Digital Commons Network^™

Representation Is Power: Traditional, Hybrid, And Digital Recruitment Results From A Non-Randomized Clinical Trial Engaging Adolescents, Taylor B Harrison, Jessica A Sinclair, Lisa J Martin, Kristin Childers-Buschle, Holly Elder, Sunyang Fu, Hongfang Liu, William B Brinkman, Melanie F Myers, Michelle L Mcgowan

Faculty, Staff and Student Publications

Clinical trials support the iterative advancement of modern medicine. However, challenges in achieving population-representativeness or participant sampling commensurate with the burden of disease can limit the generalizability and reproducibility of trial results. Here, we present the recruitment strategies and cohort profile of the Engaging Adolescents in Decisions about Return of Genomic Research Results non-randomized clinical trial (NCT0448106), where traditional, targeted hybrid, and digital recruitment methods were implemented with quota sampling to enroll diverse adolescents (ages 13-17) and young adults (ages 18-21). The largest proportion of participants enrolled through digital strategies (39.1%), followed by traditional (34.2%), and targeted hybrid strategies (23.2%). …

Multicenter Stroke Preclinical Assessment Network Analysis Of Cardiovascular Risk Factor Subgroups Treated With The Poly(Adp-Ribose) Polymerase Inhibitor Veliparib, Raymond C Koehler, Karni Bedirian, Mu-Hsun Chen, Yanrong Shi, Suyi Cao, Brooklyn D Avery, Senthilkumar S Karuppagounder, Kazi Akhter, Adnan Bibic, Valina L Dawson, Ted M Dawson, Márcio A Diniz, Jessica Lamb, Karisma A Nagarkatti, Anjali Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Andreia Lopes De Morais, Xuyan Jin, Cenk Ayata, Mariia Kumskova, Rakesh B Patel, Anil K Chauhan, Enrique C Leira, Pradip K Kamat, Mohammad B Khan, Krishnan M Dhandapani, David C Hess, Ligia S B Boisserand, Basavaraju G Sanganahalli, Lauren H Sansing, Patrick D Lyden

Faculty, Staff and Student Publications

Background: The Stroke Preclinical Assessment Network tested 6 therapeutic interventions initiated at the time of reperfusion after focal ischemic stroke in young mice, aging mice, obese mice, and spontaneously hypertensive rats. This randomized, controlled trial was conducted across 6 sites with concealed treatment and blinded neurobehavior assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages. The primary outcome was turning preference on the corner test at 1 month. The PARP (poly(ADP-ribose) polymerase) inhibitor, veliparib, was considered futile after the second stage when pooling all animal models (n=231 …

Phosphorylation Of Ryr1 At Ser2902 Decreases Ca2+ Leak In Skeletal Muscle And Susceptibility To Malignant Hyperthermia And Heat Stroke, Rachel Sue Zhen Yee, Chang Seok Lee, Ting Chang, Sung Yun Jung, Omar Yousif, Courtney Cavazos, John Colyer, Filip Van Petegem, George G Rodney, Susan L Hamilton

Faculty, Staff and Students Publications

The ryanodine receptor 1 (RYR1) is the sarcoplasmic reticulum (SR) Ca2+ release channel required for both skeletal muscle contraction and Ca2+ leak. Mutations in RYR1 cause malignant hyperthermia susceptibility (MHS) and enhanced sensitivity to heat stroke (ESHS), which can result in death due to excessive skeletal muscle thermogenesis upon exposure to volatile anesthetics or heat. Here, we investigated the molecular and physiological functions of phosphorylation of RYR1 at Ser2902 by the kinase SPEG (striated muscle preferentially expressed protein). Muscle from SPEG-deficient mice expressing RYR1 with a Ser2902 →Asp2902 (S2902D) point mutation to mimic phosphorylation by SPEG showed decreased SR Ca2+ …

Wearable Single-Channel Electroencephalography, Brain Activity, And Putting Performance In Collegiate Golfers, Pradeep Vanguri, Savannah Calleja, Valerie G. Starratt, Marissa Bonsangue

