Digital Commons Network^™

Development Of A Multi-Institutional Dataset To Validate A Novel Inflammatory Breast Cancer Diagnostic Score, Filipa Lynce, Samuel M Niman, Megumi Kai, Sean Ryan, Elizabeth Troll, Li Li, Kathy D Miller, Reshma Jagsi, Ginny Mason, Beth A Overmoyer, H T Carisa Le-Petross, Faina Nakhlis, Savitri Krishnamurthy, Beth T Harrison, Susie X Sun, Eren D Yeh, Jennifer R Bellon, Laura E Warren, Michael C Stauder, Meredith M Regan, Wendy A Woodward

Faculty, Staff and Student Publications

Background: Susan G. Komen, the Inflammatory Breast Cancer (IBC) Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to propose novel quantitative scoring rubrics for IBC diagnosis. In this study, we developed a multi-institutional clinical dataset to test and validate the proposed scoring system.

Methods: IBC (N = 988) and non-IBC (N = 332) cases were identified at 2 institutions with dedicated multidisciplinary IBC programs. The non-IBC cohort included consecutive cT4b and cT4c patients. Standard operating procedures (SOPs) were developed for all ambiguous findings and languages. Three different methods were used for the imputation of missing data, …

Human And Mouse Alzheimer's Seeds Differentially Affect Amyloid Deposition And Microglia-Dependent Plaque Response In Aged Mice, Juana Andreo-Lopez, Cristina Nuñez-Diaz, Kelly Do Huynh, Marie Minh Thu Nguyen, Celia Da Cunha, Francisco J Cantero-Molina, Cynthia Campos-Moreno, Stefania Zimbone, Francesco Bellia, Maria Laura Giuffrida, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Miriam Bettinetti-Luque, Nazaret Gamez, Catalina Valdes, Rodrigo Morales, Stefania Forner, Alessandra C Martini, Antonia Gutierrez, Frank M Laferla, David Baglietto-Vargas

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a complex neurodegenerative proteinopathy in which Aβ and tau misfold and aggregate into entities that structurally unsettle native proteins, mimicking a prion-like or "seeding" process. These Aβ and tau "seeds" can arrange in different conformations or strains that might display distinct pathogenic properties. Furthermore, recent evidence suggests that microglia play a key role in the amyloidogenic event and can modulate the propagation and aggregation processes. Here, we employed histological and molecular approaches to determine whether seeds from human AD brains compared to those from transgenic mice (3xTg-AD) are more prone to induce Aβ and tau aggregates …

Inhibition Of Methylthioadenosine Phosphorylase Protects From Experimental Acute Kidney Injury, Afaf Saliba, Yidong Chen, Jonathan W Nelson, Abhinav Vetcha, Wei Wei Wang, Li Kang, Nagarjunachary Ragi, Soumya Maity, Hamid Rabb, W Brian Reeves, Kumar Sharma

Faculty, Staff and Student Publications

Methylthioadenosine phosphorylase (MTAP) is a key enzyme in purine metabolism that may influence cellular responses to injury. We evaluated the effects of prophylactic MTAP inhibition in mouse models of ischemia-reperfusion and cisplatin-induced acute kidney injury (AKI). MTAP inhibition was confirmed by accumulation of methylthioadenosine (MTA). Treated mice showed reduced renal injury and decreased tubular damage. Transcriptomic analysis revealed protection from inflammatory and stress pathways, while maintaining oxidative phosphorylation, fatty acid metabolism, and epithelial integrity-related genes. Analysis of human single-cell RNA-seq data from the Kidney Precision Medicine Project indicated that MTAP is highly expressed in kidney injury marker-positive adaptive proximal tubule …

Associative Coding Of Conditioned Fear In The Thalamic Nucleus Reuniens In Rodents And Humans, Tuğçe Tuna, Michael S Totty, Muhammad Badarnee, Flávio Afonso Gonçalves Mourão, Shaun Peters, Mohammad R Milad, Stephen Maren

