Open Access Policy Articles

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https://hdl.handle.net/1805/3272

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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Now showing 1 - 10 of 34228

Cognitive Trajectories in Parkinson's Disease and Lewy Body Disease
(Wiley, 2025-12-23) Gallini, Julia W.; Gutierrez Gomez, Santiago; Gurnani, Ashita S.; Choi, Seo-Eun; Mukherjee, Shubhabrata; Trittschuh, Emily H.; Hohman, Timothy J.; Saykin, Andrew J.; Crane, Paul K.; Tripodis, Yorghos; Mez, Jesse; Shih, Ludy; Radiology and Imaging Sciences, School of Medicine
Background: Parkinson's disease (PD) is the second most common neurodegenerative illness after Alzheimer's disease. Dementia with Lewy bodies (DLB) shares clinical and neuropathological features with PD and requires cognitive impairment to meet clinical criteria. Although cognitive impairment is common in both PD and DLB, rates of cognitive decline can vary markedly, and associated predictors are poorly understood. This study aimed to characterize the effects of risk factors‐ particularly APOE and sex‐ on the trajectories of cognitive factor scores for memory, executive function, and language in persons with PD and DLB. Methods: Using National Alzheimer's Coordinating Center data, we identified participants with PD or DLB with a cognitively normal neuropsychological baseline and at least two total cognitive assessments. Factor scores were previously derived for language, memory and executive function. We fit three linear mixed effects models, one each for memory, executive function, and language factor scores. Predictors in these models included sex, race, baseline age, APOE genotype (1‐2 vs. 0 ε4 alleles), education, time from baseline, and interactions between sex and time and APOE and time. We also included a linear spline at the first diagnosis of mild cognitive impairment (MCI) or dementia (some participants remained cognitively normal throughout). Results: 494 participants with PD or DLB [193 (39.1%) female, mean baseline age: 71 (8.7 SD), 118 (23.9%) with 1‐2 ε4 alleles] were included. In the memory model, there was a faster rate of cognitive decline post‐MCI diagnosis (0.04 SD/yr; p = 0.001). This post‐MCI effect was significantly modified by APOE genotype (p = 0.01) but not by sex (p = 0.07). Post‐MCI diagnosis, people with 1‐2 APOE ε4 alleles declined 0.05 SD/year faster than people with 0 ε4 alleles. In the executive function and language models there was a faster rate of cognitive decline post‐MCI diagnosis (0.03 SD/yr, p = 0.02; 0.05 SD/yr, p <0.001) but these effects were not modified by APOE. Conclusions: APOE genotype was associated with an increased rate of memory decline, but not executive function or language decline in participants with PD/DLB after an MCI diagnosis. This factor may be useful for prognostication and aid in a personalized medicine approach to PD/DLB.
Loss of MMP9 leads to altered inflammation and ECM interactions in a mouse model of cerebral small vessel disease
(Wiley, 2025-12-24) Lykins, Joshua; Johnson, Sherika N.; Krick, Katelynn E.; Sudduth, Tiffany L; Rogers, Colin B.; Weekman, Erica M.; Wilcock, Donna M.; Anatomy, Cell Biology and Physiology, School of Medicine
Background: Vascular contributions to cognitive impairment and dementia (VCID) represent a major cause of dementia. Hyperhomocysteinemia (HHcy)‐driven cerebral small vessel disease (cSVD) leads to the degeneration of astrocytic end‐feet and an upregulation of matrix metalloproteinases (MMPs), which remodel the basement membrane, triggering growth factor activation and inflammation. This study explores the role of MMP9 in cSVD using MMP9‐/‐ mice subjected to a HHcy diet. Method: Six‐month‐old C57Bl6/J mice and MMP9‐/‐ mice were placed on a diet deficient in B vitamins and enriched in methionine or a control diet with normal levels of B vitamins and methionine for 12 weeks. The left hemibrain was fixed in PFA while the right brain was dissected for biochemistry. RNA was extracted from the frontal cortex and analyzed using NanoString's Mouse Neuroinflammation and Cardiovascular Disease panels. Microhemorrhage assessment via Prussian blue staining as well as Dp71, AQP4, and GFAP detected by immunohistochemistry were performed on the left hemisphere. Result: Gene expression analysis in MMP9‐/‐ mice on a control diet revealed significant reductions in inflammation‐related genes (Cd14, Slamf8, Prkcq, Lag3) and lower expression of the microglial marker P2ry12 compared to wild‐type mice. Additionally, MMP9‐/‐ mice exhibited increased expression of macrophage extracellular matrix (ECM) scavenging receptors (Cd44, Cd163, Siglec1) and enhanced regulation of the PIP3 signaling pathway across multiple cell types. Under a HHcy diet, wild‐type mice showed elevated expression of Cpa3, Reln, and the glial transcription factor EOMES, while MMP9‐/‐ mice demonstrated increased expression of PECAM1, Hira, Myd88, and Pink1. Although MMP9‐/‐ mice displayed a trend toward fewer microbleeds, the difference was not statistically significant. Conclusion: Our findings suggest that MMP9 plays a key role in the inflammatory response associated with HHcy‐induced cSVD. The absence of MMP9 led to reduced expression of several inflammation‐related genes as well as an increase in ECM interacting genes from macrophages, though differences in gene expression profiles between wild‐type and MMP9‐/‐ mice highlight distinct molecular pathways. Further studies are needed to fully understand MMP9's role in cSVD progression.
