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.indianapolis.iu.edu/). This policy shows IU Indianapolis'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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Accuracy of glutamic acid decarboxylase antibodies for the identification of adult-onset type 1 diabetes mellitus: a systematic review and meta-analysis
(Frontiers Media, 2026-03-31) Shao, Mandy M.; Scheideman, Agatha F.; Zhou, Allen M.; Kohn, Michael A.; DiMeglio, Linda A.; Quandt, Zoe; Speake, Cate; Ho, Cindy N.; Klonoff, David C.; Pediatrics, School of Medicine
Introduction: The glutamic acid decarboxylase autoantibody (GADA) test is a widely used marker to differentiate type 1 diabetes and type 2 diabetes in adults. We conducted a systematic review to estimate the sensitivity and specificity of the presence of GADA for T1D in adults with newly diagnosed diabetes. Methods: We conducted a PubMed and Embase search for studies that report both the GADA result and type 1 versus type 2 diabetes in adults diagnosed with diabetes. We calculated the sensitivity and specificity for each study. Results: We identified 19 studies involving 11,760 patients from diverse geographic settings. Across these studies, the sensitivity of GADA for identifying adult-onset type 1 diabetes varied widely (range: 0.27 to 0.83), with a pooled estimate of 0.53 (95% CI: 0.46-0.60). In contrast, specificity was consistently high, with a pooled estimate of 0.93 (95% CI: 0.89-0.96). The positive and negative likelihood ratios were 7.3 (95% CI 4.8 to 11.3) and 0.51 (0.44 to 0.58), respectively. Discussion: Our review demonstrates that GADA has high specificity and moderate sensitivity for identifying adult-onset type 1 diabetes. As a limitation, factors such as assay choice and cut-off values, as well as heterogeneity of both the type 1 and type 2 diabetes groups with regard to unmeasured genetic influences may contribute to the variability in antibody prevalence between studies. Our pooled likelihood ratios for GADA results might be useful for developing clinical and algorithmic tools to distinguish adult-onset type 1 diabetes from type 2 diabetes.
Nasal CPAP increases alveolar number in a rhesus monkey model of moderate prematurity
(European Respiratory Society, 2025-04-03) McEvoy, Cindy T.; MacDonald, Kelvin D.; Shorey-Kendrick, Lyndsey E.; Davies, Michael H.; Lund, Kelli C.; Lam, Ryan; Dozier, Brandy L.; Martin, Lauren Drew; Corcoran, Fiona; Schelonka, Robert L.; Tepper, Robert S.; Spindel, Eliot R.; Pediatrics, School of Medicine
Background: Most premature human infants are born in the moderate to late preterm (MLP) range, ≥30 to <37 weeks gestation, and demonstrate increased incidence of wheeze and respiratory illness as they age. Animal models suggest that mechanical lung distention stimulates lung growth and alveolar development. To determine if nasal continuous positive airway pressure (nCPAP) influences MLP infant lung development, we developed a rhesus monkey model of moderate prematurity, randomised to 9 days of nCPAP or sham nCPAP. Methods: Timed-pregnant fetuses were delivered by elective hysterotomy at gestational age (GA) 140±1 days (85% gestation; term=165 days; human equivalent of 32-34 weeks) or at GA-149±1 days as a relative gestational age reference (GA-control). The day after delivery, the GA-140 animals were treated with nCPAP or sham nCPAP for 9 days, 12 consecutive hours each day. Pulmonary function testing followed by necropsy for analysis of lung structure and gene expression was performed on the equivalent of GA-150 for all animals. Results: The nCPAP and sham groups were clinically similar but distinct from the GA-control group. Stereological analysis of lung structure showed significantly increased numbers of alveoli in the nCPAP group compared to the sham group. Other functional and anatomical changes were consistent with increased alveolarisation. Gene expression between the nCPAP and sham groups remained highly similar and distinct from GA-control animals. Conclusions: We show that nCPAP in MLP infants stimulates alveolarisation with relatively few other changes. How this may benefit subsequent infant respiratory health requires further study.
