Digital Commons Network^™

Effect Of Dental Treatments On Reduction Of Preterm Birth: A Systematic Review And Meta-Analysis, Camille Thomas, Shakil Ahmed, Vincenzo Berghella, Romina Brignardello-Petersen, Mohamed El-Rabbany, Catherine Devion, Stefania Ronzoni

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Periodontal disease is associated with increased risk of preterm birth. Effective management during pregnancy may reduce preterm birth, though clinical trial evidence has been inconsistent. This study aimed to assess whether treating dental disease during pregnancy reduces preterm birth.

DATA SOURCES: A systematic search was performed of EMBASE, MEDLINE, PubMed, Cochrane Library, and trial registries up to December 2023 and re-run in January 2025.

STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) enrolling pregnant persons with any dental disease randomized to receive dental treatment vs no treatment were included. No language restriction was applied.

STUDY APPRAISAL AND SYNTHESIS METHODS: Data …

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

School of Health Professions

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

Spatial Profiling Reveals Distinct Molecular And Immune Evolution Of Mouse Lung Adenocarcinoma Precancers With Or Without Carcinogen Exposure, Bo Zhu, Muhammad Aminu, Pingjun Chen, Jian-Rong Li, Chuanpeng Dong, Chenyang Li, Yanhua Tian, Shao-Wei Lu, Hong Chen, Chenxi Ma, Xin Hu, Jie Ye, Andrew Y Liu, Beibei Huang, Frank R Rojas, Parra Cuentas Edwin Roger, Ou Shi, Monique B Nilsson, Alissa Poteete, Khaja B Khan, Wei Lu, Luisa M Solis Soto, Junya Fujimoto, Cara Haymaker, Ignacio I Wistuba, Zhubo Wei, Linghua Wang, Don L Gibbons, Ken Chen, Alexandre Reuben, Jason M Schenkel, John V Heymach, Chao Cheng, Jia Wu, Jianjun Zhang

Faculty, Staff and Student Publications

Tumor evolution involves genetic, transcriptional, and phenotypic alterations that shape cancer cell behavior and interactions with the microenvironment. While single‐cell technologies have advanced our understanding of this process, spatial dynamics remain incompletely characterized. Here, whole‐exome sequencing (WES), imaging mass cytometry (IMC), and spatial transcriptomics (ST) were integrated to study molecular evolution and immune responses in two lung adenocarcinoma (LUAD) mouse models: a genetically engineered model (129S4/Sv‐KrasLSL‐G12D, termed 129S4 K) and a carcinogen‐induced precancer model (129S4 U). Compared to 129S4 K, 129S4 U tumors exhibited higher mutational, neoantigen but lower copy number variation (CNV) burdens at matched developmental timepoints, consistent with …

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

Faculty, Staff and Students Publications

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

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

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

Faculty, Staff and Students Publications

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

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

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

Faculty, Staff and Students Publications

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

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

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

Relationship Between Heart Rate Variability And Sleep Among Girls And Boys With Abdominal Pain-Related Disorders Of Gut-Brain Interaction, Kendra J Kamp, Robert L Burr, Camden E Matherne, Emily Simonds, Tasha Murphy, Margaret M Heitkemper, Rona L Levy, Robert J Shulman, Miranda A L Van Tilburg

Faculty, Staff and Students Publications

Background: Children with abdominal pain-related disorders of gut-brain interaction (AP-DGBI) often experience sleep disturbances which may be linked to the autonomic nervous system. Heart rate variability (HRV) is a non-invasive measure of autonomic nervous system activity. Our aim was to examine if HRV was associated with characteristics of disturbed sleep in children with AP-DGBI in order to elucidate the underlying physiological mechanisms of disturbed sleep.

