Medical Specialties Commons^™

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, Heather A Danhof, Ludwig Ermann Lundberg, Stefan Roos, Robert A Britton

Faculty, Staff and Students Publications

Strains of Limosilactobacillus reuteri have been used to prevent or treat various conditions; however, the mechanisms by which they exert beneficial effects are not completely understood. Infant colic is one example in which L. reuteri DSM 17938 reduces clinical symptoms. While the etiology of colic is unknown, abnormal melatonin levels in infants have been suggested as a possible contributor. L. reuteri DSM 17938 has been shown to produce adenosine from AMP via production of the extracellular enzyme 5′ectonucleotidase (5′NT). Adenosine is a potent signaling molecule that impacts several important aspects of host physiology, including the release of melatonin from the …

Mucin-Derived Sugars Act As Metabolic Brakes Controlling Growth Initiation In Akkermansia Muciniphila, Bryan D Lakey, Katherine J Wozniak, Robert A Britton, Jeffrey J Tabor

Faculty, Staff and Students Publications

Akkermansia muciniphila is a key member of the gut microbiota and plays important roles in host metabolism and health. In the colon, A. muciniphila extracts nutrients from oligosaccharide-rich mucin glycans that comprise the mucosa. However, this environment is complex and shaped by dietary inputs, microbiome metabolism, and mucin glycan composition varying across hosts, gastrointestinal regions, and physiological states. How strains of A. muciniphila integrate these nutrient signals into growth initiation and niche colonization remains unclear. Here, we compare physiological responses of a human- and mouse-derived strain of A. muciniphila, finding that dietary sugars differentially affect these isolates, suggesting host-associated …

Gut-Derived Bacterial Extracellular Vesicles: The Microbial Dark Matter Contributing To Host Inflammation And Cardiometabolic Disease, Blayne Oliver, Michael Sun, Young Seo Lee, Ssanggoo Cho, Tianyi Zhu, David Durgan, Gary Sweeney

Faculty, Staff and Students Publications

Cardiometabolic diseases (CMDs) represent a growing global health burden, with chronic inflammation and gut microbiota dysbiosis emerging as central contributors to their pathogenesis. Among the diverse microbial products influencing host physiology, bacterial extracellular vesicles (BEVs) have gained attention as potent mediators of interkingdom communication. These nanoscale vesicles, secreted by both gram-positive and gram-negative bacteria, carry a complex cargo of proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs) that interact with host pattern recognition receptors (PRRs) to modulate immune and metabolic responses. BEVs can traverse intestinal barriers, disseminate systemically, and accumulate in cardiometabolic tissues, where they influence inflammation, insulin sensitivity, …

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, Howard Bauchner, Daniel J Merenstein

Faculty, Staff and Students Publications

Many professional organizations publish clinical practice guidelines for the use of probiotics in gastrointestinal disorders. Generally, no two guidelines align perfectly, and some differ markedly. These discrepancies occur because clinical practice guidelines are not purely mechanical outputs of data synthesis. They are shaped by structured interpretation, value judgments, and predefined thresholds for uncertainty. These elements become particularly visible when effect sizes are small, heterogeneity is high, and outcomes vary in clinical relevance-as is the case with probiotic research. This article examines why discordance among probiotic guidelines is predictable and provides practical guidance for clinicians who must decide among conflicting recommendations …

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, Yuri Park, Adam M Dean, Yan Xia, Jianming Xu, Clifford C Dacso, David M Lonard, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is highly expressed in regulatory T cells (Tregs) and is important for their immunosuppressive activity. Recently, we demonstrated that disrupting SRC-3 expression in Tregs eliminates triple-negative breast cancer (TNBC) and prostate cancer in syngeneic animal models by generating an anti-tumor immune microenvironment without inducing immune-related adverse events (irAEs). Further analysis of these mice revealed that SRC-3 knockout (KO) Tregs infiltrated breast tumors and facilitated the infiltration of CD8

Characterizing Children With Chronic Kidney Disease And Severe Proteinuria In The United States: A Retrospective Analysis Using Electronic Health Records., Bradley A. Warady, Simone Heeg, Alfredo E. Farjat, Rachel Knapp, Siir Su Saydam, Alexander Vowinkel, Alain Gay, James Potts, Andrea Scalise, Gordana Atanackovic, Sascha Van Boemmel-Wegmann

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In recent years, real-world data have been increasingly used to enrich data from interventional studies on treatment effectiveness. To explore the viability of hybrid study designs in pediatric chronic kidney disease (CKD), we assessed the feasibility of identifying a real-world cohort of children with CKD and severely increased proteinuria who satisfied adapted eligibility criteria from the FIONA trial.

