CIEHS Member Publication Finder

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  • Mazzocco JC, Jagadapillai R, Gozal E, Kong M, Xu Q, Barnes GN, Freedman JH. Disruption of essential metal homeostasis in the brain by cadmium and high-fat diet. Toxicol Rep. 2020 Aug 23;7:1164-1169. doi: 10.1016/j.toxrep.2020.08.005. PMID: 32983904; PMCID: PMC7494587.
  • Tian Z, Chu T, Shields LBE, Zhu Q, Zhang YP, Kong M, Barnes GN, Wang Y, Shields CB, Cai J. Platelet-Activating Factor Deteriorates Lysophosphatidylcholine-Induced Demyelination Via Its Receptor-Dependent and -Independent Effects. Mol Neurobiol. 2020 Oct;57(10):4069-4081. doi: 10.1007/s12035-020-02003-3. Epub 2020 Jul 13. PMID: 32661728.
  • Zhang Y, Cao H, Qiu X, Xu D, Chen Y, Barnes GN, Tu Y, Gyabaah AT, Gharbal AHAA, Peng C, Cai J, Cai X. Neuroprotective Effects of Adenosine A1 Receptor Signaling on Cognitive Impairment Induced by Chronic Intermittent Hypoxia in Mice. Front Cell Neurosci. 2020 Jul 9;14:202. doi: 10.3389/fncel.2020.00202. PMID: 32733207; PMCID: PMC7363980.
  • Baba S, Smith T, Hellmann J, Bhatnagar A, Carter K, Vanhoover A, Caruso J. Space Flight Diet-Induced Deficiency and Response to Gravity-Free Resistive Exercise. Nutrients. 2020 Aug 11;12(8):2400. doi: 10.3390/nu12082400. PMID: 32796546; PMCID: PMC7468946.
  • Galbraith NJ, Gardner SA, Walker SP, Trainor P, Carter JV, Bishop C, Sarojini H, O'Brien SJ, Bhatnagar A, Polk HC Jr, Galandiuk S. The role and function of IκKα/β in monocyte impairment. Sci Rep. 2020 Jul 22;10(1):12222. doi: 10.1038/s41598-020-68018-x. PMID: 32699255; PMCID: PMC7376008.
  • Irfan AB, Arab C, DeFilippis AP, Lorkiewicz P, Keith RJ, Xie Z, Bhatnagar A, Carll AP. Smoking Accelerates Atrioventricular Conduction in Humans Concordant with Increased Dopamine Release. Cardiovasc Toxicol. 2020 Oct 12. doi: 10.1007/s12012-020-09610-5. Epub ahead of print. PMID: 33043409.
  • Rai SN, Qian C, Pan J, Seth A, Srivastava DK, Bhatnagar A. Statistical design of Phase II/III clinical trials for testing therapeutic interventions in COVID-19 patients. BMC Med Res Methodol. 2020 Aug 31;20(1):220. doi: 10.1186/s12874-020-01101-z. PMID: 32867708; PMCID: PMC745675
  • Cave MC. Environmental Pollution and the Developmental Origins of Childhood Liver Disease. Hepatology. 2020 Nov;72(5):1518-1521. doi: 10.1002/hep.31549. PMID: 32910501.
  • Lin Q, Huang Z, Cai G, Fan X, Yan X, Liu Z, Zhao Z, Li J, Li J, Shi H, Kong M, Zheng MH, Conklin DJ, Epstein PN, Kupper AW, Mohammadi M, Cai L, Li X, Li Y, Tan Y. Activating AMP-activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection from Nonalcoholic Fatty Liver Disease in Mice. Hepatology. 2020 Sep 23. doi: 10.1002/hep.31568. Epub ahead of print. PMID: 32965675.
  • Mohamed TMA, Conklin DJ. Emerging technology and platforms for cardiotoxicity testing. Toxicol Appl Pharmacol. 2020 Dec 1;408:115262. doi: 10.1016/j.taap.2020.115262. Epub 2020 Oct 2. PMID: 33017593.
  • Lynch J, Jin L, Richardson A, Conklin DJ. Tobacco Smoke and Endothelial Dysfunction: Role of Aldehydes? Curr Hypertens Rep. 2020 Aug 28;22(9):73. doi: 10.1007/s11906-020-01085-7. PMID: 32857217.
  • Miller JM, Meki MH, Ou Q, George SA, Gams A, Abouleisa RRE, Tang XL, Ahern BM, Giridharan GA, El-Baz A, Hill BG, Satin J, Conklin DJ, Moslehi J, Bolli R, Ribeiro AJS, Efimov IR, Mohamed TMA. Heart slice culture system reliably demonstrates clinical drug-related cardiotoxicity. Toxicol Appl Pharmacol. 2020 Nov 1;406:115213. doi: 10.1016/j.taap.2020.115213. Epub 2020 Aug 30. PMID: 32877659; PMCID: PMC7554180.
  • Hawkins AT, Wise PE, Chan T, Lee JT, Glyn T, Wood V, Eglinton T, Frizelle F, Khan A, Hall J, Ilyas MIM, Michailidou M, Nfonsam VN, Cowan ML, Williams J, Steele SR, Alavi K, Ellis CT, Collins D, Winter DC, Zaghiyan K, Gallo G, Carvello M, Spinelli A, Lightner AL. Diverticulitis: An Update From the Age Old Paradigm. Curr Probl Surg. 2020 Oct;57(10):100862. doi: 10.1016/j.cpsurg.2020.100862. Epub 2020 Jul 18. PMID: 33077029; PMCID: PMC7575828.
  • Shrader SH, Tong YG, Duff MB, Freedman JH, Song ZH. Involvement of dopamine receptor in the actions of non-psychoactive phytocannabinoids. Biochem Biophys Res Commun. 2020 Oct 21:S0006-291X(20)31930-6. doi: 10.1016/j.bbrc.2020.10.021. Epub ahead of print. PMID: 33097185.
  • Hein DW, Millner LM. Arylamine N-acetyltransferase acetylation polymorphisms: paradigm for pharmacogenomic-guided therapy- a focused review. Expert Opin Drug Metab Toxicol. 2020 Nov 3:1-13. doi: 10.1080/17425255.2021.1840551. Epub ahead of print. PMID: 33094670. PMCID 7790970.
  • Hong KU, Doll MA, Lykoudi A, Salazar-González RA, Habil MR, Walls KM, Bakr AF, Ghare SS, Barve SS, Arteel GE, Hein DW. Acetylator Genotype-Dependent Dyslipidemia in Rats Congenic for N-Acetyltransferase 2. Toxicol Rep. 2020 Sep 28;7:1319-1330. doi: 10.1016/j.toxrep.2020.09.011. PMID: 33083237; PMCID: PMC7553889.
  • Nardi D, Waite R, Nowak M, Hatcher B, Hines-Martin V, Stacciarini JR. Achieving Health Equity Through Eradicating Structural Racism in the United States: A Call to Action for Nursing Leadership. J Nurs Scholarsh. 2020 Oct 1. doi: 10.1111/jnu.12602. Epub ahead of print. PMID: 33002309.
  • Metcalf S, Petri BJ, Kruer T, Green B, Dougherty S, Wittliff JL, Klinge CM, Clem BF. Serine synthesis influences tamoxifen response in ER+ human breast carcinoma. Endocr Relat Cancer. 2020 Oct 1:ERC-19-0510.R2. doi: 10.1530/ERC-19-0510. Epub ahead of print. PMID: 33112838.
  • Shi H, Jin J, Hardesty JE, Falkner KC, Prough RA, Balamurugan AN, Mokshagundam SP, Chari ST, Cave MC. Corrigendum to "Polychlorinated biphenyl exposures differentially regulate hepatic metabolism and pancreatic function: Implications for nonalcoholic steatohepatitis and diabetes" [Toxicology & Applied Pharmacology, 363 (2018) 22-33]. Toxicol Appl Pharmacol. 2020 Oct 1;404:115149. doi: 10.1016/j.taap.2020.115149. Epub 2020 Jul 20. Erratum for: Toxicol Appl Pharmacol. 2019 Jan 15;363:22-33. PMID: 32702359.
  • Leggett CS, Doll MA, States JC, Hein DW. Acetylation of putative arylamine and alkylaniline carcinogens in immortalized human fibroblasts transfected with rapid and slow acetylator N-acetyltransferase 2 haplotypes. Arch Toxicol. 2020 Nov 2. doi: 10.1007/s00204-020-02901-4. Epub ahead of print. PMID: 33136180.
  • Ferragut Cardoso AP, Udoh KT, States JC. Arsenic-induced changes in miRNA expression in cancer and other diseases. Toxicol Appl Pharmacol. 2020 Oct 28;409:115306. doi: 10.1016/j.taap.2020.115306. Epub ahead of print. PMID: 33127375.
  • Mandal RK, Denny JE, Waide ML, Li Q, Bhutiani N, Anderson CD, Baby BV, Jala VR, Egilmez NK, Schmidt NW. Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility. BMC Biol. 2020 Jul 3;18(1):83. doi: 10.1186/s12915-020-00810-7. PMID: 32620114; PMCID: PMC7334859.
  • Annett RD, Chervinskiy S, Chun TH, Cowan K, Foster K, Goodrich N, Hirschfeld M, Hsia DS, Jarvis JD, Kulbeth K, Madden C, Nesmith C, Raissy H, Ross J, Saul JP, Shiramizu B, Smith P, Sullivan JE, Tucker L, Atz AM. IDeA States Pediatric Clinical Trials Network for Underserved and Rural Communities. Pediatrics. 2020 Oct;146(4):e20200290. doi: 10.1542/peds.2020-0290. Epub 2020 Sep 17. PMID: 32943534.
  • Kolonics F, Kajdácsi E, Farkas VJ, Veres DS, Khamari D, Kittel Á, Merchant ML, McLeish KR, Lőrincz ÁM, Ligeti E. Neutrophils produce proinflammatory or anti-inflammatory extracellular vesicles depending on the environmental conditions. J Leukoc Biol. 2020 Sep 18. doi: 10.1002/JLB.3A0320-210R. Epub ahead of print. PMID: 32946637.
  • Samuel G, Crow J, Klein JB, Merchant ML, Nissen E, Koestler DC, Laurence K, Liang X, Neville K, Staggs V, Ahmed A, Atay S, Godwin AK. Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers. Oncotarget. 2020 Aug 4;11(31):2995-3012. doi: 10.18632/oncotarget.27678. PMID: 32821345; PMCID: PMC7415402.
  • Satoskar AA, Shapiro JP, Jones M, Bott C, Parikh SV, Brodsky SV, Yu L, Nagaraja HN, Wilkey DW, Merchant ML, Klein JB, Nadasdy T, Rovin BH. Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study. Sci Rep. 2020 Oct 14;10(1):17179. doi: 10.1038/s41598-020-73847-x. PMID: 33057112; PMCID: PMC7560901.
  • Sears L, Sears CG, Myers JV, Brock GN, Zierold KM. Associations of the Behavioral Assessment and Research System (BARS) neurobehavioral outcomes with attention problems in children living near coal ash storage sites. Neurotoxicology. 2020 Aug 15;81:11-17. doi: 10.1016/j.neuro.2020.08.002. Epub ahead of print. PMID: 32810513.
  • Kim C, States JC, Ceresa BP. Chronic and acute arsenic exposure enhance EGFR expression via distinct molecular mechanisms. Toxicol In Vitro. 2020 Sep;67:104925. doi: 10.1016/j.tiv.2020.104925. Epub 2020 Jun 26. PMID: 32599262; PMCID: PMC7375208.
  • Bushau-Sprinkle A, Barati MT, Gagnon KB, Khundmiri SJ, Kitterman K, Hill BG, Sherwood A, Merchant M, Rai SN, Srivastava S, Clark B, Siskind L, Brier M, Hata J, Lederer E. NHERF1 Loss Upregulates Enzymes of the Pentose Phosphate Pathway in Kidney Cortex. Antioxidants (Basel). 2020 Sep 14;9(9):862. doi: 10.3390/antiox9090862. PMID: 32937931; PMCID: PMC7554817.
  • Mo Y, Zhang Y, Mo L, Wan R, Jiang M, Zhang Q. The role of miR-21 in nickel nanoparticle-induced MMP-2 and MMP-9 production in mouse primary monocytes: In vitro and in vivo studies. Environ Pollut. 2020 Dec;267:115597. doi: 10.1016/j.envpol.2020.115597. Epub 2020 Sep 4. PMID: 33254626; PMCID: PMC7708676.
  • Xie W, Kathuria H, Galiatsatos P, Blaha MJ, Hamburg NM, Robertson RM, Bhatnagar A, Benjamin EJ, Stokes AC. Association of Electronic Cigarette Use With Incident Respiratory Conditions Among US Adults From 2013 to 2018. JAMA Netw Open. 2020 Nov 2;3(11):e2020816. doi: 10.1001/jamanetworkopen.2020.20816. PMID: 33180127; PMCID: PMC7662143.
  • Cave MC. Environmental Pollution and the Developmental Origins of Childhood Liver Disease. Hepatology. 2020 Nov;72(5):1518-1521. doi: 10.1002/hep.31549. PMID: 32910501.
  • Xie C, Sun K, You Y, Ming Y, Yu X, Yu L, Huang J, Yan M. Correction to: Feasibility and efficacy of lung ultrasound to investigate pulmonary complications in patients who developed postoperative Hypoxaemia-a prospective study. BMC Anesthesiol. 2020 Nov 9;20(1):281. doi: 10.1186/s12871-020-01196-3. Erratum for: BMC Anesthesiol. 2020 Sep 1;20(1):220. PMID: 33167910; PMCID: PMC7650153.
  • Bowland, S. & Hines-Martin, V. (2020). Strengthening health in mixed-age housing communities. Journal of Health and Human Services Administration, 43(2), 218-234.
  • Song K, Xu Q, Koenig HM, Kong M, Slaughter MS, Huang Y, Clifford SP, Huang J. Validation of a Novel NeurOs Cerebral Oximetry Monitor Against the INVOS Monitor During Cardiac Surgery. J Cardiothorac Vasc Anesth. 2020 Oct 27:S1053-0770(20)31157-5. doi: 10.1053/j.jvca.2020.10.043. Epub ahead of print. PMID: 33218956.
  • Brier ME, Gooding JR, Harrington JM, Burgess JP, McRitchie SL, Zhang X, Rovin BH, Klein JB, Himmelfarb J, Sumner SJ, Merchant ML. Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients. Sci Rep. 2020 Nov 19;10(1):20202. doi: 10.1038/s41598-020-77311-8. PMID: 33214633; PMCID: PMC7677396.
  • O'Toole TE, Li X, Riggs DW, Hoetker DJ, Yeager R, Lorkiewicz P, Baba SP, Cooper NGF, Bhatnagar A. Urinary levels of the acrolein conjugates of carnosine are associated with inhaled toxicants. Inhal Toxicol. 2020 Nov 12:1-9. doi: 10.1080/08958378.2020.1845257. Epub ahead of print. PMID: 33179563.
  • Das S, Rai SN. Statistical Approach for Biologically Relevant Gene Selection from High-Throughput Gene Expression Data. Entropy (Basel). 2020 Oct 25;22(11):E1205. doi: 10.3390/e22111205. PMID: 33286973.
  • Zierold KM, Sears CG, Hagemeyer AN, Brock GN, Polivka BJ, Zhang CH, Sears L. Protocol for measuring indoor exposure to coal fly ash and heavy metals, and neurobehavioural symptoms in children aged 6 to 14 years old. BMJ Open. 2020 Nov 23;10(11):e038960. doi: 10.1136/bmjopen-2020-038960. PMID: 33234632; PMCID: PMC7684807.
  • Leggett CS, Doll MA, States JCHein DW. Acetylation of putative arylamine and alkylaniline carcinogens in immortalized human fibroblasts transfected with rapid and slow acetylator N-acetyltransferase 2 haplotypes. Arch Toxicol. 2020 Nov 2. doi: 10.1007/s00204-020-02901-4. Epub ahead of print. PMID: 33136180.
  • Mo Y, Zhang Y, Wan R, Jiang M, Xu Y, Zhang Q. miR-21 mediates nickel nanoparticle-induced pulmonary injury and fibrosis. Nanotoxicology. 2020 Nov;14(9):1175-1197. doi: 10.1080/17435390.2020.1808727. Epub 2020 Sep 14. PMID: 32924694.
  • Hines-Martin, V.P. (2020). Community displacement, environmental change and the impact on mental well-being. Archives of Psychiatric Nursing, ISSN 0883-9417. https://doi.org/10.1016/j.apnu.2020.10.012.
  • O'Toole TE, Amraotkar AA, DeFilippis AP, Rai SN, Keith RJ, Baba SP, Lorkiewicz P, Crandell CE, Pariser GL, Wingard CJ, Pope Iii CA, Bhatnagar A. Protocol to assess the efficacy of carnosine supplementation in mitigating the adverse cardiovascular responses to particulate matter (PM) exposure: the Nucleophilic Defense Against PM Toxicity (NEAT) trial. BMJ Open. 2020 Dec 28;10(12):e039118. doi: 10.1136/bmjopen-2020-039118. PMID: 33372072; PMCID: PMC7772308.
  • Metcalf S, Petri BJ, Kruer T, Green B, Dougherty S, Wittliff JL, Klinge CM, Clem BF. Serine synthesis influences tamoxifen response in ER+ human breast carcinoma. Endocr Relat Cancer. 2021 Jan;28(1):27-37. doi: 10.1530/ERC-19-0510. PMID: 33112838; PMCID: PMC7780089.
  • O'Toole TE, Li X, Riggs DW, Hoetker DJ, Baba SP, Bhatnagar A. Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk. Int J Mol Sci. 2021 Jan 30;22(3):1383. doi: 10.3390/ijms22031383. PMID: 33573153; PMCID: PMC7866516.
  • Bhattacharyya A, Seth A, Srivast N, Imeokparia M, Rai S. Coronavirus (COVID-19): A Systematic Review and Meta-analysis to Evaluate the Significance of Demographics and Comorbidities. Res Sq [Preprint]. 2021 Jan 18:rs.3.rs-144684. doi: 10.21203/rs.3.rs-144684/v1. PMID: 33469575; PMCID: PMC7814834.
  • Farley G, Riggs DW, Bhatnagar A, Hellmann J. Omega-3 polyunsaturated fatty acids modify the inverse association between systemic inflammation and cardiovascular fitness. Clin Nutr. 2021 Feb 11:S0261-5614(21)00080-7. doi: 10.1016/j.clnu.2021.02.006. Epub ahead of print. PMID: 33618966.
  • Wang X, Chen X, Xu H, Zhou S, Zheng Y, Keller BB, Cai L. Emerging roles of microRNA-208a in cardiology and reverse cardio-oncology. Med Res Rev. 2021 Feb 3. doi: 10.1002/med.21790. Epub ahead of print. PMID: 33533026.
  • Li Y, Fan H, Yuan F, Lu L, Liu J, Feng W, Zhang HG, Chen SY. Sulforaphane Protects Against Ethanol-Induced Apoptosis in Human Neural Crest Cells Through Diminishing Ethanol-Induced Hypermethylation at the Promoters of the Genes Encoding the Inhibitor of Apoptosis Proteins. Front Cell Dev Biol. 2021 Feb 9;9:622152. doi: 10.3389/fcell.2021.622152. PMID: 33634123; PMCID: PMC7900432.
  • Clifford SP, Ramirez J, Akca O, Ghafghazi S, Huang J. Perioperative Cardiac Research Considerations During the Coronavirus Disease 2019 (COVID-19) Pandemic. J Cardiothorac Vasc Anesth. 2021 Feb 5:S1053-0770(21)00089-6. doi: 10.1053/j.jvca.2021.01.052. Epub ahead of print. PMID: 33618962; PMCID: PMC7863767.
  • Cardarelli KM, Ickes M, Huntington-Moskos L, Wilmhoff C, Larck A, Pinney SM, Hahn EJ. Authentic Youth Engagement in Environmental Health Research and Advocacy. Int J Environ Res Public Health. 2021 Feb 23;18(4):2154. doi: 10.3390/ijerph18042154. PMID: 33672107; PMCID: PMC7926324.
  • Ghosh S, Whitley CS, Haribabu B, Jala VR. Regulation of Intestinal Barrier Function by Microbial Metabolites. Cell Mol Gastroenterol Hepatol. 2021;11(5):1463-1482. doi: 10.1016/j.jcmgh.2021.02.007. Epub 2021 Feb 18. PMID: 33610769; PMCID: PMC8025057.
  • Landers VD, Wilkey DW, Merchant ML, Mitchell TC, Sokoloski KJ. The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling. Viruses. 2021 Feb 27;13(3):377. doi: 10.3390/v13030377. PMID: 33673546.
  • Caster DJ, Korte EA, Merchant ML, Klein JB, Barati MT, Joglekar A, Wilkey DW, Coventry S, Hata J, Rovin BH, Harley JB, Namjou-Khales B, McLeish KR, Powell DW. Patients with Proliferative Lupus Nephritis Have Autoantibodies That React to Moesin and Demonstrate Increased Glomerular Moesin Expression. J Clin Med. 2021 Feb 16;10(4):793. doi: 10.3390/jcm10040793. PMID: 33669337; PMCID: PMC7920286.
  • Singh P, O'Toole TEConklin DJ, Hill BG, Haberzettl P. Endothelial Progenitor Cells as Critical Mediators of Environmental Air Pollution-Induced Cardiovascular Toxicity. Am J Physiol Heart Circ Physiol. 2021 Feb 19. doi: 10.1152/ajpheart.00804.2020. Epub ahead of print. PMID: 33606580.
  • Kaplin A, Junker C, Kumar A, Ribeiro MA, Yu E, Wang M, Smith T, Rai SN, Bhatnagar A. Evidence and magnitude of the effects of meteorological changes on SARS-CoV-2 transmission. PLoS One. 2021 Feb 17;16(2):e0246167. doi: 10.1371/journal.pone.0246167. PMID: 33596214; PMCID: PMC7888632.
  • McGraw KE, Riggs DW, Rai S, Navas-Acien A, Xie Z, Lorkiewicz P, Lynch J, Zafar N, Krishnasamy S, Taylor KC, Conklin DJ, DeFilippis AP, Srivastava SBhatnagar A. Exposure to Volatile Organic Compounds - Acrolein, 1,3-Butadiene, and Crotonaldehyde - is Associated with Vascular Dysfunction. Environ Res. 2021 Feb 23:110903. doi: 10.1016/j.envres.2021.110903. Epub ahead of print. PMID: 33636185.
  • Jin L, Lynch J, Richardson A, Lorkiewicz P, Srivastava S, Theis W, Shirk G, Hand A, Bhatnagar A, Srivastava S, Conklin DJ. Electronic Cigarette Solvents, Pulmonary Irritation and Endothelial Dysfunction:Role of Acetaldehyde and Formaldehyde. Am J Physiol Heart Circ Physiol. 2021 Feb 5. doi: 10.1152/ajpheart.00878.2020. Epub ahead of print. PMID: 33543686.
