Medicine and Health Sciences Commons^™

Influences On Emergency Clinician Use Of Health Information Exchange: Interview Study, Brian E. Dixon, Umesh Ghimire, Benjamin Richter, Corinne Bowditch, Saurabh Rahurkar, John T. Finnell, Joshua R. Vest

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Health information exchange (HIE) supports clinical decision-making in emergency medicine settings. Despite evidence and policies that encourage the adoption of HIE, use by clinicians is limited. Moreover, few studies examine HIE use years after adoption by hospitals or clinics.

OBJECTIVE: This study aims to examine the perceptions and use of a mature, operational HIE system by emergency department clinicians years after its implementation.

METHODS: We interviewed 21 clinicians in various roles (eg, attending physician and nurse practitioner) across multiple health systems that participate in a statewide HIE network. We asked questions about their use of the HIE system and …

Genetic Influences For Distinct Impulsivity Domains Are Differentially Associated With Early Substance Use Initiation: Results From The Abcd Study, Ethan Kinstler, Aaron J Gorelik, Sarah E Paul, Adamya Aggarwal, Emma C Johnson, Melissa A Cyders, Arpana Agrawal, Ryan Bogdan, Alex P Miller

2020-Current year OA Pubs

BACKGROUND: Impulsivity is among the strongest correlates of substance involvement (i.e. a broad continuum of substance-related behaviors), and distinct domains (e.g. sensation seeking [SS] and urgency) are differentially correlated, phenotypically and genetically, with unique substance involvement stages. Examining whether polygenic influences for distinct impulsivity domains are differentially predictive of early substance use initiation - a major risk factor for later problematic use - may improve our understanding of the role of impulsivity in addiction etiology.

METHODS: Data collected from participants of genetically inferred European ancestry enrolled in the Adolescent Brain Cognitive Development Study

RESULTS: SS-PGS was significantly associated with any …

Metabolic Impact Of Dietary Glycine Supplementation In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Paul M Yen, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine plays a central role in human metabolism, and an adequate supply is required for synthesizing glutathione (GSH), eliminating excess metabolites as acylglycine via the glycine conjugation detoxification pathway, and maintaining 1-carbon cycle activity. However, glycine is deficient in individuals with severe obesity, which may compromise these pathways and metabolic health. This exploratory study examines whether dietary glycine supplementation could correct glycine deficiency and impairments in glycine-dependent metabolic pathways. 19 participants with severe obesity (BMI 38.3 ± 5.3 kg/m2) were treated with dietary glycine (100 mg/kg/day) for two weeks. We found that treatment significantly increased the plasma concentration of glycine …

Cep76 Impairment At The Centrosome-Cilium Interface Contributes To A Spectrum Of Ciliopathies, Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A Lewis, Farid Ullah, Thomas Arbogast, Jackson P Ogden, Madeleine Harion, Marjolaine Willems, Maha S Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E Davis

Faculty, Staff and Students Publications

Dysfunction at the centrosome-cilium interface underlies a broad range of ciliopathies. Here, we identify biallelic variants in CEP76, encoding a centrosomal protein, in eight unrelated individuals presenting with neurodevelopmental, ocular, and variable additional multisystem features. Proband-derived fibroblasts and CEP76-depleted RPE1 cells display ciliary deficits, including impaired cilium formation and length, disrupted transition zone architecture, and impaired IFT88-mediated anterograde intraflagellar transport. Zebrafish cep76 mutants recapitulate key clinical phenotypes, and in vitro complementation assays confirm pathogenicity for all tested human disease-associated variants. Proteomics analysis identifies CEP76 interactors, including known partners CCP110 and CEP97, and highlights clinically and functionally relevant candidates, including …

Type I Hybrid Effectiveness-Implementation Randomised Controlled Trial To Address Intergenerational Impact Of War Trauma And Resilience Among Second-Generation Refugee Children In The Usa: Resettled Refugee Families For Healing (Rrf4h) Study Protocol, Nhial T Tutlam, Tewodros W Liyew, Theresa S Betancourt, Byron J Powell, Shenyang Guo, Mary Mckay, Fred M Ssewamala

