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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Now showing 1 - 10 of 37844

Transforming Advanced Heart Failure Programs: Addressing Institutional and Systemic Drivers of Racial and Ethnic Disparities in Care
(Wolters Kluwer, 2026) Dixon, Debra D.; Lewsey, Sabra C.; Contreras, Johanna; Shah, Kevin S.; Deen, Jason; Breathett, Khadijah; Medicine, School of Medicine
Institutional and systemic practices and policies contribute to lower-quality care and adverse outcomes among diverse racial and ethnic groups and individuals with limited economic resources. There are ample opportunities to change the trajectory of patients with heart failure (HF) across racial and ethnic groups. Multiple studies and quality improvement initiatives have demonstrated strategies to improve the care of diverse racial and ethnic populations living with HF, yet dissemination remains limited. This state-of-the-art review examines structural racism in the context of HF, outlines evidence-based strategies for HF programs to improve access to advanced HF therapies and reduce disparities in treatment outcomes, and discusses priorities for implementation and dissemination science efforts to address structural causes of disparities in HF care.
Alcohol consumption and risk of atrial fibrillation: a pairwise and network meta-analysis
(Oxford University Press, 2026) Asad, Zain Ul Abideen; Jafry, Ali Haider; Akbar, Usman; Beard, Christopher; Khan, Jehanzeb Ahmed; Krishan, Satyam; Hurera, Muhammad; Raza, Syeda Maheen; Clifton, Shari; Reese, Jessica; Khan, Safi U.; Gopinathannair, Rakesh; Torbey, Estelle; Po, Sunny S.; Baber, Usman; Stavrakis, Stavros; Sanders, Prashanthan; Medicine, School of Medicine
Aims: Despite well-established evidence linking alcohol consumption to an increased risk of atrial fibrillation (AF), a clear threshold for safe intake remains undefined. Most clinical guidelines recommend abstinence or moderation, but lack specificity regarding quantitative limits and evidence-based thresholds for primary prevention of AF. Methods and results: We performed this systematic review, pairwise meta-analysis, and network meta-analysis to assess the association and dose-response relationship between varying quantities of alcohol consumption and incident AF. The predefined alcohol intake categories included: no intake, very low (<12 g/day), low (12.1-24 g/day), moderate (24.1-48 g/day), high (48.1-60 g/day), and very high (>60 g/day). The pairwise meta-analyses compared each intake category to no intake, and a frequentist network meta-analysis was conducted to integrate direct and indirect comparisons. Pooled risk ratio (RR) for AF incidence were estimated using random-effects models, and a subgroup analysis by sex was performed. Twenty-six studies with nearly 15 million participants were included. As compared to those with no alcohol intake, very high alcohol intake was associated with a 75% increased risk of incident AF (RR 1.75; 95% CI: 1.25-2.44, P = 0.04), intake below 48 g/day was associated with modestly lower AF risk, and the lowest risk was observed at <12 g/day (RR 0.72; 95% CI: 0.63-0.83). The weighted mean follow-up was approximately 6.4 years. Network meta-analysis confirmed these findings and demonstrated a significantly increased AF risk with very high compared to low (RR 1.91), moderate (RR 2.03), and high (RR 2.00) levels. Sex-stratified analyses showed similar results. Conclusion: Alcohol consumption is associated with a nonlinear, threshold-dependent relationship with incident AF. While low to moderate intake may not increase AF risk, intake beyond 60 g/day significantly increases the AF risk. These findings may suggest that a more liberal approach to alcohol consumption, particularly at low to moderate levels, could be reasonable in the general population, though further prospective studies are needed to confirm causality and refine individual risk stratification.
