Digital Commons Network^™

13 C-Spirulina Gastric Emptying Breath Test Normative Values In Healthy Children: A Multicenter Study With Comparison To Symptomatic Children, Katja Karrento, Bruno P Chumpitazi, Liyun Zhang, Pippa Simpson, Robert J Shulman

Faculty, Staff and Students Publications

Introduction: Diagnosing pediatric gastroparesis presents a significant challenge due to lack of normative data in children. We aimed to determine normative values for gastric emptying using the nonradioactive 13 C-Spirulina gastric emptying breath test ( 13 C-GEBT) in a large cohort of healthy children (HC) and examine differences compared to children with gastroparesis-like symptoms (GLS).

Methods: A total of 301 HC ages 7-18 years completed the 13 C-GEBT with 10 different breath samples × 4 hours. 13 CO 2 excretion rate (kPCD) was determined by change in 13 CO 2 / 12 CO 2 . Outcome variables included: kPCD at …

Distribution Of Nematophagous Fungi And Soil-Transmitted Helminths In Outdoor Built Environments Across Latin America, Rojelio Mejia, Eva Mereles Aranda, Leticia Ojeda, Sandra Ocampos Benedetti, Janitzio J Guzman, Barton Slatko, Cristina Almazan, Melisa Diaz-Fernandez, Ruben Cimino, Marisa Juarez, Natalia Montellano Duran, Estefania Lorena Mansilla Flores, Paola Andrea Vargas, Amandeep Kaur, Nestor L Uzcategui, Lucia Estela Mejia, Katherine Elizabeth Keegan, Emilio Rey Mejia, Chiara Cássia Oliveira Amorim, Stefan M Geiger, Ricardo T Fujiwara, Luz Marina Llangarí-Arizo, Andrea Lopez, Natalia Romero-Sandoval, Irene Guadalupe, Liliana E Villanueva-Lizama, Julio Vladimir Cruz-Chan, Maritza Dalí Camones Rivera, Eddyson Montalvo Sabino, Carlos Pineda, Eric J Wetzel, Philip J Cooper

Faculty, Staff and Students Publications

Background: Soil-transmitted helminths (STHs) are among the most common global parasitic infections, represent a significant worldwide public health burden, and remain a source of considerable morbidity in Latin America. Nematophagous fungi (NF), such as Arthrobotrys oligospora, naturally inhabit many soil types and are known for their ability to trap and kill nematodes using specialized hyphal structures or secreted enzymes and metabolites. As they prey on different developmental stages of helminths in soil, they may represent an ecological factor influencing helminth persistence and transmission dynamics.

Methods: Using an in vitro test, Toxocara cati eggs were exposed to A. oligospora. By using …

Baseline Characteristics In The Synchronize™-2 Randomized Phase 3 Trial Of Survodutide, A Glucagon Receptor/Glp-1 Receptor Dual Agonist, For Obesity In People With Type 2 Diabetes, Sean Wharton, Carel W Le Roux, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

Materials and methods: Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m2 and T2D were randomized 1:1:1 to weekly subcutaneous …

Cyclic Amp-Dependent Regulation Of Ryanodine Receptors In Healthy And Diseased Hearts, Mohit M Hulsurkar, Isabelle Ong, Joshua A Keefe, Issam H Abu-Taha, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca2+-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca2+ release, and cardiac arrhythmias. Furthermore, cAMP influences the …

Utility And Utilization Of Transabdominal Ultrasound In Pediatric Patients With Acute Recurrent Or Chronic Pancreatitis, Nicholas Norris, David Troendle, Michael Wilschanski, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Amit S Grover, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Zachary M Sellers, Andrew T Trout, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objectives: Transabdominal ultrasound (TAUS) is frequently utilized in pediatric acute pancreatitis, but less is known about its use in acute recurrent (ARP) or chronic pancreatitis (CP). Our aim was to describe TAUS utilization and findings from the largest multicenter cohort of pediatric ARP and CP, the International Study Group of Pediatric Pancreatitis: In Search for a CuRE-2 (INSPPIRE-2).

Methods: Demographic and imaging data from physician questionnaires were obtained for patients with available TAUS data. Utilization and findings were compared between ARP and CP groups. Kappa statistics were used to compare agreement of TAUS to computed tomography (CT), magnetic resonance imaging/cholangiopancreatography …

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Utilization Of Intensive Care Interventions In Critically Ill Patients With Candidemia Versus Bacteremia: A Multicenter Retrospective Cohort Study, Mary North Jones, Masayuki Nigo, Stefano Casarin, James Kurian, Aarjav Sanghvi, Enshuo Hsu, Stephen L Jones, Ashton Connor, David B Corry, Cesar A Arias, Max W Adelman

Faculty, Staff and Students Publications

Objectives: Candida species are one of the most common causes of ICU-onset bloodstream infection (BSI). Yet, there is no robust guidance on when to initiate empiric antifungals for ICU patients suspected of BSI. We compared patients with ICU-onset candidemia vs. ICU-onset bacteremia to determine which patients may benefit from empiric antifungals.

Design: We compared characteristics between patients with bacteremia vs. candidemia at time of culture. We determined risk factors for death and constructed a multivariable regression to determine if candidemia is an independent risk factor for death.

Setting/patients: We included ICU patients from a hospital system in Houston, Texas (n …

Factors Associated With Rare Pediatric Cancer Trial Enrollment: A Report From The Children's Oncology Group Rare Tumors Committee, Brian R Englum, Jin Piao, Lindsay Younis, Reto M Baertschiger, Kenneth S Chen, Emily Christison-Lagay, Hetal Dholaria, Robyn Gartrell, M John Hicks, Junne Kamihara, Sarah G Mitchell, Manuela Orjuela-Grimm, Farzana Pashankar, Samara L Potter, Jennifer H Aldrink, Jeremy Rosenblum, Michael R Sargen, Kris Ann P Schultz, Brittani K N Seynnaeve, Mary Wedekind, Theodore W Laetsch

Faculty, Staff and Students Publications

Background: Over 90% of US children with cancer are treated at Children's Oncology Group (COG) centers, which seek to maximize enrollment in therapeutic and biobanking studies. Rare cancers have demonstrated lower than expected COG enrollment. We evaluated trends in COG rare cancer enrollment compared to US incidence from Surveillance, Epidemiology, and End Results (SEER) registries, examining the impact of COG therapeutic trials and Project:EveryChild, a cancer biobank/registry.

Procedure: COG and SEER data from 2002 to 2020 were queried for US patients younger than 18 years old with adrenocortical carcinoma (ACC), nasopharyngeal carcinoma (NPC), retinoblastoma (RB), thyroid carcinoma, and melanoma. We …

Hyperglycemia, Receptor For Advanced Glycation End Products, And Small Airways Dysfunction In Asthma, Paula Sierra Salas, Dennis T Villareal, Vickram Tejwani, Amrit Koirala, Cristian Coarfa, Meredith C Mccormack, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Background: Diabetes and insulin resistance are associated with higher risk of asthma exacerbation and preserved ratio impaired spirometry (PRISm), but the pathophysiology is unclear. These conditions may cause small airways dysfunction (SAD), which is an under-recognized cause of PRISm.

Objective: To determine whether insulin resistance and poor glucose control associate with SAD and to explore whether proteins prognostic of diabetes end-organ complications predict lung function abnormalities.

Methods: We recruited a prospective cohort of adults with physician-diagnosed asthma. Fasting insulin, glucose, hemoglobin A1c, and concentrations of 13 proteins prognostic of diabetes end-organ complications were measured. Static insulin resistance was calculated by …

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Unravelling The Molecular Mechanisms Causal To Type 2 Diabetes Across Global Populations And Disease-Relevant Tissues, Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini

Children’s Nutrition Research Center Staff Publications

Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 …

Enteral And Intravenous Supplementation Of Arginine And Citrulline Fail To Prevent Necrotizing Enterocolitis In Preterm Neonatal Pigs, Caitlin Vonderohe, Julia Garcia Mancebo, Valeria Melendez Hebib, Barbara Stoll, Inka Didelija, Sarah Elefson, Mahmoud Mohammad, Brooklynn Earls, Greg Guthrie, Doug Burrin

Children’s Nutrition Research Center Staff Publications

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants with a morality rate that approaches 50%. Arginine has been widely studied in the field of clinical nutrition as a supplement for patients experiencing critical illness because it can be metabolized into nitric oxide, an important agent for supporting immunity and microcirculation. Citrulline has received less attention but can be metabolized into arginine and has a much longer plasma half-life than arginine. We used the highly translational preterm pig model to determine the effect of intravenous and enteral supplementation of arginine and citrulline on NEC incidence in …

Circulating Metabolites, Genetics And Lifestyle Factors In Relation To Future Risk Of Type 2 Diabetes, Jun Li, Jie Hu, Huan Yun, Zhendong Mei, Xingyan Wang, Kai Luo, Marta Guasch-Ferré, Xikun Han, Buu Truong, Jordi Merino, Chengyong Jia, Miguel Ruiz-Canela, Casey M Rebholz, Eun Hye Moon, Taryn Alkis, Guning Liu, Jie Yao, Xiyuan Zhang, Bianca C Porneala, Jordi Salas-Salvadó, Thomas J Wang, Josée Dupuis, Elizabeth Selvin, Xiuqing Guo, Shilpa N Bhupathiraju, Jennifer A Brody, Yongmei Liu, Alexis C Wood, Kari E North, Su Yon Jung, Ching-Ti Liu, Nona Sotoodehnia, Simin Liu, Lesley F Tinker, A Heather Eliassen, Joann E Manson, Jose C Florez, Robert E Gerszten, Clary B Clish, Liming Liang, Rozenn N Lemaitre, Katherine L Tucker, Stephen S Rich, Jerome I Rotter, Miguel Angel Martínez-González, Kathryn M Rexrode, James B Meigs, Eric Boerwinkle, Robert C Kaplan, Frank B Hu, Bing Yu, Qibin Qi

Faculty, Staff and Student Publications

The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including …

In-Silico Trial Of Same-Day Simulation-Free Spatially Fractionated Adaptive Radiotherapy (Sf2-Art), Dennis N Stanley, Alyssa R Birchmeier, Carlos E Cardenas, Richard A Popple, Natalie Viscariello, Joel A Pogue, Courtney B Stanley, Mehran Yusuf, Michael Soike, Samuel R Marcrom, Joseph Harms

2020-Current year OA Pubs

PURPOSE: Here we present an in-silico trial of the feasibility and deliverability of a same-day, simulation-free workflow for spatially fractionated adaptive radiotherapy (SF

METHODS AND MATERIALS: Ten patients (five thoracic and five extremity), previously treated with spatially fractionated radiotherapy (SFRT), were selected for this in silico trial. A two-phase regimen was simulated: Phase 1 delivered 12 Gy SBRT to a uniform, predefined high-dose lattice and 4 Gy to the gross tumor volume (GTV); Phase 2 consisted of 4 additional fractions of 4 Gy to the GTV. The planning workflow was performed entirely in silico, without the need for CT simulation. …

Blood Dna Methylation-Predicted Plasma Protein Levels And Colorectal Cancer Survival, Alicia R Richards, Maria F Gomez, Bianca I Dowling, Esther Jean-Baptiste, Biljana Gigic, Jane C Figueiredo, Christopher I Li, David Shibata, Adetunji T Toriola, Doratha A Byrd, Cornelia M Ulrich, Paul A Stewart, Erin M Siegel, Jacob K Kresovich

2020-Current year OA Pubs

BACKGROUND: Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.

METHODS: We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with …

Associations Of Child Amygdala Development With Borderline Personality Symptoms During Adolescence, Anna Constantino-Pettit, Kirsten Gilbert, Kiran Boone, Katherine Luking, Benjamin Geselowitz, Rebecca Tillman, Diana Whalen, Joan Luby, Deanna M Barch, Alecia Vogel

2020-Current year OA Pubs

BACKGROUND: The current understanding of the neural correlates of borderline personality disorder (BPD) is limited, but some evidence suggests that alterations in limbic structures play a role in adult BPD. The developmental course of structural neural differences in BPD is unknown. Whether there is specificity for structural alterations in BPD compared to other psychiatric presentations, such as major depressive disorder (MDD), remains unexplored. In the current study, we examined childhood trajectories of 2 limbic regions that have been implicated in BPD, hippocampal and amygdala volume, as they relate to adolescent BPD symptoms compared to MDD symptoms.

METHODS: Participants (n = …

Computational Single-Neuron Mechanisms Of Visual Object Coding In The Human Temporal Lobe, Runnan Cao, Jie Zhang, Jie Zheng, Yue Wang, Peter Brunner, Jon T Willie, Shuo Wang

2020-Current year OA Pubs

Understanding how the human brain encodes visual objects involves deciphering the neural computations and circuits in the temporal lobe. Here, we recorded intracranial EEG from the human ventral temporal cortex (VTC) and medial temporal lobe (MTL), as well as single-neuron activity in the MTL, to investigate the computational mechanisms of neural object coding. The VTC exhibited axis-based feature coding, and a neural feature space could be constructed using VTC neural axes, within which visual objects clustered according to high-level categorical relationships. Importantly, MTL neurons encoded receptive fields within this VTC neural feature space, exhibiting selective responses to objects that shared …

Prediabetes Associates With Musculoskeletal Alterations Independent Of Total Body Adiposity, Alan Fappi, Clifton J Holmes, Chao Cao, Vasavi Shabrish, Aman P Aher, Karen Shen, Paul K Commean, Dwight A Towler, Dominic N Reeds, Gretchen A Meyer, Bettina Mittendorfer

2020-Current year OA Pubs

BACKGROUND: Excess adiposity is a major risk factor for insulin resistance, prediabetes, and Type 2 diabetes and increases the risk for sarcopenia and osteosarcopenia later in life. It has been proposed that altered metabolic function and musculoskeletal status in people with obesity are directly linked, presumably because they share common pathophysiological mechanisms. However, the effect of metabolic dysfunction, independent of adiposity, on musculoskeletal status is unknown.

METHODS: We performed a comprehensive assessment of musculoskeletal status in people with overweight/obesity and prediabetes (n = 12; 72% women; age: 67 ± 6 years; weight: 81 ± 11 kg; mean ± SD) and …

Evaluating The Effectiveness Of Escalating To Weekly Adalimumab Dosing For The Treatment Of Noninfectious Uveitis: A Multicenter Study, Shani Pillar, Akshay Thomas, Lynn M Hassman, Howard Chen, Sapna Gangaputra, Laura J Kopplin, Kelly Boyd, Kareem Moussa, Derek C Pham, Keren Chen, Nicholas J Jackson, Edmund Tsui

2020-Current year OA Pubs

PURPOSE: To evaluate the effectiveness of adalimumab dosage escalation in patients with noninfectious uveitis that is controlled inadequately with standard dosing.

DESIGN: Multicenter retrospective interventional case series.

PARTICIPANTS: Patients with noninfectious uveitis receiving active standard biweekly adalimumab dosing who underwent treatment escalation to weekly adalimumab dosing at 6 tertiary referral centers.

METHODS: Demographic data and clinical findings were assessed at the time of adalimumab dosage escalation and 6 months later. Mixed-model analysis was performed to analyze clinical outcomes and to assess predictive factors of success.

MAIN OUTCOME MEASURES: Treatment success composite criteria included: (1) disease quiescence (≤ 0.5+ anterior chamber …

Bet Inhibitor-Based Combinations Targeting Novel Dependencies In Mecom-Rearranged (R) Aml, Christine E Birdwell, Warren Fiskus, Christopher P Mill, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Koji Sasaki, John A Davis, Kaberi Das, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Rasoul Pourebrahim, Selina Yuan, Xiaoping Su, Michele Ceribelli, Kapil N Bhalla

Faculty, Staff and Student Publications

MECOM rearrangement in AML involves either inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), where the dislocated GATA2 enhancer drives overexpression of the transcriptional regulator EVI1, causes concomitant GATA2 repression, and promotes AML progression, aggressive phenotype and therapy refractoriness. Treatment with BET protein inhibitor (BETi) induces in vitro and in vivo efficacy in MECOM-r AML cells. Utilizing an unbiased, high-throughput drug screen, focused on mechanistically-annotated drugs, we identified BRD4, PIK3CA, mTOR, BCL-xL and XIAP as dependencies in the MECOM-r AML cells. Monotherapy with mivebresib (BETi), dactolisib (PI3K/mTORi) and LCL161 (IAPi) dose-dependently induced greater lethality in PD MECOM-r versus non-MECOM-r AML cells. RNA-Seq and/or mass spectrometry …

