Digital Commons Network^™

Seroprevalence Of Helicobacter Pylori Infection Among Asymptomatic Patients Served By A Safety-Net Healthcare System, Aaron P Thrift, Peyman Dinarvand, Luis Juarez, Jourdan Brown, Daniel Avila, Jennifer Mistica Zafiro Garcia-Villanueva, Lisa C Danek, Hammad Mahmood, Thomas Porter, Ann Gotschall, Noreen F Pirzada, Jaime J Rueda, Lee B Lu, Afroze Ali, Ijeoma Anyakorah, Sanjana J Bhattarai, Anees Fatima, Jessica Garcia, Hung V Nguyen, Bharat Joshi, Malvika Juneja, Misba S Lateef, Najda Mujtaba, Preethi V Nambi, Jay S Orr, Huma Rahman, Stephanie Nguyen, Amna Waqar, Yanyan Chen, David Y Graham, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background & aims: Helicobacter pylori screening and eradication is a cost-effective strategy for primary gastric cancer prevention in high-risk populations outside the United States. There is a paucity of population-based H pylori seroprevalence data available in high-risk U.S. groups, particularly data for low-income, uninsured patient populations.

Methods: We used data from a cross-sectional study of a largely underserved, immigrant, and minority patient population. Inclusion criteria included asymptomatic individuals 30-65 years of age without prior H pylori testing or treatment. Consented patients completed a study survey and a blood draw to screen for H pylori using IgG serology. We calculated seroprevalence …

A Smoking-Related Plasma Protein Score And Smoking-Related Cancer Risk And Mortality In The Atherosclerosis Risk In Communities Study, Meng Ru, Christopher Douville, Aghiles Guenoun, Hana Zahed, Christie M Ballantyne, Kenneth R Butler, Josef Coresh, David J Couper, Panagis Galiatsatos, Marc J Gunter, Ron C Hoogeveen, Mattias Johansson, Corinne E Joshu, P Martijn Kolijn, Christina M Lill, Jiayun Lu, Michael T Marrone, Giovanna Masala, David C Muller, Anna E Prizment, Raul Zamora-Ros, Nilanjan Chatterjee, Adrienne Tin, Elizabeth A Platz

Faculty, Staff and Students Publications

Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer.

Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and …

Protecting Minors From Medical Malpractice Act: Implications For Otolaryngology-Head & Neck Surgery, Shiven Sharma, Margo K Mckenna, Julina Ongkasuwan, Michael J Brenner

Faculty, Staff and Students Publications

No abstract provided.

Maternal Fish Intake In The Year Prior To Conception And Birth Defects, National Birth Defects Prevention Study, 1997-2011, Dorothy Kim Waller, Zeyu Miao, Renata H Benjamin, Richard Finnell, Nithya Lakshmi Mohan Dass, Eirini Nestoridi, Marcia C De Oliveira Otto, Julie Peterson, Tunu Ramadhani, Mark A Canfield

Faculty, Staff and Students Publications

Background: Epidemiologic data on the association between maternal fish intake and birth defects are sparse. Our objective was to assess associations between maternal fish intake and 52 different birth defects, most of which have not been assessed previously.

Methods: Using logistic regression, data was analyzed for 29,242 mothers of infants with birth defects and 10,973 mothers of control infants who participated in the National Birth Defects Prevention Study (NBDPS) and delivered between 1997 and 2011. We focused on associations between mothers who reported high fish intake of 2 or more servings of fish per week for the year prior to …

High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology Of Lung Cancer Consortium, Yanhong Liu, Yafang Li, Jinyoung Byun, Vikram R Shaw, Claudio Pikielny, Bo Peng, Chao Cheng, Spiridon Tsavachidis, Xiangjun Xiao, Dakai Zhu, Younghun Han, Ivan P Gorlov, Olga Y Gorlova, Michael Cole, Colette R Gaba, Erin L Crawford, Kristen Purrington, Ellen L Goode, Ping Yang, James Mckay, John K Field, Geoffrey Liu, Rayjean J Hung, Jun Xia, Jiyeon Choi, Matthew B Schabath, Jaclyn Lopiccolo, David C Christiani, Joan Bailey-Wilson, Ann G Schwartz, James C Willey, Diptasri Mandal, Susan M Pinney, Christopher I Amos

Faculty, Staff and Students Publications

Introduction: Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk. The Genetic Epidemiology of LC Consortium (GELCC) has curated valuable high-risk LC families and is uniquely positioned to uncover rare, high-penetrance variants underlying familial LC (FLC).

Methods: We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency < 1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.

Results: We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which …

Phenotypic Diversity And Outcomes In Pediatric Nmda Receptor Encephalitis: A 15-Year Retrospective Study From The Largest Children's Hospital In The United States, Alexander J Sandweiss, Timothy Erickson, Yike Jiang, Varun Kannan, Jonathan M Yarimi, Kristen S Fisher, Nikita Shukla, Tim Lotze, Eyal Muscal, Kristy O Murray

Faculty, Staff and Students Publications

Anti‐NMDAR encephalitis (NMDARE) is an autoantibody‐mediated disorder characterized by seizures, movement disorders, neurocognitive deficits, and psychosis, but the complete phenotypic heterogeneity, and outcomes are incompletely understood in children. This single‐center retrospective analysis of NMDARE at the largest pediatric hospital in the United States between 2009 and 2024 screened 115 patients diagnosed with NMDARE. 103 had sufficient clinical data available for analyses. Two‐thirds were Hispanic, disproportionate to the Houston metro area demographics, and Hispanic patients had a higher CSF white cell count and antibody titer. Approximately one‐half of the patients with idiopathic NMDARE presented with a focal cortical phenotype that localized …

Racial, Ethnic, And Neighborhood Disparities In Acute Kidney Injury In Pediatric Acute Leukemia, Wendy C Bravo, Yimei Li, Tamara P Miller, Kelly Getz, Lusha Cao, Edward Krause, Mark Ramos, Judy Lee, Maria Monica Gramatges, Karen R Rabin, Michael Scheurer, Richard Aplenc, Michelle Denburg

Faculty, Staff and Students Publications

Introduction: We sought to identify racial/ethnic and neighborhood disparities in acute kidney injury (AKI) in children with acute lymphoblastic or myeloid leukemia (ALL, AML).

Methods: Electronic health record data were retrospectively collected from patients treated for de novo pediatric ALL or AML in the multicenter Leukemia Electronic Abstraction of Records Network. AKI was defined by modified Kidney Disease Improving Global Outcomes criteria. Neighborhood-level resources were defined by the Child Opportunity Level (COL). Prevalence ratios (PRs) for AKI at diagnosis by race/ethnicity and COL were calculated using modified Poisson regression. Cox regression was used to calculate hazard ratios (HRs) of first …

Interplay Between Genetic Ancestry, Self-Reported Race And Ethnicity, And Clinical Factors In Pediatric Acute Lymphoblastic Leukemia: A Redial Consortium Report, Pragati Kore, Jennifer M Geris, Maria Leon-Camarena, Maria I Castellanos, Olga A Taylor, Veronica Garcia-Morales, Austin L Brown, Pagna Sok, Jeremy M Schraw, Van Huynh, Kathleen F Ludwig, Laura J Klesse, Sandi L Pruitt, Amy E Hughes, Kevin Tien, Kenneth M Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Maria M Gramatges, Elizabeth G Atkinson, Philip J Lupo, Michael E Scheurer, Karen R Rabin

Faculty, Staff and Students Publications

Background: Pediatric acute lymphoblastic leukemia (ALL) is the most common cancer in children, and its incidence and outcomes vary by race and ethnicity.

Methods: The Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium has assembled a cohort of patients < 25 years at diagnosis to examine genetic and neighborhood-level factors influencing ALL. As the cohort is ongoing, for this report, we examined sociodemographic and cytogenetic factors that might be associated with ALL outcome disparities.

Results: Among 2,512 patients diagnosed between 2005 and 2020, we observed distinct patterns of genetic ancestry and residential characteristics across self-reported race and ethnicity. Latino children, who comprised 55.3% of the cohort, had a mean Amerindigenous ancestry proportion of 50.9%, whereas non-Latino White children exhibited a predominantly European ancestry (mean = 78%). Neighborhood-level analysis revealed significant socioeconomic and geographic differences by …

Sustainment Of Hydroxyurea Adherence In Patients With Sickle Cell Disease, Andrew M Heitzer, Zachary Wooten, Guangjin Luo, Marsha Treadwell, Allison A King, Victor R Gordeuk, Nirmish Shah, Christina M Abrams, Sarah Mccuskee, Siera Gollan, Jennifer Longoria, Jane S Hankins, Sickle Cell Disease Implementation Consortium

2020-Current year OA Pubs

IMPORTANCE: Despite established treatment guidelines and strong therapeutic benefit, hydroxyurea remains underused among patients with sickle cell disease.

OBJECTIVE: To assess the change in self-reported hydroxyurea use (ie, taking the medication at all) and adherence (ie, the number of days taken per week) over time and to examine factors associated with the trajectory of hydroxyurea use and adherence.

DESIGN, SETTING, AND PARTICIPANTS: Data were collected through the Sickle Cell Disease Implementation Consortium, a longitudinal, multicenter, observational cohort study that recruited patients from 8 centers across the US. Data collection occurred from 2017 to 2022, and analyses were performed from January …

Cognitive Behavioral Therapy For Individuals With Low Literacy And Perinatal Depression: A Randomized Clinical Trial, Eliza Kleban, Ashleen Lee, Aminata Koroma, D Taylor Hendrixson, Joshua Duncan, Mark J Manary, Kevin B Stephenson

2020-Current year OA Pubs

IMPORTANCE: Perinatal depression is common in sub-Saharan Africa, yet treatment gaps are substantial. Cognitive behavioral therapy (CBT) is effective but relies on written materials.

OBJECTIVE: To evaluate the efficacy of a culturally adapted CBT intervention delivered by lay counselors to women with perinatal depression in rural Sierra Leone.

DESIGN, SETTING, AND PARTICIPANTS: This study was an individually randomized, outcomes assessor- and investigator-blinded, clinical trial of an adapted CBT intervention vs enhanced usual care. The trial was conducted in 6 government-run antenatal clinics in Pujehun District, Sierra Leone, which has limited infrastructure, low literacy, high maternal undernutrition, and no perinatal mental …

Inherited Tbx4 Frameshifting Variants Predicted To Escape Nonsense Mediated Decay In Two Families With Variable Phenotypes, Including Lethal Lung Developmental Disorders, Shruti A Pande, Hiuling Chan Joiner, Przemyslaw Szafranski, Tomasz Gambin, Michelle Wright, Qian Wang, Maiah Walters, Jan M Friedman, Jessica Saunders, Nicholas Avdimiretz, Cornelius F Boerkoel, Nahir Cortes-Santiago, Gail Deutsch, Pawel Stankiewicz

Faculty, Staff and Students Publications

Background: Pathogenic variants involving the transcription factor TBX4 gene have been associated with various skeletal and pulmonary abnormalities, including lethal lung developmental disorders (LLDD).

Methods: Whole-genome sequencing (WGS) with AI-powered platform for variant detection and interpretation followed by Sanger sequencing targeted variant segregation analysis were used. Reverse transcription quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) studies were performed to assess gene and protein expression levels, respectively.

Results: We describe two unrelated families with intrafamilial variability in the TBX4 phenotypic expressivity, including LLDDs. WGS analyses revealed two frameshift variants, c.1019del; p.(Arg340GlnfsTer40) in the penultimate exon and c.1167dup; p.(Arg390GlnfsTer30) in the last exon …

Culturally Tailored Materials For Smoking Cessation And Hiv Care Adherence Among Hispanic Adults: Protocol For Content Development And Formative Evaluation, Lorra Garey, Jacqueline J Charles, Ashley L Ruiz, Rodrigo Castillo-Avilés, Virmarie Correa-Fernández, Marshall K Cheney, Thomas P Giordano, Michael J Zvolensky

Faculty, Staff and Students Publications

Background: Hispanic people with HIV who smoke cigarettes experience unique stressors (eg, stigma), which contribute to health disparities. Anxiety sensitivity (AS) may worsen mood management problems, which are a leading barrier to smoking cessation. Interventions targeting AS can improve HIV-specific outcomes and smoking cessation. However, no prior research has culturally tailored an AS reduction program to improve quality of life among Hispanic people with HIV who smoke. The research team previously developed a mobile health (mHealth) intervention addressing AS reduction, smoking cessation, and HIV care management for Black people with HIV who smoke. Building on this work, this study represents …

Expanding The Mutation Spectrum Of Non-Syndromic Retinitis Pigmentosa In Consanguineous Pakistani Families: Unraveling Novel Pathogenic Variants In Rp1, Pde6b, And Prcd Genes For Precision Diagnosis, Tayyaba Shan, Nimra Mukhtar, Sayyed Hammad Ullah, Asad Ullah, Asfandyar Ahmad Khan, Yumei Li, Meng Wang, Raeesa Tehreem, Amtul Aziz, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

No abstract provided.

High Concordance Of Physician-Attestation With Manual Data Abstraction For Sickle Cell Type: An Ash Rc Data Hub Study, Alexis Thompson, Ashima Singh, Donna Neuberg, Amanda Brandow, Allison King, Sophie Lanzkron, Emily Semmel, Sam Walters, Susan Rogers, Kathleen Torres, William Wood

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. The American Society of Hematology Research Collaborative (ASH RC) has built an SCD Data Hub (DH) to facilitate research and quality improvement using real-world data. To our knowledge, we report here the first analyses from the DH, focusing on cohort demographics and accurate identification of SCD diagnosis type. DH sites have data use agreements with ASH RC to extract and transfer electronic health record (EHR) data at least quarterly. Principal investigators (PI) provided additional attestation of SCD diagnosis based on existing local data sources deemed …

Serum Metabolites Associated With Depression And Anxiety In The Hispanic Community Health Study/Study Of Latinos, Xinye Qiu, Yu Zhang, Yogesh Purushotham, Qibin Qi, Bing Yu, Jan Bressler, Krista M Perreira, Humberto Parada, Martha L Daviglus, Alejandra Cid Vega, Carmen R Isasi, Linda C Gallo, Tamar Sofer

Faculty, Staff and Student Publications

Omics signatures for psychiatric conditions have been under-investigated. In this study, we used data from a representative observational cohort study of Hispanic/Latino adults to identify serum metabolites associated with symptoms of depression or anxiety and to develop and assess metabolite risk scores (MRSs) of these phenotypes. We conducted a metabolome-wide association study of 768 metabolites with depression and anxiety symptoms, using two separate assay batches measured from baseline samples collected between June 2008 and July 2011 for discovery (batch 1: n = 4002 adults) and replication (batch 2: n = 2178 adults). We estimated the associations via survey-based generalized linear …

Risk Of Alzheimer Dementia After High-Dose Vs Standard-Dose Influenza Vaccination, Avram Samuel Bukhbinder, Yaobin Ling, Lauren Jhin, Elizabeth He, Kristofer Harris, Mya Rodriguez, Jenna Thomas, Gabriela Cruz, Kamal Phelps, Yejin Kim, Luyao Chen, Xiaoqian Jiang, Paul E Schulz

Faculty, Staff and Student Publications

Background and objectives: Previous studies, including large cohort analyses comparing vaccinated and unvaccinated adults, suggest that routine immunizations such as inactivated influenza vaccines (IIVs) may reduce Alzheimer dementia (AD) risk. Whether AD risk differs after high-dose IIV (H-IIV) vs standard-dose IIV (S-IIV) remains unexamined. We hypothesized that AD risk would be lower among adults ≥65 years after H-IIV compared with S-IIV.

Methods: This retrospective cohort study analyzed data spanning 2014-2019 from IQVIA PharMetrics Plus for Academics, a US health care claims database. Eligible participants were ≥65 years with ≥2 years of continuous medical and pharmaceutical coverage and no previous diagnostic …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND/AIM: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

MATERIALS AND METHODS: Phosphorus (³²P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

RESULTS: A total of 35 out of the 588 genes were differentially expressed, with either log₂ ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤-1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and …

Response Of Reticulocyte And Red Blood Cell Indices To Single-Dose Intravenous Iron In Pregnant Women With Moderate Iron Deficiency Anemia: Secondary Analysis Of The Rapidiron Trial, Manjunath S. Somannavar, Sudhir Mehta, Dharmesh Kumar Sharma, Seema Mehta, Yogeshkumar S, Umesh Charantimath, Benjamin E. Leiby, Michael K. Georgieff, Zubair H. Aghai, Ashalata Mallapur, Umesh Ramadurg, Radha Sangavi, Praveen Patil, J. P. Akshaykirthan, Rupsa C. Boelig, Mrutyunjaya B. Bellad, Richard J. Derman

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Iron deficiency anemia in pregnancy is a significant health concern. Reticulocyte hemoglobin equivalent (Ret-He) and immature reticulocyte fraction (IRF) are emerging as early markers, yet their response to different iron therapies in pregnancy is underexplored.

OBJECTIVE: To determine whether intravenous single-dose iron administration produces a more favorable effect on reticulocyte indices than oral iron therapy in anemic pregnant women.

METHODS: This is a secondary analysis of the RAPIDIRON Trial, a multicenter, three-arm randomized controlled trial comparing ferric carboxymaltose (FCM), ferric derisomaltose (FDM) and standard oral ferrous sulfate. Reticulocyte hemoglobin equivalent (Ret-He), Immature Reticulocyte Fraction (IRF) and other red blood …

Identifying Delays Impacting Maternal And Perinatal Deaths Using A Facility-Based Death Audit Review System Integrated With Community Engagement: A Mixed Methods Study, Zahid Memon, Wardah Ahmed, Shah Muhammad, Sajid Soofi, Shanti Chouhan, Arjumad Rizvi, Paul Barach, Zulfiqar A. Bhutta

College of Population Health Faculty Papers

BACKGROUND: Pakistan's persistently high maternal (178 per 100 000 livebirths) and neonatal (41 per 1000 livebirths) mortality ratios are compounded by lack of reliable data on the root causes and preventable risk factors, which hinders their effective use in improving care and progress toward safe, high-quality services. We sought to identify system delays impacting maternal and perinatal deaths using a facility-based death audit review system integrated with community engagement for implementing actionable solutions.

METHODS: We used a mixed methods, concurrent parallel study design at three secondary level healthcare facilities in District Matiari, Sindh, Pakistan. We reviewed 319 cases that included …

Perceived Inadequate Neighborhood Food Shopping And Cardiovascular Disease Risk: The Multi-Ethnic Study Of Atherosclerosis, Amier Haidar, Ghadi Ghanem, Rishi Rikhi, Karol E Watson, Shreela V Sharma, Michael D Shapiro

Faculty, Staff and Student Publications

Background: Individuals with access to healthy food have healthier diets, improved cardiometabolic risk profiles, and decreased cardiovascular disease (CVD). However, previous studies have focused on the neighborhood food environment as distance to and density of food retailers. Our study examines the association between an individual's perceived adequacy of neighborhood food shopping and incident CVD.

Methods: We analyzed data from 6814 participants in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals aged 45 to 84 who were enrolled in the study between 2000 and 2002 and followed longitudinally. Cox proportional hazards models estimated hazard ratios (HRs) for …

Functional Requirement For Dicer Helicase Arginine Methylation In 26 G Sirna Biogenesis And Oocyte Meiotic Program, Nick Newkirk, Shin-Yu Chen, Tokiko Furuta, Kenneth A Trimmer, Leilei Shi, Sabrina Stratton, Hongyuan Li, Xiaodong Cheng, Mark T Bedford, Swathi Arur

The Brown Foundation: Institute of Molecular Medicine

Spatiotemporal regulation of Dicer is essential for small RNA biogenesis and fertility, yet how its helicase domain is controlled remains unclear. Using Caenorhabditis elegans, we identify a regulatory role for the arginine-rich GRARR motif within helicase domain motif VI of DCR-1. Mutating conserved arginines in this sequence disrupts maternal 26 G endo-siRNA production, impairs oocyte meiosis I and II, and reduces fertility. Biochemically, an asymmetrically dimethylated DCR-1 GRA[R495*]R peptide enhances interaction with ERI-5, a tandem-Tudor protein in the ERIC complex, while loss of DCR-1(R495) diminishes this interaction in vivo. Genetically, eri-5 deletion phenocopies the dcr-1 R495K mutant, supporting a functional …

Out-Of-Pocket Costs And Antihypertensive Medication Use Among Veterans: A Natural Experiment, Alexander R. Zheutlin, Alexander Chaitoff, Daniel Addo, Joshua A. Jacobs, Catherine G. Derington, Eric L. Stulberg, Peter A. Glynn, Bernardo Modenesi, Jordana B. Cohen, Adam P. Bress

Department of Neurology Faculty Papers

BACKGROUND: Blood pressure (BP) control remains suboptimal in the United States despite available low-cost antihypertensive medications. Even small out-of-pocket medication costs may contribute to adherence. We determined whether $0 versus >$0 out-of-pocket costs for antihypertensive medications is associated with differences in adherence, discontinuation, BP control, and cardiovascular outcomes.

