Digital Commons Network^™

Use Of Robust Norming To Create A Sensitive Cognitive Summary Score In De Novo Parkinson's Disease: An Illustrative Example, Daniel Weintraub, Michael C Brumm, Ryan Kurth, Michele K York

Faculty, Staff and Students Publications

Background: Cognitive impairment is common at all stages of Parkinson's disease (PD), but there is no consensus on which neuropsychological tests to use or how to interpret cognitive battery results. A cognitive summary score (CSS) combines the richness of a neuropsychological battery with the simplicity of a single score.

Objective: The objective of this study was to determine whether a CSS created using robust norming can detect early cognitive deficits in de novo, untreated PD.

Methods: Baseline cognitive data from PD participants and healthy control participants (HCs) in the Parkinson's Progression Markers Initiative were used to (1) create a robust …

The Relationship Between Individualised Speed Thresholds And Changes In Aerobic Fitness In Elite Professional Youth Soccer Players. A Case Study, Ronan Kavanagh, Kevin Mcdaid, David Rhodes, Jill Alexander, Damian Harper, Rafael Oliveira, Kieran Berry, Mark Connor, Piotr Zmijewski, Ryland Morgans

Baltic Journal of Health and Physical Activity

Background: This study aimed to examine the dose-response relationship between training load and aspects of physical fitness in English Premier League (EPL) U23 soccer players. Materials and Methods: Seven male EPL U23 outfield soccer players (age 20.1±1.1 years) participated in this study and performed the Bronco test on five occasions within one season. Individualised running thresholds were employed using maximal aerobic speed (MAS), anaerobic speed reserve (ASR) and maximal sprint speed (MSS) values utilising a GPS system. Results: No significant differences in the Bronco performance between the tests (p > 0.05, ES = 0.101) were observed. Distance covered above 30% …

Sustained Supraventricular Tachycardia While In Active Phase Labor, Austin Gold, Mona Sadek

HCA Healthcare Journal of Medicine

Background

Supraventricular tachycardia (SVT) is one of the most common tachyarrhythmias found in young women, and SVT can be exacerbated by pregnancy. The symptoms associated with SVT frequently overlap with physiologic changes and symptoms of pregnancy which can lead to delayed or missed diagnosis.

Case Presentation

We describe the presentation and the acute management of a patient who had sustained SVT that developed during the active phase of labor. We then detail the varying management approaches of SVT in pregnancy and labor as well as refractory management options. Maternal monitoring will also be discussed as this case shows how an …

Synthetic Versus Biologic Mesh For Complex Open Ventral Hernia Repair: Three-Year Follow-Up Of A Pilot Randomized Controlled Trial, Nalia H. Dhanani, Nicole B. Lyons, Kyung Hyun Lee, Oscar A. Olavaarria, Aris R. Arakelians, Julie L. Holihan, Lillian S. Kao, Ali Siddiqui, Connor Hogan, Tunmi Anwoju, Zuhair Ali, Mike K. Liang

HCA Healthcare Journal of Medicine

Background

Biologic mesh is often used in complex hernia repair, but there has been limited clinical evidence to date to support this practice. The aim of this study was to compare clinical and patient-reported outcomes of biologic versus synthetic mesh for complex open ventral hernia repair (OVHR) at 3 years.

Methods

Patients from a single center, randomized, controlled, pilot trial comparing biologic versus synthetic mesh in complex OVHR were followed for 3 years. The primary outcome focused on major complications, namely mesh infections, hernia recurrences, reoperations, and deaths. Secondary outcomes included surgical site infections, surgical site occurrences, and patient-reported outcomes. …

Impact Of A Comprehensive Palliative Quality Improvement Initiative (Icu-Pal) In A Medical-Surgical Intensive Care Unit, Aunie M. Danyalian, Michele M. Iguina, Manjot Malhi, Umair Shaikh, Sanaz B. Kashan, Dionne Morgan, Daniel Heller, Mauricio Danckers

HCA Healthcare Journal of Medicine

Background

Early palliative care practice implementation in the intensive care unit (ICU) improves advance care planning, promotes patient and family satisfaction, and decreases health care costs. The consensus for protocolized palliative care delivery is unknown. We assessed the impact of a qualitive improvement educational intervention that promotes the identification of critically ill patients who will benefit from early expert palliative care interventions.

