Digital Commons Network^™

Modulating Alternative Splicing Of Mecp2 Is A Potential Therapeutic Strategy For Rett Syndrome, Harini P Tirumala, Li Wang, Yan Li, Sameer S Bajikar, Ashley G Anderson, Wei Wang, Alexander J Trostle, Mahla Zahabiyon, Aleksandar Bajic, Jean J Kim, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique …

Clinical Validation Of Perfusion Imaging With Pulmonary Function Test Data Using Voronoi-Based Discretization, Jorge Cisneros, Caleb J. Herrera, Yi-Kuan Liu, Lisa V. Du, Yevgeniy Vinogradskiy, Richard Castillo, Girish Nair, Edward Castillo

Department of Medicine Faculty Papers

Objective.Accurate lung function assessment is essential for diagnosing and managing diseases like chronic obstructive pulmonary disorder, pulmonary emboli, and lung cancer. Single-photon emission computed tomography (SPECT) provides valuable 3D functional imaging of ventilation and perfusion, but is limited by low spatial resolution, availability, additional radiation, and cost. Alternative methods, including CT-based perfusion (CT-P) and deep learning models, require large datasets to validate results that are often scarce. Pulmonary function tests (PFTs) offer rapid and noninvasive global lung function measures and are clinically widely used. While ventilation correlates well with PFTs, perfusion imaging presents challenges due to complex blood flow and …

Post-Traumatic Stress Disorder And Risk Of All-Cause And Cause-Specific Mortality: A Nationwide Population And Sibling-Controlled Cohort Study In Taiwan, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aims: Post-traumatic stress disorder (PTSD) may shorten life expectancy, but evidence for Asian populations and cause-specific mortality remains limited. The aim of this study is to investigate the association between PTSD and mortality risk in an Asian population.

Methods: We used Taiwan's National Health Insurance Research Database (2000-2022) to assemble a cohort of 28,777 individuals with incident PTSD and 115,108 age- and sex-matched unexposed individuals, plus a sibling cohort of 13,305 affected patients and 22,030 unaffected siblings. Cox models estimated adjusted hazard ratios (AHRs) for all-cause, unnatural-cause (suicide and accidents) and natural-cause mortality, with progressive adjustment for sociodemographic factors, comorbidity …

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

Proteomic Profiling Of Pulmonary Function And Cardiovascular Disease Risk In The Atherosclerosis Risk In Communities Study, Yura Lee, Astrid M Manuel, Ngoc Quynh H Nguyen, Christine Ladd-Acosta, Alanna C Morrison, Kari E North, Eric Boerwinkle, Amil M Shah, Zhongming Zhao, Stephanie J London, Bing Yu

Faculty, Staff and Student Publications

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of …

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …

Pregnancy, Cancer, And Radiation-A Modern Refresher, Kelly Kisling, Sandra M Meyers, Rebecca Milman, Susan Richardson, Christina Chapman, Justine Dupere, Grace Eliason, Suzanne Evans, Titania Juang, Young Lee, Jeffrey Masten, Julia Maues, Rachel Newman, Mike Silosky, Catherine Song, Catheryn Yashar, Sara Thrower

Faculty, Staff and Student Publications

Cancer occurs in ∼1 per 1000 pregnancies; thousands of patients may require radiation procedures for diagnosis and treatment each year in the United States alone. This rare but high-risk scenario, coupled with fear of radiation, has created ambiguity in the ideal management of pregnant patients. Without a comprehensive guide for the use of radiation in imaging and treatment for pregnant cancer patients, it is difficult for providers to offer optimal patient-centered care without introducing disparities. The goal of this paper is to provide guidance on the use of radiation for screening, diagnosis, staging, and treatment of cancer, while highlighting gaps …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

Sex-Related Differences In Clinical Profile, Management, And Outcomes Of Patients With Type A And B Acute Aortic Dissection: Observations From Irad, Elizabeth Jackson, Andreina Carbone, Sherene Shalhub, Chih-Wen Pai, Marek Ehrlich, Toru Suzuki, G Chad Hughes, Anil Bhan, Rumi Faizer, Antonio Cittadini, Alan Braverman, Eric Isselbacher, Kim Eagle, Christoph Nienaber, Eduardo Bossone

2020-Current year OA Pubs

BACKGROUND: Available data about sex differences in patients with acute aortic dissection (AAD) are scant and conflicting. The aim of this study is to assess sex-related differences in clinical characteristics, presentation, diagnostic findings, management, and outcomes among patients with type A (TA-AAD) and type B AAD (TB-AAD).

