April 2022-March 2023 Member Publications

Ferragut Cardoso AP, Nail AN, Banerjee M, Wise SS, States JC. miR-186 induces tetraploidy in arsenic exposed human keratinocytes. Ecotoxicol Environ Saf. 2023 Mar 27;256:114823. doi: 10.1016/j.ecoenv.2023.114823. Epub ahead of print. PMID: 36989553.
Impact Statement: Hsa-miR-186 is overexpressed in skin cancers induced by chronic arsenic exposure as well as other advanced cancers. This study shows that hsa-miR-186 overexpression in human keratinocytes induces a doubling of chromosome number and dysregulated chromosome segregation to daughter cells. These chromosomal abnormalities are characteristic of cancerous cells and support the hypothesis that hsa-miR-186 overexpression contributes to carcinogenesis.

Pavuk M, Rosenbaum PF, Lewin MD, Serio TC, Rago P, Cave MC, Birnbaum LS. Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, pesticides, and diabetes in the Anniston Community Health Survey follow-up (ACHS II): single exposure and mixture analysis approaches. Sci Total Environ. 2023 Mar 17;877:162920. doi: 10.1016/j.scitotenv.2023.162920. Epub ahead of print. PMID: 36934946.
Impact Statement: Our follow-up study results add to the body of literature that has researched associations between exposure to PCBs, other POPs, and diabetes. We found elevate odds ratios for, p,p’-DDE, trans-Nonachlor, some PCBs, and PCDDs TEQ for prevalent diabetes, but those were attenuated for incident diabetes in single exposure logistic regression models.

Ge Y, Bruno M, Nash MS, Haykal Coates N, Chorley BN, Cave MC, Beier JI. Vinyl Chloride Enhances High Fat Diet-Induced Proteome Alterations in the Mouse Pancreas Related to Metabolic Dysfunction. Toxicol Sci. 2023 Mar 9:kfad024. doi: 10.1093/toxsci/kfad024. Epub ahead of print. PMID: 36892438.
Impact Statement: Alterations in physiological processes in pancreas have been associated with various metabolic dysfunctions and can result from environmental exposures, such as chemicals and diet. We found that the protein alterations may indicate diet-mediated susceptibility in mouse pancreas induced by HFD to concurrent exposure of low levels of inhaled VC. These proteome biomarkers may lead to a better understanding of pancreas-mediated adaptive or adverse response and susceptibility to metabolic disease.

Ribble A, Hellmann J, Conklin DJ, Bhatnagar A, Haberzettl P. Fine particulate matter (PM2.5)-induced pulmonary oxidative stress contributes to increases in glucose intolerance and insulin resistance in a mouse model of circadian dyssynchrony. Sci Total Environ. 2023 Mar 18;877:162934. doi: 10.1016/j.scitotenv.2023.162934. Epub ahead of print. PMID: 36934930.
Impact Statement:Results of human and animal studies independently suggest that either ambient fine particulate matter (PM2.5) air pollution exposure or a disturbed circadian rhythm (circadian dyssynchrony) are important contributing factors to the rapidly evolving type-2-diabetes (T2D) epidemic. Our results demonstrate that circadian dyssynchrony is a novel susceptibility state for PM2.5 and suggest that PM2.5 by inducing pulmonary oxidative stress increases glucose intolerance and insulin resistance in circadian dyssynchrony.

Agbonlahor O, DeJarnett N, Hart JL, Bhatnagar A, McLeish AC, Walker KL. Racial/Ethnic Discrimination and Cardiometabolic Diseases: A Systematic Review. J Racial Ethn Health Disparities. 2023 Mar 28:1–25. doi: 10.1007/s40615-023-01561-1. Epub ahead of print. PMID: 36976513; PMCID: PMC10044132.
Impact Statement:Racial/ethnic discrimination is positively associated with increased risk of cardiometabolic disease and higher levels of cardiometabolic biomarkers. Identifying racial/ethnic discrimination as a potential key contributor to the health inequities associated with cardiometabolic diseases is important for addressing the significant burden borne by racial/ethnic minorities.

Kurlawala Z, Singh P, Hill BG, Haberzettl P. Fine Particulate Matter (PM2.5)-Induced Pulmonary Oxidative Stress Contributes to Changes in the Plasma Lipidome and Liver Transcriptome in Mice. Toxicol Sci. 2023 Mar 1:kfad020. doi: 10.1093/toxsci/kfad020. Epub ahead of print. PMID: 36857595
Impact Statement:Fine Particulate Matter (PM2.5)-Induced Pulmonary Oxidative Stress Contributes to Changes in the Plasma Lipidome and Liver Transcriptome in Mice” Our findings indicate that exposure of mice to fine particulate matter (PM2.5) induces unique changes in the plasma lipidome, which are accompanied by alterations in the liver transcriptome. These plasmatic and hepatic changes seem to depend, at least in part, on pulmonary oxidative stress.

Huang J, Mazer CD, Boisen ML, Tibi P, Baker RA, Chu D, Moffatt-Bruce S, Shore-Lesserson L. Safety of Andexanet Alfa Use in Cardiac Surgery. J Cardiothorac Vasc Anesth. 2023 Mar 5:S1053-0770(23)00128-3. doi: 10.1053/j.jvca.2023.02.039. Epub ahead of print. PMID: 36997371.
Impact Statement:There are currently no prospective clinical trials or retrospective studies describing andexanet alfa use in cardiac surgery. For the patient who has received andexanet alfa and demonstrates heparin resistance, administration of antithrombin III may be an alternative approach.

Golebiowska AA, Jala VR, Nukavarapu SP. Decellularized Tissue-Induced Cellular Recruitment for Tissue Engineering and Regenerative Medicine. Ann Biomed Eng. 2023 Mar 23. doi: 10.1007/s10439-023-03182-5. Epub ahead of print. PMID: 36952144.
Impact Statement: In this article, in collaboration with Dr. Syam P Nukavarapu, Univ of Connecticut,  we explored decellularized human cartilage as a biomaterial/ graft for tissue repair and regeneration. Our 2D and 3D chemotactic assays show that the tissue-derived biomaterials retain biochemical cues of native tissue and stimulate chemotactic migration of stem/ progenitor cells. Together, this study developed a new paradigm in tissue engineering and regenerative medicine.

Lindsey ML, Kleinbongard P, Kassiri Z, Carter JR, Hansell Keehan K, Ripplinger CM, LeBlanc AJ, Brunt KR, Kirk JA. We Asked and You Answered. Am J Physiol Heart Circ Physiol. 2023 Mar 17. doi: 10.1152/ajpheart.00084.2023. Epub ahead of print. PMID: 36930658.
Impact Statement: This purpose of this editorial was to give an update on the success that American Journal of Physiology – Heart and Circulatory Physiology has had incorporating sex as a biological variable in cardiovascular research manuscripts submitted to the journal. Unless scientifically justified, our journal now requires that research manuscripts incorporate both sexes starting in January of 2023. To summarize briefly, the scientific community has successfully embraced this requirement and we have implemented a new Table of Contents category titled, “Sex as a Biological Variable”.

Del Rosario O, Suresh K, Kallem M, Singh G, Shah A, Zheng L, Yun X, Philip NM, Putcha N, McClure MB, Jiang H, D'Alessio F, Srivastava M, Bera A, Shimoda LA, Merchant M, Rane MJ, Machamer CE, Mock J, Hagan R, Koch AL, Punjabi NM, Kolb TM, Damarla M. MK2 non-enzymatically promotes nuclear translocation of caspase-3 and resultant apoptosis. Am J Physiol Lung Cell Mol Physiol. 2023 Mar 28. doi: 10.1152/ajplung.00340.2022. Epub ahead of print. PMID: 36976920.
Impact Statement:Taken together, our results demonstrate a non-enzymatic role for MK2 in the nuclear translocation of caspase-3. Furthermore, MK2 may function as a molecular switch in regulating the transition between the cytosolic and nuclear functions of caspase-3.

Suresh K, Del Rosario O, Kallem M, Singh G, Shah A, Zheng L, Yun X, Philip NM, Putcha N, McClure MB, Jiang H, D'Alessio F, Srivastava M, Bera A, Shimoda LA, Merchant M, Rane MJ, Machamer CE, Mock J, Hagan R, Koch AL, Punjabi NM, Kolb TM, Damarla M. Tumor MK2 transcript levels are associated with improved response to chemotherapy and patient survival in non-small cell lung cancer. Physiol Genomics. 2023 Apr 1;55(4):168-178. doi: 10.1152/physiolgenomics.00155.2022. Epub 2023 Mar 6. PMID: 36878491; PMCID: PMC10042611.
Impact Statement: This study implicates MK2 in apoptosis resistance in NSCLC and suggests prognostic value of MK2 transcript levels in patients with lung adenocarcinoma.

Anderson LB, Kanneganti D, Houk MB, Holm RH, Smith T. Generative AI as a Tool for Environmental Health Research Translation. medRxiv [Preprint]. 2023 Feb 22:2023.02.14.23285938. doi: 10.1101/2023.02.14.23285938. PMID: 36865187; PMCID: PMC9980240
Impact Statement:This research has the potential to significantly impact society and public health by making scientific information more accessible to non-academic, and specifically environmental justice audiences, thereby empowering communities and promoting informed policy-making. Additionally, the widespread adoption of AI-generated plain language summaries could lead to better public understanding of health research, ultimately resulting in improved public health policies and practices.

Nail AN, Ferragut Cardoso AP, Montero LK, States JC. miRNAs and arsenic-induced carcinogenesis. Adv Pharmacol. 2023;96:203-240. doi: 10.1016/bs.apha.2022.10.002. Epub 2023 Feb 6. PMID: 36858773.
Impact Statement: Our publication provides a comprehensive resource for researchers to easily determine which miRNAs are dysregulated both in cell models for arsenic-induced cancer and in arsenic-induced human cancers.

Vielee ST, Wise JP Jr. Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence. Brain Sci. 2023 Mar 16;13(3):500. doi: 10.3390/brainsci13030500. PMID: 36979310; PMCID: PMC10046019.
Impact Statement: As we approach a new era of human history with the largest geriatric population in history, we imminently need to better understand the intersection between toxicology and aging. The term 'gerontogen' was coined in 1987 by Dr. George Martin to describe chemicals that accelerate biological aging, since then this term has received little attention. This review serves to broaden the discussion of gerontogens and considers heavy metals as a distinct class of gerontogen.

Amraotkar AR, Keith RJ, Palmer KE, Bhatnagar A. Using SARS-CoV-2 Antibody Testing in COVID-19 Research. Am J Med. 2023 Feb 11:S0002-9343(23)00080-3. doi: 10.1016/j.amjmed.2023.02.001. Epub ahead of print. PMID: 36780969; PMCID: PMC9922202.
Impact Statement: We have investigated the association between physical activity and COVID-19 severity risks by identifying prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as either self-reported or by presence of antibodies. There is a fundamental vulnerability in utilizing antibodies to determine proof of prior infection, especially in secondary data analysis from large registries. We would like to provide critical yet constructive insight on SARS-CoV-2 antibody testing in COVID-19 research, that could augment characterization of prior COVID-19 infection or future scientific works.

