Digital Commons Network^™

First Experience With Third-Party Validations: A Robust Calibration And Qa Procedure For Proton Flash Delivery, Chih-Chiang Chang, Balaji Selvaraj, Xingyi Zhao, Jacob Rembish, Paige A Taylor, Alexander Bookbinder, Chingyun Cheng, J Isabelle Choi, Charles B Simone, Haibo Lin, Minglei Kang

Faculty, Staff and Student Publications

Background: Proton FLASH radiotherapy, delivering ultra-high dose rates, shows promise in reducing normal tissue toxicity while maintaining tumor control. However, accurate dosimetry and quality assurance (QA) for FLASH remain challenging due to the extreme dose rates involved. Developing reliable calibration and QA procedures is crucial for advancing FLASH towards clinical implementation.

Purpose: To present an effective routine calibration and QA procedure for proton FLASH delivery to ensure high-quality dosimetry performance for preclinical and clinical delivery.

Methods: A high temporospatial resolution strip ionization chamber array (SICA) detector was mounted to the treatment nozzle, which was calibrated using an Advanced Markus ion …

Mapping Cardiac Electrical Abnormalities In Rodents, Ashish Kapoor, Peter A Doris

Faculty, Staff and Student Publications

No abstract provided.

Cancer-Associated Fibroblasts As Mediators Of Tissue Microenvironment Remodeling In Cancer, Fernanda G Kugeratski, Emily J Kay, Sara Zanivan

Faculty, Staff and Student Publications

Cancer-associated fibroblasts (CAFs) are a multifunctional cell population of solid tumors that substantially remodel the tumor microenvironment (TME). The combination of single-cell and spatial technologies with elegant mouse models and analysis of patient samples is enabling unprecedented advances in the characterization of CAF origins, heterogeneity, and functions within the TME. As such, the field is now evolving to delineate tissue-specific subpopulations of CAFs, their markers, and the biological context in which each subset presents with a tumor-promoting or a tumor-restraining function. In this timely review, we discuss recent advances in CAF biology in the context of emerging areas of interest …

Cancer-Induced Nerve Injury Promotes Resistance To Anti-Pd-1 Therapy, Erez N Baruch, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Xiayu Rao, Shamima Akhter, Tuany Eichwald, Tongxin Xie, Mohammad Balood, Adebayo Adewale, Shorook Naara, Hinduja N Sathishkumar, Shajedul Islam, William Mccarthy, Brandi J Mattson, Renata Ferrarotto, Michael K Wong, Michael A Davies, Sonali Jindal, Sreyashi Basu, Karine Roversi, Amin Reza Nikpoor, Maryam Ahmadi, Ali Ahmadi, Catherine Harwood, Irene Leigh, Dennis Gong, Paulino Tallón De Lara, Derrick L Tao, Tara M Davidson, Nadim J Ajami, Andrew Futreal, Kunal Rai, Veena Kochat, Micah Castillo, Preethi Gunaratne, Ryan P Goepfert, Sharia D Hernandez, Nikhil I Khushalani, Jing Wang, Stephanie S Watowich, George A Calin, Michael R Migden, Mona Yuan, Naijiang Liu, Yi Ye, William L Hwang, Paola D Vermeer, Nisha J D'Silva, Yuri L Bunimovich, Dan Yaniv, Jared K Burks, Javier Gomez, Patrick M Dougherty, Kenneth Y Tsai, James P Allison, Padmanee Sharma, Jennifer A Wargo, Jeffrey N Myers, Sebastien Talbot, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated …

Design And Development Of An Intervention To Improve The Quality And Safety Of Pediatric Dental Sedation: A Human-Centered Design Approach, Kawtar Zouaidi, Jan Yeager, Suhasini Bangar, Sayali Tungare, Urvi Mehta, Janelle Urata, Alfa-Ibrahim Yansane, Thomas Tanbonliong, Jungsoo Kim, Emily Sedlock, Krishna Kumar Kookal, Yan Xiao, Tokede Oluwabunmi, Heiko Spallek, Amy Franklin, Gregory W Olson, Joel White, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: There are gaps in understanding the experiences of children, parents, and providers during dental conscious sedation. This study aimed to capture and analyze these experiences to identify opportunities for improvement and enhance the quality and safety of pediatric dental conscious sedation.

