Digital Commons Network^™

Overcoming Maternal Antibody Interference In Swine Influenza: Advancing Dna Vaccine Strateies For Enhanced Immune Protection In Piglets, Danh Cong Lai

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Maternally derived antibodies (MDAs) play a vital role in protecting neonates from infectious diseases, but their presence at the time of vaccination can interfere with vaccine-induced immune responses, thereby reducing vaccine effectiveness. MDA interference has been documented in pigs vaccinated with whole inactivated virus (WIV) vaccines against swine influenza A virus (IAV). In this thesis, we evaluated the efficacy of a lipid nanoparticle encapsulated DNA (LNP-DNA) vaccine against swine IAV in the presence and absence of MDAs, comparing it to a WIV vaccine. In MDA-negative piglets, both the LNP-DNA and WIV vaccines induced strong immune responses and effectively prevented the …

Measures Of Muscle Strength, Rate Of Force Development, And Fatiguability Across The Menstrual Cycle, Cassidy Wisler

All NMU Master's Theses

BACKGROUND: Hormone fluctuations and inconsistencies across the menstrual cycle paired with a shortage of literature on female physiology in exercise have made understanding on female exercise performance troublesome. Performance-based research has fallen behind and the increase in women participation and current evidence does not warrant general guidance on modulating specific exercise across the menstrual cycle. PURPOSE: The purpose of this study was to determine the effects of estrogen and progesterone on muscle strength, rate of force development, and fatiguability. METHODS: Nineteen recreationally active and eumenorrheic females (25.3 ± 5.8 yrs, 73.4 ± 12.2 kgs) volunteered to participate in the study. …

Persistent Imbalance: Women’S Representation In North American Pediatric Cardiology Leadership Roles.Persistent Imbalance: Women’S Representation In North American Pediatric Cardiology Leadership Roles, Alaina K. Kipps, Audrey C. Marshall, Neha Bansal, Holly Bauser-Heaton, Nadine Choueiter, Devyani Chowdhury, Aarti Dalal, Molly Ehrlich, Lindsay R. Freud, Supriya S. Jain, Pei-Ni Jone, Kristin Laraja, Dalia Lopez-Colon, Sonal T. Owens, Christina Ronai, Ritu Sachdeva, Corey Stiver, Nicole Sutton, Terrie Vasilopoulos, Jennifer Co-Vu

Department of Pediatrics Faculty Papers

BACKGROUND: Despite recent gender parity of physicians entering pediatric cardiology, representation of women leaders lags their male colleagues.

OBJECTIVES: We sought to better understand the variation in women in leadership roles in pediatric cardiology.

METHODS: The gender of physicians in 16 prespecified leadership positions was collected by survey between July 2022 and January 2023 from pediatric cardiology programs with >5 cardiologists in North America. We analyzed the association of women leaders with center size (based on surgical volume), geographic region, presence of categorical fellowship program, and gender of division chief and department chair.

RESULTS: Across 99 centers, a median of …

Profile Of Trna-Derived Short Non-Coding Rnas During Monocyte Differentiation And Their Role In Macrophage Survival, Anahita Jayaram, Sanjeev Galande, Soroush Sharbati, Deepak A. Deshpande, Phd, Kamlesh Pawar

Center for Translational Medicine Faculty Papers

Monocytes, a type of leukocytes, are key players in immune responses, transitioning to macrophages at infection sites. Differentiation, which is crucial for macrophage survival and resistance to apoptosis, is a tightly regulated process. Based on our earlier findings implicating the 5'-fragment of tRNAHisGUG (5'-HisGUG) in macrophage biology, we specifically focused on these fragments to investigate its regulation during monocyte-to-macrophage differentiation and its role in macrophage survival. We performed small RNA sequencing during monocyte-to-macrophage differentiation using THP-1 cells and identified 5'-HisGUG as a prominently regulated tDR. Notably, transfection of 5'-HisGUG in macrophages decreased survival under apoptotic stress. We propose that 5'-HisGUG …