 El-Kersh K, Hopkins CD, Wu X, Rai SN, Cave MC, Smith MR, Go YM, Jones DP, Cai L, Huang J. Metallomics in pulmonary arterial hypertension patients. Pulm Circ. 2023 Feb 21;13(1):e12202. doi: 10.1002/pul2.12202. PMID: 36824690; PMCID: PMC9941844.
Impact Statement: Pulmonary arterial hypertension (PAH) prevalence is increasing worldwide, and the prognosis is poor with 5-year survival < 50% in high risk patients. We found significant differences between PAH and control groups in terms of metal concentrations. Silver and chromium levels are correlated with clinical indicators of PAH severities.

McGraw KE, Konkle SL, Riggs DW, Rai SN, DeJarnett N, Xie Z, Keith RJ, Oshunbade A, Hall ME, Shimbo D, Bhatnagar A. Exposure to Volatile Organic Compounds Is Associated with Hypertension in Black Adults: The Jackson Heart Study. Environ Res. 2023 Apr 15;223:115384. doi: 10.1016/j.envres.2023.115384. Epub 2023 Feb 14. PMID: 36796615.
Impact Statement: The prevalence of hypertension is higher among Black adults than among White and Hispanic adults. Nevertheless, reasons underlying the higher rates of hypertension in the Black population remain unclear but may relate to exposure to environmental chemicals such as volatile organic compounds (VOCs). We found hypertension in Black individuals may be attributed, in part, to VOC exposure from the environment or tobacco smoke.

Xie Z, Morris JD, Mattingly SJ, Sutaria SR, Huang J, Nantz MH, Fu XA. Analysis of a Broad Range of Carbonyl Metabolites in Exhaled Breath by UHPLC-MS. Anal Chem. 2023 Feb 23. doi: 10.1021/acs.analchem.2c04604. Epub ahead of print.
Impact Statement: Analysis of volatile organic compounds (VOCs) in exhaled breath (EB) has shown great potential for disease detection including lung cancer, infectious respiratory diseases, and chronic obstructive pulmonary disease. This work reports a method of ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-MS) for the analysis of a broad range of carbonyl metabolites in exhaled breath. A total of six subgroups consisting of saturated aldehydes and ketones, hydroxy-aldehydes, and hydroxy-ketones, unsaturated 2-alkenals, and 4-hydroxy-2-alkenals were identified in exhaled breath.

Yu H, Zuo Y, Xu Z, Zhao D, Yue J, Liu L, Guo Y, Huang J, Deng X, Liang P. Comparison effects of two muscle relaxant strategies on postoperative pulmonary complications in transapical transcatheter aortic valve implantation: a propensity score-matched analysis. J Cardiothorac Surg. 2023 Feb 1;18(1):50. doi: 10.1186/s13019-023-02166-9. PMID: 36721168.
Impact Statement:The rocuronium/sugammadex muscle relaxant strategy decreases the incidence of Postoperative Pulmonary Complications in patients undergoing transapical TAVR when compared to cisatracurium/neostigmine strategy.

Redding A, Samanapally H, Udoh MO, Huang J, Slaughter MS, Pahwa S. Coronary Artery Bypass Grafting complicated by post-operative coronavirus infection - two similar presentations with dissimilar outcomes. Arch Clin Cases. 2023 Feb 20;10(1):7-10. doi: 10.22551/2023.38.1001.10230. PMID: 36814673; PMCID: PMC9940284.
Impact Statement:Patients diagnosed with COVID-19 infection undergoing surgical procedures have been reported to have increased post-operative complications and mortality. This case series describes the clinical course following a CABG procedure in two patients that went on to develop COVID-19 infection post-operatively.

Liu T, Huang J, Wang X, Tu J, Wang Y, Xie C. Effect of recruitment manoeuvres under lung ultrasound-guidance and positive end-expiratory pressure on postoperative atelectasis and hypoxemia in major open upper abdominal surgery: A randomized controlled trial. Heliyon. 2023 Jan 30;9(2):e13348. doi: 10.1016/j.heliyon.2023.e13348. PMID: 36755592; PMCID: PMC9900369.
Impact Statement: In patients undergoing major open upper abdominal surgery, an intraoperative mechanical ventilation strategy without PEEP or with PEEP alone did not reduce postop pulmonary complications. However, PEEP of 5 cmH2O combined with lung #ultrasound-guided recruitment maneuvers proved feasible and beneficial to decrease the occurrence of postoperative atelectasis and hypoxemia in major open upper abdominal surgeries.

Pahwa S, Kertai MD, Abrams B, Huang J. Length of Hospital Stay as a Performance Metric-Is That a Fair Assessment? Semin Cardiothorac Vasc Anesth. 2023 Mar;27(1):5-7. doi: 10.1177/10892532231159723. Epub 2023 Feb 14. PMID: 36786418.
Impact Statement:The quality improvement programs have taken center stage discussions in hospital boardrooms. The potential avenues to predict and hopefully reduce hospital LOS in both liver transplant recipients and multiple subsets of cardiac surgery patients are critical.

Sriwastva MK, Teng Y, Mu J, Xu F, Kumar A, Sundaram K, Malhotra RK, Xu Q, Hood JL, Zhang L, Yan J, Merchant ML, Park JW, Dryden GW, Egilmez NK, Zhang HG. An extracellular vesicular mutant KRAS-associated protein complex promotes lung inflammation and tumor growth. J Extracell Vesicles. 2023 Feb;12(2):e12307. doi: 10.1002/jev2.12307. PMID: 36754903; PMCID: PMC9908562.
Impact Statement:Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an 'organiser' of protein networks to generate a new or different biological effect from that identified in EV-producing cells has never been demonstrated. Here, as a proof-of-concept, we demonstrate that EV-G12D-mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL-17A/FGF21 axis.

Li J, Sato T, Hernández-Tejero M, Beier JI, Sayed K, Benos PV, Wilkey DW, Humar A, Merchant ML, Duarte-Rojo A, Arteel GE. The plasma degradome reflects later development of NASH fibrosis after liver transplant. bioRxiv [Preprint]. 2023 Feb 1:2023.01.30.526241. doi: 10.1101/2023.01.30.526241. PMID: 36778394; PMCID: PMC9915514.
Impact Statement: Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease, and decreased survival. Lack of risk stratification strategies hamper liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.e., 'degradome') of the ECM and other proteins increase in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. To investigate whether inflammatory liver injury caused by post-LT NASH would yield a unique degradome profile, predictive of severe post-LT NASH fibrosis, we performed a retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without).

Sayed M, Park JW. miRinGO: Prediction of Biological Processes Indirectly Targeted by Human microRNAs. Noncoding RNA. 2023 Jan 22;9(1):11. doi: 10.3390/ncrna9010011. PMID: 36827544; PMCID: PMC9962180.
Impact Statement:We introduce a method to predict gene ontology (GO) annotations indirectly targeted by microRNAs. The proposed method can uncover potential biological pathways affected by indirect targets of human miRNAs especially ones related to cell differentiation and development.

ElNakieb Y, Ali MT, Elnakib A, Shalaby A, Mahmoud A, Soliman A, Barnes GN, El-Baz A. Understanding the Role of Connectivity Dynamics of Resting-State Functional MRI in the Diagnosis of Autism Spectrum Disorder: A Comprehensive Study. Bioengineering (Basel). 2023 Jan 2;10(1):56. doi: 10.3390/bioengineering10010056. PMID: 36671628; PMCID: PMC9855190.
Impact Statement: In addition to the standard observational assessment for autism spectrum disorder (ASD), recent advancements in neuroimaging and machine learning (ML) suggest a rapid and objective alternative using brain imaging. As a result of this comprehensive study, we achieve state-of-the-art accuracy, confirming the benefits of the proposed feature representation and feature engineering in extracting useful information as well as the potential benefits of utilizing ML and neuroimaging in the diagnosis and understanding of autism.

Majid S, Weisbrod RM, Fetterman JL, Keith RJ, Rizvi SHM, Zhou Y, Behrooz L, Robertson RM, Bhatnagar A, Conklin DJ, Hamburg NM. Pod-based e-liquids impair human vascular endothelial cell function. PLoS One. 2023 Jan 26;18(1):e0280674. doi: 10.1371/journal.pone.0280674. PMID: 36701344; PMCID: PMC9879485.
Impact Statement: Results of the present study provide important insights into the association of electronic cigarettes known as pods with endothelial dysfunction – a biomarker of cardiovascular harm. Our results suggest that endothelial impairment induced by e-cigarettes may be, in part, due to impaired eNOS activation to a degree similar to that seen in users of combustible cigarettes. These findings support regulation of tobacco products containing acidified nicotine, as well as the development of product and device standards to limit the generation of harmful or potentially harmful chemicals in e-cigarette aerosols.

Lü L, Yuan F, Fan H, Li Y, Liu J, Feng W, Zhang HG, Chen SY. Ethanol exposure disrupted the formation of radial glial processes and impaired the generation and migration of outer radial glial cells in forebrain organoids derived from human embryonic stem cells. Exp Neurol. 2023 Jan 18;362:114325. doi: 10.1016/j.expneurol.2023.114325. Epub ahead of print. PMID: 36669750.
Impact Statement: Maternal alcohol abuse during pregnancy can damage the developing fetus and lead to Fetal Alcohol Spectrum Disorders. This study aims to investigate the effects of ethanol exposure on the development of radial glial processes and the generation, migration, and transformation of outer radial glial cells using forebrain organoids generated from human embryonic stem cells. The results from this study provided new insight into the mechanisms underlying ethanol-induced abnormalities in fetal cortical development and FASD in humans.

Naegle MA, Kelly LA, Embree JL, Valentine N, Sharp D, Grinspun D, Hines-Martin VP, Crawford CL, Rosa WE. American academy of nursing consensus recommendations to advance system level change for nurse well-being. Nurs Outlook. 2023 Feb 1;71(2):101917. doi: 10.1016/j.outlook.2023.101917. Epub ahead of print. PMID: 36736029; PMCID: PMC9889942.
Impact Statement: This paper proposes recommendations from the AAN Expert Panels on Building Health Care System Excellence, Psychiatric Mental Health and Substance Use, and Global Health Expert Panels for the American Academy of Nursing to leverage related policy in the arenas of government and professional/healthcare organizations. Transforming health care work environments and advancing nurse well-being and equity can be accomplished through key, innovative policy changes. These will be achieved through collaboration among associations, organizations, nonprofit groups, and with the public and the media.

Wei H, Price Z, Evans K, Haberstroh A, Hines-Martin V, Harrington CC. The State of the Science of Nurses' Implicit Bias: A Call to Go Beyond the Face of the Other and Revisit the Ethics of Belonging and Power. ANS Adv Nurs Sci. 2023 Jan 10. doi: 10.1097/ANS.0000000000000470. Epub ahead of print. PMID: 36728370.
Impact Statement: This article summarizes the current state of nurses' implicit bias and discusses the phenomenon from Levinas' face of the Other and ethics of belonging, Watson's human caring and unitary caring science, and Chinn's peace and power theory. Nurses' implicit bias is a global issue; the primary sources of nurses' implicit bias include race/ethnicity, sexuality, health conditions, age, mental health status, and substance use disorders. The current research stays at the descriptive level and addresses implicit bias at the individual level. This article invites nurses to go beyond “the face of the Other” and revisit the ethics of belonging and power.

Tu W, Gawrieh S, Dasarathy S, Mitchell MC, Simonetto DA, Patidar KR, McClain CJ, Bataller R, Szabo G, Tang Q, Barton BA, Radaeva S, Sanyal AJ, Shah V; Alcoholic Hepatitis Network (AlcHepNet) Investigators. Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis. Contemp Clin Trials Commun. 2023 Jan 18;32:101074. doi: 10.1016/j.conctc.2023.101074. PMID: 36698742; PMCID: PMC9869411.
Impact Statement: Mortality is high for severe alcohol-associated hepatitis (AH). The study provided a direct comparison of the survival benefits and safety profiles of anakinra plus zinc vs. prednisone in patients with severe AH.

