Digital Commons Network^™

A Robust Convnext-Based Framework For Efficient, Generalizable, And Explainable Brain Tumor Classification On Mri, Kirti Pant, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Background: Accurate and dependable brain tumor classification from magnetic resonance imaging (MRI) is essential for clinical decision support, yet remains challenging due to inter-dataset variability, heterogeneous tumor appearances, and limited generalization of many deep learning models. Existing studies often rely on single-dataset evaluation, insufficient statistical validation, or lack interpretability, which restricts their clinical reliability and real-world deployment.

Methods: This study proposes a robust brain tumor classification framework based on the ConvNeXt Base architecture. The model is evaluated across three independent MRI datasets comprising four classes-glioma, meningioma, pituitary tumor, and no tumor. Performance is assessed using class-wise and aggregate metrics, including …

N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of …

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Elbow Ulnar Collateral Ligament Reconstruction And Repair: A Systematic Review And Meta-Analysis Of Biomechanical Studies, Austin Looney, Adeeb Hanna, Carlo Coadonato, John Sonnier, Blake Bodendorfer, Christopher Anderson, Neil Sarna, Kevin Freedman, Michael G. Ciccotti, Michael C. Ciccotti, Brandon Erickson, Steven Cohen

Rothman Institute Papers

BACKGROUND: Technical variations in elbow ulnar collateral ligament reconstruction (UCLR) include graft source, graft/tunnel configuration, and humeral and ulnar fixation. While the biomechanical performance of various constructs has been reported, these studies have small sample sizes and compare at most a few technical variations.

PURPOSE: To quantitatively synthesize the results of biomechanical investigations of UCLR and repair.

STUDY DESIGN: Systematic review.

METHODS: A systematic review and meta-analysis was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses); included articles were published between 1998 and 2020. Biomechanical metrics were utilized to compute effect sizes (standardized mean difference [SMD]) …

Clinical Workflow Of Spine Stereotactic Radiotherapy And Radiosurgery: Insights From A Single-Institution Physics Perspective, Dennis Mackin, Gizem Cifter, Yana Zlateva, Jihong Wang, Yao Ding, Muhammad Shafiq Ul Hassan, Zhiheng Wang, Parmeswaran Diagaradjane, Fada Guan, Travis C Salzillo, Shane Krafft, Jing Li, Martin C Tom, Amol J Ghia, Tina Marie Briere

Faculty, Staff and Student Publications

Spine stereotactic radiotherapy and radiosurgery (SSRS) techniques, encompassing both fractionated stereotactic treatments and single-fraction radiosurgery, are widely used for the management of spinal metastases due to their ability to deliver highly conformal radiation while limiting dose to adjacent critical structures. Clinical outcomes following SSRS, including durable local control and acceptable toxicity, have been reported previously in multiple institutional series. In this manuscript, we describe the clinical workflow used to deliver SSRS at a high-volume academic center, with emphasis on the medical physics processes that support routine clinical practice. Key elements of the workflow include patient selection, treatment region-specific immobilization, CT …

Saga/Atac Complexes Sustain Aberrant Chromatin Regulation And Promote Tumorigenesis In Diffuse Midline Glioma, Rosemary U Richard, Caitlin Bagnetto, Rebecca L Murdaugh, Brittany R Eberl, Alan L Jiao, Adam F Kebede, Barry M Zee, Margaret M Harrington, Mariella G Filbin, Akdes Serin-Harmanci, Yang Shi, Jamie N Anastas

Faculty, Staff and Students Publications

Diffuse midline gliomas (DMG) are aggressive pediatric brain tumors characterized by chromatin and transcriptional dysregulation induced by H3K27M mutations. Strategies for overcoming epigenetic dysfunction to reduce DMG tumorigenesis remain limited. We identified multiple components of the SAGA and ATAC chromatin regulatory complexes as DMG genetic dependencies and found that genetic or pharmacological inhibition of the SAGA/ATAC-associated chromatin reader SGF29 reduces DMG proliferation. Small molecules targeting SAGA/ATAC-associated histone acetylation, ubiquitination, and methylation similarly suppressed DMG growth. Further chromatin profiling and RNAseq analyses reveal that SGF29 controls H3K9ac and H3K4me3 dynamics at both H3K27M-bound and H3K27M-independent target genes linked to proliferation, differentiation, …

Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz

Department of Medical Oncology Faculty Papers

BACKGROUND: Cysteine-cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.

