Medicine and Health Sciences Commons^™

Using The Consolidated Framework For Implementation Research (Cfir) To Evaluate Complex School Settings, Carlie P. Coerver, Tricia A Zucker

Summer Research Program Abstracts

No abstract provided.

Improving Infant Health Equity: What Have We Learned, What Do We Do, Dewayne M Pursley, F Sessions Cole

2020-Current year OA Pubs

The United States neonatal and infant mortality rates have declined substantially over the last six decades. Despite these reductions, significant racial disparities in mortality and other important outcomes have persisted. While increased risk of preterm birth is a major contributor to these differences, racial inequities in risk-adjusted outcomes such as gestational age-specific and major congenital anomaly-associated mortality remain. Race-specific differences in inter- and intra-neonatal intensive care unit (NICU) practices associated with worse outcomes for infants of color suggest opportunities for reducing these disparate health outcomes during and after NICU hospitalization. Identifying NICU-based contributing factors and implementing factor-specific improvement strategies can …

Cardiorespiratory Signatures Of Necrotizing Enterocolitis: A 4-Nicu Study Of Very Low Birth Weight Infants, Sherry L Kausch, Zachary A Vesoulis, Colm P Travers, Carie Taveras, Rachel Benz, Amanda Duncan, Angela K S Gummadi, Katy N Krahn, Rakesh Sahni, Joseph Isler, Namasivayam Ambalavanan, J Randall Moorman, Douglas E Lake, Karen D Fairchild, Brynne A Sullivan

2020-Current year OA Pubs

BACKGROUND: Necrotizing enterocolitis (NEC) is a disorder in very low birth weight (VLBW, < 1500 g) infants, associated with significant morbidity and mortality. Earlier detection of NEC may improve outcomes. We hypothesized that NEC's physiological signature resembles that of sepsis and that our model developed for sepsis, the Pulse Oximetry Warning System (POWS), would also predict NEC.

OBJECTIVES: Assess relationships between continuous heart rate (HR) and oxygen saturation (SpO

METHODS: In a retrospective multicenter analysis, we studied VLBW infants at four level IV NICUs, identifying cases of late-onset sepsis (LOS) and NEC (Bell stages 2 or 3). Using HR and SpO

RESULTS: Among 3914 infants evaluated, 5% had NEC and 13% had LOS. Cardiorespiratory data analysis showed that HR/SpO

CONCLUSION: NEC shares a cardiorespiratory signature with LOS. POWS predicted NEC with a dynamic rise before clinical diagnosis.

IMPACT: A cardiorespiratory early warning score analyzing …

Thromboelastography-Guided Laparoscopic Splenectomy In A Patient With Immune Thrombocytopenia And Recent Drug-Eluting Stent Placement: A Case Report, Josue Gaona, Janki Patel

School of Medicine Student Publications and Presentations

Background

Perioperative management of patients with immune thrombocytopenia (ITP) is particularly challenging when complicated by recent coronary stenting requiring dual antiplatelet therapy (DAPT), due to competing risks of bleeding and thrombosis.

Case Presentation

We report the case of an 80-year-old male with refractory ITP and recent drug-eluting stent placement who underwent elective laparoscopic splenectomy. Although preoperative optimization with corticosteroids and intravenous immunoglobulin increased platelet count from <  20 × 109/L to 177 × 109/L, functional hemostatic adequacy remained uncertain given concurrent ITP and ongoing antiplatelet therapy. Thromboelastography (TEG) was performed using the TEG 6s system with a Global Hemostasis Cartridge. Standard TEG parameters demonstrated preserved clot initiation, formation, and strength across multiple channels, supporting progression to surgery. Laparoscopic splenectomy was completed under general anesthesia without complications or need for transfusion. The patient recovered on the general surgical ward and was discharged on Postoperative Day 3 with a platelet count of 139 × 109/L. Platelet count 2 weeks postoperatively was 343 × 109/L.

Conclusion

This case highlights the utility of TEG as a tool to guide perioperative decision-making in patients with ITP receiving antiplatelet therapy. By providing a functional assessment of coagulation, TEG can help individualize perioperative …

Venous Thromboembolism In Pediatric Intestinal Failure: A Single-Center Experience, Grant Ebel Bs, Rachel Bordelon Md, Julia Dansby Md, John Shin Bs, Ethan Porter Md, Tien Pham Np, Rn, Nutan Hebballi Phd, Essam Imseis Md, Allison Speer Md

Summer Research Program Abstracts

No abstract provided.

