Digital Commons Network^™

Enhancing Target Dose Conformity While Effectively Sparing The Spinal Cord In Proton Arc Treatment Plans For Cervical Chordomas And Chondrosarcomas, Jon Blalock

Masters Projects

Cervical spinal chordomas and chondrosarcomas present significant therapeutic challenges due to their proximity to the spinal cord and resistance to conventional radiotherapy. This retrospective study investigated the capability of proton arc therapy (PAT) to maintain or improve adequate target coverage while reducing dose to the spinal cord for cervical spinal chordomas and chondrosarcomas over standard fixed beam intensity modulated proton therapy (IMPT). While both IMPT and PAT use pencil beam scanning (PBS) to with energy modulation to deliver dose in discrete layers, IMPT relies on a limited number of fixed beam angles, whereas PAT delivers dose over an arc trajectory. …

Comparison Of Left Breast Accelerated Partial Breast Irradiation Plans: Flattening Filter Free Vmat Vs. Standard Vmat In Deep Inspiration Breath Hold And Free Breathing Techniques, Monica Albeck

Masters Projects

This retrospective planning study compared dosimetric outcomes and treatment efficiency between flattening filter free (FFF) and standard volumetric modulated arc therapy (VMAT) plans for left breast accelerated partial breast irradiation (APBI) under deep inspiration breath hold (DIBH) and free-breathing (FB) conditions. Ten patients with early stage left breast cancer were replanned to create four plans each: FFF VMAT and standard VMAT in DIBH and FB. All plans prescribed 30 Gy in 5 fractions. Measures included planning target volume (PTV) coverage, mean heart dose, ipsilateral lung V30%, contralateral breast maximum dose, and monitor units (MUs). Statistical analysis used repeated-measures ANOVA with …

The Implementation Of A Pilot Program On Puberty And Menstruation Education For Adolescent Females And Youth Development Specialists For A Gender-Specific Community Organization: A Quality Improvement Project, Cassandra Tavares

Doctor of Nursing Practice (DNP) Manuscripts

Background & Significance: Adolescent girls in the United States (U.S.) often lack adequate education and support regarding puberty and menstruation, despite the importance of this knowledge for healthy development (Schmitt et al., 2022). Only 21% of school systems serving ages 8–12 provide puberty education, and many educators feel unprepared to teach it (Schmitt et al., 2022). Purpose: This quality improvement project aimed to equip youth development specialists (YDS) at a community organization with a structured curriculum and educational tools to confidently educate adolescent females (ages 8–13) on the physical, emotional, and social aspects of puberty and menstruation. Intervention: A four-day …

Evaluating Dosimetric Outcomes In A Prostate Rapid Plan Model: A Comparison Of Prostate Treatment Plans With And Without Standardized Planning Structures, Erica Wartman

Masters Projects

Abstract

Knowledge-based planning (KBP) using RapidPlan (RP) has demonstrated the ability to produce high quality radiation therapy treatment plans while reducing time. This study evaluated whether the inclusion of department specific standardized planning structures, including rings and other optimization tools, improves plan quality when using a prostate and lymph node RP model, or if the model alone is sufficient to provide a quality plan without the use of these additional planning structures.

Ten previously treated Prostate+LN patients were replanned using the departmental RP model in Varian Eclipse treatment planning system.1 For each patient, two plans were created, one with standardized …

Mirna-Mediated Regulation Of S100b: A Review, Animesh Dali, Suhana Basnyat, Rachel Delancey, Nipun Chopra

Psychology and Neuroscience Faculty Publications

S100β is a significant signaling molecule and biomarker that is primarily expressed in the brain. At low physiological concentrations, S100β induces astrocyte maturation, microglial migration, and neural proliferation. However, high concentrations activate inflammatory and pro-apoptotic pathways. Due to this dual role, increased research is being invested into the role of S100β in neuronal homeostasis and inflammation. In fact, increased S100β expression is seen in many neuropathologies including Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, and traumatic brain injury. High S100β is generally associated with worsened disease outcome. Here, we provide an overview of the structure and role of S100β in various …

Dual-Function Polyester Nanoparticles For Amplified Anti-Inflammatory Effects, Ingrid M Heyns, Abiodun T Wahab, Raghu Ganugula, David Sheikh-Hamad, M N V Ravi Kumar, Meenakshi Arora

