Medicine and Health Sciences Commons^™

Damaged Mitochondria Coincide With Presynaptic Vesicle Loss And Abnormalities In Alzheimer’S Disease Brain, Wenzhang Wang, Fanpeng Zhao, Yubing Lu, Sandra L Siedlak, Hisashi Fujioka, Hao Feng, George Perry, Xiongwei Zhu

Faculty, Staff and Student Publications

Loss of synapses is the most robust pathological correlate of Alzheimer's disease (AD)-associated cognitive deficits, although the underlying mechanism remains incompletely understood. Synaptic terminals have abundant mitochondria which play an indispensable role in synaptic function through ATP provision and calcium buffering. Mitochondrial dysfunction is an early and prominent feature in AD which could contribute to synaptic deficits. Here, using electron microscopy, we examined synapses with a focus on mitochondrial deficits in presynaptic axonal terminals and dendritic spines in cortical biopsy samples from clinically diagnosed AD and age-matched non-AD control patients. Synaptic vesicle density within the presynaptic axon terminals was significantly …

Neurochemical Effects Of Sepsis On The Brain, Tatiana Barichello, Vijayasree V Giridharan, Carlos Henrique R Catalão, Cristiane Ritter, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB …

Design Of The Combination Effect Of Finerenone And Empagliflozin In Participants With Chronic Kidney Disease And Type 2 Diabetes Using A Uacr Endpoint Study (Confidence), Jennifer B Green, Amy K Mottl, George Bakris, Hiddo J L Heerspink, Johannes F E Mann, Janet B Mcgill, Masaomi Nangaku, Peter Rossing, Charlie Scott, Alain Gay, Rajiv Agarwal

2020-Current year OA Pubs

BACKGROUND: Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and an SGLT2i is superior to either agent alone.

METHODS: CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicenter, three-armed, parallel-group, 7.5 - to 8.5-month, Phase 2 study in 807 adults with T2D, stage 2-3 CKD and a …

A Learned Map For Places And Concepts In The Human Medial Temporal Lobe, Nora A. Herweg, Lukas Kunz, Daniel Schonhaut, Armin Brandt, Paul A. Wanda, Ashwini D. Sharan, Michael R. Sperling, Andreas Schulze-Bonhage, Michael J. Kahana

Department of Neurology Faculty Papers

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information …

Functional Effects Of Disease-Associated Variants Reveal That The S1-M1 Linker Of The Nmda Receptor Critically Controls Channel Opening, Lingling Xie, Miranda J Mcdaniel, Riley E Perszyk, Sukhan Kim, Gerarda Cappuccio, Kevin A Shapiro, Beatriz Muñoz-Cabello, Pedro A Sanchez-Lara, Katheryn Grand, Jing Zhang, Kelsey A Nocilla, Rehan Sheikh, Lluis Armengol, Roberta Romano, Tyler Mark Pierson, Hongjie Yuan, Scott J Myers, Stephen F Traynelis

Faculty, Staff and Students Publications

The short pre-M1 helix within the S1-M1 linker (also referred to as the pre-M1 linker) between the agonist-binding domain (ABD, S1) and the M1 transmembrane helix of the NMDA receptor (NMDAR) is devoid of missense variants within the healthy population but is a locus for de novo pathogenic variants associated with neurological disorders. Several de novo variants within this helix have been identified in patients presenting early in life with intellectual disability, developmental delay, and/or epilepsy. In this study, we evaluated functional properties for twenty variants within the pre-M1 linker in GRIN1, GRIN2A, and GRIN2B genes, including six novel missense …

Dear Pandemic: A Topic Modeling Analysis Of Covid-19 Information Needs Among Readers Of An Online Science Communication Campaign., Aleksandra M Golos, Sharath Chandra Guntuku, Rachael Piltch-Loeb, Lindsey J Leininger, Amanda M Simanek, Aparna Kumar, Sandra S Albrecht, Jennifer Beam Dowd, Malia Jones, Alison M Buttenheim

College of Nursing Faculty Papers & Presentations

BACKGROUND: The COVID-19 pandemic was accompanied by an "infodemic"-an overwhelming excess of accurate, inaccurate, and uncertain information. The social media-based science communication campaign Dear Pandemic was established to address the COVID-19 infodemic, in part by soliciting submissions from readers to an online question box. Our study characterized the information needs of Dear Pandemic's readers by identifying themes and longitudinal trends among question box submissions.