Predicting Three-Year Survival in Patients Receiving Maintenance Dialysis: An External Validation and Updated Multivariable Prediction Model for iChoose Kidney in Ontario, Canada
(Sage, 2026-04-10) Naylor, Kyla L.; Kang, Yuguang; McArthur, Eric; Garg, Amit X.; Patzer, Rachel E.; McKenzie, Susan; Kim, S. Joseph; Weir, Matthew; Yohanna, Seychelle; Knoll, Gregory; Treleaven, Darin; Surgery, School of Medicine
Background: A significant barrier to kidney transplantation is limited knowledge about its potential benefits. To help patients who are receiving maintenance dialysis make more informed treatment decisions, a risk calculator (iChoose Kidney) was developed in the United States to provide individualized survival estimates for dialysis versus kidney transplantation. This tool was externally validated in Ontario, Canada, and was found to accurately predict mortality (Ontario version of the tool "Dialysis vs. Kidney Transplant-Estimated Survival in Ontario Risk Calculator"). The United States risk calculator has been updated to include additional variables (e.g., dialysis modality). Objective: To externally validate the updated iChoose Kidney risk calculator in patients from Ontario, Canada, with kidney failure using more recent data, removing race (race in clinical algorithms may perpetuate racial bias in medicine) and using a refined cohort definition (i.e., restricting to patients with no recorded contraindications to transplant). Design: External validation study. Setting: Linked administrative health care databases from Ontario, Canada. Patients: 24 793 patients receiving maintenance dialysis and 5398 kidney transplant recipients from January 1, 2011, to August 31, 2021. Measurements: Three-year mortality. Methods: Model discrimination was evaluated using the C-statistic. Calibration was assessed by comparing the observed versus predicted mortality risks, and further assessed by using loess-smoothed calibration plots. To address over- or under-prediction (calibration-in-the-large), intercepts were adjusted using a correction factor. In our updated model, we used logistic regression to calculate mortality risk, incorporating the following variables: sex assigned at birth (male vs female), age (continuous), cardiovascular disease, hypertension, diabetes, time on dialysis (i.e., <6 months, 6 to 12 months, >1 to 2 years, >2 to 3 years, >3 to 5 years, >5 to 7 years, >7 to 10 years, >10 to 14 years, >14 years), and dialysis modality (peritoneal dialysis, home hemodialysis, in-center dialysis). In a post-hoc analysis, we used the simplified equations from our original Canadian external validation study of the iChoose Kidney tool (i.e., age, sex, hypertension, diabetes, cardiovascular disease, time on dialysis [<6 months, 6-12 months, >12 months]), with removal of the race variable as the only modification. Results: In the dialysis cohort, over a median follow-up of 2.5 years, 30.3% of patients died. In the kidney transplant recipient cohort, over a median follow-up of 2.9 years, 7.3% died. Our updated model had moderate discrimination (C-statistic for dialysis cohort: 0.67 [95% CI: 0.67, 0.68] and C-statistic for kidney transplant cohort: 0.76 [95% CI: 0.74, 0.79]). After recalibrating the intercepts, the observed and predicted mortality were similar between the dialysis cohort and the kidney transplant cohort. Similar results were found in a post-hoc analysis using the original model with the race variable removed. Limitations: Mortality risk estimates assume that all treatment options are readily accessible to patients. However, the average waiting time for a deceased donor kidney transplant in Ontario can be several years. Conclusions: After minor modifications, the iChoose Kidney risk calculator provides reliable survival estimates in patients with kidney failure from Ontario, Canada. Given the similarity in model performance between the updated model and the original model, with race removed, we will continue to use our original simplified model, but we will remove race. Our updated Dialysis vs. Kidney Transplant-Estimated Survival in Ontario Risk Calculator can continue to be a valuable tool for healthcare professionals to use with patients who are receiving maintenance dialysis to provide individualized survival estimates for dialysis versus transplantation, supporting informed decision-making about kidney transplantation.