Structural polymorphism of ex-vivo ALECT2 amyloid fibrils revealed by cryo-EM
(Springer Nature, 2026-04-11) Afrin, Shumaila; Nguyen, Binh An; Singh, Virender; Singh, Preeti; Bassett, Parker; Pekala, Maja; Evers, Bret; Lopez, Christian; Ahmed, Yasmin; Li, Li; Kallem, Raja Reddy; Lemoff, Andrew; Argyropoulos, Christos; Kluve-Beckerman, Barbara; Saelices, Lorena; Pathology and Laboratory Medicine, School of Medicine
ALECT2 amyloidosis is a rare systemic disease characterized by the pathological deposition of leukocyte cell-derived chemotaxin-2 (LECT2) as amyloid fibrils, primarily affecting the kidneys and liver. The molecular mechanisms underlying LECT2 aggregation remain poorly defined, hindering diagnostic and therapeutic development. Here, we present cryo-electron microscopy structures of ex-vivo ALECT2 fibrils extracted from a patient's kidney. We identified three fibril polymorphs: a predominant single-protofilament morphology and two minor double-protofilament morphologies. The dominant single-protofilament morphology comprises the full-length 133-residue LECT2 protein and retains all three native disulfide bonds. Low-resolution reconstructions of double-protofilament morphologies suggest they adopt a similar fold to the single protofilament morphology, but form paired assemblies with different inter-filament interfaces. Mass spectrometry also reveals acetylation within the fibrils. These findings offer critical insights into the structural basis of ALECT2 amyloid formation and identify molecular features that could inform future diagnostic and therapeutic approaches.
Old vs. new local ancestry inference in HCHS/SOL: a comparative study
(Oxford University Press, 2025) Chen, Xueying; Wang, Hao; Broce, Iris; Dale, Anders; Yu, Bing; Zhou, Laura Y.; Li, Xihao; Argos, Maria; Daviglus, Martha L.; Cai, Jianwen; Franceschini, Nora; Sofer, Tamar; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Hispanic/Latino populations are admixed, with genetic contributions from multiple ancestral populations. To uncover genetic associations in these populations, researchers often turn to admixture mapping, which relies on inferred counts of "local" ancestry, i.e. the source ancestral population at a locus. Local ancestries are inferred using external reference panels that represent ancestral populations, making the choice of inference method and reference panel critical. This study used a dataset of Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to evaluate how updates in local ancestry inference (LAI) affect results, specifically, the 'old' LAI performed using a popular inference method RFMix alongside 'new' inferences performed using Fast Local Ancestry Estimation (FLARE) with an updated reference panel. We compared their performance in terms of global and local ancestry correlations, as well as admixture mapping-based associations. Overall, the old and new inferences produced highly similar global and local ancestry estimates, with FLARE-based results closely matching those from RFMix in admixture mapping analyses. However, in some genomic regions, the old and new local ancestries showed relatively lower correlations (Pearson R < 0.9). Most of these regions (86.42%) were mapped to either ENCODE blacklist regions or gene clusters, compared to 7.67% of randomly-matched regions with high correlations (Pearson R > 0.97). These findings show that old and new inferences largely agree and suggest that regions of lower agreement are mostly due to genomic sequence contexts that lead to less stable inference, rather than due to the LAI software or genotyping technology used.
Clinical significance of sleepiness: an American Academy of Sleep Medicine position statement
(Springer Nature, 2025) Heffron, Thomas M.; Gurubhagavatula, Indira; Trotti, Lynn Marie; Abbasi-Feinberg, Fariha; Abreu, Alexandre Rocha; Bandyopadhyay, Anuja; Kapur, Vishesh K.; Kuhlmann, David; Martin, Jennifer L.; Olson, Eric J.; Patil, Susheel P.; Shelgikar, Anita V.; Wickwire, Emerson M.; Rowley, James A.; Pediatrics, School of Medicine
Alertness is a necessity for well-being and performance, and sleepiness is associated with cognitive and functional impairments that can have a negative impact on performance, health, mood, safety, and quality of life. In severe cases, sleepiness can lead to debilitation, injury, or death. Sleepiness is a marker of insufficient sleep and is the major patient-reported symptom associated with disorders of sleep and wakefulness such as narcolepsy and obstructive sleep apnea. Excessive sleepiness—the inability to stay awake and alert during the major waking episodes of the day—is reported by one third of US adults. It is the position of the American Academy of Sleep Medicine that sleepiness is a critical patient-reported outcome that is associated with increased risk for adverse health effects and diminished quality of life. The evaluation and management of sleepiness is essential for patient safety and patient-centered care. The health care system must support the evaluation and management of sleepiness so that patients can experience restorative sleep and daytime alertness. More research and innovation are needed to improve the treatment of sleep–wake disorders, including studies in diverse populations that support the development of tailored therapies for daytime sleepiness.
