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 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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Now showing 1 - 10 of 29173

Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders
(Springer Nature, 2025-03-12) Sheth, Udit; Öijerstedt, Linn; Heckman, Michael G.; White, Launia J.; Heuer, Hilary W.; Lago, Argentina Lario; Forsberg, Leah K.; Faber, Kelley M.; Foroud, Tatiana M.; Rademakers, Rosa; Ramos, Eliana Marisa; Appleby, Brian S.; Bozoki, Andrea C.; Darby, R. Ryan; Dickerson, Bradford C.; Domoto-Reilly, Kimiko; Galasko, Douglas R.; Ghoshal, Nupur; Graff-Radford, Neill R.; Grant, Ian M.; Hales, Chadwick M.; Hsiung, Ging-Yuek Robin; Huey, Edward D.; Irwin, David; Kwan, Justin Y.; Litvan, Irene; Mackenzie, Ian R.; Masdeu, Joseph C.; Mendez, Mario F.; Onyike, Chiadi U.; Pascual, Belen; Pressman, Peter S.; Roberson, Erik D.; Snyder, Allison; Tartaglia, M. Carmela; Seeley, William W.; Dickson, Dennis W.; Rosen, Howard J.; Boeve, Bradley F.; Boxer, Adam L.; Petrucelli, Leonard; Gendron, Tania F.; Medical and Molecular Genetics, School of Medicine
Background: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker. Methods: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and longitudinal examination of the susceptibility/risk, prognostic, and predictive performance of GFAP and NfL in the largest series of well-characterized presymptomatic FTD mutation carriers and participants with sporadic or familial FTD syndromes. Utilizing single molecule array technology, we measured GFAP and NfL in plasma from 161 controls, 127 presymptomatic mutation carriers, 702 participants with a FTD syndrome, and 67 participants with mild behavioral and/or cognitive changes. We used multivariable linear regression and Cox proportional hazard models adjusted for co-variates to examine the biomarker utility of baseline GFAP and NfL concentrations or their rates of change. Results: Compared to controls, GFAP and NfL were elevated in each FTD syndrome but GFAP, unlike NfL, poorly discriminated controls from participants with mild symptoms. Similarly, both baseline GFAP and NfL were higher in presymptomatic mutation carriers who later phenoconverted, but NfL better distinguished non-converters from phenoconverters. We additionally observed that GFAP and NfL were associated with disease severity indicators and survival, but NfL far outperformed GFAP. Nevertheless, we validated findings that the GFAP/NfL ratio may discriminate frontotemporal lobar degeneration with tau versus TDP-43 pathology. Conclusions: Our head-to-head comparison of plasma GFAP and NfL as biomarkers for FTD indicate that NfL consistently outmatched GFAP as a prognostic and predictive biomarker for participants with a FTD syndrome, and as a susceptibility/risk biomarker for people at genetic risk of FTD. Our findings underscore the need to include leading biomarkers in investigations evaluating new biomarkers if the field is to fully ascertain their performance and clinical value.
Prophylactic Absorbable Antibiotic Beads: Effect on Postoperative Drain Management Following Breast Reconstruction
(Wolters Kluwer, 2025-03-03) Ahmed, Shahnur; Hajj, John P.; Bamba, Ravinder; Danforth, Rachel M.; VonDerHaar, Richard Jason; Lester, Mary E.; Hassanein, Aladdin H.; Surgery, School of Medicine
Characterization, Enrichment, and Computational Modeling of Cross-Linked Actin Networks in Transformed Trabecular Meshwork Cells
(Association for Research in Vision and Ophthalmology, 2025) Li, Haiyan; Harvey, Devon H.; Dai, Jiannong; Swingle, Steven P.; Compton, Anthony M.; Sugali, Chenna Kesavulu; Dhamodaran, Kamesh; Yao, Jing; Lin, Tsai-Yu; Sulchek, Todd; Kim, Taeyoon; Ethier, C. Ross; Mao, Weiming; Ophthalmology, School of Medicine
Purpose: Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM). We previously developed the GTM3L cell line, which spontaneously forms fluorescently labeled CLANs, by transducing GTM3, a transformed glaucomatous TM cell line, with a lentivirus expressing the LifeAct-GFP fusion protein. Here, we determined if LifeAct-GFP viral copy numbers are associated with CLANs, developed approaches to increase CLAN incidence, and computationally studied the biomechanical properties of CLAN-containing GTM3L cells. Methods: GTM3L cells were fluorescently sorted for viral copy number analysis to determine whether increased CLAN incidence was associated with copy number. CLAN incidence was increased by combining (1) differential adhesion sorting, (2) cell deswelling, and (3) cell stiffness selection. GTM3L cells were cultured on glass or soft hydrogels for stiffness measurement by atomic force microscopy. Computational models studied the biomechanical properties of CLANs. Results: GTM3L cells had one LifeAct-GFP viral copy/cell on average, and viral copy number or LifeAct-GFP expression level did not associate with CLAN incidence rate. However, CLAN rate was increased from -0.28% to -50% by combining the three enrichment methods noted above. Further, GTM3L cells formed more CLANs on a stiff versus a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus. Conclusions: It is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the biomechanics, mechanobiology, and etiology of CLANs in the TM.
Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease
(Wiley, 2025) Brown, Ethan G.; Chahine, Lana M.; Siderowf, Andrew; Gochanour, Caroline; Kurth, Ryan; Marshall, Micah J.; Caspell-Garcia, Chelsea; Brumm, Michael C.; Stanley, Craig E., Jr.; Korell, Monica; McMahon, Bridget; Kuhl, Maggie; Fabrizio, Kimberly; Heathers, Laura; Concha-Marambio, Luis; Soto, Claudio; Chowdhury, Sohini; Coffey, Christopher S.; Foroud, Tatiana M.; Simuni, Tanya; Marek, Kenneth; Tanner, Caroline M.; Parkinson Progression Marker Initiative; Medical and Molecular Genetics, School of Medicine
Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation. Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in longitudinal assessments and further biomarker evaluation including cerebrospinal fluid alpha-synuclein seed amplification assay (aSynSAA). Results: As of January 29, 2024, 49,843 participants were sent an UPSIT and 31,293 (63%) completed it. Of UPSIT completers, 8,301 (27%) scored <15th percentile. Of 1,546 who completed DAT-SPECT, 1,060 (69%) had DAT-SPECT binding <100% expected for age and sex. Participants with an UPSIT <10th percentile (n = 1,221) had greater likelihood of low DAT-SPECT binding compared to participants with an UPSIT in the 10th to 15th percentile (odds ratio, 3.01; 95% confidence interval, 1.85-4.91). Overall, 55% (198/363) of cases with UPSIT <15th percentile and DAT-SPECT <100% had positive aSynSAA, which increased to 70% (182/260) when selecting for more severe hyposmia (UPSIT <10th percentile). Interpretation: Remote screening for hyposmia and reduced DAT-SPECT binding identifies participants with a high proportion positive aSynSAA. Longitudinal data will be essential to define progression patterns in these individuals to ultimately inform recruitment into disease modification clinical trials.
Alleviating the emotional burden on families during organ donation requests in neurologic patients declared with brain death: the role of timing and circumstances of death
(Springer Nature, 2025-03-11) Powla, Plamena P.; Turaka, Deekshitha; Fakhri, Farima; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Organ donation requests to families often occur during moments of profound grief and create an emotional burden that is compounded by the varying emotional responses to circumstances surrounding death. These responses, in turn, interact with the timing of the request to influence authorization decisions. Understanding the interplay between timing and circumstances of death is crucial for improving authorization rates and addressing the organ donor shortage. The Organ Retrieval and Collection of Health Information for Donation database was used to identify 3,289 potential donors with neurologic mechanisms of brain death. Multivariate logistic regression with interaction between timing and circumstance was used to estimate authorization rates. Results show no significant differences in authorization for requests made within 12 h of death, regardless of circumstance. However, significant differences in authorization were observed between requests made at the time of brain death and those made 12 or more hours later for natural causes, as well as those at 24 or more hours for homicide, motor vehicle accidents, and non-motor vehicle accidents. These findings indicate that the optimal timing for organ donation requests may depend on the emotional intensity of the situation. While quicker requests may be more effective in less emotionally charged cases, extending the time for families to grieve in highly distressing circumstances does not appear to negatively impact authorization rates. Tailoring the timing of donation requests to the circumstances of death, balancing sensitivity with the need for prompt decision-making, could reduce families' emotional burden, ease pressure in decision-making, and help address the shortage of organ donors.
