders_balbuena-venancio_billings_rao_burgunder_phillips_yoon_2017, title={Evaluation of Non-Specific Binding to Different Organic Polymeric Components in Flow-Based Advanced Cell Culture Systems for Toxicity Testing}, author={Enders, Jeffrey R. and Balbuena-Venancio, Pergentino and Billings, David and Rao, Lavanya and Burgunder, Erin and Phillips, Martin and Yoon, Miyoung}, year={2017}, month={Mar} }
 @article{enders_reddy_strickland_mcintire_2017, title={Identification of metabolites of brexpiprazole in human urine for use in monitoring patient compliance}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85050647074&partnerID=MN8TOARS}, DOI={10.1016/j.clinms.2017.11.001}, abstractNote={Brexpiprazole (Rexulti®) is an atypical antipsychotic prescribed for the treatment of schizophrenia. While therapeutic drug monitoring (e.g., blood testing) for adherence to prescription paradigms has been the norm, urine drug testing is increasing in popularity. Here, we identify major metabolites of brexpiprazole in urine that could be used in monitoring patient compliance. Urine samples from patients prescribed brexpiprazole were collected and analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF) to identify brexpiprazole metabolites present in urine. The carboxylic acid metabolite, OPC-3952, was found to be the most abundant metabolite of brexpiprazole present in urine. While this result is consistent with qualitative results determined in plasma, the quantitative results observed in urine are different from these earlier reports. The use of OPC-3952 in urine, as an indicator of compliance, provides a potential avenue for improved monitoring of patients who have been prescribed brexpiprazole.}, journal={Clinical Mass Spectrometry}, author={Enders, J.R. and Reddy, S.G. and Strickland, E.C. and McIntire, G.L.}, year={2017}, pages={21–24} }
 @article{cummings_strickland_enders_mcintire_2018, title={Impact of β-Glucuronidase Mediated Hydrolysis on Haldol® Urinalysis}, volume={42}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85055146515&partnerID=MN8TOARS}, DOI={10.1093/jat/bkx103}, abstractNote={Reports have suggested that patients with mental health disorders including major depressive disorder and schizophrenia have dramatically low adherence levels to prescribed medications. Patients on haloperidol (Haldol®) therapy, regardless of their disease, were found to have higher adherence levels-though still strikingly low. This work shows that high levels of the glucuronidated form of haloperidol are present in patient urine samples. Time-of-Flight (TOF) mass spectrometry experiments are consistent with both the presence of haloperidol glucuronide and that hydrolysis of haloperidol patient urine samples leads to significantly increased concentrations of free haloperidol. Urine samples collected from patients prescribed haloperidol were tested with and without hydrolysis revealing a significant increase in the number of patients testing positive when the samples were hydrolyzed before analysis. These data demonstrate that hydrolysis greatly improves the sensitivity and consistency of results for patients on haloperidol therapy resulting in positivity data that strongly correlates with the dosage form administered.}, number={4}, journal={Journal of analytical toxicology}, author={Cummings, O.T. and Strickland, E.C. and Enders, J.R. and McIntire, G.}, year={2018}, pages={214–219} }
 @misc{jeffrey_erin_l_ayodele_2017, title={METHODS OF MONITORING ADHERENCE TO LURASIDONE THERAPY}, url={https://www.lens.org/119-736-087-516-250}, number={US 2017/0192025 A1}, author={JEFFREY, ENDERS and ERIN, STRICKLAND and L, MCINTIRE GREGORY and AYODELE, MORRIS}, year={2017}, month={Jul} }
 @misc{l_jeffrey_erin_2017, title={METHODS OF MONITORING FOR ADHERENCE TO BREXPIPRAZOLE (REXULTI®) THERAPY}, url={https://www.lens.org/141-517-997-208-481}, number={US 2017/0276692 A1}, author={L, MCINTIRE GREGORY and JEFFREY, ENDERS and ERIN, STRICKLAND}, year={2017}, month={Sep} }
 @book{enders_strickland_mcintire_morris_2017, title={Methods of Monitoring Adherence to Lurasidone Therapy}, number={2015/0168431 A1}, author={Enders, J.R. and Strickland, E.C. and McIntire, G.L. and Morris, A.A.}, year={2017} }
 @book{mcintire_enders_strickland_2017, title={Methods of Monitoring for Adherence to Brexpiprazole (Rexulti®) Therapy}, number={2017/0276692 A1}, author={McIntire, G.L. and Enders, J.R. and Strickland, E.C.}, year={2017} }
