Digital Commons Network^™

Technical Considerations And Contemporary Literature Review Of The Gore Thoracic Branch Endoprosthesis®, Bruno P Schmid, Lucas R Kanamori, Hannah V Oden-Brunson, Dora Babocs, Ying Huang, Jorge Miranda, Steven Maximus, Gustavo S Oderich

Faculty, Staff and Students Publications

Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment for various thoracic aortic pathologies, including blunt thoracic aortic injury, aneurysms, and dissections. Involvement of Ishimaru Zone 2 occurs in up to 60% of TEVAR cases requiring extension across the distal aortic arch and left subclavian artery (LSA). Coverage of the LSA without revascularization increases the risk of complications such as upper extremity ischemia, stroke, and spinal cord injury. Therefore, the preservation of LSA perfusion during TEVAR is essential. Cervical debranching remains an effective alternative to preserve flow to the LSA, but it poses risks of bleeding, infection, and nerve …

An Examination Of Racial Bias In Scoring The Autism Diagnostic Observation Schedule (Ados) Module 3: An Item Response Theory Analysis, Yuen Yvonne Yu, Austin Wyman, Calliana J Faulk, Lizzy J Fulop, Rebecca L Greenberg, Rachel M Benecke, Lauren K Steinbeck, Jessica Foy, Caitlyn Kim, George O Emory, Eric A Storch, Casey J Zampella, Benjamin E Yerys, Robert T Schultz, Julia Parish-Morris, John D Herrington, Caitlin C Clements

Faculty, Staff and Students Publications

Given the rising prevalence of autism among racial minority children in the United States, but persistent service use disparities, this study examines potential bias in specific items from the autism diagnostic observation schedule (ADOS), a highly regarded autism evaluation. We leveraged unidimensional item response theory graded response models and a sample of 735 children to analyze the differential item functioning (DIF) of items within ADOS Module 3. Three items showed significant signs of racial bias: A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). On these items, Black/African American and Asian children were usually more likely to …

Differential Longitudinal Effects Of Glucose-Lowering Medications On Glucagon And C-Peptide Responses In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Steven E Kahn, Mark Tripputi, John M Lachin, Ashok Balasubramanyam, Mary Ann Banerji, Joshua Barzilay, Robert M Cohen, W Timothy Garvey, Michaela R Gramzinski, Neda Rasouli, Mary Rhee, Jesse C Seegmiller, Vatsala Singh, William I Sivitz, Michael W Steffes, Kristina Utzschneider, Ralph A Defronzo

Faculty, Staff and Students Publications

Objective: To determine the longitudinal effects on α-cell function of four classes of glucose-lowering agents added to metformin in adults with type 2 diabetes.

Research design and methods: In a multicenter, randomized study, 5,047 participants ≥30 years of age with type 2 diabetes taking 1,000-2,000 mg metformin daily, HbA1c 6.8%-8.5%, were randomized to receive insulin glargine U100, glimepiride, liraglutide, or sitagliptin. In a subset of 724 participants, baseline and longitudinal measures of α-cell function were assessed as the fasting glucagon concentration and change in glucagon from fasting to 30 min following oral glucose (glucagon index [GGI]). Whether these measures and …

Phenofit: A Framework For Determining Computable Phenotyping Algorithm Fitness For Purpose And Reuse, Laura K Wiley, Luke V Rasmussen, Rebecca T Levinson, Jennnifer Malinowski, Sheila M Manemann, Melissa P Wilson, Martin Chapman, Jennifer A Pacheco, Theresa L Walunas, Justin B Starren, Suzette J Bielinski, Rachel L Richesson

2020-Current year OA Pubs

BACKGROUND: Computational phenotyping from electronic health records (EHRs) is essential for clinical research, decision support, and quality/population health assessment, but the proliferation of algorithms for the same conditions makes it difficult to identify which algorithm is most appropriate for reuse.

OBJECTIVE: To develop a framework for assessing phenotyping algorithm fitness for purpose and reuse.

FITNESS FOR PURPOSE: Phenotyping algorithms are fit for purpose when they identify the intended population with performance characteristics appropriate for the intended application.