Time to Develop Guidelines for Spiritual Care in Serious Illness
(Mary Ann Liebert, 2024-09-06) Varner-Perez, Shelley E.; Comer, Amber R.; Fitchett, George; Medicine, School of Medicine
In 2022, a JAMA systematic review of 342 high quality studies called for spiritual care to be a routine part of care for patients with serious illness. The review's multidisciplinary panel made several recommendations for addressing patients' and families' spiritual concerns. Despite these evidence-based recommendations, there are no clinical guidelines that inform when and how such spiritual care should be provided. We propose convening a multi-disciplinary workgroup to generate specific and actionable guidelines for incorporating spiritual care in serious illness care. We suggest three workgroup priorities: (1) determining best approaches to identifying patient and family members' spiritual care needs; (2) developing ways to integrate chaplains into routine clinical care; and (3) determining best approaches to communicate availability of spiritual care. Developing these guidelines is an imperative next step to deliver high quality, person and family-centered care.
LRRK2-associated parkinsonism with and without in vivo evidence of alpha-synuclein aggregates: longitudinal clinical and biomarker characterization
(Oxford University Press, 2025-03-06) Chahine, Lana M.; Lafontant, David-Erick; Choi, Seung Ho; Iwaki, Hirotaka; Blauwendraat, Cornelis; Singleton, Andrew B.; Brumm, Michael C.; Alcalay, Roy N.; Merchant, Kalpana; Holohan Nudelman, Kelly Nicole; Dagher, Alain; Vo, Andrew; Tao, Qin; Venuto, Charles S.; Kieburtz, Karl; Poston, Kathleen L.; Bressman, Susan; Gonzalez-Latapi, Paulina; Avants, Brian; Coffey, Christopher; Jennings, Danna; Tolosa, Eduardo; Siderowf, Andrew; Marek, Ken; Simuni, Tatyana; Parkinson’s Progression Markers Initiative; Medical and Molecular Genetics, School of Medicine
Among LRRK2-associated parkinsonism cases with nigral degeneration, over two-thirds demonstrate evidence of pathologic alpha-synuclein, but many do not. Understanding the clinical phenotype and underlying biology in such individuals is critical for therapeutic development. Our objective was to compare clinical and biomarker features, and rate of progression over 4 years of follow-up, among LRRK2-associated parkinsonism cases with and without in vivo evidence of alpha-synuclein aggregates. Data were from the Parkinson's Progression Markers Initiative, a multicentre prospective cohort study. The sample included individuals diagnosed with Parkinson disease with pathogenic variants in LRRK2. Presence of CSF alpha-synuclein aggregation was assessed with seed amplification assay. A range of clinician- and patient-reported outcome assessments were administered. Biomarkers included dopamine transporter scan, CSF amyloid-beta1-42, total tau, phospho-tau181, urine bis(monoacylglycerol)phosphate levels and serum neurofilament light chain. Linear mixed-effects (LMMs) models examined differences in trajectory in CSF-negative and CSF-positive groups. A total of 148 LRRK2 parkinsonism cases (86% with G2019S variant), 46 negative and 102 positive for CSF alpha-synuclein seed amplification assay, were included. At baseline, the negative group was older than the positive group [median (inter-quartile range) 69.1 (65.2-72.3) versus 61.5 (55.6-66.9) years, P < 0.001] and a greater proportion were female [28 (61%) versus 43 (42%), P = 0.035]. Despite being older, the negative group had similar duration since diagnosis and similar motor rating scale [16 (11-23) versus 16 (10-22), P = 0.480] though lower levodopa equivalents. Only 13 (29%) of the negative group were hyposmic, compared with 75 (77%) of the positive group. The negative group, compared with the positive group, had higher per cent-expected putamenal dopamine transporter binding for their age and sex [0.36 (0.29-0.45) versus 0.26 (0.22-0.37), P < 0.001]. Serum neurofilament light chain was higher in the negative group compared with the positive group [17.10 (13.60-22.10) versus 10.50 (8.43-14.70) pg/mL; age-adjusted P-value = 0.013]. In terms of longitudinal change, the negative group remained stable in functional rating scale score in contrast to the positive group who had a significant increase (worsening) of 0.729 per year (P = 0.037), but no other differences in trajectory were found. Among individuals diagnosed with Parkinson disease with pathogenic variants in the LRRK2 gene, we found clinical and biomarker differences in cases without versus with in vivo evidence of CSF alpha-synuclein aggregates. LRRK2 parkinsonism cases without evidence of alpha-synuclein aggregates as a group exhibit less severe motor manifestations and decline. The underlying biology in LRRK2 parkinsonism cases without evidence of alpha-synuclein aggregates requires further investigation.