2020-Current year OA Pubs

INTRODUCTION: Children from refugee families resettled in the USA face higher risks of serious mental health challenges compared with their native-born peers. Research shows that refugee youth in high-income countries frequently suffer from trauma-associated disorders such as post-traumatic stress disorder (PTSD), depression and anxiety. The high prevalence of trauma-associated mental health problems among these youth may be attributed to their own trauma exposure, especially if born in conflict zones, and post-resettlement challenges like poverty, acculturation difficulties, racism and discrimination. However, they may also suffer from the effects of intergenerational trauma, where parental war trauma impacts them. This study aims to …

Time-Of-Day And Age-Related Patterns In Cerebrospinal Fluid Glucose And Protein, Joshua P Koleske, Shelei Pan, Thanda Meehan, Maren Loe, Diego M Morales, Brendan P Lucey, Erik Musiek, Jennifer M Strahle

2020-Current year OA Pubs

BACKGROUND: Known circadian variations in cerebrospinal fluid (CSF) flow and composition include fluctuations in electrolytes, hormones, and neurotransmitters. However, how commonly measured CSF constituents, such as protein and glucose, vary by time-of-day is understudied. Here, we identify and compare time-of-day differences in CSF protein and glucose from patients who underwent CSF collection during clinical care.

METHODS: Patients with CSF collected between June 2018 and May 2023 at thirteen hospitals within our institution's health system were identified. Clinical, demographic and laboratory results were recorded. CSF results were divided into 1- and 4-hour intervals based on time-of-day and patient age. Patients were …

Estrogen-Related Receptor Alpha Promotes Skeletal Muscle Regeneration And Mitigates Muscular Dystrophy, Thi Thu Hao Nguyen, Ya Xiang Huang, Svitlana Poliakova, Citu Citu, Eira Mann, Danesh H Sopariwala, Zhongming Zhao, Ashok Kumar, Vihang A Narkar

The Brown Foundation: Institute of Molecular Medicine

Skeletal muscle regeneration in chronic muscle diseases such as Duchenne Muscular Dystrophy (DMD) has remained clinically unsurmountable. Estrogen‐related receptor alpha (ERRα) plays a critical role in adult skeletal muscle metabolism and exercise fitness. Whether ERRα activation can drive muscle regeneration and mitigate dystrophy in DMD is not known. We have investigated ERRα signaling in pre‐clinical models of acute muscle injury and DMD. ERRα is induced in differentiating C2C12 myoblast and regenerating muscle. ERRα silencing suppressed proliferation and differentiation in C2C12 myoblasts. RNA sequencing revealed that angiogenic factor and proliferation genes were downregulated by ERRα knockdown in proliferating cells, whereas oxidative …

Conversion Of Failed Anatomic Total Shoulder Arthroplasty To Reverse Shoulder Arthroplasty Yields Similar Pain And Functional Outcomes To Primary Reverse Shoulder Arthroplasty But Has A Higher Baseplate Failure Rate: A Matched Cohort Study., Kevin A Hao, Trevor G Simcox, Keegan M Hones, Jonathan O Wright, Thomas W Wright, Tyler Lamonica, Bradley S Schoch, Joseph J King

Faculty, Staff and Student Publications

Background: To investigate whether patients who initially underwent anatomic total shoulder arthroplasty (aTSA) for glenohumeral osteoarthritis and were subsequently revised to reverse TSA (rTSA) due to rotator cuff failure or glenoid loosening ultimately attained a similar clinical outcome compared with those who underwent primary rTSA and identify predictors of poor outcomes in the former population.