Methods: This analysis used baseline data from a randomized control trial of 156 children ages 7-12 years with AP-DGBI. HRV was measured after dinner using a Polar monitor. Sleep disturbances were evaluated using the Children's …

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

Faculty, Staff and Students Publications

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

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

Faculty, Staff and Students Publications

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

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

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

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

Faculty, Staff and Students Publications

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

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

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

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

Faculty, Staff and Students Publications

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

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

Predictive Validity Of The Obsessive-Compulsive Inventory-4 And Florida Obsessive-Compulsive Inventory-Ii Severity Scale, Eric A Storch, Ryan J Mccarty, Maya Zehavi, Mahnoor Ahmad, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Diana Obando, Servando Rodriguez Barajas, Renee M Frederick, Jacey L Anderberg, Hannah C Moore, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Ogechi C Onyeka, Andrew D Wiese, Melisa N Sagarnaga, Joseph F Mcguire, Ygor Arzeno Ferrão, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Wayne K Goodman, James J Crowley, Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc)

Faculty, Staff and Students Publications

Efficient and accurate screening tools are crucial for improving early identification and treatment outcomes among individuals with obsessive-compulsive disorder (OCD). This study evaluated the sensitivity and specificity of two OCD screening measures: the Obsessive-Compulsive Inventory-4 (OCI-4) and the Florida Obsessive-Compulsive Inventory-II (FOCI-II) severity scale. The measures were administered in a large transnational sample of Spanish speaking Latin American adults (N = 1696) with elevated obsessive-compulsive symptomatology. Participants completed diagnostic interviews (MINI and Y-BOCS) and self-report assessments across 23 sites in 11 countries. Both measures significantly distinguished OCD from non-OCD cases, with the FOCI-II demonstrating somewhat better predictive performance (AUC = …

Parkinson's Disease As A Somato-Cognitive Action Network Disorder, Jianxun Ren, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Parkinson's disease (PD) is an incurable neurological disorder that often begins insidiously with sleep disturbances and somatic symptoms, progressing to whole-body motor and cognitive symptoms

Emerging Options And Future Strategies In Immunotherapy For Advanced Lung Squamous-Cell Carcinoma, Y Wang, R Rosell, F R Hirsch, S Lu, R Govindan, K Park, S Peters, J J Zhang

2020-Current year OA Pubs

Advanced-stage lung squamous-cell carcinoma (LUSC) remains a therapeutic challenge. Although immune checkpoint inhibitors (ICIs) have revolutionized LUSC treatment, only a small subset of LUSC patients can achieve durable clinical benefits, underscoring the need for novel strategies. Emerging immunotherapy strategies have demonstrated early evidence of promise for LUSC patients, particularly multi-specific antibodies and fusion proteins, antibody-drug conjugates, adoptive cell therapies, and cancer vaccines. Additionally, advances in multi-omics and artificial intelligence offer potential for precise immunotherapy by deciphering the complex tumor-immune microenvironment and predicting therapeutic responses. The future of LUSC treatment lies in rational multi-target and biological therapies to boost immune cytotoxicity, …

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

2020-Current year OA Pubs

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

Increased Clinical Frailty Is Associated With Aortic-Related Mortality Following Fenestrated And Branched Endovascular Repair For Thoracoabdominal Aortic Aneurysm, Silvia Chen, Elizabeth Ramirez, Blake E Murphy, Anjali Sribalaskandarajah, Martin Bunker, Joel Kruger, Karina A Newhall, Rebecca A Sorber, Sara L Zettervall, Matthew P Sweet

2020-Current year OA Pubs

OBJECTIVE: Clinical frailty is associated with reduced long-term survival after fenestrated and branched endovascular aortic repair (F/BEVAR). This study assesses the impact of phenotypic clinical frailty on perioperative outcomes and cause of death following F/BEVAR for thoracoabdominal aortic aneurysm.