Analysis approaches to combine error-prone data with a subset of validated data: an application to a multinational study of Kaposi sarcoma and HIV
(Oxford University Press, 2026-01-22) Slone, Joshua; Amorim, Gustavo; Semeere, Aggrey; Diero, Lameck; Otero, Larissa; Crabtree-Ramirez, Brenda; Tao, Ran; Duda, Stephany; Musick, Beverly; Yiannoutsos, Constantin; Lumley, Thomas; Shaw, Pamela A.; Shepherd, Bryan E.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Nitrogen Balance and Protein Quality Ingestion in Pregnant Women: Characterizing a Nutritional Scenario in a Pilot Study in Mexico
(Wiley, 2026-05-29) Granich-Armenta, Adriana; Cantoral, Alejandra; Mariscal-Moreno, Rosa María; Castiblanco-Rubio, Gina; Ramírez-Silva, Ivonne; Mendoza Jimenez, Melanie Y.; Martinez-Mier, E. Angeles; Ávila-Jiméne, Laura; Rivera Dommarco, Juan A; Dental Public Health and Dental Informatics, School of Dentistry
Nitrogen balance (NB) reflects protein metabolism and varies with diet quality. We aimed to estimate the NB using objective standardized methods and evaluate the adequacy and quality of protein intake in Mexican pregnant women. This pilot study was nested in the MAS‐Lactancia cohort and included 13 pregnant women in their third trimester. Diet was assessed through the duplicate portion method (DPM) and food diaries on two non‐consecutive days. A registered dietitian analyzed photos, recipes, and portion sizes to assess dietary quality using NOVA classification. DPM samples were analyzed by Kjeldahl method to determine nitrogen content. On the same days, 24 h‐urine was collected to measure urea and total nitrogen excretion. NB was calculated per day. The Kruskal Wallis test compares the characteristics of the participants according to NB. Mean age (SD) was 27.9 (4.2) years, at 33 (3.4) gestational weeks. Median nitrogen intake was 6.75 g/day (IQR: 6.40–9.74), representing 0.64 g protein/Kg body weight by day (IQR: 0.45–0.92). Median NB was 1.32 g (IQR: −0.15 to 2.63), with 30.7% of women in negative, 23.2% in neutral, and 46.1% in positive balance (+2). Diet quality showed high carbohydrate intake (> 70% of total calories), mainly from ultra‐processed foods. Protein came in moderate amounts from foods containing 15%–95% of the edible portion. Negative NB was more common among women with higher BMI and lower education. Over half of pregnant women were in negative or neutral NB, indicating insufficient protein intake from limited sources and low diet quality.
Cryo-EM reveals structural variability of apolipoprotein A-I amyloid fibrils across organs, mutations, and clinical presentations
(Springer Nature, 2026-04-17) Nguyen, Binh An; Fernandez-Ramirez, Maria del Carmen; Bassett, Parker; Singh, Virender; Singh, Preeti; Pękała, Maja; Villalon, Layla; Ahmed, Yasmin; Lemoff, Andrew; Evers, Bret; Lopez, Christian; Kluve-Beckerman, Barbara; Saelices, Lorena; Pathology and Laboratory Medicine, School of Medicine
Hereditary apolipoprotein A-I (AApoA‑I) amyloidosis is a rare systemic disease caused by the deposition of amyloid fibrils formed by apolipoprotein A‑I in multiple organs, leading to severe clinical outcomes. With no available therapies or diagnostic tools, defining the structure of AApoA‑I fibrils is crucial to understanding disease mechanisms and guiding intervention. Here we use cryo-electron microscopy to analyze AApoA‑I fibrils from the heart, kidney, liver, and spleen of patients carrying G26R, L90P, and R173P mutations. G26R fibrils, regardless of organ, exhibits untwisted morphologies and cannot be resolved structurally. Conversely, L90P and R173P fibrils display a compact diabolo-shaped conformation in all organs analyzed. Their high-resolution maps enable visualization of cis-Proline 66, which may represent a potential conformational switch during fibril formation. Our findings suggest that mutation-driven polymorphism may influence organ tropism and clinical presentation. This work advances our understanding of AApoA‑I fibril assembly and provides insights toward developing targeted clinical tools.