A novel commensal Neisseria species harboring the gonococcal diagnostic marker DR-9 causes false-positive Roche cobas NAAT results
(American Society for Microbiology, 2025) Ayala, Julio C.; Hutton, Shelby M.; Cartee, John C.; Reimche, Jennifer L.; Joseph, Sandeep J.; Herrod, Bridgett; LaPoint, Halie; Cao, Linda; Baldwin, Tamara; Gainey, Youli; Ermel, Aaron C.; Williams, James A.; Palavecino, Elizabeth; St. Cyr, Sancta B.; Schmerer, Matthew W.; Kersh, Ellen N.; Medicine, School of Medicine
Neisseria gonorrhoeae (Ng), the etiologic agent of gonorrhea, is the second most reported bacterial sexually transmitted infection globally. In the USA, nucleic acid amplification tests (NAATs) are considered the gold standard for diagnosis. Although NAATs are sensitive and offer high throughput, cross-reactivity with commensal Neisseria can compromise specificity. Here, we report the isolation and characterization of a novel commensal Neisseria sp. from the oropharynx of a patient with suspected gonococcal treatment failure. An initial diagnosis was made using the Roche cobas CT/NG test on the cobas 8800 system, which repeatedly yielded positive results post-treatment. A confirmatory Aptima Combo 2 (AC2, Hologic) test was negative, and multiple culture attempts failed to isolate Ng. Instead, a commensal Neisseria strain was recovered. Whole-genome sequencing revealed this isolate shared partial genomic identity with several Neisseria spp., including Ng, and carried a distinct region encoding the gonococcal diagnostic marker DR-9, the target of cobas assays. Cross-reactivity was confirmed with the cobas 4800 and 6800 platforms, but not with the AC2 assay targeting 16S rRNA. We discuss the possible origins of the DR-9 marker on this strain as well as examine its antimicrobial susceptibility profile and genomic resistance markers. These findings highlight the potential for misdiagnosis and unnecessary treatment when commensal Neisseria species harbor Ng diagnostic targets. Our study underscores the need for genomic surveillance of Ng and commensal Neisseria, not only to monitor diagnostic performance but also to track commensals that may serve as reservoirs of antimicrobial resistance determinants and contribute to the spread of resistance.IMPORTANCEAccurate diagnosis of gonorrhea is critical for effective treatment and antimicrobial stewardship. Nucleic acid amplification tests, the mainstay of gonococcal diagnostic testing, can yield false-positive results due to genetic overlap between Neisseria gonorrhoeae and commensal Neisseria species, especially from extragenital sites like the oropharynx. Prior studies, such as Hopkins et al. (2023), have recognized this limitation and proposed supplemental tests to improve specificity for oropharyngeal specimens. Here, we describe a novel commensal Neisseria strain isolated from a patient with suspected treatment failure that harbors the gonococcal diagnostic marker DR-9. This case highlights the need for confirmatory testing using an alternate gene target in cases where repeated positive tests are obtained with extragenital specimens and demonstrates the need for improved test specificity, particularly for anatomical sites such as the pharynx, which has high commensal diversity. Enhanced molecular surveillance of commensal Neisseria populations will be vital for understanding and minimizing diagnostic cross-reactivity.
