Digital Commons Network^™

Transdiagnostic Links Of Reward Processing In Obsessive-Compulsive Disorder And Depression, Kevin M Wagner, Matti Cervin, Jessica S C Cheng, Jasmine Arriaga, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Renee M Frederick, Jacey L Anderberg, Belinda E Núñez Bracho, Victor R Adorno, Leonardo F Fontenelle, Andrew D Wiese, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Objectives: Transdiagnostic models aim to uncover shared mechanisms across mental disorders. Reward responsiveness (the ability to experience pleasure from rewarding stimuli) is a plausible, yet underexplored, transdiagnostic mechanism linking obsessive-compulsive disorder (OCD) and depression. This study used network analysis to (1) examine how key reward responsiveness domains are interlinked in individuals with OCD and (2) explore how each domain is uniquely associated with OCD and depression.

Methods: A total of 1345 individuals with a history of OCD symptoms (ages 18-88, 71 % women) from Latino communities in the United States (including Puerto Rico) and nine Latin American countries completed validated …

Mitochondrial Complex Ii Orchestrates Divergent Effects In Cd4+ And Cd8+ T Cells, Keisuke Seike, Shih-Chun A Chu, Yuichi Sumii, Takashi Ikeda, Meng-Chih Wu, Laure Maneix, Dongchang Zhao, Yaping Sun, Marcin Cieslik, Pavan Reddy

Faculty, Staff and Students Publications

Mitochondrial metabolism orchestrates T cell functions, yet the role of specific mitochondrial components in distinct T cell subsets remains poorly understood. Here, we explored the role of mitochondrial complex II (MC II), the only complex from the electron transport chain (ETC) that plays a role in both ETC and metabolism, in regulating T cell functions. Surprisingly, MC II exerts divergent effects on CD4+ and CD8+ T cell activation and function. Using T cell-specific MC II subunit, succinate dehydrogenase A-deficient (SDHA-deficient) mice, we integrated single-cell RNA-seq and metabolic profiling, with in vitro and in vivo T cell functional assays to illuminate …

The Pathophysiological Role Of Mitochondrial Acid-Sensing Ion Channel 1a In Hypoxic Pulmonary Hypertension, Megan N. Tuineau

Biomedical Sciences ETDs

Pulmonary hypertension (PH) is characterized by increased pulmonary arterial constriction, pulmonary arterial remodeling, and right ventricular dysfunction. While metabolic and mitochondrial derangements are increasingly recognized as central pathogenic features, the underlying mechanisms and effectors are not yet fully understood. Acid-sensing ion channel 1a (ASIC1a) is a proton-gated cation channel involved in the development of chronic hypoxia (CH)-induced PH. ASIC1a represents a potential candidate involved in metabolic-mitochondrial dysfunction, as metabolic byproducts can act as ligands for ASIC1a. Additionally, ASIC1a has recently been identified as a mitochondrial ion channel involved in neuronal death following oxidative stress. Therefore, we hypothesize that ASIC1a functions …

Preoperative Awareness Of Nasal And Facial Aesthetic Deformities Among Rhinoplasty Candidates, Ağah Yeni̇çeri̇, Nagi̇han Gülhan Yaşar, Burak Hazir, Meli̇h Çayönü

Turkish Journal of Medical Sciences

Background/aim: This study primarily aimed to evaluate the preoperative awareness of nasal and facial anatomical deformities among patients scheduled for primary rhinoplasty. The secondary objective was to assess changes in patients’ self-perception and aesthetic expectations regarding surgical outcomes following preoperative consultation with the surgeon.

Materials and methods: In this prospective cross-sectional study, 56 adult patients seeking primary aesthetic rhinoplasty at a tertiary care center were included. Each participant completed a 10-item anatomical evaluation form. An experienced rhinoplasty surgeon independently evaluated the same parameters. Additionally, participants completed a two-item visual analogue scale (VAS) questionnaire both before and after the preoperative consultation. …

Impact Of Patient Education Meetings On Disease Knowledge In Chronic Urticaria Patients, Nazan Beyhan, Hati̇ce Eylül Bozkurt Yilmaz, Asli Çi̇ftci̇, Ömür Aydin, Di̇lşad Mungan, Betül Ayşe Si̇n, Gülfem Eli̇f Çeli̇k, Murat Türk, İnsu Yilmaz, Sevi̇m Bavbek

Turkish Journal of Medical Sciences

Background/aim: Chronic urticaria (CU) is a manageable disease with symptoms of itching and visible lesions that can disrupt daily life and reduce quality of life. The severity of symptoms can vary, and the cause is often unknown. Concerns among patients as regards to treatment and prognosis highlight the need for disease education to enhance self-management and reduce anxiety. The present study examines the effect of disease education on the knowledge level of CU patients.

