Medicine and Health Sciences Commons^™

Ins-17 Acts As A Nutrient Deprivation Signal To Mediate Adult Iis-Regulated Associative Behaviors In C. Elegans, Emily J Leptich, Priyadharshini Vijayakumar, Edward W Pietryk, Meredith I Williams, Rachana Rajupalem, Rachel N Arey

Faculty, Staff and Students Publications

Insulin/Insulin-like growth factor 1 (IGF-1) signaling (IIS) is a pleiotropic signaling pathway that functions across tissues to coordinate phenotypic changes in response to nutrient status. Thus, the ubiquity of the IIS pathway hinders efforts to elucidate the mechanisms driving specific IIS-related phenotypes. Previous research in the nematode worm C. elegans has demonstrated that loss of function of the IIS transmembrane receptor (IR) ortholog, DAF-2, results in a doubled lifespan and enhanced learning and memory behaviors in young and aged animals. However, these findings are the result of reducing DAF-2 receptor function rather than modulating ligand-receptor interactions. In the current study, …

The Association Between Physical Activity, Sedentary Time, And Sleep With Risk Of Hepatocellular Carcinoma In Patients With Cirrhosis, Samuel Ma, Yossef Alsabawi, Fasiha Kanwal, Hao Duong, Laith Elserag, Amit G Singal, Nicole E Rich, Saira Khaderi, Sumeet K Asrani, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

Background: The majority of hepatocellular carcinoma (HCC) cases arise in patients with cirrhosis, with known major risk factors of hepatitis B (HBV) or C (HCV) infection, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-associated liver disease (ALD). However, the impact of additional risk factors that act independently or jointly on the pathogenesis of HCC in cirrhosis patients is unknown. The aim of this study was to determine whether sleep, sedentariness, or physical activity levels play a role in the progression of cirrhosis to HCC.

Methods: We systematically collected data on sleep, sedentary time, and physical activity from the ongoing prospective …

Androgen Activity In The Male Embryonic Hindbrain Drives Lethal Pfa Ependymoma, Jiao Zhang, Winnie Ong, Alexandra Rasnitsyn, Ricardo Daniel Gonzalez, Rodrigo Lopez Gutierrez, Polina Balin, Amr Saadeldin, Xiaochong Wu, Maria C Vladoiu, Vicente Santa-Maria Lopez, Fernando Gonzalez-Salinas, Navneesh Yadav, Dinesh Mohanakrishnan, Kannan Boosi Narayana Rao, Raja Gopal Reddy Mooli, Hinda Najem, Sebastian Pacheco, Kaitlin Kharas, Cory Richman, David Przelicki, Evan Y Wang, Haipeng Su, Rachel Naomi Curry, Runze Yang, Michelle Masayo Kameda-Smith, Bryn Livingston, David Scott, Zaili Luo, Mingyang Xia, Namal Abeysundara, Anders W Erickson, Ncedile Mankahla, Lucas Zhongming Hu, Chu Pan, Raul Suarez, Ning Huang, Yihao Wu, Hao Wang, Tajana Douglas, Jonelle Pallota, Steven Hébert, Karen Ng, Krystin Mantione, Heather Whetstone, Hassaan Maan, Hussein Lakkis, Juyeun Lee, Sadeesh K Ramakrishnan, Yanxin Pei, Yujie Tang, Frank Y Lin, Guillermo Aldave, Marco Gallo, Robert M Friedlander, Faiyaz Notta, Laura K Donovan, Murali Chintagumpala, Bo Wang, Yun Li, Daniel D De Carvalho, Zhaolei Zhang, Ying Mao, Wei Hua, Charles Eberhart, Calixto-Hope G Lucas, Sriram Venneti, Poul H Sorensen, Alberto Delaidelli, Hao Li, Wenhao Zhou, Jason Kirk, Dean G Tang, Tao Jiang, Hailong Liu, Justin D Lathia, Hiromichi Suzuki, Jeremy N Rich, Lincoln D Stein, Nada Jabado, Vijay Ramaswamy, Q Richard Lu, Amy B Heimberger, Craig Daniels, Kulandaimanuvel Antony Michealraj, Claudia L Kleinman, Michael D Taylor

Faculty, Staff and Students Publications

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects …

Robotic Single-Incision Laparoscopic Surgery For The Management Of Endometriosis: First Experience Via The Da Vinci Sp Platform, Qiannan Yang, Daniel Y Lovell, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the feasibility and mid-term outcomes of Robotic single-port single-incision laparoscopic surgery (RSP-SILS) for endometriosis management.

