Digital Commons Network^™

Assessment Of In-Frame Indel Variants In An Unsolved Cohort Of Inherited Retinal Diseases Using Machine Learning, David E Rauch, Meng Wang, Muhammad Jafar Hussain Hafiz, Daniel C Brock, Yumei Li, Molly Marra, Mark E Pennesi, Paul Yang, Everett Lesley, Irma Lopez, Robert Koenekoop, Edward Ryan Collantes, Joanne Bolinao, Rui Chen

Faculty, Staff and Students Publications

The standard for in silico pathogenicity prediction of in-frame insertions and deletions (indels) is less established compared to other types of variations. We aimed to systematically assess the performance of in silico machine learning (ML) tools on a patient cohort with inherited retinal diseases (IRDs). The performance of four ML tools (CADD, FATHMM-indel, VEST4, and MetaRNN-indel) was compared. Among them, MetaRNN-indel showed the best overall results. MetaRNN-indel was then applied to 1013 unsolved IRD patients, identifying two likely pathogenic causal variants in two unrelated IRD patients by confirming clinical phenotypes. Hence, our findings indicate that reliable prediction of the pathogenicity …

Modulation Of Corneal Sensory Processing And Pain Responses By Dry Eye And Corneal Wounding, Ebru Yaman, Yangluowa Qu, Kaylin C Arpaia, Fairouz Elsaeidi, Uma Lakshmi Balakrishnan, Lance He, Henry Skrehot, Jehan Alam, Rui Chen, Mary Ann Stepp, Cintia S De Paiva, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Background: Dry eye disease (DED) is a multifactorial disorder of the ocular surface in which tear film instability, epithelial barrier disruption, and neurosensory dysfunction contribute to symptom generation. Although several contributing factors have been identified, how different forms of ocular surface stress affect sensory pathways and behavioral responses remains unclear.

Purpose: This study aimed to evaluate corneal barrier function, sensory responses, and pain-related behaviors across acute and chronic dry eye and corneal injury models, and to assess stimulus-specific responses associated with TRPV1 and TRPM8 mediated pathways.

Methods: Female C57BL/6 J wild type and Mmp9KO mice were evaluated in acute desiccating …

Strategies And Challenges For The Recruitment Of Young Healthy Participants In The Dietary Approaches To Longevity And Health (Dial Health) Pilot Trial, Hannah E Cabre, Courtney M Peterson, Gareth R Dutton, Kimberly L Drews, Stephanie T Broyles, Robert Dubin, Laura Q Rogers, Catherine Champagne, Dennis T Villareal, Daniel S Hsia, Leanne M Redman, Corby K Martin

Faculty, Staff and Students Publications

Background: Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.

Methods: We analyzed recruitment costs to enroll 70 participants (ages 25-49, BMI 22.0-29.9 kg/m2) across two DiAL Health sites and used NHANES data (2017-March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.

Results: Of 2049 applicants …

Differences In Gene Expression May Contribute To The Racial Differences In The Risk Of Masld, Ivan P Gorlov, Olga Y Gorlova, Aaron P Thrift

Faculty, Staff and Students Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), exhibits marked racial disparities in incidence, progression, and clinical outcomes. While diet, lifestyle, and socioeconomic factors have been shown to influence these disparities, biological mechanisms underlying racial differences in MASLD risk remain poorly understood. We hypothesized that race-associated variation in hepatic gene expression may contribute to differential susceptibility and progression of MASLD. To test this hypothesis, we analyzed publicly available gene expression data from liver biopsies obtained from over 300 Black and White individuals undergoing bariatric surgery. Gene expression profiles were compared across four histological stages: …

Sewers To Solutions: A Guide To Wastewater Pathogen Monitoring, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Wastewater-based epidemiology (WBE) is the analysis of wastewater to detect pathogen levels or activity for public health awareness or action. Pioneered in the 1940s, WBE underwent a resurgence during the COVID-19 pandemic, providing important information about number of cases, outbreaks, and seasonal impact. With advancements in detection technologies and growing interest in environmental surveillance, WBE is poised to become a standard practice in public health monitoring. Here, we provide an overview of the current state of the art of pathogen WBE, including methods of molecular detection, analysis of wastewater data, real-world applications and programs, public health interventions, and benefits and …

Editorial: Advances In Phage Applications: Deciphering Phage Biological And Ecological Mechanisms Through Metagenomics, Tasha M Santiago-Rodriguez, Gary A Toranzos

Faculty, Staff and Students Publications

No abstract provided.

