Digital Commons Network^™

Meta-Analysis Of Genetic Mapping Studies In Mice Reveals Candidate Epilepsy Modifier Genes That Are Outside The Current Drug Development Landscape., Giovanna L Durante, Anna L. Tyler, Rod C Scott, Amanda E Hernan, J Matthew Mahoney

Faculty Research 2026

OBJECTIVE: Despite decades of development in anti-seizure medications, ~30% of individuals remain refractory to all treatments, and none of the existing therapies are disease modifying. Identifying targets outside the current preclinical paradigm is critically important. This study aimed to characterize the landscape of current epilepsy treatments at the level of gene interaction networks and identify novel genetic modifiers of epilepsy as potential novel therapeutic targets.

METHODS: We performed a functional network analysis to score genes based on their interactions with known epilepsy genes, and we integrated these functional scores with population genetics data and drug tractability information. In parallel, we …

Prevalence Of, Edison Liu, Margaret Antonio, Tracy Nance, Francesca Menghi

Faculty Research 2026

PURPOSE: BRCA1 promoter methylation (BRCA1meth) affects 20%-27% of triple-negative breast cancer (TNBC) and ovarian cancer (OvCa) and has therapeutic predictive value in both cancer types. BRCA1meth is established during early embryonic development as a constitutional event, and its detection in the peripheral blood cells of unaffected women associates with increased risk for breast cancer and OvCa. Thus, facile and sensitive assessment of BRCA1meth is an important component for both risk assessment and the therapeutic management of these cancer types.

METHODS: We used the GRAIL circulating cell-free DNA (cfDNA)–based targeted meth- ylation platform to quantify BRCA1meth in cfDNA (cfBRCA1meth) from plasma …

Improving Gene Isoform Quantification With Miniquant., Haoran Li, Dingjie Wang, Qi Gao, Puwen Tan, Yunhao Wang, Xiaoyu Cai, Aifu Li, Yue Zhao, Andrew L Thurman, Seyed Amir Malekpour, Ying Zhang, Roberta Sala, Andrea Cipriano, Chia-Lin Wei, Vittorio Sebastiano, Chi Song, Nancy R Zhang, Kin Fai Au

Faculty Research 2026

RNA sequencing has been widely applied for gene isoform quantification, but limitations exist in quantifying isoforms of complex genes accurately, especially for short reads. Here we identify genes that are difficult to quantify accurately with short reads and illustrate the information benefit of using long reads to quantify these regions. We present miniQuant, which ranks genes with quantification errors caused by the ambiguity of read alignments and integrates the complementary strengths of long reads and short reads with optimal combination in a gene- and data-specific manner to achieve more accurate quantification. These results are supported by rigorous mathematical proofs, validated …

Can We Refute A Role For Infections In Alzheimer's Disease Pathogenesis?, Zena K Chatila, Michael R Duggan, Esther Silberberg, Juan Fernandez, Lavinia A Auber, Elizabeth M Bradshaw, Nikki M. Schultek

PCOM Scholarly Works

While a growing body of literature suggests a role for infections in Alzheimer's disease (AD), microbial contributions to AD remains a contentious topic, in part due to challenges in reconciling the positive evidence with studies reporting null findings. Here, we examine the evidence that argues against a role for infections in AD, while offering mechanistic hypotheses that may account for both the negative and positive findings, including dysregulated host immunity and gene-environment interactions of AD-associated genes.

Consolidation Enfortumab Vedotin And Pembrolizumab After Cisplatin Induction In Metastatic Urothelial Cancer: Outcomes Of Complete Response And Bladder Preservation, Kok Hoe Chan, Putao Cen, Tung Shu, Steven Canfield, Hui Zhao, Anneliese Gonzalez, Julie Rowe, Varaha Tammisetti, Hajar Ayoub, Angel Blanco, Mark Amsbaugh, Nizar Tannir

Faculty, Staff and Student Publications

Bladder preservation remains a highly desirable therapeutic goal in urothelial carcinoma, particularly when durable survival can be achieved. Radical cystectomy is the standard treatment for muscle-invasive disease; however, it results in irreversible bladder loss and significant morbidity. Among patients with locally advanced or metastatic urothelial carcinoma, recurrence rates after standard therapy remain high. Consolidation therapy with enfortumab vedotin and pembrolizumab following cisplatin-based induction chemotherapy has demonstrated promising efficacy, with substantial complete response rates and improved bladder preservation. This single-center retrospective analysis evaluated the efficacy and safety of enfortumab vedotin plus pembrolizumab as consolidation therapy in 11 patients with metastatic urothelial …