Methods: We did a single-center retrospective review of 63 shoulders who underwent revision rTSA after primary aTSA that failed due to glenoid component loosening (n = 32), rotator cuff failure (n = 24), or recurrent instability (n = 7). Pain and functional outcomes at minimum …

Preoperative Brain Mapping Predicts Language Outcomes After Eloquent Tumor Resection, Matthew T Muir, Kyle Noll, Sarah Prinsloo, Hayley Michener, Jeffrey I Traylor, Vinodh A Kumar, Chibawanye I Ene, Sherise Ferguson, Ho-Ling Liu, Jeffrey S Weinberg, Frederick Lang, Brian A Taylor, Stephanie J Forkel, Sujit S Prabhu

Faculty, Staff and Student Publications

When operating on gliomas near critical language regions, surgeons risk either leaving residual tumor or inducing permanent postoperative language deficits (PLDs). Despite the advent of intraoperative mapping techniques, subjective judgments frequently determine important surgical decisions. We aim to inform data-driven surgery by constructing a non-invasive mapping approach that quantitatively predicts the impact of individual surgical decisions on long-term language function. This study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (TMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language …

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Vaccine Effectiveness Against Influenza A(H1n1), A(H3n2), And B-Associated Hospitalizations, United States, 1 September 2023 To 31 May 2024, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 influenza season included sustained elevated activity from December 2023 to February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season.

METHODS: During 1 September 2023 to 31 May 2024, a multistate sentinel surveillance network of 24 medical centers in 20 US states enrolled adults aged ≥18 years hospitalized with acute respiratory illness. Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccine effectiveness (VE) against influenza-associated hospitalization …

Addressing Barriers To Care For African American Men Facing Prostate Cancer: A Scoping Review Of Navigation Programs, Ashley Nicole Smith, Brittany A. Campbell, Ghilamichael Andemeskel, Peggy Tahir, Joseph Egbunikeokye, Tisha M. Felder Phd, Msw, Barbara Cicerelli, Nynikka R. Palmer

Publications

PURPOSE

African American/Black men are disproportionately impacted by prostate cancer (PCa). Patient navigation is an evidence-based approach to address barriers to care, improve access to care and health outcomes, and reduce disparities. This scoping review provides an in-depth examination of navigation programs in PCa care across the cancer continuum, with a focus on African American/Black men in the United States.

METHODS

We conducted a comprehensive literature search through September 1st, 2023, in PubMed, Embase, Web of Science, and CINAHL Complete, using keywords and index terms within three main themes: PCa, patient navigation, and African American/Black men. We included studies that …

A Social Media Campaign And Web-Based Survey About Prostate Cancer Genetics: Mixed Methods Study, Amy Leader, Stacy Loeb, Preethi Selvan, Ashley Hunter, Rebecca Hartman, Scott Keith, Veda Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline genetic variants are important for prostate cancer (PCa) management and hereditary cancer risk assessment, but testing is underused. Furthermore, patients are often unaware of the genetic connections to PCa. Social media is increasingly serving as a source of awareness for health information and a method to gather data from a large population.

OBJECTIVE: There were three objectives: to (1) create and test social media messages related to PCa genetics and genetic testing, (2) determine which social media message was most engaging, and (3) assess knowledge of and attitudes toward PCa genetic testing through an online survey using the …

Generalizability Of Neuromuscular Coordination In The Human Upper Extremity After Stroke And Its Implications In Neurorehabilitation, Manuel Portilla-Jiménez, Yoon No Gregory Hong, Komal K Kukkar, Hyung-Soon Park, Sheng Li, Jinsook Roh

Faculty, Staff and Student Publications

Background: Previous studies have shown that stroke often impairs neuromuscular coordination (i.e., muscle synergies) across various biomechanical conditions. In our previous study, we investigated the generalizability of muscle synergies between isometric and free dynamic reaching in healthy individuals. However, the extent to which muscle synergy characteristics after stroke are generalized across these conditions remains unclear.

