Digital Commons Network^™

Changes In Child Placement After Child Abuse Pediatrics Consultation For Suspected Physical Abuse, Kristine A Campbell, Antoinette L Laskey, Daniel M Lindberg, M Katherine Henry, Porcia Vaughn, James D Anderst, Megan M Letson, Angela N Bachim, Nancy S Harper, Carmen M Coombs, Lori D Frasier, Joanne N Wood

Faculty, Staff and Students Publications

Background: The association between child abuse pediatric (CAP) assessments and child welfare outcomes is unknown.

Objective: To determine the association between a CAP determination of the likelihood of physical abuse and change in child placement. We hypothesized that child race would be associated with CAP determination of abuse likelihood and child welfare outcomes.

Participants and setting: Children under age ten years with in-person CAP consultation and referral to child protective services for suspected physical abuse at a U.S. pediatric referral center participating in CAPNET, a CAP research network, from 02/2021 to 01/2023.

Methods: We created a series of generalized estimating …

Intracranial Rhizomucor Pusillus Mucormycosis In An Adolescent Triggering A Stroke Alert: A Case Report And A Systematic Review Of Pediatric Cases, Rima El Atrache, Melissa Mizerik, Joaquin Francisco Ruiz Lopez, Eric Engstrom, Karla Patricia Salazar, Mikael C Guzman-Karlsson, Daniel Davila-Williams, Sonali Sen, Kristen S Fisher, Jennifer C Erklauer

Faculty, Staff and Students Publications

Mucormycosis is a rare, life-threatening opportunistic infection primarily affecting immunocompromised patients. The available literature on Rhizomucor pusillus (R pusillus) infections of the central nervous system (CNS) in children is very limited. We present the case of an immunocompromised adolescent with intracranial mucormycosis due to R pusillus manifesting with stroke-like symptoms. This case highlights this rare condition's diagnostic complexity and management challenges. We include a review of the available literature on pediatric R pusillus CNS infections to increase awareness among health care providers.

Drivers Of Frequent Emergency Department Use In Socioeconomically Disadvantaged Older Adults: A Qualitative Study, Anita Chary, Annika Bhananker, Michelle Suh, David Leavitt, Elise Brickhouse, Shreya Tamma, Jose Ramirez, Mariana Rios, Aanand D Naik, Margaret Samuels-Kalow, Naomi George

Faculty, Staff and Student Publications

Background: The emergency department (ED) is the safety net for and a common point of healthcare access for socioeconomically disadvantaged older adults. Little is known about socioeconomically disadvantaged older ED patients' perspectives on their health, healthcare access, and ED use. Such insights could guide tailored interventions to address unmet clinical and health-related social needs (HRSN).

Methods: We performed a qualitative study with older adults in a single public safety net hospital ED. We interviewed patients age 60+ who had ≥ 4 ED 4 visits in the past year. Semi-structured interviews explored perceived health needs and motivations underlying ED visits. We …

Maternal Sleep Disorders And Maternal And Birth Outcomes: A Retrospective Us Claims-Based Study, Anayeli Herrera Morales, Audrey C Choh, Cici X Bauer, Stefan A Czerwinski, Miryoung Lee

Faculty, Staff and Student Publications

Introduction: Sleep disturbances are commonly reported during pregnancy and have been associated with adverse maternal, fetal, and neonatal outcomes. However, self-reported sleep disturbances may not be accurately reflected in the prevalence of clinically diagnosed sleep disorders.

Methods: Using Optum's de-identified Clinformatics Data Mart Database, we conducted a cross-sectional study of 93,767 American women who were pregnant with singletons between January 1, 2015 and June 30, 2021, to (1) determine the prevalence of clinically diagnosed sleep disorders and breathing abnormalities; (2) examine their associations with maternal health outcomes; and (3) examine their associations with birth outcomes. Sleep disorders and breathing abnormalities …