METHODS: Patients who underwent F/BEVAR at a single institution from 2012 to 2024 were identified. The clinical frailty scale (CFS) was used to determine phenotypic frailty. Patients with a preoperative CFS of ≥4 (vulnerable) and a CFS of < 4 were compared. We used χ

RESULTS: We included 233 patients; 60 (25.8%) had a CFS of ≥4 and 173 (74.2%) had a CFS of < 4. Patients with a CFS of ≥4 were more likely to have chronic obstructive pulmonary disease (53% vs 27%) and were treated for slightly larger aneurysms (72 mm vs 68 mm; P = .04). There were no differences in symptomatic presentation, aneurysm extent, or operative complexity between patient groups. Additionally, there were no differences in perioperative complications including 30-day mortality, stroke, and spinal cord ischemia. Patients with a CFS of ≥4 had an increased length of hospitalization (11.3 days vs 6.9 days; P < .01) and were less likely to return to preoperative functional status (62.7% vs 86.1%; P < .01). The 3-year all-cause and aortic-related mortality rates were 35.2% and 5.7%, respectively. Patients with a CFS of ≥4 had a lower survival at 1 year (74% vs 89%), 3 years (39% vs 73%), and 5 years (25% vs 56%), compared with patients with a CFS of < 4 (P < .01). The most common causes of death among both groups were pulmonary comorbidities (14.0%), oncologic conditions (14.0%), cardiovascular comorbidities (11.2%), and procedure-related complications (11.2%). Patients with a CFS of ≥4 were more likely to die from aortic-related mortality (10.3% vs 5.9%; P = .02), pulmonary comorbidities (15.4 vs 13.2%; P = .04), systemic decline (7.7% vs 1.5%; P = .02), and infection (12.8% vs 7.4%; P = .03). Aortic-related mortality for the entire patient cohort was 2.2% and 5.7% at 1 year and 3 years, respectively. Aortic-related deaths among clinically frail patients were often due to an inability to tolerate further aortic operations (eg, arch repair), and secondary to follow-up nonadherence in patients with a CFS of < 4.

CONCLUSIONS: In an expanded …

The Win Ratio For Evaluating Edoxaban Vs Dalteparin For Cancer-Associated Venous Thromboembolism: An Analysis Of The Randomized Hokusai Venous Thromboembolism Cancer Trial, Nick Van Es, Luuk J J Scheres, Kristen M Sanfilippo, Harry Büller, Marc Carrier, Marcello Di Nisio, Michael Grosso, Renato D Lopes, William F Mcintyre, Bjorn Redfors, Annelise Segers, Peter Verhamme, Jeffrey I Weitz, Patrick M Bossuyt, Deborah M Siegal

2020-Current year OA Pubs

BACKGROUND: The Hokusai Venous Thromboembolism (VTE) Cancer trial demonstrated that edoxaban was noninferior to dalteparin for the treatment of cancer-associated venous VTE.

OBJECTIVES: We reanalyzed the trial using the win ratio, an approach that evaluates a composite of outcomes in a hierarchical order.

METHODS: Forty-nine thrombosis experts ranked 10 outcomes in order of clinical importance from all-cause death (most important) to clinically relevant nonmajor bleeding (least important). We performed unmatched pairwise comparisons between participants on edoxaban and those on dalteparin at 6- and 12-month follow-up. Within each pair, edoxaban was assigned a win, loss, or tie according to the hierarchy …

From Damage Signals To Immune Modulators: Oxidized Lipids In Immunometabolic Inflammation, Neetu Srivastava, Xiaoxiao Wan

2020-Current year OA Pubs

Oxidized lipids, once viewed as byproducts of oxidative stress, are now recognized as critical mediators linking metabolism, redox imbalance, and immunity. Generated through enzymatic and nonenzymatic oxidation of polyunsaturated fatty acids, oxidized phospholipids, lipid aldehydes, and oxidized lipoproteins act as context-dependent signals regulating immune activation, resolution, and metabolic adaptation. In metabolic inflammation, these lipids engage scavenger and Toll-like receptors to influence macrophage polarization, dendritic-cell function, and T-cell differentiation. Their context and concentration determine whether oxidized lipids amplify inflammation or promote immune tolerance. Accumulation of these species connects oxidative stress to immune dysfunction, contributing to diseases, such as atherosclerosis, obesity, diabetes, …