Soft Skills For Medical Physicists: Evolving A Profession., Tomas Kron, Julie Raffi, Shada Wadi-Ramahi, Abdelkader Toutaoui, Bilal Jalal, Peter A Sandwall, Graciela Velez, Dario Sanz, Godfrey Azangwe

Oncology Articles

PURPOSE: Medical physicists are essential healthcare professionals who bridge the gap between technology and patient care, particularly in radiation oncology and medical imaging. With the profession expanding its clinical and global roles, the need for competencies beyond technical expertise-such as communication, leadership, and cultural awareness-is increasingly evident. These competencies, commonly referred to as soft skills, are critical for patient-centered care but remain insufficiently integrated into formal education and training pathways. The aim of the present work was to identify soft skills relevant to medical physics practice and investigate where in a career they are acquired and used.

METHODS: This paper …

Prevalence And Risk Factors For Non-Hacek Gram-Negative Bacillus Endocarditis: A Retrospective Analysis, Jason H Park, Edwin Chen, Divyia E Joseph, Audrey Wanger, J Alex Viehman, Simi Padival

Faculty, Staff and Student Publications

Background: Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is challenging to diagnose and is associated with high morbidity and mortality. There is growing literature highlighting the differences in IE prevalence amongst various GNB; therefore, there is an impetus to characterize these traditionally "atypical" organisms to accurately risk stratify this complex infectious diagnosis.

Methods: This investigation was a retrospective cohort study conducted at 2 health care institutions in the USA. All hospitalized adult patients with bloodstream infection with a prespecified GNB (Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, and Serratia marcescens) between January 1, …

Neutrophil-To-Lymphocyte Ratio As A Prognostic Factor Of Survival Outcomes In Head And Neck Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy, Pablo Llerena, Praneet C. Kaki, Kathryn Nunes, Eric Mastrolonardo, Kelly Bridgham, Annie Moroco, Hani Samarah, Mouadh Barbirou, David Baek, Chun Wang, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer M. Johnson, Hushan Yang, Larry A. Harshyne, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in cancers treated with immune checkpoint inhibitors (ICI), reflecting the link between inflammation and cancer immune response. This study examines NLR's prognostic value in head and neck squamous cell carcinoma (HNSCC) patients receiving neoadjuvant ICI therapy, focusing on its potential as an independent predictor of overall survival (OS) and disease-free survival (DFS).

METHODS: We conducted a retrospective cohort study including three neoadjuvant trials: durvalumab ± metformin, nivolumab ± tadalafil, or nivolumab ± BMS-986205 from 2017 to 2022. Pre-treatment NLR was calculated using absolute neutrophil and absolute lymphocyte counts obtained before neoadjuvant …

Unilateral Online Ultrasound Stimulation Of Early Visual Cortex Suppresses Responses To Contralateral Visual Stimuli, Suraya Dunsford, Keith Murphy, Ema Darrieutort, Elsa Fouragnan, Giorgio Ganis

School of Psychology

INTRODUCTION: Transcranial ultrasound stimulation (TUS) shows great promise for inducing neuroplastic changes that persist long after stimulation. Evidence of stimulation-locked (online) neural changes would enable the development of closed-loop application of TUS. However, such responses have been difficult to distinguish from coincident neural activity caused by auditory and somatosensory effects of TUS.

METHODS: To dissociate genuine online neuromodulatory effects from peripheral confounds, we leveraged the contralateral retinotopic organization of the early visual cortex in nineteen subjects. Using a hemifield visual stimulation paradigm combined with high-precision, functional MRI-guided TUS, we applied TUS to the left early visual cortex while participants viewed …

Influence Of Exercise Training On Nitric Oxide Pathways And Their Physiological Effects, Jonas Benjamim, Stephen J Bailey, Leonardo Da Silva Gonçalves, Mia Burleigh, Mario Siervo, Andrew R Coggan, Raúl Bescos