FITNESS FOR REUSE: Phenotyping algorithms are fit for reuse when the algorithm is implementable and generalizable-that is, it identifies the same intended population …

In-Silico Trial Of Same-Day Simulation-Free Spatially Fractionated Adaptive Radiotherapy (Sf2-Art), Dennis N Stanley, Alyssa R Birchmeier, Carlos E Cardenas, Richard A Popple, Natalie Viscariello, Joel A Pogue, Courtney B Stanley, Mehran Yusuf, Michael Soike, Samuel R Marcrom, Joseph Harms

2020-Current year OA Pubs

PURPOSE: Here we present an in-silico trial of the feasibility and deliverability of a same-day, simulation-free workflow for spatially fractionated adaptive radiotherapy (SF

METHODS AND MATERIALS: Ten patients (five thoracic and five extremity), previously treated with spatially fractionated radiotherapy (SFRT), were selected for this in silico trial. A two-phase regimen was simulated: Phase 1 delivered 12 Gy SBRT to a uniform, predefined high-dose lattice and 4 Gy to the gross tumor volume (GTV); Phase 2 consisted of 4 additional fractions of 4 Gy to the GTV. The planning workflow was performed entirely in silico, without the need for CT simulation. …

Accelerated Diffusion Basis Spectrum Imaging With Tensor Computations, Kainen L Utt, Jacob S Blum, Donsub Rim, Sheng-Kwei Song

2020-Current year OA Pubs

This paper introduces an advanced framework for accelerated processing of diffusion-weighted imaging (DWI) data that utilizes an entire-image modeling approach to optimize the estimation of diffusion parameters from DWIs by mapping input diffusion data to predicted signals and estimating parameter values via a stochastic gradient descent optimizer (Adam). To validate this approach, we applied this framework to diffusion basis spectrum imaging (DBSI) and analyzed in vivo human brain and ex vivo mouse brain DWIs. Results demonstrate significant improvements to computational speed and signal-to-noise ratio (SNR) in estimated parameter maps compared to standard DBSI. Our approach is applicable to any diffusion …

Evaluation Of Large Language Models As Decision Support Tools For Head And Neck Cancer Management: A Blinded Multidisciplinary Simulation Study, Sholem Hack, Ron J. Karni, Antonino Maniaci, Christopher E. Fundakowski, Luca Castellani, Fabiola Incandela, Remo Accorona, Miguel Mayo-Yanez, Martina Violati, Lorenzo Giannini, Niccolo' Mevio, Alberto Maria Saibene

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The management of head and neck cancer relies on multidisciplinary expertise; however, access to tumor boards remains variable. Large language models (LLMs) may support guideline-based decision-making, although performance in complex oncologic scenarios is not well defined.

METHODS: Fourteen synthetic cases based on real tumor board encounters were evaluated. Five blinded comparator arms produced recommendations: a human expert, Non-RAG-GPT-4, Non-RAG-GPT-5, RAG-GPT-4, and RAG-GPT-5. Eight head and neck oncologic surgeons scored each recommendation for appropriateness, clarity, specificity, and feasibility using 5-point Likert scales. Paired permutation testing and inter-rater reliability were assessed.

RESULTS: LLM outputs showed close alignment with expert recommendations. RAG-based …

Novel R Shiny Tool For Survival Analysis With Time-Varying Covariate In Oncology Studies: Overcoming Biases And Enhancing Collaboration, Yimei Li, Yang Qiao, Fei Gao, Jordan Gauthier, Qiang Ed Zhang, Jenna Voutsinas, Wendy Leisenring, Ted Gooley, Corinne Summers, Alexandre Hirayama, Cameron Turtle, Rebecca Gardner, Jarcy Zee, Qian Vicky Wu

Wills Eye Hospital Papers

PURPOSE: Our study is motivated by evaluating the role of hematopoietic cell transplantation (HCT) after chimeric antigen receptor T-cell (CAR-T) therapy for ALL, a debated topic. Because patients may receive HCT at different times after CAR-T infusion or never, HCT post-CAR-T should be considered as a time-varying covariate (TVC).

METHODS: Standard Cox models and Kaplan-Meier (KM) curves (naïve method) assume that TVC status is known and fixed at baseline, which can yield biased estimates. Landmark analysis is a popular alternative but depends on a chosen landmark time. Time-dependent (TD) Cox model is better suited for TVC although visualizing survival curves …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

Mast Cells Promote Pathology And Susceptibility In Tuberculosis, Ananya Gupta, Vibha Taneja, Javier Rangel-Moreno, Nilofer Naqvi, Abhimanyu, Yun Tao, Mushtaq Ahmed, Kuldeep Singh Chauhan, Daniela Trejo-Ponce De Leon, Gustavo Ramírez-Martínez, Luis Jiménez-Alvarez, Cesar Luna-Rivero, Joaquin Zuniga, Deepak Kaushal, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the bacterium

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 …

Ai-Enabled Ecg Analysis Improves Diagnostic Accuracy And Reduces False Stemi Activations: A Multicenter U.S. Registry, Robert Herman, Bryn E Mumma, Jake D Hoyne, Benjamin L Cooper, Nils P Johnson, Timea Kisova, Anthony Demolder, Adam Rafajdus, Andrej Iring, Timotej Palus, Marta Belmonte, Emanuele Barbato, Suzanne J Baron, Robert Hatala, Stephen W Smith, H Pendell Meyers, Scott W Sharkey, Jozef Bartunek, Timothy D Henry

Faculty, Staff and Student Publications

Background: Timely reperfusion is critical in reducing mortality in ST-segment elevation myocardial infarction (STEMI). Although electrocardiography-guided cardiac catheterization laboratory (CCL) activation on the basis of first medical contact recognition improves system-level response, diagnostic uncertainty, particularly in atypical presentations, contributes to false positive activations (FPAs) and reperfusion delays.

