ScholarWorks IU Indianapolis
Not a member yet
51146 research outputs found
Sort by
Relation equivariant graph neural networks to explore the mosaic-like tissue architecture of kidney diseases on spatially resolved transcriptomics
No full textMotivation: Chronic kidney disease (CKD) and acute kidney injury (AKI) are prominent public health concerns affecting more than 15% of the global population. The ongoing development of spatially resolved transcriptomics (SRT) technologies presents a promising approach for discovering the spatial distribution patterns of gene expression within diseased tissues. However, existing computational tools are predominantly calibrated and designed on the ribbon-like structure of the brain cortex, presenting considerable computational obstacles in discerning highly heterogeneous mosaic-like tissue architectures in the kidney. Consequently, timely and cost-effective acquisition of annotation and interpretation in the kidney remains a challenge in exploring the cellular and morphological changes within renal tubules and their interstitial niches.
Results: We present an empowered graph deep learning framework, REGNN (Relation Equivariant Graph Neural Networks), designed for SRT data analyses on heterogeneous tissue structures. To increase expressive power in the SRT lattice using graph modeling, REGNN integrates equivariance to handle n-dimensional symmetries of the spatial area, while additionally leveraging Positional Encoding to strengthen relative spatial relations of the nodes uniformly distributed in the lattice. Given the limited availability of well-labeled spatial data, this framework implements both graph autoencoder and graph self-supervised learning strategies. On heterogeneous samples from different kidney conditions, REGNN outperforms existing computational tools in identifying tissue architectures within the 10× Visium platform. This framework offers a powerful graph deep learning tool for investigating tissues within highly heterogeneous expression patterns and paves the way to pinpoint underlying pathological mechanisms that contribute to the progression of complex diseases.
Availability and implementation: REGNN is publicly available at https://github.com/Mraina99/REGNN
Residents, Interrupted: A Blinded, Prospective Observational Study of Emergency Medicine Resident Workflow
No full textBackground: Emergency Medicine (EM) physicians routinely contend with frequent interruptions to their workflow, which can introduce errors and decrease efficiency. In Academic EM, residents serve as the main point of contact for patient care and are similarly susceptible to significant interruption burden. Our objective was to evaluate the number and characteristics of interruptions residents experience during an EM shift, including interruptions based on gender.
Methods: This was a double-blinded time-motion observation study that included 70 resident physicians (PGY1-PGY5). Data were collected by two trained observers who were blinded to the gender hypothesis. Each resident was observed for a 4-h block. Observations took place during all hours of ED operation, including overnight, in both high and low acuity settings across three Level 1 Trauma centers including an academic, a county, and a pediatric Emergency Department (ED).
Results: Observations totaled 280 h. There was no significant difference in the number of interruptions based on gender. At both non-pediatric centers, there were significantly more interruptions in the high acuity area than in the low acuity area (6.2 and 7.8 more interruptions, p = 0.043, 0.0043, respectively). Many interruptions (37%) occurred during order entry, a critical patient safety action. Charting was frequently interrupted (41.5%), which can negatively impact wellness. Residents did not return to their initial task 17% of the time and nearly 93% did not advocate stopping the interruption. When compared to nursing staff, ancillary staff, and co-residents, attending physicians most frequently caused interruptions (p < 0.0001).
Conclusions: EM residents in this study experienced frequent interruptions. Although bias has been documented throughout clinical education, we did not detect differences based on gender. Future education should address the impact of interruptions on patient safety and empower residents to improve task-switching ability. Increased awareness of the attending role in perpetuating interruptions may improve safety, on-shift education, and resident workflow
Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial
No full textThe MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient reported outcomes, and pharmacodynamic effects in PN biopsies. The objective response rate was 63.6% (21/33 participants). Median maximal PN volume decrease was 23.6% (range: −48.1%-5.5%). No disease progression relative to baseline PN volumes occurred prior to data cut-off with a median of 28 cycles completed (range: 1–78, 28 days/cycle). Participants experienced decreased tumor pain intensity and pain interference. Adverse events (AEs) were similar to those of the pediatric trial; acneiform rash was the most prevalent AE. Phosphorylation ratios of ERK1/2 decreased significantly (ERK1 median change: −64.6% [range: −99.5%-104.3%], ERK2 median change: − 57.7% [range: −99.9%-84.6%]) in paired PN biopsies (P≤0.001 for both isoforms) without compensatory phosphorylation of AKT1/2/3. The sustained PN volume decreases, associated improvement in pain, and manageable AE profile indicate selumetinib provides benefit to adults with NF1 and inoperable PNs
Evaluating the likelihood of pediatric sacral nerve stimulator explantations due to cure or complications: a survival analysis of 13-year institutional cohort
No full textIntroduction: Sacral neuromodulation (SNM) is a treatment option for children with refractory bladder and bowel dysfunction. Prior investigations have shown children may achieve cure of their symptoms following SNM implants and subsequently have their devices explanted. Herein, we present a 13-year experience of pediatric SNM placements and evaluate the likelihood of SNM explantation for any cause, for symptom resolution or complications.
Methods: An institutional retrospective review of children who underwent a 2nd stage SNM placement between November 2012 and January 2025 was performed. Reasons for SNM explantation was categorized as a cure or complication. Competing-risk time-to-event analysis was used.
Results: There were 129 SNM placements at a median of 10 years old (IQR 8.1-12.7); 88 were females (68.2%) and 41 required SNM revision (31.8%). Median follow-up was 3.5 (IQR 2.0-5.3) years. Subsequently, 46 underwent SNM explantation (35.7%). On survival analysis, median time to explantation (50%) was 6.0 (IQR 4.6-7.3) years. Among explanted, 34 were due to symptom resolution (73.9%) and 13 due to complications (4 infections; 4 pain at site; 3 for MRI requirements; 1 clinically ineffective). On competing risks analysis, 72.5% of the explantations at 6 years were for cure and 27.5% for complications. The 6-year explantation risk was 36.3% for cure and 13.8% for complications. Among 17 children who provided data after device explanation following cure (response rate: 51.5%), 16 (94%) had sustained symptom resolution at a median of 3.8 years (IQR 1.3-5.3) after explantation.
Conclusion: Approximately quarter of children with SNM placement achieved cure with increasing probability with follow-up time. More than 70% of explantations are due to cure and less than 10% were due to infections. There is high likelihood of sustained symptom resolution following explantation for cure. SNM remains a safe and viable option for children with refractory BBD with potential for cure
Weekly dihydroartemisinin–piperaquine versus monthly sulfadoxine–pyrimethamine for malaria chemoprevention in children with sickle cell anaemia in Uganda and Malawi (CHEMCHA): a randomised, double-blind, placebo-controlled trial
No full textBackground: In many sub-Saharan African countries, it is recommended that children with sickle cell anaemia receive malaria chemoprevention with monthly sulfadoxine-pyrimethamine or daily proguanil as the standard of care. However, the efficacy of these interventions is compromised by high-grade antifolate resistance of Plasmodium falciparum and poor adherence. We aimed to compare the efficacy of weekly dihydroartemisinin-piperaquine and monthly sulfadoxine-pyrimethamine for the prevention of clinical malaria in children with sickle cell anaemia in areas with high-grade sulfadoxine-pyrimethamine resistance of P falciparum in Uganda and Malawi.