Faculty, Staff and Students Publications

This study investigates a dual-acting drug delivery system using naringenin (NAR) as a folate receptor ligand to enhance intestinal uptake and encapsulated NAR for combating inflammation. The dual-acting systems were tested in vitro on cisplatin-induced human kidney-2 cells and in vivo in a mouse model of cisplatin-induced acute kidney injury (AKI). NAR-loaded passive nanoparticles [P2Ns(NAR)] and dual-acting systems [P2Ns-NAR(NAR)] showed notable advantages over unformulated NAR, reducing the required dose by up to 57 and 79%, respectively. These nanoparticles modulated immune responses, restored T cell function, and shifted macrophage polarization from proinflammatory M1 to tissue-repairing M2. In addition, P2Ns-NAR(NAR) alleviated AKI …

Correction: Development And Extensive Sequencing Of A Broadly-Consented Genome In A Bottle Matched Tumor-Normal Pair, Jennifer H Mcdaniel, Vaidehi Patel, Nathan D Olson, Hua-Jun He, Zhiyong He, Kenneth D Cole, Alexander A Gooden, Anthony Schmitt, Kristin Sikkink, Fritz J Sedlazeck, Harsha Doddapaneni, Shalini N Jhangiani, Donna M Muzny, Marie-Claude Gingras, Heer Mehta, Sairam Behera, Luis F Paulin, Alex R Hastie, Hung-Chun Yu, Victor Weigman, Alison Rojas, Katie Kennedy, Jamie Remington, Isai Salas-González, Mitch Sudkamp, Kelly Wiseman, Bryan R Lajoie, Shawn Levy, Miten Jain, Stuart Akeson, Giuseppe Narzisi, Zoe Steinsnyder, Catherine Reeves, Jennifer Shelton, Sarah B Kingan, Christine Lambert, Primo Baybayan, Aaron M Wenger, Ian J Mclaughlin, Aaron Adamson, Christopher Kingsley, Melanie Wescott, Young Kim, Benedict Paten, Jimin Park, Ivo Violich, Karen H Miga, Joshua Gardner, Brandy Mcnulty, Gail L Rosen, Rajiv Mccoy, Francesco Brundu, Erfan Sayyari, Konrad Scheffler, Sean Truong, Severine Catreux, Lesley Chapman Hannah, Doron Lipson, Hila Benjamin, Nika Iremadze, Ilya Soifer, Gat Krieger, Stephen Eacker, Mary Wood, Erin Cross, Greg Husar, Stephen Gross, Michael Vernich, Mikhail Kolmogorov, Tanveer Ahmad, Ayse G Keskus, Asher Bryant, Francoise Thibaud-Nissen, Jonathan Trow, Jacqueline Proszynski, Jeremy Wain Hirschberg, Krista Ryon, Christopher E Mason, Mital S Bhakta, J Zachary Sanborn, Elizabeth M Munding, Justin Wagner, Chunlin Xiao, Andrew S Liss, Justin M Zook

Faculty, Staff and Students Publications

No abstract provided.

Micbg406a Polymorphism Reduces Risk Of Mechanical Ventilation And Death During Viral Acute Lung Injury, Harry Pickering, Narges Alipanah-Lechner, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Chris Cotsapas, Hanno Steen, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Monica Kraft, Chris Bime, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman, Steve Bosinger, Walter Eckalbar, Carolyn S Calfee, Oscar A Aguilar, Elaine F Reed, John R Greenland, Daniel R Calabrese

Faculty, Staff and Students Publications

MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between MICBG406A and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower …

Examining Associations Between Street Vegetation And Child Firearm Violence At Microgeographic Locations In 3 Us Cities: A Case-Control Study, Zihan Lin, Gregory A. Wellenius, Jonathan Jay

Biological, Geological, and Environmental Faculty Publications

Background: Firearm violence is a leading cause of death among U.S. children under age 18. Urban vegetation, a vital component of the living environment, has been found to influence firearm violence, yet the relationship between different types of street vegetation and firearm violence with children as the victim at the microgeographic scale remains unclear.

Methods: We analyzed 2316 child firearm assault incidents from Los Angeles, New York City, and Philadelphia from 2015 to 2021. Using a spatial case-control approach, we matched assault locations with control locations within 1-km. For each location, we applied deep learning algorithms to Google Street View …

Histologic And Immune Characterization Of Cutaneous Immune-Related Adverse Events Induced By Immune Checkpoint Inhibitors, Omar Pacha, Anisha B Patel, Jonathan L Curry, Cara L Haymaker, Nejla Ozirmak Lermi, Dzifa Yawa Duose, Ken Chen, Joud Hajjar, Aung Naing

Faculty, Staff and Student Publications

Background: Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.