Faculty, Staff and Student Publications

The nucleus reuniens (RE) is a midline thalamic structure interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Recent work in both rodents and humans implicates the RE in the adaptive regulation of emotional memories, including the suppression of learned fear. However, the neural correlates of aversive learning in the RE of rodents and humans remain unclear. To address this, we recorded RE activity in humans (BOLD fMRI) and rats (fiber photometry) during Pavlovian fear conditioning and extinction. In both rats and humans, we found that conditioned stimulus (CS)-evoked activity in RE reflects the associative value of the CS. …

Associations Between Prostate Cancer And Dementia: A Nationwide Study In Sweden, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Jingkai Wei, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background and objective: Prostate cancer (PC) and dementia may commonly co-occur; yet, prior evidence for bidirectional associations is inconsistent. This study aims to determine the associations between PC and dementia in large population-based studies, which may further inform clinical care.

Methods: To assess the dementia risk in men with PC, a national cohort study was conducted in 178 746 men diagnosed with PC in 1998-2017 and 1 787 460 age-matched control men in Sweden without prior dementia. Cox regression was used to estimate hazard ratios (HRs) for Alzheimer's disease (AD) and vascular dementia (VaD) through 2018. Subanalyses explored differences by …

Master Protocol Design With Hybrid Control For Efficient Early-Phase Trial Consolidation, Alexander M Kaizer, Xiaojiang Zhan, Eric Baron, Rui Sammi Tang, David S Hong, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Master protocols represent transformations, enabling multiple therapies or diseases under a single protocol. These designs streamline therapeutic development by reducing redundancies. Suited for evolving fields such as oncology and global emergencies such as the COVID-19 pandemic, master protocols have been exemplified by studies such as RECOVERY, Solidarity, and I-SPY 2, which accelerated effective treatment identification (with I-SPY 2 focused on molecular subtypes). Recent oncology examples, such as MORPHEUS, evaluate immunotherapy combinations with shared controls. Despite advantages, their application in early-phase oncology remains underutilized amid growing regulatory emphasis on randomization for robust evidence.

Methods: US Food and Drug Administration (FDA) …

White Matter Abnormalities And Cognition In Aging And Alzheimer Disease, Christopher Peter, Aditi Sathe, Niranjana Shashikumar, Kimberly R Pechman, Abigail W Workmeister, T Bryan Jackson, Yuankai Huo, Shubhabrata Mukherjee, Jesse Mez, Logan C Dumitrescu, Katherine A Gifford, Corey J Bolton, Leslie S Gaynor, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Duygu Tosun-Turgut, Mohamad Habes, Di Wang, Arthur W Toga, Paul M Thompson, Panpan Zhang, Kurt G Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Barbara B Bendlin, Sterling C Johnson, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Paul K Crane, Michael L Cuccaro, Timothy J Hohman, Derek B Archer, Dimitrios Zaras, Yisu Yang, Alaina Durant, Praitayini Kanakaraj, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Seo-Eun Choi, Brandon Klinedinst, Michael L Lee, Phoebe Scollard, Emily H Trittschuh, Elizabeth A Sanders

Faculty, Staff and Student Publications

Importance: There has yet to be a large-scale study quantifying the association between white matter microstructure and cognitive performance and decline in aging and Alzheimer disease (AD).

Objective: To investigate the associations between tract-specific white matter microstructure and cognitive performance and decline in aging and AD-related cognitive impairment.

