Digital Commons Network^™

A Machine-Learning-Based Tool For Stroke Risk Prediction In Blunt Cerebrovascular Injury: Development And Preliminary Evaluation, Victoria Wagner, Joshua D Preston, Alejandro De Leon Castro, William F Mueller, Jonathan Nguyen, Manuel Garcia-Toca, Elizabeth R Benjamin, S Rob Todd, Jason D Sciarretta

Faculty, Staff and Student Publications

Purpose: Stroke risk correlates with the Biffl grading system in blunt cerebrovascular injury (BCVI). Although anti-thrombotic therapy is the mainstay of stroke prevention, no point-of-care clinical decision-support tool exists to guide timing for therapy. We sought to develop an interactive online calculator that incorporates patient-specific demographic and injury characteristics to estimate stroke risk and risk reduction with anti-thrombotic (AT) administration.

Methods: Data from BCVI patients (n = 1,197) at a Level I Trauma Center were retrospectively collected. Six machine learning methods were employed to predict stroke risk with and without AT therapy. Class imbalance was addressed using downsampling and/or class …

Etalanetug (E2814) In Dominantly Inherited Alzheimer's Disease: An Open-Label Phase 1b/2 Study To Assess Safety And Target Engagement In Participants With Mild To Moderate Cognitive Impairment, Erica Andreozzi, Kanta Horie, Nicolas R Barthélemy, Brian A Gordon, Shaney Flores, Tammie L S Benzinger, Eric Mcdade, Randall J Bateman, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Etalanetug (E2814) is designed to delay the clinical progression of Alzheimer's disease (AD) by binding to the microtubule binding region (MTBR) of tau implicated in seeding and spreading of tau pathology. Dominantly inherited Alzheimer's disease (DIAD) is a rare form of the disease (<  1%), having similar changes in the tau distribution and pathology to sporadic AD. Herein, we report the safety, pharmacology and biomarker results of the etalanetug Study 103 in DIAD patients.

METHODS: Study 103 enrolled participants with mild-to-moderate cognitive impairment due to DIAD who received etalanetug intravenously every 4 weeks escalating from 750 mg, 1500 mg, 3000 mg, to 4500 mg. After ascending to 4500 mg, patients received 4500 mg for up to 108 weeks. Tau pathology biomarkers, ptau217 and MTBR-tau243 were measured in CSF. Additional …

Utility Of Right Ventricular Mass Ratios In Recipients With Pulmonary Hypertension: A United Network For Organ-Sharing Database Analysis, Matthew P. Weber, Danial Ahmad, Howard J. Eisen, Eugene Storozynsky, René J. Alvarez, J. Eduardo Rame, Keshava Rajagopal, John W. Entwistle, Charles Hoopes, Vakhtang Tchantchaleishvili

Division of Cardiology Faculty Papers

PURPOSE: There is a lack of data reviewing the role of predicted cardiac mass ratio (PCMR) in transplant recipients with pulmonary hypertension (PH). In particular, the right ventricular (RV) mass ratio (RVMR) is a component of PCMR not yet studied separately for this purpose. We aimed to review the relationship of PCMR and RVMR with PH in terms of post-transplant overall survival.

METHODS: The United Network for Organ-Sharing (UNOS) database was queried for primary heart transplant (HTx) patients from 2004 to 2023. Predicted RVMR was calculated for donors and recipients. A parsimonious multivariable model Cox model was formed for risk …

Cerebellar Oligodendrocytic Α-Synuclein Pathology And Dentate Nucleus Neuronal Hypertrophy In Parkinson’S Disease, Diego Iacono, Hui Peng, John Paul Bouffard, Roger Kurlan