 @misc{jeffrey_erin_l_ayodele_2017, title={Methods of monitoring adherence to lurasidone therapy}, url={https://www.lens.org/102-095-827-858-797}, number={US 9606132 B2}, author={JEFFREY, ENDERS and ERIN, STRICKLAND and L, MCINTIRE GREGORY and AYODELE, MORRIS}, year={2017}, month={Mar} }
 @article{cummings_enders_mcintire_2017, title={Response to: Fentanyl-Norfentanyl concentrations during transdermal patch application: LC-MS-MS urine analysis}, volume={41}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85019570326&partnerID=MN8TOARS}, number={2}, journal={Journal of Analytical Toxicology}, author={Cummings, O.T. and Enders, J. and McIntire, G.L.}, year={2017}, pages={165–166} }
 @article{cummings_enders_mcintire_backer_poklis_2016, title={Fentanyl-norfentanyl concentrations during transdermal patch application: LC-MS-MS urine analysis}, volume={40}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84992220677&partnerID=MN8TOARS}, DOI={10.1093/jat/bkw067}, abstractNote={Poklis and Backer published a survey of the concentrations of fentanyl and norfentanyl that could be expected in urine from patients using Duragesic®, a transdermal fentanyl patch. That study employed a relatively small number of patient data points and analysis by Gas Chromatography/Mass Spectrometry. This work examines a larger population of patient positives for fentanyl and norfentanyl to determine whether more than a decade later the original report remains accurate in predicting the range and median levels of fentanyl and norfentanyl concentrations physicians can expect to see from their patients. Additionally, these data were transformed to develop a model that results in a near Gaussian distribution of urine drug test results. This retrospective approach was developed to transform and normalize urine drug testing results to provide a historical picture of expected patient values for this important analgesic. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from urine drug testing.}, number={8}, journal={Journal of Analytical Toxicology}, author={Cummings, O.T. and Enders, J.R. and McIntire, G.L. and Backer, R. and Poklis, A.}, year={2016}, pages={595–600} }
 @inproceedings{cummings_enders_mcintire_backer_poklis_2016, title={Fentanyl—Norfentanyl Concentrations During Transdermal Patch Application: LC-MS/MS Urine Analysis}, author={Cummings, Oneka T. and Enders, Jeffrey R. and McIntire, Gregory L. and Backer, R. and Poklis, A.}, year={2016} }
 @article{ward_enders_bell_cramer_wallace_mcintire_2016, title={Improved chiral separation of methamphetamine enantiomers using CSP-LC-MS-MS}, volume={40}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84964872507&partnerID=MN8TOARS}, DOI={10.1093/jat/bkw005}, abstractNote={To determine the true enantiomeric composition of methamphetamine urine drug testing results, chiral separation of dextro (D) and levo (L) enantiomers is necessary. While enantiomeric separation of methamphetamine has traditionally been accomplished using gas chromatography-mass spectrometry (GC-MS), chiral separation of D- and L-methamphetamine by chiral stationary phase (CSP) liquid chromatography-mass spectrometry/mass spectrometry (LC-MS-MS) has proved more reliable. Chirally selective detection of methamphetamine by GC-MS is often performed using L-N-trifluoroacetyl-prolyl chloride (TPC). L-TPC, a chiral compound, is known to have impurities that can affect the chiral composition percentages of the methamphetamine sample, potentially leading to inaccurate patient results. The comparative analysis of the samples run by GC and LC methods showed preferential bias of the GC method for producing error rates, consistent with previous research, of 8-19%. The CSP-LC-MS-MS method produces percent deviation errors of <2%. Additionally, the GC method failed to produce results that were 100% D- or L-isomer even for enantiomerically pure standards. A higher rate of D- and L-methamphetamine isomer racemization is seen in samples when analyzed by GC-MS using L-TPC-derivatizing agent. This racemization is not seen when these samples are tested with CSP-LC-MS-MS. Thus, a more accurate method of enantiomeric analysis is provided by CSP-LC-MS-MS.}, number={4}, journal={Journal of Analytical Toxicology}, author={Ward, L.F. and Enders, J.R. and Bell, D.S. and Cramer, H.M. and Wallace, F.N. and McIntire, G.L.}, year={2016}, pages={255–263} }
