Digital Commons Network^™

Optimizing Human Fcrn Mouse Models To Improve Pharmacokinetic Evaluation Of Antibody Drug Candidates., Gregory J. Christianson, Zachary M Howard, Samantha Kenney, Emily Lowell, Nijaguna Bethur, Derry C. Roopenian, Elena Gonzalo-Gil

Faculty Research 2026

The use of animal models that can reliably predict drug performance in human patients is critical to antibody therapeutic development. Along with assessing toxicity and efficacy, determining the pharmacokinetic (PK) properties of therapeutics in Tg32 and Tg276 mice is essential to preclinical characterization. While Tg32 mice have been well established as indispensable in their ability to model the PK properties of antibody therapeutics, their intact immunity leaves them capable of mounting anti-drug antibody responses that interfere with PK interpretation. Here, we demonstrate the negative impact anti-drug responses can have on PK parameters derived from Tg32 mice, and provide strong evidence …

Optimizing Human Fcrn Mouse Models To Improve Pharmacokinetic Evaluation Of Antibody Drug Candidates., Gregory J. Christianson, Zachary M Howard, Samantha Kenney, Emily Lowell, Nijaguna Bethur, Derry C. Roopenian, Elena Gonzalo-Gil

Faculty Research 2026

The use of animal models that can reliably predict drug performance in human patients is critical to antibody therapeutic development. Along with assessing toxicity and efficacy, determining the pharmacokinetic (PK) properties of therapeutics in Tg32 and Tg276 mice is essential to preclinical characterization. While Tg32 mice have been well established as indispensable in their ability to model the PK properties of antibody therapeutics, their intact immunity leaves them capable of mounting anti-drug antibody responses that interfere with PK interpretation. Here, we demonstrate the negative impact anti-drug responses can have on PK parameters derived from Tg32 mice, and provide strong evidence …

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, Micah D Forshee, Erika J Nachman, Esha R Shenoy, Heather A Danhof, Ludwig Ermann Lundberg, Stefan Roos, Robert A Britton

Faculty, Staff and Students Publications

Strains of Limosilactobacillus reuteri have been used to prevent or treat various conditions; however, the mechanisms by which they exert beneficial effects are not completely understood. Infant colic is one example in which L. reuteri DSM 17938 reduces clinical symptoms. While the etiology of colic is unknown, abnormal melatonin levels in infants have been suggested as a possible contributor. L. reuteri DSM 17938 has been shown to produce adenosine from AMP via production of the extracellular enzyme 5′ectonucleotidase (5′NT). Adenosine is a potent signaling molecule that impacts several important aspects of host physiology, including the release of melatonin from the …

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, Nuri Sung, Eunsu Kim, Yosef Gilad, Yuri Park, Adam M Dean, Yan Xia, Jianming Xu, Clifford C Dacso, David M Lonard, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is highly expressed in regulatory T cells (Tregs) and is important for their immunosuppressive activity. Recently, we demonstrated that disrupting SRC-3 expression in Tregs eliminates triple-negative breast cancer (TNBC) and prostate cancer in syngeneic animal models by generating an anti-tumor immune microenvironment without inducing immune-related adverse events (irAEs). Further analysis of these mice revealed that SRC-3 knockout (KO) Tregs infiltrated breast tumors and facilitated the infiltration of CD8

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, Geoffrey A Preidis, Hania Szajewska, Marla Cunningham, Howard Bauchner, Daniel J Merenstein

Faculty, Staff and Students Publications

Many professional organizations publish clinical practice guidelines for the use of probiotics in gastrointestinal disorders. Generally, no two guidelines align perfectly, and some differ markedly. These discrepancies occur because clinical practice guidelines are not purely mechanical outputs of data synthesis. They are shaped by structured interpretation, value judgments, and predefined thresholds for uncertainty. These elements become particularly visible when effect sizes are small, heterogeneity is high, and outcomes vary in clinical relevance-as is the case with probiotic research. This article examines why discordance among probiotic guidelines is predictable and provides practical guidance for clinicians who must decide among conflicting recommendations …