Design setting and participants: This prognostic study of aging and AD, a secondary data analysis of multisite cohort studies, acquired data from 9 cohorts between September 2002 and November 2022. Participants were eligible if they had diffusion-weighted magnetic resonance imaging (dMRI) data, domain-specific cognitive composite z scores, demographic and clinical data, were …

Nanotechnology For Immuno-Oncology, Adam J Grippin, Daeyong Lee, Eileen E Parkes, Wen Jiang, Betty Y S Kim

Faculty, Staff and Student Publications

Although the first generation of cancer immunotherapeutics produced unprecedented improvements in clinical outcomes for individuals with cancer, novel strategies to increase treatment specificity, delivery efficiency and pharmacokinetics are still needed. In this Review, we describe the potential advantages and current limitations of nanomaterials for cancer immunotherapy and highlight rational uses of nanosystems to generate potent and durable antitumor immune responses. We close with a review of the current state of clinical development of nanomedicine for cancer immunotherapy.

The Significance Of Detecting An Unusual Myeloblast Immunophenotype In A Presumptive Clinical Diagnosis Of Myelodysplastic Syndromes, Fnu Sameeta, Wei Wang, Fatima Zahra Jelloul, Okechukwu V Nwogbo, Beenu Thakral, Jie Xu, Shaoying Li, Chi Young Ok, Guilin Tang, Fuli Jia, L Jeffrey Medeiros, Sanam Loghavi, Jeffrey L Jorgensen, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.

Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.

Design.—: More than 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.

Results.—: Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but …

Bard: A Seamless Two-Stage Dose Optimization Design Integrating Backfill And Adaptive Randomization, Yixuan Zhao, Rachael Liu, Jianchang Lin, Ying Yuan

Faculty, Staff and Student Publications

One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose, followed by a randomization stage where patients are assigned to two or more doses to further assess and compare their risk-benefit profiles to identify the optimal dose. A limitation of this approach is its requirement for a relatively large sample size. To address this challenge, we propose a seamless two-stage design, BARD (Backfill and Adaptive Randomization for Dose Optimization), which incorporates two key features to reduce sample size and shorten trial duration. The first feature is the integration of …

Gd3 Synthase Drives Resistance To P53-Induced Apoptosis In Breast Cancer By Modulating Mitochondrial Function, Vivek Anand, Fouad El-Dana, Natalia Baran, Jenny Borgman, Zheng Yin, Hong Zhao, Stephen T Wong, Michael Andreeff, V Lokesh Battula

Faculty, Staff and Student Publications

TP53 mutations are common in breast cancer (BC) and are associated with poor prognosis. GD3 synthase (GD3S/ST8SIA1), a gene associated with breast cancer stem cells, is upregulated in tumors with p53 mutations. However, the functional relationship between GD3S and p53 is unknown. Here, we show that GD3S levels are highest in breast tumors with specific p53 mutations. Functional studies revealed that wild-type (WT) p53 inhibits GD3S expression, whereas mutation in p53 enhances GD3S expression by upregulating GD3S promoter activity. Moreover, we found that GD3S inhibits wild-type p53-induced apoptosis in BC cells, while BC cells harboring gain-of-function p53 mutations are dependent …

Dynamic Long-Term Prediction With Intermediate Event Information: A Flexible Model With Bivariate Time-Varying Coefficients, Yunyi Wang, Wen Li, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

The integration of time-to-intermediate event data and the evolving characteristics of patients to enhance long-term prediction has garnered significant interest, driven by the wealth of data generated from longitudinal cohorts. In this paper, we propose sequential/dynamic prediction rules by using regression models with time-varying coefficients. We introduce a class of dynamic models that not only incorporates intermediate event information but also leverages information across different landmark times. To address the challenge of right-censoring, we employ an inverse weighting technique in the estimation process. We establish the asymptotic properties of the estimated parameters and conduct extensive simulations to assess the finite …

Single-Cell Proteomic Analysis Reveals Multiple Myeloma Heterogeneity And The Dynamics Of The Tumor Immune Microenvironment In Precursor And Advanced States, Mohamed Kamal, Stephanie N Shishido, Jeremy Mason, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