Sato T, Head KZ, Li J, Dolin CE, Wilkey D, Skirtich N, Smith K, McCreary DD, Liu S, Beier JI, Singhi AD, McEnaney RM, Merchant ML, Arteel GE. Fibrosis resolution in the mouse liver: Role of Mmp12 and potential role of calpain 1/2. Matrix Biol Plus. 2022 Dec 28;17:100127. doi: 10.1016/j.mbplus.2022.100127. PMID: 36632559; PMCID: PMC9826883.
Impact Statement: These results also indicate that analysis of the plasma degradome may yield new insight into the mechanisms of fibrosis recovery, and by extension, new "theragnostic" targets. Lastly, a novel potential role for calpain activation in the degradation and turnover of proteins was identified.

Holm RH, Rempala GA, Choi B, Brick JM, Amraotkar AR, Keith RJ, Rouchka EC, Chariker JH, Palmer KE, Smith T, Bhatnagar A. SARS-CoV-2 wastewater concentration and linked longitudinal seroprevalence: a spatial analysis of strain mutation, post-COVID-19 vaccination effect, and hospitalization burden forecasting. medRxiv [Preprint]. 2023 Jan 7:2023.01.06.23284260. doi: 10.1101/2023.01.06.23284260. PMID: 36656780; PMCID: PMC9844017.
Impact Statement: Wastewater samples can be used to estimate the effects of vaccination and hospitalization burden. Our study underscores the importance of continued environmental surveillance post-vaccine and provides a proof of concept for environmental epidemiology monitoring.

Wahlang B, Gao H, Rai SN, Keith RJ, McClain CJ, Srivastava S, Cave MC, Bhatnagar A. Associations between residential volatile organic compound exposures and liver injury markers: The role of biological sex and race. Environ Res. 2023 Jan 4;221:115228. doi: 10.1016/j.envres.2023.115228. Epub ahead of print. PMID: 36610539.
Impact Statement: This study illustrated how our body’s responses to environmental chemicals are different based on biological factors such as sex, lifestyle factors such as smoking, and social constructs such as race. The research findings also highlight the significance of considering biological-social-lifestyle factor(s) interactions when addressing air pollution-related health disparities.

Bolatimi OE, Head KZ, Luo J, Gripshover TC, Lin Q, Adiele NV, Watson WH, Wilkerson C, Cai L, Cave MC, Young JL. Can Zinc Supplementation Attenuate High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease? Int J Mol Sci. 2023 Jan 16;24(2):1763. doi: 10.3390/ijms24021763. PMID: 36675277; PMCID: PMC9864360.
Impact Statement: Deficiency in the essential micronutrient zinc, the second most concentrated trace mineral in the body, impacts almost 20% of the global population and is implicated in playing a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), now the most rapidly growing contributor to liver mortality and morbidity. This study investigated the ability of zinc supplementation to attenuate diet-induce NAFLD demonstrated that a sensitive consideration of initiation and duration of administration for therapeutic intervention of zinc must be considered.

Jaggers JR, King KM, McKay T, Dyess RJ, Thrasher BJ, Wintergerst KA. Association between Intensity Levels of Physical Activity and Glucose Variability among Children and Adolescents with Type 1 Diabetes. Int J Environ Res Public Health. 2023 Jan 16;20(2):1623. doi: 10.3390/ijerph20021623. PMID: 36674378; PMCID: PMC9865470.
Impact Statement: This publication data demonstrated that the total amount of daily physical activity is important when properly managing type 1 diabetes mellitus, but time spent in moderate and vigorous physical activity (MVPA) over two weeks may have an inverse relationship with glucose variability in children and adolescents over a span of two weeks.

Berlowitz JB, Xie W, Harlow AF, Blaha MJ, Bhatnagar A, Benjamin EJ, Stokes AC. Cigarette‒E-cigarette Transitions and Respiratory Symptom Development. Am J Prev Med. 2022 Dec 2:S0749-3797(22)00509-8. doi: 10.1016/j.amepre.2022.10.006. Epub ahead of print. PMID: 36470837. 
Impact Statement: E-cigarette initiation among nonusers is associated with increased respiratory morbidity. Further research should assess the risks and benefits of E-cigarette‒assisted cigarette cessation given the reduction in symptom development rates among dual use to E-cigarette switchers.

Richardson A, Krivokhizhina T, Lorkiewicz P, D'Souza S, Bhatnagar A, Srivastava S, Conklin DJ. Effects of electronic cigarette flavorants on human platelet aggregation ex vivo. Toxicol Rep. 2022 Apr 8;9:814-820. doi: 10.1016/j.toxrep.2022.04.003. PMID: 36518374; PMCID: PMC9742839. 
Impact Statement: This study investigated the direct effects of 15 unaltered, common flavorants used in electronic cigarette liquids on human platelet aggregation. Although most flavorants did not alter ADP-induced aggregation, our study did not test other agonists of aggregation or flavorants as modified by heated conditions present in electronic cigarettes, which is recommended in order to protect public health.

Oladipupo I, Ali T, Hein DW, Pagidas K, Bohler H, Doll MA, Mann ML, Gentry A, Chiang JL, Pierson RC, Torres S, Reece E, Taylor KC. Association between cigarette smoking and ovarian reserve among women seeking fertility care. PLoS One. 2022 Dec 13;17(12):e0278998. doi: 10.1371/journal.pone.0278998. PMID: 36512605; PMCID: PMC9746951. 
Impact Statement: This cross-sectional epidemiologic study evaluated the effect of smoking on ovarian reserve among women seeking fertility counseling. The study suggests that long-term and/or heavy smoking may increase the risk of diminished ovarian reserve. This study was unique in that It stratified the study population by polycystic ovary syndrome (PCOS) status; this is important because the measure used to determine ovarian reserve (anti-Mullerian hormone levels) is impacted by PCOS.

Winrich E, Belur AD, Shine A, Jophlin LL. Takotsubo cardiomyopathy following liver transplantation and COVID-19 infection. Proc (Bayl Univ Med Cent). 2022 Aug 23;36(1):99-100. doi: 10.1080/08998280.2022.2114069. PMID: 36578602; PMCID: PMC9762796. 
Impact Statement: Takotsubo cardiomyopathy involves transient systolic dysfunction of the left ventricle thought to be caused by a physiologic stress response and associated catecholamine release. We present a previously undocumented cause of this stress response involving a 53-year-old man with hepatocellular carcinoma and alcohol-associated cirrhosis who initially presented for liver transplantation. Shortly after successful transplantation, the patient developed a COVID-19 infection and takotsubo cardiomyopathy.

He L, Vatsalya V, Ma X, Klinge CM, Cave MC, Feng W, McClain CJ, Zhang X. Metabolic Analysis of Nucleosides/Bases in the Urine and Serum of Patients with Alcohol-Associated Liver Disease. Metabolites. 2022 Nov 28;12(12):1187. doi: 10.3390/metabo12121187. PMID: 36557225; PMCID: PMC9783452. 
Impact Statement: This paper identified 12 RNA modifications that were significantly altered in human urine and serum samples from patients with alcohol-associated liver disease.

Lindsey ML, Carter JR, Ripplinger CM, Kassiri Z, Hansell Keehan K, Brunt KR, Kirk JA, Kleinbongard P, LeBlanc AJ. Sex still matters in cardiovascular research. Am J Physiol Heart Circ Physiol. 2023 Jan 1;324(1):H79-H81. doi: 10.1152/ajpheart.00643.2022. Epub 2022 Dec 9. PMID: 36487186. 
Impact Statement: This editorial is a reminder to the American Journal of Physiology-Heart and Circulatory Physiology readership that beginning in January of 2023, authors must include both sexes in original research articles submitted to the journal unless a strong scientific justification can be made as to why one sex is excluded. This decision helps increase our scientific understanding of physiology and disease in both sexes instead of the predominant male only studies in the past.

Xu R, He L, Vatsalya V, Ma X, Kim S, Mueller EG, Feng W, McClain CJ, Zhang X. Metabolomics analysis of urine from patients with alcohol-associated liver disease reveals dysregulated caffeine metabolism. Am J Physiol Gastrointest Liver Physiol. 2022 Dec 13. doi: 10.1152/ajpgi.00228.2022. Epub ahead of print. PMID: 36513601. 
Impact Statement: Excess alcohol intake causes millions of deaths annually worldwide. Asymptomatic early-stage alcohol-associated liver disease (ALD) is easily overlooked, and ALD is usually only diagnosed in more advanced stages. We explored the possibility of using polar urine metabolites as biomarkers of ALD for early-stage diagnosis and functional assessment of disease severity.

Hardesty JE, Warner JB, Song YL, Rouchka EC, McClain CJ, Warner DR, Kirpich IA. Resolvin D1 attenuated liver injury caused by chronic ethanol and acute LPS challenge in mice. FASEB J. 2023 Jan;37(1):e22705. doi: 10.1096/fj.202200778R. PMID: 36520060. 
Impact Statement: Alcohol-associated hepatitis (AH) is a subset of severe Alcohol-associated liver disease (ALD) with a high rate of mortality due to infection, severe inflammation, and ultimately multi-organ failure. There is an urgent need for novel therapeutic approaches to alleviate the human suffering associated with this condition. Our data demonstrated that Resolvin D1 (RvD1) treatment provided beneficial effects against liver injury and inflammation in an experimental animal model recapitulating features of severe AH in humans. Our results suggest that RvD1 may be a novel adjunct strategy to traditional therapeutic options for AH patients.

Koo HY, Kim MA, Min H, Hwang JY, Prajapati-DiNubila M, Kim KS, Matzuk MM, Park JW, Doetzlhofer A, Kim UK, Bok J. Follistatin regulates the specification of the apical cochlea responsible for low-frequency hearing in mammals. Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2213099120. doi: 10.1073/pnas.2213099120. Epub 2022 Dec 28. PMID: 36577057. 
Impact Statement: Using mouse genomics, this study found that follistatin (FST) is required for the maintenance of apical cochlear identity, but dispensable for its initial induction. This study will provide valuable information to study tonotopic map changes related to hearing loss.

Rai SN, Das S, Pan J, Mishra DC, Fu XA. Multigroup prediction in lung cancer patients and comparative controls using signature of volatile organic compounds in breath samples. PLoS One. 2022 Nov 30;17(11):e0277431. doi: 10.1371/journal.pone.0277431. PMID: 36449484. 
Impact Statement: Early detection of lung cancer is a crucial factor for increasing its survival rates among the detected patients. The paper reports the quantification of carbonyl VOC profiles from breath samples and identification of crucial VOCs related to lung cancer which paves the way forward for non-invasive detection of lung cancer in early stages.

Amraotkar AR, Owolabi US, Malovichko MV, Majid S, Weisbrod RM, Benjamin EJ, Fetterman JL, Hirsch GA, Srivastava S, Poudel R, Robertson RM, Bhatnagar A, Hamburg NM, Keith RJ. Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury. Vasc Med. 2022 Dec 11:1358863X221126205. doi: 10.1177/1358863X221126205. Epub ahead of print. PMID: 36503365.
Impact Statement: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin circulating angiogenic cells (CACs), indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.

