Digital Commons Network^™

An Evolutionary Preamble Towards A Multilevel Framework To Understand Adolescent Mental Health: An International Delphi Study, Federica Sancassiani, Vanessa Barrui, Fabrizio Bert, Sara Carucci, Fatma Charfi, Giulia Cossu, Arne Holte, Jutta Lindert, Simone Marchini, Alessandra Perra, Samantha Pinna, Antonio Egidio Nardi, Alessandra Scano, Cesar A Soutullo, Massimo Tusconi, Diego Primavera

Faculty, Staff and Student Publications

Background/objectives: Adolescence is a sensitive developmental window shaped by both vulnerabilities and adaptive potential. From an evolutionary standpoint, mental health difficulties in this period may represent functional responses to environmental stressors rather than mere dysfunctions. Despite increasing interest, integrative models capturing the dynamic interplay of risk and protective factors in adolescent mental health remain limited. This study presents a holistic, multi-level framework grounded in ecological and evolutionary theories to improve understanding and intervention strategies.

Methods: A two-round Delphi method was used to develop and validate the framework. Twelve experts in adolescent mental health evaluated a preliminary draft derived from the …

Human Adipose Stem Cell-Derived Small Extracellular Vesicles Modulate Glial Cell Response In Aged And Young Tbi Mouse Models, Salma S. Abdelmaboud

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of long-term neurological impairment, with aging significantly increasing vulnerability and worsening outcomes. Older individuals experience greater cognitive and motor deficits after TBI and often show diminished responses to therapeutic interventions. Both aging and TBI independently promote heightened neuroinflammation and cognitive dysfunction, increasing susceptibility to poor recovery. This study investigated the therapeutic potential of small extracellular vesicles (sEVs) derived from human adipose-derived stem cells (hASCs) to promote neurological recovery and modulate neuroinflammation in a mouse model of TBI. Male C57BL/6 mice aged 3, 15, and 20 months underwent controlled cortical impact (CCI) and …

Lewy Body Dementia Promotion By Air Pollutants, Xiaodi Zhang, Haiqing Liu, Xiao Wu, Longgang Jia, Kundlik Gadhave, Lena Wang, Kevin Zhang, Hanyu Li, Rong Chen, Ramhari Kumbhar, Ning Wang, Chantelle E Terrillion, Bong Gu Kang, Bin Bai, Minhan Park, Ma Cristine Faye Denna, Shu Zhang, Wenqiang Zheng, Denghui Ye, Xiaoli Rong, Liu Yang, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S Rosenthal, David W Nauen, Alex Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L Dawson, Francesca Dominici, Rodney J Weber, Xuan Zhang, Pengfei Liu, Ted M Dawson, Shizhong Han, Xiaobo Mao

Faculty, Staff and Student Publications

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we showed in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure raises LBD risk. Mechanistically, we found PM2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM2.5-exposed mice and …

Tet2-Mutant Myeloid Cells Mitigate Alzheimer’S Disease Progression Via Cns Infiltration And Enhanced Phagocytosis In Mice, Katie A Matatall, Trisha K Wathan, Minh Nguyen, Hu Chen, Alexandra Mcdonald, Guantong Qi, Julia A Belk, Marcus A Florez, Duy T Le, Temitope Olarinde, Caitlyn Vlasschaert, Marco M Buttigieg, Chih-Wei Fan, Saul Carcamo, Ruoqiong Cao, Daniel E Kennedy, Arushana A Maknojia, Apoorva Thatavarty, Josaura V Fernandez Sanchez, Hind Bouzid, Surabi Veeraragavan, Susan Crocker, Margaret A Goodell, Antony Rodriguez, Siddhartha Jaiswal, Michael J Rauh, Eirini P Papapetrou, Samuele G Marro, Katherine Y King

Faculty, Staff and Students Publications

No abstract provided.