Multiple myeloma (MM) is an aggressive hematologic malignancy arising from plasma cell (PC) proliferation in the bone marrow, progressing from its precursor states MGUS and SMM. Despite therapeutic advances, MM remains incurable, underscoring the need for better risk stratification and early detection. Tumor heterogeneity and dynamic immune microenvironment changes drive progression, yet bulk analyses overlook rare subpopulations critical to disease evolution and resistance. This study employed multiplexed targeted proteomics to characterize bone marrow aspirates (BMA) from 22 patients to observe the change in the distribution of PCs and tumor immune microenvironment (TiME) cells across MM disease states and controls. Bone …

De-Escalating Local Therapies Without Compromising Outcomes: Lessons From The Collision Trial, Jessica Albuquerque, Noreen S Siddiqi, Van K Morris, Hop Tran Cao, Iwan Paolucci, Bruno C Odisio

Faculty, Staff and Student Publications

No abstract provided.

Patient, Physician, And Assessor Blinding In Phase Iii Randomized Trials In Oncology: A Meta-Epidemiological Analysis, Gabrielle Brown, Pavlos Msaouel, Avital M Miller, Ramez Kouzy, Timothy A Lin, Joseph Abi Jaoude, Ethan B Ludmir, Alexander D Sherry

Faculty, Staff and Student Publications

Background: Blinding mitigates bias in randomized trials and may be especially crucial for surrogate endpoints, such as progression-free survival (PFS). Here, we characterize utilization of and factors associated with blinding in Phase III oncology trials with PFS primary endpoints.

Methods: Two-arm, superiority-design trials investigating systemic therapy were identified in May 2024 from ClinicalTrials.gov with no date limitation. Trials were required to have a PFS primary endpoint. The study outcomes were the presence of double-blind designs and blinded independent central review (BICR) for the primary endpoint. Ninety-five percent credible intervals for binary outcomes were estimated from beta distributions, and multivariable logistic …

Tert Promoter Mutations And Survival Outcomes In Adult-Type Granulosa Cell Tumors, Allison L Brodsky, Alejandra Flores Legarreta, Bryan M Fellman, Deanna Glassman, Jeffrey How, Veena Vuttaradhi, Anil K Sood, Lois Michelle Ramondetta, David Gershenson, R Tyler Hillman

Faculty, Staff and Student Publications

Objectives: To evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase (TERT) promoter mutations.

Methods: This is a retrospective cohort study using the MD Anderson Rare Gynecologic Malignancy Registry. Patients with adult granulosa cell tumors who underwent molecular testing for TERT promoter and FOXL2 c.C402G mutations were included. We used descriptive statistics to compare demographic and clinical variables and estimated progression-free and overall survival with Kaplan-Meier curves. Cox proportional hazards regression and log-rank tests were employed for comparisons, with multivariable analyses adjusting for various factors.

Results: Among 70 patients, 28 (40%) had TERT+ tumors. …

Ppp2r1a Mutations Portend Improved Survival After Cancer Immunotherapy, Yibo Dai, Anne Knisely, Mitsutake Yano, Minghao Dang, Emily M Hinchcliff, Sanghoon Lee, Annalyn Welp, Manoj Chelvanambi, Matthew Lastrapes, Heng Liu, Zhe Yuan, Chen Wang, Hao Nie, Stephanie Jean, Luis J Montaner, Jiakai Hou, Ami Patel, Shrina Patel, Bryan Fellman, Ying Yuan, Baohua Sun, Renganayaki Krishna Pandurengan, Edwin Roger Parra Cuentas, Joseph Celestino, Yan Liu, Jinsong Liu, R Tyler Hillman, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Larissa A Meyer, David M Gershenson, David Vining, Dhakshinamoorthy Ganeshan, Karen Lu, Jennifer A Wargo, Weiyi Peng, Rugang Zhang, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) therapy is effective against many cancers, although resistance remains a major issue and new strategies are needed to improve clinical outcomes1-5. Here we studied ICB response in a cohort of patients with ovarian clear cell carcinoma-a cancer type that poses considerable clinical challenges and lacks effective therapies6-8. We observed significantly prolonged overall survival and progression-free survival in patients with tumours with PPP2R1A mutations. Importantly, our findings were validated in additional ICB-treated patient cohorts across multiple cancer types. Translational analyses from tumour biopsies demonstrated enhanced IFNγ signalling, and the presence of tertiary lymphoid structures at the baseline, …