 @inproceedings{enders_2016, title={Investigation of a Large Pain Profile from Fingerstick Capillary Blood}, booktitle={New Approaches to Pain Medication Compliance Monitoring}, author={Enders, J}, year={2016}, month={Feb} }
 @misc{l_ayodele_oneka_jeffrey_2016, title={NORMALIZING MEASURED DRUG CONCENTRATIONS IN ORAL FLUIDS AND TESTING FOR POTENTIAL NON-COMPLIANCE WITH DRUG TREATMENT REGIMEN}, url={https://www.lens.org/173-764-751-938-731}, number={WO 2016/115492 A1}, author={L, MCINTIRE GREGORY and AYODELE, MORRIS and ONEKA, CUMMINGS and JEFFREY, ENDERS}, year={2016}, month={Jul} }
 @article{cummings_morris_enders_mcintire_2016, title={Normalizing oral fluid hydrocodone data using calculated blood volume}, volume={40}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84995809821&partnerID=MN8TOARS}, DOI={10.1093/jat/bkw057}, abstractNote={Oral fluid testing to assist in the assessment of treatment adherence for chronic pain patients is attractive for a number of reasons. However, efforts focused on interpreting patient results have been modest when compared to urine drug testing. This work details a retrospective approach developed to transform and normalize oral fluid testing results to provide a historical picture of patient values in this important test fluid. Using this approach, a model was developed using data from 6,800 independent patients who were both prescribed hydrocodone and tested positive (with limitations: reporting cutoff < X < upper limit of quantitation) by liquid chromatography-mass spectrometry. Patient demographic data were used to calculate the relevant parameters (e.g., calculated blood volume (CBV)) used in the transformation and normalization of the oral fluid data. The crucial normalizing factor in oral fluids was found to be the CBV which parallels the use of creatinine to normalize drug concentration levels in urine and is consistent with the view that oral fluid samples reflect plasma concentrations of the respective drugs. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from oral fluid testing.}, number={7}, journal={Journal of Analytical Toxicology}, author={Cummings, O.T. and Morris, A.A. and Enders, J.R. and McIntire, G.L.}, year={2016}, pages={486–491} }
 @article{feng_bridgewater_mcintire_enders_2016, title={The synthetic cannabinoid chemical arms race and its effect on pain medication monitoring}, volume={34}, number={4}, journal={LC-GC North America}, author={Feng, S. and Bridgewater, B. and McIntire, G.L. and Enders, J.R.}, year={2016}, pages={15–22} }
 @article{enders_mcintire_2015, title={A dilute-and-shoot LC-MS method for quantitating opioids in oral fluid}, volume={39}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84943761703&partnerID=MN8TOARS}, DOI={10.1093/jat/bkv087}, abstractNote={Opioid testing represents a dominant share of the market in pain management clinical testing facilities. Testing of this drug class in oral fluid (OF) has begun to rise in popularity. OF analysis has traditionally required extensive clean-up protocols and sample concentration, which can be avoided. This work highlights the use of a fast, 'dilute-and-shoot' method that performs no considerable sample manipulation. A quantitative method for the determination of eight common opioids and associated metabolites (codeine, morphine, hydrocodone, hydromorphone, norhydrocodone, oxycodone, noroxycodone and oxymorphone) in OF is described herein. OF sample is diluted 10-fold in methanol/water and then analyzed using an Agilent chromatographic stack coupled with an AB SCIEX 4500. The method has a 2.2-min LC gradient and a cycle time of 2.9 min. In contrast to most published methods of this particular type, this method uses no sample clean-up or concentration and has a considerably faster LC gradient, making it ideal for very high-throughput laboratories. Importantly, the method requires only 100 μL of sample and is diluted 10-fold prior to injection to help with instrument viability. Baseline separation of all isobaric opioids listed above was achieved on a phenyl-hexyl column. The validated calibration range for this method is 2.5-1,000 ng/mL. This 'dilute-and-shoot' method removes the unnecessary, costly and time-consuming extraction steps found in traditional methods and still surpasses all analytical requirements.}, number={8}, journal={Journal of Analytical Toxicology}, author={Enders, J.R. and McIntire, G.L.}, year={2015}, pages={662–667} }