Investigating Bacterial Vaginosis Pathogenesis Using Peptide Nucleic Acid-Fluorescence In Situ Hybridization With A Focus On The Roles Of Gardnerella Species, Prevotella Bivia, And Fannyhessea Vaginae, Sheridan D. George, Megan H. Amerson-Brown, Lúcia G.V. Sousa, Tyler M. Carter, Alexa H. Rinehart, Ashleigh N. Riegler, Sixto M. Leal, Kristal J. Aaron, Jiaying Hao, Ashutosh Tamhane, Chaoling Dong, John W. Lammons, Jacob H. Elnaggar, Keonte J. Graves, Paweł Łaniewski, Melissa M. Herbst-Kralovetz, Christopher M. Taylor, Nuno Cerca, Christina A. Muzny

School of Graduate Studies Faculty Publications

Background. Bacterial vaginosis (BV) is a vaginal dysbiosis characterized by polymicrobial communities of BV-associated bacteria (BVAB) adhered to the vaginal epithelium. Despite decades of research, its etiology remains unknown. We aimed to investigate BV biofilm formation over time among women who developed incident BV (iBV) using peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH), focusing on 3 key BVAB (Gardnerella species, Prevotella bivia, and Fannyhessea vaginae). Methods. Heterosexual, nonpregnant women ages 18–45 with optimal vaginal microbiota were enrolled to self-collect twice-daily vaginal specimens for 60 days. iBV was defined as a Nugent score of 7–10 on ≥ 4 consecutive specimens. For …

Neonatal Striatal Volume Is Associated With Infant Anhedonia, Melissa Nevarez-Brewster, Catherine H. Demers, Jessica L. Irwin, Laura M. Glynn, Martin A. Styner, Mercedes Hoeflich Haase, M. Camille Hoffman, Diego A. Pizzagalli, Benjamin L. Hankin, Elysia Poggi Davis

Psychology Faculty Articles and Research

Anhedonia is increasingly recognized as a transdiagnostic risk factor for psychopathology. New evidence demonstrates that anhedonia is present in infancy and early childhood. Structural variability in striatal regions involved in reward processing and pleasure seeking is concurrently linked to anhedonia, yet few studies have examined whether striatal differences presage anhedonia, and none have examined prospective associations before middle childhood. The present study examined whether neuroanatomical markers that confer risk for anhedonia can be detected as early as the neonatal period. Specifically, we tested whether the volume of striatal regions in neonates predicted the emergence of infant anhedonic behaviors at six …

An Allele-Agnostic Mutant-Kras Inhibitor Suppresses Tumor Maintenance Signals And Reprograms Tumor Immunity In Pancreatic Cancer, Kathleen M Mcandrews, Francesca Paradiso, Clint A Stalnecker, Benson S Chellakkan, Fredrik I Thege, David H Peng, Barbara A Moreno Diaz, Hikaru Sugimoto, Sarah I Patel, Krishnan K Mahadevan, Michelle L Kirtley, Danielle Wills, Amari M Sockwell, Andre Luis F Fonseca, Yunhe Liu, Kimal I Rajapakshe, Nathaniel G Yee, Phuong Thao Tran, Huda Alchikh Omar, Antonio Tedeschi, Fiorella Schischlik-Siegl, Andrew S Boghossian, Matthew G Rees, Melissa M Ronan, Jennifer A Roth, Dorothea Rudolph, Martin Aichinger, Florian Ebner, Artem V Artemov, Jesse Lipp, Laura Pisarsky, Valerie Laura Herrmann, John Park, Jörg F Rippmann, Otmar Schaaf, Vanessa Chandler, Mariah Williams, Charles E Deckard, Linghua Wang, Channing J Der, Christopher Vellano, Paola A Guerrero, Timothy P Heffernan, Raghu Kalluri, Anirban Maitra

Faculty, Staff and Student Publications

KRAS is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluate the pre-clinical efficacy of BI-2493 a panKRASi, a first-in-class allele agnostic mutant KRAS inhibitor, in pancreatic ductal adenocarcinoma (PDAC). We report effective tumor growth suppression across a broad range of models, including cell lines, patient-derived xenografts (PDXs), syngeneic orthotopic models, and prolonged survival in genetically engineered mouse …

Persistent Na+ Current Couples Spreading Depolarization To Seizures In Scn8a Gain-Of-Function Mice, Isamu Aiba, Yao Ning, Jeffrey L Noebels

Faculty, Staff and Students Publications

Spreading depolarization (SD) is a slowly propagating wave of massive cellular depolarization that transiently impairs the function of affected brain regions. Although SD typically arises as an isolated hemispheric event, we previously reported that reducing M-type potassium current (IKM) by ablation of Kcnq2 in forebrain excitatory neurons results in tightly coupled spontaneous bilateral seizure–SD complexes in the awake mouse cortex.