Methods: We did an individually randomised, parallel group, double-blind, placebo-controlled trial at two hospitals in Uganda and two hospitals in Malawi. Children (aged 6 months to 15 years) with sickle cell anaemia with a bodyweight of at least 5kg were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and weight category, to receive either weekly dihydroartemisinin-piperaquine (approximately 2·5 mg per kg bodyweight dihydroartemisinin and 20 mg per kg bodyweight per day piperaquine) or monthly sulfadoxine-pyrimethamine (approximately 25 mg per kg bodyweight sulfadoxine and 1·25 mg per kg bodyweight). Placebos matching the alternative treatment were used in each treatment group to maintain masking of the different dosing schedules from the participants and caregivers, study staff, investigators, and data analysts. All children younger than 5 years received penicillin twice daily as standard of care. The primary endpoint was the incidence of clinical malaria, defined as a history of fever in the preceding 48 h or documented axillary temperature of 37·5°C or higher plus the detection of P falciparum parasites on microscopy (any parasite density). Secondary efficacy outcomes were any malaria parasitaemia (on either microscopy or malaria rapid diagnostic test), all-cause unscheduled clinic visits, all-cause and malaria-specific hospitalisation, sickle cell anaemia-related events (including vaso-occlusive crises, acute chest syndrome, stroke), need for blood transfusion, and death. All primary and secondary outcomes were assessed in the modified intention-to-treat population, which included all participants who were randomly assigned for whom endpoint data were available. Safety was assessed in in all children who received at least one dose of the study drug. Complete case analysis was conducted using negative-binomial regression. This study was registered with Clinicaltrials.gov, NCT04844099.
Findings: Between April 17, 2021, and May 30, 2022, 725 participants were randomly assigned; of whom 724 were included in the primary analysis (367 participants in the dihydroartemisinin-piperaquine group and 357 participants in the sulfadoxine-pyrimethamine group). The median follow-up time was 14·7 months (IQR 11·2-18·2). The incidence of clinical malaria was 8·8 cases per 100 person-years in the dihydroartemisinin-piperaquine group and 43.7 events per 100 person-years in the sulfadoxine-pyrimethamine group (incidence rate ratio [IRR] 0·20 [95% CI 0·14-0·30], p<0·0001). The incidence of hospitalisation with any malaria was lower in the dihydroartemisinin-piperaquine group than the sulfadoxine-pyrimethamine group (10·4 vs 37·0 events per 100 person-years; IRR 0·29 [0·20-0·42], p<0·0001) and the number of blood transfusions was also lower in the dihydroartemisinin-piperaquine group than the sulfadoxine-pyrimethamine group (52·1 vs 72·5 events per 100 person-years; IRR 0·70 [0·54-0·90], p=0·006). The incidence of all-cause unscheduled clinic visits and all-cause hospitalisations were similar between the two groups, however, participants in the dihydroartemisinin-piperaquine group had more clinic visits unrelated to malaria (IRR 1·12 [1·00-1·24], p=0·042) and more hospitalisations with lower respiratory tract events (16·5 vs 8·5 events per 100 person-years; IRR 1·99 [1·25-3·16], p=0·0036) than participants in the sulfadoxine-pyrimethamine group. The number of serious adverse events in the dihydroartemisinin-piperaquine group was similar to that in the sulfadoxine-pyrimethamine group (vaso-occlusive crisis [154 of 367 participants dihydroartemisinin-piperaquine group vs 132 of 357 participants in the sulfadoxine-pyrimethamine group] and suspected sepsis [115 participants vs 92 participants]), with the exception of acute chest syndrome or pneumonia (51 participants vs 32 participants). The number of deaths were similar between groups (six [2%] of 367 participants in the dihydroartemisinin-piperaquine group and eight (2%) of 357 participants in the sulfadoxine-pyrimethamine group).