METHODS: We used data from the Optum® de-identified Electronic Health Record dataset (Optum® EHR) to identify and characterize children with CKD and severely increased proteinuria in records from January 2013 to December 2022. Patients were identified based on two sets of …

Touch Contamination And Associated Peritonitis In Children Undergoing Maintenance Peritoneal Dialysis., Rebecca G. Same, Natalie K. Grills, Sreejata Dutta, Alicia M. Neu, Bradley A. Warady, Brandy Begin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Infections are a leading cause of hospitalization and death in children receiving maintenance peritoneal dialysis (PD). Touch contamination is an established risk factor for development of peritonitis, but data regarding optimal management of touch contamination are limited.

METHODS: We conducted a retrospective cohort study using data submitted to the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease (SCOPE) collaborative between 10/1/2011 and 7/31/2025 to evaluate touch contamination in children. Reported touch contamination events and their management, including administration of prophylactic antibiotics and transfer set changes, were evaluated. Univariate and multivariable generalized linear mixed modeling were used …

Ambulatory Arterial Stiffness Index Among Children And Adolescents With Chronic Kidney Disease: A Report From The Chronic Kidney Disease In Children Study., Susan M. Halbach, Jennifer Roem, Michael F. Schneider, Joshua Samuels, Susan L. Furth, Bradley A. Warady, Joseph T. Flynn, Ckid Study Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: To quantify the association between ambulatory arterial stiffness index (AASI) and hypertensive status, and to identify additional predictors of AASI, including body mass index (BMI), proteinuria, and mineral metabolism, in children and adolescents with chronic kidney disease (CKD).

METHODS: We analyzed data collected from 654 participants during 1283 study visits in the Chronic Kidney Disease in Children (CKiD) prospective cohort study. AASI was calculated from ambulatory blood pressure monitoring (ABPM) data as 1 minus the slope coefficient from a least squares linear regression of diastolic blood pressure (BP) on systolic BP. Hypertensive status was determined by clinic BP and …

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Sarah Shin, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …

Families' Neighborhood Resources Predict Treatment Response For Regulating Together, A Group Therapy For Emotion Dysregulation In Autistic Youth., Walker S. Mckinney Ph.D., Lauren M. Schmitt, Jennifer R. Ruberg, Marika Coffman, Debra Reisinger, Rebecca C. Shaffer

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Autistic youth often face difficulties with emotion dysregulation (ED) and associated challenging behaviors. The Regulating Together (RT) group therapy was developed to treat ED in autistic youth ages 8-18 years and has been shown to be feasible, acceptable, and efficacious at reducing ED. Results from other clinical trials suggest the efficacy of behavioral therapies may vary based on family- or neighborhood-level social determinants of health (SDOH: "the conditions in the environments where people are born, live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks"; U.S. Department of Health …

Mtorc2-Nav1.2 Signaling Drives Early Hyperexcitability In Alzheimer’S Disease Mouse Model

Faculty, Staff and Students Publications

Hyperexcitability is a biomarker of early-stage Alzheimer’s Disease (AD) and hastens cognitive decline later in its course. Mechanistic target of rapamycin (mTOR) signaling contributes to the slope of this trajectory, as evidenced by early increased brain expression and the rescue of hyperexcitability by genetic deletion of mTOR complex 2 (mTORC2); however, a molecular mechanism directly linking mTOR signaling to membrane hyperexcitability in early-stage AD remains elusive. Here, we show that hyperactive mTOR signaling stimulates the voltage-gated Na+ channel 1.2 (Nav1.2), a previously identified downstream phosphorylation target of mTORC2 and a key regulator of membrane electrogenesis. Augmented Nav1.2 channel function induced …

A Massively Parallel Reporter Assay Of Mecp2 Cis-Regulatory Elements Reveals Genetic Candidates For Male-Biased Autism, Rebecca Meyer-Schuman, Fisher Cherry, Yang Sui, Athanasios Papastathopoulos-Katsaros, Yi Zhong, Yidan Li, Tianyun Wang, Kelsey Hennick, Druha Karunakaran, Hanna Berk-Rauch, Zhandong Liu, Aravinda Chakravarti, Tomasz Nowakowski, Evan E Eichler, Huda Zoghbi

