Digital Commons Network^™

Utilizing A Culture System For Horizontal Cells To Study Neural Circuit Assembly In The Developing Mouse Retina, Ross M Perez, Yong H Park, Ajeet Singh, Collin Todora, Marlon F Mattos, Daniela Becerril, Rajashree Venkatraman, Arlene A Hirano, Nicholas C Brecha, Rinki Ratnapriya, Benjamin J Frankfort, Elizabeth Zuniga-Sanchez

Faculty, Staff and Students Publications

The precise wiring of the nervous system relies on neurons extending their processes at the right time and place to find their appropriate synaptic partner. The mechanisms that determine when and where neurons extend their neurites during synaptogenesis remains a central question in the field. In the present study, we used a cell culture system coupled with live imaging to investigate the wiring mechanisms in the developing mouse retina. We focused on horizontal cells which are a class of interneurons in the outer mouse retina known to synapse selectively to the distinct types of photoreceptors. Previous research has shown horizontal …

Updates In Mycobacterial Keratitis Diagnosis And Treatment, Uma L Balakrishnan, Ryan T Wallace, Patricia Chévez-Barrios, Alejandro Arboleda, Masih U Ahmed

Faculty, Staff and Students Publications

Mycobacterial keratitis is an uncommon but challenging form of infectious keratitis, often associated with postsurgical eyes. Clinical presentation is variable and may be difficult to recognize, resulting in delays in diagnosis and challenges in management. Traditional diagnostic techniques from corneal scrapings are limited by slow organism growth and may yield negative results. Treatment is challenging due to antimicrobial resistance and typically requires prolonged multidrug therapy. Advances in diagnostic modalities, antimicrobial therapies, surgical approaches, and adjunctive treatments such as corneal crosslinking have improved clinicians' ability to mitigate or avoid severe visual consequences. Despite these developments, optimal management strategies remain incompletely defined, …

Common And Recurrent Dysregulated Molecular Network Of Placental Hypoxia And Associated Vasculogenesis And Angiogenesis In Fetal Growth Restriction, Wei Li, Xiaoyi Bai, Oi Ka Chan, Maran Bo Wah Leung, So Ling Lau, Chi Chiu Wang, Tak Yeung Leung

Faculty, Staff and Students Publications

Fetuses with fetal growth restriction (FGR) and selective FGR (sFGR) face elevated health risks both before and after birth. Although the underlying pathomechanisms remain unclear, placental dysfunction is recognized as a major contributing factor. By integrating untargeted transcriptomic data from FGR/sFGR placentae, this study identified 69 differentially expressed mRNAs (DEmRs) and eight differentially expressed miRNAs (DEmiRs). Functional enrichment analysis demonstrated significant enrichment in the angiogenesis and vasculogenesis pathways, with the hypoxia-related genes

Professionalism In Practice: A Novel Approach To Integrating Small Doses Of Case-Based Professionalism Education Into Monthly Grand Rounds., Allison H Taylor, Andrew Caruso, Kelley Arredondo, Ellen M Friedman, Stacey R Rose

Faculty, Staff and Students Publications

Introduction: Professionalism is a critical construct across the health professions, though learners and faculty report feeling underprepared to navigate difficult situations; education in professionalism is challenged by the absence of a universal definition, time constraints due to overcrowded curricula, and the lack of consistent messaging to learners and faculty.

Methods: Professionalism in Practice (PiP) was developed to provide small doses (∼5 minutes) of case-based professionalism education as part of an existing educational forum (Grand Rounds) to optimize attendance of both learners and faculty. Each vignette highlighted a common professionalism challenge and was aligned with an AAMC professional competency. Sessions were …

Unraveling Posttranslational Modification Complexity: Advances In Quantitative Histone Proteoform Mass Spectrometry, Karl F Poncha, Alyssa T Paparella, Nicolas L Young

Faculty, Staff and Students Publications

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Case Report: Primed Dendritic Cell Immunotherapy For Multiple Solid Tumors, Jeffrey Jones, Aly Alrabaa, William Decker, Luis Ferbeyre, Gregorio Viramontes, Rafael Gonzalez, Elideth Angulo, Antonio Zamudio, Raul Hernandez, Stephen Noga, Susana Hernandez-Reyes, Paul Zhang, Darryl Smith, Ara Karamanian, Luis Tamara, Dalton Greenwood, Matthew Halpert