Methods: A human-centered design approach was used to examine the conscious sedation experience in 2 US advanced education pediatric dental clinics. Researchers conducted field observations, interviews with providers and parents, and providers focus groups to explore experiential factors. Data were transcribed and analyzed using content thematic analysis. Insights from the data were used to explore and generate new …

Relationship Between Quantitative Mri Ute T2* Of Acl Autografts And Bmi-Normalized Knee Laxity Within The First Year After Acl Reconstruction, Alonso Figueroa, Tomasz Bugajski, Dillon Humpal, Manickam Kumaravel, Walter Lowe, Payam Zandiyeh

Faculty, Staff and Student Publications

Background: The anterior cruciate ligament reconstruction (ACLR) graft undergoes a remodeling process that affects its structural properties. Ultrashort echo time T2* (UTE-T2*) imaging has been instrumental in examining this process. However, more research is needed on the postoperative relationship between UTE-T2* of the graft and its mechanical properties.

Purpose: To longitudinally examine ACL graft changes after ACLR using UTE-T2* decay coefficients and knee laxity and explore their relationship.

Study design: Case series; Level of evidence, 4.

Methods: A total of 31 patients who underwent ACLR had magnetic resonance imaging of their knees at 1, 6, and 12 months after surgery …

Suturing Education For Athletic Trainers: An Evidence-To-Practice Review, Morgan K. Webb, Brett T. Heim, Allyson E. Ritchey, Kenya Moore, Zachary K. Winkelmann

Clinical Practice in Athletic Training

Teaching suturing skills to medical students is a critical component of their education. Implementing suturing into a comprehensive framework is developed from how professors teach the skill. Suturing is a required skill by the General Medical Council that all medical students must have, and how it is being introduced to new students is changing. This review aimed to summarize different educational interventions and determine the most efficient and cost-effective way to teach future suturing skills. The original systematic review included 25 articles in the final data synthesis. Fourteen studies were randomized control trials, six were quasi-experimental, and five were observational. …

The Role Of Fibroblast Activation Protein On Left Ventricular Growth And Extracellular Matrix Remodeling As A Function Of Age And Pressure Overload, Amelia Marie Churillo

Theses and Dissertations

Fibroblast activation protein (FAP) is abundantly expressed in cancer associated fibroblasts and contributes to extracellular matrix (ECM) remodeling. Recent studies using imaging techniques have identified increased levels of FAP in the left ventricle (LV) of patients identified as at risk for developing heart failure. However, the role of FAP in regulated LV myocardial structure and function remains unclear. This project tested two hypotheses: First, genetic ablation of FAP would modify LV structure and function and be more pronounced with aging. Second, genetic ablation of FAP would modify LV structure and function with LV pressure overload (LVPO) accompanied by ECM remodeling.

Carotenoids As Neuroprotective Agents In Multiple Sclerosis: Pathways, Mechanisms, And Clinical Prospects, Elham Nadimi, Shirin Jamal Omidi, Mahshad Ghasemi, Mohammad Hashem Hashempur, Aida Iraji

Faculty, Staff and Student Publications

Multiple sclerosis (MS) is a chronic autoimmune andneurodegenerative disorder affecting the central nervous system (CNS), characterized by demyelination and neuroinflammatory responses, oxidative stress, and immune dysregulation. The global incidence of MS is rising, demonstrating the necessity for new therapeutic agents against its complex pathophysiology. Carotenoids, naturally pigments with strong antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective activities, have been recognized as promising candidates to target MS.The antioxidant effect of astaxanthin, lycopene, β-carotene, crocin, and lutein resulted from the deactivation of reactive oxygen species (ROS), preservation of mitochondrial integrity, and prevention of lipid peroxidation. Additionally, carotenoids regulate inflammatory pathways by suppressing NF-κB activation, …

Irf6 Regulates Adherens Junction Proteins And Inflammatory Cytokines In Salivary Acinar Cells And Its Expression Is Elevated In Sjӧgren’S Syndrome, Vi Pham, Antonio Hernandes Chaves Neto, Julia Zheng, Mary Elmeniawi, Krishna Kumar Kookal, Muhammad F Walji, Mary C Farach-Carson, Walid D Fakhouri

Faculty, Staff and Student Publications

Objective: To investigate the mechanism of Interferon Regulatory Factor 6 (IRF6) function in regulating adherens junction proteins and inflammatory cytokines in human salivary acinar cells and Sjögren's syndrome biopsies.

Design: We used mouse model, salivary cell lines, and human salivary gland (SG) biopsies to investigate IRF6 function in SG cellular integrity and immunomodulation.