METHODS: Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once …

Microfluidic Capillary Transit Velocity As A Functional Measure For Sickle Cell Disease And In Vitro-Derived Red Blood Cells, Solomon Oshabaheebwa, Yuxuan Du, Christopher L. Wirth, Zoe Sekyonda, Zoe Sekyonda, Bryan L. Benson, Payam Fadaei, Yusang B. Ley, Michael A. Suster, Pedram Mohseni, Umut A. Gurkan

Faculty Scholarship

Emerging therapies in sickle cell disease (SCD) aim to restore healthy red blood cell (RBC) function, but they often yield heterogeneous cellular responses. There are no proven techniques to evaluate restored rheological functionality and heterogeneity in these RBCs. We present a biomimetic microcapillary network, high-speed imaging, and computational algorithms to analyze RBC capillary velocity profiles of the entire sample population at single-cell resolution. Using peripheral RBCs from SCD patients and healthy donors, we showed that RBC capillary transit velocity correlated with cell shape, hydrodynamic adaptability, and elongation index. Healthy RBCs exhibited a velocity distribution skewed toward higher values, whereas RBCs …

From Evaluation To Elevation: Standardized Letter Of Evaluation Domains Tied To Future Emergency Medicine Chief Residents, Abagayle Bierowski, Zaid Tayyem, Casey Morrone, Carlos Rodriguez, Chaiya Laoteppitaks, Peter Tomaselli, Dimitrios Papanagnou, Xiao Chi Zhang

Department of Emergency Medicine Faculty Papers

INTRODUCTION: The Standardized Letter of Evaluation (SLOE) is a core component of emergency medicine (EM) residency applications, designed to assess clinical performance, professionalism, and leadership potential. While its utility in selecting residency candidates is well established, its association with future leadership roles, such as chief resident, remains unclear. Identifying early indicators of leadership potential could inform both recruitment and resident development efforts. In this study we aimed to evaluate whether medical students' SLOEs are associated with subsequent selection as chief residents, offering insight into the SLOE's potential to forecast future leadership within EM.

METHODS: We conducted a retrospective review of …

Maturity-Onset Diabetes Of The Young (Mody) In A Racially/Ethnically Diverse Pediatric Population, Shilpi Relan, Guido Alarcon, Danielle Guffey, Charles G Minard, Mary E Fang, Kelly Timmons, Rona Y Sonabend, Mustafa Tosur, Maria J Redondo, Jennifer E Posey

Faculty, Staff and Students Publications

Context: Current practice guidelines recommend considering a diagnosis of maturity-onset diabetes of the young (MODY) in patients with diabetes with an affected parent but without typical features of type 1 or type 2 diabetes.

Objective: To test if these criteria apply to a real-world cohort of racially/ethnically diverse children with diabetes.

Methods: We performed a retrospective case review of electronic medical records of youth diagnosed with MODY in a large academic pediatric hospital in Southwestern United States. Cases were ascertained based on the identification of a molecular diagnosis of MODY.

Results: We studied 50 genetically confirmed cases of MODY: 60% …

Genomics Define Malignant Transformation In Myeloma Precursor Conditions, Francesco Maura, P Leif Bergsagel, Bachisio Ziccheddu, Shaji Kumar, Kylee Maclachlan, Andriy Derkach, Juan-Jose Garces, Ross Firestone, Esteban Braggio, Yan Asmann, Michael Durante, Benjamin T Diamond, Marios Papadimitriou, Malin Hultcrantz, Alessio Marella, Giancarlo Castellano, Akihiro Maeda, Marta Lionetti, Antonio Matera, Stefania Pioggia, Matteo Claudio Da Vià, Claudio De Magistris, Daniel Leongamornlert, Danny Deavila, Praneeth Reddy Sudalagunta, Rafael Renatino Canevarolo, Erin M Siegel, Phaedra Agius, Jamie Teer, Andrew Mcpherson, Yusuke Yamashita, Ariosto S Silva, Patrick Blaney, Rachid Baz, Krina K Patel, Peter Campbell, Gareth Morgan, Rafael Fonseca, Ola Landgren, Robert Z Orlowski, Kenneth H Shain, Niccolo Bolli, Saad Usmani, S Vincent Rajkumar