Faculty, Staff and Students Publications

Many patients with advanced solid tumors ultimately develop resistance to conventional therapies, with especially limited options for those experiencing rapid progression or poor performance status, highlighting the need for personalized immunotherapies capable of inducing durable responses. In this retrospective case series, we describe the clinical course and outcomes of five adults (4 male, 1 female; median age 51 years [range, 39-62]) with metastatic solid tumors who achieved complete and durable remission following doubly loaded autologous dendritic cell therapy after failure of standard treatments, such as immune checkpoint inhibition, radiation, surgery, or endocrine therapy. Five patients, including prostate adenocarcinoma (n=1), malignant …

Prevention Beyond Deterrence, Benjamin A. Barsky

Faculty Scholarship

This Article reconceptualizes preventive justice—the public safety paradigm that seeks to prevent harm before it occurs. Scholars have long documented how cities have advanced this paradigm through largely punitive measures, notably variants of broken windows policing, which posit that aggressive misdemeanor enforcement deters more serious crime. Yet in the aftermath of the 2020 George Floyd protests, and as underscored recently in City of Grants Pass v. Johnson, these measures have faced a legitimacy crisis—prompting calls for nonpunitive responses to nonviolent incidents.

This Article establishes a preventive justice approach that advances health and safety without emphasizing crime deterrence. It draws on …

Retrenchment, Segregation, And Public Education: A Five-Year Analysis Of State Exclusionary School Discipline Legislation, Thalia Gonzalez, Will Martel

Faculty Scholarship

Notwithstanding the decision in Brown v. Board of Education formally ending educational segregation and more than two decades of state reform, the legislative landscape protecting minoritized children from the structural violence of exclusionary school discipline has dramatically shifted in less than five years. From the passage of state “Teacher’s Bills of Rights” to mandatory expulsions, rescissions of prior protections, and new categories of removal, a retrenchment of anti-inclusion legislation—and its corollary, educational carcerality— has occurred. While studies of other forms of legislative retrenchment in K–12 public schools, such as anti-Critical Race Theory and Don’t Say Gay laws, literacy bans, and …

Correction: Establishing Standardized Transthoracic Echocardiography Reference Ranges For Mouse Models: Insights Into The Impact Of Anesthesia, Sex, And Age, Manuela A Oestereicher, Christopher S Ward, Elida Schneltzer, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Ghina Bou About, Mohammed Selloum, Hamid Meziane, Michelle Stewart, Lydia Teboul, Clare Norris, Dale Pimm, Marina Kan, Federico López Gómez, Robert Wilson, Mayra Monroy, Sheraz Pasha, Eva Zabrodska, Jan Prochazka, David Pajuelo Reguera, Zuzana Nichtova, Yann Herault, Sara Wells, Helen Parkinson, Jason D Heaney, Radislav Sedlacek, Xiang Gao, Martin Hrabe De Angelis, Nadine Spielmann

Faculty, Staff and Students Publications

This corrects the article "Establishing standardized transthoracic echocardiography reference ranges for mouse models: insights into the impact of anesthesia, sex, and age" in volume 12, 1695034.

Case Series Of Nizon-Isidor Syndrome By Heterozygous Variants In Med12l With Further Evidence Of Mitotic Instability In One Case With Diploid-Triploid Mosaicism, Russell Stewart, Kimberly M Ezell, Deanna S Bell, Brian Corner, Ashley Mcminn, Joy D Cogan, Rizwan Hamid, Lynette Rives, John A Phillips, Nina Paddu, Gitanjali Srivastava, Ronit Marom, Farah A Ladha, Claudia Soler-Alfonso, Rachel Franciskovich, Mary Koziura, Sumit Pruthi, Gabriele Richard, Christina B Sheedy, Undiagnosed Diseases Network, Thomas Cassini

Faculty, Staff and Students Publications

Nizon-Isidor syndrome is a rare disorder caused by heterozygous variants in MED12L, with only eight documented cases in the literature. Here, we present three additional cases of this syndrome. Proband 1 was a 7-year-old female who presented with developmental delay, right-leg hemihypertrophy, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizures, morbid obesity, and a pelvic kidney. Genome sequencing (GS) revealed a MED12L variant, NM_053002.5:c.3559+2T>G. Both computational models and transcriptomic analysis confirmed that this variant induced splice loss of MED12L exon 25. Probands 2 and 3 presented with overlapping phenotypes of developmental delay; sequencing …

