Digital Commons Network^™

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 …

Developing Endpoints For The Cardiac Burden In Myotonic Dystrophy Type 1: A Workshop Report, Julia M Hartman, Samuel Carrell, William J Groh, Thomas A Cooper, Jordana Kron, Greg Hundley, Jennifer Jordan, Amy Ladd, Man Hung, Nicholas E Johnson

Faculty, Staff and Students Publications

Cardiac disease is a well-established manifestation of myotonic dystrophy type 1 (DM1), characterized by progressive cardiac conduction slowing with increased risk of atrial and ventricular arrhythmias, heart block, and sudden cardiac death. Multiple disease modifying therapies are in clinical trials for DM1 and show promise in improving skeletal muscle weakness and myotonia. Testing the effects of these medicines, or others, in the heart is of critical importance, but requires identification of endpoints of cardiac function that accurately reflect the state of DM1 cardiac disease. To better define cardiac endpoints, the Myotonic Dystrophy Clinical Research Network (DMCRN) and the Myotonic Dystrophy …

Multi-Organ Physiologic Deficits During Exercise Identify Clinical And Molecular Predisposition To Heart Failure With Preserved Ejection Fraction, Isabela Landsteiner, Lindsey K Stolze, Tess E Peterson, Andrew Perry, Phillip Lin, Quanhu Sheng, Shilin Zhao, Kaushik Amancherla, Michael Y Mi, Takenori Ikoma, Laura P Cohen, Ilya Giverts, Joseph Campain, Joao A C Lima, Wendy S Post, Kent D Taylor, Robert Gerszten, Stephen S Rich, Russell Tracy, Peter Durda, Alexis C Wood, Rajeev Malhotra, Jerome I Rotter, Clary Clish, Matthew Nayor, Eric R Gamazon, Ravi V Shah, Gregory D Lewis

Faculty, Staff and Students Publications

Background: Exercise unmasks limitations in multi-organ system reserve capacity characteristic of heart failure with preserved ejection fraction (HFpEF). However, the metabolic and genetic underpinnings of exercise deficits, and their cumulative contribution to HFpEF severity and prognosis, remain incompletely understood.

Methods: We used invasive cardiopulmonary exercise testing (iCPET), metabolite profiling, and genomics to simultaneously characterize seven exercise physiologic deficits in HFpEF patients: reduced exercise stroke volume and heart rate, steep pulmonary capillary wedge pressure/cardiac output (PCWP/CO) slope, elevated pulmonary vascular resistance, pulmonary mechanical limitation to exercise, impaired peripheral oxygen extraction, and obesity-related exaggerated metabolic cost of initiating exercise. We first mapped …

Structure-Preserving Multivariate Hypothesis Testing For Mass Spectrometry Imaging And Single-Cell Data, Keziah E Liebenberg, Erin Craig, Robert Tibshirani, Livia S Eberlin

Faculty, Staff and Students Publications

Motivation: Mass spectrometry imaging (MSI) and single-cell RNA sequencing (scRNA-seq) offer high-resolution views into tissue and cellular heterogeneity. However, conventional statistical analyses often treat sub-measurements (pixels or cells) as independent, ignoring their nested origin from individual samples. This assumption inflates the effective sample size, increases false discoveries, and undermines biological interpretation. Pixel- or cell-level averaging avoids this but sacrifices spatial or cellular resolution.

Results: We evaluated block-SAM on both simulated and real-world datasets. In DESI-MSI data from kidney, lung, and ovarian tumors, block-SAM consistently identified fewer-but more reliable-differential features compared to traditional-SAM. For example, in the kidney dataset, traditional-SAM identified …

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 …

Implementing Measurement-Based Care In Virtual Mental Health Services For Rural Veterans: Provider Insights From A Pre-Implementation Evaluation, Amanda Heeren, Kimberly Mccoy, Lindsey Fuhrmeister, Natalie Suiter, Jan A Lindsay, Chloe Hoang, Laura Marsh, John Fortney, Carolyn Turvey

Faculty, Staff and Students Publications

Background

Measurement-Based Care (MBC) uses repeated standardized psychological assessments to monitor treatment progress and guide clinical decision-making. Although MBC improves outcomes when results are discussed collaboratively, adoption across the Veterans Health Administration (VHA) remains below 50%, particularly in virtual and rural settings. This pre-implementation evaluation explored provider perspectives to inform development of a digital MBC workflow for rural tele-mental health settings.

