Digital Commons Network^™

Distinct Adipose Progenitor Cells Emerging With Age Drive Active Adipogenesis, Guan Wang, Gaoyan Li, Anying Song, Yutian Zhao, Jiayu Yu, Yifan Wang, Wenting Dai, Martha Salas, Hanjun Qin, Leonard Medrano, Joan Dow, Aimin Li, Brian Armstrong, Patrick T Fueger, Hua Yu, Yi Zhu, Mengle Shao, Xiwei Wu, Lei Jiang, Judith Campisi, Xia Yang, Qiong A Wang

Children’s Nutrition Research Center Staff Publications

Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat undergo extensive adipogenesis during middle age. Thus, despite the low turnover rate of adipocytes in young adults, adipogenesis is unlocked during middle age. Transplantations quantitatively showed that APCs in middle-aged mice exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, the committed preadipocyte, age-enriched (CP-A), emerging at this age. CP-As demonstrated elevated proliferation and adipogenesis activity. Pharmacological and genetic manipulations indicated that leukemia inhibitory factor receptor signaling was …

Development And Evaluation Of A Non-Invasive Brain-Spine Interface Using Transcutaneous Spinal Cord Stimulation, Carolyn Atkinson, Lorenzo Lombardi, Meredith Lang, Rodolfo Keesey, Rachel Hawthorn, Zachary Seitz, Eric C Leuthardt, Peter Brunner, Ismael Seáñez

2020-Current year OA Pubs

Motor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of …

Deciphering Distinct Genetic Risk Factors For Ftld-Tdp Pathological Subtypes Via Whole-Genome Sequencing, Cyril Pottier, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe and Australia, and meta-analysis with the Dementia-seq cohort. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyzes, we further identify genome-wide significant loci specific to each of the three …

Investigating The Role Of Blood Models In Predicting Rupture Status Of Intracranial Aneurysms, Zonghan Lyu, Mostafa Rezaeitaleshmahalleh, Nan Mu, Jingfeng Jiang

Michigan Tech Publications

Purpose. Selecting patients with high-risk intracranial aneurysms (IAs) is of clinical importance. Recent work in machine learning-based (ML) predictive modeling has demonstrated that lesion-specific hemodynamics within IAs can be combined with other information to provide critical insights for assessing rupture risk. However, how the adoption of blood rheology models (i.e., Newtonian and Non-Newtonian blood models) may influence ML-based predictive modeling of IA rupture risk has not been investigated.Methods and Materials.In this study, we conducted transient CFD simulations using Newtonian and non-Newtonian rheology (Carreau-Yasuda [CY]) models on a large cohort of 'patient-specific' IA geometries (>100) under pulsatile flow conditions to …

Difference In Clinical Presentation And Surgical Outcomes In Pediatric And Adult Patients With Chiari Malformation Type 1: A Single Center Retrospective Study, Erik Öhlén, Victor Gabriel El-Hajj, Victor E. Staartjes, Pascal Jabbour, Erik Edström, Adrian Elmi-Terander

Department of Neurosurgery Faculty Papers

INTRODUCTION: Chiari malformation type 1 (CM1) is a common congenital disorder affecting both children and adults. Although pediatric and adult CM1 patients share many characteristics, the differences between the groups are not fully described.

METHOD: A comparative analysis was made of two previously defined cohorts of adult and pediatric non-syndromic CM1, surgically treated at the study center. Clinical outcomes were assessed using the Chicago Chiari outcome scale (CCOS) and radiological outcomes were measured as change in cerebellar tonsil and syringomyelia status.

RESULTS: A total of 209 patients (73 pediatric, 136 adults) were included, with median ages of 11 and 33 …

High-Grade Astrocytoma With Piloid Features: A Single-Institution Case Series And Literature Review, Eric A Goethe, Subhiksha Srinivasan, Swaminathan Kumar, Sujit S Prabhu, Maria A Gubbiotti, Sherise D Ferguson

Faculty, Staff and Student Publications

High-grade astrocytoma with piloid features (HGAP) is a recently described primary brain tumor and the first requiring a specific methylation pattern for diagnosis, as its histologic features are often compatible with other tumors such as glioblastoma (GBM). Characterized by molecular alterations in CDKN2A/B, NF1, BRAF, FGFR1, and ATRX, they may be located anywhere in the CNS but show a predilection for the posterior fossa. Reports are limited to retrospective case series, and the standard of care is not yet established. We performed a retrospective review of electronic medical records of all patients with HGAP at our institution. Records were queried …

Implementation Of The Extension For Community Healthcare Outcomes Model For Hypertension Education Of Frontline Health Care Workers In The Federal Capital Territory, Nigeria: Explanatory Sequential Mixed Methods Evaluation, Abigail S Baldridge, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Extension for Community Healthcare Outcomes (ECHO) model was adapted for hypertension education of community health extension workers in the Federal Capital Territory, Nigeria, and delivered as a 7-part series.

OBJECTIVE: This study aims to evaluate implementation outcomes of the hypertension ECHO series mapped to the first 3 levels of the Kirkpatrick model. Outcomes included reach, appropriateness (level 1), effectiveness (level 2), and penetration (level 3).

METHODS: From August 2022 to April 2023, 7 hypertension ECHO sessions were delivered via Zoom (Zoom Video Communications, Inc) to a health care worker audience including targeted community health extension workers at 12 …

Physical Activity Measurement Reactivity Among Midlife Adults With Elevated Risk For Cardiovascular Disease: Protocol For Coordinated Analyses Across Six Studies., Kiri Baga, Gabrielle M Salvatore, Iris Bercovitz, Amanda L Folk, Ria Singh, Laura M König, Meghan L Butryn, Jacqueline A Mogle, Danielle Arigo

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death in the United States, and adults aged 40-60 years with specific health conditions are at particularly elevated risk for developing CVD. Physical activity (PA) is a key cardioprotective behavior and many interventions exist to promote PA in this group. Effective promotion requires accurate assessment of PA behavior; as PA is often estimated by averaging across multiple days, a threat to accurate assessment is measurement reactivity, or an atypical increase in PA behavior at the start of measurement periods that may bias conclusions. Evidence for PA measurement reactivity is equivocal, though …

Impact Of Antidiabetic Medication Type On A New Episode Of Depression: A Retrospective Cohort Study In Texas, Usa, Lin-Na Chou, Mukaila A Raji, Holly M Holmes, Yong-Fang Kuo

Faculty, Staff and Student Publications

Objectives: To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.

Design: A retrospective cohort study.

Setting: A population-based study using the Texas Medicare data.

Interventions: 11 common antihyperglycaemic medication types, alone and in combinations: metformin-only, five non-metformin-containing regimens (dipeptidyl peptidase-4 inhibitor (DPP4i) only, sulfonylureas (SU) only, thiazolidinediones (TZD) only, SU/DPP4i and SU/TZD) and five metformin-containing combination treatments (metformin/DPP4i, metformin/SU, metformin/TZD, metformin/SU/DPP4i and metformin/SU/TZD).

Participants: This study included 59 057 type 2 diabetes (T2D) patients from a cohort of Texas Medicare beneficiaries who were aged ≥66 years, …

Development And Validation Of A Dynamic Real-Time Risk Prediction Model For Intensive Care Units Patients Based On Longitudinal Irregular Data: Multicenter Retrospective Study, Zhuo Zheng, Jiawei Luo, Yingchao Zhu, Lei Du, Lan Lan, Xiaobo Zhou, Xiaoyan Yang, Shixin Huang

Faculty, Staff and Student Publications

Background: Timely and accurate prediction of short-term mortality is critical in intensive care units (ICUs), where patients' conditions change rapidly. Traditional scoring systems, such as the Simplified Acute Physiology Score and Acute Physiology and Chronic Health Evaluation, rely on static variables collected within the first 24 hours of admission and do not account for continuously evolving clinical states. These systems lack real-time adaptability, interpretability, and generalizability. With the increasing availability of high-frequency electronic medical record (EMR) data, machine learning (ML) approaches have emerged as powerful tools to model complex temporal patterns and support dynamic clinical decision-making. However, existing models are …

Impact Of Age On Biology, Presentation And Outcomes In Marginal Zone Lymphoma: Results From A Multicenter Cohort Study, Pallawi Torka, Natalie S. Grover, Timothy J. Voorhees, Reem Karmali, Kaitlin Annunzio, Marcus P. Watkins, Andrea Anampa-Guzmán, Heather Reves, Montreh Tavakkoli, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Geoffrey Shouse, Adam J. Olszewski, Narendranath Epperla

Department of Medicine Faculty Papers

Given the paucity of age-specific data about biology, presentation, and treatment outcomes in adults with MZL, we sought to evaluate differences between younger (≤ 70 years) and older (> 70 years) patients with MZL in a large retrospective cohort treated in the contemporary era (2010 onwards). The primary objective was progression-free survival (PFS), while secondary objectives included the evaluation of overall survival (OS) and the cumulative incidence of transformation between the 2 groups. A total of 598 patients were included in the analysis and among these 32% were > 70 years of age. There were no age-based differences in the prevalence …

5-Year Outcomes After Transcatheter Or Surgical Aortic Valve Replacement In Low-Risk Patients With Aortic Stenosis., John K Forrest, Steven J Yakubov, G Michael Deeb, Hemal Gada, Mubashir A Mumtaz, Basel Ramlawi, Tanvir Bajwa, John Crouch, William Merhi, Stephane Leung Wai Sang, Neal S Kleiman, George Petrossian, Newell B Robinson, Paul Sorajja, Ayman Iskander, Pierre Berthoumieu, Didier Tchétché, Christopher Feindel, Eric M Horlick, Shigeru Saito, Jae K Oh, Yoojin Jung, Michael J Reardon

Heart and Vascular Articles

BACKGROUND: The Evolut Low Risk trial demonstrated that transcatheter aortic valve replacement (TAVR) was noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke at 2 years. Outcomes at 5 years have not been reported.

OBJECTIVES: This study sought to evaluate 5-year clinical and hemodynamic outcomes with TAVR vs surgery in patients from the Evolut Low Risk trial.

METHODS: We randomly assigned low-risk patients with severe aortic stenosis to TAVR or surgery. The primary endpoint was a composite of all-cause mortality or disabling stroke. Secondary endpoints included clinical, echocardiographic, and quality-of-life outcomes through 5 years.

RESULTS: A …

Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis In 24 539 Individuals, Yezhi Pan, Chuan Bi, Zhenyao Ye, Hwiyoung Lee, Jiaao Yu, Luba Yammine, Tianzhou Ma, Peter Kochunov, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Introduction: Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored.

Aims and methods: We conducted a whole-brain analysis on 24 539 adults aged 40 and above from the United Kingdom Biobank cohort. Subjects were categorized into individuals who use nicotine and those who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging. We employed a network analysis method to assess the systematic effects of tobacco …

Dna Methylation Signature Of A Lifestyle-Based Resilience Index For Cognitive Health, Wei Zhang, David Lukacsovich, Juan I Young, Lissette Gomez, Michael A Schmidt, Eden R Martin, Brian W Kunkle, X Steven Chen, Deirdre M O'Shea, James E Galvin, Lily Wang

Faculty, Staff and Students Publications

Cognitive resilience (CR) contributes to the variability in risk for developing and progressing in Alzheimer's disease (AD) among individuals. Beyond genetics, recent studies highlight the critical role of lifestyle factors in enhancing CR and delaying cognitive decline. DNA methylation (DNAm), an epigenetic mechanism influenced by both genetic and environmental factors, including CR-related lifestyle factors, offers a promising pathway for understanding the biology of CR. We studied DNAm changes associated with the Resilience Index (RI), a composite measure of lifestyle factors, using blood samples from the Healthy Brain Initiative (HBI) cohort. After corrections for multiple comparisons, our analysis identified 19 CpGs …

The Havcr1-Centric Host Factor Network Drives Zika Virus Vertical Transmission, Wenzhe Yu, Jun Tao, Hongmin Cao, Wanshan Zheng, Beiang Zhang, Yue Zhang, Peiqun Xu, Yiwei Zhang, Xuan Liu, Yinan Wang, Han Cai, Gang Liu, Fan Liu, Haibin Wang, Haiyan Zhao, Indira U Mysorekar, Xiaoqian Hu, Bin Cao

Center on Aging Staff Publications

Zika virus (ZIKV) vertical transmission results in devastating congenital malformations and pregnancy complications; however, the specific receptor and host factors facilitating ZIKV maternal-fetal transmission remain elusive. Here, we employ a genome-wide CRISPR screening and identify multiple placenta-intrinsic factors modulating ZIKV infection. Our study unveils that hepatitis A virus cellular receptor 1 (HAVCR1) serves as a primary receptor governing ZIKV entry in placental trophoblasts. The GATA3-HAVCR1 axis regulates heterogeneous cell tropism in the placenta. Notably, placenta-specific Havcr1 deletion in mice significantly impairs ZIKV transplacental transmission and associated adverse pregnancy outcomes. Mechanistically, the immunoglobulin variable-like domain of HAVCR1 binds to ZIKV via …

Disuse-Driven Plasticity In The Human Thalamus And Putamen, Roselyne J Chauvin, Dillan J Newbold, Ashley N Nielsen, Ryland L Miller, Samuel R Krimmel, Athanasia Metoki, Anxu Wang, Andrew N Van, David F Montez, Scott Marek, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Jarod L Roland, Abraham Z Snyder, Benjamin P Kay, Marcus E Raichle, Timothy O Laumann, Evan M Gordon, Nico U F Dosenbach

2020-Current year OA Pubs

Subcortical plasticity has mainly been studied using invasive electrophysiology in animals. Here, we leverage precision functional mapping (PFM) to study motor plasticity in the human subcortex during 2 weeks of upper-extremity immobilization with daily resting-state and motor task fMRI. We found previously that, in the cortex, limb disuse drastically impacts disused primary motor cortex functional connectivity (FC) and is associated with spontaneous fMRI pulses. It remains unknown whether disuse-driven plasticity pulses and FC changes are cortex specific or whether they could also affect movement-critical nodes in the thalamus and striatum. Tailored analysis methods now show spontaneous disuse pulses and FC …

Functional Protein Biomarkers Based On Distributions Of Expression Levels In Single-Cell Imaging Data, Misung Yi, Tingting Zhan, Hallgeir Rui, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: The intra-tumor heterogeneity of protein expression is well recognized and may provide important information for cancer prognosis and predicting treatment responses. Analytic methods that account for spatial heterogeneity remain methodologically complex and computationally demanding for single-cell protein expression. For many functional proteins, single-cell expressions vary independently of spatial localization in a substantial proportion of the tumor tissues, and incorporation of spatial information may not affect the prognostic value of such protein biomarkers.

RESULTS: We developed a new framework for using the distributions of functional single-cell protein expression levels as cancer biomarkers. The quantile functions of single-cell expressions are used …

Parapneumonic Empyema Complicating Community-Acquired Pneumonia: Etiology In The Era Of Pneumococcal Vaccination And Role Of Molecular Diagnosis, Antonio C Arrieta, Stephanie Osborne, Lindsay R Grant, Bradford D Gessner, Anne J Blaschke, Kristina G Hulten, Delma J Nieves, Ashley Miller, Cody Bender, Raul Isturiz, Ronika Alexander, Shannon M Nielsen, Linda B Lamberth, Alejandro Cane, Adriano Arguedas

Faculty, Staff and Students Publications

Background: Impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease is well described; pneumococcus is infrequently identified by culture in pneumonia. Yield is higher when pleural fluid is cultured. Polymerase chain reaction (PCR) in pleural fluid samples improves pathogen identification, particularly in the case of S. pneumoniae.

Methods: Healthy children with empyema who underwent pleural fluid drainage were eligible. Demographics and PCV immunization status were collected. Blood/pleural fluid cultures were obtained. Pleural fluid samples were sent for PCR for pathogen. Serotyping was done by Neufeld-Quellung reaction on pneumococcus isolates, and PCR in culture negative cases.

Results: From December 2018 to …

Unmet Supportive Care Needs In Patients With Advanced Cancer And Its Impact On Distress, Kayla W Miranda, Benjamin L Musher, Hoda J Badr

Faculty, Staff and Students Publications

Purpose: Patients with advanced cancer endure considerable physical and emotional distress without sufficient supportive care. This cross-sectional study examined the relationship between cancer-related symptoms, supportive care needs, and distress levels in patients with advanced lung, head and neck, or gastrointestinal cancers.

Methods: 158 patients were assessed for symptom burden and distress levels using the M.D. Anderson Symptom Inventory (MDASI) and unmet needs using the Supportive Care Needs Survey (SCNS-34) within one month of treatment initiation. Pearson correlations and multiple regression analyses were used to explore associations between supportive care needs and distress.

Results: Distress levels were moderate across the study …

Center-Ing Black Voices: Incorporating Lived Experience Across The Research Process To Advance Equity In Drug Treatment And Outcomes, Devin E Banks, Maria E Paschke, Kaytryn D Campbell, Daje D Bradshaw-Glenn, Rashmi Ghonasgi, Burton Barr, Arial Collins, Gerald Dennis, Keith Lofton, Alfred Long, Harriet Montgomery, Andreas Prince, Rachel P Winograd

2020-Current year OA Pubs

BACKGROUND: Black people in the United States face persistent and increasing inequities in addiction treatment access and drug overdose death. Incorporating people with lived experience through community based participatory research (CBPR) approaches can improve understanding of drivers of and solutions to such inequities. However, practical and systemic challenges limit incorporating Black people with lived experience with substance use across each step of the research process. This paper describes the methods, recommendations, and lessons learned from a research team and Black-led community advisory board (CAB) working together across the research process to promote equity in harm reduction and addiction treatment.

METHODS: …

Partnering With Social Media Influencers To Promote Hpv Vaccination In Diverse Communities, Amy Leader, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Preethi Selvan, Kayla Madden, Joshua Banks, Angela Sustaita-Ruiz

Department of Medical Oncology Faculty Papers

BACKGROUND: While human papillomavirus (HPV) vaccination is one of the most effective ways to prevent HPV-related cancers, many children and adolescents remain unvaccinated. Resistance often stems from parental vaccine hesitancy and mistrust of the health care system, both of which may be higher in communities of color. Partnering with social media influencers may be an effective method for disseminating health messages. We tested the impact of HPV social media posts developed by influencers on outcomes of knowledge, attitudes, and intentions to vaccinate.

METHODS: Ten social media influencers who identified as African American or Hispanic created posts about the HPV vaccine. …

Childhood Sexual Abuse And Posttraumatic Growth Among African American Women, Joyce B. Mckinley

Doctoral Dissertations and Projects

The purpose of this qualitative descriptive phenomenological study was to explore how African American women describe their lived experience of childhood sexual abuse (CSA), the resulting changes in their relationships with others, and how survivors describe experiences of posttraumatic growth (PTG). Childhood sexual abuse is a significant public health issue in the United States, with African American youth disproportionately impacted. Research has shown that racism-related stressors are related, and African Americans often draw on cultural and familial strengths. This study aims to describe factors contributing to PTG among African American women survivors of CSA. Based on the review of the …

Rnase1-Driven Alk-Activation Is An Oncogenic Driver And Therapeutic Target In Non-Small Cell Lung Cancer, Zhengyu Zha, Chunxiao Liu, Meisi Yan, Cong Chen, Cheng Yu, Yaohui Chen, Chenhao Zhou, Lu Li, Yi-Chuan Li, Hiro Yamaguchi, Leiguang Ye, Tong Liu, Ying-Nai Wang, Heng-Huan Lee, Wen-Hao Yang, Li-Chuan Chan, Baozhen Ke, Jennifer L Hsu, Lieming Ding, Dong Ji, Peng Pan, Yiran Meng, Yue Pu, Lunxu Liu, Mien-Chie Hung

Faculty, Staff and Student Publications

Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harboring common oncogenic driver mutations such as EGFR, KRAS, and ALK rearrangement. However, ~35-50% of NSCLC patients without tyrosine kinase mutation or rearrangement (non-mutated) cannot benefit from these targeted treatments, highlighting the urgent need for novel therapeutic strategies for this patient population. In this study, we report a non-canonical role of human secretory ribonuclease 1 (RNase1), which binds to and activates wild-type ALK in lung cancer cells, thereby triggering its downstream signaling pathway. RNase1-driven ALK-activation (RDAA) cells exhibit enhanced cell proliferation, migration, …

Responding To Leadership Change: A Qualitative Multi-Case Study Of Female Pastors And Their Congregations, Sharon Britz

Doctoral Dissertations and Projects

The purpose of this qualitative multi-case study was to explore the lived experiences of female senior pastors and their congregants who have embraced leadership change from male to female. Although many denominations openly accept and ordain female pastors, and the number of women in pastoral leadership roles has risen, many women in ministry still face obstacles. Guided by the theory of change, in conjunction with liberation theology, this study addressed a gap in research related to the experience of female pastors in ministerial leadership, as minimal similar studies exist, and no other studies within the Congregational Christian Church were found. …

Progesterone Signaling In Oviductal Epithelial Cells Modulates The Immune Response To Support Preimplantation Embryonic Development, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Ryan M Marquardt, Feyza Nur Arguc, Peter F Lais, San-Pin Wu, Sarayut Winuthayanon, Haval Shirwan, Esma S Yolcu, Mark I Hunter, James K Pru, John P Lydon, Francesco J Demayo, Wipawee Winuthayanon

Faculty, Staff and Students Publications

More than 60% of pregnancy losses occur during the first trimester, highlighting the need to understand the role of the oviduct in early pregnancy. In this study, we conditionally ablated the classical progesterone receptor (Pgr) in oviductal epithelial cells, called the Pgrd/d mouse model. We found that 40% of embryos collected from Pgrd/d females were nonviable or developmentally delayed, indicating that epithelial PGR expression is crucial for embryonic development. Single-cell RNA sequencing revealed up-regulation of proinflammatory genes, including interleukin-22 (IL-22), in the epithelial cells of Pgrd/d females. Pharmacological inhibition of inflammation using nonsteroidal anti-inflammatory drugs …

Enhancement Of The Endocannabinoid System Through Monoacylglycerol Lipase Inhibition Relieves Migraine-Associated Pain In Mice, Elizaveta Mangutov, Yaseen Awad-Igbaria, Kendra Siegersma, Francois Gastambide, Ayodeji A Asuni, Amynah A A Pradhan

2020-Current year OA Pubs

BACKGROUND: Migraine affects over 1 billion people worldwide and is a leading cause of disability. Targeting the cannabinoid system offers a promising approach for pain and migraine relief. This study evaluated a novel monoacylglycerol lipase (MAGL) inhibitor to prolong endocannabinoid action in acute and chronic mouse models of migraine. It also examined MAGL and cannabinoid receptor 1 (CB

METHODS: C57BL6/J male and female mice received the human migraine trigger nitroglycerin (NTG) acutely or every other day for 9 days. Allodynia was assessed by von Frey hair stimulation of the periorbital area. A single dose of MAGL inhibitor (ABD-1970) was tested …

Determining Potential Immunomodulatory Drug Efficacy In Sepsis Using Elispot, Andrew H Walton, Dale F Osborne, Ethan B Davitt, Anne M Drewry, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

This study evaluated the ability of ELISpot to identify potential immuno-modulatory drug therapies in sepsis. ELISpot was performed ex vivo on whole blood from septic patients and healthy controls. Innate and adaptive immunity were evaluated by production of TNF-α and IFN-γ, respectively. Drug efficacy was determined by their effects to modulate the both the number of cytokine-producing cells and amount of cytokine produced per cell. The corticosteroid dexamethasone was evaluated for its ability to down modulate TNF-α and IFN-γ production. The TLR7/8 agonist resiquimod (R848) and T cell stimulants IL-7 and anti-PD-1 mAb were tested for their ability to enhance …

Mendelian Randomization Study Of Sleep Traits And Risk Of Colorectal Cancer, Olympia Dimopoulou, Yin Cao, Et Al.

2020-Current year OA Pubs

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using …

Reduced Venetoclax Exposure To 7 Days Vs Standard Exposure With Hypomethylating Agents In Newly Diagnosed Aml Patients, Christophe Willekens, Alexandre Bazinet, Samy Chraibi, Alex Bataller, Justine Decroocq, Naszrin Arani, Benjamin Carpentier, Caitlin Rausch, Delphine Lebon, Abhishek Maiti, Nicolas Gauthier, Nicholas Short, Sarah Bonnet, Koji Sasaki, Sabine Khalife-Hachem, Mahesh Swaminathan, Jean-Baptiste Micol, Florence Pasquier, Christophe Marzac, Damien Roos-Weil, Laurent Pascal, Naval Daver, Tapan Kadia, Didier Bouscary, Farhad Ravandi, Arnaud Pages, Hagop Kantarjian, Stéphane De Botton, Courtney Dinardo

Faculty, Staff and Student Publications

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7 + 7" regimen) from the first cycle (n = 82) vs patients treated with standard dose HMA + VEN (std-HMA/VEN) …

Kras Mutation Detection By Liquid Biopsy For Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Abdelrahman Yousef, Mark W Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L Lewis, Paul M Roy, Mohammad Fanaeian, Sali Albarouki, Luca F Castelnovo, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching-Wei Tzeng, Michael P Kim, Naruhiko Ikoma, Jess E Maxwell, Matthew H G Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (N = 186) in metastatic cases and in 52.4% (N = 43) of localized disease. KRAS mutations were detected in 64.6% (N = 148) of metastatic cases and 16% (N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7-4.3, P <  0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% (KRAS) and 33% (TP53) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.