  • Poirier MC, Marsili L, Fossi MC, Godard-Codding CAJ, Hernandez-Ramon EE, Si N, Divi KV, Divi RL, Kerr I, Wise JP, Wise CF, Wise SS, Aboueissa AM, Wise JTF, Wise JP. Polycyclic Aromatic Hydrocarbon-DNA Adducts in Gulf of Mexico Sperm Whale Skin Biopsies Collected in 2012. Toxicol Sci. 2021 Feb 10:kfab016. doi: 10.1093/toxsci/kfab016. Epub ahead of print. PMID: 33566103
  • Haweel R, Shalaby A, Mahmoud A, Seada N, Ghoniemy S, Ghazal M, Casanova MF, Barnes GN, El-Baz A. A Robust DWT-CNN Based CAD System for Early Diagnosis of Autism Using Task-based fMRI. Med Phys. 2020 Dec 30. doi: 10.1002/mp.14692. Epub ahead of print. PMID: 33378589.
  • Fontenele RS, Kraberger S, Hadfield J, Driver EM, Bowes D, Holland LA, Faleye TOC, Adhikari S, Kumar R, Inchausti R, Holmes WK, Deitrick S, Brown P, Duty D, Smith T, Bhatnagar A, Yeager RA, Holm RH, Hoogesteijn von Reitzenstein N, Wheeler E, Dixon K, Constantine T, Wilson MA, Lim ES, Jiang X, Halden RU, Scotch M, Varsani A. High-throughput sequencing of SARS-CoV-2 in wastewater provides insights into circulating variants. medRxiv [Preprint]. 2021 Jan 25:2021.01.22.21250320. doi: 10.1101/2021.01.22.21250320. PMID: 33501452; PMCID: PMC7836124.
  • Stokes AC, Xie W, Wilson AE, Yang H, Orimoloye OA, Harlow AF, Fetterman JL, DeFilippis AP, Benjamin EJ, Robertson RM, Bhatnagar A, Hamburg NM, Blaha MJ. Association of Cigarette and Electronic Cigarette Use Patterns With Levels of Inflammatory and Oxidative Stress Biomarkers Among US Adults: Population Assessment of Tobacco and Health Study. Circulation. 2021 Jan 4. doi: 10.1161/CIRCULATIONAHA.120.051551. Epub ahead of print. PMID: 33390037.
  • Harlow AF, Fetterman JL, Ross CS, Robertson RM, Bhatnagar A, Benjamin EJ, Stokes AC. Association of device type, flavours and vaping behaviour with tobacco product transitions among adult electronic cigarette users in the USA. Tob Control. 2021 Jan 21:tobaccocontrol-2020-055999. doi: 10.1136/tobaccocontrol-2020-055999. Epub ahead of print. PMID: 33479031
  • Li J, Liu L, Zhou WQ, Cai L, Xu ZG, Rane MJ. Roles of Krüppel-like factor 5 in kidney disease. J Cell Mol Med. 2021 Feb 1. doi: 10.1111/jcmm.16332. Epub ahead of print. PMID: 33523554.
  • Yearwood EL, Hines-Martin VP. Editorial: Impact of social determinants of health on mental health. Arch Psychiatr Nurs. 2021 Feb;35(1):A1-A2. doi: 10.1016/j.apnu.2020.12.001. Epub 2021 Jan 8. PMID: 33593523.
  • Wei P, Li J, Huang J, Zhang T, Tang W. Radial artery catheterisation pressure monitoring with a closed intravascular catheter system and ultrasound-guided dynamic needle tip positioning technique. Br J Anaesth. 2021 Jan 26:S0007-0912(20)31055-2. doi: 10.1016/j.bja.2020.12.033. Epub ahead of print. PMID: 33514485.
  • Eldeirawi K, Huntington-Moskos L, Nyenhuis SM, Polivka B. Increased disinfectant use among adults with asthma in the era of COVID-19. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1378-1380.e2. doi: 10.1016/j.jaip.2020.12.038. Epub 2020 Dec 29. PMID: 33385592; PMCID: PMC7832809
  • Swovick K, Firsanov D, Welle KA, Hryhorenko JR, Wise JP Sr, George C, Sformo TL, Seluanov A, Gorbunova V, Ghaemmaghami S. Interspecies Differences in Proteome Turnover Kinetics Are Correlated With Life Spans and Energetic Demands. Mol Cell Proteomics. 2021 Jan 7;20:100041. doi: 10.1074/mcp.RA120.002301. Epub ahead of print. PMID: 33639418.
  • Riggs DW, Yeager RConklin DJ, DeJarnett N, Keith RJ, DeFilippis AP, Rai SNBhatnagar A. Residential Proximity to Greenness Mitigates the Hemodynamic Effects of Ambient Air Pollution. Am J Physiol Heart Circ Physiol. 2021 Jan 8. doi: 10.1152/ajpheart.00689.2020. Epub ahead of print. PMID: 33416460.
  • Oshunbade AA, Kassahun-Yimer W, Valle KA, Hamid A, Kipchumba RK, Kamimura D, Clark D 3rd, White WB, DeFilippis AP, Blaha MJ, Benjamin EJ, O'Brien EC, Mentz RJ, Rodriguez CJ, Fox ER, Butler J, Keith RJ, Bhatnagar A, Marie Robertson R, Correa A, Hall ME. Cigarette Smoking, Incident Coronary Heart Disease, and Coronary Artery Calcification in Black Adults: The Jackson Heart Study. J Am Heart Assoc. 2021 Apr 6;10(7):e017320. doi: 10.1161/JAHA.120.017320. Epub 2021 Mar 23. PMID: 33754833.
    Impact Statement: In Black individuals cigarette smoking can exacerbate heart failure and increase the risk of hospital admissions for heart failure
  • Keith R, Bhatnagar A. Cardiorespiratory and Immunologic Effects of Electronic Cigarettes. Curr Addict Rep. 2021 Mar 5:1-11. doi: 10.1007/s40429-021-00359-7. Epub ahead of print. PMID: 33717828; PMCID: PMC7935224.
    Impact Statement: This review discusses evidence showing that the use of e-cigarettes is associated with a range of cardiovascular and immunological changes that could be detrimental to health
  • Ohanyan V, Raph SM, Dwenger MM, Hu X, Pucci T, Mack G, Moore JB 4th, Chilian WM, Bhatnagar A, Nystoriak MA. Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins. Circ Res. 2021 Mar 19;128(6):738-751. doi: 10.1161/CIRCRESAHA.120.317715. Epub 2021 Jan 27. PMID: 33499656.
    Impact Statement: This study shows that the increase in oxygen demand in the heart, due to exercise or exertion, is met by increase blood flow in the heart, which is regulated by potassium channels and their subunits.
  • Men H, Cai H, Cheng Q, Zhou W, Wang X, Huang S, Zheng Y, Cai L. The regulatory roles of p53 in cardiovascular health and disease. Cell Mol Life Sci. 2021 Mar;78(5):2001-2018. doi: 10.1007/s00018-020-03694-6. Epub 2020 Nov 11. PMID: 33179140
    Impact Statement: Except for regulating a myriad of genes to maintain normal cell functions, this study found the important roles of p53 in the cardiovascular physiological and pathological conditions as revealed by this review: primarily, p53 determines the fates of cardiomyocytes by regulating metabolism and programmed cell death and also regulates cell cycle arrest and angiogenesis in non-myocytes, thus participating in the regulation of CVDs.
  • Wahlang B, Alexander NC 2nd, Li X, Rouchka EC, Kirpich IA, Cave MC. Polychlorinated biphenyls altered gut microbiome in CAR and PXR knockout mice exhibiting toxicant-associated steatohepatitis. Toxicol Rep. 2021 Mar 10;8:536-547. doi: 10.1016/j.toxrep.2021.03.010. PMID: 33777700; PMCID: PMC7985695 
    Impact Statement: This publication elucidated mechanism by which polychlorinated biphenyls and their nuclear receptor targets, PXR and CAR, modulate the gut:liver axis thereby impacting susceptibility to obesity-related diseases.
  • O'Brien SJ, Ellis CT, McDowell J, Galandiuk S, Polk HC Jr. Anal squamous cell carcinoma incidentally found at hemorrhoidectomy. Surgery. 2021 Mar;169(3):610-616. doi: 10.1016/j.surg.2020.08.026. Epub 2020 Sep 29. PMID: 33004218.
    Impact Statement: Anal cancer (SSCA) is on the rise and Kentucky now has the second highest incidence rate. Although this cancer is strongly associated with Human Papilloma Virus (HPV), it doesn’t completely explain its temporal trend. Three percent of all SCCA cases in KY were found at the time of hemorrhoidectomy.
  • Hill BG, Rood B, Ribble A, Haberzettl P. Fine particulate matter (PM2.5) inhalation-induced alterations in the plasma lipidome as promoters of vascular inflammation and insulin resistance. Am J Physiol Heart Circ Physiol. 2021 Mar 5. doi: 10.1152/ajpheart.00881.2020. Epub ahead of print. PMID: 33666505
    Impact Statement: We found that inhalation of fine particulate matter air pollution induces vascular inflammation and insulin resistance via circulating plasma constituents possibly by promoting a unique form of dyslipidemia that dependents on pulmonary oxidative stress.
  • Kumar A, Ren Y, Sundaram K, Mu J, Sriwastva MK, Dryden GW, Lei C, Zhang L, Yan J, Zhang X, Park JWMerchant ML, Teng Y, Zhang HG. miR-375 prevents high-fat diet-induced insulin resistance and obesity by targeting the aryl hydrocarbon receptor and bacterial tryptophanase (tnaA) gene. Theranostics. 2021 Feb 19;11(9):4061-4077. doi: 10.7150/thno.52558. PMID: 33754048; PMCID: PMC7977461.
    Impact Statement: The molecular mechanisms that mediate diet-based prevention of insulin resistance are not well understood. In this proof-of-concept study, ginger-derived nanoparticles (GDNP) were used to examine a role for GDNP-supplemented diet in amelioration of high-fat diet (HFD) induced insulin resistance. Using multiple lines of inquiry, this study revealed that oral administration of GDNP to HFD mice improved host glucose tolerance and insulin response via (1) regulating VAMP7 induction, (2) enhanced the exosomal accumulation of microRNA miR-375 culminating in (3) the inhibition of arylhydrocarbon receptor (AhR) expression and signaling
  • Hardesty JE, Wahlang B, Prough RA, Head KZ, Wilkey D, Merchant M, Shi H, Jin J, Cave MC. Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis. Environ Health Perspect. 2021 Mar;129(3):37010. doi: 10.1289/EHP8222. Epub 2021 Mar 31. PMID: 33788613; PMCID: PMC8011667
    Impact Statement: Our initial research demonstrated that some PCBs bind to the Epidermal Growth Factor Receptor (EGFR) and terminate its activation of normal gene expression in liver. We sought to establish whether co-treatment with epidermal growth factor, a ligand activator for EGFR, would reverse this inhibition by PCBs. While EGR did reverse the action of PCBs as proposed, there were other downstream effects caused by EGR suggesting the growth factor probably wouldn't serve as a therapeutic agent to prevent PCB toxicity due to its side effects.
  • Das S, Rai SN. SwarnSeq: An improved statistical approach for differential expression analysis of single-cell RNA-seq data. Genomics. 2021 Mar 1;113(3):1308-1324. doi: 10.1016/j.ygeno.2021.02.014. Epub ahead of print. PMID:33662531.
    Impact Statement
    : This publication discusses the development of an efficient method for analysis of Single-cell RNA sequencing data. This new method is compared with 11 methods on 10 data sets.
  • Fuqua JL, Rouchka EC, Waigel S, Sokoloski K, Chung D, Zacharias W, Zhang M, Chariker J, Talley D, Santisteban I, Varsani A, Moyer S, Holm RH, Yeager RA, Smith T, Bhatnagar A. A rapid assessment of wastewater for genomic surveillance of SARS-CoV-2 variants at sewershed scale in Louisville, KY. medRxiv [Preprint]. 2021 Mar 26:2021.03.18.21253604. doi: 10.1101/2021.03.18.21253604. PMID: 33791725; PMCID: PMC8010757. 
    Impact Statement: This paper describes preliminary observations and methodological refinements for wastewater-based surveillance of SARS-CoV-2 variants of concern. This work will inform future wastewater-based COVID-19 surveillance and targeted response to the spread of variants
  • Yuan J, Zhang Y, Zhang Y, Mo Y, Zhang Q. Effects of metal nanoparticles on tight junction-associated proteins via HIF-1α/miR-29b/MMPs pathway in human epidermal keratinocytes. Part Fibre Toxicol. 2021 Mar 19;18(1):13. doi: 10.1186/s12989-021-00405-2. PMID: 33740985; PMCID: PMC7980342.
    Impact Statement: The results of this study have demonstrated whether and how exposure to metal nanoparticles causes skin diseases such as skin inflammation and allergy, which also provided tools for evaluating the health effects of other metal nanomaterials. This study not only leads to a better understanding of the mechanisms by which metal nanoparticles induce skin inflammation and allergy, but also provide scientific evidence to prevent and control them.
  • Tarran R, Barr RG, Benowitz NL, Bhatnagar A, Chu HW, Dalton P, Doerschuk CM, Drummond MB, Gold DR, Goniewicz ML, Gross ER, Hansel NN, Hopke PK, Kloner RA, Mikheev VB, Neczypor EW, Pinkerton KE, Postow L, Rahman I, Samet JM, Salathe M, Stoney CM, Tsao PS, Widome R, Xia T, Xiao D, Wold LE. E-Cigarettes and Cardiopulmonary Health. Function (Oxf). 2021 Feb 8;2(2):zqab004. doi: 10.1093/function/zqab004. PMID: 33748758; PMCID: PMC7948134.
    Impact Statement: This article describes the proceedings and discussions at an NIH workshop on e-cigarette. The paper reviews current evidence relating the use of e-cigarettes to cardiovascular and pulmonary health and how to address major gaps in our knowledge of the long-term health effects of e-cigarettes.
  • Jiang C, Liu G, Cai L, Deshane J, Antony V, Thannickal VJ, Liu RM. Divergent Regulation of Alveolar Type 2 Cell and Fibroblast Apoptosis by Plasminogen Activator Inhibitor 1 in Lung Fibrosis. Am J Pathol. 2021 Apr 20:S0002-9440(21)00154-1. doi: 10.1016/j.ajpath.2021.04.003. Epub ahead of print. PMID: 33887217
    Impact Statement: This study revealed that increased PAI-1 expression may contribute to the apoptosis paradox observed in idiopathic pulmonary fibrosis (IPF) and aging lungs through dichotomous regulation of p53 expression in these cells, which supports the critical role of PAI-1 in IPF pathophysiology and suggests that small molecule PAI-1 inhibitors may have therapeutic potential for IPF.
  • Duan X, Wei N, Wei J, Zhu Y, Kang Y, He Y, Huang J, Wang S. Effect of High-Flow Nasal Cannula Oxygen Therapy on Pediatric Patients With Congenital Heart Disease in Procedural Sedation: A Prospective, Randomized Trial. J Cardiothorac Vasc Anesth. 2021 Mar 27:S1053-0770(21)00273-1. doi: 10.1053/j.jvca.2021.03.031. Epub ahead of print. PMID:33934982.
    Impact Statement: This study looks at how High flow nasal cannula is effective for pediatric patients with non-cyanotic congenital heart disease who require procedural sedation.
  • Xu Q, Samanapally H, Nathala P, Salunkhe V, Furmanek S, Cahill MN, McGuffin T, Mohammad T, Marsili B, Petrey J, Carrico R, Ramirez J, Akca O, Clifford SP, Pahwa S, Roser L, Kong M, Huang J; Center of Excellence for Research in Infectious Diseases (CERID) Coronavirus Study Group on behalf of the COVID-19 CardioVascular Research Group (COVID-CVRG). Outcomes and Risk Factors for Cardiovascular Events in Hospitalized COVID-19 Patients. J Cardiothorac Vasc Anesth. 2021 Mar 27:S1053-0770(21)00277-9. doi: 10.1053/j.jvca.2021.03.035. Epub ahead of print. PMID: 33867235; PMCID: PMC7997853.
    Impact Statement: This study found cardiovascular events were prevalent and associated with worse outcomes in hospitalized patients with COVID-19. Outcomes of cardiovascular events in African American and white COVID-19 patients were similar after propensity score matching analysis. There were common and unique risk factors for cardiovascular events in African American COVID-19 patients when compared with white patients.
  • Latif RK, Clifford SP, Byrne KR, Maggard B, Chowhan Y, Saleem J, Huang J. Hyperoxia After Return of Spontaneous Circulation in Cardiac Arrest Patients. J Cardiothorac Vasc Anesth. 2021 Mar 8:S1053-0770(21)00209-3. doi: 10.1053/j.jvca.2021.03.007. Epub ahead of print. PMID: 33875350.
    Impact Statement: This article looks at a strategy of precise control of arterial oxygenation where O2 therapy is titrated against a pre-specified PaO2 or SaO2 target range has been provided to healthcare providers. The best PaO2 target may vary based on patientrelated factors, such as age, severe cardiac ischemia, cerebral ischemia, pulmonary edema or untreated anemia.
  • Jala VR, Bodduluri SR, Ghosh S, Chheda Z, Singh R, Smith ME, Chilton PM, Fleming CJ, Mathis SP, Sharma RK, Knight R, Yan J, Haribabu B. Absence of CCR2 reduces spontaneous intestinal tumorigenesis in the ApcMin/+ mouse model. Int J Cancer. 2021 Jan 26. doi: 10.1002/ijc.33477. Epub ahead of print. PMID: 33497467
    Impact Statement: In this paper, we showed that deletion of chemokine receptor (CCR2), which is responsible for migration of inflammatory macrophages to the tumor sites, significantly reduced colon tumor burden and progression and increased overall survival of colon cancer mice. In addition, we also identified novel role for CCR2 in migration of Th17 cells (known to promote colonic inflammation and colon tumors) into tumors, where deletion of CCR2 significantly reduced these cells and promoted tumor killing CD8+ T cells. Therefore, targeting CCR2 in colon cancer patients potentially reduce tumor burden and benefit the patients.
  • Abdel-Rahman SM, Paul IM, Hornik C, Sullivan JE, Wade K, Delmore P, Sharma G, Benjamin DK, Zimmerman KO. Racial and Ethnic Diversity in Studies Funded Under the Best Pharmaceuticals for Children Act. Pediatrics. 2021 May;147(5):e2020042903. doi: 10.1542/peds.2020-042903. Epub 2021 Apr 12. PMID: 33846237. 
    Impact Statement: This study demonstrated enrollment of diverse racial and ethnic populations in pediatric studies conducted with funding from BPCA, fulfilling the legislation's expectation to ensure adequate representation of all children.
  • Knight L, Pahud BA, Scheffler M, Euteneuer JC, Allen C, Ross J, Ali W, Meyer M, Purohit PJ, Zimmerman KO, Sullivan JE; ECHO IDeA States Pediatric Clinical Trials Network. Capacity Building in a New Clinical Trials Network Through Inter-Network Collaboration. J Pediatr. 2021 Apr 30:S0022-3476(21)00414-5. doi: 10.1016/j.jpeds.2021.04.062. Epub ahead of print. PMID: 33940019. 
    Impact Statement: This publication reflects the positive impact of inter-network collaboration and mentoring of an established network with a new network which allowed for substantial growth and resources for the new network.
  • Zhou B, Gentry A, Xu Q, Young JL, Yan X, Pagidas K, Yang Y, Watson WH, Kong M, Cai LFreedman JH. Effects of cadmium and high-fat diet on essential metal concentration in the mouse testis. Toxicol Rep. 2021 Mar 20;8:718-723. doi: 10.1016/j.toxrep.2021.03.016. PMID: 33889501; PMCID: PMC8047427.
    Impact Statement: This report addresses the impact of environmental factors on the increasing prevalence male infertility.
  • Speer RM, Toyoda JH, Croom-Perez TJ, Liu KJ, Wise JP. Particulate Hexavalent Chromium Inhibits E2F1 Leading to Reduced RAD51 Nuclear Foci Formation in Human Lung Cells. Toxicol Sci. 2021 Apr 27;181(1):35-46. doi: 10.1093/toxsci/kfab019. PMID: 33677506; PMCID: PMC8081024.
    Impact Statement: Chromium is a known human carcinogen that is common in our environment, but we do not know how it causes cancer. A key toxic action of chromium is to damage DNA strands while simultaneously inhibiting the repair of that damage, but we do not know how chromium inhibits this repair. This study provides an important step forward in understanding how chromium inhibits that repair.
  • Ferragut Cardoso AP, Banerjee M, Nail AN, Lykoudi A, States JC. miRNA Dysregulation is an Emerging Modulator of Genomic Instability. Semin Cancer Biol. 2021 May 9:S1044-579X(21)00132-2. doi: 10.1016/j.semcancer.2021.05.004. Epub ahead of print. PMID: 33979676
    Impact Statement: Induction of genomic instability and dysregulation of miRNAs, are both key processes involved in carcinogenesis. However, how these two processes interact is only beginning to be understood. This review summarizes the literature evidence supporting a causal role of miRNA dysregulation in generating genomic instability and consequently carcinogenesis. Current knowledge gaps and possible approaches to address them are also discussed.
  • Banerjee M, Ferragut Cardoso A, Al-Eryani L, Pan J, Kalbfleisch TS, Srivastava S, Rai SNStates JC. Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer. Arch Toxicol. 2021 May 25. doi: 10.1007/s00204-021-03084-2. Epub ahead of print. PMID: 34032870.
    Impact Statement: Skin cancer is a well-known outcome of chronic environmental arsenic exposure, but the molecular mechanisms are not well understood. This investigation examined the changes in gene expression in a longitudinal study using a well-established cell line model of chronic arsenic exposure-induced squamous cell carcinoma and RNA-seq. The results reveal that the landscape of differentially expressed mRNA and the miRNAs regulating those mRNAs change considerably during cancer development and provide novel insight into the molecular events leading to skin cancer chronic from arsenic exposure.
  • Huang S, Wang J, Men H, Tan Y, Lin Q, Gozal E, Zheng Y, Cai L. Cardiac metallothionein overexpression rescues diabetic cardiomyopathy in Akt2-knockout mice. J Cell Mol Med. 2021 May 30. doi: 10.1111/jcmm.16687. Epub ahead of print. PMID: 34053181.
    Impact Statement: Akt2 play important role in the glucose metabolism of the heart, but its function is down-regulated under diabetic condition. The new study shows that although we previously showed that metallothionein (MT) preserved Akt2 activity along with the prevention of diabetic cardiomyopathy, but, in the absence of Akt2 gene MT may stimulate alternative or Akt2 downstream pathways to protect from diabetic cardiomyopathy. This may provide a new strategy to prevent diabetic complications.
  • Morrissey SM, Geller AE, Hu X, Tieri D, Ding C, Klaes CK, Cooke EA, Woeste MR, Martin ZC, Chen O, Bush SE, Zhang HG, Cavallazzi R, Clifford SP, Chen J, Ghare S, Barve SS, Cai L, Kong M, Rouchka EC, McLeish KR, Uriarte SM, Watson CT, Huang J, Yan J. A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients. JCI Insight. 2021 May 10;6(9):148435. doi: 10.1172/jci.insight.148435. PMID: 33986193.