Genome-Wide Association Study Provides Novel Insight Into The Genetic Architecture Of Severe Obesity, Mohanraj Krishnan, Mohammad Yaser Anwar, Anne E Justice, Geetha Chittoor, Hung-Hsin Chen, Rashedeh Roshani, Alyssa Scartozzi, Rachel R Dickerson, Roelof A J Smit, Michael H Preuss, Nathalie Chami, Benjamin S Hadad, Esteban J Parra, Miguel Cruz, Qin Hui, Peter W F Wilson, Yan V Sun, Xiaoyu Zhang, Gregorio V Linchangco, Sharon L R Kardia, Jessica D Faul, David R Weir, Lawrence F Bielak, Heather M Highland, Kristin L Young, Baiyu Qi, Yujie Wang, Myriam Fornage, Christopher Haiman, Iona Cheng, Ulrike Peters, Charles Kooperberg, Steven Buyske, Joseph B Mccormick, Susan P Fisher-Hoch, Frida Lona-Durazo, Jesus Peralta, Jamie Gomez-Zamudio, Stephen S Rich, Kendra R Ferrier, Ethan M Lange, Christopher R Gignoux, Eimear E Kenny, Genevieve L Wojcik, Kelly Cho, Michael J Gaziano, Luc Djousse, Shuwei Liu, Dhananjay Vaidya, Renée De Mutsert, Navya S Josyula, Christopher R Bauer, Wei Zhao, Ryan W Walker, Jennifer A Smith, Leslie A Lange, Mariah C Meyer, Ching-Ti Liu, Lisa R Yanek, Miryoung Lee, Laura M Raffield, Ruth J F Loos, Penny Gordon-Larsen, Jennifer E Below, Kari E North, Mariaelisa Graff

The Brown Foundation: Institute of Molecular Medicine

Severe obesity (SevO) is a primary driver of cardiovascular diseases (CVD), cardiometabolic diseases (CMD) and several cancers, with a disproportionate impact on marginalized populations. SevO is an understudied global health disease, limiting knowledge about its mechanisms and impacts. In genome-wide association study (GWAS) meta-analyses of the tail end of the BMI distribution (≥95th percentile BMI) and two SevO phenotypes [Obesity Class III BMI ≥ 40 kg/m2 and Obesity Class IV BMI ≥ 50 kg/m2] in 159,359 individuals across eleven ancestrally diverse population-based studies followed by replication in 480,897 individuals across six ancestrally diverse studies, we identified and replicated three novel …

Utilization Of Outpatient Mental Health Services During And 2 Years After The Covid-19 Pandemic, Michelle A Hayek, Hye-Chung Kum, Sulki Park, Robert Ohsfeldt, Mark A Lawley, Michelle J Bovin

The Brown Foundation: Institute of Molecular Medicine

Objective: Analyze the impact of COVID-19 on outpatient mental health (OP-MH) utilization patterns, particularly telehealth, across eight different MH conditions with a 2-year follow-up.

Methods: This population-based cohort study uses a 5% random sample of Medicare beneficiaries aged ≥18 and newly diagnosed with one of the eight MH disorders: psychotic, depressive, bipolar, anxiety, trauma-related, substance-use, other MH disorders, and two or more MH disorders. Monthly OP-MH utilization patterns were compared among patients in 2020-2021 newly diagnosed in 2019 to comparable prepandemic cohorts newly diagnosed in 2017. Multiple logistic regression models were conducted to examine differences in telehealth utilization across MH …

Preoperative Focused Echocardiography On Patients With Fractured Neck Of Femur. Echonof-Iii Trial: Study Protocol For A Multicenter Randomized Controlled Trial, Ximena Cid-Serra, Alistair Royse, Andrea Bowyer, David Canty, Daniel Sessler, Sandy Clarke-Errey, Andre Denault, Dina Logiudice, Guy Ludbrook, D-Yin Lin, Yang Yang, Kavi Haji, Lisa Zucherrelli, Andrew J Palmer, Benjamin Piper, Thar Nyan Lwin, Stefan Dieleman, David Eccleston, Alwin Chuan, Richard Cooper, Gregory Henderson, Colin Royse

Faculty, Staff and Student Publications

Background: Hip fractures are common in older people and are associated with high perioperative mortality. Prompt surgical intervention within the first 48 h of fraction reduces complications; however, surgical urgency often precludes a comprehensive preoperative cardiac evaluation. Preliminary data suggests that performing a focused cardiac ultrasound (FCU) before surgery may reduce postoperative complications. We therefore propose to test the primary hypothesis that FCU reduces a 30-day composite of mortality and serious complications.

Methods: We plan a definitive multicenter pragmatic randomized trial that will enroll 2000 adults with hip fractures. Participants will be randomized before surgery to either receive FCU as …

Five-Year Change In Sleep Duration And Incident Alzheimer’S Disease And Related Dementias Among Lower-Income Older Adults, Hui Shi, Loren Lipworth, Qian Xiao, Xijing Han, Michael Mumma, Laura M Keohane, Danxia Yu, Corey J Bolton, Derek B Archer, Timothy J Hohman, Kelsie M Full

Faculty, Staff and Student Publications

Introduction: Little is known about change in sleep duration over time and Alzheimer's Disease and Related Dementias (ADRD) risk.

