Digital Commons Network^™

Individualized Functional And Structural Language Lateralities In Temporal Lobe Epilepsy And Their Impact On Memory, Ankeeta Ankeeta, Qirui Zhang, Sam Sharifzadeh Javidi, Shilpi Modi, Michael R. Sperling, Joseph I. Tracy

Department of Neurology Faculty Papers

The basis and impact of functional asymmetries in the brain, particularly language lateralization, are not fully understood, and the relationship between functional and structural asymmetries remains largely untested. This study investigated the degree to which asymmetries in hemispheric language laterality are concordant with asymmetries in gray matter (GM) structure and whether the hemispheric organization of memory is influenced by functional language asymmetries. Structural and functional MR data was acquired from 261 individuals, including those with unilateral temporal lobe epilepsy (LTLE = 96, RTLE = 69) and matched with healthy participants (HPs = 96). Functional language laterality indices (LIs) were calculated …

Cytokine Release Syndrome And Neurotoxicity Following Cd19 Car-T In B-Cell Lymphoma, Roni Shouval, Christopher Strouse, Soyoung Kim, Temitope Oloyede, Sairah Ahmed, Farrukh T Awan, Danny Luan, Veronika Bachanova, Talha Badar, Merav Bar, Pere Barba, Amer M Beitinjaneh, Amanda Cashen, Bhagirathbhai Dholaria, Mahmoud Elsawy, Siddhartha Ganguly, Praveen Ramakrishnan Geethakumari, Uri Greenbaum, Hamza Hashmi, Laquisa C Hill, Michael D Jain, Tania Jain, Partow Kebriaei, Adam S Kittai, Frederick L Locke, Premal D Lulla, Elena Mead, Joseph P Mcguirk, Alberto Mussetti, Taiga Nishihori, Amanda L Olson, Martina Pennisi, Miguel-Angel Perales, Peter A Riedell, Wael Saber, Abu-Sayeef Mirza, Margarida Magalhaes-Silverman, Elizabeth J Shpall, Mohamed Sorror, Kitsada Wudhikarn, Cameron J Turtle, Amy Moskop, Marcelo C Pasquini

Faculty, Staff and Students Publications

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity. In this registry study by the Center for International Blood and Marrow Transplant Research, we studied CRS and ICANS in 1916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.9%, tisagenlecleucel 25.1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival (OS). Risk …

Performance Of Stool Xpert Mtb/Rif Ultra For Detection Of Mycobacterium Tuberculosis Among Adults Living With Hiv: A Multicentre, Prospective Diagnostic Study, George W Kasule, Sabine Hermans, Sozinho Acacio, Alexander Kay, Joachim Kikoyo Nsubuga, Carlos Fernández-Escobar, Nosisa Shiba, Lucia Carratalá-Castro, Derrick Semugenze, Patricia Mwachan, Shilzia Munguambe, Joanna Ehrlich, Elisa Lopez-Varela, Andrew R Dinardo, Frank Cobelens, Christoph Lange, Moses Joloba, Anna M Mandalakas, Willy Ssengooba, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: When people living with HIV develop pulmonary tuberculosis, it often manifests without detectable acid-fast bacilli on sputum microscopy. We aimed to assess the diagnostic accuracy of stool Xpert MTB/RIF Ultra (hereafter, Ultra) for Mycobacterium tuberculosis detection among adults with HIV.

Methods: This multicentre, prospective diagnostic accuracy study was done in outpatient and inpatient health centres in Eswatini, Mozambique, and Uganda. We enrolled adults aged 15 years and older with HIV with presumptive tuberculosis. We evaluated the diagnostic accuracy of stool Ultra using the simple one-step processing method against a composite microbiological reference standard (CMRS) including three WHO-recommended tuberculosis diagnostic …

Military Inhalational Exposures Outside The Theater Of Conflict And Chronic Respiratory Symptoms, Reza Hosseini, Eric Garshick, Martin D Slade, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Glenn Kuschner, Octavian C Ioachimescu, Michael Jerrett, Philippe R Montgrain, Susan P Proctor, Christine H Wendt, Cherry Wongtrakool, Emily S Wan, Paul D Blanc, Carrie A Redlich

Faculty, Staff and Students Publications

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Design, setting, and participants: This cross-sectional study used data from the US Department of Veterans Affairs Service and Health Among Deployed Veterans study. US veterans who served between October 7, 2001, and …