Methods: A retrospective analysis was conducted on 50 adult women with endometriosis who underwent RSP-SILS via the da Vinci SP platform between November 2023 and July 2025.

Results: Median total operative time was 142 min, robot dock time was 3 min, and robot console time was 99 min. Median estimated blood loss was 25 mL. No conversion occurred. Reported mid-term outcomes included 1 case each of pelvic haematoma, Clostridioides difficile colitis, and umbilical surgical site infection, as well as 3 cases of …

Methodological Progress Note: Logic Models, Molly J Horstman, Kyler M Godwin

Faculty and Staff Publications

Logic models are an accessible tool to organize the planning, management, and evaluation of programs across healthcare disciplines. This methodological progress note describes the five standard components of a logic model (Inputs, Activities, Outputs, Outcomes, and Impact) and provides guidance for developing a logic model. Logic models offer a visual representation of the work and theory of a program and should be created with input from all interested parties. Logic models are living tools that need to be revised as programs evolve and new information becomes available.

Kidney Disease And Heart Failure: Recent Advances And Current Challenges: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Carolyn S P Lam, Biykem Bozkurt, David Z I Cherney, Justin A Ezekowitz, Meg J Jardine, Sadiya S Khan, Magdalena Madero, Mark J Sarnak, Jozine M Ter Maaten, Michael Cheung, Jennifer M King, Morgan E Grams, Michel Jadoul, Nisha Bansal

Faculty, Staff and Students Publications

Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, which elevates the risks of hospitalization, disease progression, and death. Despite advances in treating each condition independently, many challenges remain in diagnosing and managing them in combination. In March 2024, Kidney Disease: Improving Global Outcomes (KDIGO) held the Controversies Conference on Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Discussions highlighted the complex, bidirectional relationship between HF and CKD, including shared risk factors and overlapping pathophysiology as well as nuances in interpreting biomarkers such as natriuretic peptides and serum creatinine. Sodium-glucose cotransporter-2 inhibitors, renin-angiotensin-aldosterone system inhibitors, and emerging …

All-Cause And Cause-Specific Mortality In Patients With Bipolar Ii Disorder, Chih-Wei Hsu, Yang-Chieh Brian Chen, Edward Chia-Cheng Lai, Andrew A Nierenberg, Michael Berk, Sheng-Yu Lee, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Importance: Whether bipolar II disorder (BD-II) is associated with increased long-term mortality remains uncertain because most studies have not distinguished BD-II from bipolar I disorder (BD-I).

Objective: To examine whether BD-II is associated with elevated all-cause and cause-specific mortality compared with population controls, unaffected siblings, and those with BD-I.

Design, setting, and participants: This population-based, retrospective cohort study used data from Taiwan's National Health Insurance Database from January 1, 2000, to December 31, 2022. Individuals 12 years or older with 2 or more psychiatrist-assigned BD-II diagnoses were individually matched to 4 controls without BD-II by sex and birthdate. Additional comparisons …

Weaning Drives Microbiome-Mediated Epigenetic Regulation To Shape Immune Memory In Mice, Li Yang, Robert C Peery, Shirui Zhou, Xiaomin Chen, Leah M Farmer, Fabiola Gutierrez, Stephanie Fowler, Lanjing Zhang, Julia M Salamat, Karen Riggins, Jiejun Shi, Lanlan Shen

