Medicine and Health Sciences Commons^™

Use Of Naltrexone For Treating Binge Eating And Food Obsession Related To Trauma: A Case Report And Literature Review, Rebecca K. Hicks, Iram Kingson, Jordan Gaal, Suzanne Holroyd

Marshall Journal of Medicine

Impulse-control disorders, including those related to eating behaviors, are complex conditions with limited pharmacologic treatment options. While naltrexone is primarily used for opioid and alcohol dependence, emerging research suggests it may also be effective in managing a variety of impulse-driven conditions. As a pure opioid antagonist, naltrexone’s mechanism of action involves the inhibition of opioid receptors on dopaminergic neurons involved in the reward pathway of the brain, thereby reducing the reinforcing effects of substances such as alcohol and opioids. Research suggests that through this mechanism of action, naltrexone shows promise in treating impulsive behaviors also driven by the reward pathway, …

Sex-Dependent Differences In Cardiac Function And Strain In Doxorubicin-Induced Cardiomyopathy, Anna J. A. Webb, Bea O. Cabot, Aasish Chowdary, Wilhelm S. Smith, Benjamin Zeidler, Cortland H. Johns, Craig J. Goergen

Discovery Undergraduate Interdisciplinary Research Internship

Doxorubicin is a chemotherapeutic agent used to treat many types of cancer. While effective, doxorubicin can cause cardiomyopathy, a disease affecting the heart muscle. Although the effects of doxorubicin on the heart are well studied, the mechanisms leading to cardiomyopathy are not well understood. Previous studies have used murine models to study the cardiotoxicity of doxorubicin. These reports showed that cardiac dysfunction is more pronounced in male compared to female mice. The goal of this study is to further evaluate sex differences in doxorubicin induced cardiomyopathy using 4-dimensional strain mapping techniques. In this study, both female and male C57Bl/6J mice …

Dosimetric Comparisons Of 6mv, 6fff, 10mv, And 10fff On Vmat Planning In Patients With Endometrial Cancer, Madisin M. Depas

Masters Projects

Purpose: This study aimed to evaluate the dosimetric and efficiency impacts of different photon beam energies—6MV, 6 flattening filter free (FFF), 10MV, and 10FFF—on volumetric modulated arc therapy (VMAT) plans for endometrial cancer, with attention to target coverage, organ at risk (OAR) sparing, and treatment efficiency.

Methods: A retrospective analysis was conducted on 25 patients with post-hysterectomy endometrial cancer. Each patient received four VMAT plans with varying energies. Planning metrics assessed included planning target volume (PTV) dose maximum (Dmax), conformity index (CI), heterogeneity index (HI), OAR doses (bladder, bowel, rectum), and total monitor units (MU). Correlations were drawn …

Integrating Circulating Tumor Dna Into Clinical Management Of Colorectal Cancer: Practical Implications And Therapeutic Challenges, Nikhil Vojjala, Viktoriya Gibatova, Raj N Shah, Sakshi Singal, Rishab Prabhu, Geetha Krishnamoorthy, Karen Riggins, Nagaishwarya Moka

Faculty, Staff and Students Publications

The American Cancer Society estimates that over 152,000 new cases of colorectal cancer (CRC) were diagnosed in 2024, with more than 105,000 cases affecting the colon and 46,000 involving the rectum. CRC remains the second leading cause of cancer-related deaths in the United States, with an estimated 53,010 deaths in 2024. In the era of precision medicine, which incorporates molecular and environmental information into clinical decision-making, identifying patients harboring a deficiency in Deoxyribonucleic acid (DNA) repair allowed for targeted immunotherapies and significantly reduced CRC-related mortality. A significant advancement in this domain is the application of liquid biopsy, which has emerged …

Systematic Review Of Parkinsonism In Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some cases, CTX also includes parkinsonism. The goals of this study are to develop a data source that provides improved characterization and awareness of parkinsonism in CTX.

Methods: We conducted a systematic review of the literature according to PRISMA guidelines to identify all published individuals diagnosed with CTX and parkinsonism. Clinical signs, imaging findings and treatment response to …

Unveiling Spatial Heterogeneity In Medulloblastoma: A Multi-Omics Analysis Of Cellular State And Geographical Organization, Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang

Faculty, Staff and Students Publications

Background: Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.