METHODS: We conducted a retrospective analysis of questions submitted from August 24, 2020, to August 24, 2021. We used Latent Dirichlet Allocation topic modeling to identify 25 topics among the submissions, then used thematic analysis to …

Assessment Of Bladder Pressure And Discomfort Symptoms: How Do Overactive Bladder Differ From Interstitial Cystitis/Bladder Pain Syndrome Patients?, Angelíca Gousse, Joel Vetter, H Henry Lai

2020-Current year OA Pubs

BACKGROUND: To better understand the sensation of bladder "pressure" and "discomfort", and how they are similar or distinct from the "pain" and "urgency" symptoms in IC/BPS and OAB.

METHODS: IC/BPS and OAB patients rated their bladder pain, pressure, discomfort, and urinary urgency on separate 0-10 numeric rating scales (NRS). Their NRS ratings were compared between IC/BPS and OAB, and Pearson correlations were performed.

RESULTS: Among IC/BPS patients (n = 27), their mean numeric ratings of pain, pressure, discomfort, and urinary urgency were almost identical (6.6 ± 2.1, 6.0 ± 2.5, 6.5 ± 2.2, and 6.0 ± 2.8 respectively). The three-way …

Covariate-Specific Evaluation Of Continuous Biomarker, Ziyi Li, Yijian Huang, Dattatraya Patil, Mark Rubin, Martin G Sanda

Faculty, Staff and Student Publications

Diagnostic tests usually need to operate at a high sensitivity or specificity level in practice. Accordingly, specificity at the controlled sensitivity, or vice versa, is a clinically sensible performance metric for evaluating continuous biomarkers. Meanwhile, the performance of a biomarker may vary across sub-populations as defined by covariates, and covariate-specific evaluation can be informative. In this article, we develop a novel modeling and estimation method for covariate-specific specificity at a controlled sensitivity level. Unlike existing methods which typically adopt elaborate models of covariate effects over the entire biomarker distribution, our approach models covariate effects locally at a specific sensitivity level …

Interaction Analysis Of Ancestry-Enriched Variants With Apoe-Ɛ4 On Mci In The Study Of Latinos-Investigation Of Neurocognitive Aging, Einat Granot-Hershkovitz, Rui Xia, Yunju Yang, Brian Spitzer, Wassim Tarraf, Priscilla M Vásquez, Richard B Lipton, Martha Daviglus, Maria Argos, Jianwen Cai, Robert Kaplan, Myriam Fornage, Charles Decarli, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in …

Microwave Ablation As A Primary Versus Secondary Treatment For Hepatocellular Carcinoma., Philip Lee, Ajay Makkena, Mohamed Tantawi, Felipe Velasquez-Botero, John R. Eisenbrey, Colette M. Shaw

Department of Radiology Faculty Papers

PURPOSE: The purpose of this study was to analyze and compare the outcomes of percutaneous microwave ablation (MWA) when used as a primary vs. secondary treatment for hepatocellular carcinoma (HCC).

METHODS: The clinical data of 192 patients with HCC treated with MWA between January 2012 and July 2021 were reviewed retrospectively, with 152 patients being treatment naïve (primary treatment) vs. 40 who had residual or recurrent disease following previous trans-arterial chemoembolization or trans-arterial radioembolization (secondary treatment). The primary outcomes were primary technical efficacy, 1- and 3-year local recurrence-free survival (RFS) and overall survival (OS), local recurrence rates, and adverse events. …

The Emergence Of A Virus Variant: Dynamics Of A Competition Model With Cross-Immunity Time-Delay Validated By Wastewater Surveillance Data For Covid-19, Bruce Pell, Samantha Brozak, Tin Phan, Fuqing Wu, Yang Kuang

Faculty, Staff and Student Publications

We consider the dynamics of a virus spreading through a population that produces a mutant strain with the ability to infect individuals that were infected with the established strain. Temporary cross-immunity is included using a time delay, but is found to be a harmless delay. We provide some sufficient conditions that guarantee local and global asymptotic stability of the disease-free equilibrium and the two boundary equilibria when the two strains outcompete one another. It is shown that, due to the immune evasion of the emerging strain, the reproduction number of the emerging strain must be significantly lower than that of …

Dissemination And Implementation Of A Text Messaging Campaign To Improve Health Disparities Among Im/Migrant Workers, Ellie Cherryhomes, Shannon Guillot-Wright