Here we find that enhanced persistent Na+ current attributable to gain-of-function mutations in Scn8a (N1768D/+, hereafter D/+) produces a similar compound cortical excitability phenotype. Chronic direct-current (DC)-band EEG recording detected spontaneous bilateral seizure–SD complexes accompanied by seizures with …

Intronic Fgf14 Gaa Repeat Expansions Impact Progression And Survival In Multiple System Atrophy., Viorica Chelban, David Pellerin, Nirosen Vijiaratnam, Hamin Lee, Yen Yee Goh, Lauren Brown, Sara Sambin, Danielle Seilhean, Stephane Lehericy, Pablo Iruzubieta, Rahema Mohammad, Eleanor Self, Annarita Scardamaglia, Cameron Lee, Miriama Ostrozovicova, Marie-Josée Dicaire, Christine Girges, Emil K. Gustavsson, David Murphy, Toby Curless, Joshua Laß, Joanne Trinh, Timothy Rittman, James B. Rowe, Marios Hadjivassiliou, Neil Archibald, Matt C. Danzi, Catherine Ashton, Virginie Roth, Marion Wandzel, Warren A. Cheung, Djordje O. Gveric, Bart De Vil, Jordan Follett, P Nigel Leigh, Lukas Beichert, Tomi Pastinen, Céline Bonnet, Mathilde Renaud, Wassilios G. Meissner, Anne Sieben, David Crosiers, Patrick Cras, Stephan Zuchner, Jean-Christophe Corvol, Matthew J. Farrer, Matthis Synofzik, Bernard Brais, Tom Warner, Huw R. Morris, Zane Jaunmuktane, Tom Foltynie, Henry Houlden

Manuscripts, Articles, Book Chapters and Other Papers

Partial phenotypic overlap has been suggested between multiple system atrophy and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. In this study, we investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases (193 clinically diagnosed and 464 pathologically confirmed) and 1003 controls. The FGF14 repeat locus was genotyped using long-range PCR and bidirectional repeat-primed PCRs, and expansions were confirmed with targeted long-read Oxford Nanopore Technologies sequencing. We identified 19 multiple system atrophy cases carrying an FGF14 …

Commensal Colonization Of Candida Albicans In The Mouse Gastrointestinal Tract Is Mediated Via Expression Of Candidalysin And Adhesins, Kelsey E Mauk, Pedro Miramón, Michael C Lorenz, Léa Lortal, Julian R Naglik, Bernhard Hube, Lynn Bimler, Farrah Kheradmand, David B Corry

Faculty, Staff and Students Publications

The ubiquitous fungal pathogen Candida albicans has the potential to either asymptomatically colonize the gastrointestinal (GI) tract or become an invasive pathogen through mechanisms that remain incompletely understood. Here we explored the fungal, host, and environmental factors that influence the ability of C. albicans to colonize the mouse GI tract using a representative clinical strain, CLCA10. After a single gavage challenge (5 × 106 CFU C. albicans), specific pathogen-free (SPF) mice remained colonized with C. albicans strain CLCA10, but not other Candida species, for at least 58 days with the fungus confined largely to the gut luminal …

Chp1 Promotes Lipid Droplet Growth And Regulates The Localization Of Key Enzymes For Triacylglycerol Synthesis, Guang Yang, Ximing Du, Dougall Norris, Armella Zadoorian, Yuyuan Zheng, Mingming Gao, Andrew J Brown, Shane T Grey, Chun Zhou, Hongyuan Yang