Materials and methods: Patients with CU who presented to the allergy clinics of two tertiary university hospitals were invited to inperson education sessions including slide presentations …

Validity And Reliability Of The Turkish Version Of The Topical Corticosteroid Phobia (Topicop) Scale, Esra Ağaoğlu, Hi̇lal Kaya Erdoğan, Hi̇lal Çavuş, Selma Meti̇ntaş

Turkish Journal of Medical Sciences

Background/aim: Concerns about the use of topical corticosteroids (TCSs), commonly referred to as corticophobia, are widespread among dermatology patients and often lead to nonadherence to TCS treatment. This study aimed to evaluate the validity and reliability of the Turkish version of the topical corticosteroid phobia (TOPICOP) scale.

Materials and methods: The TOPICOP scale comprises 12 items grouped into 2 dimensions: beliefs (6 items) and worries (6 items). For cultural adaptation, the scale was forward and backward translated. The final Turkish version was administered to 123 patients with chronic dermatoses who rated their perceptions of TCSs using a 4-point Likert scale. …

Moltkia Coerulea Extracts Alleviate Caspase-3 Activity Via Reducing Oxidative Stress In Lps-Induced Neurotoxicity In Bv-2 Cells, Asli Can Ağca, Derya Altay, Hüdaverdi̇ Kul, Asli F. Ceylan, Betül Sever Yilmaz

Turkish Journal of Medical Sciences

Background/aim: Moltkia coerulea, a medicinal plant traditionally used for its neuroprotective properties, contains diverse phenolic compounds. However, its mechanisms of action in neuroinflammation remain unclear. We hypothesized that extracts of M. coerulea may protect microglial cells from lipopolysaccharide (LPS)-induced oxidative stress and apoptosis by modulating reactive oxygen species (ROS) and caspase-3 activity.

Materials and methods: Aqueous and methanol extracts (5–50 μg/mL) were tested in BV-2 microglial cells. Cell viability was assessed by MTT assay, while ROS generation and caspase-3 activity were measured using fluorescence-based kits. The effective concentration (10 μg/mL) was selected for mechanistic assays based on viability data and …

Assessing The Efficiency Of Methods To Teach Adolescents About Testicular Cancer And Testicular Self-Examination, Ayşe Gül Güven, Laden Jafari̇, Murat Doğuş Günel, Özlem Akbulut

Turkish Journal of Medical Sciences

Background/aim: Due to the increasing incidence of testicular cancer (TC), early testicular self-examination (TSE) in adolescent males is crucial for early detection and treatment. However, it is uncertain which method is best for teaching about TC and TSE in this age group. This study aimed to assess the effectiveness of formal (face to face with model) and informal (video presentation) approaches in male adolescents about TC and TSE.Material and methods: This intervention study was conducted in 2 high schools, and included a study group (n = 142) and a control group (n = 102). In the study group, a video …

Electrochemical Detection Of No And Ca2+ During Cold Atmospheric Plasma Treatment Of Acute Wounds: Sensor Selectivity And Stability In The Plasma-Bio-System, Jonathan E. Thomas, Kristina Pattison, Suneel Kumar, Gagana Karkada, Duncan Trosan, Aunic Goodin, Jason Rainone, Dnyaneshwari Rananavare, Vandana Miller, Francois Berthiaume, Katharina Stapelmann

Kimmel Cancer Center Faculty Papers

Cold atmospheric plasmas (CAP) are a versatile tool in medical applications like wound healing. Its therapeutic benefits are partially attributed to the generation of biologically active reactive oxygen and nitrogen species (RONS). Characterization of RONS, however, typically only occurs after treatment. Here we report the first real-time in situ detection of CAP-generated nitric oxide (NO), and the simultaneous detection of cellular calcium ions (Ca²⁺) release using electrochemical sensors during CAP treatment of murine wounds. In vivo, NO rose rapidly within the first minute of CAP treatment but accumulated less overall than in PBS, reflecting reactions with wound-bed targets. In situ …