Journal for Sports Neuroscience

Wearable Electroencephalography (EEG) is a noninvasive method for assessing brain activity. Outside of the context of a traditional medical or laboratory setting, this technology may provide insight into the study of brain activity during activity or sport. In golf, for example, similar research revealed associations in skilled golfers between activity in the alpha brain wave and conscious control of motor activity during putting. The purpose of this research was to further investigate the association between brain-wave activity and athlete performance using a wearable single-channel EEG device during putting in collegiate golfers. Male and Female golfers (n = 11) from …

Bat Observation During A Solar Eclipse In Georgia, Dalton C. Brantley, Graham B. Moore, Catherine H. Borer

Georgia Journal of Science

Eclipses are astronomical phenomena that occur infrequently enough, either spatially or temporally, that for most animals, experiencing an eclipse may only happen once in a lifetime. Thus, an eclipse can provide a unique combination of meteorological and environmental conditions, through which animal behavior can be evaluated. In this study we observed and documented bat behavior (order Chiroptera) in northwest Georgia during a partial solar eclipse in 2024. Using passive acoustic monitors at locations recognized as high quality bat habitat, we detected a single hoary bat (Lasiurus cinereus) 5 minutes before the solar eclipse peak. The bat was first …

In Vitro Screening Of Antibacterial Efficacy Of Moringa Oleifera And Thymus Vulgaris Methanolic Extracts Against Different Escherichia Coli Strains And Their In Vivo Effects Against E. Coli-Induced Infection In Broiler Chickens, Majid Ali, Naila Chand, Sarzamin Khan, Rifat Ullah Khan, Babar Maqbool, Shabana Naz, Ala Abudabos, Abdul Hafeez, Ibrahim A. Alhidary

Food and Animal Sciences Faculty Research

This study evaluated the antibacterial efficacy and growth-promoting potential of Moringa oleifera and Thymus vulgaris methanolic extracts in broiler chickens challenged with Escherichia coli O78. In vitro antibacterial screening using agar well diffusion and disc diffusion assays revealed that ciprofloxacin exhibited the strongest inhibitory effect, followed by tetracycline and enrofloxacin, whereas among plant extracts, T. vulgaris was more effective than M. oleifera. The optimal combination (M100T150; 100 mg M. oleifera + 150 mg T. vulgaris) produced the largest inhibition zones against E. coli strains. For the in vivo trial, 540 Ross-308 broiler chicks were distributed into six treatment groups in …

10.06.2025 Ored Connect, Liz Williamson

ORED Newsletter

• Field Fest
• AAAS Membership
• MIG Application Opportunity
• Contest to Promote Safe Lab Practices

Consciousness Below Scuba Depths, Michael Vecchione

Animal Sentience

Abstract: Jennifer Mather has nicely summarized what is known about consciousness in shallow water octopods as well as what is known about shallow water squids and cuttlefish. However, once she gets below SCUBA depths, she misses out on most of cephalopod diversity. I have attempted to add this aspect and perhaps some evolutionary biology to this target article.

Atg16l1 Controls Mammalian Vacuolar Proton Atpase, Thabata L A Duque, Masroor Paddar, Einar Trosdal, Ruheena Javed, Lee Allers, Michal H Mudd, Prithvi Akepati, Soumya R Mishra, Michelle Salemi, Brett Phinney, Shawn B Bratton, Thomas Wileman, Vojo Deretic

Faculty, Staff and Student Publications

The mechanisms governing mammalian proton pump V-ATPase function are of fundamental and medical interest. The assembly and disassembly of cytoplasmic V1 domain with the membrane-embedded V0 domain of V-ATPase is a key aspect of V-ATPase localization and function. Here, we show that the mammalian protein ATG16L1, primarily appreciated for its role in canonical autophagy and in noncanonical membrane atg8ylation processes, controls V-ATPase. ATG16L1 knockout elevated V-ATPase activity, increased V1 presence on endomembranes, and increased the number of acidified intracellular compartments. ATG16L1's ability to efficiently bind V-ATPase was required for its inhibitory role in endolysosomal acidification and for control of Mycobacterium …

Squamous Non-Small Cell Lung Cancer: Current And Emerging Treatment Options, Paul K Paik, Jianjun Zhang, Howard Jack West, Jonathan W Riess