METHODS: We included veterans with newly diagnosed hypertension who initiated antihypertensive medication in the Veterans Health Administration from 2004 to 2022. A fuzzy regression discontinuity design with 2-stage residual inclusion leveraged differences in medication copay policy at a 50% service-connected disability threshold (≥50% service-connected disability: $0 out-of-pocket cost versus < 50%: $8 monthly cost). Outcomes included 1-year medication nonadherence (proportion of days covered < 80%), 1-year medication discontinuation (no medication in the final 90 days of the study year), 1-year BP control (systolic BP/diastolic BP < 140/90 mm Hg and < 130/80 mm Hg) and cardiovascular disease events (myocardial infarction, coronary revascularization, peripheral artery disease, or stroke).

RESULTS: Among 417 …

Chemotherapy-Induced Activation Of Caspase-1 And Il-1Α Release By Cancer Cells Remotely Skews Myelopoiesis To Drive Pro Tumorigenic Systemic Neutrophil-Dominant Inflammation, Stephen Qr Wong, Kazukuni Hayashi, Ethan J Subel, Yung Hsing Huang, Hongbo Gao, Haley E Garcia, Sophie J Porter, Mustafa Karabicici, Xen Ping Hoi, Mark D Alonzo, Armine Kasabyan, Efrosini Tsouko, Crystal S Shin, Lisa Bouchier-Hayes, Dimitrios Korentzelos, Chen Chen, Michael Brooks, Zheng Yin, Renil S Titus, Lan Zhou, Yinan Gong, Yulin Li, Stephen Tc Wong, Ziad El-Zaatari, Dharam Kaushik, Raj Satkunasivam, Fotis Nikolos, Keith S Chan

Faculty, Staff and Students Publications

While chemotherapy-induced tumor cell death is known to modulate the local immune landscape, its systemic impact on distant bone marrow—a site essential for immune cell maturation—remains underexplored. Here, we show that gemcitabine chemotherapy induces inflammatory caspase-1-dependent pyroptosis in epithelial cancer cells (epiCaspase-1). Despite its inflammatory nature, epiCaspase-1-mediated cell death is non-immunogenic. Clinically, elevated expression of an epiCaspase-1 gene signature correlates with worse patient outcomes. Mechanistically, epiCaspase-1 triggers the noncanonical release of IL-1α through NINJ1 lytic pores, remotely skewing bone marrow hematopoiesis towards granulocyte-monocyte progenitors and mature neutrophil output. This systemic reprogramming elevates the neutrophil-to-lymphocyte ratio (NLR) in both peripheral blood …

Maternal Inflammation Alters Nuclear And Mitochondrial Dna Methylation Patterns In Neonatal Brain Monocytes, Andrew Ebenezer, Jonathan Hicks, Brooke Hollander, Alexander Hone, Mona Batish, Robert Akins, Adam Marsh, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic ischemic encephalopathy (HIE) is a common birth complication that can cause death or lifelong disabling conditions like cerebral palsy, epilepsy, and autism. It is well established that maternal infection and inflammation are significant risk factors for HIE but reasons for this increase in neurological risk to the offspring remain unknown. Inflammation or infection are associated with epigenetic changes and may contribute to the increased risk of neurodevelopmental disability in exposed offspring. Here, we analyzed and compared DNA methylation patterns in brain monocytes isolated from control, maternal immune activation (MIA), and an inflammation sensitized HIE (IS-HIE) CF-1 mouse model …

Sex-Specific Autosomal Susceptibility Loci In Systemic Sclerosis: A Genome-Wide Association Study, Inmaculada Rodriguez-Martin, Martin Kerick, Carlos Rangel-Peláez, Carlos Rosa-Baez, Gonzalo Borrego-Yaniz, Lourdes Ortiz-Fernández, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José Luis Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcón-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Background: Systemic sclerosis is an immune-mediated inflammatory disease with marked sex differences in prevalence and severity. Although genome-wide association studies (GWAS) have advanced the understanding of systemic sclerosis genetics, sex-aware approaches remain scarce. We aimed to address this gap by examining autosomal sex-specific genetic factors in systemic sclerosis.