Department of Neurology Faculty Papers

Idiopathic Parkinson's disease (iPD) research has historically prioritized basal ganglia dysfunction and neuronal Lewy body pathology, often overlooking cerebellar and non-neuronal cells contributions. This study investigates cerebellar neuropathology in iPD, specifically focusing on neuronal and non-neuronal cells of the dentate nucleus (DN) and its adjacent white matter (DN-WM). We systematically assessed autopsy-confirmed iPD brains vs. age-matched controls using immunohistochemistry and stereology-based morphometry methods. The study evaluated α-synuclein pathology, other common age-related co-occurring pathologies (β-amyloid, Tau, neuroinflammation), myelin integrity (Luxol-Fast-Blue), and neuronal volumetric changes in the DN of the cerebellum. In iPD brains, we identified intracytoplasmic α-synuclein inclusions within oligodendrocytes across …

Epigenome-Wide Association Study Of Blood Proteome In The Atherosclerosis Risk In Communities Study, Yang Li, Aditya Surapaneni, Zulema Rodriguez-Hernandez, Pascal Schlosser, Eugene P Rhee, Eric Boerwinkle, Bing Yu, Megan L Grove, Kelly V Ruggles, Josef Coresh, Morgan Grams

Faculty, Staff and Student Publications

Characterizing the relationship between DNA methylation and circulating proteins is critical to understanding the epigenetic regulation of the human plasma proteome. Here, we performed an epigenome-wide association study of 5,032 circulating proteins in 1,449 White and 315 Black participants from the Atherosclerosis Risk in Communities cohort. We identified 12,500 significant protein quantitative trait methylation (pQTM)-protein associations involving 1,647 proteins. Among 7,796 unique pQTMs, 14.7% were classified as cis-pQTMs, which were enriched for fundamental cellular processes, whereas trans-pQTMs were predominantly linked to immune-related functions. Trans-pQTMs also exhibited stronger associations with demographic, lifestyle, and clinical traits as compared with cis-pQTMs. We identified …

Bi-Allelic Variants In Ap5z1 And Ap5b1 Lead To Retinal Degeneration, Hafiz Muhammad Jafar Hussain, Meng Wang, Paul Yang, Behnoosh Tasharrofi, Yumei Li, Rebecca Lynn Clark, Emma Fale-Olsen, Grace Waldow, Mohammad Keramatipour, Mostafa Asadollahi, Mark E Pennesi, Rui Chen

Faculty, Staff and Students Publications

Inherited retinal diseases (IRDs) comprise a diverse group of disorders that frequently lead to progressive vision impairment and blindness. Despite advances in genetic testing, a significant number of IRD cases remain genetically unsolved, often due to unidentified disease-associated genes or variants. This study reports additional cases for the newly discovered IRD genes of the AP-5 complex. A comprehensive ophthalmological evaluation was performed for all patients, including retinal imaging (multimodal imaging), visual field testing, and electroretinogram (ERG) testing. Whole-genome and -exome sequencing (WGS and WES) were performed for clinically unsolved IRD patients, and data were analyzed to identify underlying causal variants. …

Contributing Factors Of Contralateral Breast Cancer In Patients With Brca Mutation (On-Brca Ii Study, Korea-Bsg 11), Seon-Hi Shin, Sung Gwe Ahn, Jai Min Ryu, Sae Byul Lee, Hyung Seok Park, Eun-Shin Lee, Janghee Lee, Byeongju Kang, Sanghwa Kim, Eun Young Kim, Young-Joon Kang, Sun Young Min, Moohyun Lee, Se-Kang Kim, Hong-Kyu Kim, Chihwan David Cha

Faculty, Staff and Students Publications

Background: The cumulative risk of contralateral breast cancer (CBC) in BRCA1/2 carriers is remarkably higher than in non-carriers. This study aimed to investigate the clinicopathological predictors associated with the risk of metachronous CBC among breast cancer patients with BRCA1/2 mutations using correspondence analysis.