Faculty, Staff and Student Publications

The glycerol-3-phosphate (G-3-P) pathway is central to the synthesis of triacylglycerols (TAGs) and glycerophospholipids, essential for membrane biogenesis and lipid storage. The first and rate-limiting step in this pathway is catalyzed by glycerol-3-phosphate acyltransferases (GPATs), with microsomal GPAT3 and GPAT4 being evolutionarily conserved and predominant in most tissues. While previous studies have implicated Calcineurin B homologous protein 1 (CHP1) as a cofactor for GPAT4, the broader role of CHP1 in regulating microsomal GPATs and TAG biosynthesis remains unclear. Here, we demonstrate that CHP1 is a critical regulator of both GPAT3 and GPAT4, essential for their stability, enzymatic activity, and lipid …

Functional Connectivity Predicting Transdiagnostic Treatment Outcomes In Internalizing Psychopathologies, Kai Zhang, Heide Klumpp, Jagan Jimmy, K Luan Phan, Mohammed R Milad, Zhenfu Wen

Faculty, Staff and Student Publications

Importance: Predicting treatment outcomes for internalizing psychopathologies (IPs), such as depression and anxiety, holds promise for advancing precision medicine. The extent to which whole-brain functional connectivity (FC) can predict treatment responses for patients with IPs across different therapeutic modalities remains unclear.

Objective: To examine whether pretreatment FC patterns predict multidimensional treatment outcomes in patients with IPs and whether predictive performance generalizes across diagnoses and treatment modalities.

Design, setting, and participants: This prognostic study analyzed baseline neuroimaging and clinical data from patients with IPs enrolled in 1 of 2 randomized clinical trials (conducted from December 2013 to February 2018 and September …

Barriers And Facilitators To Surgical Trainee Psychological Safety, Jennifer H Chen, Alyssa A Pradarelli, Julie Evans, Niki Matusko, Norah N Naughton, Roy Phitayakorn, John T Mullen, Lily Chang, Melissa Johnson, Thavam Thambi-Pillai, Jon Ryckman, Melissa Alvarez-Downing, Nell Maloney Patel, Sebastiano Cassaro, Felicia Ivascu, David T Hughes, Gurjit Sandhu

Faculty, Staff and Students Publications

Importance: Although psychological safety has been shown to be imperative for effective learning, specific factors associated with its presence in surgical training have not been well characterized.

Objective: To identify barriers and facilitators to psychological safety for surgical trainees in the clinical learning environment.

Design, setting, and participants: This qualitative study was conducted from February 20 to May 2, 2024, among 25 trainees in general surgery and 3 surgical subspecialty programs at 9 teaching hospitals-4 university-based, 3 community-based, and 2 community-based, university-affiliated hospitals.

Exposure: Participation in surgical training.

Main outcomes and measures: Participants were asked to share their perspectives and …

Efficacy Of Atr Kinase Inhibitor Elimusertib Monotherapy Or Combination In Tumors With Dna Damage Response Pathway And Other Genomic Alterations, Kaushik Varadarajan, Christian X Cruz Pico, Kurt W Evans, Maria Gabriela Raso, Yasmeen Qamar Rizvi, Xiaofeng Zheng, Dhruv Chachad, Timothy P Diperi, Bailiang Wang, Stephen M Scott, Ming Zhao, Argun Akcakanat, Antje M Wengner, Timothy A Yap, Funda Meric-Bernstam

Faculty, Staff and Student Publications

The ataxia telangiectasia and RAD3-related (ATR) kinase functions with ataxia telangiectasia-mutated (ATM) kinase as a modulator of DNA damage response (DDR). We assessed the antitumor effects of the ATR inhibitor elimusertib (BAY-1895344) in patient-derived xenograft (PDX) models with DDR alterations. Antitumor activity was assessed by change in tumor volume (TV) from baseline. Responses were categorized as follows: partial response (PR), ≥30% decrease in TV; ≥20% increase in TV, progressive disease; and non-PR/progressive disease, stable disease (SD). Event-free survival was defined as time for tumor doubling (EFS-2). Of 21 PDX models tested, 11 had significant prolongation of EFS-2 with elimusertib monotherapy. …