Methods: Electromyographic signals from eight upper extremity muscles were recorded from 14 chronic stroke survivors with mild-to-severe motor impairment and eight age-range matched controls while performing isometric force generation and point-to-point dynamic reaching tasks. Non-negative matrix factorization was applied to identify muscle synergy characteristics underlying …

Landscape And Clinicopathologic Features Of Ras Pathway Mutations In Chronic Myelomonocytic Leukemia, Guillermo Montalban-Bravo, Sanam Loghavi, Ziyi Li, Kelly Chien, Rashmi Kanagal-Shamanna, Alex Bataller, Anuya Natu, Mark Gurney, Alexandre Bazinet, Danielle Hammond, Koji Sasaki, Gautam Borthakur, Mahesh Swaminathan, Courtney Dinardo, Tapan Kadia, Farhad Ravandi, Naval Daver, Nicholas Short, Naveen Pemmaraju, Ghayas Issa, Terra L Lasho, Christy M Finke, Aref Al-Kali, Clifford Csizmar, Hassan Alkhateeb, Naseema Gangat, Abhishek A Mangaonkar, Carlos Bueso-Ramos, Ayalew Tefferi, Hagop Kantarjian, Guillermo Garcia-Manero, Mrinal M Patnaik

Faculty, Staff and Student Publications

RAS pathway (RASp) mutations induce proliferative features, and promote transformation in chronic myelomonocytic leukemia (CMML). However, the unique clonal landscape and hierarchy of distinct RASp mutations remain unexplored. To characterize the landscape, architecture, and implications of unique RASp mutations in CMML, we evaluated a cohort of 814 patients with CMML. We identified 461 RASp mutations among 342 patients (42%). N/KRAS and CBL mutations were the most common, frequently involved the P-loop or RING domains, respectively, and frequently appeared as dominant events (63% and 65%, respectively). BRAF, NF1, and PTPN11 mutations spanned throughout the gene structure, and frequently appeared as subclonal …

Optimizing Genetic Ancestry Adjustment In Dna Methylation Studies: A Comparative Analysis Of Approaches, Kira D Höffler, Seyma Katrinli, Matthew W Halvorsen, Anne-Kristin Stavrum, Kevin S O'Connell, Alexey Shadrin, Srdjan Djurovic, Ole A Andreassen, James J Crowley, Jan Haavik, Kristen Hagen, Gerd Kvale, Kerry Ressler, Bjarne Hansen, Jair C Soares, Gabriel R Fries, Alicia K Smith, Stéphanie Le Hellard

Faculty, Staff and Student Publications

Background: Genetic ancestry is an important factor to account for in DNA methylation studies because genetic variation influences DNA methylation patterns. One approach uses principal components (PCs) calculated from CpG sites that overlap with common SNPs to adjust for ancestry when genotyping data is not available. However, this method does not remove technical and biological variations, such as sex and age, prior to calculating the PCs. The first PC is therefore often associated with factors other than ancestry.

Methods: We developed and adapted the adapted EpiAnceR+ approach, which includes (1) residualizing the CpG data overlapping with common SNPs for control …

Drug-Eluting Resorbable Scaffold Versus Balloon Angioplasty For Below-The-Knee Peripheral Artery Disease: 2-Year Results From The Life-Btk Trial., Brian G Derubertis, Ramon L Varcoe, Prakash Krishnan, Marc P Bonaca, David J O'Connor, Richard Pin, David C Metzger, Andrew Holden, Jen-Kuang Lee, Osamu Iida, Ehrin J Armstrong, Steven W C Kum, Raghu Kolluri, Danielle R Bajakian, Lawrence A Garcia, Mehdi H Shishehbor, Shawn Yu, Karine Ruster, Brad J Martinsen, Zsuzsanna Igyarto, Sahil A Parikh