 @article{mitchell_strickland_enders_shapiro_payne_mcintire_2015, title={An Initial Look at Ketamine and Norketamine: Levels in a Pain Management Population}, volume={39}, url={https://www.soft-tox.org/files/toxtalk/SOFT_ToxTalk_v39-3.pdf}, number={3}, journal={ToxTalk}, publisher={Society of Forensic Toxicologists}, author={Mitchell, C. and Strickland, E.C. and Enders, J.R. and Shapiro, I. and Payne, C. and McIntire, G.L.}, year={2015}, pages={7–10} }
 @article{cummings_morris_strickland_enders_mcintire_2015, title={Haldol Analysis in Urine: The Impact of Beta-Glucuronidase Hydrolysis}, volume={39}, url={https://www.soft-tox.org/files/toxtalk/SOFT_ToxTalk_v39-3.pdf}, number={3}, journal={ToxTalk}, author={Cummings, O.T. and Morris, A.A. and Strickland, E.C. and Enders, J.R. and McIntire, G.L.}, year={2015}, pages={12–14} }
 @misc{jeffrey_erin_l_ayodele_2015, title={METHODS OF MONITORING ADHERENCE TO LURASIDONE THERAPY}, url={https://www.lens.org/142-044-808-933-676}, number={US 2015/0168431 A1}, author={JEFFREY, ENDERS and ERIN, STRICKLAND and L, MCINTIRE GREGORY and AYODELE, MORRIS}, year={2015}, month={Jun} }
 @article{enders_mcintire_morris_hitchcock_2015, title={Rapid Analysis of Selected Benzodiazepines by Automated SPE-MS/MS}, volume={13}, url={https://www.chromatographyonline.com/view/rapid-analysis-selected-benzodiazepines-automated-spe-ms-ms}, number={2}, journal={Current Trends in Mass Spectrometry}, author={Enders, J.R. and McIntire, G.L. and Morris, A.A. and Hitchcock, J.C.}, year={2015}, pages={8–15} }
 @inproceedings{enders_mcintire_2015, title={Rapid Mass Spectrometry Based Urine Drug Screening of 27 Antipsychotic and Antidepressant Medications}, author={Enders, Jeffrey R. and McIntire, Gregory L.}, year={2015} }
 @article{marasco_enders_seale_mclean_wikswo_2015, title={Real-time cellular exometabolome analysis with a microfluidic-mass spectrometry platform}, volume={10}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84923770649&partnerID=MN8TOARS}, DOI={10.1371/journal.pone.0117685}, abstractNote={To address the challenges of tracking the multitude of signaling molecules and metabolites that is the basis of biological complexity, we describe a strategy to expand the analytical techniques for dynamic systems biology. Using microfluidics, online desalting, and mass spectrometry technologies, we constructed and validated a platform well suited for sampling the cellular microenvironment with high temporal resolution. Our platform achieves success in: automated cellular stimulation and microenvironment control; reduced non-specific adsorption to polydimethylsiloxane due to surface passivation; real-time online sample collection; near real-time sample preparation for salt removal; and real-time online mass spectrometry. When compared against the benchmark of “in-culture” experiments combined with ultraperformance liquid chromatography-electrospray ionization-ion mobility-mass spectrometry (UPLC-ESI-IM-MS), our platform alleviates the volume challenge issues caused by dilution of autocrine and paracrine signaling and dramatically reduces sample preparation and data collection time, while reducing undesirable external influence from various manual methods of manipulating cells and media (e.g., cell centrifugation). To validate this system biologically, we focused on cellular responses of Jurkat T cells to microenvironmental stimuli. Application of these stimuli, in conjunction with the cell’s metabolic processes, results in changes in consumption of nutrients and secretion of biomolecules (collectively, the exometabolome), which enable communication with other cells or tissues and elimination of waste. Naïve and experienced T-cell metabolism of cocaine is used as an exemplary system to confirm the platform’s capability, highlight its potential for metabolite discovery applications, and explore immunological memory of T-cell drug exposure. Our platform proved capable of detecting metabolomic variations between naïve and experienced Jurkat T cells and highlights the dynamics of the exometabolome over time. Upregulation of the cocaine metabolite, benzoylecgonine, was noted in experienced T cells, indicating potential cellular memory of cocaine exposure. These metabolomics distinctions were absent from the analogous, traditional “in-culture” UPLC-ESI-IM-MS experiment, further demonstrating this platform’s capabilities.}, number={2}, journal={PLoS ONE}, author={Marasco, C.C. and Enders, J.R. and Seale, K.T. and McLean, J.A. and Wikswo, J.P.}, year={2015} }
