Open Access Policy Articles

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The IUPUI Faculty Council adopted an open access policy on October 7th, 2014 (available from: https://openaccess.iupui.edu/policy). 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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Metabolomic Analysis Uncovers Energy Supply Disturbance as an Underlying Mechanism of the Development of Alcohol‐Associated Liver Cirrhosis
(Wiley, 2021-03-08) Huang, Ying; Niu, Ming; Jing, Jing; Zhang, Zi-teng; Zhao, Xu; Chen, Shuai-shuai; Li, Shan-shan; Shi, Zhu; Huang, Ang; Zou, Zheng-Sheng; Yu, Yue-cheng; Xiao, Xiao-he; Liangpunsakul, Suthat; Wang, Jia-bo; Medicine, School of Medicine
Alcohol-associated liver disease (ALD) is caused by alcohol metabolism's effects on the liver. The underlying mechanisms from a metabolic view in the development of alcohol-associated liver cirrhosis (ALC) are still elusive. We performed an untargeted serum metabolomic analysis in 14 controls, 16 patients with ALD without cirrhosis (NC), 27 patients with compensated cirrhosis, and 79 patients with decompensated ALC. We identified two metabolic fingerprints associated with ALC development (38 metabolites) and those associated with hepatic decompensation (64 metabolites) in ALC. The cirrhosis-associated fingerprint (eigenmetabolite) showed a better capability to differentiate ALC from NC than the aspartate aminotransferase-to-platelet ratio index score. The eigenmetabolite associated with hepatic decompensation showed an increasing trend during the disease progression and was positively correlated with the Model for End-Stage Liver Disease score. These metabolic fingerprints belong to the metabolites in lipid metabolism, amino acid pathway, and intermediary metabolites in the tricarboxylic acid cycle. Conclusion: The metabolomic fingerprints suggest the disturbance of the metabolites associated with cellular energy supply as an underlying mechanism in the development and progression of alcoholic cirrhosis.
Acute alcohol does not impair attentional inhibition as measured with Stroop interference scores but impairs Stroop performance
(Springer, 2021-06) Riedel, P.; Wolff, W.; Spreer, M.; Petzold, J.; Plawecki, M.H.; Goschke, T.; Zimmermann, U.S.; Smolka, M.N.; Psychiatry, School of Medicine
Rationale: Inhibition is a core executive function and refers to the ability to deliberately suppress attention, behavior, thoughts, and/or emotions and instead act in a specific manner. While acute alcohol exposure has been shown to impair response inhibition in the stop-signal and Go/NoGo tasks, reported alcohol effects on attentional inhibition in the Stroop task are inconsistent. Notably, studies have operationalized attentional inhibition variably and there has been intra- and inter-individual variability in alcohol exposure. Objective: This study aimed to examine the acute effects of alcohol on attentional inhibition, considering previous limitations. Methods: In a single-blind, cross-over design, 40 non-dependent participants with a medium-to-high risk drinking behavior performed a Counting Stroop task (CST) under a baseline and an arterial blood alcohol concentration (aBAC) clamp at 80 mg%. Attentional inhibition was assessed as the alteration of reaction times (RT), error rates (ER), and inverse efficiency scores (IES) between incongruent and congruent trials (interference score). Stroop performance was also assessed regardless of trial-type. Results: Compared to saline, acute alcohol exposure via an aBAC clamp did not affect CST interference scores but increased RTs and IES in both incongruent and congruent trials. Conclusions: Attentional inhibition (Stroop interference score) was not impaired by clamped moderate alcohol exposure. Acute alcohol impaired Stroop performance evidenced by a general increase in response times. Our findings suggest that response and attentional inhibition do not share the same neurocognitive mechanisms and are affected differently by alcohol. Results could also be explained by automated behaviors known to be relatively unaffected by acute alcohol.