Faculty, Staff and Student Publications

Although the pharmacologic management of non-small cell lung cancer (NSCLC) has advanced substantially in the past 2 decades, disparities in the applicability to different histologic subtypes remain. Several treatment options are not suitable for squamous NSCLC, with use restricted to nonsquamous NSCLC (eg, bevacizumab and pemetrexed) because of safety concerns or comparative activity. Differences in mutational landscapes and a lack of matched targeted therapies specific to squamous NSCLC oncogenic aberrations present additional limitations. In the absence of suitable targeted therapies, immunotherapy with or without chemotherapy is the mainstay of squamous NSCLC treatment; however, survival-related outcomes remain poorer for patients with …

Inflammation And Mutational Burden Differentially Associated With Nivolumab Or Ipilimumab Combination Efficacy In Colorectal Cancer, Ming Lei, Michael J Overman, Jin Yao, Thierry André, Sara Lonardi, Heinz-Josef Lenz, Massimo Aglietta, Fabio Gelsomino, Ray Mcdermott, Ka Yeung Mark Wong, Michael A Morse, Eric Van Cutsem, Alain Hendlisz, Dana B Cardin, Bart Neyns, Andrew Hill, Anuradha Krishnamurthy, Franklin Chen, Samith Kochuparambil, Robert R Jenq, Sandzhar Abdullaev, Beilei He, Ruslan Novosiadly, Scott Kopetz

Faculty, Staff and Student Publications

Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Here, we report exploratory biomarker analyses from CheckMate 142 evaluating associations between various tissue biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures is associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability are associated with improved response per investigator …

Assessing A Community Health Worker-Facilitated, Digitally Delivered, Family-Centered Diabetes Management Program: Single-Arm Quasi-Experimental Study, Zenong Yin, Vanessa L Errisuriz, Heather Cuevas, Bertha E Flores, Laura Delfausse, Christina Galvan, Jing Wang, Chengdong Li, Renata Morfin, Shiyu Li, Maysa Sapargeldiyeva, Giliane Yza Muyna, Minyu Zhang, Vanessa Sweet, Deborah Parra-Medina

Faculty, Staff and Student Publications

Background: The high prevalence of type 2 diabetes (T2D) and associated complications disproportionately affect low-income Latino populations, who also experience disparities in diabetes self-management (DSM), including poor medication adherence, physical activity, diet, and glycemic control.

Objective: This study examined, through an academic-community partnership, the effectiveness of ¡Salud, Salud! (an evidence-based, family-centered diabetes self-management education and support [DSMES] program) on primary (glycemic control and quality of life) and secondary (social, psychological, and behavioral factors related to T2D management) outcomes among low-income Latino adults with T2D or prediabetes.

Methods: In total, 81 adults (mean age 48.90 years, SD 12.57; n=57, 70.4%, female; …

Quantitative Proteomics Identifies Conserved Proteins And Altered Regulation Of Mucin-16 In Low Grade Serous Ovarian Cancers, Christopher M Tarney, Paulette Mhawech-Fauceglia, Jonathan D Ogata, Julie Oliver, Tamara Abulez, Philip A Branton, Saeid Movahedi-Lankarani, Brian L Hood, Kelly A Conrads, Kendal Rosalik, Kwong-Kwok Wong, David M Gershenson, Sanghoon Lee, Anil K Sood, Robert C Bast, Kathleen M Darcy, Neil T Phippen, G Larry Maxwell, Thomas P Conrads, Nicholas W Bateman

Faculty, Staff and Student Publications

BACKGROUND: Low-grade serous ovarian carcinoma (LGSOC) is a rare and largely chemoresistant subtype of epithelial ovarian cancer. Unlike treatment for high-grade serous ovarian cancer (HGSOC), management options for LGSOC patients are limited, in part, due to a lack of deep molecular characterization of this disease. To address this limitation, we aimed to define highly conserved proteome alterations in LGSOC by performing deep quantitative proteomic analysis of tumors collected from LGSOC and HGSOC patients or normal fallopian tube tissues and validating proteins within two independent proteomic datasets of LGSOC and HGSOC tumors.