Identification Of Cand1 As A Dna-Dependent Protein Kinase-Regulated Coactivator Of Androgen Receptor And The Arv7 Splice Variant, Ross A Hamilton, Basil Paul, Ping Yi, Kimal Rajapakshe, Anil K Panigrahi, Sandra L Grimm, Cristian Coarfa, Anna Malovannaya, Nancy L Weigel, David M Lonard, Charles E Foulds

Faculty, Staff and Students Publications

ARv7, the most prevalent androgen receptor (AR) variant in castration-resistant prostate cancer, lacks the ligand binding domain (LBD), rendering it resistant to LBD-targeted therapies. Identifying new therapeutic targets requires defining the coregulators and associated regulatory enzymes that govern AR and ARv7 transcriptional activity. Here, we have developed a cell-free DNA pulldown assay employing androgen response elements (AREs) to isolate and characterize the AR- and ARv7-associated coregulator complexes formed on DNA. Mass spectrometry analyses of ARE DNA pulldowns revealed previously unrecognized AR and ARv7 associating coregulators, such as cullin-associated NEDD8-dissociated protein 1 (CAND1), in addition to previously known coregulators. ARv7 showed …

Helicobacter Pylori And Cancer: What's The Link?, Elettra Merola, Giovanni Mario Pes, David Yates Graham, Maria Pina Dore

Faculty, Staff and Students Publications

Helicobacter pylori (H. pylori) is a human bacterial pathogen that causes one of the most common chronic bacterial infections worldwide. The microorganism has been classified by the International Agency for Research on Cancer as a Group I carcinogen. While the etiological link to gastric cancer is well established, the precise molecular and cellular mechanisms driving this transformation are highly complex and incompletely understood. Fundamentally, the infection results from the chronic presence of acute on chronic gastric mucosal inflammation. H. pylori pathogenicity is increased by bacterial virulence factors including the cytotoxin-associated gene A (CagA) and Vacuolating cytotoxin A (VacA) …

Genomic And Structural Analysis Of Major Antigenic Proteins’ Variability In The Human Relapsing Fever Spirochete Borrelia Persica, Dor Shwartz, Yaarit Nachum-Biala, Reinhard K Straubinger, Ofir Segev, Asaf Levy, Job E Lopez, Gad Baneth

Faculty, Staff and Students Publications

Antigenic variation enables immune evasion of pathogens, yet the mechanisms for the rapid change in their antigens without loss of structural and functional features are not fully known. Tick-borne relapsing fever (TBRF) spirochetes of the genus Borrelia can be used as a model because their variable major proteins (Vmps) drive antigenic variation followed by recurrent waves of bacteremia. In this study we generated the genome of Borrelia persica LMU-C01 and evaluated Vmp structure across relapsing fever Borrelia species. Borrelia persica was found to have a genome of 1.7Mb with one linear chromosome, 12 linear and one circular plasmids. Telomeric hairpin …

Autologous Multiantigen-Targeted T Cell Therapy For Pancreatic Cancer: A Phase 1/2 Trial, Benjamin L Musher, Spyridoula Vasileiou, Brandon G Smaglo, Catherine S Robertson, Mengfen Wu, Tao Wang, Ayumi Watanabe, Manik Kuvalekar, Yovana Velazquez, Shamika Ketkar, Tamadar Al Doheyan, Penelope G Papayanni, Aakash Shah, Natalia Lapteva, Bambi J Grilley, George Van Buren, Premal D Lulla, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, Ann M Leen

Faculty, Staff and Students Publications

T cell therapy has proven challenging for pancreatic ductal adenocarcinoma (PDAC), partly due to heterogeneous expression of tumor-associated antigens (TAAs). To address tumor heterogeneity and mitigate immune evasion, an ex vivo expanded, polyclonal, T helper 1 cell-polarized T cell product targeting five TAAs—PRAME, SSX2, MAGEA4, Survivin and NY-ESO-1—was developed. These antigens were chosen based on their tumor specificity, oncogenicity, immunogenicity and level of expression. In a phase 1/2 trial, this autologous nonengineered T cell product was administered (1 × 107 cells m−2 per infusion) monthly to patients with advanced PDAC responding (arm A, n = 13) or refractory (arm B, …

Therapeutic Potential Of Hookworm Proteins In Promoting Regulatory Immune Responses To Modulate Trypanosoma Cruzi Induced Liver Inflammation And Oxidative Stress, Maria Jose Villar, Cristina Poveda, Bin Zhan, Maya Gonsoulin, Kathryn M Jones

Faculty, Staff and Students Publications

Background: Chronic Trypanosoma cruzi infection causes significant liver pathology, and current antiparasitic treatments often worsen hepatic damage. Hookworm-derived proteins have shown immunomodulatory effects in inflammatory diseases, including T. cruzi-induced myocarditis.