Feasibility Of Using Electronic Medical Records To Identify Postdischarge Mental Health Screening Documentation In Trauma Patients., Kellie Girardot, Julie L Otte

Emergency Medicine and Trauma

BACKGROUND: Injury leads to long-term physical and mental health challenges, yet inpatient screening for post-traumatic stress disorder and depression remains inconsistent, and postdischarge mental health is poorly understood, particularly in less resourced trauma centers where emerging symptoms may go unrecognized.

OBJECTIVE: To evaluate the feasibility of using the electronic medical record to identify postdischarge mental health screening documentation in adult trauma patients within 6 months after discharge.

METHODS: This retrospective descriptive feasibility study was conducted at a midwestern US regional Level II trauma center serving a predominantly rural catchment area. Adult trauma patients admitted between January 1 and December 31, …

Development Of An Educational Curriculum For The Surgical Implantation Of Dbs Systems, David Bieber, Rany T Abdallah, Alaa Ab-Elsayed, Adam R Burkey, Dario J Englot, Kunal Gupta, Charles N Munyon, Casey H Halpern, Kai J Miller, Joshua M Rosenow, Ahmed M Raslan, Konstantin V Slavin, Jennifer A Sweet, Sameer Sheth, Nestor Tomycz, Ashwin Viswanathan, Chengyuan Wu, Jeffrey S Raskin

Faculty, Staff and Students Publications

Background: Deep-brain stimulation (DBS) systems are implanted for movement disorders, epilepsy, and psychiatric conditions. Neurologic surgery remains the only discipline credentialed to implant DBS devices, although significant practice variation exists, partly due to heterogeneous training. The North American Neuromodulation Society (NANS) education committee offers a granular recommendation for the progression of an early learner through the practitioner level. It is contextualized within the six-core competency rubric for the surgical implantation of DBS devices.

Materials and methods: Guided by the Accreditation Council for Graduate Medical Education (ACGME) core competencies, a subcommittee of the NANS education committee met virtually and in-person over …

A Nationwide Central Diagnosis For Pediatric Cns Tumors In Japan: The Jccg Brain Tumor And Pathology Committees, Yoshiko Nakano, Junko Hirato, Takako Yoshioka, Tetsuya Takimoto, Sumihito Nobusawa, Kaishi Satomi, Ran Tomomasa, Seiji Yamada, Taku Homma, Shoh Sasaki, Ayako Yamazaki, Maki Sakaguchi, Yasuhide Takeuchi, Nei Fukazawa, Kai Yamasaki, Kohei Fukuoka, Yui Shinohara Kimura, Yuki Nagayama, Yohei Inoue, Akira Miyahira, Ema Yoshioka, Asako Katsuma, Hayato Fukusumi, Tomoko Shofuda, Yuko Hibiya, Yuko Matsushita, Mai Honda Kitahara, Yuki Yomoda, Miho Kato, Michael D Taylor, Yasuhito Arai, Tatsuhiro Shibata, Hiroaki Sakamoto, Keita Terashima, Yoshiki Arakawa, Toshihiro Kumabe, Ryo Nishikawa, Junichi Hara, Yonehiro Kanemura, Koichi Ichimura

Faculty, Staff and Students Publications

In 2016, the Japan Children's Cancer Group launched a nationwide research initiative to provide central diagnosis incorporating pathology review and molecular profiling for pediatric central nervous system (CNS) tumors. Over the first eight years, 2224 cases were registered. Non-next-generation sequencing analyzes, such as pyrosequencing and NanoString, were routinely performed, mainly for glioma, medulloblastoma, and ependymoma. Additional analyzes, including methylation profiling and RNA sequencing, were conducted for selected diagnostically challenging cases. The most common diagnoses were low-grade glioma (26%), medulloblastoma (18%), germ cell tumor (16%), high-grade glioma (12%), and ependymoma (11%). Diagnostic or targetable alterations were detected in nearly half of …

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …

Quality Domains In Home-Based Pediatric Hospice And Palliative Care: Adolescent And Young Adult Perspectives, Daniel H Grossoehme, Claire A Crawford, Jhansi Chandra Ellakula, Toluwalase Ajayi, Justin N Baker, Sarah Friebert, Lisa Humphrey, Jillann Jarrell, Rachel Thienprayoon, Pamela S Hinds

Faculty, Staff and Students Publications

Background: Current United States palliative care practice guidelines are intended to cover care across all age groups. Previous research with pediatric providers and caregivers concluded that pediatric hospice and palliative care have unique attributes. Not known is how adolescent hospice and palliative care patients understand quality palliative care. The purpose of this study was to characterize and define quality of care domains as described by adolescent and young adult patients receiving home-based hospice and palliative care.

Methods: Semi-structured interviews with 10-26 year-olds who received home-based hospice and/or palliative care visits in the prior three years at six diverse sites in …

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Human Exposure To Spirochete-Infected Ornithodoros Turicata In A Residential Setting In The Austin, Texas Metropolitan Area, Serhii Filatov, Bonny Mayes, Sarah M Gunter, Alexander R Kneubehl, Job E Lopez

Faculty, Staff and Students Publications

A central Texas resident found an engorged Ornithodoros turicata tick attached to their ankle while at home. The tick tested positive for Borrelia turicatae, an agent for soft tick-borne relapsing fever. Three weeks earlier, the patient started experiencing febrile episodes, rash, and nausea, yet the etiological agent went undiagnosed.

Mental Health Stigma In Latin American Youth With Obsessive-Compulsive Disorder, Ryan J Mccarty, Matias Jensen, Elissa Paz Jensen Santa Cruz, Melisa N Sagarnaga, Pamela Claisse Quiroz, Tomás Miño, Paola Giusti-Rodriguez, Mayra C Martinez Mallen, Maria B Moyano, Dayan Berrones, Jacey L Anderberg, Renee M Frederick, Hannah C Moore, Josselyn S Muñoz, Vanessa Zavala Cruz, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Working Group (Gttoc), Ogechi C Onyeka, Andrew D Wiese, James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is an impairing mental health condition that affects individuals across the lifespan. Some literature has evaluated mental health stigma in adults with OCD but limited attention has been given to youth, as well as those of Latino ancestry. The present study reported the extent of stigma experiences among Latin American youth with OCD, as well as examined sociodemographic, clinical and psychological correlates. 235 youth with clinician confirmed diagnoses of OCD from 10 North and South American countries completed questionnaires assessing stigma experiences, symptomatology, and functioning. Sociodemographic and clinical variables were also collected. The average OCD stigma response …

Beyond Lactate: Real-Time Resuscitation Targets For Septic Shock During Critical Care Transport, James L Li, Aaron J Lacy, Michael J Defilippo

2020-Current year OA Pubs

No abstract provided.

A Call To Investigate The Association Between Histoplasmosis And Fatigue, Christian Hendrix, Julio Zuniga-Moya, Andrej Spec, Patrick Mazi

2020-Current year OA Pubs

Historically, infections are subjectively associated with fatigue, a common yet poorly delineated syndrome. The impact on patient quality of life is the ultimate justification to evaluate fatigue in patients with infections. While fungal infections are subjectively associated with fatigue, there are minimal quantifiable fungal research outcomes that evaluate histoplasmosis and fatigue.

Homework Adherence In Exposure-Based Cbt For Youth With Obsessive-Compulsive Disorder: Clinical Outcomes And Predictors Across Treatment, Abigail E Pine, Qimin Liu, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire

Faculty, Staff and Students Publications

Exposure-based cognitive behavioral therapy (CBT) is the frontline treatment for pediatric obsessive-compulsive disorder (OCD), but not all youth fully respond to this treatment. While multiple factors may influence CBT response, homework adherence in CBT is a modifiable target that can improve treatment outcomes. This report examines the relationship between homework adherence and clinical outcomes in a large sample of youth with OCD who received exposure-based CBT. Here, 137 youth with OCD between 7 and 17 years old (M = 12.42, SD = 2.88) participated in a randomized controlled trial of exposure-based CBT. Homework adherence was monitored weekly, and OCD severity …

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

An Examination Of Buprenorphine And Norbuprenorphine Concentrations In Inpatients Receiving Medications For Opioid Use Disorder, Michèle Haykal, Benjamin Li, Andres Avellaneda Ojeda, Roberto Sanchez, Nancy Shenoi, Asim Shah, Nidal Moukaddam

Faculty, Staff and Students Publications

Background: Interpretation of urine buprenorphine and norbuprenorphine concentrations is widely used to assess adherence during treatment for opioid use disorder. However, the relationships between dose, timing of sample collection, and metabolite ratios remain unclear, leading to potential misinterpretation in clinical practice.