METHODS: Formalin-fixed, paraffin-embedded LGSOC (n = 12), HGSOC (n …

Strain-Specific Variability In Viral Kinetics, Cytokine Response, And Cellular Damage In Air-Liquid Cultures Of Human Nasal Organoids After Infection With Sars-Cov-2, Gina M Aloisio, Trevor J Mcbride, Letisha Aideyan, Emily M Schultz, Ashley M Murray, Anubama Rajan, Erin G Nicholson, David Henke, Laura Ferlic-Stark, Amal Kambal, Hannah L Johnson, Elina A Mosa, Fabio Stossi, Sarah E Blutt, Pedro A Piedra, Vasanthi Avadhanula

Faculty, Staff and Students Publications

SARS-CoV-2 variants have demonstrated distinct epidemiological patterns and clinical presentations throughout the COVID-19 pandemic. Understanding variant-specific differences at the respiratory epithelium is crucial for understanding their pathogenesis. Here, we utilized human nasal organoid air-liquid interface (HNO-ALI) cell cultures to compare the viral replication kinetics, innate immune response, and epithelial damage of six different strains of SARS-CoV-2 (B.1.2, WA, Alpha, Beta, Delta, and Omicron). All variants replicated efficiently in HNO-ALIs, but with distinct replication kinetic patterns. The Delta variant exhibited delayed replication kinetics, achieving a steady state at 6 days post-infection compared to 3 days for other variants. Cytokine analysis revealed …

Causal Ai-Based Clinical And Radiomic Analysis For Optimizing Patient Selection In Combined Immunotherapy And Sabr In Early-Stage Nsclc: A Secondary Analysis Of The Phase Ii I-Sabr Trial, Maliazurina B Saad, Eman Showkatian, Vivek Verma, Qasem Al-Tashi, Muhammad Aminu, Xinyan Xu, Muhamed Qayati Mohamed, Morteza Salehjahromi, Sheeba J Sujit, Yuliya Kitsel, Steven H Lin, Zhongxing Liao, Saumil Gandhi, David Qian, David Jaffray, Caroline Chung, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, Jia Wu, Joe Y Chang

Faculty, Staff and Student Publications

Background: The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named "I-SABR-SELECT") based on clinical and radiomic factors to address which patients should receive additional immunotherapy.

Methods: The discovery/validation cohorts were from the I-SABR trial, with external validation from the single-arm …

Advancing Modified Barium Swallow Pre-Sorting With Deep Learning: A New Paradigm For The First Step Analysis In X-Ray Swallowing Study, Shitong Mao, Mohamed A Naser, Sheila Buoy, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Purpose: Modified barium swallow (MBS) exams are pivotal for assessing swallowing function and include diagnostic video segments imaged in various planes, such as anteroposterior (AP or coronal plane) and lateral (or mid-sagittal plane), alongside non-diagnostic 'scout' image segments used for anatomic reference and image set-up that do not include bolus swallows. These variations in imaging files necessitate manual sorting and labeling, complicating the pre-analysis workflow.

Methods: Our study introduces a deep learning approach to automate the categorization of swallow videos in MBS exams, distinguishing between the different types of diagnostic videos and identifying non-diagnostic scout videos to streamline the MBS …

The Effects Of Plastic Mulch And Irrigation On Hemp Chemistry And Leaf Endophytes, Allison Rietman, Connor Morozumi, Robert C. Pearce, Natalie Christian

Journal of Agricultural Hemp Research

As an emerging crop, cultivation techniques for industrial hemp (Cannabis sativa L.) are still being developed and optimized. For example, irrigation and plastic mulching are some management practices that have been touted for their benefits in improving crop quality. Both techniques ensure ample water availability, which has often been attributed to improving hemp cannabinoid and terpene composition. In this study, we examined how supplemental irrigation implemented in a plastic mulch system influenced the cannabinoid and terpene profiles of one cultivar of CBD hemp, Lifter. We grew industrial hemp in field with plastic mulch and applied regular irrigation to one group …