Methods: This retrospective study included patients who underwent BRCA testing between January 2008 and December 2018. The inclusion criterion was patients being between 20 and 80-years-old with invasive breast cancer (pT1-3, N0-3). We performed univariate and multivariate survival analyses to assess the risks associated with BRCA mutations, and conducted correspondence analysis to identify contributing factors for CBC …

Co-Occurrence Of Transcriptionally Distinct Persister Cell States Underpins Neoadjuvant Therapy Resistance In Triple-Negative Breast Cancer, Yu Zhang, Fatemeh Ahmadi Moughari, Ioanna Mavrommati, Nora J Doleschall, Kate Moore, Gareth Muirhead, Ram Rajaram Srinivasan, Ping Gong, Jonathan T Lei, Amy Fleming, Hwei Minn Khoo, Naomi Guppy, Gabrielle Elshtein, Mohammed Inayatullah, Vijay K Tiwari, Lacey E Dobrolecki, Michael T Lewis, Syed Haider, Rachael Natrajan

Faculty, Staff and Students Publications

Background

Although the addition of neoadjuvant immune checkpoint blockade to chemotherapy has improved patient outcome in early triple‑negative breast cancer (TNBC), some patients continue to have poor disease outcomes.

Methods

To characterise neoadjuvant chemotherapy (NAC) resistant cell populations that persist post-NAC, we created a high-resolution single-cell atlas of 129,433 cells from fourteen TNBC patient-derived xenograft (PDX) models with residual disease post-NAC. We identified transcriptionally distinct cancer subpopulations or cell states using unsupervised clustering and characterised‑ their regulatory network as well as clinical associations with treatment response, metastatic progression and survival. Findings were validated using multiple independent TNBC cohorts.

Results

Four …

Trajectories Of Plasma And Csf Mtbr-Tau243 And Phosphorylated-Tau Species Across The Alzheimer's Disease Continuum, Lyduine E Collij, Gemma Salvadó, Kanta Horie, Nicolas R Barthélemy, Tobey J Betthauser, Olof Strandberg, Ruben Smith, Sebastian Palmqvist, Suzanne E Schindler, Rik Ossenkoppele, Shorena Janelidze, Niklas Mattsson-Carlgren, Randall J Bateman, Oskar Hansson

2020-Current year OA Pubs

To efficiently implement plasma and cerebrospinal fluid (CSF) biomarkers for staging and prognosis of Alzheimer disease (AD), we must understand their dynamics across disease progression. We analyzed participants from the Swedish BioFINDER-2 study with mass spectrometry measurements of plasma and CSF tau species, including eMTBR-tau243/MTBR-tau243 and phosphorylation occupancies (%p-tau). Disease duration was estimated using Aβ-PET and tau-PET with the SILA algorithm. Bootstrapped LOESS models showed that %p-tau217 changes earliest, increasing just before Aβ-PET positivity. Other p-tau species changed later, with smaller dynamic ranges and earlier ceiling effects. %p-tau205 and MTBR-tau243 changes aligned with tau-PET positivity onset, while MTBR-tau243-especially plasma eMTBR-tau243-tracked …

An Innovative Curriculum To Empower Trainees And Faculty To Address Patient-Initiated Identity-Based Misconduct In The Clinical Learning Environment, Nkanyezi Ferguson, Lauren E. Hock, Patrick Barlow, Aisha S. Jamison, Marcy E. Rosenbaum, Nicole Del Castillo

Department of Medicine Faculty Papers

Introduction: Training residents and attending physicians on effective communication strategies to manage biased patient and visitor comments is lacking. The I-RESPOND toolkit curriculum provides strategies for addressing identity-based misconduct in the clinical setting. Methods: Resident physicians and faculty in 12 departments at a single academic center participated in the workshop between June 2021 and February 2022. The workshop consisted of interactive didactics, an introduction to the I-RESPOND toolkit, and opportunities to practice communication strategies with formative feedback. Retrospective pre/postworkshop survey instruments and a follow-up survey were used to evaluate the workshop and subsequent experiences. Results: Sixty-six (32%) of 204 participants …

Contraception In The Ed: Understanding Education And Opportunities For Clinicians To Advise Patients, Hannah B. Lewis, Teagan R. Mccarthy, Dara Kass, Jennifer L. Kahoud

Department of Emergency Medicine Faculty Papers

Introduction: The United States faces a high rate of unwanted pregnancies. Despite this, many people continue to face barriers to accessing contraception. The emergency department (ED) can help bridge these gaps, but emergency clinicians must first feel comfortable offering contraceptive services. In this study, we sought to determine emergency clinician comfort in prescribing contraceptives and educating patients on their use. We also gauged clinician interest in receiving education specifically geared toward contraceptive care.