Objective: This study evaluates recombinant hookworm proteins AIP-1 and AIP-2 for treating liver inflammation in a murine model of chronic Chagas disease (CD).

Methods: Female BALB/c mice infected with T. cruzi were treated with AIP-1 or AIP-2 (1 mg/kg) for seven days. Controls were untreated or received aspirin (25 mg/kg) for 14 days. Liver tissues were analyzed for parasite burden (quantitative polymerase chain reaction - qPCR), histopathology (H&E, Picrosirius Red), …

Molecular Heterogeneity Of Hpv-Associated Cancers And Strategies To Overcome Treatment Resistance, Sara Rasouli, Weiyi Gong, Raegan Wood, Danyal Daneshdoust, Anam Khan, Rani Mahyoob, Chongwen Cao, Zihao Yu, Nagireddy Putluri, Gennady Shvets, Haichang Li, Bo Zhao, Xuefeng Liu, Jenny Li

Faculty, Staff and Students Publications

Human papillomavirus (HPV) is a major driver of global cancer incidence, responsible for nearly all cervical cancers and a significant proportion of oropharyngeal, anal, and other anogenital cancers. Despite the availability of effective vaccines, HPV-associated cancers persist due to persistent infection, immune evasion, and the virus's ability to integrate into the host genome, contributing to molecular heterogeneity and therapeutic resistance. Here, we summarize molecular heterogeneity and the emerging combined therapeutic strategies. High-risk HPV types, notably HPV16 and HPV18, initiate carcinogenesis through persistent infection of epithelial basal cells and through the actions of the E6 and E7 oncoproteins, which disrupt the …

Δnp63 Defines An Exocrine-Committed Subset Of Murine Pancreatic Progenitor Cells, Katarina Coolens, Melissa Van Der Vliet, Jente Van Campenhout, Natalia Del Pozo, Alejo Torres-Cano, Catharina Olsen, Jianming Xu, Rose-Anne Romano, Heiko Lickert, Meritxell Rovira, Isabelle Houbracken, Jonathan Baldan, Francisco X Real, Francesca M Spagnoli, Ilse Rooman

Faculty, Staff and Students Publications

No abstract provided.

Intraoperative Neurophysiological Monitoring In Full-Endoscopic Cervical Endoscopic Ulbd, Miles Hudson, Sarah Esposito, Mark M Zaki, Simon M Glynn, Osama N Kashlan, John Ogunlade, Chandan Krishna, Joshua Bakhsheshian, Christoph P Hofstetter

2020-Current year OA Pubs

No abstract provided.

Application Of Heron's Formula, Hidefumi Katsuura

Faculty Research, Scholarly, and Creative Activity

We apply Heron's formula to obtain a generalized Ptolemy's theorem, to prove Euler's formula for the volume of a tetrahedron, and to prove Klain's theorem on reversible tetrahedra. After that, we prove triangle inequalities derived from a tetrahedron, find an inequality on the circumradius of a tetrahedron, find a volume expression of an isosceles tetrahedron, and give a condition for four points in the space to be co-planar.

Empowering Students To Engage With Climate Change Action: A Project-Based Module For Artificial Intelligence Literacy And Sustainability Thinking, Gabriel Granco, Yu Chen, Heather Macias, Yunfei Hou, Frank A. Gomez

Faculty Research, Scholarly, and Creative Activity

There is a growing need to prepare students to address complex environmental challenges, particularly climate change and the expanding role of artificial intelligence (AI). This article examines the adaptation of the Artificial Intelligence for Social Good (AI4SG) Ideation module, a pitch- and project-based teaching framework designed to integrate AI literacy and sustainability education. Implemented in an upper division climate change course, the module combines project-based learning, culturally responsive pedagogy, and geographic thinking to guide students in developing community-oriented AI proposals aligned with the United Nations Sustainable Development Goals (SDGs). Students were encouraged to approach their communities not through deficit lenses, …

Artificial Intelligence And Data Science In Agriculture Specialty Crops And Climate Change Modeling, Chandrasekar Vuppalapati

Faculty Research, Scholarly, and Creative Activity

Specialty crops—fruits, vegetables, nuts, horticulture, and nursery crops—are a powerful engine of agricultural growth, contributing nearly one-fifth of U.S. farm revenues and driving a $1.6 trillion global market. As demand rises and climate challenges intensify, growers need smarter tools to stay competitive. This book brings together AI, data science, climate modeling, and economic forecasting to help farmers and innovators improve yields, manage risk, enhance sustainability, and secure long-term profitability. Designed for agricultural leaders, technologists, and policymakers, it delivers practical, future-ready solutions to strengthen specialty crop resilience and global food security. Presents the applications of data science and AI to agriculture …