Rare Heterozygous Missense Variants In Vsx2 Are Associated With Retinal Detachment, Daniel C Brock, Justin S Dhindsa, Yifan Chen, Vida Ravanmehr, Jonathan Mitchell, Fengyuan Hu, Xiaoyin Li, Likhita Nandigam, Quanli Wang, Kevin Wu, Jessica C Butts, Hardeep S Dhindsa, Benjamin J Frankfort, Nicholas M Tran, Slavé Petrovski, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

Retinal detachment (RD) is a sight-threatening emergency requiring urgent intervention to prevent permanent vision loss. While both environmental and genetic risk factors contribute to RD, its complete genetic architecture remains unknown. Here, we performed the largest whole genome sequencing-based case-control study in RD to date, including data from 7,276 RD cases and 236,741 controls in the UK Biobank. Through variant- and gene-level association analyses, we identified VSX2 as a genetic determinant of RD risk while confirming established associations including FAT3, RDH5, and COL2A1. Gene-level collapsing analysis revealed that rare heterozygous missense variants in VSX2 confer a 2.8-fold …

Training In Medications For Opioid Use Disorder And Buprenorphine Prescribing In The Post X-Waiver Era: Insights From A Nationwide, Multispecialty Survey, Sung In H Kim-Vences, Justin Nguyen, Jacqueline M Hirth, Kyle P Suen, Colleen A Keough, Roger Zoorob, Alicia A Kowalchuk

Faculty, Staff and Students Publications

Objective: The January 2023 repeal of the X-waiver aimed to reduce regulatory barriers to buprenorphine prescribing and enhance patient access to medications for opioid use disorder (MOUD). Its impact on prescribing by non-addiction-trained physicians, the integration of MOUD training into residency programs, and the role of mandated training on clinical practice remain unclear.

Methods: A 2024 online survey assessed physicians' awareness of the X-waiver repeal, exposure to MOUD training, and changes in buprenorphine prescribing. Multivariable logistic regression evaluated the independent effect of MOUD training and whether mandatory versus voluntary formats influenced prescribing behavior.

Results: Among 959 physicians (42.7 % residents), …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Purpuric Pityriasis Rosea In A 7-Year-Old Girl: A Rare Variant With Generalized Involvement, Ying-Ying Qian, Ya-Fen Wu, Ting Zhang, Ji-Bing Li, Si-Yuan Song, Wei Li

Faculty, Staff and Students Publications

A 7-year-old girl presented with a 10-day history of generalized purpura and petechiae. The eruption began with a solitary violaceous macule on the trunk and progressed within 1 week to multiple oval and round dark-red to violaceous purpuric macules, ecchymoses, and petechiae affecting the face, trunk, and extremities. Lesions were distributed parallel to skin cleavage lines with a characteristic “Christmas-tree” pattern on the back (Fig 1). No oropharyngeal lesions were noted on examination, and the patient denied sore throat or oral discomfort. She reported no pruritus, pain, fever, or systemic symptoms.

Rethinking The Centrality Of Brain Areas In Understanding Functional Organization, Benjamin Yost Hayden, Sarah R Heilbronner, Seng Bum Michael Yoo

Faculty, Staff and Students Publications

Parcellation of the cerebral cortex into functionally modular brain areas is foundational to cognitive and systems neuroscience. Here, we question the central status of brain areas from the perspectives of neuroanatomy and electrophysiology. We argue that the major ostensible determinants of brain function, such as cytoarchitecture and connectivity, seldom produce convergent parcellations. Brain areas themselves are just one of several equally important organizing principles; others include macroscale gradients, distributed networks, layers, columns and patches. We further argue that the evidence for a close correspondence between areal parcellation and cognitive function is weaker than is generally supposed. Indeed, many important cognitive …

Accelerated Diffusion Basis Spectrum Imaging With Tensor Computations, Kainen L Utt, Jacob S Blum, Donsub Rim, Sheng-Kwei Song

2020-Current year OA Pubs

This paper introduces an advanced framework for accelerated processing of diffusion-weighted imaging (DWI) data that utilizes an entire-image modeling approach to optimize the estimation of diffusion parameters from DWIs by mapping input diffusion data to predicted signals and estimating parameter values via a stochastic gradient descent optimizer (Adam). To validate this approach, we applied this framework to diffusion basis spectrum imaging (DBSI) and analyzed in vivo human brain and ex vivo mouse brain DWIs. Results demonstrate significant improvements to computational speed and signal-to-noise ratio (SNR) in estimated parameter maps compared to standard DBSI. Our approach is applicable to any diffusion …

Neural Cells Are Susceptible To Historic And Recently Emerged Oropouche Virus Strains, Kaleigh A. Connors, Maris R. Pedlow, Zachary D. Frey, Marjorie Cornejo Pontelli, Sean P. J. Whelan, W. Paul Duprex, Leonardo D'Aiuto, Zachary P. Wills, Amy L. Hartman

2020-Current year OA Pubs

Oropouche fever is a re-emerging global viral threat caused by infection with Oropouche virus (OROV). While disease is generally self-limiting, historical and recent reports of neurologic involvement highlight the importance of understanding the neuropathogenesis of OROV. In this study, we characterize viral replication kinetics in neurons, microglia, and astrocytes derived from immortalized, primary, and induced pluripotent stem cell-derived cells, which are all permissive to infection with the prototypic OROV BeAn19991. We demonstrate cell-type dependent replication kinetics with both historic and recently emerged viral strains. Further, we show that ex vivo rat brain slice cultures can be infected by all OROV …

Phase 1 Study Of Inbrx-105, A Tnfrsf9 (4-1bb) And Pd-L1 Bispecific Antibody, In Patients With Select Solid Tumors, Jong Chul Park, Doug R Adkins, Et Al.

2020-Current year OA Pubs

PURPOSE: INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.

PATIENTS AND METHODS: This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously once every 2 weeks or 4 weeks in parts 1 (single-agent dose escalation; 0.001-3 mg/kg) and 2 (single-agent expansion) or once every 3 weeks in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R …

Divergent Humoral Immune Signatures In Response To Klebsiella Pneumoniae Bacteremia, Paeton L Wantuch, Nadia Wattad, David A Rosen

2020-Current year OA Pubs

OBJECTIVES: Klebsiella pneumoniae is an increasingly threatening global pathogen with high rates of antibiotic resistance and no licensed vaccines available. Despite its worldwide importance, little is known about the human adaptive immune response to K. pneumoniae infection.

METHODS: Herein we observed the longitudinal antibody responses of three immunocompetent patients hospitalized with K. pneumoniae bacteremia. We analyzed the human serum for antibody titers and in vitro functionality. Further, serum function was evaluated via an in vivo mouse model.

RESULTS: We found that in each case, anti-K. pneumoniae antibodies against the infecting strain were still detectable a year after the initial infection. …

Patient-Reported Outcomes In The Serena-6 Trial Of Camizestrant Plus Cdk4/6 Inhibitor In Patients With Advanced Breast Cancer And Emergent Esr1 Mutations During First-Line Endocrine-Based Therapy, E L Mayer, C Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: In SERENA-6, switching from aromatase inhibitor (AI) to camizestrant with continuation of CDK4/6 inhibitor (CDK4/6i) guided by emergence of ESR1 mutations (ESR1-mut) during first-line AI-CDK4/6i in patients with hormone receptor (HR)-positive advanced breast cancer (ABC) resulted in statistically significant and clinically meaningful improvement in progression-free survival compared with AI-CDK4/6i and reduction in the risk of deterioration in global health status (GHS)/quality of life (QoL) (hazard ratio 0.54). Here we report additional data from patient-reported outcomes (PROs).

PATIENTS AND METHODS: Patients completed PRO questionnaires at pre-specified timepoints, including the European Organisation for Research and Treatment of Cancer (EORTC) oncology-specific EORTC …