Nature-Inspired Metaheuristics For Optimizing Dose-Finding And Computationally Challenging Clinical Trial Designs, Weng Kee Wong, Yevgen Ryeznik, Oleksandr Sverdlov, Ping-Yang Chen, Xinying Fang, Ray-Bing Chen, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Metaheuristics are commonly used in computer science and engineering to solve optimization problems, but their potential applications in clinical trial design have remained largely unexplored. This article provides a brief overview of metaheuristics and reviews their limited use in clinical trial settings. We focus on nature-inspired metaheuristics and apply one of its exemplary algorithms, the particle swarm optimization (PSO) algorithm, to find phase I/II designs that jointly consider toxicity and efficacy. As a specific application, we demonstrate the utility of PSO in designing optimal dose-finding studies to estimate the optimal biological dose (OBD) for a continuation-ratio model with four parameters …

Optimization Of Mhealth Behavioral Interventions For Patients With Chronic Lymphocytic Leukemia: The Health4cll Study, Che Young Lee, Max J Gordon, Melissa M Markofski, Emily C Lavoy, Susan K Peterson, Liang Li, Sara Fares, Miranda Baum, Margaret Pace, Danielle Walsh, Alessandra Ferrajoli, Karen Basen-Engquist

Faculty, Staff and Student Publications

Purpose: This pilot study of a diet and physical activity intervention (HEALTH4CLL) was conducted to reduce fatigue and improve physical function (PF) in patients with chronic lymphocytic leukemia (CLL).

Methods: The HEALTH4CLL study used a randomized factorial design based on the multiphase optimization strategy (MOST). Patients received diet, exercise, and body weight management instructional materials plus a Fitbit and were randomized to undergo one of 16 combinations of 4 evidence-based mHealth intervention strategies over 16 weeks. Patients' fatigue, PF, health-related quality of life, behavior changes, and program satisfaction and retention were assessed. Paired t-tests were used to examine changes in …

Orp2 Regulates Free Cholesterol Accumulation In Hepatocytes During Mash, Jin Wu, Yudi Zhao, Liwen Qiu, Qiaoli Chen, Xiaowei Wang, Jingwen Gu, Yan Liang, Yingjie Zhang, Hong-Yu Wang, Yang Liu, Xiaoqin Wu, Shuai Chen, Feng-Jung Chen, Mingming Gao, Hongyuan Yang

Faculty, Staff and Student Publications

Background: Cholesterol crystals in hepatocytes are known to strongly associate with human metabolic dysfunction-associated steatohepatitis. However, it remains unclear which molecular pathway(s) regulates free cholesterol accumulation and the formation of cholesterol crystals in hepatocytes. In cultured cell lines, oxysterol-binding protein-related protein 2 (ORP2) functions to deliver cholesterol to the plasma membrane from endosomal compartments.

Methods: Here, we generated liver-specific ORP2 knockout (ORP2-LKO) mice and characterized their metabolic phenotypes on chow and high-fat diet.

Results: The ORP2-LKO mice developed much more severe hepatic steatosis than floxed control mice after high-fat diet feeding. They also demonstrated more severe liver inflammation and damage. …