Mtorc2-Nav1.2 Signaling Drives Early Hyperexcitability In Alzheimer’S Disease Mouse Model, Nolan M Dvorak, Jeffrey L Noebels

Faculty, Staff and Students Publications

Hyperexcitability is a biomarker of early-stage Alzheimer’s Disease (AD) and hastens cognitive decline later in its course. Mechanistic target of rapamycin (mTOR) signaling contributes to the slope of this trajectory, as evidenced by early increased brain expression and the rescue of hyperexcitability by genetic deletion of mTOR complex 2 (mTORC2); however, a molecular mechanism directly linking mTOR signaling to membrane hyperexcitability in early-stage AD remains elusive. Here, we show that hyperactive mTOR signaling stimulates the voltage-gated Na+ channel 1.2 (Nav1.2), a previously identified downstream phosphorylation target of mTORC2 and a key regulator of membrane electrogenesis. Augmented Nav1.2 channel function induced …

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Farah Kazzaz, Sarah Shin, Harry Karmouty-Quintana, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …

Emotional Urgency And Lack Of Perseverance Are Linked To Anxiety Sensitivity And Improve During Early Recovery From Opioid Use Disorder., Breanna A. Mcnaughton-Long, Abigail J. Pleiman, Carmen Buchfink, Chrysantha B. Davis, Rayus Kuplicki, Martin P. Paulus, Hung-Wen Yeh, Maëlle C M Gueguen, Jennifer L. Stewart

Manuscripts, Articles, Book Chapters and Other Papers

Few studies have identified how facets of impulsivity relate to recovery in opioid use disorder (OUD). Treatment-enrolled individuals with OUD (n = 167) and healthy controls (CTL; n = 46) completed the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency (UPPS-P) Impulsive Behavior Scale along with demographic and clinical measures at visit 1. Over the next three months, abstinence and return to use were documented for participants with OUD (via self-report, alcohol breathalyzer, urine drug screen, and secondary contact communication). Participants with OUD who returned to use (n = 59) did not complete further study visits, whereas those who remained abstinent …

Clinical Function Assignment Of Nat2 Alleles By The Clinical Pharmacogenetics Implementation Consortium Pharmacogene Curation Expert Panel., Bailey M. Tibben, David W. Hein, Michelle Whirl-Carrillo, Andrea Gaedigk, Michael T. Eadon, Rodney F. Minchin, Sotiria Boukouvala, Adalberto Rezende Santos, Roseann S. Donnelly, José A G Agúndez, Kelly E. Caudle

Manuscripts, Articles, Book Chapters and Other Papers

NAT2 encodes arylamine N-acetyltransferase 2, a key enzyme in the phase II metabolism of arylamines and arylhydrazines. NAT2 is highly polymorphic, resulting in variable distributions of rapid and poor metabolizers across global populations. Here, we detail the process undertaken by the Clinical Pharmacogenetics Implementation Consortium (CPIC) NAT2 Pharmacogene Curation Expert Panel (PCEP) to assign clinical function to NAT2 star (*) alleles using CPIC's standard terminology. Given the observed impact of NAT2 genetic variability on drug response, CPIC convened the NAT2-PCEP to standardize clinical allele function assignments. The NAT2-PCEP is comprised of multidisciplinary and international members, including researchers, clinicians, and implementers …

The Epidemiology Of Kidney And Urinary Tract Infections In Pediatric Chronic Kidney Disease: Prevalence, Risk Factors And Association With Gfr Decline In The Chronic Kidney Disease In Children Study., Derek K. Ng, Andrea R. Molino, Siyao Zhang, Emily J. Stonebrook, Craig S. Wong, Pratyush Gyawali, Kimberly J. Reidy, Susan L. Furth, Bradley A. Warady, Jeffrey J. Fadrowski, Ckid Study Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Urinary tract and kidney infections are potential complications in pediatric chronic kidney disease (CKD), especially among patients with congenital anomalies of the kidney and urinary tract (CAKUT). We characterized the prevalence of self-reported infections from childhood through young adulthood; evaluated risk factors; and quantified the association with CKD progression.

METHODS: Infections in the past year were self-reported at annual Chronic Kidney Disease in Children (CKiD) study visits. Age-specific infection prevalences were stratified by sex and CKD diagnoses (glomerular, non-glomerular non-CAKUT, CAKUT low-risk for infections, and three CAKUT high-risk categories: reflux nephropathy, obstructive uropathy, and other high-risk). Repeated measures logistic …

Streamlining Diagnosis Of Bardet-Biedl Syndrome: New Diagnostic Algorithm With Updated Criteria., Jeremy J. Pomeroy, Jesse Richards, Brooke Sweeney, Seema Kumar, Katie E. Queen, Joshua Zaritsky, Carl H. Cramer, Elias I. Traboulsi, Brittni A. Scruggs, Erica E. Davis, Ekaterina Keifer, Emma Mcgibbon, Timothy Ogden, Bendert De Graaf, Tonia Hymers, Elizabeth Forsythe, Philip Beales

Manuscripts, Articles, Book Chapters and Other Papers

Considerable advances have been made in our understanding of Bardet-Biedl syndrome (BBS), particularly in its core clinical features and molecular genetics, warranting an update to the existing diagnostic criteria framework. Using a rigorous, evidence-based, and consensus-driven process, a multidisciplinary group of international experts and patient-led organizations developed an updated diagnostic algorithm. This algorithm provides practical, updated guidance for clinicians, including a pathway for accurately incorporating genetic findings into the diagnostic process. We recommend that a clinical diagnosis requires either 4 major criteria or 3 major and 2 minor criteria. Revised major criteria are retinal dystrophy, obesity (or overweight in individuals <  2 years old), congenital anomalies of the kidney and urinary tract or chronic kidney disease, hypogonadism/genital anomalies, neurodevelopmental/neurocognitive manifestations, and postaxial polydactyly. The diagnosis can also be established with a positive genetic testing result in patients exhibiting ≥ 1 major criterion, provided that genetic findings should be interpreted in the context of the patient's clinical presentation, age, family history, and overlap with related ciliopathies. These consensus criteria offer a simple algorithm incorporating updated definitions for major and minor criteria and genetic testing to support a timely and accurate diagnosis of patients with BBS, inform genetic counseling, and potentially facilitate earlier access to treatment. Trial Registration: CRIBBS Registry; ClinicalTrials.gov: NCT02329210.

Ambulatory Blood Pressure Thresholds And Left Ventricular Hypertrophy In Children Aged 6-12 Years: A Pediatric Nephrology Research Consortium Study., Afsana Jahan, Matthew Schuchman, Mahie Abdullah, Meghan Mclaughlin, Emilia Maria Cadiz, Eshanika Manchanda, Aftab Chishti, Maggie Murphy, Sarah Twichell, Alexandra Mazo, Dmitry Samsonov, Aesha Maniar, Hannah Kim, Francis Lomanta, Ashok Chakravarthy Patibandla, Rachel Frank, Tarak Srivastava, Ikuyo Yamaguchi, Christine Sethna

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To evaluate the diagnostic performance of ambulatory blood pressure monitoring (ABPM) thresholds for predicting left ventricular hypertrophy (LVH) in children aged 6-12 years.

STUDY DESIGN: A retrospective, multicenter study was conducted across 11 Pediatric Nephrology Research Consortium sites and included children aged 6-12 years who underwent ABPM and 2-dimensional echocardiography for diagnostic assessment of elevated BP. The diagnostic accuracy of fixed ABPM thresholds and the current 95th percentile for sex and height were assessed using area under the receiver operating characteristic, sensitivity, specificity, and Youden index. Multivariable logistic regression models, adjusted for age, sex, and body mass index z-score, …

Peritoneal Dialysis Catheter Complications In Neonates With Kidney Failure., Shannon Reinert, Maanasa Yarlagadda, Alexander Bondoc, Donna Claes, Stefanie Riddle, Meredith P. Schuh

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Neonates with kidney failure require placement of a peritoneal dialysis catheter (PD-C) shortly after birth. PD-C malfunction and peritonitis, both common in this population, are associated with PD failure. The aim of this study was to describe our center's PD-C-related practices and outcomes in neonates with kidney failure.

METHODS: We performed a retrospective chart review of neonates who required kidney replacement therapy (KRT) within the first 30 days of life from 01/2018-12/2023. We evaluated for PD-C duration, PD-C replacement or revision, and peritonitis.

RESULTS: Twenty-four neonates had PD-C placed for chronic dialysis at a median of 9.7 days and …

Androgens Mediate Sexual Dimorphism In Pilarowski-Bjornsson Syndrome., Kimberley Jade Anderson, Eirny Tholl Thorolfsdottir, Ilana M. Nodelman, Sara Tholl Halldorsdottir, Stefania Benonisdottir, Malak A. Alghamdi, Naif A M Almontashiri, Brenda J. Barry, Matthias Begemann, Jacquelyn F. Britton, Sarah Burke, Benjamin Cogne, Ana S A Cohen, Carles De Diego Boguñá, Evan E. Eichler, Elizabeth C. Engle, Jill A. Fahrner, Laurence Faivre, Mélanie Fradin, Nico Fuhrmann, Christine W. Gao, Gunjan Garg, Dagmar Grečmalová, Mina Grippa, Jacqueline R. Harris, Kendra Hoekzema, Tova Hershkovitz, Sydney Hubbard, Katrien Janssens, Julie A. Jurgens, Stanislav Kmoch, Cordula Knopp, Meral Aktas Koptagel, Farah A. Ladha, Pablo Lapunzina, Tobias Lindau, Marije Meuwissen, Andreina Minicucci, Emily Neuhaus, Mathilde Nizon, Lenka Nosková, Kristen Park, Chirag Patel, Rolph Pfundt, Pankaj Prasun, Nils Rahner, Nathaniel H. Robin, Carey Ronspies, Jasmin Roohi, Jill Rosenfeld, Margarita Saenz, Carol J. Saunders, Zornitza Stark, Isabelle Thiffault, Sarah Thull, Danita Velasco, Clara Velmans, Jolijn Verseput, Antonio Vitobello, Tianyun Wang, Karin Weiss, Ingrid M. Wentzensen, Genay Pilarowski, Thor Eysteinsson, Madelyn Gillentine, Kári Stefánsson, Agnar Helgason, Gregory D. Bowman, Hans Tomas Bjornsson

Manuscripts, Articles, Book Chapters and Other Papers

Sex-specific penetrance in autosomal-dominant Mendelian conditions is largely understudied. The neurodevelopmental disorder Pilarowski-Bjornsson syndrome (PILBOS) was initially described in females. Here, we describe the clinical and genetic characteristics of the largest PILBOS cohort to date, showing that both sexes can exhibit PILBOS features, although males are overrepresented. A mouse model carrying a human-derived Chd1 missense variant (Chd1^R616Q/+) displays female-restricted phenotypes, including growth deficiency, anxiety, and hypotonia. Orchiectomy unmasks a growth-deficiency phenotype in male Chd1^R616Q/+ mice, while testosterone rescues the phenotype in females, implicating androgens in phenotype modulation. In the gnomAD and UK Biobank databases, rare missense variants …

Current State And Needs Of Clinical Laboratories In Selected Countries In Africa, Merih Tesfazghi, Anne E Tebo, Roa Harb, Anthony O Okorodudu, Lee Schroeder, Jeannette Guarner, Christine Bales, Jack Ladenson, Allison Targowski, Kerry Cosby, Olajumoke Oladipo

2020-Current year OA Pubs

The Africa Working Group, under the auspices of the Global Laboratory Quality Initiative of the Association for Diagnostics & Laboratory Medicine (ADLM), conducted several educational workshops in Africa to promote laboratory quality in the region. The challenges faced in maintaining quality in clinical laboratories in low-resource countries may differ from region to region and country to country. To better understand current gaps and inform our engagement with partners in Africa, a needs assessment survey was distributed to 1427 ADLM members in Africa and further disseminated through local partners, resulting in 121 responses from participants across 8 countries in the region. …

Hunting For Microsatellite Instability In Long-Read Data With Owl., Zev Kronenberg, Byunggil Yoo, Khi Pin Chua, Mark J P Chaisson, Lisa Lansdon, William J. Rowell, Guilherme De Sena Brandine, Jocelyne Bruand, Egor Dolzhenko, Kobe Ikegami, Jay Sarthy, Kie Kyon Huang, Patrick Tan, Shruti Bhise, Everett Fan, Mark Mendoza, Emily O'Donnell, Tomi Pastinen, Elizabeth R. Lawlor, Scott N. Furlan, Midhat S. Farooqi, Michael A. Eberle

Manuscripts, Articles, Book Chapters and Other Papers

Microsatellite instability (MSI) is a key biomarker of mismatch repair deficiency and response to immunotherapy, yet most existing genomic detection methods are optimized for short-read sequencing and rely on a panel of homopolymer markers, limiting the ability to characterize genome-wide and motif-specific patterns of instability. Here we present Owl, a bioinformatic tool for quantifying MSI from long-read (PacBio) genomic data. Owl leverages a genome-wide marker set of more than 140,000 microsatellite repeats ranging from 1-6 bp in length to measure MSI across a phased genome. Using a wrap-around alignment algorithm, Owl constructs repeat-length distributions at each marker site and flags …

Cerebellar Atrophy In Pediatric-Onset Opsoclonus-Myoclonus-Ataxia Syndrome: A Large International Cohort Study, Rebecca Macrae, Kierstin Hederstedt, Christopher Cortina, Kumaran Deiva, Andrea Klein, Ming Lim, Thomas Rossor, Elizabeth A Sokol, Yasmin Khakoo, Nikita Malani Shukla, Timothy E Lotze, Wendy G Mitchell, Sarah Hopkins, Bo Zhang, Mark P Gorman

Faculty, Staff and Students Publications

Background and objectives: Pediatric-onset opsoclonus-myoclonus-ataxia syndrome (POOMAS) is a rare, neuroinflammatory syndrome that targets the cerebellum and can cause irreversible cerebellar structural changes, namely cerebellar atrophy. We investigated the frequency of cerebellar atrophy, as well as associated risk factors and functional outcome measures, using the largest active POOMAS registry.

Methods: This was a retrospective observational study of participants with POOMAS with disease onset from 1995 to 2025 using data from the multinational, multicenter POOMAS registry. Variables were compared between the cerebellar atrophy subgroups using the Fisher exact test or Wilcoxon rank-sum test.

Results: Of participants with follow-up imaging, cerebellar atrophy …

An Observational Study Of The Effect Of Concomitant Levetiracetam On Apixaban Concentrations In A Hospital Cohort, Chazmyn Riley, Kevin Lam, Cristina Micale, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the lack of evidence of a mechanism-based drug interaction, some professional organizations have advised caution coadministering apixaban and levetiracetam. Eligible patients taking apixaban with or without levetiracetam for any indication for at least 72 h were screened from the electronic medical records. Plasma samples from 77 patients were retrieved from salvaged clinical blood collections. Apixaban minimum and maximum concentrations (Cmin and Cmax) were compared using descriptive statistics in R. While the median Cmin and Cmax appear to be marginally elevated, there were no apparent differences relative to apixaban alone. These findings suggest no apparent interaction of levetiracetam and support …

Single Immunoglobulin Interleukin1-Related Receptor-Twist1 Axis Regulates Barrier Function In Neonatal Intestine., Aparna Venkatraman, Wei Yu, Heather Menden, Sherry M. Mabry, Joshua Wheatley, Shahid Umar, Susana Chavez-Bueno, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: The genetic basis of impaired intestinal barrier function in preterm infants is poorly understood. Variants in single immunoglobulin interleukin1-related receptor, a negative regulator of Toll-like receptor signaling, have been identified in preterm infants with necrotizing enterocolitis. We hypothesized that single immunoglobulin interleukin1-related receptor variants associated with necrotizing enterocolitis impair gut barrier function to pathobionts. The aim of this study was to determine how single immunoglobulin interleukin1-related receptor genetic variants disrupt neonatal intestinal barrier integrity and promote susceptibility to Gram-negative bacteria implicated in sepsis and necrotizing enterocolitis pathogenesis.

METHODS: Transgenic mice and preterm infant-derived enteroids expressing SIGIRR variants …

Prediction Model For Children With Anaphylaxis Who May Not Require Emergency Department Care: A Multicenter Retrospective Cohort Study., Timothy E. Dribin, David Schnadower, Hugh A. Sampson, Yin Zhang, Nanhua Zhang, Stephen B. Freedman, Mark I. Neuman, David C. Brousseau, Rakesh D. Mistry, Stephanie Boyd, Yonatan Wolnerman, Patrick S. Walsh, Craig Vander Wyst, Vandana Thapar, Jonathan Strutt, Geetanjali Srivastava, Nidhi V. Singh, Christopher J. Russo, Christian D. Pulcini, Thuy L. Ngo, Jo-Ann O. Nesiama, Matthew M. Moake, Ashley M. Metcalf, Tamar R. Lubell, Juhee Lee, Chari D. Larsen, Karen Y. Kwan, Curtis L. Knoles, Kajal Khanna, Julia F. Freeman, Justin R. Davis, Alicia Daggett, Joanna S. Cohen, Ari R. Cohen, Wee-Jhong Chua, Sri S. Chinta, Brittany Boswell, Kelly R. Bergmann, Paul L. Aronson, Kenneth A. Michelson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The 2023 US Anaphylaxis Practice Parameter indicated that some patients receiving epinephrine in the community might avoid emergency department (ED) visits; however, the criteria and safety of this approach remain unproven.

OBJECTIVE: To derive and validate a clinical prediction model for identifying children at risk of receiving epinephrine after arriving at the ED.

METHODS: We conducted a 31-center retrospective cohort study of children aged 6 months to less than 18 years who received 1 prehospital dose of epinephrine for allergic reactions between 2016 and 2019. The outcome was receipt of epinephrine after ED arrival. We used least absolute shrinkage …

Skin Carotenoid Scores Are A Valid Approximation Of Fruit And Vegetable Intake Among Adults With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Elizabeth Gates, Melissa N Laska, Andrew R Dinardo, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoid score (SCS) as measured using pressure-mediated reflection spectroscopy has been validated among adults with normal and overweight body mass index, with little validation research among adults with obesity. Therefore, the purpose of this exploratory study was to examine the validity of SCS as an approximation of fruit and vegetable intake among adults with obesity. We used samples from adults with obesity from three prior studies: The first study examined the validity of SCS among 213 adults, 34 with obesity; the second, examined sensitivity of SCS to a β-carotene-rich juice intervention among 162 adults, 14 with obesity; the third …

Hydroxyethyl Starch And Perioperative Complications: A Systematic Review And Meta-Analysis, Daniel I Sessler, Lorenzo Pradelli, Massimiliano Povero, Daniel Chappell, E Wang

Faculty, Staff and Student Publications

Background: Based on renal injury reported in critically ill and septic patients, the U.S. Food and Drug Administration issued a black box warning regarding hydroxyethyl starch (HES 130/0.4) use in 2013 and expanded the warning to surgical and trauma patients in 2021. Similarly, the European Medicines Agency initiated withdrawal of hydroxyethyl starch in 2022. This study was a new meta-analysis focused on renal injury designed to complement a 2021 meta-analysis of perioperative hydroxyethyl starch use, adding 45 trials and 6,895 patients. The focus was acute kidney injury and preoperative-to-postoperative change in creatinine concentration in surgical patients.

Methods: This study searched …

Characterization Of Mettl3/14-Mediated M6a Modification In Human Transcriptome Using Nanopore Direct Rna Sequencing, Emily Kurtyan, Andrew J. Stein, Kelly J. Abdalla, Zhangerjiao Yuan, Miten Jain, Fadia Ibrahim

Department of Biochemistry and Molecular Biology Faculty Papers

Post-transcriptional RNA modifications modulate diverse aspects of RNA metabolism. N6-methyladenosine (m6A), one of the most abundant internal RNA modifications, is deposited by the core methyltransferase complex, METTL3 and METTL14. Oxford Nanopore Technologies (ONT) platform permits direct, single RNA molecule sequencing while preserving native modifications. However, without rigorous benchmarking, the accuracy and reproducibility of modification detection remain uncertain. Here, we leveraged ONT to comprehensively profile bona fide m6A modifications in cellular RNAs at single-nucleotide resolution by integrating two direct RNA sequencing chemistries (RNA002 and RNA004) with the m6Anet and Dorado modification-detection models. We independently depleted METTL3 and METTL14 in human cells …

Inosine-Triphosphate-Pyrophosphatase Activity As A Potential Predictor Of Methotrexate Remission In Juvenile Idiopathic Arthritis., Sofia Sindici Forgiarini, Marianna Lucafò, Debora Curci, Davide Selvestrel, Valentina Moressa, Sofia Pagarin, Barbara Bellich, Martina Franzin, Alberto Tommasini, Mara L. Becker, Laura Ramsey, Susan D. Thompson, Carl D. Langefeld, Federica Corba, Edoardo Marrani, Gabriele Simonini, Gabriele Stocco, Giuliana Decorti, Andrea Taddio, Serena Pastore

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Methotrexate (MTX) is the first-line therapy for juvenile idiopathic arthritis (JIA), but up to 40% of patients do not respond to it. Low inosine triphosphate pyrophosphatase (ITPA) activity has been associated with reduced clinical remission. We investigated the role and underlying mechanisms of ITPA in vitro.

METHODS: ITPA enzymatic activity was measured by high-performance liquid chromatography with ultraviolet detection in erythrocyte lysates from patients with JIA (enrolled in Trieste, Italy; Florence, Italy; and Kansas City, Missouri) receiving weekly MTX (10-15 mg/m²) for at least 12 months. Remission was evaluated by Wallace et al criteria. ITPA rs1127354, which …

Association Between Estimated Time With Low Glomerular Filtration Rate And Access To Transplant Among Youth With Advanced Chronic Kidney Disease., Elaine Ku, Timothy Copeland, Charles E. Mcculloch, Jonathan D. Savant, Bradley A. Warady, Susan L. Furth, Sarah Kizilbash, Daniel I. Feig, Roshan P. George, Joseph T. Flynn, Judith Jerry-Fluker, Matthew B. Matheson, Sandra Amaral, Ckid Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Slower chronic kidney disease (CKD) progression allows more time for transplant preparation. Whether differences in CKD progression by race/ethnicity associate with preemptive or living donor transplantation in youth has not been well studied.

METHODS: We examined the association between time spent with low eGFR (between 10-30 mL/min/1.73 m²) and odds of preemptive or living donor transplantation among youth with CKD. eGFR was estimated using the bedside Schwartz (if < 18 years) and CKD-EPI 2021 equations (if ≥ 18 years) and the CKiD U25 equation in sensitivity analysis. Time spent with low eGFR was compared by race/ethnicity.

RESULTS: Among 333 youth with CKD (median age 11 years [IQR 7,14]), median time spent with low eGFR was 28.8 months. 77% were preemptively waitlisted, and 45% received preemptive …

The Rise And Fall Of Lateral Electrical Surface Stimulation (Less) Through The Lens Of Srs Archives., Ali Rezazadeh Shirazi, Jay I. Kumar, Katie Dold, George H. Thompson, Andrew G. King, Richard M. Schwend, John P. Lubicky, Jay Shapiro, Behrooz A. Akbarnia, History Committee Of The Scoliosis Research Society

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Lateral electrical surface stimulation (LESS), commercially known as the ScoliTron™, emerged in the late 1970s as a noninvasive alternative to bracing for adolescent idiopathic scoliosis. Early clinical reports generated considerable enthusiasm and adoption, but the technique was ultimately abandoned. This study examined the rise and fall of LESS through a combined analysis of the Scoliosis Research Society (SRS) archives and published literature, with the goal of understanding factors that influence the adoption, evaluation, and abandonment of innovation in scoliosis care.

METHODS: A structured historical review was conducted using archival materials from the Scoliosis Research Society (SRS), including meeting abstracts, …

Patient-Specific Computational Fluid Dynamics Modeling Of Airway Collapse In Infants With Robin Sequence., Gautam Jalori, Michael Barbour, Michael Bindschadler, Kelly Evans, John P. Dahl, Alberto Aliseda

Manuscripts, Articles, Book Chapters and Other Papers

Robin Sequence (RS) is a congenital condition in which patients experience dynamic, periodic obstruction or collapse of the upper airway due to an underdeveloped jaw and a posteriorly displaced tongue. Current clinical techniques for evaluating airway obstruction do not provide quantifiable data and fail to account for the dynamic nature of obstruction or collapse. There is no standardized criterion to characterize obstruction or collapse severity. This study presents the first method that extracts airway motion from 4-dimensional computed tomography and performs a patient-specific, moving-mesh computational fluid dynamics (CFD) analysis of RS patients with complete airway collapse or obstruction. To quantify …

Ovarian Cancer Tumor Immune Profiles Associated With Intrauterine Device And Oral Contraceptive Use., Jennifer M. Mongiovi, Ana Babic, Naoko Sasamoto, Mary K. Townsend, Allison F. Vitonis, Mollie Barnard, Jonathan Hecht, T Rinda Soong, Jose R. Conejo-Garcia, Lauren C. Peres, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Francesmary Modugno, Brooke L. Fridley, Shelley S. Tworoger, Kathryn L. Terry

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Non-hormonal intrauterine devices (IUDs) create an inflammatory uterine environment while oral contraceptives (OC) suppress ovulation and have different associations with ovarian cancer risk. We have evaluated the associations of these two contraceptive exposures with ovarian tumor immune infiltration.

METHODS: This study assessed associations of IUD and OC use with tumor immune features via multiplex immunofluorescence in 24 ovarian tumor tissue microarrays from four case-control and two cohort studies. Multivariable-adjusted beta-binomial models estimated the odds of tumor T cell positivity by contraceptive history.

RESULTS: High-grade serous tumors had the highest percentage of tumor cells positive for total T cells (CD3+ …

Spinal Cord Imaging For Multiple Sclerosis: Advances, Priorities, And Opportunities, Cornelia Laule, Matthew R Brier, Et Al.

2020-Current year OA Pubs

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of …

Crosstalk Between Upr And Mitochondria: The Triad Of Er-Mitochondria Contacts, Ca²⁺, And Ros, Ester Zito, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum (ER) stress is triggered by several cellular perturbations causing protein misfolding, and activates the unfolded protein response (UPR), an initially adaptive signaling network that aims to restore ER and cellular homeostasis. Growing evidence indicates that UPR signaling extends beyond ER proteostasis, influencing mitochondrial function and bioenergetics through ER-mitochondria contact sites (ERMCs). The CHOP-ERO1A-IP3R axis has a primary role in recruiting mitochondria to adaptive UPR. However, its sustained activation renders UPR signaling maladaptive, leading to mitochondrial dysfunction through both outer mitochondrial membrane permeabilization (OMMP) and mitochondrial permeability transition pore (mPTP) opening, ultimately contributing to irreversible cell injury and disease …