Federal Protections For Farmworker Health In The United States: A Scoping Review Of Three Decades Of Research, Kaitlyn Alvarez Noli, Stephane Labossiere, Becca Berkey, Joseph G. Grzywacz

Faculty Research, Scholarly, and Creative Activity

Objectives: This scoping review characterizes the scope, methods, and framing of empirical research evaluating the Field Sanitation Standard (FSS) and Worker Protection Standard (WPS) of the U.S. Environmental Protection Agency and the U.S. Department of Labor respectively. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we identified empirical studies (1990–2024) assessing elements of either the FSS or WPS. Two reviewers screened and extracted study characteristics, designs, populations, and regulatory elements. Framing analysis of 1226 segments, identified using a large language model, from the studies' abstracts and introductions examined how authors conceptualized farmworkers' need for protection. …

Generation Of Impact Factor-Driven Security Rating Questionnaire Using Llms For Aiot Applications, Yuna Han, Simon Shim, Deva Kumar Gajulamandyam, Yeji Choi, Hyunwoo Lee, Hangbae Chang

Faculty Research, Scholarly, and Creative Activity

Industry 4.0 has transformed industries by accelerating the adoption of artificial intelligence of things (AIoT); however, it has also led to security risks, such as data leakage. Existing data protection research focuses on network layers, whereas application-layer rating systems rely on subjective evaluations, limiting consistency and applicability. This study proposes a scalable and objective AIoT security rating framework that clarifies ambiguities in the five-question rating system of the Korean Intellectual Property Office and unifies fragmented managerial and technical rating systems. By leveraging large language models (LLMs), the framework integrates a security rating model based on 14 impact factors with automated …

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

Breaking The Cycle: Rethinking Bar Exam Scoring And Portability For Nextgen Examinees, Steven Foster, Nachman Gutowski

Scholarly Works

The development of the NextGen Bar Exam presents a crucial opportunity to address longstanding challenges in both bar exam scoring and portability concerns. The reliance on recent graduates' performance on the Uniform Bar Examination (UBE) as a baseline for setting future standards is flawed due to relative scoring and scaling. In addition to concerns regarding how the future bar exam is scored, there are also concerns regarding how the new scoring metric on the NextGen bar exam will be used for portability and, more specifically, what will happen between 2026 and 2028 as the NextGen bar exam is progressively adopted …

Beyond Restless Sleep: A Cross-Sectional Study Of Obstructive Sleep Apnea Risk, Aging Biomarkers, And Chronic Low Back Pain, Khalid W Freij, Fiona Bat Agbor, Philemon Domoyeri, Kiari R Kinnie, Asia M Wiggins, Demario S Overstreet, Tammie L Quinn, Shivraj S Grewal, S Justin Thomas, Walid W Freij, Shameka L Cody, Michael A Owens, Robert E Sorge, Burel R Goodin, Edwin N Aroke

2020-Current year OA Pubs

This secondary data analysis aimed to determine the nature of the relationship between obstructive sleep apnea (OSA) risk, biological age acceleration, and nonspecific chronic low back pain (CLBP). In total, 199 adults aged 18-82 years who filled both STOPBANG and pain questionnaires subsetted for secondary analysis. Based on the STOPBANG questionnaire, 104 had a low OSA risk and 95 had an intermediate or high OSA risk. Dunedin Pace of Aging Computed from the Epigenome (DunedinPACE), Horvath's, Hannum's, PhenoAge, and GrimAge clocks were used to determine biological age and pace of biological aging. Individuals with low OSA risk reported increased DunedinPACE …

Civil Rights Microviolations, Michael Kagan, Alissa Cooley Yonesawa

Scholarly Works

No abstract provided.

An Integrated View Of The Structure And Function Of The Human 4d Nucleome, Job Dekker, Ting Wang, Daofeng Li, Et Al.

2020-Current year OA Pubs

The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project

Lost Before Forgetting: Objective Driving Metrics Track Navigation Deficits Tied To Preclinical Alzheimer's Disease, Yiqi Zhu, Ramkrishna K Singh, Semere Bekena, David C Brown, Chen Chen, Matthew Blake, Jean-François Trani, Ganesh M Babulal

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Navigation is a complex, multisensory process in which subtle changes may emerge before the onset of symptomatic Alzheimer's disease (AD). This study investigated whether navigation abilities were associated with amyloid and tau pathology in cognitively normal older adults.