Stakeholder Criteria For Trust In Artificial Intelligence-Based Computer Perception Tools In Health Care: Qualitative Interview Study, Ansh Rai, Meghan E Hurley, John Herrington, Eric A Storch, Casey J Zampella, Julia Parrish-Morris, Anika Sonig, Gabriel Lázaro-Muñoz, Kristin Kostick-Quenet

Faculty, Staff and Students Publications

Background: Computer perception (CP) technologies hold significant promise for advancing precision mental health care systems, given their ability to leverage algorithmic analysis of continuous, passive sensing data from wearables and smartphones (eg, behavioral activity, geolocation, vocal features, and ambient environmental data) to infer clinically meaningful behavioral and physiological states. However, successful implementation critically depends on cultivating well-founded stakeholder trust.

Objective: This study aims to investigate, across adolescents, caregivers, clinicians, and developers, the contingencies under which CP technologies are deemed trustworthy in health care.

Methods: We conducted 80 semistructured interviews with a purposive sample of adolescents (n=20) diagnosed with autism, Tourette …

Genetic Modifiers And Ascertainment Drive Variable Expressivity Of Complex Disorders, Matthew Jensen, Corrine Smolen, Anastasia Tyryshkina, Lucilla Pizzo, Jiawan Sun, Serena Noss, Deepro Banerjee, Matthew Oetjens, Hermela Shimelis, Cora M Taylor, Vijay Kumar Pounraja, Hyebin Song, Laura Rohan, Emily Huber, Laila El Khattabi, Ingrid Van De Laar, Rafik Tadros, Connie R Bezzina, Marjon Van Slegtenhorst, Janneke Kammeraad, Paolo Prontera, Jean-Hubert Caberg, Harry Fraser, Siddharth Banka, Anke Van Dijck, Charles Schwartz, Els Voorhoeve, Patrick Callier, Anne-Laure Mosca-Boidron, Nathalie Marle, Mathilde Lefebvre, Kate Pope, Penny Snell, Amber Boys, Paul J Lockhart, Myla Ashfaq, Elizabeth Mccready, Margaret Nowacyzk, Lucia Castiglia, Ornella Galesi, Emanuela Avola, Teresa Mattina, Marco Fichera, Maria Grazia Bruccheri, Giuseppa Maria Luana Mandarà, Francesca Mari, Flavia Privitera, Ilaria Longo, Aurora Curró, Alessandra Renieri, Boris Keren, Perrine Charles, Silvestre Cuinat, Mathilde Nizon, Olivier Pichon, Claire Bénéteau, Radka Stoeva, Dominique Martin-Coignard, Sophia Blesson, Cedric Le Caignec, Sandra Mercier, Marie Vincent, Christa L Martin, Katrin Mannik, Alexandre Reymond, Laurence Faivre, Erik Sistermans, R Frank Kooy, David J Amor, Corrado Romano, Joris Andrieux, Santhosh Girirajan

Faculty, Staff and Student Publications

Variable expressivity of disease-associated variants implies a role for secondary variants that modify clinical features. We assessed the effects of modifier variants on the clinical outcomes of 2,455 individuals with primary variants. Among 124 families with the 16p12.1 deletion, distinct rare and common variant classes conferred risks for specific developmental features, including short tandem repeats for neurological defects. Network analysis suggested distinct mechanisms involving 16p12.1 genes and secondary variants specific to each proband. Within disease and population cohorts of 976 individuals with the 16p12.1 deletion, we found opposing effects of secondary variants on clinical features across ascertainments. Additional analysis of …

Rare Epigenetic Alterations Are Conserved Across Hematopoietic Differentiation Stages After Mycobacterial Infection, Brandon T Tran, Pamela N Luna, Ruoqiong Cao, Duy T Le, Apoorva Thatavarty, Laure Maneix, Bailee N Kain, Scott Koh, Andre Catic, Katherine Y King