Efficacy And Safety Of Pyrimidine Nucleos(T)Ide Therapy In Thymidine Kinase 2 Deficiency, Michio Hirano, Caterina Garone, Richard Haas, Carmen Paradas, Fernando Scaglia, Irene Rebollo Mesa, Carl Chiang, Anny-Odile Colson, Susan Vanmeter, Cristina Domínguez-González

Faculty, Staff and Students Publications

Thymidine kinase 2 deficiency (TK2d) (MIM 609560) is an ultra-rare, autosomal recessive mitochondrial myopathy caused by TK2 variants, leading to mitochondrial DNA depletion and/or multiple deletions. People with thymidine kinase 2 deficiency experience progressive myopathy, bulbar weakness and respiratory insufficiency, often losing the ability to walk, eat and breathe independently. Doxecitine and doxribtimine represents the first approved treatment for patients with thymidine kinase 2 deficiency with age of symptom onset ≤12 years by the US Food and Drug Administration and the European Medicines Agency; previously, disease management was limited to supportive care. We investigated the efficacy and safety of pyrimidine …

The Words Community Dwelling, Spanish-Preferring Mexican/Mexican American Adults Use To Talk About Alzheimer’S Disease And Genetic Testing: Implications For Education And Outreach, Jamie C Fong, Fatima I Chavez, Karla Silos, Mirna L Arroyo-Miranda, Gabriela Castro Castro, Mark E Kunik, Joshua M Shulman, Luis D Medina

Faculty, Staff and Students Publications

Introduction: Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E (APOE) Ɛ4, underscoring gaps in understanding genetic risk across H/L heritage groups. H/L adults remain underrepresented in AD research that uses genetic data for participant stratification. To inform culturally appropriate educational materials for 16 million U.S. Spanish speakers, we identified culturally salient words Spanish-preferring H/L adults use to describe AD and genetic testing beyond APOE.

Methods: Community-residing, Spanish-preferring Mexican/Mexican American adults (n = 14) completed freelisting interviews, a method eliciting …

Highly Variable Expressivity Of A Cnv Deletion Involving Tbx4 In Three Deceased Siblings With Lung Developmental Disorder And Their Mildly Affected Mother And Grandfather, Przemyslaw Szafranski, Tomasz Gambin, Michal Kadlof, Michał Denkiewicz, Dariusz Plewczynski, Hyun Jeong Kim, Gail Deutsch, Nahir Cortes-Santiago, Salmo Raskin, Paweł Stankiewicz

Faculty, Staff and Students Publications

Single nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving TBX4 have been associated with pulmonary arterial hypertension, ischiocoxopodopatellar syndrome, and lethal lung developmental disorders (LLDDs). Thus far, all large CNV deletions encompassing entire TBX4 have been found to have arisen de novo. Here, we present a three-generation family with three neonate siblings who died within 35-66 days due to histopathologically diagnosed LLDD. Whole-genome sequencing identified an ~108-kb CNV deletion encompassing TBX4 in all three infants. The deletion was also found in their mother with a history of pneumonia and persistent thick upper airway secretions and in the maternal grandfather …

Suicidal Ideation In Spinocerebellar Ataxia, Levi Peppel, Ruo-Yah Lai, Christian Rummey, Puneet Opal, Jeremy D Schmahmann, Christopher M Gomez, Henry Paulson, Theresa A Zesiewicz, Susan Perlman, George Wilmot, Sarah H Ying, Chiadi U Onyike, Khalaf O Bushara, Michael D Geschwind, Karla P Figueroa, Stefan M Pulst, Sub H Subramony, Antoine Duquette, Tetsuo Ashizawa, Ali G Hamedani, Marie Y Davis, Sharan R Srinivasan, Matthew R Burns, Nadia Amokrane, Lauren R Moore, Vikram G Shakkottai, Liana S Rosenthal, Sheng-Han Kuo, Chi-Ying R Lin

Faculty, Staff and Students Publications

Objective: Suicidal ideation has not been extensively studied in spinocerebellar ataxias (SCAs). The authors examined whether individuals with SCAs have increased suicidal ideation and related factors.