School of Health Professions

Nitric oxide (NO) is a critical signalling molecule in cardiovascular, metabolic, and muscular function. Endogenous NO production occurs via two primary metabolic pathways: 1) the classical nitric oxide synthases (NOS) pathway, and 2) the alternative (nitrate-nitrite-NO) pathway, in which inorganic nitrate (NO 3 -) is sequentially reduced to nitrite (NO 2 -) and other NO intermediates (e.g., S-nitrosothiol). The latter pathway relies heavily on the oral microbiota, which catalyze the two-electron partial reduction of NO 3 - to NO 2 -, which is influenced by oral physiology, microbial composition and salivary flow. While the role of exercise training in enhancing …

Improving Vaccination In People With Ckd: Report From A National Kidney Foundation Working Group, Susan F. Massengill, Kenneth A. Andreoni, Keith A. Bellovich, Cheryl Courtlandt, Vimal K. Derebail, David L. Feldman, Gia J. Oh, John W. Sleasman, Kristina A. Bryant, Improving Vaccination In Ckd Working Group

Department of Surgery Faculty Papers

People with chronic kidney disease (CKD) are particularly vulnerable to vaccine-preventable infections. Therefore, the National Kidney Foundation organized a multidisciplinary working group, including people with CKD and family care partners, to develop recommendations to improve vaccination rates, vaccination effectiveness, and health care for the CKD population. A modified Delphi process was used to achieve consensus on the recommendations. Recommendations on vaccination in CKD patients were organized into these categories: (1) patient preferences; (2) assessing the vaccination status of patients with CKD; (3) assessing vaccine response in patients with CKD; (4) vaccination of immunocompromised patients; (5) vaccination in posttransplant patients; (6) …

Finding Significant Hits In Networks: A Network-Based Tool For Analyzing Gene-Level P-Values To Identify Significant Genes Missed By Standard Methods, Sandeep Acharya, Vaha Akbary Moghaddam, Wooseok J Jung, Yu S Kang, Shu Liao, Michael A Province, Michael R Brent

2020-Current year OA Pubs

Finding Significant Hits in Networks (FISHNET) uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate, nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of genome-wide association studies P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low purely by chance are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect chance and more …

Apoe And Plasma Ad Biomarkers: The Role Of Genetic Ancestry In Hispanics/Latinos, Caitlin Cheung, Natasha Z Anita, Paola Filigrana, Myriam Fornage, Kevin A Gonzalez, Linda C Gallo, Carmen R Isasi, Robert C Kaplan, Xihao Li, Freddie Márquez, Humberto Parada, Krista M Perreira, Alberto R Ramos, Tatjana Rundek, Wassim Tarraf, Fernando D Testai, Charles Decarli, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

Background: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.

Methods: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.

Results: ε4 was associated with lower Aβ42/40 and higher p-tau181and …

Incidence Of Cancers Among Children Living With Hiv In Malawi After Widespread Availability Of Antiretroviral Therapy: A Population-Based Study, Casey L Mcatee, Fatsani Manase, William Kamiyango, Jimmy Villiera, Mark Zobeck, Joseph Mhango, Allison Silverstein, Samuel Maloya, Apatsa Matatiyo, Eluness Simwela, Honour Mhango, Desire Hellings, Brigid O'Brien, Claudia Wallrauch, Tom Heller, Matthew Painschab, Kate Westmoreland, Atupele Mpasa, Rizine Mzikamanda, Nmazuo Ozuah, Joseph Lubega, Nader Kim El-Mallawany, Carl E Allen, Michael E Scheurer

Faculty, Staff and Students Publications

Purpose: Few data describe the modern epidemiology of pediatric HIV-associated cancers in sub-Saharan Africa, home to over 80% of the world's children living with HIV. This study evaluated the incidence of cancers among these children over 15 years after widespread antiretroviral therapy (ART) adoption in Malawi.