Faculty, Staff and Students Publications

Autism affects male individuals four times more often than female individuals, yet the basis of this sex bias remains unclear. One hypothesis is that this sex bias is due to genetic variants in X chromosome genes where haploinsufficiency causes neurodevelopmental disorders (NDDs). In heterozygous XX female probands, a complete loss-of-function variant in one of these genes often causes syndromic NDD, but the same variant is too deleterious for survival in hemizygous XY males. A mild hypomorphic variant, however, may be tolerated in a female carrier but may produce milder neurological phenotypes in a male proband. We tested this by investigating …

Multiple Quality Control Checkpoints Safeguard Small Nuclear Rna Biogenesis And Prevent Assembly Of Aberrant Spliceosomes, Tiantai Ma, Claire Huntington, Zhuoyi Song, Rea M Lardelli, Eric L Van Nostrand, Jens Lykke-Andersen

Faculty, Staff and Students Publications

Defective small nuclear (sn)RNAs are produced from hundreds of human snRNA pseudogenes and mutant snRNA genes associated with human developmental disorders. Machineries that prevent defective snRNAs from disrupting pre-mRNA splicing remain poorly defined. Here, we identify multiple checkpoints in snRNA biogenesis monitored by quality control machineries that subject defective snRNAs to degradation and prevent their assembly into spliceosomes. We show that variant U1 snRNAs produced from human pseudogenes, some at rates approaching canonical snRNAs, are impaired in 3' cleavage and targeted for degradation by the NEXT-exosome while failures in subsequent protein assembly steps promote NEXT-exosome- or terminal uridylyl transferase 4/7-mediated …

Use Of Extracorporeal Membrane Oxygenation In Neonates With Congenital Anomalies Of The Kidney And Urinary Tract: A Multicenter Survey Of Current Practices Across Chnc And Pedi-Ecmo Centers., Syed Ahmed, Burhan Mahmood, John M. Daniel Iv, Sandy Johng, Amy Strong, John Ibrahim, June Hu, Kara Short, Kelsey Montgomery, Keri Drake, Kushal Bhakta, Leslie Lusk, Mary Revenis, Pratibha Thakkar, Ruth Seabrook, Samir Pandya, Sarah Keene, Sharada Gowda, Suma Hoffman, Tahagod Mohamed, Tara Beck, Tasnim Najaf, Robert Digeronimo, Natalie Rintoul, Abhishek Makkar

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: This study aimed to characterize practices and decision-making for extracorporeal membrane oxygenation (ECMO) for congenital anomalies of the kidney and urinary tract (CAKUT).

METHODS: General practices (GP) section inquired about institutional practices and barriers, ECMO criteria, and dialysis. The hypothetical cases (HC) illustrated four clinical scenarios with varying degrees of renal severity for ECMO candidacy.

RESULTS: Then, 99 (42 centers) and 91 (38 centers) physicians completed the GP and HC components, respectively. The majority considered ECMO on a case-by-case basis (66%). Bilateral renal agenesis was the most common diagnosis for exclusion (52%). Prenatal markers used for ECMO exclusion included …

Establishment Of A Diabetes-Tailored Data Intelligence Platform Enhances Clinical Care, Enables Risk-Based Monitoring, And Facilitates Population-Health-Based Approaches At A Pediatric Diabetes Network., Brent Lockee, Craig Vandervelden, Daniel R. Tilden, Kelsey Panfil, Erin M. Tallon, Emily Dewit, Katie Noland, David D. Williams, Harpreet Gill, Susana R. Patton, Priya Prahalad, Juan Espinoza, Amey Waghmode, Mitchell Barnes, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patient-generated health data (PGHD) represents an opportunity to customize care, particularly in type 1 diabetes (T1D) care where continuous glucose monitor (CGM) and insulin pump usage continues to rise. Previous solutions to integrating CGM data into the electronic health record (EHR) have been limited in their ability to integrate data from multiple sources, ensure data fidelity, integrate data from multiple data streams, and rapidly adapt to changes in data output from numerous vendors. We developed a novel data infrastructure contained outside of the EHR to provide an alternative approach to PGHD integration, enable diabetes centers to identify and predict …

Impact Of Neighborhood And Individual Social Drivers Of Health On Outcomes Following Congenital Heart Surgery., Andrew Well, Heather Van Diest, Brett R. Anderson, Wei Zhang, Kathleen Carberry, Alexandra Lamari-Fisher, Jeremy Affolter, Erin A Gottlieb, Jeffery P. Jacobs, Charles D. Fraser, Carlos M. Mery

Manuscripts, Articles, Book Chapters and Other Papers

Background Despite advances in congenital heart surgery (CHS) and improvements in outcomes, disparities continue to exist. Social Drivers of Health (SDoH) have been associated with many aspects of health and wellness including congenital heart disease. The goal was to evaluate the impact of individual and neighborhood-level SDoH on outcomes following CHS.

