Digital Commons Network^™

Clinical And Demographic Characteristics Of Hospitalized Patients With Xylazine-Related Wounds, Elizabeth Novick, Nikhil Seval, Dagan Coppock, Mollie Tucker, Daniel Taupin, John Zurlo, Carolyn Kramer

Department of Medicine Faculty Papers

OBJECTIVES: Little is known about the demographic and clinical features of patients with xylazine-related wounds. We sought to characterize hospitalized patients with substance use disorder (SUD) and xylazine-related wounds seen for infectious diseases consultation.

METHODS: We retrospectively reviewed the medical records of 193 patients diagnosed with SUD at 3 Philadelphia hospitals between October 2023 and January 2024. Patients were identified as either being diagnosed with (n=73) or without (n=120) xylazine-related wounds. We compared the demographic and clinical features between the 2 groups.

RESULTS: Patients diagnosed with wounds were younger ( P < 0.001), more likely to be White or Hispanic and less likely to be Black/AA ( P < 0.001), more likely to have tested positive for fentanyl ( P < 0.001), amphetamines ( P < 0.001), and cocaine ( P 0.001), more likely to acknowledge injection ( P < 0.001), and more likely to leave the hospital by patient-directed discharge (PDD) ( P < 0.001). Most patients had multiple wounds (75%), and more than half (53%) had at least one wound greater than 10 cm at its widest dimension. Although most patients diagnosed with wounds received antibiotics, many did not have symptoms or signs of infection.

CONCLUSIONS: Xylazine-related wounds are highly associated with illicitly manufactured …

Prevalence Of Low Energy (Lea) Risk In Division Iii Female Distance Athletes, Ciara Murphy

Masters Theses/Capstone Projects

Context 

Low energy availability (LEA) occurs when energy intake is insufficient to support normal physiological functions after exercise (Loucks, 2011). Prolonged LEA can negatively affect metabolic functions, reproductive health, and bone density, and contribute to the development of the female athlete triad and relative energy deficiency in sport (RED-S) (Papageorgiou, 2017).

Objective

The objective of this study was to explore the prevalence of LEA among Division III female distance athletes.

Design

Cross-sectional study

Setting

Online questionnaire administered through Qualtrics

Participants 

A total of 12 Division III female distance athletes (ages 18-23).

Intervention

Anonymous, electronic questionnaire assessing symptoms associated with low …

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.

A Novel Approach To Defining Progression In Mds And Precursor Myeloid Conditions In The Mds Natural History Study, Amy E Dezern, Matthew Walter, Et Al.

2020-Current year OA Pubs

Patients at risk for progression from myeloid precursor states (idiopathic cytopenia of undetermined significance [ICUS] and clonal cytopenia of undetermined significance [CCUS]) to myelodysplastic syndrome (MDS) are not well defined. Epidemiologic risk factors, clonal changes for MDS development, and evolution from one MDS state to another were available in the MDS Natural History Study (NHS), a prospective cohort enrolled at diverse US sites. Extensive clinical data and biospecimens were collected at baseline and follow-up. A total of 1177 (56%) individuals with MDS or MDS-related precursor conditions (ICUS/idiopathic dysplasia of undetermined significance [IDUS], CCUS, and MDS/myeloproliferative neoplasm overlap) were enrolled and …

Familial Healthy Aging And Longevity: The Role Of Spouses, Søren Netra, Angéline Galvin, Matthew Keys, Katrine Lawaetz Kristensen, Jacob Krabbe Pedersen, Bharat Thyagarajan, Svetlana Ukraintseva, Mary K Wojczynski, Dorret I Boomsma, Kaare Christensen

2020-Current year OA Pubs

BACKGROUND: Families with exceptional longevity often experience delayed onset of age-related diseases and reduced mortality across generations-a pattern influenced by shared genetic and behavioral factors. While several studies have focused on the members of longevity-enriched families (LEF), little is known about the health trajectories of the spouses marrying into these families. Given prior evidence of substantially reduced mortality among spouses of LEF members, determining whether this advantage reflects selection, shared environments, or behavioral convergence is essential for understanding the mechanisms that underlie intergenerational health transmission.

METHODS: We conducted a multigenerational, retrospective matched cohort study using nationwide Danish civil and health …

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 …

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

2020-Current year OA Pubs

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 …

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 …

How Survivors Of Exploitation Who Use Drugs Navigate Systems Of Care: An Analysis Of Survivor Insights Using The Intersectional Risk Environment, Theresa Anasti, Hilary Thibodeau, Nathaniel A Dell, Kathleen Preble, Lauren Grimes, Lindsay B Gezinski

2020-Current year OA Pubs

BACKGROUND: Drug-related risks such as adverse health outcomes, overdose, and violent victimization vary across populations due to the marginalization of identities, structural inequities, and differing environments. Discrimination and criminalization exacerbate drug-related risks specifically for survivors of sexual exploitation who use drugs. This study aims to understand how survivors who are not currently utilizing intensive treatment services perceive their risk environment, including available resources, and identify possible mechanisms to address health equity. Emphasizing the role of harm reduction and the expertise of lived experience, this paper encourages innovative approaches to supporting survivors.

METHODS: A research team conducted seventeen semi-structured interviews with …

Pediatric Thyroid Cancer Lung Metastases And Rai: Long-Term Results, Ryan C Mueller, Nikhil Rammohan, Anthony J Apicelli, Ana Maria Arbelaez, Farrokh Dehdashti, Barry A Siegel, Vikas Prasad, Perry W Grigsby, Stephanie Markovina

2020-Current year OA Pubs

OBJECTIVES: Children with differentiated thyroid cancer (DTC) often present with lung metastases but historically have good outcomes. Radioactive iodine (RAI) is commonly used to treat these children. Given the rarity of this condition, little evidence detailing long-term outcomes and risk of radiation pneumonitis exists.