Methods: We conducted a retrospective population-based cohort study leveraging multiple independent data sources comprehensive of all cancer diagnoses among children living with HIV in Northern and Central Malawi between 2010 and 2024. HIV-associated cancers were defined as those cancers with well-established epidemiologic associations with HIV. Cumulative incidence and average annual percent change were estimated …

Online Tutorial On Survival Analysis For Biomarker Discovery, Jaka Kokošar, Ela Praznik, Martin Špendl, Nancy P Moreno, Alana Newell, Gad Shaulsky, Blaž Zupan

Faculty, Staff and Students Publications

In biomedicine, survival analysis addresses time-to-event data to study outcomes like patient survival and treatment response, and supports biomarker discovery. Yet, teaching this analysis is often hindered by mathematical and programming barriers. We present a structured, hands-on tutorial that goes beyond a typical online guide-offering integrated video lectures, literature, quizzes, and practical exercises. Built around Orange Data Mining, an open and free no-code visual analytics platform, the tutorial covers key concepts such as censoring, Kaplan-Meier curves, group comparisons, and biomarker discovery through real-world datasets. Organized in four pedagogical units, it progresses from basic survival data analysis to gene and gene-set …

Examining Sleep-Related Problems In Youth With Misophonia, Kevin M Wagner, Matti Cervin, Catherine E Rast, Mered Parnes, Nicholas Murphy, Samuel Spencer, Eric A Storch, Andrew G Guzick

Faculty, Staff and Students Publications

The relationship between misophonia and sleep-related problems (SRPs) in youth is underexplored. This paucity of research is concerning because SRPs might be elevated among youth with misophonia. If left untreated, SRPs can contribute to long-term health consequences. Thus, in this study we examined the link between misophonia and SRPs in youth aged 8 to 17. In this study, we compared SRPs in 102 children and adolescents with clinically significant misophonia to SRPs in a normative youth sample and a sample of 94 youth with anxiety disorders. We also examined the extent to which SRPs were associated with misophonia severity. Approximately …

Risk Factors For Acute Rejection In Pediatric Lung Transplantation And Its Impact On Graft Failure, Sophie Li, Spoorthi Kamepalli, David Moreno Mcneill, Selena Li, Abbas Rana

Faculty, Staff and Students Publications

Background: Although acute rejection is a common complication of lung transplantation, few studies have analyzed risk factors for acute rejection in pediatric lung transplant patients. The purpose of this study was to examine risk and protective factors for acute rejection in pediatric lung transplantation and its impact on graft failure.

Methods: A retrospective analysis was performed on lung transplant data for a cohort of 906 pediatric patients from the Organ Procurement and Transplantation Network (OPTN) Database between October 1, 1987, and June 30, 2023. Multivariable logistic regression was conducted to identify risk and protective factors for acute rejection, adjusting for …

How Does Frailty Impact Peri-Operative And Speech Recognition Outcomes For Cochlear Implants In Veterans?, Kaitlyn A Brooks, Benjamin D Lovin, Alex D Sweeney, Angela S Peng, Nathan R Lindquist

Faculty, Staff and Students Publications

Objective: To investigate the association of frailty with post-cochlear implant (CI) admission, morbidity, and CI-aided word recognition outcomes in veterans.

Study design: Retrospective cohort.

Setting: Single-institution tertiary care Veterans Health Administration (VHA) hospital.

Methods: Veterans who underwent cochlear implantation between 1998 to 2024 were included. The Modified 5-Item Frailty Index (mFI-5) score was used to characterize preoperative frailty. Outcomes of interest were admission from post-anesthesia care unit (PACU), relative risk (RR) of admission among frail patients, and relationship between frailty and post-CI word recognition score (WRS). Ordinal data were analyzed via logistic regression and Chi square tests; a multivariate linear …

Lean On Me: Social Factors And Diabetes Outcomes Among Young Adults With Type 1 Diabetes Prior To Transitioning To Adult Care, Caroline M Roberts, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Randi Streisand, Barbara J Anderson, Tricia S Tang, Siripoom Mckay, Katherine Gallagher, Sridevi Devaraj, Marisa E Hilliard

Faculty, Staff and Students Publications

Aims: Little is known about how different aspects of social relationships relate to diabetes self-management and glycaemic outcomes in young adults with type 1 diabetes (T1D). We examined relationships of general and diabetes-specific social variables with diabetes self-management and HbA1c. We hypothesized diabetes-specific factors would more strongly associate with self-management and HbA1c than general social factors.