Methods: The authors studied patients with genetically confirmed SCAs enrolled in the Clinical Research Consortium for the Study of Cerebellar Ataxia cohort, examining the percentages of patients with SCA subtypes 1, 2, 3, and 6 who reported suicidal ideation and comparing findings with nationally representative data from the National Survey on Drug Use and Health (NSDUH). Clinical characteristics that may contribute to suicidal ideation in SCAs, including age, disease duration, sex, ataxia severity, depression, …

Age-Related Variations Of The Hemodynamic Response Function Spatially Resolved Across Human Cerebral Cortex, Nooshin J Fesharaki, Amanda Taylor, David Ress

Faculty, Staff and Students Publications

Normal aging leads to regional vascular and neural alterations. Age-related impairments in neurovascular coupling (NVC) affect the blood-oxygen-level-dependent (BOLD) hemodynamic response function (HRF) measured with functional magnetic resonance imaging, causing changes in both amplitude and temporal dynamics. Previously, global, systematic age-related changes in HRF characteristics were demonstrated, consistent with known microvascular aging effects. In this follow-up study, a standard space was used to compare spatially resolved cortical HRF dynamics between sex-balanced groups of young and older adults. The results showed substantial age-related differences in both HRF amplitude and timing across distinct cortical regions. Nearly twice as much cortical area exhibited …

Quantifying Uncertainty In Landscape Evolution And Provenance Analysis: Insights From Statistical And Numerical Modelling, Vivian Carmello Grom

LSU Doctoral Dissertations

Landscape evolution models (LEMs) and detrital zircon provenance are widely used to investigate Earth surface processes, yet both face challenges related to quantifying model behavior and interpreting sedimentary signals under realistic, heterogeneous conditions. This thesis addresses these challenges through analysis and case studies that develop and apply new approaches for analyzing landscape dynamics and assessing uncertainties in sediment provenance.

Chapter 1 introduces a quantitative framework for evaluating LEM outputs using Shannon Entropy, Moran’s I, and Geary’s C. Applied to simulations with steady uplift, periodic uplift, spatially variable uplift, and a timeseries of DEMs, these metrics capture spatial organization and information …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Wenyi Wang, Pavithra Nagarajan, Heming Wang, Michael R Brown, Amy R Bentley, Qin Hui, Aldi T Kraja, John L Morrison, Jeffrey R O'Connel, Songmi Lee, Karen Schwander, Traci M Bartz, Lisa De Las Fuentes, Mary F Feitosa, Xiuqing Guo, Xu Hanfei, Sarah E Harris, Zhijie Huang, Mart Kals, Christophe Lefevre, Massimo Mangino, Yuri Milaneschi, Peter J Van Der Most, Natasha L Pacheco, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Quan Sun, Yasuharu Tabara, Dina Vojinovic, Yujie Wang, Stefan Weiss, Qian Yang, Wei Zhao, Wanying Zhu, Md Abu Yusuf Ansari, Hugues Aschard, Pramod Anugu, Themistocles L Assimes, John Attia, Laura D Baker, Christie Ballantyne, Lydia Bazzano, Eric Boerwinkle, Brain Cade, Hung-Hsin Chen, Wei Chen, Yii-Der Ida Chen, Zekai Chen, Kelly Cho, Ileana De Anda-Duran, Latchezar Dimitrov, Anh Do, Todd Edwards, Tariq Faquih, Aroon Hingorani, Susan P Fisher-Hoch, J Michael Gaziano, Sina A Gharib, Ayush Giri, Mohsen Ghanbari, Hans Jörgen Grabe, Mariaelisa Graff, C Charles Gu, Jiang He, Sami Heikkinen, James Hixson, Yuk-Lam Ho, Michelle M Hood, Serena C Houghton, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Tuomas O Kilpeläinen, Pirjo Komulainen, Henry J Lin, Gregorio V Linchangco, Annemarie I Luik, Jintao Ma, James B Meigs, Joseph B Mccormick, Cristina Menni, Ilja M Nolte, Jill M Norris, Lauren E Petty, Hannah G Polikowsky, Laura M Raffield, Stephen S Rich, Renata L Riha, Thomas C Russ, Edward A Ruiz-Narvaez, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, Tamar Sofer, Botong Shen, Jingxian Tang, Kent D Taylor, Maris Teder-Laving, Rima Triatin, Michael Y Tsai, Henry Völzke, Kenneth E Westerman, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Xiaofeng Zhu, Jennifer E Below, Simon R Cox, Michelle Evans, Myriam Fornage, Ervin R Fox, Nora Franceschini, Sioban D Harlow, Elizabeth Holliday, M Arfan Ikram, Tanika Kelly, Timo A Lakka, Deborah A Lawlor, Changwei Li, Ching-Ti Liu, Reedik Mägi, Alisa K Manning, Fumihiko Matsuda, Alanna C Morrison, Matthias Nauck, Kari E North, Brenda Wjh Penninx, Michael A Province, Bruce M Psaty, Jerome I Rotter, Tim D Spector, Lynne E Wagenknecht, Ko Willems Van Dijk, Lifelines Cohort Study, Million Veteran Program, Cashell E Jaquish, Peter Wf Wilson, Patricia A Peyser, Patricia B Munroe, Paul S De Vries, W James Gauderman, Yan V Sun, Han Chen, Clint L Miller, Thomas W Winkler, Dabeeru C Rao, Susan Redline, Diana Van Heemst