Habil MR, Doll MA, Hein DW. Acetyl coenzyme A kinetic studies on N-acetylation of environmental carcinogens by human N-acetyltransferase 1 and its NAT1*14B variant. Front Pharmacol. 2022 Oct 28;13:931323. doi: 10.3389/fphar.2022.931323. PMID: 36386142; PMCID: PMC9650386. 
Impact Statement: Chinese hamster ovary (CHO) cells stably transfected with human NAT1*4 (reference allele) or NAT1*14B (variant allele) were utilized to determine AcCoA kinetic parameters for N-acetyltransferase activity towards p-aminobenzoic acid and arylamine carcinogens 4-aminobiphenyl, β-naphthylamine, benzidine and 3,4-dimethylaniline. N-acetylation rates for each substrate were greater when catalyzed by NAT1*4 which also exhibited higher affinity for AcCoA compared to NAT1*14B. The results provide further insights into differences in carcinogen metabolism among individuals possessing the NAT1*14B haplotype.

Hong KU, Tagnedji AH, Doll MA, Walls KM, Hein DW. Upregulation of cytidine deaminase in NAT1 knockout breast cancer cells. J Cancer Res Clin Oncol. 2022 Nov 3. doi: 10.1007/s00432-022-04436-w. Epub ahead of print. PMID: 36329350. 
Impact Statement: This study presents a novel, potential therapeutic approach for breast cancer that express N-acetyltransferase 1 (NAT1). NAT1 deletion in breast cancer results in upregulation of cytidine deaminase which makes the cells sensitive to certain cytidine analogs.

Hong KU, Gardner JQ, Doll MA, Stepp MW, Wilkey DW, Benz FW, Cai J, Merchant ML, Hein DW. Dataset for proteomic analysis of arylamine N-acetyltransferase 1 knockout MDA-MB-231 breast cancer cells. Data Brief. 2022 Sep 24;45:108634. doi: 10.1016/j.dib.2022.108634. PMID: 36426076; PMCID: PMC9679541. 
Impact Statement: This study identifies global changes in proteome in parental vs. NAT1 knockout breast cancer cells and potential mechanisms by which NAT1 contributes to breast cancer cell growth.

Ali AS, Sheikh D, Chandler TR, Furmanek S, Huang J, Ramirez JA, Arnold F, Cavallazzi R. Cardiovascular complications are the primary drivers of mortality in hospitalized patients with SARS-CoV-2 community-acquired pneumonia. Chest. 2022 Nov 18:S0012-3692(22)04161-7. doi: 10.1016/j.chest.2022.11.013. Epub ahead of print. PMID: 36410493.
Impact statement: In hospitalized patients with COVID-19 pneumonia, once patients develop cardiovascular complications, the risk of death is extremely high. Cardiovascular complications are the primary drivers of mortality.

Petri BJ, Klinge CM. m6A readers, writers, erasers, and the m6A epitranscriptome in breast cancer. J Mol Endocrinol. 2022 Nov 1:JME-22-0110. doi: 10.1530/JME-22-0110. Epub ahead of print. PMID: 36367225. 
Impact Statement: This is a review of the current state of knowledge on the altered levels of the writers, readers, and erasers of the m6A epitranscriptomic modification in RNA in breast cancer.

McLeish AC, Smith T, Riggs DW, Hart JL, Walker KL, Keith RJ, Anderson L, Sithu I, Pinilla-Baquero J, Srivastava S, Bhatnagar A. Community-Based Evaluation of the Associations Between Well-Being and Cardiovascular Disease Risk. J Am Heart Assoc. 2022 Nov 15;11(22):e027095. doi: 10.1161/JAHA.122.027095. Epub 2022 Nov 12. PMID: 36370026. 
Impact Statement:In a community‐based cohort, individuals reporting higher levels of well‐being have lower odds of hypertension and dyslipidemia as well as lower rates of age‐dependent increase in vascular stiffness.

Cui K, Gao X, Wang B, Wu H, Arulsamy K, Dong Y, Xiao Y, Jiang X, Malovichko MV, Li K, Peng Q, Wei Lu Y, Zhu B, Zheng R, Wong S, Cowan DB, Linton M, Srivastava S, Shi J, Chen K, Chen H. Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression. Circ Res. 2022 Nov 29. doi: 10.1161/CIRCRESAHA.122.321723. Epub ahead of print. PMID: 36444722.
Impact statement: Our findings suggest that targeting Epsins in lesional macrophages may offer therapeutic benefits for advanced atherosclerosis by reducing CD36-mediated lipid uptake and increasing ABCG1-mediated cholesterol efflux.

Petri BJ, Piell KM, Wahlang B, Head KZ, Andreeva K, Rouchka EC, Cave MC, Klinge CM. Polychlorinated biphenyls alter hepatic m6A mRNA methylation in a mouse model of environmental liver disease. Environ Res. 2023 Jan 1;216(Pt 3):114686. doi: 10.1016/j.envres.2022.114686. Epub 2022 Oct 28. PMID: 36341798.
Impact Statement: This is first report to demonstrate that PCB exposure in vivo alters the m6A landscape in liver genes in a HFD-fed mouse model of nonalcoholic fatty liver disease (NAFLD). Pathway analysis of differentially expressed genes with altered numbers of m6A peaks includes lipoprotein metabolism. m6A peaks were dependent on the type of PCB (PCB 126 vs. Aroclor 1260 or the combined exposure to PCB 126 + Aroclor 1260) and may be involved in the dysregulation of lipoprotein metabolism genes in this mouse model of NAFLD progression.

Gripshover TC, Wahlang B, Head KZ, Young JL, Luo J, Mustafa MT, Kirpich IA, Cave MC. The environmental pollutant, polychlorinated biphenyl 126, alters liver function in a rodent model of alcohol-associated liver disease. Alcohol Clin Exp Res. 2022 Nov 14. doi: 10.1111/acer.14976. Epub ahead of print. PMID: 36377258. 
Impact Statement: Various environmental toxicants are known to modify or enhance fatty liver disease (FLD) in high-fat diet models. Findings from the present study suggest that they interact with other lifestyle factors such as alcohol consumption to reprogram intermediary metabolism resulting in exacerbated ethanol-associated systemic malnutrition in alcohol-associated liver disease (ALD).

Tan Y, El-Kersh K, Watson SE, Wintergerst KA, Huang J, Cai L. Cardiovascular effects of environmental metal antimony: Redox dyshomeostasis as the key pathogenic driver. Antioxid Redox Signal. 2022 Nov 24. doi: 10.1089/ars.2022.0185. Epub ahead of print. PMID: 36424825. 
Impact Statement: Compared to other heavy metals, antimony has been less addressed. Although exposure to antimony has been potentially linked epidemiologically and even experimentally to cardiovascular diseases (CVDs), whether antimony alone or combined with other metals can contribute to the pathogenesis of CVDs and underlying mechanisms remain unclear. This review addresses this gap in knowledge by presenting the current available evidence that highlights the potential role of antimony in the pathogenesis of CVDs, most likely via antimony-mediated redox dyshomeostasis, and urges more direct evidence from pre-clinical and mechanistic studies.

Westcott CE, Sokoloski KJ, Rouchka EC, Chariker JH, Holm RH, Yeager RA, Moore JB 4th, Elliott EM, Talley D, Bhatnagar A, Smith T. The Detection of Periodic Reemergence Events of SARS-CoV-2 Delta Strain in Communities Dominated by Omicron. Pathogens. 2022 Oct 28;11(11):1249. doi: 10.3390/pathogens11111249. PMID: 36365000; PMCID: PMC9697103. 
Impact statement: This publication will enhance knowledge on the unexpected reemergence of SARS-CoV-2 variants and corresponding infectious disease dynamics. It also contributes additional perspectives on the usefulness of disease surveillance through wastewater.

Zierold KM, Myers JV, Brock GN, Sears CG, Zhang CH, Sears L. Indoor coal ash and school and social competency among children aged 6-14 years. J Expo Sci Environ Epidemiol. 2022 Nov 17. doi: 10.1038/s41370-022-00500-2. Epub ahead of print. PMID: 36396715. 
Impact Statement: Children living near coal burning power plants and coal ash disposal sites may be at increased risk for neurobehavioral problems due to the known neurotoxins in by-products of coal burning. A sample of indoor air and behavior ratings in 280 children living within 10 miles of a coal power plant found that 43% of homes had fly ash, a by product of coal burning, in the home and that the presence of fly ash was associated with increased rates of school learning problems after controlling for possible confounding factors. Results indicated that childhood exposure to pollution may impact school learning possibly through the effects of heavy metals in the coal ash which have been shown to impact learning and behavior.

Boakye E, Dzaye O, Erhabor J, Osuji N, Obisesan O, Osei AD, Bhatnagar A, Robertson RM, Blaha MJ. Impact of the Food and Drug Administration enforcement policy on flavored e-cigarettes on the online popularity of disposable e-cigarettes: analyses of Google search query data. BMC Public Health. 2022 Oct 19;22(1):1937. doi: 10.1186/s12889-022-14367-3. PMID: 36258175; PMCID: PMC9580152.
Impact Statement: The impact of the U.S. Food and Drug Administration's (FDA) initial enforcement policy on flavored cartridge-based e-cigarettes and subsequent notice for the removal of flavored disposable electronic cigarettes (e-cigarettes) such as Puff Bar from the market has not been well evaluated. We, therefore, sought to examine the impact of the e-cigarette flavor-related policy changes on the online popularity of Puff Bar, a prototypic disposable e-cigarette. The tracking of online search data demonstrates rapid public recognition of the FDA's announcements of tobacco regulatory actions.

Adhikari S, Kumar R, Driver EM, Bowes DA, Ng KT, Sosa-Hernandez JE, Oyervides-Muñoz MA, Melchor-Martínez EM, Martínez-Ruiz M, Coronado-Apodaca KG, Smith T, Bhatnagar A, Piper BJ, McCall KL, Parra-Saldivar R, Barron LP, Halden RU. Occurrence of Z-drugs, benzodiazepines, and ketamine in wastewater in the United States and Mexico during the Covid-19 pandemic. Sci Total Environ. 2022 Oct 12;857(Pt 2):159351. doi: 10.1016/j.scitotenv.2022.159351. Epub ahead of print. PMID: 36243065; PMCID: PMC9595400.
Impact Statement: This study measured ketamine concentration in wastewater in the United States, which reflected some of the highest ketamine consumption rates presented in the literature in the United States using Wastewater-based epidemiology (WBE). The present study highlights the need for monitoring substance use during high-stress events, such as the COVID-19 pandemic, and illustrates the utility of WBE to provide data that cannot be obtained by other means to determine actual drug use, which is the sum of both licit and illicit drug sourcing and consumption.

Carll AP, Arab C, Salatini R, Miles MD, Nystoriak MA, Fulghum KL, Riggs DW, Shirk GA, Theis WS, Talebi N, Bhatnagar A, Conklin DJ. E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice. Nat Commun. 2022 Oct 25;13(1):6088. doi: 10.1038/s41467-022-33203-1. PMID: 36284091; PMCID: PMC9596490. 
Impact Statement: Our findings in mice indicate e-cigarette aerosols can rapidly disrupt cardiac conduction and cause cardiac arrhythmias. Similar effects in humans could precipitate severe cardiac events, including atrial or ventricular fibrillation, and cardiac arrest. The findings provide new insight to the public, clinicians, and regulatory agencies about the potential health impacts of e-cigarettes and their individual ingredients. The findings of the paper were reported worldwide by over 320 news outlets.