Objectives: The aim of this study was to evaluate the diagnostic performance and operational impact of artificial intelligence (AI)-based electrocardiographic (ECG) analysis in real-world STEMI triage across a multicenter U.S. registry.

Methods: A total of 1,032 patients with suspected STEMI who triggered emergent CCL activation at 3 geographically diverse percutaneous coronary intervention centers …

A Universal Of Human Social Cognition: Children From 17 Communities Process Gaze In Similar Ways, Manuel Bohn, Julia Christin Prein, Agnes Ayikoru, Florian M. Bednarski, Ardain Dzabatou, Michael C. Frank, Annette M.E. Henderson, Joan Isabella, Josefine Kalbitz, Patricia Kanngiesser, Dilara Keşşafoğlu, Bahar Köymen, Maira V. Manrique-Hernandez, Shirley Magazi, Lizbeth Mújica-Manrique, Julia Ohlendorf, Damilola Olaoba, Wesley R. Pieters, Sarah Pope-Caldwell, Katie Slocombe, Robert Z. Sparks, Jahnavi Sunderarajan, Wilson Vieira, Zhen Zhang, Yufei Zong, Roman Stengelin, Daniel B.M. Haun

School of Psychology

Theoretical accounts typically assume that key features of human socio-cognitive development are universal. This paper reports a large-scale cross-cultural study (17 communities, diverse ethnicities, N = 1,377, 709 female, mean = 5.50 years, -collected March 2022 to January 2024) on gaze following in early childhood. To test for universality, cognitive processing signatures were derived from a computational model treating gaze following as social vector estimation. Results showed substantial variation between communities and individuals. Yet, the processing signature was found in all communities. Individual differences in performance were related to children's familiarity with the data-collection device but not opportunities for social …

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 …

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, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

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 …

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% …

Diagnostic Performance Of Non-Hyperemic Pressure Ratios Versus Fractional Flow Reserve Stratified By Coronary Artery: A Systematic Review And Meta-Analysis Of Individual Patient Data, Tatyana Storozhenko, Damien Collison, Nils P Johnson, Koshiro Sakai, Takuya Mizukami, Toshiro Shinke, Hitoshi Matsuo, Daniel Munhoz, Dimitri Buytaert, Hirohiko Ando, Brian Ko, Abdul Ihdayhid, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Ketina Arslani, Antonio Maria Leone, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Bjarne L Nørgaard, Michael Maeng, Liyew Desta, Andy Yong, Hiromasa Otake, Yu Takahashi, Daniele Andreini, Jonathon Leipsic, Bon-Kwon Koo, Paola Monique Barbato, Jozef Bartunek, Emanuele Barbato, Jeroen Sonck, Bernard De Bruyne, Carlos Collet

Faculty, Staff and Student Publications

BACKGROUND: In the assessment of coronary physiology, non-hyperemic pressure ratios (NHPRs) provide an alternative to fractional flow reserve (FFR) without the need for hyperemic agents, reducing procedural time, side effects, and costs. However, it remains unclear whether NHPRs have similar diagnostic performance in the different coronary arteries. This study evaluates the diagnostic performance of NHPRs compared with FFR, stratified by coronary artery, in stable patients with coronary artery disease.

METHODS: We conducted a systematic review and individual patient-level data meta-analysis from prospective studies involving patients with intermediate to severe coronary stenosis who underwent physiological assessment with NHPRs and FFR. NHPRs …

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 …

A Programmable Genetic Platform For Engineering Noninvasive Biosensors, Asish N Chacko, Kaamini M Dhanabalan, Jinyang Wan, Roy Chien, Nolan T Anderson, Binzhi Xu, Katie Pham, Ritu Tiwari, Arnab Mukherjee

Faculty, Staff and Student Publications

Creating genetic sensors for noninvasive visualization of biological activities in optically opaque tissues holds immense potential for basic research and the development of genetic and cell-based therapies. Magnetic resonance imaging (MRI) stands out among deep tissue imaging methods for its ability to generate high-resolution images without ionizing radiation. However, the adoption of MRI as a mainstream biomolecular technology has been hindered by the lack of adaptable methods to link molecular events with genetically encodable contrast. Here, we introduce modular aquaporin-based protease-activatable probes for enhanced reporting (MAPPER), a platform for the systematic creation of genetic sensors for MRI. To develop MAPPER, …