Methods: Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE …

Immediate-Use Rescue Medication And The Epilepsy Monitoring Unit: Experiences From An Expert Panel, Evelyn K. Shih, Brin E. Freund, Michael R. Sperling, Danielle A. Becker, Proleta Datta, Sandra Dewar, Edward Faught, Tracy Glauser, R. Edward Hogan, Randa Jarrar, Andres M. Kanner, David King-Stephens, Rebecca E. Matthews, Patricia Penovich, M. Scott Perry, Eric B. Segal, Joseph Sirven, John M. Stern, James W. Wheless, Enrique Carrazana, Adrian L. Rabinowicz, William O. Tatum

Department of Neurology Faculty Papers

BACKGROUND: People with epilepsy (PWE) may experience seizure clusters, broadly defined as ≥2 seizures that occur in close proximity. In epilepsy monitoring units (EMUs), seizure clusters can spontaneously occur during long-term videoelectroencephalogram monitoring (LTVEM) or as a result of antiseizure medication dose adjustments. In this survey, we examined the experiences and practices of expert clinicians with seizure clusters in EMUs.

METHODS: A 55-item survey was sent to members of an Epilepsy Education Council who are epilepsy experts. Items described experiences, treatment practices, and negative outcomes with seizure clusters in EMUs.

RESULTS: Of the 15 experts (aged 43-77 y), 14 are …

The Effect Of Coadministration Of D156844 And Ar42 (Rec-2282) On The Survival And Motor Phenotype Of Mice With Spinal Muscular Atrophy, Ashlee W. Harris, Rod C. Scott, Matthew E. R. Butchbach

Department of Pediatrics Faculty Papers

Spinal muscular atrophy (SMA) is characterized by degeneration of spinal motor neurons and is a leading genetic cause of pediatric death worldwide. SMA results from the loss of or pathological variant in the survival motor neuron 1 (SMN1) gene. Disease severity is dependent on the number of copies of the orthologous SMN2 gene, which is nearly identical to SMN1 except for some key nucleotide differences. As disease severity is inversely related to SMN2 copy number, most SMA therapeutics trials have focused on identifying ways to increase SMN2 expression at different levels of gene regulation. Other studies have investigated compounds which …

Incidence Of Cytogenetic Abnormalities Detected By Fish Analysis In Multiple Myeloma Cases: A Seven-Year Study From A Cytogenetic Laboratory In King Chulalongkorn Memorial Hospital, Thailand (2018–2024), Montakarn Tansatit, Nutcharee Jongpornchai, Suwannee Songchart, Kittipornpan Krajokpap, Hudadini Da-Oh

Chulalongkorn Medical Journal

Background: Multiple myeloma (MM) is a genetically heterogeneous plasma cell malignancy with cytogenetic abnormalities influencing prognosis and treatment outcomes. Fluorescence in situ hybridization (FISH) is crucial for detecting clinically significant abnormalities, including IGH translocations and deletions (e.g., del(17p)), particularly in non-dividing plasma cells. However, cost and accessibility challenges limit comprehensive testing in resource-constrained settings like Thailand. Objectives: To investigate the incidence of cytogenetic abnormalities detected by FISH in MM cases over seven years in a Thai population, highlighting regional trends and barriers to comprehensive testing. Methods: A retrospective analysis was conducted on 360 bone marrow samples from MM patients between …

Dosimetric Comparison Of Organ-At-Risk Constraints Across Multi-Resolution Levels In Eclipse Planning Optimization, Ji Hyun Jeon

Masters Projects

Background: In inverse treatment planning, the timing of applying organ-at-risk (OAR) constraints during the optimization process can influence dosimetric outcomes. This study investigates the effects of introducing OAR constraints at different stages of the multi-resolution optimization process within the Eclipse Treatment Planning System (TPS).

Purpose: To determine the optimal resolution level for applying OAR constraints that achieves the best dosimetric balance between target coverage and normal tissue sparing.