Faculty, Staff and Student Publications

The use of short message service (SMS) text messaging technology has grown in popularity over the last twenty years, but there is limited data on the design and feasibility of campaigns to reduce work-related injury, particularly among rural workers, non-native English speakers, and illiterate or low-literacy populations. Although there is a critical need for tech equity or 'TechQuity' interventions that reduce injury and enhance the wellbeing of under-reached communities, the barriers and benefits to implementation must be empirically and systematically examined. Thus, our team used D&I science to design and implement an 18-week texting campaign for under-reached workers with a …

Geographic Variations And The Associated Factors In Adherence To And Persistence With Adjuvant Hormonal Therapy For The Privately Insured Women Aged 18-64 With Breast Cancer In Texas, Junghyun Kim, Man S Kim, Suja S Rajan, Xianglin L Du, Luisa Franzini, Tae Gi Kim, Sharon H Giordano, Robert O Morgan

Faculty, Staff and Student Publications

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a …

Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H Elnaggar, Victoria O Huynh, Daniel Lin, R Tyler Hillman, Chike O Abana, Molly B El Alam, Katarina C Tomasic, Tatiana V Karpinets, Ramez Kouzy, Jae L Phan, Jennifer Wargo, Emma B Holliday, Prajnan Das, Melissa P Mezzari, Nadim J Ajami, Erica J Lynn, Bruce D Minsky, Van K Morris, Andrea Milbourne, Craig A Messick, Ann H Klopp, P Andrew Futreal, Cullen M Taniguchi, Kathleen M Schmeler, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.

METHODS: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …

Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski

Faculty, Staff and Student Publications

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was …

Clinical Outcomes Associated With Npm1 Mutations In Patients With Relapsed Or Refractory Aml, Ghayas C Issa, Aram Bidikian, Sangeetha Venugopal, Marina Konopleva, Courtney D Dinardo, Tapan M Kadia, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Musa Yilmaz, Nicholas J Short, Abhishek Maiti, Koji Sasaki, Lucia Masarova, Sherry Pierce, Koichi Takahashi, Guilin Tang, Sanam Loghavi, Keyur Patel, Michael Andreeff, Kapil Bhalla, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P < .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.

Alzheimer's Disease Genetic Risk And Cognitive Reserve In Relationship To Long-Term Cognitive Trajectories Among Cognitively Normal Individuals, Corinne Pettigrew, John C Morris, Jason Hassenstab, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Both Alzheimer's disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition.

METHODS: Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by …

Relationships Among Biochemical Measures In Children With Diabetic Ketoacidosis, Nicole S Glaser, Michael J Stoner, Maria Y Kwok, Kimberly S Quayle, Kathleen M Brown, Jeff E Schunk, Jennifer L Trainor, Julie K Mcmanemy, Leah Tzimenatos, Arleta Rewers, Lise E Nigrovic, Jonathan E Bennett, Sage R Myers, Mckenna Smith, T Charles Casper, Nathan Kuppermann

Faculty, Staff and Students Publications

OBJECTIVES: Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions.

METHODS: We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode.

RESULTS: pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). …

Adult Asthma Associated With Roadway Density And Housing In Rural Appalachia: The Mountain Air Project (Map)., W Jay Christian, John Flunker, Beverly May, Susan Westneat, Wayne T Sanderson, Nancy Schoenberg, Steven R Browning

UK CARES Faculty Publications

BACKGROUND: Appalachian Kentucky is a rural area with a high prevalence of asthma among adults. The relative contribution of environmental exposures in the etiology of adult asthma in these populations has been understudied.

OBJECTIVE: This manuscript describes the aims, study design, methods, and characteristics of participants for the Mountain Air Project (MAP), and focuses on associations between small area environmental exposures, including roadways and mining operations, and lifetime and current asthma in adults.

METHODS: A cohort of residents, aged 21 and older, in two Kentucky counties, was enrolled in a community-based, cross-sectional study. Stratified cluster sampling was used to select …

Structural And Functional Analysis Of Human Pannexin 2 Channel, Zhihui He, Yonghui Zhao, Michael J Rau, James A J Fitzpatrick, Rajan Sah, Hongzhen Hu, Peng Yuan