Methods Retrospective review of the Society of Thoracic Surgeons Congenital Heart Surgery Database from 2014 to 2022 linked via ZIP code with the Centers for Disease Control and Prevention Social Vulnerability Index (SVI). ZIP codes were ranked by their SVI score with the first quintile the least vulnerable and …

Relationship Extraction For Adverse Drug Events In Clinical Notes Using Large Language Models: A Retrospective Cross-Sectional Study, Joseph M Plasek, Yiming Li, Mary G Amato, Dinah Foer, Diane L Seger, Shayma Alzaidi, Huiyuan Zhou, Gretchen Purcell Jackson, David W Bates, Li Zhou

Faculty, Staff and Students Publications

Background: Adverse drug events (ADEs) are a critical indicator of patient safety but are often documented only in free-text clinical notes. The potential of recent advances in natural language processing (NLP), particularly generative large language models (LLMs), to identify ADEs remains understudied. This study aimed to compare the performance of multiple LLMs in identifying ADE-Drug relationships in inpatient and ambulatory clinical notes.

Methods: We used clinical notes from the 2018 National NLP Clinical Challenge (n2c2) ADE dataset (inpatient; n = 505) and from outpatient encounters (n = 2555) between October 1, 2018, and December 31, 2019, at a large academic …

Natural History Of Pi-Rads 3 Lesions On Serial Prostate Mpmri, Ron Marom, Yuval Rand, Meitar Atias, Sophie Barnes, Ibrahim Fahoum, Gal Keren-Paz, Mario Sofer, Ofer Yossepowitch, Snir Dekalo, Avi Beri, Roy Mano

Faculty, Staff and Students Publications

Objective: PI-RADS 3 lesions on prostate multiparametric MRI (mpMRI) are indeterminate findings with debated management. We evaluated their radiologic evolution on follow-up mpMRI and correlated imaging changes with biopsy outcomes.

Methods: We retrospectively identified 166 men with at least one PI-RADS 3 lesion on initial mpMRI and at least one follow-up mpMRI without intervening treatment. Lesions were classified at follow-up as regressed (downgraded to PI-RADS ≤ 2), stable (remained PI-RADS 3), or progressed (upgraded to PI-RADS 4-5). Lesions were stratified by zonal location. MRI-targeted biopsy results were reviewed when available (n = 64).

Results: On follow-up, 52% of lesions regressed, …

Comparative Performance Of Predictive Nomograms For Pathological Upstaging In Clinical T1 Renal Masses: An Independent External Validation, Michael Vainrib, Amos Neheman, Omri Schwarztuch Gildor

Faculty, Staff and Students Publications

Background: Preoperative identification of pathological upstaging (≥ pT3a) in clinical T1 (cT1) renal masses is critical for surgical planning. We externally validated three established predictive models, Barra, Nocera, and Mei, to assess their discrimination, calibration, and clinical utility in a contemporary cohort.

Patients and methods: We retrospectively reviewed patients undergoing surgery for cT1 renal masses at our institution. The primary endpoint was pathological upstaging to pT3a. Model performance was evaluated using the Area Under the Curve (AUC) for discrimination and the Brier Score for overall accuracy. Calibration was assessed using parametric and nonparametric Loess-smoothed curves. Clinical utility was quantified using …

Identifying Burnout In Pediatric Clinicians Using Wearable Biometric Data: Development And Feasibility Study., Thomas Ayres, George E. Quaye, Harpreet Gill, Addison M. Pritchett Ms, Catherine Koertje, J Steven Leeder, Brooke L. Fridley, Tiffany Addington

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Addressing the burnout epidemic among health care providers remains one of the foremost challenges of modern health care systems. Past researchers have turned to passively gathered biometric data from wearable devices to identify key variables that predict burnout. However, this has resulted in limited success.

OBJECTIVE: This pilot and feasibility study aimed to test the feasibility and accuracy of developing an Extreme Gradient Boosting machine learning model to classify health care providers as being at higher or lower risk of burnout based on their biometric data.