Interpretation: Malaria chemoprophylaxis with weekly dihydroartemisinin-piperaquine in children with sickle cell anaemia is safe and considerably more efficacious than monthly sulfadoxine-pyrimethamine. However, monthly sulfadoxine-pyrimethamine was associated with fewer episodes of non-malaria-related illnesses, especially in children 5 years or older not receiving penicillin prophylaxis, which might reflect its antimicrobial effects. In areas with high P falciparum antifolate resistance, dihydroartemisinin-piperaquine should be considered as an alternative to sulfadoxine-pyrimethamine for malaria chemoprevention in children younger than 5 years with sickle cell anaemia receiving penicillin-V prophylaxis. However, there is need for further studies in children older than 5 years
Unlocking Superior MFH Performance Below Hergt’s Biological Safety Limit: SPION-Based Magnetic Nanoplatforms Deliver High Heating Efficiency at Low AMF
No full textSuperparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention for Magnetic Fluid Hyperthermia (MFH)-based cancer therapy. However, achieving high heating efficiency under a biologically safe Alternating Magnetic Field (AMF) remains a challenge. This study investigates the synthesis and optimization of SPIONs encapsulated in TPGS-stabilized PLGA nanoparticles (TPS-NPs) using a modified single emulsion solvent evaporation (M-SESE) method. The aim was to achieve efficient magnetic heating under biologically safe AMF conditions while maintaining biocompatibility and colloidal stability, making these magnetic nanoplatforms suitable for MFH-based cancer treatment. TPS-NPs were characterized using various techniques, including Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), and Superconducting Quantum Interference Device (SQUID) magnetometry, to evaluate their hydrodynamic size (Dh), zeta potential (ζ), encapsulation efficiency, and superparamagnetic properties. Calorimetric MFH studies demonstrated superior heating efficiency, with Specific Absorption Rate (SAR) and Intrinsic Loss Power (ILP) values optimized at an AMF of 4.1 GAm-1s-1, remaining within Hergt's biological safety limit (~5 GAm-1s-1). These findings suggest that SPION-encapsulated TPS-NPs exhibit enhanced heat induction, making them promising candidates for MFH-based cancer therapy. The study highlights their potential as multifunctional nanoplatforms for magnetic hyperthermia therapy, paving the way for clinical translation in oncology for advanced cancer treatment
Identification of the Distinct Immune Microenvironment Features Associated with Progression Following High-Dose Melphalan and Autologous Stem Cell Transplant in Multiple Myeloma
No full textA key treatment for patients with multiple myeloma is high-dose melphalan followed by autologous stem cell transplant (ASCT). It can provide a deep response with long-term remission. However, some patients progress quickly, and it is not clear why. In this study, we performed single-cell RNA and T-cell receptor sequencing of the immune microenvironment of 40 patients before and after ASCT to determine if differences in the immune composition could define those who would progress. Clear differences in cell populations were identified in progressors, including increased T-cell infiltration, decreased T-cell receptor diversity, and decreased frequency of monocytes and CD56bright NK cells. We identified cell interactions that predicted progression, including increased frequency of CD8+ exhausted T cells and stromal cells and decreased frequency of CD56bright NK cells and plasmacytoid dendritic cells. We propose and validate a model of progression that can also be determined by flow cytometry. Together, these data highlight the importance of the immune microenvironment in understanding responses to ASCT
Assessing Behavioral Trends and Survey Outcomes to Support Autism Intervention Across School Sites
Get PDFThis project focused on analyzing behavioral and clinical data from autism support classrooms as part of a Spring 2025 internship at the HANDS in Autism® Interdisciplinary Training and Resource Center. The work involved REDCap data entry, Classwide Data Rating (C-WDR) review, survey distribution, and AESIIS structured interview training. Using tools like Excel, Python, and Power BI, visual dashboards were created to illustrate behavior trends across multiple site visits. The data revealed improvements in student behavior over time, though staff engagement declined by the third visit. This project provided hands-on experience in research protocols, structured data collection, and interdisciplinary teamwork. It strengthened technical skills, deepened understanding of autism intervention strategies, and reinforced the intern’s commitment to using data-driven methods to enhance educational and healthcare outcomes for individuals with ASD
HIV drug resistance, early treatment outcomes and impact of guidelines compliance after protease inhibitor‐based second‐line failure in a dedicated resistance clinic in western Kenya: a retrospective cohort study
Get PDFIntroduction: Data on drug resistance, viral outcomes and guidelines compliance following protease inhibitor (PI)-based second-line failure in low- and middle-income countries are limited, particularly in the era of dolutegravir-containing antiretroviral therapy (ART).
Methods: We conducted a retrospective cohort study of people living with HIV (PLWH) ≥3 years old with second-line viral failure (VF, ≥1000 copies/ml) at the Academic Model Providing Access to Healthcare from 2011 to 2021. We assessed resistance prevalence and patterns at second-line VF, stratified by PI (atazanavir/ritonavir or lopinavir/ritonavir), and examined correlations of resistance and treatment strategies with VF at 6-18 months post-genotype. Analyses employed inverse probability weighting, adjusting for calendar year, age, gender, ART duration, PI at genotyping and class-specific resistance, and considered guidelines-supported versus unsupported strategies.
Results: Of 187 participants (median age 41 years, 54% female, 41% on atazanavir/ritonavir, 59% on lopinavir/ritonavir-based ART), 91% had any resistance (NRTI 79%, NNRTI 80%, major PI 37%, dual-class 36%, triple-class 37%). Predicted resistance to third-line options was 67% for etravirine or rilpivirine and 10% for darunavir/ritonavir. Despite higher resistance detected on atazanavir/ritonavir versus lopinavir/ritonavir, predicted darunavir/ritonavir resistance was similar. At median 9 months post-genotype, 95% of 173 participants with available data were on a guidelines-supported regimen (55% second-line; 45% third-line, 86% dolutegravir-based), of whom 28% had post-genotype VF. Of the 5% not on guidelines-supported regimens, 71% had post-genotype VF. Adjusted odds of VF were higher for guidelines-unsupported versus supported regimens (OR = 4.52; 95% CI 1.02-26.24), and odds of VF were 97% lower for those on third-line versus second-line (OR = 0.07; 95% CI 0.02-0.20).
Conclusions: We found high levels of drug resistance and early VF following PI-based second-line failure in Kenya. Treatment guidelines compliance and switches to third-line, even within guidelines recommendations, improved early viral outcomes. Findings highlight the vulnerability of PLWH with advanced ART experience and resistance profiles, and the importance of following guidelines and improving access to third-line and drug resistance testing, particularly in the new ART era
A cross-sectional survey of community health workers and their roles in Indiana
No full textBackground: In the US, there is a lack of information about the community health worker (CHW) workforce, which is critical to inform workforce policy, development, and training initiatives. In this manuscript, we report the results of a cross-sectional workforce survey of CHWs in Indiana.
Methods: We conducted a statewide electronic survey of CHWs in Indiana. Eligible participants were self-reported CHWs and over the age of 18. The survey was adapted from an existing tool and included questions about CHWs' demographics, employer, compensation, and roles and responsibilities. The survey was pilot-tested and distributed in partnership with the state's CHW professional association. Data were collected anonymously using REDCap. Bivariate correlations were examined between salary and demographics, employer type, training, and length of employment. Analyses were conducted using SAS version 9.4.
Results: Among 282 participants that met eligibility, a majority were female (92%) with 39% identifying as Black/African American, 38% as White, and 13% as Hispanic/Latino. Over 40% held at least a Bachelor's degree, and 20% were multilingual. CHWs worked under various job titles - only half reported that their official job title was as a CHW - and for a variety of organizations with about half working for either a health system or academic employer. Respondents had a median of 2 years of experience as a CHW. The majority of CHWs were employed full-time (85%) and had completed a training program (83%). Their scopes of practice varied but CHWs were most engaged in activities related to culturally relevant communication, care coordination, coaching, and social support. Lower salary was significantly associated with less education and working as a CHW for less than one year, but not with other demographic characteristics, employer type, or having completed a training program.
Conclusion: This study offers a snapshot of Indiana's CHW workforce, highlighting that it is predominantly female but diverse demographically, in employment setting, job title, and roles played. The findings provide insights to guide workforce development and planning efforts by employers, professional associations, health departments, and policymakers to strengthen and expand this essential workforce in Indiana and beyond