Methods: We conducted an online survey of ED residents, attendings, and advanced practice clinicians at Thomas Jefferson Univerity Hospital and affiliates in both the urban and suburban …

Multi-Trait Polygenic Scores For Copd And Copd Exacerbations Implicate Druggable Proteins, Chengyue Zhang, Iain R Konigsberg, Yixuan He, Jingzhou Zhang, Tinashe Chikowore, William B Feldman, Xiaowei Hu, Yi Ding, Bogdan Pasaniuc, Diana Chang, Qingwen Chen, Jessica A Lasky-Su, Julian Hecker, Martin D Tobin, Jing Chen, Sean Kalra, Katherine A Pratte, Hae Kyung Im, Emily S Wan, Ani Manichaikul, Edwin K Silverman, Russell P Bowler, Leslie A Lange, Victor E Ortega, Alicia R Martin, Michael H Cho, Matthew R Moll

Faculty, Staff and Student Publications

BACKGROUND

We constructed multi-trait polygenic risk scores (PRSs) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validated their performance in diverse cohorts, and identified PRS-related proteins for potential therapeutic targeting.

METHODS

PRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic White participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2–4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), Mass General Brigham Biobank (n = 15,152), and All of Us (n = 118,566). …

The Effects Of Orexin Receptor Antagonism During Early Withdrawal In Stimulant Use Disorder: Protocol For A Proof-Of-Concept Study, Heather Webber, Nikky Tran, Rita Blake, Sarah Goldman, Trevor George, Bill Bailey, Robert Suchting, Jin Yoon, Jessica Vincent, Michael Weaver, Joy Schmitz, Scott Lane

Faculty, Staff and Student Publications

Background: Stimulant use disorders (StimUDs), including cocaine and methamphetamine use disorders, remain a major public health concern in the United States with no US Food and Drug Administration (FDA)-approved pharmacological treatments. The early recovery period following stimulant use is marked by sleep disturbances, heightened stress reactivity, and dysregulated reward processing, contributing to high rates of resumption of use. Evidence from animal and human studies supports the orexin neuropeptide system as a promising therapeutic target for minimizing these disruptive mechanisms. Suvorexant, an FDA-approved dual orexin receptor antagonist for insomnia, has previously been shown to improve sleep, reduce stress, and attenuate craving …

High-Throughput Multiplex Detection Of Respiratory Pathogens: Multicenter Evaluation Of The Nxtag Respiratory Pathogen Panel V2 Assay., Marisa C. Nielsen, Ping Ren, Sri Bharathi Kavuri, Karissa Culbreath, Rangaraj Selvarangan, Dithi Banerjee, Blake W. Buchan, Rachel Behounek, Janet Farhang

Manuscripts, Articles, Book Chapters and Other Papers

Respiratory tract infections remain a major cause of global morbidity, highlighting the need for rapid and accurate diagnostic testing. This multicenter study evaluated the clinical and analytical performance of the updated NxTAG Respiratory Pathogen Panel v2 (RPPv2), a high-throughput multiplex molecular assay designed to detect 21 viral and bacterial respiratory pathogens. A total of 2,145 nasopharyngeal swab specimens, including both prospectively enrolled and archived specimens, were analyzed across five U.S. clinical sites. The NxTAG RPPv2 was assessed against FDA-cleared molecular assays and bi-directional sequencing, with contrived specimens used to supplement low-prevalence targets. Valid results were obtained for 99.7% of specimens …

The Gut Microbiota Shapes The Human And Murine Breath Volatilome, Ariel J Hernandez-Leyva, Amalia Z Berna, Maggie H Bui, Yang Liu, Anne L Rosen, Michael A Lint, Samantha A Whiteside, Natalia Jaeger, Ryan T Mcdonough, Nikhilesh Joardar, Jesús Santiago-Borges, Christopher P Tomera, Wentai Luo, Audrey R Odom John, Andrew L Kau