Methods: Data were collected from patients on a psychiatry unit who were either inducted on or continued buprenorphine therapy and underwent urine testing for buprenorphine and its metabolite, norbuprenorphine. Urine samples were collected 16 to 786 min after the last buprenorphine dose. Norbuprenorphine-to-buprenorphine ratios were calculated. Data analysis using Python included polynomial regression and random forest models.

Results: Daily …

Blinded, Bias-Controlled Multi-Rater Evaluation Of Human-Versus-Ai Brain Metastasis Segmentation Using A Hybrid Foundation-Model Framework, Yiding Han, Enze Zhu, Mhd Hasan Ai Mekdash, Omar Awad, Piyush Pathak, Shixiao Liang, Daniel Allan Hamstra, Xizhe Zhang, Zaid Ali Siddiqui, Baozhou Sun

Faculty, Staff and Students Publications

Background: Accurate segmentation of brain metastases (BM) is essential for diagnosis, stereotactic radiosurgery planning, and longitudinal assessment. However, manual contouring is time-intensive, limiting clinical scalability, and exhibits substantial inter-observer variability. This variability complicates objective assessment of automated segmentation methods and challenges interpretation of model performance.

Purpose: To address these limitations, we developed TUM-SAM, a hybrid foundation-model framework for fully automated BM segmentation, and introduced a bias-controlled, blinded multi-rater evaluation paradigm to determine whether AI-based BM segmentation has reached expert-level performance and whether AI-generated contours are preferred by human experts under unbiased assessment.

Methods: TUM-SAM integrates nnU-Net-based lesion detection with a …

Hypovascular Aggressive Angiomyxoma In A Pregnant Adolescent: A Case Report And Review Of Its Multimodal Imaging Appearances, Kyler Shin, Kweku Agyepong, Craig Kym, Mohammad Ghasemi-Rad, David Léon

Faculty, Staff and Students Publications

Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that primarily arises in the perineum and pelvis of young females. It is sometimes identified incidentally on pelvic examination and obstetric imaging. Although asymptomatic at small sizes, AAM is typically hypervascular and can grow large enough to complicate a patient's obstetric and gynecologic course of treatment. While AAM is a rare diagnosis reported in the literature, there are limited descriptions of its multimodal radiologic appearance, and uncommonly, it can present as a hypovascular mass. We describe a rare case of hypovascular AAM in pregnancy that did not respond favorably to targeted embolization, …

Comprehensive Assessment Of Direct And Passive Smoking Across The Pancreatitis Spectrum, Samuel Han, Dhiraj Yadav, Jun Xu, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Liang Li, Stephen J Pandol, Walter G Park, Guru Trikudanathan, Stephen K Van Den Eeden, Santhi Swaroop Vege, Darwin L Conwell, Christie Y Jeon, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Smoking is a key risk factor for pancreatitis, contributing to pathogenesis and disease progression. Data regarding second-hand smoking, or passive smoking (PS) exposure, are lacking. We therefore aimed to assess the impact of PS exposure across the pancreatitis spectrum.

Methods: We analyzed baseline data from the PROCEED study, a multicenter study in the United States including patients with acute (AP), recurrent acute (RAP), and chronic (CP) pancreatitis. Participants detailed their individual smoking history and PS exposure, which was compared between AP, RAP, and CP subgroups. Participant factors and clinical characteristics were compared by level of individual and PS exposure. …

Jak Inhibition In Pnpt1-Related Mitochondrial Interferonopathy: A Case Report And Review Of Mitochondrial-Immune Crosstalk, Dan Ross Brooks, Hyun Yong Koh, Taylor Martin Kerrins, Steven Lang, Emily Bland, Rui Yang, Sarah Kogan Nicholas, Stephanie Jean Sikkink, Stephen Kralik, Christine Eng, Chaya Nautiyal Murali, Seema Lalani, Pilar Lenglet Magoulas, Lisa Emrick, Kristen Sydney Fisher, Fernando Scaglia

Faculty, Staff and Students Publications

Biallelic pathogenic variants in PNPT1 cause combined oxidative phosphorylation deficiency 13 (COXPD13) (MIM #614932), linking mitochondrial dysfunction to type I interferon (IFN) activation through cytosolic leakage of mitochondrial double‐stranded RNA (mt‐dsRNA). This mechanism connects mitochondrial disease to interferonopathies such as Aicardi–Goutières syndrome (AGS). We describe a 7‐month‐old female infant with compound heterozygous PNPT1 variants presenting with severe hypotonia, feeding difficulties necessitating gastrostomy, dystonia, and elevated serum lactate. Brain magnetic resonance imaging (MRI) demonstrated marked cerebellar, brainstem, and basal ganglia atrophy, with a lactate peak on MR spectroscopy (consistent with an inverted doublet). Serum immune profiling revealed a mild but elevated …

Biphasic Sleep Is A Feature Of Sleep Disturbance In Syngap1-Rd, Aida Doucoure, Het Patel, Mark A Abboud, Alice Sperry, Sarah K Wanigatunga, Deana Crocetti, Heather Volk, Adam P Spira, Stewart H Mostofsky, Vaishnav Krishnan, Constance Smith-Hicks

Faculty, Staff and Students Publications

Study objectives: Sleep problems are common in children with SYNGAP1-Related Disorder (SYNGAP1-RD). The use of devices that objectively estimate sleep are complicated by co-occurring sensory disorders in this population. We examined the feasibility and validity of wrist actigraphy to examine sleep and rest-activity rhythms (RAR).

Methods: Data from five children with SYNGAP1-RD and 42 typically developing children were analyzed. All children were asked to wear the Actiwatch-2 for 14 continuous days and caregivers were asked to complete a sleep diary and the Children Sleep Health Questionnaire (CSHQ). Parametric (alpha, beta, acrophase, amplitude, up/down mesor, mesor), nonparametric (intradaily variability, interdaily stability, …

Statistics Of Natural Scenes Shape Contextual Modulation In The Visual Cortex, Jiakun Fu, Suhas Shrinivasan, Luca Baroni, Zhuokun Ding, Paul G Fahey, Paweł A Pierzchlewicz, Nikos Karantzas, Kayla Ponder, Rachel Froebe, Lydia Ntanavara, Taliah Muhammad, Konstantin F Willeke, Eric Wang, Zhiwei Ding, Dat Tran, Stelios Papadopoulos, Saumil Patel, Jacob Reimer, Alexander S Ecker, Xaq Pitkow, Jan Antolik, Fabian H Sinz, Ralf M Haefner, Andreas S Tolias, Katrin Franke

Faculty, Staff and Students Publications

Vision is context dependent, with neuronal responses shaped not only by local features but also by surrounding visual input. While classical studies, using grating stimuli, show that iso-oriented surrounds suppress responses more than orthogonal surrounds, the role of contextual modulation under natural stimulus conditions remains less clear. Using recordings from mouse primary visual cortex (V1), we trained convolutional neural network models to predict neuronal responses to natural images and synthesized surround stimuli that selectively suppressed or facilitated responses to optimal center inputs. In vivo experiments confirmed these predictions. Facilitatory surrounds resembled naturalistic continuations of the optimal center stimulus, consistent with …

Incidence And Outcomes Of Treatment-Associated Hepatotoxicity During Pediatric Acute Lymphoblastic Leukemia Induction Therapy: A Reducing Ethnic Disparities In Acute Leukemia (Redial) Consortium Report, Ashley N Chavana, Emily J Mason, John P Woodhouse, Olga A Taylor, Monica M Gramatges, Joanna S Yi, Sandi Pruitt, M Brooke Bernhardt, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Marley Roberts, Rodrigo Erana, Juan Carlos Bernini, Hong Zhu, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Steven D Mittelman, Van Huynh, Etan Orgel, Austin L Brown

Faculty, Staff and Students Publications

No abstract provided.