Molecular Determinants Of Sotorasib Clinical Efficacy In Krasg12c-Mutated Non-Small-Cell Lung Cancer, Ferdinandos Skoulidis, Bob T Li, Adrianus Johannes De Langen, David S Hong, Herve Lena, Juergen Wolf, Grace K Dy, Alessandra Curioni Fontecedro, Pascale Tomasini, Vamsidhar Velcheti, Anthonie J Van Der Wekken, Christophe Dooms, Luis Paz-Ares Rodriguez, Giannis Mountzios, Adrian Sacher, Ernest Nadal, Sebastien Couraud, Sang-We Kim, Kenneth O'Byrne, Danilo Rocco, Ryo Toyozawa, Izabela Chmielewska, Colin R Lindsay, Antreas Hindoyan, Lata Mukundan, Tomasz Wilmanski, Abraham Anderson, Christine Ardito-Abraham, Amrita Pati, Anita Reddy, Bhakti Mehta, Martin Schuler

Faculty, Staff and Student Publications

Molecular determinants of KRAS(G12C)inhibitor efficacy in KRASG12C-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRASG12C-mutated NSCLC co-mutational subsets and transcriptional subtypes. We also identify low expression of TTF1 and KEAP1 co-mutations/NRF2 activation as major determinants of sotorasib anti-tumor efficacy and adverse prognostic features. Exploratory analyses highlight potential tumor cell-extrinsic contributors to sotorasib anti-tumor activity and suggest …

Computed Tomography Radiomics-Based Cross-Sectional Detection Of Mandibular Osteoradionecrosis In Head And Neck Cancer Survivors, Serageldin Kamel, Laia Humbert-Vidan, Zaphanlene Kaffey, Sarah Mirbahaeddin, Abdulrahman Abusaif, David T A Fuentes, Kareem Wahid, Cem Dede, Mohamed A Naser, Renjie He, Ahmed W Moawad, Khaled M Elsayes, Melissa M Chen, Adegbenga O Otun, Jillian Rigert, Mark S Chambers, Andrew Hope, Erin Watson, Kristy K Brock, Katherine Hutcheson, Lisanne Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Abdallah S R Mohamed, Md Anderson Head And Neck Cancer Symptom Working Group

Faculty, Staff and Student Publications

Purpose: This study aims to identify radiomic features from contrast-enhanced CT (CECT) scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in head and neck cancer (HNC) patients treated with radiotherapy (RT).

Materials and methods: CECT images from 150 patients with confirmed ORN diagnosis (2008-2018) at MD Anderson Cancer Center (MDACC) were analyzed (80 % train, 20 % test). Radiomic features were extracted using PyRadiomics from manually segmented ORN regions and automated contralateral healthy mandible regions. Correlation analysis (r > 0.95) reduced features for model training. A random Forest (RF) classifier with Recursive Feature Elimination identified discriminative features. Explainability was assessed …

Mitophagy’S Impacts On Cancer And Neurodegenerative Diseases: Implications For Future Therapies, Jason Huang, Vincent Truong Pham, Shaozi Fu, Gang Huang, Ya-Guang Liu, Lei Zheng

Faculty, Staff and Student Publications

Substantial evidence supports an inverse relationship between cancer and neurodegenerative diseases (NDDs), but few studies investigate the biological mechanisms underlying this phenomenon. While previous explanations-such as inflammation, reactive oxygen species (ROS), genetic mutations, and cell death-remain significant, they ultimately converge on mitophagy. This review identifies mitophagy as a pivotal factor in the development of both cancer and NDDs, while also evaluating specific mechanisms and processes to clarify how mitophagy connects these opposing disease trajectories. By examining these factors, we aim to uncover the underlying mechanisms that explain the inverse relationship between cancer and NDDs, which will help develop therapeutic strategies …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R Cox, Rabie Habib, Michael J Bolt, Jessica B Felix, Claudia E Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M Hartig

Faculty, Staff and Student Publications

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Temporal Disparities In Diagnosis: The Critical Impact Of Laboratory Workflow Inefficiencies On Outcomes In Metabolic And Cardiovascular Disorders, Evans Dzreke, Celene Dzreke, Ramseyer Adekorang Asamoah, David Kanze