Pathlength, Altitude And Angle Of Incidence Dependence Of Remote Water Raman Scattering, Whitney E. Schuler, Paige K. Williams, Zechariah B. Kitzhaber, Caitlyn M. English, Tammi L. Richardson, Nikos Vitzilaios, Michael L. Myrick

Faculty Publications

A small remote Raman sensor was used to measure the Raman scattering signal from clear, still water as a function of water depth (12 cm and 396 cm depth), sensor distance above the water surface (20–300 cm), and angle of incidence (0–80°) to the normal of the water surface. Under thick- and thin-sample conditions, the signal depends on either the inverse, or the inverse square, of sensor distance from the water surface, respectively. A model is derived that fits data for different sensor distances, water depths, and angles of incidence. Fits to the measured data are consistent with the known …

Notes On Reproduction, Seasonality, And Roost Sites For Silver-Haired Bats (Lasionycteris Noctivagans) In Western Nebraska, Joseph W. Paysen, Dawson V. Kosmicki, Keith Geluso

Transactions of the Nebraska Academy of Sciences and Affiliated Societies

Silver-haired Bats (Lasionycteris noctivagans) are a migratory species found throughout the United States, southern Canada, and northern Mexico. Throughout their range, Silver-haired Bats roost in various tree species, generally within decaying features like cavities and exfoliated bark. Herein we report on additional reproductive and seasonal data as well as the first data on trees used as roost sites by Silver-haired Bats in Nebraska. We captured individuals along a small tributary of the North Platte River at Ash Hollow State Historical Park, Garden County, Nebraska, and tracked bats to their roosts. At this location, we documented lactation on 17 …

Impact Of Irrigation And Micronutrient Treatments On Insect Herbivore Population Dynamics In Soybean, Rahul Debnath, Justin George, Ammar B. Bhandari, Rupesh Kariyat, Gadi V.P. Reddy, James P. Glover, Tulsi P. Kharel, Krishna N. Reddy

Entomology and Plant Pathology Faculty Publications and Presentations

Soybean production is substantially affected by insect pests, necessitating the implementation of appropriate management strategies. Effective irrigation and fertilizer regimes have been found to affect pest populations in agroecosystems. However, their interactive effects on herbivore incidence are less understood. This study reports the abundance and diversity of insect pests, especially hemipteran, lepidopteran, and stink bug species complexes, encountered on soybeans throughout their vegetative and reproductive growth stages under varying irrigation and micronutrient treatments. First, we compared total and major insect pest population densities in irrigated and rainfed conditions. Afterwards, we evaluated how the frequency of insect pests on soybean was …

Post-Rt Head And Neck Dce-Mri: Association Between Mandibular Dose And Ve, Brandon Reber, Renjie He, Moamen R Abdelaal, Abdallah S R Mohamed, Samuel L Mulder, Laia Humbert Vidan, Clifton D Fuller, Stephen Y Lai, Kristy K Brock

Faculty, Staff and Student Publications

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging modality that can quantify tissue permeability and blood flow. Due to vasculature changes resulting from radiation therapy (RT), DCE-MRI quantitative parameters should be significantly different in regions receiving a high radiation dose compared to regions receiving a low radiation dose. This study sought to determine whether a significant difference exists in post-head-and-neck-cancer (HNC)-RT DCE-MRI quantitative parameters (Ktrans and ve) between regions of the mandible receiving a high radiation dose and regions of the mandible receiving a low radiation dose.

Methods: DCE-MRI was acquired from HNC subjects post-RT. The DCE-MRI …

Assessing Spatial Variability In Observed Infectious Disease Spread In A Prospective Time-Space Series, Chih-Chieh Wu, Chien-Hsiun Chen, Shann-Rong Wang, Sanjay Shete

Faculty, Staff and Student Publications

Most of the growing prospective analytic methods in space-time disease surveillance and intended functions of disease surveillance systems focus on earlier detection of disease outbreaks, disease clusters, or increased incidence. The spread of the virus such as SARS-CoV-2 has not been spatially and temporally uniform in an outbreak. With the identification of an infectious disease outbreak, recognizing and evaluating anomalies (excess and decline) of disease incidence spread at the time of occurrence during the course of an outbreak is a logical next step. We propose and formulate a hypergeometric probability model that investigates anomalies of infectious disease incidence spread at …