Novel Biomolecule‐Infused Gelatin Injectable for Treatment of Recurrent Laryngeal Nerve Injury
(Wiley, 2025) Tadikonda, Ananya; Anekal, Sunjay; Chen, Lena W.; Sobczak, Gabriel; Wesson, Troy; Jackson, Carmilya; Egan, Marisa A.; Liu, Julie C.; Finnegan, Patrick R.; Halum, Stacey; Otolaryngology -- Head and Neck Surgery, School of Medicine
Objective: Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve injury (RLN) is a major cause of voice disorders. We have recently identified three biomolecules (agrin, acetylcholine, and neuregulin) with the potential to promote reinnervation after RLN injury. This study aimed to determine if a gelatin injectable with the reinnervating biomolecules will induce site-specific amplification of neurotrophic factor release and reinnervation after RLN injury in unilateral vocal fold paralysis. Methods: C57BL/6 mice underwent RLN transection with the following treatment allocations: saline control (N = 16), biomolecule cocktail only (N = 16), and biomolecule-infused gelatin (N = 16). All injectables were delivered into the denervated thyroarytenoid muscle. Assessment of glottic function was determined via laryngeal electromyography (L-EMG) and stimulated video laryngoscopy post-RLN transection on days 7 and 28. Histopathology analysis via immunohistochemistry (IHC) and genetic analysis via quantitative polymerase chain reaction (qPCR) were utilized to characterize reinnervation and gene expression changes within the harvested larynges. Results: Both biomolecule treatment groups had enhanced reinnervation of the adductor complex, as indicated by higher stimulated L-EMG area under the curve (p < 0.001), adduction during stimulation (p < 0.002), midline resting position (p < 0.002), and the presence of innervated neuromuscular junctions on IHC. qPCR results suggest both biomolecule treatments resulted in elevated neurotrophic and angiogenic factor expression from the injected muscle. Conclusions: Injectable biomolecule-infused gelatin may serve as a novel long-term therapeutic for glottic functional restoration by redirecting existing mechanisms of synkinesis via site-specific neurotrophic factor release.
The Editorial Decision-Making Process: Evaluating Aims & Scope Alignment
(SAGE Publications, 2025-03-01) Herzog, Patricia Snell
This editorial describes the decision-making process involved in the peer-reviewed interdisciplinary social science journal Review of Religious Research . Inspired by visuals of how a bill becomes a law, this decision-tree visualization walks readers through the process for how a manuscript becomes a published article. Article publication is a social process that involves many experts: the editor plus multiple reviewers and sometimes editorial board members. This step-by-step description leads toward three important takeaways. First is myth busting editorial gatekeeping by recognizing the importance of peer reviewers and editorial board members. Second is a rationale for reviewer recommendations to editors and explanation of what is acceptable to state directly to authors versus the role of confidential comments to the editor. Third is the crucial importance of the journal Aims & Scope in assessing fit with this journal. Clarifying how manuscript decisions get made can build author understanding, further socialize reviewers, and accentuate the weight of editorial board member input for quality reviewing.
Decentralized Biobanking Pathway to Precision Medicine: Futures Study
(JMIR, 2025-12-01) Gross, Marielle; Dewan, Ananya; Sabharwal, Kennedy; Linkous, Amanda; Eifler, M.; Sanchez, William; Miller, Robert; Macis, Mario; Rubin, Joshua C.; Radiation Oncology, School of Medicine
Background: Biobank privacy policies remove identifiers from donated specimens, siloing patients, discounting multimodal data, and hindering precision medicine. Decentralized biobanking is a new paradigm that unlocks value by uniting patients, specimens, scientists, and physicians in a blockchain-backed platform with robust incentives, governance, and ethical oversight. Informed by a real-world pilot, this mixed methods futures study explores how we advance decentralized biobanking from theory to practice. Objective: This study aimed to define the implementation strategy, synthesize pilot experiences into future vision, and highlight the implications and potential roadblocks. Methods: We applied backcasting from 2021 to 2024 through ethnography, alignment exercises, surveys, interviews, site visits, and futures workshops to map biospecimen supply chains and define principles for decentralized biobanking, using a breast cancer biobank for prototyping and software development. A decentralized biobanking app was piloted to engage breast cancer biobank members in participatory visioning. Thematic analysis of pilot experiences revealed a technology-enabled future vision. We systematically analyzed the pilot event via a Futures Wheel, organizing participant quotes as first-order effects, indirect effects, and anticipated implications. Results: Backcasting unveiled a pathway for designing an initial app for patients to track their biospecimens within institutional databases. We defined the "rails, rules, and tools" for a long-term, effective, and structurally just Biomediverse. Pilot enrollment was robust, and concurrent biobank enrollment was increased. Qualitative themes revealed impact on dignity, recognition, understanding, belonging, ownership, and empowerment. A vision for the future emerged from user journeys: "From 'Lab Rat' to Research Partner," vividly depicted as a path transitioning from sterile graveyard to flourishing community garden. Primary themes were matched to first-order effects, indirect effects, and future implications, culminating in gratitude and unity, network effects reinforced by reciprocity, as well as potential for compensation and precision medicine. Conclusions: Reconnecting patients with their donated biospecimens via decentralized biobanking apps unlocks value for patients and aligns incentives across the Biomediverse. We illuminate the future person-centered biomedical data economy and put forward the goal of enabling all US biospecimen donors with decentralized biobanking by 2030.