Faculty, Staff and Student Publications

Background and aims: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

Methods: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Spatial Evolution In Temporal Dynamics Of Hemodynamic Response Function In Human Superior Colliculi With Ultra-High-Resolution Mri At 9.4t, Nooshin J Fesharaki, Artemy Vinogradov, David Ress, Jung Hwan Kim

Faculty, Staff and Student Publications

The superior colliculus (SC) plays a crucial role in multisensory integration, visual information processing, saccadic target selection, visual selective attention, and decision making. In particular, the SC has a key role in oculomotor coordination, following a rostro-caudal organization. The rostral SC, which corresponds to foveal representation, is linked to fixation, microsaccades, smooth pursuit, and vergence adjustments. In contrast, the caudal SC, representing more peripheral visual field, is associated with the large gaze shifts (saccades). However, evidence regarding whether this functional gradient is preserved in the human SC remains limited. In this study, we employed a sequence-following visual-motor task to specifically …

Use Of A Medication Management Algorithm In Depressed Youth Living With Hiv: Secondary Analysis Of A Multisite Randomized Controlled Trial, Graham J Emslie, Beth D Kennard, Kristin Baltrusaitis, Sophia M Jones, Jessica M Jones, Jaime G Deville, Kathleen Pitts, David E Shapiro, Allison Eliscu, Larry K Brown

Faculty, Staff and Students Publications

Objectives: Depression is a prevalent co-occurring condition in youth living with HIV. This report is a secondary analysis of a multisite cluster randomized trial evaluating the efficacy of a health and wellness cognitive behavioral therapy (CBT) combined with a medication management algorithm utilizing measure-based care (COMB-R) compared with enhanced standard of care (ESC). We describe and compare antidepressant prescribing strategies (i.e., antidepressant treatment, type of antidepressant) for youth living with HIV at COMB-R sites to those at ESC sites over the 24-week intervention. We also describe self-reported adherence to antidepressants.

Methods: Participants (12-24 years) were youth living with HIV diagnosed …

Mir-302 Regulates Pancreatic Progenitor Pool And Pancreatic Size, Ziyue Z Yang, Caroline G Snider, Ronald J Parchem

Faculty, Staff and Students Publications

Disruptions in pancreatic development can lead to health issues such as pancreatic agenesis and congenital diabetes mellitus. Understanding pancreatic organogenesis is critical for elucidating disease mechanisms and developing regenerative therapies. The pancreas consists of endocrine and exocrine cells, both of which are derived from multipotent progenitor cells (MPCs). MPC proliferation and differentiation are tightly controlled by multiple mechanisms, including post-transcriptional regulation by miRNAs. However, these regulatory factors are not fully understood. Here, we profiled miRNA expression in MPCs and identified that mir-302 was highly enriched during the earliest stages of pancreatic development. Loss of mir-302 resulted in reduced pancreatic size …

Amino Acids And Lean Mass Accretion In Preterm Neonates, Antonio C Ramos Dos Santos, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Purpose of review: This review evaluates recent evidence on how total protein and energy intake, amino acid composition, and nutrient delivery modality influence protein synthesis in preterm neonates, with the goal of informing nutritional strategies to support optimal lean mass accretion and growth.

