Medical Sciences Commons^™

Myocardial T1 And T2 Values Are Associated With Patient Age In Healthy Pediatric Heart Transplant Recipients, Andrew A Lawson, Robyn G Lottes, Defne Magnetta, Andrada Popescu, Kae Watanabe, Cynthia K Rigsby, Michael Markl, Nazia Husain

Faculty, Staff and Students Publications

Background: In pediatric heart transplant recipients (PHTR), myocardial T1 and T2 values are elevated in the setting of acute rejection and with cardiac allograft vasculopathy. In normal, healthy children, T1 and T2 values vary with patient age. Our goal was to identify associations between T1, extracellular volume fraction (ECV), and T2 values and patient- and donor-characteristics in PHTR without history of significant graft pathology.

Methods: We performed a single-center, retrospective chart review of consecutive cardiac magnetic resonance (CMR) studies in PHTR from 2017 to 2023. Exclusion criteria were a prior CMR during the study period, history of any prior antibody-mediated …

Spatial Transcriptomics Reveals Coordinated Endothelial And Epithelial Activator Protein-1 Activation In Chronic Lung Allograft Dysfunction, Yasufumi Goda, Tatsuhiko Naito, Mudassir M Banday, Andrew S Potter, Igor Odintsov, Kapil Patel, Nicole Davis, Stefi Lee, Amit Gaggar, Ivan Rosas, Gabriel Loor, Don Hayes, Nirmal S Sharma

Faculty, Staff and Students Publications

Chronic lung allograft dysfunction (CLAD) limits long-term lung graft survival, yet its specific gene expression profiles remain unclear. We performed comprehensive spatial transcriptomic analyses of human lungs from CLAD patients, non-CLAD transplant recipients, and non-transplanted controls. In CLAD, AP-1 target genes, including JUNB and FOS, were significantly upregulated in both the epithelium and endothelium, whereas anti-fibrotic genes such as A2M and surfactant proteins (SFTPA1,2) were upregulated in non-CLAD. The lymphocyte population in CLAD was predominantly composed of T cells, with elevated JAK3-IL7R signaling. TNF and IL-17 signaling pathways were commonly activated in both the epithelium and endothelium, with JUNB and …

Systematic Identification Of Cell-Cell Interactions Associated With The Severity Of Patients With Alzheimer’S Disease, Zijian Zhang, Naail Chowdhury, Jing Dong, Lang Wu, Chao Cheng

Faculty, Staff and Students Publications

Background

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder involving dysfunction across multiple brain regions. While accumulating evidence has implicated the roles of diverse cell types, including neurons, glia, and vascular cells in AD pathogenesis, it is still poorly understood how cell type interactions drive or respond to the disease progression and severity.

Objective

This study aimed to systematically characterize cell-type–specific alterations and intercellular communication changes associated with AD progression.

Methods

We leveraged the transcriptome profiling and a previously established statistical framework to present a comprehensive mapping of the cellular interaction landscape in the human brain of AD.

Results …

Plasticity And Language In The Anaesthetized Human Hippocampus, Kalman A Katlowitz, Eric R Cole, Elizabeth A Mickiewicz, Shraddha Shah, Melissa Franch, Joshua A Adkinson, James L Belanger, Raissa K Mathura, Domokos Meszéna, Matthew Mcginley, William Muñoz, Garrett P Banks, Sydney S Cash, Chih-Wei Hsu, Angelique C Paulk, Nicole R Provenza, Andrew J Watrous, Ziv Williams, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Sarah R Heilbronner, Robert Kim, Nuttida Rungratsameetaweemana, Benjamin Y Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

Consciousness is a fundamental component of cognition1, but the degree to which higher-order pattern recognition relies on it remains disputed2,3. Here we demonstrate the persistence of oddball discrimination, semantic processing and online prediction in individuals under general-anaesthesia-induced loss of consciousness4,5. Using high-density Neuropixels microelectrodes6 to record both single-unit and local-field-potential neural activity in the human hippocampus while playing a series of tones to anaesthetized patients, we found that hippocampal neurons and local oscillations retained some detection of oddball tones. This effect size grew over the course of the experiment …

Human Neuronal Firing Varies With The Frequency Of Local Field Potential Oscillations, Zahra Jourahmad, Raissa K Mathura, Layth S Mattar, Melissa C Franch, Danika L Paulo, Mohammed Hasen, Nicole R Provenza, Benjamin Y Hayden, Sameer A Sheth, Eleonora Bartoli, Andrew J Watrous