Children’s Nutrition Research Center Staff Publications

During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, …

Ethical Controversies In Organ Procurement: A National Survey On Public Perceptions Of Thoracoabdominal Normothermic Regional Perfusion, Trevor M Bibler, Jill Oliver Robinson, Adam Omelianchuk, Tariq Nisar, Savitri Fedson, Ariel N Levchenko, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Thoracoabdominal normothermic regional perfusion (TA-NRP) would likely expand the quantity and quality of organs procured after controlled circulatory death donation in the United States, yet its ethical permissibility remains contested. We surveyed a representative sample of US adults (n = 975) with the goal of assessing their perspectives on the ethical permissibility of TA-NRP. After reading a neutral description of TA-NRP, participants judged its permissibility, reviewed 5 critic and 5 supporter arguments (in random order), and chose which argument they found most convincing. Multivariable logistic regression examined predictors of agreeing with critics. Before exposure to the arguments, 51.5% stated that …

Dental Insurance Status Among Formerly Incarcerated Older Adults, Alexander Testa, Rafael Samper-Ternent, Dylan B Jackson, Kyle T Ganson, Vahed Maroufy, Jason M Nagata, Ana C Neumann

Faculty, Staff and Student Publications

Formerly incarcerated individuals have poorer oral health and less frequent dental care utilization than the general population. However, prior work has overlooked the relationship between prior incarceration and disparities in dental insurance coverage. Using data from the Health and Retirement Study (n = 11,638), findings from multiple logistic regression analyses demonstrate that formerly incarcerated older adults are significantly less likely to have dental insurance coverage (odds ratio [OR] = 0.745, 95% confidence interval [CI] = 0.608, 0.912). After accounting for the income-to-poverty ratio, this association was no longer statistically significant. Analyses using the Karlson-Holm-Breen method demonstrated that approximately 45% of …

Sexual Health And Relationship Education Needs Of People In Recovery For An Opioid Use Disorder, J Michael Wilkerson, Kathryn R Gallardo, I Niles Zoschke, Hannah L N Stewart, Serena A Rodriguez, Michael U Anosike, Jason Pullin, Sheryl A Mccurdy

Faculty, Staff and Student Publications

People in recovery with histories of sex and drug-linked behavior (SDB) have an increased risk of substance use recurrence. However, sexual health concerns remain largely unaddressed by recovery support services researchers and practitioners. The purpose of this analysis was to describe the sex and relationship concerns of people in recovery for an opioid use disorder living in level II and level III recovery homes. Recovery homes are sober living homes that the National Association for Recovery Residences classifies into four levels based on staffing and service provision. We interviewed 93 residents and thematically analyzed 92 of the resulting transcripts; one …

Robo2 Variants Associated With Atrial Septal Defect Define A Novel Regulatory Element, Seong Won Kim, Michael Parfenov, Laura Rodriguez-Murillo, David A Conner, Arun Sharma, Inga Peter, Feng Xiao, Olivia Layton, Angela Tai, Tarsha Ward, Lauren K Wasson, Joshua M Gorham, Erica Mazaika, Valentina N Lagomarsino, Tracy L Young-Pearse, Elizabeth Goldmuntz, Hiroko Wakimoto, A J Agopian, David M Mckean, Steven R Depalma, William T Pu, Christine E Seidman, Bruce D Gelb, Jonathan G Seidman

Faculty, Staff and Student Publications

Background: Atrial septal defects (ASDs) are a prevalent type of congenital heart disease. Previous GWAS (Genome-Wide Association Studies) have identified common variants associated with ASDs, though their mechanisms remain unknown. We aimed to expand insights into the architecture of common variants associated with ASD risk and elucidate functional mechanisms.

Methods: We conducted a GWAS using isolated ASD cases and healthy controls and replicated findings in an independent cohort. We examined epigenetic marks within this ASD locus in human induced pluripotent stem cell-derived cardiomyocytes and fetal human hearts. We characterized the consequences of deletions introduced by CRISPR-Cas9 mutagenesis of human induced …

The All-Payer Claims Database After The Gobeille Supreme Court Decision: Assessing The Impact On Fatal Opioid-Related Overdose Research, Jack Cordes, Cici Bauer, Dana Bernson, Marc R Larochelle, Wenjun Li, Jiahao Cao, Olaf Dammann, Thomas J Stopka

Faculty, Staff and Student Publications

Objective: To determine the consequences of the Gobeille v. Liberty Mutual Supreme Court decision on the representativeness of the Massachusetts all-payer claims database (APCD). The loss of individuals captured in the APCD may vary demographically, geographically, and in the capture of fatal opioid-related overdose (OOD).