Methods: ADRD cases were identified among Southern Community Cohort Study participants enrolled in Medicare. Sleep duration was reported at enrollment and first study follow-up and categorized (short (< 7 hours), recommended (7-9) and long (> 9)), change was calculated between timepoints. Adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD.

Results: We identified 2,093 ADRD cases among 17,945 participants. Compared to maintaining optimal sleep duration (7-9 hours) over 5 years, suboptimal changes were associated with 20-69% greater ADRD risk: adjusted …

Steroid Hormone Biosynthesis And Dietary Related Metabolites Associated With Excessive Daytime Sleepiness, Tariq Faquih, Kaitlin S Potts, Pavithra Nagarajan, Bing Yu, Robert Kaplan, Carmen R Isasi, Qibin Qi, Kent D Taylor, Peter Y Liu, Satu J Strausz, Hanna M Ollila, Tianyi Huang, Russell P Tracy, Craig Johnson, Stephen S Rich, Clary B Clish, Jerome I Rotter, Susan Redline, Tamar Sofer, Heming Wang

Faculty, Staff and Student Publications

Background: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large-scale single- and pathway-level metabolomics analyses.

Methods: Metabolomics data were available for 877 metabolites in 6071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each …

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 …

Utility Of Whole-Slide Imaging For Rapid Evaluation Of Thyroid Fna: A Multireader Prospective Study, Mohammed S Ahmed, Dianna Klippel-Almaraz, Sara E Amin, Gloria H Sura, Uma Rani Kundu, Wendong Yu, Jogn M Stewart, Qiong Gan, Savitri Krishnamurthy

Faculty, Staff and Student Publications

Background: Rapid on-site evaluation (ROSE) of thyroid fine-needle aspiration biopsy (FNAB) improves diagnostic adequacy and facilitates ancillary molecular testing. In this prospective, multireader study, the authors evaluated the feasibility of using whole-slide images (WSIs) for ROSE to determine specimen adequacy and preliminary categorization (according to The Bethesda System for Reporting Thyroid Cytopathology [Bethesda]) of image-guided thyroid FNABs compared with conventional light-microscopic (LM) examination of the same specimens in a referral cancer center.

Methods: The authors evaluated 98 ultrasound-guided thyroid FNAB cases. Smears were stained with Papanicolaou and Diff-Quik and were scanned at ×20 magnification using a Leica Aperio CS2 scanner. …

Does Stem Design Affect Primary Stability Of Splined Tapered Fluted Stems? A Biomechanical Cadaver Study, Shuyang Han, Daniel C Mascarenhas, Camryn A Pletka, Jonathan E Gold, Sabir K Ismaily, Matthew Cao, Matthew W Brewer, Robert Frangie, Philip C Noble, David Rodriguez-Quintana

Faculty, Staff and Student Publications

Background: Tapered fluted stems are an excellent solution for revision hip arthroplasty following periprosthetic fractures. However, existing implant designs differ in terms of the number of splines, taper angle, and cross-sectional design, and there is a lack of knowledge on the biomechanical effect of these design variations. Therefore, the objective of this study was to compare the primary stability of two representative stem designs and the extent and distribution of stem-bone contact in a periprosthetic fracture model. It was hypothesized that a greater number of splines would lead to greater stability.

Methods: There were six pairs of cadaver femora included …

Role Of Exchange Proteins Directly Activated By Camp Signaling In Vascular Remodeling, Xiaodong Cheng, Hua Liu, Wenbo Zhang, Wenli Yang, Fang Mei

Faculty, Staff and Student Publications

Vascular remodeling is a complex process involving the coordinated actions of multiple cellular signaling pathways in various cell types, leading to structural and functional changes in blood vessels. These changes can be adaptive, as in wound healing, or maladaptive, as seen in chronic vascular diseases such as atherosclerosis, hypertension, and retinopathy. Exchange proteins directly activated by cAMP (EPACs) are key players in cAMP-mediated cell signaling, distinct from the more traditionally studied protein kinase A pathway. EPAC proteins are guanine nucleotide exchange factors for the small G proteins Rap1 and Rap2. Recent studies have also revealed noncanonical functions of EPAC1 involving …

Ixekizumab Improves Signs, Symptoms, And Quality Of Life In Patients With Axial Spondyloarthritis Irrespective Of Symptom Duration, Victoria Navarro-Compán, John D Reveille, Proton Rahman, José A Maldonado-Cocco, Marina Magrey, Rebecca Bolce, Tommaso Panni, Andris Kronbergs, Martin Rudwaleit

Faculty, Staff and Student Publications

Introduction: The objective of this study was to assess treatment response to ixekizumab, an interleukin-17A antagonist, by shorter versus longer symptom duration (< 5 years vs. ≥ 5 years) in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) up to 52 weeks.