Coordinated Regulation By Lncrnas Results In Tight Lncrna-Target Couplings, Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James De Bony De Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin

Faculty, Staff and Student Publications

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research. We developed BigHorn to computationally infer lncRNA-DNA interactions that mediate transcription and chromatin-remodeling factor activity. Its accurate inference enabled the identification of lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. These lncRNAs may act as molecular chaperones, regulating the stability and translation of mRNAs they helped transcribe, leading to tightly coupled expression profiles. Our analysis suggests that lncRNAs regulate cancer genes across tumor contexts, thus propagating the effects of non-coding alterations to …

The Impact Of Utilizing Injectable Platelet-Rich Fibrin And Collagen Plugs For Maintaining The Tooth Extraction Socket: A Review Study, Esraa Hameed Hassan, Ali H. Abbas Alhussaini

Al-Esraa University College Journal for Medical Sciences

Tooth extraction initiates a cascade of biological changes that result in alveolar bone resorption, compromising both the esthetic and functional outcomes of future dental rehabilitations, particularly implant placement. Socket preservation strategies have emerged as crucial interventions aimed at minimizing post-extraction ridge collapse. This review explores the synergistic effects of injectable platelet-rich fibrin (I-PRF) and collagen plugs in enhancing socket preservation outcomes. Collagen plugs serve as biocompatible scaffolds, promoting hemostasis, cellular migration, and angiogenesis, while supporting soft tissue healing and bone regeneration. Concurrently, I-PRF-an autologous, growth factor-rich biomaterial-provides a dynamic reservoir of platelets, leukocytes, and key cytokines such as Platelet-Derived Growth …

Clearance Of Acute Bilateral Idiopathic Central Corneal Stromal Haze Likely Due To Topical Losartan, Karen Asfar, Jad F. Assaf, Jeremiah Gendy, Sadeer Hannush, Shady T. Awwad

Wills Eye Hospital Papers

To report the use of topical losartan as a potential treatment of acute bilateral central corneal stromal haze in a patient presenting with a syndrome resembling central toxic keratopathy (CTK).Patient and Clinical Findings:A 51-year-old man presented with clinically significant central corneal stromal haze bilaterally 6 days after a periorbital and facial contact dermatitis secondary to pesticide exposure. Uncorrected and corrected distance visual acuity (UDVA and CDVA) were 20/80 and 20/70 in the right eye, and 20/200- and 20/150+ in the left eye, respectively. After unsuccessful treatment with topical antivirals, antibiotics and corticosteroids, the patient started off-label treatment with topical losartan …

Practicing Dentistry In The Age Of Periodontal Risk Management, Roger N. Warren D.D.S., Liana Umbrio D.D.S., Leena Palomo D.D.S., M.S.D.

The New York State Dental Journal

Purpose of review: To provide clinicians with knowledge of periodontal risk assessment that can be applied chairside effortlessly.

Recent findings: Detecting periodontal risk factors early may reduce the morbidity of oral and systemic diseases, as oral and systemic health can have a bidirectional relationship.

Summary: Dental professionals are equipped with evidence-based risk factors to predict and prevent the progression of periodontal disease. Implementing chairside risk assessment allows for prevention and early intervention, potentially reducing healthcare costs and promoting simpler solutions in an unpredictable economy.

A Brief Guide To Statistical Analysis Of Grouped Data In Preclinical Research, Colby J Vorland, Lilian Golzarri-Arroyo, David B Allison

Children’s Nutrition Research Center Staff Publications

Clustering and nesting (C&N) arise in many preclinical studies such as when animals are group-housed, share litters, or in cell culture. Ignoring C&N undermines the validity of analyses. We explain how C&N arise and valid designs and analyses.