17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin
(American Society for Clinical Investigation, 2021-03-15) Frump, Andrea L.; Albrecht, Marjorie; Yakubov, Bakhtiyor; Breuils-Bonnet, Sandra; Nadeau, Valérie; Tremblay, Eve; Potus, Francois; Omura, Junichi; Cook, Todd; Fisher, Amanda; Rodriguez, Brooke; Brown, R. Dale; Stenmark, Kurt R.; Rubinstein, C. Dustin; Krentz, Kathy; Tabima, Diana M.; Li, Rongbo; Sun, Xin; Chesler, Naomi C.; Provencher, Steeve; Bonnet, Sebastien; Lahm, Tim; Medicine, School of Medicine
Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ER-α), attenuates PAH-induced RV failure (RVF) by upregulating the procontractile and prosurvival peptide apelin via a BMPR2-dependent mechanism. We found that ER-α and apelin expression were decreased in RV homogenates from patients with RVF and from rats with maladaptive (but not adaptive) RV remodeling. RV cardiomyocyte apelin abundance increased in vivo or in vitro after treatment with E2 or ER-α agonist. Studies employing ER-α–null or ER-β–null mice, ER-α loss-of-function mutant rats, or siRNA demonstrated that ER-α is necessary for E2 to upregulate RV apelin. E2 and ER-α increased BMPR2 in pulmonary hypertension RVs and in isolated RV cardiomyocytes, associated with ER-α binding to the Bmpr2 promoter. BMPR2 is required for E2-mediated increases in apelin abundance, and both BMPR2 and apelin are necessary for E2 to exert RV-protective effects. E2 or ER-α agonist rescued monocrotaline pulmonary hypertension and restored RV apelin and BMPR2. We identified what we believe to be a novel cardioprotective E2/ER-α/BMPR2/apelin axis in the RV. Harnessing this axis may lead to novel RV-targeted therapies for PAH patients of either sex.
A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway
(Springer, 2021-06) Najar, Mohd Altaf; Rex, D.A.B.; Modi, Prashant Kumar; Agarwal, Nupur; Dagamajalu, Shobha; Karthikkeyan, Gayathree; Vijayakumar, Manavalan; Chatterjee, Aditi; Sankar, Uma; Prasad, T.S. Keshava; Anatomy and Cell Biology, School of Medicine
Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine-protein kinase belonging to the Ca2+/calmodulin-dependent protein kinase subfamily. CAMKK2 has an autocatalytic site, which gets exposed when Ca2+/calmodulin (CAM) binds to it. This results in autophosphorylation and complete activation of CAMKK2. The three major known downstream targets of CAMKK2 are 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPKα), calcium/calmodulin-dependent protein kinase 1 (CAMK1) and calcium/calmodulin-dependent protein kinase 4 (CAMK4). Activation of these targets by CAMKK2 is important for the maintenance of different cellular and physiological processes within the cell. CAMKK2 is found to be important in neuronal development, bone remodeling, adipogenesis, and systemic glucose homeostasis, osteoclastgensis and postnatal myogensis. CAMKK2 is reported to be involved in pathologies like Duchenne muscular dystrophy, inflammation, osteoporosis and bone remodeling and is also reported to be overexpressed in prostate cancer, hepatic cancer, ovarian and gastric cancer. CAMKK2 is involved in increased cell proliferation and migration through CAMKK2/AMPK pathway in prostate cancer and activation of AKT in ovarian cancer. Although CAMKK2 is a molecule of great importance, a public resource of the CAMKK2 signaling pathway is currently lacking. Therefore, we carried out detailed data mining and documentation of the signaling events associated with CAMKK2 from published literature and developed an integrated reaction map of CAMKK2 signaling. This resulted in the cataloging of 285 reactions belonging to the CAMKK2 signaling pathway, which includes 33 protein-protein interactions, 74 post-translational modifications, 7 protein translocation events, and 22 activation/inhibition events. Besides, 124 gene regulation events and 25 activator/inhibitors involved in CAMKK2 activation were also cataloged. The CAMKK2 signaling pathway map data is made freely accessible through WikiPathway database ( https://www.wikipathways.org/index.php/Pathway:WP4874 ). We expect that data on a signaling map of CAMKK2 will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on CAMKK2 and its utility in the development of biomarkers and therapeutic targets.