Heart and Vascular Articles

BACKGROUND: Limited treatment options exist for infrapopliteal disease in patients with chronic limb-threatening ischemia (CLTI), a condition associated with a high risk of limb loss. Interventional management of diseased infrapopliteal vessels with percutaneous transluminal angioplasty (PTA) is associated with high rates of restenosis and reintervention. In the LIFE-BTK randomized controlled trial (Pivotal Investigation of Safety and Efficacy of BRS Treatment-Below the Knee), the drug-eluting resorbable scaffold (DRS) demonstrated superior 12-month efficacy compared with PTA in a selected CLTI population with predominantly noncomplex, mildly to moderately calcified lesions. This report presents the 2-year safety and efficacy outcomes of the Esprit BTK …

Effect Of Age On Isth-Bat Scores And Low Vwf Diagnosis In The Zimmerman Program, Ferdows Atiq, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

An essential component of low von Willebrand factor (VWF)/type 1 von Willebrand disease (VWD) diagnosis is to identify patients with an increased bleeding phenotype, as most individuals with VWF levels in the 30 to 50 IU/dL range do not bleed. The International Society on Thrombosis and Haemostasis-bleeding assessment tool (ISTH-BAT), widely used for assessing bleeding severity, has recently been shown to be age dependent. Although age may also influence ISTH-BAT scores in individuals with VWF levels between 30 and 50 IU/dL, and subsequently affect low VWF diagnosis, this relationship has not been investigated. Therefore, we analyzed 325 participants from the …

The Effect Of Telehealth-Based Medical Nutrition Therapy On Cardiovascular Disease Risk Factors In A Rural Population: A Secondary Analysis Of Outcomes Related To Nutrition, Health And Well-Being From The Healthy Rural Hearts Randomised Controlled Trial, Tracy L. Schumacher, Erin D. Clarke, Jaimee Herbert, Anna Jansson, Chris Oldmeadow, Megan E. Rollo, Penny Milson, Carissa Alderton, Leanne J. Brown, Jennifer T. May Phd, Rn, Anp-Bc, Annabelle Williams, Michelle Guppy, Shanthi Ramanathan, John Attia, Clare E. Collins

Publications

BACKGROUND: Adults in rural Australia are at elevated risk of cardiovascular disease (CVD). To date, no intervention trials have evaluated the impact of dietitian delivered nutrition therapy using telehealth exclusively in patients recruited in the primary care setting. The primary aim was to assess effectiveness of telehealth delivered Medical Nutrition Therapy (MNT) on change in dietary intake energy, reported as percent energy derived from nutrient-dense (core) foods. Secondary aims included assessment of the intervention effects on percentage weight loss, quality of life, health literacy and patient engagement in their health (patient activation).

METHODS: This was a secondary data analysis of …

Integrated Single-Cell Multiomic Profiling Of Caudate Nucleus Suggests Key Mechanisms In Alcohol Use Disorder, Nicholas C Green, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

Alcohol use disorder (AUD) induces complex transcriptional and regulatory changes across multiple brain regions including the caudate nucleus, which remains understudied. Using paired single-nucleus RNA-seq and ATAC-seq on caudate samples from 143 human postmortem brains, including 74 with AUD, we identified 17 distinct cell types. A significant portion of the alcohol-related differences in gene expression were accompanied by a corresponding difference in chromatin accessibility within the gene. We observed transcriptional differences in medium spiny neurons that impact RNA metabolism and immune response pathways. A small cluster of D1/D2 hybrid neurons showed AUD-induced differences distinct from the D1 and D2 types, …

Development And Validation Of Clinical Screening Systems For Cushing Disease In The United States, Jorge E. Salcedo-Sifuentes, Sonal Mehta, Carter M. Suryadevara, Marvin Bergsneider, Kevin C. J. Yuen, Paul A. Gardner, Julie M. Silverstein, Albert H. Kim, James J. Evans, Garni Barkhoudarian, Juan C. Fernandez-Miranda, William T. Couldwell, Robert C. Rennert, Varun R. Kshettry, Kyle C. Wu, Carolina Benjamin, Gabriel Zada, Michael R. Chicoine, Jamie J. Van Gompel, Michael P. Catalino, Michael Karsy, Adam Mamelak, Ildiko Torok, Trevor Low, Won Kim, Donato R. Pacione, Nidhi Agrawal