Ontology Accelerates Few-Shot Learning Capability Of Large Language Model: A Study In Extraction Of Drug Efficacy In A Rare Pediatric Epilepsy, Pedram Golnari, Katrina Prantzalos, Veronica Hood, Mary Anne Meskis, Lori L Isom, Karen Wilcox, Jack M Parent, Dennis Lal, Samden D Lhatoo, Howard P Goodkin, Elaine C Wirrell, Kelly G Knupp, Manisha Patel, Jeffrey A Loeb, Joseph E Sullivan, Lauren Harte-Hargrove, Brandy E Fureman, Jeffrey Buchhalter, Satya S Sahoo

Faculty, Staff and Student Publications

OBJECTIVE: Dravet Syndrome (DS) is a developmental and epileptic encephalopathy that is characterized by severe, prolonged motor seizures and high resistance to multiple antiseizure medications (ASMs) with multiple comorbidities. Evaluating the efficacy of new drugs in DS preclinical models and mapping them to human phenotypes of DS through analysis of published literature is an important goal for improving outcomes in this rare pediatric epilepsy.

MATERIALS AND METHODS: Large language models (LLM) have demonstrated great promise in parsing published literature; however, the performance of LLMs falls short in medical applications. In this study, we investigate the effectiveness of domain ontology developed …

Coenzyme Q Headgroup Intermediates Can Ameliorate A Mitochondrial Encephalopathy, Guangbin Shi, Claire Miller, Sota Kuno, Alejandro G Rey Hipolito, Salsabiel El Nagar, Giulietta M Riboldi, Megan Korn, Wyatt C Tran, Zixuan Wang, Lia Ficaro, Tao Lin, Quentin Spillier, Begoña Gamallo-Lana, Drew R Jones, Matija Snuderl, Soomin C Song, Adam C Mar, Alexandra L Joyner, Roy V Sillitoe, Robert S Banh, Michael E Pacold

Duncan NRI Faculty and Staff Publications

Decreased brain levels of coenzyme Q10 (CoQ10), an endogenously synthesized lipophilic antioxidant1,2, underpin encephalopathy in primary CoQ10 deficiencies3,4 and are associated with common neurodegenerative diseases and the ageing process5,6. CoQ10 supplementation does not increase CoQ10 pools in the brain or in other tissues. The recent discovery of the mammalian CoQ10 headgroup synthesis pathway, in which 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) makes 4-hydroxymandelate (4-HMA) to synthesize the CoQ10 headgroup precursor 4-hydroxybenzoate (4-HB)7, offers an opportunity to pharmacologically restore CoQ10 synthesis and mechanistically treat CoQ10 deficiencies. To test whether 4-HMA …

Randomized Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain: 540 Mg Vs. 900 Mg Dose Comparison, Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns

Children’s Nutrition Research Center Staff Publications

Aims: There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.

Methods: Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 …

High-Resolution Mapping Of Alcohol-Related Brain Connectivity In Adults Using 7t Fmri And Multivoxel Pattern Classification, Alan N. Francis, Ihsan Salloum

School of Medicine Publications

Background: Emerging evidence suggests that alcohol use disrupts large-scale brain network interactions, particularly within the triple network model-comprising the Salience Network (SN), Default Mode Network (DMN), and Frontoparietal Network (FPN). However, few studies have examined how these connectivity alterations vary across the full spectrum of alcohol consumption, especially using ultra-high-field imaging and data-driven approaches. This study leverages 7 Tesla resting-state fMRI and multivariate pattern analysis (MVPA) to characterize distinct brain connectivity patterns across heavy, moderate, and non-drinking adults, aiming to identify neural signatures that differentiate alcohol use severity levels.

Methods: We analyzed resting-state functional connectivity data from 69 adults (Mean …

Combining Lumipulse P-Tau217 And Aβ42/40 As Confirmatory Tests For Aβ Positivity Prior To Disease-Modifying Therapy, James D. Doecke, Ahmed Chenna, Mintzu Lo, Youssouf Badal, Brandon Yee, Robert Martone, Christos Petropoulos, Christopher J. Fowler, Simon Laws, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher C. Rowe, Colin L. Masters, John Winslow

Research outputs 2022 to 2026

Introduction: For a blood-based biomarker to be considered a confirmatory test for the detection of abnormal amyloid beta (Aβ) levels, the sensitivity and specificity must be equivalent to that of current cerebrospinal fluid tests. Methods: In the current study we assessed the ability of phosphorylated tau (p-tau)217 and Aβ42/40 from the Lumipulse G p-tau217 and β-amyloid ratio (1-42/1-40) tests, individually and combined, to predict Aβ positron emission tomography status in two sub-cohorts from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing. Results: Testing an Alzheimer's disease continuum cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy for …

A Large-Scale Multi-Centre Study Characterising Atrophy Heterogeneity In Alzheimer's Disease, Vikram Venkatraghavan, Damiano Archetti, Pierrick Bourgeat, Chenyang Jiang, Mara Ten Kate, Anna C. Van Loenhoud, Rik Ossenkoppele, Charlotte E. Teunissen, Elsmarieke Van De Giessen, Yolande A.L. Pijnenburg, Giovanni B. Frisoni, Béla Weiss, Zoltán Vidnyánszky, Tibor Auer, Stanley Durrleman, Alberto Redolfi, Simon M. Laws, Paul Maruff, Neil P. Oxtoby, Andre Altmann, Daniel C. Alexander, Wiesje M. Van Der Flier, Frederik Barkhof, Betty M. Tijms

Research outputs 2022 to 2026

Previous studies identified atrophy-based Alzheimer's disease(AD) subtypes linked to distinct clinical symptoms, but their consistency across subtyping approaches remains unclear. This large-scale study evaluates subtype concordance using two data-driven approaches. In this work, we analyzed data from n=10,011 patients across 10 AD cohorts spanning Europe, the US, and Australia, extracting regional volumes using Freesurfer. To characterize atrophy heterogeneity in the AD continuum, we developed a two-step approach, Snowphlake (Staging NeurOdegeneration With PHenotype informed progression timeLine of biomarKErs), to identify subtypes and atrophy-event sequences within each subtype. Results were compared with SuStaIn (Subtype and Stage Inference), which jointly estimates subtypes and …

Current Controversies In Prenatal Diagnosis 2: Conventional Postmortem Examination Remains The Gold Standard For The Anatomical Examination Of Fetal Loss, J Ciaran Hutchinson, Lorraine Potocki, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

A comprehensive postmortem examination is an essential component of a work-up after stillbirth. Its findings can support accurate counseling of parents about causes and risk of recurrence. It also supports providers' decisions about most appropriate testing and management plans for future pregnancy to prevent recurrence. Informing parents about fetal autopsy and obtaining their consent is challenging, and conducting a fetal autopsy requires expertise that is, not universally available. Newer non-invasive or minimally invasive methods such as postmortem MRI and targeted biopsies can replace or supplement autopsies, but one must recognize that expertise in these methods is likewise not broadly available. …

The Effect Of Tert Promoter Mutation On Predicting Meningioma Outcomes: A Multi-Institutional Cohort Analysis, Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Christopher W Mount, Ulrich Schüller, Sandro Santagata, Felix Sahm, Tejus A Bale, Christina Jackson, Timothy E Richardson, Chunyu Cai, Farshad Nassiri, Gelareh Zadeh, David Kaul, David Capper, Stephen T Magill, John G Golfinos, Chandra Sen, Akash J Patel, David R Raleigh, Jennifer Moliterno, Donato Pacione, Matija Snuderl, Wenya Linda Bi

Duncan NRI Faculty and Staff Publications

Background: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing.

Methods: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of …

Unbound Bilirubin And Risk Of Severe Neurodevelopmental Impairment In Extremely Low Birthweight Newborns, Cody C Arnold, Ivana Maric, Ronald J Wong, Jon E Tyson, David K Stevenson

Faculty, Staff and Student Publications

Background: Unbound bilirubin (UB) was measured on day 5 ± 1 in 1101 ELBW newborns in the Aggressive vs Conservative Phototherapy randomized controlled trial. We accessed this dataset to quantify the UB-mediated risk of severe neurodevelopmental impairment (sNDI) in extremely low birthweight (ELBW) newborns.

Methods: UB levels were standardized within laboratories as z-score percentiles. A dichotomous UB exposure variable was based on sharply increased risk of sNDI at the 85th percentile (UBz>85th). Targeted maximum likelihood estimation with ensemble machine learning (TMLE + ML) and logistic regression (LR) were used to estimate sNDI risk attributable to UBz>85th.

Results: UB …

Beyond Frequency Of Use: Exploring Additional Metrics For Quantifying Cocaine Use And Their Relation To Life Functioning And Treatment Outcome, Samantha Ellis, Rachel Sun, Angela Heads, Jin Ho Yoon, Heather Webber, Joy Schmitz, Margaret Wardle

Faculty, Staff and Student Publications

Background: Frequency of use - the number of days of use - is the most common metric for quantifying cocaine use and the most common target of treatment. However, frequency may not capture all important aspects of cocaine use. This study examined how other aspects of cocaine use (typical amount spent, variability etc.) relate to life functioning and cocaine use disorder (CUD) treatment outcomes.

Method: This is a secondary analysis of 3 clinical trials for CUD, N = 207 for the life functioning analysis and N = 173 for the outcomes analysis. Eight metrics of use were calculated from baseline …

Immune Impacts Of Fire Smoke Exposure, Mary M Johnson, Abhinav Kaushik, Olivia A Kline, Eric M Smith, Xiaoying Zhou, Yagiz Pat, Laura Buergi, Juan Aguilera, Shifaa Alkotob, Elisabeth M Simonin, Alberto Favaro, Miguel Couto, Oscar Bennett, R Sharon Chinthrajah, Ella Parsons, Mohamed Shamji, Marshall Burke, Melissa Bondy, Mubeccel Akdis, Cezmi A Akdis, Kari C Nadeau

Faculty, Staff and Student Publications

Fire smoke exposure has become a global health concern and is associated with increased morbidity and mortality. There is a lack of understanding of the specific immune mechanisms involved in smoke exposure with preventative and targeted interventions needed. After exposure to fire smoke, which includes PM2.5, toxic metals and per- and polyfluoroalkyl substances (PFAS), epidemiology-based studies demonstrate increases in respiratory (e.g. asthma exacerbations), cardiac (e.g. myocardial infarctions, arrhythmias), neurologic (e.g. stroke) and pregnancy-related (e.g. low birthweight, premature births) outcomes. However, mechanistic studies exploring how smoke exposure disrupts cellular homeostasis are lacking. Therefore, we collected blood from smoke-exposed individuals (n …

Outcomes In Systemic Sclerosis-Associated Interstitial Lung Disease Based On Serological Profiles With A Focus On Anticentromere And Anti-Rna Polymerase Iii Antibodies, Elizabeth R Volkmann, Shervin Assassi, Christopher P Denton, Rozeta Simonovska, Steven Sambevski, Margarida Alves, Elana J Bernstein

Faculty, Staff and Student Publications

Objective: We aimed to compare the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) based on serological status.

Methods: In a posthoc analysis of the SENSCIS trial (nintedanib vs placebo in SSc-ILD; ClinicalTrials.gov: NCT02597933), we analyzed the rate of decline in forced vital capacity (FVC) over 52 weeks in 3 subsets: (1) positive for anticentromere antibody (ACA), (2) positive for anti-RNA polymerase III antibody (ARA), and (3) negative for ACA, ARA, and antitopoisomerase I antibody (ATA).