Large Language Models for Translational Cancer Informatics
(American Society of Clinical Oncology, 2025) Pan, Yining; Wang, Yanfei; Wang, Guangyu; Su, Jing; Topaloglu, Umit; Song, Qianqian; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Purpose: Cancer remains a leading cause of death worldwide. The growing volume of high-throughput single-cell and spatial transcriptomic data sets-particularly those related to cancer-offers immense opportunities as well as analytical challenges for effective data analysis and interpretation. Large language models (LLMs), pretrained on vast data sets and capable of various biomedical tasks, offer a promising solution. This review explores the application of LLMs in cancer research from both cellular and pathologic perspectives, aiming to showcase their potential in advancing precision oncology. Materials and methods: We systematically review current LLMs in analyzing single-cell RNA sequencing, spatial transcriptomic, and histology image data, emphasizing their relevance to cancer biology and translational research. Results: A total of 24 LLMs, published or in preprint between 2022 and 2025, were selected for review. In single-cell transcriptomics, LLMs have primarily been used for cell type annotation, batch integration, and drug-response prediction. In spatial transcriptomics, LLMs support multislide and multimodal spatial data integration, gene expression imputation, niche and region label prediction, spatial domain identification, cell-cell communication inference, and marker gene detection. In computational pathology, LLMs have been applied to cancer subtyping, detection of rare malignancies, genomic mutation prediction, image segmentation, as well as cross-modal retrieval. Despite these advances, many models remain underoptimized for cancer-specific applications, highlighting the need for domain-specific fine-tuning and scalable adaptation strategies. Conclusion: LLMs have the potential to significantly advance cancer research by providing scalable and effective tools for analyzing and interpreting single-cell, spatial transcriptomic, and pathology data. Future efforts should prioritize tailoring these models to cancer-specific contexts to enhance their utility in uncovering disease mechanisms, identifying biomarkers, and informing therapeutic strategies.
Infant Respiratory Syncytial Virus Immunization Coverage in the Vaccine Safety Datalink: 2023–2024
(American Academy of Pediatrics, 2025) Irving, Stephanie A.; Crane, Bradley; Weintraub, Eric S.; Patel, Suchita A.; Razzaghi, Hilda; Daley, Matthew F.; Dixon, Brian; Donahue, James G.; Fuller, Candace C.; Fuller, Sharon; Getahun, Darios; Glenn, Sungching C.; Hambidge, Simon J.; Jackson, Lisa A.; Jacobson, Karen B.; Kharbanda, Elyse O.; Maro, Judith C.; O'Leary, Sean T.; Schmidt, Teresa; Sznajder, Katharine; Weinfield, Nancy S.; Williams, Joshua T. B.; Zerbo, Ousseny; Naleway, Allison L.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Background and objectives: In 2023, the Advisory Committee on Immunization Practices recommended either Abrysvo, a vaccine administered during pregnancy, or nirsevimab, a monoclonal antibody administered to infants after birth, to protect infants from respiratory syncytial virus (RSV). Our objective was to assess the proportion of infants immunized against RSV through antenatal RSV vaccination or receipt of nirsevimab among linked pregnancy-infant dyads. Methods: Using data from 10 Vaccine Safety Datalink health systems and a validated algorithm, we identified pregnant women aged 12 to 55 years with a live birth of 32 weeks' gestation or more from September 22, 2023, through March 31, 2024. We identified RSV vaccination using electronic health records supplemented with immunization information system (registry) data. Among infants from eligible pregnancies, we identified nirsevimab administered through March 31, 2024. We assessed infant RSV immunization, defined as exposure to antenatal RSV vaccination or receipt of nirsevimab, stratified by race and ethnicity, age, and birth month. Results: A total of 36 949 eligible infants were included from 43 722 pregnancies. Overall, 72% of infants were immunized against RSV; estimates were highest among infants born to non-Hispanic (NH) Asian mothers (84%). Disparities were identified by race, with 60% coverage among infants born to NH Black or NH Middle Eastern or North African mothers. Coverage was 59% to 78% by birth month, with nirsevimab more commonly administered to infants born earlier in the season. Conclusions: In this population of infants, 72% were immunized against RSV. Although overall coverage was high, disparities in immunization by race and ethnicity are a call to action.

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