End-Stage Renal Disease Treatment Choices Model and Use of Home Dialysis and Kidney Transplant
(American Medical Association, 2026-04-03) Dixit, Meehir N.; Koukounas, Kalli G.; Drewry, Kelsey M.; Wilk, Adam S.; Lee, Yoojin; Patzer, Rachel E.; Mehrotra, Rajnish; Rivera-Hernandez, Maricruz; Meyers, David J.; Kim, Daeho; Shah, Ankur D.; Schmid, Christopher H.; Trivedi, Amal N.; Surgery, School of Medicine
Importance: To increase the use of home dialysis and kidney transplant, the Centers for Medicare & Medicaid Services launched the End-Stage Renal Disease Treatment Choices (ETC) model, a mandatory, randomized pay-for-performance program applied to 30% of US hospital referral regions. Its impact after 4 years of implementation is uncertain. Objective: To assess the ETC model's impact on home dialysis, kidney transplant, and transplant waitlist, as well as measure the rate of financial penalties. Design, setting, and participants: This retrospective cross-sectional study used traditional Medicare claims and enrollment data for beneficiaries with kidney failure linked to concurrent transplant data from the United Network for Organ Sharing from January 1, 2017 (4 years before model implementation), to September 30, 2024 (3.75 years postimplementation). Exposures: Receiving dialysis treatment in a region randomly assigned to the ETC model. Main outcomes and measures: Primary outcomes were rates of home dialysis, kidney transplant, and transplant waitlist, as well as facility-level financial penalization. Facility-level financial penalties were assessed using Centers for Medicare & Medicaid Services-published performance data. Results: The study population included 795 232 persons with kidney failure (mean [SD] age, 61.8 [14.4] years; 41.5% female), reflecting 20 729 696 person-months from January 1, 2017, to September 30, 2024. The rate of home dialysis increased from 12.8% to 16.7% of attributed patient-months in ETC regions (change of 3.9 percentage points [pp]) and from 13.7% to 17.3% in control regions (change of 3.7 pp), yielding an adjusted differences-in-differences of -0.1 pp (95% CI, -0.6 to 0.5 pp). The number of kidney transplants per 1000 patient-months increased from 3.3 to 4.5 in ETC regions (change of 1.2) and from 3.4 to 4.4 in control regions (change of 1.0), resulting in a differences-in-differences of 0.2 pp (95% CI, -0.1 to 0.4 pp). The percentage of patients per month on the transplant waitlist decreased from 16.1% to 15.5% in ETC regions (change of -0.5 pp) and from 17.7% to 16.7% in control regions (change of -1.0 pp). The adjusted differences-in-differences for transplant waitlist was 0.6 pp (95% CI, -0.3 to 1.6 pp). The proportion of ETC facilities receiving financial penalties increased from 13.8% in 2021 to 25.1% in 2023. Subgroup analyses showed no meaningful differential effects of the model. Conclusions and relevance: This cross-sectional study shows that after nearly 4 years, the ETC model was not associated with meaningful increases in home dialysis, kidney transplant, or transplant waitlist, while the proportion of facilities receiving financial penalties increased. Future value-based payment models may need to move beyond narrowly targeted financial incentives to address the broader structural and patient-level barriers that influence access to complex specialty care.