2020-Current year OA Pubs

The pannexin 2 channel (PANX2) participates in multiple physiological processes including skin homeostasis, neuronal development, and ischemia-induced brain injury. However, the molecular basis of PANX2 channel function remains largely unknown. Here, we present a cryo-electron microscopy structure of human PANX2, which reveals pore properties contrasting with those of the intensely studied paralog PANX1. The extracellular selectivity filter, defined by a ring of basic residues, more closely resembles that of the distantly related volume-regulated anion channel (VRAC) LRRC8A, rather than PANX1. Furthermore, we show that PANX2 displays a similar anion permeability sequence as VRAC, and that PANX2 channel activity is inhibited …

Epigenetic And Transcriptomic Characterization Reveals Progression Markers And Essential Pathways In Clear Cell Renal Cell Carcinoma, Yige Wu, Nadezhda V Terekhanova, Wagma Caravan, Nataly Naser Al Deen, Preet Lal, Siqi Chen, Chia-Kuei Mo, Song Cao, Yize Li, Alla Karpova, Ruiyang Liu, Yanyan Zhao, Andrew Shinkle, Ilya Strunilin, Cody Weimholt, Kazuhito Sato, Lijun Yao, Mamatha Serasanambati, Xiaolu Yang, Matthew Wyczalkowski, Houxiang Zhu, Daniel Cui Zhou, Reyka G Jayasinghe, Daniel Mendez, Michael C Wendl, Melissa A Reimers, Russell K Pachynski, Aadel A Chaudhuri, Milan G Chheda, Benjamin D Humphreys, James J Hsieh, Li Ding, Feng Chen, Et Al.

2020-Current year OA Pubs

Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor …

Clinical Features And Shared Mechanisms Of Chronic Gastritis And Osteoporosis, Tao Han, Yili Zhang, Baoyu Qi, Ming Chen, Kai Sun, Xiaokuan Qin, Bowen Yang, He Yin, Aili Xu, Xu Wei, Liguo Zhu

Faculty, Staff and Student Publications

Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified …

Psychosocial Predictors Of Early Postpartum Depressive And Anxious Symptoms In Primiparous Women And Their Partners., Erin J Henshaw, Marie Cooper, Teresa Wood, Stacey N Doan, Sanchita Krishna, Marie Lockhart

OhioHealth Research Institute Articles

BACKGROUND: While the majority of research on postpartum depressive and anxious symptoms has focused on mothers, a growing body of research suggests a need to understand the role of the partner's health and relationship quality as predictors of postpartum maternal depression, while also better understanding correlates of partner or paternal depression in the postpartum period. The purpose of the current study is to evaluate mother and partner stress, anxiety, mood, infant care support, and relationship quality as predictors of perinatal depressive and anxious symptoms in first time mothers and partners during the postpartum hospital stay.

METHODS: First time parent couples …

Validation Of A Farsi Version Of The Eating Pathology Symptoms Inventory (F-Epsi) Among Iranian Adolescents, Reza N Sahlan, Jessica F Saunders, Ellen E Fitzsimmons-Craft

2020-Current year OA Pubs

PURPOSE: Limited research has validated eating pathology assessments in Iranian adolescent boys and girls. In particular, the measures that have been validated do not capture both boys' and girls' eating behaviors in adolescence. The purpose of the current study was to validate a Farsi version of the Eating Pathology Symptoms Inventory (F-EPSI) for use in Iranian adolescents.

METHODS: Participants (N = 913; 85.3% girls) were adolescents who completed a battery of questionnaires including the F-EPSI. In addition, F-EPSI data for Iranian adolescents were compared with those of previously published data of adult Iranian college students.

RESULTS: Confirmatory Factor Analysis (CFA) …

Sexual Behaviors, Contraception Use And Barriers Among Adolescents And Young Adults In Rural Haiti., Abbey R. Masonbrink, Emily A. Hurley, Nikolaus Schuetz, Jonathan Rodean, Emily Rupe, Kemi Lewis, Marie Daphnée Boncoeur, Melissa K. Miller

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adolescents and young adults (AYAs) in Haiti experience a high unintended pregnancy rate, in part due to unmet contraception needs. Little is known about AYA opinions of and experiences with contraception that may explain remaining gaps in coverage. We aimed to describe barriers and facilitators to contraception use among AYAs in Haiti.