Sagaram M, Royer AJ, Hu H, Rajhans A, Parthasarathy R, Krishnasamy SS, Mokshagundam SP, Kong M, Schwandt ML, Parajuli D, Cave MC, Vatsalya V. Illustration of Gut-Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function. Cells. 2022 Oct 1;11(19):3100. doi: 10.3390/cells11193100. PMID: 36231061; PMCID: PMC9563601. 
Impact Statement: This research investigated mechanisms for the thyroid dysfunction associated with alcohol use. Mechanistic biomarkers were measured in human subjects.

Conklin DJ. How Irritating! Electronic Cigarettes Not "95% Safer" Than Combustible Cigarettes: Recent Mechanistic Insights Into Endothelial Dysfunction. Arterioscler Thromb Vasc Biol. 2022 Nov;42(11):1351-1354. doi: 10.1161/ATVBAHA.122.318468. Epub 2022 Oct 26. PMID: 36288291.
Impact Statement: This invited Editorial highlights findings of human and animal studies that demonstrate the negative vascular consequences of exposure to electronic cigarette aerosols or their constituents, i.e., vaping. Moreover, the animal study demonstrates a novel mechanism whereby irritating constituents in aerosols can harm blood vessels. This Editorial encourages FDA to regulate the level of irritants in tobacco product aerosols to lower levels in order to protect human health.

Furmanek S, Salunkhe V, Pahwa S, Samanapally H, Nathala P, Xu Q, Ali T, Deepti F, Glynn A, McGuffin T, Titus D, Farah I, Jones CM, Ramirez JA, Clifford SP, Arnold FW, Kong M, Roser L, Huang J; Center of Excellence for Research in Infectious Diseases Coronavirus Study Group on behalf of the COVID-19 CardioVascular Research Group. Correlations of Before and After Event Echocardiographic Parameters with Troponin and BNP in Hospitalized COVID-19 Patients With Cardiovascular Events. J Cardiothorac Vasc Anesth. 2022 Sep 2:S1053-0770(22)00593-6. doi: 10.1053/j.jvca.2022.08.024. Epub ahead of print. PMID: 36184474; PMCID: PMC9436869. 
Impact Statement: Left heart systolic and diastolic dysfunction before a cardiovascular event were correlated with initial myocardial injury levels and increase in right heart size on after-event echocardiography was correlated with maximal myocardial injury in COVID-19 patients.

Mehra S, Srinivasan S, Singh S, Zhou Z, Garrido V, Silva IC, Totiger TM, Dosch AR, Dai X, Dawra RK, Jala VR, Shi C, Datta J, VanSaun M, Merchant N, Nagathihalli N. Urolithin A attenuates severity of chronic pancreatitis associated with continued alcohol intake by inhibiting PI3K/AKT/mTOR signaling. Am J Physiol Gastrointest Liver Physiol. 2022 Oct 1;323(4):G375-G386. doi: 10.1152/ajpgi.00159.2022. Epub 2022 Sep 13. PMID: 36098401.
Impact Statement: Heavy alcohol consumption is the dominant risk factor for chronic pancreatitis (CP); however, treatment and prevention strategies for alcoholic chronic pancreatitis (ACP) remains limited. The present study demonstrates that ACP induction in C57BL/6 mice causes significant acinar cell injury, pancreatic stellate cell (PSC) activation, exocrine function insufficiency, and an increased fibroinflammatory response when compared with alcohol or CP alone. Our novel findings presented here demonstrate the utility of Uro A as an effective therapeutic agent in attenuating alcoholic chronic pancreatitis (ACP) severity with alcohol continuation after established disease, through suppression of the PI3K/AKT/mTOR signaling pathway.

Kouokam JC ,Meaza I, Wise JP Sr. Inflammatory effects of hexavalent chromium in the lung: A comprehensive review. Toxicol Appl Pharmacol. 2022 Nov 15;455:116265. doi: 10.1016/j.taap.2022.116265. Epub 2022 Oct 5. PMID: 36208701. 
Impact Statement: Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium [Cr(VI)], which is used in multiple settings, resulting in widespread environmental and occupational exposures as well as heavy use. This work provides insights into the mechanisms by which Cr(VI) induces lung inflammation.

SenthilKumar G, Gutierrez Huerta CA, Freed JK, Beyer AM, Fancher IS, LeBlanc AJ. New Developments in Translational Microcirculatory Research. Am J Physiol Heart Circ Physiol. 2022 Oct 28. doi: 10.1152/ajpheart.00566.2022. Epub ahead of print. PMID: 36306213. 
Impact Statement:This is a mini-review highlighting the original research papers and review articles that were submitted to the American Journal of Physiology- Heart and Circulatory Physiology Call for Papers collection: New Developments in Translational Microcirculatory Research. In addition to putting disease- and location-dependent original research articles into context of the existing literature, we discuss the state-of-the-art reviews on both coronary endothelial function and assessing microvascular health in different organ systems, as well as how to establish rigor in clinical trial design.

Warner JB, Guenthner SC, Hardesty JE, McClain CJ, Warner DR, Kirpich IA. Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease. World J Gastroenterol. 2022 Sep 28;28(36):5280-5299. doi: 10.3748/wjg.v28.i36.5280. PMID: 36185629; PMCID: PMC9521517.
Impact Statement: This review provides basic information on liver-targeting drug delivery platforms, including their benefits and limitations, and summarizes the current research efforts to apply them to the treatment of ALD in rodent models. We also discuss gaps in knowledge in the field, which when addressed, may help to increase the efficacy of novel therapies and better translate them to humans.

Cummins TD, Powell DW, Wilkey DW, Brady M, Benz FW, Barati MT, Caster DJ, Klein JB, Merchant ML. Quantitative Mass Spectrometry Normalization in Urine Biomarker Analysis in Nephrotic Syndrome. Glomerular Dis. 2022 Jul;2(3):121-131. doi: 10.1159/000522217. Epub 2022 Jan 27. PMID: 36199623; PMCID: PMC9529004. 
Impact Statement:For this report, we analyzed urine samples from patients with focal segmental glomerulosclerosis (FSGS) as proof of principle of development of an innovative method for identifying novel diagnostic markers for chronic kidney disease (CKD). We present a mass spectrometry-based method utilizing multiplex tandem mass tag (TMT) quantification and improved protein quantification using reporter ion normalization to urinary creatinine to analyze urinary proteins from patients with a form of nephrotic syndrome (FSGS). Our findings provide support for the utility of this method for identification of novel diagnostic markers of CKD and identify SERPINA1 and ORM1 as promising candidate diagnostic markers for FSGS.

Peart NJ, Hwang JY, Quesnel-Vallières M, Sears MJ, Yang Y, Stoilov P, Barash Y, Park JW, Lynch KW, Carstens RP. The global Protein-RNA interaction map of ESRP1 defines a post-transcriptional program that is essential for epithelial cell function. iScience. 2022 Sep 23;25(10):105205. doi: 10.1016/j.isci.2022.105205. PMID: 36238894; PMCID: PMC9550651.
Impact Statement:The genome-wide binding sites of the epithelial splicing regulators, ESRP 1/2, were thoroughly examined with high-throughput sequencing (RNA-seq and eCLIP-seq) in epithelial cells of mouse epidermis. This study provides a transcriptome-wide map of ESRP1 binding and regulation in epithelial cells which is essential to understand disease-related splicing regulation.

Shi H, Prough RA, McClain CJ, Song M. Different Types of Dietary Fat and Fructose Interactions Result in Distinct Metabolic Phenotypes in Male Mice. J Nutr Biochem. 2022 Oct 19:109189. doi: 10.1016/j.jnutbio.2022.109189. Epub ahead of print. PMID: 36272691. 
Impact Statement:Fat and fructose are the two major components over-represented in the Western diet. The aim of this study was to determine the combined effects of different types of dietary fat and fructose on the development of nonalcoholic fatty liver disease (NAFLD) in a murine model. Our study shed light on the role of different types of dietary fat and fructose interaction on the development of metabolic disorders and provides preclinical evidence that would be helpful for future clinical studies on the prevention and treatment of NAFLD.

Shuck B, Hart JL, Walker KL, Rai J, Srivastava S, Srivastava S, Rai S, Bhatnagar A, Keith RJ. Workplace Culture and Biomarkers of Health Risk. Int J Environ Res Public Health. 2022 Sep 21;19(19):11920. doi: 10.3390/ijerph191911920. PMID: 36231223; PMCID: PMC9565767. 
Impact Statement:Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. Our finding were consistent with an important relationship between workplace environment and sympathetic nervous system activity.

Wise JP Jr. The intersection between toxicology and aging research: A toxic aging coin perspective. Front Aging. 2022 Sep 21;3:1014675. doi: 10.3389/fragi.2022.1014675. PMID: 36213344; PMCID: PMC9532842. 
Impact Statement:This perspective paper serves as a call for expanding research at the intersection of toxicology and aging, taking a dual view of this intersection as (1) how age impacts toxic effects, and (2) how chemicals accelerate aging and act as 'gerontogens.' We are entering a new world paradigm where a significant portion (~20%) of our population will reach a geriatric age and continue living as geriatrics for multiple decades, but there is a detrimental lack of data considering how geriatrics may be distinctly affected by chemicals from other age groups. Similarly, the term 'gerontogen' was coined in 1987, but since its introduction there has been little research into how chemicals act as gerontogens. In this paper I introduce the concept of a "toxic aging coin" to emphasize this dual intersection, and discuss the relevance of both sides in the context of the brain (my area of expertise), though it could be applied to any organ system.

Wise SS, Lu H, Speer RM, Wise JP, Young J, Toyoda JH, Meaza I, Croom-Perez TJ, Kouokam JC, Specht A, Liu KJ, Hoyle GW, Wise JP. Chromium distribution in an oropharyngeal aspiration model for hexavalent chromium in rats. Toxicol Appl Pharmacol. 2022 Oct 22:116294. doi: 10.1016/j.taap.2022.116294. Epub ahead of print. PMID: 36283442.
Impact Statement:Particulate Cr(VI) is a well-known lung carcinogen but the early and initiating carcinogenic mechanisms are still poorly understood. Establishing an accurate and relevant exposure regimen is crucial to further our understanding for environmentally relevant exposures. We evaluated an oropharyngeal aspiration exposure route for zinc chromate particles in Wistar rats and found that oropharyngeal aspiration provides a practicable exposure route for chronic and sub-chronic exposures of Cr(VI) particles.

Young JL, Xin Y, Rajesh M, Cai L. Editorial: Cardiovascular diseases related to diabetes and obesity - volume II. Front Endocrinol (Lausanne). 2022 Oct 5;13:1044326. doi: 10.3389/fendo.2022.1044326. PMID: 36277685; PMCID: PMC9583653. 
Impact Statement:Despite our advances at the bench and in the clinic, approximately 17.9 million people die each year from CVDs, accounting for 32% of all deaths globally . Therefore, it is imperative to better understand the underlying mechanisms involved in the pathogenesis of obesity- and diabetes-related cardiovascular events to develop more effective, targeted therapies aimed at prevention and attenuation of disease progression. This editorial introduces the second volume of a special issue on Cardiovascular diseases related to diabetes and obesity, compiling recent clinical, pre-clinical and basic research studies as well as review articles aimed at filling the knowledge gaps and expanding our understanding of the complicated and intertwined relationship between obesity, diabetes, and CVDs.