RESEARCH DESIGN AND METHODS: Among 285 cognitively unimpaired older adults, navigation and objective driving behaviors were assessed using the self-reported Santa Barbara Sense of Direction Scale (SBSOD) and a datalogger, respectively. Amyloid and tau burden were quantified using PET-MRI 2 years post-initial driving data collection. Linear mixed-effects models were used to evaluate the associations between biomarker status and longitudinal …

Legal Ethics Of Ai Snake Oil: Navigating The Hype, Harm, And Hope Of Legal Ai, Drew Simshaw

Scholarly Works

This paper argues that the legal ethics of AI extend far beyond competence and hallucinations. It shows how AI often functions as a mirror, exposing deeper ethical questions about institutional incentives, lawyer wellbeing, access to justice, and AI's broader social and environmental impacts.

Advancing Inter-Brain Synchrony Measurement: A Comparative Hyperscanning Study Of Diffuse Optical Tomography And Functional Near-Infrared Spectroscopy, Shuo Guan, Yuhang Li, Yingbo Geng, Dongyun Li, Qiong Xu, Peisong Niu, Dalin Yang, Adam Eggebrecht, Yingchun Zhang, Rihui Li

2020-Current year OA Pubs

Inter-brain synchrony (IBS), measured by hyperscanning, refers to the synchronization of multiple individuals' brain activities during social interactions. Traditional fNIRS-based hyperscanning suffers shortcomings like low spatial resolution and high susceptibility to superficial interference, causing imprecise estimation of IBS in complex social tasks. This study aims to fill the knowledge gap by comprehensively assessing diffuse optical tomography (DOT), an enhanced alternative to fNIRS, can benefit hyperscanning studies of complex social interactions. Sixteen dyads were engaged in both collaborative and individual tangram puzzle tasks, and their brain activities were recorded simultaneously using DOT and fNIRS. We found that DOT demonstrated significantly stronger …

Memoir: The Brain, Neuroethics, And Bioethics, Leslie C. Griffin

Scholarly Works

This Essay examines how developments in neuroscience (or brain science) affect our views of law, medicine, ethics, and religion. Part I shows how lack of clarity about brain death can lead to premature organ donation. Part II argues that health care too often provides inadequate brain care and incomplete rehabilitation. Part III explains why recovery may be possible for those braininjured patients who are told it is not. Part IV demonstrates how the fear of a brain-injured patient oddly affects my perspective on Tort and Criminal Law, which are being influenced by neuroscientific advances. Part V examines the new developments …

Knowledge, Interest, And Willingness Of Hematologists And Oncologists To Care For Adults With Vascular Anomalies, Bryan A Sisk, Anna M Kerr, Sally Cohen-Cutler, Margaret T Lee, Katie Harmoney, Alexandra Borst, Shelley E Crary, Shelbie Fishman, Stephanie Chen, Danielle Cicka, Stephanie Milam, Christine Bereitschaft, Kristen M Sanfilippo

2020-Current year OA Pubs

BACKGROUND: Vascular anomalies (VAs) are rare diseases that cause significant morbidity. Adults with VAs struggle to access expert care. Hematologists and oncologists in adult medicine are positioned to provide expert care, but no prior studies have characterized their openness to this role.

OBJECTIVES: This study characterized the experience, confidence, willingness, and motivating factors for hematologists/oncologists to care for adults with VAs.

METHODS: We surveyed United States hematologists and oncologists in adult medicine between October 2024 and March 2025. The questionnaire assessed knowledge, experience, confidence, and willingness to care for adults with VAs, as well as open-ended questions assessing factors influencing …

Modeling Clinical Relevance And Risk In Yttrium-90 Radioembolization Of The Liver: Lung Shunt Fraction Variability According To Imaging Modality, Cancer Type, And Tumor Size, M Allan Thomas, Tharun Alamuri, Ryan C Lee, Dan Giardina, John Karageorgiou, Naganathan Mani, Daniel A Braga, Christopher D Malone

2020-Current year OA Pubs

PURPOSE: To test the hypothesis that lung shunt fraction (LSF) in yttrium-90 (

MATERIALS AND METHODS: This was a retrospective analysis of 354 consecutive cases from a 34-month period at a single institution. Cancer type (hepatocellular carcinoma [HCC] vs non-HCC) and maximum tumor size were tracked. LSF was computed from planar imaging (LSF

RESULTS: Median LSF was significantly different (all P < .001) among LSF

CONCLUSIONS: Despite significant variations with imaging modality and correction methods, consistent trends in LSF magnitude with cancer type and tumor size were still uncovered. The relative risk of observing clinically relevant LSF can be modeled for different liver tumor …