Digital Commons Network^™

Characteristics Associated With Eurolupus Versus Modified National Institutes Of Health Cyclophosphamide Regimen Use In Children And Young Adults With Lupus Nephritis, Christine S Wang, Rebecca E Sadun, Wenru Zhou, Kristen R Miller, Stacy P Ardoin, Christine Bearer, Emily Hause, Joyce Hui-Yuen, Nicole Ling, Maria Pereira, Meredith Riebschleger, Kelly Rouster-Stevens, Aliese Sarkissian, Julia Shalen, William Daniel Soulsby, Marinka Twilt, Eveline Y Wu, Laura B Lewandowski, Scott E Wenderfer, Jennifer C Cooper

Faculty, Staff and Students Publications

Objective: To determine the demographic and clinical characteristics associated with use of the EuroLupus or modified National Institutes of Health (NIH) cyclophosphamide (CYC) regimen for treatment of lupus nephritis (LN) at North American pediatric centers.

Methods: A retrospective cohort study was conducted at 11 North American centers. Patients < 22 years of age with active LN treated with CYC using the EuroLupus or NIH regimen between July 2014 and June 2021 were included. Data were extracted via electronic medical record review. Demographic and clinical characteristics were compared at CYC initiation. A multivariable generalized estimating equation with logit link was fit to model EuroLupus use. An exchangeable correlation structure was used to account for correlation within centers. Independent variables were chosen using elastic net regression.

Results: The cohort consisted of 191 patients (85 EuroLupus, 106 NIH) with a median age of 15.3 years at CYC initiation. In multivariable analysis, characteristics significantly associated with EuroLupus regimen use (vs NIH regimen use) included more recent year of CYC initiation, longer disease duration, Hispanic ethnicity and Asian race (as compared …

The Microstructure Of Metastatic Bone Lesions Suggests Tumor Mediated Alterations In Bone Mineralization, Hanwen Fan, Zhan Xu, Carla Berrospe Rodriguez, Noah Dover, Andrei Demkov, Morgan Lilly, Guillermo Aguilar, Larry J Suva, Xiang H-F Zhang, Yuxiao Zhou

Faculty, Staff and Students Publications

Breast, prostate and lung cancer cells frequently metastasize to bone, leading to disruption of the bone microstructure. This study utilized mechanical testing coupled with micro-CT imaging, digital volume correlation (DVC), and atomic force microscopy (AFM) nanomechanical testing to examine the mechanical property variations in mouse long bones (tibia) with metastatic lung cancer cell involvement, spanning from the whole-bone scale to the microstructural level. In addition, we also investigated how metastatic invasion alters the morphology of hydroxyapatite nanocrystals in bone at the nanometer scale. The biochemical composition within metastatic lesions was assessed using Raman spectroscopy and correlated with AFM mechanical testing …

Gene Therapy Cm-Yapon Protects The Mouse Heart From Myocardial Infarction, Fansen Meng, Jeffrey D Steimle, Elizabeth Straight, Rich G Li, Yuka Morikawa, Zohaib Iqbal, Bing Xie, Jun Wang, Wyatt G Paltzer, Yi Zhao, Chang-Ru Tsai, Lin Liu, Maggie Lim, Rita A Schack, Daniel Ramirez, Katherine Carlson, Vaibhav Deshmukh, Jason M Karch, Robia G Pautler, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Myocardial infarction (MI) affects millions of people worldwide, causing irreversible injury to the heart and impairing cardiac function1. In both mouse and pig MI models, activating YAP in cardiomyocytes (CMs) stimulates regenerative repair2,3. Here we developed an adeno-associated virus 9 (AAV9)-based therapy, termed CM-YAPon, which enables transient expression of an active YAP variant (YAP5SA) in CMs following exposure to the small molecule LMI070. A single LMI070 dose in mice triggers YAP5SA expression, CM cell cycle re-entry, and reprogramming of the cardiac microenvironment. YAP5SA induction after MI rapidly improves cardiac function while pre-MI induction confers …

Alternative Splicing Of The Snap23 Microexon Is Regulated By Mbnl, Qki, And Rbfox2 In A Tissue-Specific Manner And Is Altered In Striated Muscle Diseases, Gabrielle M Gentile, R Eric Blue, Grant A Goda, Bryan B Guzman, Rachel A Szymanski, Eunice Y Lee, Nichlas M Engels, Emma R Hinkle, Hannah J Wiedner, Aubriana N Bishop, Jonathan T Harrison, Hua Zhang, Xander H T Wehrens, Daniel Dominguez, Jimena Giudice