Faculty, Staff and Students Publications

Infection leads to durable cell-autonomous changes in hematopoietic stem and progenitor cells (HSPCs), resulting in production of innate immune cells with heightened immunity. The mechanisms underlying this phenomenon, termed central trained immunity, remain poorly understood. We hypothesized that infection induces histone modifications leading to changes in chromatin accessibility that are conserved during differentiation from HSPCs to myeloid progenitors and monocytes. We conducted genome-wide surveillance of histone marks H3K27ac and H3K4me3 and chromatin accessibility in hematopoietic stem cells, multipotent progenitor 3, granulocyte-monocyte progenitors, monocytes and macrophages of naïve and Mycobacterium avium infected mice. Interferon signaling pathways and related transcription factor binding …

Intouch Week Of December 8, 2025, New York Medical College

InTouch

No abstract provided.

Imaging Reactive Oxygen Species With L-012 Reveals Neutrophil Extracellular Trap Formation In Pancreatic Ductal Adenocarcinoma, Angisha Basnet, Kaitlyn M Landreth, Michael Sestito, Kristen Ranson, Seth T Gammon, David Piwnica-Worms, Brian A Boone, Tracy W Liu

Faculty, Staff and Student Publications

Neutrophils, key effector cells of the innate immune system, combat pathogens through mechanisms including the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). While these responses are critical for host defense, prolonged elevation of ROS and dysregulated NETosis mediated by neutrophils have been implicated in autoimmune diseases, chronic inflammation, and cancer. In pancreatic ductal adenocarcinoma (PDAC), a highly aggressive and inflammatory malignancy, an increase in neutrophils infiltrating the tumor microenvironment promotes cancer progression and metastasis through increased ROS production and NET release. Using bioluminescence imaging with the reporter L-012 and NET assays, we assessed …

Effect Of Various Lactobacillus Probiotic Strains On Oral Antihypertensive Drug Response: A Systematic Review, Khoirunnisa Ramadhani, Keri Lestari

Pharmacology and Clinical Pharmacy Research

Hypertension is a major risk factor for cardiovascular disease, and the effectiveness of antihypertensive therapy can be influenced by metabolic and systemic inflammatory factors associated with gut microbiota conditions. Probiotic strains from the genus Lactobacillus have been reported to modulate antihypertensive effects through complex biological mechanisms. This article evaluates experimental evidence from seven in vivo studies on the influence of Lactobacillus strains on the response to antihypertensive drugs, including pharmacodynamic mechanisms and drug–probiotic interactions. The combination of Lactiplantibacillus plantarum with amlodipine enhanced nitric oxide production, increased eNOS expression, reduced IL-6 levels, and improved drug bioavailability, leading to greater blood pressure …

Optimization Of Guava Leaf Extract Cream Formulation Through Variations Of Xanthan Gum And Stearic Acid For Wound Cure In Rats, Ayudia Cipta Khairani, Mia Ariasti

Pharmacology and Clinical Pharmacy Research

Cuts are among the most common skin injuries caused by sharp objects and can lead to infection if not properly treated. Natural ingredients such as guava leaves have been widely investigated for their wound-healing potential. Guava leaves contain bioactive compounds including flavonoids, saponins, alkaloids, and tannins, which contribute to anti-inflammatory, antibacterial, and tissue regeneration processes. This study aimed to formulate and evaluate the physical properties and wound-healing effectiveness of guava leaf ethanol extract cream with varying concentrations of xanthan gum and stearic acid as emulsifiers. The extract was obtained by maceration using 70% ethanol and formulated into four cream formulas …

Β-Glucan As A Potential Modulator Of Tgf-Β Signaling And Emt-Driven Resistance In Triple-Negative Breast Cancer, Hanifa Dinda Hayati, Riezki Amalia, Gemilang Lara Utama, Dika Pramita Destiani

Pharmacology and Clinical Pharmacy Research

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks expression of estrogen, progesterone, and HER2 receptors, limiting the effectiveness of targeted therapies and making chemotherapy the primary treatment option. However, resistance to chemotherapy remains a major clinical challenge, often driven by dysregulation of the transforming growth factor-β (TGF-β) signaling pathway. TGF-β plays a dual role in cancer, initially acting as a tumor suppressor but later promoting tumor progression through mechanisms such as epithelial–mesenchymal transition (EMT), immune evasion, and the establishment of cancer stemness. This review aims to explore the role of TGF-β signaling and EMT …