Methods: We analysed baseline data from 100 young adults with T1D (Mage = 19.9 ± 1.3 years) enrolled in a randomized controlled trial of a paediatric to adult care transition intervention. We examined associations of self-reported general and diabetes-specific social factors with self-reported self-management …

Hes V2.0 Validation And Performance Compared To Galad And Asap In The Heds Cohort, Hashem B El-Serag, Camden Lopez, Michelle Luster, K Rajender Reddy, Neehar Parikh, Amit G Singal, Jorge A Marrero, Aaron P Thrift, Jagpreet Chhatwal, Ziding Feng, Stephanie Page-Lester, Qingchun Jin, Nabihah Tayob, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: We previously developed HES V2.0, a biomarker panel (age, ALT, platelets, etiology, AFP, AFP-L3, DCP, and their 1-year gradients) for early detection of hepatocellular carcinoma (HCC) among patients with cirrhosis. We externally validated HES V2.0 and compared its performance with HES V1.0, GALAD, and ASAP.

Methods: We conducted a PRoBE (prospective specimen-collection, retrospective blinded-evaluation) cohort study in the HEDS (Hepatocellular Carcinoma Early Detection Strategy) cohort of 1,485 patients with cirrhosis, of whom 119 developed HCC. Patient- and test-level true positive rates (TPR) for HCC were calculated at 6, 12, and 24 months before diagnosis, using thresholds at …

Defining The Society Of Pediatric Liver Transplantation (Split) Research Agenda: A Delphi Consensus Project, Sharad I Wadhwani, Pooja Reddy Spector, Amy G Feldman, Katryn N Furuya, Kayla Hartjes, Chaowapong Jarasvaraparn, Beau Kelly, Stacee M Lerret, Krupa Mysore, Arti Pawaria, Philip Rosenthal, Amy Shui, Voytek Slowik, Sarah Taylor, Jennifer Vittorio, Pamela L Valentino

Faculty, Staff and Students Publications

Background: Despite major advances in surgical and medical management, only one-third of pediatric liver transplant (LT) recipients remain morbidity-free at 10 years. The Society of Pediatric Liver Transplantation (SPLIT) published a research agenda over 10 years ago, and much progress has been made since then. An updated consensus-driven SPLIT research agenda could guide future research and funding priorities. We aimed to identify and prioritize key research needs across the continuum of pediatric LT care using a modified Delphi consensus approach.

Methods: We conducted a three-round modified Delphi process among SPLIT members. In round 1, participants submitted open-ended research priorities. In …

Adenovirus Disease Following Pediatric Liver Transplantation: 10-Year Experience From A Large Pediatric Transplant Program, Anna M Banc-Husu, Sara Hassan, N Thao N Galvan, Elizabeth A Moulton, Jeremy M Schraw, Kathleen Hosek, Dana Cerminara, Flor M Munoz, Krupa Mysore

Faculty, Staff and Students Publications

Background: Human adenovirus in immunocompromised patients can be life-threatening. We describe the prevalence, clinical presentation, and treatment of adenovirus after pediatric liver transplantation at a large transplant center.

Methods: We performed a retrospective cohort study of adenovirus infection in children from 2013 to 2022. We compared incidence, clinical characteristics, and outcomes of post-transplant children by adenovirus treatment status.

Results: Adenovirus disease developed in 26% (84/320) children after liver transplant. Median age at liver transplant was 17.5 months, 48% were female; 50% had biliary atresia. Fever (53%), gastrointestinal symptoms (48%), and hepatitis (41%) were the most common clinical presentations at diagnosis. …

Comparing Observed With Self-Reported Hand Hygiene Adherence Among Bedside Nurses And Physicians At Two Hospitals In The United States, Prathit A Kulkarni, M Todd Greene, Sanjay Saint, Karen E Fowler, Serene Jacob, Laura Dillon, Michelle Espiritu, Nathan Houchens, Huberta T Cozart, Barbara W Trautner

Faculty, Staff and Students Publications

Background: Hand hygiene is a core component of infection prevention in healthcare settings. One potential reason for lack of adherence to recommended hand hygiene practices is erroneous self-perception. We aimed to compare perceptions about hand hygiene compliance with objective data.

Methods: Direct observations of hand hygiene performance by nurses and physicians during typical workflow in inpatient general medicine wards were conducted from 12 September 2022 to 27 October 2022 at two academic Veterans Affairs medical centers. Participants were surveyed regarding perceptions about their hand hygiene performance relative to recommended practices.

Results: Among nurses, hand hygiene was performed in 1,397/3,690 (37.9%) …

Interpretable Ensemble Machine Learning Prediction Of Nonadherence And The Risk Of Nonpersistence Of Targeted Disease-Modifying Antirheumatic Agents In Older Adults With Rheumatoid Arthritis, Yinan Huang, Sandeep K Agarwal

Faculty, Staff and Students Publications

Purpose: Ensemble machine learning (ML) demonstrated potential for improving predictions based on big health care data. We developed and validated interpretable ensemble ML models in evaluating the nonadherence and nonpersistence of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA).

Methods: This retrospective study used 5% Medicare claims data including older (aged ≥65 years) patients initiating b/tsDMARDs (the index date) between 2013 and 2019, who were diagnosed with RA (the International Classification of Diseases, Ninth and Tenth revision codes). Nonadherence, defined as medication possession ratio < 80%, was evaluated during the 12-month follow-up. Nonpersistence was defined as duration (in days) from the index date until treatment gap ≥60 days during the follow-up period, with death and insurance disenrollment as censoring criteria. Data were split into 75% for model training and 25% for evaluation, with patients' demographics and clinical characteristics measured in the baseline period. Machine learning ensemble classification models (random forest, eXtreme Gradient Boosting [XGBoost], and prediction rule ensembles [PRE]) evaluated the binary nonadherence outcome and ML ensemble survival models (random survival forest, XGBoost survival, and PRE survival) assessed time until nonpersistence. Using the testing cohort, concordance index (C-index) was reported for the ML survival models and AUC was reported for ML classification models.

Findings: We identified 3927 eligible patients with RA (mean age 73 ± …

Segmental And Multifocal Isolated Dystonias: Similarities And Differences, Hyder A Jinnah, Vittorio Velucci, Daniele Belvisi, Gamze Kilic-Berkmen, Joel S Perlmutter, Laura J Wright, Christine Klein, Jeanne S Feuerstein, Steven Bellows, Joseph Jankovic, Cynthia Comella, Richard L Barbano, Aparna Wagle Shukla, Stephen G Reich, Mark S Ledoux, Alberto J Espay, Kevin R Duque, Florence C F Chang, Victor S C Fung, Sarah Pirio-Richardson, Carmen Terranova, Emile S Moukheiber, Sarah Idrissi, Barbara Vitucci, Susan H Fox, Samuel Frank, Natividad Stover, Brian D Berman, Rachel Saunders-Pullman, William G Ondo, Christopher L Groth, Marcello Esposito, Laura Avanzino, Francesco Bono, Roberto Erro, Marcello Mario Mascia, Antonella Muroni, Alfredo Berardelli, Giovanni Defazio

Faculty, Staff and Students Publications

Background: Whether the traditional distinction between segmental and multifocal dystonia is clinically or scientifically useful remains unclear.

Objective: To evaluate whether idiopathic isolated adult-onset segmental and multifocal dystonia can be differentiated based on clinical features other than the contiguity of affected body regions.

Methods: We compared data on segmental and multifocal dystonia from two large dystonia databases established in the USA and Italy that used similar criteria for patient recruitment and assessment.

Results: Compared to segmental dystonia, multifocal dystonia was characterized by a higher proportion of men, a younger age at dystonia onset, a greater frequency of upper limb dystonia, …

Impulsivity In Cerebellar Ataxia: An Online, Multidimensional Assessment, Brooke Chasalow, Yakov Flaumenhaft, Yael De Picciotto, Chi-Ying R Lin, Leila Montaser-Kouhsari, William Saban

Faculty, Staff and Students Publications

While considered a motor control structure, the cerebellum contributes to non-motor functions, including impulsivity. However, whether it contributes to impulsivity in a domain-specific manner remains unknown. Studies on cerebellar ataxia (CA), a common model for cerebellar dysfunction, typically have small sample sizes, limiting robustness. In a multicenter cross-sectional study, we investigated the cerebellum's role in various forms of impulsivity by comparing large cohorts of CA to age- and education-matched neurotypical healthy (NH) controls. Additionally, to examine the ability to identify individuals with CA using impulsivity features alone, we developed supervised machine learning (ML) models. In experiment 1 (CA = 140, …