Methods: Thirteen prostate cancer treatment plans were generated using an anonymized pelvic CT dataset from The Cancer Imaging Archive. All plans were developed in GVSU Virtual Eclipse TPS using the Photon Optimizer …

Immunomodulatory Effects Of Gold Nanoparticles: Impacts On Immune Cells And Mechanisms Of Action, Khadijeh Koushki, Prapannajeet Biswal, Geraldine Vidhya Vijay, Mahvash Sadeghi, Sajad Dehnavi, Ngoc Tuyet Tra, Sai Kumar Samala, Mahdieh Yousefi Taba, Arjun Balaji Vasan, Emily Han, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Traditional anti-inflammatory medications-such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs-are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we …

Updates In Contemporary Management Of Singleton Pregnancies Complicated By A Short Cervix, Moti Gulersen, Vincenzo Berghella, Eran Bornstein

Department of Obstetrics and Gynecology Faculty Papers

Singleton pregnancies complicated by a short cervical length (≤25 mm) are at significantly increased risk for spontaneous preterm birth. Several treatment strategies aimed at reducing this risk and improving perinatal outcomes have been evaluated, including vaginal progesterone, cervical cerclage, and cervical pessary. This review summarizes the latest evidence regarding the efficacy of these interventions. Vaginal progesterone and/or cervical cerclage have been identified as proven evidence-based practices for preterm birth prevention and improve neonatal outcomes. Vaginal progesterone reduces the risk of preterm birth < 35 weeks by 27% (relative risk 0.73, 95% confidence interval 0.58-0.90). Cervical cerclage has been shown to reduce the risk of preterm birth < 35 weeks by 30% (relative risk 0.70, 95% confidence interval 0.55-0.89) in patients with a short cervical length and prior preterm birth. In contrast, recent data suggest that cervical pessary should no longer be considered a management option for these patients. A continued focus on individualized, evidence-based approaches remains essential to optimizing outcomes in this high-risk population.

Hand Hygiene Knowledge, Attitudes, Practices, And Hand Dirtiness Of Primary School Students Before And After A Behavioral Change Intervention During The Covid-19 Pandemic, Belize 2022-2023, Anh N Ly, Christina Craig, Kelsey Mcdavid, Dian Maheia, Yolanda Gongora, Francis Morey, Russell Manzanero, Alexandra Medley, Allison Stewart, Allison Lino, Ramiro Quezada, Rosalva Blanco, Vickie Romero, Gerhaldine Morazan, Ella Hawes, Oluwadara Okeremi, Kanako Ishida, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) can prevent the spread of infectious diseases and school absenteeism. However, limited data exist on HH practices at schools. Our study assesses the impact of a pilot HH intervention in 12 schools in Belize during the coronavirus disease 2019 (COVID-19) pandemic. After a national assessment of existing water, sanitation, and hygiene resources (December 2021-January 2022), 12 pilot schools were selected to evaluate an HH intervention, which included environmental nudges and HH education. Baseline assessments occurred in March 2022, the HH intervention was implemented during October 2022-May 2023, and follow-up assessments were conducted in June 2023. Student knowledge, …

Mri-Based Radiomics For Outcome Stratification In Pediatric Osteosarcoma, Esther Ngan, Dolores Mullikin, Ashok J Theruvath, Ananth V Annapragada, Ketan B Ghaghada, Andras A Heczey, Zbigniew A Starosolski

Faculty, Staff and Students Publications

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. \

Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor …

Saudi Heart Association Position Statement On Troponin Use For Cardiovascular Risk Screening In Asymptomatic Populations, Waleed Alhabeeb, Abdulhalim Jamal Kinsara, Fahad Alnouri, Hussein Alamri, Owayed Alshammeri, Turki Albacker, Khalid Al Faraidy, Wail , Alkashkari, Shukri Alsaif, Mohammed Balghith, Anwar Abdullah Borai

Journal of the Saudi Heart Association

Background: Cardiovascular disease (CVD) remains the leading cause of death and disability globally. In Saudi Arabia, the burden of CVD is exceptionally high, with age-standardized mortality and prevalence rates that far exceed global averages. The current CVD risk prediction tools have several limitations, and those classified as low to intermediate risk still experience cardiovascular events, underscoring the urgent need to address CVD through effective screening and prevention strategies.