METHODS: We conducted a cross-sectional survey and semi-structured qualitative interviews with a convenience sample of AYA females aged 14-24 in two rural communities in Haiti. The survey and semi-structured interviews assessed demographics, sexual health and pregnancy prevention behaviors and explored contraception opinions and experiences according to Theory …

Protocol And Biomarker Strategy For A Multi-Site Randomized Controlled Trial Examining Biological Mechanisms And Dosing Of Active Music Engagement In Children With Acute Lymphoblastic Leukemia And Lymphoma And Parents., Sheri L. Robb, Kristen A. Russ, Steven J. Holochwost, Kristin Stegenga, Susan M. Perkins, Seethal A. Jacob, Amanda K. Henley, Jessica A. Maclean

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Music therapy is a standard palliative care service in many pediatric and adult hospitals; however, most research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. This study builds on prior work examining psychosocial mechanisms of action underlying an Active Music Engagement (AME) intervention, designed to help manage emotional distress and improve positive health outcomes in young children with cancer and parents (caregivers), by examining its effects on biomarkers of stress and immune function.

METHODS: This two-group randomized controlled trial (R01NR019190) is designed to examine biological mechanisms of effect and dose-response …

Rewired M6a Epitranscriptomic Networks Link Mutant P53 To Neoplastic Transformation, An Xu, Mo Liu, Mo-Fan Huang, Yang Zhang, Ruifeng Hu, Julian A Gingold, Ying Liu, Dandan Zhu, Chian-Shiu Chien, Wei-Chen Wang, Zian Liao, Fei Yuan, Chih-Wei Hsu, Jian Tu, Yao Yu, Taylor Rosen, Feng Xiong, Peilin Jia, Yi-Ping Yang, Danielle A Bazer, Ya-Wen Chen, Wenbo Li, Chad D Huff, Jay-Jiguang Zhu, Francesca Aguilo, Shih-Hwa Chiou, Nathan C Boles, Chien-Chen Lai, Mien-Chie Hung, Zhongming Zhao, Eric L Van Nostrand, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Students Publications

N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing …

Intolerance Of Uncertainty And Attitudes Towards Persons Living With Disabilities In Medical Students: Is There A Correlation?, Martinique Ogle, Dimitrios Papanagnou, Md, Kestrel Reopelle, Frances Rusnack, Jordan Feingold-Link, Maria Poluch, Nethra S. Ankam

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Patients living with a disability experience an illness trajectory that may be uncertain. While navigating clinical uncertainty has been well-researched, health professionals' intolerance of uncertainty for patients living with disabilities has yet to be explored. We examined the relationship between medical students' intolerance of uncertainty with their attitudes towards people living with disabilities to better inform curricular efforts.

METHODS: We employed a survey-based design consisting of the Intolerance of Uncertainty Scale (IUS) and Disability Attitudes in Healthcare (DAHC) Scale to medical students upon completion of core clerkships (end of third-year of training). Data were de-identified. Mean DAHC and IUS …

Health-Related Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy: A Scoping Review, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Lauren M Andring, Yimin Geng, Ramez Kouzy, J Andrew Livingston, Susan K Peterson, Andrew J Bishop, Grace L Smith, Jillian R Gunther, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is a critical component of treatment for adolescents and young adults (AYAs, age 15-39 years old) diagnosed with cancer. Limited prior studies have focused on AYAs receiving RT despite the potentially burdensome effects of RT. We reviewed the literature to assess health-related quality of life (HRQOL) in AYAs with cancer who received RT.

Methods: The MEDLINE, EMBASE, and Web of Science databases were searched in January 2022 to identify studies that analyzed HRQOL measured by patient-reported outcomes in AYAs who received RT. After title (n = 286) and abstract (n = 58) screening and full-text review …

Defects In Lipid Homeostasis Reflect The Function Of Tango2 In Phospholipid And Neutral Lipid Metabolism, Agustin Leonardo Lujan, Ombretta Foresti, Conor Sugden, Nathalie Brouwers, Alex Mateo Farre, Alessio Vignoli, Mahshid Azamian, Alicia Turner, Jose Wojnacki, Vivek Malhotra

Faculty, Staff and Students Publications

We show that TANGO2 in mammalian cells localizes predominantly to mitochondria and partially at mitochondria sites juxtaposed to lipid droplets (LDs) and the endoplasmic reticulum. HepG2 cells and fibroblasts of patients lacking TANGO2 exhibit enlarged LDs. Quantitative lipidomics revealed a marked increase in lysophosphatidic acid (LPA) and a concomitant decrease in its biosynthetic precursor phosphatidic acid (PA). These changes were exacerbated in nutrient-starved cells. Based on our data, we suggest that TANGO2 function is linked to acyl-CoA metabolism, which is necessary for the acylation of LPA to generate PA. The defect in acyl-CoA availability impacts the metabolism of many other …