Digital Commons Network^™

Multiple Subcortical And Subcortico-Cortico Dynamic Network Reconfigurations Characterize Focal-To-Bilateral Tonic-Clonic Seizures, Shilpi Modi, A. Ankeeta, Walter Hinds, Michael R. Sperling, Xiaosong He, Joseph I. Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes …

C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol

Duncan NRI Faculty and Staff Publications

Purpose: GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.

Methods: We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.

Results: Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented …

Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker

Faculty, Staff and Students Publications

Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).

Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).

Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), …

Fetal Body Composition And Organ Volume Trajectories In Association With Maternal Perceived Stress Or Depressive Symptoms In The Fetal 3d Study, Alexandra Jean-Louis, Jessica L Gleason, Zhen Chen, Kathryn A Wagner, William A Grobman, Roger B Newman, Wesley Lee, Robert Gore-Langton, Seth Sherman, John Owen, Deborah A Wing, Daniel W Skupski, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Objectives: Evaluate associations between maternal perceived stress and depressive symptoms, and fetal body composition and organ volumes.

Methods: In the NICHD Fetal 3D Study (2015-2019; n = 2457), stress and depressive symptoms were assessed at enrollment (10-13 weeks). High stress was defined as a Perceived Stress Scale (PSS) score ≥15 and high depressive symptoms, defined as an Edinburgh Postnatal Depression Scale (EPDS) score ≥10. Fetal body composition and organ volumes (cerebellar, lung, liver, and kidney) were measured up to five times between 15 and 40 weeks using three-dimensional (3D) ultrasound technology. Trajectories of body composition and organ volumes across pregnancy …

Phospho-Rpa2 Predicts Response To Platinum And Parp Inhibitors In Homologous Recombination-Proficient Ovarian Cancer, Angela Schab, Amanda Compadre, Rebecca Drexler, Megan Loeb, Kevin Rodriguez, Joshua Brill, Carmen Sandoval, Brooke Sanders, Lindsay Kuroki, Carolyn Mccourt, Andrea R. Hagemann, Premal Thaker, David Mutch, Matthew Powell, Ian S. Hagemann, Lulu Sun, Priyanka Verma, Elena Lomonosova, Dineo Khabele, Mary M. Mullen, Et Al.

2020-Current year OA Pubs

BACKGROUNDTreatment of tubo-ovarian high-grade serous carcinoma (HGSC) includes cytoreductive surgery, platinum-based chemotherapy, and often poly(ADP-ribose) polymerase (PARP) inhibitors. While homologous recombination (HR) deficiency is a well-established predictor of therapy sensitivity, over 50% of HR-proficient HGSCs also exhibit sensitivity. Currently, there are no biomarkers to identify which HR-proficient HGSCs will be sensitive to standard-of-care therapy. Replication stress may serve as a key determinant of response.METHODSWe evaluated phospho-RPA2-T21 (p-RPA2) foci via immunofluorescence as a biomarker of replication stress in formalin-fixed, paraffin-embedded HGSC samples collected at diagnosis from patients treated with platinum chemotherapy (discovery cohort, n = 31; validation cohort, n = 244) …

Evaluation Of Internally Cooled Radiofrequency Ablation Targeting Multiple Shoulder Nerves For Chronic Shoulder Pain Relief And Function Restoration: A Prospective Study, Mitsukuni Yoshida, Peter K Park, Loc V Thang

2020-Current year OA Pubs

OBJECTIVE: Shoulder pain is a prevalent musculoskeletal disorder, affecting up to 70% of adults over their lifetimes. Recently, radiofrequency ablation (RFA) has gained attention as a treatment for joint pain. This study aims to evaluate the efficacy of internally cooled RFA (icRFA) in alleviating shoulder pain and improving both qualitative and quantitative measures of shoulder function.

DESIGN: Prospective cohort study.

SUBJECTS: Patients with chronic shoulder pain (n = 35) who responded positively to diagnostic blocks of the suprascapular nerve (SSN), axillary nerve (AN), and lateral pectoral nerve (LPN).

METHODS: Patients underwent icRFA targeting the SSN, AN, and LPN. Treatment response …

Distinct Patterns Of Weight Gain, Age, And Subcortical Microstructure In Early Adolescence, Shana Adise, Zhaolong Adrian Li, Jonatan Ottino-González, Filip Morys, Peter A Chiarelli, Tamara Hershey

2020-Current year OA Pubs

IMPORTANCE: Associations between childhood obesity and brain microstructural differences have been observed. It remains unknown whether these associations are driven by sex-specific excessive weight gain. Restriction spectrum imaging characterizes brain tissue microstructural health via water diffusion, where the restricted normalized isotropic (RNI) compartment assesses neuronal and glial cellularity, which may reflect neuroinflammation, synaptic pruning, or both.

OBJECTIVE: To identify associations among RNI scaling factor values, normal neurodevelopment, and weight gain during early adolescence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Adolescent Brain Cognitive Development (ABCD) Study, a 10-year, ongoing, multisite longitudinal cohort study conducted among youths …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Antonina I Frolova, Et Al.

2020-Current year OA Pubs

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 …

Choroid Plexus Apocrine Secretion Shapes Csf Proteome During Mouse Brain Development, Ya'el Courtney, Joshua P Head, Neil Dani, Olga V. Chechneva, Frederick B Shipley, Yong Zhang, Michael J Holtzman, Cameron Sadegh, Towia A Libermann, Maria K Lehtinen

2020-Current year OA Pubs

The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT

Mayo Normative Studies: Regression-Based Normative Data For Remote Self-Administration Of The Stricker Learning Span, Symbols Test, And Mayo Test Drive Screening Battery Composite And Validation In Individuals With Mild Cognitive Impairment And Dementia, Nikki H Stricker, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

No abstract provided.

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Pancreatic Neuroendocrine Neoplasm (Pnen) Cohort, Sandip Pravin Patel, Jillian Fisher, Young Kwang Chae, Luisa Solis Soto, Anup Kasi, Bhavana Konda, Mark Walshauser, Edwin Parra, Jiexin Zhang, Caroline Duault, Edgar Gonzalez-Kozlova, Ganiraju Manyam, Jianhua Zhang, Hong Chen, Dzifa Yawa Duose, Caddie Laberiano Fernandez, Raja Luthra, Gheath Al-Atrash, Seunghee Kim-Schulze, Holden T Maecker, Ignacio I Wistuba, Sacha Gnjatic, J Jack Lee, Jianjun Zhang, Christine M Magner, Helen X Chen, Elad Sharon, Megan Othus, Christopher W Ryan, Charles Blanke, Cara L Haymaker, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.

Experimental design: Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative …

"Holy Cow, Where Do I Sign Up?" Attitudes Of Military Veterans Toward Epigenomic Biomarker Toxic Exposure Testing, Stacey Pereira, Calvin Apodaca, Kyle Slominski, Rachele K Lipsky, Cristian Coarfa, Cheryl L Walker, Amy L Mcguire, Lea Steele, Drew A Helmer

Center for Medical Ethics and Health Policy Staff Publications

Introduction: After the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics Promise to Address Comprehensive Toxics (PACT) Act in 2022, there has been a great interest in studying toxic exposures encountered during military service. Development of epigenomic biomarkers for exposures could facilitate understanding of exposure-related health effects, but such testing could also provide unwanted information.

Materials and methods: We explored attitudes toward epigenomic biomarker research and the potential to test for past exposures using semistructured interviews with Veterans (n = 22) who experienced potentially harmful exposures.

Results: Twenty Veterans said they would hypothetically want to receive …

Hydration Status And Acute Kidney Injury Biomarkers In Ncaa Female Soccer Athletes During Preseason Conditioning, Daniel E Newmire, Erica M Filep, Jordan B Wainwright, Heather E Webb, Darryn S Willoughby

Faculty, Staff and Students Publications

Exercise training in extreme temperatures concurrent with hypohydration status may potentiate the development of acute kidney injury (AKI) in young, healthy persons.

Background/Objectives: It is unknown how repeated training bouts in ambient higher temperatures and humidity may influence measures of AKI. The purpose of this study was to investigate hydration status and renal biomarkers related to AKI in NCAA Division I female soccer athletes during preseason conditioning.

Methods: A convenience sample of n = 21 athletes were recruited (mean ± SEM; age: 19.3 ± 0.25 y; height: 169.6 ± 1.36 cm; mass: 68.43 ± 2.46 kg; lean body …

Anti-Transforming Growth Factor-Β Treatment Shows Increased Bone Mass And Strength In A Novel Mouse Model For Osteogenesis Imperfecta Type I, Ellen Busschers, Yuqing Chen-Everson, Mary Adeyeye, I-Wen Song, Emily Busse, Alexis Castellon, Oscar Ruiz, Nicole Meyers, Yangjin Bae, Catherine Ambrose, Brendan Lee

Faculty, Staff and Students Publications

Anti-transforming growth factor beta (TGF-β) is a promising approach for the treatment of osteogenesis imperfecta (OI). To date, preclinical and clinical studies for the use of anti-TGF-β therapy have focused on moderate to severe OI caused by qualitative defects in collagen. However, the majority of OI patients are represented by type I OI. Mutations resulting in the haploinsufficiency of type I collagen is the cause of OI type I in the majority of patients. To study the effect of anti-TGF-β therapy in type I OI, we generated a novel mouse model for OI type I. CMV-CRE mice were crossed to …

Low Frequency, High Complexity: Assessing Skill Decay In Transesophageal Echocardiography Post-Simulation Training, Enyo Ablordeppey, Emily Terian, Collyn T Murray, Laura Wallace, Wendy Huang, Erica Blustein, Alexander Croft, Ernesto Romo, Mansi Agarwal, Daniel Theodoro

2020-Current year OA Pubs

INTRODUCTION: Resuscitative transesophageal echo (rTEE) is a promising adjunct to cardiac arrest resuscitation. However, it is a high-acuity diagnostic tool that is rarely used in this setting and its safety establishment is limited because of low occurrence. High-acuity, low occurrence skills such as rTEE during cardiac arrest inevitably decay. In this study we examined the content and percentage of rTEE skill decay following simulation-based education (SBE).

METHODS: Resuscitative TEE-naïve emergency physicians (EP) were trained using a combination of clinical exposure, web-based didactics, and monthly hands-on sessions with a high-fidelity rTEE simulator for four months. The COVID-19 pandemic created a natural …

Assessing The Impact Of Home Environmental Exposures On Allergic Rhinitis Using Real-Time Air Quality Monitoring And Symptom Assessment: Observational Feasibility Study., Aero Cavalier, Anthony I. Dick, Vickie Johnson Ii, Emily Cramer, Kamal Eldeirawi, Jayant Pinto, Sharmilee M. Nyenhuis, Victoria S. Lee

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Rhinitis is the most common sinonasal condition and poses a significant cost burden. Rhinitis symptom control is associated with exposure to environmental triggers (eg, aeroallergens, pollutants, and irritants). While people spend much of their time at home, studies examining the association of rhinitis symptoms with home environmental exposures, especially in low-income, urban, and racial or ethnic minorities, are limited. Frequently, 3 types of surveys are used in ecological momentary assessment (EMA): a survey conducted at a predetermined rate, an event-triggered survey, and a follow-up survey to gauge behavioral changes in response to the event.

OBJECTIVE: This study aims to …

Characterization And Clinical Implications Of P53 Dysfunction In Patients With Myelodysplastic Syndromes, Matteo Zampini, Elena Riva, Luca Lanino, Elisabetta Sauta, Rita Antunes Dos Reis, Rosa Maria Andres Ejarque, Giulia Maggioni, Alberto Termanini, Alessandra Merlotti, Alessia Campagna, Lorenzo Dall'olio, Austin Kulasekararaj, Michela Calvi, Clara Di Vito, Arturo Bonometti, Daoud Rahal, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Rossella Caselli, Serena Albertazzi, Gabriele Todisco, Marta Ubezio, Laura Crisafulli, Alessandro Frigo, Enrico Lugli, Ettore Mosca, Pamela Acha, Serena Ghisletti, Francesco Nicassio, Armando Santoro, Maria Diez-Campelo, Francesc Solé, Lionel Ades, Uwe Platzbecker, Valeria Santini, Pierre Fenaux, Torsten Haferlach, David Sallman, Guillermo Garcia-Manero, Domenico Mavilio, Daniel Remondini, Gastone Castellani, Saverio D'Amico, Amer M Zeidan, Rami Komrokji, Shahram Kordasti, Francesca Ficara, Matteo Giovanni Della Porta, Calr Consortium

Faculty, Staff and Student Publications

Purpose: Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients and methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients.

Results: Biallelic TP53 inactivation was a powerful driver …

Multi-Ancestry Genome-Wide Association Analyses Incorporating Snp-By-Psychosocial Interactions Identify Novel Loci For Serum Lipids, Amy R Bentley, Michael R Brown, Solomon K Musani, Karen L Schwander, Thomas W Winkler, Mario Sims, Tuomas O Kilpeläinen, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Jin-Fang Chai, Kumaraswamy Naidu Chitrala, Nora Franceschini, Mariaelisa Graff, Xiuqing Guo, Fernando P Hartwig, Andrea R V R Horimoto, Elise Lim, Yongmei Liu, Alisa K Manning, Ilja M Nolte, Raymond Noordam, Melissa A Richard, Albert V Smith, Yun Ju Sung, Dina Vojinovic, Rujia Wang, Yujie Wang, Mary F Feitosa, Sarah E Harris, Leo-Pekka Lyytikäinen, Giorgio Pistis, Rainer Rauramaa, Peter J Van Der Most, Erin Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Dan E Arking, Donna K Arnett, Christie Ballantyne, Eric Boerwinkle, Yii-Der Ida Chen, Martha L Daviglus, Lisa De Las Fuentes, Paul S De Vries, Joseph A C Delaney, Amanda M Fretts, Lynette Ekunwe, Jessica D Faul, Linda C Gallo, Sami Heikkinen, Georg Homuth, M Arfan Ikram, Carmen R Isasi, Jost Bruno Jonas, Liisa Keltikangas-Järvinen, Pirjo Komulainen, Aldi T Kraja, Jose E Krieger, Lenore Launer, Lifelines Cohort Study, Jianjun Liu, Kurt Lohman, Annemarie I Luik, Ani W Manichaikul, Pedro Marques-Vidal, Yuri Milaneschi, Stanford E Mwasongwe, Jeffrey R O'Connell, Kenneth Rice, Stephen S Rich, Pamela J Schreiner, Lars Schwettmann, James M Shikany, Xiao-Ou Shu, Jennifer A Smith, Harold Snieder, Nona Sotoodehnia, E Shyong Tai, Kent D Taylor, Lesley Tinker, Michael Y Tsai, André G Uitterlinden, Cornelia M Van Duijn, Diana Van Heemst, Melanie Waldenberger, Robert B Wallace, Hwee-Lin Wee, David R Weir, Wen-Bin Wei, Ko Willems Van Dijk, Gregory Wilson, Jie Yao, Kristin L Young, Xiaoyu Zhang, Wei Zhao, Xiaofeng Zhu, Alan B Zonderman, Ian J Deary, Christian Gieger, Hans Jörgen Grabe, Timo A Lakka, Terho Lehtimäki, Albertine J Oldehinkel, Martin Preisig, Ya-Xing Wang, Wei Zheng, Michele K Evans, Michael Province, James Gauderman, Vilmundur Gudnason, Catharina A Hartman, Bernardo L Horta, Sharon L R Kardia, Charles Kooperberg, Ching-Ti Liu, Dennis O Mook-Kanamori, Brenda Wjh Penninx, Alexandre C Pereira, Patricia A Peyser, Bruce M Psaty, Jerome I Rotter, Xueling Sim, Kari E North, Dabeeru C Rao, Laura Bierut, Clint L Miller, Alanna C Morrison, Charles N Rotimi, Myriam Fornage, Ervin R Fox

Faculty, Staff and Student Publications

Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of genetic loci that influence lipids. We conducted a genome-wide gene-by-psychosocial factor interaction (G×Psy) study in up to 133,157 individuals to evaluate if G×Psy influences serum lipid levels. We conducted a two-stage meta-analysis …

Monoclonal Antibodies Targeting The Fimh Adhesin Protect Against Uropathogenic E. Coli Uti, Edward D B Lopatto, Jesús M Santiago-Borges, Denise A Sanick, Sameer Kumar Malladi, Philippe N Azimzadeh, Morgan W Timm, Isabella F Fox, Aaron J Schmitz, Jackson S Turner, Shaza M Sayed Ahmed, Lillian Ortinau, Nathaniel C Gualberto, Jerome S Pinkner, Karen W Dodson, Ali H Ellebedy, Andrew L Kau, Scott J Hultgren

2020-Current year OA Pubs

As antimicrobial resistance increases, urinary tract infections (UTIs) are expected to pose an increased burden in morbidity and expense on the health care system, increasing the need for alternative antibiotic-sparing treatments. Most UTIs are caused by uropathogenic

Clinical And Radiological Features Of Atypical Adrenal Masses-A Multicenter Retrospective Study, Vania Balderrama-Brondani, Ruaa Al-Ward, Katja Kiseljak-Vassiliades, Lauren Fishbein, Danielle Dawes, Oksana Hamidi, Reza Pishdad, Juan Pablo Perdomo Rodriguez, Mohamad Anas Sukkari, Joseph R Grajo, Hans Kumar Ghayee, Sara Bedrose, Roland L Bassett, Amir H Hamrahian, Mouhammed Amir Habra

Faculty, Staff and Students Publications

Context: The natural history and malignant potential of cases classified as atypical adrenal masses (AAMs) are unknown.

Objective: To describe the radiological characteristics and clinical outcomes of AAMs.

Design and participants: A multicenter retrospective study. Patients ≥18 years old with AAMs [diameter of 10-39 mm on first imaging study and pre-contrast attenuation of >10 Hounsfield units (HU) on computed tomography] were studied. We excluded adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with genetic predisposition to adrenal neoplasms. Data are presented as percentages and median values with interquartile ranges (IQRs).

Results: We included 217 …

The Maturity-Onset Diabetes Of The Young (Mody) Calculator Overestimates Mody Probability In Hispanic Youth, Guido Alarcon, Anh Nguyen, Angus Jones, Beverley Shields, Maria J Redondo, Mustafa Tosur

Children’s Nutrition Research Center Staff Publications

Context: The applicability of the maturity-onset diabetes of the young (MODY) risk calculator to non-White European populations remains unknown.

Objective: We aimed to test its real-world application in Hispanic youth.

Methods: We conducted a retrospective chart review of Hispanic youth (< 23 years) with diabetes (n = 2033) in a large pediatric tertiary care center in the United States. We calculated MODY probability for all subjects, splitting them into 2 cohorts based on the original model: individuals who were started on insulin within 6 months of diabetes diagnosis (Cohort 1) and those who were not (Cohort 2).

Results: Cohort 1 consisted of 1566 individuals (median age [25p, 75p]: 16 [13, 19] years, 49% female), while Cohort 2 comprised 467 youth (median age [25p, 75p]: 17 [15, 20] years, 62% female). The mean MODY probability was 5.9% and 61.9% in Cohort 1 and Cohort 2, respectively. The mean probability for both cohorts combined was 18.8%, suggesting an …

Single-Cell Expression Analysis Of Ductal Carcinoma In Situ Identifies Complex Genotypic-Phenotypic Relationships Altering Epithelial Composition, Xiaodi Qin, Xiaoke Luo, Graham A Colditz, Shu Jiang, Et Al.

2020-Current year OA Pubs

UNLABELLED: Ductal carcinoma in situ (DCIS) is a risk factor for subsequent invasive breast cancer (IBC). To identify events in DCIS that lead to invasive cancer, we performed single-cell RNA sequencing on DCIS lesions and matched normal breast tissue. Inferred copy-number variation was used to identify neoplastic epithelial cells from clinical specimens, which contained a mixture of DCIS and normal ducts. Phylogenetic analysis demonstrated intratumoral clonal heterogeneity that was associated with significant gene expression differences. Classification of epithelial cells into mammary cell states revealed that subclones contained a mixture of cell states, suggesting an ongoing pattern of differentiation after neoplastic …

Type I Interferon Protects Against Bone Loss In Periodontitis By Mitigating An Interleukin (Il)-17-Neutrophil Axis, Jinmei Zhang, Qiong Ding, Angela X Wang, Maoxuan Lin, Ning Yu, Kevin Moss, Megumi A Williamson, Di Miao, Julie T Marchesan, Erliang Zeng, Wei Shi, Hongli Sun, Yu Leo Lei, Shaoping Zhang

Faculty, Staff and Student Publications

Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in an exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid …

Asymmetric Cingulum Bundle Connectivity Is Modulated By Paracingulate Sulcus Morphology, Isabel A Danstrom, Joshua A Adkinson, Meghan E Robinson, Lu Lin, Atul Maheshwari, Ben Shofty, Garrett Banks, Mohammed Hasen, Sameer A Sheth, Alica M Goldman, Eleonora Bartoli, Sarah R Heilbronner, Kelly R Bijanki

Faculty, Staff and Students Publications

The cingulum bundle (CB) is a group of axons supporting connectivity among several functional brain networks relevant in healthy and diseased states. The paracingulate sulcus (PCS) is present in at least one cerebral hemisphere across 70% of the population. PCS presence versus absence is linked to differences in structure and function of the anterior cingulate cortex, though the influence of PCS on the white matter of the CB remains unknown. The objective of this work was to define the CB electrographic connectivity profile and determine the impact of PCS morphology on CB engagement. Single-pulse electrical stimulation in combination with stereo-electroencephalography …

Clinical Profile Of Patients With Monocular Elevation Deficiency Undergoing Strabismus Surgery, Mohamad Reza Akbari, Babak Masoomian, Elham Azizi, Mohammed Omer Mahmood, Arash Mirmohammadsadeghi, Ali Majdi, Masoud Khorrami-Nejad

Wills Eye Hospital Papers

PURPOSE: To provide a comprehensive evaluation of the visual, refractive, and strabismic characteristics of patients with monocular elevation deficiency (MED) undergoing strabismus surgery.

METHODS: The medical records of patients at a single institution who were diagnosed with and underwent surgery for MED were reviewed retrospectively. Visual acuity, refractive error, angle of deviation, abnormal head posture (AHP), presence of ptosis, prevalence of amblyopia and strabismic patterns were analyzed, with MED eyes compared with fellow eyes.

RESULTS: A total of 105 patients were included. Mean cylindrical refractive error was significantly higher in MED eyes compared with fellow eyes (-1.40 ± 1.70 D …

Integrated Metabolomics And Spatial Transcriptomics Of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism As A Biomarker Of Progression, Ricardo A León-Letelier, Yihui Chen, Rongzhang Dou, Ehsan Irajizad, Michele T Yip-Schneider, Ranran Wu, Rahmah Ejaz, Hamid K Rudsari, Yaxi Li, Rachelle Spencer, Riccardo Ballarò, Jody Vykoukal, Mark Hurd, Jennifer B Dennison, Kim-Anh Do, Anirban Maitra, Jianjun Zhang, Samir Hanash, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

Purpose: We conducted metabolomics and spatial cell transcriptomics of intraductal papillary mucinous neoplasms (IPMN), recognized pancreatic cancer precursors, to identify oncometabolites that inform upon risk of malignancy of IPMNs.

Experimental design: Untargeted metabolomic analyses were performed on cystic fluid from 125 patients with low-grade (LG) dysplasia or high-grade (HG) dysplasia with/without concurrent pancreatic ductal adenocarcinoma (PDAC; IPMN/PDAC). Predictive performance of individual metabolites for identifying HG or PDAC/IPMN was determined and compared with CA19-9 performance. Data were intersected with metabolic profiles of resected IPMN tissues and murine Kras;Gnas IPMN cell lines as well as spatial and single-cell transcriptomics of IPMNs.

Results: …

Real-World Outcomes For Young Adult Patients Receiving Cd19 Car T-Cell Therapy., Hannah Lust, Liora M. Schultz, Soyang Kwon, Gregory W. Roloff, Ibrahim Aldoss, Christina Baggott, Samuel John, Jenna E. Rossoff, Kevin O. Mcnerney, Vanessa A. Fabrizio, Julie-An Talano, Amy Moskop, Kevin J. Curran, Christine L. Phillips, Nicole Karras, Susanne H C Baumeister, Stacy L. Cooper, Michelle Hermiston, Prakash Satwani, Muna Qayed, Sunil S. Raikar, Margaret Macmillan, Erin Hall, Khanh Nguyen, Ryan D. Cassaday, Noam E. Kopmar, Vamsi K. Kota, John Mathews, Paul Shaughnessy, Marc S. Schwartz, Abdullah Ladha, George Yaghmour, Muthu V. Kumaran, Veronika Bachanova, Sean Tracy, Tamer Othman, Marlise R. Luskin, Evan C. Chen, Anjani S. Advani, Nikeshan Jeyakumar, Katharine Miller, Amy Zhang, Katherine C. Sutherland, Bijal D. Shah, Lori Muffly, Rawan Faramand

Manuscripts, Articles, Book Chapters and Other Papers

Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 chimeric antigen receptor T-cell therapy (CAR T) products for young adults (YA) with relapsed/refractory B-cell acute lymphoblastic leukemia. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Using retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe the efficacy and safety of tisa-cel and brexu-cel in 70 YAs (18-26 years; tisa-cel, n = 50; brexu-cel, n = 20). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed more frequently …

Olfaction And Plasma Biomarkers Of Alzheimer Disease And Neurodegeneration In The Atherosclerosis Risk In Communities Study, Srishti Shrestha, Xiaoqian Zhu, Michael E Griswold, Priya Palta, Kevin J Sullivan, Honglei Chen, Andrea Lauren Christman Schneider, Abhay Moghekar, Megan L Grove, Bharat Thyagarajan, James Russell Pike, Rebecca F Gottesman, B Gwen Windham, Thomas H Mosley, Jennifer A Deal, Vidyulata Kamath

Faculty, Staff and Student Publications

Background and objectives: Investigation of olfactory impairment, an early manifestation of Alzheimer disease (AD), in relation to plasma biomarkers of AD and neurodegeneration could provide insights into the disease's pathophysiology. Because few such studies based on large, diverse, community-based populations exist, we investigated associations of odor identification ability with plasma biomarkers of AD and other neurodegenerative pathologies in community-dwelling Black and White older adults.

Methods: This cross-sectional investigation included participants from the Atherosclerosis Risk in Communities study who attended visit 5 (2011-2013) and who completed olfactory testing and brain MRI examinations and had plasma biomarkers measured (namely, amyloid-beta [Aβ]42/Aβ40 ratio, …