Methods

In this observational study, we examined the impact of an educational intervention that promoted (1) early detection of palliative care triggers (PCT) during ICU multidisciplinary rounds (MDRs), (2) admission and 48-hour pain assessment, and (3) family meetings …

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

Nanometer Condensate Organization In Live Cells Derived From Partitioning Measurements, Christina Dollinger, Evdokiia Potolitsyna, Abigail G Martin, Archish Anand, Gandhar K Datar, Jeremy D Schmit, Joshua A Riback

Faculty, Staff and Students Publications

Biomolecules associate, forming condensates that house essential biochemical processes, including ribosome biogenesis. Unraveling how condensates shape macromolecular assembly and transport requires cellular measurements of nanoscale structure. Here, we determine the organization around and between specific proteins at nanometer resolution within condensates, deploying thermodynamic principles to interpret partitioning measurements of designed protein probes. When applied to the nucleolus as a proof of principle, the data reveals considerable inhomogeneity, deviating from that expected within a liquid-like phase. The inhomogeneity can be attributed to ribosome biogenesis, with the local meshwork weakening as biogenesis progresses, facilitating transport. Beyond introducing an innovative modality for biophysical …

Tau Oligomers Resist Phase Separation, Lathan Lucas, Phoebe S Tsoi, Josephine C Ferreon, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Tau is a microtubule-associated protein that undergoes liquid-liquid phase separation (LLPS) to form condensates under physiological conditions, facilitating microtubule stabilization and intracellular transport. LLPS has also been implicated in pathological Tau aggregation, which contributes to tauopathies such as Alzheimer's disease. While LLPS is known to promote Tau aggregation, the relationship between Tau's structural states and its phase separation behavior remains poorly defined. Here, we examine how oligomerization modulates Tau LLPS and uncover key distinctions between monomeric, oligomeric, and amyloidogenic Tau species. Using dynamic light scattering and fluorescence microscopy, we monitored oligomer formation over time and assessed oligomeric Tau's ability to …

Inhibition Of Il-6 Trans-Signaling Promotes Post-Stroke Functional Recovery In A Sex And Dose-Dependent Manner, Cassandra Hall, Dustin T Nguyen, Kate Mendoza, Chunfeng Tan, Anjali Chauhan

Faculty, Staff and Student Publications

Introduction: Elevated circulating IL-6 levels are associated with poorer outcomes after stroke, and increased serum IL-6 levels are linked to a higher risk of stroke. IL-6 binds to soluble IL-6 receptors (sIL-6R) and subsequently to ubiquitously expressed gp130, initiating proinflammatory trans-signaling. This study tested the hypothesis that inhibiting IL-6 trans-signaling by administering soluble (s) gp130 improves long-term functional outcomes in young mice after stroke.

Methods: Recombinant mouse gp130Fc chimera (sgp130) was administered one hour after middle cerebral artery occlusion (MCAO) followed by twice-weekly administration for 2 weeks in mice (8-15 weeks old). Behavioral assessments were done on days 7 and …

Conformational Flexibility Is A Critical Factor In Designing Broad-Spectrum Human Norovirus Protease Inhibitors, Son Pham, Boyang Zhao, Neetu Neetu, Banumathi Sankaran, Ketki Patil, Sasirekha Ramani, Yongcheng Song, Mary K Estes, Timothy Palzkill, B V Venkataram Prasad

Faculty, Staff and Students Publications

UNLABELLED: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein. Thus, it is an ideal target for developing antiviral small-molecule inhibitors. While rupintrivir, a potent small-molecule inhibitor of several picornavirus proteases, effectively inhibits GI.1 protease, it is an order of magnitude less effective against GII protease. Other GI.1 protease inhibitors also tend to be less effective against GII proteases. …

Human Intestinal Enteroids For Evaluating The Persistence Of Infectious Human Norovirus In Raw Surface Freshwater, Malak A Esseili, Revati Narwankar, Riya Hooda, Veronica Costantini, Mary K Estes, Jan Vinjé, Issmat I Kassem