Clinical Evaluation Of The Healgen Rapid Covid-19 Antigen Test As A Point-Of-Care Diagnostic Tool, Stephen A Young, Hua Zhang, Jose Rodriguez, David Mishkin, Ward Paine, Li Seyfried, Latisha Hargrove, Dennis L Broyles, Chermaen Lindberg, Anurag Purushothaman, Stacey House

2020-Current year OA Pubs

BACKGROUND: Development of readily available Rapid COVID-19 Antigen tests essential for promptly identifying SARS-CoV2 infection and preventing its spread.

METHODS: This study evaluated the clinical performance of the Healgen Rapid COVID-19 antigen test as a point-of-care diagnostic tool with 806 evaluable subjects who were within 6 days post-symptom onset. The results from the Healgen test were compared to the results from Emergency Use Authorization (EUA) approved SARS-CoV-2 RT-PCR tests.

RESULTS: Out of the 806 evaluable subjects, 140 tested positive and 640 tested negative for SARS-CoV-2 with the Healgen COVID-19 test, showing good agreement with the EUA RT-PCR results. There were …

Validation Of Established Thyroid Ultrasound Volume Norms In A Chernobyl Cohort, Lydia B. Zablotska, Robert J. Mcconnell, Aleksandr V. Rozhko, Patrick O'Kane, Vasilina Yauseyenka, Mark P. Little, Victor Minenko, Vladimir Drozdovitch, Tamara Moskvicheva, Maureen Hatch, Tamara Yeudachkova, Kiyohiko Mabuchi, Elizabeth K. Cahoon

Department of Radiology Faculty Papers

OBJECTIVE: To establish thyroid ultrasound volume norms appropriate for studies of diffuse goiter in a cohort of children and adolescents from an iodine-deficient population exposed to 131I by the Chernobyl fallout.

METHODS: A cohort of 11,970 Belarusians aged ≤18 years at the time of the 1986 Chernobyl accident with individual thyroid radiation dose estimates was screened 10-18 years later. From these, a low-dose subset of 2,392 with no thyroid diseases was selected to construct age- and sex-specific normative values for thyroid ultrasound volume, compared to Belarusian Ministry of Health (MOH) norms and existing WHO and European standards.

RESULTS: Cohort-specific values …

Immediate Skin-To-Skin Contact And Postpartum Hemorrhagic Morbidity, Rachel L Wiley, Ipsita Ghose, Dana R Canfield, Minhazur R Sarker, Hector Mendez-Figueroa, Suneet Chauhan

Faculty, Staff and Students Publications

Objective: To examine rates of postpartum hemorrhagic (PPH) morbidity among patients who did and did not have immediate skin-to-skin contact (SSC).

Methods: This study was a retrospective cohort of all non-anomalous, term singleton vaginal births at a Level IV center over 2 years. Exclusion criteria included COVID-19. Immediate SSC was defined as at least 60 min of direct contact initiated between parturient and neonate within 10 min of birth. The primary outcome was a composite of maternal morbidity related to PPH compared among those with and without immediate SSC. We used multivariable Poisson regression adjusted for possible confounders with robust …

Short-Term Neurologic Outcomes In Pediatric Extracorporeal Membrane Oxygenation Are Proportional To Bleeding Severity Graded By A Novel Bleeding Scale, Katherine Doane, Danielle Guffey, Laura L Loftis, Trung C Nguyen, Matthew A Musick, Amanda Ruth, Ryan D Coleman, Jun Teruya, Christine Allen, Melania M Bembea, Brian Boville, Jamie Furlong-Dillard, Santosh Kaipa, Mara Leimanis, Matthew P Malone, Lindsey K Rasmussen, Ahmed Said, Marie E Steiner, Deanna T Tzanetos, Heather Viamonte, Linda Wallenkamp, Arun Saini

Faculty, Staff and Students Publications

Patients admitted to a pediatric intensive care unit (PICU) need individualized nutrition support that is tailored to their particular disease severity, nutritional status, and therapeutic interventions. We aim to evaluate how calories and proteins are provided during the first seven days of hospitalization for children in critical condition with organ dysfunction (OD). A single-center retrospective cohort study of children aged 2–18 years, mechanically ventilated > 48 h, and admitted > 7 days to a PICU from 2016 to 2017 was carried out. Nutrition support included enteral and parenteral nutrition. We calculated scores for the Pediatric Sequential Organ Failure Assessment (pSOFA) on days …