METHODS: Data about 11 586 patients enrolled in the IRAD (International Registry of Acute Aortic Dissection) from 1996 to 2022, were analyzed; 7819 (67.5%) experienced TA-AAD and 3867 (33.0%) TB-AAD. Men and women were compared with regard to diagnosis, treatment, and in-hospital and long-term survival.

RESULTS: One third of patients were women (TA-AAD, …

Ifn Signaling Is Associated With Radiotherapy Response In Malignant Peripheral Nerve Sheath Tumors., Iowis Zhu, Julian Chien, Gabriel E Rech, Kanish Mirchia, Sixuan Pan, Kaeli Miller, Joanna Pak, Rosanna Wustrack, Varun Monga, Steve E Braunstein, Mark D Adams, Line Jacques, Melike Pekmezci, S John Liu, Harish N Vasudevan

Faculty Research 2026

Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs are not understood. Here, we combined bulk and single-cell transcriptomics, genome-wide CRISPR interference screens, and multiplatform molecular analysis across MPNST cells, mouse allograft models, and patients' samples to understand the mediators of the radiation response. Our data revealed that MPNSTs, but not benign plexiform neurofibromas, induced a type I IFN signature that functionally mediated the radiation response. Moreover, irradiation of …

Ifn Signaling Is Associated With Radiotherapy Response In Malignant Peripheral Nerve Sheath Tumors., Iowis Zhu, Julian Chien, Gabriel E Rech, Kanish Mirchia, Sixuan Pan, Kaeli Miller, Joanna Pak, Rosanna Wustrack, Varun Monga, Steve E Braunstein, Mark D Adams, Line Jacques, Melike Pekmezci, S John Liu, Harish N Vasudevan

Faculty Research 2026

Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs are not understood. Here, we combined bulk and single-cell transcriptomics, genome-wide CRISPR interference screens, and multiplatform molecular analysis across MPNST cells, mouse allograft models, and patients' samples to understand the mediators of the radiation response. Our data revealed that MPNSTs, but not benign plexiform neurofibromas, induced a type I IFN signature that functionally mediated the radiation response. Moreover, irradiation of …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

An Ai Approach To Differentiating Lung Squamous Cell Carcinoma From Metastases Of Other Origins, Mark G Evans, Jennifer Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony Karnezis, Casey Bales, George Sledge, David Spetzler, Ari Vanderwalde, Matthew Oberley, Balazs Halmos, Hossein Borghaei, Farah Abdulla, David Bryant, Fred Hirsch, Hassan Ghani

Department of Medical Oncology Faculty Papers

IMPORTANCE: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions.

OBJECTIVE: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life …

Surface Morphometrics Reveals Local Membrane Thickness Variation In Organellar Subcompartments, Michaela Medina, Ya-Ting Chang, Hamidreza Rahmani, Mark Frank, Zidan Khan, Daniel Fuentes, Frederick A Heberle, M Neal Waxham, Benjamin A Barad, Danielle A Grotjahn

Faculty, Staff and Student Publications

Lipid bilayers form the basis of organellar architecture, structure, and compartmentalization in the cell. Decades of biophysical, biochemical, and imaging studies on purified or in vitro-reconstituted liposomes have shown that variations in lipid composition influence the physical properties of membranes, such as thickness and curvature. However, similar studies characterizing these membrane properties within the native cellular context have remained technically challenging. Recent advancements in cellular cryo-electron tomography (cryo-ET) imaging enable high-resolution, three-dimensional views of native organellar membrane architecture preserved in near-native conditions. We previously developed a "Surface Morphometrics" pipeline that generates surface mesh reconstructions to model and quantify cellular membrane …

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …

The Relationship Between Apparent Potentiation And The Magnitude Of The Control Response, Joe Henry Steinbach, Gustav Akk

2020-Current year OA Pubs

The effect of a potentiating drug on ion channel function is typically evaluated by comparing current responses to the control agonist in the presence and absence of the potentiator. Differences in ratios of responses are then taken as proof of distinct potentiation properties when comparing modulation by different compounds. In these experiments, the concentration of the agonist is typically kept low to generate a small fractional control response. The precise relative magnitude of the control response is, however, not standardized among labs and can range from a concentration producing a response equal to just 2% of maximal (EC2) to over …