Faculty, Staff and Students Publications

Globally, human norovirus (HuNoV) is the leading cause of foodborne illnesses. Norovirus transmission to fresh produce can occur via several sources, including contaminated irrigation water. HuNoV RNA has been detected in freshwater resources, but knowledge about virus infectivity is limited due to a historical lack of a HuNoV cell culture. Recently, HuNoV was shown to replicate in human intestinal enteroids (HIE). The objective of this study was to use HIE to evaluate the persistence of infectious HuNoV in raw (i.e. biologically active) surface freshwater. The virus was spiked into freshwater microcosms sampled from three freshwater ponds and then incubated inside …

Immunological Biomarkers Of Response And Resistance To Treatment With Cabozantinib And Nivolumab In Recurrent Endometrial Cancer, Vladimir Roudko, Diane Marie Del Valle, Emir Radkevich, Geoffrey Kelly, Xie Hui, Manishkumar Patel, Edgar Gonzalez-Kozlova, Kevin Tuballes, Howard Streicher, Swati Atale, Lisa Wang, Benito Czinczin, Seunghee Kim-Schulze, Ignacio I Wistuba, Cara L Haymaker, Gheath Al-Atrash, Ganiraju Manyam, Jianjun Zhang, Ryan Thompson, Mayte Suarez-Farinas, Stephanie Lheureux, Sacha Gnjatic

Faculty, Staff and Student Publications

Background: Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone.

Methods and results: Using Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific …

Clostridioides Difficile Colonization Is Not Mediated By Bile Salts And Utilizes Stickland Fermentation Of Proline In An In Vitro Model, Xiaoyun Huang, April E Johnson, Joshua N Brehm, Thi Van Thanh Do, Thomas A Auchtung, Hugh C Mccullough, Armando I Lerma, Sigmund J Haidacher, Kathleen M Hoch, Thomas D Horvath, Joseph A Sorg, Anthony M Haag, Jennifer M Auchtung

Faculty, Staff and Students Publications

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; …

Ultra-Low Extracorporeal Volume Microfluidic Leukapheresis Is Safe And Effective In A Rat Model, Mubasher Iqbal, Alexandra L Mclennan, Anton Mukhamedshin, Mai T P Dinh, Qisheng Liu, Jacob J Junco, Arvind Mohan, Poyyapakkam R Srivaths, Karen R Rabin, Thomas P Fogarty, Sean C Gifford, Sergey S Shevkoplyas, Fong W Lam

Faculty, Staff and Students Publications

Leukapheresis is a potentially life-saving therapy for children with symptomatic hyperleukocytosis. However, the standard centrifugation-based approach exposes pediatric patients to significant complications due to its large extracorporeal volume, high flow rates, and considerable platelet loss. Here, we tested whether performing cell separation with a high-throughput microfluidic technology could alleviate these limitations. In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood, while minimizing platelet losses. Multiplexed devices connected in parallel allowed for faster, clinically relevant flow rates in vitro with no difference in leukocyte collection efficiency. When connected to …

Author Correction: Assessment Of Human Leukocyte Antigen-Based Neoantigen Presentation To Determine Pan-Cancer Response To Immunotherapy, Jiefei Han, Yiting Dong, Xiuli Zhu, Alexandre Reuben, Jianjun Zhang, Jiachen Xu, Hua Bai, Jianchun Duan, Rui Wan, Jie Zhao, Jing Bai, Xuefeng Xia, Xin Yi, Chao Cheng, Jie Wang, Zhijie Wang

Faculty, Staff and Students Publications

No abstract provided.