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …

To Pause With A Cliffhanger Or A Temporary Closure? The Differential Impact Of Serial Versus Episodic Narratives On Children's Physical Activity Behaviors, Amy Shirong Lu, Melanie C Green, Caio Victor Sousa, Jungyun Hwang, I-Min Lee, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Research has supported the effectiveness of narratives for promoting health behavior, but different narrative presentation formats (serial vs. episodic) have seldom been compared. Suspense theories suggest that serial narratives, which do not provide a full resolution at the end of an episode, may create higher motivation for continued engagement with a story. Forty-four 8 to 12-year-old children were randomly assigned to watch an animation series designed for an existing active video game in which the plot was delivered either continuously across multiple episodes (serial) or in multiple yet relatively independent self-contained episodes (episodic). Controlling for social desirability, children who watched …

High-Impact Chronic Pain And Cognitive Decline Among Mexicans Aged 60 And Older From 2012 To 2018, Sadaf Arefi Milani, Sirena Gutierrez, Brandon O'Grady, Rebeca Wong, Rafael Samper-Ternent, Brian Downer

Faculty, Staff and Student Publications

Pain is associated with cognitive decline, but prior research has not considered differences between high- and low-impact chronic pain or low-and middle-income countries, such as Mexico. Our objective was to evaluate the association between high-impact chronic pain and cognitive decline among older adults in Mexico. We used data from the 2012-2018 Mexican Health and Aging Study (MHAS), a nationally representative study of older Mexican adults (60+). Pain, measured at each wave, was categorized as high-impact chronic pain (pain that limits daily activities), low-impact chronic pain (pain that did not limit daily activities), and no chronic pain. Cognition was measured at …

Diet, Gut Microbiota, And Histidine Metabolism Toward Imidazole Propionate Production In Relation To Type 2 Diabetes, Hongbo Yang, Kai Luo, Brandilyn A Peters, Yi Wang, Yanbo Zhang, Martha Daviglus, Amber Pirzada, Christina Cordero, Bing Yu, Robert D Burk, Robert Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Objective: To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people.

Research design and methods: In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008-2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ∼12 years (n = 4,632). In a subsample with gut microbiota data during a follow-up visit (2016-2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake. …

Exploring The Efficacy Of Various Minimally Invasive Surgery (Mis) Techniques In Spinal Fusion For Degenerative Spondylolisthesis: A Systematic Review, Yolanda V. Gutierrez, Blake Martin, Joshua Nwose, Alyssa A. Sepulveda, Ronald Shaju, Aamir Ahmad, Robert H. Ablove

School of Medicine Publications

Degenerative spondylolisthesis is a common etiology of low back pain characterized by the anterior displacement of one vertebral body relative to the one below it. A key contributing factor is intervertebral disc degeneration, which compromises spinal stability. In patients with a lack of neurological issues, conservative treatment is recommended. If conservative treatment is ineffective, surgery is deemed the next step, involving decompression and fusion of the vertebrae. Over the past several decades, minimally invasive surgical (MIS) techniques have been developed and refined. This systematic review aims to compare different types of MIS techniques for the treatment of degenerative spondylolisthesis to …

Models Of Care For Indigenous Children In Rural And Remote Settings: A Global Scoping Review, Joseph Freeman, Thomas Stubbs, Verity Chadwick, Anita Pickard, Tuguy Esgin, Elizabeth J. Elliott, Alexandra Martiniuk

Research outputs 2022 to 2026

Indigenous communities internationally have demonstrated remarkable strength despite significant challenges. Health disparities among Indigenous peoples persist due to historical injustices and ongoing racial discrimination, not inherent vulnerabilities. Disparities are rooted in a legacy of colonisation, systemic exclusion, and socio-economic inequities impacting access to healthcare, education, and employment. Preliminary searches show limited literature on models of care for remote living Indigenous children. This review aimed to identify internationally, effective models of care for Indigenous children in rural and remote areas. A scoping review was conducted, analysing literature on models of care for remote Indigenous children. This study followed the JBI’s Scoping …