The Impact Of Off-Site Manufacturing Technology On The Project Management Triangle In The Saudi Housing Sector, Saad S. Almady, Ahmed M. Alhazmi, Essam S. Almahmoud

Mansoura Engineering Journal

This study examines the impact of Off-Site Manufacturing (OSM) and construction sites on housing projects in the Kingdom of Saudi Arabia. The study aims to strike a balance between achieving the highest quality, lowest cost, and expedited construction of housing units. OSM technology involves the production of construction components outside the site, followed by their transportation and installation on the final site. The study seeks to assess the contribution of OSM’s utilization in enhancing project performance, measured against the project management triangle (quality, cost, and time), and compare it with the traditional construction method. To achieve this objective, a residential …

Advancing Peptide-Based Vaccines Against Candida: A Comparative Perspective On Liposomal And Synthetic Formulations, Hong Xin

School of Graduate Studies Faculty Publications

The growing threat of multidrug-resistant fungal pathogens, especially Candida auris, has underscored the need for effective antifungal vaccines. This commentary highlights recent advances in peptide-based vaccination using the SNAP (Spontaneous Nanoliposome Antigen Presentation) platform, focusing on the FM-SNAP vaccine, a bivalent liposomal formulation targeting the surface-expressed peptides fructose bisphosphate aldolase (Fba) and methionine synthase (Met6). Compared to earlier constructs such as MP12, FM-SNAP achieves superior immunogenicity and long-lasting protection at lower antigen doses. It elicits balanced Th1/Th2 cytokine responses and demonstrates durable efficacy in both immunocompetent and complement-deficient mouse models. The platform's compatibility with clinically approved adjuvants (MPLA and QS-21), …

A Multidecadal Analysis Of Groundwater Level And Streamflow Decline In Southern Forest Catchments, Western Australia, Richard J. George, Rose-Anne Bell, W. Lachlan Mccaw, Gregory Paul Raper

Natural Resources Research Articles

Previous analysis of hydrological data in the eucalypt dominated forests of Western Australia’s Darling Ranges show that reduced winter rainfall over the last 50 years has lowered groundwater levels and diminished streamflow by up to 70%. Consequently, climate-independent reverse osmosis seawater desalination and groundwater resources now supply Perth and nearby regional areas, as runoff from forested catchments is no longer sufficient or reliable. In the high rainfall (~1200 mm/yr) mixed forest areas dominated by Eucalyptus diversicolor (karri) and Eucalyptus marginata (jarrah) 200 km to the south of Perth (the ‘Southern Forest’), similar analysis of climate impacts on watertables has not …

A Mast Cell Receptor Mediates Post-Stroke Brain Inflammation Via A Dural-Brain Axis, Ruchita Kothari, Mostafa W Abdulrahim, Hyun Jong Oh, Daniel H Capuzzi, Collin B Kilgore, Sumil K Nair, Yaowu Zhang, Nathachit Limjunyawong, Sarbjit S Saini, Jennifer E Kim, Justin M Caplan, Fernanado L Gonzalez, Christopher M Jackson, Chetan Bettegowda, Judy Huang, Bhanu P Ganesh, Chunfeng Tan, Raymond C Koehler, Rafael J Tamargo, Louise D Mccullough, Risheng Xu, Xinzhong Dong

Faculty, Staff and Student Publications

The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal …

Rare Variants In Prkci Cause Van Der Woude Syndrome And Other Features Of Peridermopathy, Kelsey Robinson, Sunil K Singh, Rachel B Walkup, Dorelle V Fawwal, Kendra M Vilfort, Amanda Koloskee, Azeez Fashina, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, Wendy K Chung, David J Cutler, Michael P Epstein, Brooklynn Gasser, Lord J J Gowans, Jacqueline T Hecht, Anuj Mankad, Lina Moreno Uribe, Daryl A Scott, Gary M Shaw, Mary Ann Thomas, Seth M Weinberg, Eric C Liao, Harrison Brand, Mary L Marazita, Robert J Lipinski, Jeffrey C Murray, Robert A Cornell, Elizabeth J Leslie-Clarkson

Faculty, Staff and Student Publications

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of ∼1 in 35,000 live births, it is the most common form of syndromic clefting. Most VWS is attributed to variants in IRF6 (∼70%) or GRHL3 (∼5%), leaving up to 25% of individuals without a molecular diagnosis. Both IRF6 and GRHL3 function in a transcriptional regulatory network (TRN) governing differentiation of periderm, a single epithelial cell layer preventing pathological adhesions during palatogenesis. Periderm disruption can elicit a spectrum of phenotypes, including lip pits and OFCs, pterygia, and severe …

Preclinical Models Of Melanoma Leptomeningeal Disease To Assess Intrathecal Checkpoint Blockade, Renato A Guerrieri, Grant M Fischer, Jacob R Cortez, Barbara G Knighton, Debora A Ledesma, Courtney W Hudgens, Yimmy F Delcid, Qianghua Hu, Christian Y B Onana, Fernando C L Carapeto, Michael T Tezlaff, Jason T Huse, Patrick Hwu, Elizabeth M Burton, Isabella C Glitza Oliva, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

Leptomeningeal disease (LMD) is a subtype of central nervous system metastatic disease that is associated with poor patient outcomes and limited treatment options. There is an unmet need to develop preclinical models of LMD to expedite and improve the development of new therapeutics. Here, we describe the development of multiple orthotopic immunocompetent murine models of melanoma LMD, including their use to assess the efficacy of systemic and/or intrathecal immunotherapy. LMD was established by direct intrathecal injection of murine cell lines (B16-F10, BP, D4M, D4M-UV2, MC38-gp100, RMS, YUMM3.1, and YUMMER1.7) into the cisterna magna of C57BL/6 mice. Tumor take rate, distribution, …

Long-Term Outcomes In Flt3-Mutated Acute Myeloid Leukemia After Frontline Hypomethylating Agent, Venetoclax And A Flt3 Inhibitor, Nicholas J Short, Sanam Loghavi, Musa Yilmaz, Omer Karrar, Kunhwa Kim, Courtney D Dinardo, Tapan M Kadia, Manuel Maroun, Gautam Borthakur, Ghayas C Issa, Joseph Jabbour, Betul Oran, Elizabeth J Shpall, Uday Popat, Keyur P Patel, Mark Routbort, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Triplet regimens with a hypomethylating agent, venetoclax and a FLT3 inhibitor yield high rates of response in newly diagnosed FLT3-mutated AML. However, the long-term outcomes and patterns of relapse with these triplet regimens are not well-established. In this retrospective analysis, 73 patients with newly diagnosed FLT3-mutated AML received a frontline FLT3 inhibitor-containing triplet regimen. The composite complete remission (CR) and CR with incomplete hematologic recovery (CRi) rate was 93%. Next-generation sequencing FLT3-ITD MRD negativity (sensitivity: 0.005%) was achieved in 60% of patients after cycle 2 and 90% after cycle 4. The estimated 3-year relapse-free survival (RFS) for FLT3-ITD-mutated and FLT3 …

Reversible Arginine Methylation Of Pi3kc2Α Controls Mitotic Spindle Dynamics, Yena Cho, Jee Won Hwang, Mark T Bedford, Dong Hee Na, Dae-Geun Song, Su-Nam Kim, Yong Kee Kim

Faculty, Staff and Student Publications

Microtubules, composed of αβ-tubulin dimers, undergo dynamic polymerization and are fundamental to cell structure and function. In the current study, we discovered that phosphatidylinositol 3-kinase class 2α (PI3KC2α) acts as a novel regulatory factor in microtubule dynamics. Specifically, asymmetric dimethylation of PI3KC2α at the R175 residue (R175me2a) by coactivator-associated arginine methyltransferase 1 (CARM1) enhances its interaction with α-tubulin, stabilizing microtubule assembly. Furthermore, lysine Demethylase 4 A (KDM4A) serves as an arginine demethylase for PI3KC2α R175me2a. During mitosis, protein kinase C (PKC)-mediated phosphorylation of KDM4A results in its dissociation from PI3KC2α, preventing demethylation and increasing R175me2a levels. This facilitates spindle formation …