Methods

Using the Alacrity Center’s Discover, Design, Build, and Test model and User Centered Design, we conducted a pre-implementation survey of mental health providers at a VHA Medical Center providing care to rural and highly rural Veterans in South …

Regulation Of Mitochondrial Ros By C15orf48 In A Basal Cell Subpopulation Contributes To Chemotherapy Resistance In Tnbc, Yan Jiang, Noor M Abdulkareem, Amanda L Rinkenbaugh, Yuan Qi, Steven W Wall, Xiaomei Zhang, Jiansu Shao, Sabrina Jeter-Jones, Shirong Cai, Faiza Baameur Hancock, Gloria V Echeverria, Jeffrey T Chang, Helen Piwnica-Worms

Faculty, Staff and Students Publications

Systemic neoadjuvant chemotherapy, often combined with immunotherapy, is the standard of care for early-stage, non-breast cancer susceptibility gene (BRCA)-mutant triple negative breast cancer (TNBC). However, up to 70% of patients retain residual disease after treatment, which is linked to recurrence and mortality within 5 years. To define mechanisms of resistance, we performed single-cell RNA sequencing on orthotopic TNBC patient-derived xenografts during a cycle of treatment with doxorubicin and cyclophosphamide (AC). Clustering identified four tumor epithelial cell populations, with basal cells enriched in residual tumors. These basal cells up-regulated C15ORF48, a paralog of the mitochondrial cytochrome c oxidase associated subunit FA4 …

Nanog Proximity Proteomics Maps Neighborhood Hubs Linked To Mesenchymal Stem Cell Stemness And Chromatin Control, Kyoung-Jae Choi, Michail Tyryshkin, Harathi Jonnagaddala, Allan Chris M Ferreon, Marian Kalocsay, Josephine C Ferreon

Faculty, Staff and Students Publications

NANOG overexpression has been reported to reverse aging-associated decline in mesenchymal stem/stromal cell (MSC) function, but the molecular machinery engaged by NANOG in MSCs remains incompletely defined. Here, we applied APEX proximity labeling coupled with quantitative mass spectrometry to define the NANOG proximity interactome (proxeome) in human MSCs. Of 1040 quantified proteins, 828 were significantly enriched in the APEX-NANOG (H2O2 labeling) samples, consistent with a broad NANOG-centered neighborhood rather than a single stoichiometric complex. Enriched proteins encompass RNA-processing pathways (including splicing/RNP factors and selected m6A-related proteins), transcriptional coactivation and elongation control (Mediator and 7SK/P-TEFb regulators), chromatin repression/poising modules (Polycomb and …

Leadless Pacing And The Emerging Era Of Combined Procedures In Adult Congenital Heart Disease, Srikant Das, Brock A Karolcik, Taylor S Howard

Faculty, Staff and Students Publications

No abstract provided.

Empiric Azithromycin Alters The Upper Respiratory Microbiome And Resistome Without Anti-Inflammatory Benefit In Covid-19, Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C Lydon, Joanna Schaenman, Carolyn S Calfee, Esther Melamed, John Greenland, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Linda N Geng, Bali Pulendran, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, William B Messer, Mark M Davis, Kari C Nadeau, Monica Kraft, Christian Bime, David J Erle, Mark A Atkinson, Scott C Brakenridge, Lauren I R Ehrlich, Ruth R Montgomery, Albert C Shaw, Catherine L Hough, David A Hafler, Alison D Augustine, Patrice M Becker, Bjoern Peters, Al Ozonoff, Annmarie Hoch, Seunghee Kim-Schulze, Florian Krammer, Steven Bosinger, Walter Eckalbar, Matthew C Altman, Michael Wilson, Leying Guan, Holden Maecker, Hanno Steen, Impacc Network, Joann Diray-Arce, Nadine Rouphael, Steven H Kleinstein, Naresh Doni Jayavelu, Elaine F Reed, Ofer Levy, Victoria T Chu, Charles R Langelier

Faculty, Staff and Students Publications

Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression …

Feasibility Of A Large Language Model Chatbot To Support Parental Understanding In The Picu, R Brandon Hunter, Satid Thammasitboon, Sreya Rahman, Sriya Kakarla, Pamela Petersen, Shelley Kumar, Thomas Rappold, Sanjiv Mehta

Faculty, Staff and Students Publications

Objectives: To evaluate the feasibility of a large language model (LLM)-based chatbot for answering parental questions in the PICU and inform design of a randomized controlled trial (RCT).