Methods: Based on a chromosomal definition of sex, we conducted a sex-stratified autosomal meta-analysis of GWAS in systemic sclerosis. We retrieved patient-level and control data from a previous GWAS for systemic sclerosis and newly recruited participants from an international multicentre collaboration (data cutoff June 1, 2024). Adult patients (aged ≥18 years) were …

A Digital Diabetes Prevention Program For Hispanic Adolescents (Fit24+): Protocol For A Feasibility Randomized Controlled Trial, Erica G Soltero, Marbelly Partida, Sandra Mihail, Lizette Villanueva, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Maria J Redondo, Matthew Buman, Debbe Thompson

Faculty, Staff and Students Publications

Background: Hispanic youth are disproportionately impacted by obesity and subsequent type 2 diabetes (T2D) yet remain underrepresented in diabetes prevention research. Digital health interventions hold promise for increasing the accessibility to and engagement in disease prevention programming, particularly among high-risk populations. However, there is a significant gap in the literature regarding digital T2D prevention programs for adolescents or Hispanic youth.

Objective: The objective of this article is to describe the protocol for examining the feasibility of a 12-week digital diabetes prevention program among Hispanic adolescents with obesity.

Methods: Participants (N=40; aged 12-16 years) will be randomized (1:1) to a 12-week …

Inflammation- And Resolution-Programmed Myeloid Circuits Govern Therapeutic Resistance In Epithelial And Mesenchymal Triple-Negative Breast Cancer, Liqun Yu, Charlotte Rivas, Fengshuo Liu, Yichao Shen, Ling Wu, Zhan Xu, Yunfeng Ding, Xiaoxin Hao, Weijie Zhang, Hilda L Chan, Jun Liu, Bo Wei, Yang Gao, Luis Becerra-Dominguez, Yi-Hsuan Wu, Siyue Wang, Tobie D Lee, Xuan Li, Xiang Chen, David G Edwards, Xiang H-F Zhang

Faculty, Staff and Students Publications

Single-cell analysis of human triple-negative breast cancer revealed heterogeneous macrophage populations with opposing phenotypes - proinflammatory and proresolution of inflammation. Paradoxically, both subsets accumulated in therapy-refractory residual tumors but showed inverse correlations across patients, suggesting mutually exclusive resistance mechanisms. Inflammatory macrophages localized preferentially to epithelial-like tumors, whereas proresolution macrophages were enriched in mesenchymal-like tumors. Mouse models faithfully recapitulated these patterns. After chemoimmunotherapy, mesenchymal-like tumors expanded proresolution macrophages through phagocytosis/efferocytosis, ω-3 fatty acid uptake, and resolvin production. Macrophage-secreted C1q emerged as a principal antagonist of T cell function by targeting mitochondria and inducing metabolic dysfunction. By contrast, epithelial-like tumors accumulated inflammatory …

Dasatinib And Quercetin Senolytic Treatment Delays Early Onset Intervertebral Disc Degeneration In Sm/J Mice, Emanuel J. Novais, Olivia K. Ottone, Sanjana Jagannath, Esther Jesutofunmi Akande, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice or senescence status, DQ-treated mice showed lower grades of degeneration and a decreased abundance of senescence markers, including p19ARF, p21, and the senescence-associated secretory phenotype (SASP). DQ improved disc cell viability and phenotype retention and retarded fibrosis …

A Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …

A Machine-Learning-Based Tool For Stroke Risk Prediction In Blunt Cerebrovascular Injury: Development And Preliminary Evaluation, Victoria Wagner, Joshua D Preston, Alejandro De Leon Castro, William F Mueller, Jonathan Nguyen, Manuel Garcia-Toca, Elizabeth R Benjamin, S Rob Todd, Jason D Sciarretta

Faculty, Staff and Student Publications

Purpose: Stroke risk correlates with the Biffl grading system in blunt cerebrovascular injury (BCVI). Although anti-thrombotic therapy is the mainstay of stroke prevention, no point-of-care clinical decision-support tool exists to guide timing for therapy. We sought to develop an interactive online calculator that incorporates patient-specific demographic and injury characteristics to estimate stroke risk and risk reduction with anti-thrombotic (AT) administration.

Methods: Data from BCVI patients (n = 1,197) at a Level I Trauma Center were retrospectively collected. Six machine learning methods were employed to predict stroke risk with and without AT therapy. Class imbalance was addressed using downsampling and/or class …