    Impact Statement: Our data suggest that a subset of low density neutrophil population contributes to COVID-19-associated coagulopathy, systemic inflammation, and acute respiratory distress syndrome. The frequency of this neutrophil subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.
  • Tevis DS, Flores SR, Kenwood BM, Bhandari D, Jacob P 3rd, Liu J, Lorkiewicz PK, Conklin DJ, Hecht SS, Goniewicz ML, Blount BC, De Jesús VR. Harmonization of acronyms for volatile organic compound metabolites using a standardized naming system. Int J Hyg Environ Health. 2021 May 4;235:113749. doi: 10.1016/j.ijheh.2021.113749. Epub ahead of print. PMID: 33962120.
    Impact Statement: Increased interest in volatile organic compound (VOC) exposure has led to an increased need for consistent, systematic, and informative naming of VOC metabolites. Harmonizing the naming of VOC metabolites will lead to more uniform dissemination of knowledge regarding VOC exposures and their relationships with public health.
  • DuPre NC, Karimi S, Zhang CH, Blair L, Gupta A, Alharbi LMA, Alluhibi M, Mitra R, McKinney WP, Little B. County-level demographic, social, economic, and lifestyle correlates of COVID-19 infection and death trajectories during the first wave of the pandemic in the United States. Sci Total Environ. 2021 May 3;786:147495. doi: 10.1016/j.scitotenv.2021.147495. Epub ahead of print. PMID: 33971599; PMCID: PMC8091799.
    Impact Statement: This study identifies and maps counties with similar COVID-19 epidemic curves and highlights that communities with higher proportions of youth, communities of color, smokers, and workers in healthcare, service and goods industries can reduce viral spread by targeting vaccination programs to these populations and increasing access and education on non-pharmaceutical interventions.
  • Xu Q, Liu Y, Cepulis D, Jerde A, Sheppard RA, Tretter K, Oppy L, Stevenson G, Bishop S, Clifford SP, Liu P, Kong M, Huang J. Implementing an Electronic Hand Hygiene System Improved Compliance in the Intensive Care Unit. Am J Infect Control. 2021 May 27:S0196-6553(21)00383-7. doi: 10.1016/j.ajic.2021.05.014. Epub ahead of print. PMID: 34052312. 
    Impact Statement: A sensor-based electronic hand hygiene system improved hand hygiene compliance in the ICU. Significant variations among providers in terms of hand hygiene compliance. Hand rubbing duration in partial compliance occurrences did not change significantly over time.
  • Song K, Xu Q, Knott VH, Zhao CB, Clifford SP, Kong M, Slaughter MS, Huang Y, Huang J. Liposomal Bupivacaine-Based Erector Spinae Block for Cardiac Surgery. J Cardiothorac Vasc Anesth. 2021 May;35(5):1555-1559. doi: 10.1053/j.jvca.2020.09.115. Epub 2020 Sep 20. PMID: 33046362. 
    Impact Statement: Liposomal bupivacaine–based single-shot bilateral erector spinae block could reduce total opioid consumption intraoperatively, as well as at 4 and 12 hours after extubation in cardiac surgery.
  • Gu Z, Li F, Liu Y, Jiang M, Zhang L, He L, Wilkey DW, Merchant M, Zhang X, Deng ZB, Chen SY, Barve S, McClain CJ, Feng W. Exosome-Like Nanoparticles From Lactobacillus rhamnosusGG Protect Against Alcohol-Associated Liver Disease Through Intestinal Aryl Hydrocarbon Receptor in Mice. Hepatol Commun. 2021 Feb 5;5(5):846-864. doi: 10.1002/hep4.1679. PMID: 34027273; PMCID: PMC8122379.
    Impact Statement: Alcohol use disorders will effect nearly 1 in 7 Americans across their lifespan and contribute to more than 85,000 deaths annually. Wenke Feng, PhD, Professor of Medicine and his collaborators including some in the CIEHS, demonstrated that small exosome-like nanoparticles purified from Lactobacillus rhamnosus GG (LGG) growth cultures can protect the gut and the liver from alcohol-induced, bacterial endotoxin damage. Probiotics, such as LGG, represent an important part of a healthy lifestyle, are freely available for over-the-counter purchase, and may be one approach to mitigate the damaging effects of alcohol abuse.
  • Teng Y, Xu F, Zhang X, Mu J, Sayed M, Hu X, Lei C, Sriwastva M, Kumar A, Sundaram K, Zhang L, Park JWChen SY, Zhang S, Yan J, Merchant ML, Zhang X, McClain CJ, Wolfe JK, Adcock RS, Chung D, Palmer KE, Zhang HG. Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12. Mol Ther. 2021 May 11:S1525-0016(21)00257-4. doi: 10.1016/j.ymthe.2021.05.005. Epub ahead of print. PMID: 33984520; PMCID: PMC8110335.
    Impact Statement: COVID-19 is a disease affecting the pulmonary system with devastating inflammation. Our results show that a tiny nanovesicles called exosomes released from SARS-CoV-2 infected lung epithelia cells are preferentially taken up by lung macrophages that subsequently induce lung inflammation. Ginger exosome-like nanoparticles (GELNs) miRNA inhibits the SARS-CoV-2 induced lung inflammation and viral replication. Therefore, GELNs are a potential therapeutic agent to treat COVID-19
  • Guardiola JJ, Hardesty JE, Beier JI, Prough RA, McClain CJ, Cave MC. Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development. Int J Mol Sci. 2021 May 11;22(10):5093. doi: 10.3390/ijms22105093. PMID: 34065028; PMCID: PMC8150673.
    Impact Statement: The results of this study help us understand why vinyl chloride causes liver cancer in chemical plant workers. Some of the blood tests we identified could possibly be used to test at-risk workers for cancer.
  • O'Brien SJ, Kalbflesich T, Srivastava S, Pan J, Rai S, Petras RE, Ronquillo N, Polk HC Jr, Galandiuk S. Decreased Tumoral Expression of Colon-Specific Water Channel Aquaporin 8 Is Associated With Reduced Overall Survival in Colon Adenocarcinoma. Dis Colon Rectum. 2021 May 13. doi: 10.1097/DCR.0000000000002071. Epub ahead of print. PMID: 33990498.
    Impact Statement: In collaboration with Dr. Galandiuk, we explore gene signatures for overall survival in colon adenocarcinoma on The Cancer Genome Atlas data repository. We find that Low AQP8 expression is a risk factor for worse overall survival in colon cancer patients.
  • Linder MW, Egger ME, Van Meter T, Rai SN, Valdes R Jr, Hall MB, Wu X, Alghamdi N, Chesney JA. Longitudinal Relationship between Idylla Plasma ctBRAF V600 Mutation Detection and Tumor Burden in Patients with Metastatic Melanoma. Mol Diagn Ther. 2021 May 10. doi: 10.1007/s40291-021-00528-4. Epub ahead of print. PMID: 33970440.
    Impact Statement: In collaboration with Dr. Linder, we find statistically significant relationship between changes in plasma ctDNA and radiographic imaging among patients with metastatic melanoma. This can supplement early detection of progression and relapse in this population.
  • Majid S, Keith RJ, Fetterman JL, Weisbrod RM, Nystoriak J, Wilson T, Stokes AC, Blaha MJ, Srivastava S, Robertson RM, Bhatnagar A, Hamburg NM. Lipid profiles in users of combustible and electronic cigarettes. Vasc Med. 2021 May 20:1358863X211009313. doi: 10.1177/1358863X211009313. Epub ahead of print. PMID: 34013801.
    Impact Statement: The present study provides insights into the associations of novel tobacco product use with known markers of cardiovascular health. Importantly, when compared to never users, we found use of there earlier generation of electronic cigarettes with and without combustible cigarette use to be associated with lower levels of HDL cholesterol and higher triglycerides.
  • Al-Rabadi LF, Caza T, Trivin-Avillach C, Rodan AR, Andeen N, Hayashi N, Williams B, Revelo MP, Clayton F, Abraham J, Lin E, Liou W, Zou CJ, Ramkumar N, Cummins T, Wilkey DW, Kawalit I, Herzog C, Storey A, Edmondson R, Sjoberg R, Yang T, Chien J, Merchant M, Arthur J, Klein J, Larsen C, Beck LH Jr. Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy. J Am Soc Nephrol. 2021 May 5;32(7):1666–81. doi: 10.1681/ASN.2020101395. Epub ahead of print. PMID: 33952630; PMCID: PMC8425645.
  • Reynolds LM, Zamora C, Lee UJ, Stokes AC, Benjamin EJ, Bhatnagar A, Payne TJ, Rodriguez CJ. Tobacco Use Prevalence and Transitions From 2013 to 2018 Among Adults With a History of Cardiovascular Disease. J Am Heart Assoc. 2021 Jun 9:e021118. doi: 10.1161/JAHA.121.021118. Epub ahead of print. PMID: 34102851.
    Impact Statement: This study shows that even though it is well known that smoking is bad for your heart, even those with heart disease continue to smoke. Less than 10% of those with heart disease enroll in tobacco cessation programs, although some switch to e-cigarette.
  • Wang X, Chen XX, Yu HT, Tan Y, Lin Q, Keller BB, Zheng Y, Cai L. Engineered cardiac tissues: a novel in vitro model to investigate the pathophysiology of mouse diabetic cardiomyopathy. Acta Pharmacol Sin. 2021 Jun;42(6):932-941. doi: 10.1038/s41401-020-00538-8. Epub 2020 Oct 9. PMID: 33037406; PMCID: PMC8149662.
    Impact Statement: Rodent diabetic models, used to understand the pathophysiology of diabetic cardiomyopathy (DCM), remain several limitations. Engineered cardiac tissue (ECT) with 3D in vitro heart model was used to investigate the structural and functional effect of advanced glycation end-products (AGEs), as the most important pathogenic factor for DCM’s development; This study shows the first time that AGEs-treated murine ECTs recapitulate the key features of DCM's functional, structural, cellular, and molecular pathogenesis as observed in the heart of diabetic mice. This approved that this ex vivo model can be used to investigate cellular structure-function relationships, signaling pathways relevant to DCM and pharmaceutical intervention strategies.
  • Gozal E, Jagadapillai R, Cai J, Barnes GN. Potential Crosstalk between Sonic Hedgehog-Wingless-related Integration Site Signaling and Neurovascular Molecules: Implications for Blood Brain Barrier Integrity in Autism Spectrum Disorder. J Neurochem. 2021 Jun 25. doi: 10.1111/jnc.15460. Epub ahead of print. PMID: 34169527.
    Impact Statement: Autism spectrum disorder (ASD) is a neurodevelopmental disease and its pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although brain inflammation, immunity, and oxidative stress are involved. The blood brain barrier (BBB) plays a critical role in controlling brain homeostasis and immune response. The permissive BBB opens the ‘gate’ for environmental ‘saboteurs’ and trigger the pathological events in ASD. In this review, the authors examined the current knowledge on Sonic Hedgehog/Wingless-related integration site (Shh/Wnt) pathways and their roles in BBB function in ASD. The interactions between Wnt-b-catenin and Shh pathways are critical to maintain BBB integrity in the mature brain to prevent influx of pathogens and inflammatory cells. Disruption of the Shh/Wnt crosstalk may compromise the BBB development and function. The ASD patients with genetic mutations of key components of these pathways show severe ASD symptoms. Mechanisms involving ASD-related mutations of Shh/Wnt signaling cause BBB leaks and neuroinflammation, suggesting the BBB integrity plays a vital role in gene-environment interactions in ASD pathogenesis.
  • Lei C, Teng Y, He L, Sayed M, Mu J, Xu F, Zhang X, Kumar A, Sundaram K, Sriwastva MK, Zhang L, Chen SY, Feng W, Zhang S, Yan J, Park JW,Merchant ML, Zhang X, Zhang HG. Lemon exosome-like nanoparticles enhance stress survival of gut bacteria by RNase P-mediated specific tRNA decay. iScience. 2021 May 5;24(6):102511. doi: 10.1016/j.isci.2021.102511. PMID: 34142028; PMCID: PMC8188359.
    Impact Statement: Since most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and overcoming bile salt damage to probiotics is a great challenge. In this study, a tiny nanoparticle called exosomes-like nanoparticles (ELNs) isolated from lemon significantly increased the percentage of lactobacillaceae in the presence of bile. This finding is significant because we daily consume a variety of plant-derived products which contain ELNs in our diet. Our findings provide a foundation to further determine whether other types of ELNs also contribute to enhance the survivability of probiotics in gut in general.
  • Lin Q, Huang Z, Cai G, Fan X, Yan X, Liu Z, Zhao Z, Li J, Li J, Shi H, Kong M, Zheng MH, Conklin DJ, Epstein PN, Wintergerst KA, Mohammadi M, Cai L, Li X, Li Y, Tan Y. Activating Adenosine Monophosphate-Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice. Hepatology. 2021 Jun;73(6):2206-2222. doi: 10.1002/hep.31568. PMID: 32965675; PMCID: PMC8082952.
    Impact statement: Although fibroblast growth factor 1 (FGF1) protects against nonalcoholic fatty liver disease in type 2 diabetic and obese mice, but its clinically translational study was limited mainly because its hyperproliferation has potentially tumorigenic risk, to overcome which, we engineered an FGF1 (i.e., FGF1ΔHBS) that dramatically diminished it’s proliferative potential, yet maintains full metabolic activity of wild-type FGF1. This new FGF1ΔHBS is approved effective for preventing and reversing liver steatosis and steatohepatitis by activating AMPK via hepatocyte FGFR4, and also potentially applied towards clinical use.
  • Saha S, Roy P, Corbitt C, Kakar SS. Application of Stem Cell Therapy for Infertility. Cells. 2021 Jun 28;10(7):1613. doi: 10.3390/cells10071613. PMID: 34203240.
    Impact statement: Infertility affects about 15% of couples globally. Conventional therapies and assisted reproductive technologies (e.g., in vitro fertilization) are effective for many but not all cases. This review explains new fertility treatment possibilities using stem cell therapies, many of which are in clinical trials now.
  • Tang W, Liu H, Wei P, Huang J, Lyu W, Zhou H, Zhou J, Li Y, Li J. Decrease in cerebral oxygen saturation and the increase in heart rate is a prewarning window of hypotension after spinal anesthesia for cesarean section: A pilot observational study. J Clin Anesth. 2021 Jun 1;73:110360. doi: 10.1016/j.jclinane.2021.110360. Epub ahead of print. PMID: 34087657.
    Impact Statement: We identified that decrease in cerebral oxygen saturation and increase in heart rate can predict hypotension after spinal anesthesia in pregnant patients for C Section.
  • Tibi P, McClure RS, Huang J, Baker RA, Fitzgerald D, Mazer CD, Stone M, Chu D, Stammers AH, Dickinson T, Shore-Lesserson L, Ferraris V, Firestone S, Kissoon K, Moffatt-Bruce S. STS/SCA/AmSECT/SABM Update to the Clinical Practice Guidelines on Patient Blood Management. Ann Thorac Surg. 2021 Jun 8:S0003-4975(21)00556-7. doi: 10.1016/j.athoracsur.2021.03.033. Epub ahead of print. PMID: 34217505.
    Impact Statement: A multidisciplinary panel of experts was convened by STS, which includes members of the Society of Cardiovascular Anesthesiologists (SCA), the American Society of ExtraCorporeal Technology (AmSECT), and the Society for the Advancement of Blood Management (SABM), to review the latest data on patient blood management and to update the 2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines.
  • Dukka H, Byrd P, Qian C, Baughman G, Butt S, Rai SN. Occupational percutaneous injuries and exposures in a dental teaching environment: A 10-year report. J Dent Educ. 2021 Jun 27. doi: 10.1002/jdd.12731. Epub ahead of print. PMID: 34180052.
    Impact statement: Occupational percutaneous injuries (PIs) are an ongoing issue that occurs globally, especially in an academic environment and are woefully underreported. Our results showed that uncovered dental burs and needlesticks continue to be the predominant cause of PIs in a teaching environment. Collection and reporting of such events could be useful in observing any trends and implementation of corrective actions to prevent such injuries, which could lead to potential cross infections.
  • Zierold KM, Myers JV, Brock GN, Sears CG, Sears LL, Zhang CH. Nail Samples of Children Living near Coal Ash Storage Facilities Suggest Fly Ash Exposure and Elevated Concentrations of Metal(loid)s. Environ Sci Technol. 2021 Jul 6;55(13):9074-9086. doi: 10.1021/acs.est.1c01541. Epub 2021 Jun 16. PMID: 34132542.
    Impact statement: The effect of coal ash exposure on children's health is not known but is a concern due to the potential toxins contained in the coal-power-plant byproduct. The study found an increased heavy metal body burden in children living near coal ash storage sites indicating an increased risk for potential neurotoxic exposure from metals contained in coal ash.
  • Bushau-Sprinkle AM, Barati MT, Zheng Y, Watson WH, Gagnon KB, Khundmiri SJ, Kitterman KT, Clark BJ, Siskind LJ, Doll MA, Brier ME, Coventry S, Lederer ED. Na/H Exchange Regulatory Factor 1 Deficient Mice Show Evidence of Oxidative Stress and Altered Cisplatin Pharmacokinetics. Antioxidants (Basel). 2021 Jun 28;10(7):1036. doi: 10.3390/antiox10071036. PMID: 34203453.
    Impact statement: Cisplatin is an effective cancer treatment drug, but up to one third of patients must stop taking this drug because of kidney toxicity. This paper identifies NHERF1 as a protein that protects against cisplatin nephrotoxicity by altering the redox environment of the kidney.
  • Jin L, Lorkiewicz P, Xie Z, Bhatnagar A, Srivastava S, Conklin DJ. Acrolein but not its metabolite, 3-Hydroxypropylmercapturic acid (3HPMA), activates vascular transient receptor potential Ankyrin-1 (TRPA1): Physiological to toxicological implications. Toxicol Appl Pharmacol. 2021 Jul 13:115647. doi: 10.1016/j.taap.2021.115647. Epub ahead of print. PMID: 34271065.
    Impact Statement: Exposure to acrolein is linked with cardiopulmonary toxicity and cardiovascular disease (CVD) risk in humans, yet the mechanisms by which acrolein exposure confers CVD risk is unclear. This study showed that acrolein in isolated blood vessels is vasorelaxant at low levels (physiological) yet vasotoxic at high levels (toxicological), while the major metabolite of acrolein, 3-hydroxypropyl mercapturic acid (3HPMA), was weakly vasoactive and non-toxic indicating it likely does not directly account for vascular injury. These findings support the continued use of 3HPMA as a biomarker of acrolein exposure and warrant further research on mechanisms of acrolein-induced vascular injury to develop interventions that can protect human health.
  • Cai L. Prevention or therapy of the cardiomyopathy by fine O-GlcNAcylation balance: hopes and concerns. Cardiovasc Res. 2021 Jul 12:cvab226. doi: 10.1093/cvr/cvab226. Epub ahead of print. PMID: 34254135.
    Impact Statement: This is a commentary for a recent study that has brought us many hopes for the potential gene therapy for diabetic cardiomyopathy (DCM). The authors first noticed the significant increase in O-GlcNAc modified proteins in the heart tissues of patients with diabetes, which was positively and inversely correlated with their HbA1c or blood glucose levels and with cardiac ejection fraction, respectively. Then the authors transferred O-GlcNAcase gene with adeno-associated viral vector to diabetic mice with diastolic dysfunction, a typical early feature of DCM. The gene therapy significantly reduced diabetes-increased expression of O-GlcNAc proteins and expressions of pro-fibrotic genes coding the proteins involved in fibrosis, and interstitial and perivascular type I and type III collagen deposition and improved diastolic dysfunction. Therefore, this is a milestone study to confirm the potential therapeutic reversion of DCM by correcting the balance of O-GlcNacylation in the diabetic heart, even though there remain some unanswered issues.
  • Tian Y, Wang Z, Zheng X, Song W, Cai L, Rane M, Zhao Y. KLF15 negatively regulates cardiac fibrosis by which SDF-1β attenuates cardiac fibrosis in type 2 diabetic mice. Toxicol Appl Pharmacol. 2021 Jul 23;427:115654. doi: 10.1016/j.taap.2021.115654. Epub ahead of print. PMID: 34310909. 
    Impact statement: Tian et. al. demonstrated that T2D decreased cardiac function and KLF15 expression, while increasing cardiac fibrosis. SDF-1 increased KLF-15 expression, decreased cardiac fibrosis, and increased cardiac function in T2D mice, providing a novel therapeutic option for treatment of cardiac fibrosis in T2D patients.
  • Karimi SM, Salunkhe SS, White KB, Little BB, McKinney WP, Mitra R, Chen Y, Adkins ER, Barclay JA, Ezekekwu E, He CX, Hurst DM, Popescu MM, Swinney DN, Johnson DA, Hollenbach R, Moyer SS, DuPré NC. Prevalence of unmasked and improperly masked behavior in indoor public areas during the COVID-19 pandemic: Analysis of a stratified random sample from Louisville, Kentucky. PLoS One. 2021 Jul 28;16(7):e0248324. doi: 10.1371/journal.pone.0248324. PMID: 34319978; PMCID: PMC8318281.
    Impact Statement: During the height of the COVID-19 pandemic in 2020 when vaccines were not largely available, we observed mask usage in Louisville's public areas. Differences in mask usage were observed by geographic areas, size and type of public area, and by perceived age and sex, which can aid public health practitioners in their efforts to promote COVID-19 prevention practices.
  • Stover AM, Kurtzman R, Walker Bissram J, Jansen J, Carr P, Atkinson T, Ellis CT, Freeman AT, Turner K, Basch EM. Stakeholder Perceptions of Key Aspects of High-Quality Cancer Care to Assess with Patient Reported Outcome Measures: A Systematic Review. Cancers (Basel). 2021 Jul 20;13(14):3628. doi: 10.3390/cancers13143628. PMID: 34298841; PMCID: PMC8306432. 
    Impact Statement: This systematic review showed that patients and other stakeholders perceive high-quality cancer care to be adequate control of physical and psychosocial symptoms. Results were used to inform feasibility testing of patient reported outcome measures (PROMs) as performance measures in six U.S. cancer centers.
  • Li X, Haberzettl P, Conklin DJ, Bhatnagar A, Rouchka EC, Zhang M, O'Toole TE. Exposure to Fine Particulate Matter Air Pollution Alters mRNA and miRNA Expression in Bone Marrow-Derived Endothelial Progenitor Cells from Mice. Genes (Basel). 2021 Jul 10;12(7):1058. doi: 10.3390/genes12071058. PMID: 34356074; PMCID: PMC8307414.
    Impact Statement: Exposure to fine air borne particulate matter is associated with cardiovascular, immunological, and cognitive disorders, but the mechanism for this is unclear. This study provides evidence that such exposures alters the expression of protein at the genetic level and that this can occur in a group of bone marrow stem cells. This mechanism may underlie adverse outcomes associated with other inhalation exposures, such as that to cigarette smoke.
  • Muluhngwi P, Klinge CM. Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells. Cancers (Basel). 2021 Jul 14;13(14):3530. doi: 10.3390/cancers13143530. PMID: 34298743; PMCID: PMC8307416.