Faculty, Staff and Students Publications

The reprogramming of alternative splicing networks during development is a hallmark of tissue maturation and identity. Alternative splicing of microexons (small, genomic regions ≤ 51 nucleotides) functionally regulate protein-protein interactions in the brain and is altered in several neuronal diseases. However, little is known about the regulation and function of alternatively spliced microexons in striated muscle. Here, we investigated alternative splicing of a microexon in the synaptosome-associated protein 23 (Snap23) encoded gene. We found that inclusion of this microexon is developmentally regulated and tissue-specific, as it occurs exclusively in adult heart and skeletal muscle. The alternative region is …

Same Data, Different Analysts: Variation In Effect Sizes Due To Analytical Decisions In Ecology And Evolutionary Biology, Elliot Gould, Hannah S. Fraser, Timothy H. Parker, Shinichi Nakagawa, Simon C. Griffith, Peter A. Vesk, Fiona Fidler, Daniel G. Hamilton, Robin N. Abbey-Lee, Jessica K. Abbott, Luis A. Aguirre, Carles Alcaraz, Irith Aloni, Drew Altschul, Kunal Arekar, Jeff W. Atkins, Joe Atkinson, Christopher M. Baker, Meghan Barrett

Faculty Research, Scholarly, and Creative Activity

Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different fields and has found substantial variability among results despite analysts having the same data and research question. Many of these studies have been in the social sciences, but one small “many analyst” study found similar variability in ecology. We expanded the scope …

Identifying Climate Refugia And Bright Spots For Highly Mobile Species, Nerea Lezama-Ochoa, Heather Welch, Jennifer A. Brown, Scott R. Benson, Karin A. Forney, Briana Abrahms, Mercedes Pozo Buil, Michael G. Jacox, Barbara A. Muhling, Owen R. Liu, Thomas A. Clay, Ryan Freedman, Danielle Lipski, Steven J. Bograd, Elliott L. Hazen, Stephanie Brodie

Faculty Research, Scholarly, and Creative Activity

Climate-driven shifts in species distributions can undermine the effectiveness of protected areas. We present a framework to facilitate climate change adaptation planning by identifying where highly migratory species habitats will persist (climate refugia), emerge (bright spots), disappear (dark spots), or remain unsuitable based on model analysis by 2100. When applied to eight species in the California Current System, we found that, on average, 37% of habitats are expected to be climate refugia, 9% are bright spots, and 13% are dark spots within National Marine Sanctuaries by 2100. Species responses differ: leatherback turtles may find refuge near U.S. coastal waters (18%), …

The (Birthweight) Gains From Trade: Chinese Imports And Infant Health In Sub-Saharan Africa, Jorge M. Aguero, Patralekha Ukil

Faculty Research, Scholarly, and Creative Activity

A growing literature has documented broad negative impacts of Chinese imports to advanced economies, mainly due to the competition of these imports with local production. However, for countries with a smaller manufacturing sector and which have not experienced a structural transformation away from agriculture, Chinese imports could have positive effects. We find evidence supporting this claim using a sample of over 350,000 births from 25 countries in Sub-Sahara Africa. Our identification compares the birthweight of biological siblings born at different levels of Chinese imports to their country. We find that an increase in Chinese imports of $100 (constant USD) is …

Reply To Chaïbi And Tandjaoui-Lambiotte And To Young And Scott, Joan B Soriano, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Emerging Tick-Borne Disease Risk In An Urban Center Of Harris County, Texas, Alisa Nelson, Michelle Downey, Maya Murry, Brianna Weber, Erik Aguirre, Richard Scott Mccrea, Jerrod Mims, Max Vigilant, Courtney Standlee, Kristy O Murray, Alex Kneubehl, Eric L Brown, Heather T Essigmann, Sarah M Gunter

Faculty, Staff and Students Publications

Background: Tick-borne diseases are an endemic and emerging public health concern in the United States. Ongoing tick range expansion, invasive species, and newly identified pathogens are rapidly altering disease epidemiology. Surveillance is critical to understanding vector ecology and disease risk. Harris County, Texas, with nearly five million residents and diverse ecological zones, offers a unique setting to study local tick dynamics.