Department of Neurosurgery Faculty Papers

PURPOSE: Clinical screening systems (CSSs) for Cushing syndrome (CS) validated in Europe have not been evaluated for CS or Cushing disease (CD) in the United States (US). We aimed to evaluate existing CSSs in US patients and develop two new symptom-based CSSs to identify patients with high pre-test probability of disease warranting referral for definitive biochemical workup-one for broad CS screening and one specifically for CD.

METHODS: Data were obtained from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID)-comprising 615 patients who underwent transnasal transsphenoidal resection for CD at one of 11 US pituitary centers, the Centers …

Just-In-Time Adaptive Intervention To Improve Hiv Prevention And Substance Use In Youth Experiencing Homelessness (My-Ride): Protocol For A Randomized Controlled Trial, Diane Santa Maria, Nikhil Padhye, Michael Businelle, Natasha Slesnick, Stefani Ricondo, Marguerita Lightfoot

Faculty, Staff and Students Publications

Background: Youth who are experiencing homelessness face a higher risk of HIV infection compared to their housed peers, and suicide and overdose remain the leading causes of death among homeless youth. Just-in-Time Adaptive Interventions (JITAIs) are gaining momentum for HIV prevention and substance use research. Yet, most interventions for homeless youth have not addressed modifiable real-time factors.

Objective: This paper describes the development and implementation of a randomized attention-controlled trial to assess the efficacy of motivating youth to reduce infections, disconnections, and emotional dysregulation (MY-RIDE), a JITAI to improve HIV prevention and substance use in homeless youth.

Methods: This study …

Dissecting Regulatory Non-Coding Gwas Loci Reveals Fibroblast Causal Genes With Pathophysiological Relevance To Heart Failure, Richard Gill, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Heart failure is caused in part by cardiac remodeling processes that include the death of cardiac myocytes and their replacement by cardiac fibroblasts. Here, we hypothesize that cardiac fibroblasts may harbor epigenetic contexts in which heart disease-associated non-coding SNPs perturb gene expression relevant to disease. To test this, we utilized male primary cardiac fibroblasts to generate high-resolution Hi-C data and integrate it with functional genomic information to annotate and link putative distal regulatory elements in heart disease-associated loci to gene promoters. We identify several target genes with established roles in cardiac fibrosis and/or heart disease (GJA1, TBC1D32, CXCL12, IL6R, and …

The Effect Of Type 2 Diabetes Genetic Predisposition On Non-Cardiovascular Comorbidities, Ana Luiza Arruda, Ozvan Bocher, Henry J Taylor, Davis Cammann, Satoshi Yoshiji, Xianyong Yin, Chi Zhao, Jingchun Chen, Alexis C Wood, Ken Suzuki, Josep M Mercader, Cassandra N Spracklen, James B Meigs, Marijana Vujkovic, George Davey Smith, Jerome I Rotter, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini

Faculty, Staff and Students Publications

Type 2 diabetes is associated with a range of non-cardiovascular non-oncologic comorbidities. To move beyond associations and evaluate causal effects between type 2 diabetes genetic predisposition and 21 comorbidities, we apply Mendelian randomization analysis using genome-wide association studies across multiple genetic ancestries. Additionally, leveraging eight mechanistic clusters of type 2 diabetes genetic profiles, each representing distinct biological pathways, we investigate causal links between cluster-stratified type 2 diabetes genetic predisposition and comorbidity risk. We identify causal effects of type 2 diabetes genetic predisposition driven by distinct genetic clusters. For example, the risk-increasing effects of type 2 diabetes genetic predisposition on cataracts …

Sti Testing And Diagnosis Rates Among Patients With Mpox In 2 Populous Us Cities, 2022, Shauna H Gunaratne, Karen J Vigil, Simian Huang, Nina Kumenda, Jacob Mclean, Clare Delaurentis, Delivette Castor, Jason Zucker

Faculty, Staff and Student Publications

Background: Mpox is recognized as a sexually transmitted infection, and the 2022 epidemic and 2024 resurgence of mpox cases through sexual transmission highlighted the need for sexually transmitted infection (STI) testing. Our objective was to observe rates of STI testing and STI diagnoses in patients with confirmed mpox in Houston, Texas and New York City, New York (NY).