Data sources and study setting: We used 2013-2021 data from the Massachusetts Public Health Data Warehouse (PHD), which links person-level APCD records to other datasets. The APCD includes commercially-insured health claims mandatorily reported pre-Gobeille. Post-Gobeille, reporting from self-insured plans, a subset of commercially-insured plans, became voluntary.

Study design: In a repeated cross-sectional design, we compared …

Transfusion In Transit: A Decade Of Prehospital Blood Transfusion In Pediatric Trauma, Krysta M Sutyak, Eunise C Chen, Lea Mock, Rudolfo Cabrera, Jeannette M Joly, Kuojen Tsao, Bryan A Cotton, David E Meyer, Charles S Cox, Kevin P Lally, Natalie A Drucker

The Brown Foundation: Institute of Molecular Medicine

Background: Prehospital blood transfusion improves mortality in adults, with limited evidence in children. This study describes prehospital blood transfusion in pediatric trauma patients and the impact on shock index, pediatric adjusted (SIPA).

Methods: This study is a retrospective cohort study of trauma patients younger than 18 years who received blood transfusions during helicopter transport to a Level 1 pediatric trauma center from 2011 to 2023. Primary outcome was change in SIPA at time of emergency department (ED) arrival with prehospital transfusion. Secondary subgroup analysis was performed based on transport origin.

Results: Of 137 patients, 58% (80 of 137 patients) were …

Natural Language Generation In Healthcare: A Review Of Methods And Applications, Mengxian Lyu, Xiaohan Li, Ziyi Chen, Jinqian Pan, Cheng Peng, Sankalp Talankar, Yonghui Wu

Faculty, Staff and Student Publications

Objective: This study presents a systematic review of natural language generation (NLG) methods and applications in the medical domain, providing quantitative and qualitative analyses to answer four key research questions regarding methods, evaluation, applications, and challenges of NLG in healthcare.

Methods: We searched PubMed, ACM Digital Library, Web of Science, Science Direct, Scopus, Embase, and ACL Anthology for NLG-related studies in healthcare from 2018 to 2024. Out of 3,988 research articles, 113 met the inclusion criteria and were analyzed across data modality, model architecture, evaluation metrics, and application domain.

Results and conclusion: NLG in healthcare has grown substantially, with annual …

Traumatic Brain Injury And Risk Of Early-Onset Dementia: A Population-Based Cohort Study, Aishwarya Saravanan, Katherine Giorgio, Natalia Lakomski, Andrea L C Schneider, Barbara A Olson-Bullis, Behnam Sabayan, James S Pankow, Paul S De Vries, Kristine Yaffe, Alexa Beiser, Abbas Dehghan, Elizabeth A Peterson, Rachel Zmora, John J Stephen, Denise Scholtens, Maxwell Mansolf, Lenore J Launer, Richard F Maclehose, Pamela L Lutsey, Norrina B Allen, Sanaz Sedaghat

Faculty, Staff and Student Publications

Introduction: We investigated the association between traumatic brain injury (TBI) and incidence of early-onset dementia (EOD) versus late-onset dementia (LOD).

Methods: We included 501,710 UK Biobank participants (average age 56.5). Over a median 13.6 years of follow-up, 836 developed EOD (before 65) and 8947 developed LOD (after 65). We estimated hazard ratios (HRs) for TBI's association with EOD and LOD using Cox proportional hazard models with TBI as a time-varying exposure and coefficient.