Methods: From January 2021 to December 2022, we conducted weekly tick surveillance across 63 sites in Harris County (City of Houston), Texas. Ticks were morphologically identified and tested for Rickettsia, Borrelia, Ehrlichia, and Anaplasma via real-time PCR. Samples positive …

A Β-Lactamase Inhibitory Protein Mutant Displays High Potency And A Broad Inhibition Profile Due To An Altered Binding Mode With Β-Lactamases, Paola Rivera, Shuo Lu, Dignite Ngango, Banumathi Sankaran, Bidadi Venkataram Prasad, Timothy Palzkill

Faculty, Staff and Students Publications

β-lactamase enzymes inactivate β-lactam antibiotics, leading to drug resistance. The β-lactamase inhibitory protein (BLIP) is a naturally occurring inhibitor of β-lactamases, with inhibition constants (Ki) ranging from picomolar to micromolar values. For example, BLIP inhibits CTX-M-14 β-lactamase with a Ki of 330 nM, whereas the Ki for CTX-M-15 is 3 nM, despite CTX-M-14 and CTX-M-15 sharing 83% sequence identity. We used a genetic screen to identify a BLIP mutant, E73W, that potently inhibited CTX-M-14. Subsequent purification and testing of BLIP E73W revealed that it is a potent, broad-spectrum inhibitor of class A β-lactamases. We determined …

Education Research: Eeg Instruction: Findings From A Scoping Review, Andres Fernandez, Maryam Asoodar, Gregory Laynor, Alexis Peedin, Jeffrey B Ratliff, Urvashi Vaid, Swati A Karmarkar, Moushumi Sur, Vivianne Van Kranen-Mastenbroek, Dimitrios Papanagnou, Marian H J M Majoie, Dorene F Balmer, Satid Thammasitboon

Faculty, Staff and Students Publications

Background and objectives: Although EEG interpretation is a key skill in neurology, EEG instruction is variable and its landscape remains underexplored. Thus, we conducted a scoping review to expand the literature by providing a structured mapping of the EEG instruction literature and a foundation for future research in EEG instruction.

Methods: We followed a structured methodological framework for scoping reviews and report the findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Research questions explored theoretical frameworks, methodologies, learner populations, instructional methods, and assessment approaches. Eligibility criteria were iteratively modified to focus …

Hes V20 Surpasses Galad For Hcc Detection: A Review Of Multi-Dimensional Biomarker Scores And Studies, Fouad Jaber, Hashem B El-Serag

Faculty, Staff and Students Publications

This was a narrative review of select studies published through September of 2024. We review the shift toward multi-dimensional scores such as HCC early detection screening (HES), GALAD, ASAP, and mt-HBT represents a significant advancement in biomarker research for hepatocellular carcinoma (HCC) detection. Unlike single biomarker approaches, these scores integrate various clinical and biochemical factors to enhance predictive accuracy by reflecting different complementary aspects of disease progression and HCC oncogenesis. Proper testing and validation of biomarker scores in phase 3 biomarker studies is essential before wide use can be recommended. We also review the comparative performance of biomarker scores in …

The Neonatal Gut Microbiome In Health And Disease, Geoffrey A Preidis

Faculty, Staff and Students Publications

No abstract provided.

Adrenomedullin Overexpression Protects Mice From Experimental Bronchopulmonary Dysplasia And Associated Pulmonary Hypertension, Shyam Thapa, Poonam Sarkar, M Waleed Gaber, Roberto Barrios, Madhulata Chauhan, Chandrasekhar Yallampalli, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) or BPD-PH is a lung disease of infants with significant morbidity. Adrenomedullin (Adm) is an angiogenic peptide that signals through calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2 (RAMP2). Adm deficiency potentiates hyperoxia-induced experimental BPD-PH in mice; however, whether Adm overexpression can mitigate this lung disease is unclear. Thus, we tested the hypothesis that Adm overexpression attenuates hyperoxia (HO)-induced murine experimental BPD-PH by using a novel transgenic mouse that overexpresses Adm globally (Admhi/hi mice). One-day-old Admhi/hi mice or their wild-type littermates (Adm+/+ mice) were exposed to …

Evaluating Covid-19 Severity Prediction And Immune Dynamics With Nulisaseq: Insights From The Impacc Study, Koji Abe, Tyson H Holmes, Tran T Nguyen, Seunghee Kim-Schulze, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Joanna Schaenman, Elaine F Reed, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Holden T Maecker

Faculty, Staff and Students Publications

The National Institutes of Health-funded IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) evaluated longitudinal clinical and immunological features of human patients hospitalized for COVID-19. This study focuses on comparing the novel NULISAseq assay with the Olink platform using a subset of participants to assess their efficacy in predicting COVID-19 severity and understanding immune response dynamics. Our findings reveal that NULISAseq could provide superior detectability and dynamic range across various targets. Elastic net analysis demonstrated that specific proteins, including amphiregulin, effectively predict COVID-19 severity from sera at admission (samples drawn within 96 h of admission), with a test area under the …

Publisher Correction: Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

No abstract provided.

Part Ii Common Questions And Misconceptions About Creatine Supplementation: What Does The Scientific Evidence Really Show?, Jose Antonio, Ann F Brown, Darren G Candow, Philip D Chilibeck, Stacey J Ellery, Scott C Forbes, Bruno Gualano, Andrew R Jagim, Chad Kerksick, Richard B Kreider, Sergej M Ostojic, Eric S Rawson, Michael D Roberts, Hamilton Roschel, Abbie E Smith-Ryan, Jeffrey R Stout, Mark A Tarnopolsky, Trisha A Vandusseldorp, Darryn S Willoughby, Tim N Ziegenfuss

Faculty, Staff and Students Publications

Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults. As a follow-up, the purpose …

Cross-Species Standardised Cortico-Subcortical Tractography, Stephania Assimopoulos, Shaun Warrington, Davide Folloni, Katherine Bryant, Ali-Reza Mohammadi-Nejad, Wei Tang, Saad Jbabdi, Sarah R Heilbronner, Rogier B Mars, Stamatios N Sotiropoulos

Faculty, Staff and Students Publications

Despite their importance for brain function, cortico-subcortical white matter tracts are under-represented in diffusion magnetic resonance imaging tractography studies. Their non-invasive mapping is more challenging and less explored compared to other major cortico-cortical bundles. We introduce a set of standardised tractography protocols for delineating tracts between the cortex and various deep subcortical structures, including the caudate, putamen, amygdala, thalamus, and hippocampus. To enable comparative studies, our protocols are designed for both human and macaque brains. We demonstrate how tractography reconstructions follow topographical principles obtained from tracers in the macaque and how these translate to humans. We show that the proposed …

Transcriptional Coregulator Zmiz1 Modulates Estrogen Responses That Are Essential For Healthy Endometrial Function, Sylvia C Hewitt, Frank Orellana, Ryan M Marquardt, Myeongjin Yi, Cynthia J Willson, Mark Y Chiang, Yong Song, Goutham Venkata Naga Davuluri, Christopher Day, Ramakrishna Kommagani, Joseph Rodriguez, Asgerally T Fazleabas, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen is a critical regulator of endometrial health. Aberrant estrogen stimulation can result in infertility, endometrial cancer, and endometriosis. Here, we identified Zinc Finger MIZ-Type Containing 1 (Zmiz1) as a coregulator of uterine estrogen signaling. ZMIZ1 is colocalized with an estrogen receptor α–binding (ESR1-binding) super enhancer. ZMIZ1 mutations are found in endometrial cancer and its RNA levels trend toward reduction in endometrium of patients with endometriosis. ZMIZ1 is dynamically expressed in human endometrial tissues during the menstrual cycle. Disrupting ZMIZ1 in cultured human endometrial stromal cells resulted in impaired cell proliferation and decidual differentiation. Ablation of Zmiz1 using …

Cerebellar Purkinje Cell Stripe Patterns Reveal A Differential Vulnerability And Resistance To Cell Loss During Normal Aging In Mice, Sarah G Donofrio, Cheryl Brandenburg, Amanda M Brown, Tao Lin, Hsiang-Chih Lu, Roy V Sillitoe

Faculty, Staff and Students Publications

Age-related neurodegenerative diseases involve reduced cell numbers and impaired behavioral capacity. Neurodegeneration and behavioral deficits also occur during aging, and notably in the absence of disease. The cerebellum, which modulates movement and cognition, is susceptible to cell loss in both aging and disease. Here, we demonstrate that cerebellar Purkinje cell loss in aged mice is not spatially random but rather occurs in a pattern of parasagittal stripes. We also find that aged mice exhibit impaired motor coordination and more severe tremor compared to younger mice. However, the relationship between patterned Purkinje cell loss and motor dysfunction is not straightforward. Examination …

Hemophagocytic Lymphohistiocytosis In A Pediatric Lung Transplant Recipient, Sunil Chickmagalur, Anna Schrader, Dallas Parrish, David Moreno Mcneill, Maria C Gazzaneo, Ernestina Melicoff-Portillo, Nahir Cortes-Santiago

Faculty, Staff and Students Publications

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication of solid organ transplantation and is a syndrome of systemic hyperinflammation secondary to dysregulation of the inflammatory response, primarily involving lymphocytes and macrophages. It is often fatal and therefore early recognition and treatment are crucial. Among 11 adult cases of HLH in post-lung transplant cases found in the literature, only one patient survived.