Active Bone Marrow Dose Reconstruction In A Large-Scale Cohort Study Of Cancer Patients Treated With Photon Radiotherapy, Keith T Griffin, Kishan J Pithadia, Yeon Soo Yeom, Lior Braunstein, Kelly L Bolton, Lindsay M Morton, Choonsik Lee

2020-Current year OA Pubs

BACKGROUND: Previous studies have investigated the dose-response relationship between external beam radiotherapy (EBRT) and leukemia by reconstructing the mean active bone marrow (ABM) dose as part of the exposure assessment. However, no prior study has leveraged electronic medical records (EMR) to reconstruct ABM dose and dose-volume in an EBRT patient population.

PURPOSE: To support future studies on the relationship between radiation exposure and adverse health effects among EBRT patients, we demonstrate methods to retrospectively calculate ABM dose and dose-volume metrics in a large patient cohort using EMR.

METHODS: We retrieved complete EMR for 639 individuals (five pediatric and 634 adult) …

Cholecalciferol (Vitamin D3) Is An Agonist Of The Alzheimer's Disease-Associated Immune Receptor Trem2, Hunter B Dean, Ryan A Tuckey, Rory A Greer, Jessica A Greven, Shan-Zhong Yang, Daniel S Elston, Gunnar N Eastep, Yuwei Song, Thomas J Brett, Yuhua Song, Erik D Roberson

2020-Current year OA Pubs

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is one of the strongest genetic risk factors for late-onset Alzheimer's disease (AD). Several TREM2 ligands are known, including charged lipids and AD-associated proteins like apolipoprotein E and amyloid-β, but the full range of endogenous ligands for TREM2 remains unknown. Here we combined virtual screening of the Human Metabolome Database with molecular dynamics simulations, binding free energy estimation, and biolayer interferometry to identify novel TREM2 ligands and map their binding sites. Cholecalciferol, the unmodified parent form of vitamin D3, emerged as a top candidate. Structural modeling indicated that cholecalciferol binds TREM2 at …

Cdk4/6 Inhibition Mitigates Chemotherapy-Induced Expansion Of Tp53-Mutant Clonal Hematopoiesis, Irenaeus C C Chan, Giulia Petrone, J Scott Beeler, Duc Tran, Griffen Mustion, Catrina Fronick, Carlos Cruchaga, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Therapy-related myeloid neoplasm (tMN) is a fatal consequence of exposure to cytotoxic therapy administered in the treatment of cancer. Individuals with pre-existing TP53 clonal hematopoiesis (CH) are at high risk of tMN, with avoidance of therapy being the only strategy to reduce tMN risk. Here, in four randomized clinical trials, we show that the CDK4/6 inhibitor trilaciclib, given in conjunction with a variety of chemotherapeutic regimens and across diverse populations of patients with cancer, mitigates chemotherapy-related expansion of CH clones with mutations in DNA damage response genes, including TP53. This finding was also observed in a syngeneic mouse model of …

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Faculty, Staff and Students Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

Aggregation Of Gene Regulatory Information And Knowledge On Fair Principles Enables Discovery Of Pathogenic Gene Regulatory Variants, Keyang Yu, Haoquan Zhao, Andrea S Wilderman, Tierra R Farris, Jessie E Arce, David Chen, Andrew R Jackson, Yiran Guo, Qi Li, Bosko Jevtic, Dubravka Jevtic, Vuk Milinovic, Yuankun Zhu, Jeremy Costanza, Eric D Wenger, Christopher Nemarich, Lisa Anderson, Aleksandar Mihajlović, Kristin Ardlie, Shaine A Morris, Matthew E Roth, Deanne M Taylor, Adam C Resnick, Lilei Zhang, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Motivation: Methods for sharing gene regulatory information and knowledge on FAIR principles, particularly in the context of tissue-specific gene regulation, remain poorly defined and implemented, hampering discovery and clinical genetic diagnosis.