Perceived Effects Of Verbal Orders On In-Patient Medication Reconciliation And Safety: A Multi-Center Cross-Sectional Study, Yahaya Jafaru, Abubakar K. Sahabi, Mohammed M. Sani

Pharmacology and Clinical Pharmacy Research

Medication reconciliation presents significant challenges for healthcare professionals, particularly due to communication gaps that contribute to patient safety incidents. The aim of the study was to investigate the perceived effect of verbal orders on in-patient medication reconciliation and safety. The study was a cross-sectional survey with nurse employees of the three tertiary hospitals in Kebbi State, Nigeria as population of the study. The instrument for the data collection was a 21-items researcher-constructed self-administered questionnaire. Chi-square and binomial regression analysis were used in data analysis. Over two-thirds (70.7%) of the respondents reported a negative perceived effect on the patient’s compliance. The …

Fgf13 Regulates Vgsc-Independent Cardiomyocyte Impulse Propagation Via Cx43 Trafficking, Lala Tanmoy Das, Mattia Malvezzi, Aravind R Gade, Maiko Matsui, Margaret Mckay, Eric Q Wei, Matea J Zelich, Keon Mazdisnian, Jared Kushner, Bi-Xing Chen, Isabella Distefano, Daniel Roybal, Lin Yang, Lisa Stoll, James C Lo, Marian Kalocsay, Fadi G Akar, Steven O Marx, Geoffrey S Pitt

Faculty, Staff and Student Publications

Background: FHF (fibroblast growth factor homologous factor) variants associate with arrhythmias. Although FHFs are best characterized as regulators of voltage-gated sodium channel (VGSC) gating, recent studies suggest broader, non-VGSC-related functions, including regulation of Cx43 (connexin 43) gap junctions and hemichannels, mechanisms that have generally been understudied or disregarded.

Methods: We assessed cardiac conduction and cardiomyocyte action potentials in mice with constitutive cardiac-specific Fgf13 ablation (cFgf13KO) while targeting Cx43 gap junctions and hemichannels pharmacologically. We characterized FGF13 regulation of Cx43 abundance and subcellular distribution. With proximity labeling proteomics, we investigated novel candidate mechanisms underlying FGF13 regulation of Cx43. …

Hsp90 Buffers Deleterious Genetic Variations In Brca1, Brant Gracia, Xing-Han Zhang, Patricia Montes, Tin Chanh Pham, Min Huang, Junjie Chen, Georgios Ioannis Karras

Faculty, Staff and Student Publications

Protein-folding chaperone heat shock protein 90 (HSP90) buffers genetic variation in diverse organisms, but the clinical significance of HSP90 buffering in human disease remains unclear. Here, we show that HSP90 buffers mutations in the BRCT domain of BRCA1. HSP90-buffered BRCA1 mutations result in protein variants that retain interactions with partner proteins and strongly rely on HSP90 for protein stability and function in cell survival. Moreover, HSP90-buffered BRCA1 variants confer poly (ADP-ribose) polymerase (PARP) inhibitor resistance in cancer cells. Low-level HSP90 inhibition overcomes this resistance, revealing a cryptic and mutant-specific HSP90-contingent synthetic lethality. Furthermore, by stabilizing metastable variants across the entirety …

The Lived Experiences Of Mothers Of Children With Down Syndrome Using Teleot Services: A Phenomenological Study, Tumini Umukoro

Doctoral Dissertations and Projects

In response to the COVID-19 lockdown in the United States, therapy services for children with developmental delays transitioned to telehealth services. The purpose of this qualitative study was to explore the lived experiences of mothers of children diagnosed with Down syndrome (DS) who received occupational therapy services through telehealth (teleOT) using interpretative phenomenological analysis (IPA). Bronfenbrenner's ecological system theory was the framework used to address the research questions: RQ1: What are the lived experiences of mothers of children with DS regarding teleOT services? RQ2: How do mothers of children with DS perceive the benefits and challenges of telehealth OT services? …