Case: We report the first known pediatric case of HLH following lung transplantation. The patient, a previously healthy adolescent, developed end-stage bullous lung disease secondary to acute respiratory distress syndrome (ARDS) and underwent bilateral lung transplantation. Two months posttransplant, …

Lilrb4 Regulates Circadian Disruption-Induced Mammary Tumorigenesis Via Non-Canonical Wnt Signaling Pathway, Olajumoke Ogunlusi, Mrinmoy Sarkar, Kayla Carter, Arhit Chakrabarti, Devon J Boland, Tristan Nguyen, James Sampson, Christian Nguyen, Danielle Fails, Yava Jones-Hall, Loning Fu, Gus Wright, Da Mi Kim, James J Cai, Bani Mallick, Alex C Keene, Jeff R Jones, Tapasree Roy Sarkar

Faculty, Staff and Students Publications

Epidemiological studies have shown that circadian rhythm disruption (CRD) is associated with the risk of breast cancer. However, the role of CRD in mammary gland morphology and aggressive basal mammary tumorigenesis and the molecular mechanism underlying CRD-induced carcinogenesis remain unknown. To investigate the effect of CRD on aggressive tumorigenesis, a genetically engineered mouse model of aggressive breast cancer was used. The impact of CRD on the tumor microenvironment was investigated using the tumors from LD12:12 and CRD mice via scRNA-seq, flow cytometry, multiplexing immunostaining, and realtime PCR. The effect of LILRB4-immunotherapy on CRD-induced tumorigenesis was also investigated. Here we investigated …

Biochemical And Clinical Response To A Sulfur-Restricted Diet In Ethylmalonic Encephalopathy, Steven H Lang, Andres Caceres Salgado, Matthew T Snyder, Brandy Rawls-Castillo, Aaron Williams, Charul Gijavanekar, Sarah H Elsea, Xia Wang, Mary Elizabeth M Tessier, Claudia Soler-Alfonso, Fernando Scaglia

Faculty, Staff and Students Publications

Introduction: Ethylmalonic encephalopathy (EE) is an often-severe inborn error of metabolism caused by biallelic variants in the ETHE1 gene leading to impaired detoxification of hydrogen sulfide (H2S). H2S is produced both exogenously by anerobic intestinal bacteria as well as by the endogenous catabolism of the sulfur-containing amino acids methionine and cysteine. Existing therapies including metronidazole, N-acetylcysteine (NAC), and orthotopic liver transplantation (OLT) have been pursued with the objective of reducing or detoxifying exogenously produced H2S. However, strategies to reduce endogenously produced H2S using a methionine and cysteine restricted diet are an understudied therapeutic avenue.

Methods: We performed an open-label, …

Clinical Exome Sequencing Efficacy And Phenotypic Expansions Involving Non-Isolated Congenital Anomalies Of Kidney And Urinary Tract (Cakut+), E Andres Rivera-Munoz, Xiaonan E Zhao, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Jennifer E Posey, Daryl A Scott

Faculty, Staff and Students Publications

Congenital Anomalies of Kidney and Urinary Tract (CAKUT) can occur in isolation or in conjunction with one or more non-CAKUT associated congenital anomalies or neurodevelopmental disorders (CAKUT+). A molecular cause is not identified in most individuals with CAKUT+. This is due, in part, to uncertainty regarding the efficacy of genetic testing and an incomplete understanding of the genes that cause CAKUT+. Here, we use data from 515 individuals with CAKUT+ (n = 500) or isolated CAKUT (n = 15) to determine the efficacy of clinical exome sequencing (cES) and to identify new phenotype expansions that involve CAKUT. We determined that …

Genetics Services In Latin America: A Descriptive Study Of Availability And Utilization Of Genetics In Healthcare, Ryan J German, Erin Atkinson, Eric A Storch, Claudia Soler-Alfonso, Sonia Margarit, Philip J Lupo, Stacey Pereira