 @inproceedings{hitchcock_smith_enders_mcintire_2014, title={Cross-Platform Comparison of Rapid Benzodiazepine Analyses}, author={Hitchcock, Jennifer C. and Smith, Jeremy P. and Enders, Jeffrey R. and McIntire, Gregory L.}, year={2014} }
 @inproceedings{enders_mitchell_geyer_mcintire_2014, title={Easy to Automate Extraction of THC Metabolites for LC-MS/MS Analysis}, author={Enders, Jeffrey R. and Mitchell, Christopher B. and Geyer, Roland and McIntire, Gregory L.}, year={2014} }
 @inproceedings{enders_morris_mcintire_2014, title={Oral Fluid Pain Management Panel by "Dilute and Shoot" LC-MS/MS}, author={Enders, Jeffrey R. and Morris, Ayodele A. and McIntire, Gregory L.}, year={2014} }
 @inproceedings{enders_morris_mcintire_2014, title={Oral Fluid Testing for Buprenorphine and THC by "Dilute and Shoot LC-MS/MS}, author={Enders, Jeffrey R. and Morris, Ayodele A. and McIntire, Gregory L.}, year={2014} }
 @inproceedings{enders_morris_mcintire_2014, title={Oral Fluid Testing for Opiates by Dilute and Shoot LC-MS/MS}, author={Enders, Jeffrey R. and Morris, Ayodele A. and McIntire, Gregory L.}, year={2014} }
 @misc{quantitative analysis using rapid technologies_2014, journal={Rapid Urine Drug Testing by Mass Spectrometry}, year={2014}, month={Oct} }
 @inproceedings{hitchcock_enders_morris_mcintire_2014, title={Rapid Analysis of Selected Benzodiazepines by Automated SPE/MS/MS}, author={Hitchcock, Jennifer C. and Enders, Jeffrey R. and Morris, Ayodele A. and McIntire, Gregory L.}, year={2014} }
 @article{strickland_enders_monge_wallace_mcintire_2014, title={Screening Analysis of Heroin Samples for Possible Cutting Agents and Adulterants}, volume={38}, url={https://www.soft-tox.org/files/toxtalk/SOFT_ToxTalk_v38-3.pdf}, number={3}, journal={ToxTalk}, publisher={Society of Forensic Toxicologists to the Publisher}, author={Strickland, E.C. and Enders, J.R. and Monge, J. and Wallace, F. and McIntire, G.L.}, year={2014}, pages={12–16} }
 @inproceedings{enders_hitchcock_park_morris_mcintire_2013, title={A Quantitative Inspection of ESI Glucuronide Degradation}, author={Enders, Jeffrey R. and Hitchcock, Jennifer C. and Park, Cade W. and Morris, Ayodele A. and McIntire, Gregory L.}, year={2013} }
 @article{enders_marasco_wikswo_mclean_2012, title={A Dual-Column Solid Phase Extraction Strategy for Online Collection and Preparation of Continuously Flowing Effluent Streams for Mass Spectrometry}, volume={84}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac3021032}, DOI={10.1021/ac3021032}, abstractNote={Current desalination techniques for mass spectrometry-based protocols are problematic for performing temporal response studies where increased temporal resolution requires small samples and faster sampling frequencies, which greatly increases the number of samples and sample preparation time. These challenges are pertinent to cellular dynamics experiments, where it is important to sample the biological system frequently and with as little sample waste as possible. To address these needs, we present a dual-column online solid phase extraction (SPE) approach capable of preconcentrating and preparing a constantly perfusing sample stream, with minimal to no sample loss. This strategy is evaluated for use in microfluidic bioreactor studies specifically aimed at characterizing suitable sample flow rates, temporal resolving power, and analyte concentrations. In this work, we demonstrate that this strategy may be used for flow rates as low as 500 nL/min, with temporal resolving power on the order of 3 min, with analyte loadings ranging from femtomoles to picomoles for metabolites. Under these conditions, recoveries of ca. 80% are obtained even at femtomole loadings.}, number={20}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Enders, Jeffrey R. and Marasco, Christina C. and Wikswo, John P. and McLean, John A.}, year={2012}, month={Sep}, pages={8467–8474} }