Design: Prospective single-arm feasibility study conducted from August 2024 to December 2024.

Setting: Quaternary PICU.

Subjects: Fourteen parents of children admitted to the PICU.

Interventions: Parents engaged in 10-minute sessions with a HIPAA-compliant GPT-4o- (Generative Pretrained Transformer 4o, OpenAI, San Francisco, CA) based chatbot prompted with patient-specific electronic health record (EHR) data.

Measurements and main results: Feasibility was assessed through four criteria: parental engagement and satisfaction, provider perceptions, accuracy and safety, and …

Body Mass Index And Survival In Children Receiving Extracorporeal Membrane Oxygenation, Pilar Anton-Martin, Keith Baxelbaum, Shilpa Vellore, Erika O'Neil, Vinai Modem, Sameer Thadani

Faculty, Staff and Students Publications

Importance: Underweight and obesity represent opposite ends of the nutritional risk spectrum that negatively affect children's health worldwide. Both conditions have been associated with increased mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support.

Objective: To investigate the association of underweight and obesity status with pediatric ECMO outcomes using body mass index (BMI) z scores.

Design, setting, and participants: This retrospective cohort analysis used data from the Extracorporeal Life Support Organization (ELSO) database from January 1, 2019, to December 31, 2023. Participants included all pediatric patients from international ECMO centers aged 29 days to 18 years who received ECMO …

Development And Internal Validation Of A Pretransplant Biomarker Panel For Mortality Prediction Following Liver Transplant, Guergana G Panayotova, Sopio Simonishvili, Lianhua Jin, Duc T Nguyen, Edward A Graviss, Yong Qin, Anastasia Xynogala, Tumininu Ayorinde, Laurie J Minze, Alexander Lemenze, Krupa R Mysore, Julie M Corkrean, Linda W Moore, Flavio Paterno, Ashish Saharia, Constance M Mobley, Arpit Amin, Mark J Hobeika, Xian C Li, Paul J Gaglio, R Mark Ghobrial, James V Guarrera, Keri E Lunsford

Faculty, Staff and Students Publications

Importance: Current pretransplant clinical scoring systems fail to accurately estimate post-liver transplant (LT) survival, making recipient selection challenging. Persistent immune dysfunction contributes to early LT recipient mortality but is not captured by existing models.

Objective: To identify plasma biomarkers of pretransplant immune dysfunction and to develop a biomarker-based pre-LT risk stratification tool to predict post-LT mortality.

Design, setting, and participants: Prospective biomarker analysis of consecutively enrolled adult LT recipients was conducted. Healthy controls were included for baseline comparison. Patients undergoing LT at Houston Methodist Hospital (October 1, 2013, to December 31, 2017) and Rutgers/University Hospital (January 1, 2019, to March …

Physiological Peristaltic-Like Reactions Of The Tracheobronchial Tree Move Pulmonary Mycobacterium Tuberculosis Bacilli Into The Gastrointestinal Tract, Andrew R Dinardo, George W Kasule, Alberto L Garcia-Basteiro, Stool4tb Global Partnership

Faculty, Staff and Students Publications

No abstract provided.

Rethinking "Very High-Risk" Ascvd: Most Patients Qualify, Few Are Distinct?, Michael D Shapiro, Yuzhi Xi, Tammy Jiang, Xiao Zhang, Lori D Bash, Swapnil Rajpathak, Laura Gellis, Robert Hilkert, Erin D Michos, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Cardiovascular Outcomes With Icosapent Ethyl By Burden Of Standard Modifiable Cardiovascular Risk Factors In Reduce-It, Rahul Aggarwal, Deepak L Bhatt, Michael Miller, Christie M Ballantyne, Eliot A Brinton, Terry A Jacobson, Steven B Ketchum, Jean-Claude Tardif, Matthew J Budoff, Gemma A Figtree, Ph Gabriel Steg

Faculty, Staff and Students Publications

No abstract provided.