Results: In Irf6-null mice, we observed myoepithelial cell detachment from acinar cells of major SGs, and the acini were remarkably disorganized compared to wild-type littermates. At the molecular level, the acinar differentiation markers E-cadherin and MIST1 were markedly reduced in Irf6-null embryonic SG, while the proinflammatory cytokines, …

From Nociception In Aneural Animals To Human Suffering: Toward A Comparative Biology Of Pain, Edgar T Walters

Faculty, Staff and Student Publications

Pain is a core feature of human life, but systematic comparisons of this biological trait across taxa have been rare. A broadly accepted definition based on human experience emphasizes dual features of pain: a sensory (discriminative) component for sensing and monitoring tissue injury, and an affective (emotional) component to motivate avoidance of tissue distress. Conscious pain is coupled to unconscious nociception (detection of incipient or existing injury). This Review considers nociception and pain across phyla within a comparative framework, addressing basic questions about evolutionary origins, mechanisms and functions of pain. The occurrence of adaptive cellular responses to injury in virtually …

Epigenetic Age Acceleration Mediates Treatment Effects On Cardiometabolic And Cardiovascular Risk In Childhood Cancer Survivors, Xiaoxi Meng, Tiffany Eulalio, Yoonji Kim, John Easton, Heather L Mulder, Emily Walker, Geoffrey Neale, Nan Song, Kyla Shelton, Rebecca M Howell, Mengqi Xing, Sedigheh Mirzaei, Deo Kumar Srivastava, Bonnie Ky, Stephanie B Dixon, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Zhaoming Wang

Faculty, Staff and Student Publications

BACKGROUND: Childhood cancer survivors are at increased risk for epigenetic age acceleration (EAA) and subsequent morbidities, including cardiometabolic risk factors (CMRFs) and cardiovascular diseases, because of prior genotoxic treatments.

OBJECTIVES: The aim of this study was to evaluate the mediating role of EAA in the relationship between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.

METHODS: This study included 2,939 5-year survivors from SJLIFE (St. Jude Lifetime Cohort) who underwent DNA methylation profiling using peripheral blood mononuclear cells. EAA was calculated using 3 established epigenetic clocks: DunedinPACE, PCPhenoAge, and GrimAge2. Treatment data, including body region-specific radiotherapy (RT) and …

Epidemiology Of Lower Extremity Amputations In The United States: An Analysis Of The Global Burden Of Disease Database From 1990 To 2019., Peter B Spencer, Cameron J Sabet, Gabrielle Dykhouse, Taylor J Manes, Phillip C Mckegg, Ambrose Loc T Ngo, Ayah Ibrahim, Jack Weick

Surgery Articles

BACKGROUND: Lower extremity amputations (LEAs) are medically, psychologically, and functionally devastating. The objective of our study was to evaluate region- and sex-specific differences of unilateral and bilateral LEAs across the United States (US) from 1990 to 2019.

METHODS: The Global Burden of Disease database was used to analyze years lived with disability (YLDs), prevalence, and incidence rates per 100,000 people for LEAs in the US from 1990 to 2019. Data were stratified into four US Census Bureau-defined regions: Northeast, Midwest, South, and West. Differences between regions and sexes were assessed, with statistical significance defined as p < 0.05.

RESULTS: From 1990 to …

Chimeric Antigen Receptor Natural Killer (Car-Nk) Cells: From Preclinical Promise To Clinical Reality In Cancer Immunotherapy, Hunter Cassidy Cochran, Kevin Ashkan Ghobadi, Armin Ghobadi

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents an emerging frontier in cancer immunotherapy. CAR-NK cells offer the potential for "off-the-shelf" treatments with a favorable safety profile, due in part to their innate capacity for HLA-unrestricted tumor targeting and an absence of graft-versus-host disease. Landmark clinical studies using cord blood - derived CAR-NK cells and another employing iPSC-derived CAR-NK cells have reported impressive response rates, durable remissions, and minimal toxicity. Furthermore, a growing landscape of ongoing clinical trials is exploring innovative strategies to enhance persistence, overcome solid tumor challenges, and prevent antigen escape. These advances collectively underscore the …

