Digital Commons Network^™

Rsv Can Infect The Human Nasal Epithelium Via The Basolateral Route And Shows Distinct Subgroup Infectivity And Basal Cell Tropism, Ashley Murray, Divya Nagaraj, Emily M Schultz, Gina Aloisio, Erin Nicholson, Sarah E Blutt, Vasanthi Avadhanula, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) causes millions of lower respiratory tract infections (LRTIs) in young children, older adults, and immunocompromised populations every year. RSV infection initiates in the upper respiratory tract and can progress to the lower airways, resulting in bronchiolitis, pneumonia, and even death. RSV primarily infects epithelial cells apically, but we hypothesized that basolateral exposure of the respiratory epithelium could provide an alternative mechanism of infection that contributes to LRTI development. Using a human nose organoid-air-liquid interface (HNO-ALI) model, we performed apical and basolateral inoculations with contemporaneous RSV strains (RSV/A/Ontario [RSV/A/ON] and RSV/B/Buenos Aires [RSV/B/BA]) representing the two RSV …

Identification Of Acute Kidney Injury In African Children Hospitalized With Malaria: A Multinational Individual Participant Data Meta-Analysis, Caitlin Bond, Anthony Batte, Folake Afolayan, Nicholas M Anstey, Quique Bassat, Philip A Bejon, James A Berkley, Rhys D R Evans, Stuart L Goldstein, Michael T Hawkes, Olayinka Ibrahim, Peace Imani, Chandy C John, Kevin C Kain, Claire Liepmann, Kevin Marsh, Ruth Namazzi, Margaret Nakuya, Nicole O'Brien, Lere P Oluwadare, Robert O Opoka, Jonathan Sserunkuuma, Hunter Wynkoop, Andrea L Conroy, Malaria Associated Kidney Injury And Disease Consortium In Africa (Makid-Africa)

Faculty, Staff and Students Publications

Background: Historically, acute kidney injury (AKI) has been an underappreciated complication in children with severe malaria. We conducted an individual patient data meta-analysis to model the impact of AKI and its complications on inpatient mortality in African children hospitalized with malaria.

Methods: Studies were identified using MEDLINE, EMBASE, Scopus, and PubMed with no language restrictions, as well as through outreach at scientific meetings. Investigators were contacted about participation in the study. Eligible studies included African children hospitalized with Plasmodium falciparum malaria, a serum creatinine measurement, and mortality assessed. The primary exposure was AKI, defined using Kidney Disease Improving Global Outcomes …

Using Polygenic Risk Scores To Evaluate Definitions Of Self-Reported Sleep Phenotypes Across Cohorts, Annah B Wyss, Michael Brown, Xiang Li, Brian W Spitzer, Zhijie Huang, Heming Wang, Richa Saxena, Linda Gallo, Qibin Qi, Wassim Tarraf, Robert Kaplan, Melissa Lamar, Hector M González, Charles Decarli, Myriam Fornage, Jerome I Rotter, Stephen S Rich, Kent D Taylor, Xiuqing Guo, Alexis C Wood, Peter Y Liu, Susan R Heckbert, Chloé Sarnowski, Jan Bressler, Alanna C Morrison, Bing Yu, Pamela L Lutsey, Carmen R Isasi, Susan Redline, Tamar Sofer

Faculty, Staff and Students Publications

Study objectives: Since genome-wide association studies (GWAS) of sleep phenotypes have been conducted in differing populations and definitions of sleep phenotypes vary across studies, we investigated associations between several polygenic risk scores (PRSs) and potential sleep definitions among multiethnic cohorts.

Methods: Using data from four cohorts (HCHS/SOL, ARIC, MESA, BHS, N = 16 895), we considered multiple definitions of short and long sleep, insomnia, and excessive daytime sleepiness (EDS). PRSs were developed based on summary statistics from GWAS in European ancestry individuals from the UK Biobank (UKB) and from GWAS conducted in a multiethnic population from the Million Veteran Program …

Functional Divergence Of Capicua Isoforms Explains Differential Tissue Vulnerability In Neurological Disease, Hamin Lee, Esmeralda Villavicencio Gonzalez, Elias M Rivera, Mark A Durham, Ronald Richman, Elizabeth H-Y Chu, Kailey Xia, Hu Chen, Zhandong Liu, Surabi Veeraragavan, Binoy Shivanna, Huda Y Zoghbi

