Public Health Commons^™

Influence And Excess: A Study Of Alcohol’S Governmental, Societal, Biochemical, And Enzymatic Impact In The U.S And Other Countries Around The World, Thomas W. Snider

Senior Honors Theses

The conduct of the thesis is to explore the intricacies of alcohol consumption. The thesis will outline the history of alcohol and the societal pressures and conduct of drinking with relation to the government. After the history of alcohol has been defined, the thesis will move into the chemistry portion, delineating the absorption, digestion, metabolism, and excretion of alcohol. This is the portion of the thesis that will contain the quantitative data and source material as much research has already been conducted regarding these components of alcohol consumption. The condition of the research is that the data will be collected …

The Frontal Assessment Battery In Older Multilingual Kenyan Adults, Anne Njoki Gitere, Anne Nyambura, Karen Blackmon, Levi Muyela, Rachel Maina, Olivera Nesic Taylor,, Jasmit Shah, Dilraj Sokhi, Sylvia Mbugua, Samuel Gitau, Sheila Waa, Juzar Hooker, Zul Merali, Chinedu Momoh, Karen Blackmon

Brain and Mind Institute

Background: The Frontal Assessment Battery (FAB) was developed as a short (6-item) bedside assessment of executive dysfunction in older adults with suspected neurodegeneration. This study describes psychometric features of the FAB in multilingual Kenyan adults with and without clinical diagnosis of dementia.

Method: The FAB consists of six items assessing verbal abstract reasoning, lexical fluency, motor learning, and inhibitory control. The score on each item ranges from 0-3, with higher scores indicating better performance. Bilingual English-Swahili study personnel translated, blind back-translated, and applied consensus-driven cultural adaptations. FAB was then administered to 95 participants [71 cognitively unimpaired (CU) controls; 24 people …

Perceptions And Attitudes On Biospecimen Sample Collection For Dementia Research In Kenya, Lucy Kamau, Chinedu Momoh, Karen Blackmon, Caroline Kiio, Jasmit Shah, Vaibhav Narayan, Irene Meier, Olivera Nesic Taylor,, Zul Merali, Edna Bosire

Brain and Mind Institute

Background: Biospecimen sample collection is crucial in dementia diagnosis and evaluation. Limited research exists from African Countries including Kenya on people's perception on biospecimen sample collection for dementia- a disease that is largely unknown. Our aim was to understand the public perceptions towards collection of biospecimen samples for dementia research in Kenya.

Method: We conducted 8 focused group discussions (FGDs; age and gender stratified) in Nairobi to understand people's perceptions about different biospecimens (urine, saliva, blood, tears, hair, cerebrospinal fluid (CSF) and the brain samples). An open-ended FGD guide was used for the discussions, each lasting about 90 minutes.

Result: …

Bridging The Gap: From Early Recognition To Timely Referral For Cardiac Implantable Electronic Devices Infections, M Rizwan Sohail, Sarwat Khalil, Molly L Paras, Christopher B Granger, Andrew Uehlin, Yu-Rong Gao, Zerelda Esquer Garrigos

Faculty, Staff and Students Publications

An increasing number of patients are living with cardiac implantable electronic devices (CIEDs). When a patient with a CIED is hospitalized with concern for infection or positive blood cultures from any source, recognizing and managing a possible CIED infection is critical due to its significant morbidity and mortality risk. Internists are often the first to evaluate these patients and must consider the possibility of an underlying device infection. Gram-positive bacteremia carries a high risk of CIED infection, often necessitating cardiac imaging. In contrast, hematogenous seeding with gram-negative bacteremia is infrequent. Patients with clinical or imaging evidence of device infection should …

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

Faculty, Staff and Students Publications

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

Using Robotic Single-Port Vnotes For Gynaecological Oncology: Omentectomy In A Patient With An Ovarian Granulosa Cell Tumor-A Case Study, Chunhua Zhang, Qing Li, Fang Fang, Xiaoming Guan

Faculty, Staff and Students Publications

Background: Robotic single-port transvaginal natural orifice transluminal endoscopic surgery (RSP-vNOTES) is an emerging minimally invasive approach that combines the advantages of robotic surgery with scarless transvaginal access. Its application in gynecologic oncology remains limited, particularly for omentectomy during ovarian cancer staging.

Methods: We present the case of a 45-year-old woman with an ovarian granulosa cell tumor (GCT) who underwent supplemental staging surgery following unilateral oophorectomy. Using a single-port robotic system via the transvaginal route, hysterectomy, right salpingo-oophorectomy, and omentectomy were performed. Key technical steps included enhanced visualization with gauze placement and use of an additional robotic arm for omental traction. …

Promoting Professionalism In Medical Education: A Toolbox For Effective Feedback And Remediation, Matthew R Carroll, Gal Barak, Tracy Byrne, Huma Farid

Faculty, Staff and Students Publications

No abstract provided.

Impact Of A Maternal Early Warning System And Severe Hypertension Safety Bundle On Timely Treatment Of Hypertensive Emergencies: A Quality Improvement And Health Equity Initiative, Towana D Sims, Lauren Shubert, Stacie Denning, Lena Shay, Celeste Green, Christina Davidson

Faculty, Staff and Students Publications

Background: Hypertensive disorders of pregnancy are a leading cause of pregnancy-related morbidity and mortality. Timely treatment of a hypertensive emergency has the potential to reduce preeclampsia-related morbidity and mortality.

Objective: To evaluate the impact of quality improvement and patient safety initiatives on timely treatment of hypertensive emergencies in pregnancy and racial and ethnic disparities.

Setting: Maternity teaching hospital in Texas Medical Center.

Population: Pregnant and postpartum women with hypertensive emergencies.

Methods: A retrospective chart review of all hospital deliveries with a hypertensive emergency was conducted from 1 January 2017 through 31 December 2024. During the study period, our hospital implemented …

Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly

Center on Aging Staff Publications

Objective: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.

Methods: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50th percentile Area Deprivation Index, indicating low …

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

Faculty, Staff and Students Publications

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

Sars-Cov-2 Rna-Binding Protein Suppresses Extracellular Mirna Release, Hyejin Mun, Chang Hoon Shin, Qingxuan Fei, Andrea Estefania Lopez Giraldo, Kyoung-Min Choi, Ji Won Lee, Kyungmin Kim, Kyung-Won Min, Leilei Shi, Mark T Bedford, Dong-Chan Kim, Yoo Lim Chun, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Ryan T Westrope, Michelle Shay, Edward Nguyen, Junho K Hur, Abigail Agyenda, Nam Chul Kim, Sung-Ung Kang, Woonghee Lee, Je-Hyun Yoon

Faculty, Staff and Student Publications

SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, …

Frequency, Duration, And Cost Of Pulmonary Exacerbations Among Patients With Bronchiectasis, Maitreyee Mohanty, Claudia Leiras, Haiyan Sun, Reina Rau, John Fastenau, Joseph Feliciano, Sunjay R Devarajan

Faculty, Staff and Students Publications

Background: In administrative claims database studies of bronchiectasis, pulmonary exacerbations are usually defined using a fixed period for their start and end, which prevents assessment of exacerbation duration and thereby limits assessment of exacerbation characteristics. Here, we applied a novel cost-based algorithm to characterize exacerbations.

Methods: This cohort study used the Merative MarketScan Commercial Claims and Encounters database, 1-Jan-2016 to 31-Dec-2022. Patients ≥18 years with bronchiectasis (≥2 outpatient or ≥1 inpatient claim with bronchiectasis; no cystic fibrosis) had 12 months of continuous enrollment before (baseline) and ≥12 months after (follow-up) index (first bronchiectasis claim). Cost-based exacerbations were identified by compound …

Knowledge, Attitude And Practice Of Butchers Regarding Crimean Congo Hemorrhagic Fever In An Endemic Area Of Iran, Mohammad Amin Gorouhi, Abbas Aghaei Afshar, Najmeh Mansoori, Parya Jangipour Afshar, Leila Shirani-Bidabadi, Ismaeil Alizadeh, Nariman Shahhosseini

Chulalongkorn Medical Journal

Background: In endemic countries, Crimean-Congo hemorrhagic fever (CCHF) is an important zoonotic disease with significant public health implications. Previous studies in Iran suggests that CCHF poses a significant health risk to slaughterhouse workers and butchers. The main objecive of this study was to investigate the knowledge, attitude, and practice of butchers regarding CCHF at their workplace in an endemic area in southeastern Iran.

Methods: A descriptive cross-sectional study was conducted from January to March 2022 in Zarand city. In total, 60 butchers were included in the city. Statistical analysis was performed using SPSS version 22.

Results: The average scores of …

Interplay Of Menopause, Coronary Artery Calcium Score And Cardiovascular Disease Risk, Tanisha Mishra, Diksha Sanjana Pasnoor, Murtaza Gandhi, Nida Mohamed, Shaylika Chauhan, Kokou Adompreh-Fia, Kesha Mayank Doshi, Prerana Sevella, Rupak Desai

Abington Jefferson Health Papers

BACKGROUND: Postmenopausal women face an increased risk of cardiovascular disease (CVD) due to estrogen withdrawal, which exacerbates traditional cardiovascular risk factors such as dyslipidemia, glucose intolerance, and hypertension. Coronary Artery Calcium Score (CACS), a well-established marker of subclinical atherosclerosis, has emerged as a key predictor of adverse cardiovascular events. Despite the recognized association between menopause and heightened CVD risk, there remains a paucity of literature exploring the specific role of menopause in influencing CACS and its implications for cardiovascular morbidity and mortality.

AIM: To examine the interplay between menopause, CACS, and cardiovascular health by synthesizing existing literature.

METHODS: A comprehensive …

Hemorrhage-Related Maternal Morbidity Of Secondary Compared To Primary Postpartum Hemorrhage, Matthew R Carroll, Sarah Tounsi, Jessica L Gerard, Susan M Leong-Kee, Laurie S Swaim, Mark A Turrentine

Faculty, Staff and Students Publications

Objectives: To compare a composite hemorrhage-related maternal morbidity in individuals with secondary to primary postpartum hemorrhage and treatment interventions utilized.

Methods: A retrospective case-control study of deliveries complicated by secondary postpartum hemorrhage was performed at a tertiary care center. To estimate a clinically relevant increase of 50 % in the composite maternal hemorrhage-related maternal morbidity (35-53 % absolute increase) in individuals with secondary postpartum hemorrhage, a correlation coefficient of 0.2, at an 80 % power with a p < 0.05 with a two-sided test would require 95 individuals with secondary postpartum hemorrhage be matched to 95 individuals with a primary postpartum hemorrhage. Logistic regression analysis was used to evaluate the outcome of the composite of hemorrhage-related maternal morbidity.

Results: From January 2018 through December 2022, 33,026 deliveries occurred, and 94 individuals were identified that were admitted with secondary postpartum hemorrhage, …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

Development Of A Low-Barrier, Reimbursable Take-Home Naloxone Program At A Regional Health System, Kory S. London, Sejal Patel, Drew Lockstein, Jamal Rashid, Dennis Goodstein, Richard Pacitti, Tareva Warrick-Stone, Frederick Randolph, Alan Cherney, Karen Alexander, Megan Reed

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: Take-home naloxone (THN) programs in emergency departments (ED) can reduce opioid overdose deaths by providing naloxone directly to at-risk patients before discharge. However, sustainable models that integrate reimbursement and workflow alignment remain limited.

METHODS: A reimbursable ED-led THN program was developed across a large regional health system. The program used electronic health record (EHR)-integrated ordering, on-site kit dispensing, and third-party insurance billing when available. Kits were stocked in automated medication dispensing systems and supplemented by city-provided stock for uninsured patients. Pilot outcomes included kits dispensed and reimbursement rates across eight participating EDs.

RESULTS: A total of 2,520 naloxone kits …

Be Faster Community Of Practice To Increase Rapid Initiation Of Antiretroviral Therapy In Houston, Texas: A Pre-Post Intervention Study, Naomi Sequeira, Bich N Dang, Melanie Goebel, Monisha Arya, Avishek Ghosh-Hajra, Kathryn Fergus, Shital M Patel

Faculty, Staff and Students Publications

Background: Rapid initiation of antiretroviral therapy (Rapid ART) is a key strategy of the Ending the HIV Epidemic (EHE) initiative. The Baylor College of Medicine Extension for Community Healthcare Outcomes (ECHO) Facilitating Antiretroviral Start Earlier (BE FASTER) program was developed to address this call-to-action. The program uses the ProjectECHO tele-mentoring model as an implementation tool in Harris County, a priority EHE jurisdiction. The authors present results on the acceptability and feasibility of the BE FASTER program.

Methods: Multidisciplinary health professionals from 5 Ryan White Part A funded agencies formed the community of practice. The BE FASTER program included 9 monthly …

Application Of Freezetb, A Targeted Nanopore Sequencing Assay, For Identification Of Drug Resistance And Lineages Among Pulmonary Tuberculosis Cases In Alaska, Bryce Inman, Jeremy Butler, Soren George-Nichol, Ganna Kovalenko, Theresa Savidge, Yvette Vergnetti, Catherine Pongratz, Elizabeth Bee, Andrew R Dinardo, Alexander Kay, Anna Mandalakas, Eric Bortz, Tara E Ness

Faculty, Staff and Students Publications

Alaska has the highest incidence of tuberculosis (TB) in the United States, with 8% mortality while undergoing TB treatment. With a quarter of TB cases lacking sputum culture to enable drug resistance testing, FreezeTB aimed to develop tools tailored to meet the challenges in Alaska while being translatable to other settings. We designed a rapid and cost-effective laboratory workflow and software to identify drug-resistant mutations in Mycobacterium tuberculosis using targeted next-generation sequencing (tNGS). FreezeTB, a Fast, Reliable, Economical Evaluation tool to Zap Endemic Tuberculosis, amplifies 22 gene loci associated with resistance to 16 anti-tuberculosis drugs. M. tuberculosis isolates from Alaska …

Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver, Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO®), a tyrosine kinase inhibitor, is approved for treating tenosynovial giant cell tumor in adults. However, its potential to cause fatal liver injury has prompted the U.S. FDA to issue a black box warning, and the mechanisms underlying its hepatotoxicity remain largely unknown. As biotransformation may contribute to PEX-induced hepatotoxicity, understanding its metabolism is essential. Our previous research indicated that PEX forms reactive metabolites in human and mouse liver microsomes and in human hepatocytes. We investigated PEX metabolism and liver distribution in mice with a focus on metabolite characterization. Our data shows that PEX is mainly excreted into …

Vitamin D Is Glucoprotective In Aging Males But Not Females, Olivia Z B Ginnard, Maria Morales, Ji Youn Youn, Yong Xu, Stephanie R Sisley

Faculty, Staff and Students Publications

Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vitamin D deficiency in older adults. However, there is a discrepancy between clinical trials in adults on the efficacy of vitamin D treatment in prediabetes and diabetes. In addition, human data indicates there may be sexual dimorphism in the effect of vitamin D deficiency on dysglycemia that is more pronounced in men. These incongruities may be due to our limited understanding of the underlying mechanisms of vitamin D in …

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

A Practical Primer On How To Detect And Treat Depression In Ckd, L Parker Gregg, Lynnel Goodman, Ella Q Carroll, S Susan Hedayati

Faculty, Staff and Students Publications

Detection and management of depression have special considerations in people with kidney disease. Screening should be done every 6-12 months using a self-reported questionnaire. Clinicians should rule out symptoms from medical conditions such as dialysis inadequacy or hypothyroidism and confirm the presence of sadness or anhedonia. Sertraline has shown limited efficacy and an increased risk for adverse effects such as gastrointestinal symptoms, so cautious, gradual dose titration is warranted. Cognitive behavioral therapy has potential benefit for depressive symptoms in people with kidney disease. Current trials are evaluating behavioral activation therapy. Physical activity has many benefits and likely improves depression.

Discovery Of A Novel Small Molecule Degrader Of Wild Type And Mutant Estrogen Receptors Using Dna Encoded Libraries, Anil Kumar Devakrishnan, Chandrashekhar Madasu, Yong Wang, Ramkumar Modukuri, Kurt M Bohren, Kevin R Mackenzie, Damian W Young, Suzanne A W Fuqua, Martin M Matzuk, Murugesan Palaniappan

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) variants with mutations in the ligand binding domain (LBD) are less sensitive than wild type to standard-of-care drugs that bind ERα directly. To identify novel small-molecule drugs that target ERα mutants, we screened our multibillion-compound DNA-encoded libraries against ERα LBD variants. CDD-1274, which was highly enriched with all three variants, blocked spontaneous coactivator peptide recruitment to mutant ERα LBDs and inhibited estradiol-driven proliferative markers in several ER-positive breast cancer cell lines, but not in ER-negative breast cancer cells. We demonstrated that CDD-1274 induced proteasomal degradation of ERα variants in breast cancer cell lines and caused Y537S …

Immunogenomic Diversity Of Triple-Negative Breast Cancers In Obese And Non-Obese Black And White Women, Fokhrul Hossain, Denise Danos, Jovanny Zabaleta, Xiao-Cheng Wu, Luis Del Valle, Chindo Hicks, Jiande Wu, Jerneja Tomsic, Susan Neuhausen, Yuan Chun Ding, Kavitha Mukund, Zahra Mesrizadeh, Shankar Subramaniam, Augusto Ochoa, Victoria Seewaldt, Lucio Miele

School of Medicine Faculty Publications

Racial disparities in incidence and outcomes of triple-negative breast cancer (TNBC) have been attributed to ancestry, socioeconomic factors and/or obesity. We studied 253 TNBCs from 128 Black and 125 White women. Arms were balanced for age, AJCC stage, histological grade and molecular subtypes, and differed significantly in BMI distribution, obesity, and Area Deprivation Index. We examined survival rates, whole-transcriptome RNASeq and genetic ancestry. In our sample, Black race or obesity were not intrinsically predictive of poor outcomes. TNBC molecular portraits varied with stage and biological aggressiveness, irrespective of race. We identified a novel group of TNBCs with a distinctive luminal-like …

Preclinical Efficacy Of Tasquinimod-Based Combinations In Advanced Myeloproliferative Neoplasms In Blastic Phase, Warren Fiskus, Lucia Masarova, Christopher P Mill, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Taghi Manshouri, Andrew Dunbar, Surbhi Sharma, Tapan M Kadia, Courtney D Dinardo, Prithviraj Bose, Naveen Pemmaraju, Sanam Loghavi, Xiaoping Su, Raajit K Rampal, Marie Törngren, Kapil N Bhalla

Faculty, Staff and Students Publications

The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. A8 and A9 are secreted into the extracellular space and plasma, in which they interact with Toll-like receptor 4, receptor for advanced glycation end products, and CD33. In these studies, we determined the preclinical efficacy of tasquinimod (TQ) against advanced myeloproliferative neoplasm (MPN) cell lines and patient-derived (PD) CD34+ blastic phase (BP; >5% blasts in the peripheral blood) MPN cells. TQ induced loss of viability in cell lines and PD MPN-BP cells, but not in normal CD34+ progenitor cells. In TQ-treated PD …

‘In Texas, Everybody Wants Antibiotics’: Reducing Inappropriate Antibiotic Expectations And Use With A Provider-Patient Communication Tool In Primary Care, Ashley Collazo, Paige Wermuth, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Roger Zoorob, Barbara Wells Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Background/objective: Patients often expect antibiotics for self-limiting diseases, pressuring providers to prescribe antibiotics unnecessarily. These expectations also contribute to the unsafe practice of taking antibiotics without a prescription (non-prescription use), such as pills retained from prior prescriptions or antibiotics from non-medical sources. Previous work shows that non-prescription use is due to strong, widely held misconceptions regarding the curative power of antibiotics. To reduce unnecessary use of antibiotics, we developed and pilot-tested a patient-focused, bilingual (English and Spanish) educational tool with patient and provider stakeholder input. The tool, a trifold brochure, included information on safe antibiotic use, potential antibiotic harms and …

Social Determinants Of Health Patterns In Children With Severe Disease Due To Sars-Cov-2 Infection-An Exploratory Approach, Joshua Prabhu, Sebastian Acosta, Fabio Savorgnan, Ananth V Annapragada, Usha Sethuraman

Faculty, Staff and Students Publications

Background/Objectives: Research on the association of adverse social determinants of health (SDOH) with severe pediatric coronavirus disease (COVID-19) is limited. We examined associations between SDOH patterns and COVID-19 severity in children.

Methods: We conducted a prospective, observational study of children (< 18 years) with symptomatic SARS-CoV-2 infection evaluated in an urban pediatric emergency department (March 2021-April 2022) in Detroit, Michigan. Caregivers completed a 34-item survey based on the Healthy People 2030 framework. Severe disease was defined as the occurrence of respiratory/cardiac failure or death within four weeks of diagnosis. Continuous and categorical variables were described using medians and percentages, respectively. Associations between disease severity and risk factors were determined using chi-square tests. Association rule mining was used for feature selection, followed by multivariate logistic regression.

Results: We analyzed data from 354 children [6-12 years: 31.1%, Female: 51.1%, Black: 59%, not Hispanic: 84.7%, public insurance: 77.1%, chronic condition: 27.4%]. Of the total, 113 children had severe disease. Most caregivers were 30-44 years old (53.1%), had less than a college degree (70.4%), and income < USD 50,000 (75.2%). Adverse SDOH reported included food/housing insecurity (24.6%), no support (64.7%), unmet childcare needs (35.9%), and lack of transportation (12.7%). After controlling for age, sex, medical history, income, and obesity, severe disease was associated with caregiver use of drugs/alcohol (OR:5.92, p < 0.001) and social discrimination/lack of support (OR: 1.74, p = 0.030).

Conclusions: Two SDOH patterns (caregiver use of drugs/alcohol …

Mutant P53 Variants Differentially Impact Replication Initiation And Activate Cgas-Sting To Affect Immune Checkpoint Inhibition, Kang Liu, Lidija A Wilhelms Garan, Fang-Tsyr Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

Prior research shows that Akt-dependent phosphorylation of TopBP1 in S phase results in the switch of TopBP1/Treslin binding to TopBP1/E2F1 binding, which is important to prevent replication re-initiation in late S and G2 phases. Here, we demonstrate that contact, but not conformational, mutant p53 can override this switch by binding to both TopBP1 and Treslin, thereby facilitating persistent TopBP1/Treslin interaction in late S and G2 phases, which ultimately leads to over-firing of replication initiation. This increases micronuclei formation, which is further enhanced by genotoxic stressors such as doxorubicin, PARP inhibitors, or ATR inhibitors. Consequently, contact mutant p53 increases the sensitivity …

Disparate Leukemia Mutations Converge On Nuclear Phase-Separated Condensates, Gandhar K Datar, Elmira Khabusheva, Archish Anand, Joshua Beale, Marwa Sadek, Chun-Wei Chen, Evdokiia Potolitsyna, Nayara Alcantara-Contessoto, Guangyuan Liu, Josephine De La Fuente, Christina Dollinger, Anna Guzman, Alejandra Martell, Katharina Wohlan, Abhishek Maiti, Nicholas J Short, S Stephen Yi, Vibeke Andresen, Bjørn Tore Gjertsen, Brunangelo Falini, Rachel E Rau, Lorenzo Brunetti, Nidhi Sahni, Margaret A Goodell, Joshua A Riback

Faculty, Staff and Students Publications

During cancer development, mutations promote changes in gene expression that cause transformation. Leukemia associated with aberrant HOXA expression is driven by translocations of nucleoporin genes or KMT2A as well as mutations in NPM1. The mechanistic convergence of these disparate mutations remains elusive. Here, we demonstrate that mutant nucleophosmin 1 (NPM1c) forms nuclear condensates in human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to recruit NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting …