Digital Commons Network^™

Response Of Ipsc-Derived Neurons From Individuals With Treatment-Resistant Depression To (2 R, 6 R)-Hydroxynorketamine And Reelin: An Exploratory Study, Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu, Nirmala Akula, Brandi Quintanilla, Shiyong Peng, Greg H Jones, Anton Schulmann, Mani Yavi, Ioline D Henter, Francis J Mcmahon, Lisa E Kalynchuk, Carlos A Zarate, Hector J Caruncho

Faculty, Staff and Student Publications

Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to model in animal phenotypes, suggesting that other experimental and translational models must be considered to properly address and research novel therapeutics. Reelin, an endogenous glycoprotein downregulated in depression, has shown rapid antidepressant-like effects akin to those of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine. Interestingly, the antidepressant-like effects of both ketamine and reelin affect mechanistic target of rapamycin complex 1 (mTORC1) activity and that of its related downstream signalers. (2 R,6 R)-hydroxynorketamine (HNK) is a major metabolite of ketamine that, at …

Development Of A Low-Barrier, Reimbursable Take-Home Naloxone Program At A Regional Health System, Kory S. London, Sejal Patel, Drew Lockstein, Jamal Rashid, Dennis Goodstein, Richard Pacitti, Tareva Warrick-Stone, Frederick Randolph, Alan Cherney, Karen Alexander, Megan Reed

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: Take-home naloxone (THN) programs in emergency departments (ED) can reduce opioid overdose deaths by providing naloxone directly to at-risk patients before discharge. However, sustainable models that integrate reimbursement and workflow alignment remain limited.

METHODS: A reimbursable ED-led THN program was developed across a large regional health system. The program used electronic health record (EHR)-integrated ordering, on-site kit dispensing, and third-party insurance billing when available. Kits were stocked in automated medication dispensing systems and supplemented by city-provided stock for uninsured patients. Pilot outcomes included kits dispensed and reimbursement rates across eight participating EDs.

RESULTS: A total of 2,520 naloxone kits …

Unveiling Humility In Emergency Medicine Chief Residents: A Thematic Exploration Of Standard Letters Of Evaluation, Abagayle Bierowski, Ridhima Ghei, Casey Morrone, Xiao C. Zhang, Dimitrios Papanagnou

Department of Medicine Faculty Papers

INTRODUCTION: Although humility is a key leadership trait linked to collaboration and trust, current residency application processes lack methods to identify it. By examining whether themes of humility appear in the Standardized Letters of Evaluation (SLOE) of medical students who later became emergency medicine (EM) chief residents, we sought to determine the presence of humility-related traits in SLOEs and explore their potential to inform the identification of applicants with leadership potential during residency selection.

METHODS: Two independent reviewers examined 104 SLOEs (52 chief, 52 non-chief) from 2015-2021, representing 43 students (21 who later assumed chief resident positions and 22 who …

Aqueous Humor Biomarkers In Ocular Oncology: Insights And Advances, Lara Cheslow, Signe Caksa, Rachel E. Cain, Scott A. Waldman, Andrew A. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ocular malignancies, though relatively rare, pose significant risks to patients' vision, quality of life, and potential for developing metastatic disease. Due to the eye's complicated and delicate anatomy, diagnosing ocular malignancy and monitoring its progression can be technically challenging. Current approaches include direct tumor biopsy, vitreous humor sampling, and imaging. However, these techniques are associated with rare, yet potentially severe, side effects and can be invasive or limited in detecting microscopic disease. Recent studies have introduced aqueous humor sampling as a promising, minimally invasive alternative to diagnose ocular malignancy, guide therapeutic management, monitor response to treatment, and track early recurrence. …

Ultra-Low-Field Portable Magnetic Resonance Imaging Feasibility And Safety In Pediatric And Neonatal Extracorporeal Membrane Oxygenation: A Single-Center Year-Long Experience., Jessica S. Wallisch, Asdis Finnsdottir Wagner, John M. Daniel Iv, Allison Taber, Maura Sien, Sarah Foster, Nathan S. Artz, Timothy Zinkus, Hung-Wen Yeh, Jose A. Pineda, Patrick M. Kochanek, Sherwin S. Chan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improving outcomes, extracorporeal membrane oxygenation (ECMO) remains associated with high rates of acute brain injury, impacting survival and outcomes. Clinical imaging modalities, including computed tomography and standard-field magnetic resonance imaging (≥1.5 Tesla), have either limited early detection of ischemic-type injuries or are incompatible with ECMO, causing diagnostic delays. A Food and Drug Administration-cleared ultra-low-field portable magnetic resonance imaging (pMRI; 0.064 Tesla) has shown promise in acute brain injury detection and use with MRI-unsafe equipment, but pediatric ECMO data are limited.

METHODS: This institutional review board-approved, single-center study was conducted at a quaternary children's hospital. Neonatal and pediatric patients …

Estimated Impact Of 2022–2023 Influenza Vaccines On Annual Hospital Burden In The United States, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Annalise Cramer, Spencer J Fox, Rebecca K Borchering, Matthew Biggerstaff, Lauren Ancel Meyers

Faculty, Staff and Student Publications

During the COVID-19 pandemic early years, infection prevention measures suppressed transmission of seasonal influenza and other respiratory viruses. The early onset and moderate severity of the US 2022-2023 influenza season may have resulted from reduced use of nonpharmaceutical interventions or lower population immunity after 2 y of limited influenza virus circulation. We used a mathematical model of influenza virus transmission that incorporates vaccine-derived protection against both infection and severe disease to estimate the impact of influenza vaccines on healthcare burden. Assuming reported levels of past vaccine effectiveness (VE) against infection and hospitalization, we estimate that influenza vaccines prevented 69,886 (95% …

Sex Differences In Atherosclerotic Coronary Artery Disease Patterns, Kazumasa Ikeda, Daniel Munhoz, Sofie Brouwers, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Ketina Arslani, Antonio Maria Leone, Domenico Galante, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Koshiro Sakai, Tatyana Storozhenko, Bruno R Da Costa, Gianluca Campo, Colin Berry, Damien Collison, Thomas Johnson, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad Ali, Bernard De Bruyne, Frederic Bouisset, Takashi Kubo, Nobuhiro Tanaka, Kazuhiro Satomi, Nils P Johnson, Carlos Collet, Takuya Mizukami

Faculty, Staff and Student Publications

Background: Sex differences in coronary artery disease (CAD) have been increasingly recognized, as women present with distinct clinical characteristics and outcomes compared with men. This study investigated the impact of sex on pathophysiological CAD patterns (focal versus diffuse) in stable patients undergoing percutaneous coronary interventions (PCI).

Methods: We conducted a subanalysis of the PPG Global (Pullback Pressure Gradient Global Registry) study, a multicenter, prospective trial including 993 patients (236 [23.8%] women and 757 [76.2%] men) with hemodynamically significant CAD, defined as fractional flow reserve ≤0.80. The pullback pressure gradient metric categorized CAD patterns as focal or diffuse. Patient-reported outcomes were …

Vessel-Specific Myocardial Mass In Patients With Stable Coronary Artery Disease, Nikolaos Stalikas, Takuya Mizukami, Frederic Bouisset, Kazumasa Ikeda, Atomu Tajima, Daniel Munhoz, Thabo Mahendiran, Adriaan Wilgenhof, Koshiro Sakai, Bjarne Noorgard, Thomas Engstroem, Jonathon Leipsic, Giulio Stefanini, Antonio Bartorelli, Timothy Fairbairn, Alan Bagnall, Brian Ko, Nils P Johnson, Colin Berry, Divaka Perera, Evald Høj Christiansen, Toshiro Shinke, Hiromase Otake, Bon Kwon Koo, Emanuele Barbato, Salvatore Brugaletta, Damien Collison, Gianluca Campo, Eric Van Belle, Tommaso Goori, Lokien Van Nunen, Adam Witkowski, Patricio Astudillo, James Spratt, Tetsuya Amano, Hirohiko Ando, Georgios Sianos, Jeroen Sonck, Daniele Andreini, Bernard De Bruyne, Carlos Collet

Faculty, Staff and Student Publications

Background: Assessing the myocardial mass at risk is essential in evaluating patients with coronary artery disease. This study aims to establish reference values for vessel-specific myocardial mass derived from coronary computed tomography angiography, providing a quantitative assessment of the myocardial mass subtended by each epicardial vessel.

Methods: Left ventricular (LV) and vessel-specific myocardial mass were calculated from coronary computed tomography angiography using the Voronoi method in patients with stable coronary artery disease. Myocardial mass was quantified for each epicardial coronary artery with a diameter >1.5 mm.

Results: We included 948 patients with 9228 epicardial coronary artery branches. Mean age was …

Using Machine Learning For Early Prediction Of In-Hospital Mortality During Icu Admission In Liver Cancer Patients, Zhuo Zheng, Jinhong Xia, Jiawei Luo, Lei Du, Xiaobo Zhou, Xiaoyan Yang, Yan Xia, Mengyao Liu, Shixin Huang

Faculty, Staff and Student Publications

Liver cancer has a high incidence and mortality rate globally, particularly in patients requiring intensive care unit (ICU) admission. Early prediction of in-hospital mortality for these patients is crucial, yet lacking reliable tools. This study aims to develop and evaluate machine learning (ML) models for predicting in-hospital mortality in critically ill liver cancer patients admitted to the ICU. This retrospective study used data from the MIMIC-III and MIMIC-IV databases, including 862 patients from MIMIC-III (training cohort) and 692 patients from MIMIC-IV (validation cohort). The study focused on patients diagnosed with liver cancer, identified by specific ICD codes. Four ML algorithms, …

Insights Into The Relevance Of Targeting Fibroblasts To Control Cancer, Viktoria Boeker, Raghu Kalluri

Faculty, Staff and Student Publications

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) have garnered significant research attention in the last decade. As key stromal cells of the TME, studies have explored them as a potential target for controlling cancer. Using high-throughput technologies like single-cell RNA sequencing coupled with proteomics, the classification of different CAF subgroups reveals a complex system that varies by cancer type. Unraveling novel big data, potentially through AI platforms, will be key to identifying the role of CAFs in tumor progression and therapy escape mechanisms, enabling new therapies that manipulate CAFs to increase patients' survival. We summarize and discuss new developments …

Voices: Future Directions In Targeting The Tumor Microenvironment, Tanja De Gruijl, Catherine Sautès-Fridman, Daniela S Thommen, Michael A Curran

Faculty, Staff and Student Publications

What do you envision as the most promising future directions for therapeutic strategies aimed at modulating the tumor microenvironment?

Prognosis And Treatment Response Stratification According To Loss Of Proofreading (Lop), Giulia Maddalena, Fadl A Zeineddine, Saikat Chowdhury, Mohammad A Zeineddine, Abdelrahman M Yousef, Francesca Bergamo, Sara Lonardi, Timothy A Yap, Michael Geoffrey White, Michael J Overman, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

Background: Only a subset of polymerase epsilon (POLE) mutations is associated with hypermutant phenotype; we hypothesized that only loss-of-proofreading (LOP) POLE mutations are associated with favorable immunotherapy response.

Methods: This retrospective cohort study included a pan-cancer cohort of 69,223 patients from cBioPortal and a cohort of patients with 41 POLE mutant metastatic colorectal (CRC) treated with immunotherapy at the MD Anderson Cancer Center between January 2017 and May 2023. We evaluated prognosis according to POLE mutation functionality.

Results: In the pan-cancer cBioPortal cohort (n=69,223) POLE was mutated in 2.8% (1,965) of tumors; of these, only 7.5% (n=148) had …

Identification Of Therapeutic Targets For Renal Medullary Carcinoma Via Integrated Genomic And Transcriptomic Profiling, Pavlos Msaouel, Nizar M Tannir, Funda Meric-Bernstam, Jennifer M King, Martin H Voss, Jessica P Cheng, Susan S Thomas, Zita D Lim, Menuka Karki, Rong He, Giannicola Genovese, Rahul A Sheth, Davis R Ingram, Diana Shamsutdinova, Khalida M Wani, Wei-Lien Wang, Alexander J Lazar, Dominique Knipper-Davis, Amber Berlinski, Tayla Soares, Danil Stupichev, Kirill Kryukov, Suren Davitavyan, Anna Novokreshchenova, Dmitry Lebedev, Stanislav Kurpe, Andrey Kravets, Dmitrii Belousov, Michael Hensley, Alexander Bagaev, Francesca Paradiso, Vladimir Kushnarev

Faculty, Staff and Student Publications

Renal medullary carcinoma (RMC) is a rare but highly aggressive kidney cancer that resists conventional therapies. To identify therapeutic targets, this study employs histopathologic, genomic, and transcriptomic profiling of 25 RMC samples. TROP2, EPCAM, CLDN6, and CDH6 are significantly overexpressed compared with other renal and solid tumors. Pathway analyses indicate Hippo pathway upregulation and a tumor microenvironment rich in fibroblasts and neutrophils. We subsequently explore treatment of four heavily pretreated patients, all with high TROP2 expression, using sacituzumab govitecan, a TROP2-targeted antibody-drug conjugate. Of these four patients, one patient achieves a partial response with symptom improvement, two patients maintain stable …

Two Unrelated Pseudomonas Aeruginosa Phages Require The Exopolysaccharide Psl For Infection, Kristen Amyx-Sherer, Leila C Awasthi, Amanda Zheng, Anna Johannesman, Michele Leroux, Courtney Reichhardt

2020-Current year OA Pubs

Bacteria commonly protect themselves from a variety of threats by forming biofilms, which are communities of bacteria that are tightly packed together within an extracellular matrix. Biofilm formation has generally been thought to protect bacteria from phage infection. The opportunistic pathogen Pseudomonas aeruginosa produces biofilm matrices that can contain three distinct exopolysaccharides that contribute to the difficulty in treating infected patients. Here, we demonstrate that two diverse P. aeruginosa phages have evolved to exploit this biofilm matrix to access the bacterial cells by both binding to and degrading a major biofilm exopolysaccharide, Psl. We examined the effect of these phages …

Depth-Variant Deconvolution Applied To Widefield Microscopy For Rapid Large-Volume Tissue Imaging, Daniel D Lee, Kevin A Telfer, Mark A J Koenis, Yim K Lee, Kevin W Namink, Brian T Saunders, Heyun Lee, Hailey Kelley, Heather S Ruiz, Joseph P Gaut, Gwendalyn J Randolph, Bernd H Zinselmeyer

2020-Current year OA Pubs

Innovations in 3D tissue imaging have revolutionized research, but limitations stemming from lengthy protocols and equipment accessibility persist. Widefield microscopy is fast and accessible but often excluded from 3D imaging workflows due to its lack of optical sectioning. Here we combine tissue clearing with a commercial depth-variant deconvolution approach that we optimized for large-volume widefield imaging. By implementing prefiltering with z-brick splitting, we achieve subnuclear axial resolution in tissues to a depth of 500 µm in multi-tile scan images. We illustrate the utility of this method in a model of ileitis and to gain a 3D perspective in thick brain …

Bladder Health And The Urogenital Microbiome In Community-Dwelling Adult Females, L Brubaker, D Mcdonald, S Putnam, C Brennan, C S Fok, C E Lewis, J L Lowder, M G Mueller, L M Rickey, E R Mueller, S J Song, K Rudser, R Knight, E S Lukacz, Plus Consortium

2020-Current year OA Pubs

UNLABELLED: Despite the established association with lower urinary tract symptoms, the relationship between a healthy bladder and the urogenital microbiome is unknown. This observational cohort study of 435 community-dwelling women examined bladder health and function using a validated instrument. Voided urine samples were self-collected, shipped to a repository, and underwent 16S rRNA amplicon sequencing. Two hundred seventy-four (56%) samples were retained following a limit-of-detection analysis for low biomass samples. A differential abundance analysis showed that

IMPORTANCE: There is increasing awareness that human microbiomes impact health and modulate certain health conditions. Recently, investigators developed a validated assessment of bladder health in …

Improved Technical Outcomes With Converting Thrombectomy Techniques After Failed First Pass Recanalization, Hidetoshi Matsukawa, Charles Matouk, Kazutaka Uchida, Sami Al Kasab, Mohammad-Mahdi Sowlat, Sameh Samir Elawady, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Q Wolfe, Ansaar T Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Adam S Arthur, Hugo Cuellar, Brain M Howard, Daniele G Romano, Omar Tanweer, Justin R Mascitelli, Isabel Fragata, Adam Polifka, Joshua W Osbun, Roberto Javier Crosa, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Richard Williamson, Pedro Navia, Peter Kan, Reade Andrew De Leacy, Shakeel A Chowdhry, Mohamad Ezzeldin, Alejandro M Spiotta, Shinichi Yoshimura, Ali M Alawieh

Faculty, Staff and Students Publications

Background: A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes.

Methods: This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization. Propensity score matching identified a 1:1 matched cohort of patients in whom EVT technique was changed after a failed first pass and those with the same technique …

Does Preoperative Arthritis Affect The Outcomes Of Superior Capsular Reconstruction? A Systematic Review, Tae-Hoon Park, Hyungsuk Kim, Sukil Kim, Jongin Lee, Gerald R. Williams, Hyun Seok Song

Rothman Institute Papers

BACKGROUND: The optimal indications for superior capsular reconstruction (SCR) in cases of massive irreparable rotator cuff tears (RCTs) accompanied by degenerative arthritis remain controversial.

METHODS: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase (Elsevier), and Google Scholar. Studies were included if they documented Hamada grade and reported clinical and radiographic outcomes after SCR for irreparable RCTs. American Shoulder and Elbow Surgeons (ASES) score, visual analog scale for pain (pVAS), active range of motion, and acromiohumeral distance (AHD) were analyzed.

RESULTS: In all 7 studies, there was no consistent …

Tlr2 Agonism Suppresses Myeloid Leukemogenesis By Reprogramming Leukemia Stem Cells, Michael E. Lawler, Jennifer S. Romer-Seibert, Michael S. Bowman, Ramkrishna Mitra, Christine M. Eischen, Robert L. Bowman, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The consequences of activated innate immune signaling in acute myeloid leukemia (AML) is not well understood. Using ligands directed at the toll-like family receptors (TLR) in models of high-risk AML, we uncover that TLR2 ligands exert unique antileukemic effects that are distinct from other TLRs. Although TLR2 signaling broadly induces inflammatory gene expression in AML cells, at the single-cell level, cell-type-dependent, divergent transcriptional responses coordinate cellular outputs of proliferation, differentiation, cell death, and activation of immune cell function. TLR2 ligands were the only TLR agonists capable of extending survival of AML-bearing mice through leukemia stem cell (LSC) reprogramming that elevated …

Cordmilk: Umbilical Cord Milking Versus Early Cord Clamping On Short-And Long-Term Outcomes In Neonates Who Are Non-Vigorous At Birth-Study Protocol Of A Multi-Center, Cluster-Randomized, Crossover-Controlled Trial, S. Yogeshkumar, Sunil S. Vernekar, Sangappa M. Dhaded, Kiran Talekar, Benjamin E Leiby, Rebecca Hartman, Yvonne Vaucher, Nitin Chouthai, Meenakshi Girish, Manish Jain, Shuchi Jain, Seema Parvekar, Vinita Jain, Alka Patankar, Milind Suryawanshi, Manish Tiwari, Manjushri Waikar, Nidhi Nashine, Deepali Ambike, Mahesh Asalkar, Rajesh Kulkarni, Sandhya Haribhaktha, Hemraj Narkhede, Sudha Chaudhari, Milind Kamble, Deepti Shrirame, Balchandra Falke, Seema Mehta, Asha Verma, Sunil Gothwal, Shivaprasad S. Goudar, Richard Derman, Anup Katheria, Zubair H. Aghai

Department of Radiology Faculty Papers

BACKGROUND: Facilitating placental transfusion-the transfer of blood from the placenta to the newborn-via delayed cord clamping (DCC) or umbilical cord milking (UCM) at birth has been shown to improve iron stores in healthy term infants and may positively impact long-term neurodevelopmental outcomes. Infants who are non-vigorous at birth and at risk of developing hypoxic-ischemic encephalopathy (HIE) are particularly likely to benefit from placental transfusion. This process may offer neuroprotection by enhancing cardiopulmonary transition, supporting cardiac preload, improving systemic and cerebral perfusion, delivering stem cells and neurotrophic factors, and preventing iron deficiency. While DCC is not currently recommended for non-vigorous term …

Autostent: A Semi-Automated Approach To Designing Customized 3d-Printed Oral Radiation Stents For Patients With Head And Neck Cancer, Anshuman Agrawal, Rance B Tino, Mohamed Zaid, Millicent Roach, Lianchun Xiao, Mark S Chambers, Anna Lee, Eugene J Koay

Faculty, Staff and Student Publications

Background: Oral stents may reduce toxicities during radiation therapy for head and neck cancer (HNC). Customized 3D-printed oral stents offer faster production and achieve comparable patient-reported outcomes to conventionally fabricated stents. However, their design process remains time-consuming, lacks standardization, and relies heavily on skilled technicians. We hypothesized that semi-automating the design process for 3D-printed, mouth-opening, tongue-depressing (MOTD) stents could standardize the design workflow and decrease design time.

Methods: Using oral stent design principles established over decades by oral oncologists, we created a customized computer program (Autostent) using MATLAB to semi-automate the design process of MOTD stents. We subsequently compared Autostent …

Multiomic Analysis Reveals A Key Bcat1 Role In Mtor Activation By B Cell Receptor And Tlr9, Rui Guo, Yizhe Sun, Matthew Y Lim, Hardik Shah, Joao A Paulo, Rahaman A Ahmed, Weixing Li, Yuchen Zhang, Haopeng Yang, Liang Wei Wang, Daniel Strebinger, Nicholas A Smith, Meng Li, Merrin Man Long Leong, Michael Lutchenkov, Jin Hua Liang, Zhixuan Li, Yin Wang, Rishi Puri, Ari Melnick, Michael R Green, John M Asara, Adonia E Papathanassiu, Duane R Wesemann, Steven P Gygi, Vamsi K Mootha, Benjamin E Gewurz

Faculty, Staff and Student Publications

B lymphocytes play major adaptive immune roles, producing antibodies and driving T cell responses. However, how immunometabolism networks support B cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B cell transcriptional, translational, and metabolomic responses to B cell receptor (BCR), TLR9, CD40-ligand (CD40L), IL-4, or combinations thereof. T cell-independent BCR/TLR9 costimulation, which drives malignant and autoimmune B cell states, highly induced transaminase branched chain amino acid transaminase 1 (BCAT1), which localized to lysosomal membranes to support branched chain amino acid synthesis and mTORC1 activation. BCAT1 inhibition …

High-Sensitivity Plasma Proteomics Reveals Disease-Specific Signatures And Predictive Biomarkers Of Alzheimer's Disease Phenotypes In A Large Mixed-Dementia Cohort, Katherine Gong, Jigyasha Timsina, Muhammad Ali, Yike Chen, Menghan Liu, Ciyang Wang, Cyril Pottier, Geoffrey K Feld, Gyujin Heo, Tammie L S Benzinger, Cyrus A Raji, Beau Ances, Brian A Gordon, Julie K Wisch, Suzanne E Schindler, John C Morris, David M Holtzman, Laura Ibanez, Carlos Cruchaga

2020-Current year OA Pubs

Novel plasma assays enabled accurate blood-based biomarkers for neurodegenerative diseases with minimally invasive options for clinical use. Large-scale studies encompassing multiple neurodegenerative diseases using novel multiplex platforms are essential to uncover disease-specific biomarkers and pathways. We generated and analyzed plasma biomarker data using the NULISAseq™ CNS Panel from 3,232 participants with Alzheimer disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal dementia (FTD), Parkinson disease (PD) and cognitively unimpaired individuals, from the Charles F. and Joanne Knight Alzheimer Disease Research Center. We identified proteins associated with disease status and AD-related phenotypes (Clinical Dementia Rating®, CSF Aβ42/Aβ40, Amyloid-PET, and Tau-PET). These proteins …

Dietary Sources Of Sodium Intake In Nigerian Adults: A Population-Based Cross-Sectional Study, Clementina E Okoro, Erica L Jamro, Guhan Iyer, Mark D Huffman, Et Al.

2020-Current year OA Pubs

Nigeria seeks to address the growing burden of hypertension and related diseases by reducing excessive dietary sodium through national dietary policymaking. This study aims to describe the levels and sources of dietary sodium intake among Nigerian adults to inform these policies. From June 2023 to July 2023, adults aged 18 to 69 years old were recruited from the Federal Capital Territory, Kano, and Ogun states to participate in a population-based, cross-sectional demographic health survey. Data were also collected to assess levels and dietary sources of sodium through four 24-h dietary recalls by trained study personnel. The primary analyses included the …

Ptbp1 Variants Displaying Altered Nucleocytoplasmic Distribution Are Responsible For A Neurodevelopmental Disorder With Skeletal Dysplasia, Aymeric Masson, Catherine Gooch, Et Al.

2020-Current year OA Pubs

Polypyrimidine tract-binding protein 1 (PTBP1) is a heterogeneous nuclear ribonucleoprotein primarily known for its alternative splicing activity. It shuttles between the nucleus and cytoplasm via partially overlapping N-terminal nuclear localization (NLS) and export (NES) signals. Despite its fundamental role in cell growth and differentiation, its involvement in human disease remains poorly understood. We identified 27 individuals from 25 families harboring de novo or inherited pathogenic variants - predominantly start-loss (89%) and, to a lesser extent, missense (11%) - affecting NES/NLS motifs. Affected individuals presented with a syndromic neurodevelopmental disorder and variable skeletal dysplasia with disproportionate short stature with short limbs. …

Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas

Department of Neurology Faculty Papers

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients …

Intersectional Stigma And Resilience In The Uptake Of Cervical Cancer Prevention Services In Nigeria: A Qualitative Study, Agatha Eileen Wapmuk, Titilola Abike Gbaja-Biamila, Ekenechukwu Kokelu, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is one of the leading causes of death among women in Africa, but stigma often delays cervical cancer prevention. We explore the perceptions, enablers and nurturers through the lens of intersectional stigma in the uptake of cervical cancer prevention services in Nigeria.

METHOD: Indepth interviews and focus group discussions were conducted among women aged 30-65 years and girls aged 9-26 years in Lagos, Nigeria. Data were analysed thematically. Using the relationships and expectation domain of the PEN-3 cultural model, we identified perceptions, enablers and nurturers related to the uptake of primary and secondary cervical cancer prevention services …

The Effects Of Marital Status, Partner Drinking, And Sex Differences On The Likelihood Of Remission From Alcohol Use Disorder, Christina Garasky, Alexis Duncan, Fanghong Dong, Jared Balbona, Andrey Anokhin, Emma Johnson, Arpana Agrawal, Kathleen Bucholz, Vivia Mccutcheon, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Marriage is associated with improved health and alcohol outcomes, yet prior research has often combined diverse non-marital relationships, obscuring whether benefits are unique to marriage or a result of strong interpersonal relationships. This study examines whether marriage, compared to cohabitation, exclusive dating, or being single, is associated with alcohol use disorder (AUD) remission and whether this varies by sex and partner drinking.

METHOD: Participants were adults from the Collaborative Study on the Genetics of Alcoholism Lifespan Study (n = 1494; 54.4% female) who met criteria for lifetime DSM-5 AUD. Multivariate logistic regression models examined the association between marital status …

Effects Of Residual Pah Exposure From Firefighters’ Skin And Turnout Gear On Biospecimen Microrna Expression, Jooyeon Hwang, Jenny R Gipson, Chao Xu, Timothy Vanwagoner, Xin Xu, Robert J Agnew, Willard M Freeman

Faculty, Staff and Student Publications

Firefighters are routinely exposed to polycyclic aromatic hydrocarbons (PAHs) during fire suppression activities, molecular biomarkers reflecting such exposure remain underexplored. Thus, we explored an integrated exposure assessment framework linking PAH contamination on turnout gear and skin to changes in microRNA (miRNA) expression in skin and blood biospecimens. Our goals are to evaluate the relationship between fire-related PAH exposure and miRNA expression profiles in firefighters, and to identify candidate miRNA biomarkers of occupational exposure. This prospective study enrolled 25 firefighters. PAHs on turnout gear and skin were quantified post-fire using gas chromatography/mass spectrometry. Concurrently, skin tape strips and blood were collected …

Multisite Assembly Of Gateway Induced Clones (Magic): A Flexible Cloning Toolbox For Use In Vertebrate Model Systems, William B Gillespie, Yuwen Zhang, Oscar E Ruiz, Juan Cerda, Joshua Ortiz-Guzman, Michelle Sherman, Williamson D Turner, Gabrielle Largoza, Lili E Mosser, Esther Fujimoto, Chi-Bin Chien, Kristen M Kwan, Benjamin R Arenkiel, W Patrick Devine, Joshua D Wythe

Duncan NRI Faculty and Staff Publications

Here, we present MultiSite Assembly of Gateway Induced Clones (MAGIC), which leverages Gateway-based recombinatorial cloning technology for rapid, modular assembly of plasmids to facilitate transgenesis in cells and vertebrate animal models. The MAGIC collection of plasmids spans a range of in vitro and in vivo uses, from tools for optically and chemically tunable gene expression, to simultaneous expression of microRNAs and fluorescent reporters, to a suite of distinct subcellular compartmental fluorescent reporters, to Cre and Dre recombinase-dependent gene expression. MAGIC system components are compatible with existing MultiSite Gateway Tol2 systems currently used in zebrafish and mammalian lentiviral and adenoviral Destination …