Recent findings: Preterm neonates exhibit anabolic resistance to feeding due to impaired insulin and amino acid signaling in skeletal muscle. Enteral nutrition, especially fortified human milk, supports better lean mass accretion and neurodevelopment than parenteral nutrition. Intermittent bolus feeding and pulsatile leucine supplementation during continuous feeding further enhance mTORC1-dependent translation initiation signaling and protein synthesis efficiency in …

Courts Of Indian Offenses, Courts Of Indian Resistance, Alexandra Fay

Articles, Chapters in Books and Other Contributions to Scholarly Works

No abstract provided.

Comparing Rotational Thromboelastometry And Standard Coagulation Assays For Predicting Intraoperative Bleeding In Pediatric Liver Transplantation, Kirby Deshotels, Trung Nguyen, Jun Teruya, Muhammed Umair M Mian, Kelby Fuller, Sanjiv Harpavat, Anna Banc-Husu, Amir Navaei, John Goss, Moreshwar Desai, Arun Saini

Faculty, Staff and Students Publications

Background: Utility of preoperative rotational thromboelastometry (ROTEM) over standard coagulation assays (SCAs) in predicting intraoperative bleeding during orthotopic liver transplantation (OLT) in children with liver failure (LF) remains unclear.

Methods: In this single-center retrospective cohort of pediatric OLT recipients, we compared the predictive values of preoperative ROTEM parameters (intrinsic pathway (INTEM) maximum clot firmness (MCF), extrinsic pathway (EXTEM) clotting time (CT), INTEM CT, and fibrinogen-based (FIBTEM) MCF) and the corresponding SCAs (platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen level, respectively) for significant intraoperative bleeding (blood loss of > 22 mL/kg; i.e., ≥ 85th percentile for …

Once-Weekly Navepegritide In Children With Achondroplasia: The Approach Randomized Clinical Trial, Ravi Savarirayan, Ciara Mcdonnell, Carlos A Bacino, Daniel G Hoernschemeyer, Janet M Legare, M Jennifer Abuzzahab, Paul L Hofman, Philippe M Campeau, Josep Maria De Bergua Domingo, Leanne M Ward, Kevin Smit, Alden Smith, Meng Mao, Michael S Ominsky, Lærke C Freiberg, Aimee D Shu, Hanne B Hove

Faculty, Staff and Students Publications

Importance: Historically considered a skeletal dysplasia characterized by disproportionate short stature, achondroplasia is a condition with multisystemic effects due to the widespread expression of the fibroblast growth factor receptor 3 variant throughout the body, impacting muscle, neurological function, cardiorespiratory health, and health-related quality of life.

Objective: To evaluate the efficacy, safety, and tolerability of once-weekly navepegritide, an investigational prodrug of C-type natriuretic peptide, while assessing benefits beyond growth that may have important implications for complications and health-related quality of life in children with achondroplasia.

Design, setting, and participants: Enrollment for this pivotal phase 2b, randomized, double-blind, placebo-controlled trial (APPROACH) was …

Latent Factor Modeling Reveals Unexpected Spatial Heterogeneity In Human Alzheimer's Disease Brain Transcriptomes, Rami Al-Ouran, Chaozhong Liu, Linhua Wang, Zhijian Yu, Ying-Wooi Wan, Chaohao Gu, Xiqi Li, Gerarda Cappuccio, Mirjana Maletic-Savatic, Aleksandar Milosavljevic, Joshua M Shulman, Hu Chen, Zhandong Liu

Faculty, Staff and Students Publications

Alzheimer's disease is characterized by complex molecular and cellular heterogeneity, which complicates efforts to identify consistent biomarkers and therapeutic targets. To better characterize the heterogeneity, we applied latent factor modeling to RNA sequencing data from approximately 2,500 human Alzheimer's disease brain samples, uncovering underlying patterns in gene expression. These transcriptional groups demonstrated unique gene expression profiles related to synaptic and neuronal pathways, vasculature development, and protein folding and antigen processing. Notably, this latent factor reflects variation in spatial sampling. Adjusting for the latent factor improved the identification of differentially expressed genes in disease samples. This finding suggests that spatial heterogeneity …

Dynamic Progression Of Ectopic Lymphoid Structure Formation In Lacrimal Glands Of A Sjögren’S Disease Murine Model, Sara Abdelhamid, Alison V Ramirez, Emre Aksan, Elizaveta A Demianova, Cintia S De Paiva, Maria C Edman, J Andrew Mackay, Sarah F Hamm-Alvarez

Faculty, Staff and Students Publications

Background: Sjögren's Disease (SjD) is a chronic autoimmune condition characterized by lymphocytic infiltration of lacrimal glands (LG) and salivary glands (SG). In SG, these immune structures have properties of ectopic lymphoid structures (ELS) and appear to play a critical role in disease pathology. While the presence of ELS in patients' SG biopsies is linked to disease severity, their presence and composition in LG has not been well characterized.