Mentorship, work-life balance, and opportunities amongst cardiothoracic surgery trainees
(Elsevier, 2025-11-20) Shehata, Dena G.; Holler, Emma; Lopez, Edilin; Pan, Jennifer Megan; Varghese, Thomas K., Jr.; Doty, Adam A.; Erkmen, Cherie P.; Cooke, David T.; Odell, David D.; Freeman, Kirsten; Servais, Elliot L.; Hu, Yue-Yung; Bilimoria, Karl Y.; Ceppa, DuyKhanh P.; Watkins, Ammara A.; Surgery, School of Medicine
Objective: Cardiothoracic surgery training is demanding. Mentorship, belonging, work-life balance, support, and opportunities are critical factors for career satisfaction and retention. This study explores gender differences in these key areas amongst cardiothoracic surgery trainees. Methods: A cross-sectional national survey was conducted with the 2024 Thoracic Surgery Directors Association In-Training Exam. The 18-item questionnaire consisted of multiple choice and Likert-scale questions regarding mentorship, belonging, work-life balance, and perceptions of opportunities, support, and program fairness. Data were summarized using frequencies and percentages; groups were compared using either χ2 or Fisher exact test. Results: A total of 440 trainees participated from 74 programs (74.3% response rate); 31% (n = 137) women, 64% men (n = 281), and 5% (n = 22) gender not disclosed. Female trainees less frequently reported a strong sense of belonging in their program (82% vs 90%; P = .04), were more dissatisfied with time for personal life (42% vs 32%; P = .02), more frequently considered leaving the program (20% vs 11%; P = .01) and expressed dissatisfaction with becoming a cardiothoracic surgeon (9% vs 4%; P = .02). Female trainees were less likely to perceive that opportunities were distributed fairly (75% vs 83%; P = .04) and were also less likely to feel that residency is a level playing field (71% vs 83%; P = .005). Conclusions: Gender disparities exist in cardiothoracic surgery training, with female trainees reporting greater dissatisfaction with work-life balance, mentorship, opportunities, support, and career choice compared with their male counterparts.
Representing dental restoration materials in the oral health and disease ontology
(BioMed Central, 2026-04-16) Dutta, Nivedita; DeBellis, Michael; Chanda, Nripen; Diehl, Alexander D.; Wilson, Finn; Rocha, Mateus; Diller, Mattew; Chandrasekharan, Gopikrishnan M.; Duncan, William D.; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and Engineering
Background: Semantic clarity and standardization in representing dental restoration materials are essential for ensuring interoperability across research and clinical settings. However, existing ontologies, including those in the Open Biological and Biomedical Ontology (OBO) Foundry, provide minimal coverage of this clinically relevant domain. Methods: Guided by OBO Foundry principles, developed an ontological extension of the Oral Health and Disease (OHD) ontology to formally represent dental restoration materials. The modeling process included iterative expert input to ensure clinical accuracy and precise terminology. Logical definitions and subclass hierarchies were created to classify materials by composition and microstructure. Results: The extended ontology introduces a logically structured taxonomy of dental restoration materials using genus-differentia definitions. Its class hierarchy aligns with domain-specific classification systems and captures current and emerging material types. Reuse of class from the Chemical Entities of Biological Interest (ChEBI) and the Environment Ontology (ENVO) as well as relations from the Relation Ontology (RO) supports semantic integration with related biomedical ontologies. Conclusion: This work highlights how domain-informed ontology design can effectively capture complex material knowledge. The extensive collaboration integrates expertise from ontology engineers, academic researchers, and practicing clinicians. This approach enables the capture of intricate, often-disregarded real clinical factors, resulting in a model that reflects both the structural properties of materials and their practical use. The extended OHD ontology improves the semantic representation of dental restoration materials and provides a scalable foundation for advancing oral health informatics. Supplementary Information: The online version contains supplementary material available at 10.1186/s13326-026-00352-x.
Validity evidence for the new ENDO Mentor Suite and its use in the Fundamentals of Endoscopic Surgery examination
(Springer, 2026) Deravi, Noosha D.; Miller, Payton M.; Hunt, Maya L.; Mischna, Jessica; Martinez, Jose M.; Pauli, Eric M.; Ritter, E. Matthew; Surgery, School of Medicine
Background: The Fundamentals of Endoscopic Surgery (FES) manual skills exam is a simulation-based assessment originally developed on the GI Mentor II (GIM) with strong validity evidence. Surgical Science has since released the ENDO Mentor Suite (ES), for which validity evidence was previously demonstrated in a small, randomized study. However, there were minor scoring discrepancies for Loop Reduction and Mucosal Inspection. This follow-up study aims to determine if the ES introduces a threat to validity in the form of construct irrelevant variance through analysis of FES examinee performance. Methods: Retrospective analysis of FES examinee data, including demographics and performance, was conducted following the integration of the ES as a testing platform in 2023. Task and total scores were obtained through a standardized computer-based algorithm. Examinees without self-reported demographics were excluded from analysis. Performance and pass rates were compared between ES and GIM examinees using standard statistical methods and sensitivity analyses within a non-inferiority framework. Results: Of 1,121 FES examinees, 436 (39%) provided demographic information. Simulator groups were similar in demographics and endoscopy experience. There were small statistically discernable differences in Retroflexion and Tool Targeting scores between ES and GIM examinees. However, total scores (ES 70 ± 12 vs GIM 69 ± 11, p = 0.55) and pass rates (ES 88% vs GIM 83%, p = 0.25) were similar. Sensitivity analyses also confirmed a similar pattern of non-inferiority. Conclusion: The ES does not introduce construct irrelevant variance, supporting its use in the FES manual skills exam. This is demonstrated by similar overall performance and pass rates between ES and GIM examinees. Additionally, previously reported variability in Loop Reduction and Mucosal Inspection were not redemonstrated within this larger sample. Given that over half of examinees were excluded from this analysis, measures to improve quality control on demographic reporting will be essential for additional validity investigations.