Faculty, Staff and Student Publications

Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify …

Simulated Complex Cells Contribute To Object Recognition Through Representational Untangling, Mitchell B Slapik, Harel Z Shouval

Faculty, Staff and Student Publications

The visual system performs a remarkable feat: it takes complex retinal activation patterns and decodes them for object recognition. This operation, termed "representational untangling," organizes neural representations by clustering similar objects together while separating different categories of objects. While representational untangling is usually associated with higher-order visual areas like the inferior temporal cortex, it remains unclear how the early visual system contributes to this process-whether through highly selective neurons or high-dimensional population codes. This article investigates how a computational model of early vision contributes to representational untangling. Using a computational visual hierarchy and two different data sets consisting of numerals …

The Use Of Artificial Intelligence In Decreasing Vaccine Skepticism And Hesitancy, Nathaniel Wolf, Nhan Nguyen, Rojelio Mejia

Faculty, Staff and Students Publications

Purpose of review: Recent advances in artificial intelligence (AI) coincide with decreases in confidence in vaccines. This review examines studies that analyze and mitigate vaccine skepticism by implementing artificial intelligence strategies in various ways.

Recent findings: Studies have explored public attitudes towards vaccines using AI to analyze language in social media postings and interactions, scrutinize AI responses to vaccine-related queries, and attempt to use AI to directly influence vaccine hesitancy. Findings show that AI can be effective in addressing vaccine hesitancy in various ways, including, but not limited to, directly interacting with vaccine-hesitant groups, identifying reasons for vaccine hesitancy, and …

B Lymphocytes Impede Tregs To Erode Islet Tolerance In Type 1 Diabetes, Christopher S Wilson, Blair T Stocks, Alexander C Falk, Daniel J Moore

Faculty, Staff and Students Publications

B lymphocytes are thought to drive β-cell destruction in type 1 diabetes (T1D) by activating anti-islet T cells. However, the observation that autoreactive T-cell activation and disease progression can occur without B cells challenges this view. Still, preclinical and clinical studies have shown that B-cell depletion alleviates β-cell destruction, suggesting a critical role for B cells in T1D. Our findings propose an alternative function for B cells, impairing regulatory T cells (Tregs) that would otherwise protect islets. In the NOD islet transplant model, we show that B-cell absence enables transplant tolerance, allowing Tregs to become responsive to immune therapy and …

A Review Of 3d-Printed Medical Devices For Cancer Radiation Therapy., Radiah Pinckney, Santosh Kumar Parupelli, Peter Sandwall, Sha Chang, Salil Desai

Oncology Articles

This review explores the transformative role of three-dimensional (3D) printing in radiation therapy for cancer treatment, emphasizing its potential to deliver patient-specific, cost-effective, and sustainable medical devices. The integration of 3D printing enables rapid fabrication of customized boluses, compensators, immobilization devices, and GRID collimators tailored to individual anatomical and clinical requirements. Comparative analysis reveals that additive manufacturing surpasses conventional machining in design flexibility, lead time reduction, and material efficiency, while offering significant cost savings and recyclability benefits. Case studies demonstrate that 3D-printed GRID collimators achieve comparable dosimetric performance to traditional devices, with peak-to-valley dose ratios optimized for spatially fractionated radiation …

Cleft Feeding: Practical Tips For Pediatricians, Michael Smith, Leah Hunt, Brenda Fetter, Hannah J. Bergman

Pediatrics in Practice: A CME Podcast

Feeding infants with cleft lip and palate can be challenging. In this episode, a pediatric surgeon, occupational therapist, and speech pathologist share practical strategies for pediatricians—from pre- and post-surgery care to therapy techniques and key red flags. Learn how to guide families and collaborate effectively for the best outcomes.

Note: This episode is not awarded CME.

Click here to stream the podcast episode.