    Impact Statement: Although breast cancer patients whose initial breast tumor expressed estrogen receptor alpha (ERα) are successfully treated with drugs targeting ERα, many patients develop resistance to these endocrine therapies and disease progression to metastasis remains a major clinical problem. This paper summarizes the role of long non-coding RNAs (lncRNA) regulated by miR-29 in endocrine-resistant breast cancer cells and clinical samples.
  • Perpich JD, Yakoumatos L, Johns P, Stocke KS, Fitzsimonds ZR, Wilkey DW, Merchant ML, Miller DP, Lamont RJ. Identification and characterization of a UbK family kinase in Porphyromonas gingivalis that phosphorylates the RprY response regulator. Mol Oral Microbiol. 2021 Jul 9. doi: 10.1111/omi.12347. Epub ahead of print. PMID: 34241965.
    Impact Statement: Porphyromonas gingivalis is a major pathogen in periodontal diseases and possesses an array of colonization and virulence factors contributing to retention, survival, and proliferation in the dynamic and diverse ecosystems of the oral cavity. The P. gingivalis genome contains one system, the orphan response regulator (RR) RprY, that controls heterotypic community development. This study employed multiple approaches including in vitro kinase assays and phosphoproteomics to delineate the system by which RprY is activated.
  • Paré G, Vitry J, Merchant ML, Vaillancourt M, Murru A, Shen Y, Elowe S, Lahoud MH, Naccache PH, McLeish KR, Fernandes MJ. The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release. Front Immunol. 2021 Jun 21;12:650808. doi: 10.3389/fimmu.2021.650808. PMID: 34234773; PMCID: PMC8256872.
    Impact Statement: The myeloid inhibitory C-type lectin receptor CLEC12A limits neutrophil activation and pro-inflammatory pathways in experimental models of inflammatory arthritis. Phosphoproteomic analysis identified candidate signaling molecules regulated by CLEC12A. Further studies defined early molecular events underpinning CLEC12A signaling in human neutrophils modulating cytokine synthesis. Targeting this pathway could be useful therapeutically to dampen inflammation.
  • Srivastava DK, George EO, Lu Z, Rai SN. Impact of unequal censoring and insufficient follow-up on comparing survival outcomes: Applications to clinical studies. Stat Methods Med Res. 2021 Jul 7:9622802211017592. doi: 10.1177/09622802211017592. Epub ahead of print. PMID: 34232837. 
    Impact statement: Clinical trials with survival endpoints are typically designed to enroll patients for a specified number of years, (usually 2-3 years) with another specified duration of follow-up (usually 2-3 years). With random accrual time and follow-up time lead to complex censoring patterns. Conflicting findings were observed for comparing cardiovascular events in patients who took Rofecoxib (Vioxx). Here, using extensive simulation studies, we assess the impact of such censorings on statistical procedures for comparing two treatment groups. Clinical studies with survival outcome should be properly designed to maintain power by considering the censoring patterns.
  • Zhang CH, Sears L, Myers JV, Brock GN, Sears CG, Zierold KM. Proximity to coal-fired power plants and neurobehavioral symptoms in children. J Expo Sci Environ Epidemiol. 2021 Jul 13:1–11. doi: 10.1038/s41370-021-00369-7. Epub ahead of print. PMID: 34257388; PMCID: PMC8275639.
    Impact statement: This study used geospatial mapping to determine if child behavior problems were associated with proximity to coal-burning power plants with coal ash storage sites containing known neurotoxins. Results indicated that children living closer to these coal-burning plants had increased risk of anxiety, ADHD and social problems suggesting a need for further consideration of environmental exposures in improving child neurobehavioral health.
  • Maharaj AR, Wu H, Zimmerman KO, Muller WJ, Sullivan JE, Sherwin CMT, Autmizguine J, Rathore MH, Hornik CD, Al-Uzri A, Payne EH, Benjamin DK Jr, Hornik CP; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity. Paediatr Drugs. 2021 Jul 23. doi: 10.1007/s40272-021-00460-4. Epub ahead of print. PMID: 34302290.
    Impact Statement: The aim of this study was to develop a pharmacokinetic model to evaluate ceftazidime pharmacokinetics in a cohort that included a predominate number of children and adolescents with obesity and assess the efficacy of two different dosing strategies. The results show that dosing 40 mg/kg every six hours intravenously (maximum dose 8 grams/day) met the target minimum inhibitory concentration for efficacy. This research is critical because obese patients tend to have poorer outcomes with infections therefore dosing antibiotics appropriately may improve their outcome.
  • Coleman CJ, Yeager RA, Riggs DW, Coleman NC, Garcia GR, Bhatnagar A, Pope CA. Greenness, air pollution, and mortality risk: A U.S. cohort study of cancer patients and survivors. Environ Int. 2021 Jul 29;157:106797. doi: 10.1016/j.envint.2021.106797. Epub ahead of print. PMID: 34332301. 
    Impact statement: This paper enables samples sites to be selected to ensure objective and equitable estimates for COVID-19 infection prevalence throughout Louisville, Kentucky. With such sampling, wastewater testing data is utilized to inform public health response and variant tracking.
  • Yeager R, Holm RH, Saurabh K, Fuqua JL, Talley D, Bhatnagar A, Smith T. Wastewater Sample Site Selection to Estimate Geographically Resolved Community Prevalence of COVID-19: A Sampling Protocol Perspective. Geohealth. 2021 Jul 1;5(7):e2021GH000420. doi: 10.1029/2021GH000420. PMID: 34222738; PMCID: PMC8240399. 
     Impact Statement: We found that cancer patients living in areas with high levels of vegetation had a higher likelihood of cancer survival. We also found that this association was not impacted by air pollution, as some have suspected
  • El-Gamal FEA, Elmogy M, Mahmoud A, Shalaby A, Switala AE, Ghazal M, Soliman H, Atwan A, Alghamdi NS, Barnes GN, El-Baz A. A Personalized Computer-Aided Diagnosis System for Mild Cognitive Impairment (MCI) Using Structural MRI (sMRI). Sensors (Basel). 2021 Aug 11;21(16):5416. doi: 10.3390/s21165416. PMID: 34450858; PMCID: PMC8400990.
    Impact Statement: Several factors hinder the diagnosis of Alzheimer's disease at an early stage, in particular, the divergence of 10-15 years between the onset of the underlying neuropathological changes and patients becoming symptomatic. This study surveyed patients with mild cognitive impairment (MCI), who were at risk of conversion to AD, with a local/regional-based computer-aided diagnosis system. The experimental results showed an encouraging performance of the proposed system when compared with related work.
  • Pfeiffer JA, Hart JL, Wood LA, Bhatnagar A, Keith RJ, Yeager RA, Smith T, Tomlinson M, Gilkey D, Kerstiens S, Gao H, Srivastava S, Walker KL. The importance of urban planning: Views of greenness and open space is reversely associated with self-reported views and depressive symptoms. Popul Med. 2021 Jul;3:20. doi: 10.18332/popmed/139173. PMID: 34368779; PMCID: PMC8341459.
    Impact Statement: The purpose of this study was to examine the relationship between views of greenness and Patient Health Questionnaire–9 (PHQ-9) score. The findings suggest urban greening interventions that focus on greenness satisfaction may be a strategy to reduce depression.
  • Haberzettl P, Jin L, Riggs DW, Zhao J, O'Toole TE, Conklin DJ. Fine particulate matter air pollution and aortic perivascular adipose tissue: Oxidative stress, leptin, and vascular dysfunction. Physiol Rep. 2021 Aug;9(15):e14980. doi: 10.14814/phy2.14980. PMID: 34327871; PMCID: PMC8322754.
    Impact Statement: Levels of fine particulate matter (PM2.5) air pollution are associated with chronic cardiovascular disease in humans; however, understanding of the early changes that foster chronic vascular disease is incomplete. Because perivascular adipose tissue (PVAT) inflammation is implicated in chronic vascular diseases, we investigated early changes in aortic PVAT following short-term air pollution exposure in mice. We found that PM2.5-exposed mice had changes consistent with oxidative stress, vascular dysfunction and insulin resistance in aortic PVAT. The PM2.5-induced changes were absent in mice with overexpression of extracellular superoxide dismutase in the lungs implicating pulmonary oxidative stress as necessary in detrimental vascular changes in PM2.5-exposed mice. As our study connects inhaled PM2.5 and pulmonary oxidative stress with vascular derangement, we expect future research will test potential interventions that may protect public health from the deleterious cardiovascular effects of air pollution exposure.
  • Sritapan Y, Feldmann J, Huang J, Sangroula D. A case of amniotic fluid embolism complicated by undiagnosed patent foramen ovale. Eur J Obstet Gynecol Reprod Biol. 2021 Aug 9:S0301-2115(21)00404-8. doi: 10.1016/j.ejogrb.2021.08.004. Epub ahead of print. PMID: 34462168.
    Impact Statement: Amniotic fluid embolism (AFE) is a rare leading cause of unpredictable maternal death in industrialized countries We present the management and sudden hemodynamic collapse of a patient due to a suspected AFE complicated by an undiagnosed patent foramen ovale.
  • Castner J, Huntington-Moskos L, May A. Generating Data Visualizations of Longitudinal Cohort Ambient Air Pollution Exposure: Report-Back Intervention Development in Participatory Action Research. Comput Inform Nurs. 2021 Aug 18. doi: 10.1097/CIN.0000000000000821. Epub ahead of print. PMID: 34412083.
    Impact Statement: This work discusses the intentional use of data visualizations in the report back of research findings to community members. Open-source tools can be effectively used to create data visualizations, discuss environmental exposure findings, and promote science literacy.
  • Biyik-Sit R, Kruer T, Dougherty S, Bradley JA, Wilkey DW, Merchant ML, Trent JO, Clem BF. Nuclear Pyruvate Kinase M2 (PKM2) Contributes to Phosphoserine Aminotransferase 1 (PSAT1)-Mediated Cell Migration in EGFR-Activated Lung Cancer Cells. Cancers (Basel). 2021 Aug 4;13(16):3938. doi: 10.3390/cancers13163938. PMID: 34439090; PMCID: PMC8391706.
    Impact Statement: Phosphoserine aminotransferase 1 (PSAT1) expression has been observed in multiple tumor types and is associated with poorer clinical outcomes. PSAT1’s role in cancer progression has not been fully characterized. Biochemical studies identified an interaction of PSAT1 with pyruvate kinase M2 (PKM2). Further studies demonstrated in response to epidermal growth factor receptor activation, PSAT1 contributed to lung cancer cell migration, in part, by promoting nuclear PKM2 translocation.
  • Das S, Rai SN. Statistical Approach of Gene Set Analysis with Quantitative Trait Loci for Crop Gene Expression Studies. Entropy (Basel). 2021 Jul 23;23(8):945. doi: 10.3390/e23080945. PMID: 34441085; PMCID: PMC8391627.
    Impact Statement: Most of the human diseases and plants traits are complex quantitative in nature and controlled by polygenes. Hence, the developed method, and the software tool will help the researchers to establish the link between the genotypes (e.g., gene sets) with the phenotypes (e.g., complex traits). This may have substantial application in molecular crop breeding and establishing the biological basis of diseases.
  • Sears L, Myers JV, Sears CG, Brock GN, Zhang C, Zierold KM. Manganese body burden in children is associated with reduced visual motor and attention skills. Neurotoxicol Teratol. 2021 Aug 21;88:107021. doi: 10.1016/j.ntt.2021.107021. Epub ahead of print. PMID: 34428495.
    Impact Statement: Manganese is an essential trace element however overexposure can lead to neurotoxicity. This study looked at children living near coal ash storage sites who may be at risk for manganese overexposure. Neuropsychological testing found that children with the highest Mn levels had poorer eye hand coordination and reduced ability to sustain attention compared to those with low Mn levels. Findings are in agreement with previous studies supporting the need to monitor child environmental exposures due to the potential for increased neurobehavioral problems.
  • Boakye E, Obisesan OH, Uddin SMI, El-Shahawy O, Dzaye O, Osei AD, Benjamin EJ, Stokes AC, Robertson RM, Bhatnagar A, Blaha MJ. Cannabis vaping among adults in the United States: Prevalence, trends, and association with high-risk behaviors and adverse respiratory conditions. Prev Med. 2021 Sep 11;153:106800. doi: 10.1016/j.ypmed.2021.106800. Epub ahead of print. PMID: 34520787.
    Impact Statement: The e-cigarette or vaping product-use-associated lung injury outbreak in the United States has raised concerns about the potential health effects of cannabis vaping, a method of cannabis use that is becoming increasingly popular. Although the study found there was no association between cannabis vaping and asthma or other respiratory symptoms, the increasing trends of cannabis vaping, particularly among young adults, raise concern and underscore the need for continued surveillance.
  • Hamorsky KT, Bushau-Sprinkle AM, Kitterman K, Corman JM, DeMarco J, Keith RJ, Bhatnagar A, Fuqua JL, Lasnik A, Joh J, Chung D, Klein J, Flynn J, Gardner M, Barve S, Ghare SS, Palmer KE. Serological assessment of SARS-CoV-2 infection during the first wave of the pandemic in Louisville Kentucky. Sci Rep. 2021 Sep 14;11(1):18285. doi: 10.1038/s41598-021-97423-z. PMID: 34521900; PMCID: PMC8440627.
    Impact Statement: Serological assays intended for diagnosis, sero-epidemiologic assessment, and measurement of protective antibody titers upon infection or vaccination are essential for managing the SARS-CoV-2 pandemic. We developed an Enzyme-linked Immunosorbent Assay (ELISA) methods for measuring IgG, IgA, and IgM responses to SARS-CoV-2, Spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins. Our analyses demonstrate a broad immune response among individuals and suggest some non-RBD specific S IgG and IgA antibodies neutralize SARS-CoV-2.
  • Dunlap NE, van Berkel V, Cai L. COVID-19 and low-dose radiation therapy. Radiat Med Prot. 2021 Sep 10. doi: 10.1016/j.radmp.2021.09.004. Epub ahead of print. PMID: 34522905; PMCID: PMC8429076.
    Impact Statement: Global health authorities working on the COVID-19 outbreak continue to explore methods to reduce the rate of its transmission to healthy individuals. Low dose radiation (LDR) as an alternative approach has attracted more attention due to its several advantages compared to the current drugs and medicines. To date more than 10 case reports and pilot clinical trial preliminary outcomes are available from different countries, therefore, this summarized the potential rationales and mechanisms of LDR therapy for COVID-19 patients, and its current clinical status and potential use.
  • Roberts AM, Moulana NZ, Jagadapillai R, Cai L, Gozal E. Intravital Assessment of Pre-capillary Pulmonary Arterioles of Type-1 Diabetic Mice Shows Oxidative Damage and Increased Tone in Response to NOS Inhibition. J Appl Physiol (1985). 2021 Sep 30. doi: 10.1152/japplphysiol.00395.2021. Epub ahead of print. PMID: 34590907.
    Impact Statement: Diabetes is characterized by hyperglycemia, metabolic dysfunction, inflammation systemic vascular complications and oxidative damage affecting multiple organs but its effect on the lung and its large capillary network, have often been disregarded. This study finds that diabetes-induced changes in the lung involve microvascular dysfunction, platelet activation and altered vasoreactivity potentially impairing alveolar perfusion. Elucidating the mechanisms of diabetes-induced microangiopathy may provide novel therapeutic strategies to prevent or reverse diabetes consequences on multiple organs.
  • Klinge CM, Piell KM, Petri BJ, He L, Zhang X, Pan J, Rai SN, Andreeva K, Rouchka EC, Wahlang B, Beier JI, Cave MC. Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver. Environ Epigenet. 2021 Sep 17;7(1):dvab008. doi: 10.1093/eep/dvab008. PMID: 34548932; PMCID: PMC8448424.
    Impact Statement: A goal of our research is to understand how exposure to persistent environmental pollutants may contribute to the rise in metabolic diseases, including nonalcoholic fatty liver disease, seen in human populations. This publication is the first examination of how a high fat diet and PCB exposure affect post-transcriptional chemical modifications of RNA in mice as a model for nonalcoholic fatty liver disease.
  • Nabeta HW, Kouokam JC, Lasnik AB, Fuqua JL, Palmer KE. Novel Antifungal Activity of Q-Griffithsin, a Broad-Spectrum Antiviral Lectin. Microbiol Spectr. 2021 Sep 8:e0095721. doi: 10.1128/Spectrum.00957-21. Epub ahead of print. PMID: 34494857.
    Impact Statement: Although multiple antifungals have been developed against Candida species, the currently increasing candidiasis incidence and resistance acquired by some strains demand new agents. In this study, Q-griffithsin (Q-GRFT), an algal protein with broad-spectrum activity against enveloped viruses, showed growth-inhibitory effects on several Candida strains, suggesting its potential use to tackle such infections.
  • Koo H, Hwang JY, Jung S, Park H, Bok J, Park JW. Position Specific Alternative Splicing and Gene Expression Profiles Along the Tonotopic Axis of Chick Cochlea. Front Mol Biosci. 2021 Sep 8;8:726976. doi: 10.3389/fmolb.2021.726976. PMID: 34568429; PMCID: PMC8456117.
    Impact Statement: Our study shows another level of genetic regulation to accomplish the task of frequency discrimination in chick cochlea. We found that many genes involved in sound sensing and processing undergo progressively different alternative splicing along the tonotopic axis. This differentiated transcriptome along the tonotopic axis suggests that the cochlea expresses different combinations of proteins depending on cochlear location, although encoded in the same set of genes, to have unique functional properties suitable for sensing different sound frequencies.
  • O'Brien SJ, Scheurlen K, Rochet A, Fiechter C, Paas M, Pan J,Rai SN, Galandiuk S. Increased Expression of Long Non-coding RNA H19 is Associated With Colon Cancer Recurrence. J Surg Res. 2021 Sep 11;269:59-68. doi: 10.1016/j.jss.2021.08.004. Epub ahead of print. PMID: 34520983.
    Impact Statement: This study focuses on the analysis of an oncogenic long non-coding RNA H19 and its association with worse recurrence-free survival in patients with colon cancer, and in particular stage II colon cancer. These results suggest that H19 may have a specific role in the risk stratification of patients and may help inform decisions regarding the use and/or escalation of adjuvant therapy.
  • Wise JP Jr, Young JL, Cai J, Cai L. Current understanding of hexavalent chromium [Cr(VI)] neurotoxicity and new perspectives. Environ Int. 2021 Sep 20;158:106877. doi: 10.1016/j.envint.2021.106877. Epub ahead of print. PMID: 34547640.
    Impact Statement: This review paper discusses the neurotoxicity of hexavalent chromium [Cr(VI)], a widely recognized human carcinogen and health hazard, drawing from literature studying humans, animals, and cell cultures over the last 50+ years. Traditionally, Cr(VI) has not been considered a neurotoxicant and Cr(VI) neurotoxicity has been largely left out of discussions pertaining to human health and regulations protecting health. This review conclusively describes Cr(VI) as a neurotoxicant and calls for increased efforts to consider Cr(VI) neurotoxicity research and regulations.
  • Wood LA, Tomlinson MM, Pfeiffer JA, Walker KL, Keith RJ, Smith T, Yeager RA, Bhatnagar A, Kerstiens S, Gilkey D, Gao H, Srivastava S, Hart JL. Time spent outdoors and sleep normality: A preliminary investigation. Popul Med. 2021 Mar;3:7. doi: 10.18332/popmed/132119. Epub 2021 Mar 4. PMID: 34485920; PMCID: PMC8411876.
    Impact Statement: This study found associations between sleep normality and lower odds of bodily pain and depression. These findings will contribute to public health by adding to the overall knowledge base on the role of sleep on health and to provide a base for related investigation.
  • Caster DJ, Merchant ML. Collagen Remodeling Biomarkers in Lupus Nephritis. Kidney360. 2021 Sep 30;2(9):1395-1398. doi: 10.34067/KID.0004732021. PMID: 35373099; PMCID: PMC8786132.
  • Bhatnagar A. Cardiovascular Effects of Particulate Air Pollution. Annu Rev Med. 2021 Oct 13. doi: 10.1146/annurev-med-042220-011549. Epub ahead of print. PMID: 34644154.
    Impact Statement: Reviews current state of knowledge about the effects of air pollution on cardiovascular disease and mortality. It discusses the mechanisms by which exposure to air pollution affects cardiovascular risk factors and the subclinical progression of cardiovascular disease states.
  • Singh M, Kapoor A, Bhatnagar A. Physiological and Pathological Roles of Aldose Reductase. Metabolites. 2021 Sep 27;11(10):655. doi: 10.3390/metabo11100655. PMID: 34677370; PMCID: PMC8541668.
    Impact Statement: Reviews the role of aldose reductase in glucose metabolism and the detoxification of reactive aldehydes generated from the oxidation of membrane lipids and how the enzyme participates in the manifestation of the secondary complications of diabetes.
  • Malovichko MV, Abplanalp WT, McFall SA, Taylor BS, Wickramasinghe NS, Sithu ID, Zelko IN, Uchida S, Hill BG, Sutaria SR, Nantz MH, Bhatnagar A,Conklin DJ, O'Toole TE, Srivastava S. Subclinical markers of cardiovascular toxicity of benzene inhalation in mice. Toxicol Appl Pharmacol. 2021 Nov 15;431:115742. doi: 10.1016/j.taap.2021.115742. Epub 2021 Oct 5. PMID: 34624356.
    Impact Statement: Benzene is a ubiquitous environmental pollutant. Recent population-based studies suggest that benzene exposure is associated with an increased risk for cardiovascular disease. However, it is unclear whether benzene exposure by itself is sufficient to induce cardiovascular toxicity. We examined the effects of benzene inhalation (50 ppm, 6 h/day, 5 days/week, 6 weeks) or HEPA-filtered air exposure on the biomarkers of cardiovascular toxicity in male C57BL/6J mice. Together, these data suggest that benzene exposure induces endothelial injury, enhances platelet activation and inflammatory processes; and circulatory levels of endothelial cell and platelet-derived microparticles and platelet-leukocyte aggregates are excellent biomarkers of cardiovascular toxicity of benzene.
  • Xiong L, Zhou B, Liu H, Cai L. Comprehensive Review of Cadmium Toxicity Mechanisms in Male Reproduction and Therapeutic Strategies. Rev Environ Contam Toxicol. 2021 Oct 8. doi: 10.1007/398_2021_75. Epub ahead of print. PMID: 34618232.
    Impact Statement: Cadmium (Cd) has been widely studied as an environmental pollutant for many years with several organs, and this review focused on toxic effects of Cd exposure on male reproductive system. Currently preclinical animal studies have confirmed many proteins and intracellular signaling pathways involved in the pathological process of Cd-induced male reproductive damage and potential measures for prophylaxis and treatment, which primarily include antioxidants, anti-inflammatory agents, and essential ion supplement. The underlying mechanisms for Cd-induced toxicity on male reproductive function was comprehensively discussed, which may provide guidance for the treatment and prevention of Cd-induced male reproductive toxicity.
  • Li J, Jin S, Barati MT, Rane S, Lin Q, Tan Y, Cai L, Rane MJ. ERK and p38 MAPK inhibition controls NF-E2 degradation and profibrotic signaling in renal proximal tubule cells. Life Sci. 2021 Oct 26:120092. doi: 10.1016/j.lfs.2021.120092. Epub ahead of print. PMID: 34715142.