Methods: This post hoc analysis used data from three randomized, placebo-controlled trials including patients with r-axSpA from COAST-V [biologic disease-modifying anti-rheumatic drug (bDMARD)-naïve] and COAST-W (tumor necrosis factor inhibitor-experienced) and patients with nr-axSpA from COAST-X (bDMARD-naïve). Patients received ixekizumab (80 mg every 2 or 4 weeks) or placebo through Week 16 and ixekizumab to Week 52. Assessments included the Assessment in SpondyloArthritis international Society 40% improvement (ASAS40) and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity …

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 …

Testing Measurement Invariance Of Self-Report And Interview Measures Of Borderline Personality Disorder Across Ethnic/Racial Groups Of Inpatient Adolescents, Salome Vanwoerden, Eric D Sumlin, Veronica Mclaren, Carla Sharp

Faculty, Staff and Student Publications

Borderline personality disorder (BPD) is a severe mental disorder that onsets during adolescence. Research examining sociocontextual differences in BPD presentation is limited and provides mixed results, highlighting the importance of further investigation and the evaluation of potential measure effects. This study assessed measurement invariance of two widely used adolescent measures (self-report—the Borderline Personality Features Scale for Children and semistructured interview—Childhood Interview of Diagnostic and Statistical Manual Borderline Personality Disorder) of BPD. Comparisons across inpatient psychiatric settings (n = 521 at a private inpatient; n = 378 at a public inpatient) and across self-identified Hispanic/Latinx (n = 193), Black …

Launching! To Adulthood, A Culturally Adapted Treatment Program For Military-Dependent Autistic Young Adults And Their Military Parents: A Pilot Study, Antonio F Pagán, Jordan Kenemore, Maj Mark Ahlenius, Linda Hernandez, Stephen Armstrong, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

Introduction: Military-dependent young adults (17-25 years old) with autism spectrum disorder (ASD) face significant barriers to accessing services during their transition to adulthood. Frequent relocations, disrupted care, and limited ASD-tailored interventions exacerbate the challenges for these families, with many young adults experiencing a "service cliff" as they age out of pediatric care and school-based services. Addressing these gaps is critical, particularly given the rising mental health challenges and executive dysfunction in this population. This study evaluates the preliminary efficacy of an adapted telehealth intervention, the Military-Launching! program, designed to support young adults with ASD and their military families.

Materials and …

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 …

In Situ Programming Of The Tumor Microenvironment To Alleviate Immunosuppression For Pancreatic Cancer Immunotherapy, Man Sun, Huan Zhang, Yarui Ma, Simiao Wang, Jiayi Chen, Yaxin Cui, Yun Zhang, Siyuan Hu, Dan Zhou, Pengchen Zhang, Yahui Liu, Betty Y S Kim, Wen Jiang, Xiaobing Wang, Zhaogang Yang

Faculty, Staff and Student Publications

Recent studies have highlighted the pivotal role of the cGAS‐STING pathway in cancer immunotherapy. However, clinical trials with cGAS‐STING pathway agonists have faced setbacks thanks to their short biological half‐life, lack of tumor specificity, and potential to promote tumor immune evasion. To address these challenges, a novel exosome‐based drug delivery platform, termed cmExoaCD11b is developed, designed to precisely target and reprogram the tumor microenvironment (TME) in situ for pancreatic cancer immunotherapy. cmExoaCD11b is engineered to encapsulate high copy numbers of IL‐12 mRNA and 2′3’‐cGAMP (cGAMP) and is functionalized with CD11b antibodies for targeted delivery to macrophages. Notably, cmExoaCD11b facilitated the …

Leveraging Existing Cohort Studies Of Mexican Women To Better Understand Hispanic Health And Cancer Risk, Dalia Stern, Liliana Gomez-Flores-Ramos, Britton Trabert, V Wendy Setiawan, Loïc Le Marchand, Henry Gomez, Paul A Scheet, Humberto Parada, Amber Pirzada, Martin Lajous, Leslie V Farland

Faculty, Staff and Student Publications

Background: Hispanics have been historically underrepresented in epidemiologic cancer research. Existing cohort studies focused on recruiting Hispanic participants have been relatively small, making studying cancer outcomes challenging. Therefore, we aimed to compare the distribution of cancer risk factors among Hispanic women of Mexican heritage (HWMH) participating in existing cohorts to explore the possibility of future data pooling efforts.