Health & Biomedical Sciences Faculty Publications

Diagnostic delays and laboratory process inefficiencies constitute a common but unaddressed dilemma in contemporary healthcare, quietly undermining patient outcomes in metabolic and cardiovascular illnesses where immediate intervention is critical. This seminal work goes beyond traditional operational viewpoints to demonstrate diagnostic inefficiency as an independent, adjustable risk factor with far-reaching implications. We rigorously quantified the impact of delayed test processing and reporting on clinical outcomes using a comprehensive mixed-methods approach that included multi-center retrospective cohort analysis (N=128,743 patients), real-time workflow mapping across 37 laboratories, in-depth case reviews, and economic modeling. Our findings challenged conventional wisdom by indicating that each 24-hour increase …

The Resilience Of The Human Lungs: Evolution, Smoke, And Disease, Joan B Soriano, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Molecular Maestro In The Lung: The Sphingolipid Rheostat, Joselyn Rojas-Quintero, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Differences In Wait-List Mortality: Temporary Vs Durable Circulatory Support Devices, Mahwash Kassi, Salma Zook, Duc Nguyen, Katelyn Ingram, Sapna Legha, Rayan Yousefzai, Ju Kim, Imad Hussain, Cindy M Martin, Janardhana Gorthi, Adeel Ahsan Syed, Nadia Fida, Arvind Bhimaraj, Edward A Graviss, Ashrith Guha

Faculty, Staff and Students Publications

Background: In 2018, changes in the United Network for Organ Sharing (UNOS) allocation system led to a shift in practices, making durable left ventricular assist devices less desirable as a bridge to transplantation compared to temporary mechanical circulatory support. This study compares the composite outcome of waitlist mortality and delisting incidence at 1 year between these two support types.

Methods: All actively listed adult patients on mechanical circulatory support listed for heart transplantation under the current UNOS system from October 2018 to October 2021 were included, excluding those with right ventricular devices, biventricular devices, total artificial hearts, and extracorporeal membrane …

Insights Into The Molecular Mechanism Of Pulmonary Vein Stenosis In Pediatric Patients With Congenital Heart Disease, Alyssa B Kalustian, Pengfei Ji, Lalita Wadhwa, Christopher A Caldarone, Manish Bansal, Athar M Qureshi, Jeffrey S Heinle, Ravi K Birla

Faculty, Staff and Students Publications

Objective: Pediatric pulmonary vein stenosis (PVS) is associated with substantial morbidity and mortality for the subset of patients with recurrent or progressive disease. The molecular mechanisms underlying the development and trajectory of PVS remain unclear. This study characterizes the transcriptome of clinical and phenotypic subtypes of PVS.

Methods: Bulk RNA sequencing analysis was performed on human pulmonary vein tissue samples obtained from surgical interventions for pediatric patients with PVS. Transcriptomic profiles were compared for primary versus postrepair PVS as well as aggressive versus nonaggressive clinical phenotypes. Principal component analysis was performed, the differential gene expression quantified, and pathway analysis conducted …

The 2024 Think Tank On Prevention Of Sudden Cardiac Death In The Young: Pathway To Survival A Report From The Cardiac Safety Research Consortium, Jordan E Ezekian, Charles C Anderson, Peter F Aziz, Samia Baluch, Stuart Berger, Martha Lopez-Anderson, Vincent Miller, Yoshihide Mitani, Silvana Molossi, Valarie Morrow, Victoria L Vetter, Elizabeth Vickers Saarel, Bhavya Trivedi, Salim F Idriss, 2024 Think Tank Participants

Faculty, Staff and Students Publications

Sudden cardiac arrest and death in the young is a critical public health issue. It occurs in children of any age, sex, racial or ethnic demographic, or socioeconomic status. Importantly, it can affect any individual-athlete and nonathlete alike. Prevention of sudden death in the young is of high importance not only because of the loss of a young life but also because of the substantial impact to families and to society at large. This White Paper summarizes the proceedings of a third national Think Tank on prevention of sudden cardiac death in the young. The Think Tank, which convened on …