Layperson Views about the Design and Evaluation of Decision Aids: A Public Deliberation
(Sage, 2021-07) Schwartz, Peter H.; O’Doherty, Kieran C.; Bentley, Colene; Schmidt, Karen K.; Burgess, Michael M.; Medicine, School of Medicine
Purpose: We carried out the first public deliberation to elicit lay input regarding guidelines for the design and evaluation of decision aids, focusing on the example of colorectal ("colon") cancer screening. Methods: A random, demographically stratified sample of 28 laypeople convened for 4 days, during which they were informed about key issues regarding colon cancer, screening tests, risk communication, and decision aids. Participants then deliberated in small and large group sessions about the following: 1) What information should be included in all decision aids for colon screening? 2) What risk information should be in a decision aid and how should risk information be presented? 3) What makes a screening decision a good one (reasonable or legitimate)? 4) What makes a decision aid and the advice it provides trustworthy? With the help of a trained facilitator, the deliberants formulated recommendations, and a vote was held on each to identify support and alternative views. Results: Twenty-one recommendations ("deliberative conclusions") were strongly supported. Some conclusions matched current recommendations, such as that decision aids should be available for use with and without providers present (conclusions 1-4) and should support informed choice (conclusion 9). Some conclusions differed from current recommendations, at least in emphasis-for example, that decision aids should disclose cost of screening (conclusion 11) and should be kept simple and understandable (conclusion 14). Deliberants recommended that decision aids should disclose the baseline risk of getting colon cancer (conclusions 15, 17). Limitations: Single location and medical decision. Conclusions: Guidelines for design of decision aids should consider putting a greater focus on disclosing cost and keeping decision aids simple, and they possibly should recommend disclosing less extensive amounts of quantitative information than currently recommended.
Loneliness Interacts With Cognition in Relation to Healthcare and Financial Decision Making Among Community-Dwelling Older Adults
(Oxford University Press, 2020-11-23) Stewart, Christopher C.; Yu, Lei; Glover, Crystal M.; Mottola, Gary; Bennett, David A.; Wilson, Robert S.; Boyle, Patricia A.; Neurology, School of Medicine
Background and objectives: Cognition is a known determinant of healthcare and financial decision making in old age. Social vulnerabilities also might play a role in such decisions; however, the evidence for this is less clear. Here, we examined the association of loneliness with decision making and tested the hypothesis that loneliness is associated with decision making via its interaction with global cognition. Research design and methods: Participants were 1,121 nondemented older adults from the Rush Memory and Aging Project. Healthcare and financial decision making was assessed via a performance-based measure; loneliness was assessed via the De Jong Gierveld Loneliness Scale; and cognition was assessed via a 19-test neuropsychological battery. Results: In a regression model adjusted for age, sex, and education, global cognition was associated with decision making (B = 2.43, SE = 0.14, p < .001) but loneliness was not (B = -0.04, SE = 0.11, p = .72). However, in a model including the interaction of loneliness with global cognition, the interaction was significant (B = 0.44, SE = 0.20, p = .03), such that the detrimental effect of loneliness on decision making was stronger when cognition was low. In secondary analyses examining the interaction of loneliness with 5 specific cognitive domains, the interaction between loneliness and working memory with decision making was significant (B = 0.35, SE = 0.15, p = .02). Discussion and implications: Our results suggest that loneliness compromises healthcare and financial decision making among older adults with lower global cognition and, more specifically, lower working memory.