Localizing Beta Synchronous Neurons in the STN Using Directional DBS Recordings and Patient-Specific Biophysical Models
(Elsevier, 2026) Noor, M. Sohail; Jadapalli, Jeevan; Walker, Harrison C.; McIntyre, Cameron C.; Neurological Surgery, School of Medicine
Objective: Local field potentials (LFPs) exhibit abnormally elevated beta-band power in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). To better understand these signals, we coupled advanced biophysical models with experimental LFP recordings to characterize the neural sources underlying beta oscillations in PD patients. Methods: Patient-specific biophysical models simulated LFPs with detailed representation of the directional DBS electrodes in the local neuroanatomy, as well as the ionic currents generated by STN neural activity. We then used the models to perform source localization of a beta synchronous volume of STN neurons in each patient. We also compared the utility of various referencing schemes for source localization. Results: The beta synchronous volumes typically localized to the posterior STN. We also identified a novel vertical-directional bipolar referencing scheme that demonstrated superior source localization. Conclusions: Our results support the hypothesis that beta synchronous STN neurons cluster into distinct focal areas, as opposed to being uniformly distributed throughout the nucleus. Significance: This proof-of-concept study demonstrates that patient-specific models characterizing the spatiotemporal characteristics of beta oscillations in the STN can be used to define a patient-specific target volume for DBS therapy.
Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer's Disease
(medRxiv, 2026-04-01) Lin, Wenjing; Beric, Aleksandra; Wisch, Julie K.; Baker, Bryce; Jerome, Gina; Minton, Matthew; Preminger, Sam; Stauber, Jennifer; Schindler, Suzanne E.; Dage, Jeffrey L.; Allegri, Ricardo; Aguillon, David; Benzinger, Tammie; Chhatwal, Jasmeer; Daniels, Alisha; Day, Gregory S.; Devenney, Emma; Fox, Nick C.; Goate, Alison; Gordon, Brian A.; Barthélemy, Nicolas R.; Hassenstab, Jason; Huey, Edward; Ikeuchi, Takeshi; Jayadev, Suman; Jucker, Mathias; Ishiguro, Takanobu; Lee, Jae-Hong; Levey, Allan I.; Levin, Johannes; Morris, John C.; Perrin, Richard J.; Renton, Alan; Roh, Jee Hoon; Xiong, Chengjie; Bateman, Randall J.; Ances, Beau M.; Cruchaga, Carlos; Karch, Celeste M.; Supnet-Bell, Charlene; Llibre-Guerra, Jorge; McDade, Eric; Dominantly Inherited Alzheimer Network; Ibanez, Laura; Neurology, School of Medicine
Background: Increasing evidence suggests that accurate prediction of Alzheimer's disease (AD) symptom onset requires more than amyloid- and tau-centric biomarkers such as cerebrospinal fluid (CSF) Aβ42/40, total tau and p-tau181 and plasma p-tau217. Autosomal dominant AD (ADAD), caused by pathogenic PSEN1, PSEN2 and APP mutations with predictable age at symptom onset, presents a unique opportunity to characterize the chronological changes in proteins beyond amyloid and tau and clarify them as early biomarkers of disease onset or as biomarkers related to disease staging and progression monitoring. Methods: We measured 972 CSF samples corresponding to 484 participants of the Dominantly Inherited Alzheimer Disease Network (DIAN) using the NULISASeq 120 CNS Disease Panel. We first benchmarked the technology against gold-standard measurements followed by the identification of proteins that were differentially abundant in relation to mutation status and symptomatology. Next, we determined the chronological emergence of protein changes in relation to the estimated years to onset (EYO). Finally, we assessed whether specific protein measures improved the prediction of EYO in the ADAD. Findings: NULISA measurements were comparable to those previously published. We demonstrated that known early alterations in CSF amyloid and tau were followed by inflammatory and neurodegenerative