Confluent Soft Nodules On Buttocks, Awa Bakayoko, Chiamaka Ohanenye, Jason B. Lee, Shaan Patel, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Aberrant Choroid Plexus Formation Drives The Development Of Treatment-Related Brain Toxicity, Tamara Bender, Esther Schickel, Celine Schielke, Jürgen Debus, David R Grosshans, Marco Durante, Insa S Schroeder

Faculty, Staff and Student Publications

Brain tumors are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity to the normal tissue including post-irradiation contrast enhanced lesions often linked to necrosis. The poorly understood mechanisms behind such brain lesions were studied using cerebral organoids. Here we show that irradiation of such organoids leads to dose-dependent growth retardation and formation of liquid-filled cavities but is not correlated with necrosis. Instead, the radiation-induced changes comprise of an enhancement of cortical hem markers, altered neuroepithelial stem cell differentiation, and an increase of ZO1+/AQP1+/CLDN3+-choroid plexus (CP)-like structures accompanied by an upregulation of IGF2 mRNA, …

Clinical Variability In Presentation And Management Of Quadricuspid Aortic Valve: A Case Series, Douglas Corsi, Brooke Kelly, Nikta Nair, Meiqi Luo, Brian Osler, Sung-Hae Cho, Praveen Mehrotra, David H Wiener, Drew Johnson

Division of Cardiology Faculty Papers

• Rare presentation of three QAV cases with varied clinical manifestations is reported. • Multimodal imaging is crucial for accurate QAV diagnosis and classification. • QAV is often associated with aortic regurgitation requiring intervention. • Surgical repair is preferred over replacement in suitable patients with QAV. • Long-term follow-up is essential for patients with QAV, even if asymptomatic.

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Neural Signal Analysis In Chronic Stroke: Advancing Intracortical Brain-Computer Interface Design, Nabila Shawki, Alessandro Naopli, Carlos E. Vargas-Irwin, Christopher K. Thompson, John P. Donoghue, Mijail D. Serruya

Department of Medicine Faculty Papers

INTRODUCTION: Intracortical Brain-computer interfaces (iBCIs) are a promising technology to restore function after stroke. It remains unclear whether iBCIs will be able to use the signals available in the neocortex overlying stroke affecting the underlying white matter and basal ganglia.

METHODS: Here, we decoded both local field potentials (LFPs) and spikes recorded from intracortical electrode arrays in a person with chronic cerebral subcortical stroke performing various tasks with his paretic hand, with and without a powered orthosis. Analysis of these neural signals provides an opportunity to explore the electrophysiological activities of a stroke affected brain and inform the design of …

At-Home Stroke Neurorehabilitation: Early Findings With The Neuroexo Bci System, Juan José González-España, Lianne Sánchez-Rodríguez, Maxine Annel Pacheco-Ramírez, Jeff Feng, Kathryn Nedley, Shuo-Hsiu Chang, Gerard E Francisco, Jose L Contreras-Vidal

Faculty, Staff and Student Publications

Background: Democratized access to safe and effective robotic neurorehabilitation for stroke survivors requires innovative, affordable solutions that can be used not only in clinics but also at home. This requires the high usability of the devices involved to minimize costs associated with support from physical therapists or technicians.

Methods: This paper describes the early findings of the NeuroExo brain-machine interface (BMI) with an upper-limb robotic exoskeleton for stroke neurorehabilitation. This early feasibility study consisted of a six-week protocol, with an initial training and BMI calibration phase at the clinic followed by 60 sessions of neuromotor therapy at the homes of …

The Bacterial Microbiome Modulates The Initiation Of Brain Metastasis By Impacting The Gut-To-Brain Axis, Matteo Massara, Michelle Ballabio, Bastien Dolfi, Golnaz Morad, Vladimir Wischnewski, Eleni Lamprou, Joao Lourenco, Stéphanie Claudinot, Hector Gallart-Ayala, Rui Santalla Méndez, Annamaria Kauzlaric, Nadine Fournier, Ashish V Damania, Matthew C Wong, Julijana Ivanisevic, Nadim J Ajami, Jennifer A Wargo, Johanna A Joyce

Faculty, Staff and Student Publications

Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM …

Immune Checkpoint Inhibitors Plus Debulking Surgery For Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes And Immunological Correlates Of A Prospective Pilot Trial, Sangeeta Goswami, Jianjun Gao, Sreyashi Basu, Daniel D Shapiro, Jose A Karam, Rebecca Slack Tidwell, Kamran Ahrar, Matthew T Campbell, Yu Shen, Alexandro E Trevino, Aaron T Mayer, Alexsandra B Espejo, Christian Seua, Marc D Macaluso, Yulong Chen, Wenbin Liu, Zhong He, Shalini S Yadav, Ying Wang, Priya Rao, Li Zhao, Jianhua Zhang, Sonali Jindal, Nizar M Tannir, Andrew Futreal, Linghua Wang, Padmanee Sharma

Faculty, Staff and Student Publications

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing …

Semaglutide And Nonarteritic Anterior Ischemic Optic Neuropathy, Cindy X Cai, Michelle Hribar, Sally Baxter, Kerry Goetz, Swarup S Swaminathan, Alexis Flowers, Eric N Brown, Brian Toy, Benjamin Xu, John Chen, Aiyin Chen, Sophia Wang, Cecilia Lee, Theodore Leng, Joshua R Ehrlich, Andrew Barkmeier, Karen R Armbrust, Michael V Boland, David Dorr, Danielle Boyce, Thamir Alshammari, Joel Swerdel, Marc A Suchard, Martijn Schuemie, Fan Bu, Anthony G Sena, George Hripcsak, Akihiko Nishimura, Paul Nagy, Thomas Falconer, Scott L Duvall, Michael Matheny, Benjamin Viernes, William O'Brien, Linying Zhang, Benjamin Martin, Erik Westlund, Nestoras Mathioudakis, Ruochong Fan, Adam Wilcox, Albert Lai, Jacqueline C Stocking, Sahar Takkouche, Lok Hin Lee, Yangyiran Xie, Izabelle Humes, David B Mccoy, Mohammad Adibuzzaman, Raymond G Areaux, William Rojas-Carabali, James Brash, David A Lee, Nicole G Weiskopf, Louise Mawn, Rupesh Agrawal, Hannah Morgan-Cooper, Priya Desai, Patrick B Ryan

Faculty, Staff and Student Publications

Importance

Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D).

Objective

To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network.

Design, Setting, and Participants

This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non–GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion …

Correlation Of Gnas Mutational Status With Oncologic Outcomes In Patients With Resected Intraductal Papillary Mucinous Neoplasms, Julia S. Evans, Kylee Shivok, Hui Hsuan Chen, Eliyahu Gorgov, Wilbur Bowne, Aditi Jain, Phd, Harish Lavu, Charles J. Yeo, Avinoam Nevler

SKMC Student Presentations and Publications

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic …

Benefits Of Equilibrium Between Microbiota- And Host-Derived Ligands Of The Aryl Hydrocarbon Receptor After Stroke In Aged Male Mice, Pedram Peesh, Maria P Blasco-Conesa, Ahmad El Hamamy, Romeesa Khan, Gary U Guzman, Parisa Honarpisheh, Eric C Mohan, Grant W Goodman, Justin N Nguyen, Anik Banerjee, Bryce E West, Kyung Ae Ko, Janelle M Korf, Chunfeng Tan, Huihui Fan, Gabriela D Colpo, Hilda Ahnstedt, Lucy Couture, Solji Roh, Julia K Kofler, Jose F Moruno-Manchon, Michael E Maniskas, Jaroslaw Aronowski, Rodney M Ritzel, Juneyoung Lee, Jun Li, Robert M Bryan, Anjali Chauhan, Venugopal Reddy Venna, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Recent studies have highlighted the crucial role of microglia (MG) and their interactions with the gut microbiome in post-stroke neuroinflammation. The activation of immunoregulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, is influenced by a dynamic balance of ligands derived from both the host and microbiota. This study aimed to investigate the association between stroke-induced dysbiosis and the resultant imbalance in AHR ligand sources (loss of microbiota-derived [indole-based] and increase of host-derived [kynurenine-based]) after stroke. Microbiota-derived AHR ligands decreased in human plasma and remained low for days following an ischemic stroke highlighting the translational significance. Transient-middle-cerebral-artery-occlusion was performed in …

Trends In Ischemic Stroke Hospitalization And Outcomes In The United States Pre- And Peri-Covid-19 Pandemic: A National Inpatient Sample Study, Alibay Jafarli, Mario Di Napoli, Rachel S Kasper, Jeffrey L Saver, Louise D Mccullough, Setareh Salehi-Omran, Behnam Mansouri, Vasileios Arsenios Lioutas, Mohammed Ismail, Afshin A Divani

Faculty, Staff and Student Publications

Background/Objectives: The COVID-19 pandemic impacted healthcare systems globally, disrupting the management and treatment of acute ischemic stroke (AIS). Understanding how AIS admissions, treatments, and outcomes were affected is critical for improving stroke care in future crises. The objective of this work was to assess the COVID-19 pandemic's impact on AIS admissions, treatment patterns, complications, and patient outcomes in the U.S. from 2016 to 2021, focusing on differences between pre-pandemic (2016-2019) and peri-pandemic (2020-2021) periods.

Methods: This is a retrospective cohort study using the National Inpatient Sample (NIS) database, analyzing weighted discharge records of AIS patients over six years. Data encompass …

The Potential Of Using Screening Tools For Bipolar Disorder To Predict Lithium Response, Delfina Janiri, Mario Pinto, Silvia Montanari, Ester Maria Marzo, Greta Sfratta, Guglielmo Donofrio, Alexia Koukopoulos, Giovanni Camardese, Alessio Simonetti, Lorenzo Moccia, Gianna Autullo, Gabriele Sani

Faculty, Staff and Students Publications

Background/Objectives: Lithium is the gold standard for treating Bipolar Disorder (BD), but its effectiveness varies widely. While clinical and environmental factors may influence response, it remains unclear if screening tools can reliably predict lithium response outcomes. This study explores this potential using two widely used screening instruments for BD.

Methods: A total of 146 patients with BD were evaluated. Lithium response was assessed using the Alda Scale, while hypomanic and manic symptoms were characterized through the Hypomania Checklist-32 (HCL-32) and the Mood Disorder Questionnaire (MDQ). Group differences in HCL-32 and MDQ scores were analyzed using ANOVA, and a multivariate model …

Single-Cell Analysis Of Neoplastic Plasma Cells Identifies Myeloma Pathobiology Mediators And Potential Targets, Luz Yurany Moreno Rueda, Hua Wang, Keiko Akagi, Minghao Dang, Amishi Vora, Li Qin, Hans C Lee, Krina K Patel, Pei Lin, David E Mery, Fenghuang Zhan, John D Shaughnessy, Qing Yi, Yang Song, Bo Jiang, Maura L Gillison, Sheeba K Thomas, Donna M Weber, Lixia Diao, Jing Wang, Isere Kuiatse, Elisabet E Manasanch, David E Symer, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models. Moreover, functional studies show a …

Mitochondrial Defects And Metabolic Vulnerabilities In Lynch Syndrome-Associated Msh2-Deficient Endometrial Cancer, Mikayla Borthwick Bowen, Brenda Melendez, Qian Zhang, Diana Moreno, Leah Peralta, Wai Kin Chan, Collene Jeter, Lin Tan, M Anna Zal, Philip L Lorenzi, Kenneth Dunner, Richard K Yang, Russell R Broaddus, Joseph Celestino, Nisha Gokul, Elizabeth Whitley, Deena M Scoville, Tae Hoon Kim, Jae-Wook Jeong, Rosemarie Schmandt, Karen Lu, Hyun-Eui Kim, Melinda S Yates

Faculty, Staff and Student Publications

Lynch syndrome (LS), caused by inherited mutations in DNA mismatch repair genes, including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, mechanisms driving LS-associated EC (LS-EC) remain unclear. We investigated MSH2 loss in EC pathogenesis using a mouse model (PR-Cre Msh2LoxP/LoxP, abbreviated Msh2KO), primary cell lines, human tissues, and human EC cells with isogenic MSH2 knockdown. By 8 months, 58% of Msh2KO mice developed endometrial atypical hyperplasia (AH), a precancerous lesion. At 12-16 months, 50% of Msh2KO mice exhibited either AH or ECs with histologic similarities to human LS-ECs. Transcriptomic profiling of EC from Msh2KO …