Advanced Artificial Intelligence Vs Simpler Models For 1-Year Death Prediction Among Patients Receiving Hemodialysis, Karthikeyan K, Jennifer E Flythe, Patrick H Pun, Wolfgang C Winkelmayer, David Carlson

Faculty, Staff and Students Publications

Objectives: We evaluated the data requirement for modern AI tools to outperform simpler models in predicting short-term mortality in over 500 000 patients with hemodialysis-dependent kidney failure.

Materials and methods: We compared logistic regression, boosting, and transformers using increasingly complex feature sets (from last-visit data to full trajectories). Performance was measured using the area under the ROC curve (AUC-ROC) and the Precision-Recall curve (AUC-PR) across training data sizes ranging from 500 to 490 197 samples.

Results: Using features with temporal information is beneficial across all models. On the full dataset, Transformers (AUC-ROC = 0.8568) and boosting (AUC-ROC = 0.8598) perform …

Driveline Infections Among Patients Supported With Left Ventricular Assist Devices: A Single Center Sixteen-Year Longitudinal Profile, Anh Nguyen, Alexis Shafii, Gabriel Loor, Andrew Civitello, O Howard Frazier, Todd Rosengart, Kenneth Liao

Faculty, Staff and Students Publications

Background: Left ventricular assist device (LVAD) driveline infections significantly impact patient outcomes. This study aimed to identify their risk factors.

Methods: We analyzed LVAD data from our institutional Intermacs database (January 1, 2008-December 31, 2023), combining primary implants and pump exchanges. Patient characteristics were summarized as frequencies for categorical variables and median (IQR) for continuous variables. The nature of repeated infection events was handled by the Andersen-Gill method within a multivariable Cox proportional hazards model for cause-specific hazard of driveline infections, accounting for death and heart transplant as competing risks.

Results: Our cohort included 1026 LVAD implants. Median patient age …

The International Pediatric Headache Didactic Series: A Novel Curriculum Innovation, Sara Pavitt, Sruthi Ilangovan, Zoë Allen, Samantha L Irwin, Irene Patniyot

Faculty, Staff and Students Publications

Objectives: The International Pediatric Headache Didactic Series (IPHDS) was developed to provide free, comprehensive pediatric headache education to healthcare professionals worldwide. The objective of this study was to describe the design, implementation, and impact of this prospective educational intervention.

Background: Headache is the most common neurological symptom within the pediatric population. Yet, only nine fellowships are offered in pediatric headache medicine. Limitations in access to education and training are often cited as reasons for diagnostic and management barriers. To address this gap, the IPHDS was established in July 2022.

Methods: IPHDS is a recurring series consisting of 23 biweekly lectures. …

Complement Anaphylatoxin C5a-Induced Mouse Lymphatic Functions Modulate Interactions Between Endothelial Cells And T Lymphocytes, Haydn E Rich, Yi-Dong Li, Kathryn D Hok, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Anthony Shadid, Rajarajan A Thandavarayan, Hari Krishna Yalamanchili, Marie-Francoise Doursout, Tingting Weng-Mills, Faraz Bishehsari, Nirmal K Banda, Kristin L Eckel-Mahan, Marcos I Restrepo, Pooja Shivshankar

Faculty, Staff and Students Publications

The lymphatic system is a highly branched endothelial tubular network that facilitates the migration of immune cells from the peripheral tissues to lymph nodes (LNs) and other lymphoid organs. Complement factors are essential for innate and adaptive immune functions. Complement anaphylatoxin C5a is crucial in vascular endothelial cell activation and lymphocyte polarization. Understanding the impact of C5a and its cognate receptor C5ar1 signaling on lymphatic function could provide new insights into the mechanisms of immune dysregulation observed in chronic inflammatory diseases. We demonstrate that acute C5a challenge in wildtype C57B6/J mice significantly reduced lymph propulsion compared to their C5ar1-deficient counterparts. …

Aht Diagnoses: The Influences Of Clinical Presentation And Evidence Of Impact, Ruairi Smith-Dewey, Angela Bachim, Colleen Bressler, Kristine Campbell, Lori Frasier, Christopher Greeley, Danielle Horton, Nicole Johnson, Jan Leonard, Megan M Letson, Caitlin Mcnamara, Ashley Sherman, Shalon Nienow, Stuart Sommers, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Background: The frequency of abusive head trauma (AHT) diagnoses by child abuse pediatricians (CAPs), especially regarding external evidence of head impact, has been questioned.