Results: TBI was associated with higher risk of both EOD (HR: 4.06 [95% confidence interval: 3.13, 5.26]) and LOD (HR: 2.51 [2.31, 2.72]. Among participants included in …

Continuous Versus Bolus Norepinephrine Administration To Treat Hypotension After Induction Of General Anaesthesia In Low-To-Moderate Risk Noncardiac Surgery Patients: A Randomised Trial, Kristen K Thomsen, Finn Külls, Christina Vokuhl, Linda Krause, Dominik Müller, Max Bossemeyer, Mirja Wegge, Alina Kröker, Alina Bergholz, Christian Zöllner, Daniel I Sessler, Bernd Saugel

Faculty, Staff and Student Publications

Background: Hypotension after induction of general anaesthesia (postinduction hypotension) is common in patients undergoing noncardiac surgery and frequently requires treatment with vasopressors such as norepinephrine. We tested the hypothesis that giving norepinephrine continuously using a syringe infusion pump, compared with giving it as repeated manual boluses, reduces postinduction hypotension within 15 min after starting induction of general anaesthesia in low-to-moderate risk noncardiac surgery patients.

Methods: Patients undergoing elective noncardiac surgery were randomised to either continuous norepinephrine infusion or manual bolus norepinephrine administration intravenously during induction of general anaesthesia. In both groups, norepinephrine was administered through a peripheral venous catheter. Blood …

Predicting Ventilation From Single Breathing Phase Non-Contrast Ct Using Swin Transformers, Yi-Kuan Liu, Hsu-Ting Kuo, Alaa Melek, Richard Castillo, Yevgeniy Vinogradskiy, Lili Zhao, Girish Nair, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Pulmonary ventilation imaging enables functional avoidance radiotherapy treatment plans by quantifying regional lung function. However, current clinical standards, such as 99𝑚Tc-based single-photon emission computed tomography (SPECT), rely on radioactive tracers, which can introduce imaging deposition artifacts. CT ventilation imaging (CTVI) methods based on both physical models and deep learning approaches currently require multiple CT images as input, such as the inhale/exhale phases of a 4DCT. While the theoretical foundation of physics-based CTVI is built on multi-phase information, the feasibility of single-phase deep learning CTV models has not been determined.

PURPOSE: While deep learning methods have predicted SPECT ventilation from …

Computed Tomography For Four-Dimensional Dose Calculation: Effect Of Detector Array Length, Inhwan Yeo, Qianyi Xu

Department of Radiation Oncology Faculty Papers

PURPOSE: Four-dimensional computed tomography (4DCT) is susceptible to a geometrical error when respiration changes upon patient shift. 4DCT using 16-cm detector arrays, not needing the shift, has been shown to improve geometrical accuracy, compared with a conventional 4DCT (4-cm array), albeit with some Hounsfield unit discrepancies. The 4DCTs were validated for 4D planning.

MATERIALS AND METHODS: A lung-mimicking phantom containing a spherical target with ten respiratory traces and three tumor-shaped targets with their traces was respectively imaged when, to each of the ten-positions/phases, the lung was moved (1) step-wisely by helical scan at each movement (ground truth; 4DCT_GT), …

Factors Associated With Child Protective Services Referrals In Young Children With Isolated Skull Fractures., Karli Breeden-Carino, Joanne N. Wood, Cindy W. Christian, Tagrid M. Ruiz-Maldonado, Daniel M. Lindberg, Angela Bachim, Lori Frasier, Terra N. Frazier, Nancy S. Harper, Sara E. Kruczek, Farah Brink, Jennifer E. Wolford, Jan Leonard, M Katherine Henry

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Many young children with isolated skull fractures are referred to child protective services (CPS) despite being assessed to have a low likelihood of abuse. We sought to identify factors associated with CPS referrals in this population and to quantify hospital-level variation.

METHODS: We performed a multicenter retrospective cross-sectional study of children < 2 years with skull fractures with or without a small underlying intracranial hemorrhage (ICH) and no additional injuries undergoing a child abuse pediatrics (CAP) subspecialty evaluation. We explored associations between demographic factors, clinical characteristics, psychosocial risk factors, and hospital site with CPS referral status. We performed multivariable logistic regression, adjusting for transfer status and all significant covariates from unadjusted analyses. We utilized marginal standardization to calculate the estimated probability of CPS referrals at each site, adjusting for all factors in the final model.