Institutional Practices Drive Antibiotic Variability In Neonatal Intensive Care Units: Baseline Evidence To Inform National Stewardship Interventions In Oman, Abdullah Alqayoudhi, Manoj Malviya, Sathiya Murthi, Mohammed Rasik Nv, Adil Said Al-Wahaibi, Raya Al-Habsi, Said Al-Balushi, Talal Alwardi, Agha Hatif Shamsi, Halah Bait Raidan, Aamera Al-Majrafi, Preethi Kiran, Eyad Hani Abu Abu Alhaijaa, Kawther Al Amri, Khalfan Al Abdali, Mohammed S. Al Reesi, Nasser Al-Shafouri, Amal Al-Jabri, Sachin Shah, Said Al-Kindi, Zubair H. Aghai, Mohammed Al-Yahmadi, Amal Al-Maani

Department of Pediatrics Faculty Papers

Background: Antibiotic overuse in Neonatal Intensive Care Units (NICUs) is a major contributor to antimicrobial resistance and adverse neonatal outcomes. This study aims to evaluate baseline antibiotic utilization (AU), identify factors influencing variability, and assess the impact of neonatal characteristics and sepsis incidence. Methods: A multicenter retrospective analysis examined AU in seven NICUs from 2019 to 2023, involving 25,532 neonatal admissions during national antibiotic stewardship program implementation. Data encompassed neonatal clinical parameters, sepsis incidence, and AU metrics, including days of therapy (DOT) per 1000 patient-days. Statistical analyses included correlation assessments and multivariate regression to identify determinants of antibiotic use. Results: …

Single-Cell Rna Sequencing Suggests Different Progenitor Lineages Between Idh Mutant And Idhwt Glioma, Iyad Alnahhas, Allison Kayne, Mehak Khan, Wenyin Shi

Department of Neurology Faculty Papers

Introduction Single-cell RNA sequencing has elucidated the heterogeneity in cancer. Single-cell glioblastoma (GBM) analyses have also proposed the resemblance of GBM cells to radial glia and outer radial glia (oRG) supporting the hypothesis that remnants of developmental tissue get reactivated in cancer. A recent study isolated neural progenitor cells (NPCs) from developing fetal human brain (gestational week 17-19) and classified NPCs based on their expression of THY1 (CD90), CD24 and EGFR. Ventricular radial glia are THY1⁻CD24⁻EGFR⁺ whereas oRG are THY1⁻CD24⁻EGFR⁻. Early neuron precursors are CD24⁺THY1⁻EGFR …

Bridging Hypoxia And Vision Loss: The Emerging Role Of Connexins In Local And Systemic Eye Diseases, Xianping Zhang, Yalong Cheng, Jean X Jiang, Yuting Li

Faculty, Staff and Student Publications

Hypoxic eye diseases represent a pivotal yet often underappreciated contributor to the onset and progression of many retinal disorders. When hypoxia persists or exceeds the tissue's compensatory capacity, it triggers pathological retinal neovascularization, blood-retinal barrier disruption, and neuronal apoptosis, ultimately resulting in irreversible visual impairment. Connexins (Cxs) form gap junction channels and hemichannels and regulate retinal cell proliferation, differentiation, and survival, thereby playing a central regulatory role in the pathogenesis of hypoxic ocular diseases. In addition to gap junctions, Cx hemichannels promote transmission of molecules between intra- and extracellular environments, further influencing retinal homeostasis under hypoxic stress. This review synthesizes …

Understanding The Compatibility Of Fluoride-Based Radiopharmaceutical Reaction Solutions And Pdms, Mark Mc Veigh, Charles Frech, Mai Lin, Robert Ta, H Charles Manning, Leon M Bellan

Faculty, Staff and Student Publications

Microfluidic devices offer unique and exciting benefits when applied to radiopharmaceutical manufacturing, and these platforms are now starting to be integrated into commercial products. The field has strayed away from the use of polydimethylsiloxane (PDMS), the most common microfluidic device material, due to its suspected incompatibility with 18F, the most commonly used radionuclide. However, existing literature provides conflicting conclusions as to the existence and extent of this incompatibility. In this study, we use several analytical instruments to uncover the underlying interaction between fluoride and PDMS. SEM imaging and profilometry confirm the reactive relationship between the two materials and suggest that …

Autograft Enlargement After The Ross Procedure In Pediatric Patients: Somatic Growth Or Pathologic Dilatation?, Ioannis Zoupas, Alexander C Mills, Scott D Olson, Damien J Lapar

Faculty, Staff and Student Publications

Purpose of ReviewPulmonary autograft autotransplantation represents a popular surgical approach for pediatric patients requiring aortic valve replacement due to the potential for autograft enlargement to accommodate somatic growth. Nevertheless, autograft dilatation and the subsequent need for reintervention are quite common. Published data suggest that autograft enlargement may result from pathological passive remodeling rather than active somatic growth and vice versa. The present review serves to comprehensively evaluate available evidence related to the fate of the pulmonary autograft after the Ross procedure as it relates to the etiology, risk factors and patterns of autograft failure.ResultsStudies present conflicting results supporting both pathological …

Diet-Responsive Genetic Determinants Of Intestinal Colonization In The Yeast Candida Albicans, Musfirat Shubaita, Mazen Oneissi, Elena Lindemann-Pérez, Cecilia Fadhel Alvarez, Anne-Marie Krachler, Diana M Proctor, J Christian Pérez

Faculty, Staff and Student Publications

Dietary components influence microbial composition in the digestive tract. Although often viewed as energy sources, dietary components are likely to shape microbial determinants of intestinal colonization beyond metabolism. Here, we report that a dietary long-chain fatty acid enhances the yeast Candida albicans colonization of the murine gut partly by eliciting modifications to the fungal cell surface. Mice fed an oleic acid-rich diet were readily colonized by C. albicans and exhibited higher fungal load in feces compared with rodents fed an isocaloric control diet. Surprisingly, β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for C. …

Real-World Multicenter Assessment Of Sustained Clinical Outcomes After Digital Deep Brain Stimulation, Alireza Gharabaghi, Sergiu Groppa, Elena Casas, Alfons Schnitzler, Laura Muñoz-Delgado, Vicky L. Marshall, Jessica Karl, Lin Zhang, Ramiro Alvarez, Mary S. Feldman, Michael J. Soileau, Lan Luo, Benjamin L. Walter, Chengyuan Wu, Hong Lei, Damian M. Herz, Devyani Nanduri, Claudia A. Salazar, Corneliu Luca, Daniel Weiss

Department of Neurosurgery Faculty Papers

Remote, internet-based deep brain stimulation programming for Parkinson's disease accelerates clinical benefits postoperatively by improving access to therapy adjustments compared to in-clinic optimization. After completion of the initial digital programming phase, we show that clinical outcomes, quality of life, and safety remain sustained over at least twelve months under routine care conditions. Embedding a randomized trial within a larger cohort study enables long-term, real-world evaluation, offering a scalable and pragmatic model for assessing complex digital interventions in routine clinical care. (NCT05269862 registered on 2022-03-08 and NCT04071847 registered on 2019-08-28).

Disease Burden Of Asthma Patients Utilizing Short-Acting Beta-2 Agonist-Only Inhalers As Rescue In The United States, Njira Lugogo, Rena C. Moon, Yen Chung, Joy David, Omar Motawakel, Ning A. Rosenthal, Neil Skolnik

Department of Family & Community Medicine Faculty Papers

Purpose: We aimed to describe the disease burden of asthma and examine relationships between short-acting beta-2 agonist (SABA) use and asthma exacerbations. Patients and Methods: This retrospective cohort study used geographically diverse Premier Healthcare Database (PHD) and linked insurance claims (10/01/2021-09/30/2022) for US patients aged ≥18 years with a SABA-only prescription and a history of asthma exacerbation within 12 months before index date (the earliest SABA prescription date). Three asthma control groups were defined based on SABA usage: well controlled-low (0–1 prescriptions), not well controlled-medium (2–3 prescriptions), very poorly controlled-high (≥4 prescriptions). Four asthma severity groups were defined using asthma …

Genome-Wide Gene By Sleepiness Interaction Analysis For Sleep Apnea, Pavithra Nagarajan, Nuzulul Kurniansyah, Jiwon Lee, Sina A Gharib, Yushan Xu, Yiyan Zhang, Brian Spitzer, Tariq Faquih, Hufeng Zhou, Eric Boerwinkle, Han Chen, Daniel J Gottlieb, Xiuqing Guo, Nancy L Heard-Costa, Bertha A Hidalgo, Daniel Levy, Peter Y Liu, Hao Mei, Rebecca Montalvan, Sutapa Mukherjee, Kari E North, George T O'Connor, Lyle J Palmer, Sanjay R Patel, Bruce M Psaty, Shaun M Purcell, Laura M Raffield, Stephen S Rich, Jerome I Rotter, Richa Saxena, Albert V Smith, Katie L Stone, Xiaofeng Zhu, Topmed Sleep Trait Working Group, Brian E Cade, Tamar Sofer, Susan Redline, Heming Wang

Faculty, Staff and Student Publications

Study objectives: Excessive daytime sleepiness (EDS), influenced by environmental and social-behavioral factors, is reported by a subset of patients with sleep apnea-a group that may be at elevated cardiovascular risk. However, it is unclear whether sleep apnea with and without EDS have distinct genetic underpinnings. In this study, we perform gene-by-EDS interaction analyses for apnea hypopnea index, a diagnostic marker of sleep apnea severity, to understand EDS's influence on its underlying genetic risk.

Methods: Discovery interaction analyses for common variants and gene-based rare variants were conducted respectively using multi-ethnic Trans-Omics for Precision Medicine (N = 11 619) data, followed by …

Identifying Priority Research Questions For Decentralized Wastewater, Bryan W Brooks, Timothy Callahan, Jacob K Stanley, Jamie Holodak, Kevin M Stroski, Alissa H Cox, Thomas W Groves, Anish Jantrania, Jeff C Moeller, Kris Neset, Christopher Walker, Harry Zhang, Amal Bakchan, Kelly D Alley, Jim Bell, Allison Blodig, Eric Casey, Donna Cosper, Victor D'Amato, Mark A Elliott, Greg Graves, Roxanne Groover, Robert Himschoot, Mary G Lusk, Jillian Maxcy-Brown, David Meints, Rojelio Mejia, Matt Pace, Benjamin J Ryan, Brian Scheffe, Tom Schimelfenig, June E Wolfe, Sara F Heger

Faculty, Staff and Students Publications

Decentralized wastewater treatment and reuse represent critical infrastructure across the rural-periurban-urban continuum around the world. Effective, efficient, resilient, and equitable implementation of on-premise technologies and management systems is part of a One Water approach and necessary to protect public health and the environment, yet inconsistent delivery of essential public health services persists in many regions, including across states, tribes, and territories of the United States. We initiated a groundbreaking effort to understand challenges and to identify research opportunities related to the science and practice of decentralized wastewater. A horizon scanning exercise using a bottom up and transparent key questions approach …

The Biomedical Landscape Of Genomic Structural Variation In The Qatari Population, Elbay Aliyev, Najeeb Syed, Alessia Visconti, Taghi Aliyev, Aziz Belkadi, Mohammadmersad Ghorbani, Niccolò Rossi, Haroon Naeem, Geethanjali Devadoss Gandhi, Gaurav Thareja, Aljazi Al-Maraghi, Waleed Aamer, Amal Abdulsalam Ibrahim, Rulan Shaath, Farooq Omar Al-Ajli, Rozaimi Mohamad Razali, Fritz J Sedlazeck, Sonia Davila, Ammira Akil, Karsten Suhre, Younes Mokrab, Mario Falchi, Khalid A Fakhro

Faculty, Staff and Students Publications

We present a large-scale study of structural variation (SV) in the Qatari population, based on short-read whole-genome sequencing (WGS) of 6,141 individuals, identifying 153,946 variants across 5 classes reflecting the region's diversity and evolutionary history. Leveraging consanguinity and biobank phenotypes, we identify >180 putative gene knockouts, and use proteomics to show functional consequences in homozygotes. Conversely, 52 genes show significant depletion of homozygous deletions, eight of which cause severe pediatric disease or murine embryonic lethality. Examining phenotypic extremes uncovers several non-exonic homozygous deletions with large effect, including in SPIRE2 (creatinine), MAGI2 (leanness) and a chr19 microRNA cluster (extreme obesity). Further, …

Spatial Omics At The Forefront: Emerging Technologies, Analytical Innovations, And Clinical Applications, Yunhe Liu, Yibo Dai, Linghua Wang

Faculty, Staff and Student Publications

Spatial omics transforms our understanding of cancer by revealing how tumor cells and the microenvironment are organized, interact, and evolve within tissues. Here, we synthesize advances in spatial technologies that map tumor ecosystems with unprecedented fidelity. We highlighted analytical breakthroughs-including multimodal integration and emerging spatial foundation models-that resolve functional niches and spatial communities, converting spatial patterns into mechanistic insights. We summarize how spatially organized features, from immune hubs to microbiota and neural interfaces, shape tumor evolution and clinical outcomes. We then outline how spatial approaches illuminate precancer biology, metastatic adaptation, and therapy response. Bridging discovery and translation, we provide a …