Methods: The properties and time course of apparent ELS development in LG from the male non-obese diabetes free (NOR) sub-strain of the Non-Obese Diabetic (NOD) mice was investigated at stages encompassing early …

Disrupted Intrathalamic And Thalamocortical Structural Covariance Networks In Posttraumatic Stress Disorder, Nick Steele, Ahmed Hussain, Delin Sun, C Lexi Baird, Courtney Russell, Neda Jahanshad, Lauren E Salminen, Miranda Olff, Jessie L Frijling, Dick J Veltman, Saskia B J Koch, Laura Nawijn, Mirjam Van Zuiden, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Sheri Koopowitz, Yuval Neria, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Benjamin Suarez-Jimenez, Ashley A Huggins, Jennifer Stevens, Kerry Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Ivan Rektor, Pavel Říha, Milissa L Kaufman, Lauren A M Lebois, Justin T Baker, Anthony King, Israel Liberzon, Mike Angstadt, Nicholas D Davenport, Seth G Disner, Scott R Sponheim, Thomas Straube, David Hofmann, Guang Ming Lu, Rongfeng Qi, Amit Etkin, Adi Maron-Katz, Xin Wang, Austin Kunch, Hong Xie, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven E Bruce, Josh Cisler, Marisa Ross, Ryan Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Brandee Feola, Jennifer U Blackford, Bunmi O Olatunji, Geoffrey May, Steven M Nelson, Evan M Gordon, Chadi G Abdallah, Ruth Lanius, Maria Densmore, Jean Théberge, Richard W J Neufeld, Paul M Thompson, Rajendra A Morey

Faculty, Staff and Students Publications

The thalamus is a heterogeneous structure crucial for corticocortical communication, affective–perceptual integration, motor preparation, and memory-related functions. Posttraumatic stress disorder (PTSD) is characterized by various symptoms that likely relate to thalamic functions. Group-level and individual differential structural covariance (SC) analyses were conducted on intrathalamic, thalamocortical, and thalamosubcortical volumetric networks by segmenting structural MRI data from 2,784 subjects (PTSD n = 1,306; controls n = 1,478) into 25 thalamic nuclei per hemisphere. We found that PTSD was associated with stronger intrathalamic and thalamocortical network strength and stronger SC between the limbic thalamus and the somatomotor and auditory thalamus. PTSD severity was …

Using Lotilaner Ophthalmic Solution, 0.25% To Treat Demodex Blepharitis In Patients Who Were Initially Misdiagnosed: A Case Series, Laura M Periman, Richard Lindstrom, Paul Karpecki, Brandon Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Selina Mcgee, Kelly K Nichols, Stephen Pflugfelder, Christopher E Starr, Nandini Venkateswaran, Elizabeth Yeu, Cecelia Koetting

Faculty, Staff and Students Publications

Introduction: Demodex blepharitis (DB) is a chronic ocular inflammation caused by Demodex mite infestation of the eyelid. DB is often misdiagnosed, as some of its clinical findings and patient-reported outcomes overlap with those of other ocular surface diseases. The Demodex Expert Panel on Treatment and Eyelid Health (DEPTH) has reached consensus on the symptomatology, diagnosis, and treatment of DB. Consensus findings from the DEPTH group include that collarettes are pathognomonic for DB and that lotilaner ophthalmic solution, 0.25%, the first and only FDA-approved treatment for DB, should be the first-line treatment for the disease. This case series highlights two instances …

Improving Compliance With Safe Sleep Guidelines For Vulnerable Patients In A Community Safety Net Hospital Neonatal Intensive Care Unit, Andrew Beverstock, Samantha Carlton, Hillary Lee, Thomas Lu, Kelsi Morgan, Ashlee Smith-Patel, Kelli Phillips, Joseph Hagan, Pablo Lohmann, Caraciolo Fernandes, Lisa Owens, Daniela Dinu

Faculty, Staff and Students Publications

Objectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.

Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to …