Clonal Evolution Of Hematopoietic Stem Cells After Autologous Stem Cell Transplantation, Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Linda Zhang, Jennifer Padilla, Li Zhao, Joanne I Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Satoko Ogata, Sarah Hanache, Hui Yang, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Daisuke Nakada, Gheath Al-Atrash, Jeffery Molldrem, P Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi

Faculty, Staff and Student Publications

The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal hematopoiesis is not well defined. We conducted whole-genome sequencing on 1,276 single-cell-derived hematopoietic stem and progenitor cell (HSPC) colonies from ten patients with multiple myeloma treated with chemotherapies and six normal donors. Melphalan treatment significantly increased the mutational burden, producing a distinctive mutation signature, whereas other chemotherapeutic agents had minimal effects. Consequently, the clonal diversity and architecture of post-treatment HSPCs resemble those observed in normal elderly individuals, particularly through the progression of oligoclonal hematopoiesis, thereby suggesting that chemotherapy accelerates clonal aging. Integrated …

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

Duncan NRI Faculty and Staff Publications

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

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

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

A Phase 2 Trial Of Short-Term Intravenous N-Acetylcysteine In Biliary Atresia After Kasai Portoenterostomy, Sanjiv Harpavat, Kristin A Borovsky, Michael E Scheurer, Laurel Cavallo, Franca E Erhiawarie, Sanjeev Vasudevan, Adam M Vogel, Dana Cerminara, Elizabeth M Tessier, Kalyani R Patel, Sridevi Devaraj, Benjamin L Shneider

Center for Medical Ethics and Health Policy Staff Publications

Background: For infants with biliary atresia, the only treatment that can establish bile flow and delay need for liver transplant is the Kasai portoenterostomy (KP). Unfortunately, the KP has variable success. In this study, we hypothesized that intravenous N-acetylcysteine (IV NAC) treatment following KP would improve bile flow.

Methods: This was a phase 2 study following the two-stage "minimax" trial design. Participants received IV NAC (150 mg/kg/day) for 7 days after KP, and the primary endpoint was achieving total serum bile acids (TSBA) ≤10 μmol/L within 24 weeks of KP. Secondary endpoints were clinical markers and the occurrence of sentinel …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige K Boneski, Hiromi Sesaki, Ruteja A Barve, John A Collins, Makarand V Risbud

2020-Current year OA Pubs

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Exploitable Mechanisms Of Antibody And Car Mediated Macrophage Cytotoxicity, Tianyi Liu, Alexander B Kim, Young Ah Goo, Minsoo Son, Jaenyeon Kim, Carl J Deselm, Et Al.

2020-Current year OA Pubs

Macrophages infiltrate solid tumors and either support survival or induce cancer cell death through phagocytosis or cytotoxicity. To uncover regulators of macrophage cytotoxicity towards cancer cells, we perform two co-culture CRISPR screens using CAR-macrophages targeting different tumor associated antigens. Both identify ATG9A as an important regulator of this cytotoxic activity. In vitro and in vivo, ATG9A depletion in cancer cells sensitizes them to macrophage-mediated killing. Proteomic and lipidomic analyses reveal that ATG9A deficiency impairs the cancer cell response to macrophage-induced plasma membrane damage through defective lysosomal exocytosis, reduced ceramide production, and disrupted caveolar endocytosis. Depleting non-cytotoxic macrophages using CSF1R inhibition …

I2moe: Interpretable Multimodal Interaction-Aware Mixture-Of-Experts, Jiayi Xin, Sukwon Yun, Jie Peng, Inyoung Choi, Jenna L Ballard, Tianlong Chen, Qi Long

Faculty, Staff and Student Publications

Modality fusion is a cornerstone of multimodal learning, enabling information integration from diverse data sources. However, vanilla fusion methods are limited by