Zhang Y, Du L, Yan J, Bai Q, Niu Q, Mo Y, Zhang Q, Nie J. Prenatal benzo[a]pyrene exposure impairs hippocampal synaptic plasticity and cognitive function in SD rat offspring during adolescence and adulthood via HDAC2-mediated histone deacetylation. Ecotoxicol Environ Saf. 2022 Nov;246:114180. doi: 10.1016/j.ecoenv.2022.114180. Epub 2022 Oct 17. PMID: 36265406.
Impact Statement: Benzo[a]pyrene (B[a]P) is a widespread carcinogenic pollutant in the environment. Although previous studies have demonstrated the neurodevelopmental toxicity of B[a]P, the precise mechanisms underlying the neurotoxic effects induced by prenatal B[a]P exposure remain largely unknown. Our results suggest that prenatal B[a]P exposure impairs cognitive function and hippocampal synaptic plasticity of offspring in adolescence and adulthood, and HDAC2-mediated histone deacetylation plays a crucial role in these deficits.

Banerjee M, Yaddanapudi K, States JC. Zinc supplementation prevents mitotic accumulation in human keratinocyte cell lines upon environmentally relevant arsenic exposure. Toxicol Appl Pharmacol. 2022 Sep 24;454:116255. doi: 10.1016/j.taap.2022.116255. Epub ahead of print. PMID: 36162444.
Impact Statement: Dysregulated cell cycle is an early event in several chronic arsenic exposure-induced diseases. In this work, we demonstrate that environmentally relevant arsenic exposure leads to accumulation of human skin cell lines exclusively in mitosis as early as 24 hours and this can be prevented by zinc supplementation.

Smith T, Holm RH, Keith RJ, Amraotkar AR, Alvarado CR, Banecki K, Choi B, Santisteban IC, Bushau-Sprinkle AM, Kitterman KT, Fuqua J, Hamorsky KT, Palmer KE, Brick JM, Rempala GA, Bhatnagar A. Quantifying the relationship between sub-population wastewater samples and community-wide SARS-CoV-2 seroprevalence. Sci Total Environ. 2022 Sep 6;853:158567. doi: 10.1016/j.scitotenv.2022.158567. Epub ahead of print. PMID: 36084773; PMCID: PMC9444845.
Impact Statement: Robust epidemiological models relating wastewater to community disease prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community disease prevalence due to inherent biases. This study conducted serial stratified randomized samplings to estimate the prevalence of SARS-CoV-2 antibodies and the analysis indicates that wastewater may provide robust estimates of community spread of infection, in line with the modeled prevalence estimates obtained from stratified randomized sampling, and is therefore superior to publicly available health data.

Adhihetty PK, Halder S, Jasinski JB, Fu XA, Nantz MH. Harnessing the cation-π interactions of metalated gold monolayer-protected clusters to detect aromatic volatile organic compounds. Talanta. 2022 Sep 13;253:123915. doi: 10.1016/j.talanta.2022.123915. Epub ahead of print. PMID: 36155323.
Impact Statement: The paper investigated chemiresistors made from carboxylate-linked alkali metals bound to the surface of gold monolayer- protected clusters formulated on microfabricated interdigitated electrodes. Sensor responses to aromatic and non-aromatic VOCs are consistent with a model for cation-π interactions arising from association of electron-rich aromaticπ-systems to metal ions. The sensors are promising for detection of benzene, toluene, ethylbenzene and xylene.

Salazar-González RA, Doll MA, Hein DW. N-acetyltransferase 2 genetic polymorphism modifies genotoxic and oxidative damage from new psychoactive substances. Arch Toxicol. 2022 Sep 23. doi: 10.1007/s00204-022-03383-2. Epub ahead of print. PMID: 36138126.
Impact Statement: The use of new psychoactive substances (NPS) as drugs of abuse is common and increasingly popular, particularly among youth. We investigated the gene-environment interaction between N-acetyltransferase 2 (NAT2) genetic polymorphism and toxicity after exposure to these chemicals. We found that exposure to these psychoactive substances results in genotoxic and oxidative damage that is modified by the NAT2 genetic polymorphism.

Habil MR, Salazar-González RA, Doll MA, Hein DW. N-acetyltransferase 2 acetylator genotype-dependent N-acetylation and toxicity of the arylamine carcinogen β-naphthylamine in cryopreserved human hepatocytes. Arch Toxicol. 2022 Sep 16. doi: 10.1007/s00204-022-03381-4. Epub ahead of print. PMID: 36112171.
Impact Statement: We used cryopreserved human hepatocytes that express rapid, intermediate, and slow acetylator N-acetyltransferase 2 (NAT2) genotypes to measure the N-acetylation of β-naphthylamine (BNA) which is one of the aromatic amines found in cigarette smoke including E-cigarettes. We investigated the role of NAT2 genetic polymorphism in genotoxicity and oxidative stress induced by BNA. We found that the N-acetylation of BNA is NAT2 genotype dependent in cryopreserved human hepatocytes and document an important role for NAT2 genetic polymorphism in modifying BNA-induced genotoxicity and oxidative damage.

Hong KU, Gardner JQ, Doll MA, Stepp MW, Wilkey DW, Benz FW, Cai J, Merchant ML, Hein DW. Proteomic analysis of arylamine N-acetyltransferase 1 knockout breast cancer cells: Implications in immune evasion and mitochondrial biogenesis. Toxicol Rep. 2022 Jul 19;9:1566-1573. doi: 10.1016/j.toxrep.2022.07.010. PMID: 36158865; PMCID: PMC9500399.
Impact Statement: This paper reveals potential and novel mechanisms by which arylamine N-acetyltransferase 1 (NAT1) contributes to breast cancer growth. Delineating these mechanisms will help us not only better-understand breast cancer biology but also identify new therapeutic approaches.

Hong KU, Salazar-González RA, Walls KM, Hein DW. Transcriptional Regulation of Human Arylamine N-Acetyltransferase 2 Gene by Glucose and Insulin in Liver Cancer Cell Lines. Toxicol Sci. 2022 Sep 26:kfac103. doi: 10.1093/toxsci/kfac103. Epub ahead of print. PMID: 36156098.
Impact Statement: This paper reports, for the first time, that a xenobiotic metabolic enzyme, arylamine N-acetyltransferase 2 (NAT2) is induced by glucose and insulin in liver cancer cells. Our findings implicates NAT2 in lipid and cholesterol homeostasis. NAT2 is a potentially important genetic factor that alters the risk of hyperlipidemia which raises the risk of cardiometabolic disorders.

Liang S, Pang Z, Zhou N, Liu Z, Guo Q, Huang J, Zou W. Development and validation of a prediction model for catheter-related bladder discomfort: a prospective observational study. Br J Anaesth. 2022 Sep 23:S0007-0912(22)00461-5. doi: 10.1016/j.bja.2022.08.018. Epub ahead of print. PMID: 36163078.
Impact Statement: Urinary catheterisation is a routine practice in the perioperative period. However, patients undergoing surgery with an indwelling urinary catheter frequently complain of an urge to void or discomfort in the supra-pubic region after emerging from general anaesthesia in the PACU, known as catheter-related bladder discomfort (CRBD), which could cause major distress. The goal of this observational study was to develop a prediction model that can be used to assess risks of developing CRBD in patients undergoing surgery.

Huang J, El-Kersh K, Mann KK, James KA, Cai L. Overview of the cardiovascular effects of environmental metals: New preclinical and clinical insights. Toxicol Appl Pharmacol. 2022 Sep 17;454:116247. doi: 10.1016/j.taap.2022.116247. Epub ahead of print. PMID: 36122736.
Impact Statement: Environmental causes of cardiovascular diseases (CVDs) are global health issues. In particular, an association between metal exposure and CVDs has become evident but causal evidence still lacks. The symposium at the Society of Toxicology 2022 annual meeting addressed epidemiological, clinical, pre-clinical animal model-derived and mechanism-based evidence by five presentations and the data summarized by the presenters infers a potential causal link between multiple metals and CVDs and defines differences and commonalities. Therefore, summary of these presentations may accelerate the development of efficient preventive and therapeutic strategies by facilitating collaborations among multidisciplinary investigators.

Ghosh S, Moorthy B, Haribabu B, Jala VR. Cytochrome P450 1A1 is essential for the microbial metabolite, Urolithin A-mediated protection against colitis. Front Immunol. 2022 Sep 8;13:1004603. doi: 10.3389/fimmu.2022.1004603. PMID: 36159798; PMCID: PMC9493474.
Impact Statement: Previously, we showed that treatment with microbial metabolite Urolithin A mitigated ulcerative colitis in mice (Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway | Nature Communications). The current publication described that Urolithin A requires expression of host Cytochrome P450 1A1 to protect against chemical-induced colitis in mouse models and enhancement of gut barrier function.

Ait-Aissa K, Norwood-Toro LE, Terwoord J, Young M, Paniagua LA, Hader SN, Hughes WE, Hockenberry JC, Beare JE, Linn J, Kohmoto T, Kim J, Betts DH, LeBlanc AJ, Gutterman DD, Beyer AM. Noncanonical Role of Telomerase in Regulation of Microvascular Redox Environment With Implications for Coronary Artery Disease. Function (Oxf). 2022 Sep 3;3(5):zqac043. doi: 10.1093/function/zqac043. PMID: 36168588; PMCID: PMC9508843. 
Impact Statement: This study is the first evidence that mitochondrial telomerase reverse transcriptase (TERT), independent of its nuclear functions, plays a critical physiological role in preserving NO-mediated vasodilation in the microcirculation. Additionally, the balance of mitochondrial to nuclear TERT is fundamentally altered in states of human disease, like CVD, that are driven by increased expression of dominant negative splice variants.

Rowe G, Heng DS, Beare JE, Hodges NA, Tracy EP, Murfee WL, LeBlanc AJ. Stromal Vascular Fraction Reverses the Age-Related Impairment in Revascularization following Injury. J Vasc Res. 2022 Sep 8:1-15. doi: 10.1159/000526002. Epub ahead of print. PMID: 36075199.
Impact Statement: This study reveals the negative effect that advancing age has on stimulating new vessel growth (angiogenesis) in baseline and ischemic injury; however, treatment with stromal vascular fraction therapy from young donors can reverse the impairment.

Warner JB, Zirnheld KH, Hu H, Floyd A, Kong M, McClain CJ, Kirpich IA. Analysis of alcohol use, consumption of micronutrient and macronutrients, and liver health in the 2017-2018 National Health and Nutrition Examination Survey. Alcohol Clin Exp Res. 2022 Sep 20. doi: 10.1111/acer.14944. Epub ahead of print. PMID: 36124871.
Impact Statement: Alcohol use is a major global healthcare burden that contributes to numerous adverse health outcomes, including liver disease. Many factors influence individual susceptibility to alcohol-associated diseases, including nutritional factors. The objective of the current study was to examine inter-relations among alcohol, dietary micronutrients and macronutrient consumption, and liver health by analyzing data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Our findings suggest that the category of heavy drinkers in the 2017-2018 NHANES consisted of generally healthy individuals with high-energy intake and no evidence of liver steatosis or fibrosis.

Lei C, Sun R, Xu G, Tan Y, Feng W, McClain CJ, Deng Z. Enteric VIP-producing neurons maintain gut microbiota homeostasis through regulating epithelium fucosylation. Cell Host Microbe. 2022 Sep 13:S1931-3128(22)00418-8. doi: 10.1016/j.chom.2022.09.001. Epub ahead of print. PMID: 36150396.
Impact Statement: Interactions between the enteric nervous system (ENS) and intestinal epithelium are thought to play a vital role in intestinal homeostasis. How the ENS monitors the frontier with commensal and pathogenic microbes while maintaining epithelial function remains unclear. We further demonstrate that perturbation of enteric neurons leads to gut dysbiosis through α1,2-fucosylation in the steady state and results in increased susceptibility to alcohol-associated liver disease (ALD).