responses suggesting that clinical manifestation of AD happens before the inflammatory processes is fully developed. Finally, we found a multi-protein composite approach for predicting EYO that outperformed single biomarker values. Interpretation: Our results suggest that the main CSF proteomic landscape changes in ADAD are due to the presence of a pathogenic mutation and occur prior to symptom onset. Improved performance of multi-protein composite to predict EYO compared to single biomarker values highlights the added value of multiplex proteomic signatures for biomarker panel development.
The role of trust and relationship building in the ethical recruitment of youth living with HIV in research: perspectives from Kenyan youth living with HIV, their caregivers and subject matter experts
(BioMed Central, 2026-03-02) Chory, Ashley; Boal, Ava; Nyandiko, Winstone; Aluoch, Josephine; Scanlon, Michael; Gillette, Emma; Koros, Hillary; Ashimosi, Celestine; Beigon, Whitney; Munyoro, Dennis; Lidweye, Janet; Nyagaya, Jack; DeLong, Allison; Kantor, Rami; Naanyu, Violet; Vreeman, Rachel; Center for Global Health
Background: Inclusion of youth (10–24 years) living with HIV (YLWH) in clinical research is critical to addressing their unique vulnerabilities and improving care outcomes. Examining the role of trust and relationship building in research decision-making is critical to designing ethical recruitment and engagement strategies. Methods: We conducted in-depth, semi-structured interviews with YLWH (10–24 years, enrolled in HIV care at Academic Model Providing Access to Healthcare (AMPATH) in western Kenya), caregivers (parents and guardians) of YLWH, and other subject matter experts (SMEs). Interviews focused on barriers, facilitators, and strategies to improve participant-researcher trust and relationship building, with a particular focus on recruitment and engagement strategies. Interviews were conducted with 99 participants (53% male): 40 YLWH [median age 17.5, (range 11–24), 50% female], 20 caregivers of enrolled YLWH (70% female), and 39 SMEs (33% female; 46% community leaders, 26% healthcare providers, 15% clinical researchers, 8% social scientists, 3% international research experts, 2% laboratory experts). Results: All groups indicated trust could be built and broken through research processes. YLWH and SMEs viewed participant identification and study recruitment through medical records as a violation of trust, indicating that their HIV status and health information should remain confidential between themselves and their clinical team. All groups preferred recruitment through existing clinician-YLWH relationships, emphasizing the importance of privacy and confidentially; this strategy was viewed as stronger and more ethical. Losses of confidentiality and mistakes in sample collection that require participants to attend additional, unnecessary research visits or provide additional samples were identified by all groups as additional barriers to relationship-building. YLWH and caregivers discussed researcher characteristics that support relationship-building, emphasizing the importance of positive demeanors and non-stigmatizing behaviors by research personnel. YLWH and SMEs discussed operational needs that foster relationship-building, including proper communication about study procedures, reliably reporting results to participants, and receiving future benefits. Conclusions: Trusting participant-researcher relationships plays an important role in YLWH research decision making and greatly influence the development of ethical recruitment strategies. Study participants highlighted more appropriate and ethical recruitment strategies, stemming from strong participant-researcher relationships. Supplementary Information: The online version contains supplementary material available at 10.1186/s12910-026-01426-2.

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