METHODS: We conducted a 3-month pilot and feasibility study where health care providers …

Incidence And Outcomes Of Human Adenovirus Infection And Disease In A Multicenter Cohort Of Pediatric Allogeneic Hematopoietic Cell Transplant Recipients., Brian T. Fisher, Jesse A. Blumenstock, Craig L K Boge, Sydney Shuster, Alix E. Seif, Michael Green, Marian G. Michaels, Jessie L. Alexander, Monica I. Ardura, Jeffery J. Auletta, Tamara P. Miller, Diego R. Hijano, William J. Muller, Jennifer E. Schuster, Abby M. Green, Daniel E. Dulek, Yun Li, Adriana E. Kajon, Michael Grimley, Lara Danziger-Isakov

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Human adenovirus (HAdV) among pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients can result in asymptomatic infection with risk for disease progression. There are limited data defining HAdV infection, disease, and case-fatality rates in a HAdV polymerase chain reaction (PCR) surveillance testing era. The current study aimed to define these outcomes using a priori definitions applied by a central review committee.

METHODS: Pediatric allo-HCT recipients were followed up for 180 days after HCT at 10 pediatric institutions. Blood and stool specimens were collected 0-7 days prior to allo-HCT for serum HAdV immunoglobulin G and stool HAdV PCR testing. Clinical data, …

Progressive Remodeling Of Global Protein Interaction Networks In A Mouse Model Of Tauopathy, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

Faculty, Staff and Students Publications

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes …

Progressive Remodeling Of Global Protein Interaction Networks In A Mouse Model Of Tauopathy, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

Faculty, Staff and Students Publications

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes …

Recommendations For The Management Of Spontaneous Intracranial Hypotension With Spinal Longitudinal Epidural Csf Collection: A Delphi Study, Soyoun Choi, Ian Carroll, Deborah I. Friedman, Peter G. Kranz, Eugene Lee, Manjit Matharu, Simy Parikh, Henrik W. Schytz, Marcio N. Portes Souza, Yen-Feng Wang, Hsiangkuo Yuan, Mi Ji Lee

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES

Spontaneous intracranial hypotension (SIH) results from spinal CSF leakage. Epidural blood patch (EBP) is an important first-line treatment. However, pre-EBP, intra-EBP, and post-EBP practice varies widely owing to limited consensus guidance. We aimed to develop expert consensus statements to support clinical decision-making in SIH management, including peri-EBP practices, focusing on patients with spinal longitudinal epidural CSF collection (SLEC) before definitive leak type classification.

METHODS

An international multidisciplinary Delphi process was conducted between January 2024 and July 2025, involving experts in neurology, neurosurgery, radiology, and anesthesiology. Consensus was defined a priori as ≥70% agreement for strong agreement, 60%-69% …

Fgfr1/Klb-Mfg-E8 Maintains Microvascular Integrity And Adaptive Cardiac Remodeling, Sanskruti R Gare, Nasser H Alatawi, Xinyi Chen, Jiayan Zhang, Claire Ross, Oveena Fonseka, Yihua Han, Namrita Kaur, Andrea Ruiz-Velasco, Xiangjun Zhao, Yingjuan Liu, Riham R E Abouleisa, Susanne S Hille, Tao Wang, Sabu Abraham, Bernard D Keavney, Martin K Rutter, Elizabeth J Cartwright, Gareth Howell, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Faculty, Staff and Students Publications

Background: Endothelial defects in the heart are a contributor to cardiac pathological remodeling and dysfunction, which can be influenced by cardiomyocytes. Here, we explore cardioprotective crosstalk between cardiomyocytes and endothelial cells under diabetic conditions.

Methods: Type 2 diabetes was induced in male and female mice using a high-fat, high-sucrose diet in conjunction with low-dose streptozotocin. Cardiomyocyte-specific deletion of FGFR1 (fibroblast growth factor receptor 1) or KLB (beta-Klotho) was achieved by crossing floxed mice with αMHC (alpha-myosin heavy chain)-Cre transgenic mice, while the treatment potential was assessed by recombinant adeno-associated virus 9 delivery systems or administration of recombinant protein. Various in …

Using Implementation Research Frameworks To Identify Facilitators And Barriers To Implementation Of Ferric Carboxymaltose Intravenous Iron Among Moderately Anemic Postpartum Women Participating In A Trial In India, Umesh Charantimath, Valerie L. Flax, Ashwini Dandappanavar, Anika Hannan, Mrityunjay C. Metgud, Avinash Kavi, Manjunath Somannavar, Shivaprasad S. Goudar, Simal Thind, Rosemary Frasso, Lauren Wiener, Sabrina Larosa, Cecilia Rasco, Elizabeth M. Mcclure, Richard Derman