Results: We specified FAIR principles for tissue-specific gene regulatory information and knowledge; implemented them by developing a registry of regulatory elements and aggregating FAIR gene regulatory information from several major sources; developed computational tools that utilize these FAIR resources; and demonstrated their utility by associating gene regulatory variants with major subtypes of congenital heart disease.

In Vitro Studies Of The Effects Of Antithrombotic Zn-Dipicolylamine-Harboring Liposomes (Dpals) On Serum Albumin And Human Umbilical Vein Endothelial Cells, Michelle Tanujaya, Gianna Cai, Jia Patel, Zana Moldavsky, Yumna Ejaz, Malia Mahazabin Ahmed, Sangsang Duong, Lawrence E. Goldfinger, Koon Y. Pak, Brian D. Gray, Parkson Lee-Gau Chong

Cardeza Foundation for Hematologic Research

Thrombosis remains a leading cause of cardiovascular morbidity and mortality. During thrombosis, activated platelets and endothelial cells expose phosphatidylserine (PS) on their outer membranes, creating a surface that accelerates clot formation. Current antithrombotic therapies, such as heparin and warfarin, carry significant bleeding risks, highlighting the need for safer alternatives. In response, we developed a PS-targeting liposomal formulation composed of Zn-dipicolylamine (DPA)-cyanine-3[22,22] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (molar ratio 3:97). This DPA-harboring liposome (DPAL) binds selectively to PS-rich surfaces such as activated platelets and has demonstrated efficacy in reducing thrombosis in mouse models, with minimal bleeding. In the present study, we examined the interaction …

Alpha And Beta Emitters In Translational Nuclear Medicine: Clinical Advances, Challenges, And Future Direction, Hanieh Karimi, Thomas H. Shaffer, Erik Stauff, Vinay V. R. Kandula, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Radiopharmaceutical therapy (RPT) has emerged as a transformative modality in oncology, particularly for patients with metastatic or inoperable tumors. By leveraging molecularly targeted carriers conjugated to cytotoxic radionuclides, RPT enables precise delivery of ionizing radiation to tumor sites while minimizing off-target effects. Central to this approach are alpha (α) and beta (β) particle-emitting radionuclides. This review aims to provide a comprehensive overview of all clinically relevant alpha and beta emitters and incorporates the most recent advances from 2017-2025, offering a comprehensive and up-to-date perspective. Alpha and beta emitters hold significant promises for the future, especially in nuclear medicine, energy, and …

Multi-Ancestry Genome-Wide Association Study And Meta-Analysis Of Lung Function Decline, Bonnie K Patchen, Jingwen Zhang, Nathan Gaddis, Traci M Bartz, Jing Chen, Catherine Debban, Hampton Leonard, Ngoc Quynh H Nguyen, Jungkyun Seo, Courtney Tern, Richard Allen, Dawn L Demeo, Myriam Fornage, Carl Melbourne, Melyssa Minto, Matthew Moll, George T O'Connor, Tess Pottinger, Bruce M Psaty, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Jeran Stratford, Chengyue Zhang, R Graham Barr, Michael H Cho, Sina A Gharib, Ani Manichaikul, Kari North, Elizabeth C Oelsner, Eleanor M Simonsick, Martin D Tobin, Bing Yu, Seung Hoan Choi, Josée Dupuis, Patricia A Cassano, Dana B Hancock

The Brown Foundation: Institute of Molecular Medicine

Background

Despite evidence for a genetic component, few genetic associations with lung function decline have been identified. We aimed to evaluate genome-wide associations and putative downstream functionality of genetic variants for lung function decline.

