Altering the intracellular trafficking of Necator americanus GST-1 antigen yields novel hookworm mRNA vaccine candidates.

Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens.

Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.

Extracorporeal Membrane Oxygenation in Children with Pulmonary Atresia and Intact Ventricular Septum: Mortality and Associated Outcomes.

Data on outcomes of extracorporeal membrane oxygenation (ECMO) are limited in patients with pulmonary atresia intact ventricular septum (PAIVS). The objective of this study was to describe the use of ECMO and the associated outcomes in patients with PAIVS. We retrospectively reviewed neonates with PAIVS who received ECMO between 2009 and 2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS).

Twelve tips on applying AI tools in HPE scholarship using Boyer's model.

AI has changed the landscape of health professions education. With the hype now behind us, we find ourselves in the phase of reckoning, considering what's next; where do we start and how can educators use these powerful tools for daily teaching and learning. We recognize the great need for training to use AI meaningfully for education.

Molecular logic for cellular specializations that initiate the auditory parallel processing pathways.

The cochlear nuclear complex (CN), the starting point for all central auditory processing, encompasses a suite of neuronal cell types highly specialized for neural coding of acoustic signals. However, the molecular logic governing these specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple hitherto unknown subtypes with anatomical and physiological identity.

Short-term Postoperative Complications of Lymphatic Malformation Surgical Excision: A 20-Year Institutional Review.

Objective: To evaluate outcomes and postoperative complications following surgical resection of lymphatic malformations (LMs) at a single multidisciplinary vascular anomalies center.

Methods: A single-center retrospective review of all patients ≤21 years old who underwent surgical resection of a lymphatic malformation at a quaternary referral center with a multidisciplinary vascular anomalies team from 2004 to 2024. Data pertaining to postoperative outcomes and treatments was abstracted.

Ferumoxytol-enhanced MRI of retroplacental clear space disruption in placenta accreta spectrum.

Introduction: Placenta accreta spectrum (PAS) occurs when the placenta is pathologically adherent to the myometrium. An intact retroplacental clear space (RPCS) is a marker of normal placentation. In this study, we investigate use of the FDA-approved iron supplement ferumoxytol for contrast-enhanced MRI of the RPCS in mouse models of normal pregnancy and PAS.

Untargeted metabolomics analysis as a potential screening tool for 3-methylglutaconic aciduria syndromes.

The 3-methylglutaconic aciduria (3-MGA-uria) syndromes comprise a heterogeneous group of inborn errors of metabolism defined biochemically by detectable elevation of 3-methylglutaconic acid (3-MGA) in the urine. In type 1 (or primary) 3-MGA-uria, distal defects in the leucine catabolism pathway directly cause this elevation. Secondary 3-MGA-uria syndromes, however, are unrelated to leucine metabolism-specific defects but share a common biochemical phenotype of elevated 3-MGA.

Artificial Intelligence in Health Professions Education assessment: AMEE Guide No. 178.

Health Professions Education (HPE) assessment is being increasingly impacted by Artificial Intelligence (AI), and institutions, educators, and learners are grappling with AI's ever-evolving complexities, dangers, and potential. This AMEE Guide aims to assist all HPE stakeholders by helping them navigate the assessment uncertainty before them. Although the impetus is AI, the Guide grounds its path in pedagogical theory, considers the range of human responses, and then deals with assessment types, challenges, AI roles as tutor and learner, and required competencies.

Advancing Monogenic Diabetes Research and Clinical Care by Creating a Data Commons: The Precision Diabetes Consortium (PREDICT).

Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium (PREDICT).

Intraoperative cardiac arrest in patients undergoing congenital cardiac surgery.

Objective: To describe intraoperative cardiac arrest in patients undergoing congenital heart surgery.

Methods: The Society of Thoracic Surgeons Congenital Heart Surgery Database was queried. Predictors of intraoperative cardiac arrest were assessed using univariate and multivariable analyses.

Achieving excellence in paediatric cardiac care in resource limited and resource plentiful settings and building successful care networks across different countries.

Background: The delivery of paediatric cardiac care across the world occurs in settings with significant variability in available resources. Irrespective of the resources locally available, we must always strive to improve the quality of care we provide to our patients and simultaneously deliver such care in the most efficient and cost-effective manner. The development of cardiac networks is used widely to achieve these aims.

Prevention and Management of Infectious Complications in Pediatric Patients With Cancer: A Survey Assessment of Current Practices Across Children's Oncology Group Institutions.

Introduction: While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers.

Methods: An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution.

Results: The response rate was 57% (129/227 institutions).

Pancreatic organogenesis mapped through space and time.

The spatial organization of cells within a tissue is dictated throughout dynamic developmental processes. We sought to understand whether cells geometrically coordinate with one another throughout development to achieve their organization. The pancreas is a complex cellular organ with a particular spatial organization.

Exploration of Cytokines and Microbiome Among Males and Females with Diarrhea-Predominant Irritable Bowel Syndrome.

Background: Whether pathophysiological factors differ between males and females with irritable bowel syndrome-diarrhea (IBS-D) remains to be tested. To better understand potential sex differences, males with IBS-D were compared to naturally cycling females and to females with IBS-D taking hormonal contraception on plasma levels of cytokines and gut microbiome characteristics.

Methods: Males and females with Rome III IBS-D completed questionnaires and kept a daily symptom diary for 28 days.

Long-term kidney outcomes in survivors of Wilms tumor: a single-center retrospective cohort study.

Background: Several studies have investigated long-term kidney outcomes in survivors of Wilms tumor (WT). However, many have small sample sizes, and there is a wide variation in reported outcomes. The aim of this study is to investigate the long-term kidney outcomes in survivors of WT (S-WT), including those patients considered to be at high risk for poor kidney outcomes, and using updated estimated glomerular filtration rate (eGFR) equations.

A National Assessment of Pediatric Surgical Critical Care Fellowship Structure: Defining the Training Experience.

Background: Pediatric Surgical Critical Care (PSCC) is a unique specialty incorporating fundamental principles of surgical, neonatal, and pediatric critical care. This study aims to characterize the current landscape of PSCC training to identify opportunities for educational standardization and improvement.

Methods: An anonymous electronic survey-based assessment was distributed to the program directors (PDs) of all current ACGME-accredited PSCC fellowships (n = 14).

Neuroimaging of postoperative pediatric cerebellar mutism syndrome: a systematic review.

Background: Postoperative pediatric cerebellar mutism syndrome (ppCMS) poses serious morbidity after posterior fossa tumor surgery. Neuroimaging studies aim to understand its pathophysiology, yet these vary in methodology and outcome measures. Therefore, we systematically reviewed the current literature to evaluate the evidence for differences in neuroimaging features between children with and without ppCMS.

AN ONLINE SPIKE DETECTION AND MONITORING FRAMEWORK IN IEEG RECORDED USING BRAIN INTERCHANGE DEVICE.

In this study, we developed and validated an online analysis framework in MATLAB Simulink for recording and analysis of intracranial electroencephalography (iEEG). This framework aims to detect interictal spikes in patients with epilepsy as the data is being recorded. An online spike detection was performed over 10-minute interictal iEEG data recorded with Brain Interchange CorTec in three human subjects.

Randomized, observer-blind, controlled Phase 1 study of the safety and immunogenicity of the Na-GST-1/Alhydrogel hookworm vaccine with or without a CpG ODN adjuvant in hookworm-naïve adults.

Background: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host.

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum.

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites.

Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure.

Biomolecular condensates play key roles in the spatiotemporal regulation of cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ) as a model system, revealing how its material properties and cellular function depend on its ultrastructure.