2020-Current year OA Pubs

The gut microbiota is crucial to health, yet implementation of microbiota-based therapeutics is limited by the lack of rapid diagnostics. We hypothesize that breath contains gut microbe-derived volatile organic compounds (VOCs) reflecting microbiota composition and metabolism. In healthy children, we found that breath VOC composition (or volatilome), assessed by gas chromatography-mass spectrometry, correlates with gut microbiome composition and function. By capturing exhaled breath from human-stool-colonized and monocolonized gnotobiotic mice, we profiled breath VOCs and discovered that murine breath is also significantly influenced by the gut microbiome. VOCs from cultured gut microbes were identified in vivo in monocolonized gnotobiotic colonized mice. …

Reference Proteins To Improve Core 1 And Core 2 Alzheimer's Disease Csf And Plasma Biomarkers, Linda Karlsson, Nicolas R Barthélemy, Kanta Horie, Suzanne E Schindler, Brian A Gordon, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Concentration-based fluid biomarkers represent an informative and cost-effective way to detect and monitor Alzheimer's disease (AD) pathology. However, non-AD-related interindividual variation in biofluids can also affect biomarker concentrations. Here, we investigated whether normalization of CSF and plasma biomarkers to reference proteins, such as amyloid-β40 (Aβ40) and non-phosphorylated mid-region tau (np-tau), improves their robustness and reliability of representing AD pathology load. Using the Swedish BioFINDER-2 cohort [n = 1702, 50.7% male, mean (standard deviation) age 68.4 (12.2) years], we compared the associations between tau/Aβ-PET load and fluid biomarkers alone versus biomarkers in a ratio with a reference protein (Aβ40 or np-tau) …

Versatile Smad2 And Smad3 Epitope-Tagged Mouse Models For Genomic Profiling Of Tgfβ Signaling: Uncovering Gdf9-Smad2/3 Targets, Zian Liao, Qian Zhang, Keisuke Shimada, Kaori Nozawa, Suni Tang, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Transforming growth factor β (TGFβ) signaling pathways are integral for a plethora of biological processes. SMAD2 and SMAD3 are the principal transcriptional effectors of TGFβ superfamily ligands, yet quantitative, genome-wide mapping of their DNA-associated complexes under physiological contexts has remained limited due to the lack of specific, robust models. Here, we generated two versatile epitope-tagged mouse models in which endogenous SMAD2 and SMAD3 proteins are globally tagged with hemagglutinin (HA) and podoplanin (PA) sequences, respectively, enabling high-fidelity profiling of SMAD2 and SMAD3 binding across tissues. To demonstrate the broad application of our models, we exemplified the usage of our lines …

Relative Impact Of Multidomain Lifestyle Interventions On Deficit Accumulation Frailty Over 24 Months In The U.S. Pointer Trial, Mark A Espeland, Kayloni Olson, Christy C Tangney, Darren R Gitelman, Maryjo Cleveland, Amber A Thro, Yitbarek N Demesie, Heather M Snyder, Rachel A Whitmer, Pankaja Desai, Rifat Alam, Lucia Crivelli, Thomas M Holland, Olivia Preissle, Rema Raman, Michele K York, Laura D Baker

Faculty, Staff and Students Publications

Background: Multidomain lifestyle interventions hold promise as approaches to slow aging. Deficit accumulation frailty indices (FIs) are increasingly used to capture aging processes. Frailty is highly associated with increased mortality and chronic disease risk, but the degree to which multidomain lifestyle changes impact frailty is not clear.