Methods: We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial copy number variations (CNVs) patterns and niches were analyzed to investigate the cellular interactions.

Results: Three main malignant cell populations were identified, including progenitor-like, cycling, and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous …

Precision Medicine And Beyond: Evolving Roles Of Targeted Therapy, Immunotherapy, And Artificial Intelligence In Oncology, Linwei Li, Anika Doppalapudi, Jennifer Escamilla, Annu Karithara, Christine Pham, Angel Phillip, Sriya Gullapalli, Lois Baldado, Arjun Bellamkonda, Daniela Gonzalez, Amin Ibrahim, David Sta. Maria, Kaitlyn Ybanez, Hugo Zamarron, Shizue Mito

School of Medicine Publications

Precision medicine in oncology is an evolving therapeutic approach that leverages genetic, clinical, and biomarker data to tailor treatments to individual patients. This review explores the three core pillars of modern precision oncology: targeted therapy, immunotherapy, and the integration of artificial intelligence (AI) into clinical practice. Targeted therapies, including monoclonal antibodies and antibody-drug conjugates, selectively inhibit molecular pathways involved in tumor growth. While conventional chemotherapy remains the backbone of treatment and has improved remission rates, its cytotoxic nature limits broader applicability and increases the risk of comorbidities. Immunotherapies, particularly immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies, have transformed …

Retrotransposon Methylation Profiles And Survival In Black Women With High-Grade Serous Ovarian Carcinoma, Christelle Colin-Leitzinger, Katherine A Lawson-Michod, Courtney E Johnson, Irma M Vlasac, Sean Yoder, Tania Mesa, Dana Roeber, Chad Huff, Michelle A T Hildebrandt, Kristin Haller, Anthony J Alberg, Elisa V Bandera, Melissa Bondy, Michele L Cote, Theresa Hastert, Edward S Peters, Paul D Terry, Andrew B Lawson, Andrew Berchuck, Brooke L Fridley, Jing-Yi Chern, Jennifer A Doherty, Jeffrey R Marks, Joellen M Schildkraut, Brock C Christensen, Lucas A Salas, Lauren C Peres

Faculty, Staff and Student Publications

Introduction: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

Methods: Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters …

Long-Term Testosterone Pellet Insertion In Women With Low Libido Shows No Evidence Of Erythrocytosis And A Minimal Side Effect Profile, Beatriz S Hernandez, Gal Saffati, Katherine A Lowrey, Amit Reddy, Bridget S Park, Jeffrey J Song, Gabrielle Lyon, Mohit Khera

Faculty, Staff and Students Publications

Background: Testosterone therapy for low libido in women has become increasingly prevalent in recent years. While numerous testosterone formulations exist and have been studied in women, there has been little data assessing the safety and efficacy of subcutaneous testosterone pellet use in this population. The primary objective of this study is to understand the biochemical effects and side effect profile of female patients who underwent testosterone pellet insertion in a clinical practice.

Methods: A retrospective chart review of female patients who underwent testosterone pellet insertion from 2009 to 2022 was undertaken. Women taking 75 and 100 mg testosterone pellets were …

In Silico Prediction Of Cytotoxic T-Cell Epitopes From Helicobacter Pylori Virulence Factors Using An Immunoinformatics Approach, Demy Valerie Chacon, Kiana Alika Co, Daphne Noreen Enriquez, Aubrey Love Labarda, Reanne Eden Manongsong, Edward Kevin B. Bragais

Biology Faculty Publications

Background: Helicobacter pylori infects approximately half of the global population, leading to gastric and duodenal ulcers. Despite the availability of antibiotics, challenges such as patient reluctance, high treatment costs, and antibiotic resistance limit their effectiveness, making vaccination a promising alternative. This study used immunoinformatics to identify candidate epitopes for a multiepitope vaccine construct against H. pylori.

