The proprotein convertase BLI-4 promotes collagen secretion prior to assembly of the Caenorhabditis elegans cuticle.

Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular puncta. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and the control of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.

In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe's Disease.

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.

A transient apical extracellular matrix relays cytoskeletal patterns to shape permanent acellular ridges on the surface of adult C. elegans.

Epithelial cells secrete apical extracellular matrices to form protruding structures such as denticles, ridges, scales, or teeth. The mechanisms that shape these structures remain poorly understood. Here, we show how the actin cytoskeleton and a provisional matrix work together to sculpt acellular longitudinal alae ridges in the cuticle of adult C. elegans. Transient assembly of longitudinal actomyosin filaments in the underlying lateral epidermis accompanies deposition of the provisional matrix at the earliest stages of alae formation. Actin is required to pattern the provisional matrix into longitudinal bands that are initially offset from the pattern of longitudinal actin filaments. These bands appear ultrastructurally as alternating regions of adhesion and separation within laminated provisional matrix layers. The provisional matrix is required to establish these demarcated zones of adhesion and separation, which ultimately give rise to alae ridges and their intervening valleys, respectively. Provisional matrix proteins shape the alae ridges and valleys but are not present within the final structure. We propose a morphogenetic mechanism wherein cortical actin patterns are relayed to the laminated provisional matrix to set up distinct zones of matrix layer separation and accretion that shape a permanent and acellular matrix structure.

The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

Common and Divergent Features of T Cells from Blood, Gut, and Genital Tract of Antiretroviral Therapy-Treated HIV+ Women.

T cells residing in mucosal tissues play important roles in homeostasis and defense against microbial pathogens. The gut and female reproductive tract (FRT) are both tolerogenic environments, but they differ in the kinds of foreign Ags they need to tolerate. How these different environments influence the properties of their T cells is poorly understood, but important for understanding women's health. We recruited antiretroviral therapy-suppressed women living with HIV who donated, within one visit, blood and tissue samples from the ileum, colon, rectosigmoid, endometrium, endocervix, and ectocervix. With these samples, we conducted 36-parameter cytometry by time of flight phenotyping of T cells. Although gut and FRT T cells shared features discriminating them from their blood counterparts, they also harbored features distinguishing them from one another. These included increased proportions of CD69+ T resident memory cells of the T effector memory phenotype, as well as preferential coexpression of CD69 and CD103, on the gut-derived cells. In contrast, CD69+CD103+ T resident memory CD8+ T cells from FRT, but not those from gut, preferentially expressed PD1. We further determined that a recently described population of CXCR4+ T inflammatory mucosal cells differentially expressed multiple other chemokine receptors relative to their blood counterparts. Our findings suggest that T cells resident in different tolerogenic mucosal sites take on distinct properties.

Phase I study of liver depot gene therapy in late-onset Pompe disease.

Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement therapy (ERT) by creating a liver depot for acid α-glucosidase (GAA) production. We report initial safety and bioactivity of the first dose (1.6 × 1012 vector genomes/kg) cohort (n = 3) in a 52-week open-label, single-dose, dose-escalation study (NCT03533673) in patients with late-onset Pompe disease (LOPD). Subjects discontinued biweekly ERT after week 26 based on the detection of elevated serum GAA activity and the absence of clinically significant declines per protocol. Prednisone (60 mg/day) was administered as immunoprophylaxis through week 4, followed by an 11-week taper. All subjects demonstrated sustained serum GAA activities from 101% to 235% of baseline trough activity 2 weeks following the preceding ERT dose. There were no treatment-related serious adverse events. No subject had anti-capsid T cell responses that decreased transgene expression. Muscle biopsy at week 24 revealed unchanged muscle glycogen content in two of three subjects. At week 52, muscle GAA activity for the cohort was significantly increased (p < 0.05). Overall, these initial data support the safety and bioactivity of AAV8-LSPhGAA, the safety of withdrawing ERT, successful immunoprophylaxis, and justify continued clinical development of AAV8-LSPhGAA therapy in Pompe disease.

Machine Learning Quantification of Pulmonary Regurgitation Fraction from Echocardiography.

Assessment of pulmonary regurgitation (PR) guides treatment for patients with congenital heart disease. Quantitative assessment of PR fraction (PRF) by echocardiography is limited. Cardiac MRI (cMRI) is the reference-standard for PRF quantification. We created an algorithm to predict cMRI-quantified PRF from echocardiography using machine learning (ML). We retrospectively performed echocardiographic measurements paired to cMRI within 3 months in patients with ≥ mild PR from 2009 to 2022. Model inputs were vena contracta ratio, PR index, PR pressure half-time, main and branch pulmonary artery diastolic flow reversal (BPAFR), and transannular patch repair. A gradient boosted trees ML algorithm was trained using k-fold cross-validation to predict cMRI PRF by phase contrast imaging as a continuous number and at > mild (PRF ≥ 20%) and severe (PRF ≥ 40%) thresholds. Regression performance was evaluated with mean absolute error (MAE), and at clinical thresholds with area-under-the-receiver-operating-characteristic curve (AUROC). Prediction accuracy was compared to historical clinician accuracy. We externally validated prior reported studies for comparison. We included 243 subjects (median age 21 years, 58% repaired tetralogy of Fallot). The regression MAE = 7.0%. For prediction of > mild PR, AUROC = 0.96, but BPAFR alone outperformed the ML model (sensitivity 94%, specificity 97%). The ML model detection of severe PR had AUROC = 0.86, but in the subgroup with BPAFR, performance dropped (AUROC = 0.73). Accuracy between clinicians and the ML model was similar (70% vs. 69%). There was decrement in performance of prior reported algorithms on external validation in our dataset. A novel ML model for echocardiographic quantification of PRF outperforms prior studies and has comparable overall accuracy to clinicians. BPAFR is an excellent marker for > mild PRF, and has moderate capacity to detect severe PR, but more work is required to distinguish moderate from severe PR. Poor external validation of prior works highlights reproducibility challenges.

Long COVID Prevalence, Disability, and Accommodations: Analysis Across Demographic Groups.

PURPOSE: This paper examines the prevalence of long COVID across different demographic groups in the US and the extent to which workers with impairments associated with long COVID have engaged in pandemic-related remote work. METHODS: We use the US Household Pulse Survey to evaluate the proportion of all adults who self-reported to (1) have had long COVID, and (2) have activity limitations due to long COVID. We also use data from the US Current Population Survey to estimate linear probability regressions for the likelihood of pandemic-related remote work among workers with and without disabilities. RESULTS: Findings indicate that women, Hispanic people, sexual and gender minorities, individuals without 4-year college degrees, and people with preexisting disabilities are more likely to have long COVID and to have activity limitations from long COVID. Remote work is a reasonable arrangement for people with such activity limitations and may be an unintentional accommodation for some people who have undisclosed disabilities. However, this study shows that people with disabilities were less likely than people without disabilities to perform pandemic-related remote work. CONCLUSION: The data suggest this disparity persists because people with disabilities are clustered in jobs that are not amenable to remote work. Employers need to consider other accommodations, especially shorter workdays and flexible scheduling, to hire and retain employees who are struggling with the impacts of long COVID.

When is the best time to screen and evaluate for treatable genetic disorders?: A lifespan perspective.

This paper focuses on the question of, "When is the best time to identify an individual at risk for a treatable genetic condition?" In this review, we describe a framework for considering the optimal timing for pursuing genetic and genomic screening for treatable genetic conditions incorporating a lifespan approach. Utilizing the concept of a carousel that represents the four broad time periods when critical decisions might be made around genetic diagnoses during a person's lifetime, we describe genetic testing during the prenatal period, the newborn period, childhood, and adulthood. For each of these periods, we describe the objectives of genetic testing, the current status of screening or testing, the near-term vision for the future of genomic testing, the advantages and disadvantages of each approach, and the feasibility and ethical considerations of testing and treating. The notion of a "Genomics Passbook" is one where an early genomic screening evaluation could be performed on each individual through a public health program, with that data ultimately serving as a "living document" that could be queried and/or reanalyzed at prescribed times during the lifetime of that person, or in response to concerns about symptoms of a genetic disorder in that individual.

Whole-genome sequencing holds the key to the success of gene-targeted therapies.

Rare genetic disorders affect as many as 3%-5% of all babies born. Approximately 10,000 such disorders have been identified or hypothesized to exist. Treatment is supportive except in a limited number of instances where specific therapies exist. Development of new therapies has been hampered by at least two major factors: difficulty in diagnosing diseases early enough to enable treatment before irreversible damage occurs, and the high cost of developing new drugs and getting them approved by regulatory agencies. Whole-genome sequencing (WGS) techniques have become exponentially less expensive and more rapid since the beginning of the human genome project, such that return of clinical data can now be achieved in days rather than years and at a cost that is comparable to other less expansive genetic testing. Thus, it is likely that WGS will ultimately become a mainstream, first-tier NBS technique at least for those disorders without appropriate high-throughput functional tests. However, there are likely to be several steps in the evolution to this end. The clinical implications of these advances are profound but highlight the bottlenecks in drug development that still limit transition to treatments. This article summarizes discussions arising from a recent National Institute of Health conference on nucleic acid therapy, with a focus on the impact of WGS in the identification of diagnosis and treatment of rare genetic disorders.

Bi-allelic Loss-of-Function Variants in NUP188 Cause a Recognizable Syndrome Characterized by Neurologic, Ocular, and Cardiac Abnormalities.

Nucleoporins (NUPs) are an essential component of the nuclear-pore complex, which regulates nucleocytoplasmic transport of macromolecules. Pathogenic variants in NUP genes have been linked to several inherited human diseases, including a number with progressive neurological degeneration. We present six affected individuals with bi-allelic truncating variants in NUP188 and strikingly similar phenotypes and clinical courses, representing a recognizable genetic syndrome; the individuals are from four unrelated families. Key clinical features include congenital cataracts, hypotonia, prenatal-onset ventriculomegaly, white-matter abnormalities, hypoplastic corpus callosum, congenital heart defects, and central hypoventilation. Characteristic dysmorphic features include small palpebral fissures, a wide nasal bridge and nose, micrognathia, and digital anomalies. All affected individuals died as a result of respiratory failure, and five of them died within the first year of life. Nuclear import of proteins was decreased in affected individuals' fibroblasts, supporting a possible disease mechanism. CRISPR-mediated knockout of NUP188 in Drosophila revealed motor deficits and seizure susceptibility, partially recapitulating the neurological phenotype seen in affected individuals. Removal of NUP188 also resulted in aberrant dendrite tiling, suggesting a potential role of NUP188 in dendritic development. Two of the NUP188 pathogenic variants are enriched in the Ashkenazi Jewish population in gnomAD, a finding we confirmed with a separate targeted population screen of an international sampling of 3,225 healthy Ashkenazi Jewish individuals. Taken together, our results implicate bi-allelic loss-of-function NUP188 variants in a recessive syndrome characterized by a distinct neurologic, ophthalmologic, and facial phenotype.

Age-related changes in left ventricular vortex and energy loss patterns: from newborns to adults.

Left ventricular vortex formation optimizes the effective transport of blood volume while minimizing energy loss (EL). Vector flow mapping (VFM)-derived EL patterns have not been described in children, especially in those less than 1 yr of age. A prospective cohort of 66 (0 days-22 yr, 14 patients ≤ 2 mo) cardiovascularly normal children was used to determine left ventricular (LV) vortex number, size (mm2), strength (m2/s), and energy loss (mW/m/m2) in systole and diastole and compared across age groups. One early diastolic (ED) vortex at the anterior mitral leaflet and one late diastolic (LD) vortex at the LV outflow tract (LVOT) were seen in all newborns ≤ 2 mo. At >2 mo, two ED vortices and one LD vortex were seen, with 95% of subjects > 2 yr demonstrating this vortex pattern. Peak and average diastolic EL acutely increased in the same 2 mo-2-yr period and then decreased within the adolescent and young adult age groups. Overall, these findings suggest that the growing heart undergoes a transition to adult vortex flow patterns over the first 2 yr of life with a corresponding acute increase in diastolic EL. These findings offer an initial insight into the dynamic changes of LV flow patterns in pediatric patients and can serve to expand our understanding of cardiac efficiency and physiology in children.NEW & NOTEWORTHY This research article demonstrates, for the first time, echocardiographic evidence of a transition in left ventricular vortex patterns from the newborn to the adult period, with an associated change in cardiac efficiency, marked by increased energy loss, during infancy.

Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome.

Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal neurologic activity. We report six individuals from three unrelated families harboring biallelic deleterious variants in CAPN15 with phenotypes overlapping those previously described for this disorder. Of the individuals affected, four demonstrate radiographic evidence of the classical triad of Dandy-Walker malformation including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation. Cerebellar anomalies have not been previously reported in association with CAPN15-related disease. Here, we present three unrelated families with findings consistent with oculogastrointestinal neurodevelopmental syndrome and cerebellar pathology including Dandy-Walker malformation. To corroborate these novel clinical findings, we present supporting data from the mouse model suggesting an important role for this protein in normal cerebellar development. Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy-Walker malformation with biallelic CAPN15 variants, thereby expanding the neurologic spectrum among patients affected by CAPN15-related disease.

Cardiac problems in the fetus: a review for pediatric providers.

PURPOSE OF REVIEW: The aim of this study was to provide pediatric providers with a review of the diagnosis and management of fetal cardiac disease in the current era. RECENT FINDINGS: Prenatal detection of congenital heart disease (CHD) has improved but is still imperfect. In experienced hands, fetal echocardiography can detect severe CHD as early as the first trimester and a majority of more subtle conditions in the second and third trimesters. Beyond detection, a prenatal diagnosis allows for lesion-specific counseling for families as well as for development of a multidisciplinary perinatal management plan, which may involve in-utero treatment. Given the diversity of cardiac diagnoses and the rarity of some, collaborative multicenter fetal cardiac research has gained momentum in recent years. SUMMARY: Accurate diagnosis of fetal cardiac disease allows for appropriate counseling, pregnancy and delivery planning, and optimization of immediate neonatal care. There is potential for improving fetal CHD detection rates. Fetal interventions are available for certain conditions, and fetal and pediatric cardiac centers have developed management plans specific to the expected postnatal physiology.

Normative ranges of biventricular volumes and function in healthy term newborns.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used in newborns with congenital heart disease. However, reporting on ventricular volumes and mass is hindered by an absence of normative data in this population. DESIGN/METHODS: Healthy term (37-41 weeks gestation) newborns underwent non-sedated, free-breathing CMR within the first week of life using the 'feed and wrap' technique. End-diastolic volume (EDV), end-systolic volume (ESV) stroke volume (SV) and ejection fraction (EF) were calculated for both left ventricle (LV) and right ventricle (RV). Papillary muscles were separately contoured and included in the myocardial volume. Myocardial mass was calculated by multiplying myocardial volume by 1.05 g/ml. All data were indexed to weight and body surface area (BSA). Inter-observer variability (IOV) was performed on data from 10 randomly chosen infants. RESULTS: Twenty healthy newborns (65% male) with a mean (SD) birth weight of 3.54 (0.46) kg and BSA of 0.23 (0.02) m2 were included. Normative LV parameters were indexed EDV 39.0 (4.1) ml/m2, ESV 14.5 (2.5) ml/m2 and ejection fraction (EF) 63.2 (3.4)%. Normative RV indexed EDV, ESV and EF were 47.4 (4.5) ml/m2, 22.6 (2.9) ml/m2 and 52.5 (3.3)% respectively. Mean LV and RV indexed mass were 26.4 (2.8) g/m2 and 12.5 (2.0) g/m2, respectively. There was no difference in ventricular volumes by gender. IOV was excellent with an intra-class coefficient > 0.95 except for RV mass (0.94). CONCLUSION: This study provides normative data on LV and RV parameters in healthy newborns, providing a novel resource for comparison with newborns with structural and functional heart disease.

An intersectional analysis of long COVID prevalence.

BACKGROUND: Long COVID symptoms - which include brain fog, depression, and fatigue - are mild at best and debilitating at worst. Some U.S. health surveys have found that women, lower income individuals, and those with less education are overrepresented among adults with long COVID, but these studies do not address intersectionality. To fill this gap, we conduct an intersectional analysis of the prevalence and outcomes of long COVID in the U.S. We posit that disparities in long COVID have less to do with the virus itself and more to do with social determinants of health, especially those associated with occupational segregation and the gendered division of household work. METHODS: We use 10 rounds of Household Pulse Survey (HPS) data collected between June 2022 and March 2023 to perform an intersectional analysis using a battery of descriptive statistics that evaluate (1) the prevalence of long COVID and (2) the interference of long COVID symptoms with day-to-day activities. We also use the HPS data to estimate a set of multivariate logistic regressions that relate the odds of having long COVID and activity limitations due to long COVID to a set of individual characteristics as well as intersections by sex, race/ethnicity, education, and sexual orientation and gender identity. RESULTS: Findings indicate that women, some people of color, sexual and gender minorities, and people without college degrees are more likely to have long COVID and to have activity limitations from long COVID. Women have considerably higher odds of developing long COVID compared to men, a disparity exacerbated by having less education. Intersectional analysis by gender, race, ethnicity, and education reveals a striking step-like pattern: college-educated men have the lowest prevalence of long COVID while women without college educations have the highest prevalence. Daily activity limitations are more evenly distributed across demographics, but a different step-like pattern is present: fewer women with degrees have activity limitations while limitations are more widespread among men without degrees. Regression results confirm the negative association of long COVID with being a woman, less educated, Hispanic, and a sexual and gender minority, while results for the intersectional effects are more nuanced. CONCLUSIONS: Results point to systematic disparities in health, highlighting the urgent need for policies that increase access to quality healthcare, strengthen the social safety net, and reduce economic precarity.