Results: Among study participants who underwent baseline serological evaluation, 32/549 (5.8%) were ACA positive, 98/528 (18.6%) were ARA positive, and 127/526 (24.1%) were …

Bone Quality Response To Lifestyle Intervention In Older Adults With Obesity (Limb-Q Trial): A Randomised Controlled Trial, Giulia Gregori, Sanjay Mediwala, Michael Liebschner, Daeseung Kim, Mon S Bryant, Nina Klonis, Reina Armamento-Villareal, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Lifestyle interventions for weight loss might exacerbate age-related bone loss and osteoporosis. However, there is limited knowledge about their effects on bone quality. We examined whether lifestyle intervention can preserve or enhance bone quality, despite reductions in bone mineral density.

Methods: The Lifestyle Intervention to Improve Bone Quality (LIMB-Q) study was a randomised controlled trial conducted at Baylor College of Medicine and the Michael E DeBakey VA Medical Center (Houston, TX, USA) including older adults (aged 65-85 years) with obesity (BMI ≥30 kg/m2). Participants were randomly assigned to receive either an intensive lifestyle intervention (intensive lifestyle group, consisting of …

Critical Care Cadets: A Serious Game For Managing Mechanical Ventilation, Daniel Hassumani, Satid Thammasitboon, Fong Lam, Aarti Bavare, Moushumi Sur, Shelley Kumar, Thomas Reeves, Brian Rissmiller

Faculty, Staff and Students Publications

Background: Pediatric critical care medicine (PCCM) fellows require proficiency in mechanical respiratory support and ventilator management strategies. Traditional training methods have limitations, and there is a need to expedite the learning process. Serious games have emerged as effective supplements to traditional teaching methods, promoting knowledge acquisition through immersive and engaging experiences. However, there is a void in the context of complex decision making in mechanical ventilation management.

Objective: To develop a serious game to enhance the knowledge and practical strategies of PCCM fellows in mechanical ventilation management.

Methods: The game was designed on the basis of theory-informed design principles and …

High-Resolution Peripheral Quantitative Computed Tomography Reliability And Accuracy Of Bone Density And Morphology Properties In Children, Roman J Shypailo, Chadi Calarge, Punam K Saha, Xiaoliu Zhang, Xiaojie Chen, Stephanie Dinh, Xiaofan Huang, Babette S Zemel, Fida Bacha

Faculty, Staff and Students Publications

Volumetric bone density, microarchitecture, and strength measures using HR-pQCT are valuable measures of bone health in pediatrics. Our cross-sectional study evaluated bone measure reproducibility in pediatric participants using repeat HR-pQCT (XtremeCT II, Scanco Medical) scans of non-dominant distal tibia and radius of 30 healthy children and adolescents (7-17 yr, 47% female) by 2 technicians. Additionally, we examined HR-pQCT and micro-CT of 26 cadaveric distal tibia specimens to evaluate agreement between the modalities. All HR-pQCT scans were analyzed using manufacturer-provided software (Image Processing Language, Scanco Medical) and a fully automated, previously validated, in-house algorithm, offering measures of bone microstructure (eg, trabecular …

Predicting Clinical Success Of Ct-Based Functional Drained Liver Volume Assessment In Malignant Biliary Obstruction, Ethan Y Lin, Bruno C Odisio, Koustav Pal, Iwan Paolucci, Ryan P Kempen, Nicolas Cardenas, Paige Reed, Ketan Y Shah, Ahmed Awad, Rahul A Sheth, David Fuentes, Alda Tam

Faculty, Staff and Student Publications

Purpose

To compare the predictive accuracy of subjective versus objective assessment of three-dimensional functional drained liver volume (fDLV) for clinical success after percutaneous transhepatic biliary drainage (PTBD).

Materials and Methods

This retrospective study included patients with malignant biliary obstruction and hyperbilirubinemia who underwent de novo PTBD between January 2016 and February 2017. Clinical success was defined as achieving total bilirubin level less than 1.8 mg/dL (30.8 μmol/L) within 30 days after PTBD. Seven interventional radiologists independently categorized subjective fDLV into four groups: less than 30%, 30%–50%, 51%–75%, and greater than 75% of the total liver volume. Objective fDLV was calculated …