Objectives: To compare CAP diagnoses in subjects with subdural hemorrhage (SDH) across clinical presentations, including subgroups with and without external evidence of head impact. Additionally, we aimed to describe subjects with SDH and concomitant suspicious injuries (CSI) without evidence of head impact.

Participants and setting: Multicenter retrospective study including subjects < 24 months old with SDH.

Methods: Subjects were divided into groups based on clinical presentations: Ill SDH only, Non-ill SDH only, and SDH + CSI. Groups were subcategorized based on presence/absence …

Confessions In Cases Of Child Physical Abuse-A Capnet Study, Margaret R Russell, Antoinette L Laskey, Henry T Puls, Suzanne P Starling, Joanne N Wood, Daniel M Lindberg, Nancy S Harper, Caitlin R Mcnamara, Angela N Bachim, Farah W Brink, Lori D Frasier, James D Anderst, Porcia Vaughn, Kristine A Campbell

Faculty, Staff and Students Publications

Objective: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

Methods: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

Results: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

Conclusions: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Fronto-Cerebellar Features Associate With Cognitive Dysfunction In Childhood-Onset Systemic Lupus Erythematosus, Hanne Van Der Heijden, Gabrielle Alonzi, Amanda Cao, Raquel Van Gool, Merve Koç Yekedüz, Lise Vrolix, Itamar Ronen, Vanessa Rameh, Kyle Mcbrearty, Aditi Deokar, Robert P Sundel, Eyal Muscal, Joseph Gonzalez-Heydrich, Andrea Knight, Joyce C Chang, Jaymin Upadhyay

Faculty, Staff and Students Publications

Objective: Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE.

Methods: Patients with cSLE (N=20) and age- and sex-matched healthy controls (HCs, N=20) completed questionnaires and multiple neurocognitive tests. The Systemic Lupus Erythematosus Disease Activity Index 2000 and laboratory markers were used to monitor patients' clinical status. Neuroimaging assessments included functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and structural MRI.

Results: cSLE patients demonstrated moderate disease activity with high inflammation and immune dysregulation, alongside low medication adherence. Relative to HCs, cSLE patients …

Trauma-Related Compulsions In Obsessive-Compulsive Disorder: Functional Insights From Factor Analysis, Caitlin M Pinciotti, Max Thorsson, Gregor Horvath, Matti Cervin

Faculty, Staff and Students Publications

Resisting obsessive-compulsive disorder (OCD) compulsions is a key predictor of exposure and response prevention (ERP) effectiveness, yet trauma-exposed individuals with OCD endorse more severe compulsions and are more likely to be labelled 'treatment resistant.' Among trauma-exposed individuals, compulsions are theorised to function to prevent future trauma and cope with trauma-related responses. Recent findings suggest that certain compulsions in the context of trauma exposure differentially impact treatment outcomes, yet missing from extant literature is a larger empirically derived conceptualisation for how trauma may impact the underlying function of compulsions. In a sample of 662 adult patients enroled in intensive OCD treatment …

Dominant Clones Leverage Developmental Epigenomic States To Drive Ependymoma, Alisha S Kardian, Hua Sun, Siri Ippagunta, Nicholas Laboe, Srinidhi Varadharajan, Kwanha Yu, Hsiao-Chi Chen, Erik Emanus, Tuyu Zheng, Riley M Deneen, Jon P Connelly, Yong-Dong Wang, Jiangshan Zhan, Hengxi Liu, Kimberley Lowe, Taylor Bugbee, Rakesh Pathak, Amanda Bland, Sanya Mehta, Sophie Cochiolo, Amir Arabzade, Blake Holcomb, Kaitlin M Budd, Gabriele Kembuan, Tristen Wright, Emma Caesar, Maxwell Park, Amelia Hancock, David Gee, Joel Murdoch, Yi Xiao, Samuel K Mcbrayer, Thomas E Merchant, Jun Qi, Adam D Durbin, Lindsay A Schwarz, Li Wang, Andrew M Donson, Nicholas K Foreman, Sameer Agnihotri, Alfonso Lavado, Suzanne J Baker, David W Ellison, Hyun Kyoung Lee, Shondra M Pruett-Miller, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

ZFTA–RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA–RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse …

Androgen Activity In The Male Embryonic Hindbrain Drives Lethal Pfa Ependymoma, Jiao Zhang, Winnie Ong, Alexandra Rasnitsyn, Ricardo Daniel Gonzalez, Rodrigo Lopez Gutierrez, Polina Balin, Amr Saadeldin, Xiaochong Wu, Maria C Vladoiu, Vicente Santa-Maria Lopez, Fernando Gonzalez-Salinas, Navneesh Yadav, Dinesh Mohanakrishnan, Kannan Boosi Narayana Rao, Raja Gopal Reddy Mooli, Hinda Najem, Sebastian Pacheco, Kaitlin Kharas, Cory Richman, David Przelicki, Evan Y Wang, Haipeng Su, Rachel Naomi Curry, Runze Yang, Michelle Masayo Kameda-Smith, Bryn Livingston, David Scott, Zaili Luo, Mingyang Xia, Namal Abeysundara, Anders W Erickson, Ncedile Mankahla, Lucas Zhongming Hu, Chu Pan, Raul Suarez, Ning Huang, Yihao Wu, Hao Wang, Tajana Douglas, Jonelle Pallota, Steven Hébert, Karen Ng, Krystin Mantione, Heather Whetstone, Hassaan Maan, Hussein Lakkis, Juyeun Lee, Sadeesh K Ramakrishnan, Yanxin Pei, Yujie Tang, Frank Y Lin, Guillermo Aldave, Marco Gallo, Robert M Friedlander, Faiyaz Notta, Laura K Donovan, Murali Chintagumpala, Bo Wang, Yun Li, Daniel D De Carvalho, Zhaolei Zhang, Ying Mao, Wei Hua, Charles Eberhart, Calixto-Hope G Lucas, Sriram Venneti, Poul H Sorensen, Alberto Delaidelli, Hao Li, Wenhao Zhou, Jason Kirk, Dean G Tang, Tao Jiang, Hailong Liu, Justin D Lathia, Hiromichi Suzuki, Jeremy N Rich, Lincoln D Stein, Nada Jabado, Vijay Ramaswamy, Q Richard Lu, Amy B Heimberger, Craig Daniels, Kulandaimanuvel Antony Michealraj, Claudia L Kleinman, Michael D Taylor

Faculty, Staff and Students Publications

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects …

Robotic Single-Incision Laparoscopic Surgery For The Management Of Endometriosis: First Experience Via The Da Vinci Sp Platform, Qiannan Yang, Daniel Y Lovell, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the feasibility and mid-term outcomes of Robotic single-port single-incision laparoscopic surgery (RSP-SILS) for endometriosis management.

Methods: A retrospective analysis was conducted on 50 adult women with endometriosis who underwent RSP-SILS via the da Vinci SP platform between November 2023 and July 2025.

Results: Median total operative time was 142 min, robot dock time was 3 min, and robot console time was 99 min. Median estimated blood loss was 25 mL. No conversion occurred. Reported mid-term outcomes included 1 case each of pelvic haematoma, Clostridioides difficile colitis, and umbilical surgical site infection, as well as 3 cases of …

Robotic-Assisted Transumbilical Single-Site And Transvaginal Notes Resection Of Abdominal Wall Cesarean Scar Endometriosis: Two Case Reports, Xiaoming Guan, Qiannan Yang, Victoria Zhang, Chunhua Zhang

Faculty, Staff and Students Publications

No abstract provided.

A Comprehensive Review Of Tear Fluid Proteome Alterations In Dry Eye Disease: Insights Into Pathophysiology And Biomarker Potential, Saleh Ahmed, Steven Safille, Victoria Clifton, Shruti Sharma, Cintia S De Paiva, Ashok Sharma

Faculty, Staff and Students Publications

Tear fluid is a highly specialized and dynamic biofluid composed of proteins, lipids, mucins, and electrolytes that is essential for maintaining ocular surface integrity, immune defense, and tear film stability. Growing evidence from tear proteomic studieshas revealed extensive alterations in protein composition in dry eye disease (DED), reflecting a complex interplay between local ocular surface pathology and systemic inflammatory influences. This review summarizes proteomic findings from 50 published studies to identify tear proteins that are consistently upregulated or downregulated in DED and to interpret their biological relevance in the context of ocular surface homeostasis. Across studies, proteins upregulated in DED …

Rexinoid Net-3ib Promotes Resident Macrophage Gene Expression And Mitigates Desiccation-Induced Ocular Surface Disease, Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, Karen Zheng, Hiroki Kakuta, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.

Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled …