The evolutionarily conserved choroid plexus contributes to the homeostasis of brain ventricles in zebrafish.

The choroid plexus (ChP) produces cerebrospinal fluid (CSF). It also contributes to brain development and serves as the CSF-blood barrier. Prior studies have identified transporters on the epithelial cells that transport water and ions from the blood vasculature to the ventricles and tight junctions involved in the CSF-blood barrier. Yet, how the ChP epithelial cells control brain physiology remains unresolved. We use zebrafish to provide insights into the physiological roles of the ChP. Upon histological and transcriptomic analyses, we identify that the zebrafish ChP is conserved with mammals and expresses transporters involved in CSF secretion. Next, we show that the ChP epithelial cells secrete proteins into CSF. By ablating the ChP epithelial cells, we identify a reduction of the ventricular sizes without alterations of the CSF-blood barrier. Altogether, our findings reveal that the zebrafish ChP is conserved and contributes to the size and homeostasis of the brain ventricles.

Coxsackievirus A24 causing acute conjunctivitis in a 2023 outbreak in Vietnam.

OBJECTIVES: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam METHODS: RNA-sequencing was used to identify pathogens before and during the outbreak. RESULTS: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. CONCLUSIONS: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

Mucoadhesive, antioxidant, and lubricant catechol-functionalized poly(phosphobetaine) as biomaterial nanotherapeutics for treating ocular dryness.

Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC1-co-DMA1) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC1-co-DMA1) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC1-co-DMA1) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.

SARS-CoV-2 Omicron Subvariants Do Not Differ Much in Binding Affinity to Human ACE2: A Molecular Dynamics Study.

The emergence of the variant of concern Omicron (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exacerbates the COVID-19 pandemic due to its high contagious ability. Studies have shown that the Omicron binds human ACE2 more strongly than the wild type. The prevalence of Omicron in new cases of COVID-19 promotes novel lineages with improved receptor binding affinity and immune evasion. To shed light on this open problem, in this work, we investigated the binding free energy of the receptor binding domain of the Omicron lineages BA.2, BA.2.3.20, BA.3, BA4/BA5, BA.2.75, BA.2.75.2, BA.4.6, XBB.1, XBB.1.5, BJ.1, BN.1, BQ.1.1, and CH.1.1 to human ACE2 using all-atom molecular dynamics simulation and the molecular mechanics Poisson-Boltzmann surface area method. The results show that these lineages have increased binding affinity compared to the BA.1 lineage, and BA.2.75 and BA.2.75.2 subvariants bind ACE2 more strongly than others. However, in general, the binding affinities of the Omicron lineages do not differ significantly from each other. The electrostatic force dominates over the van der Waals force in the interaction between Omicron lineages and human cells. Based on our results, we argue that viral evolution does not further improve the affinity of SARS-CoV-2 for ACE2 but may increase immune evasion.

Understanding the Solid-Electrolyte-Interface (SEI) Formation in Glyme Electrolyte Using Time-Of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS).

Lithium-ion batteries are commonly used for energy storage due to their long lifespan and high energy density, but the use of unsafe electrolytes poses significant health and safety concerns. An alternative source is necessary to maintain electrochemical efficacy. This research demonstrates new safe glyme-based electrolytes for silica/carbon (SiOx/C) nanocomposite derived from Australian rice husk (RH). The quality of SiOx/C was preserved by using deep eutectic solvent-based pre-treatment and single-step carbonization, which was confirmed through the X-ray analysis of the crystalline phase of silica. The electrochemical assessment of SiOx/C anode using various glyme-based electrolytes for LIBs was carried out. Among them, the resultant half cells based on diglyme electrolyte is superior to others with the first discharge capacity at 1274 mAh/g and a reversible discharge capacity of 759.7 mAh/g. Ex-situ SEM and Time-of-Flight Secondary Ion Mass Spectrometry (ToF- SIMS) analysis of the electrode indicated that diglyme not only improves the capacity but also sustains the electrode architecture for longer cycle life with more LiF-based components and also showed the absence of HF components. Importantly, the addition of fluoroethylene carbonate (FEC) additive enhanced the cycling stability. These results provide a new perspective on developing advanced SiOx/C anode using glyme electrolytes for Li-ion batteries.

Pediatric suicide: Review of a preventable tragedy.

Concepts of suicide are explored in this issue with a focus on suicide in children and adolescents. The epidemiology of pediatric suicide in the United States is reviewed; also, risk and protective factors, as well as prevention strategies, are discussed. Suicide in the pediatric athlete and the potential protective effect of exercise are examined. In addition, this analysis addresses the beneficial role of psychological management as well as current research on pharmacologic treatment and brain stimulation procedures as part of comprehensive pediatric suicide prevention. Though death by suicide in pediatric persons has been and remains a tragic phenomenon, there is much that clinicians, other healthcare professionals, and society itself can accomplish in the prevention of pediatric suicide as well as the management of suicidality in our children and adolescents.

Automatic categorization of self-acknowledged limitations in randomized controlled trial publications.

OBJECTIVE: Acknowledging study limitations in a scientific publication is a crucial element in scientific transparency and progress. However, limitation reporting is often inadequate. Natural language processing (NLP) methods could support automated reporting checks, improving research transparency. In this study, our objective was to develop a dataset and NLP methods to detect and categorize self-acknowledged limitations (e.g., sample size, blinding) reported in randomized controlled trial (RCT) publications. METHODS: We created a data model of limitation types in RCT studies and annotated a corpus of 200 full-text RCT publications using this data model. We fine-tuned BERT-based sentence classification models to recognize the limitation sentences and their types. To address the small size of the annotated corpus, we experimented with data augmentation approaches, including Easy Data Augmentation (EDA) and Prompt-Based Data Augmentation (PromDA). We applied the best-performing model to a set of about 12K RCT publications to characterize self-acknowledged limitations at larger scale. RESULTS: Our data model consists of 15 categories and 24 sub-categories (e.g., Population and its sub-category DiagnosticCriteria). We annotated 1090 instances of limitation types in 952 sentences (4.8 limitation sentences and 5.5 limitation types per article). A fine-tuned PubMedBERT model for limitation sentence classification improved upon our earlier model by about 1.5 absolute percentage points in F1 score (0.821 vs. 0.8) with statistical significance (p<.001). Our best-performing limitation type classification model, PubMedBERT fine-tuning with PromDA (Output View), achieved an F1 score of 0.7, improving upon the vanilla PubMedBERT model by 2.7 percentage points, with statistical significance (p<.001). CONCLUSION: The model could support automated screening tools which can be used by journals to draw the authors' attention to reporting issues. Automatic extraction of limitations from RCT publications could benefit peer review and evidence synthesis, and support advanced methods to search and aggregate the evidence from the clinical trial literature.

Tandem Mass Spectrometry across Platforms.

PubChem serves as a comprehensive repository, housing over 100 million unique chemical structures representing the breadth of our chemical knowledge across numerous fields including metabolism, pharmaceuticals, toxicology, cosmetics, agriculture, and many more. Rapid identification of these small molecules increasingly relies on electrospray ionization (ESI) paired with tandem mass spectrometry (MS/MS), particularly by comparison to genuine standard MS/MS data sets. Despite its widespread application, achieving consistency in MS/MS data across various analytical platforms remains an unaddressed concern. This study evaluated MS/MS data derived from one hundred molecular standards utilizing instruments from five manufacturers, inclusive of quadrupole time-of-flight (QTOF) and quadrupole orbitrap "exactive" (QE) mass spectrometers by Agilent (QTOF), Bruker (QTOF), SCIEX (QTOF), Waters (QTOF), and Thermo QE. We assessed fragment ion variations at multiple collisional energies (0, 10, 20, and 40 eV) using the cosine scoring algorithm for comparisons and the number of fragments observed. A parallel visual analysis of the MS/MS spectra across instruments was conducted, consistent with a standard procedure that is used to circumvent the still prevalent issue of mischaracterizations as shown for dimethyl sphingosine and C20 sphingosine. Our analysis revealed a notable consistency in MS/MS data and identifications, with fragment ions' m/z values exhibiting the highest concordance between instrument platforms at 20 eV, the other collisional energies (0, 10, and 40 eV) were significantly lower. While moving toward a standardized ESI MS/MS protocol is required for dependable molecular characterization, our results also underscore the continued importance of corroborating MS/MS data against standards to ensure accurate identifications. Our findings suggest that ESI MS/MS manufacturers, akin to the established norms for gas chromatography mass spectrometry instruments, should standardize the collision energy at 20 eV across different instrument platforms.

Protective Role of MAVS Signaling for Murine Lipopolysaccharide-Induced Acute Kidney Injury.

Despite treatment advances, acute kidney injury (AKI)-related mortality rates are still high in hospitalized adults, often due to sepsis. Sepsis and AKI could synergistically worsen the outcomes of critically ill patients. TLR4 signaling and mitochondrial antiviral signaling protein (MAVS) signaling are innate immune responses essential in kidney diseases, but their involvement in sepsis-associated AKI (SA-AKI) remains unclear. We studied the role of MAVS in kidney injury related to the TLR4 signaling pathway using a murine LPS-induced AKI model in wild-type and MAVS-knockout mice. We confirmed the importance of M1 macrophage in SA-AKI through in vivo assessment of inflammatory responses. The TLR4 signaling pathway was upregulated in activated bone marrow-derived macrophages, in which MAVS helped maintain the LPS-suppressed TLR4 mRNA level. MAVS regulated redox homeostasis via NADPH oxidase Nox2 and mitochondrial reverse electron transport in macrophages to alleviate the TLR4 signaling response to LPS. Hypoxia-inducible factor 1α (HIF-1α) and AP-1 were key regulators of TLR4 transcription and connected MAVS-dependent reactive oxygen species signaling with the TLR4 pathway. Inhibition of succinate dehydrogenase could partly reduce inflammation in LPS-treated bone marrow-derived macrophages without MAVS. These findings highlight the renoprotective role of MAVS in LPS-induced AKI by regulating reactive oxygen species generation-related genes and maintaining redox balance. Controlling redox homeostasis through MAVS signaling may be a promising therapy for SA-AKI.

Theoretical insights into the HO●-induced oxidation of chlorpyrifos pesticide: Mechanism, kinetics, ecotoxicity, and cholinesterase inhibition of degradants.

The oxidation of the common pesticide chlorpyrifos (CPF) initiated by HO● radical and the risks of its degradation products were studied in the gaseous and aqueous phases via computational approaches. Oxidation mechanisms were investigated, including H-, Cl-, CH3- abstraction, HO●-addition, and single electron transfer. In both phases, HO●-addition at the C of the pyridyl ring is the most energetically favorable and spontaneous reaction, followed by H-abstraction reactions at methylene groups (i.e., at H19/H21 in the gas phase and H22/H28 in water). In contrast, other abstractions and electron transfer reactions are unfavorable. However, regarding the kinetics, the significant contribution to the oxidation of CPF is made from H-abstraction channels, mostly at the hydrogens of the methylene groups. CPF can be decomposed in a short time (5-8 h) in the gas phase, and it is more persistent in natural water with a lifetime between 24 days and 66 years, depending on the temperature and HO● concentration. Subsequent oxidation of the essential radical products with other oxidizing reagents, i.e., HO●, NO2●, NO●, and 3O2, gave primary neutral products P1-P15. Acute and chronic toxicity calculations estimate very toxic levels for CPF and two degradation products, P7w and P12w, in aquatic systems. The neurotoxicity of these products was investigated by docking and molecular dynamics. P7w and P12w show the most significant binding scores with acetylcholinesterases, while P8w and P13w are with butyrylcholinesterase enzyme. Finally, molecular dynamics illustrate stable interactions between CPF degradants and cholinesterase enzyme over a 100 ns time frame and determine P7w as the riskiest degradant to the neural developmental system.

Health equity in pediatrics: Current concepts for the care of children in the 21st century (Dis Mon).

This is an analysis of important aspects of health equity in caring for children and adolescents written by a multidisciplinary team from different medical centers. In this discussion for clinicians, we look at definitions of pediatric health equity and the enormous impact of social determinants of health in this area. Factors involved with pediatric healthcare disparities that are considered include race, ethnicity, gender, age, poverty, socioeconomic status, LGBT status, living in rural communities, housing instability, food insecurity, access to transportation, availability of healthcare professionals, the status of education, and employment as well as immigration. Additional issues involved with health equity in pediatrics that are reviewed will include the impact of the COVID-19 pandemic, behavioral health concepts, and the negative health effects of climate change. Recommendations that are presented include reflection of one's own attitudes on as well as an understanding of these topics, consideration of the role of various healthcare providers (i.e., community health workers, peer health navigators, others), the impact of behavioral health integration, and the need for well-conceived curricula as well as multi-faceted training programs in pediatric health equity at the undergraduate and postgraduate medical education levels. Furthermore, ongoing research in pediatric health equity is needed to scrutinize current concepts and stimulate the development of ideas with an ever-greater positive influence on the health of our beloved children. Clinicians caring for children can serve as champions for the optimal health of children and their families; in addition, these healthcare professionals are uniquely positioned in their daily work to understand the drivers of health inequities and to be advocates for optimal health equity in the 21st century for all children and adolescents.

Spatial communication systems across languages reflect universal action constraints.

The extent to which languages share properties reflecting the non-linguistic constraints of the speakers who speak them is key to the debate regarding the relationship between language and cognition. A critical case is spatial communication, where it has been argued that semantic universals should exist, if anywhere. Here, using an experimental paradigm able to separate variation within a language from variation between languages, we tested the use of spatial demonstratives-the most fundamental and frequent spatial terms across languages. In n = 874 speakers across 29 languages, we show that speakers of all tested languages use spatial demonstratives as a function of being able to reach or act on an object being referred to. In some languages, the position of the addressee is also relevant in selecting between demonstrative forms. Commonalities and differences across languages in spatial communication can be understood in terms of universal constraints on action shaping spatial language and cognition.

Betainization of Polydopamine/Polyethylenimine Coating for Universal Zwitterionization.

Biofoulants can adhere to multiple surfaces, degrading the performance of medical devices and industrial facilities and/or causing nosocomial infection. The surface immobilization of zwitterionic materials can prevent the initial attachment of the foulants but lacks extensive implementation. Herein, we propose a facile, universal, two-step surface modification strategy to improve fouling resistance. In the first step, the substrates were immersed in a codeposition solution containing dopamine and branched polyethylenimine (PEI) to form a "primer" layer (PDA/PEI). In the second step, the primer layers were treated with 1,3-propane sultone to betainize primary/secondary/tertiary amine moieties of PEI, generating zwitterions on substrates. After betainization, PS-grafted PDA/PEI (PDA/PEI/S) via a ring-opening alkylation reaction manifested changes in wettability. X-ray photoelectron spectroscopy revealed the presence of zwitterionic moieties on the PDA/PEI/S surfaces. Further investigations using ellipsometry and atomic force microscopy were conducted to scrutinize the relation among the PEI content, film thickness, primer stability, and betainization. As a result, zwitterion-decorated substrates prepared under optimal conditions can exhibit high resistance against bacterial fouling, achieving a 98.5% reduction in bacterial attachment. In addition, the method shows a substrate-independent property, capable of successfully applying it on organic and inorganic substrates. Finally, the newly developed approach shows excellent biocompatibility, displaying no significant difference compared with blank control samples. Overall, we envision that the facile surface modification strategy can further promote the preparation of zwitterion-decorated materials in the future.

Methodology reporting improved over time in 176,469 randomized controlled trials.

OBJECTIVES: To describe randomized controlled trial (RCT) methodology reporting over time. STUDY DESIGN AND SETTING: We used a deep learning-based sentence classification model based on the Consolidated Standards of Reporting Trials (CONSORT) statement, considered minimum requirements for reporting RCTs. We included 176,469 RCT reports published between 1966 and 2018. We analyzed the reporting trends over 5-year time periods, grouping trials from 1966 to 1990 in a single stratum. We also explored the effect of journal impact factor (JIF) and medical discipline. RESULTS: Population, Intervention, Comparator, Outcome (PICO) items were commonly reported during each period, and reporting increased over time (e.g., interventions: 79.1% during 1966-1990 to 87.5% during 2010-2018). Reporting of some methods information has increased, although there is room for improvement (e.g., sequence generation: 10.8-41.8%). Some items are reported infrequently (e.g., allocation concealment: 5.1-19.3%). The number of items reported and JIF are weakly correlated (Pearson's r (162,702) = 0.16, P < 0.001). The differences in the proportion of items reported between disciplines are small (<10%). CONCLUSION: Our analysis provides large-scale quantitative support for the hypothesis that RCT methodology reporting has improved over time. Extending these models to all CONSORT items could facilitate compliance checking during manuscript authoring and peer review, and support metaresearch.

From volcanoes to the bench: Advantages of novel hyperthermoacidic archaeal proteases for proteomics workflows.

Here we introduce hyperthermoacidic archaeal proteases (HTA-Proteases©) isolated from organisms that thrive in nearly boiling acidic volcanic springs and investigate their use for bottom-up proteomic experiments. We find that HTA-Proteases have novel cleavage specificities, show no autolysis, function in dilute formic acid, and store at ambient temperature for years. HTA-Proteases function optimally at 70-90 °C and pH of 2-4 with rapid digestion kinetics. The extreme HTA-Protease reaction conditions actively denature sample proteins, obviate the use of chaotropes, are largely independent of reduction and alkylation, and allow for a one-step/five-minute sample preparation protocol without sample manipulation, dilution, or additional cleanup. We find that brief one-step HTA-Protease protocols significantly increase proteome and protein sequence coverage with datasets orthogonal to trypsin. Importantly, HTA-Protease digests markedly increase coverage and identifications for ribonucleoproteins, histones, and mitochondrial membrane proteins as compared to tryptic digests alone. In addition to increased coverage in these classes, HTA-Proteases and simplified one-step protocols are expected to reduce technical variability and advance the fields of clinical and high-throughput proteomics. This work reveals significant utility of heretofore unavailable HTA-Proteases for proteomic workflows. We discuss some of the potential for these remarkable enzymes to empower new proteomics methods, approaches, and biological insights. SIGNIFICANCE: Here we introduce new capabilities for bottom-up proteomics applications with hyperthermoacidic archaeal proteases (HTA-Proteases©). HTA-Proteases have novel cleavage specificity, require no chaotropes, and allow simple one-step/five-minute sample preparations that promise to reduce variability between samples and laboratories. HTA-Proteases generate unique sets of observable peptides that are non-overlapping with tryptic peptides and significantly increase sequence coverage and available peptide targets relative to trypsin alone. HTA-Proteases show some bias for the detection and coverage of nucleic acid-binding proteins and membrane proteins relative to trypsin. These new ultra-stable enzymes function optimally in nearly boiling acidic conditions, show no autolysis, and do not require aliquoting as they are stable for years at ambient temperatures. Used independently or in conjunction with tryptic digests, HTA-Proteases offer increased proteome coverage, unique peptide targets, and brief one-step protocols amenable to automation, rapid turnaround, and high-throughput approaches.

Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the devastating global COVID-19 pandemic announced by WHO in March 2020. Through unprecedented scientific effort, several vaccines, drugs and antibodies have been developed, saving millions of lives, but the fight against COVID-19 continues as immune escape variants of concern such as Delta and Omicron emerge. To develop more effective treatments and to elucidate the side effects caused by vaccines and therapeutic agents, a deeper understanding of the molecular interactions of SARS-CoV-2 with them and human cells is required. With special interest in computational approaches, we will focus on the structure of SARS-CoV-2 and the interaction of its spike protein with human angiotensin-converting enzyme-2 (ACE2) as a prime entry point of the virus into host cells. In addition, other possible viral receptors will be considered. The fusion of viral and human membranes and the interaction of the spike protein with antibodies and nanobodies will be discussed, as well as the effect of SARS-CoV-2 on protein synthesis in host cells.

Heart rate variability during auricular acupressure at the left sympathetic point on healthy volunteers: a pilot study.

Introduction: This research is a pilot, single-blinded study investigating heart rate variability (HRV) during auricular acupressure at the left sympathetic point (AH7) in healthy volunteers. Methods: There were 120 healthy volunteers with hemodynamic indexes (heart rate, blood pressure) within normal ranges, randomly divided into two groups AG and SG (in each group having a gender ratio 1:1, aged 20-29), to receive either auricular acupressure using ear seed (AG) or sham method using adhesive patches without seed (SG) at the left sympathetic point while lying in a supine position. Acupressure intervention lasted 25 min, and HRV was recorded by a photoplethysmography device-namely, Kyto HRM-2511B and Elite appliance. Results: Auricular acupressure at the left Sympathetic point (AG) led to a significant reduction in heart rate (HR) (p < 0.05) and a considerable increase in HRV parameters demonstrated by HF (High-frequency power) (p < 0.05), compared to sham auricular acupressure (SG). However, no significant changes in LF (Low-frequency power) and RR (Respiratory rate) (p > 0.05) were observed in both groups during the process. Conclusion: These findings suggest that auricular acupressure at the left sympathetic point may activate the parasympathetic nervous system while a healthy person is lying relaxed.

Intermediate outcome for the single-stage surgical repair of aortopulmonary window associated with interrupted aortic arch.

OBJECTIVES: Aortopulmonary window (APW) associated with an interrupted aortic arch (IAA) is a rare cardiac malformation with significant mortality and morbidity. The goal of this study was to report the intermediate outcomes of single-stage repair concentrating on the surgical techniques and postoperative reintervention for this rare cardiac lesion. METHODS: Eleven patients were diagnosed with IAA-associated APW and underwent single-stage surgical repair at Vietnam National Children's Hospital. RESULTS: The APW anatomy types were types I, II and III in 1, 4 and 6 patients, respectively. The IAA morphology was type A in 9 patients and type B in 2 patients. The median age was 27 [interquartile range (IQR) 6-79] days, and the median weight was 3.5 (IQR 2.8-4.5) kg. The aortic arch was repaired using direct end-to-side tissue anastomosis in 7 patients, and patch aortoplasty was performed in 4 patients. Six patients underwent APW closure with an intra-aortic baffle, and 5 patients required right pulmonary artery detachment and reimplantation. One early death occurred. Four patients required reinterventions: 1 patient required reoperation due to aortic stenosis and 3 required balloon angioplasty for either recurrent aortic arch stenosis (n = 1) or right pulmonary stenosis (n = 2) with a mean follow-up time of 3.1 years (IQR 0.5-4.3 years). CONCLUSIONS: Single-stage repair of IAA-associated APW can be achieved with good survival outcomes in children. However, the need for repeat reintervention or reoperation remains high, and the growth of both the aorta and pulmonary arteries should follow carefully as the patient grows. CLINICAL REGISTRATION NUMBER: VNCH-RICH-18-96.