Methods: The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) was a 2-year randomized clinical trial to compare two multidomain lifestyle interventions designed to increase exercise, improve diet, and promote social and cognitive stimulating activities and health monitoring. The Structured intervention incorporated greater structure, intensity, and accountability …

Ex Vivo Effect Of Apixaban On Hemostatic Biomarkers In Children With Heart Disease: A Saxophone Trial Substudy, Ghada A Aborkhees, Amy J Barr, Kevin Dietrich, Christoph Male, Zhaoqing Wang, Chen Yao, R Mark Payne, Andrew C Glatz, Paul Monagle, Kristin M Burns, Alison M Reedy, Joshua L Dyme, Peter H Schafer, Antoinette Ajavon-Hartmann, Lesley G Mitchell

2020-Current year OA Pubs

BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin.

METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for …

The Ki-67 Proliferation Index And Recurrence Risk Of Intracranial Meningioma: A Multicenter, Retrospective Cohort Study Of 5,050 Patients, Christian Mirian, Lasse Rehné Jensen, Tareq A Juratli, Andrea Daniela Maier, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Pedro Góes, Aria Jamshidi, Ricardo Komotar, Michael Ivan, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Ian Law, David Scheie, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

Purpose: The Ki-67 proliferation index (Ki-67 PI) has been associated with meningioma recurrence, yet its clinical utility remains debated. Whether Ki-67 PI provides prognostic information across subgroups defined by both WHO grade and extent of resection remains to be investigated.

Methods: We analyzed 5,050 patients with intracranial meningiomas from the international PERNS cohort (42 centers, diagnosed between 1989-2019) who underwent surgical resection without postoperative radiotherapy. Ki-67 PI prognostic accuracy was assessed up to 10 years postoperatively by using ROC analyses and estimating its association with the risk of recurrence.

Results: Results demonstrated that the prognostic value of Ki-67 PI differed …

Untangling Impacts Of Socioeconomic Position, Chronic Disease, And Low-Level Pm2.5 Exposure On Mortality Among Native American Medicare Beneficiaries, Judy Wendt Hess, Wenyaw Chan

Faculty, Staff and Student Publications

Ambient fine particulate matter (PM2.5) is associated with increased mortality at concentrations below current regulatory standards. Studies of low-level exposure often rely on large administrative cohorts whose geographic and demographic composition may influence observed associations. In a prior analysis, we observed an association between long-term PM2.5 and all-cause mortality among Native American Medicare beneficiaries living in zip codes within the lowest decile of PM2.5 exposure. The present study, a case-control analysis of 1,713,399 low-PM2.5-exposed beneficiaries enrolled in traditional Medicare during 2015-2016, evaluated whether this association could be explained by geographic context, socioeconomic position (SEP), or baseline health status. We used …

Translationally-Relevant Tumor Resection Model For Murine Preclinical Models Of Oral Squamous Cell Carcinoma, Gemalene M Sunga, Alejandra Cobos Perez, Andrea H Molina, Nourhan Hussein, Neeraja Dharmaraj, Andrew Sikora, Simon Young

Faculty, Staff and Student Publications

Currently, the first-line treatment for the most common form of head and neck squamous cell carcinoma (HNSCC), oral cavity squamous cell carcinoma (OSCC), is surgical resection, followed by risk-adapted treatments, such as chemoradiotherapy. However, with the current standard of care and even the emergence of new treatments, such as checkpoint blockade, the overall survival for advanced, recurrent disease remains high, and the prevalence of head and neck cancer is projected to continue to increase in the coming years. Thus, deeper investigation into current standard-of-care modalities, in addition to novel therapeutics, is necessary to translate potential and promising treatment options to …

Organ Procurement Organization Utilization Of Portable Hypothermic Oxygenated Machine Perfusion In Liver Transplantation: The First Us Experience, Christine E. Haugen, Muhammad Bilal Moeen-Ud-Din, Abdalla M. Hadhoud, Achintya Kaw, James R. Butler, James V. Guarrera, Sherry Quire, Ralph C. Quillin

Department of Surgery Faculty Papers

BACKGROUND: Advanced machine perfusion techniques have increased the use of hard-to-place organs, effectively changing the liver transplantation landscape. Liver transplantation machine perfusion has been driven largely by industry or individual transplant centers. We describe the implementation of a portable, organ procurement organization-initiated hypothermic oxygenated machine perfusion strategy for liver transplantation as a proof of concept.

METHODS: Surgeons and staff at a regional organ procurement organization (Indiana Donor Network) were trained to use and cannulate liver allografts using a portable hypothermic oxygenated machine perfusion platform. We evaluated all liver transplantations recovered and placed on hypothermic oxygenated machine perfusion (N = 18) …

Integrating Maternal Pelvic Floor And Mental Health In Occupational Therapy, Diana S. Theodore, Lesley Sally Khan-Farooqi, Amanda Ciecior, Teresa Martinez, Brooke Caldwell

Spring 2026 OTD Capstone Symposium

This poster highlights an integrated occupational therapy approach to maternal pelvic floor and mental health. Postpartum recovery is often addressed in fragmented ways, separating physical symptoms from emotional and functional impact. This work emphasizes the connection between pelvic floor function, nervous system regulation, and daily activities. Drawing from clinical experiences across acute, outpatient, and community settings, this project presents practical, client-centered strategies to support recovery. Key areas include breathing, bowel and bladder health, and functional movement. By focusing on occupational performance, such as toileting, mobility, sleep, and caregiving. This approach demonstrates the role of occupational therapy in supporting whole-person postpartum …

Multiscale Metabolic Covariance Networks Uncover Stage-Specific Biomarker Signatures Across The Alzheimer's Disease Continuum., Juan Antonio K Chong Chie, Scott A Persohn, Ravi S Pandey, Olivia R Simcox, Gregory W. Carter, Paul Salama, Paul R Territo, The Alzheimer’S Disease Neuroimaging Initiative

Faculty Research 2026

INTRODUCTION: Functional connectomics studies leverage the power of interregional brain relationships using graph theory of glycolytic metabolism to establish neural connections and their roles in cognition and disease and to monitor therapeutic responses.

METHODS: Using a retrospective clinical population (N = 431) from ADNI, we evaluated disease changes using metabolic covariance analysis. In addition, we developed a novel region set enrichment analysis (RSEA) to detect brain functional changes based on metabolic variations. Results were aligned with transcriptomic signatures and clinical cognitive assessments (CCAs).

RESULTS: Our findings highlight sexual dimorphic changes across the disease spectrum, which suggest brain network reorganization occurs …

White Matter Microstructure Alterations In Social Anxiety Disorder: A Mega-Analysis Across Twelve Cohorts In The Enigma-Anxiety Working Group, Eline F Roelofs, Nynke A Groenewold, Kinga Farkas, Alyssa H Zhu, Si Gao, Tiana Borgers, Udo Dannlowski, Kira Flinkenflügel, Dominik Grotegerd, Tim Hahn, Andreas Jansen, Elisabeth J Leehr, Tilo T J Kircher, Hannah Meinert, Igor Nenadić, Frederike Stein, Benjamin Straube, Tamer Demiralp, Raşit Tükel, P Michiel Westenberg, Jochen Bauer, Anna Kraus, Alexander G G Doruyter, Christine Lochner, David Hofmann, Thomas Straube, André Zugman, Monica E Calkins, Raquel E Gur, Ruben C Gur, Bart S Larsen, Theodore D Satterthwaite, Theresa M Slump, Roman A Vogler, Suzanne N Avery, Jennifer U Blackford, Jacqueline A Clauss, Su Lui, Sophia I Thomopoulos, Robert R J M Vermeiren, Neda Jahanshad, Peter V Kochunov, Paul M Thompson, Daniel S Pine, Dan J Stein, Nic J A Van Der Wee, Janna Marie Bas-Hoogendam

Faculty, Staff and Student Publications

Background: Studies investigating social anxiety disorder (SAD) have reported inconsistent alterations in white matter (WM) microstructure. The ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-Anxiety Working Group investigated differences in the microstructure of 25 WM tracts between individuals with SAD and healthy control (HC) participants in a mega-analysis.