Pharmacokinetic Profiles Of Sertraline In Pregnancy As A Predictor Of Postpartum Depressive Symptoms, Sílvia M. Illamola, Zachary N. Stowe, Marc L. Kalin, Michael D. Evans, Catherine M.T. Sherwin, Maged M. Costantine, D. Jeffrey Newport, James C. Ritchie, Angela K. Birnbaum

Pediatrics Faculty Publications

Aim: To characterize pharmacokinetic changes of sertraline and its metabolite during pregnancy and postpartum, and their relationship to maternal postpartum depressive symptoms. Methods: This was a prospective observational, longitudinal study of pregnant women with a major depressive disorder treated with sertraline (N = 185 women, 205 pregnancies). Women were enrolled at <16 weeks' gestation and followed at 4-8 week intervals throughout pregnancy and the first postpartum year. Baseline measures included structured clinical interviews and demographic information. Drug and metabolite concentrations and psychometric measures (study outcomes) (ie, Hamilton Rating Scale for depression - 17 item, Beck Depression Inventory, Edinburgh Postnatal Depression Scale [EPDS], Clinical Global Impression [CGI]) were measured at follow-up visits. Serum sertraline and N-desmethylsertraline exposure were reported asstandardized 24-h concentration-to-dose (C/D) and parent to metabolite (P/M) ratios. Linear mixed-effects and latent trajectory models were used to characterize longitudinal patterns in concentration measures across pregnancy and postpartum, and their association with study outcomes. Results: Mean 24-h C/D ratios showed high variability throughout pregnancy and postpartuM.T.hat were characterized by three trajectories for sertraline and five for N-desmethylsertraline and P/M ratio corresponding to different sertraline pharmacokinetic profiles. At postpartum, sertraline drug exposure was inversely associated with higher EPDS score (P < .05), while N-desmethylsertraline exposure was associated with higher scores for all measured depression scales (P < .001). Higher P/M ratios had higher CGI scores (P < .05) postpartum. Conclusion: Sertraline pharmacokinetic profiles varied across pregnant women and were associated with postpartum depressive symptoms. The use of therapeutic monitoring may provide clinical insight that can be useful for identifying patients with a potential toward depressive symptoms.

Single-Nucleus Transcriptomics, Pharmacokinetics, And Pharmacodynamics Of Cdk4/6 And Mtor Inhibition In A Phase 0/1 Trial Of Recurrent High-Grade Glioma., Kevin C Johnson, An-Chi Tien, Jun Jiang, James Mcnamara, Yu-Wei Chang, Chelsea Montgomery, Anita Desantis, Leonel Elena-Sanchez, Yoko Fujita, Seongho Kim, Avishay Spitzer, Paul Gabriel, William F Flynn, Elise T Courtois, Amy Hong, Jocelyn Harmon, Yoshie Umemura, Artak Tovmasyan, Jing Li, Shwetal Mehta, Roel G W Verhaak, Nader Sanai

Faculty Research 2026

BACKGROUND: Outcomes for adult patients with high-grade glioma (HGG) remain poor, necessitating new treatment strategies. Key challenges include poor drug penetration in the brain and malignant cell state plasticity. Phase 0 studies identify agents that achieve target modulation through pharmacologically relevant brain concentrations.

METHODS: A Phase 0/1 clinical trial combined the 2 targeted inhibitors ribociclib (CDK4/6 inhibitor) and everolimus (mTOR inhibitor) in recurrent HGG patients, aiming to identify brain-penetrant combinations and assess their impact on malignant cell states. We enrolled 24 patients with recurrent HGG, characterized by CDKN2A/B deletion or CDK4/6 amplification, PTEN loss or PIK3CA mutations, and wildtype retinoblastoma …

Meta-Analysis Of Genetic Mapping Studies In Mice Reveals Candidate Epilepsy Modifier Genes That Are Outside The Current Drug Development Landscape., Giovanna L Durante, Anna L. Tyler, Rod C Scott, Amanda E Hernan, J Matthew Mahoney

Faculty Research 2026

OBJECTIVE: Despite decades of development in anti-seizure medications, ~30% of individuals remain refractory to all treatments, and none of the existing therapies are disease modifying. Identifying targets outside the current preclinical paradigm is critically important. This study aimed to characterize the landscape of current epilepsy treatments at the level of gene interaction networks and identify novel genetic modifiers of epilepsy as potential novel therapeutic targets.

METHODS: We performed a functional network analysis to score genes based on their interactions with known epilepsy genes, and we integrated these functional scores with population genetics data and drug tractability information. In parallel, we …

Meta-Analysis Of Genetic Mapping Studies In Mice Reveals Candidate Epilepsy Modifier Genes That Are Outside The Current Drug Development Landscape., Giovanna L Durante, Anna L. Tyler, Rod C Scott, Amanda E Hernan, J Matthew Mahoney

Faculty Research 2026

OBJECTIVE: Despite decades of development in anti-seizure medications, ~30% of individuals remain refractory to all treatments, and none of the existing therapies are disease modifying. Identifying targets outside the current preclinical paradigm is critically important. This study aimed to characterize the landscape of current epilepsy treatments at the level of gene interaction networks and identify novel genetic modifiers of epilepsy as potential novel therapeutic targets.

METHODS: We performed a functional network analysis to score genes based on their interactions with known epilepsy genes, and we integrated these functional scores with population genetics data and drug tractability information. In parallel, we …

Neutrophil-To-Lymphocyte Ratio As A Prognostic Factor Of Survival Outcomes In Head And Neck Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy, Pablo Llerena, Praneet C. Kaki, Kathryn Nunes, Eric Mastrolonardo, Kelly Bridgham, Annie Moroco, Hani Samarah, Mouadh Barbirou, David Baek, Chun Wang, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer M. Johnson, Hushan Yang, Larry A. Harshyne, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in cancers treated with immune checkpoint inhibitors (ICI), reflecting the link between inflammation and cancer immune response. This study examines NLR's prognostic value in head and neck squamous cell carcinoma (HNSCC) patients receiving neoadjuvant ICI therapy, focusing on its potential as an independent predictor of overall survival (OS) and disease-free survival (DFS).

METHODS: We conducted a retrospective cohort study including three neoadjuvant trials: durvalumab ± metformin, nivolumab ± tadalafil, or nivolumab ± BMS-986205 from 2017 to 2022. Pre-treatment NLR was calculated using absolute neutrophil and absolute lymphocyte counts obtained before neoadjuvant …

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 …

Improving Vaccination In People With Ckd: Report From A National Kidney Foundation Working Group, Susan F. Massengill, Kenneth A. Andreoni, Keith A. Bellovich, Cheryl Courtlandt, Vimal K. Derebail, David L. Feldman, Gia J. Oh, John W. Sleasman, Kristina A. Bryant, Improving Vaccination In Ckd Working Group

Department of Surgery Faculty Papers

People with chronic kidney disease (CKD) are particularly vulnerable to vaccine-preventable infections. Therefore, the National Kidney Foundation organized a multidisciplinary working group, including people with CKD and family care partners, to develop recommendations to improve vaccination rates, vaccination effectiveness, and health care for the CKD population. A modified Delphi process was used to achieve consensus on the recommendations. Recommendations on vaccination in CKD patients were organized into these categories: (1) patient preferences; (2) assessing the vaccination status of patients with CKD; (3) assessing vaccine response in patients with CKD; (4) vaccination of immunocompromised patients; (5) vaccination in posttransplant patients; (6) …

Apoe And Plasma Ad Biomarkers: The Role Of Genetic Ancestry In Hispanics/Latinos, Caitlin Cheung, Natasha Z Anita, Paola Filigrana, Myriam Fornage, Kevin A Gonzalez, Linda C Gallo, Carmen R Isasi, Robert C Kaplan, Xihao Li, Freddie Márquez, Humberto Parada, Krista M Perreira, Alberto R Ramos, Tatjana Rundek, Wassim Tarraf, Fernando D Testai, Charles Decarli, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

Background: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.

Methods: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.

Results: ε4 was associated with lower Aβ42/40 and higher p-tau181and …

Online Tutorial On Survival Analysis For Biomarker Discovery, Jaka Kokošar, Ela Praznik, Martin Špendl, Nancy P Moreno, Alana Newell, Gad Shaulsky, Blaž Zupan

Faculty, Staff and Students Publications

In biomedicine, survival analysis addresses time-to-event data to study outcomes like patient survival and treatment response, and supports biomarker discovery. Yet, teaching this analysis is often hindered by mathematical and programming barriers. We present a structured, hands-on tutorial that goes beyond a typical online guide-offering integrated video lectures, literature, quizzes, and practical exercises. Built around Orange Data Mining, an open and free no-code visual analytics platform, the tutorial covers key concepts such as censoring, Kaplan-Meier curves, group comparisons, and biomarker discovery through real-world datasets. Organized in four pedagogical units, it progresses from basic survival data analysis to gene and gene-set …

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 …

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. …

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 ± …