Deep enteroscopy in children: techniques, applications, and future directions
(Frontiers Media, 2025-03-12) Hoskins, Brett J.; Pediatrics, School of Medicine
Deep enteroscopy, encompassing push enteroscopy (PE) and balloon-assisted enteroscopy (BAE), has revolutionized the diagnosis and treatment of pediatric small bowel disorders. This review examines the evolving role of these techniques in managing conditions such as obscure gastrointestinal bleeding, Crohn's disease, polyposis syndromes, strictures, and small bowel tumors. While PE is effective for both diagnostic and therapeutic interventions in the proximal small bowel, its limited insertion depth has driven the adoption of BAE techniques. These include single-balloon enteroscopy (SBE) and double-balloon enteroscopy (DBE), which provide deeper and more comprehensive access. Both BAE modalities offer greater insertion depth and stability, enabling advanced therapeutic interventions such as polypectomy, stricture dilation, and hemostasis. Pediatric-specific data demonstrate high diagnostic yields for BAE, with comparable outcomes between SBE and DBE. These techniques have proven safe across diverse indications, though younger children may experience slightly higher complication rates due to anatomical considerations. Despite these advancements, challenges persist, including a limited evidence base in pediatrics, barriers to training, and the need for standardized protocols. Additionally, emerging innovations such as artificial intelligence offer opportunities to enhance diagnostic accuracy and procedural efficiency. Comparative analyses of PE, BAE, and capsule endoscopy are necessary to refine procedural selection and optimize outcomes in pediatric patients. Furthermore, structured pediatric training programs and simulation-based learning could address competency gaps, ensuring safe and effective application of these techniques. By addressing current research gaps, embracing technological advancements, and tailoring approaches to pediatric populations, deep enteroscopy can continue to transform the management of small bowel disorders in children.
Impact of Fecal Microbiota Transplant Formulations, Storage Conditions, and Duration on Bacterial Viability, Functionality, and Clinical Outcomes in Patients with Recurrent Clostridioides difficile Infection
(MDPI, 2025-03-04) Shaheen, Mohamed; McDougall, Chelsea; Chan, Leona; Franz, Rose; Wong, Karen; Giebelhaus, Ryland T.; Nguyen, Gwen; Nam, Seo Lin; de la Mata, A. Paulina; Yeo, Sam; Harynuk, James J.; Pakpour, Sepideh; Xu, Huiping; Kao, Dina; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10-20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.
Bayesian mixed model inference for genetic association under related samples with brain network phenotype
(Oxford University Press, 2024) Tian, Xinyuan; Wang, Yiting; Wang, Selena; Zhao, Yi; Zhao, Yize; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Genetic association studies for brain connectivity phenotypes have gained prominence due to advances in noninvasive imaging techniques and quantitative genetics. Brain connectivity traits, characterized by network configurations and unique biological structures, present distinct challenges compared to other quantitative phenotypes. Furthermore, the presence of sample relatedness in the most imaging genetics studies limits the feasibility of adopting existing network-response modeling. In this article, we fill this gap by proposing a Bayesian network-response mixed-effect model that considers a network-variate phenotype and incorporates population structures including pedigrees and unknown sample relatedness. To accommodate the inherent topological architecture associated with the genetic contributions to the phenotype, we model the effect components via a set of effect network configurations and impose an inter-network sparsity and intra-network shrinkage to dissect the phenotypic network configurations affected by the risk genetic variant. A Markov chain Monte Carlo (MCMC) algorithm is further developed to facilitate uncertainty quantification. We evaluate the performance of our model through extensive simulations. By further applying the method to study, the genetic bases for brain structural connectivity using data from the Human Connectome Project with excessive family structures, we obtain plausible and interpretable results. Beyond brain connectivity genetic studies, our proposed model also provides a general linear mixed-effect regression framework for network-variate outcomes.

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