Mechanisms Coordinating Exit From The Stem Cell State In Mammals, Emily J Park, Florencia Levin-Ferreyra, Bruno Di Stefano

Faculty, Staff and Students Publications

Differentiation requires coordinated exit from the stem cell state, during which gene regulatory networks sustaining self-renewal are dismantled, while lineage-specific programs are activated. This transition is governed by chromatin modifications, transcriptional networks, RNA processing, translational control, and metabolic rewiring that must operate with temporal precision. Despite significant progress in identifying individual regulatory components, understanding how these layers integrate to orchestrate irreversible cell fate commitment remains a fundamental challenge. This review examines common and unique regulatory principles governing stem cell exit, from totipotency during early embryogenesis to tissue-specific stem cell differentiation in adults. We synthesize recent findings on regulatory mechanisms across …

Nuclear-Specific Reductive Carboxylation Of Alpha-Ketoglutarate Fuels Histone Acetylation To Induce Chromatin Accessibility And Gene Activation, Abhisha Sawant Dessai, Nadya A Elhalawany, Tao Dai, Justine J Jacobi, Christian Prechtl, Alphonse N Dimeck, Sierra R Morton, Mark D Long, Prashant K Singh, Nagireddy Putluri, Mariana Lopes, Song Liu, Dominic J Smiraglia, Katerina V Gurova, Peder J Lund, Leah A Gates, Sung Yun Jung, Subhamoy Dasgupta

Faculty, Staff and Students Publications

Mitochondria remain at the core of cell metabolism, whereas the nucleus integrates cellular and environmental signals to activate genes. However, the mechanisms that directly link cellular metabolism to gene regulation are not well understood. Here we show, a metabolic pathway in the nucleus controls acetylation of histones by nuclear localization of mitochondrial enzymes aconitase (ACO2) and isocitrate dehydrogenase (IDH2). Metabolic tracing studies show that IDH2 and ACO2 catalyze reductive carboxylation of α-ketoglutarate to rapidly synthesize citrate to increase nuclear acetyl-CoA pool. Genetic and proteomic analyses reveal nuclear IDH2 and ACO2 form a complex with KAT2A/GCN5 for acetylation of histones to …

Genetics Of Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous xanthomatosis (CTX) is rare, autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in CYP27A1, which encodes sterile 27 hydroxylase, a key enzyme in bile acid biosynthesis. Enzyme deficiency results in reduced cholic and chenodeoxycholic acid synthesis with accumulation of cholestanol, bile acid intermediates, and bile alcohols, producing a progressive multisystem disorder characterized by chronic diarrhea, juvenile-onset cataracts, tendons xanthomas, and neurological dysfunction. Although CTX typically begins in childhood, diagnosis is frequently delayed until adulthood, limiting the benefit of effective disease modifying therapy with chenodeoxycholic acid. Since the identification of CYP27A1, more than 200 pathogenic variants have …

Evaluation Of The Impact Of A Pathology Trainee-Driven Manual Review Process For Reference Testing At A Large Academic Center, Carly Maucione, Christopher W Farnsworth, Mark A Zaydman

2020-Current year OA Pubs

BACKGROUND: Increasing reliance on and complexity of laboratory testing necessitates laboratory stewardship initiatives to ensure appropriate test ordering, especially as reference testing costs continue to rise. Prospective manual review processes, although demanding of resources, have been shown to be cost-effective, but literature addressing the value of such a process is lacking.

METHODS: The pathology trainee-driven manual review process of 444 chemistry and microbiology tests on approval at a large academic center was reviewed. Data were extracted from an internal-use call-log and analyzed for test volumes, cancellation rates, and cost savings. A hypergeometric distribution was used to model random variation in …

Modern Molecular Profiling Recontextualizes The Nrg/Rtog 0539 Trial And Reveals Hidden High-Risk And Radiotherapy-Resistant Meningiomas, Leeor S Yefet, Clifford Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Meningiomas exhibit clinical heterogeneity. Radiotherapy (RT) remains the only adjuvant therapy, but tumor-control is variable, and biomarkers are limited. NRG/RTOG-0539 is the first prospective phase 2 trial to stratify meningioma patients for adjuvant RT based on clinical risk. Here, we apply modern molecular tools to this cohort and identify correlates of RT response.

METHODS: Tumor tissue from 100 RTOG-0539 patients was profiled using DNA methylation arrays, RNA sequencing, and whole-exome sequencing. Recurrence scores, Molecular Groups, gene expression, and copy number alterations were compared across clinical groups and between RT responders and non-responders; non-response was defined as progression or death …