Methods: A panel of Saudi experts reviewed evidence on the use of high-sensitivity cardiac troponin (hs-cTn) to enhance cardiovascular risk assessment among seemingly healthy individuals. Consensus recommendations tailored to the Saudi context …

Reframing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Me/Cfs): Biological Basis Of Disease And Recommendations For Supporting Patients., Priya Agarwal, Kenneth J Friedman

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a worldwide challenge. There are an estimated 17-24 million patients worldwide, with an estimated 60 percent or more who have not been diagnosed. Without a known cure, no specific curative medication, disability lasting years to being life-long, and disagreement among healthcare providers as to how to most appropriately treat these patients, ME/CFS patients are in need of assistance. Appropriate healthcare provider education would increase the percentage of patients diagnosed and treated; however, in-school healthcare provider education is limited. To address the latter issue, the New Jersey Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Association (NJME/CFSA) has developed …

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Information Theory Optimization Of Signals From Small-Angle Scattering Measurements, Robert P Rambo, John A Tainer

Faculty, Staff and Student Publications

Small-angle X-ray scattering (SAXS) of particles in solution informs on the conformational states and assemblies of biological macromolecules (bioSAXS) outside of cryo- and solid-state conditions. In bioSAXS, the SAXS measurement under dilute conditions is resolution limited, and through an inverse Fourier transform, the measured SAXS intensities directly relate to the physical space occupied by the particles via the P(r)-distribution. Yet, this inverse transform of SAXS data has been historically cast as an ill-posed, ill-conditioned problem requiring an indirect approach. Here, we show that through the applications of matrix and information theories, the inverse transform of SAXS intensity data is a …

Phase 2 Study Of Zilovertamab Vedotin In Participants With Metastatic Solid Tumors, Funda Meric-Bernstam, Martin Gutierrez, Enrique Sanz-Garcia, Diego Villa, Jun Zhang, Jennifer Friedmann, Fengting Yan, Mark A Socinski, John Sarantopoulos, Luis E Raez, Quincy S Chu, Maxime Chénard-Poirier, Manash Chatterjee, Hong Ren, Qi Liu, Douglas A Levine, Komal L Jhaveri

Faculty, Staff and Student Publications

Purpose: Zilovertamab vedotin, an antibody‒drug conjugate targeting receptor tyrosine kinase‒like orphan receptor 1 (ROR1), had manageable safety and promising antitumor activity in participants with relapsed or refractory non-Hodgkin lymphomas. We evaluated zilovertamab vedotin in participants with previously-treated metastatic solid tumors.

Methods: This phase 2, open-label, nonrandomized study (NCT04504916) enrolled participants with metastatic triple-negative breast cancer, hormone receptor‒positive (HR+) breast cancer, nonsquamous non‒small-cell lung cancer, platinum-resistant ovarian cancer, or pancreatic cancer. Participants received zilovertamab vedotin ≤2.5 mg/kg once every 3 weeks (Q1/3W) or < 1.75 mg/kg twice every 3 weeks (Q2/3W). Primary endpoint was objective response rate (ORR) per RECIST v1.1 by blinded independent central review. ROR1 protein expression was correlated with clinical outcomes.

Results: 102 participants were enrolled (Q1/3W, n=70; Q2/3W, n=32). ORR was 1% (95% CI, 0%‒8%) with …

Rare Variants In Bmal1 Are Associated With A Neurodevelopmental Syndrome, Vishnu Anand Cuddapah, Dechun Chen, Bumsik Cho, Rebecca Moore, Mohnish Suri, Hana Safraou, Frederic Tran-Mau-Them, Ashley Wilson, Jacqueline Odgis, Atteeq U Rehman, Carol Saunders, Shiva Ganesan, Vaidehi Jobanputra, Stephen W Scherer, Ingo Helbig, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Children with neurodevelopmental disorders exhibit highly penetrant sleep and circadian dysfunction, but the underlying mechanisms are unclear. We asked whether a subset of individuals with neurodevelopmental disorders might have genetic variants in genes known to drive circadian rhythms. Through international collaboration, we identified ten individuals with very rare genetic variants in BMAL1, a core component of the molecular clock. These individuals exhibited overlapping signs and symptoms including developmental delay, autism spectrum disorder, and variably penetrant marfanoid features. We functionally tested the identified BMAL1 variants in cell culture and in vivo and found disrupted BMAL1 function. These findings demonstrate that …

