Digital Commons Network^™

Concussion Knowledge, Attitudes, And Behaviors: A Comparison Study Of Youth Athletes And Their Parents, Summer D Ott, Sukhnandan K Cheema, Holden Axel, Seema S Aggarwal, Natalie R Parks, Nikhil Gattu, Philip Schatz

Faculty, Staff and Student Publications

Objective: Given the rising participation in high school athletics and the concerning trend of underreporting concussions, this study aims to identify and compare factors influencing sports-related concussion (SRC) awareness and reporting among youth athletes to their parents.'

Methods: Surveys were completed by 239 student-athletes (ages 13-19) and their parents, using a modified Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version (RoCKAS-ST) and demographic questionnaires. Statistical analyses, including paired sample t-tests, ANOVAs, and Spearman's correlations, compared knowledge and attitudes between groups and examined demographic influences.

Results: Parents showed significantly higher concussion knowledge (CKI: t(230) = 5.18, p < .001) and safer attitudes (CAI: t(230) = 10.62, p < .001) than their children. Knowledge scores varied significantly by race and socioeconomic status, with White parents scoring higher than Hispanic and African American parents (F(3,224) = 8.97, p < .001). Child knowledge scores also differed by race (F(4,223) = 3.73, p = .006) …

Sleep Eeg And Respiratory Biomarkers Of Sudden Unexpected Death In Epilepsy (Sudep): A Case-Control Study, Oman Magana-Tellez, Rama Maganti, Norma J Hupp, Xi Luo, Sandhya Rani, Johnson P Hampson, Manuela Ochoa-Urrea, Sudha S Tallavajhula, Rup K Sainju, Daniel Friedman, Maromi Nei, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Background: Sudden unexpected death in epilepsy (SUDEP) is the most common category of epilepsy-related mortality. Centrally mediated respiratory dysfunction has been observed to lead to death in the majority of cases of SUDEP. SUDEP also mainly occurs during nighttime sleep. This study seeks to identify sleep EEG and sleep-related respiratory biomarkers of SUDEP risk.

Methods: In this case-control study, we compared demographic, clinical, EEG, and respiratory data from people with epilepsy who later died of SUDEP (the SUDEP group) with data from age and sex-matched living people with epilepsy, classified as high risk of SUDEP (with ≥1 generalised tonic-clonic seizure …

A Comparative Study Of Clinically Used Fast Monte Carlo Dose Engines For Proton Therapy, Sherif M Gadoue, Narayan Sahoo

Faculty, Staff and Student Publications

Background: Several fast Monte Carlo (MC) codes have been implemented and used to simulate proton transport and calculate patient doses in proton therapy. The resulting dose is typically compared to full MC codes, rather than other fast MC codes.

Purpose: The primary goal of this study was to compare the gamma pass rates (GPRs) of dose calculation from different fast MC codes to evaluate the accuracy of the computation and modeling among these codes.

Methods: Two GPU codes and one CPU MC code were commissioned to model our clinical proton beamline at University of Texas MD Anderson Cancer Center. The …

Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Bruno Vincenzi, Jose Antonio Gonzalez Lopez, Lee Cranmer, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

Background: Perivascular epithelioid cell tumors (PEComa) are a rare family of mesenchymal tumors that include several subtypes. There are very limited data describing the natural history of patients with extra-visceral retroperitoneal PEComas of the retroperitoneum. The aim of this study is to describe the clinical features, treatment patterns, outcomes, and diagnostic challenges of primary extra-visceral retroperitoneal or abdominopelvic PEComa over the past decade.

Patients and methods: This is a retrospective analysis of all extra-visceral, non-renal, retroperitoneal, or abdominopelvic PEComas treated at participating centers over the past 10 years.