Material and methods: The protein variability server was utilized for conservation analysis. The epitopes were screened for antigenicity, allergenicity, toxicity, cross-reactivity, and population coverage. Selected epitopes were docked with their corresponding human leukocyte antigen (HLA) alleles, and thermodynamic quantities were determined. Five virulence …

Who Benefits From Active Music Engagement During Cancer Treatment? Associations Of Sociodemographic Characteristics And Risk Factors With Moderators Of Intervention Effects., Steven J. Holochwost, Elizabeth Harman, Kristin Stegenga, Seethal A. Jacob, Sheri L. Robb

Manuscripts, Articles, Book Chapters and Other Papers

Young children and their parents experience frequent and repeated exposure to potentially traumatic events during treatment for cancer. Active Music Engagement (AME) is a dyadic music therapy intervention that has been found to mitigate traumatic stress symptoms among parents who screened high for traumatic stress symptoms (TSS) and reported higher levels of child distress with cancer-related hospitalizations/treatment (child distress). The current study examined sociodemographic characteristics and risk factors that were associated with higher levels of parent TSS and child distress as a means to identify families that may benefit most from AME in the future. Data were collected from the …

Structural Variants: Mechanisms, Mapping, And Interpretation In Human Genetics, Shruti Pande, Moez Dawood, Christopher M Grochowski

Faculty, Staff and Students Publications

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an …

Epigenomic Diagnosis And Prognosis Of Acute Myeloid Leukemia., Francisco Marchi, Vivek M. Shastri, Richard J. Marrero, Nam H K Nguyen, Antonella Öttl, Ann-Kathrin Schade, Marieke Landwehr, Olga Krali, Jessica Nordlund, Matin Ghavami, Fernando Sckaff, Vikash K. Mansinghka, Xueyuan Cao, William Slayton, Petr Starostik, Christopher R. Cogle, Raul C. Ribeiro, Jeffrey E. Rubnitz, Jeffery Klco, Abdelrahman Elsayed, Alan S. Gamis, Timothy J. Triche, Rhonda Ries, E Anders Kolb, Richard Aplenc, Todd Alonzo, Stanley Pounds, Soheil Meshinchi, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

Despite the critical role of DNA methylation, clinical implementations harnessing its promise have not been described in acute myeloid leukemia. Utilizing DNA methylation from 3314 leukemia patient samples across 11 harmonized cohorts, we describe the Acute Leukemia Methylome Atlas, which includes robust models capable of accurately predicting AML subtypes. A genome-wide prognostic model as well as a targeted panel of 38 CpGs significantly predict five-year survival in our pediatric and adult test cohorts. To accelerate rapid clinical utility, we develop a specimen-to-result protocol that uses long-read nanopore sequencing and machine learning to characterize patients' whole genomes and epigenomes. Clinical validation …

A Phase I Trial Of Evorpacept, Lenalidomide And Rituximab For Patients With B-Cell Non-Hodgkin Lymphoma, Paolo Strati, Lei Feng, Andrey Tyshevich, Darya Shavronskaya, Julia Alesse, Noel English, Elizabeth Sheehan, Nikita Syzrantsev, Alexander Nesmelov, Tony Z Zhuang, Dai Chihara, Jason R Westin, Sairah Ahmed, Luis E Fayad, Jared Henderson, Kylie Dent, Elizabeth Mcchesney, Sattva S Neelapu, Christopher R Flowers

Faculty, Staff and Student Publications

Introduction: SIRPα+ macrophages can mediate resistance to lenalidomide and rituximab (R2) in patients with B-cell non-Hodgkin lymphoma (B-NHL). Evorpacept (ALX148) is a novel CD47 blocker that abrogates interactions between lymphoma cells and SIRPα+ macrophages.

Methods: Adult patients with B-NHL who had received at least 2 prior lines of systemic therapy were included in this single arm phase I study (NCT05025800). Evorpacept was administered intravenously (IV), in a 28-day cycle, until progression, at two dose levels (DL): 30 mg/Kg on day (D) 1 and D15 (DL1), or 60 mg/Kg on day 1 (DL2); rituximab 375 mg/m2 IV was given …

A Data Assimilation Framework For Predicting The Spatiotemporal Response Of High-Grade Gliomas To Chemoradiation, Hugo J M Miniere, David A Hormuth, Ernesto A B F Lima, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shanker, Wasif Talpur, Sara Thrower, Jodi Goldman, Sophia Ty, Caroline Chung, Thomas E Yankeelov

Faculty, Staff and Student Publications

Background: High-grade gliomas are highly invasive and respond variably to chemoradiation. Accurate, patient-specific predictions of tumor response could enhance treatment planning. We present a novel computational platform that assimilates MRI data to continually predict spatiotemporal tumor changes during chemoradiotherapy.