Pka-Driven Spp1 Activation As A Novel Mechanism Connecting The Bone Microenvironment To Prostate Cancer Progression, Pablo Sanchis, Agustina Sabater, Julia Lechuga, Jimena Rada, Rocio Seniuk, Gaston Pascual, Mora Gatti, Juan Bizzotto, Peter D A Shepherd, Jun Yang, Javier Cotignola, Elba Vazquez, Joaquin Mateo, Pia Valacco, Estefania Labanca, Christopher Logothetis, Geraldine Gueron, Nicolas Anselmino

Faculty, Staff and Student Publications

Prostate cancer (PCa) bone metastasis (BM) poses a significant clinical challenge due to the heterogeneity of treatment responses and patient outcomes. In this study, we examined the role of Protein Kinase A (PKA) signaling in modulating the expression of osteopontin (SPP1/OPN), a protein associated with poor prognosis, within a subset of PCa BM patients. By integrating multi-omics results we identified a novel mechanism in which bone-derived type-I collagen (Col1a1) and fibronectin (Fn1) stimulate SPP1 expression in PCa cells through the activation of PKA signaling. This bone-induced regulation of SPP1 was confirmed both in vitro, using PCa-bone co-culture systems (PC3 or …

Perioperative Antibiotic Administration Review: An Analysis Of Outpatient Surgeries At Ohiohealth Doctors Hospital., Rayyan Bhutta, Thomas Shneker, Samantha Currier, Alexander Caskey, Vincent Relli-Dempsey, Matthias Franzen, Samir Patel

Surgery Articles

INTRODUCTION: A vital part of preventing surgical site infections (SSIs) is perioperative antibiotic prophylaxis. Antibiotics must be administered within a certain window of time, usually 15 to 60 minutes prior to the surgical incision, for them to be effective. The most frequently utilized medication, cefazolin, can be administered quickly by intravenous push (IVP), but other medications, such as vancomycin and clindamycin, need longer infusion times. Antibiotic efficacy declines, and the risk of SSIs is increased when scheduling requirements are not followed. With special focus on time, dosage, and variation by surgery type, this study evaluates adherence to perioperative antibiotic administration …

Tofacitinib Ameliorates Campylobacter-Induced Intestinal Pathology By Suppressing Ifnγ Producing Ilcs And T Cells, Anna A Korchagina, Sergey A Shein, Wayne T Muraoka, Justin Nguyen, Qiangxing Chen, Anna A Tumanova, Austin W Todd, Carlos E Rivera, Rita Tamayo, Paolo Casali, Ekaterina Koroleva, Alexei V Tumanov

Faculty, Staff and Student Publications

Patients with autoimmune diseases are more susceptible to foodborne infections, which can be exacerbated by immunosuppressive therapy. Tofacitinib, a JAK/STAT pathway inhibitor, was recently approved for the treatment of ulcerative colitis, yet its effects on the pathogenesis of intestinal infections remain unclear. Here, we examined the impact of oral tofacitinib treatment in a mouse model of Campylobacter jejuni (C. jejuni) infection. Our results show that early tofacitinib administration attenuates intestinal pathology without affecting bacterial colonization. Specifically, tofacitinib suppressed CXCL1, CXCL2, CCL2 chemokine expression by intestinal epithelial cells, limiting recruitment of monocytes and neutrophils to the gut. In addition, JAK/STAT inhibition …

Systematic Review And Meta-Analysis Of Microrna-7-5p Expression And Biological Significance In Head And Neck Squamous Cell Carcinoma, Rikki A.M. Brown, Michael Phillips, Andrew J. Woo, Omar Kujan, Stephanie Flukes, Louise N. Winteringham, Larissa C. Dymond, Fiona Wheeler, Brianna Pollock, Dianne J. Beveridge, Elena Denisenko, Peter J. Leedman

Research outputs 2022 to 2026

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas …

Temporal Eating Patterns And Ultra-Processed Food Consumption Assessed From Mobile Food Records Of Australian Adults, Janelle D. Healy, Satvinder S. Dhaliwal, Christina M. Pollard, Amelia J. Harray, Lauren Blekkenhorst, Fengqing Zhu, Deborah A. Kerr

Research outputs 2022 to 2026

Background/Objective: Temporal eating patterns and ultra-processed food (UPF) consumption have independently been associated with obesity and non-communicable diseases. Little is known about the temporal patterns of UPF consumption, as data is challenging to collect. Temporal data can be extracted from mobile food records (mFRs). The aim of this study was to identify the temporal eating patterns of those consuming UPFs using an mFR. Methods: A combined sample of 243 young (18–30 years) and 148 older (>30 years) adults completed a 4-day mFR. The time of eating was extracted from the mFR image metadata. UPFs were identified using the NOVA …