 @inproceedings{enders_2012, title={Development of a Platform for Online Analysis of the Metabolic Footprint}, author={Enders, J}, year={2012} }
 @misc{hines_enders_mclean_2012, title={Multidimensional Separations by Ion Mobility-Mass Spectrometry}, ISBN={0471976709 9780471976707 0470027312 9780470027318}, url={http://dx.doi.org/10.1002/9780470027318.a9313}, DOI={10.1002/9780470027318.a9313}, abstractNote={Abstract
          Ion mobility‐mass spectrometry (IM‐MS) couples gas‐phase structural separations by IM with mass‐to‐charge separations by MS. The utility of this integration of multidimensional separation dimensions is manifold, including (i) high throughput multidimensional separations, (ii) separation of chemical noise, and (iii) rapid information in structural biology. This article introduces the unique advantages of IM‐MS in biological fields ranging from systems biology to structural biology, the context of which is introduced by a historical perspective of key advances accomplished over the last century. Contemporary and emerging technology for performing IM‐MS is presented, and applications using conformational data sets in proteomics, glycomics, and lipidomics are described.}, journal={Encyclopedia of Analytical Chemistry}, publisher={John Wiley & Sons, Ltd}, author={Hines, Kelly M. and Enders, Jeffrey R. and McLean, John A.}, year={2012}, month={Dec} }
 @inproceedings{enders_marasco_seale_wikswo_mclean_2012, title={Online analysis of a constant-perfusion cell culture microfluidic device for exometabolomic measurements}, author={Enders, Jeffrey R. and Marasco, Christina and Seale, Kevin and Wikswo, John and Mclean, John A.}, year={2012} }
 @inproceedings{enders_2012, title={Strategies and Challenges in Dynamic Systems Biology Analysis Using Structural Mass Spectrometry”}, booktitle={Ion Mobility MS: Applying Ion Mobility-Mass Spectrometry to Challenges in Proteomics and Systems Biology}, author={Enders, J}, year={2012} }
 @inproceedings{enders_marasco_goodwin_may_seale_wikswo_mclean_2011, title={A Microfluidic-Ion Mobility-Mass Spectrometry Platform for Presymptomatic Diagnoses of CBW Agent Exposure}, author={Enders, Jeffrey R. and Marasco, Christina and Goodwin, Cody and May, Jody and Seale, Kevin and Wikswo, John and McLean, John A.}, year={2011} }
 @article{enders_goodwin_marasco_seale_wikswo_mclean_2011, title={Advanced Structural Mass Spectrometry for Systems Biology: Pulling the Needles from Haystacks}, volume={9}, number={3}, journal={Current Trends in Mass Spectrometry}, author={Enders, J.R. and Goodwin, C.R. and Marasco, C.C. and Seale, K.T. and Wikswo, J.P. and McLean, J.A.}, year={2011}, pages={18–23} }
 @inproceedings{enders_marasco_goodwin_may_seale_wikswo_mclean_2011, title={Development of a Platform for Online Acquisition of Empirical Systems Biology Data}, author={Enders, Jeffrey R. and Marasco, Christina and Goodwin, Cody and May, Jody and Seale, Kevin and Wikswo, John and McLean, John A.}, year={2011} }
 @inproceedings{enders_marasco_goodwin_may_seale_wikswo_mclean_2011, title={Microfluidic-Coupled Ion Mobility-Mass Spectrometry Platform for Real-Time, Temporally-Resolved Analysis of Excreted Cellular Materials}, author={Enders, Jeffrey R. and Marasco, Christina and Goodwin, Cody and May, Jody and Seale, Kevin and Wikswo, John and McLean, John A.}, year={2011} }
 @inbook{enders_kliman_sundarapandian_mclean_2011, title={Peptide and Protein Analysis Using Ion Mobility-Mass Spectrometry}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84873040022&partnerID=MN8TOARS}, DOI={10.1002/9781118116555.ch6}, abstractNote={This chapter contains sections titled: Ion Mobility–Mass Spectrometry: Instrumentation and Separation Selectivity Characterizing and Interpreting Peptide and Protein Structures Applications of IM-MS to Peptide and Protein Characterizations Future Directions Acknowledgments References}, booktitle={Protein and Peptide Mass Spectrometry in Drug Discovery}, author={Enders, J.R. and Kliman, M. and Sundarapandian, S. and Mclean, J.A.}, year={2011}, pages={139–174} }
 @inproceedings{mclean_enders_may_seale_wikswo_2010, title={Advanced Structural Mass Spectrometry for Systems Biology – Towards Presymptomatic Diagnosis of Threat Agent Exposure}, author={McLean, John and Enders, Jeffrey and May, Jody and Seale, Kevin and Wikswo, John}, year={2010} }
