Digital Commons Network^™

The Resilient Study: A Retrospective, Descriptive, Correlational Investigation Of Correlates Of Oral Endocrine Therapy Adherence In Older Women With Breast Cancer., Sunny Y. Ruggeri, Cynthia L. Russell Lippincott, Gregory L. Alexander, Rebecca J. Bartlett Ellis, Steven R. Chesnut, Lori A. Erickson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Breast cancer is the most prevalent and costly cancer. Oral endocrine therapy (OET) improves survival rates and quality of life while reducing recurrence, mortality, morbidity, and medical costs. However, adherence to OET is challenging because OET is prescribed for 5-10 years. Determinants of OET nonadherence (NA) among women aged 65 and older remain poorly characterized. Existing studies are limited, often focusing on small, single-site samples and focusing on patient-level rather than multi-level determinants. Despite the unique needs of older women, research on OET-NA remains scarce.

OBJECTIVE: This study identified multi-level determinants of OET-NA in older women using ecological systems …

Targeted Epigenome Sequencing Of Eosinophils Reveals Cpg Sites And Regulatory Variants Associated With Asthma., Rébecca Dionne-Gagné, Anne-Marie Madore, Anne-Marie Boucher-Lafleur, Tomi Pastinen, Catherine Laprise

Manuscripts, Articles, Book Chapters and Other Papers

Eosinophils are pro-inflammatory cells that play a central role in asthmatic inflammation. However, few studies have examined their methylation profiles in asthma, all relying on microarray-based approaches. Here, an epigenome-wide association study in 183 purified eosinophil samples from the Saguenay-Lac-Saint-Jean asthma family cohort was performed using a custom sequencing panel targeting 4,609,564 CpGs in immune regulatory regions. Two CpG sites in MAEA and SLC9A2 genes, known to be involved in immune function, were significantly associated with asthma, while five additional sites showed suggestive associations. Integration with genotype data (7,829,429 variants) and expression counts (17,513 genes) identified significant quantitative trait loci-mediated …

Leading With Hope: A Clinical Communication Campaign To Promote Partner Hiv Testing In Assisted Partner Notification And Antenatal Care Programs In Uganda., Emily A. Hurley, Violet Gwokyala, Linda Kisaakye Nabitaka, Jolly Beyeza Kashesya, Mercylynn Agasha, Florence Namaganda, Nikolaus Schuetz, J Nalubega Ross, Joseph K B Matovu, Rhoda Wanyenze, Glenn Wagner, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

Among heterosexual couples in sub-Saharan Africa, fears of relationship dissolution and inability to bear healthy children following an HIV-positive result remain barriers to HIV testing. Recently expanded availability of pre-exposure prophylaxis (PrEP) affords a critical opportunity to promote HIV testing with reassuring communication that highlights use for relationship preservation and healthy childbearing. We aimed to develop a theoretically-grounded communication intervention to promote partner HIV testing within assisted partner notification (APN) and antenatal care (ANC) programs in Uganda. Through an 18-month iterative co-creation process, we developed the HOPE Clinical Communication Campaign (HOPE-CCC) in collaboration with a project advisory board (PAB) of …

Treatment Of Haemophilia A Without Inhibitors: Real-World Treatment Patterns And Clinical Outcomes In The Us., Allison P. Wheeler, Lauren Amos Md, Shveta Gupta, Sylvie Bozzi, Gandarvaka Miles, Kalyani Hawaldar, Andrew Wilson, Gillian Hanson, Emily Cibelli, Amanda Wilson, Siddhi Umarje, Anne-Laure Tardy, Jennifer Dumont, Graham Neill, Alix Arnaud

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Despite available prophylactic therapies for haemophilia A, breakthrough bleeding and consequent pain and joint damage still occur.

AIM: To provide insights into the unmet treatment needs of people with moderate-to-severe haemophilia A in the US.

METHODS: For this descriptive, observational cohort study, eligible participants diagnosed with moderate-to-severe haemophilia A were enrolled in the PicnicHealth database on or before 3 October 2022. Three patient groups were established to identify: (1) treatment patterns; (2) clinical outcomes by therapy class (standard half-life [SHL] factor VIII [FVIII]; extended half-life FVIII [EHL]; emicizumab); (3) health-related quality of life (HRQoL) using the Patient-Reported Outcomes Measuring …

Population Pharmacokinetics And Dosing Simulations Of Pentobarbital In The Pediatric Population, Victoria Etges Helfer, Lorena Medina-Aymerich, William J. Muller, Marisa Meyer, Amira Al-Uzri, Russell Mcculloh, Chi D. Hornik, Stephen J. Balevic, Rachel G. Greenberg, Daniel K. Benjamin, Sarah G. Anderson, Daniel Gonzalez

Department of Pediatrics Faculty Papers

Pentobarbital is a barbiturate with sedative and anticonvulsant properties, occasionally used in pediatric patients for preoperative sedation, deep sedation during mechanical ventilation, and seizure control. Despite its long-standing clinical use, age-appropriate dosing remains challenging due to variability across studies and limited pediatric pharmacokinetic (PK) data. This study (NCT01431326) aimed to characterize the population pharmacokinetics of pentobarbital in pediatric patients (birth to 21 years) and evaluate dosing strategies using model-based simulations. A two-compartment population PK model, allometrically scaled to total body weight, adequately described pentobarbital plasma concentrations, with no additional covariates identified as significant. Simulations were conducted across four age groups: …

Assessing Trauma Triage Tools: The Cribari Matrix Method And Modified Need For Trauma Intervention., Olivia Houck, Nathaniel C Brophy, Danielle Rossler, Roxanna Giambri, Deanah Moore, Sara Arida, Melody Campbell, Richard L George

Emergency Medicine and Trauma

BACKGROUND: Assessment of triage procedures is crucial for improving patient care. Most programs evaluate under- and over-triage using the ISS-based Cribari Matrix Method (CMM), but tools such as the critical-intervention-based Need for Trauma Intervention (NFTI) and its time-critical modified version (mNFTI) focus on identifying patients who need immediate resources. The mNFTI has seen limited empirical inquiry in assessing triage procedures.

OBJECTIVE: To assess accuracy and agreement rates between mNFTI and CMM.

METHODS: This multicenter, retrospective cohort study compared triage classifications in trauma patients using 2019 trauma registry data from trauma centers across 5 trauma systems in Ohio, United States. Patients …

Severe, Non-Apneic Respiratory Dysfunction And Hypoxia Following Generalized Convulsive Seizures, Haley E Pysick, Rup K Sainju, Roshni Nair, Deidre N Dragon, Eduardo Bravo, Laura Vilella, Xiaojin Li, Samden D Lhatoo, George B Richerson, Brian K Gehlbach

Faculty, Staff and Student Publications

Objective: Sudden unexpected death in epilepsy (SUDEP) is a devastating consequence of some generalized convulsive seizures (GCS). Recent work has focused on seizure related apnea as a biomarker of SUDEP risk, frequently without characterizing the adequacy of non-apneic ventilation or identifying other dysfunctional breathing patterns. We hypothesized that GCS frequently induce immediate, severe, non-apneic respiratory dysfunction that can induce critical hypoxia and bradycardia and sought to characterize breathing patterns after GCS.

Methods: Adult patients admitted to an epilepsy monitoring unit were studied. The effects of GCS on breathing and heart rate were analyzed using nasal pressure transducers, chest and abdominal …

Estrogen As A Therapeutic Agent: Targeting Endotheliopathy And Coagulopathy In Trauma, Niruktha Raghavan, Mira Patel, Bryan A Cotton, Julia Coleman, Donald Jenkins

Faculty, Staff and Student Publications

Background: Traumatic injury remains a leading cause of death, often due to uncontrolled hemorrhage and trauma-induced coagulopathy (TIC). TIC is critically triggered by the endotheliopathy of trauma, involving endothelial cell injury and glycocalyx degradation. Despite conventional advances, the stable casualty rate underscores the urgent need for new precision resuscitation strategies that acknowledge factors like biological sex.

Design: The central hypothesis is that estrogen confers a survival advantage in hormonally active females through a dual action: endothelial cell stabilization (halting glycocalyx shedding) and its inherent procoagulant effect. The analysis assesses the therapeutic potential of both exogenous estrogen and female-derived blood products …

Are Drains After Trauma Splenectomy Associated With Organ Space Surgical Site Infections?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Seokhun Kim, William D Rieger, Renee W Green, Gabrielle E Hatton, Lillian S Kao

Faculty, Staff and Student Publications

Introduction: Left upper quadrant (LUQ) drain use after trauma splenectomy varies, with minimal existing data to guide practice. We aimed to investigate the association of LUQ drains with organ space surgical site infection (OS-SSI) after splenectomy. We hypothesized that LUQ drains after trauma splenectomy are associated with increased odds of OS-SSI.

Patients and methods: A retrospective study of adult blunt trauma patients who underwent splenectomy from 7/2018 to 6/2024 was performed. We excluded patients who survived < 5 days after operation, and those with an intraoperatively identified pancreatic injury. Demographics, surgical details, and drain information were abstracted from the medical record. Inverse probability of treatment weighting (IPTW) was used to balance variables between patients who did and did not receive an LUQ drain after splenectomy. Multivariable logistic regression with IPTW was performed to estimate the association of LUQ drains with OS-SSI.

Results: Of 179 patients, 68% (n = 121) were male, the median age was 38 years (interquartile range 28, 55), and 27% (n = …

An Assessment Of Green Plasma: The In Vitro Hemostatic Superiority Of A Currently Discarded Blood Product, Samantha C Redden, David J Sun, Yao-Wei W Wang, Elizabeth Hartwell, Jessica C Cardenas, Scott D Olson, Bryan A Cotton

Faculty, Staff and Student Publications

Introduction: Recent studies have linked trauma patient outcomes to the plasma donor's sex, with premenopausal females associated with improved survival and lower organ failure. Currently, green-colored plasma (due to oral contraceptive use) is removed from the donor pool. We set out to evaluate the hemostatic potential of green plasma.

Study design & methods: We obtained 90 units of plasma from our regional blood center: 30 units of visible green plasma and 60 units of standard-color plasma divided between male and female donors. We collected clinical data such as age, sex, ethnicity, and number of pregnancies. We then assessed the hemostatic …

Aspirin And Preterm Birth Among Pregnant People With Increased Heat Exposure: Secondary Analysis Of A Randomized Clinical Trial, Gabriella Meltzer, Luke Duttweiler, Sarah Saleem, Kartik Shankar, Manolo Mazariegos, Antoinette Tshefu, Jackie Patterson, Elwyn Chomba, Waldemar Carlo, Shivaprasad Goudar, Richard Derman, Archana Patel, Patricia Hibberd, Edward Liechty, Fabian Essamai, Edwin Asturias, Denise Babineau, Janet Moore, Cascade Tuholske, Andrew Zimmer, Brent Coull, Elizabeth Mcclure, Robert Goldenberg, Nancy Krebs, Matthew Hoffman, Blair Wylie

Global Health Articles

IMPORTANCE: Scalable interventions are urgently needed to mitigate the adverse effects of heat on pregnancy and newborn health.

OBJECTIVE: To evaluate whether low-dose aspirin modifies the association between heat exposure and preterm birth.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the Global Network for Women's and Children's Health Research Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) randomized, double-blinded, placebo-controlled clinical trial was conducted from March 2016 to June 2018. Statistical analyses were performed from June 2024 to June 2025. The study settings included the Democratic Republic of Congo, Zambia, Kenya, Guatemala, Pakistan, and Belagavi and Nagpur, …

2-Aminobutyrate Mediates The Impact Of Air Pollution On Blood Biomarkers Of Alzheimer’S Disease, Anum Saeed, Chris Mckennan, Jane E Clougherty, Peidi Zhou, Sheila Tripathy, Ellen J Kinnee, Jiaxuan Duan, Kevin Kip, Xuemei Zeng, Victor Villemagne, Tharick Pascoal, Mark Mapstone, Eric A Whitsel, Oscar I Lopez, Christie Ballantyne, Thomas K Karikari, Bing Yu, Steven Reis, Annie Cohen

Faculty, Staff and Students Publications

Introduction: We examined the impact of mid-life metabolites on late-life Alzheimer's disease (AD) plasma biomarkers and whether these metabolites mediate air pollution effects.

Methods: In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) cohort, we applied high-dimensional regression and meditation models, adjusting for observed and latent confounders, with replication in the Atherosclerosis Risk in Communities (ARIC) study. Exposures included mid-life fine particulate matter (PM2.5), black carbon, metals, and metabolites. Outcomes were: late-life plasma p-tau(181, 217, and 231) and amyloid beta 42/40 (Simoa assays).

Results: In the Heart SCORE study, seven lipid- and amnio acid-pathway metabolites measured in mid-life were …

Plasma Proteins Associated With Psychosocial Factors And Heart Disease: The Jackson Heart Study, Sara N O'Brien, Madeline G Gillman, Michael D Green, Daniel E Cruz, James S Floyd, Susan Hankinson, Daniel H Katz, Xiaojuan Liu, Michelle C Odden, Bruce M Psaty, Alexander P Reiner, Jerome I Rotter, Stephen S Rich, Robert E Gerszten, Amil Shah, Mario Sims, Usman A Tahir, Lesley F Tinker, Alexis C Wood, Bing Yu, Anthony S Zannas, Laura M Raffield, Láshauntá M Glover

Faculty, Staff and Students Publications

Background: Knowledge of proteomic mechanisms explaining the link between psychosocial stress and cardiovascular disease is limited. This study aimed to (1) identify plasma proteins associated with psychosocial factors and (2) assess associational pathways between psychosocial factors, identified proteins, and incident cardiovascular disease events in a discovery cohort, JHS (Jackson Heart Study), and 2 replication cohorts, the CHS (Cardiovascular Health Study), and the MESA (Multi-Ethnic Study of Atherosclerosis).

Methods: JHS participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were included (n=2143, mean age=55.3). Depressive symptoms and perceived stress scores were measured via the 20-item Center for Epidemiological Studies …

Stance And Gait Analysis Of Apollo Astronauts On The Moon, Faye Y Chiou-Tan, Conrad Li, Jason P Caffrey, Millard Reschke, Timothy R Macaulay

Faculty, Staff and Students Publications

Introduction/aim: As humans return to the Moon, safe efficient ambulation and fall prevention on the lunar surface are key concerns. The analysis of gait from archived Apollo mission video footage is now possible with pose estimation video analysis software. Thus, this study aims to retrospectively quantify parameters of Apollo astronauts' stance and gait on the Moon.

Methods: Publicly available National Aeronautics and Space Administration (NASA) footage of astronauts ambulating on the Lunar surface was examined using body pose analysis software. Goniometric lower limb joint/torso angles and width of base of stance and gait were derived. Gait cycle stance phase, swing …

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 …

From Low Field To High Value: Robust Cortical Mapping From Low-Field Mri, Karthik Gopinath, Timothy Coalson, Matthew F Glasser, David Van Essen, Et Al.

2020-Current year OA Pubs

Three-dimensional reconstruction of cortical surfaces from MRI for subsequent morphometric analysis is fundamental for understanding brain structure. While high-field Magnetic Resonance Imaging (HF-MRI) is the standard in research and clinical settings, its relatively limited availability hinders widespread use. Low-field MRI (LF-MRI), particularly portable systems, offers a cost-effective and accessible alternative. However, existing cortical surface analysis tools, such as FreeSurfer, are optimized for high-resolution HF-MRI and struggle with the lower signal-to-noise ratio (SNR) and resolution of LF-MRI. In this work, we present a machine learning method for 3D reconstruction and analysis of portable LF-MRI scans over a range of contrasts and …

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 …

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 …

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 …

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 …

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 …

Cerebellar Oligodendrocytic Α-Synuclein Pathology And Dentate Nucleus Neuronal Hypertrophy In Parkinson’S Disease, Diego Iacono, Hui Peng, John Paul Bouffard, Roger Kurlan

Department of Neurology Faculty Papers

Idiopathic Parkinson's disease (iPD) research has historically prioritized basal ganglia dysfunction and neuronal Lewy body pathology, often overlooking cerebellar and non-neuronal cells contributions. This study investigates cerebellar neuropathology in iPD, specifically focusing on neuronal and non-neuronal cells of the dentate nucleus (DN) and its adjacent white matter (DN-WM). We systematically assessed autopsy-confirmed iPD brains vs. age-matched controls using immunohistochemistry and stereology-based morphometry methods. The study evaluated α-synuclein pathology, other common age-related co-occurring pathologies (β-amyloid, Tau, neuroinflammation), myelin integrity (Luxol-Fast-Blue), and neuronal volumetric changes in the DN of the cerebellum. In iPD brains, we identified intracytoplasmic α-synuclein inclusions within oligodendrocytes across …

Multi-Trait Polygenic Scores For Copd And Copd Exacerbations Implicate Druggable Proteins, Chengyue Zhang, Iain R Konigsberg, Yixuan He, Jingzhou Zhang, Tinashe Chikowore, William B Feldman, Xiaowei Hu, Yi Ding, Bogdan Pasaniuc, Diana Chang, Qingwen Chen, Jessica A Lasky-Su, Julian Hecker, Martin D Tobin, Jing Chen, Sean Kalra, Katherine A Pratte, Hae Kyung Im, Emily S Wan, Ani Manichaikul, Edwin K Silverman, Russell P Bowler, Leslie A Lange, Victor E Ortega, Alicia R Martin, Michael H Cho, Matthew R Moll

Faculty, Staff and Student Publications

BACKGROUND

We constructed multi-trait polygenic risk scores (PRSs) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validated their performance in diverse cohorts, and identified PRS-related proteins for potential therapeutic targeting.

METHODS

PRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic White participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2–4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), Mass General Brigham Biobank (n = 15,152), and All of Us (n = 118,566). …

Contraception In The Ed: Understanding Education And Opportunities For Clinicians To Advise Patients, Hannah B. Lewis, Teagan R. Mccarthy, Dara Kass, Jennifer L. Kahoud

Department of Emergency Medicine Faculty Papers

Introduction: The United States faces a high rate of unwanted pregnancies. Despite this, many people continue to face barriers to accessing contraception. The emergency department (ED) can help bridge these gaps, but emergency clinicians must first feel comfortable offering contraceptive services. In this study, we sought to determine emergency clinician comfort in prescribing contraceptives and educating patients on their use. We also gauged clinician interest in receiving education specifically geared toward contraceptive care.

Methods: We conducted an online survey of ED residents, attendings, and advanced practice clinicians at Thomas Jefferson Univerity Hospital and affiliates in both the urban and suburban …

Versatile Smad2 And Smad3 Epitope-Tagged Mouse Models For Genomic Profiling Of Tgfβ Signaling: Uncovering Gdf9-Smad2/3 Targets, Zian Liao, Qian Zhang, Keisuke Shimada, Kaori Nozawa, Suni Tang, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Transforming growth factor β (TGFβ) signaling pathways are integral for a plethora of biological processes. SMAD2 and SMAD3 are the principal transcriptional effectors of TGFβ superfamily ligands, yet quantitative, genome-wide mapping of their DNA-associated complexes under physiological contexts has remained limited due to the lack of specific, robust models. Here, we generated two versatile epitope-tagged mouse models in which endogenous SMAD2 and SMAD3 proteins are globally tagged with hemagglutinin (HA) and podoplanin (PA) sequences, respectively, enabling high-fidelity profiling of SMAD2 and SMAD3 binding across tissues. To demonstrate the broad application of our models, we exemplified the usage of our lines …

Reference Proteins To Improve Core 1 And Core 2 Alzheimer's Disease Csf And Plasma Biomarkers, Linda Karlsson, Nicolas R Barthélemy, Kanta Horie, Suzanne E Schindler, Brian A Gordon, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Concentration-based fluid biomarkers represent an informative and cost-effective way to detect and monitor Alzheimer's disease (AD) pathology. However, non-AD-related interindividual variation in biofluids can also affect biomarker concentrations. Here, we investigated whether normalization of CSF and plasma biomarkers to reference proteins, such as amyloid-β40 (Aβ40) and non-phosphorylated mid-region tau (np-tau), improves their robustness and reliability of representing AD pathology load. Using the Swedish BioFINDER-2 cohort [n = 1702, 50.7% male, mean (standard deviation) age 68.4 (12.2) years], we compared the associations between tau/Aβ-PET load and fluid biomarkers alone versus biomarkers in a ratio with a reference protein (Aβ40 or np-tau) …

Regulation Of Mitochondrial Ros By C15orf48 In A Basal Cell Subpopulation Contributes To Chemotherapy Resistance In Tnbc, Yan Jiang, Noor M Abdulkareem, Amanda L Rinkenbaugh, Yuan Qi, Steven W Wall, Xiaomei Zhang, Jiansu Shao, Sabrina Jeter-Jones, Shirong Cai, Faiza Baameur Hancock, Gloria V Echeverria, Jeffrey T Chang, Helen Piwnica-Worms

Faculty, Staff and Students Publications

Systemic neoadjuvant chemotherapy, often combined with immunotherapy, is the standard of care for early-stage, non-breast cancer susceptibility gene (BRCA)-mutant triple negative breast cancer (TNBC). However, up to 70% of patients retain residual disease after treatment, which is linked to recurrence and mortality within 5 years. To define mechanisms of resistance, we performed single-cell RNA sequencing on orthotopic TNBC patient-derived xenografts during a cycle of treatment with doxorubicin and cyclophosphamide (AC). Clustering identified four tumor epithelial cell populations, with basal cells enriched in residual tumors. These basal cells up-regulated C15ORF48, a paralog of the mitochondrial cytochrome c oxidase associated subunit FA4 …

Multiscale Metabolic Covariance Networks Uncover Stage-Specific Biomarker Signatures Across The Alzheimer's Disease Continuum., Juan Antonio K Chong Chie, Scott A Persohn, Ravi S Pandey, Olivia R Simcox, Gregory W. Carter, Paul Salama, Paul R Territo, The Alzheimer’S Disease Neuroimaging Initiative

Faculty Research 2026

INTRODUCTION: Functional connectomics studies leverage the power of interregional brain relationships using graph theory of glycolytic metabolism to establish neural connections and their roles in cognition and disease and to monitor therapeutic responses.

METHODS: Using a retrospective clinical population (N = 431) from ADNI, we evaluated disease changes using metabolic covariance analysis. In addition, we developed a novel region set enrichment analysis (RSEA) to detect brain functional changes based on metabolic variations. Results were aligned with transcriptomic signatures and clinical cognitive assessments (CCAs).

RESULTS: Our findings highlight sexual dimorphic changes across the disease spectrum, which suggest brain network reorganization occurs …

Dental Insurance Status Among Formerly Incarcerated Older Adults, Alexander Testa, Rafael Samper-Ternent, Dylan B Jackson, Kyle T Ganson, Vahed Maroufy, Jason M Nagata, Ana C Neumann

Faculty, Staff and Student Publications

Formerly incarcerated individuals have poorer oral health and less frequent dental care utilization than the general population. However, prior work has overlooked the relationship between prior incarceration and disparities in dental insurance coverage. Using data from the Health and Retirement Study (n = 11,638), findings from multiple logistic regression analyses demonstrate that formerly incarcerated older adults are significantly less likely to have dental insurance coverage (odds ratio [OR] = 0.745, 95% confidence interval [CI] = 0.608, 0.912). After accounting for the income-to-poverty ratio, this association was no longer statistically significant. Analyses using the Karlson-Holm-Breen method demonstrated that approximately 45% of …