Methods: Tumor growth and response to chemoradiation was described using a two-species reaction-diffusion model of enhancing and non-enhancing regions of the tumor. Two evaluation scenarios were used to test the predictive accuracy of this model. In scenario 1, the model was calibrated on a patient-specific basis (n = 21) to weekly MRI data during the course of chemoradiotherapy. A data assimilation …

Xpert Mtb/Rif Ultra Assay For Pulmonary Tuberculosis And Rifampicin Resistance In Adults And Adolescents, David J Horne, Jerry S Zifodya, Adrienne E Shapiro, Elizabeth Chandler Church, Jonah S Kreniske, Alexander W Kay, Katie Scandrett, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

Background: Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects tuberculosis and rifampicin resistance. This review updates a comparative accuracy Cochrane review of Xpert MTB/RIF and Xpert Ultra as Xpert Ultra has replaced Xpert MTB/RIF.

Objectives: To determine the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) for detecting pulmonary tuberculosis and rifampicin resistance in adults and adolescents with presumptive tuberculosis based on signs or symptoms or with an abnormal chest x-ray suggestive of tuberculosis.

Search methods: We searched seven databases including CENTRAL, MEDLINE, and Embase, plus two trial registers (ClinicalTrials.gov …

Lessons In Longevity From Blood Stem Cells Under Protein Stress, André Catic

Center on Aging Staff Publications

Blood stem cells are among the body's longest-living cells despite being highly vulnerable to proteotoxic damage, which accelerates their aging. To maintain protein homeostasis (proteostasis), hematopoietic stem cells (HSCs) employ mechanisms such as reduced translation rates, high chaperone activity, autophagy, and selective protein degradation. These strategies mitigate protein misfolding, maintain quiescence, and preserve regenerative potential. Disruptions in proteostasis can lead to the elimination of impaired HSCs through differentiation or apoptosis, ensuring the integrity of the stem cell pool. Due to the systemic impact of the blood on aging and its experimental and clinical accessibility, investigating HSC proteostasis provides insights into …

Cell Type-Specific Purifying Selection Of Synonymous Mitochondrial Dna Variation, Caleb A Lareau, Patrick Maschmeyer, Yajie Yin, Jacob C Gutierrez, Ryan S Dhindsa, Anne-Sophie Gribling-Burrer, Sebastian Zielinski, Yu-Hsin Hsieh, Lena Nitsch, Veronika Dimitrova, Benan Nalbant, Frank A Buquicchio, Tsion Abay, Robert R Stickels, Jacob C Ulirsch, Patrick Yan, Fangyi Wang, Zhuang Miao, Katalin Sandor, Bence Daniel, Vincent Liu, Paul L Mendez, Petra Knaus, Manpreet Meyer, William J Greenleaf, Anshul Kundaje, Redmond P Smyth, Mathias Munschauer, Leif S Ludwig, Ansuman T Satpathy

Duncan NRI Faculty and Staff Publications

While somatic variants are well-characterized drivers of tumor evolution, their influence on cellular fitness in nonmalignant contexts remains understudied. We identified a mosaic synonymous variant (m.7076A > G) in the mitochondrial DNA (mtDNA)-encoded cytochrome c-oxidase subunit 1 (MT-CO1, p.Gly391=), present at homoplasmy in 47% of immune cells from a healthy donor. Single-cell multiomics revealed strong, lineage-specific selection against the m.7076G allele in CD8+ effector memory T cells, but not other T cell subsets, mirroring patterns of purifying selection of pathogenic mtDNA alleles. The limited anticodon diversity of mitochondrial tRNAs forces m.7076G translation to rely on wobble pairing, unlike the Watson-Crick-Franklin pairing …