Faculty, Staff and Students Publications

Many neurological diseases impact specific brain regions despite widespread expression of the disease-related protein. Spinocerebellar ataxia type 1 (SCA1) primarily affects the cerebellum, though Ataxin-1 (ATXN1) is widely expressed. We previously showed that intensified interaction between mutant ATXN1 and Capicua (CIC) drives SCA1 pathogenesis in the cerebellum, whereas ATXN1 loss augments amyloid β production in the hippocampus and cortex. CIC, however, forms a complex with ATXN1 and its paralog, Ataxin-1-like (ATXN1L), yet knockout of either yields completely different phenotypes. To determine whether this could be due to CIC having two isoforms, we generated mice bearing either the long (CIC-L) or …

Epilepsy-Associated Digenic Variants Affecting An Actin-Mitochondria-Glutamate Pathway Promote Seizure Susceptibility, Shenzhao Lu, Mengqi Ma, Shabab B Hannan, Mingxi Deng, Hu Chen, Zhijian Yu, Lindsey D Goodman, Haein Kim, Yun Zhao, Sandeep Kumar Dubey, Wen-Wen Lin, Xueyang Pan, Debdeep Dutta, Vishnu Anand Cuddapah, Jill A Rosenfeld, Xi Luo, Zhandong Liu, Joshua M Shulman, Hugo J Bellen

Faculty, Staff and Students Publications

Epilepsy affects approximately 50 million people worldwide, yet more than half of individuals with a presumed genetic cause still lack a molecular diagnosis despite the identification of over 1,000 monogenic epilepsy genes. This diagnostic gap is unlikely to be resolved by improved variant detection alone, suggesting that variants affecting the same biological pathway may combine to cause disease. By studying epilepsy-associated actin regulatory genes, we identified a conserved "actin-mitochondria-glutamate (AMG) pathway". We demonstrate that reduced actin polymerization promotes DRP1-mediated mitochondrial fission, increases reactive oxygen species (ROS) levels, and enhances glutamatergic transmission, leading to seizures. The glial innate immune pathway, a …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, Robert B Lindell, Samir U Sayed, Jose S Campos Duran, Sydney A Sheetz, Apoorva Babu, Montana S Knight, Andrea A Mauracher, Ceire A Hay, Peyton E Conrey, Julie C Fitzgerald, Nadir Yehya, Stephen T Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M Behrens, David T Teachey, Lisa R Forbes Satter, Alexandra F Freeman, Jenna Re Bergerson, Steven M Holland, Jennifer W Leiding, Scott L Weiss, Mark W Hall, Deanne M Taylor, Rui Feng, E John Wherry, Nuala J Meyer, Sarah E Henrickson

Faculty, Staff and Students Publications

BACKGROUND

Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.

METHODS

We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.

RESULTS

Unsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group (“Group C”) characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a …

Strategies To Increase Attendance In Substance Use Disorder Group Treatment: Results From A Randomized Controlled Trial, Liliane Cambraia Windsor, Heather A Jones, Carla Ellis, Kennya Hooper, Andrea Rucker, Salma Musaad, Moses Okumu

Faculty, Staff and Students Publications

Background: Attendance in substance-use-disorder group-treatment is challenging with only 32% of patients attending at least one session (Substance Abuse and Mental Health Services Administration and Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2023 admissions to and discharges from substance use treatment services reported by single state agencies, Bethesda, 2025). The present study tested a set of strategies to increase group session attendance in Community Wise, an innovative evidence-based group-intervention delivered in harm-reduction-community-based agencies and designed to reduce alcohol and substance use among people with substance-use-disorders living in predominantly Black and disinvested communities. We examined: (1) …

Uncovering Phenotypic Expansion In Axin2-Related Disorders Through Precision Animal Modeling, Nathalie M Aceves-Ewing, Denise G Lanza, Paul C Marcogliese, Di Lu, Chih-Wei Hsu, Hirokazu Hashimoto, Matthew Gonzalez, Audrey E Christiansen, Tara L Rasmussen, Alex J Ho, Angelina Gaspero, Cher Sha, Mary E Dickinson, Bo Yuan, Brian J Shayota, Stephanie Pachter, Xiaolin Hu, Debra Lynn Day-Salvatore, Laura Mackay, Oguz Kanca, Michael F Wangler, Lorraine Potocki, Jill A Rosenfeld, Richard Alan Lewis, Hsiao-Tuan Chao, Brendan Lee, Lauren Blieden, Barry N Wasserman, Dorine A Bax, Nicola K Ragge, Sukyeong Lee, Undiagnosed Diseases Network, Baylor College Of Medicine Center For Precision Medicine Models, Shinya Yamamoto, Hugo J Bellen, Lindsay C Burrage, Jason D Heaney

Faculty, Staff and Students Publications

Purpose: Heterozygous pathogenic variants in AXIN2 (HGNC 904) cause oligodontia-colorectal cancer syndrome (ODCRCS). We identified five individuals with de novo, heterozygous variants (NM_004655.4:c.196G>A p.(Glu66Lys), c.197A>G p.(Glu66Gly), and c.199G>A p.(Gly67Arg)) in AXIN2. Common phenotypes among these individuals included ectodermal dysplasia, global developmental delay, microcephaly, and limb, ophthalmologic, and genitourinary abnormalities.

Methods: Structural modeling was performed to predict the impact of these variants on AXIN2. A prime editing N1 screen of mouse embryos was performed to test whether the p.Glu66Lys variant produces a phenotype. Drosophila models were used to test the effect of this variant on Wnt signaling.

Results: …

Thanks For The Signal-Now What? Program Director Perspectives On How Preference Signals Are Shaping General Surgery Residency Recruitment, John M Woodward, Connie Y Gan, Darci C Foote, Tasha Posid, Nicole M Santucci, Noosha D Deravi, Caitlin Silvestri, Kirstyn E Brownson, Erika Simmerman Mabes, Rondi Gelbard, Milanie Milan, Nina Zhao, Dylan R Nieman, Martha Godfrey, Benjamin D Ferguson, Joseph C L'Huillier, Colleen Mcdermott, Prajjwol Luitel, Olabisi Sheppard, Jennifer H Chen, Emma G Burke, Jenny M Guido, Ladonna Kearse, Jonathan Davies, Trenton Foster, Sarah Lund

Faculty, Staff and Students Publications

Objective: We aimed to explore general surgery program director (PD) experiences with and perspectives on preference signaling in a 15-signal system.

Design: We performed qualitative analysis of de-identified transcripts from semi-structured interviews of general surgery PDs.

Setting: General surgery PDs across the United States.

Participants: All general surgery PDs in the spring of 2025 were invited to participate. Fifteen PDs volunteered to participate in semi-structured interviews (73% university-based, 53% programs with < 8 residents/class).

Results: PDs highlighted that signals saved time when utilized as a screening tool, which gave PDs more time for holistic review of applications. PDs also felt signaling increased equity …

Pneumococcal Colonization In Pediatric Patients Undergoing Hematopoietic Cell Transplantation, Liset Olarte, Jennifer E Schuster, Ibrahim Ahmed, Kristina G Hulten

Faculty, Staff and Students Publications

Despite the increased risk of invasive pneumococcal disease among pediatric hematopoietic cell transplant (HCT) recipients, pneumococcal colonization has not been evaluated in this population. We prospectively assessed longitudinal pneumococcal colonization in 22 pediatric HCT recipients from conditioning therapy to 100 days post-HCT. A higher likelihood of pneumococcal colonization was observed in the late post-HCT period (weeks 9-14) compared with the early post-HCT period (weeks 1-8), with odds increasing with each additional week after conditioning.IMPORTANCEThis is the first study to longitudinally evaluate pneumococcal colonization in pediatric hematopoietic cell transplant (HCT) recipients from the onset of conditioning therapy to 100 days post-HCT. …

Tau Pathology In Epilepsy: Emerging Mechanisms And Translational Opportunities, Arjune Sen, Xin You Tai, Aristea Galanopoulou, Maria Thom, Eleonora Aronica, Lucy Vivash, Martin Hardmeier, Action Amos, Stephan Rueegg, Matthias Koepp, Yaroslav Winter, Christoph Helmstaedter, Jeffrey L Noebels, Hilal A Lashuel, Terence J O'Brien

Faculty, Staff and Students Publications

The onset of epilepsy in adulthood occurs most commonly after 55 years of age. Given the ageing global population, this disorder represents an increasing burden on healthcare and society. The bidirectional link between epilepsy and dementia is a focus of intense research with underlying tau pathology highlighted as a potential mechanistic link. In this review, we examine the evidence for tau-related neurodegenerative processes in epilepsy beginning with how changes in biochemical and structural properties of the tau protein can lead to abnormal phosphorylation and pathological aggregation. We consider the role of tau in seizure occurrence and cognitive difficulties in experimental …

Single-Nucleotide Rna M6a Mapping In Bovine Preimplantation Development Reveals Site-Specific Regulation Of Rpl12 At Zygotic Genome Activation, Rajan Iyyappan, Yichi Niu, Yang Li, Hao Ming, Kinga Pajdzik, Noah R Rakestraw, Piyush K Jain, Chuan He, Chenghang Zong, Zongliang Jiang

Faculty, Staff and Students Publications

RNA N6-methyladenosine (m6A) is a key regulator of gene expression during early embryogenesis. Using SAC-seq (m6A-selective allyl chemical labeling and sequencing), an antibody-independent m6A profiling method, we generated the first single-nucleotide-resolution m6A map of bovine oocytes and preimplantation embryos. We observed both coordinated and uncoupled relationships between m6A modification and expression of protein-coding and noncoding genes. Integrative analysis of the transcriptome, m6A epitranscriptome, and translatome revealed dynamic m6A remodeling, particularly in ribosomal protein genes. Functional interrogation of a specific m6A site within the RPL12 transcript demonstrated that loss of this modification reduces protein synthesis, disrupts translation-related gene expression, impairs zygotic …

Reducing Communicable-Disease Risk After Earthquakes: Vaccination And Prevention Lessons For Venezuela's Doublet, Alfonso J Rodriguez-Morales, Ivan Arturo Rodríguez-Sabogal, Adriana Sucari, Wendy Moncada, Lili Vanessa Hernández-Serrano, Florencia Escarrá, Pasesa Pascuala Quispe-Torrez, Francisco Javier Membrillo, Tomás Orduna, Susana Lloveras, Tânia S S Chaves, Miguel M Cabada, Cecilia Perret, René Echavarría, Ana F Ribeiro, Melinda Tanabe, Fernando Bazzino, Maximiliano Ramirez, Baruch Diaz, Karen Mirna Loro Morejón, Karen Daly, Reinaldo Rosas, Maria Belen Lopez, Cristina Miranda, Marisa Liliana Fernandez, Yasemin Özsürekçi, Wasin Matsee, Yenddy Carrero, Cristian Biscayart, Sergio Cimerman, Maria L Avila-Aguero, Roberto Debbag, Jose Brea, Alejandro Risquez, Jaime David Acosta-España, Rolando Ulloa-Gutierrez, Carlos Espinal, Carlos N Torres-Martinez, Marta González-Sanz, Aula Abbara, Jill Weatherhead, Bernal Cordero, Virgilio Lezcano, Amanda Guerrero, Herberth Maldonado, Luis Cuellar, Ines Ceron, Yori Roque, Melisa Florentin, Rosa Infante, Ana Carvajal, Lily M Soto-Ávila, Marbelys Hernández, Hector Villaroel, Gianmary Miozzi, Rafael Navas, Moraima Hernández, Carlos Pérez-Vega, Manuela Mérida, David A Forero-Peña, Juan-Carlos Navarro, Claudia Beltrán-Arroyave, Mario Masana

Faculty, Staff and Students Publications

No abstract provided.

High-Order Brain Interactions During Ketamine-Induced State Changes: A Functional Marker Of Response In Late-Life Treatment-Resistant Depression?, Krisha Shah, Rubén Herzog, Alan C Swann, Brittany O'Brien, Rahul Balakrishnan, Sanjay J Mathew, Nicholas Murphy

Faculty, Staff and Students Publications

Ketamine is a fast-acting intervention for treatment-resistant depression (TRD), yet only a subset of patients show robust clinical response, and the underlying neural mechanisms remain unclear. High-order interactions (HOI) derived from multivariate information theory provide a framework for examining nonlinear dependencies among brain regions beyond pairwise connectivity. One such metric, the O-information, captures the balance between synergistic and redundant interactions across three or more variables. In this secondary analysis of a randomized, double-blind, midazolam-controlled trial (NCT02556606), we examined EEG-derived HOI in 30 late-life veterans with TRD following a single 40-minute intravenous infusion of ketamine (0.1, 0.25, 0.5 mg/kg; n = …

Multiplexed Plasmon-Enhanced Lateral Flow Assay For Early Diagnosis Of Acute Kidney Injury, Heng Guo, Yuxiong Liu, Ravi Jada, Ying Liu, Carissa Ng, Aquiles Payte, Jiaying Xu, Connor Malone, Jie Zhao, Kedhareswara Sairam Pasupuleti, Arda Aidan Arikan, Sameer Thadani, Srikanth Singamaneni, Ayse Akcan Arikan, Limei Tian

Faculty, Staff and Students Publications

Early diagnosis of acute kidney injury (AKI) remains a major clinical challenge due to the delayed and insensitive nature of conventional markers such as serum creatinine. Urinary protein biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC), provide earlier and complementary information on kidney injury, but their clinical translation is limited by the lack of rapid, quantitative, and multiplexed point-of-care (POC) diagnostic tests. Here, we report a multiplexed plasmonic-fluor-based lateral flow assay (p-LFA) that enables sensitive, quantitative, and simultaneous detection of NGAL and CysC. By harnessing ultrabright plasmonic-fluor nanolabels and ratiometric fluorescence analysis, the p-LFA achieves picogram-per-milliliter analytical sensitivity …

Bi-Allelic Loss-Of-Function Variants In Tmem63b Cause Syndromic Surfactant Dysfunction Disorder, Sock Hoai Chan, Audra N Iness, Jill A Rosenfeld, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Child-Eu Registry, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol

Faculty, Staff and Students Publications

Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen …

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 …

Evidence-Based Classification Of Genes Implicated In Skeletal Disorders Using The Clingen Curation Framework, Ryan F Webb, Hannah Mccurry, Amanda Girod, Madeline Hughes, Emma Wilcox, Mayher Patel, Eleanor C Broeren, Kezang C Tshering, Marina Distefano, Lorenzo D Botto, Lindsay C Burrage, Valérie Cormier-Daire, Juan Dong, Nadja Ehmke, Deborah Krakow, Shahida Moosa, Geert Mortier, Sandesh Nagamani, Loren Pena, Pedro A Sanchez-Lara, Andrea Superti-Furga, Sheila Unger, Danita Velasco, Matthew L Warman, Kerry Brown, Deepika D'Cunha Burkardt, Carlos R Ferreira

Faculty, Staff and Students Publications

More than 770 genetic skeletal disorders have been described, most with disease-causing variants reported in 1 of over 550 different genes. The ClinGen Skeletal Disorders Gene Curation Expert Panel was established to determine the strength of the evidence that supports specific gene-disease relationships (GDRs). Such information can assist clinical testing laboratories in choosing genes that should be included on diagnostic panels. Nine genes accounting for the most frequently encountered skeletal dysplasias (COL1A1, COL1A2, COL2A1, FGFR3, SLC26A2, TRPV4, COMP, ALPL, and SOX9) associated in the medical literature with 26 different skeletal disorders were reviewed using a semi-quantitative scoring framework. This framework …

Author Correction: Plasticity And Language In The Anaesthetized Human Hippocampus, Kalman A Katlowitz, Eric R Cole, Elizabeth A Mickiewicz, Shraddha Shah, Melissa Franch, Joshua A Adkinson, James L Belanger, Raissa K Mathura, Domokos Meszéna, Matthew Mcginley, William Muñoz, Garrett P Banks, Sydney S Cash, Chih-Wei Hsu, Angelique C Paulk, Nicole R Provenza, Andrew J Watrous, Ziv Williams, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Sarah R Heilbronner, Robert Kim, Nuttida Rungratsameetaweemana, Benjamin Y Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

This corrects the article "Plasticity and language in the anaesthetized human hippocampus" in volume 654 on page 714.

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, …

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 …

Clinical Features And Dental Pathologies In Maxillary Sinus Fungal Balls And Odontogenic Sinusitis, Eunice Im, Lane Donaldson, Avraham Adelman, Nithin D Adappa, Yi-Wei Chen, Nikita Chapurin, Jennifer E Douglas, Glen E D'Souza, Jacob Eide, Maria Espinosa, Chia-Hsiang Fu, Meha G Fox, Rohit Garg, Edward C Kuan, Michael A Kohanski, Marta Kwiatkowska, Kevin Li, Derek H Liu, Tran Bao Locke, Chih-Feng Lin, Chadi Makary, Alice Ottavi, Peter Papagiannopoulos, James N Palmer, Charles C L Tong, Bobby A Tajudeen, Sanjena Venkatesh, Kimberly Wei, Frederick Yoo, Alison J Yu, Jun Jin, Alberto M Saibene, John R Craig

Faculty, Staff and Students Publications

Objectives: While maxillary sinus fungal balls (MSFB) can be associated with odontogenic conditions (MSFBO), MSFBO clinical and dental features have not been compared to odontogenic sinusitis (ODS). This multicenter study aimed to compare characteristics of MSFB, MSFBO, and ODS.

Methods: A multicenter international retrospective cohort study was conducted on adults with MSFBs and ODS who underwent sinus surgery. First in MSFBs, it was determined whether different dental conditions were more likely in FB versus non-FB sides. Second, clinical features and dental pathologies were compared between MSFBO and ODS. For analyses, dental conditions were considered individually and as two groups: infectious …

Adlm Guidance Document On Incorporating Gender Diversity In Pathology And Laboratory Medicine, Tiffany A Thomas, Gabrielle N Winston-Mcpherson, Ina Amarillo, Alisha D Berry, Caroline J Davidge-Pitts, Sridevi Devaraj, Zil Goldstein, Brad S Karon, Brooke M Katzman, Mahmoud A Khalifa, Hung S Luu, James H Nichols, Tracy L Stockley, Michelle R Stoffel, Dina N Greene, Matthew D Krasowski

Faculty, Staff and Students Publications

Background: The first international clinical standards of care for the gender-diverse population were formulated in the late 1970s. In the last 15 years, multiple subspecialty societies within the United States have developed clinical care guidelines for those with gender dysphoria, including gender-affirming hormone therapy (GAHT) and surgical treatments. To date, there are no pathology- and laboratory medicine-specific recommendations in the United States for the gender-diverse population.

Content: This document outlines pathology- and laboratory medicine-specific recommendations for providing optimal care to the gender-diverse population, with a predominant focus on the adult population. The scope of this document focuses on the following …

Upholding Our Promise: Negotiating Belonging And Professional Identity Formation In Underrepresented In Medicine Pediatric Residents, Oriaku A Kas-Osoka, Courtney A Gilliam, Lahia Yemane, Candice Taylor Lucas, Rebecca Blankenburg, H Mollie Grow, Laura Kester-Prakash, Jyothi Marbin, Patricia Poitevien, Audrea M Burns

Faculty, Staff and Students Publications

Objective: To explore UIM pediatric residents' perspectives on how belonging impacts PIF and Well-BP.

Methods: We conducted a national qualitative study grounded in a critical interpretivist paradigm using virtual focus groups with UIM pediatric residents between June 2022 and April 2023. Data were analyzed by 4 authors using reflexive thematic analysis until theoretical sufficiency was reached. Member-checking was conducted to ensure the trustworthiness of the themes.

Results: Twenty-four UIM pediatric residents across 20 programs participated. Five themes emerged as follows: 1) Belonging is a dynamic process shaped by daily affirmations and invalidations; 2) Clinical learning environments often erode belonging through …

Cytokine-Based Strategies To Improve Prognostic Enrichment Of Pediatric Ards, E Scott Halstead, Todd M Umstead, Zissis C Chroneos, Cainan Riccio-Baum, S Rameeza Allie, Daniel J Mckeone, Debbie Spear, Ryan A Nofziger, Ronald C Sanders, Danielle Ahn, Jasmine C Dowell, Asdis F Wagner, Neal J Thomas, Prithvi Sendi, W Joshua Frazier, Courtney M Rowan, Parag N Jain, Dalia A Bashir, Stuart H Friess, Brian M Varisco, Jocelyn Grunwell, Aline B Maddux, Stephen T Famularo, Nadir Yehya

Faculty, Staff and Students Publications

Background: Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS has been described in adults using IL-6, TNFR1, and bicarbonate, and has prognostic utility. We investigated the application of this traditional parsimonious signature to pediatric ARDS patients and tested whether we could improve prognostic enrichment using other cytokines.

Methods: We leveraged a prospective multicenter cohort study of 500 children with ARDS (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome [LEOPARDS]; NCT04113434) study. Plasma samples were obtained within 24 h …

Reclassifying Pediatric Nafld Using The Steatotic Liver Disease Framework: A Multicenter Retrospective Study From The Nash Crn, Tin Bo Nicholas Lam, Katherine P Yates, Sheila L Noon, Kimberly P Newton, Mark H Fishbein, Jean P Molleston, Stavra A Xanthakos, Ajay K Jain, Miriam B Vos, Niviann M Blondet, Krupa R Mysore, Cynthia A Behling, Laura A Wilson, Jeffrey B Schwimmer

Faculty, Staff and Students Publications

Background and aims: The terminology for hepatic steatosis and NAFLD was revised under the umbrella of steatotic liver disease, with metabolic dysfunction-associated steatotic liver disease (MASLD) as the primary subtype. MASLD is defined by hepatic steatosis plus at least 1 cardiometabolic risk factor. A new category, Met-ALD, describes MASLD with alcohol consumption below the defined thresholds for alcohol-associated liver disease (ALD). While adult studies have demonstrated strong concordance between NAFLD and MASLD, the applicability of this framework in children remains unclear.

Approach and results: We assessed children clinically diagnosed with NAFLD and enrolled in the NASH CRN who had available …

Epinephrine Underuse For Anaphylaxis In Infants And Toddlers: A Practical Review For Pediatricians, Stephanie Leeds, Aikaterini Anagnostou, Michael Pistiner, Jay Lieberman, Nicole B Ramsey, Rachael Griffiths, Julie Wang

Faculty, Staff and Students Publications

A recent consensus report defined anaphylaxis as a serious allergic reaction that may involve the skin/mucosa, respiratory, cardiovascular, and/or gastrointestinal systems that can progress rapidly and may cause death. Epinephrine treatment is recommended in suspected anaphylaxis cases; however, numerous barriers exist to consistent, widespread epinephrine use, including difficulty identifying anaphylaxis signs and symptoms; challenges recognizing when to use epinephrine; low propensity of prescribing and filling prescriptions; low epinephrine carrying rates; knowledge gaps in epinephrine administration techniques; fears of contacting emergency medical services; use of antihistamines, inhaled bronchodilators, and other medications as first-line agents over epinephrine; and limited epinephrine device availability …

Age-Appropriate Low Dosing For Food Protein-Induced Enterocolitis Syndrome Oral Food Challenges: Proposing A Standardized Approach, Sara Anvari, Mary Grace Baker, Theresa Bingemann, J Andrew Bird, Terri Brown-Whitehorn, Antonella Cianferoni, Raquel Durban, Malika Gupta, Erin Hosein, George Konstantinou, Stephanie Leonard, Melanie A Ruffner, Allison Schaible, Amy M Scurlock, Pooja Varshney, Antonella Muraro, Alessandro Fiocchi, Alexandra F Santos, Stefania Arasi, Marta Vazquez-Ortiz, Hideaki Morita, Ichiro Nomura, Julia E M Upton, Michael Levin, Eric Lee, Cesar Galvan, Rodrigo Hoyos-Bachiloglu, Pantipa Chatchatee, Kirsten Beyer, George Du Toit, Purificacion Gonzalez-Delgado, Lydia Su Yin Wong, Marion Groetch, Anna Nowak-Wegrzyn

Faculty, Staff and Students Publications

Current oral food challenge (OFC) protocols for food protein-induced enterocolitis syndrome (FPIES) exhibit significant variability, creating potential for inconsistent diagnostic outcomes and severe reactions. Based on the published evidence and our clinical experience, we propose a practical, standardized OFC dosing protocol that emphasizes patient safety, goals based on age-appropriate servings (AASs), and clinical monitoring. A recent systematic review reported that most patients with persistent FPIES who underwent OFCs reacted to just 25% of an AAS, with low rates of severe reactions. Thus, we recommend that most patients undergoing a medically supervised FPIES OFC receive a cumulative dose of 25% AAS, …