Methods: We used baseline data of HWMH from three US-based studies, the Mexican American Cohort (MAC; n = 19,797; 2001-2017), the Multiethnic Cohort (MEC; n = 18,007; 1993-1996), and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 4,022; 2008-2011), and …

Sex Disparities In Chlamydia And Gonorrhea Treatment In Us Adult Emergency Departments: A Systematic Review And Meta-Analysis, Rachel E Solnick, Rahi Patel, Ethan Chang, Carmen Vargas-Torres, Maaz Munawar, Carlin Pendell, Judith E Smith, Ethan Cowan, Keith E Kocher, Roland C Merchant

Faculty, Staff and Student Publications

BACKGROUND: Empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common in U.S. emergency departments (EDs) due to the delayed availability of test results. Local studies have identified sex-based disparities in sexually transmitted infection (STI) care, with females potentially receiving less empiric treatment than males. This study evaluates how STI treatment aligns with laboratory-confirmed results to quantify potential overtreatment and undertreatment rates and investigates sex differences for these outcomes.

METHODS: We conducted a preregistered (PROSPERO #241429) systematic review and meta-analysis of studies published between January 2010 and January 2025 in U.S. EDs, excluding studies conducted exclusively in pediatric settings. …

Which Score For What? Operationalizing Standardized Cognitive Test Performance For The Assessment Of Change, Cristan Farmer, Audrey Thurm, Tanvi Das, E Martina Bebin, Jonathan A Bernstein, Elizabeth Berry-Kravis, Joseph D Buxbaum, Charis Eng, Thomas Frazier, Antonio Y Hardan, Alexander Kolevzon, Darcy A Krueger, Julian A Martinez-Agosto, Hope Northrup, Craig M Powell, Latha Valluripalli Soorya, Joyce Y Wu, Mustafa Sahin, Developmental Synaptopathies Consortium

Faculty, Staff and Student Publications

Developmental domains, such as cognitive, language, and motor, are key concepts of interest in longitudinal studies of intellectual and developmental disabilities (IDD). Normative scores (e.g., IQ) are often used to operationalize performance on standardized tests of these concepts, but it is the interval-distributed person-ability scores that are intended for the assessment of within-individual change. Here we illustrate the use and interpretation of several Stanford Binet, 5th Edition score types (IQ, extended IQ, Z-normalized raw score, developmental quotient, raw sum score, age equivalent, and ability score) using data from two longitudinal studies of rare genetic conditions associated with IDD. We found …

Trop2 Expression In Salivary Gland Adenoidcystic Carcinoma (Acc) According To Histologic Subtype: Therapeutic Implications, Juliana Mota Siqueira, Yoshitsugu Mitani, Mario L Marques-Piubelli, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mutsumi Mitani, Giovanna Lopes Carvalho, Fabio Daumas Nunes, Leandro Luongo Matos, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC …

Mucinous Cystic Neoplasms Of The Pancreas And Liver Share A Similar Dna Methylation Profile With Mucinous Ovarian Tumors, Zoe Leoni, Teodor G Calina, Tobias Janik, Elena Grafenhorst, Eliane T Taube, Christopher Cm Neumann, Baoqing Chen, Elena I Braicu, Jalid Sehouli, Thomas Malinka, Wenzel Schöning, Johann Pratschke, George A Calin, David S Klimstra, Jamal K Benhamida, Irene Esposito, Markus Möbs, David Horst, Simon Schallenberg, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

The origin of mucinous cystic neoplasms (MCNs) remains a major challenge in hepato-pancreato-biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian-like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian-like stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome-wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN-P) and six hepatic MCNs (MCN-L). Using immunohistochemistry and targeted DNA sequencing, we unequivocally established the diagnosis of MCN. Unsupervised DNA methylation profile analysis of reference classes of pancreatic neoplasms (11 …