Validation Of A Mind Diet Screener In Older Adults, Desarae A. Dempsey, Puja Agarwal, Shane Fernandez, Jared R. Brosch, Sujuan Gao, Daniel O. Clark, Frederick W. Unverzagt, Liana G. Apostolova, David G. Clark, Martin R. Farlow, Sunu Mathew, Sophia Wang, Michelle Quirke, Yolanda Graham-Dotson, Colette Blach, Leyla Schimmel, Rima Kaddurah-Daouk, Andrew J. Saykin, Shannon L. Risacher

Research outputs 2022 to 2026

Introduction: Higher adherence to the Mediterranean-DASH (Dietary Approaches to Stop Hypertension) Intervention for Neurodegenerative Delay (MIND) diet has been associated with reduced Alzheimer's disease (AD) risk. This study assessed the validity of a brief 15-item MIND diet screener compared to a comprehensive food frequency questionnaire (FFQ). Methods: The validity of an adapted MIND diet screener relative to the VioScreen FFQ was evaluated in 92 older adults from the Indiana Alzheimer's Disease Research Center (IADRC). Correlation coefficients and tertile-based classification statistics were used, and FFQ nutrient profiles were examined across screener-based MIND diet tertiles. Results: MIND diet scores from the screener …

What Community Members With Chronic Illness Teach Future Healthcare Professionals In A Longitudinal Interprofessional Education Program: A Focus Group Study, Rachel White, Maria Brucato, Amber King, Anne B. Mitchell, Nethra S. Ankam

Department of Medicine Faculty Papers

INTRODUCTION: Nearly 50% of Americans have at least one chronic illness. Preparing future healthcare providers for interprofessional collaborative practice (IPCP) and person-centred care through community-based interprofessional education (IPE) can improve outcomes for this growing population. Partial programme theories predict that patients' participation as teachers in health professions education contributes to students' development of patient-centredness. Role theory asserts that behaviours are shaped by assigned roles; therefore, community members with chronic illness who assume roles of health mentors in an IPE curriculum are predicted to teach students about their patient experiences. Yet, this teaching outcome and the lessons health mentors teach in …

Repeated Withdrawal Of A Glpr Agonist Induces Hyperleptinemia And Deteriorates Metabolic Health In Obese Aging Um-Het3 Mice, Nisi Jiang, Jiyuan Yin, Noah Lawrence, Jieyi Meng, Laurence T Maeyens, Ziying Xu, Xin Li, Mbolle Ekane, Ariana Chaudhary, Pengju Cao, Guannan Li, Carolina Solis-Herrera, Yi Zhu, Shangang Zhao

Children’s Nutrition Research Center Staff Publications

GLP-1-based therapy is highly effective in combating aging-associated metabolic diseases. However, the metabolic effects of frequent withdrawal from this therapy in aged, obese mice have not been previously studied. In this study, aged obese UM-HET3 mice were assigned to three groups: Group 1 received no liraglutide treatment (Lira OFF); Group 2 underwent 3 cycles of treatment followed by withdrawal (Lira ON/OFF); and Group 3 remained on continuous treatment (Lira ON). As expected, mice in Group 3 showed reduced body weight and food intake, along with improved metabolic health. In contrast, mice in Group 2 developed hyperleptinemia and visceral fat expansion, …

Mapping The Geographic Distribution Of Dimorphic Mycoses Using A Us Commercial Insurance Database, Reid Goodman, Adriana M Rauseo, Samuel L Windham, Julio C Zuniga-Moya, William G Powderly, Andrej Spec, Patrick B Mazi

2020-Current year OA Pubs

BACKGROUND: The dimorphic mycoses (DMs) histoplasmosis, blastomycosis, and coccidioidomycosis are classically thought to be geographically restricted to specific regions of the United States. The current scientific consensus is that these geographic boundaries are expanding, but the extent of this expansion remains uncertain.

METHODS: This study is a retrospective analysis of >21 million (annually) commercially insured individuals within the United States during 2007-2016. Diagnosis of histoplasmosis, coccidioidomycosis, and blastomycosis were identified using

RESULTS: There were 37 513 histoplasmosis, 14 987 coccidioidomycosis, and 2207 blastomycosis diagnoses during 2007-2016 within 387 Metropolitan Statistical Areas. DMs were consistently diagnosed outside their historical hyperendemic regions. …

Predictive Gene Expression Signatures For Alzheimer's Disease Using Post-Mortem Brain Tissue, Ashley Duche, Oliver Tan, Andrius Baskys, Rachita K. Sumbria, Moom R. Roosan

Pharmacy Faculty Articles and Research

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau protein aggregates in the brain. These pathological features manifest in specific regions, but mechanisms rendering some areas more susceptible to early AD-related changes remain poorly understood. To address this, we developed predictive gene expression signatures to explore molecular mechanisms underlying regional vulnerability to AD pathology.