Faculty, Staff and Students Publications

Neural oscillations play a critical role in shaping neuronal firing patterns. While phase-locked neuronal firing ("phase tuning") has been extensively studied in animal models and human invasive recordings, much less is known about whether neurons show preferential firing at specific oscillatory frequencies, termed frequency tuning. Here, we employ human intracranial recordings across several brain regions including hippocampus, entorhinal cortex, anterior and posterior cingulate cortex, and orbitofrontal cortex to test the hypothesis that neurons exhibit frequency-specific firing. We analyzed 357 single units recorded simultaneously with local field potentials in 19 neurosurgical patients during awake resting. We estimated the instantaneous frequency of …

Barrett’S Esophagus-Associated Genetic Loci In African Americans: A Case-Control Study Using The All Of Us Research Program, Ashwin Rao, Jinyoung Byun, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

Background and aims: Barrett's esophagus is the only known precursor lesion to esophageal adenocarcinoma (EAC). Barrett's esophagus and EAC are less common in African Americans than in non-Hispanic Whites. Studies in European populations have identified Barrett's esophagus-associated risk loci; however, none have examined loci in African Americans cohorts. We conducted a case-control targeted replication study to investigate previously identified Barrett's esophagus risk loci in an African Americans cohort in the All of Us (AoU) Research Program.

Methods: We abstracted phenomic and genomic data from 108 African Americans with Barrett's esophagus and 778 African Americans controls in the AoU database. We …

Comparison Of Different “Familial Chylomicronemia Syndrome” Clinical Diagnosis Scoring Systems In Patients With Persistent Chylomicronemia, Diane Brisson, Miriam Larouche, Nathalie Laflamme, Seyedmohammad Saadatagah, Jean Bergeron, Christie M Ballantyne, Daniel Gaudet

Faculty, Staff and Students Publications

Background: Chylomicronemia is associated with extreme hypertriglyceridemia and an increased risk of acute pancreatitis and cardiometabolic complications. Rarely, chylomicronemia persists despite control of secondary causes and conventional treatments. The most severe form of persistent chylomicronemia (PC) is familial chylomicronemia syndrome (FCS). Diagnosis scoring systems have been developed to help clinicians differentiate FCS from other causes of chylomicronemia.

Objective: To assess the ability of FCS diagnosis scoring systems to discriminate FCS from other forms of PC.

Methods: This study included 413 Caucasians presenting a history of chylomicronemia, among whom 65 (15.7%) met the criteria of PC. The performance of 3 FCS …

Validity And Utility Of A Single-Item Patient-Reported Measure Of Treatment-Related Bother In Rheumatoid Arthritis: A Cross-Sectional Omeract Study, Dorthe B Berthelsen, Tobias Haugegaard, Mohammed M Kamso, Peter Tugwell, Lee S Simon, John P A Ioannidis, Caroline Flurey, Maarten Boers, Marieke Voshaar, Pam Richards, Beverly Shea, Daniel E Furst, Jasvinder A Singh, Randall Stevens, Thasia Woodworth, Susan J Bartlett, Glen S Hazlewood, Robin Christensen

Faculty, Staff and Students Publications

Objectives: To assess the construct validity of a modified single-item measure of bother due to side effects (the GP5 item) from the Functional Assessment of Chronic Illness Therapy (FACIT) system by comparing it to current symptomatic side effects from the Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PROCTCAE) reported by patients with rheumatoid arthritis (RA).

Methods: Through a cross-sectional, web-based survey we collected information on the frequency of symptomatic side effects and bother from side effects related to RA medications. We applied multiple correspondence analysis (MCA) to reduce 80 symptomatic side effects into key dimensions (≥5% of …

Non-Isolated Dandy-Walker Malformation: Exome Sequencing Efficacy And Phenotypic Expansions, Sarah Araji, Xiaonan Zhao, Jill A Rosenfeld, Seema R Lalani, Daryl A Scott

Faculty, Staff and Students Publications

Dandy-Walker malformation (DWM) is a rare congenital abnormality of the posterior fossa and the cerebellum and has an incidence of 1 in 10 000 to 30 000 births. Although DWM can present in isolation, it is often associated with other central nervous system (CNS) abnormalities or extra-CNS anomalies (DWM+). A molecular cause is not identified in the majority of individuals with DWM+. This is due, in part, to uncertainty regarding optimal testing strategies and an incomplete understanding of the genetic causes of DWM+. In this study, we analyzed clinical exome sequencing (cES) data from 91 individuals with DWM+ to determine …