Sleep Drive, Not Total Sleep Amount, Increases Seizure Risk, Vishnu Anand Cuddapah, Cynthia T Hsu, Fernanda Valle Sirias, Yongjun Li, Hrishit M Shah, Christopher Saul, Samantha Killiany, Camilo Guevara, Joy Shon, Zhifeng Yue, Gabrielle L Gionet, Mary E Putt, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Sleep loss has been associated with increased seizure risk since antiquity. Using automated video detection of spontaneous seizures in Drosophila epilepsy models, we show that seizures worsen only when sleep restriction raises homeostatic "sleep drive," not simply when total sleep amount falls. This is supported by the paradoxical finding that acute activation of sleep-promoting circuits worsens seizures, because it increases sleep drive without changing sleep amount. Sleep-promoting circuits become hyperactive after sleep loss and are associated with increased whole-brain activity. During sleep restriction, optogenetic inhibition of sleep-promoting circuits to reduce sleep drive protects against seizures. Downregulation of the 5HT1A serotonin …

Maximizing Relief: The Benefits Of Combining Lateral Femoral Cutaneous Nerve Block With Sciatic Nerve Block In The Emergency Department, Courtney Smith, Taryn Hoffman

Florida Journal of Emergency Medicine (FJEM)

Low back pain accounts for more than 2.6 million emergency department (ED) visits annually, with 40% of Americans experiencing sciatica at some point in their lives. Our case report describes a patient presenting with atraumatic right-sided low back pain and paresthesias in her right leg. We utilized a combination of a transgluteal sciatic nerve block and a lateral femoral cutaneous nerve block to achieve improved pain relief after an initial isolated transgluteal sciatic nerve block left her with persistent anterolateral thigh pain.

We detail the technique for performing this procedure under ultrasound guidance. Our patient experienced significant pain improvement and …

"Star Sign" Of Subarachnoid Hemorrhage, Shivani Ruf

Florida Journal of Emergency Medicine (FJEM)

A 60-year-old female who was brought to the emergency department after a syncopal episode. She was found to have a subarachnoid hemorrhage (SAH) from a ruptured anterior communicating artery aneurysm. Her CT showed the classic "star sign" of SAH.

Elderly Woman With Bilateral Finger Pain, Eric Boccio, Claudia Risi

Florida Journal of Emergency Medicine (FJEM)

N/A

Paroxysmal, Severe, And Unilateral Facial Pain In Adult Male, Eric Boccio, Joshua Mcfarlane, Jeannine Bobadilla

Florida Journal of Emergency Medicine (FJEM)

No abstract provided.

Superficial Cervical Plexus Block For Postoperative Pain Management In Occipital Craniotomies: A Narrative Review, Shahab Ahmadzadeh, Bennett M. Ford, Alex V. Hollander, Mary Kathleen Luetkemeier, Tomasina Q. Parker-Actlis, Sahar Shekoohi

School of Medicine Faculty Publications

Post-craniotomy pain is common yet often sub-optimally managed because systemic opioids can obscure postoperative neurologic examinations. The superficial cervical plexus block (SCPB) has, therefore, emerged as a targeted regional anesthesia option for occipital craniotomies. The SCPB targets the C2-C4 nerves to anesthetize the occipital scalp region, covering the lesser occipital nerve territory that lies within typical posterior scalp incisions. Clinical evidence shows the block is effective in reducing acute postoperative pain after occipital craniotomy and diminishes opioid requirements. Studies have demonstrated successful and long-lasting analgesia, reductions in 24-h opioid consumption, and a lower incidence of severe pain. Moreover, the technique …

Dosimetric Effects Of Pinnacle³ Version 18.0 Advanced Auto-Planning Settings In Oropharyngeal Vmat Optimization, Emily Sanden

Masters Projects

This study evaluated the impact of Pinnacle³ version 18.0 auto-planning advanced settings modulation amount, monitor unit (MU) level, and dose fall-off priority on volumetric modulated arc therapy (VMAT) plan quality for bilateral oropharyngeal cancer. A total of 64 plans were generated using all possible combinations of low, medium, high, and very high settings for each parameter. A standardized base of tongue case was optimized once per plan using a single-time point approach, with planned target volume 1 (PTV1) (6996 cGy) and planned target volume 2 (PTV2) (5412 cGy) coverage evaluated. Each parotid gland, the spinal cord, brainstem, and the oral …

A Novel Microdosimetry-Based Formalism For Cell Survival Modelling Applicable To Hypofractionated Radiotherapy, Oleg N Vassiliev, Radhe Mohan

Faculty, Staff and Student Publications

Objectives

Hypofractionated radiotherapy requires reliable cell survival models for doses much higher than the standard 2 Gy, for which the linear-quadratic (LQ) model is not applicable. We developed an alternative approach applicable to both low doses and high doses used in hypofractionated treatments and radiobiological experiments.

Approach.

We combined a standard microdosimetric technique with a recently introduced non-LQ cell survival model. Our formulation accounts for cell damage by multi-track events involving any number of particles. This is necessary for modelling cell survival at therapeutic doses. We characterise each cell type by the size �� of the sensitive volume (SV) and …

Use Of Cholic Acid In Smith-Lemli-Opitz Syndrome (Slos): Real-World Patient Outcomes, Edwin Ferren, Paul R Hillman, Amy Kritzer, Joseph Ray, Alvaro Serrano, Hope Northrup, Paige Roberts, Rana Dutta, Tiziano Pramparo, Pamela Vig, Robert D Steiner

Faculty, Staff and Student Publications

Background: Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis caused by biallelic pathogenic variants in DHCR7, which encodes the enzyme 7-dehydrocholesterol reductase (DHCR7). SLOS is a multisystemic disorder affecting various aspects of health, including growth, development, behavior, and quality of life, underscoring the need for safe, efficacious interventions that limit disease burden. DHCR7 enzyme deficiency leads to a "metabolic block" resulting in decreased cholesterol production and accumulation of its precursor 7-dehydrocholesterol and the secondary isomer 8-dehydrocholesterol. Reduced cholesterol synthesis, in turn, leads to decreased levels of cholic acid (CA), an endogenous bile acid synthesized from cholesterol and …

Melanoma Antigens In Pediatric Medulloblastoma Contribute To Tumor Heterogeneity And Species-Specificity Of Group 3 Tumors, Rebecca R J Collins, Rebecca R Florke Gee, Sima Tozandehjani, Tara Bayat, Maria Camila Hoyos Sanchez, Juan Sebastian Solano Gutierrez, Barbara Breznik, Anna K Lee, Samuel T Peters, Jon P Connelly, Shondra M Pruett-Miller, Martine F Roussel, Dinesh Rakheja, Heather S Tillman, Patrick Ryan Potts, Klementina Fon Tacer

Faculty, Staff and Student Publications

Medulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB (G3 MB) subtype accounts for about 25% of MB and is associated with the worst outcomes. Herein, we report that more than half of G3 MB tumors express melanoma antigens (MAGEs), which are potential prognostic and therapeutic markers. MAGEs are cancer-testis antigens, aberrantly expressed in several adult cancers, and associated with poorer prognosis and therapy resistance; however, their role in pediatric cancers is mostly unknown. This study aimed to determine whether MAGEs are activated and important in pediatric MB. We obtained formalin-fixed paraffin-embedded tumor samples of 34 patients, …

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

Silent Misplacement: Leadless Pacemaker In The Left Ventricle Discovered Over A Year Later-How Did It End Up There? Could It Explain The Stroke?, Abdalhakim Shubietah, Amir Singh, Qutaiba Qafisheh, Pouyan Razminia, Muath Baniowda, Abdalrahman Assaassa, Hosam I. Taha, Roaa Aljunaidi

Division of Cardiology Faculty Papers

Introduction: Leadless intracardiac pacemakers (LICPs) reduce lead-related complications but may be malpositioned in patients with unrecognized structural defects. We report a 69-year-old man with high-grade AV block whose LICP, intended for right ventricular placement, was found in the left ventricle via an undiagnosed ostium secundum ASD after presenting with multifocal embolic strokes 16 months later. Case Presentation: Stroke workup for acute right-sided symptoms revealed the LICP in the LV and a large, previously undiagnosed ASD with bidirectional shunting and severe pulmonary hypertension. Embolic infarcts were attributed to either paradoxical embolism or device-related thromboembolism. Due to high surgical risk, …