Methods

We conducted genome-wide association study (GWAS) analyses of decline in FEV1, FVC, and FEV1/FVC in 52,056 White (N = 44,988), Black (N = 5,788), Hispanic (N = 550), and Chinese American (N = 730) participants across seven general population cohorts. GWAS analyses were stratified by cohort, ancestry, and sex. Results were combined in cross-ancestry and ancestry-specific meta-analyses. Significant variants available in …

Profiling The Genomic Landscape And Evolutionary History Of Polyploid Giant Cancer Cells In Undifferentiated Pleomorphic Sarcomas, Amy L Bowes, Sara Waise, Tom Lesluyes, Thomas Butters, Christie English, Haixi Yan, Annelien Verfaillie, Christopher Davies, Jianan Chen, Emma Nye, Richard Stone, Jiten Manji, Adrienne M Flanagan, Jonas Demeulemeester, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo

Faculty, Staff and Student Publications

Polyploid giant cancer cells (PGCCs), characterised by multinucleation and atypical nuclear morphology, are a common feature of undifferentiated pleomorphic sarcomas. While PGCCs may be a critical substrate for cancer evolution, their formation pathways and genomic consequences remain underexplored. In this study, we characterise PGCCs in ten pleomorphic sarcomas and use topographic single-cell DNA sequencing (scDNA-seq) to investigate their genomic landscape. We selected PGCCs based on their nuclear morphology, including mononucleated or multinucleated bizarre, misshapen nuclei, and analysed them at single-cell resolution. Histopathological analysis showed that PGCCs were often randomly distributed throughout the tumour and did not appear in clusters, suggesting …

Profiling The Genomic Landscape And Evolutionary History Of Polyploid Giant Cancer Cells In Undifferentiated Pleomorphic Sarcomas, Amy L Bowes, Sara Waise, Tom Lesluyes, Thomas Butters, Christie English, Haixi Yan, Annelien Verfaillie, Christopher Davies, Jianan Chen, Emma Nye, Richard Stone, Jiten Manji, Adrienne M Flanagan, Jonas Demeulemeester, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo

Faculty, Staff and Student Publications

Polyploid giant cancer cells (PGCCs), characterised by multinucleation and atypical nuclear morphology, are a common feature of undifferentiated pleomorphic sarcomas. While PGCCs may be a critical substrate for cancer evolution, their formation pathways and genomic consequences remain underexplored. In this study, we characterise PGCCs in ten pleomorphic sarcomas and use topographic single-cell DNA sequencing (scDNA-seq) to investigate their genomic landscape. We selected PGCCs based on their nuclear morphology, including mononucleated or multinucleated bizarre, misshapen nuclei, and analysed them at single-cell resolution. Histopathological analysis showed that PGCCs were often randomly distributed throughout the tumour and did not appear in clusters, suggesting …

Aav Gene Therapy For Mps Iva With Induction Of Immune Tolerance Via Oral Administration Of Epitope Peptides Of N-Acetylgalactosamine-6-Sulfate Sulfatase, Sampurna Saikia, Yasuhiko Ago, Fnu Nidhi, Shaukat Khan, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by the accumulation of undegraded glycosaminoglycans due to the deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme. MPS IVA manifests as progressive systemic skeletal dysplasia. Gene therapy (GT) is potentially a one-time treatment in which the enzyme is continuously produced, circulated, and delivered to target tissues. However, immune responses to gene products can diminish therapeutic efficacy. We hypothesized that oral delivery of tolerogenic peptides induces immune tolerance to human GALNS (hGALNS) in MPS IVA mice, enhancing therapeutic efficacy. Neonatal mice deficient in mouse GALNS (mGALNS) were treated orally with three T-cell/B-cell epitope peptides or hGALNS …

Comparing Ckd Populations With T1d And T2d: A Perspective Based On The Fine-One And Fidelity Populations, Hiddo J L Heerspink, Janet B Mcgill, Et Al.

2020-Current year OA Pubs

Chronic kidney disease (CKD) is a common comorbidity of both type 1 diabetes (T1D) and type 2 diabetes (T2D) and is associated with increased mortality, end-stage kidney disease and cardiovascular disease risk. Despite standard-of-care treatment with renin-angiotensin system inhibitors added to blood pressure and glycaemic control, people with CKD and T1D have a residual risk of CKD progression. Advances in therapeutic management have been limited over the past 3 decades, especially compared with CKD in T2D, for which new treatment options have emerged in the last 5 years. In this review article we discuss the similarities and differences between T1D …