METHODS: We conducted a retrospective analysis of patients < 20 years old who received RAI for DTC lung metastases between 1973 and 2018. Disease-free survival (DFS) was calculated from diagnosis to last follow-up. Overall survival and rates of acute and late radiation pneumonitis were determined by chart review and obituary searches.

RESULTS: Sixteen patients met eligibility criteria. Fourteen presented with thyroid, nodal, and lung disease; one presented with thyroid and nodal disease with nodal and lung recurrence; and one presented with thyroid-only disease with nodal and lung recurrence. All patients underwent thyroidectomy, 10 underwent neck dissection, and four underwent …

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 …

Sex-Aware Genome-Wide Assessment Of De Novo Variants In Autism Across Coding And Noncoding Regions, Tychele N Turner

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) shows a consistent sex bias, yet how sex shapes de novo variant (DNV) risk across coding and noncoding sequence remains unclear. I analyzed DNVs in > 41,000 parent–child sequenced trios from three ASD family-based cohorts and compared DNV characteristics and enrichment patterns in males and females. Notably, these trios included individuals with ASD as well as those without ASD. I developed a new sex-aware DNV caller (HAT-FLEX) and thoroughly evaluated each candidate DNV using an additional tool introduced in this study, SNOW, to generate a high-confidence callset. RESULTS: I identified enrichment of missense and loss-of-function (LOF) …

A Risk-Based Model For Unplanned Cesarean Delivery Following Induction Of Labor In Term Hypertensive Nulliparas., Avihu Krieger, Michal Axelrod, Baha Sibai, Shalom Mazaki-Tovi, Michal Fishel Bartal

Faculty, Staff and Student Publications

Purpose: To develop a practical risk-stratification framework for unplanned cesarean delivery (CD) among term nulliparous individuals with hypertensive disorders of pregnancy (HDP) undergoing induction of labor (IOL).

Methods: This was a retrospective cohort study at a single tertiary care center (January 2010-March 2025) of nulliparous individuals with singleton gestations diagnosed with HDP undergoing IOL at ≥ 37 + 0 weeks. We excluded multiple gestations, major fetal anomalies, planned CD, or intrauterine fetal death. We included demographic and pregnancy characteristics available prior to induction and evaluated association with unplanned CD. Stepwise backward logistic regression was used to build a model for …

Delivering Safe Sleep And Breastfeeding Education To Pregnant And New Mothers Through Private Facebook Groups: Study Protocol For A 4-Armed Randomized Controlled Trial, Rebecca F Carlin, Margaret G Parker, Ann L Kellams, Fern R Hauck, Stephen Kerr, Benjamin T Cornwell, Marc T Kiviniemi, Nicole Geller, Katherine E Boguszewski, Michael J Corwin, Eve R Colson, Rachel Y Moon

2020-Current year OA Pubs

BACKGROUND: Annually, more than 3500 US infants die suddenly and unexpectedly. Many sudden unexpected infant deaths (SUID) are preventable with greater adherence to safe infant sleep guidelines. There are racial and economic disparities in guideline adherence and SUID rates. Education alone has proven ineffective at altering behavior for many parents, and social networks and social norms regarding infant care have been found to influence rates of unsafe sleep. Using the power of social networks to shape social norms by delivering education through moderated online social media groups provides a unique opportunity to influence these practices in large groups of parents. …

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 …

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 …

Natural History Of 15 Patients With Autosomal Dominant Wfs1 Pathogenic Variants Associated With Sensorineural Hearing Loss And Optic Atrophy, Jessica P Roberts, Abby F Tang, Daniela Hernandez, Brianna Carman, Liam Oiknine, Cris Brown, Stacy Hurst, Yunshuo Tang, Fumihiko Urano

2020-Current year OA Pubs

OBJECTIVE: Autosomal dominant pathogenic variants in WFS1 cause a spectrum of disorders with phenotypic manifestations including low-frequency sensorineural hearing loss, optic nerve atrophy accompanied by low- to mid-frequency sensorineural hearing loss, non-syndromic diabetes mellitus, and early-onset cataracts. These conditions are generally milder than autosomal recessive Wolfram syndrome, except for Hattersley-Urano syndrome. Despite growing recognition of these disorders, data on clinical progression and long-term outcomes remain limited. This study aims to expand knowledge on disease severity and progression in autosomal dominant WFS1-related disorders. APPROACH: Clinical data were obtained from the Washington University International Registry and Clinical Study for Wolfram Syndrome and …

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 …

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 …

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 …

Enhanced Dietary Monitoring Using Fecal Genomics For Childhood Malnutrition Interventions, Ammara Aqeel, Najeeha T Iqbal, Sanam Iram Soomro, Sheraz Ahmed, Teresa K Mcdonald, Olivia Osborne, Sharon Jiang, Nolan Ives, Kazi Ahsan, Fayaz Umrani, Michael J Barratt, Jeffrey I Gordon, Syed Asad Ali, Lawrence A David

2020-Current year OA Pubs

Ready-to-use therapeutic and supplementary foods (RUTF/RUSF) are a primary treatment for childhood malnutrition in Community Management of Acute Malnutrition (CMAM) programs. However, measuring intervention compliance is labor intensive and unreliable. We applied FoodSeq, a fecal genomic dietary assessment biomarker, in malnourished infants (3-15 months) from Matiari, Pakistan. FoodSeq identified a significant increase in the abundance of DNA from chickpea, a primary RUSF ingredient, during RUSF administration and captured region-specific complementary feeding practices, including age-inappropriate feeding practices such as wide-spread tea consumption. Our findings highlight the potential of dietary genomics as an empirical and scalable tool for compliance monitoring and dietary …

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 …