Anwar MY, Baldassari AR, Polikowsky HG, Sitlani CM, Highland HM, Chami N, Chen HH, Graff M, Howard AG, Jung SY, Petty LE, Wang Z, Zhu W, Buyske S, Cheng I, Kaplan R, Kooperberg C, Loos RJF, Peters U, McCormick JB, Fisher-Hoch SP, Avery CL, Taylor KC, Below JE, North KE. Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations. BMC Med Genomics. 2022 Sep 10;15(1):192. doi: 10.1186/s12920-022-01352-3. PMID: 36088317; PMCID: PMC9464371. 
Impact Statement: Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.

Nong Y, Guo Y, Ou Q, Gumpert A, Tomlin A, Zhu X, Bolli R. PU.1 inhibition does not attenuate cardiac function deterioration or fibrosis in a murine model of myocardial infarction. Mol Cell Biochem. 2022 Sep 17. doi: 10.1007/s11010-022-04561-7. Epub ahead of print. PMID: 36114991. 

Feehan J, Hariharan R, Buckenham T, Handley C, Bhatnagar A, Baba SP, de Courten B. Carnosine as a potential therapeutic for the management of peripheral vascular disease. Nutr Metab Cardiovasc Dis. 2022 Jul 16:S0939-4753(22)00295-2. doi: 10.1016/j.numecd.2022.07.006. Epub ahead of print. PMID: 35973888.
Impact statement: The aim of this research is to evaluate the potential role of carnosine in the management of peripheral vascular disease. We found that carnosine may have a role as an adjunct treatment for peripheral vascular disease alongside typical exercise and surgical interventions, and may be used in high risk individuals to aid in the prevention of atherogenesis.

Benowitz NL, Goniewicz ML, Halpern-Felsher B, Krishnan-Sarin S, Ling PM, O'Connor RJ, Pentz MA, Robertson RM, Bhatnagar A. Tobacco product use and the risks of SARS-CoV-2 infection and COVID-19: current understanding and recommendations for future research. Lancet Respir Med. 2022 Sep;10(9):900-915. doi: 10.1016/S2213-2600(22)00182-5. Epub 2022 Aug 16. PMID: 35985357; PMCID: PMC9381032.
Impact statement: Results from epidemiological studies of the effects of cigarette smoking on SARS-CoV-2 infection are conflicting, and further research is needed to establish whether or not smoking affects susceptibility to SARS-CoV-2 infection.

Ye F, Sun C, Xie Y, Wang B, Cai L. Editorial: Medical Application and Radiobiology Research of Particle Radiation. Front Public Health. 2022 Jul 22;10:955116. doi: 10.3389/fpubh.2022.955116. PMID: 35942260; PMCID: PMC9356341.
Impact statement: Applications of particle radiation technology has been extensively applied in the medical and biological fields. Proper protection from radiation has been a top priority ever since the recognition of the harmful effects of radiation on the human. In this Research Topic, we invited scientists studying high-energy charged particles either for cancer treatment or for radiobiology research, with 15 articles including a total of 92 authors, to discuss for the radiotherapy for cancers, radiation protection and radiation biology research advance. This editorial was and also briefly introduced the contents of the fifteen publications, with a hope to set the stage for delving further in deciphering the crucial link between cancer radiotherapy and radiation protection.

Dai X, Wang K, Fan J, Liu H, Fan X, Lin Q, Chen Y, Chen H, Li Y, Liu H, Chen O, Chen J, Li X, Ren D, Li J, Conklin DJ, Wintergerst KA, Li Y, Cai L, Deng Z, Yan X, Tan Y. Nrf2 transcriptional upregulation of IDH2 to tune mitochondrial dynamics and rescue angiogenic function of diabetic EPCs. Redox Biol. 2022 Aug 28;56:102449. doi: 10.1016/j.redox.2022.102449. Epub ahead of print. PMID: 36063728.
Impact statement: This study reveals novel actions of the transcription factor Nrf2 in protecting proangiogenic endothelial progenitor cell (EPC) functions by regulating mitochondrial dynamics via upregulating IDH2 expression in both human diabetics and murine model of diabetes. This study fills the gaps in knowledge about why and how EPC dysfunction occurs in diabetes, and it provides the scientific groundwork for developing new therapies for diabetic patients with ischemic vascular diseases.

Blair LK, Warner ET, James P, Hart JE, VoPham T, Barnard ME, Newton JD, Murthy DJ, Laden F, Tamimi RM, DuPre NC. Exposure to natural vegetation in relation to mammographic density in a Massachusetts-based clinical cohort. Environ Epidemiol. 2022 Jul 19;6(4):e216. doi: 10.1097/EE9.0000000000000216. PMID: 35975164; PMCID: PMC9374192.
Impact Statement: We examined the association between greenness and mammographic density-a strong breast cancer risk factor-to determine whether greenness influences breast tissue composition independent of lifestyle factors. We found greenness exposures were not associated with mammographic density. Prior observations of a protective association between greenness and breast cancer may not be driven by differences in breast tissue composition, as measured by mammographic density, but rather other mechanisms.

Habil MR, Salazar-González RA, Doll MA, Hein DW. Differences in β-naphthylamine metabolism and toxicity in Chinese hamster ovary cell lines transfected with human CYP1A2 and NAT2*4, NAT2*5B or NAT2*7B N-acetyltransferase 2 haplotypes. Arch Toxicol. 2022 Aug 30. doi: 10.1007/s00204-022-03367-2. Epub ahead of print. PMID: 36040704.
Impact statement: β-naphthylamine (BNA) is an important arylamine carcinogen that is classified as a Group 1 human urinary bladder carcinogen by the International Agency for Research on Cancer. The purpose of this study was to investigate BNA metabolism and toxicity in Chinese hamster ovary cells transfected with human CYP1A2 and either human N-acetyltransferase 2 alleles NAT2*4 (rapid acetylator allele), NAT2*5B (common slow acetylator allele in Europe), or NAT2*7B (common slow acetylator allele in Asia). The study showed that NAT2 genetic polymorphisms modulate BNA N-acetylation and its associated mutagenicity and DNA damage and further suggests that heterogeneity within the "slow" NAT2 acetylator phenotype should be incorporated into cancer risk studies among the individuals exposed to BNA.

Cheryl L. Woods-Giscombe, Edilma L. Yearwood, Dave Ngugi, Lilian Bravo, Patty R. Wilson, Pamela Minarik, Jada Brooks, Tamar Rodney, Shaquita Starks, Mia Pasini, Mary Louise Tatum, Vicki Hines Martin. Honoring the past and charting the future: The International Society of Psychiatric Mental Health Nurses' commitment to advance diversity and equity in mental health care, Archives of Psychiatric Nursing, 2022, ISSN 0883-9417
Impact statement: The International Society of Psychiatric-Mental Health Nurses is committed as an organization and as members to continue addressing health disparities for improvement of mental health outcomes in underserved communities. As a committee, we recognize significant mental health disparities exist within populations, such as racially and ethnically diverse and LGBTQ+ communities. We will continue addressing health disparities in our research and initiatives and work collaboratively to push the profession forward by introducing innovative strategies for promoting mental health workforce diversity.

Tracy EP, Nair R, Rowe G, Beare JE, Beyer A, LeBlanc AJ. Adipose Stromal Vascular Fraction Reverses Mitochondrial Dysfunction and Hyperfission in Aging-Induced Coronary Microvascular Disease. Am J Physiol Heart Circ Physiol. 2022 Aug 26. doi: 10.1152/ajpheart.00311.2022. Epub ahead of print. PMID: 36018760.
Impact Statement: This study details how the mitochondria in small vessels from the heart become dysfunctional as a result of aging alone, and that this dysfunction can lead to mismanaged blood flow. When old rats were treated with an infusion of regenerative cells from adipose tissue, or fat, the mitochondria exhibit positive effects, similar to the youth phenotype, and this results in improved vascular function.

Tracy EP, Dukes M, Beare J, Rowe G, Nair R, LeBlanc AJ. Stromal Vascular Fraction Restores Vasodilatory Function by Reducing Oxidative Stress in Aging-Induced Coronary Microvascular Disease. Antioxid Redox Signal. 2022 Aug 11. doi: 10.1089/ars.2021.0249. Epub ahead of print. PMID: 35950616.
Impact Statement: In advancing age, even without comorbidities, there is a shift in reactive oxygen species balance in the circulation and that leads the body more susceptible to the onset of cardiovascular disease. This study demonstrates that a cell therapy derived from adipose tissue can tip the balance back to a more youthful phenotype and also elicit improved vascular reactivity to circulating catecholamines. This renders the aging heart more resistant and impervious to heart disease.

Amraotkar AR, Bushau-Sprinkle AM, Keith RJ, Hamorsky KT, Palmer KE, Gao H, Rai SN, Bhatnagar A. Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity after SARS-CoV-2 Vaccination. Vaccines (Basel). 2022 Aug 20;10(8):1363. doi: 10.3390/vaccines10081363. PMID: 36016250; PMCID: PMC9416221.
Impact Statement: The impact of chronic health conditions (CHCs) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. The presence of any CHC, especially chronic kidney disease or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

Lee S, Zhang Y, Newhams M, Novak T, Thomas PG, Mourani PM, Hall MW, Loftis LL, Cvijanovich NZ, Tarquinio KM, Schwarz AJ, Weiss SL, Thomas NJ, Markovitz B, Cullimore ML, Sanders RC, Zinter MS, Sullivan JE, Halasa NB, Bembea MM, Giuliano JS, Typpo KV, Nofziger RA, Shein SL, Kong M, Coates BM, Weiss ST, Lange C, Su HC, Randolph AG; PALISI Pediatric Intensive Care Influenza (PICFlu) Investigators and the TOPMed Investigators. DDX58 is Associated with Susceptibility to Severe Influenza Virus Infection in Children and Adolescents. J Infect Dis. 2022 Aug 20:jiac350. doi: 10.1093/infdis/jiac350. Epub ahead of print. PMID: 35986912.
Impact Statement: Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children. We focused specifically on interferon regulatory genes, as they are the host’s first defense against influenza invasion. This manuscript shows evidence associating common gene variants in DDX58 (RIG-I gene) with disease susceptibility for severe influenza infection in children. Retinoic acid–inducible gene I (RIG-I) may be essential for preventing life-threatening influenza-associated disease.

Smith T, Holm RH, Yeager R, Moore JB 4th, Rouchka EC, Sokoloski KJ, Elliott EM, Talley D, Arora V, Moyer S, Bhatnagar A. Combining Community Wastewater Genomic Surveillance with State Clinical Surveillance: A Framework for SARS-CoV-2 Public Health Practice. Food Environ Virol. 2022 Aug 18:1–7. doi: 10.1007/s12560-022-09531-2. Epub ahead of print. PMID: 35982363; PMCID: PMC9387882.
Impact Statement: This study aimed to develop a framework for combining community wastewater surveillance with state clinical surveillance for the confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants within the community and to provide recommendations on how to expand on such research and apply the findings in public health responses. This paper presents evidence that complementary wastewater and clinical testing are cost-effectively enhanced when used in combination, as they provide a strong tool for a joint public health framework.