Cost-effectiveness protocol for treating adult HIV-infected patients with Kaposi sarcoma in resource-limited settings: a phase III, randomized, open-label, non-inferiority study of paclitaxel and pegylated liposomal doxorubicin
(BioMed Central, 2025-11-24) Chapola, John C.; Kleber, Selena L.; Krown, Susan E.; Painschab, Matthew; Medicine, School of Medicine
Background: This paper presents the rationale and plan for a cost-effectiveness analysis conducted alongside an open-label, prospective, randomized, two-arm, multicenter, non-inferiority study by the Consortium for Advancing the Prevention and Management of Cancer in People with HIV (AMC) in sub-Saharan Africa. The study compares two commonly used chemotherapy agents, paclitaxel (PTX) and pegylated liposomal doxorubicin (PLD), administered intravenously with concomitant antiretroviral therapy (ART) for the treatment of adult persons living with Human Immunodeficiency Virus (HIV) (PLWH) with severe Kaposi sarcoma (KS) according to WHO guidelines. The two regimens are commonly used in high-resource settings but have not been formally compared in lower-resource settings. Methods: This study uses a decision-tree model to evaluate the cost-effectiveness of PTX versus PLD for treating severe KS in adults living with HIV. A health system perspective and a two-year time horizon will be applied. Costs, including medications, labs, and hospitalizations, will be estimated using micro-costing and time-and-motion analyses. Health outcomes will be measured in Quality Adjusted Life years using PROMIS 29 + 2 utility scores. Sensitivity analyses will include Daily adjusted life years and Years of Life Lost. Discussion: This research will provide valuable insights into the cost-effectiveness of these treatments in managing KS. The results of this analysis will have important implications for healthcare providers and policymakers, offering guidance on the optimal treatment approach for HIV-infected individuals with KS.
Negating the Finite, Negating the Infinite: What’s Up with Negation at the Origin of Philosophy?
(2025-04-08) De Tienne, Andre
This PowerPoint-based presentation discusses research in the metaphysics of negation. It is concerned with the concept of origin and origination from the standpoint of a cosmogonic metaphysics and grounds the inquiry in the Presocratic approach to it, including Hesiod, Thales, Anaximander (and his conception of the apeiron), itself compared with Anaximenes's “aerometaphysics.” The presentation includes a comparison with Charles Peirce's own metaphysics of the original Nothing.
Civic Integration of Displaced Youth: Immigrant Organizations and Police Athletic Leagues as Examples of Methods for Nonprofit Analyses
(Emerald, 2025-09-25) Paarlberg, Afshan; Estorcien, Vernise; Herzog, Patricia Snell
This chapter focuses on displaced youth civic integration and the role of nonprofit initiatives. The first section summarizes immigrant and youth civic integration. These theories are then explored within applications to studying philanthropic organizations that provide immigrant legal aid and mentoring to displaced youth. Then, two empirical examples are presented. The first example explores the role of immigrant nonprofits in supporting the legal rights and social inclusion of children and youth refugees, asylum seekers, and unaccompanied minors. The second example examines refugees and asylum seekers within a broader context of youth mentoring activities in police athletic leagues (PALs). Both examples illustrate how researchers can access existing national public big data sources based on nonprofit 990 tax forms, navigate the limitations of pre-existing categorizations in identifying specific types of nonprofits, and identify a relevant sample of philanthropic and nonprofit organizations. In describing the processes in these two examples, this chapter aims to help emerging scholars and researchers understand more generally how studies can draw upon existing data while integrating a particular lens based on the study’s aims, in this case by focusing on organizations serving displaced youth.
The Clinical View of Sepsis-Associated AKI: How Basic Science Can Help Solve This Problem
(Elsevier, 2025) Odum, James D.; Hasson, Denise C.; Stanski, Natalja L.; Gómez, Hernando; Soranno, Danielle E.; Pediatrics, School of Medicine
The global health impact of sepsis is difficult to understate. As a complication of sepsis, the development of sepsis-associated acute kidney injury (SA-AKI) significantly increases the risk of mortality. Although several epidemiological risk factors for SA-AKI are known, the heterogeneity of this syndrome-across patients, pathogens, and treatment responses-has hindered therapeutic innovation and contributed to persistently poor outcomes. Precision medicine offers a promising framework to address this complexity, yet a substantial translational gap remains between mechanistic insights from preclinical models and the therapeutic strategies used in clinical practice. To bridge this gap, researchers should consider aligning preclinical models with human sepsis and embrace SA-AKI heterogeneity to identify treatable, mechanistically informed subtypes (endotypes). These efforts could enable the development of personalized therapies aimed at reducing the burden of SA-AKI.

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