Effects of Qigong Exercise on Physical and Psychological Health among African Americans
(Sage, 2021-06) Chang, Pei-Shiun; Lu, Yvonne; Nguyen, Chi Mai; Suh, Youngnok; Luciani, Mary; Ofner, Susan; Powell, Savannah; School of Nursing
Interventions are needed to address physical and psychological health in middle-aged and older African Americans (AAs). The purpose of this pilot study was to evaluate the feasibility and potential benefits of an eight-week Qigong exercise on physical ability and function, balance, frailty, depression and anxiety, and spiritual well-being in AAs using a single-group design. Fifteen AAs with a mean age of 64 years received Qigong exercise over 16 semi-weekly, one-hour sessions. The majority were female (93.3%) and college-level educated (53.3%). Repeat chair stands, physical function, and spiritual well-being improved significantly (p < .05) with effect sizes ranging from .45 to .87. Over 52% of participants showed improved depression scores, fast gait speed, and standing balance. Nearly 42% demonstrated some frailty improvement over baseline. No adverse events were reported. Qigong exercise potentially improves the physical ability and function, and spiritual well-being of AAs and needs further testing in a randomized clinical trial.
Fifteen-year experience with pericardiectomy at a tertiary referral center
(BMC, 2021-06-22) Faiza, Zainab; Prakash, Anjali; Namburi, Niharika; Johnson, Bailey; Timsina, Lava; Lee, Lawrence S.; Medicine, School of Medicine
Purpose: Pericardiectomy has traditionally carried relatively high perioperative mortality and morbidity, with few published reports of intermediate- and long- term outcomes. We investigated our 15-year experience performing pericardiectomy at our institution. Methods: Retrospective study of all patients who underwent pericardiectomy at our institution between 2005 and 2019. Baseline demographics, intraoperative details, and postoperative outcomes including long-term survival were analyzed. Results: Sixty-three patients were included in the study. 66.7% of subjects underwent isolated pericardiectomy while 33.3% underwent pericardiectomy concomitantly with another cardiac surgical procedure. The most common indications for pericardiectomy were constrictive (79.4%) and hemorrhagic (9.5%) pericarditis. Preoperatively, 76.2% of patients were New York Heart Association class II and III, while postoperatively, 71.4% were class I and II. One-, three-, five-, and ten- year overall mortality was 9.5, 14.3, 20.6, and 25.4%, respectively. Overall pericarditis recurrence rate was 4.8%. Conclusion: Pericardiectomy carries relatively high overall mortality rates, which likely reflects underlying disease etiology and comorbidities. Patients with prior cardiac intervention, history of dialysis, and immunocompromised state are associated with worse outcomes.
Efficacy of tailored messages to improve behavioral intent to accept HPV vaccination among mothers may be moderated by sociodemographics
(Elsevier, 2021-05-29) Feemster, Kristen A.; Head, Katharine J.; Panozzo, Catherine A.; O'Dell, Sean M.; Zimet, Gregory D.; Kornides, Melanie L.; Pediatrics, School of Medicine
We assessed differences in response to a tailored recommendation intervention for HPV vaccine by participants’ sociodemographic characteristics in this exploratory sub-analysis of a larger web-based, randomized-controlled trial on tailored messaging among mothers with low intent to vaccinate their 11–14-year-old child against HPV. The intervention consisted of pre-recorded video messages tailored to 1–5 common concerns about HPV vaccine. In these exploratory analyses, we used generalized linear models to assess differences in post-intervention intent across intervention arms, stratified by sociodemographic characteristics among 496 trial participants. We found significantly higher post-intervention intent in the intervention participants versus the control group among mothers: 1) with younger children; 2) with white vs. black children; 3) with Non-Hispanic children; 4) who were younger; 5) with some college or vocational training; with household incomes of ≥$100,000; and 7) with 1–2 children. Our findings of effect modification by certain sociodemographic factors such as age, race/ethnicity, and household income should be considered when designing similar tailored messaging interventions.

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