Endothelium- And Fibroblast-Derived C-Type Natriuretic Peptide Prevents The Development And Progression Of Aortic Aneurysm, Aisah A Aubdool, Amie J Moyes, Cristina Perez-Ternero, Reshma S Baliga, Jaspinder Singh Sanghera, M Taaha Syed, Kareemah Jaigirdar, Anmolpreet K Panesar, Janice C Tsui, Yanming Li, Hernan G Vasquez, Ying H Shen, Scott A Lemaire, Juliette Raffort, Ziad Mallat, Hong S Lu, Alan Daugherty, Adrian J Hobbs

Faculty, Staff and Students Publications

Background: Thoracic (TAA) and abdominal (AAA) aortic aneurysm are life-threatening diseases characterized by dilation, inflammation, and structural weakness; development of pharmacological therapies is desperately needed. CNP (C-type natriuretic peptide) plays a key role in vascular homeostasis, mediating vasodilator, anti-inflammatory, and antiatherogenic actions. Since such processes drive AA, we determined the role of endogenous CNP in offsetting pathogenesis.

Methods: Tissue from patients with AA was analyzed to determine the consequences on CNP signaling. Ascending and suprarenal aortic diameters were assessed at baseline and following Ang II (angiotensin II; 1.44 mg/kg per day) infusion in wild-type, endothelium-restricted (ecCNP-/-), fibroblast-restricted (fbCNP-/-), global CNP …

Ad-Sge-Dkk3 Gene Therapy Overcomes Resistance To Immune Checkpoint Blockade In Pleural Mesothelioma, Hee-Jin Jang, Meera Patel, Daniel Y Wang, Sung Wook Kang, Jong Min Choi, Claire Lee, Monica Vilchis, Ji Seon Shim, Sonali Mitra, Priyanka Ranchod, Allen Kuncheria, William Hudson, Peter Jindra, Veronica Lenge De Rosen, Maheshwari Ramineni, Ernest Ramsay Camp, Farrah Kheradmand, R Taylor Ripley, Shawn S Groth, Hyun-Sung Lee, Bryan M Burt

Faculty, Staff and Students Publications

Purpose: Immune checkpoint inhibitors (ICI) have limited efficacy in pleural mesothelioma. We investigated the role of Dickkopf WNT signaling pathway inhibitor 3 (DKK3) in overcoming treatment resistance.

Patients and methods: We performed preclinical studies to elucidate DKK3's role in ICI-resistant mouse mesothelioma. Based on these findings, we conducted a single-arm, phase II clinical trial of a combination of Ad-SGE-DKK3 and nivolumab for chemotherapy-refractory epithelioid pleural mesothelioma, with the objective response rate as the primary outcome.

Results: DKK3 was significantly reduced in human epithelioid mesothelioma. Overexpression of DKK3 in cancer cells activated the p53 pathway, enhanced glycolysis, increased surface PD-L1, and …

Glioblastoma-Instructed Astrocytes Suppress Tumour-Specific T Cell Immunity, Camilo Faust Akl, Brian M Andersen, Zhaorong Li, Federico Giovannoni, Martin Diebold, Liliana M Sanmarco, Michael Kilian, Luca Fehrenbacher, Florian Pernin, Joseph M Rone, Hong-Gyun Lee, Gavin Piester, Jessica E Kenison, Joon-Hyuk Lee, Tomer Illouz, Carolina M Polonio, Léna Srun, Jazmin Martinez, Elizabeth N Chung, Anton Schüle, Agustin Plasencia, Lucinda Li, Kylynne Ferrara, Mercedes Lewandrowski, Craig A Strathdee, Lorena Lerner, Christophe Quéva, Iain C Clark, Benjamin Deneen, Judy Lieberman, David H Sherr, Jack P Antel, Michael A Wheeler, Keith L Ligon, E Antonio Chiocca, Marco Prinz, David A Reardon, Francisco J Quintana

Faculty, Staff and Students Publications

Glioblastoma is the most common and aggressive primary brain cancer and shows minimal response to therapies. The immunosuppressive tumour microenvironment in glioblastoma contributes to the limited therapeutic response. Astrocytes are abundant in the central nervous system and have important immunoregulatory roles. However, little is known about their role in the immune response to glioblastoma1. Here we used single-cell and bulk RNA sequencing of clinical glioblastoma samples and samples from preclinical models, multiplexed immunofluorescence, in vivo CRISPR-based cell-specific genetic perturbations and in vitro mouse and human experimental systems to address this gap in knowledge. We identified an astrocyte subset …

Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja

Faculty, Staff and Students Publications

Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).

Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …

First-In-Human Phase 1 Study Of Khk2455 Monotherapy And In Combination With Mogamulizumab In Patients With Advanced Solid Tumors, Timothy A Yap, Olivier Rixe, Capucine Baldini, Ursa Brown-Glaberman, Sergey Efuni, David S Hong, Christophe Massard, Jameel Muzaffar, Andreea Varga, Emrullah Yilmaz, Yuta Ikawa, Lisa H Shiue, Yi Liu, Matthew W Hruska, Henry Zhao, Akihiro Tokunaga, Solmaz Sahebjam

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that degrades tryptophan (Trp) to kynurenine (Kyn), which suppresses effector T cells and reduces antitumor activity. KHK2455 is a long-acting selective IDO1 inhibitor that blocks the heme component of the IDO holoenzyme. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody targeting CCR4. KHK2455 + mogamulizumab demonstrated enhanced antitumor activity in preclinical studies, which led to a first-in-human, two-part, multicenter, open-label, phase 1, dose-escalation, cohort-expansion trial (ClinicalTrials.gov identifier NCT02867007) evaluating the safety/tolerability, pharmacokinetics, and IDO1 activity of KHK2455 alone and in combination with mogamulizumab in patients with treatment-refractory advanced solid tumors. …

Genome-Wide Association Meta-Analysis Of Human Olfactory Identification Discovers Sex-Specific And Sex-Differential Genetic Variants, Franz Förster, David Emmert, Katrin Horn, Janne Pott, Johannes Frasnelli, Mohammed Aslam Imtiaz, Konstantinos Melas, Valentina Talevi, Honglei Chen, Christoph Engel, Michele Filosi, Myriam Fornage, Martin Gögele, Markus Löffler, Thomas H Mosley, Cristian Pattaro, Peter Pramstaller, Srishti Shrestha, N Ahmad Aziz, Monique M B Breteler, Kerstin Wirkner, Markus Scholz, Christian Fuchsberger

Faculty, Staff and Student Publications

Smelling is a human sense, expressing strong sexual dimorphisms. We aim to improve the knowledge of the genetics of human olfactory perception by performing an exploratory genome-wide association meta-analysis of up to 21,495 individuals of European ancestry. By sex-stratified and overall analysis of the identification of twelve odours and an identification score, we discovered ten independent loci, seven of them novel, with trait-wise genome-wide significance (p <  5 × 10−8) involving five odours. Seven of these loci, including four novel ones, are also significant using a stricter study-wide significance threshold (p <  3.85 × 10−9). Loci were predominantly located within clusters of olfactory receptors. Two loci were female-specific while one was sex-differential with respective candidate genes containing androgen response elements. Two-sample Mendelian randomization was applied to search for causal relationships between sex hormones, odour identification and neurodegenerative diseases. A causal negative effect was detected for Alzheimer’s disease on the identification score. These findings deepen our understanding of the genetic basis of olfactory perception and its interaction with sex, prioritizing mechanisms for further molecular research.

Dietary Patterns, Serum Metabolites, And Risk Of Cardiovascular Disease In United States Hispanic/Latino Adults: A Prospective Analysis Of The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Hongbo Yang, Yi Wang, Kai Luo, Yasmin Mossavar-Rahmani, Christina Cordero, Robert J Ostfeld, Claudia Martinez, Luis Maldonado, Amber Pirzada, Martha Daviglus, Bing Yu, Frank B Hu, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Background: Healthy dietary patterns are recommended to prevent cardiovascular disease (CVD), yet the relationships among healthy dietary patterns, blood metabolite profile, and incident CVD are not well understood.

Objectives: This study aimed to assess the associations of healthy dietary patterns and related serum metabolite profiles with incident CVD in United States Hispanic/Latino adults.

Methods: The study included 13,922 participants aged 18-74 y from the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores, including Healthy Eating Index (HEI)-2020, healthful Plant-based Diet Index (hPDI), and alternate Mediterranean diet score (aMED), were constructed at baseline (2008-2011) based on 2 24-h dietary recalls. …

Pulmonary Complications Associated With Sugammadex Or Neostigmine In Patients Recovering From Advanced Diagnostic Or Interventional Bronchoscopy: A Retrospective Two-Centre Analysis, Ehab Farag, Karan Shah, Maged Argalious, Basem Abdelmalak, Thomas Gildea, John Seif, Shuyi Li, Edward J Mascha, Daniel I Sessler

Faculty, Staff and Student Publications

Background: Many diagnostic and interventional procedures are performed in bronchoscopy suites in high-risk patients. Minor impairment in respiratory muscle function caused by incomplete reversal of neuromuscular block can contribute to postoperative pulmonary complications (PPCs). We assessed whether there are fewer serious PPCs after diagnostic or therapeutic bronchoscopy when neuromuscular block is reversed with sugammadex rather than neostigmine.

Methods: This is a retrospective cohort study for bronchoscopy under general anaesthesia with the use of neuromuscular blockers between July 2016 and June 2022. The primary outcome was a composite of PPCs. The secondary outcome was hypoxaemia. We used inverse probability of treatment …

Hybrid Deep Learning Approaches For Accurate Electricity Price Forecasting: A Day-Ahead Us Energy Market Analysis With Renewable Energy, Rahman Md. Saifur, Hassan Reza

Faculty, Staff and Student Publications

Forecasting day-ahead electricity prices is a crucial research area. Both wholesale and retail sectors highly value improved forecast accuracy. Renewable energy sources have grown more influential and effective in the US power market. However, current forecasting models have shortcomings, including inadequate consideration of renewable energy impacts and insufficient feature selection. Many studies lack reproducibility, clear presentation of input features, and proper integration of renewable resources. This study addresses these gaps by incorporating a comprehensive set of input features, while these features are engineered to capture complex market dynamics. The model’s unique aspect is its inclusion of renewable-related inputs, such as …

Investigation Of A Pathogenic Inversion In Unc13d And Comprehensive Analysis Of Chromosomal Inversions Across Diverse Datasets, Tugce Bozkurt-Yozgatli, Ming Yin Lun, Jesse D Bengtsson, Ugur Sezerman, Ivan K Chinn, Zeynep Coban-Akdemir, Claudia M B Carvalho

Faculty, Staff and Student Publications

Inversions are known contributors to the pathogenesis of genetic diseases. Identifying inversions poses significant challenges, making it one of the most demanding structural variants (SVs) to detect and interpret. Recent advancements in sequencing technologies and the development of publicly available SV datasets have substantially enhanced our capability to explore inversions. However, a cross-comparison in those datasets remains unexplored. In this study, we reported a proband with familial hemophagocytic lymphohistiocytosis type-3 carrying a splicing variant (c.1389+1G>A) in trans with an inversion present in 0.006345% of individuals in gnomAD (v4.0) that disrupts UNC13D. Based on this result, we investigate the features …

The Impact Of Household Dysfunction On Dating Violence Perpetration Among Adolescents In The United States: A Scoping Review, Sumaita Choudhury, Melissa F Peskin, Timothy J Walker, Emily T Hébert, Nivedhitha Parthasarathy, Kaitlyn L Zajack-Garcia, Lea Sacca, Christine M Markham

Faculty, Staff and Student Publications

Adverse childhood experiences, such as household dysfunction (HD), play a central role in how adolescents establish, experience, and navigate the challenges of relationship formation, maintenance, and dissolution. HD exposures have been independently associated with dating violence (DV) perpetration in both adolescents and adults. However, research examining the association between the concurrent effect of HD on DV perpetration, especially among adolescents remains scarce. Thus, we conducted a scoping review to accumulate and summarize existing research regarding the impact of HD on DV perpetration among adolescents aged 10 to 17 years in the United States. We used three electronic databases, Medline (Ovid), …

Renal G Protein-Coupled Estrogen Receptor 1 Regulates The Epithelial Sodium Channel Promoting Natriuresis To A Greater Extent In Females, Victoria L Nasci, Jean C Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh M Pochynyuk, James D Stockand, Eman Y Gohar

Faculty, Staff and Student Publications

Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat …

High-Impact Chronic Pain And Cognitive Decline Among Mexicans Aged 60 And Older From 2012 To 2018, Sadaf Arefi Milani, Sirena Gutierrez, Brandon O'Grady, Rebeca Wong, Rafael Samper-Ternent, Brian Downer

Faculty, Staff and Student Publications

Pain is associated with cognitive decline, but prior research has not considered differences between high- and low-impact chronic pain or low-and middle-income countries, such as Mexico. Our objective was to evaluate the association between high-impact chronic pain and cognitive decline among older adults in Mexico. We used data from the 2012-2018 Mexican Health and Aging Study (MHAS), a nationally representative study of older Mexican adults (60+). Pain, measured at each wave, was categorized as high-impact chronic pain (pain that limits daily activities), low-impact chronic pain (pain that did not limit daily activities), and no chronic pain. Cognition was measured at …

Diet, Gut Microbiota, And Histidine Metabolism Toward Imidazole Propionate Production In Relation To Type 2 Diabetes, Hongbo Yang, Kai Luo, Brandilyn A Peters, Yi Wang, Yanbo Zhang, Martha Daviglus, Amber Pirzada, Christina Cordero, Bing Yu, Robert D Burk, Robert Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Objective: To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people.

Research design and methods: In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008-2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ∼12 years (n = 4,632). In a subsample with gut microbiota data during a follow-up visit (2016-2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake. …

Evolving Hemodynamics In Fontan Circulation: Age-Driven Insights In Patients With Interrupted Inferior Vena Cava And Hepatoazygos Shunt, Vikas Kannojiya, Akshita Sahni, Emily Eickhoff, Neha Zacharia, Nicole St Clair, Noah Schulz, Peter E Hammer, Pedro J Del Nido, Rahul H Rathod, David M Hoganson, Vijay Govindarajan

Faculty, Staff and Student Publications

Patients with interrupted inferior vena cava (I-IVC) and azygos continuation who undergo Fontan completion via hepatoazygos shunting exhibit unique hemodynamic challenges. This study evaluates age-related shifts in systemic venous return dominance, hepatic flow distribution (HFD), power loss (PL), and flow disturbances using patient-specific computational fluid dynamics (CFD). Data analysis from 95 patients with I-IVC showed a nonlinear shift in upper-to-lower body systemic flow dominance with ratios of 2, 1, and 0.5 (correlating to ages ∼3, ∼10, and ∼20, respectively). CFD simulations for 17 selected patients revealed a trend of increasing HFD toward the right pulmonary artery, with median splits of …

Prevalence, Treatment Patterns, Burden, And Factors Related To Treatment Failure With Sodium-Glucose Cotransporter 2 Inhibitor In Adults With Type 2 Diabetes In The United States, Xi Tan, Yiwen Cao, Yan Wang, Joanna Boland, Mico Guevarra, Lin Xie, Yan Song, Min Ji Kwak

Faculty, Staff and Student Publications

Aims: To evaluate treatment failure of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among adults with type 2 diabetes (T2D) and assess associated risk factors and clinical and economic outcomes in the real-world setting.

Methods: Adults with T2D who initiated SGLT2i were selected from the Komodo's Healthcare Map, an administrative claims database (2016-2024). Treatment failure was defined as discontinuation, add-on/switching, or uncontrolled glycated hemoglobin (HbA1c) without action. Risk factors, treatment patterns, and clinical and economic burden were assessed.

Results: Among 237,295 eligible adults, the overall rate of treatment failure with SGLT2i was 77.3 %, with a median time to failure of 9.14 …

Efficacy And Safety Of Mechanical Thrombectomy In Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients On Low-Dose Aspirin, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and …

Endovascular Therapy For Late-Window M2-Segment Middle Cerebral Artery Occlusion: Analysis Of The Clear Study, Simon Winzer, Daniel P O Kaiser, Muhammad M Qureshi, Alicia C Castonguay, Daniel Strbian, Raul G Nogueira, Simon Nagel, Jean Raymond, Mohamad Abdalkader, Jelle Demeestere, João Pedro Marto, Hiroshi Yamagami, Kanta Tanaka, Sunil A Sheth, Anne Dusart, Patrik Michel, Marta Olive Gadea, Marc Ribo, Osama O Zaidat, Diogo C Haussen, Hilde Henon, Mahmoud H Mohammaden, Markus A Möhlenbruch, James E Siegler, Ajit S Puri, Johannes Kaesmacher, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Nicolas Martinez-Majander, Stefania Nannoni, Lieselotte Vandewalle, Flavio Bellante, Milagros Galecio-Castillo, Sergio Salazar-Marioni, Pekka Virtanen, Anke Wouters, Rita Ventura, Jessica Jesser, Adnan Mujanovic, Liqi Shu, Abiya Qureshi, Zhongming Qiu, Hesham E Masoud, Manuel Requena, Mikko Sillanpää, Wei Hu, Eugene Lin, Charlotte Cordonnier, Daniel Roy, Shadi Yaghi, Davide Strambo, Urs Fischer, Santiago Ortega-Gutierrez, Robin Lemmens, Peter A Ringleb, Thanh N Nguyen, Volker Puetz

Faculty, Staff and Student Publications

Background: There is uncertainty about whether patients with M2 occlusion benefit from endovascular therapy (EVT) in the late (6-24-hour) time window. We evaluated the clinical outcomes of patients with M2 occlusion selected for EVT compared with those who received medical management (MM) in the late window.

Methods: This multinational cohort study was conducted at 66 sites across 10 countries (January 2014 to May 2022). We included consecutive patients with late-window stroke due to M2 occlusion, baseline National Institutes of Health Stroke Scale score of ≥5, and premorbid modified Rankin Scale score of ≤2 who received EVT or MM alone. The …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Arun Jeyabalan, Arkady Khodursky, Alison B Moe, Manfred Lee, Maneesh Jain, Laura Goetzl, Elizabeth F Sutton, Pamela M Simmons, George R Saade, Antonio Saad, Luis D Pacheco, Esther Park-Hwang, Antonina I Frolova, Ebony B Carter, Ai-Ris Y Collier, Daniel G Kiefer, Vincenzo Berghella, Rupsa C Boelig, Michal A Elovitz, Cynthia Gyamfi-Bannerman, Joseph R Biggio, Kara Rood, William A Grobman, Carrie Haverty, Morten Rasmussen

Faculty, Staff and Student Publications

Importance: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

Objective: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

Design, setting, and participants: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Automated Mycoplasma Genitalium Molecular Macrolide Resistance Detection And Nucleic Acid Target Semi-Quantitation: Patient Demographic Considerations, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Michael E Newcomb, Brian Mustanski, Erik Munson

Faculty, Staff and Student Publications

Recent work has optimized parameters of a real-time reverse transcriptase PCR-based laboratory-developed test on the Panther Fusion system which detects Mycoplasma genitalium-specific macrolide resistance-associated mutations LDT (MRM-LDT) from primary swab and urine specimens. In this study, MRM-LDT was applied to a large multi-demographic study set to further characterize M. genitalium resistance in the United States. A total of 2,145 primary clinical specimens testing positive for M. genitalium 16S rRNA by transcription-mediated amplification (TMA) were initially titered by the same assay using serial 10-fold dilutions to determine relative target nucleic acid burden. Specimens were then processed for MRM-LDT. Findings were stratified …

Long-Term Exposure To Multiple Air Pollutants And Multi-Level Socioeconomic Status: Joint Effects On Age-Related Macular Degeneration, Subsequent Ocular Comorbidity, And Death In Middle-Aged And Older Adults, Yang Yang, Liangkai Chen, Qichen Liu, Min Mu, Jing Huang, Guangming Zhang, Qianqian Song

Faculty, Staff and Student Publications

Background: Both air pollution and socioeconomic status (SES) are recognized as significant determinants of health outcomes. However, no study has explored the combined effects of air pollutants and SES on (1) age-related macular degeneration (AMD) incidence; (2) trajectories from baseline to AMD, subsequent ocular comorbidity (OCMD), and mortality; and (3) life expectancy in middle-aged and older adults.

Methods: Using UK Biobank data, we created two composite air pollution scores (APS) and assessed SES at individual and neighborhood levels. OCMD was defined as glaucoma or cataract occurrence after AMD diagnosis. Cox proportional hazard regression models, multistate models, and life tables were …