Faculty, Staff and Students Publications

Genetic services are expanding globally, but access remains limited in low-resource regions such as Latin America. Understanding current service availability, barriers, and facilitators is critical to guide capacity building and improve patient care. We conducted a cross-sectional survey of healthcare professionals providing genetic services in Latin America. The survey, available in Spanish and English, assessed genetic services, referral patterns, testing availability, barriers, facilitators, and perceived needs. Descriptive statistics summarized quantitative data, and thematic analysis was applied to open-ended responses. Eighty-five respondents from 18 countries reported broad clinical activity across pediatric, cancer, and adult-onset genetic conditions. Commonly ordered tests included karyotype, …

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The United States, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

(Abstracted from JAMA 2025;333(24):2176-2187) The development of childhood vaccine protocols has led to the elimination of many infectious diseases from the United States, including measles, rubella, diphtheria, and polio, by maintaining herd immunity. In recent years, especially since the COVID-19 pandemic, vaccination rates have declined due to policy changes, misinformation, distrust, and broader societal shifts.

Where, How, And How Much? A Multicenter Cohort Study Of The Relationship Across Lupus Decision-Aid Modality, Place Of Administration, Interruption And Viewing Completeness, And Patient-Reported Outcomes, Jasvinder A Singh, Mark Beasley, Larry R Hearld

Faculty, Staff and Students Publications

Objective: We assessed whether shared decision-making (SDM) and patient acceptability, feasibility, and overall satisfaction with a computerized patient decision aid (PtDA) for patients with systemic lupus erythematosus (SLE) differs by PtDA setting, modality, and the viewing experience.

Methods: Patients with SLE were invited to view a self-administered computerized SLE PtDA during regular clinic visits at 15 rheumatology clinics in an implementation trial. Patients completed a survey that included SDM measures including the decision conflict scale (DCS), Preparation for Decision Making (PDM) scale, and CollaboRATE scale, and we measured perceived patient acceptability, feasibility, and satisfaction. Patients viewed the SLE PtDA in …

A Deep Generative Model For Deciphering Cellular Dynamics And In Silico Drug Discovery In Complex Diseases, Yumin Zheng, Jonas C Schupp, Taylor Adams, Geremy Clair, Aurelien Justet, Farida Ahangari, Xiting Yan, Paul Hansen, Marianne Carlon, Emanuela Cortesi, Marie Vermant, Robin Vos, Laurens J De Sadeleer, Ivan O Rosas, Ricardo Pineda, John Sembrat, Melanie Königshoff, John E Mcdonough, Bart M Vanaudenaerde, Wim A Wuyts, Naftali Kaminski, Jun Ding

Faculty, Staff and Students Publications

Human diseases are characterized by intricate cellular dynamics. Single-cell transcriptomics provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in silico drug interventions. Here we introduce UNAGI, a deep generative neural network tailored to analyse time-series single-cell transcriptomic data. This tool captures the complex cellular dynamics underlying disease progression, enhancing drug perturbation modelling and screening. When applied to a dataset from patients with idiopathic pulmonary fibrosis, UNAGI learns disease-informed cell embeddings that sharpen our understanding of disease progression, leading to the identification of potential therapeutic drug candidates. Validation using proteomics reveals …

Plasma Metabolomic And Proteomic Signatures Of Blood Pressure Management After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Juan Pablo Lewinger, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Todd M Jenkins, Stephanie Sisley, Stephen R Daniels, Douglas I Walker, Max T Aung, Erika Garcia, Rob Mcconnell, Sandrah P Eckel, Michele A La Merrill, Tanya L Alderete, Zhuanghua Chen, Frank D Gilliland, Thomas H Inge, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Background: Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery.

Methods: We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and …

Sleep-Disordered Breathing Subtypes And Future Diet Quality In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Cecilia Castro-Diehl, Tianyi Huang, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Tamar Sofer, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Objectives: Sleep-disordered breathing (SDB) and diet quality impact cardiometabolic disease, but few studies have examined if SDB influences diet quality. This study estimated the association between SDB subtypes (with and without sleepiness) and future diet quality in the Multi-Ethnic Study of Atherosclerosis.

Methods: Probable SDB was characterized by self-reported physician-diagnosed sleep apnea (PDSA) or habitual snoring and subtyped by presence or absence of sleepiness. A food frequency questionnaire measured diet 1.6 years before, and 7.8 years after SDB assessment. Diet quality was measured with the Alternate Healthy Eating Index-2010 (AHEI). Mean differences in AHEI at follow-up by SDB subtypes were …