Wnt-Directed Cxcl12-Expressing Apical Papilla Progenitor Cells Drive Tooth Root Formation, Mizuki Nagata, Gaurav T Gadhvi, Taishi Komori, Yuki Arai, Hiroaki Manabe, Angel Ka Yan Chu, Ramandeep Kaur, Meer Ali, Yuntao Yang, Chiaki Tsutsumi-Arai, Yuta Nakai, Yuki Matsushita, Nicha Tokavanich, W Jim Zheng, Joshua D Welch, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

The tooth root is a critical component of the tooth anchored to surrounding alveolar bones. Tooth root formation is driven by cells in the apical papilla (AP) that generate new dentin-forming odontoblasts at the root-forming front. Mesenchymal stem cells have been isolated from AP for regenerative use; however, how AP cells physiologically coordinate tooth root formation remains undefined. We find that CXCL12+ cells emerge in AP under hypoxic environments at the onset of tooth root formation. Using Cxcl12-creER-based cell-lineage analysis, we further find that CXCL12+ AP cells contribute not only to odontoblasts but also to cementum-forming cementoblasts of the elongating …

Aggressive, Adaptive, And Underestimated: From Allergy To Arboviruses, The Rise Of The Lone Star Tick, Emily Ellen Owens Pickle

Theses and Dissertations

Once considered a nuisance with little medical importance, the lone star tick (Amblyomma americanum, Acari:Ixodidae) has emerged as a formidable vector driving a new era of public health threats across the United States of America. This dissertation traces the rise of the lone star tick from obscurity to infamy, exploring its expanding geographic range, unique immunologic impacts on humans, and role in the transmission of emerging tickborne viruses. Through a series of integrated studies, this work characterizes the epidemiology, immunology, and ecological context of tick-borne diseases in the southeastern U.S., with a particular focus on α-Gal syndrome (AGS), …

Inorganic Nanoparticle And Nanoplastic Transformations And The Impact On Biouptake By Freshwater Algal Cells Using Single Cell And Single Particle Inductively Coupled Plasma Mass Spectrometry, Elizabeth Carey Bair

Theses and Dissertations

The ubiquitous presence of nanoparticles (NPs) and nanoplastics (NPPs) and their effects on environmental and human health is a significant concern. They are used in every aspect of our lives, and while they offer many benefits, there are concerns about their impacts on ecosystems and human health. The primary aim of this dissertation is to quantify NP and NPP transformations in the presence of algae and determine how those transformations influence bioavailability. The methodology involves two complementary analytical techniques: single particle (SP) and single cell (SC) inductively coupled plasma mass spectrometry (ICP-MS). These techniques are tested and applied to two …

Interconnections Of Insulin/Igf-1 Signaling And Autophagy Abnormalities In Alzheimer’S Disease, Wang Liao, Jinfeng Xuan, Woo-In Ryu, Mariana K Bormann, Yoon Lee, Haley Dion, Elizabeth Evangelista, Ruiyi Li, Lucas Trambaiolli, Jun Liu, Arthur J Siegel, Brent P Forester, Bruce M Cohen, Kai-Christian Sonntag

Faculty, Staff and Student Publications

Introduction: Impaired insulin (INS) and insulin-like growth factor 1 (IGF-1) signaling are features of both brain aging and late-onset Alzheimer's disease (LOAD). However, their exact underlying mechanisms and cause-and-effect linkages, including the downstream regulation of endocytosis and autophagy, are still not well understood.

Methods: We investigated INS/IGF-1 signaling and its connection with endocytic and autophagic processes in fibroblasts from LOAD patients and healthy young or old control individuals.