Investigating The Correlation Between Scleral Spur Angle And Intraocular Lens Tilt, Dylan Mcbee, Karim Kozhaya, Li Wang, Douglas D Koch, Allison J Chen, Mitchell P Weikert

Faculty, Staff and Students Publications

Purpose: To evaluate the correlation between the preoperative vertex-scleral spur angle (Vtx-SSA) and postoperative horizontal intraocular lens (IOL) tilt after routine cataract surgery.

Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.

Design: Prospective case series.

Methods: This study enrolled patients who underwent uneventful phacoemulsification cataract extraction with IOL implantation. The Anterion and Eyestar 900 swept-source optical coherence tomographers (SS-OCTs) were used to determine Vtx-SSA and lens tilt (crystalline and IOL) measurements, respectively. Tilt vectors were decomposed into orthogonal, vertical, and horizontal components to explore preoperative correlations independently. The Pearson correlation coefficient and linear regression analysis were used to …

Plasma Biomarkers Of Brain Injury In Critically Ill Children Receiving Extracorporeal Membrane Oxygenation, Matthew L Friedman, Michael J Bell, Bonnie A Brooks, Adam S Himebauch, Asavari Kamerkar, Kerri Larovere, Laura L Loftis, Jose A Pineda, Ahmed Said, Hitesh S Sandhu, Martin Stengelin, Catherine Demos, Mark S Wainwright, Alina N West, Allan Barnes, Allen D Everett, Ryan J Felling, Sue J Hong, Jennifer L Roem, Cynthia F Salorio, Derek K Ng, Melania M Bembea

Faculty, Staff and Students Publications

Importance: Timely identification of acute brain injury (ABI) in children receiving extracorporeal membrane oxygenation (ECMO) support is critical for early neuroprotective interventions.

Objectives: To determine if elevations in plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels in children receiving ECMO precede new ABI confirmed by neuroimaging, and if they are associated with mortality and functional outcomes.

Design, setting, and participants: This was a prospective observational cohort study conducted from 2019 to 2023, with 18-month follow-up completed in 2025. Children aged 2 days to younger than 18 years at ECMO cannulation were recruited from 11 US …

Routine Transfusion Of Rh(D)-Positive Rbcs To Rh(D)-Negative Patients Designated As Do Not Resuscitate Conserves Rh(D)-Negative Red Blood Cell Inventory, Julie Katz Karp, Jovanna Everetts, Juliana Guarente, Angelica Vivero, Tiffany Bohr, Mary Harach

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: A minority of blood donors are Rh(D)-negative, and Rh(D)-negative red blood cell (RBC) products are often overutilized. As such, Rh(D)-negative RBCs may be difficult to maintain in blood bank inventory.

Study design and methods: We changed our blood bank laboratory policy to approve non-alloimmunized Rh(D)-negative patients to receive Rh(D)-positive RBCs for routine transfusion under defined criteria. Those criteria included Rh(D)-negative males (all ages) and females (aged >50 years) who were designated as do not resuscitate (DNR), either with or without intubation, in the electronic medical record.

Results: From August 15, 2024 through August 15, 2025, a total of 204 …

Association Of Infection Frequency And Incident Clonal Hematopoiesis Of Indeterminant Potential, Ajibike Lapite, Vernon A Burk, James Decuir, Junichi Ishigami, Seyedmohammad Saadatagah, Pradeep Natarajan, Christie M Ballantyne, Elizabeth A Platz, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis of indeterminant potential (CHIP) is an age-related phenomenon associated with increased risk of hematologic malignancy. Preclinical studies have shown that infection is a driver of CHIP; clinical studies in people living with HIV suggest a relationship between chronic infection and CHIP, but the association between infection frequency and incident CHIP in the general population remains unknown. We leveraged the atherosclerosis risk in communities study to design a closed prospective cohort study. CHIP was determined based on whole-exome sequencing at 2 time points 20 years apart. Included were 3,367 individuals without cancer or CHIP at time 1 and without …

Coxfa4l2 Upregulation Preserves Residual Cytochrome C Oxidase Activity In Coxfa4-Related Leigh-Like Encephalopathy, Micol Falabella, Sandra Lopez Calcerrada, Jana Aref, Jiaze Gao, William L Macken, Chiara Pizzamiglio, Renata Kabiljo, Anna Lucia Francavilla, Pauline Gaignard, Antoine Pouzet, Jonathan Levy, Giulia Barcia, Jamie K Leighton, Efstathia Chronopoulou, Germaine Pierre, Riza Köksal Özgül, Ali Dursun, Rebecca Halligan, Helen Mundy, Javeria Raza Alvi, Tipu Sultan, William James Craigen, Lisa Emrick, Jill A Rosenfeld, Gehad Elmakkawy, Jihye Kim, Joseph J Gleeson, Aboulfazl Rad, Gabriela Oprea, Maqbool Hussain, Khalil Ur Rehman, Sadia Riaz, Robert W Taylor, Vincent Procaccio, Maha S Zaki, Erika Fernandez-Vizarra, Ciro Leonardo Pierri, Michael G Hanna, Henry Houlden, Reza Maroofian, Cristina Ugalde, Jan-Willem Taanman, Robert D S Pitceathly

Faculty, Staff and Students Publications

Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes. COXFA4 (cytochrome c oxidase subunit FA4), formerly NDUFA4, is a nuclear-encoded COX subunit, but its role in disease remains poorly defined. We report the largest genetically confirmed cohort of COXFA4-related PMD to date, comprising 13 individuals from 12 families with biallelic pathogenic COXFA4 variants. All present …

Efficacy And Safety Of A Bodyweight-Adjusted Higher Dose Of Ocrelizumab In Relapsing (Musette) And Primary Progressive (Gavotte) Multiple Sclerosis: Two Multicentre, Randomised, Double-Blind, Parallel-Group Phase 3b Trials., Stephen L Hauser, Gavin Giovannoni, Xavier Montalban, Jiwon Oh, Amit Bar-Or, Maria Pia Sormani, Martin S Weber, Sharon Stoll, Jacqueline A Nicholas, Tetyana Nehrych, Robert Bonek, Krzysztof Selmaj, Maciej Maciejowski, Dusanka Zecevic, Catarina Raposo, Rebecca Owen, Ulrike Bonati, Katrin Madjar, Eva Harfst, Qing Wang, Anastasiia Raievska, Marianna Manfrini, Hans-Martin Schneble, Ludwig Kappos, Musette And Gavotte Study Groups

Neuroscience Articles

BACKGROUND: Ocrelizumab is a humanised anti-CD20 monoclonal antibody approved for people with relapsing (RMS) or primary progressive multiple sclerosis (PPMS). In a post-hoc analysis of phase 3 trials in RMS and PPMS using a 600 mg dose, higher exposure to ocrelizumab was associated with greater B-cell depletion and lower risk of confirmed disability progression. Here, we prospectively assessed the efficacy and safety of a high dose of ocrelizumab in patients with RMS or PPMS.

METHODS: Two multicentre, double-blind, phase 3 controlled trials were conducted to compare high-dose ocrelizumab with the approved 600 mg dose of the drug in patients with …

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …

Acidic Extracellular Ph-Induced Pth Secretion In Male Mouse Parathyroids Is Ogr1-Dependent, Yanmei Yang, Mengcun Chen, Mingshu Cui, Elisabeth Lashbrooks, Bin Wang

Center for Translational Medicine Faculty Papers

The role of extracellular acidity in regulating PTH secretion in cultured mouse parathyroid glands (PTGs) has not been studied to date, largely because of the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid, which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in …

Childcare Challenges Among Surgical Trainees And Faculty: A Single-Institution Study, Emma G Burke, Sarah Peiffer, Melissa Koci, Lindsay Dean, Kristy L Rialon, Michele Loor, Alice King

Faculty, Staff and Students Publications

Background: Previous studies have demonstrated the challenges of parenthood in surgical training and careers. However, certain aspects of childrearing for surgeons remain understudied. We aim to leftacterize the complexity and costs of childcare amongst surgical trainees and faculty.

Methods: An anonymous, self-administered survey was conducted within the Department of Surgery at a large academic medical center. Both male and female trainees and faculty were included in the analysis. Chi-square or Fisher's Exact test was performed.

Results: Forty-six respondents provided information about childcare costs, with 37% of respondents being residents or fellows. Trainees worked longer workhours (p = 0.003) than their …

Repurposing Semaglutide As An Adjunctive Treatment For Cocaine Use Disorder: Protocol For A Randomised Controlled Trial, Luba Yammine, Francesco Versace, Charles E Green, Heather E Webber, Jin Ho Yoon, Absalon D Gutierrez, Samuel J Leonard, Michael F Weaver, Joy Schmitz

Faculty, Staff and Student Publications

Introduction: Cocaine use disorder (CUD) is a significant public health concern in the USA, with considerable prevalence and mortality and no Food and Drug Administration (FDA)-approved pharmacotherapies. Recent advances in addiction science emphasise the need for novel, mechanism-based treatments. Glucagon-like peptide-1 receptor agonists, such as semaglutide, have shown promise in modulating reward-related behaviours and may offer therapeutic benefits for CUD. We present a study protocol evaluating semaglutide, as an adjunct to cognitive behavioural therapy (CBT), as a novel approach for treating CUD.

Methods and analysis: This is a randomised, double-blind, placebo-controlled trial enrolling 75 treatment-seeking adults with CUD. Participants will …

Association Of Polygenic Risk Scores With Aortic Valve Calcium: The Multi-Ethnic Study Of Atherosclerosis, Seamus P Whelton, Jie Yao, Clary Clish, Alexis C Wood, Kent D Taylor, Michael J Blaha, Matthew Budoff, Natalie Marrero, George Thanassoulis, Wendy S Post, Xiuqing Guo, Jerome I Rotter

Faculty, Staff and Students Publications

Background: Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors.

Methods: We included 6812 participants in MESA (Multi-Ethnic Study of Atherosclerosis) with computed tomography-measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross-sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at …

Cardiac Hdac3 Disruption Contributes To Hdac Inhibitor-Induced Qt Prolongation, Jiao Lu, Christopher Ward, Sichong Qian, Lilei Zhang, Jiang Chang, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, …

Selective And Differential Roles Of Pvhcrh Neurotransmitters In Diet-Induced Obesity In Mice, Zhiying Jiang, Yuhan Cao, Michelle He, Cunjin Su, Runzhou Yang, Maojie Yang, Jing Cai, Hongli Li, Yuanzhong Xu, Shi-Bin Li, Hiroshi Yamaguchi, Luis De Lecea, Benjamin R Arenkiel, Qingchun Tong

The Brown Foundation: Institute of Molecular Medicine

Stress and diet are known to synergistically promote risks of obesity but the underlying neural basis remains elusive. Corticotropin-releasing hormone neurons in the paraventricular hypothalamus (PVHCRH) are stress responsive and release both CRH and glutamate. Here we generated a mouse model with gain or loss of release in CRH or glutamate from PVHCRH neurons. While these models showed no changes in body weight when fed chow, they exhibited contrasting effects when fed high-fat high-caloric diets (HFD). Whereas disrupting glutamate release from PVHCRH neurons led to diet-induced obesity (DIO), that of CRH caused no impact. Conversely, augmented CRH release led to …

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R Rao, Barbara C Jobst, Jerzy P Szaflarski, John D Rolston, Lesley C Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C Dugan, David E Burdette, Angela Y Peters, Atif Sheikh, Kevin F Haas, Dileep R Nair, Lilit Mnatsakanyan, Imran H Quraishi, Meriem K Bensalem-Owen, Rns System Pas Study, Michael J Doherty, Babak Razavi, Tiffany L Fisher, Christopher Skidmore, Pradeep N Modur, Tawnya M Constantino, Vicenta Salanova, Andrew J Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E Maciver, Sanjay E Patra, Edward F Chang, Jon T Willie, Ryder Gwinn, Travis Stoub, John M Stern, Tami Crabtree, Cairn G Seale, Sharon C Mcfadden, Jacob F Norman, Lise Johnson, Martha J Morrell

Faculty, Staff and Student Publications

Background and objectives: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

Methods: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Water-Soluble Fullerene Derivatives Mitigate Cranial Radiation-Induced Neuroinflammation And Cognitive Dysfunction, Naren Gundapaneni, Iona Hill, Lydia W T Cheung, Khadijeh Koushki, Alyssa Fausnaught, Phuoc Minh Quan Mai, Arjun Vasan, Prapannajeet Biswal, Ashutosh Tripathi, Anilkumar Pillai, Vijayasree V Giridharan, Tatiana Barichello, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Radiotherapy is widely used to treat malignant and benign brain tumors. A major constraint, however, is the low tolerance of normal brain tissue to radiation. Cranial irradiation-induced injury manifests as inflammatory responses and neurodegeneration, which jointly contribute to progressive cognitive decline. These complications can restrict the delivery of optimal therapeutic doses, cause persistent neurological symptoms, and ultimately compromise quality of life. Thus, neuroprotective agents have emerged as a strategy to safeguard normal tissues from radiation-induced neurotoxicity. This study investigated the efficacy of a highly soluble [60]fullerene (C60) derivative, C60-ser, a carbon-based nanomaterial, to mitigate radiation-induced brain injury. Oral administration of …

Natural History Of Ngly1 Deficiency: Motor Function & Clinical Features, Grace Morrison, Selina Dwight, Hal Landy, William F Mueller, Pam Ventola, Regina Deck, Becky Schweighardt, Matt Wilsey, Kevin J Lee, Bernhard Suter

Faculty, Staff and Students Publications

N-glycanase 1 (NGLY1) Deficiency is an ultra-rare neurodevelopmental disorder caused by biallelic loss-of-function mutations in the NGLY1 gene, leading to severe impairments in neurocognitive and motor function abilities in the affected patient population. Its core clinical features include global developmental delay, hyperkinetic movement disorders, elevation of liver transaminases, (hypo)alacrima, and progressive sensorimotor neuropathy. Due to the range of phenotypes and severity within the confirmed patient population, ongoing characterization of the disease is critical. A prospective natural history study (NHS) was conducted to further elucidate disease phenotypes and examine any changes in neurocognitive or motor function over a one-year period. Fifteen …

Pharmacogenomic-Guided Prescribing And Polypharmacy Across Age Groups In Obsessive-Compulsive Disorder: A Retrospective Study, Sheldon R Garrison, Matthew W Boyer, Anthony W Zoghbi, Rachel A Schwartz, Nicolette Weisensel, Martin E Franklin, Madeline M Hartig, Maharaj Singh, Sreya Vadapalli

Faculty, Staff and Students Publications

Background: This study evaluated medication utilization in children, adolescents, and adults with obsessive-compulsive disorder (OCD), a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors. Although first-line treatments include selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), the heterogeneous biological underpinnings contribute to suboptimal outcomes, with 40-60% of individuals not responding to SSRIs. This complex phenotype often leads to psychotropic polypharmacy, which may be mitigated by incorporating combinatorial pharmacogenomic (PGx) testing into protocol-based care to identify potential gene-drug interactions.

Methods: A retrospective review was conducted of individuals with OCD aged 8 to 65 years who received either …

Large-Scale Genetic Characterization Of Parkinson’S Disease In The African And African Admixed Populations, Fulya Akçimen, Kimberly Paquette, Peter Wild Crea, Kathryn Step, Emily Waldo, Mathew J Koretsky, Paula Saffie-Awad, Charles Achoru, Funmilola Taiwo, Simon Ozomma, Gerald Onwuegbuzie, Marzieh Khani, Spencer Grant, Lukman Owolabi, Chiamaka Okereke, Olajumoke Oshinaike, Emmanuel Iwuozo, Suleyman Can Akerman, Paul Suhwan Lee, Shyngle Oyakhire, Nosakhare Osemwegie, Kensuke Daida, Sani Abubakar, Adedunni Olusanya, Mariam Isayan, Christiane Alvarez, Rami Traurig, Adebimpe Ogunmodede, Sarah Samuel, Mary B Makarious, Fadimatu Sa'ad, Rashidat Olanigan, Kristin Levine, Ewere Marie Ogbimi, Dan Vitale, Francis Odiase, Francis Ojini, Olanike Odeniyi, Zih-Hua Fang, Nkechi Obianozie, Deborah A Hall, Ernest Nwazor, Tao Xie, Francesca Nwaokorie, Mahesh Padmanaban, Paul Nwani, Ejaz A Shamim, Alero Nnama, David Standaert, Morenikeji Komolafe, Marissa Dean, Godwin Osaigbovo, Elizabeth Disbrow, Ismaila Ishola, Ashley Rawls, Frank Imarhiagbe, Shivika Chandra, Cyril Erameh, Vanessa Hinson, Naomi Louie, Ahmed Idowu, J Solle, Scott A Norris, Abdullahi Ibrahim, Camilla Kilbane, Gauthaman Sukumar, Lisa M Shulman, Daniel Ezuduemoih, Julia Staisch, Sarah Breaux, Clifton Dalgard, Erin R Foster, Abiodun Bello, Andrew Ameri, Raquel Real, Erica Ikwenu, Huw R Morris, Roosevelt Anyanwu, Erin Furr Stimming, Kimberley Billingsley, Wemimo Alaofin, Pilar Alvarez Jerez, Osigwe Agabi, Dena G Hernandez, Rufus Akinyemi, Sampath Arepalli, Laksh Malik, Raymond Owolabi, Yakub Nyandaiti, Hampton L Leonard, Kolawole Wahab, Oladunni Abiodun, Carlos F Hernandez, Fatima Abdulai, Hirotaka Iwaki, Soraya Bardien, Christine Klein, John Hardy, Henry Houlden, Kamalini Ghosh Galvelis, Mike A Nalls, Nabila Dahodwala, Whitley Aamodt, Emily Hill, Alberto Espay, Stewart Factor, Chantale Branson, Cornelis Blauwendraat, Andrew B Singleton, Oluwadamilola Ojo, Lana M Chahine, Njideka Okubadejo, Sara Bandres-Ciga

Faculty, Staff and Student Publications

Elucidating the genetic contributions to Parkinson's disease aetiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11 827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity in prioritized early onset and familial cases. Our study identified rare GBA1 coding variants to be the most frequent mutations among patients with Parkinson's disease, with a frequency of 4% in our case cohort. Of the 18 …

Apathy, Effort-Based Decisions And Brain Integrity In Alzheimer’S And Parkinson’S Diseases, Lee-Anne Morris, Hideo Suzuki, Seonjoo Lee, Zekai Jin, Bryan B Chen, Ana Marin, Edward D Huey, Yunglin Gazes, Sarah R Heilbronner, Campbell J Le Heron, Nora Vanegas-Arroyave

Faculty, Staff and Students Publications

Apathy, or loss of motivation, is a prominent syndrome accompanying both Alzheimer's and Parkinson's diseases, in addition to other disorders. One approach to understanding motivational loss is to examine the processes underlying goal-directed behaviour. Weighing up rewarding outcomes against the effort costs required to obtain them (effort-based decision-making) is a core computation when deciding to act for outcomes. Although a growing body of evidence points to disruption of this computation in people with apathy, which underlying decision parameters drive this disruption, their neural associations and whether these would generalize or differ across brain disorders have not been examined. People with …

Randomised Controlled Trial Comparing Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy For The Management Of Severe Open Tibia Fracture Wounds: Beads Versus Vac (Bvv) Protocol, Lucas S Marchand, Gerard Slobogean, Nathan N O'Hara, Anthony D Harris, David W Grainger, Lehana Thabane, Mohit Bhandari, Gregory J Della Rocca, Patrick J Kellam, Robert D Zura, Debra Marvel, Jeffrey L Wells, I Leah Gitajn, Kyle J Jeray, Robert V O'Toole, Zachary M Working, Roman M Natoli, Patrick F Bergin, Jennifer E Hagen, Ashley E Levack, Ernesto Guerra-Farfan, Gregory M Schrank, Joan N Hebden, Franca Mossuto, Cassandra Tsoutsounakis, David Pogorzelski, Hailey Pineda, Sofia Bzovsky, Sheila Sprague, Bvv Investigators

Faculty, Staff and Student Publications

Introduction: Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds.

Methods and analysis: …

Experiences Of Discrimination, Paternal Support, And Hypertensive Disorders Of Pregnancy (Hdp) In The Miehr Study, Houston, Texas, Tahereh Alinia, Elaine Symanski, Juan Manuel Alvarez, Kristina Walker Whitworth

Faculty, Staff and Students Publications

Background: Discrimination is a psychosocial stressor that, through activation of stress-response pathways, may influence risk of adverse perinatal health outcomes. However, few studies have evaluated the association between discrimination and hypertensive disorders of pregnancy (HDP), and none have explored effect modification by race or paternal support, which may buffer the adverse effects of discrimination.

Methods: We included 1,847 non-Hispanic Black and White participants from the Maternal and Infant Environmental Health Riskscape (MIEHR) study. Krieger's validated Experiences of Discrimination (EOD) scale was used to assess occurrence (yes/no) and frequency (once, 2-3, ≥ 4 times) of discrimination in nine situations. We created …