Results: A total of 77 patients from 13 centers were included. The …

Cancer-Induced Nerve Injury Promotes Resistance To Anti-Pd-1 Therapy, Erez N Baruch, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Xiayu Rao, Shamima Akhter, Tuany Eichwald, Tongxin Xie, Mohammad Balood, Adebayo Adewale, Shorook Naara, Hinduja N Sathishkumar, Shajedul Islam, William Mccarthy, Brandi J Mattson, Renata Ferrarotto, Michael K Wong, Michael A Davies, Sonali Jindal, Sreyashi Basu, Karine Roversi, Amin Reza Nikpoor, Maryam Ahmadi, Ali Ahmadi, Catherine Harwood, Irene Leigh, Dennis Gong, Paulino Tallón De Lara, Derrick L Tao, Tara M Davidson, Nadim J Ajami, Andrew Futreal, Kunal Rai, Veena Kochat, Micah Castillo, Preethi Gunaratne, Ryan P Goepfert, Sharia D Hernandez, Nikhil I Khushalani, Jing Wang, Stephanie S Watowich, George A Calin, Michael R Migden, Mona Yuan, Naijiang Liu, Yi Ye, William L Hwang, Paola D Vermeer, Nisha J D'Silva, Yuri L Bunimovich, Dan Yaniv, Jared K Burks, Javier Gomez, Patrick M Dougherty, Kenneth Y Tsai, James P Allison, Padmanee Sharma, Jennifer A Wargo, Jeffrey N Myers, Sebastien Talbot, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated …

Chromosome 20q Gene Signature Associated With Colorectal Cancer Progression, Jennifer Carter Jones, Apurva M Hegde, Yu-Jing Huang, Ganiraju Manyam, Vibhuti Srivastava, Jee Hoo Song, Yulan Cheng, Ralf Krahe, Warapen Treekitkarnmongkol, Stephen J Meltzer, Scott Kopetz, Stanley R Hamilton, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression …

Grpa-Prs: A Risk Stratification Method To Identify Genetically-Regulated Pathways In Polygenic Diseases, Xiaoyang Li, Brisa S Fernandes, Andi Liu, Jingchun Chen, Xiangning Chen, Zhongming Zhao, Yulin Dai

Faculty, Staff and Student Publications

Introduction: Polygenic risk score (PRS) assesses genetic risk for diseases, yet some high-risk individuals avoid illness while low-risk individuals develop it. We hypothesize that unknown counterfactors may reverse PRS predictions, offering insights into disease mechanisms and interventions.

Methods: We developed a novel framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification in Alzheimer's disease (AD) and schizophrenia (SCZ) cohorts. We calculated PRS models, stratified individuals by risk and diagnosis, and analyzed differential GRPas. For AD, analyses were further conducted with and without apolipoprotein E (APOE) effects, and across APOE haplotype.

Results: In AD, we identified several well-known AD-related pathways, including …

Relationship Between Quantitative Mri Ute T2* Of Acl Autografts And Bmi-Normalized Knee Laxity Within The First Year After Acl Reconstruction, Alonso Figueroa, Tomasz Bugajski, Dillon Humpal, Manickam Kumaravel, Walter Lowe, Payam Zandiyeh

Faculty, Staff and Student Publications

Background: The anterior cruciate ligament reconstruction (ACLR) graft undergoes a remodeling process that affects its structural properties. Ultrashort echo time T2* (UTE-T2*) imaging has been instrumental in examining this process. However, more research is needed on the postoperative relationship between UTE-T2* of the graft and its mechanical properties.

Purpose: To longitudinally examine ACL graft changes after ACLR using UTE-T2* decay coefficients and knee laxity and explore their relationship.

Study design: Case series; Level of evidence, 4.

Methods: A total of 31 patients who underwent ACLR had magnetic resonance imaging of their knees at 1, 6, and 12 months after surgery …

Bipolar Spinal Correction Reduces Transfusion Rate And Hospital Stay Compared With Traditional Posterior Spinal Fusion In Children With Scoliosis Secondary To Cerebral Palsy, Kristopher Lundine, Matthias Lu, Timothy C Borden, Samuel Yoon, Mia Percival, Michael B Johnson

Faculty, Staff and Student Publications

Purpose: Patients with neuromuscular scoliosis due to Cerebral Palsy (CP) are complex due to their curve severity and associated medical comorbidities. Spinal fusion is associated with high risk of peri-operative complications and large blood loss requiring allogenic red blood cell (RBC) transfusion. In June 2017, our tertiary paediatric institution implemented a new minimally-invasive approach for the treatment of neuromuscular scoliosis, Bipolar Spinal Correction (Bipolar), a technique first published by Miladi et al. in 2018. This study represents an analysis of the initial experience of this technique to see if it achieves the goal of minimally invasive surgery by decreasing surgical …

Lesion Absorbed Dose-Response Relationship In Patients With Metastatic Castration-Resistant Prostate Cancer Undergoing [177lu]Lu-Psma-617 Radiopharmaceutical Therapy, Milan Grkovski, Simone S Krebs, Joseph A O'Donoghue, Jonathan Kuten, Audrey Mauguen, Parnian Shobeiri, Daniel Lafontaine, Maria Thor, Finn Augensen, Josef J Fox, Neeta Pandit-Taskar, Mark P Dunphy, Lisa Bodei, John L Humm, Heiko Schöder

Faculty, Staff and Student Publications

The relationship between lesion absorbed dose (AD) and response in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) remains poorly understood. The objective of this work was to investigate the AD-response relationship at both the patient and lesion levels.