Results: Compared to control old-age cells, protein levels in the INS/IGF-1 signaling cascade were elevated in LOAD cells, but activation of AKT was reduced. The activation of the INS/IGF-1/AKT/FOXO1 or mTOR axes …

Exploring Differential Impacts Of A Parent Intervention On Reading And Toy Play Across Ethnic And Linguistic Groups, Sarah Surrain, Susan H. Landry, Tricia A. Zucker, Yoonkyung Ch

Faculty, Staff and Student Publications

The ways that parents respond to their children’s initiations and guide their learning are associated with subsequent language development. Responsive parenting interventions have shown positive impacts on parent behaviors and child outcomes. However, less is known about how intervention effects vary for families from different linguistic and ethnic backgrounds. This secondary analysis of a randomized controlled trial of Play and Learning Strategies examines the effect of the intervention for three subgroups: Spanish-dominant Latine families (n = 142), English-dominant Latine families (n = 112), and non-Latine families (n = 137). Parents of preschool-aged children (M age = …

Inhibition Of The Gsk3Β/Nav16 Complex Suppresses Early-Stage Alzheimer’S Hyperexcitability, Timothy John Baumgartner, Manuel Silva-Pérez, Zahra Haghighijoo, Nolan Michael Dvorak, Aditya Kumar Singh, Nana Aboadwe Goode, Jully Singh, Berenice Gutierrez Grebenkova, Mate Marosi, Jessica Di Re, Leandra Koff, Wissarut Wijitrmektong, Manu Bala, Hanyue Liao, Marijn Lijffijt, Adam Thomas Szafran, Michael James Bolt, Michael A Mancini, Gregory D Cuny, Diana Shu-Lian Chow, Agenor Limon, Jeannie Chin, Fernanda Laezza

Faculty, Staff and Students Publications

Introduction: Network hyperexcitability (NH) is observed in patients with early-stage Alzheimer's disease (AD), emerging decades before cognitive decline. A key molecular determinant of NH is voltage-gated Na+ channel 1.6 (Nav1.6), which mediates action potential firing in CA1 hippocampal neurons. Ameliorating NH through inhibition of the glycogen-synthase kinase 3β (GSK3β/Nav1.6 complex may provide immediate benefits to cognition and memory and slow AD progression.

Methods: Hight-throughput virtual screening and multiple in vitro biological assays were utilized to identify compound 1063. Patch-clamp electrophysiology and electroencephalogram recordings were utilized to functionally assess 1063 in models of AD neuropathology.

Results: Building on previous studies identifying …

Development And Diversity Of Astrocytes, Michael R Williamson, Sanjana Murali, Benjamin Deneen

Faculty, Staff and Students Publications

Proper development of the central nervous system (CNS) depends on astrocytes, which are the most abundant glial cells in the CNS. Here, we provide an overview of astrocyte ontogeny and morphogenesis, highlighting mechanisms that regulate astrocyte development. In addition, we describe the roles of astrocytes in regulating the development of other CNS cell types, with emphasis on neural circuits and vascular networks. We also discuss evidence for astrocyte diversity and its implications for CNS development. Finally, we pose open questions related to astrocyte development and its intersection with astrocyte diversity.

Quality Of Life Outcomes Following Total Temporomandibular Joint Replacement: A Systematic Review Of Long-Term Efficacy, Functional Improvements, And Complication Rates Across Prosthesis Types, Luis Eduardo Almeida, Samuel Zammuto, Louis G. Mercuri

School of Dentistry Faculty Research and Publications

Introduction:

Total temporomandibular joint replacement (TMJR) is a well-established surgical solution for patients with severe TMJ disorders. It aims to relieve chronic pain, restore jaw mobility, and significantly enhance quality of life. This systematic review evaluates QoL outcomes following TMJR, analyzes complication profiles, compares custom versus stock prostheses, explores pediatric applications, and highlights technological innovations shaping the future of TMJ reconstruction.

Methods:

A systematic search of PubMed, Embase, and the Cochrane Library was conducted throughout April 2025 in accordance with PRISMA 2020 guidelines. Sixty-four studies were included, comprising 2387 patients. Results: Primary outcomes assessed were QoL improvement, pain reduction, and …