Pharmacodynamics, Efficacy, And Safety Of Intraputaminal Eladocagene Exuparvovec Administered To Pediatric Patients With Aromatic L-Amino Acid Decarboxylase Deficiency Using An Mr-Compatible Cannula: 48 Weeks Of Follow-Up, Daniel J Curry, Phillip L Pearl, Scellig S D Stone, Donald L Gilbert, Sudhakar Vadivelu, Bruria Ben-Zeev, Matthew Vestal, Muhammad Zafar, Chun-Hwei Tai, Sheng-Che Chou, Zion Zibly, Lior Ungar, Mered Parnes, Mariam Hull, Lisa Emrick, Christian Werner, Alexis Krolick, Vinay Penematsa, Antonia Wang, Rezwanur Rahman, Lee Golden, Yin-Hsiu Chien, Paul Wuh-Liang Hwu

Faculty, Staff and Students Publications

Aromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare pediatric neurotransmitter disorder that typically necessitates lifelong care, and that carries a risk of childhood mortality. Eladocagene exuparvovec gene therapy is designed to restore AADC production. Study GT‐002 (NCT04903288) is a phase 2, multicenter, open‐label trial assessing the pharmacodynamics, safety, and efficacy of eladocagene exuparvovec administered to the putamen bilaterally in pediatric patients with AADC deficiency using a magnetic resonance (MR)‐compatible cannula. Patients received eladocagene exuparvovec at 1.8 × 1011 vector genomes via the SmartFlow MR‐compatible cannula in a single operative session. Endpoints include the change from baseline in …

Predicting Mortality And Costs After Emergency Department Visits By People With Dementia: Timing And Location Matter, Jason K Bowman, Christine S Ritchie, Kei Ouchi, Kyler M Godwin, James A Tulsky, Joan M Teno

Faculty, Staff and Students Publications

Background: People with dementia have high rates of emergency department (ED) and hospital utilization, high mortality and costs, and other poor outcomes. To successfully impact the care trajectories of these patients, health care systems must pragmatically identify the correct target population. This study described patterns of ED utilization by people with dementia and explored the accuracy of administrative data models to predict mortality and costs.

Methods: Retrospective cohort study of a 20% random sample of Traditional Medicare (TM) beneficiaries with dementia, age ≥ 66 years, and an index ED visit in 2018. One-year mortality and high costs were described, and …

Validation Of Longitudinal Biomarker Screening Algorithms For Hcc Detection In Patients With Cirrhosis, Amit G Singal, Qingchun Jin, Jorge Marrero, Neehar D Parikh, Anna S Lok, Camden Lopez, Stephanie Page-Lester, Lewis R Roberts, Rajender Reddy, Michelle Luster, Saira Khaderi, Sumeet K Asrani, Hashem B El-Serag, Fasiha Kanwal, Ziding Feng, Nabihah Tayob

Faculty, Staff and Students Publications

Background: Blood-based biomarker panels, including GALAD, have been proposed as an alternative to abdominal ultrasound for hepatocellular carcinoma (HCC) surveillance. Studies suggest longitudinal evaluation of biomarkers can improve test performance; however, no large studies have validated these findings.

Methods: We leveraged the HCC Early Detection Strategy (HEDS) study (n=1019 patients with cirrhosis; 99 incident HCC) and Texas HCC Consortium (THCCC) (n=2345 patients with cirrhosis; 126 incident HCC) to compare the performance of fixed-threshold GALAD (cutoff of -1.36), and 4 longitudinal algorithms: longitudinal GALAD, PALAD, mFB-ALAD, and mPEB-ALAD. The HEDS cohort was used to derive longitudinal algorithms, and external validation was …

Development Of Retrieval-Augmented Generation-Based Large Language Model For Drug-Induced Liver Injury Using Livertox Data, Ashwin Rao, George Cholankeril, Avegail Flores, Gagan Sood, Terrence E White, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

Background: Idiosyncratic DILI is a complex clinical challenge requiring timely and accurate decision support. LiverTox, curated by the National Institute of Health (NIH), offers a comprehensive DILI evidence base, but its encyclopedia-like format hinders point-of-care use. Health care providers increasingly use general large language models (LLMs) for clinical care, raising safety concerns due to LLM hallucinations or misinformation. We hypothesize that retrieval-augmented generation (RAG) integration-grounding LLM responses in LiverTox content-would enable accurate DILI decision support.

Methods: We processed 1343 LiverTox drug monographs into 8759 indexed segments using BioBERT embeddings. We developed a RAG pipeline that employs drug-specific prioritization, section-aware weighting, …