Zierold KM, Sears CG, Myers JV, Brock GN, Zhang CH, Sears L. Exposure to coal ash and depression in children aged 6-14 years old. Environ Res. 2022 Aug 6;214(Pt 3):114005. doi: 10.1016/j.envres.2022.114005. Epub ahead of print. PMID: 35944620. 
Impact Statement:Children living near coal power plants and coal ash storage sites may be at increased risk for neurobehavioral problems due to known neurotoxic metals contained in coal ash. Indoor air was sampled in 280 homes of children living within 10 miles of a coal burning power plant and results indicated that 43% of children had coal ash in the home. These children were at increased risk of a depressive disorder compared to children without coal ash in the home. Results indicate an increased risk for depression in children exposed to coal ash in the home. 

Boakye E, Osuji N, Erhabor J, Obisesan O, Osei AD, Mirbolouk M, Stokes AC, Dzaye O, El Shahawy O, Hirsch GA, Benjamin EJ, DeFilippis AP, Robertson RM, Bhatnagar A, Blaha MJ. Assessment of Patterns in e-Cigarette Use Among Adults in the US, 2017-2020. JAMA Netw Open. 2022 Jul 1;5(7):e2223266. doi: 10.1001/jamanetworkopen.2022.23266. PMID: 35867060.
Impact Statement: In this study, a slight decrease in the prevalence of current e-cigarette use was found between 2018 and 2020; this decrease was mainly observed among young adults aged 18 to 20 years. In contrast, daily e-cigarette use consistently increased, particularly among young adults aged 21 to 24 years. This increase in daily use suggests greater nicotine dependence among those who use e-cigarettes, warranting continued surveillance.

Mirbolouk M, Boakye E, Obisesan O, Osei AD, Dzaye O, Osuji N, Erhabor J, Stokes AC, El-Shahawy O, Rodriguez CJ, Hirsch GA, Benjamin EJ, DeFilippis AP, Marie Robertson R, Bhatnagar A, Blaha MJ. E-cigarette use among high school students in the United States prior to the COVID-19 pandemic: Trends, correlates, and sources of acquisition. Prev Med Rep. 2022 Jul 22;29:101925. doi: 10.1016/j.pmedr.2022.101925. PMID: 35911577; PMCID: PMC9326337.
Impact Statement: Youth e-cigarette use remains a significant public health problem with a concerning emerging pattern of more frequent use. Also, with the increasing proportion of youth tobacco users making quit attempts, age-appropriate cessation programs need to be assessed and made available to aid cessation efforts. Finally, the sources of e-cigarettes among youth are changing; continued surveillance is therefore required to inform effective and timely policies.

Poudel R, Daniels LB, DeFilippis AP, Hamburg NM, Khan Y, Keith RJ, Kumar RS, Strokes AC, Robertson RM, Bhatnagar A. Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections. PLoS One. 2022 Jul 15;17(7):e0270763. doi: 10.1371/journal.pone.0270763. PMID: 35839264; PMCID: PMC9286231.
Impact Statement: Among a large population of patients admitted for COVID-19, smoking was associated with a higher risk of severe COVID-19, including death or mechanical ventilation, independent of sociodemographic characteristics and medical history.

Kuehl PJ, McDonald JD, Weber DT, Khlystov A, Nystoriak MA, Conklin DJ. Composition of aerosols from thermal degradation of flavors used in ENDS and tobacco products. Inhal Toxicol. 2022 Aug 1:1-10. doi: 10.1080/08958378.2022.2103602. Epub ahead of print. PMID: 35913821.
Impact Statement: Because flavors are important components of electronic cigarettes that enhance the appeal of electronic cigarettes to youth, we investigated the effects of thermal degradation on common flavors used in electronic cigarettes. Unsurprisingly, thermal degradation at low and high temperatures led to a variety of degradation products that included harmful and potentially harmful constituents (HPHCs). The toxicity of inhaled flavor-derived degradation products needs greater study to protect public health.

Liu W, Luo T, Wang F, Zhang D, Liu T, Huang J, Xu S. Effect of Preoperative Thoracic Paravertebral Blocks on Emergence Agitation During Tracheal Extubation: A Randomized Controlled Trial. Front Med (Lausanne). 2022 Jun 22;9:902908. doi: 10.3389/fmed.2022.902908. PMID: 35814746; PMCID: PMC9257130.
Impact Statement: Preoperative thoracic paravertebral block was associated with less Emergence Agitation during tracheal extubation when compared with ICNB in patients undergoing thoracoscopic lobectomy.

Sangroula D, Maggard B, Abdelhaleem A, Furmanek S, Clemons V, Marsili B, Stikes R, Hill M, Sigdel A, Clifford SP, Huang J, Akca O, Logsdon MC. Hemodynamic changes associated with neuraxial anesthesia in pregnant women with covid 19 disease: a retrospective case-control study. BMC Anesthesiol. 2022 Jun 9;22(1):179. doi: 10.1186/s12871-022-01719-0. PMID: 35681119; PMCID: PMC9178224.
Impact Statement: : Incidence and severity of hypotension after neuraxial blocks were similar between COVID-19 positive and COVID-19 negative parturients.

Nyenhuis S, Cramer E, Grande M, Huntington-Moskos L, Krueger K, Bimbi O, Polivka B, Eldeirawi K. Utilizing Real-time Technology to Assess the Impact of Home Environmental Exposures on Asthma Symptoms: Protocol for an Observational Pilot Study. JMIR Res Protoc. 2022 Aug 2;11(8):e39887. doi: 10.2196/39887. PMID: 35916686.
Impact Statement: It is estimated that over 60% of adults with asthma have uncontrolled symptoms, representing a substantial health and economic impact. Findings from this feasibility study will support a powered study to address the impact of home environmental exposures on asthma symptoms and develop tailored, home-based asthma interventions that are responsive to the changing home environment and home routines.

Ghosh S, Singh R, Vanwinkle ZM, Guo H, Vemula PK, Goel A, Haribabu B, Jala VR. Microbial metabolite restricts 5-fluorouracil-resistant colonic tumor progression by sensitizing drug transporters via regulation of FOXO3-FOXM1 axis. Theranostics. 2022 Jul 18;12(12):5574-5595. doi: 10.7150/thno.70754. PMID: 35910798; PMCID: PMC9330515.
Impact Statement: This research has shown that a metabolite produced by gut microbes from a component found in pomegranates and berries can help improve the effectiveness of chemotherapy used to treat colorectal cancer.

Tracy EP, Rowe G, LeBlanc AJ. Cell therapy-induced recovery of dysfunctional microvasculature. Aging (Albany NY). 2022 Jul 13;14(13):5296-5298. doi: 10.18632/aging.204183. Epub 2022 Jul 13. PMID: 35832022; PMCID: PMC9320541.
Impact Statement: The objective of this editorial was to address additional points of consideration in understanding the intricate mechanistic underpinnings surrounding the use of cell therapy in treating microvascular dysfunction. Additionally, the authors provide a summary graphic of these potential contributing mechanisms and also suggest new avenues worth investigating.

El-Kersh K, Danielle Hopkins C, Wu X, Rai SN, Cai L, Huang J. Plasma level of antimony correlates with pulmonary arterial hypertension severity. Curr Res Toxicol. 2022 Jun 27;3:100080. doi: 10.1016/j.crtox.2022.100080. PMID: 35800661; PMCID: PMC9254336.
Impact Statement:  In our pilot study, significantly higher antimony levels in blood and plasma of pulmonary hypertension patients when compared to controls. We also found a Significant correlation between plasma antimony level and all the prognostic hemodynamic parameters of PAH.

Jagadapillai R, Qiu X, Ojha K, Li Z, El-Baz A, Zou S, Gozal E, Barnes GN. Potential Cross Talk between Autism Risk Genes and Neurovascular Molecules: A Pilot Study on Impact of Blood Brain Barrier Integrity. Cells. 2022 Jul 15;11(14):2211. doi: 10.3390/cells11142211. PMID: 35883654; PMCID: PMC9315816.
Impact Statement: Autism Spectrum Disorder (ASD) is a common pediatric neurobiological disorder with up to 80% of genetic etiologies. Systems biology approaches may make it possible to test novel therapeutic strategies targeting molecular pathways to alleviate ASD symptoms. Although our research is preliminary, our data demonstrate the potential for developing novel therapeutic strategies based on clinically derived data, genomics, cognitive neuroscience, and basic neuroscience methods.

Nilima N, Mani K, Kaushik S, Rai SN. Cervical Cancer Screening and Associated Barriers among Women in India: A Generalized Structural Equation Modeling Approach. Cancers (Basel). 2022 Jun 23;14(13):3076. doi: 10.3390/cancers14133076. PMID: 35804848; PMCID: PMC9264854.
Impact Statement: Exploring the barriers and facilitators of cervical cancer screening is essential to reduce the incidence and mortality, particularly in India. There is a paucity of studies presenting the mediation effects of known barriers and facilitators. The study investigates individual-level social barriers, facilitators, and the factors that mediate the relationships between suspected factors and cervical cancer screening. Understanding the mediation analysis and the effect of mediators will help us acquire a profound understanding of the mechanism of action, which will facilitate in devising strategies keeping the most important factor and their mediators in mind.

Das S, Rai A, Rai SN. Differential Expression Analysis of Single-Cell RNA-Seq Data: Current Statistical Approaches and Outstanding Challenges. Entropy (Basel). 2022 Jul 18;24(7):995. doi: 10.3390/e24070995. PMID: 35885218; PMCID: PMC9315519.
Impact Statement: With the advent of single-cell RNA-sequencing (scRNA-seq), it is possible to measure the expression dynamics of genes at the single-cell level. We critically discuss the underlying statistical principles of the approaches and distinctly divide them into six major classes, i.e., generalized linear, generalized additive, Hurdle, mixture models, two-class parametric, and non-parametric approaches. This study will serve as a guide to genome researchers and experimental biologists to objectively select options for their analysis.

Petri BJ, Piell KM, Wahlang B, Head KZ, Andreeva K, Rouchka EC, Pan J, Rai SN, Cave MC, Klinge CM. Multiomics analysis of the impact of polychlorinated biphenyls on environmental liver disease in a mouse model. Environ Toxicol Pharmacol. 2022 Jul 6;94:103928. doi: 10.1016/j.etap.2022.103928. Epub ahead of print. PMID: 35803474.
Impact Statement: Exposure to polychlorinated biphenyls (PCBs) has been implicated in a variety of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). The combined insult of this toxicant exposure and a high-fat, western diet causes an accumulation of lipids in the liver than can progress to fibrosis and cirrhosis. This study employed a multi-omics approach to address the miRNA-mRNA-protein network dysregulated in NAFLD. Results show that exposure of mice to PCBs and high fat diet drastically altered the mRNA and miRNA transcriptomes in liver and identified unique inverse relationships between altered miRNA and selected mRNA targets that may play a role in reprogramming the liver during NAFLD progression.

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.

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. 

Hardesty J, Day L, Warner J, Warner D, Gritsenko M, Asghar A, Stolz A, Morgan T, McClain C, Jacobs J, Kirpich I. Hepatic Protein and Phosphoprotein Signatures of Alcohol-Associated Cirrhosis and Hepatitis. Am J Pathol. 2022 Jul;192(7):1066-1082. doi: 10.1016/j.ajpath.2022.04.004. Epub 2022 Apr 28. PMID: 35490715; PMCID: PMC9253914. 

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.