Digital Commons Network^™

A Phase I Study Of The Pharmacokinetics, Pharmacodynamics, And Safety Of Liposomal Bupivacaine For Sciatic Nerve Block In The Popliteal Fossa For Bunionectomy, Daniel I Sessler, Xiaodong Bao, David Leiman, Jia Song, Jason Chittenden, Alexander Voelkner, Alparslan Turan, Jeffrey Gadsden

Faculty, Staff and Student Publications

This trial assessed the pharmacokinetics, pharmacodynamics, and safety of liposomal bupivacaine given via ultrasound-guided popliteal sciatic nerve block with or without immediate-release bupivacaine hydrochloride in adults having bunionectomies. Forty-five adults were enrolled into four sequential cohorts: (1) liposomal bupivacaine 266 mg with bupivacaine hydrochloride 50 mg; (2) liposomal bupivacaine 133 mg with bupivacaine hydrochloride 50 mg; (3) liposomal bupivacaine 266 mg; or (4) bupivacaine hydrochloride 100 mg. Outcomes included pharmacokinetics (e.g., bupivacaine maximum plasma concentration [C

Development And Evaluation Of An Automated Multimodal Mobile Detection Of Oral Cancer Imaging System To Aid In Risk-Based Management Of Oral Mucosal Lesions, Ruchika Mitbander, David Brenes, Jackson B Coole, Alex Kortum, Imran S Vohra, Jennifer Carns, Richard A Schwarz, Ida Varghese, Safia Durab, Sean Anderson, Nancy E Bass, Ashlee D Clayton, Hawraa Badaoui, Loganayaki Anandasivam, Rachel A Giese, Ann M Gillenwater, Nadarajah Vigneswaran, Rebecca Richards-Kortum

Faculty, Staff and Student Publications

Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage, although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders, which are associated with an increased risk of oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation. This study reports the development and evaluation of the mobile detection of oral cancer (mDOC) imaging system and an automated algorithm that generates a referral recommendation from mDOC images. mDOC …

Evaluating Artifact-Free Four-Dimensional Computer Tomography With 16 Cm Detector Array, Inhwan Yeo, Wei Nie, Jiajin Fan, Mindy Joo, Michael Correa, Qianyi Xu

Department of Radiation Oncology Faculty Papers

PURPOSE: To evaluate a 16 cm-array axial four-dimensional computer tomography (4DCT) in comparison with a 4 cm-array 4DCT in the presence of respiration irregularity.

METHOD: Ten traces of lung tumor motion from CyberKnife treatments were imported to move the lung cylinder, containing a spherical target, of a phantom. Images were acquired for the lung that moved to each of the 10-positions/phases (1) step-wisely by nominal helical scan at each movement (ground truth), (2) continuously by 4D scan with the 16 cm array, and (3) the same with the 4 cm array, involving table shift. Irregularities, consisting of baseline shift and/or …

Eight Weeks Of High-Intensity Interval Training Alters The Tongue Microbiome And Impacts Nitrate And Nitrite Levels In Previously Sedentary Men, Annabel Simpson, Andrea M. Pilotto, Lorenza Brocca, Raffaele Mazzolari, Bob T. Rosier, Miguel Carda-Dieguez, Patricia Casas-Agustench, Raul Bescos, Simone Porcelli, Alex Mira, Chris Easton, Fiona L. Henriquez, Mia Burleigh

School of Health Professions

Nitric oxide (∗NO) is a key signalling molecule, produced enzymatically via ∗NO synthases (NOS) or following the stepwise reduction of nitrate to nitrite via oral bacteria. Exercise training upregulates NOS expression and improves systemic health, but its effect on oral health, and more particularly the oral microbiome, has not been investigated. We used an exercise training study design to investigate changes in the tongue dorsum microbiome, and in nitrate and nitrite levels in the saliva, plasma and muscle, before, during and after an exercise training period. Eleven untrained males (age 25 ± 5 years, mass 64.0 ± 11.2 kg, stature …

Vitamin D-Related Genetic Variants And Prostate Cancer Risk In Black Men, Tracy M Layne, Joseph H Rothstein, Xiaoyu Song, Shaneda Warren Andersen, Emma K T Benn, Weiva Sieh, Robert J Klein

Faculty, Staff and Student Publications

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Methods: We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide …

The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.

Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Jatin Shah, Denái R Milton, David S Hong, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Hung Chu, Yan Li, Mark L Frederiks, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …

Semi-Parametric Testing For Ordinal Treatment Effects In Time-To-Event Data Via Dynamic Dirichlet Process Mixtures Of The Inverse-Gaussian Distribution., Jonathan A Race, Amy S Ruppert, Yvonne Efebera, Michael L Pennell

Ambulatory and Primary Care Articles

Time-to-event data often violate the proportional hazards assumption under which the log-rank test is optimal. Such violations are especially common in the sphere of biological and medical data where heterogeneity due to unmeasured covariates or time varying effects are common. A variety of parametric survival models have been proposed in the literature which make more appropriate assumptions on the hazard function, at least for certain applications. One such model is derived from the first hitting time paradigm which assumes that a subject's event time is determined by a latent stochastic process reaching a threshold value. Several random effects specifications of …

Calcium-Sensing Receptor As A Novel Target For The Treatment Of Idiopathic Pulmonary Fibrosis, Kasope Wolffs, Renjiao Li, Bethan Mansfield, Daniel A Pass, Richard T Bruce, Ping Huang, Rachel Paes De Araújo, Bahareh Sadat Haddadi, Luis A J Mur, Jordanna Dally, Ryan Moseley, Rupert Ecker, Harry Karmouty-Quintana, Keir E Lewis, A John Simpson, Jeremy P T Ward, Christopher J Corrigan, Renata Z Jurkowska, Benjamin D Hope-Gill, Daniela Riccardi, Polina L Yarova

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and no curative therapies. Fibroblast activation by transforming growth factor β1 (TGFβ1) and disrupted metabolic pathways, including the arginine-polyamine pathway, play crucial roles in IPF development. Polyamines are agonists of the calcium/cation-sensing receptor (CaSR), activation of which is detrimental for asthma and pulmonary hypertension, but its role in IPF is unknown. To address this question, we evaluated polyamine abundance using metabolomic analysis of IPF patient saliva. Furthermore, we examined CaSR functional expression in human lung fibroblasts (HLFs), assessed the anti-fibrotic effects of a CaSR antagonist, NPS2143, in TGFβ1-activated normal …

Safety Outcomes Of Antiplatelet Therapy During Endovascular Treatment Of Tandem Lesions In Acute Ischemic Stroke Patients, Mudassir Farooqui, Afshin A Divani, Milagros Galecio-Castillo, Ameer E Hassan, Mouhammad A Jumaa, Marc Ribo, Michael Abraham, Nils Petersen, Johanna Fifi, Waldo R Guerrero, Amer M Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Albert J Yoo, Guillermo Linares, Nazli Janjua, Darko Quispe-Orozco, Asad Ikram, Wondewossen G Tekle, Syed F Zaidi, Cynthia B Zevallos, Federica Rizzo, Tiffany Barkley, Reade De Leacy, Jane Khalife, Mohamad Abdalkader, Sergio Salazar-Marioni, Jazba Soomro, Weston Gordon, Aaron Rodriguez-Calienes, Juan Vivanco-Suarez, Charoskhon Turabova, Maxim Mokin, Dileep R Yavagal, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Risk of hemorrhage remains with antiplatelet medications required with carotid stenting during endovascular therapy (EVT) for tandem lesion (TLs). We evaluated the safety of antiplatelet regimens in EVT of TLs. This multicenter study included anterior circulation TL patients from 2015 to 2020, stratified by periprocedural EVT antiplatelet strategy: (1) no antiplatelets, (2) single oral, (3) dual oral, and (4) intravenous IV (in combination with single or dual oral). Primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were any hemorrhage, favorable functional status (mRS 0-2) at 90 days, successful reperfusion (mTICI score ≥ 2b), in-stent thrombosis, and mortality at 90 …

Whole-Body Hypothermia For Neonatal Encephalopathy In Preterm Infants 33 To 35 Weeks' Gestation: A Randomized Clinical Trial, Roger G Faix, Abbot R Laptook, Seetha Shankaran, Barry Eggleston, Dhuly Chowdhury, Roy J Heyne, Abhik Das, Claudia Pedroza, Jon E Tyson, Courtney Wusthoff, Sonia L Bonifacio, Pablo J Sánchez, Bradley A Yoder, Matthew M Laughon, Diana M Vasil, Krisa P Van Meurs, Margaret M Crawford, Rosemary D Higgins, Brenda B Poindexter, Tarah T Colaizy, Shannon E G Hamrick, Lina F Chalak, Robin K Ohls, Michele E Hartley-Mcandrew, Kevin Dysart, Carl T D'Angio, Ronnie Guillet, Stephen D Kicklighter, Waldemar A Carlo, Gregory M Sokol, Sara B Demauro, Anna Maria Hibbs, C Michael Cotten, Stephanie L Merhar, Roopali V Bapat, Heidi M Harmon, Elizabeth Sewell, Sarah Winter, Girija Natarajan, Ricardo Mosquera, Susan R Hintz, Nathalie L Maitre, Kristen L Benninger, Myriam Peralta-Carcelen, Abbey C Hines, Andrea F Duncan, Deanne E Wilson-Costello, Andrea Trembath, William F Malcolm, Michele C Walsh

Faculty, Staff and Student Publications

Importance: Hypothermia begun less than 6 hours after birth reduces death or disability in infants with encephalopathy due to hypoxia-ischemia at 36 or more weeks' gestation. Trials of hypothermia for infants younger than 36 weeks' gestation are lacking.

Objective: To assess the probability that hypothermia at less than 6 hours after birth decreases death or disability in infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy.

Design, setting, and participants: This randomized clinical trial was conducted between July 2015 and December 2022 for infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy at less …

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …

The Impact Of Atlas Parcellation On Functional Connectivity Analysis Across Six Psychiatric Disorders, Xiaoya Wu, Chuang Liang, Juan Bustillo, Peter Kochunov, Xuyun Wen, Jing Sui, Rongtao Jiang, Xiao Yang, Zening Fu, Daoqiang Zhang, Vince D Calhoun, Shile Qi

Faculty, Staff and Student Publications

Neuropsychiatric disorders are associated with altered functional connectivity (FC); however, the reported regional patterns of functional alterations suffered from low replicability and high variability. This is partly because of differences in the atlas and delineation techniques used to measure FC-related deficits within/across disorders. We systematically investigated the impact of the brain parcellation approach on the FC-based brain network analysis. We focused on identifying the replicable FCs using three structural brain atlases, including Automated Anatomical Labeling (AAL), Brainnetome atlas (BNA) and HCP_MMP_1.0, and four functional brain parcellation approaches: Yeo-Networks (Yeo), Gordon parcel (Gordon) and two Schaefer parcelletions, among correlation, group difference, …

International Multispecialty Expert Physician Preoperative Identification Of Extranodal Extension In Patients With Oropharyngeal Cancer Using Computed Tomography: Prospective Blinded Human Inter-Observer Performance Evaluation, Onur Sahin, Serageldin Kamel, Kareem A Wahid, Cem Dede, Nicolette Taku, Renjie He, Mohamed A Naser, Christina S Sharafi, Antti Mäkitie, Benjamin H Kann, Kimmo Kaski, Jaakko Sahlsten, Joel Jaskari, Moran Amit, Gregory M Chronowski, Eduardo M Diaz, Adam S Garden, Ryan P Goepfert, Jeffrey P Guenette, G Brandon Gunn, Jussi Hirvonen, Frank Hoebers, Katherine A Hutcheson, Nandita Guha-Thakurta, Jason Johnson, Diana Kaya, Shekhar D Khanpara, Kristofer Nyman, Stephen Y Lai, Miriam Lango, Kim O Learned, Anna Lee, Carol M Lewis, Anastasios Maniakas, Amy C Moreno, Jeffrey N Myers, Jack Phan, Kristen B Pytynia, David I Rosenthal, Vlad C Sandulache, Dawid Schellingerhout, Shalin J Shah, Andrew G Sikora, Abdallah S R Mohamed, Melissa M Chen, Clifton D Fuller, Multidisciplinary Oropharyngeal Cancer Extra‐Nodal Extension (Opc Ene) Assessment Working Group

Faculty, Staff and Students Publications

Background: Pathologic extranodal extension (pENE) is a crucial prognostic factor in oropharyngeal cancer (OPC), but determining pENE from imaging has high inter-observer variability. The role of clinician specialty in the accuracy of imaging-detected extranodal extension (iENE) remains unclear. The purpose of this study is to assess the influence of clinician specialty on the accuracy of preoperative iENE detection in human papillomavirus (HPV)-positive OPC using computed tomography (CT) imaging.

Methods: This prospective observational study evaluated pretherapy CT images from 24 HPV-positive OPC patients (30 scans, including duplicates). Thirty-four expert observers (11 radiologists, 12 surgeons, 11 radiation oncologists) assessed iENE and reported …

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Lin Y Hung, Nuno D Alves, Andrew Del Colle, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …

Ethics Of Learning Surgical Autonomy In Safety-Net Hospital Systems With Patients Who Are Incarcerated, Kala T Pham, Rachel W Davis

Faculty, Staff and Students Publications

Safety-net hospitals care for patients who are incarcerated and are key environments in which surgical trainees learn to wield their professional autonomy. This article explores ethical questions raised by surgical trainees' participation in carceral care and canvasses possible responses to those questions.

Dysregulation Of Mirna Expression And Excitation In Mef2c Autism Patient Hipsc-Neurons And Cerebral Organoids, Dorit Trudler, Swagata Ghatak, Michael Bula, James Parker, Maria Talantova, Melissa Luevanos, Sergio Labra, Titas Grabauskas, Sarah Moore Noveral, Mayu Teranaka, Emily Schahrer, Nima Dolatabadi, Clare Bakker, Kevin Lopez, Abdullah Sultan, Parth Patel, Agnes Chan, Yongwook Choi, Riki Kawaguchi, Pawel Stankiewicz, Ivan Garcia-Bassets, Piotr Kozbial, Michael G Rosenfeld, Nobuki Nakanishi, Daniel H Geschwind, Shing Fai Chan, Wei Lin, Nicholas J Schork, Rajesh Ambasudhan, Stuart A Lipton

Faculty, Staff and Students Publications

MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic …

De Novo Variants In Rybp Are Associated With A Severe Neurodevelopmental Disorder And Congenital Anomalies, Monika Weisz-Hubshman, Lindsay C Burrage, Sharayu V Jangam, Jill A Rosenfeld, Sandra Von Hardenberg, Anke Bergmann, Manuela Friederike Richter, Malgorzata Rydzanicz, Rafal Ploski, Agnieszka Stembalska, Wendy K Chung, Rebecca R Hernan, Foong Y Lim, Theresa Brunet, Steffen Syrbe, Boris Keren, Solveig Heide, David R Murdock, Hongzheng Dai, Fan Xia, Shamika Ketkar, Brian Dawson, Vinodh Narayanan, Hillary K Graves, Undiagnosed Diseases Network, Michael F Wangler, Carlos Bacino, Brendan Lee

Duncan NRI Faculty and Staff Publications

Purpose: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.

Methods: Functional consequences of RYBP variants were assessed using in vitro cellular and in vivo Drosophila melanogaster studies.

Results: We described 7 individuals with heterozygous de novo variants of RYBP and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. We showed that all single-nucleotide variants in RYBP localize to the N-terminal domain of …

Opioid Prescribing Patterns And The Effect Of Chronic Kidney Disease In Pediatric Urology Population: A Retrospective Cohort Analysis., Kristen M. Meier, Darren Ha, Carter Sevick, Eliza D. Blanchette, Megan A. Brockel, Vijaya M. Vemulakonda, Kyle O. Rove

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Significant efforts have been undertaken to decrease opioid prescribing, but there is little research into patient-specific factors presenting as barriers in the pediatric surgical population. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be a safe and effective alternative to opioids for pain control, however, concerns about their impact on renal function limit their use in patients with chronic kidney disease (CKD). Data is limited on the interplay of CKD on opioid prescribing.

OBJECTIVE: We hypothesized that opioid reduction efforts were successful, but patients with CKD would be more likely to receive an opioid prescription than those without CKD. …

Inborn Errors Of Immunity Reveal Molecular Requirements For Generation And Maintenance Of Human Cd4+ Il-9-Expressing Cells, Geetha Rao, Corinne D Mack, Tina Nguyen, Natalie Wong, Kathryn Payne, Lisa Worley, Paul E Gray, Melanie Wong, Peter Hsu, Michael O Stormon, Kahn Preece, Daniel Suan, Michael O'Sullivan, Annaliesse K Blincoe, Jan Sinclair, Satoshi Okada, Sophie Hambleton, Peter D Arkwright, Kaan Boztug, Polina Stepensky, Megan A Cooper, Liliana Bezrodnik, Kari C Nadeau, Hassan Abolhassani, Roshini S Abraham, Mikko R J Seppänen, Vivien Béziat, Jacinta Bustamante, Lisa R Forbes Satter, Jennifer W Leiding, Isabelle Meyts, Emmanuelle Jouanguy, Stéphanie Boisson-Dupuis, Gulbu Uzel, Anne Puel, Jean-Laurent Casanova, Stuart G Tangye, Cindy S Ma

Faculty, Staff and Students Publications

Background: CD4+ T cells play essential roles in adaptive immunity. Distinct CD4+ T-cell subsets-TH1, TH2, TH17, TH22, T follicular helper, and regulatory T cells-have been identified, and their contributions to host defense and immune regulation are increasingly well defined. IL-9-producing TH9 cells were first described in 2008 and appear to play both protective and pathogenic roles in human immunity. However, key requirements for generating human TH9 cells remain incompletely defined.

Objective: We sought to define signaling pathways that regulate IL-9 production by human CD4+ T cells.

Methods: Human naive and memory CD4+ T cells were cultured under different conditions, and …

Ethical Considerations For Sharing Aggregate Results From Pragmatic Clinical Trials, Stephanie R Morain, Abigail Brickler, Joseph Ali, Patricia Pearl O'Rourke, Kayte Spector-Bagdady, Benjamin Wilfond, Vasiliki Rahimzadeh, Caleigh Propes, Kayla Mehl, David Wendler

Center for Medical Ethics and Health Policy Staff Publications

A growing literature has explored the ethical obligations and current practices related to sharing aggregate results with research participants. However, no prior work has examined these issues in the context of pragmatic clinical trials. Several characteristics of pragmatic clinical trials may complicate both the ethics and the logistics of sharing aggregate results. Among these characteristics include that pragmatic clinical trials may affect the rights, welfare, and interests of not only patient-subjects but also clinicians, meaning that results may be owed to a broader range of groups than typically considered in other research contexts. In addition, some pragmatic clinical trials are …

Words Of Advice: How To Write The Story Of A Patient For A Problem-Based Learning Session In A Healthcare Education Program, Andrew D Bergemann, Matthew Mcmillin, Miriah C Gillispie-Taylor, Gareth Gingell, R Taylor Surles, Rachel Wallace

Faculty and Staff Publications

Medical education is in the process of a pedagogical revolution. Traditional lectures are playing a progressively smaller role, with more of the content being delivered through student-centered small-group sessions. Problem-based learning (PBL) has become a centerpiece of education for many medical schools, in large part because of its focus on the learners identifying their own knowledge gaps. As junior scientists seek faculty appointments in institutions focused on healthcare education, they will find that skills in PBL are valued by the academic community. Among the necessary skills is the capability to lead efforts in PBL case writing. The cases, each of …

Subacute Neuropathy Post-Liver Transplantation In Zellweger Spectrum Disorder: A Case Report, Clarissa Gonzalez, Madelyn J Cohen, Juhee Hong, Daniel Calame, Kavitha Marri, Sanjiv Harpavat, Michael F Wangler, Krupa Mysore

Faculty, Staff and Students Publications

Peroxisome biogenesis disorders-Zellweger spectrum disorder (PBD-ZSD) is a rare genetic disease caused by mutations in the genes involved in peroxisome biogenesis. PBD-ZSD presentations vary in severity, and treatment of PBD-ZSD remains supportive focused on specific complications. A few reported cases of the use of liver transplantation to treat either neurological symptoms or liver dysfunction and cirrhosis in PBD-ZSD have been published. In this case report, we document the course of a 16-year-old boy diagnosed with PBD-ZSD and a delayed and unexpected neuropathy that developed after undergoing orthotopic liver transplantation (OLT) for which the indication was liver cirrhosis. Following OLT, the …

Multi-Omic Analysis Of Biological Aging Biomarkers In Long-Term Calorie Restriction And Endurance Exercise Practitioners: A Cross-Sectional Study, Giovanni Fiorito, Valeria Tosti, Silvia Polidoro, Beatrice Bertozzi, Nicola Veronese, Edda Cava, Francesco Spelta, Laura Piccio, Dayna S Early, Daniel Raftery, Paolo Vineis, Luigi Fontana

2020-Current year OA Pubs

Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR practitioners, 41 age- and sex-matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood-biomarkers. Additionally, a subset of …

Quantitative And Visual Benefits Of Data-Driven Motion Correction On Oncologic Pet/Ct: A Prospective Cross-Sectional Study, Semra Ince, M Allan Thomas, Malak Itani, Christopher Swingle, Richard Laforest, Adeel Haq, Genevieve Muñoz, Saeed Ashrafinia, Paul Schleyer, Richard L Wahl, Tyler J Fraum

2020-Current year OA Pubs

RATIONALE AND OBJECTIVE: Conventional positron emission tomography (PET) respiratory gating utilizes a fraction of acquired PET counts (i.e., optimal gate [OG]), whereas elastic motion correction with deblurring (EMCD) utilizes all PET counts to reconstruct motion-corrected images without increasing image noise. Our aim was to assess the quantitative and visual impacts of EMCD-based motion correction on FDG-PET and DOTATATE-PET images relative to OG and ungated (UG) images.

MATERIALS AND METHODS: This prospective, single-center study enrolled adults undergoing FDG or DOTATATE oncologic PET/CT between June 2020 and October 2022. Subjects underwent a standard-of-care (SOC) PET acquisition while wearing a respiratory gating belt. …

G-Distance: On The Comparison Of Model And Human Heterogeneity, Lenard Dome, Andy J. Wills

School of Psychology

Models are often evaluated when their behavior is at its closest to a single, sometimes averaged, set of empirical results, but this evaluation neglects the fact that both model and human behavior can be heterogeneous. Here, we develop a measure, g-distance, which considers model adequacy as the extent to which models exhibit a similar range of behaviors to the humans they model. We define g as the combination of two easily interpretable dimensions of model adequacy: accommodation and excess flexibility. We apply this measure to five models of an irrational learning effect, the inverse base-rate effect. g-Distance identifies two models, …

Associations Of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, And Cognitive Performance, Ruijin Lu, Krish Shah, Cristina D Toedebusch, Ashley Hess, Rachel Richardson, Emmanuel Mignot, Suzanne E Schindler, Tammie L S Benzinger, Shaney Flores, Jason Hassenstab, Chengjie Xiong, John C Morris, David M Holtzman, Brendan P Lucey

2020-Current year OA Pubs

OBJECTIVE: Cerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls. In this study, we tested the association between CSF orexin-A concentrations, AD biomarkers, and cognitive performance in older adults with and without symptomatic AD.

METHODS: Two hundred and seventy community-dwelling older adults underwent standardized cognitive assessments, sleep monitoring with a single-channel …