    Impact Statement: Li et. al. demonstrated p38 and ERK MAPK-dependent proteasomal degradation of the anti-fibrotic protein NF-E2 in TGF-β treated human renal proximal (HK-11) cells. Moreover, activation of the proteasome and loss of NF-E2 expression, induced JNK activation and CTGF expression. In contrast, proteasomal inhibition and NF-E2 over-expression, inhibited TGF-β-induced JNK activation an CTGF expression HK-11 cells and type 1 diabetic kidneys. Thus, NF-E2 could serve as a therapeutic target to generate therapies to prevent progression of renal fibrosis, chronic kidney disease, and renal failure associated with diabetes.
  • Zelko IN, Dassanayaka S, Malovichko MV, Howard CM, Garrett LF, Uchida S, Brittian KR, Conklin DJ, Jones SP, Srivastava S. Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction. Toxicol Sci. 2021 Oct 27:kfab125. doi: 10.1093/toxsci/kfab125. Epub ahead of print. PMID: 34718823.
    Impact Statement: Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. It is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.
  • DeJarnett N. Joining Forces With Environmental Health Professionals. J Public Health Manag Pract. 2021 Nov-Dec 01;27(6):621-622. doi: 10.1097/PHH.0000000000001430. PMID: 34554999.
    Impact Statement: This article describes concrete actions leaders in public health practice can take alongside local environmental health practitioners to champion climate sustainability, including evaluating capacity for climate action, fostering strategic partnerships, supporting career pathways, connecting with grassroots groups, and using storytelling as a communications tool.
  • Huang J, Firestone S, Moffatt-Bruce S, Tibi P, Shore-Lesserson L. 2021 Clinical Practice Guidelines for Anesthesiologists on Patient Blood Management in Cardiac Surgery. J Cardiothorac Vasc Anesth. 2021 Sep 24:S1053-0770(21)00845-4. doi: 10.1053/j.jvca.2021.09.032. Epub ahead of print. PMID: 34654633.
    Impact Statement: This 2021 STS/SCA/AmSECT/SABM updated patient blood management guideline stresses the importance of an evidence-based, multimodal, and multidisciplinary approach to preserving a patient’s blood and conserving resources so as to optimize outcomes in patients who are at high risk for transfusion.
  • Huntington-Moskos L, Rayens MK, Wiggins AT, Butler KM, Hahn EJ. Use of Theory-Driven Report Back to Promote Lung Cancer Risk Reduction. Int J Environ Res Public Health. 2021 Oct 11;18(20):10648. doi: 10.3390/ijerph182010648. PMID: 34682394; PMCID: PMC8536114.
    Impact Statement: The goal of this work is to highlight the role of a report back process in prompting health behavior change. Report back is active sharing of research findings with participants to prompt behavior change. In particular, research on a theory-driven report back process for environmental risk reduction is limited. Our research team sought to evaluate the impact of a stage-tailored report back process with participants who had high home radon and/or air nicotine levels. We found that tailored report back of research findings to individual participants reduced radon exposure and changed the health behavior necessary to remediate radon and SHS exposure.
  • Wahlang B, Gripshover TC, Gao H, Krivokhizhina T, Keith RJ, Sithu ID, Rai SN, Bhatnagar A, McClain CJ, Srivastava S, Cave MC. Associations between residential exposure to volatile organic compounds (VOCs) and liver injury markers. Toxicol Sci. 2021 Oct 20:kfab119. doi: 10.1093/toxsci/kfab119. Epub ahead of print. PMID: 34668566.
    Impact Statement: This publication investigated the effects of volatile organic compounds (VOCs), often found in air, and their contribution to liver disease, in Louisville community residents. The results from the study demonstrated significant positive associations between these environmental chemicals and liver disease biomarkers, which were more pronounced in smokers. These findings can help in better risk assessment of daily VOC exposures and provide some insight on how lifestyle factors such as smoking can contribute to liver disease risk.
  • Zelko IN, Taylor BS, Das TP, Watson WH, Sithu ID, Wahlang B, Malovichko MV, Cave MC, Srivastava S. Effect of vinyl chloride exposure on cardiometabolic toxicity. Environ Toxicol. 2021 Oct 30. doi: 10.1002/tox.23394. Epub ahead of print. PMID: 34717031.
    Impact Statement: Vinyl chloride (VC) is an organochlorine mainly used to manufacture its polymer polyvinyl chloride, which is extensively used in the manufacturing of consumer products. Recent studies suggest that chronic low dose VC exposure affects glucose homeostasis in high fat diet-fed mice. Our data suggest that even in the absence of high fat diet, exposure to VC (0.8 ppm, 6 h/day, 5 day/week, for 12 weeks) induces glucose intolerance (1.0 g/kg, i.p.) in male C57BL/6 mice.
  • Rouchka EC, Chariker JH, Saurabh K, Waigel S, Zacharias W, Zhang M, Talley D, Santisteban I, Puccio M, Moyer S, Holm RH, Yeager RA, Sokoloski KJ, Fuqua J, Bhatnagar A, Smith T. The Rapid Assessment of Aggregated Wastewater Samples for Genomic Surveillance of SARS-CoV-2 on a City-Wide Scale. Pathogens. 2021 Oct 1;10(10):1271. doi: 10.3390/pathogens10101271. PMID: 34684220; PMCID: PMC8541652.
    Impact Statement: This paper describes a collaborative effort between Louisville Metro Public Health and Wellness, The Louisville Metropolitan Sewer District, and the University of Louisville to monitor COVID-19 and track variant spread through testing of wastewater samples over a 28 week period. The information gained from this work enabled targeted public health efforts including outreach to at-risk communities and the deployment of mobile and community-focused vaccination campaigns.
  • Banerjee M, Al-Eryani L, Srivastava S, Rai SN, Pan J, Kalbfleisch TS, States JC. Delineating the Effects of Passaging and Exposure in a Longitudinal Study of Arsenic-Induced Squamous Cell Carcinoma in a HaCaT Cell Line Model. Toxicol Sci. 2021 Nov 3:kfab129. doi: 10.1093/toxsci/kfab129. Epub ahead of print. PMID: 34730829.
    Impact Statement: This work provides strong evidence of the requirement for passage matched controls in long term (chronic) exposure studies in cultured cells. Using passage matched controls identifies changes in gene expression that are related to the passage of time and not to the exposure, thus reducing artifacts that otherwise would be interpreted as due to the exposure.
  • Petriello MC, Mottaleb MA, Serio TC, Balyan B, Cave MC, Pavuk M, Birnbaum LS, Morris AJ. Serum concentrations of legacy and emerging per- and polyfluoroalkyl substances in the Anniston Community Health Surveys (ACHS I and ACHS II). Environ Int. 2021 Nov 8;158:106907. doi: 10.1016/j.envint.2021.106907. Epub ahead of print. PMID: 34763231.
    Impact Statement: We participate in a longstanding multicenter and interagency collaboration examining the metabolic health effect of PCB and dioxin exposures in residents living near a former PCB production facility in Anniston, Alabama. PFAS exposures have also been associated with metabolic diseases. Here we determined higher concentrations of PFAS in Anniston participants than the general US residential population. This finding will allow us to examine associations between PFAS exposures and previously collected disease biomarkers in this cohort.
  • Jin L, Conklin DJ. A novel evaluation of endothelial dysfunction ex vivo: "Teaching an Old Drug a New Trick". Physiol Rep. 2021 Nov;9(21):e15120. doi: 10.14814/phy2.15120. PMID: 34755498; PMCID: PMC8579072.
    Impact Statement: Endothelial dysfunction (ED) is sine qua non of atherosclerosis and other cardiovascular diseases in humans, yet the mechanisms that contribute to ED are still being investigated. Our study demonstrates a novel methodological twist using an old drug (L-NAME) to screen for ED in murine aorta following acute exposure to toxicants including air pollution, aldehydes, and tobacco-derived aerosols. This approach complements currently existing tools providing greater insight into the mechanisms of vascular injury due to environmental toxicants.
  • Leggett CS, Doll MA, Salazar-González RA, Habil MR, Trent JO, Hein DW. Identification and characterization of potent, selective, and efficacious inhibitors of human arylamine N-acetyltransferase 1. Arch Toxicol. 2021 Nov 16. doi: 10.1007/s00204-021-03194-x. Epub ahead of print. PMID: 34783865.
    Impact Statement: The study identifies potent, selective, and efficacious inhibitors of human arylamine N-acetyltransferase 1 (NAT1) important in the activation of arylamine carcinogens. The ability to inhibit NAT1 could reduce breast cancer metastasis particularly to bone.
  • Wang L, Cai H, Wang Y, Liu J, Chen T, Liu J, Huang J, Guo Q, Zou W. Enhanced recovery after elective craniotomy: A randomized controlled trial. J Clin Anesth. 2022 Feb;76:110575. doi: 10.1016/j.jclinane.2021.110575. Epub 2021 Nov 2. PMID: 34739947.
    Impact Statement: Implementation of an enhanced recovery after elective craniotomy protocol had significant benefits over conventional perioperative management. It was associated with a significant reduction in postoperative length of stay, medical cost, and postoperative complications.
  • Polivka BJ, Eldeirawi K, Huntington-Moskos L, Nyenhuis SM. Mask Use Experiences, COVID-19, and Adults with Asthma: A Mixed-Methods Approach. J Allergy Clin Immunol Pract. 2021 Nov 14:S2213-2198(21)01262-9. doi: 10.1016/j.jaip.2021.10.071. Epub ahead of print. PMID: 34785392; PMCID: PMC8590602.
    Impact Statement: This study reports that most adults with asthma reported wearing a mask in public places. Lower asthma control and longer daily mask wearing were associated with more self-reported problems with wearing masks. To increase wearability, study participants recommended using a comfortable mask that fits, staying calm, breathing slowly and deeply were recommended. Recommendations also included taking safe “mask breaks” when needed.
  • Kotla NG, Isa ILM, Rasala S, Demir S, Singh R, Baby BV, Swamy SK, Dockery P, Jala VR, Rochev Y, Pandit A. Modulation of Gut Barrier Functions in Ulcerative Colitis by Hyaluronic Acid System. Adv Sci (Weinh). 2021 Nov 10:e2103189. doi: 10.1002/advs.202103189. Epub ahead of print. PMID: 34761543.
    Impact Statement: This study was accomplished in collaboration (lead the project) with Drs. Yury Rochev, Abhay Pandit, CÚRAM, SFI Research Centre for Medical Devices, National University of Ireland Galway, Galway, H91 W2TY, Ireland. The goal of this study is to discover the compounds and mechanisms that can enhance gut barrier function in ulcerative colitis conditions. Current study showed that treatment with biphasic hyaluronan (HA) enema suspension, naïve-HA systems protect against gut barrier dysfunction in ulcerative colitis by increasing tight junction proteins. These studies provide novel approaches to target ulcerative colitis.
  • Lindsey ML, LeBlanc AJ, Ripplinger CM, Carter JR, Kirk JA, Hansell Keehan K, Brunt KR, Kleinbongard P, Kassiri Z. Reinforcing rigor and reproducibility expectations for use of sex and gender in cardiovascular research. Am J Physiol Heart Circ Physiol. 2021 Nov 1;321(5):H819-H824. doi: 10.1152/ajpheart.00418.2021. Epub 2021 Sep 15. PMID: 34524922.
    Impact Statement: This is an editorial from the Editor-in-chief and the 7 Associate Editors of the American Journal of Physiology Heart and Circulatory Physiology that states our expectation that males and females be incorporated into all studies unless a very strong rationale prevents the authors from doing so, starting in 2023. Some examples of rationale include examining processes that occur only in one sex (i.e. cardiovascular complications of pregnancy), or testing the effects of oral contraceptives on cardiovascular health. By including studies utilizing both sexes/genders, this will result in a more complete, unbiased and reliable data set that more accurately mirrors the population.
  • Schneider G, Kaliappan A, Nguyen TQ, Buscaglia R, Brock GN, Hall MB, DeSpirito C, Wilkey DW, Merchant ML, Klein JB, Wiese TA, Rivas-Perez HL, Kloecker GH, Garbett NC. The Utility of Differential Scanning Calorimetry Curves of Blood Plasma for Diagnosis, Subtype Differentiation and Predicted Survival in Lung Cancer. Cancers (Basel). 2021 Oct 23;13(21):5326. doi: 10.3390/cancers13215326. PMID: 34771491; PMCID: PMC8582427.
    Impact Statement: The recent increase in the number of lung cancer cases unrelated to the well-known risk factors, and the high false-positive rate of low-dose CT scans, indicate a need to develop new, non-invasive methods for lung cancer detection. Our results using differential scanning calorimetry (DSC) supported by targeted proteomic studies suggests the DSC curve features could be useful for differentiation of lung cancer patients from controls with some capable of distinction between subtypes and stages of lung cancer.
  • Trace ME, Feygin YB, Williams PG, Winders Davis D, Brothers KB, Sullivan JE, Calhoun AW. Attention-Deficit/Hyperactivity Disorder Practice Patterns: A Survey of Kentucky Pediatric Providers. J Dev Behav Pediatr. 2021 Nov 17. doi: 10.1097/DBP.0000000000001037. Epub ahead of print. PMID: 34799539.
    Impact Statement: Kentucky ranks among the highest in the nation for attention-deficit/hyperactivity disorder (ADHD) prevalence in children aged 4 to 17 years. In 2011, the American Academy of Pediatrics (AAP) released a clinical practice guideline based on the DSM-IV. A guideline revision based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) was released in October 2019. In this study, we assessed and described a sample of Kentucky pediatric providers' ADHD practices using the 2011 guideline and DSM-5 diagnostic criteria. Although pediatricians in the KY AAP that responded adhere to the DSM-5 criteria for diagnosing ADHD, pediatric providers' practices would benefit from education in improvements in pharmacotherapy titration, surveillance of coexisting conditions associated with ADHD, discussion of psychosocial interventions, and school support strategies.
  • ElNakieb Y, Ali MT, Elnakib A, Shalaby A, Soliman A, Mahmoud A, Ghazal M, Barnes GN, El-Baz A. The Role of Diffusion Tensor MR Imaging (DTI) of the Brain in Diagnosing Autism Spectrum Disorder: Promising Results. Sensors (Basel). 2021 Dec 7;21(24):8171. doi: 10.3390/s21248171. PMID: 34960265; PMCID: PMC8703859.
    Impact Statement: Autism spectrum disorder (ASD) diagnosis is usually subjective, and scores can vary from one specialist to another. Previous literature suggests differences in brain development, environmental, and/or genetic factors play a role in developing autism, yet scientists still do not know exactly the pathology of this disorder. This paper provides a study of implementing feature engineering tools to find discriminant insights from brain imaging of white matter connectivity and using a machine learning framework for an accurate classification of autistic individuals.
  • Men H, Young JL, Zhou W, Zhang H, Wang X, Xu J, Lin Q, Tan Y, Zheng Y, Cai L. Early-Life Exposure to Low-Dose Cadmium Accelerates Diethylnitrosamine and Diet-Induced Liver Cancer. Oxid Med Cell Longev. 2021 Nov 28;2021:1427787. doi: 10.1155/2021/1427787. PMID: 34876963; PMCID: PMC8645401.
    Impact Statement: Although maternal exposure to cadmium causes obesity and metabolic changes in the offspring, including nonalcoholic fatty liver disease-like pathology, whether maternal cadmium exposure accelerates liver cancer in the offspring is unknown. This study investigated the impact of early-life exposure to cadmium on the incidence and potential mechanisms of hepatocellular carcinoma (HCC) in offspring subjected to postweaning HCC induction, and confirmed that early-life exposure to low-dose cadmium accelerates liver cancer development induced by a DEN/HFCD in male mice, probably due to chronic lipotoxicity and inflammation.
  • Bao T, Liu J, Leng J, Cai L. The cGAS-STING pathway: more than fighting against viruses and cancer. Cell Biosci. 2021 Dec 14;11(1):209. doi: 10.1186/s13578-021-00724-z. PMID: 34906241; PMCID: PMC8670263.
    Impact Statement: In the classic cGAS-stimulator of interferon genes (STING) pathway, downstream signals can control the production of type I interferon (IFN) and NF-κB to promote the activation of pro-inflammatory molecules, which are mainly induced during antiviral responses. However, this review mainly highlights the functions of the cGAS-STING pathway in chronic inflammatory diseases, with focus on the important role of cGAS-STING pathway in the chronic inflammatory status in diabetes and diabetes-related complications.
  • Zhou W, Young JL, Men H, Zhang H, Yu H, Lin Q, Xu H, Xu J, Tan Y, Zheng Y, Cai L. Sex differences in the effects of whole-life, low-dose cadmium exposure on postweaning high-fat diet-induced cardiac pathogeneses. Sci Total Environ. 2021 Dec 5;809:152176. doi: 10.1016/j.scitotenv.2021.152176. Epub ahead of print. PMID: 34875320.
    Impact Statement: We previously showed the development of cardiac remodeling (hypertrophy or fibrosis) in mice with either post-weaning high-fat diet (HFD, 60% kcal fat) feeding or exposure to chronic low-dose cadmium. Here, we determined whether whole-life exposure to environmentally relevant, low-dose cadmium affects the susceptibility of offspring to post-weaning HFD-induced cardiac pathologies and function, and confirmed that whole-life 5 ppm cadmium exposure significantly increases the susceptibility of female offspring to HFD-induced cardiac remodeling and dysfunction.
  • Li F, Chen J, Liu Y, Gu Z, Jiang M, Zhang L, Chen SY, Deng Z, McClain CJ, Feng W. Deficiency of Cathelicidin Attenuates High-Fat Diet Plus Alcohol-Induced Liver Injury through FGF21/Adiponectin Regulation. Cells. 2021 Nov 27;10(12):3333. doi: 10.3390/cells10123333. PMID: 34943840; PMCID: PMC8699208.
    Impact Statement: Alcohol consumption and obesity are known risk factors of steatohepatitis. In this paper, Dr. Wenke Feng, Professor of Medicine, and his collaborators, including some in the CIEHS, demonstrated that deficiency of CRAMP is against a high-fat diet plus acute alcohol-induced liver injury. These results suggest that targeting CRAMP could be an effective approach for the prevention/treatment of high-fat diet plus alcohol consumption-induced steatohepatitis.
  • Zhao CB, Yu J, Kong M, Han J, Du H, Huang J. Ketamine for Monitored Anesthesia Care during Transcatheter Aortic Valve Replacement. J Perianesth Nurs. 2021 Dec 28:S1089-9472(21)00147-7. doi: 10.1016/j.jopan.2021.06.007. Epub ahead of print. PMID: 34972624.
    Impact Statement: Employing Ketamine as an adjunct during monitored anesthesia care for transcatheter aortic valve replacement is a feasible option.
  • Majumder S, Pushpakumar S, Juin SK, Jala VR, Sen U. Toll-like receptor 4 mutation protects the kidney from Ang-II-induced hypertensive injury. Pharmacol Res. 2021 Dec 9;175:106030. doi: 10.1016/j.phrs.2021.106030. Epub ahead of print. PMID: 34896544.
    Impact Statement: This article describes the mechanism of how TLR4 activation suppresses autophagy, induces apoptosis and kidney injury in Ang-II-induced hypertension, and TLR4 mutation protects the kidney.
  • Das S, Rai A, Merchant ML, Cave MC, Rai SN. A Comprehensive Survey of Statistical Approaches for Differential Expression Analysis in Single-Cell RNA Sequencing Studies. Genes (Basel). 2021 Dec 2;12(12):1947. doi: 10.3390/genes12121947. PMID: 34946896; PMCID: PMC8701051.
    Impact Statement: Differential Expression (DE) analysis in presence of noises from different sources remains a key challenge in Single-cell RNA-sequencing (scRNA-seq) studies. Earlier practices for addressing this involved borrowing methods from bulk RNA-seq, which are based on non-zero differences in average expressions of genes across cell populations. We evaluate the performance of 19 widely used methods in terms of 13 performance metrics on 11 real scRNA-seq datasets. Our findings suggest that some bulk RNA-seq methods are quite competitive with the single-cell methods, but their performance depends on the underlying models. However, the multi-criteria and combined-data analysis indicates that DECENT and EBSeq are the best options for DE analysis. Our evaluation provides proper guidelines for selecting the proper tool which performs best under particular experimental settings in the context of the scRNA-seq.
  • Xu F, Mu J, Teng Y, Zhang X, Sundaram K, Sriwastva MK, Kumar A, Lei C, Zhang L, Liu QM, Yan J, McClain CJ, Merchant ML, Zhang HG. Restoring Oat Nanoparticles Mediated Brain Memory Function of Mice Fed Alcohol by Sorting Inflammatory Dectin-1 Complex Into Microglial Exosomes. Small. 2021 Dec 13:e2105385. doi: 10.1002/smll.202105385. Epub ahead of print. PMID: 34897972.
    Impact Statement: This study focuses on the molecular mechanism(s) underlying how oat nanoparticles (oatN) contributes to the inhibition of microglial cell mediated inflammation. The findings from this study are significant in that it provides a basis for developing mechanism-driven novel approaches for prevention of microglial cell mediated chronic inflammation of the brain via non-invasive oral administration.
  • Wu B, Pal S, Kang J, Guo Y. Distributional independent component analysis for diverse neuroimaging modalities. Biometrics. 2021 Oct 25. doi: 10.1111/biom.13594. Epub ahead of print. PMID: 34694629.
    Impact Statement: Analysis of images derived from various neuroimaging modalities involves some common goals such as dimension reduction, denoising, and feature extraction. However, since these modalities have vastly different data characteristics, the current analysis is usually performed using distinct analytical tools that are only suitable for a specific imaging modality. In this paper, we present a Distributional Independent Component Analysis (DICA) that represents a new approach that performs decomposition on the distribution level, providing a unified framework for extracting features across imaging modalities with different scales and representations.
  • Wu B, Pal S, Kang J, Guo Y. Rejoinder to discussions of "distributional independent component analysis for diverse neuroimaging modalities". Biometrics. 2021 Nov 15. doi: 10.1111/biom.13588. Epub ahead of print. PMID: 34780668.
    Impact Statement: This paper provides results and comments to address the questions raised in the discussions of our recent publication entitled "Distributional independent component analysis for diverse neuroimaging modalities".
  • Aqil F, Munagala R, Agrawal AK, Jeyabalan J, Tyagi N, Rai SN, Gupta RC. Anthocyanidins Inhibit Growth and Chemosensitize Triple-Negative Breast Cancer via the NF-κB Signaling Pathway. Cancers (Basel). 2021 Dec 13;13(24):6248. doi: 10.3390/cancers13246248. PMID: 34944868; PMCID: PMC8699375.
    Impact Statement: Breast cancer is the most common female cancer diagnosed in the U.S. and the second most common cause of cancer death in women. Chemotherapeutics used to treat breast cancer often have side effects, which are sometimes life-threatening. Moreover, the tumors can develop resistance over time, making breast cancer treatment challenging. In this paper, we show that the oral administration of colored pigments isolated from bilberry/blueberry, called anthocyanidins (Anthos), significantly decrease tumor volume, inhibit the growth and metastasis of breast cancer, sensitize drug-resistant tumor cells, and exhibit a lower rate of lymph node and lung metastasis, compared to control. These mechanistic insights are expected to be valuable for clinical translation of berry Anthos, either alone or as adjuvant to chemotherapy, for the treatment of breast cancer patients.
  • Yusuf M, Pan J, Rai SN, Eldredge-Hindy H. Financial Toxicity in Women With Breast Cancer Receiving Radiation Therapy: Final Results of a Prospective Observational Study. Pract Radiat Oncol. 2021 Dec 9:S1879-8500(21)00301-5. doi: 10.1016/j.prro.2021.11.003. Epub ahead of print. PMID: 34896597.
    Impact Statement: In this prospective study of women with BC receiving RT, distinct factors including surgery type were significantly associated with FT. FT was strongly correlated with health-related QoL. Increased characterization of the relationship between FT and health-related QoL for women with BC receiving RT and defining clinical predictors of FT may help guide future studies investigating optimal targeted interventions for patients with BC at high risk for FT.
  • Ferragut Cardoso AP, Banerjee M, Al-Eryani L, Sayed M, Wilkey DW, Merchant ML, Park JW, States JC. Temporal Modulation of Differential Alternative Splicing in HaCaT Human Keratinocyte Cell Line Chronically Exposed to Arsenic for up to 28 Wk. Environ Health Perspect. 2022 Jan;130(1):17011. doi: 10.1289/EHP9676. Epub 2022 Jan 24. PMID: 35072517; PMCID: PMC8785870.
    Impact Statement: The majority of human genes encode multiple protein isoforms. The isoforms are produced from mRNA isoforms edited from the primary transcripts by alternative splicing. This manuscript uses a model cell culture system to show that exposure to an inorganic arsenic compound that naturally contaminates drinking water in many parts of the world markedly disrupts the alternative splicing producing many errant mRNAs, and that the mRNA isoforms produced change over time with chronic exposure. One of the targets of the arsenic appears to be the splicing factor network itself.
  • Ghosh S, Banerjee M, Haribabu B, Jala VR. Urolithin A attenuates arsenic-induced gut barrier dysfunction. Arch Toxicol. 2022 Feb 5. doi: 10.1007/s00204-022-03232-2. Epub ahead of print. PMID: 35122514.
    Impact Statement: Chronic exposure to inorganic arsenic leads to an increase in both the onset and progression of several human diseases targeting multiple organs (liver, kidney, bladder, skin, intestines, and central nervous system), which is referred to as ‘arsenicosis’. Gut microbial Urolithin A is derived from ellagic acid and ellagitannins (major poly phenolic components in berries and pomegranate) by gut commensal bacteria. The current study reports the beneficial effects of Urolithin A against adverse effects of trivalent arsenic on human gut epithelia, where treatment with Urolithin A protected against arsenic-induced gut epithelial damage. These studies will pave a pathway for preventive and therapeutic applications to mitigate arsenic-elicited adverse health effects, which are currently unavailable.
  • Lorkiewicz P, Keith R, Lynch J, Jin L, Theis W, Krivokhizhina T, Riggs D, Bhatnagar A, Srivastava S, Conklin DJ. Electronic Cigarette Solvents, JUUL E-Liquids, and Biomarkers of Exposure: In Vivo Evidence for Acrolein and Glycidol in E-Cig-Derived Aerosols. Chem Res Toxicol. 2022 Jan 19. doi: 10.1021/acs.chemrestox.1c00328. Epub ahead of print. PMID: 35044764.
    Impact Statement: In this study, we identify the formation of 2 toxicants, acrolein and glycidol, from the e-cigarette solvent vegetable glycerin. This finding may improve public health via use of a potential biomarker of e-cigarette use such that e-cigarette use can be quantified. Subsequently, the amount of e-cigarette use can be associated with biomarkers of harm including those that reflect cardiorespiratory injury. Overall, this finding may allow us to better predict health risks of chronic use of e-cigarettes.
  • Cave MC, Pinkston CM, Rai SN, Wahlang B, Pavuk M, Head KZ, Carswell GK, Nelson GM, Klinge CM, Bell DA, Birnbaum LS, Chorley BN. Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey. Environ Health Perspect. 2022 Jan;130(1):17003. doi: 10.1289/EHP9467. Epub 2022 Jan 6. PMID: 34989596; PMCID: PMC8734566.
    Impact Statement: This environmental epidemiology study determined associations between PCB pollutant exposures and liver disease in residents living near a chemical plant.
  • Fan H, Li Y, Yuan F, Lu L, Liu J, Feng W, Zhang HG, Chen SY. Up-regulation of microRNA-34a mediates ethanol-induced impairment of neural crest cell migration in vitro and in zebrafish embryos through modulating epithelial-mesenchymal transition by targeting Snail1. Toxicol Lett. 2022 Jan 14;358:17-26. doi: 10.1016/j.toxlet.2022.01.004. Epub ahead of print. PMID: 35038560.
    Impact Statement: Fetal alcohol spectrum disorder (FASD) is among the most devastating consequences of the widespread use and abuse of alcohol in pregnant women. The prevalence of FASD in the United States and Western European countries is estimated to be as high as 1–5 per 100 children. The findings from this study elucidate a novel mechanism by which alcohol impairs neural crest cell migration through modulating microRNAs and epithelial-mesenchymal transition and suggests that miR- 34a may represent a novel therapeutic target for the development of approaches to ameliorate or prevent FASD.
  • Abouleisa RRE, Salama ABM, Ou Q, Tang XL, Solanki M, Guo Y, Nong Y, McNally L, Lorkiewicz PK, Kassem KM, Ahern BM, Choudhary K, Thomas R, Huang Y, Juhardeen HR, Siddique A, Ifthikar Z, Hammad SK, El-Baz AS, Ivey KN, Conklin DJ, Satin J, Hill BG, Srivastava D, Bolli R, Mohamed TMA. Transient Cell Cycle Induction in Cardiomyocytes to Treat Subacute Ischemic Heart Failure. Circulation. 2022 Jan 21. doi: 10.1161/CIRCULATIONAHA.121.057641. Epub ahead of print. PMID: 35061545.
    Impact Statement: In this study, we gained mechanistic insights into the process of forced cardiomyocyte proliferation and advanced the clinical feasibility of this approach by minimizing the oncogenic potential of the cell cycle factors via use of a novel transient and cardiomyocyte-specific viral construct. These findings may lead to clinical interventions to repair the heart after acute heart attack and to delay or prevent progression to heart failure.
  • Zhao J, Gomes D, Jin L, Mathis SP, Li X, Rouchka EC, Bodduluri H, Conklin DJ, O'Toole TE. Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice. Ecotoxicol Environ Saf. 2022 Jan 27;232:113239. doi: 10.1016/j.ecoenv.2022.113239. Epub ahead of print. PMID: 35093814.
    Impact Statement: Modern society produces and uses huge amounts of plastics and a large percentage of these ultimately accumulate in water systems and landfills, where they eventually degrade into particles of smaller size. While emerging evidence has documented that these microplastics are abundant in water supplies and the food chain where their human consumption is inevitable, the health consequences of such consumption are not completely known. In this study, we supplied mice with drinking water containing different sizes and doses of polystyrene beads and found that they developed obesity and showed early signs of insulin resistance/diabetes. Thus, the consumption of microplastics may promote early cardiovascular disease.
  • Carlisle SM, Trainor PJ, Doll MA, Hein DW. Human Arylamine N-Acetyltransferase 1 (NAT1) Knockout in MDA-MB-231 Breast Cancer Cell Lines Leads to Transcription of NAT2. Front Pharmacol. 2022 Jan 3;12:803254. doi: 10.3389/fphar.2021.803254. PMID: 35046826; PMCID: PMC8762260.
    Impact Statement: RNAseq was utilized to interrogate differential gene expression across three biological replicates of previously constructed and characterized MDA-MB-231 breast cancer cell lines expressing parental, increased, decreased, or knockout levels of N-acetyltransferase 1 (NAT1). 3,889 genes were significantly associated with NAT1 N-acetylation activity; 1,756 were positively associated and 2,133 were negatively associated with enrichment of genes involved in cell adhesion.
  • Rayens MK, McGeeney T, Wiggins A, Bucher A, Ickes M, Huntington-Moskos L, Clark P, Hahn E. Smoke-free Ordinances and Youth Tobacco Use in Kentucky. Am J Health Promot. 2022 Jan 27:8901171211066913. doi: 10.1177/08901171211066913. Epub ahead of print. PMID: 35081759.
    Impact Statement: Nearly half of U.S. youth are not protected by smoke-free laws. This study underscores the association between comprehensive laws and decreased likelihood for both cigarette and smokeless tobacco use among high school students in a state with high use rates overall.
  • Kotla NG, Singh R, Baby BV, Rasala S, Rasool J, Hynes SO, Martin D, Egan LJ, Vemula PK, Jala VR, Rochev Y, Pandit A. Inflammation-specific targeted carriers for local drug delivery to inflammatory bowel disease. Biomaterials. 2022 Feb;281:121364. doi: 10.1016/j.biomaterials.2022.121364. Epub 2022 Jan 5. PMID: 35066288.
    Impact Statement: Delivering drugs directly to the inflamed intestinal sites to treat inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis, is highly challenging. In collaboration with Drs. Kotla, Yury Rochev and Abhay Pandit from CÚRAM, SFI Research Centre for Medical Devices, National University of Ireland Galway, Ireland, we report the development of a strong anionic charged inflammation targeted nanocarriers (IT-NCs) loaded with an immunosuppressant model drug. The results suggest that IT-NCs have promising therapeutic potential as delivery carriers' in colitis management.
  • Speer RM, Meaza I, Toyoda JH, Lu Y, Xu Q, Walter RB, Kong M, Lu H, Kouokam JC, Wise JP Sr. Particulate hexavalent chromium alters microRNAs in human lung cells that target key carcinogenic pathways. Toxicol Appl Pharmacol. 2022 Jan 28:115890. doi: 10.1016/j.taap.2022.115890. Epub ahead of print. PMID: 35101437.
    Impact Statement: microRNAs play a role in virtually all biological processes, and thus, it is essential to understand their role in human disease, in particular cancer. Our recent publication is at the forefront of understanding how hexavalent chromium-altered microRNAs contribute to environmental carcinogenesis and advances the fields of environmental toxicology, human health, and cancer research. This work provides cancer researchers valuable data to better understand pathways to target cancer treatments and risk assessors information to update safety standards to better protect public health.
  • Faulkner CS, White CM, Manatsathit W, Lamb B, Vatsalya V, McClain CJ, Jophlin LL. Blood phosphatidylethanol (PEth) positivity associates with unfavorable waitlist-related outcomes for patients medically appropriate for liver transplant. Alcohol Clin Exp Res. 2022 Jan 31. doi: 10.1111/acer.14786. Epub ahead of print. PMID: 35102553.
    Impact Statement: Excessive alcohol use is a leading etiology of liver disease and indication for liver transplantation. This study explores the association of phosphatidylethanol (PEth) results with liver transplant waitlist-focused patient outcomes. This study reporting a comprehensive account of PEth utilization at a liver transplant center demonstrates that liver transplant waitlist-related outcomes associate with PEth test results.
  • Oh YJ, Dent MW, Freels AR, Zhou Q, Lebrilla CB, Merchant ML, Matoba N. Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans. Mol Ther. 2022 Jan 22:S1525-0016(22)00030-2. doi: 10.1016/j.ymthe.2022.01.030. Epub ahead of print. PMID: 35077861.
    Impact Statement: Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. CIEHS members assisting the lab of Nobuyuki Matoba, Ph.D. (UL Department of Pharmacology & Toxicology and Brown Cancer Center) showed that a fusion protein termed a ‘lectibody’ comprised of the high-mannose glycan-binding lectin Avaren and human immunoglobulin G1 (IgG1) Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon, and blood cancers at nanomolar concentrations. Proteomics studies identified specific AvFc interaction with epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R). AvFc blocked EGFR and IGF1R signaling in cell culture models of cancer and induced potent Fc-mediated cytotoxic effects and significantly restricted A549 and H460 tumor growth in severe combined immunodeficiency (SCID) mice. These findings provided evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.
  • Sriwastva MK, Deng ZB, Wang B, Teng Y, Kumar A, Sundaram K, Mu J, Lei C, Dryden GW, Xu F, Zhang L, Yan J, Zhang X, Park JW, Merchant ML, Egilmez NK, Zhang HG. Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway. EMBO Rep. 2022 Jan 7:e53365. doi: 10.15252/embr.202153365. Epub ahead of print. PMID: 34994476.
    Impact Statement: Proof of concept research demonstrated that exosome-like nanoparticles (MBELNs) derived from edible mulberry bark conferred protection against colitis in a mouse model through promoting heat shock protein family A (Hsp70) member 8 (HSPA8)-mediated activation of the AhR signaling pathway and induction of COP9 Constitutive Photomorphogenic Homolog Subunit 8 (COPS8). The results suggest that MBELNs represent an undescribed mode of inter-kingdom communication in the mammalian intestine and edible plant-derived ELNs may hold the potential as new agents for the prevention and treatment of gut-related inflammatory disease.
  • Das S, Rai SN. Statistical methods for analysis of single-cell RNA-sequencing data. MethodsX.2021 Nov 17;8:101580. doi: 10.1016/j.mex.2021.101580. PMID: 35004214; PMCID: PMC8720898.
    Impact Statement: Analyzing the Single-cell RNA-sequencing (scRNA-seq) data in presence of biological confounding factors including dropout events is a challenging task. In this article, we present a novel statistical approach for various analyses of the scRNA-seq Unique Molecular Identifier (UMI) counts data, including model-based fitting of observed UMI data, cell type detection, estimation of cell capture rates, estimation of gene specific model parameters, estimation of the sample mean, and sample variance of the genes.
  • Bhattacharyya A, Chakraborty T, Rai SN. Stochastic forecasting of COVID-19 daily new cases across countries with a novel hybrid time series model. Nonlinear Dyn. 2022 Jan 13:1-16. doi: 10.1007/s11071-021-07099-3. Epub ahead of print. PMID: 35039713; PMCID: PMC8754528.
    Impact Statement: In this paper, we develop a hybrid forecasting model that can generate real-time out-of-sample forecasts of COVID-19 outbreaks for five profoundly affected countries, namely the USA, Brazil, India, the UK, and Canada. A novel hybrid approach based on the Theta method and autoregressive neural network (ARNN) model, named Theta-ARNN (TARNN) model. Daily new cases of COVID-19 are nonlinear, non-stationary, and volatile; thus, a single specific model cannot be ideal for future prediction of the pandemic. The proposed method outperforms traditional univariate and hybrid forecasting models for the test datasets on an average.
  • Riggs DW, Malovichko MV, Gao H, McGraw KE, Taylor BS, Krivokhizhina T, Rai SN, Keith RJ, Bhatnagar A, Srivastava S. Environmental exposure to volatile organic compounds is associated with endothelial injury. Toxicol Appl Pharmacol. 2022 Jan 16;437:115877. doi: 10.1016/j.taap.2022.115877. Epub ahead of print. PMID: 35045333.
    Impact Statement: In this study, we hypothesized that ambient exposure to VOCs amplifies cardiovascular disease (CVD) risk by depleting circulating angiogenic cells (CACs). We found that Low-level ambient exposure to VOCs is associated with CAC depletion, which could compromise endothelial repair and angiogenesis, and exacerbate CVD risk. 
  • Jin J, Wahlang B, Thapa M, Head KZ, Hardesty JE, Srivastava S, Merchant ML, Rai SN, Prough RA, Cave MC. Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver. Acta Pharm Sin B. 2021 Dec;11(12):3806-3819. doi: 10.1016/j.apsb.2021.10.014. Epub 2021 Oct 21. PMID: 35024308; PMCID: PMC8727924.
    Impact Statement: PCB pollutant exposures activate the aryl hydrocarbon receptor and are associated with liver disease. This study used genetic mouse models to determine the role of this receptor and PCBs acting through this receptor in liver disease.
  • Ritzenthaler JD, Torres-Gonzalez E, Zheng Y, Zelko IN, Van Berkel V, Nunley DR, Kidane B, Halayko AJ, Summer R, Watson WH, Roman J. The pro-fibrotic and senescence phenotype of old lung fibroblasts is reversed or ameliorated by genetic and pharmacological manipulation of Slc7a11 expression. Am J Physiol Lung Cell Mol Physiol. 2022 Jan 5. doi: 10.1152/ajplung.00593.2020. Epub ahead of print. PMID: 34984918.
    Impact Statement: Fibroblasts from the lungs of old mice have low expression of the transporter for the amino acid cystine and high expression of markers of senescence and genes associated with fibrosis. Restoration of the cystine transporter made the old cells look more like young cells. These findings point the way toward new therapies designed to counteract the disrepair responses typically seen in the aging lung.
  • Xiong L, Zhou B, Young JL, Xu J, Wintergerst K, Cai L. Effects of whole-life exposure to low-dose cadmium with post-weaning high-fat diet on offspring testes in a male mouse model. Chem Biol Interact. 2022 Feb 1;353:109797. doi: 10.1016/j.cbi.2022.109797. Epub 2022 Jan 5. PMID: 34998821.
    Impact Statement: Several studies have reported testicular impairments caused by cadmium (Cd) or obesity alone, therefore, this study examined the combined effect of Cd and obesity on the testes and its underlying mechanism remains unclear. demonstrated that exposure to Cd or HFD alone significantly disrupted testicular structure and increased germ cell apoptosis at both 10 and 24 weeks. However, co-exposure to Cd and HFD did not induce the toxic effects that were induced by either alone, which was associated with the activation of the JAK/STAT pathway. These unexpected results need to be further investigated in the future study.
  • Young JL, Cave MC, Xu Q, Kong M, Xu J, Lin Q, Tan Y, Cai L. Whole life exposure to low dose cadmium alters diet-induced NAFLD. Toxicol Appl Pharmacol. 2022 Feb 1;436:115855. doi: 10.1016/j.taap.2021.115855. Epub 2022 Jan 3. PMID: 34990729; PMCID: PMC8796138.
    Impact Statement: This study is one of the first to investigate the impact of whole life cadmium exposure (in utero throughout adulthood) on the development high fat diet-induced Nonalcoholic fatty liver disease NAFLD, taking into consideration that environmental exposures can be life-long, spanning multiple windows of susceptibility. Results confirm the multi-hit nature of NAFLD and highlight the urgent need to better understand the interaction of diet and environmental exposures, such as heavy metals, in driving disease severity and progression.
  • Mo Y, Zhang Y, Zhang Y, Yuan J, Mo L, Zhang Q. Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway. J Nanobiotechnology. 2021 Nov 17;19(1):370. doi: 10.1186/s12951-021-01117-7. PMID: 34789290; PMCID: PMC8600818.
    Impact Statement: Nickel nanoparticles (Nano-Ni) are increasingly used in industry and biomedicine with the development of nanotechnology. However, the genotoxic and carcinogenic effects of Nano-Ni and the underlying mechanisms are still unclear. This study unraveled the mechanisms underlying Nano-Ni-induced cell malignant transformation. The combined effects of Nano-Ni-induced DNA damage and DNA repair defects through HIF-1α/miR-210/Rad52 pathway probably contribute to Nano-Ni-induced genomic instability and ultimately cell transformation. Our findings will provide information to further elucidate the molecular mechanisms of Nano-Ni-induced genotoxicity and carcinogenicity.
  • Kumar A, Sundaram K, Mu J, Dryden GW, Sriwastva MK, Lei C, Zhang L, Qiu X, Xu F, Yan J, Zhang X, Park JW, Merchant ML, Bohler HCL, Wang B, Zhang S, Qin C, Xu Z, Han X, McClain CJ, Teng Y, Zhang HG. High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance. Nat Commun. 2021 Jan 11;12(1):213. doi: 10.1038/s41467-020-20500-w. PMID: 33431899; PMCID: PMC7801461.
  • Xie W, Tackett AP, Berlowitz JB, Harlow AF, Kathuria H, Galiatsatos P, Fetterman JL, Cho J, Blaha MJ, Hamburg NM, Robertson RM, DeFilippis AP, Hall ME, Bhatnagar A, Benjamin EJ, Stokes AC. Association of Electronic Cigarette Use with Respiratory Symptom Development among US Young Adults. Am J Respir Crit Care Med. 2022 Jan 28. doi: 10.1164/rccm.202107-1718OC. Epub ahead of print. PMID: 35089853.
    Impact Statement: This study aimed to determine whether e-cigarette use is associated with the development of respiratory symptoms in young adults. The research found that former and current e-cigarette use was associated with higher odds of developing wheezing-related respiratory symptoms, after accounting for cigarette smoking and other combustible tobacco product use.
  • Cohen JE, Krishnan-Sarin S, Eissenberg T, Gould TJ, Berman ML, Bhatnagar A, Barnett TE, Soule E, Popova L, Tan ASL, Blank MD, Ling PM, O'Connor R. Balancing Risks and Benefits of E-Cigarettes in the Real World. Am J Public Health. 2022 Feb;112(2):e1-e2. doi: 10.2105/AJPH.2021.306607. PMID: 35080942; PMCID: PMC8802586.
    Impact Statement: This publication is a review of Balfour's article entitled "Balancing Consideration of the Risks and Benefits of E-Cigarettes". We challenge the public health and scientific community to move away from characterizing scientists as “opponents” or “supporters” of e-cigarettes.
  • Zhang H, Wang Y, Men H, Zhou W, Zhou S, Liu Q, Cai L. CARD9 Regulation and its Role in Cardiovascular Diseases. Int J Biol Sci. 2022 Jan 1;18(3):970-982. doi: 10.7150/ijbs.65979. PMID: 35173530; PMCID: PMC8771857.
    Impact Statement: CARD9 is an adaptor protein expressed on myeloid cells and located downstream of pattern recognition receptors (PRRs), which transduces signals involved in innate immunity, has been extensively investigated in various fungal diseases. However, this review summarized the information for its regulating role in activating p38 MAPK, NF-κB, and NLRP3 inflammasome in various CVDs via promoting the production of proinflammatory cytokines and chemokines, leading to cardiac remodeling and dysfunction.
  • Sundaram K, Mu J, Kumar A, Behera J, Lei C, Sriwastva MK, Xu F, Dryden GW, Zhang L, Chen S, Yan J, Zhang X, Park JW, Merchant ML, Tyagi N, Teng Y, Zhang HG. Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis. Theranostics. 2022 Jan 1;12(3):1220-1246. doi: 10.7150/thno.65427. PMID: 35154484; PMCID: PMC8771565.
    Impact Statement: Obesity is a global epidemic and reversing obesity induced chronic inflammation including brain inflammation is a hallmark of obesity via the gut-brain axis. This study demonstrated that garlic exosome-like nanoparticles (GaELNs) that inhibit systemic as well as brain inflammatory activity and reverse a HFD induced obesity in mice. These results demonstrate how nanoparticles from a healthy diet can inhibit unhealthy high-fat diet induced brain inflammation and reveal a link between brain microglia/diet to brain inflammatory disease outcomes via diet-derived exosome-like nanoparticles.
  • Salazar-González RA, Doll MA, Hein DW. Arylamine N-Acetyltransferase 1 Activity is Regulated by the Protein Acetylation Status. Front Pharmacol. 2022 Jan 27;13:797469. doi: 10.3389/fphar.2022.797469. PMID: 35153780; PMCID: PMC8828969
    Impact Statement: Histone deacetylases (HDACs) and Sirtuins (SIRT) may have an important role on the N-acetyltransferase 1 (NAT1) acetylation status, affecting its catalytic capacity and having an impact on the downstream functions of this protein. We investigated the contribution of Lysine deacetylases (KDAC) in the catalytic activity of NAT1 using two different breast cancer cell lines: MDA-MB-231 (ER-, PR-, HER2-) and ZR-75-1 (ER+, PR+, HER2+) and tested the ability of Sirtuin and HDAC inhibitors to impact the transcription, translation and function of NAT1. We transiently knocked down (KD) Sirtuin 1/2 and evaluated the role of these specific proteins in the same experimental outcomes. The results show that the acetylation status of NAT1 is an important factor that might have a relevant role in the progression of cancer.
  • Doll MA, Ray AR, Salazar-González RA, Shah PP, Vega AA, Sears SM, Krueger AM, Hong KU, Beverly LJ, Hein DW. Deletion of arylamine N-acetyltransferase 1 in MDA-MB-231 human breast cancer cells reduces primary and secondary tumor growth in vivo with no significant effects on metastasis. Mol Carcinog. 2022 Feb 8. doi: 10.1002/mc.23392. Epub ahead of print. PMID: 35133049.
    Impact Statement: Previous studies showed that inhibition or depletion of N-acetyltransferase (NAT1) in human breast cancer cells diminishes anchorage-independent growth in culture, suggesting that NAT1 contributes to breast cancer growth and metastasis. Metastasis of parental and NAT1 knockout (KO) cells was investigated in vivo in a mouse xenograft model. NAT1 KO MDA-MB-231 cells produced primary tumors smaller than those formed by parental cells, which was contributed by an increased rate of apoptosis in KO cells. The frequency of lung metastasis, however, was not altered in NAT1 KO cells suggesting that NAT1 contributes to primary and secondary tumor growth in vivo in MDA-MB-231 breast cancer cells but does not appear to affect its metastatic potential.
  • Nathala P, Salunkhe V, Samanapally H, Xu Q, Furmanek S, Fahmy OH, Deepti F, Glynn A, McGuffin T, Goldsmith DC, Petrey J, Ali T, Titus D, Carrico R, Ramirez J, Antimisiaris D, Clifford SP, Pahwa S, Roser L, Kong M, Huang J; Center of Excellence for Research in Infectious Diseases (CERID) Coronavirus Study Group on behalf of the COVID-19 Cardiovascular Research Group (COVID-CVRG). Electrocardiographic Features and Outcome: Correlations in 124 Hospitalized Patients With COVID-19 and Cardiovascular Events. J Cardiothorac Vasc Anesth. 2022 Jan 13:S1053-0770(22)00042-8. doi: 10.1053/j.jvca.2022.01.011. Epub ahead of print. PMID: 35165040; PMCID: PMC8757653.
    Impact Statement: In hospitalized patients with COVID-19 and cardiovascular events, electrocardiogram at various stages of COVID-19 hospitalization showed significantly different features with dissimilar clinical outcome correlations.
  • Xu Q, Liu Y, Cepulis D, Jerde A, Sheppard RA, Reichle W, Scott L, Oppy L, Stevenson G, Bishop S, Clifford SP, Liu P, Kong M, Huang J. Hand Hygiene Behaviours Monitored by an Electronic System in the Intensive Care Unit-A Prospective Observational Study. J Hosp Infect. 2022 Feb 2:S0195-6701(22)00032-9. doi: 10.1016/j.jhin.2022.01.017. Epub ahead of print. PMID: 35122887.
    Impact Statement: Patterns of healthcare workers’ hand hygiene behaviors are complex and variable, which could facilitate targeted and personalized interventions to improve hand hygiene compliance.
  • Zhang G, Kang Y, Cathey D, LeBlanc AJ, Cai J, Cai L, Wang S, Huang J, Keller BB. Sulforaphane Does Not Protect Right Ventricular Systolic and Diastolic Functions in Nrf2 Knockout Pulmonary Artery Hypertension Mice. Cardiovasc Drugs Ther. 2022 Feb 14. doi: 10.1007/s10557-022-07323-1. Epub ahead of print. PMID: 35157168.
    Impact Statement: Nrf2 is essential in sulforaphane-mediated prevention of right ventricular dysfunction and pulmonary hypertension. Increasing Nrf2 activity in patients by supplements or intakes of vegetables may have therapeutic potential for pulmonary hypertension.
  • Tracy EP, Steilberg V, Rowe G, Benson D, Nunes SS, Hoying J, Murfee WL, LeBlanc AJ. State of the Field: Cellular Therapy Approaches in Microvascular Regeneration. Am J Physiol Heart Circ Physiol. 2022 Feb 18. doi: 10.1152/ajpheart.00674.2021. Epub ahead of print. PMID: 35179976.
    Impact Statement: This is a comprehensive review that gives the most recent update on cellular and exosomal therapeutic approaches in treating vascular and microvascular dysfunction. Relevant and recent clinical and animal studies utilizing cellular therapies to restore vascular function are highlighted throughout the text, and the figures and tables provided in the review are particularly helpful visual representations and also an excellent reference guide.
  • Cummins TD, Korte EA, Bhayana S, Merchant ML, Barati MT, Smoyer WE, Klein JB. Advances in proteomic profiling of pediatric kidney diseases. Pediatr Nephrol. 2022 Feb 26. doi: 10.1007/s00467-022-05497-2. Epub ahead of print. PMID: 35220505.
    Impact Statement: Early detection of adult and pediatric CKD and detailed mechanistic understandings of the kidney damage may be helpful in delaying or curtailing disease progression. Clinically, serum creatinine and albumin levels can be indicative of CKD, but often are a lagging indicator only significantly affected once kidney function has severely diminished. The evolution of proteomics and mass spectrometry technologies has begun to provide a powerful research tool in defining these mechanisms and identifying novel biomarkers of CKD. This review addresses the potential for improving the clinical toolkit toward better treatment of pediatric kidney diseases aided by current and future development of proteomic applications.
  • Kumar A, Sundaram K, Teng Y, Mu J, Sriwastva MK, Zhang L, Hood JL, Yan J, Zhang X, Park JW, Merchant ML, Zhang HG. Ginger nanoparticles mediated induction of Foxa2 prevents high-fat diet-induced insulin resistance. Theranostics. 2022 Jan 1;12(3):1388-1403. doi: 10.7150/thno.62514. PMID: 35154496; PMCID: PMC8771553.
    Impact Statement: High-fat diets (HFD) are known to increase the risk of obesity and type 2 diabetes. While diet manipulation is a foundation of prevention and treatment of obesity and diabetes, the molecular mechanisms mediating diet-based prevention of insulin resistance remain open. Here, we report that treatment with orally administered ginger-derived nanoparticles (GDNP) prevents insulin resistance by restoring homeostasis in gut epithelial Foxa2 mediated signaling in mice fed a high-fat diet (HFD).
  • Smith HAB, Besunder JB, Betters KA, Johnson PN, Srinivasan V, Stormorken A, Farrington E, Golianu B, Godshall AJ, Acinelli L, Almgren C, Bailey CH, Boyd JM, Cisco MJ, Damian M, deAlmeida ML, Fehr J, Fenton KE, Gilliland F, Grant MJC, Howell J, Ruggles CA, Simone S, Su F, Sullivan JE, Tegtmeyer K, Traube C, Williams S, Berkenbosch JW. 2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility. Pediatr Crit Care Med. 2022 Feb 1;23(2):e74-e110. doi: 10.1097/PCC.0000000000002873. PMID: 35119438.
    Impact Statement: The Society of Critical Care Medicine Practice guidelines for managing pediatric patients who require pain relief, sedation and other medications provides guidance to keep the patients comfortable and safe. These guidelines provide comprehensive clinical practice guidance for those caring for critically ill infants and children with one of the goals being to prevent adverse and long term effects from these medications.
  • Coleman CJ, Yeager RA, Pond ZA, Riggs DW, Bhatnagar A, Arden Pope C 3rd. Mortality risk associated with greenness, air pollution, and physical activity in a representative U.S. cohort. Sci Total Environ. 2022 Feb 14;824:153848. doi: 10.1016/j.scitotenv.2022.153848. Epub ahead of print. PMID: 35176374.
    Impact Statement: This study found that physical inactivity and exposure to air pollution were highly associated with mortality risk and that risk was especially lower among highly active individuals in areas with higher greenness. This study contributes evidence that greener environments are associated with lower risk of mortality and may help ameliorate the effects of exposure to air pollution, especially among highly active individuals.
  • Wang X, Chen X, Zhou W, Men H, Bao T, Sun Y, Wang Q, Tan Y, Keller BB, Tong Q, Zheng Y, Cai L. Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/NRF2 pathways. Acta Pharm Sin B. 2022 Feb;12(2):708-722. doi: 10.1016/j.apsb.2021.10.005. Epub 2021 Oct 15. PMID: 35256941; PMCID: PMC8897044.
    Impact Statement: The role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) was comprehensively examined by examining the expression of key regulators of ferroptosis in type 2 diabetic mice with cardiomyopathy and a new ex vivo DCM model. Diabetes or AGEs was found to induce ferroptosis, reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels and typically morphological changes in cardiomyocytes, and inhibition of ferroptosis with ferrostatin-1 and deferoxamine, as well as Nrf2 activator, sulforaphane, prevented cardiac remodeling and dysfunction. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation.
  • Wise JTF, Salazar-González RA, Habil MR, Doll MA, Hein DW. Expression of arylamine N-acetyltransferase 2 activity in immortalized human bronchial epithelial cells. Toxicol Appl Pharmacol. 2022 Mar 27;442:115993. doi: 10.1016/j.taap.2022.115993. Epub ahead of print. PMID: 35353990.
    Impact Statement: A recent meta-analysis reported N-acetyltransferase 2 (NAT2) slow and intermediate phenotypes had a significantly increased risk of lung cancer. NAT2 activity in humans is thought to be restricted to liver and gastrointestinal tract, and no studies to our knowledge have reported the expression of NAT2 activity in immortalized human lung epithelial cells. Given the importance of NAT2 in cancer and inhalation of various carcinogens directly into the lungs, we investigated NAT2 activity and documented that it is expressed and functional in human lung epithelial cells.
  • Hein DW, Doll MA, Habil MR. Human N-Acetyltransferase 1 and 2 Differ in Affinity Towards Acetyl-Coenzyme A Cofactor and N-Hydroxy-Arylamine Carcinogens. Front Pharmacol. 2022 Feb 25;13:821133. doi: 10.3389/fphar.2022.821133. PMID: 35281898; PMCID: PMC8914035.
    Impact Statement: Following recombinant expression in bacteria, yeast, and mammalian cells, we report significant differences in affinity between human N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) for its required co-factor acetyl coenzyme A, as well as for N-hydroxy-arylamines activated via O-acetylation. The findings provide important information to understand the relative contribution of human NAT1 vs NAT2 towards N-acetylation and O-acetylation reactions in human hepatic and extrahepatic tissues.
  • Doll MA, Hein DW. 560G>A (rs4986782) (R187Q) Single Nucleotide Polymorphism in Arylamine N-Acetyltransferase 1 Increases Affinity for the Aromatic Amine Carcinogens 4-Aminobiphenyl and N-Hydroxy-4-Aminobiphenyl: Implications for Cancer Risk Assessment. Front Pharmacol. 2022 Feb 22;13:820082. doi: 10.3389/fphar.2022.820082. PMID: 35273499; PMCID: PMC8902414.
    Impact Statement: Human arylamine N-acetyltransferase 1 (NAT1) catalyzes the N-acetylation of arylamine carcinogens such as 4-aminobiphenyl (ABP), and following N-hydroxylation, the O-acetylation of N-hydroxy-arylamine carcinogens such as N-hydroxy-ABP (N-OH-ABP). The effects of individual single nucleotide polymorphisms (SNPs) in the NAT1 coding exon on Michaelis-Menten kinetic constants was assessed for ABP N-acetyltransferase and N-OH-ABP O-acetyltransferase activity following transfection of human NAT1 into COS-1 cells. 560G>A (rs4986782) (R187Q) significantly reduced the apparent Km for ABP and N-OH-ABP a finding that was not observed with any of the other NAT1 SNPs tested. These findings suggest that the role of the 560G>A (rs4986782) (R187Q) SNP cancer risk assessment may be modified by exposure level to aromatic amine carcinogens such as ABP.
  • Latif RK, Clifford SP, Ghafghazi S, Phipps Z, Chen JJ, Sangroula D, Khan AZ, Saleem J, Farah I, Huang J, Businger JR. Echocardiography and Management for Cardiac Trauma. J Cardiothorac Vasc Anesth. 2022 Feb 12:S1053-0770(22)00120-3. doi: 10.1053/j.jvca.2022.02.010. Epub ahead of print. PMID: 35305892.
    Impact Statement: This review article aims to analyze the pathophysiology of cardiac injuries in patients with trauma and the role of echocardiography for the accurate diagnosis of cardiac injury in trauma. This review, additionally, will offer a patient-centered, team-based, early management plan with a treatment algorithm to help improve the quality of care among these patients with cardiac trauma.
  • Lu L, Che J, Cheng W, Dong R, Huang J, Yang Z, Lu J. A Retrospective Study of the Relationship Between Blood Transfusion and 30-Day Postoperative Outcomes in Patients Undergoing Isolated Off-Pump Coronary Artery Bypass Grafting. Braz J Cardiovasc Surg. 2022 Mar 3. doi: 10.21470/1678-9741-2021-0031. Epub ahead of print. PMID: 35244374.
    Impact Statement: Perioperative blood transfusion increases the risks of postoperative pulmonary infection and short-term mortality in off-pump coronary artery bypass grafting patients.
  • Fulghum KL, Audam TN, Lorkiewicz PK, Zheng Y, Merchant M, Cummins TD, Dean WL, Cassel TA, Fan TWM, Hill BG. In vivo deep network tracing reveals phosphofructokinase-mediated coordination of biosynthetic pathway activity in the myocardium. J Mol Cell Cardiol. 2022 Jan;162:32-42. doi: 10.1016/j.yjmcc.2021.08.013. Epub 2021 Sep 3. PMID: 34487754; PMCID: PMC8766935.
    Impact Statement: This study tested how phosphofructokinase-1 (PFK1) activity controls the fate of glucose-derived carbon in murine hearts in vivo. PFK1 activity was regulated by cardiac-specific overexpression of kinase- or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transgenes in mice (termed GlycoLo or GlycoHi mice, respectively). Stable isotope (C13) labeled glucose and deep network metabolic tracing revealed that low rates of PFK1 activity, potentially regulated by physical channeling, promoted selective routing of glucose-derived carbon to the purine synthesis pathway to form 5-aminoimidazole-4-carboxamide ribonucleotide. Additionally, PFK1 influenced glucose-derived carbon deposition in glycogen, but did not affect hexosamine biosynthetic pathway activity. These studies demonstrate the utility of deep network tracing to identify metabolic channeling and changes in biosynthetic pathway activity in the heart in vivo and present new potential mechanisms by which metabolic branch point reactions modulate biosynthetic pathways.
  • Dongfeng Wu, Shesh N. Rai and Albert Seow. Estimation of preclinical state onset age and sojourn time for heavy smokers in lung cancer. Statistics and Its Interface. 15 (3), 2022. Published Feb 14, 2022.
    Impact Statement: Using the pre-existing large data, we have devolved model to predict onset of early- stage of lung cancer in heavy smokers. The mean age (in years) to make the transition into the preclinical state was 70.94 or 71.15 for male and female heavy smokers respectively. About 90% of heavy smokers who are at risk for lung cancer would enter the preclinical state in age interval (55.7, 85.8) for males and (54.2, 87.7) for females, and the transition peaked around age 69 for both genders. Based on the result, low-dose CT should be started at age 55 and ended before 85 for heavy smokers. This provided important information to policy makers.
  • Jessica Sparks, Xiaoyong Wu, Mika Kessans Knable, Shesh N. Rai, Vivek Sharma. Predictors of thrombosis in patients treated with bevacizumab. Thrombosis Update. 6, 2022 (DOI: https://doi.org/10.1016/j.tru.2021.100095). Published March, 2022.
    Impact Statement: We study the predictors of thrombosis in cancer patients treated with bevacizumab using a single center comprehensive retrospective cohort. The thrombotic events occurred in 24/116 (20.7%) of the hypertension cohort compared to 8/87 (9.2%) of the normotensive patients (p = 0.026) and in 15/52 (28.8%) of hyperlipidemic patients vs 17/151 (11.3%) of those with normal lipids (p = 0.003). The Khorana score was not a significant predictor in this population. In further analyzing our data, we found increasing thrombotic events with each addition of the most telling predictors of thromboses in our population: hypertension, hyperlipidemia, and greater than trace proteinuria, such that patients with all three risk factors present vs none had an odds ratio of 6.786 (p = 0.004). Incorporating these three risk factors into a clinical risk score may help stratify patients into lower and higher risk categories which may assist clinicians in making decisions about the use of prophylactic anticoagulation in this population.
  • States JC, Peters JM. 2020-2021 Toxicological Sciences Paper of the Year. Toxicol Sci. 2022 Mar 28;186(2):177-178. doi: 10.1093/toxsci/kfac020. PMID: 35348797.
    This editorial announced the SOT Paper of the Year.
  • Xiong L, Bin Zhou, Young JL, Wintergerst K, Cai L. Exposure to low-dose cadmium induces testicular ferroptosis. Ecotoxicol Environ Saf. 2022 Mar 7;234:113373. doi: 10.1016/j.ecoenv.2022.113373. Epub ahead of print. PMID: 35272187.
    Impact Statement: As an environmental pollutant, cadmium (Cd) has been widely reported to induce male infertility due to its gonadotoxicity. This study found for the first time that exposure to 5 ppm Cd significantly decreased the expression of SLC7A11, a marker of ferroptosis in mice, along with the expression of SLC40A1 mRNA and ferritin heavy chain (FTH) protein, whereas there was no obvious change in the mRNA expression of Tfrc, ZIP8, ZIP14, and NCOA4, suggesting that 5 ppm Cd exposure increased testicular ferroptosis, probably due to the reduction of stored iron export potency.
  • Dwenger MM, Raph SM, Reyzer ML, Lisa Manier M, Riggs DW, Wohl ZB, Ohanyan V, Mack G, Pucci T, Moore JB 4th, Hill BG, Chilian WM, Caprioli RM, Bhatnagar A, Nystoriak MA. Pyridine nucleotide redox potential in coronary smooth muscle couples myocardial blood flow to cardiac metabolism. Nat Commun. 2022 Apr 19;13(1):2051. doi: 10.1038/s41467-022-29745-z. PMID: 35440632; PMCID: PMC9018695.
    Impact Statement: This study shows that coronary dilation to increase myocardial blood flow during increased contractile demand is controlled by voltage-gated potassium channel. This metabolic sensitivity of the potassium channel is due to the ancillary subunits that bind to pyridine nucleotides to alter the gating characteristics of the channel.
  • Wang K, Sun S, Zhang G, Lu Z, Chen H, Fan X, Gu C, Pan X, Lin Q, Chen O, Cai L, Dai X, Wang X, Lu C, Yan X, Tan Y. CXCR7 Agonist TC14012 Improves Angiogenic Function of Endothelial Progenitor Cells via Activating Akt/eNOS Pathway and Promotes Ischemic Angiogenesis in Diabetic Limb Ischemia. Cardiovasc Drugs Ther. 2022 Apr 26. doi: 10.1007/s10557-022-07337-9. Epub ahead of print. PMID: 35471717.
    Impact Statement: Endothelial progenitor cells (EPCs) play a critical role in repairing damaged vessels and triggering ischemic angiogenesis, but their number is reduced, and function is impaired under diabetic conditions. Improving EPC function has been considered a promising strategy to ameliorate diabetic vascular complications. In the present study, we showed that CXCR7 agonist TC14012 can prevent EPCs from high level of glucose-induced dysfunction and apoptosis, improve eNOS activity and NO production via CXCR7/Akt signal pathway, and promote EPC mobilization and diabetic ischemia angiogenesis.
  • Lustig RH, Collier D, Kassotis C, Roepke TA, Ji Kim M, Blanc E, Barouki R, Bansal A, Cave MC, Chatterjee S, Choudhury M, Gilbertson M, Lagadic-Gossmann D, Howard S, Lind L, Tomlinson CR, Vondracek J, Heindel JJ. Obesity I: Overview and molecular and biochemical mechanisms. Biochem Pharmacol. 2022 May;199:115012. doi: 10.1016/j.bcp.2022.115012. Epub 2022 Apr 5. PMID: 35393120; PMCID: PMC9050949.
    Impact Statement: The review article examines the molecular mechanisms contributing to obesity that may be impacted by environmental chemicals.
  • Heindel JJ, Howard S, Agay-Shay K, Arrebola JP, Audouze K, Babin PJ, Barouki R, Bansal A, Blanc E, Cave MC, Chatterjee S, Chevalier N, Choudhury M, Collier D, Connolly L, Coumoul X, Garruti G, Gilbertson M, Hoepner LA, Holloway AC, Howell G 3rd, Kassotis CD, Kay MK, Ji Kim M, Lagadic-Gossmann D, Langouet S, Legrand A, Li Z, Le Mentec H, Lind L, Monica Lind P, Lustig RH, Martin-Chouly C, Munic Kos V, Podechard N, Roepke TA, Sargis RM, Starling A, Tomlinson CR, Touma C, Vondracek J, Vom Saal F, Blumberg B. Obesity II: Establishing causal links between chemical exposures and obesity. Biochem Pharmacol. 2022 May;199:115015. doi: 10.1016/j.bcp.2022.115015. Epub 2022 Apr 5. PMID: 35395240.
    Impact Statement: This review article examines the evidence that environmental chemicals have contributed to obesity.
  • Polivka BJ, Huntington-Moskos L, Folz R, Barnett R. CE: Environments & Health: Chemicals in the Home That Can Exacerbate Asthma. Am J Nurs. 2022 May 1;122(5):34-39. doi: 10.1097/01.NAJ.0000829776.73698.e0. PMID: 35394947.
    Impact Statement: The authors describe how the use of cleaning and disinfectant products may affect asthma and asthma-related symptoms and report the findings of a recent study they conducted that identified how these products could reduce asthma control in older adults.
  • Eldeirawi KM, Nyenhuis SM, Huntington-Moskos L, Polivka BJ. COVID-19 Related Anxiety Is Associated with Uncontrolled Asthma in Adults. Ann Allergy Asthma Immunol. 2022 Apr 22:S1081-1206(22)00308-8. doi: 10.1016/j.anai.2022.04.011. Epub ahead of print. PMID: 35470038; PMCID: PMC9033292.