 @inproceedings{enders_marasco_goodwin_seale_wikswo_mclean_2010, title={Characterizing the Saccharomyces cerevisiae respiratory oscillation exometabolome by ion mobility-mass spectrometry}, author={Enders, Jeffrey R. and Marasco, Christina and Goodwin, Cody and Seale, Kevin and Wikswo, John and McLean, John}, year={2010} }
 @inproceedings{may_sundarapandian_enders_seale_wikswo_mclean_2010, title={Development of a Multi-Channel Ion Mobility-Mass Spectrometer for High-Throughput Interrogation of Cellular Response}, author={May, Jody and Sundarapandian, Sevugarajan and Enders, Jeffrey R. and Seale, Kevin T. and Wikswo, John P. and McLean, John A.}, year={2010} }
 @inproceedings{may_enders_sundarapandian_seale_wikswo_mclean_2010, title={Development of a Multiplexed (8-Channel) Ion Mobility-Mass Spectrometer Chemical Analyzer for Rapid Interrogation of Biochemical Response}, author={May, Jody and Enders, Jeffrey R. and Sundarapandian, Sevugarajan and Seale, Kevin and Wikswo, John and McLean, John A.}, year={2010} }
 @inproceedings{may_enders_sundarapandian_seale_wikswo_mclean_2010, title={High-Throughput Ion Mobility-Mass Spectrometry Strategies for Monitoring Cellular Response in Real Time}, author={May, Jody C. and Enders, Jeffrey R. and Sundarapandian, Sevugarajan and Seale, Kevin T. and Wikswo, John P. and Mclean, John A.}, year={2010} }
 @inproceedings{marasco_enders_seale_mclean_wikswo_2010, title={Investigating Leukocyte Dynamic Response to Stimuli in an Integrated Microfluidic-Ion Mobility-Mass Spectrometer}, author={Marasco, Christina and Enders, Jeffrey and Seale, Kevin and McLean, John and Wikswo, John}, year={2010} }
 @book{mclean_fenn_enders_2010, title={Structurally selective imaging mass spectrometry by imaging ion mobility-mass spectrometry}, volume={656}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-81055146017&partnerID=MN8TOARS}, DOI={10.1007/978-1-60761-746-4_21}, abstractNote={This chapter describes the utility of structurally based separations combined with imaging mass spectrometry (MS) by ion mobility-MS (IM-MS) approaches. The unique capabilities of combining rapid (mus-ms) IM separations with imaging MS are detailed for an audience ranging from new to potential practitioners in IM-MS technology. Importantly, imaging IM-MS provides the ability to rapidly separate and elucidate various types of endogenous and exogenous biomolecules (e.g., nucleotides, carbohydrates, peptides, and lipids), including isobaric species. Drift tube and traveling wave IM-MS instrumentation are described and specific protocols are presented for calculating ion-neutral collision cross sections (i.e., apparent ion surface area or structure) from experimentally obtained IM-MS data. Special emphasis is placed on the use of imaging IM-MS for the analysis of samples in life sciences research (e.g., thin tissue sections), including selective imaging for peptide/protein and lipid distributions. Future directions for rapid and multiplexed imaging IM-MS/MS are detailed.}, journal={Methods in Molecular Biology}, author={McLean, J.A. and Fenn, L.S. and Enders, J.R.}, year={2010}, pages={363–383} }
 @inproceedings{enders_goodwin_marasco_may_seale_wikswo_mclean_2010, title={Temporal Analysis of Biological Fluid for the Analysis of Cellular Signaling and Response Using Ion Mobility-mass Spectrometry Analyses}, author={Enders, Jeffrey R. and Goodwin, Cody and Marasco, Christina and May, Jody and Seale, Kevin and Wikswo, John and McLean, John}, year={2010} }
 @article{enders_marasco_kole_nguyen_sevugarajan_seale_wikswo_mclean_2010, title={Towards monitoring real-time cellular response using an integrated microfluidics-matrix assisted laser desorption ionisation/nanoelectrospray ionisation-ion mobility-mass spectrometry platform}, volume={4}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-78149440921&partnerID=MN8TOARS}, DOI={10.1049/iet-syb.2010.0012}, abstractNote={The combination of microfluidic cell trapping devices with ion mobility-mass spectrometry offers the potential for elucidating in real time the dynamic responses of small populations of cells to paracrine signals, changes in metabolite levels and delivery of drugs and toxins. Preliminary experiments examining peptides in methanol and recording the interactions of yeast and Jurkat cells with their superfusate have identified instrumental set-up and control parameters and online desalting procedures. Numerous initial experiments demonstrate and validate this new instrumental platform. Future outlooks and potential applications are addressed, specifically how this instrumentation may be used for fully automated systems biology studies of the significantly interdependent, dynamic internal workings of cellular metabolic and signalling pathways.}, number={6}, journal={IET Systems Biology}, author={Enders, J.R. and Marasco, C.C. and Kole, A. and Nguyen, B. and Sevugarajan, S. and Seale, K.T. and Wikswo, J.P. and McLean, J.A.}, year={2010}, pages={416–427} }