Methods: Sixty-five patients underwent serial SPECT/CT imaging after receiving 7.31 ± 0.27 GBq of [177Lu]Lu-PSMA-617. Single-time-point (STP) (Hänscheid approximation at 72 h) and multiple-time-point voxelwise dosimetry were performed. Patient response was evaluated by changes in serum prostate-specific antigen level before and after cycle 1 of RPT. The response of individual lesions was evaluated by the change in the …

Succinate Dehydrogenase B (Sdhb) Overexpression With Enzymatic Dysfunction Defines A Distinct Subtype Of Undifferentiated Pleomorphic Sarcoma, Miguel Esperança-Martins, Brian A Van Tine, Alliny C S Bastos, Et Al.

2020-Current year OA Pubs

UNLABELLED: Undifferentiated pleomorphic sarcoma (UPS) remains one of the most clinically aggressive and poorly characterized soft-tissue sarcoma subtypes. To uncover distinctive molecular traits for UPS, a multiomics analysis of UPS compared with leiomyosarcoma (LMS) and liposarcoma (LPS) was performed. Transcriptomic profiling revealed that UPS exhibits overexpression of genes encoding succinate dehydrogenase (SDH) subunits, particularly SDHB, SDHC, and SDHD, distinguishing it from LMS and dedifferentiated LPS. This finding was validated using The Cancer Genome Atlas Sarcoma dataset. High SDHB expression in UPS was significantly associated with shorter overall survival, shorter recurrence-free survival, and shorter overall survival from the date of first …

Alterations In Region-Specific Gray Matter Volume Underlying Callous Unemotional Traits In Adolescents, Johannah Bashford-Largo, Ru Zhang, R James R Blair, Karina S Blair, Jaimie Elowsky, Matthew Dobbertin, Ahria J Dominguez, Melissa Hatch, Tyler Patrick, Sahil Bajaj

Faculty, Staff and Student Publications

Background: Callous-unemotional (CU) traits during adolescence, for example, shallow affect or lack of remorse, have been shown to be a risk marker for antisocial behavior. Only a few studies have investigated structural brain alterations underlying CU traits, and findings are inconclusive. The study examines CU symptomatology and gray matter volume (GMV) associations.

Methods: Structural brain MRI data were collected from a sample of 578 adolescents (60% male) with a mean age of 14.85 years (SD = 2.30; range = 10-19 years). CU traits were indexed via the Inventory for Callous Unemotional Traits (ICU). Region-wise volumetric parameters were obtained following parcellation …

Family History Of Substance Use And Stressful Life Events Impact Adolescent Maturation Of Cerebral White Matter, Yizhou Ma, Ashley Acheson, Corneliu Bolbocean, Mustafa N Mithaiwala, Si Gao, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Xiaoming Du, A Ankeeta, Alia Warner, Antonio F Pagán, L Elliot Hong, Peter Kochunov

Faculty, Staff and Student Publications

Family history (FH) of substance use disorders (SUDs) and stressful life events (SLEs) are known risk factors for SUDs in adolescents and young adults. Cross‐sectional studies suggest that FH and SLEs affect adolescent white matter (WM) development and form abnormal WM patterns. Here, we examined the effects of FH, SLEs and their interaction on WM integrity in youths in the Adolescent Cognitive Brain Development (ABCD) study at baseline and 2‐ and 4‐year follow‐ups. ABCD youths (N = 8939, age ± SD = 9.9 ± 0.6 years, 4302 female) completed baseline diffusion tensor imaging, of which 5661 repeated the scan …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …

Is Bedtime Use Of Kratom (Mitragyna Speciosa) A Sleep Aid Or Disruptor? Examining Its Daily Effects And Individual Differences, Chung Jung Mun, Patricia Timmons, Leigh V Panlilio, Christopher D Verrico, Ynhi T Thomas, C Austin Zamarripa, David H Epstein, Kirsten E Smith

Faculty, Staff and Students Publications

Kratom (Mitragyna speciosa) is a psychoactive botanical native to Southeast Asia increasingly used in the U.S. for various self-reported benefits, including sleep improvement. However, empirical evidence concerning kratom’s effects on sleep is limited. Here, we examined the association between bedtime kratom use and self-reported sleep outcomes in naturalistic settings across consecutive days, while also exploring sex and chronic pain status as potential moderators. A secondary analysis was conducted using the data from a 15-day ecological momentary assessment (EMA) study of 357 U.S. adults who reported regularly using kratom. Participants made daily reports of their bedtime kratom use and …

Aging Affects Lipid Homeostasis In Lacrimal Glands By Upregulating Lipogenesis And Changing Its Specificity, Seher Yuksel, Prashant Kumar, Sydney E Krenz, Kaitlin K Scholand, Zhiyuan Yu, Anastasiia Ivanova, Helen P Makarenkova, Sarah F Hamm-Alvarez, Igor A Butovich, Cintia S De Paiva

Faculty, Staff and Students Publications

Purpose: The lacrimal gland (LG) develops age-related alterations. This study investigated the lipid content of the accumulated secretions within the murine aged LG.

Methods: C57BL/6J animals of different ages (3 months, 12 months, and 20-26 months) were used. Published data of bulk RNA sequencing of aged LGs were used to investigate lipid pathways. Exorbital LGs were excised for histology or PCR. Histologic sections were stained with standard histochemical stains or immunostained using anti-adiponectin, anti-perilipin 2 antibodies, and BODIPY dye. LG lipidomes were investigated using unbiased, untargeted high-resolution liquid chromatography/mass spectrometry (LC/MS), and the data were processed using unbiased, untargeted principal …

Inhibition Of Ros1 Activity With Lorlatinib Reversibly Suppresses Fertility In Male Mice, Yuki Oyama, Kentaro Shimada, Haruhiko Miyata, Rie Iida-Norita, Chihiro Emori, Maki Kamoshita, Seiya Oura, Ryohei Katayama, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Background: Inhibition of sperm maturation in the epididymis is a promising post-testicular strategy for short-acting male contraceptives. It has been shown that ROS1, a receptor tyrosine kinase expressed in the epididymis, is essential for epididymal differentiation, sperm maturation, and male fertility in mice. However, it is unknown if inhibition of ROS1 suppresses male fertility reversibly.

Objectives: Our study aimed to investigate the effects of ROS1 inhibitor administration in male mice on sperm function and fertility.

Materials and methods: We used lorlatinib, an anti-cancer drug that inhibits ROS1. We treated 10-week-old sexually mature male mice with lorlatinib for 3 weeks and …

Protein Kinase Rock1 Activates Mitochondrial Fission Linking To Oxidative Stress And Muscle Atrophy, Meijun Si, Jihong Chen, Rizhen Yu, Hongchun Lin, Feng Li, Sungyun Jung, Sandhya S Thomas, Farhard R Danesh, Yanlin Wang, Hui Peng, Zhaoyong Hu

Faculty, Staff and Students Publications

Introduction: Chronic kidney disease (CKD) is associated with protein-energy wasting, characterized by a reduction in muscle mass and strength. Although mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of muscle wasting, underlying mechanisms remain unclear.

Methods: Here, we used transcriptomic analysis, metabolomics analyses, and mouse gene manipulation to investigate the effects of mitochondrial plasticity and oxidative stress on muscle wasting the subtotal nephrectomy mouse models of CKD. The mice with CKD were age- and sex-matched to sham-operated controls.

Results: Through these approaches, Rho-associated kinase ROCK1 emerged as a key molecule responsible for the observed mitochondrial fission and oxidative …

High Prevalence Of Abnormal Baseline Lung Function In Pediatric And Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report From The Transpire Study, Jane Koo, Richard Cooper, Stephanie L Edwards, Adam Lane, Sara Katherine Loveless, Lauren Strecker, Kelly E Lake, Kasiani C Myers, Christopher Towe, Jessica Patti, Laura L Walkup, Kathryn A Wikenheiser-Brokamp, Margaret L Macmillan, Philip Lacher, Tamara Griffin, Merve Tekman, Gabriel Salinas Cisneros, Kevin Wu, Matthew S Zinter, Fernando A Urrego, K Scott Baker, Matthew F Abts, Sheri Ballard, Jason L Freedman, Alexander Caraballo, Lisa R Young, Maureen B Josephson, Julian L Allen, Devaney M Camburn, Erin E Doherty, Mashid Sababi Azamian, Martha Arredondo, Manuel Silva-Carmona, Leslie E Lehmann, Wai Wong, Jonathan M Gaffin, William Mcalpine, Mona Li, Samuel B Goldfarb, Jason C Woods, Stella M Davies

Faculty, Staff and Students Publications

Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.

Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.

Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), …

Effects Of The Kcnq (Kv7) Channel Opener Ezogabine On Resting-State Functional Connectivity Of Striatal Brain Reward Regions, Depression, And Anhedonia In Major Depressive Disorder: Results From A Randomized Controlled Trial, Avijit Chowdhury, Sarah Boukezzi, Sara Costi, Sara Hameed, Yael Jacob, Ramiro Salas, Dan V Iosifescu, Ming-Hu Han, Alan Swann, Sanjay J Mathew, Laurel Morris, James W Murrough

Faculty, Staff and Students Publications

Background: Major depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests that targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.

Methods: A double-blind, randomized, placebo-controlled clinical trial in individuals with MDD ages 18 to 65 years compared daily dosing with ezogabine (n= 19) with placebo (n …

Using Latent Patient-Centered Fear Extinction Profiles To Guide Treatment In Pediatric Ocd, Katherine M Ingram, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire

Faculty, Staff and Students Publications

Background: While exposure with response prevention (ERP) is the frontline treatment for pediatric obsessive-compulsive disorder (OCD), not all patients benefit. Impairments in extinction learning are implicated in pediatric OCD's etiology and treatment, with impaired pre-treatment extinction learning associated with worse ERP outcomes. However, available methods for assessing patients' difficulties with fear extinction are costly and underdeveloped. In response, we used person-centered profiles to characterize latent fear extinction patterns among youth with OCD, and investigated the degree to which scores on common rating scales correspond to profile membership.

Methods: Youth with OCD (n=98) completed a diagnostic clinical battery followed by a …

Bi-Allelic Loss-Of-Function Variants In Poc5 Cause A Syndromic Retinal, Endocrine, And Neuromuscular Ciliopathy, Anneke T Vulto-Van Silfhout, Ingrid M Jazet, Suzanne Yzer, Jeroen Pas, Serwet Demirdas, Elisabeth F C Van Rossum, Alberta A H J Thiadens, Ronald Van Beek, Lonneke Haer-Wigman, Daniela Q C M Barge-Schaapveld, Charlotte Brasch-Andersen, Simon Frost, Miriam Bauwens, Elfride De Baere, Irina Balikova, Filip Van Den Broeck, Monika Weisz-Hubshman, Pascal Joset, Peter Miny, Isabel Filges, Susanne Kohl, Pietro De Angeli, Laura Kühlewein, Jan-Philipp Bodenbender, Tobias Haack, Karin Poths, Lidia Fernandez-Caballero, Marta Corton, Fiona Blanco Kelly, Carmen Ayuso, Peggy Martínez-Esteban, John Vissing, Jordi Díaz-Manera, Volker Straub, Ana Töpf, Siying Lin, Gavin Arno, William L Macken, Jennifer Spillane, Radha Ramachandran, Erik De Vrieze, Tjakko Van Ham, Susanne Roosing, Machteld M Oud

Faculty, Staff and Students Publications

Purpose: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants.

Methods: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines.

Results: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with …

Implementation Of A Package Of Emergency Care Interventions And Clinical Outcomes, Corey B Bills, Paul Wesseh, Catherine Cooper, Taylor W Burkholder, Lane Epps, Michael Jaung, Emilie J Calvello Hynes, Alex Mayah, John K Shakpeh, Kayla Enriquez

Faculty, Staff and Students Publications

Importance: Investments in emergency care systems are vital to ensuring universal health coverage and improving health outcomes in low- and middle-income countries.

Objective: To assess whether a package of emergency care interventions is associated with improved patient mortality and clinical care quality.

Design, setting, and participants: This pre-post quality improvement study was conducted at a single urban referral hospital emergency unit (EU) in Monrovia, Liberia, to assess clinical and educational outcomes resulting from the implementation of a package of interventions from January 1, 2018, through June 30, 2019. Final analysis was performed in November 2023. Data from a random subset …

Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).

Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.

Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …

Lac-Phe Induces Hypophagia By Inhibiting Agrp Neurons In Mice, Hailan Liu, Veronica L Li, Qingzhuo Liu, Yao Liu, Cunjin Su, Hueyxian Wong, Na Yin, Hesong Liu, Xing Fang, Kristine M Mcdermott, Hueyzhong Wong, Meng Yu, Longlong Tu, Jonathan C Bean, Yongxiang Li, Mengjie Wang, Yue Deng, Yuhan Shi, Olivia Z Ginnard, Yuxue Yang, Junying Han, Megan E Burt, Sanika V Jossy, Chunmei Wang, Yongjie Yang, Benjamin R Arenkiel, Dong Kong, Yang He, Jonathan Z Long, Yong Xu

Faculty, Staff and Students Publications

Lactate-derived N-lactoyl-phenylalanine (Lac-Phe) was recently identified as an lactate-derived circulating metabolite that reduces feeding and obesity, but mechanisms that underlie the metabolic benefits of Lac-Phe remain unknown. Here we demonstrated that Lac-Phe directly inhibits hypothalamic neurons that express Agouti-related protein (AgRP), resulting in an indirect activation of anorexigenic neurons in the paraventricular nucleus of the hypothalamus (PVH). We also found that both AgRP inhibition and PVH activation are required to mediate Lac-Phe-induced hypophagia. Further, we show that Lac-Phe inhibits AgRP neurons via activating the ATP-sensitive potassium (KATP) channel, and inhibition of the KATP channel blunts effects of Lac-Phe to suppress …

Family Income And Polygenic Scores Are Independently But Not Interactively Associated With Cognitive Performance Among Youth Genetically Similar To European Reference Populations, S E Paul, N M Elsayed, S M C Colbert, R Bogdan, A S Hatoum, D M Barch

2020-Current year OA Pubs

Cognitive abilities are heritable and influenced by socioeconomic status (SES). It is critical to understand the association between SES and cognition beyond genetic propensity to inform potential benefits of SES-based interventions and to determine if such associations vary across (i) cognitive domains, (ii) facets of SES, and/or (iii) genetic propensity for different aspects of cognition. We examined the contributions of neighborhood socioeconomic advantage, family income, and polygenic scores (PGS) for domains of cognition (i.e., general cognitive ability, executive function, learning and memory, fluid reasoning) in a sample of children (ages 9-10;

Microglia Regulate Gabaergic Neurogenesis In Prenatal Human Brain Through Igf1, Diankun Yu, Samhita Jain, Andi Wangzhou, Beika Zhu, Wenyuan Shao, Elena J Coley-O'Rourke, Stacy De Florencio, Jaeyeon Kim, Jennifer Ja-Yoon Choi, Mercedes F Paredes, Tomasz J Nowakowski, Eric J Huang, Xianhua Piao

2020-Current year OA Pubs

GABAergic neurons are essential cellular components of neural circuits. Their abundance and diversity have increased significantly in the human brain, contributing to the expanded cognitive capacity of humans

A Modification To The Brand Transfer For Claw Hand: The Four-Tailed Extensor Carpi Radialis Brevis To Lateral Band Transfer, Lauren E Wessel, Nirbhay S Jain, Ambika E Paulson, Carrie Bettlach, Mitchell A Pet, Amy M Moore

2020-Current year OA Pubs

BACKGROUND: Claw deformity is a devastating consequence of low ulnar nerve palsy, resulting in loss of finger function. Traditionally, the Brand transfer is a favored intervention but requires lengthy grafts and bulky tenorrhaphies, risking adhesions in the lumbrical canal. We present a modified Brand tendon transfer, which extends the extensor carpi radialis brevis (ECRB) into 4 tails for individual grafting into the lateral band, decreasing adhesion risk and graft length need.

METHODS: Nine consecutive patients with claw hand were examined in detail to confirm the diagnosis and appropriateness for claw-correction surgery by the senior author. All patients underwent our modified …

Spatial Multiomics Of Acute Myocardial Infarction Reveals Immune Cell Infiltration Through The Endocardium, Florian Wünnemann, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Myocardial infarction (MI) continues to be a leading cause of death worldwide. Even though it is well established that the complex interplay between different cell types determines the overall healing response after MI, the precise changes in the tissue architecture are still poorly understood. In this study, we generated an integrative cellular map of the acute phase after murine MI using a combination of imaging-based transcriptomics (Molecular Cartography) and antibody-based highly multiplexed imaging (Sequential Immunofluorescence). This enabled us to evaluate cell type compositions and changes at subcellular resolution over time. We observed the recruitment of leukocytes to the infarcted heart …