Methods: Post-mortem brain tissues from participants of the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) were used to derive gene expression signatures from six brain regions affected at varying …

Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …

Dean's Update, October 2025, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

Pacap Signalling Network In The Nucleus Accumbens Core Regulates Reinstatement Behaviour In Rat, Samrat Bose, Gregory Simandl, Evan M. Hess, Linghai Kong, Nicholas Raddatz, Brian Maunze, Sujean Choi, David A. Baker

Biomedical Sciences Faculty Research and Publications

Cocaine use disorder (CUD) lacks FDA-approved treatments, partly due to the difficulty of creating therapeutics that target behaviour-related neural circuits without disrupting signalling throughout the brain. One promising candidate for circuit-selective neuromodulation is pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with pleiotropic behavioural actions whose signalling network spans the gut–brain axis. Here, we investigated the potential existence and function of an endogenous PACAP signalling network within the nucleus accumbens core (NAcc), which is a structure that integrates emotional, cognitive and reward processes underlying behaviour. We found that PACAP and its cognate receptor, PAC1R, are endogenously expressed in the rat NAcc …

Brugia Malayi And Other Filarial Parasite Species In Animals In Areas Endemic For Lymphatic Filariasis In Belitung District, Indonesia, Irina Diekmann, Taniawati Supali, Kerstin Fischer, Elisa Iskandar, Noviani Sugianto, Yossi Destani, Rahmat Alfian, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

BACKGROUND: Brugia malayi is the most common cause of lymphatic filariasis (LF) in Indonesia. A zoophilic ecotype that infects both humans and animals occur in Belitung District in Indonesia. The district received five annual rounds of mass drug administration (MDA) between 2006 and 2010 and passed three transmission assessment surveys (TAS) in subsequent years. However, a survey in five villages in 2021 showed a microfilaria (Mf) prevalence of 2.1% in humans. The reappearance of B. malayi infection in humans may be due to reintroduction from animal reservoirs. The goal of this study was to determine B. malayi prevalence in potential …

Enhanced Control Of Liposomal Drug Release By Drug-Aptamer Complexes, Xiangang Huang, Yang Li, Matthew Torre, Rachelle Shao, Wei Zhang, Zihan Wang, Daniel S Kohane, Christopher B Weldon

Duncan NRI Faculty and Staff Publications

Conventional diffusion-controlled drug delivery systems (DDS) can have undesirable initial burst release, leading to potential systemic toxicity, and the rate of basal release can deplete content, shortening the duration of effect. Here, it is hypothesized that conventional drug delivery systems-using liposomes as an example-can be enhanced by incorporation of an aptamer that binds specifically to the encapsulated drug. Affinity of the aptamer to the drug within liposomes (Lipo-Apt) would slow release. It is demonstrated that this approach works with a range of relatively small and hydrophilic molecules, including tetrodotoxin (TTX), serotonin (Ser), and kanamycin (Kan). The in vivo utility of …

Phosphorylation At Serine 214 Correlates With Tau Seeding Activity In An Age-Dependent Manner In Two Mouse Models For Tauopathies And Is Required For Tau Transsynaptic Propagation, Pablo Martinez, Nur Jury-Garfe, Henika Patel, Yanwen You, Abigail Perkins, Yingjian You, Audrey Lee-Gosselin, Ruben Vidal, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Background

Tau aggregation and propagation are hallmark features of Alzheimer's disease and related tauopathies. The molecular identity and post-translational modifications that contribute to tau seeding activity remain incompletely understood.

Objective

To characterize the temporal dynamics of tau seeding activity and identify specific phosphorylated tau species associated with tau propagation in vivo.

Methods

We profiled tau seeding activity using a FRET-based biosensor cell line and correlated it with the abundance of phospho- and conformational tau species in two transgenic mouse models of tauopathy (P301S-1N4R and P301S-0N4R). Immunohistochemistry and subcellular fractionation were used to examine the spatial distribution of tau species. Functional …