Unconventional Binding Of Calmodulin To Chk2 Kinase Inhibits Catalytic Activity, Christopher R Horne, Tingting Wang, Samuel N Young, Toby A Dite, Hunter G Nyvall, Sushant Suresh, Katherine A Davies, Abner Gonzalez Castro, Vineet Vaibhav, Lucy J Mather, Laura F Dagley, Matthew J Belousoff, Gerard Manning, Anthony R Means, John E Burke, Janni Petersen, John W Scott, James M Murphy

Faculty, Staff and Students Publications

Calmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+ sensor. Ca2+ binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory pseudosubstrate sequence C-terminal to the kinase domain in members of the Ca2+-CaM-dependent protein kinase (CAMK) family and relieves inhibition to promote catalytic activity. Here, we report an unexpected mechanism by which CaM can bind CHK2 kinase to inhibit its kinase activity. Using biochemical, biophysical and structural mass spectrometry, we identify a direct interaction of Ca2+-CaM with the CHK2 …

Avaren-Fc's Effects On Lymphoma Cells., Jacob Hahn

Electronic Theses and Dissertations

This thesis investigates the therapeutic potential of Avaren-Fc (AvFc), a novel lectin fusion protein that integrates the Fc region of human IgG1 with the engineered lectin Avaren, specifically targeting lymphoma. The study delineates the in vitro binding capabilities of Avaren-Fc with a human B-cell lymphoma cell line, a canine B-cell lymphoma cell line, healthy canine peripheral blood mononuclear cells (PBMCs), and healthy human PBMCs. AvFc was shown to exhibit significant binding to human lymphoma cells. Furthermore, the direct cytotoxicity of Avaren-Fc against canine lymphoma cells, canine lymphoma cells and healthy canine PBMCs was assessed. It was found that there is …

Host-Intrinsic Factors Determine Anti-Tumor Efficacy Of Exercise In Pancreatic Ductal Adenocarcinoma, Sumedha Pareek

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.

In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a …

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Ddt Exposure Induces Microglial Activation And Disease-Associated Microglial Signatures: Relevance To Mechanisms Of Alzheimer’S Disease, Isha Mhatre-Winters, Aseel Eid, Nicole Blum, Yoonhee Han, Ferass M Sammoura, Long-Jun Wu, Jason R Richardson

The Brown Foundation: Institute of Molecular Medicine

Background: Alzheimer's disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models.

Objective: Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice.

Methods: DDT-induced inflammatory and disease-associated microglial (DAM) gene expression were determined in PMG by qPCR and immunocytochemistry, with and without pretreatment with the sodium channel antagonist tetrodotoxin (TTX). Furthermore, …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Periostin Promotes Sarcoma Growth By Promoting Tumor-Associated Macrophage Migration And Differentiation, Jin-Fen Xiao, Kristin Ishaya, Emily Y Ko, Annaliese Fowler, Marina T Broz, Jlenia Guarnerio

Faculty, Staff and Student Publications

Soft-tissue sarcomas (STS) are characterized by abundant extracellular matrix (ECM) deposition, yet the functional contribution of specific ECM components remains poorly understood. In this study, we identify periostin (POSTN), a matricellular protein, as a regulator of sarcoma progression and the tumor immune microenvironment. Analysis of human sarcoma datasets revealed that high POSTN expression correlates with poor prognosis and elevated expression of ECM-related and myeloid cell–associated genes. In murine genetic models of sarcoma, tumors expressing high levels of Postn displayed enhanced expression of ECM genes and monocyte-recruiting cytokines. Functional silencing of Postnin vivo reduced tumor growth without altering tumor cell …

Bayesian Integrated Learning Of Longitudinal Dose-Response Relationships Via Decentralized Clinical Trials, Jingyi Zhang, Tuo Wang, Yongming Qu, Fangrong Yan, Suyu Liu, Ruitao Lin

Faculty, Staff and Student Publications

Decentralized clinical trials (DCTs) extend trial activities beyond traditional sites, enhancing access, convenience, efficiency, and result generalizability. They are particularly promising for chronic conditions like diabetes and obesity, which require longer study durations to evaluate drug effects. However, decentralized data collection raises concerns about increased variability and potential biases. This paper presents a novel Bayesian integrated learning procedure to analyze dose-response relationships using longitudinal data from a phase II DCT that combines centralized and decentralized data collection. We generalize a parametric exponential decay model to handle mixed data sources and apply Bayesian spike-and-slab priors to address biases and uncertainties from …