Methods: We analyzed data from 487 individuals with SAD and 1604 HC participants (ages 8-65 years) from 12 cohorts worldwide. Analyses and quality control were performed using standardized ENIGMA diffusion tensor imaging protocols. We primarily examined fractional anisotropy (FA) as the main parameter of WM microstructure. Linear mixed-effects analyses were conducted to …

Sialidosis Type I: How To Alleviate Disabling Myoclonic Seizures? - A Multicenter Analysis Of Eight Cases And Review Of The Literature, Janina Gburek-Augustat, Shao Ching Tu, Marwan Shinawi, Isabel Alfradique-Dunham, Manouela Valtcheva, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sialidosis type I (ST-1) is an autosomal-recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs).

METHODS: We describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January …

The Integrated 31-Gene Expression Profile Test Identifies Low-Risk Patients With Cutaneous Melanoma Who Can Forego The Slnb Procedure: Results From A Prospective, Multicenter Trial., Timothy Beard, J Michael Guenther, Stanley P Leong, Maki Yamamoto, Samuel Dierks, Brenda Sickle-Santanello, Andrew Ward, Mark Cripe, Parth Shah, Shawn Young

Oncology Articles

AIMS: Prospectively confirm use of the integrated 31-gene expression profile test (i31-SLNB) in patients with cutaneous melanoma to predict sentinel lymph node biopsy (SLNB) positivity and assess recurrence rates in those considered low risk by i31-SLNB who did not have an SLNB.

METHODS: Patients with T1-T4 tumors being considered for SLNB who received 31-gene expression profile (31-GEP) testing in the multi-center, prospective DECIDE study were included (n = 912). Kaplan-Meier analysis was used to estimate recurrence-free survival (RFS).

RESULTS: Among 430 patients with T1-T4 tumors who had an SLNB, the positivity rate was 2.6% (3/114) in those with < 5% i31-SLNB-predicted risk versus 21.4% (28/131) in those with >10% predicted …

Lyplal1 Rare Loss-Of-Function Variants In Humans And Deletion In Human Hepatoma Cells Protect Against Masld, Rawdat Hussain, Chinmay Raut, Ponnandy Prabhu, Akram Irshaid, Yash Hegde, Yue Chen, Asmita Pant, Antonino Oliveri, Xiaochao Wei, Lishi Yin, Tiffany L Russell, Brian Halligan, Clay F Semenkovich, Elizabeth K Speliotes

2020-Current year OA Pubs

Genetic variants near LYPLAL1 are associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) in humans, but their impact on LYPLAL1 function is unknown. We identified LYPLAL1 loss-of-function variants from UK BioBank (UKBB) whole-exome sequencing data that had AlphaMissense or GPN-MSA scores in the top 20% of LYPLAL1 variants for being disruptive. We aggregated these variants and carried out burden analysis for effects on MRI Proton Density-Fat Fraction (MRI-PDFF) and ICD-based MASLD in UKBB. Rare loss-of-function LYPLAL1 variants were associated with reduced MRI-PDFF and ICD diagnosed MASLD across sexes. We used CRISPR to knockout and overexpress LYPLAL1 in human hepatoma cells …

Promoting Community And Social Participation In Chronic Stroke: A Pilot Study Of The Engage Intervention, Elizabeth Skidmore, Carolyn Baum, Jessica Kersey, Emily Kringle, Kelsey Voltz-Poremba, Sular Gordon, Tina Harris, Heidi Fischer, Maureen Gecht, Michelle Furman, Joy Hammel

2020-Current year OA Pubs

BACKGROUND: Survivors of stroke report low levels of community and social participation, even years after stroke. ENGAGE is a community-based intervention that merges social learning, guided problem solving, and supervised practice to collaboratively identify, generate, and apply solutions to challenges with community and social participation after stroke.

OBJECTIVE: We examined the feasibility, acceptability, and safety of ENGAGE and characterized within group changes in community and social participation outcomes.

METHODS: Community-dwelling survivors of stroke, occupational therapy providers, and occupational therapy scientists partnered to co-design the essential and structural elements of ENGAGE, as well as to evaluate ENGAGE using a multi-site single-arm …