Methods: This was a retrospective cohort study involving manual review of confirmed mpox cases at three large clinical centers in Houston, Texas and New York City, NY. Descriptive statistics were calculated for rates of STI testing and new diagnoses of syphilis, chlamydia …

Germline Determinants Of Toxicity And Efficacy In Patients With Large B-Cell Lymphoma Treated With Car T-Cell Therapy, Paolo Strati, Amanda Brandt, Anath C Lionel, Jared Henderson, Jason R Westin, Sherry Adkins, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed, Christopher Flowers, Sattva S Neelapu, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline determinants of response and toxicity after CART has not yet been described.

Methods: Genome-wide genotyping was performed in 170 patients with LBCL treated with standard of care axicabtagene ciloleucel. Polygenic risk score instruments for blood cell traits and inflammatory markers were obtained from the PGS Catalog and analyzed using PRSice-2. Exploratory gene-based and genome-wide association study analyses were performed. Genetic ancestry of the patients with LBCL was …

Hydroxyapatite Microspheres Induce Durable Pleurodesis And Are Rapidly Cleared By Pleural Osteoclasts, Yusuke Tanaka, Yuki Takahashi, Yuma Shindo, Lori B. Pitstick, Steven L. Teitelbaum, Wei Zou, Xiangning Wang, Jason C. Woods, Kathryn A. Wikenheiser-Brokamp, Francis X. Mccormack

2020-Current year OA Pubs

Talc pleurodesis is highly effective for preventing recurrence of pneumothorax and pleural effusion, but it can be complicated by dissemination, acute lung injury, lead exposure, and foreign body-induced chronic inflammation and pain. Our objective is to develop a safe, biodegradable, contaminant-free particle for pleurodesis. We used mouse models of pneumothorax and malignant pleural effusion to compare the efficacy and safety of pleurodesis with talc and hydroxyapatite microspheres (HAM). Intrapleural instillation of microspheres induced pleural adhesions, fibrosis, and symphysis as effectively as talc and resulted in more durable protection from experimental pneumothorax. HAM and talc both induced an osteoclastogenic, inflammatory, and …

Gabaergic Interneurons Contribute To The Fatal Seizure Phenotype Of Cln2 Disease Mice, Keigo Takahashi, Nicholas R. Rensing, Elizabeth M. Eultgen, Letitia L. Williams, Sophie H. Wang, Hemanth R. Nelvagal, Steven Q. Le, Marie S. Roberts, Balraj Doray, Edward B. Han, Patricia I. Dickson, Michael Wong, Mark S. Sands, Jonathan D. Cooper

2020-Current year OA Pubs

The cellular etiology of seizures in CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a deficiency of tripeptidyl peptidase 1 (TPP1), remains elusive. Given that Cln2R207X/R207X mice display fatal spontaneous seizures and an early loss of several cortical GABAergic interneuron populations, we hypothesized that these 2 events might be causally related. To study the cell-autonomous effects of interneuron-specific TPP1 deficiency, we first generated transgenic mice expressing loxP-flanked lysosomal membrane-tethered TPP1 (TPP1LAMP1 mice) on the Cln2R207X/R207X genetic background, and then crossed TPP1LAMP1 mice with Vgat-Cre mice. These Vgat-Cre; TPP1LAMP1 mice accumulated storage material in cortical and striatal interneurons. Vgat-Cre; …