Open Access Policy Articles

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The IUPUI Faculty Council adopted an open access policy on October 7th, 2014 (available from: This policy shows IUPUI's commitment to disseminating the fruits of research and scholarship as widely as possible. Open access policies increase authors’ rights, readership and citation rates for scholarly articles. The opt out provision ensures that all faculty authors have the freedom to publish in the journal of their choice.

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    Risk of antibiotics associated with Clostridioides difficile infection: Antibiotic stewardship in action
    (Cambridge University Press, 2022-08-26) Dysangco, Andrew T.; Pierce, Tamra M.; Bravata, Dawn M.; Medicine, School of Medicine
    We examined risk associated with antibiotics used for Clostridioides difficile infection (CDI) at a single site from 2018 through 2020. Overall, 78 patients had nonrecurrent infections. Among inpatient antibiotics, intravenous meropenem had the highest CDI rate (3.56 per 1,000 days of therapy; n = 2 cases). Among outpatient antibiotics, metronidazole had the highest rate (0.071 per 1,000 pills dispensed; n = 3 cases).
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    Current Perspectives of Neuroendocrine Regulation in Liver Fibrosis
    (MDPI, 2022-11-26) Li, Bowen; Wang, Hui; Zhang, Yudian; Liu, Ying; Zhou, Tiejun; Zhou, Bingru; Zhang, Ying; Chen, Rong; Xing, Juan; He, Longfei; Salinas, Jennifer Mata; Koyama, Sachiko; Meng, Fanyin; Wan, Ying; Medicine, School of Medicine
    Liver fibrosis is a complicated process that involves different cell types and pathological factors. The excessive accumulation of extracellular matrix (ECM) and the formation of fibrotic scar disrupt the tissue homeostasis of the liver, eventually leading to cirrhosis and even liver failure. Myofibroblasts derived from hepatic stellate cells (HSCs) contribute to the development of liver fibrosis by producing ECM in the area of injuries. It has been reported that the secretion of the neuroendocrine hormone in chronic liver injury is different from a healthy liver. Activated HSCs and cholangiocytes express specific receptors in response to these neuropeptides released from the neuroendocrine system and other neuroendocrine cells. Neuroendocrine hormones and their receptors form a complicated network that regulates hepatic inflammation, which controls the progression of liver fibrosis. This review summarizes neuroendocrine regulation in liver fibrosis from three aspects. The first part describes the mechanisms of liver fibrosis. The second part presents the neuroendocrine sources and neuroendocrine compartments in the liver. The third section discusses the effects of various neuroendocrine factors, such as substance P (SP), melatonin, as well as α-calcitonin gene-related peptide (α-CGRP), on liver fibrosis and the potential therapeutic interventions for liver fibrosis.
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    The role of trauma and positive youth development in polysubstance use among rural middle school students: a latent class analysis
    (BMC, 2022-12-14) Zervos, Andrew P.; Hensel, Devon J.; James, Rebecca; Hunt, Abby; Ott, Mary A.; Pediatrics, School of Medicine
    Background: Rural youth often begin developing polysubstance use and other risk behaviors during middle school. However, little polysubstance use research focuses on rural middle school youth. Our research uses Latent Class Analysis to understand existing patterns of rural middle school polysubstance use and risk and protective factors associated with polysubstance use. Methods: We used survey data from a rural middle school pregnancy prevention program (N = 2,708). The survey included measures of demographics, lifetime substance use, trauma (adverse childhood experiences and bullying victimization) and aspects of youth development (parent communication on drugs and alcohol, parent connectedness and school connectedness). We used latent class analysis to produce participant polysubstance use profiles and multinomial regression to examine associations between polysubstance use, demographics, trauma and aspects of youth development. Results: We categorized our participants into four latent classes. Our analysis classified 2.2% of participants as Regular Polysubstance users, 6.9% as Polysubstance experimenters, 19% as Vape + Alcohol experimenters and 71.9% as Non-Users. More adverse childhood experiences were associated with greater risk of polysubstance use and experimentation. Bullying was positively associated with greater risk of vape and alcohol experimentation. Higher reported parental and school connectedness were associated with lower risk of high frequency polysubstance use. Higher reported school connection was also associated with lower risk of polysubstance experimentation. Conclusion: Rural substance use prevention programs should begin during middle school, as polysubstance use development is common among rural middle schoolers. These programs should be trauma informed and focus on connectedness as a modifiable factor to reduce risk of polysubstance use development.
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    Frequency and nature of endoscopic and pathologic errors leading to referral for endoscopic resection to a tertiary center
    (Thieme, 2022-12-15) Lahr, Rachel E.; McWhinney, Connor D.; Cummings, Oscar W.; Rex, Douglas K.; Medicine, School of Medicine
    Background and study aims: We anecdotally encounter cases where referring endoscopists made errors in endoscopic interpretation of a colorectal lesion, sometimes combined with pathology errors at the referring centers, resulting in referral to our center for endoscopic resection. In this paper, we describe the frequency and nature of endoscopic and pathology errors leading to consultation for endoscopic resection. Patients and methods: Review of 760 consecutive referrals to our center over a 26-month interval. Results: In total, 28 (3.7 %) of all referred patients had ≥ 1 lesion that did not require any resection after investigation. There were 12 cases (1.6 % of all referrals) involving errors by both the referring endoscopist and the pathologist at the referring center. Errors commonly involved the ileocecal valve, lipomas, and mucosal prolapse changes. There were 15 additional referrals (2.0 % of all referrals) where no neoplastic lesion was identified at our center and either no biopsy was taken at the referring center (n = 9 patients, 10 lesions), the patient was referred although biopsy showed no neoplasia (n = 6), or the referring doctor correctly interpreted the lesion (lipoma), but the outside pathologist incorrectly reported adenoma (n = 1). Conclusions: Endoscopists at tertiary centers should expect referrals to clarify the nature of colorectal lesions as neoplastic or non-neoplastic. Community endoscopists with equivocal endoscopic findings and unexpected or equivocal pathology results can consider pathology review at their center or at an expert center before referral for endoscopic or surgical resection.
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    Incidental adrenal hemangioma clinically suspicious for malignancy: diagnostic considerations and review of the literature
    (e-Century Publishing, 2022-11-15) Toklu, Ani; Mesa, Hector; Collins, Katrina; Pathology and Laboratory Medicine, School of Medicine
    Adrenal hemangiomas are rare lesions often found incidentally during unrelated diagnostic work-up. We report a case of a 67-year-old man with history of hypertension, hyperlipidemia, anemia, arthralgia, joint swelling and unexplained weight loss, which prompted imaging studies. Computed tomography scan revealed a 5.4 cm adrenal mass. The patient had no clinical manifestations of adrenal medullary or cortical hyperfunction. Urine and plasma metanephrines and aldosterone/renin ratio were within normal range. The patient was taking prednisone for hand and ankle swelling, precluding assessment for Cushing syndrome. Given the size of the lesion, the possibility of malignancy was considered, and the patient elected for surgical management. The left adrenalectomy specimen weighed 54 g and revealed a 4.9 cm tan-brown mass with congested cut surface and a thin rim of residual adrenal gland parenchyma. Histologic examination showed thick and thin-walled vessels intermingled with adrenocortical elements at the periphery characteristic of a hemangioma. Surgical resection is the mainstay treatment for large, isolated adrenal masses to exclude malignancy and prevent retroperitoneal hemorrhage. Herein, we report a case of adrenal hemangioma, review a variety of other diagnostic considerations occurring in the adrenal gland, and highlight useful distinguishing features to assist in accurate diagnosis.
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    A discovery-based proteomics approach identifies protein disulphide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes
    (Elsevier, 2023) Syed, Farooq; Singhal, Divya; Raedschelders, Koen; Krishnan, Preethi; Bone, Robert N.; McLaughlin, Madeline R.; Van Eyk, Jennifer E.; Mirmira, Raghavendra G.; Yang, Mei-Ling; Mamula, Mark J.; Wu, Huanmei; Liu, Xiaowen; Evans-Molina, Carmella; Pediatrics, School of Medicine
    Background: Stress responses within the β cell have been linked with both increased β cell death and accelerated immune activation in type 1 diabetes (T1D). At present, information on the timing and scope of these responses as well as disease-related changes in islet β cell protein expression during T1D development is lacking. Methods: Data independent acquisition-mass spectrometry was performed on islets collected longitudinally from NOD mice and NOD-SCID mice rendered diabetic through T cell adoptive transfer. Findings: In islets collected from female NOD mice at 10, 12, and 14 weeks of age, we found a time-restricted upregulation of proteins involved in stress mitigation and maintenance of β cell function, followed by loss of expression of protective proteins that heralded diabetes onset. EIF2 signalling and the unfolded protein response, mTOR signalling, mitochondrial function, and oxidative phosphorylation were commonly modulated pathways in both NOD mice and NOD-SCID mice rendered acutely diabetic by T cell adoptive transfer. Protein disulphide isomerase A1 (PDIA1) was upregulated in NOD islets and pancreatic sections from human organ donors with autoantibody positivity or T1D. Moreover, PDIA1 plasma levels were increased in pre-diabetic NOD mice and in the serum of children with recent-onset T1D compared to non-diabetic controls. Interpretation: We identified a core set of modulated pathways across distinct mouse models of T1D and identified PDIA1 as a potential human biomarker of β cell stress in T1D.
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    S‐Nitroso‐L‐cysteine and ventilatory drive: A pediatric perspective
    (Wiley, 2022) Hubbard, Dallin; Tutrow, Kaylee; Gaston, Benjamin; Pediatrics, School of Medicine
    Though endogenous S‐nitroso‐l‐cysteine (l‐CSNO) signaling at the level of the carotid body increases minute ventilation (v̇E), neither the background data nor the potential clinical relevance are well‐understood by pulmonologists in general, or by pediatric pulmonologists in particular. Here, we first review how regulation of the synthesis, activation, transmembrane transport, target interaction, and degradation of l‐CSNO can affect the ventilatory drive. In particular, we review l‐CSNO formation by hemoglobin R to T conformational change and by nitric oxide (NO) synthases (NOS), and the downstream effects on v̇E through interaction with voltage‐gated K+ (Kv) channel proteins and other targets in the peripheral and central nervous systems. We will review how these effects are independent of—and, in fact may be opposite to—those of NO. Next, we will review evidence that specific elements of this pathway may underlie disorders of respiratory control in childhood. Finally, we will review the potential clinical implications of this pathway in the development of respiratory stimulants, with a particular focus on potential pediatric applications.
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    Forced expiratory flows and diffusion capacity in infants born from mothers with pre‐eclampsia
    (Wiley, 2022) Ren, Clement L.; Slaven, James E.; Haas, David M.; Haneline, Laura S.; Tiller, Christina; Hogg, Graham; Bjerregaard, Jeffrey; Tepper, Robert S.; Biostatistics, School of Public Health
    Rationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO) were performed at 6 months corrected age. Measurements and main results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into nonsevere (N = 41) and severe (N = 105) groups. There was no significant difference in DLCO and DLCO/alveolar volume among the three groups. Forced vital capacity was similar among the three groups, but the nonsevere Pre-E group had significantly higher forced expiratory flows than the other two groups. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two groups. Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.
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    Image Fusion Involving Real-Time Transabdominal or Endoscopic Ultrasound for Gastrointestinal Malignancies: Review of Current and Future Applications
    (MDPI, 2022-12-19) Singh, Ben S.; Cazacu, Irina M.; Deza, Carlos A.; Rigaud, Bastien S.; Saftoiu, Adrian; Gruionu, Gabriel; Guionu, Lucian; Brock, Kristy K.; Koay, Eugene J.; Herman, Joseph M.; Bhutani, Manoop S.; Medicine, School of Medicine
    Image fusion of CT, MRI, and PET with endoscopic ultrasound and transabdominal ultrasound can be promising for GI malignancies as it has the potential to allow for a more precise lesion characterization with higher accuracy in tumor detection, staging, and interventional/image guidance. We conducted a literature review to identify the current possibilities of real-time image fusion involving US with a focus on clinical applications in the management of GI malignancies. Liver applications have been the most extensively investigated, either in experimental or commercially available systems. Real-time US fusion imaging of the liver is gaining more acceptance as it enables further diagnosis and interventional therapy of focal liver lesions that are difficult to visualize using conventional B-mode ultrasound. Clinical studies on EUS guided image fusion, to date, are limited. EUS-CT image fusion allowed for easier navigation and profiling of the target tumor and/or surrounding anatomical structure. Image fusion techniques encompassing multiple imaging modalities appear to be feasible and have been observed to increase visualization accuracy during interventional and diagnostic applications.
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    Modeling Contingency in Veteran Community Reintegration: A Mixed Methods Approach
    (Sage, 2023) Rattray, Nicholas A.; Miech, Edward J.; True, Gala; Natividad, Diana; Laws, Brian; Frankel, Richard M.; Kukla, Marina; Medicine, School of Medicine
    Researchers need approaches for analyzing complex phenomena when assessing contingency relationships where specific conditions explain an outcome only when combined with other conditions. Using a mixed methods design, we paired configurational methods and qualitative thematic analysis to model contingency in veteran community reintegration outcomes, identifying combinations of conditions that led to success or lack of success in community reintegration among US military veterans. This pairing allowed for modeling contingency at a detailed level beyond the capabilities of either approach alone. Our analysis revealed multiple contingent relationships at work in explaining reintegration, including social support, purpose, cultural adjustment, and military separation experiences. This study contributes to the field of mixed methods by pairing a mathematical cross-case method with a qualitative method to model contingency.