 @article{enders_mclean_2009, title={Chiral and structural analysis of biomolecules using mass spectrometry and ion mobility-mass spectrometry}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77953007110&partnerID=MN8TOARS}, DOI={10.1002/chir.20806}, abstractNote={AbstractThis report describes the strategies for gas‐phase chiral and structural characterization of biomolecules using mass spectrometry (MS) and ion mobility‐MS (IM‐MS) techniques. Because both MS and IM‐MS do not directly provide chiral selectivity, methodologies for adding a chiral selector are discussed in the context of (i) host–guest (H–G) associations, (ii) diastereomeric collision‐induced dissociation (CID) methods, (iii) ion–molecule reactions, and (iv) the kinetic method. MS techniques for the analysis of proteins and protein complexes are briefly described. New advances in performing rapid 2D gas‐phase separations on the basis of IM‐MS are reviewed with a particular emphasis on the different forms of IM instrumentation and how they are used for chiral and/or structural biomolecular studies. This report is not intended to be a comprehensive review of the field, but rather to underscore the contemporary techniques that are commonly or increasingly being used to complement measurements performed by chiroptical methodologies. Chirality 21:E253–E264, 2009. © 2009 Wiley‐Liss, Inc.}, number={1 E}, journal={Chirality}, author={Enders, J.R. and Mclean, J.A.}, year={2009} }
 @inproceedings{enders_sundarapandian_seale_wikswo_mclean_2009, title={Combining microfluidic cell trapping with real time monitoring of biomolecular exudates by ion mobility-mass spectrometry}, author={Enders, Jeffrey R. and Sundarapandian, Sevugarajan and Seale, Kevin and Wikswo, John P. and McLean, John A.}, year={2009} }
 @inproceedings{enders_sundarapandian_seale_wikswo_mclean_2009, title={Measuring real-time cellular responses to chemical and biological warfare agents using structural mass spectrometry techniques}, author={Enders, Jeffrey R. and Sundarapandian, Sevugarajan and Seale, Kevin and Wikswo, John P. and McLean, John A.}, year={2009} }
 @inproceedings{enders_sundarapandian_kole_nguyen_seale_wikswo_mclean_2009, title={Microfluidic-ion mobility-mass spectrometry for assessing cellular response in real time}, author={Enders, Jeffrey R. and Sundarapandian, Sevugarajan and Kole, Ayeeshik and Nguyen, Bao and Seale, Kevin and Wikswo, John P. and McLean, John A.}, year={2009} }
 @inproceedings{enders_sundarapandian_seale_wikswo_mclean_2009, title={Microfluidic-ion mobility-mass spectrometry for assessing cellular response in real time}, author={Enders, J and Sundarapandian, Sevugarajan and Seale, Kevin T. and Wikswo, John P. and McLean, John A.}, year={2009} }
 @inproceedings{enders_sundarapandian_seale_wikswo_mclean_2009, title={Real time analysis of cell signaling and response using microfluidic cell trapping-ion mobility-mass spectrometry}, author={Enders, Jeffrey R. and Sundarapandian, Sevugarajan and Seale, Kevin and Wikswo, John P. and McLean, John A.}, year={2009} }
 @inproceedings{enders_sundarapandian_seale_wikswo_mclean_2008, title={Dynamic Biomolecular Measurements of Cellular Response by Ion Mobility-Mass Spectrometry: A New Strategy for Systems Biology}, author={Enders, Jeffrey R. and Sundarapandian, Sevugarajan and Seale, Kevin and Wikswo, John P. and McLean, John A.}, year={2008} }
 @inproceedings{enders_fenn_aldersley_ferris_joshi_mclean_zagorevski_2008, title={Ion Mobility Mass Spectrometry of the products of oligomerization of activated nucleotides with Montmorillonite}, author={Enders, Jeffrey R. and Fenn, Larissa S. and Aldersley, Michael F. and Ferris, James P. and Joshi, Prakash C. and Mclean, John A. and Zagorevski, Dmitri}, year={2008} }