College of Population Health Faculty Papers

Postpartum anemia affects approximately 75% of women in India. We conducted this implementation research (IR) related to the use of ferric carboxymaltose (FCM) intravenous (IV) iron as part of a trial in anemic postpartum women. The aim of the IR study was to understand potential facilitators and barriers to implementation of single-dose FCM IV iron. This is a mixed-methods study in three secondary-level healthcare facilities in Belagavi, India, designed to explore selected Consolidated Framework for Implementation Research constructs and Proctor’s framework elements. Quantitative data were gathered via surveys of postpartum women who received IV FCM (n = 308) and from …

Discover To Deliver Pediatric Futures: Viewpoints Of Future Medicine From A Pediatric Health Care System., Vanessa Watkins, Ken Chang, Laura Sarff, Jared Vavroch, Dawn Wolff, Lori A. Erickson

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric health care systems face increasing uncertainty driven by rapid technological change, workforce shifts and shortages, environmental threats, and evolving family and community needs. Pediatrics requires future-focused considerations that go beyond adult systems, including family-centered care, developmental trajectories, and long-term societal impacts on child well-being. While the future cannot be predicted, futures medicine methods offer structured approaches to anticipate change and support proactive, values-driven planning. This Viewpoint describes the application of pediatric futures methods within an academic, independent nonprofit pediatric health system and proposes a practical framework that connects future readiness to strategic decision-making and daily care delivery. Futures medicine …

Aberrant One-Carbon Metabolism And Ancestral Genetics Underlie Edematous Severe Acute Malnutrition, Aarti Jajoo, Jared Redmond, Aparna Haldipur, Solome Zewdu, Emilyn Banfield, Shanker Swaminathan, Sharon Howell, Orgen Brown, Roa Sadat, Nancy J Hall, Kwesi Marshall, Katharina V Schulze, Thaddaeus May, Marvin E Reid, Carolyn Taylor-Bryan, Mark J Manary, Indi Trehan, Mamana Mbiyavanga, Wisdom A Akurugu, Colin A Mckenzie, Dhriti Sengupta, Elizabeth G Atkinson, Ananyo Choudhury, Neil A Hanchard

Faculty, Staff and Students Publications

Edematous severe childhood malnutrition is distinct from the non-edematous form of malnutrition and remains a major cause of under-five mortality. Its etiology remains unclear, although aberrant one-carbon metabolism has emerged as a potential contributor. Here, we assess genetic variants at loci known to influence one-carbon metabolism, and determine their association with edematous malnutrition in Jamaica and Malawi. Six loci show evidence of association, including four related to homocysteine and folate metabolism - AHCYL1, PRICKLE2, GABBR2, and PLD2, with SNPs at the latter three also having direct effects on homocysteine-related metabolites in Mendelian Randomization. Collectively, one-carbon metabolism-related variants were significantly associated …

Single-Nuclei Transcriptomics Reveals Cellular Senescence In Pediatric Anthracycline-Induced Cardiomyopathy, Hanna J Tadros, Yi Zhao, Lalita Wadhwa, Iki Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Chemotherapy drugs that fight childhood cancer can age heart cells prematurely. We found this "cellular aging" throughout the hearts of children with treatment-related heart failure.

Notch2 Vus Interpretation In Pediatric Cholestasis: A 365-Variant Landscape And Genotype-Phenotype Analysis Of 7 Cases, Brett J. Hoskins, Tiziano Pramparo, Shannon M. Vandriel, Chaowapong Jarasvaraparn, Michael J. Wilsey, Voytek Slowik, Lakshmi Kunam, Janis M. Stoll, Ruben E. Quiros-Tejeira, Simon Lam, Wikrom Karnsakul

Manuscripts, Articles, Book Chapters and Other Papers

Background/Objectives: Interpretation of NOTCH2 variants of uncertain significance (VUSs) remains challenging in pediatric cholestasis and suspected Alagille syndrome (ALGS) due to incomplete penetrance, phenotypic variability, and extensive genetic variation. Although disease-specific variant classification criteria have identified pathogenic hotspots within epidermal growth factor (EGF)-like repeats 8-12 and ankyrin repeat domains 3-6, characterizing these VUSs requires a robust framework. Methods: We reviewed aggregate deidentified data from 519 multigene cholestasis panel entries and evaluated genotype-phenotype data from a consortium cohort of 7 pediatric patients with heterozygous NOTCH2 VUSs using a clinical-genomic prioritization framework informed by disease-specific ACMG criteria and domain location. …