    Impact statement: The COVID-19 pandemic has disproportionately affected people with chronic diseases, including asthma; these impacts were both physically and psychologically. Our findings underscore the need for health care providers to assess for the ongoing psychological impact of the pandemic and refer to mental health specialists.
  • Hodges NA, Lampejo AO, Shang H, Rowe G, LeBlanc AJ, Katz AJ, Murfee WL. Viewing Stromal Vascular Fraction de novo Vessel Formation and Association with Host Microvasculature Using the Rat Mesentery Culture Model. Microcirculation. 2022 Apr 25:e12758. doi: 10.1111/micc.12758. Epub ahead of print. PMID: 35466504.
    Impact Statement: This study describes the use of the rat mesentery culture model as a novel tool to investigate cell therapy transplantation. Additionally, this model allows us to visualize many different cell types that are involved in microvascular growth over time using time-lapse microscopy.
  • Shiri F, Feng H, Petersen KE, Sant H, Bardi GT, Schroeder LA, Merchant ML, Gale BK, Hood JL. Separation of U87 glioblastoma cell-derived small and medium extracellular vesicles using elasto-inertial flow focusing (a spiral channel). Sci Rep. 2022 Apr 12;12(1):6146. doi: 10.1038/s41598-022-10129-8. PMID: 35414673; PMCID: PMC9005724.
    Impact Statement: Developing advanced methods to isolate nanoscale and microscale cell-derived extracellular vesicle (EV) types and subtypes are of significant interest to the EV research community in general given their functional, diagnostic and therapeutic potential. The elasto-inertial focusing system developed in the manuscript is a novel compact microfluidic device that mechanistically works like gold standard differential ultracentrifugation for EV isolation. Because of its compact size, it can potentially be integrated with other microfluidic lab-on-a-chip and similar technologies to enable scalable, continuous separation of small microliter to milliliter volume limited samples upstream or downstream on EV chip-based detection and capture devices.
  • Lin Q, Chen O, Wise JP Jr, Shi H, Wintergerst KA, Cai L, Tan Y. FGF1ΔHBS delays the progression of diabetic nephropathy in late-stage type 2 diabetes mouse model by alleviating renal inflammation, fibrosis, and apoptosis. Biochim Biophys Acta Mol Basis Dis. 2022 Apr 18;1868(8):166414. doi: 10.1016/j.bbadis.2022.166414. Epub ahead of print. PMID: 35447340.
    Impact Statement: Elderly adults are at higher risk for developing diabetic complications including diabetic nephropathy (DN), contributing to excess morbidity and mortality in elderly individuals. A non-mitogenic variant of fibroblast growth factor 1 (FGF1ΔHBS) was found to prevent DN in an early-stage (2-month-old) type 2 diabetes (T2D) mouse model. The present study demonstrated that FGF1ΔHBS was also able to delay the progression of renal dysfunction likely through activating PPARα to prevent renal tubule cell death in late-stage T2D, exhibiting a promising translational potential in treating DN in elderly T2D individuals by ameliorating renal inflammation, fibrosis, and apoptosis.
  • Faleye TOC, Driver EM, Bowes DA, Holm RH, Talley D, Yeager R, Bhatnagar A, Smith T, Varsani A, Halden RU, Scotch M. Detection of Human, Porcine and Canine Picornaviruses in Municipal Sewage Sludge Using Pan-Enterovirus Amplicon-based Long-read Illumina Sequencing. Emerg Microbes Infect. 2022 Apr 27:1-25. doi: 10.1080/22221751.2022.2071173. Epub ahead of print. PMID: 35475464.
    Impact Statement: The findings of this paper show that sludge from different stages wastewater treatment can be used for surveillance of viruses from humans and other animals. These results could be applied to improve population coverage and cost-effectiveness of largescale wastewater surveillance for viral disease outbreaks.
  • Zhang Y, Mo Y, Yuan J, Zhang Y, Mo L, Zhang Q. MMP-3 activation is involved in copper oxide nanoparticle-induced epithelial-mesenchymal transition in human lung epithelial cells. Nanotoxicology. 2021 Dec;15(10):1380-1402. doi: 10.1080/17435390.2022.2030822. Epub 2022 Feb 2. PMID: 35108494.
    Impact Statement: Copper oxide nanoparticles (Nano-CuO) are widely used in medical and industrial fields and our daily necessities. However, the biosafety assessment of Nano-CuO is far behind their rapid development. Our study demonstrated that Nano-CuO exposure caused mitochondrial ROS generation, MAPKs activation, and MMP-3 upregulation. Nano-CuO exposure also caused cells to undergo EMT, which was through Nano-CuO-induced dysregulation of ROS/MAPKs/MMP-3 pathway. Our findings will provide further understanding of the potential mechanisms involved in metal nanoparticle-induced various toxic effects including EMT and pulmonary fibrosis.
  • Nail AN, McCaffrey LM, Banerjee M, Ferragut Cardoso AP, States JC. Chronic arsenic exposure suppresses ATM pathway activation in human keratinocytes. Toxicol Appl Pharmacol. 2022 Jul 1;446:116042. doi: 10.1016/j.taap.2022.116042. Epub 2022 May 2. PMID: 35513056.
    Impact Statement: Our research sheds direct light on the most accepted explanation for the mode of action of arsenic carcinogenicity in arsenic’s major target organ, skin. Arsenic is known to induce DNA breaks without directly interacting with DNA. We have discovered that a major signaling protein for DNA break repair, ataxia telangiectasia-mutated (ATM), has reduced activation in human keratinocytes chronically exposed to inorganic arsenic. ATM plays an important role in DNA repair by activating enzymes that can fix DNA strand breaks in cells, preventing the accumulation of mutations in cells and carcinogenesis. Thus, it could be hypothesized that arsenic-induced tumors may be more sensitive to certain cancer treatments that induce DNA damage or inhibit DNA repair, such as radiotherapy or PARP inhibitors, respectively. Based on these findings, additional studies are needed determine whether arsenic-induced tumors are sensitive to specific chemotherapeutic regimens. Results from these future studies could be used to design new strategies to treat arsenic-induced cancers.
  • Berlowitz JB, Xie W, Harlow AF, Hamburg NM, Blaha MJ,  Bhatnagar A, Benjamin EJ, Stokes AC. E-Cigarette Use and Risk of Cardiovascular Disease: A Longitudinal Analysis of the PATH Study (2013-2019). Circulation. 2022 May 17;145(20):1557-1559. doi: 10.1161/CIRCULATIONAHA.121.057369. Epub 2022 May 6. PMID: 35514292.
    Impact Statement: Despite increasing popularity of electronic cigarettes (e-cigarettes), the long-term health effects of habitual e-cigarette use remain unclear. Our results suggest that combining smoking with e-cigarette use does not reduce cardiovascular disease (CVD) events and that quitting both products is required to ensure a mitigation of risk.
  • Gibson JM, Chu T, Zeng W, Wethall AC, Kong M, Mellen N, Devlin Phinney LA, Cai J. Perinatal methadone exposure attenuates myelination and induces oligodendrocyte apoptosis in neonatal rat brain. Exp Biol Med (Maywood). 2022 Apr 27:15353702221090457. doi: 10.1177/15353702221090457. Epub ahead of print. PMID: 35475383.
    Impact statement:  Methadone (MTD) is a common medication treatment for opioid use disorder (OUD) during pregnancy. In this study, pregnant rats were administrated a dosing approximately equivalent to the OUD treatment and the effects of passive in utero and postnatal MTD exposure on myelin development was investigated in neonatal rat brain. The findings reveal the potential mechanism(s) underlying the association between myelin impairment and antenatal opioid exposure. Our study alongside others concerns for fetal brain development when using MTD to manage the OUD during pregnancy. Improved understanding of the effects of opioid exposure will allow us to design treatments for OUD during pregnancy that minimize effects on the fetal brain or target postnatal treatment to mitigate the effects of antenatal opioid exposure.
  • Halder S, Xie Z, Nantz MH, Fu XA. Integration of a micropreconcentrator with solid-phase microextraction for analysis of trace volatile organic compounds by gas chromatography-mass spectrometry. J Chromatogr A. 2022 Apr 22;1673:463083. doi: 10.1016/j.chroma.2022.463083. Epub ahead of print. PMID: 35508097.
    Impact statement:  This paper reports a simple method of integrating microfabricated preconcentrators with commercial SPME fibers in a two-stage concentration processes to achieve rapid and reliable measurement of trace VOCs in environmental air by GC–MS. This approach has been demonstrated for measurements of toxic VOCs including benzene, toluene, ethylbenzene, xylene (BTEX) and trichloroethene (TCE).
  • Monreal G, Koenig SC, Slaughter MS, Morello GF, Prina SR, Tompkins LH,  Huang J, Gellman BN, Dasse KA. Feasibility testing of the Inspired Therapeutics NeoMate mechanical circulatory support system for neonates and infants. PLoS One. 2022 May 11;17(5):e0266822. doi: 10.1371/journal.pone.0266822. PMID: 35544516; PMCID: PMC9094552.
    Impact statement: In this article, we present the development of the prototype Inspired Therapeutics NeoMate System for pediatric left ventricular assist device (LVAD) support, and feasibility testing in static mock flow loops (H-Q curves), dynamic mock flow loops (hemodynamics), and in an acute healthy ovine model (hemodynamics and clinical applicability).
  • Sagaram M, Parthasarathy R, Condon SL, Closson CF, Kong M, Schwandt ML, Jophlin LL, Feng W, Barve AJ, Vatsalya V. Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis. Int J Mol Sci. 2022 May 23;23(10):5852. doi: 10.3390/ijms23105852. PMID: 35628661; PMCID: PMC9143806.
    Impact Statement: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury.
  • Teng Y, Mu J, Xu F, Zhang X, Sriwastva MK, Liu QM, Li X, Lei C, Sundaram K, Hu X, Zhang L, Park JW, Hwang JY, Rouchka EC, Zhang X, Yan J, Merchant ML, Zhang HG. Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death. Cell Host Microbe. 2022 May 25:S1931-3128(22)00265-7. doi: 10.1016/j.chom.2022.05.005. Epub ahead of print. PMID: 35654045.
    Impact Statement: The gut microbiome has recently revealed itself to be a major player in human health and disease. Here, Drs. Huang-Ge Zhang and collaborators including CIEHS members Michael Merchant and Jun Won Park, show that a small metabolite, isoamylamine (IAA) produce by the bacteria Ruminococcaceae is enriched in aged mice and elderly people. Interestingly a bacteriophage belonging to the Myoviridae family that infects Ruminococcaceae are reduced in these settings. IAA induced cognitive declines in young mice is reversed by Myoviridae phage administration. IAA promoted apoptosis of microglial cells through a p53 dependent mechanism. Our results linked microbiome metabolites to direct transcriptional co-regulation of genomic DNA. These findings suggest a molecular mechanism connecting gut metabolism to gene expression in the brain with implications for disease development.
  • Bhattacharyya A, Pal S, Mitra R,  Rai S. Applications of Bayesian shrinkage prior models in clinical research with categorical responses. BMC Med Res Methodol. 2022 Apr 28;22(1):126. doi: 10.1186/s12874-022-01560-6. PMID: 35484507; PMCID: PMC9046716.
    Impact Statement: Developing accurate prediction method benefits personalized medicine, involving patient’s demographic, history, and gene signatures. Bayesian shrinkage models have emerged as popular and flexible methods of variable selection in regression settings. This work discusses variable selection and illustrates its application to multiple clinical studies, such as Pima Indians Diabetes, Colon cancer, ADNI, and OASIS Alzheimer’s data sets. Informative priors can be used for robust and efficient prediction with accuracy of 91.6% (95% CI: 88.5, 94.7). The proposed method is robust to conduct both variable selection and prediction.
  • Miller HA, Rai SN, Yin X, Zhang X, Chesney JA, van Berkel VH, Frieboes HB. Lung cancer metabolomic data from tumor core biopsies enables risk-score calculation for progression-free and overall survival. Metabolomics. 2022 May 14;18(5):31. doi: 10.1007/s11306-022-01891-x. PMID: 35567637.
    Impact Statement:  Metabolomics has emerged as a powerful method to provide insight into cancer progression, including separating patients into low- and high-risk groups for overall (OS) and progression-free survival (PFS). This proof-of-concept study evaluates metabolites as biomarkers obtained directly from tumor core biopsies along with covariates age, sex, pathological stage at diagnosis (I/II vs. III/VI), histological subtype, and treatment vs. no treatment. A prediction model is developed to stratify patients into low- and high-risk groups based on log-transformed intensities of key metabolites. Risk scores based on 10 metabolites for OS and 5 metabolites for PFS were significant predictors of survival. Risk scores were validated with SPLS-DA classification model (AUROC 0.868 for OS and AUROC 0.755 for PFS, when combined with covariates. Thus, metabolomic analysis of lung tumor core biopsies has the potential to differentiate patients into low- and high-risk groups based on OS and PFS events and probability.
  • King KM, McKay T, Thrasher BJ, Wintergerst KA. Maximal Oxygen Uptake, VO2 Max, Testing Effect on Blood Glucose Level in Adolescents with Type 1 Diabetes Mellitus. Int J Environ Res Public Health. 2022 May 3;19(9):5543. doi: 10.3390/ijerph19095543. PMID: 35564936; PMCID: PMC9102981.
    Impact Statement: Individuals with type 1 diabetes face many challenges when participating in sporting activities and general exercise. This publication offers some glucose control guidance for athletes participating in maximal aerobic exercise. In addition to benefiting individuals with T1D, this article may also be beneficial to coaches, physical educators, and parents of children participating in sporting activities.
  • Yuan J, Wang T, Wang L, Li P, Shen H, Mo Y,  Zhang Q, Ni C. Transcriptome-wide association study identifies PSMB9 as a susceptibility gene for coal workers' pneumoconiosis. Environ Toxicol. 2022 May 4. doi: 10.1002/tox.23554. Epub ahead of print. PMID: 35506645.
    Impact Statement: Coal workers' pneumoconiosis (CWP) is a type of typical occupational lung disease caused by prolonged inhalation of coal mine dust. The individuals' different genetic background may underlie their different susceptibility to develop pneumoconiosis, even under the same exposure level. This study aimed to identify susceptibility genes associated with CWP. We have identified PSMB9 as a novel susceptibility gene for CWP and provided important insights into the further exploration of the CWP pathogenesis.
  • Bastick JC, Banerjee M, States JC. Zinc supplementation prevents arsenic-induced dysregulation of ZRANB2 splice function. Environ Toxicol Pharmacol. 2022 Jun 25;94:103921. doi: 10.1016/j.etap.2022.103921. Epub ahead of print. PMID: 35764259.
    Impact Statement: This publication adds support to the hypothesis that zinc supplementation could mitigate the toxic effects of chronic low level arsenic exposure.
  • Jiang M, Li F, Liu Y, Gu Z, Zhang L, Lee J, He L, Vatsalya V, Zhang HG, Deng Z, Zhang X, Chen SY, Guo GL, Barve S, McClain CJ, Feng W. Probiotic-derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation. Hepatology. 2022 Jun 11. doi: 10.1002/hep.32608. Epub ahead of print. PMID: 35689610.
    Impact Statement: Intestinal farnesoid X receptor (FXR) plays a critical role in alcohol-associated liver disease (ALD). We aimed to investigate whether alcohol-induced dysbiosis increased intestinal microRNA194 (miR194) that suppressed Fxr transcription and whether Lactobacillus rhamnosus GG-derived exosome-like nanoparticles (LDNPs) protected against ALD through regulation of intestinal miR194-FXR signaling in mice.
  • Sutaria SR, Gori SS, Morris JD, Xie Z, Fu XA, Nantz MH. Lipid Peroxidation Produces a Diverse Mixture of Saturated and Unsaturated Aldehydes in Exhaled Breath That Can Serve as Biomarkers of Lung Cancer-A Review. Metabolites. 2022 Jun 18;12(6):561. doi: 10.3390/metabo12060561. PMID: 35736492; PMCID: PMC9229171.
    Impact Statement: The paper provides a comprehensive review of saturated and unsaturated aldehydes in exhaled breath and their sources from lipid peroxidation. Some of these aldehydes in exhaled breath have been reported as biomarkers of lung cancer.
  • Wise JTF, Salazar-González RA, Walls KM, Doll MA, Habil MR, Hein DW. Hexavalent chromium increases the metabolism and genotoxicity of aromatic amine carcinogens 4-aminobiphenyl and β-naphthylamine in immortalized human lung epithelial cells. Toxicol Appl Pharmacol. 2022 Jun 2;449:116095. doi: 10.1016/j.taap.2022.116095. Epub ahead of print. PMID: 35662664.
    Impact Statement: Human carcinogens to which humans are exposed by inhalation include 4-aminobiphenyl, β-naphthylamine and hexavalent chromium. Whereas the effects of the individual carcinogens have been investigated, this study investigated the effects of co-exposure of these carcinogens in human lung cells. The study documented that hexavalent chromium increased N-acetyltransferase 1 activity contributing to increased genotoxicity from 4-aminobiphenyl or β-naphthylamine.
  • Yan K, Mei Z, Zhao J, Prodhan MAI, Obal D, Katragadda K, Doelling B, Hoetker D, Posa DK, He L, Yin X, Shah J, Pan J, Rai S, Lorkiewicz PK, Zhang X, Liu S, Bhatnagar A, Baba SP. Integrated Multilayer Omics Reveals the Genomic, Proteomic, and Metabolic Influences of Histidyl Dipeptides on the Heart. J Am Heart Assoc. 2022 Jun 22:e023868. doi: 10.1161/JAHA.121.023868. Epub ahead of print. PMID: 35730646.
    Impact Statement: To identify histidyl dipeptide-mediated responses in the heart, we used an integrated triomics approach, which involved genome-wide RNA sequencing, global proteomics, and unbiased metabolomics to identify the effects of cardiospecific transgenic overexpression of the carnosine synthesizing enzyme, carnosine synthase (Carns), in mice. Our result showed that higher myocardial levels of histidyl dipeptides were associated with extensive changes in the levels of several microRNAs, which target the expression of contractile proteins, β-fatty acid oxidation, and citric acid cycle (TCA) enzymes. Global proteomic analysis showed enrichment in the expression of contractile proteins, enzymes of β-fatty acid oxidation, and the TCA in the Carns transgenic heart. Integration of multiple data sets suggested that β-fatty acid oxidation and TCA pathways exhibit correlative changes in the Carns transgenic hearts at all 3 levels. Conclusions Taken together, these findings reveal a central role of histidyl dipeptides in coordinated regulation of myocardial structure, function, and energetics.
  • Kumar R, Adhikari S, Driver EM, Smith T, Bhatnagar A, Lorkiewicz PK, Xie Z, Hoetker JD, Halden RU. Towards a novel application of wastewater-based epidemiology in population-wide assessment of exposure to volatile organic compounds. Sci Total Environ. 2022 Jun 27:157008. doi: 10.1016/j.scitotenv.2022.157008. Epub ahead of print. PMID: 35772546.
    Impact Statement: This is the first study to utilize wastewater to detect urinary biomarkers of volatile organic compounds (VOCs) exposure. These preliminary results suggest the wastewater-based epidemiology approach as a potentially powerful tool to assess community health exposures to indoor and outdoor air pollutants.
  • Polivka BJ, Huntington-Moskos L, Antimisiaris DE, Cavallazzi RS, Folz RJ. Phenotyping older adults with asthma by means of cluster analysis. Ann Allergy Asthma Immunol. 2022 Jun 10:S1081-1206(22)00501-4. doi: 10.1016/j.anai.2022.06.003. Epub ahead of print. PMID: 35697194.
    Impact Statement:  Whereas a number of publications have identified asthma phenotypes in adults, few have focused only on older adults. As a component of a randomized controlled trial of older adults (≥50 years old) with persistent asthma, Baptist et al identified 4 phenotypic clusters. The purpose of this study was to compare findings from the Baptist et al study with cluster analysis findings from a cohort of older adults with asthma participating in a longitudinal observational study.
  • McLeish KR, Shrestha R, Vashishta A, Rane MJ, Barati MT, Brier ME, Lau MG, Hu X, Chen O, Wessel CR, Spalding T, Bush SE, Ijemere K, Hopkins CD, Cooke EA, Tandon S, Manning T, Uriarte SM, Huang J, Yan J. Differential Functional Responses of Neutrophil Subsets in Severe COVID-19 Patients. Front Immunol. 2022 May 31;13:879686. doi: 10.3389/fimmu.2022.879686. PMID: 35711435; PMCID: PMC9197482.
    Impact Statement:  Normal Density Neutrophils and Low Density Neutrophils from COVID-19 patients possess complementary functional capabilities that may act cooperatively to determine disease severity. We predict that global neutrophil responses that induce COVID-19 ARDS will vary depending on the proportion of neutrophil subsets.
  • Brady MP, Chava S, Tandon S, Rane MJ, Barati MT, Caster DJ, Powell DW. Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis. J Clin Med. 2022 Jun 3;11(11):3199. doi: 10.3390/jcm11113199. PMID: 35683585; PMCID: PMC9181282.
    Impact Statement:  Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus and current diagnostics and treatments are inadequate. Our report identifies a potential diagnostic marker for LN and will therefore provide impactful insight for improved LN patient care.
  • Watson WH, Ritzenthaler JD, Torres-Gonzalez E, Arteel GE, Roman J. Mice lacking α4 nicotinic acetylcholine receptors are protected against alcohol-associated liver injury. Alcohol Clin Exp Res. 2022 Jun 20. doi: 10.1111/acer.14893. Epub ahead of print. PMID: 35723023.
    Impact Statement: Liver disease associated with long-term heavy drinking of alcoholic beverages is a major health problem with no FDA-approved therapies. In this paper, we describe a previously unknown mediator of alcohol’s adverse effects on the liver: the alpha4 subunit of nicotinic acetylcholine receptors. These neurotransmitter receptors are known to be important in the brain, where they are involved in the reward pathways activated by both nicotine and alcohol. The discovery that they are also expressed in the liver and contribute to some of the earliest manifestations of alcohol-associated liver disease points to a new target for potential therapeutic interventions.
  • Rajesh M, Xin Y, Young JL, Cai L. Editorial: Cardiovascular Diseases Related to Diabetes and Obesity. Front Endocrinol (Lausanne). 2022 May 23;13:916142. doi: 10.3389/fendo.2022.916142. PMID: 35677720; PMCID: PMC9169566.
    Impact Statement:  Worldwide, the prevalence of obesity continues rising unabated due to the rapid urbanization in the developed and developing countries and poor lifestyle habits. Obesity is also attributed to the development of major cardiovascular diseases (CVD), diabetes, arthritis, behavioral changes, depression, cancers, and hepatic diseases. Therefore, a special issue focus on the CVDs related to diabetes and obesity has been released, for which this editorial was and also briefly introduced the contents of the twelve publications, with a hope to set the stage for delving further in deciphering the crucial link between obesity and diabetes.
  • Nie J, Zhang Y, Ning L, Yan Z, Duan L, Xi H, Niu Q, Zhang Q. Phosphorylation of p53 by Cdk5 contributes to benzo[a]pyrene-induced neuronal apoptosis. Environ Toxicol. 2021 Sep 16. doi: 10.1002/tox.23374. Epub ahead of print. PMID: 34529316.