Intrauterine enzyme replacement therapies for lysosomal storage disorders: Current developments and promising future prospects.

Lysosomal storage disorders (LSDs) are a group of monogenic condition, with many characterized by an enzyme deficiency leading to the accumulation of an undegraded substrate within the lysosomes. For those LSDs, postnatal enzyme replacement therapy (ERT) represents the standard of care, but this treatment has limitations when administered only postnatally because, at that point, prenatal disease sequelae may be irreversible. Furthermore, most forms of ERT, specifically those administered systemically, are currently unable to access certain tissues, such as the central nervous system (CNS), and furthermore, may initiate an immune response. In utero enzyme replacement therapy (IUERT) is a novel approach to address these challenges evaluated in a first-in-human clinical trial for IUERT in LSDs (NCT04532047). IUERT has numerous advantages: in-utero intervention may prevent early pathology; the CNS can be accessed before the blood-brain barrier forms; and the unique fetal immune system enables exposure to new proteins with the potential to prevent an immune response and may induce sustained tolerance. However, there are challenges and limitations for any fetal procedure that involves two patients. This article reviews the current state of IUERT for LSDs, including its advantages, limitations, and potential future directions for definitive therapies.

A C. elegans Zona Pellucida domain protein functions via its ZPc domain.

Zona Pellucida domain (ZP) proteins are critical components of the body's external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model organism C. elegans, we investigated the aECM assembly of one ZP protein, LET-653, which shapes several tubes. Contrary to prevailing models, we find that LET-653 localizes and functions via its ZPc domain. Furthermore, we show that ZPc domain function requires cleavage at the LET-653 C-terminus, likely in part to relieve inhibition of the ZPc by the ZPn domain, but also to promote some other aspect of ZPc domain function. In vitro, the ZPc, but not ZPn, domain bound crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping.

Midterm Outcomes and Cardiac Magnetic Resonance Imaging following Multisystem Inflammatory Syndrome in Children.

At midterm follow-up visits performed at a median of 7 months (IQR 6.0-8.4 months), 16 patients with multisystem inflammatory syndrome in children had resolution of left ventricular dysfunction and most had resolution of coronary aneurysms. On cardiovascular magnetic resonance imaging, no patients had late gadolinium enhancement.

Poor diet quality and adverse eating behaviors in young survivors of childhood cancer.

BACKGROUND: The long-term impact of childhood cancer treatment on dietary intake is likely to be complex, and the length of time dietary behaviors are affected after childhood cancer treatment is unknown. AIM: The aim of this study was to determine the diet quality in childhood cancer survivors recently off treatment and explore possible contributing factors that may affect diet quality in this population. METHODS: Participants were 65 parents and/or carers of childhood cancer survivors (CCS) (aged 2-18 years), recently off treatment, and 81 age-matched controls. Participants completed two self-administered dietary intake and eating behavior questionnaires. Study data were explored to determine between group differences, bivariate analysis using Spearman correlations was used to determine the relationship between diet quality and identified variables, and hierarchical cluster analysis was completed to characterize specific variables into clusters. RESULTS: One hundred and forty-six parents of children aged 2-18 years completed the study (65 parents of CCS and 81 control). CCS had a significantly poorer diet quality score than the age-matched controls (32.25 vs 34.83, P = 0.028). CCS had significantly higher parent-reported rates of "picky eating" behavior than the control group (2.31 vs 1.91; P = 0.044). Factors such as picky eating, emotional overeating, and body mass index z-score might drive diet quality in survivors. CONCLUSIONS: CCS were found to have poorer diet quality and more likely to have parents report picky eating behaviors. The outcomes highlighted the need for a tailored intervention aimed at improving healthy eating behaviors in CCS after treatment for cancer.