Secretogranin 2 Binds Lilrb4 Resulting In Immunosuppression, Xing Yang, Ryan Huang, Meng Fang, Yubo He, Jingjing Xie, Xiaoye Liu, Chengcheng Zhang, Qi Lou, Mi Deng, Wei Xiong, Cheryl Lewis, Zade Sadek, Ankit Gupta, Lianqi Chen, Xuewu Zhang, Lei Guo, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are important in a variety of physiological and pathological contexts, including tumor development, but how hormones might regulate their activity is unclear. Secretogranins, a family of secretory proteins in endocrine and neuronal cells, are proposed to function as prohormones or hormones, but their specific receptors are unknown. Here we show that secretogranin 2 (SCG2), a granin family member, functionally interacts with leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytic cells. Tumor-derived SCG2 promotes tumor growth in myeloid-specific LILRB4 transgenic mice in a T cell-dependent manner, whereas SCG2 deficiency in host mice impairs tumor progression and reduces infiltration of …

Spatial Colocalization And Molecular Crosstalk Of Myofibroblastic Cafs And Tumor Cells Shape Lymph Node Metastasis In Oral Squamous Cell Carcinoma, Ken Furudate, Shuya Kasai, Tadashi Yoshizawa, Yuya Sasaki, Kohei Fujikura, Shintaro Goto, Ryohei Ito, Koki Takagi, Tomoyuki Tanaka, Hiroshi Kijima, Kosei Kubota, Ken Itoh, Wataru Kobayashi, Koichi Takahashi

Faculty, Staff and Student Publications

Lymph node metastasis (LNM) is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). Previous research has implicated the partial epithelial-to-mesenchymal transition of tumor cells and myofibroblastic cancer-associated fibroblasts (myCAFs) in the LNM process. However, the underlying molecular mechanisms remain poorly understood. Here, we conducted a comprehensive molecular analysis integrating original and publicly available OSCC data from bulk genome and transcriptome, single-cell transcriptome, and spatial transcriptome analyses. We found that myCAFs were quantitatively and functionally activated in LNM-positive samples and spatially colocalized with OSCC cells within the invasive tumor front (ITF), providing a niche that may facilitate …

Reliability And Clinical Utility Of Heroin Craving Questionnaire Factors In Treatment-Enrolled Individuals With Opioid Use Disorder., April C. May, Breanna A. Mcnaughton-Long, Chrysantha B. Davis, Abigail J. Pleiman, Carmen Buchfink, Rayus Kuplicki, Hung-Wen Yeh, Martin P. Paulus, Jennifer L. Stewart

Manuscripts, Articles, Book Chapters and Other Papers

Psychometric properties of opioid craving assessments are underexamined, limiting their potential utility for treatment studies of opioid use disorder (OUD). To address this gap, the current study aimed to evaluate the predictive utility of the Heroin Craving Questionnaire (HCQ) for future substance use outcomes. Treatment-enrolled participants with OUD (n = 128) completed the Heroin Craving Questionnaire (HCQ) at baseline and were followed up to assess future return to use versus abstinence. Individuals who maintained abstinence at each of three follow-up visits also completed the HCQ again. Exploratory factor analysis (EFA) was performed on baseline HCQ items, and extracted factors were …

Plasma Lipidome Dysregulation In Frontotemporal Dementia Reveals Shared, Genotype-Specific, And Severity-Linked Alterations., Yohannes A Ambaw, Peter A Ljubenkov, Shubham Singh, Abdi Hamed, Sebastian Boland, Adam L Boxer, Tobias C Walther, Robert V Farese

Duncan NRI Faculty and Staff Publications

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Results: FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) …

Walking Interventions And Cognitive Health In Older Adults: A Systematic Review Of Randomized Controlled Trials, Jongwon Lee, Delia West, Christine Pellegrini, Jingkai Wei, Sara Wilcox, Jean Neils-Strunjas, A Caroline Rudisill, Daniela B Friedman, David X Marquez, Jenna Dzwierzynski, Joyce Balls-Berry, Rachelle Gajadhar, Chih-Hsiang Yang

2020-Current year OA Pubs

ObjectiveThis systematic review summarizes the effectiveness and the dose of walking interventions on specific cognition domains in older adults, including executive function, memory, attention, processing speed, and global cognition.Data sourcePublished randomized controlled trials in PubMed, Embase, and Web of Science until 10 May 2023.Study Inclusion and Exclusion CriteriaStudies include older adults without Alzheimer's or related dementias, involving a walking intervention and performance-based neuropsychological assessments for executive function, memory, processing speed, attention, or global cognition.Data ExtractionTwo independent research assistants reviewed 8424 studies and included 17 studies.Data SynthesisParticipant demographics, intervention features (type, intensity, time, frequency, duration, format, and context), cognitive assessment tools, …