Rescue Of Male Infertility By Human Prss55 In Transgenic Mice Establishes A Contraceptive Research Model, Courtney M Sutton, Kohei Umezu, Daisuke Mashiko, Masahito Ikawa, Irina V Larina, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of non-hormonal male contraceptives requires validated preclinical models. This study investigated whether human orthologs of two mouse testis-specific serine proteases, PRSS55 and TMPRSS12, both essential for male fertility in mice, could functionally rescue the infertility phenotypes of their respective knockout mouse lines. We generated transgenic mouse lines expressing human PRSS55 with either an extracellularly or intracellularly positioned C-terminal 3xFLAG tag (RES GPI or RES TM), and a line expressing human TMPRSS12 with a C-terminal 3xFLAG tag (T12 RES), all on their respective mouse null backgrounds. Fertility was assessed through continuous mating trials, and sperm parameters were evaluated. Both …

Survival To Hospital Discharge In The Fetus With Moderate To Severe Mitral Regurgitation Either In Isolation Or In Combination With Aortic Valve Stenosis Or Atresia, A Fetal Heart Society Collaborative Study, Betul Yilmaz Furtun, Kavitha Pundi, Anita Moon-Grady, Nicole Cresalia, Asela Nieuwsma, Sarah K Gelehrter, Bhawna Arya, Mary T Donofrio, Christopher Statile, Ann Kavanaugh-Mchugh, Lindsay Freud, Elijah Bolin, Megan Warner, Sowmya Balasubramanian, James Strainic, Carol Wittlieb-Weber, Nelangi M Pinto, Lisa Hornberger, Shaine A Morris

Faculty, Staff and Students Publications

Background: Case series report high mortality after fetal diagnosis of moderate to severe mitral regurgitation in combination with left atrial dilation, hydrops, or restrictive atrial septum. However, overall outcomes and specific high-risk features remain unclear.

Methods: We performed a multicenter retrospective cohort study of fetuses with ≥moderate mitral regurgitation and normal cardiac connections evaluated January 1, 2005 to January 31, 2016. Fetuses undergoing fetal cardiac intervention (FCI) were described separately. We assessed associations between fetal echocardiographic features and discharge mortality using mixed logistic regression and classification and regression tree modeling, stratified by studies performed < 28 and ≥28 weeks gestational age (GA).

Results: Of 67 fetuses, 96% had …

Leishmania In Texas: A Contemporary One Health Scoping Review Of Vectors, Reservoirs, And Human Health, Morgan H Jibowu, Richard Chung, Nina L Tang, Sarah Guo, Leigh-Anne Lawton, Brendan J Sullivan, Dawn M Wetzel, Sarah M Gunter

Faculty, Staff and Students Publications

Leishmaniasis, a vector-borne neglected tropical disease, affects over 6.2 million people globally. Case acquisition is increasingly recognized in the United States, and in Texas, most reported cases are locally acquired and speciated to Leishmania mexicana. We conducted a scoping literature review to systematically assess contemporary research on Leishmania in humans, animals, reservoir hosts, or vectors in Texas after 2000. Out of 22 eligible studies, the most prevalent themes were case reports, followed by studies on domestic animals, reservoirs, and vectors, with several studies bridging multiple disciplines. Climate change, urbanization, and habitat encroachment appear to be driving the northward expansion …

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Three Things We Can Do Now To Reduce The Risk Of Avian Influenza Spillovers, Kenneth B Yeh, William P Bahnfleth, Elaine Bradford, Carol Cardona, Kristen K Coleman, Peter J Hudson, Bernadeta Dadonaite, Rebecca J Hutchins, Anthony Maresso, C Raina Macintyre, Matthew Scotch

Faculty, Staff and Students Publications

No abstract provided.

Evaluating Parotid Gland Dose Between Electronic Tissue Compensation And Field In Field Treatment Techniques For Parotid Sparing In Whole-Brain Radiotherapy, Joesph E. Bodgonas

Masters Projects

Purpose:

The parotid glands are essential to salivary function and patient quality of life, yet they are not routinely prioritized as organs at risk (OARs) during whole-brain radiotherapy (WBRT). With growing recognition of long-term side effects like xerostomia in patients with prolonged survival after WBRT, parotid-sparing techniques warrant investigation. This study compares radiation dose to the parotid glands using three different 3D conformal WBRT planning approaches: field-in-field (FiF) with blocking, electronic tissue compensation (eCOMP) without blocking, and eCOMP with blocking.

Methods and Materials:

A retrospective study was conducted on 20 patients previously treated with 3D conformal WBRT. Original eCOMP plans …