RESULTS: Of 528 children, 303 (57.4%) were referred to CPS, with 86.5% referred before CAP consultation. In multivariable logistic regression, presence of psychosocial risk factors (OR 4.00; 95% CI 2.25, 7.11), in-person CAP consult (OR 3.93; 1.61, 9.62), inflicted or no trauma history provided (OR 6.15; 3.30, 11.45), …

Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)—with deletions and duplications typically associated with reduced and increased protein levels, respectively—and uncovered previously unknown protein–protein interactions …

Dominant Clones Leverage Developmental Epigenomic States To Drive Ependymoma, Alisha S Kardian, Hua Sun, Siri Ippagunta, Nicholas Laboe, Srinidhi Varadharajan, Kwanha Yu, Hsiao-Chi Chen, Erik Emanus, Tuyu Zheng, Riley M Deneen, Jon P Connelly, Yong-Dong Wang, Jiangshan Zhan, Hengxi Liu, Kimberley Lowe, Taylor Bugbee, Rakesh Pathak, Amanda Bland, Sanya Mehta, Sophie Cochiolo, Amir Arabzade, Blake Holcomb, Kaitlin M Budd, Gabriele Kembuan, Tristen Wright, Emma Caesar, Maxwell Park, Amelia Hancock, David Gee, Joel Murdoch, Yi Xiao, Samuel K Mcbrayer, Thomas E Merchant, Jun Qi, Adam D Durbin, Lindsay A Schwarz, Li Wang, Andrew M Donson, Nicholas K Foreman, Sameer Agnihotri, Alfonso Lavado, Suzanne J Baker, David W Ellison, Hyun Kyoung Lee, Shondra M Pruett-Miller, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

ZFTA–RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA–RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse …

A Comprehensive Review Of Tear Fluid Proteome Alterations In Dry Eye Disease: Insights Into Pathophysiology And Biomarker Potential, Saleh Ahmed, Steven Safille, Victoria Clifton, Shruti Sharma, Cintia S De Paiva, Ashok Sharma

Faculty, Staff and Students Publications

Tear fluid is a highly specialized and dynamic biofluid composed of proteins, lipids, mucins, and electrolytes that is essential for maintaining ocular surface integrity, immune defense, and tear film stability. Growing evidence from tear proteomic studieshas revealed extensive alterations in protein composition in dry eye disease (DED), reflecting a complex interplay between local ocular surface pathology and systemic inflammatory influences. This review summarizes proteomic findings from 50 published studies to identify tear proteins that are consistently upregulated or downregulated in DED and to interpret their biological relevance in the context of ocular surface homeostasis. Across studies, proteins upregulated in DED …

Comprehensive Profiling Of The Human Tear Fluid Mirnome Using Small Rna Sequencing, Garrett Jones, Drew Mayernik, Saleh Ahmed, Eliza Williams, Jeremy Altman, Tae Jin Lee, Amy Estes, Cintia S De Paiva, Pamela Martin, Shruti Sharma, Ashok Sharma

Faculty, Staff and Students Publications

Purpose: To generate a comprehensive profile of microRNAs (miRNAs) present in human tear fluid using next-generation sequencing (NGS), establish a reference miRNome for healthy human tear fluid, and investigate whether miRNA expression varies by sex, race, or age.

Methods: Tear samples were collected from 32 adults using Schirmer strips. RNA was isolated using the miRNeasy Serum/Plasma Kit, and cDNA libraries were prepared using the QIAseq miRNA Library Kit. Barcoded libraries were sequenced on the NovaSeq 6000 platform. Bioinformatic analyses included adapter trimming, alignment to miRBase, normalization with DESeq2, and functional annotation using multiMiR and clusterProfiler. Differential expression analysis was performed …

Rexinoid Net-3ib Promotes Resident Macrophage Gene Expression And Mitigates Desiccation-Induced Ocular Surface Disease, Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, Karen Zheng, Hiroki Kakuta, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.

Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled …

Development And Internal Validation Of A Pretransplant Biomarker Panel For Mortality Prediction Following Liver Transplant, Guergana G Panayotova, Sopio Simonishvili, Lianhua Jin, Duc T Nguyen, Edward A Graviss, Yong Qin, Anastasia Xynogala, Tumininu Ayorinde, Laurie J Minze, Alexander Lemenze, Krupa R Mysore, Julie M Corkrean, Linda W Moore, Flavio Paterno, Ashish Saharia, Constance M Mobley, Arpit Amin, Mark J Hobeika, Xian C Li, Paul J Gaglio, R Mark Ghobrial, James V Guarrera, Keri E Lunsford

Faculty, Staff and Students Publications

Importance: Current pretransplant clinical scoring systems fail to accurately estimate post-liver transplant (LT) survival, making recipient selection challenging. Persistent immune dysfunction contributes to early LT recipient mortality but is not captured by existing models.

Objective: To identify plasma biomarkers of pretransplant immune dysfunction and to develop a biomarker-based pre-LT risk stratification tool to predict post-LT mortality.

Design, setting, and participants: Prospective biomarker analysis of consecutively enrolled adult LT recipients was conducted. Healthy controls were included for baseline comparison. Patients undergoing LT at Houston Methodist Hospital (October 1, 2013, to December 31, 2017) and Rutgers/University Hospital (January 1, 2019, to March …

The International Pediatric Headache Didactic Series: A Novel Curriculum Innovation, Sara Pavitt, Sruthi Ilangovan, Zoë Allen, Samantha L Irwin, Irene Patniyot

Faculty, Staff and Students Publications

Objectives: The International Pediatric Headache Didactic Series (IPHDS) was developed to provide free, comprehensive pediatric headache education to healthcare professionals worldwide. The objective of this study was to describe the design, implementation, and impact of this prospective educational intervention.

Background: Headache is the most common neurological symptom within the pediatric population. Yet, only nine fellowships are offered in pediatric headache medicine. Limitations in access to education and training are often cited as reasons for diagnostic and management barriers. To address this gap, the IPHDS was established in July 2022.

Methods: IPHDS is a recurring series consisting of 23 biweekly lectures. …

Confessions In Cases Of Child Physical Abuse-A Capnet Study, Margaret R Russell, Antoinette L Laskey, Henry T Puls, Suzanne P Starling, Joanne N Wood, Daniel M Lindberg, Nancy S Harper, Caitlin R Mcnamara, Angela N Bachim, Farah W Brink, Lori D Frasier, James D Anderst, Porcia Vaughn, Kristine A Campbell

Faculty, Staff and Students Publications

Objective: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

Methods: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

Results: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

Conclusions: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Distinct Effects Of Complement C4a And C4b Copy Numbers In Systemic Sclerosis Serological And Clinical Subtypes, Javier Martínez-López, Carlos Rangel-Peláez, Inmaculada Rodriguez-Martin, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José L Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Gianluca Moroncini, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcon-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera, Martin Kerick

Faculty, Staff and Student Publications

Objective: Complement component 4 (C4), encoded by C4A and C4B within the major histocompatibility complex (MHC) on chromosome 6, regulates the immune response and clears immune complexes. The variable copy number (CN) of C4 genes and retroviral human endogenous retrovirus K (HERV-K) element influence its function. Given the relationship of C4 CN with systemic sclerosis (SSc) risk, we assessed associations with SSc clinical and serologic subtypes.

Methods: We compared imputed C4 CNs across SSc subgroups (4,049 anticentromere positive [ACA+]; 2,200 anti-topoisomerase I [ATA+]; 577 anti-RNA polymerase [ARA+]; 1,078 triple-negative [TN] patients; 6,295 limited cutaneous SSc [lcSSc]; and 2,946 diffuse cutaneous …

How I Do It: The Transtracheal Approach For Awake Cricopharyngeal Botulinum Toxin Injection, Andrew Tritter, Alexander Simko, Karim Asi

Faculty, Staff and Student Publications

This transtracheal technique for cricopharyngeal botulinum toxin injection is a safe and effective option for chemodenervation of this muscle in the awake patient. Its advantages include reduced risk of toxin spread to intrinsic laryngeal muscles, the ability to administer higher doses of botulinum toxin, improved access to the entire length of the cricopharyngeus, and avoidance of general anesthesia.