The Itrail Making Test (Itmt): An Evaluation Of Novel Testing Paradigms, Hidden Indices Of Measurement, And Diagnostic Accuracy In Parkinson’S Disease, Donnchadh Murphy, Jonathan Scott, Craig Newman, Rupert Noad

Peninsula Medical School

Introduction: The Trail Making Test (TMT) is an important test when assessing for cognitive difficulties in people with Parkinson’s Disease (PD). However, the pencil-and-paper format can be susceptible to administration and scoring errors and may disproportionately reflect motor impairments rather than cognitive performance. The current study sought to evaluate the reliability and diagnostic accuracy of two novel computerized versions of the TMT: iTMT-Tap and iTMT-Drag. Method: This study used a quasi-experimental diagnostic accuracy design, and included 34 healthy controls, 28 people with Parkinson’s disease with normal cognition (PD-NC), and 31 people with Parkinson’s disease mild cognitive impairment (PD-MCI). Participants were …

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 …

The Impact Of Skin Tone On Performance Of Pulse Oximeters Used By Nhs England Covid Oximetry @Home Scheme: Measurement And Diagnostic Accuracy Study, Exakt Study Investigators, Daniel S Martin, James C Doidge, Doug Gould, Tasnin Shahid, Alex Cowden, Walton N Charles, Amelia Francis Johnson, Roger Garrett, Catherine Mbema, Olusegun Olusanya, Eugene Healy, Kathryn Rowan, Paul Mouncey, David A Harrison

Peninsula Medical School

OBJECTIVES: To assess the impact of skin tone on the measurement and diagnostic accuracy of five fingertip pulse oximeters used by patients in the NHS (National Health Service) England COVID Oximetry @home scheme.

DESIGN: Measurement and diagnostic accuracy study (exploring pulse oximeter accuracy across skin tones-EXAKT).

SETTING: Twenty four intensive care units in England between June 2022 and August 2024.

PARTICIPANTS: 903 critically ill adults admitted to intensive care units screened for or enrolled into a trial evaluating different approaches to oxygen therapy.

INTERVENTIONS: Pulse oximetry derived peripheral oxygen saturation (SpO2) measurements were compared with paired arterial oxygen saturation (SaO2) …

Primate Gut Microbiota Induce Evolutionarily Salient Changes In Mouse Neurodevelopment., Alex R Decasien, Jacob E Aronoff, Elizabeth K Mallott, Sahana Kuthyar, Sriram Chitta, Brian T Layden, Maria L Savo Sardaro, Stanton Gray, Lawrence E Williams, Emma R Liechty, Hyo M Lee, Won Lee, James P Curley, Christopher W Kuzawa, Katherine R Amato

Faculty Research 2026

Multiple primate species, including humans, evolved brains that are exceptionally large relative to their body sizes. These large brains coevolved with metabolic adaptations that enhance cerebral energy supply, including increased circulating glucose levels. While the gut microbiota (GM) is known to influence host metabolism, its potential role in primate brain evolution remains unclear. To investigate this, we inoculated germ-free mice with the GMs of primate species selected to separate the effects of brain size (encephalization) from phylogenetic relatedness: humans (large-brained, Catarrhini), macaques (smaller-brained, Catarrhini), and squirrel monkeys (large-brained, Platyrrhini). We first show that differences in brain gene expression between mice …

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 …

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 …

An Integrated Single-Cell And Spatial Transcriptomic Atlas Of Thyroid Cancer Progression Identifies Prognostic Fibroblast Subpopulations, Matthew A Loberg, George J Xu, Sheau-Chiann Chen, Hua-Chang Chen, Claudia C Wahoski, Kailey P Caroland, Megan L Tigue, Heather A Hartmann, Jean-Nicolas Gallant, Courtney J Phifer, Andres A Ocampo, Dayle K Wang, Reilly G Fankhauser, Kirti A Karunakaran, Chia-Chin Wu, Maxime Tarabichi, Sophia M Shaddy, James L Netterville, Sarah L Rohde, Carmen C Solórzano, Lindsay A Bischoff, Naira Baregamian, Barbara A Murphy, Jennifer H Choe, Jennifer R Wang, Eric C Huang, Quanhu Sheng, Luciane T Kagohara, Elizabeth M Jaffee, Ryan H Belcher, Ken S Lau, Fei Ye, Ethan Lee, Vivian L Weiss

Faculty, Staff and Student Publications

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts …