Public Health Commons^™

Breastfeeding Initiation, Duration, And Associated Factors Among People With Hepatitis C Virus Infection, Jennifer L Grasch, Jessica A De Voest, George R Saade, Brenna L Hughes, Uma M Reddy, Maged M Costantine, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection.

METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and …

Migraines, Vasomotor Symptoms, And Cardiovascular Disease In The Coronary Artery Risk Development In Young Adults Study, Catherine Kim, Pamela J Schreiner, Zhe Yin, Rachael Whitney, Stephen Sidney, Imo Ebong, Deborah A Levine

Faculty, Staff and Student Publications

Objective: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes.

Methods: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) …

Diras3 Induces Autophagy And Enhances Sensitivity To Anti-Autophagic Therapy In Kras-Driven Pancreatic And Ovarian Carcinomas, Gamze Bildik, Joshua P Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R Orellana, Olivier De Wever, Mark S Carey, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal …

Performance Characteristics Of Sepsis Screening Tools During Antepartum And Postpartum Admissions, Melissa E Bauer, Matt Fuller, Vesela Kovacheva, Rania Elkhateb, Kristen Azar, Morgan Caldwell, Vanna Chiem, Mindy Foster, Ronald Gibbs, Brenna L Hughes, Rebecca Johnson, Nobin Kottukapally, Melissa G Rosenstein, Magdalena Sanz Cortes, Laurence E Shields, Sylvia Sudat, Caitlin D Sutton, Paloma Toledo, Austin Traylor, Kurt Wharton, Elliott Main

Faculty, Staff and Students Publications

Objective: To evaluate the performance characteristics of existing screening tools for the prediction of sepsis during antepartum and postpartum readmissions.

Methods: This was a case-control study using electronic health record data obtained between 2016 and 2021 from 67 hospitals for antepartum sepsis admissions and 71 hospitals for postpartum readmissions up to 42 days. Patients in the sepsis case group were matched in a 1:4 ratio to a comparison cohort of patients without sepsis admitted antepartum or postpartum. The following screening criteria were evaluated: the CMQCC (California Maternal Quality Care Collaborative) initial sepsis screen, the non-pregnancy-adjusted SIRS (Systemic Inflammatory Response Syndrome), …

Performance Characteristics Of Sepsis Screening Tools During Delivery Admissions, Elliott K Main, Matt Fuller, Vesela P Kovacheva, Rania Elkhateb, Kristen Azar, Morgan Caldwell, Vanna Chiem, Mindy Foster, Ronald Gibbs, Brenna L Hughes, Rebecca Johnson, Nobin Kottukapally, Magdalena Sanz Cortes, Melissa G Rosenstein, Laurence E Shields, Sylvia Sudat, Caitlin D Sutton, Paloma Toledo, Austin Traylor, Kurt Wharton, Melissa E Bauer

Faculty, Staff and Students Publications

Objective: To evaluate the screening performance characteristics of existing tools for the diagnosis of sepsis during delivery admissions.

Methods: This was a case-control study using electronic health record data, including vital signs and laboratory results, for all delivery admissions of patients with sepsis from 59 nationally distributed hospitals. Patients with sepsis were matched by gestational age at delivery in a 1:4 ratio with patients without sepsis to create a comparison group. Patients with chorioamnionitis and sepsis were compared with a complete cohort of patients with chorioamnionitis without sepsis. Multiple screening criteria for sepsis were evaluated: the CMQCC (California Maternal Quality …

Incongruity Between T Cell Receptor Recognition Of Breast Cancer Hotspot Mutations Esr1 Y537s And D538g Following Exogenous Peptide Loading Versus Endogenous Antigen Processing, Paul Shafer, Wingchi K Leung, Mae Woods, Jong Min Choi, Carlos M Rodriguez-Plata, Arushana Maknojia, Andres Mosquera, Lauren K Somes, Jarrett Joubert, Anthony Manliguez, Rashi Ranjan, Bryan Burt, Hyun-Sung Lee, Bing Zhang, Suzanne Fuqua, Cliona Rooney, Ann M Leen, Valentina Hoyos

Faculty, Staff and Students Publications

T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease. Through IFN-γ ELISpot screening of in vitro expanded neopeptide-stimulated T cell lines from healthy donors and MBC patients, we identified reactivity towards 11 of …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …

Estrogen Signaling In The Dorsal Raphe Regulates Binge-Like Drinking In Mice, Valeria C Torres Irizarry, Bing Feng, Xiaohua Yang, Nirali Patel, Sarah Schaul, Lucas Ibrahimi, Hui Ye, Pei Luo, Leslie Carrillo-Sáenz, Penghua Lai, Maya Kota, Devin Dixit, Chunmei Wang, Amy W Lasek, Yanlin He, Pingwen Xu

Faculty, Staff and Students Publications

Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had …

Susceptible Windows Of Prenatal And Postnatal Fine Particulate Matter Exposures And Attention-Deficit Hyperactivity Disorder Symptoms In Early Childhood, Wei-Jen Chen, Alison M Rector-Houze, Mònica Guxens, Carmen Iñiguez, Michael D Swartz, Elaine Symanski, Jesús Ibarluzea, Antonia Valentin, Aitana Lertxundi, Llúcia González-Safont, Jordi Sunyer, Kristina W Whitworth

Faculty, Staff and Student Publications

Few prior studies have explored windows of susceptibility to fine particulate matter (PM_2.5) in both the prenatal and postnatal periods and children’s attention-deficit/hyperactivity disorder (ADHD) symptoms.

We analyzed data from 1,416 mother-child pairs from the Spanish INMA (INfancia y Medio Ambiente) Study (2003–2008). Around 5 years of age, teachers reported the number of ADHD symptoms (i.e., inattention, hyperactivity/impulsivity) using the ADHD Diagnostic and Statistical Manual of Mental Disorders. Around 7 years of age, parents completed the Conner’s Parent Rating Scales, from which we evaluated the ADHD index, cognitive problems/inattention, hyperactivity, and oppositional subscales, reported as age- and sex-standardized …

Multivalent Cytomegalovirus Glycoprotein B Nucleoside Modified Mrna Vaccines Did Not Demonstrate A Greater Antibody Breadth, Hsuan-Yuan Wang, Leike Li, Cody S Nelson, Richard Barfield, Sarah Valencia, Cliburn Chan, Hiromi Muramatsu, Paulo J C Lin, Norbert Pardi, Zhiqiang An, Drew Weissman, Sallie R Permar

Faculty, Staff and Student Publications

Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy. To determine whether vaccination with multiple HCMV gB genotypes could increase the breadth of anti-HCMV gB humoral and cellular responses, we immunized 18 female …

The Impact Of The Turkish Population Variome On The Genomic Architecture Of Rare Disease Traits, Zeynep Coban-Akdemir, Xiaofei Song, Francisco C Ceballos, Davut Pehlivan, Ender Karaca, Yavuz Bayram, Tadahiro Mitani, Tomasz Gambin, Tugce Bozkurt-Yozgatli, Shalini N Jhangiani, Donna M Muzny, Richard A Lewis, Pengfei Liu, Eric Boerwinkle, Ada Hamosh, Richard A Gibbs, V Reid Sutton, Nara Sobreira, Claudia M B Carvalho, Chad A Shaw, Jennifer E Posey, David Valle, James R Lupski

Faculty, Staff and Student Publications

PURPOSE: The variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated for insights on the genomic architecture of disease.

METHODS: We generated and analyzed a database of variants derived from exome sequencing data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits and 643 unaffected relatives.

RESULTS: Using uniform manifold approximation and projection, we showed that the TK genomes are more similar to those of Europeans and consist of 2 main subpopulations: clusters 1 and 2 (

CONCLUSION: Our findings support the notion that …

Frequency Specific Optogenetic Stimulation Of The Locus Coeruleus Induces Task-Relevant Plasticity In The Motor Cortex, Ching-Tzu Tseng, Hailey F Welch, Ashley L Gi, Erica Mina Kang, Tanushree Mamidi, Sahiti Pydimarri, Kritika Ramesh, Alfredo Sandoval, Jonathan E Ploski, Catherine A Thorn

Faculty, Staff and Student Publications

The locus ceruleus (LC) is the primary source of neocortical noradrenaline, which is known to be involved in diverse brain functions including sensory perception, attention, and learning. Previous studies have shown that LC stimulation paired with sensory experience can induce task-dependent plasticity in the sensory neocortex and in the hippocampus. However, it remains unknown whether LC activation similarly impacts neural representations in the agranular motor cortical regions that are responsible for movement planning and production. In this study, we test whether optogenetic stimulation of the LC paired with motor performance is sufficient to induce task-relevant plasticity in the somatotopic cortical …

Protecting Human And Animal Health: The Road From Animal Models To New Approach Methods, Barbara L F Kaplan, Alan M Hoberman, William Slikker, Mary Alice Smith, Emanuela Corsini, Thomas B Knudsen, M Sue Marty, Sonya K Sobrian, Suzanne C Fitzpatrick, Marcia H Ratner, Donna L Mendrick

Faculty, Staff and Student Publications

Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacological, and regulatory research to provide safety assessments for drugs and chemicals. There are concerns that animals do not provide sufficient information on toxicity and/or efficacy to protect the target population, so scientists are utilizing the principles of replacement, reduction, and refinement (the 3Rs) and increasing the development and application of new approach methods (NAMs). NAMs are any technology, methodology, approach, or assay used …

Impact Of An Integrated Health, Nutrition, And Early Child Stimulation And Responsive Care Intervention Package Delivered To Preterm Or Term Small For Gestational Age Babies During Infancy On Growth And Neurodevelopment: Study Protocol Of An Individually Randomized Controlled Trial In India (Small Babies Trial), Ranadip Chowdhury, Rukman Manapurath, Ingvild Fossgard Sandøy, Ravi Prakash Upadhyay, Neeta Dhabhai, Saijuddin Shaikh, Harish Chellani, Tarun Shankar Choudhary, Abhinav Jain, Jose Martines, Nita Bhandari, Tor A Strand, Sunita Taneja

Faculty, Staff and Student Publications

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating.

METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata …

Unsatisfactory Fecal Immunochemical Tests For Colorectal Cancer Screening: Prevalence, Reasons, And Subsequent Testing, Po-Hong Liu, Rasmi G Nair, Celette Sugg Skinner, Caitlin C Murphy, Eric J Kim, Cynthia Ortiz, Lei Wang, Ellen Hu, Jacquelyn M Lykken, Theodore R Levin, Beverly B Green, Erin E Hahn, Noel Santini, Ethan A Halm

Faculty, Staff and Student Publications

BACKGROUND: Fecal immunochemical test (FIT) is an effective colorectal cancer screening modality. Little is known about prevalence, reasons, and testing after unsatisfactory FIT, or a FIT that cannot be processed by the laboratory due to inadequate stool specimen or incomplete labeling.

METHODS: Our retrospective cohort study examined unsatisfactory FIT among average-risk individuals aged 50-74 years in a large, integrated, safety-net health system who completed an index FIT from 2010 to 2019. We determined prevalence of unsatisfactory FIT and categorized reasons hierarchically. We used multivariable logistic regression models to identify factors associated with: (i) unsatisfactory FIT; and (ii) subsequent testing within …

Neonatal Intensive Care Unit Resource Use For Infants At 22 Weeks' Gestation In The Us, 2008-2021, Matthew A Rysavy, Monica M Bennett, Kaashif A Ahmad, Ravi M Patel, Zubin S Shah, Dan L Ellsbury, Reese H Clark, Veeral N Tolia

Faculty, Staff and Student Publications

IMPORTANCE: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks' gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown.

OBJECTIVE: To characterize recent trends in NICU resource utilization for infants born at 22 weeks' gestation compared with other extremely preterm infants (≤28 weeks' gestation) and other NICU-admitted infants.

DESIGN, SETTING, AND PARTICIPANTS: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. …

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Faculty, Staff and Student Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Efficacy And Safety Of Autologous Tumor-Infiltrating Lymphocytes In Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, And Pancreatic Ductal Adenocarcinoma, Rodabe Amaria, Anne Knisely, David Vining, Scott Kopetz, Michael J Overman, Milind Javle, Mara B Antonoff, Ching-Wei D Tzeng, Robert A Wolff, Shubham Pant, Kathryn Lito, Kelly Rangel, Bryan Fellman, Ying Yuan, Karen H Lu, Donastas Sakellariou-Thompson, Cara L Haymaker, Marie-Andrée Forget, Patrick Hwu, Chantale Bernatchez, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.

METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was …

Racial/Ethnic Disparities In The Association Between Patient Care Experiences And Receipt Of Initial Surgical Breast Cancer Care: Findings From Seer-Cahps, Mariana Arevalo, Trevor A Pickering, Sally W Vernon, Kayo Fujimoto, Melissa F Peskin, Albert J Farias

Faculty, Staff and Student Publications

PURPOSE: We determined whether racial/ethnic differences in patient experiences with care influence timeliness and type of initial surgical breast cancer treatment for a sample of female Medicare cancer patients.

METHODS: We conducted a retrospective cohort study using the linked Epidemiology and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) dataset. The outcomes were: (1) time-to-initial surgical treatment, and (2) type of treatment [breast conserving surgery (BCS) vs. mastectomy]. The indicators were reports of four types of patient experiences with care including doctor communication, getting care quickly, getting needed care, and getting needed Rx. Interaction terms in each multivariable logistic …

Gut Microbiome Of Patients With Breast Cancer In Vietnam, Sang M Nguyen, Huong T T Tran, Jirong Long, Martha J Shrubsole, Hui Cai, Yaohua Yang, Lan M Nguyen, Giang H Nguyen, Chu V Nguyen, To V Ta, Jie Wu, Qiuyin Cai, Wei Zheng, Thuan V Tran, Xiao-Ou Shu

Faculty, Staff and Student Publications

PURPOSE: Gut microbiota play an important role in human health, including cancer. Cancer and its treatment, in turn, may alter the gut microbiome. To understand this complex relationship, we profiled the gut microbiome of 356 Vietnamese patients with breast cancer.

MATERIALS AND METHODS: Stool samples were collected before chemotherapy, with 162 pre- and 194 postsurgery. The gut microbiome was measured by shotgun metagenomic sequencing. Associations of gut microbial diversity, taxa abundance, and gut microbiome health index (GMHI) with sociodemographic, clinical factors, and tumor characteristics were evaluated.

RESULTS: Postsurgery samples were associated with significantly lower α- and β-diversities (

CONCLUSION: Our …

Anatomy Of The Female Reproductive Tract Organs Of The Brown Anole (Anolis Sagrei), Bonnie K Kircher, Edward L Stanley, Richard R Behringer

Faculty, Staff and Student Publications

Female reproduction in squamate reptiles (lizards and snakes) is highly diverse and mode of reproduction, clutch size, and reproductive tract morphology all vary widely across this group of ~11,000 species. Recently, CRISPR genome editing techniques that require manipulation of the female reproductive anatomy have been developed in this group, making a more complete understanding of this anatomy essential. We describe the adult female reproductive anatomy of the model reptile the brown anole (Anolis sagrei). We show that the brown anole female reproductive tract has three distinct anterior-to-posterior regions, the infundibulum, the glandular uterus, and the nonglandular uterus. The infundibulum has …

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Using Mobile Technology For Family-Based Prevention In Families With Low Incomes: Lessons From A Randomized Controlled Trial Of A Childhood Obesity Prevention Program, Thomas G Power, Susan S Baker, Karen V Barale, M Catalina Aragón, Jane D Lanigan, Louise Parker, Karina Silva Garcia, Garry Auld, Nilda Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Researchers are increasingly using web-based technologies to deliver family-based, prevention programming. Few studies have examined the success of such approaches for families with low incomes. The purpose of this study was to describe the level of in-class and online engagement in a childhood obesity prevention program for parents with low incomes, to examine the demographic correlates of parent engagement, and to examine dosage effects on parental feeding outcomes as a function of online exposure. All participants attended in-class nutrition education classes (Eating Smart · Being Active) as part of the Expanded Food and Nutrition Education Program (EFNEP) in Colorado and …

Herpes Zoster And Risk Of Incident Parkinson's Disease In Us Veterans: A Matched Cohort Study, Louis Tunnicliffe, Rimona S Weil, Judith Breuer, Maria C Rodriguez-Barradas, Liam Smeeth, Christopher T Rentsch, Charlotte Warren-Gash

Faculty, Staff and Students Publications

Background: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear.

Objective: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs.

Methods: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes.

Results: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years …

The Human Vaginal Microbiota: From Clinical Medicine To Models To Mechanisms, Samantha Ottinger, Clare M Robertson, Holly Branthoover, Kathryn A Patras

Faculty, Staff and Students Publications

The composition of the vaginal microbiota is linked to numerous reproductive health problems, including increased susceptibility to infection, pregnancy complications, and impaired vaginal tissue repair; however, the mechanisms contributing to these adverse outcomes are not yet fully defined. In this review, we highlight recent clinical advancements associating vaginal microbiome composition and function with health outcomes. Subsequently, we provide a summary of emerging models employed to identify microbe-microbe interactions contributing to vaginal health, including metagenomic sequencing, multi-omics approaches, and advances in vaginal microbiota cultivation. Last, we review new in vitro, ex vivo, and in vivo models, such as organoids and humanized …

Effect Of Russian Current Expert Modes On Quadriceps Muscle Torque In Healthy Adults: A Single-Blinded Randomized Controlled Trial, Ansam Hasan, Ibrahim Moustafa, Tamer Shousha

Faculty, Staff and Student Publications

BACKGROUND: Russian current (RC), a well-known neuromuscular electrical stimulation operating at 2500 Hz, has demonstrated significant strength improvement over traditional exercises due to its high tolerance and low pain provocation. Despite extensive NMES parameter research, the specific effects of expert modes, particularly ON2 and Rest, remain unexplored. This study investigates the direct effect of these expert modes on quadriceps muscle strength in healthy adults.

METHODS: This is a single-blind, randomization-controlled trial. Forty-eight healthy university students (31 females, 17 males) were assigned in two randomized experimental groups either the ON2 or Rest mode for a 15-minute electrical stimulation session. Quadriceps maximum …

Prenatal Cocaine Exposure And Its Influence On Pediatric Epigenetic Clocks And Epigenetic Scores In Humans, Thiago Wendt Viola, Christina Danzer, Victor Mardini, Claudia Szobot, João Henrique Chrusciel, Laura Stertz, Joy M Schmitz, Consuelo Walss-Bass, Gabriel R Fries, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale …

Epha2- And Hdac-Targeted Combination Therapy In Endometrial Cancer, Robiya Joseph, Santosh K Dasari, Sujanitha Umamaheswaran, Lingegowda S Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T Powell, Mary Sobieski, Yuan Liu, Mark Seungwook Kim, Sara Corvigno, Katherine Foster, Pahul Hanjra, Thanh Chung Vu, Mamur A Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N Westin, Anil K Sood

Faculty, Staff and Student Publications

Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival …

Evaluation Of Potential Biomarkers For Lenvatinib Plus Pembrolizumab Among Patients With Advanced Endometrial Cancer: Results From Study 111/Keynote-146, Vicky Makker, Matthew H Taylor, Carol Aghajanian, Allen L Cohn, Marcia S Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E Dutcus, Yukinori Minoshima, Mark J Messing

Faculty, Staff and Student Publications

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

METHODS: Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell-inflamed gene expression profile (Tcell …

Analysis Of Breast Cancer Mortality In The Us-1975 To 2019, Jennifer L Caswell-Jin, Liyang P Sun, Diego Munoz, Ying Lu, Yisheng Li, Hui Huang, John M Hampton, Juhee Song, Jinani Jayasekera, Clyde Schechter, Oguzhan Alagoz, Natasha K Stout, Amy Trentham-Dietz, Sandra J Lee, Xuelin Huang, Jeanne S Mandelblatt, Donald A Berry, Allison W Kurian, Sylvia K Plevritis

Faculty, Staff and Student Publications

IMPORTANCE: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear.

OBJECTIVE: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality.

DESIGN, SETTING, AND PARTICIPANTS: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by …