Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (< 10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median < 1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo León. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR > 1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.
Robin sequence (RS) is a rare congenital condition characterized by retrognathia, glossoptosis, and upper airway obstruction, with highly variable respiratory severity at birth. Prenatal measurement of the inferior facial angle (IFA) is used to support diagnosis, but its prognostic value for respiratory outcomes remains uncertain. This study assessed whether fetal MRI-measured IFA predicts early respiratory status in infants with RS. We conducted a retrospective monocentric study including consecutive infants with prenatal suspicion and postnatal confirmation of RS who underwent fetal MRI between 2009 and 2021. Respiratory status was assessed at delivery and at 6 months and categorized as room air breathing, noninvasive respiratory support, or intubation/tracheostomy. Five blinded operators independently measured the IFA and the anteroposterior skull size (APSS) on median sagittal MRI slice. Interobserver agreement was evaluated using intraclass correlation coefficients. Potential predictors of respiratory outcomes were analyzed using ordinal logistic regression. Among 43 infants, 72% required respiratory support at birth. More than half required ongoing respiratory assistance during early infancy. IFA values did not differ across respiratory outcome categories and were not associated with respiratory status at birth or during follow-up. Interobserver reliability was poor for IFA measurements, whereas APSS showed excellent agreement. In multivariable analyses, higher gestational age at birth was the only factor associated with reduced respiratory morbidity during the first 6 months.  These findings indicate that, although IFA is useful for diagnosing RS, it lacks reproducibility and prognostic value for respiratory outcomes, highlighting the need for delivery in specialized centers. • In Pierre Robin sequence, no reliable prenatal predictor of respiratory status at birth exists. Although the inferior facial angle is used for prenatal diagnosis, its ability to predict neonatal respiratory severity is unknown. • The inferior facial angle in prenatal fetal MRI shows limited predictive value for respiratory status at birth and during early infancy in infants with Robin sequence, with substantial measurement variability reducing its reliability as an isolated prognostic imaging marker.
The study aimed to investigate the prevalence of osteoporosis in children and adolescents with transfusion-dependent thalassemia (TDT) and evaluate the diagnostic value of different osteoporosis indicators. Clinical data were collected from children and adolescents with TDT treated with blood transfusion between March 2022 and January 2024 at Huizhou Central People's Hospital and Huizhou First Hospital. The patients were grouped according to the presence of osteoporosis (International Society for Clinical Densitometry [ISCD] criteria). Of 138 patients included in the study, 48 (34.8%) had osteoporosis. The patients with osteoporosis mainly had asymptomatic grade I fractures of the spine. Using the dual-X-ray absorptiometry (DXA) standards from the World Health Organization, height-corrected TBLH Z-score ≤-2 was associated with osteoporosis (30.4% vs. 14.9%, P = 0.035), displaying 30.4% sensitivity and 85.1% specificity. According to the Chinese DXA standards, height-corrected and age-specific Z-scores ≤-2 were not associated with osteoporosis. The prevalence of osteoporosis among children and adolescents with TDT was 34.8%, indicating the need for screening for osteoporosis in that population. In TDT, the diagnosis of osteoporosis requires early detection of spinal fractures because bone density assessed by DXA is of limited value.
Government-led repurposing programmes are reshaping the division of labour in pharmaceutical innovation. A new power drafted into the European Union pharmaceutical reform package will allow the European Medicines Agency (EMA) to add new therapeutic indications to marketed medicines without the marketing authorization holder's consent. Companies oppose this power, but in weighing up enacting the power, society has a poor understanding of its potential to help patients. This study offers the first empirical assessment of the promise of the power. It analyses 198 medicines from 12 years, comparing EMA-authorized labels with those authorized by the US Food and Drug Administration and a leading reference for off-label uses. Sixty-seven per cent of the medicines have at least one additional use supported by clinical evidence, yielding 320 potential new uses. Of these, 39 per cent are for new diseases and 61 per cent for new patient cohorts, a third of the latter concerning paediatric populations. Commentators generally omit discussing repurposing for new patient cohorts, even though it is a focus of the European Commission. The study's results suggest that the power could be used to authorize a meaningful number of evidence-based uses, especially those already authorized in the USA, while also revealing a policy synergy for neglected populations.
As sensory pathways and neural interactions develop, the encoding of exogenous input becomes increasingly complex, reflecting greater functional integration and differentiation in cortical and subcortical networks. We hypothesize that integrating how the developing brain processes exogenous information improves the evaluation of cerebral maturation. We developed a predictive model of cerebral age that integrates two complementary dimensions: the brain's processing of auditory stimulation and endogenous spontaneous neural activity. High-density EEGs were recorded from 74 premature neonates, born between 27 and 35 weeks of gestational age, and tested within their first week of life during rest and auditory stimulation. Calculating an adapted version of the perturbational complexity index, we demonstrate that the spatiotemporal complexity of neural responses to auditory stimulation increases with increasing gestational age at birth. While models based on the characteristics of spontaneous neural activity (linear slope of the aperiodic component and inter-burst interval) yield acceptable estimates of cerebral age, incorporating measures of neural complexity in response to exogenous stimuli significantly enhances predictive accuracy. These findings establish response complexity to auditory stimulation as a robust and automated biomarker of cerebral maturation. The integrated endogenous-exogenous framework can serve to recognize at-risk premature newborns and improve neurodevelopmental assessment. We designed a complexity index to measure how distributed cortical networks respond to auditory stimulation in premature newborns and showed its systematic modulation with neurodevelopment. We developed a predictive model of cerebral age integrating spontaneous and stimulus-driven EEG activity in premature newborns. We show that endogenous and exogenous neural markers offer complementary insights, enhancing evaluation of cerebral maturation and early detection of at-risk infants.
Ongoing neurodevelopmental care is essential for children with congenital heart disease (CHD). Understanding delivery and uptake of neurodevelopmental care pathways can inform implementation and resource planning. This study applied simulation modelling to explore outcomes from a neurodevelopmental care pathway for children with CHD. The model was developed using data from a Queensland program to explore health service interactions for neurodevelopmental screening, formal assessment, and early intervention, up to five years. Modelling was intended to provide a baseline understanding of the pathway, rather than evaluating against a reference standard. Hypothetical scenarios explored how changes in screening and referrals influenced the identification of developmental concerns, and how developmental concern severity affected intervention referrals. Based on available data, 58% of the cohort remained under routine surveillance and 25% had accessed early intervention for one or more developmental delays. Scenarios defined by increased screening projected up to 55% of the cohort having a developmental concern identified during screening and 45% having a developmental delay identified following assessment. Simulation modelling was useful for understanding outcomes from a neurodevelopmental pathway and how differences in screening and assessment affected health service interactions. Findings may inform policy and resource planning for future neurodevelopmental pathways. This study shows that simulation modelling is a useful approach for evaluating a neurodevelopmental care pathway for children with CHD, to understand movement through neurodevelopmental screening, assessment, and interventions. Scenario-based modelling provides insights into factors influencing pathway engagement, contributing evidence to strengthen understanding of service gaps and areas where improvements can most effectively impact engagement and resourcing. This study identifies neurodevelopmental screening as the most influential stage impacting downstream outcomes, underscoring its importance as a strategic intervention point. This study's approach provides a general framework for evaluating similar pathways and a potential baseline for assessing future policy or service changes.
This contemporary review examines health care disparities that pediatric patients may experience throughout the perioperative period, focusing on the ambulatory surgery setting. Existing literature focused on outcomes during inpatient procedures; however, disparities may manifest preoperatively, intraoperatively and postoperatively in the outpatient setting. Inequities related to race/ethnicity, geographic location, language barriers, insurance status, and utilization of perioperative services are highlighted. Strategies to mitigate these disparities in the ambulatory setting include selecting patients carefully, encouraging accreditation of facilities, and increasing the number of fellowship-trained pediatric anesthesiologists. Future opportunities include system-level changes to promote more equitable perioperative care in the ambulatory setting.
Group B Streptococcus (GBS) is a leading cause of early-onset neonatal sepsis (EOS). Intrapartum antibiotic prophylaxis (IAP) based on maternal GBS screening significantly reduces the incidence of neonatal GBS disease. We report a term neonate who developed early-onset GBS sepsis and meningitis despite a negative maternal GBS screening result obtained at 39 weeks of gestation. The infant presented with respiratory distress, poor feeding, and hypotonia shortly after birth. Blood culture confirmed GBS bacteremia, and cerebrospinal fluid (CSF) analysis supported concurrent meningitis. He was successfully treated with intravenous antibiotics, initially with penicillin and ceftazidime, then escalated to vancomycin for better central nervous system penetration following meningitis diagnosis, before de-escalation back to penicillin. Total antibiotic duration was 17 days. Cranial imaging revealed small hemorrhagic foci in the left centrum semiovale and periventricular area, which resolved on follow-up MRI. This case highlights the potential for false-negative maternal GBS screening and underscores the importance of clinical vigilance. Empirical antibiotic therapy for suspected neonatal sepsis should be considered based on clinical presentation, even when maternal screening is negative.
This review synthesizes best practices for ambulatory pediatric tonsillectomy with or without adenoidectomy in ambulatory surgery centers. It emphasizes rigorous patient selection-particularly for severe obstructive sleep apnea, age, obesity, and complex comorbidities-along with individualized anesthetic plans (induction and airway choice), multimodal opioid-sparing analgesia, and robust post-operative nausea and vomiting prophylaxis. Standardized post-anesthesia care unit monitoring, discharge criteria, caregiver education, and escalation pathways address common complications (airway events, hemorrhage, pain, dehydration). Preparedness-pediatric advanced life support-certified staff, emergency equipment, and transfer agreements-underpins safety. Quality-improvement initiatives and emerging tools offer avenues to further reduce morbidity and unplanned admissions.
This study reviewed pediatric cases managed by the Aeromedical Evacuation Squadron (AMES) of the Japan Air Self-Defense Force and analyzed patient characteristics. Pediatric transportation cases (n = 34) between 2006 and 2023 were reviewed. Data on patient age, main disease, transportation purpose and distance, and use of mechanical ventilators or extracorporeal membrane oxygenation (ECMO) were obtained by referring to the records. The average (standard deviation) patient age was 5.7 (5.8) years (range: 0-16 years), and 17 patients (50%) were younger than 1 year of age. Furthermore, 10 (58.8%) of these 17 children were younger than 7 months of age and 1 child was under 1 month of age. The most common diseases in the overall patient population were cardiovascular diseases (CVDs, n = 18) and respiratory diseases (RDs, n = 14). The purposes of transportation in cases of 17 patients with CVDs and 3 patients with RDs were the implantation of a ventricular assist device and lung transplantation, respectively. The average transportation distance was 453.7 (218.6) (range: 176.9-962.8) miles or 730.2 (351.8) (range: 284.7-1,549.5) km, and in 8 cases, the transportation distance was > 600 miles. Of the patients, 29 (85.3%) were fitted with a ventilator, of whom 8 received ECMO (6 with CVDs and 2 with RDs). In all cases, physicians from the transporting hospitals were on board. There were no cases of cardiac arrest during the transportation. AMES plays an important role, especially in the long-distance transportation of critically ill children.
In the UK, healthy children and pregnant women are no longer offered COVID-19 vaccination. This study assessed the outcomes of children and women-of-childbearing-age admitted to a large London hospital with SARS-CoV-2. Electronic records of children and women-of-childbearing-age with a positive SARS-CoV-2 PCR (January 2023-September 2024) were reviewed. Hospital Episode Statistics (HES) database disease-coding accuracy was evaluated. Over 20 months, 334/4764 (7.0%) SARS-CoV-2 tests in children were positive; 150/334 (44.9%) were hospitalised (representing 0.81% of 18,412 childhood admissions); of these, 121 were non-incidental infections (0.66% of childhood admissions), including 26/121 (21.4%) with severe COVID-19 (0.14% of childhood admissions). COVID-19 was the sole diagnosis in 68 healthy children (55 infants, 13 older children), including five with severe COVID-19. In non-pregnant women, 295/7,181 (4.1%) tests were positive, 95 (95/295, 32.2%) were hospitalised; 12 (12.6%) were non-incidental, including two at-risk women with severe COVID-19. In pregnant women, 46/124 (37.1%) tests were positive (representing 0.82% of 5,630 pregnancies); nine (9/46, 19.6%) were hospitalised (0.15% of pregnancies), including four with non-incidental COVID-19, (0.07% of pregnancies), and none had severe COVID-19. Comparison with HES found 19/29 (65.5%) of incidental infections in children and 37/88 (42.0%) in women were coded as primary COVID-19 hospitalisations, while 15/150 (10.0%) of admissions in children and 36/104 (34.6%) of admissions in women had no associated ICD-10 code. Rates of severe COVID-19 were low. National databases for SARS-CoV-2 surveillance need to capture disease activity more accurately.
Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that imposes significant personal and societal burdens. Traditional diagnostic approaches, which rely on behavioral assessments, are susceptible to subjectivity and variability, underscoring the need for objective and automated diagnostic tools. This study develops an ADHD-specific, biologically informed multi-stream deep learning framework for pediatric brain MRI classification, in which a Vision Transformer (ViT) and an Enhanced Convolutional Neural Network (ECNN) are integrated with Raw MRI, Phase Spectrum Transform (PST), and Quantile Histogram Equalization with Denoising (QHED) representations to capture complementary global and local neuroanatomical characteristics. The architecture leverages complementary modeling capacities by combining global contextual representations from ViT with localized discriminative features extracted by ECNN across a biologically informed multi-stream preprocessing strategy, including Raw MRI to preserve global anatomy, Phase Spectrum Transform (PST) to highlight cortical boundary irregularities, and Quantile Histogram Equalization with Denoising (QHED) to enhance subtle gray-white matter contrasts. Experimental evaluations conducted on a stratified pediatric MRI dataset demonstrated that the proposed ViT+ECNN model achieved a classification accuracy of 99.4%, precision of 99.3%, recall of 99.5%, and an F1-score of 0.99, substantially outperforming standalone ViT and ECNN configurations. These findings indicate that hybrid transformer-convolutional models can substantially enhance diagnostic accuracy and offer a promising approach for supporting early identification and intervention in ADHD.
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Cross-study inconsistencies in autism spectrum disorder (ASD) blood microRNA biomarker studies suggest that methodological heterogeneity may substantially limit reproducibility. We conducted an exploratory meta-analysis of publicly available ASD blood miRNA datasets from the Gene Expression Omnibus, applying rigorous inclusion criteria and standardized analytical protocols. Three datasets were included (GSE89596, GSE67979, GSE222046) comprising 614 miRNAs across 90 participants (45 ASD, 45 controls). Random-effects meta-analysis was performed using Hedges' g effect sizes, with comprehensive heterogeneity assessment and leave-one-dataset-out cross-validation. No miRNAs survived multiple testing correction (Benjamini-Hochberg FDR < 0.05), though seven candidate signals showed consistent evidence with unadjusted p < 0.01 and large effect sizes. These candidates demonstrated near-zero between-study heterogeneity and consistent directionality across validation analyses. Potential age-related and platform-related differences were observed, with near-zero correlation between adult and pediatric effect sizes (Kendall's τ = -0.022); however, these two sources of variability were fully confounded in the available data and could not be separated. Some miRNAs exhibited extreme between-study variability (I² > 80%), indicating substantial methodological differences. Cross-validation revealed that excluding the single adult dataset reduced sign consistency from 89.9% to 68.9%. Our findings suggest that age-related and methodological factors, including technical platform differences, may contribute to limited reproducibility in ASD blood miRNA research, and that blood-derived signals should be interpreted as potentially reflecting peripheral physiological states rather than central disease mechanisms. A supplementary cross-tissue analysis using post-mortem prefrontal cortex data (GSE59286; n = 45) provided direct empirical support for this interpretation: the majority of blood candidate miRNAs showed no corresponding expression in brain tissue, with only hsa-miR-29c-5p demonstrating directional concordance across both tissues. These findings suggest that age stratification, platform harmonization, and cross-tissue validation should be considered essential prerequisites for reliable ASD miRNA biomarker discovery, rather than optional refinements.
To evaluate the association between myo-inositol supplementation and the risk of fetal macrosomia in pregnant women with a history of large-for-gestational-age infants, and to assess its relationship with gestational weight gain in women with overweight or obesity. A prospective observational study was conducted in antenatal clinics and the Almaty Center for Perinatology and Pediatric Cardiac Surgery. Myo-inositol supplementation was recommended as part of routine clinical practice and taken daily for up to 6 months. Participants attended four visits: baseline (<12 weeks), 20 weeks, 30 weeks, and delivery. The main group included women with a BMI of 25-35 kg/m² and a history of delivering infants weighing >4000 g. The comparison group was formed using a clinical risk scoring system to improve group comparability. Gestational weight gain was significantly lower in the myo-inositol group (11.82 kg) compared with the comparison group (17.85 kg; p<0.001). The incidence of macrosomia was lower in women who used myo-inositol supplementation (5.9% vs. 55.9%). Mean neonatal birth weight was also lower in the supplementation group (3658.9 g vs. 3972.5 g), with a mean difference of 313.6 g (95% CI 173.5-453.8). Emergency cesarean delivery occurred less frequently in the supplementation group (3.9% vs. 15.7%), indicating improved obstetric outcomes. In this high-risk cohort, the use of myo-inositol supplementation was associated with lower gestational weight gain and a lower incidence of fetal macrosomia. These findings suggest a potential beneficial role of myo-inositol in the prevention of excessive fetal growth; however, randomized controlled trials are needed to confirm causality.
Preoxygenation is a key component of prehospital emergency anesthesia (PHEA), reducing hypoxemia and increasing safe apnea time. Delayed sequence intubation (DSI) involves the use of sedation without blunting respiratory drive to facilitate optimization, primarily oxygenation, before paralytic administration and subsequent intubation in patients with agitation who are unable to tolerate preoxygenation. This scoping review explored the evidence supporting DSI in emergency and prehospital practice. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided scoping review was conducted. MEDLINE and Embase were searched from inception to May 5, 2025, for studies reporting DSI. Primary studies, case series, case reports, and guidelines involving adult or pediatric patients were included; reviews, editorials, and letters were excluded. Titles, abstracts, and full texts were independently screened by 2 reviewers, with disagreements resolved by a third. Fourteen studies met the inclusion criteria. Across these studies, 310 DSI cases were reported, including 140 performed prehospital by physician- and paramedic-led teams. Emergency department evidence suggests that DSI may reduce hypoxemia in agitated patients compared with rapid sequence intubation (RSI), with 1 randomized controlled trial reporting hypoxemia rates of 8% versus 35% (P = .001). Evidence specific to prehospital DSI was limited to retrospective studies, with no randomized controlled trials identified. Limited evidence suggests that DSI can be performed by teams already delivering PHEA using an RSI technique and may reduce hypoxemia in those patients unable to tolerate preoxygenation. Further prospective research directly comparing RSI and DSI techniques in the prehospital setting is required to inform future practice.
A 3-year-old male passenger developed acute respiratory distress approximately 30 minutes after takeoff during an international flight from the United States to Addis Ababa. Despite multiple rounds of nebulized albuterol and escalating oxygen therapy, his respiratory status progressively deteriorated. A multidisciplinary team of onboard physicians administered epinephrine and hydrocortisone from the emergency medical kit while coordinating with ground medical control. The aircraft was subsequently diverted to Athens, Greece, where the child was handed over to emergency services and later stabilized. This case highlights the challenges of managing pediatric respiratory distress in-flight and the critical importance of prompt coordination, adequate medical supplies, and crew preparedness.
Functional validation of candidate genes in congenital anomalies of the kidneys and urinary tract (CAKUT) and other disorders is essential for translating genetic discoveries into clinical applications. Conditional knockout mouse models are indispensable for studying gene function in complex organ systems. The Short Conditional intrON (SCON) system accelerates the generation of such models by inserting the artificial SCON into a coding exon. SCON is designed to be spliced out after transcription, without affecting gene expression. Upon Cre activity, SCON is converted into the ΔSCON allele which cannot be spliced out, introducing premature termination codons (PTCs) to inactivate the gene. Previous validation of the SCON system in mice has focused primarily on phenotypic outcomes. Here, we provide a molecular characterization of the SCON system in Cdh12-a candidate gene implicated in kidney damage in CAKUT. We found that both Cdh12SCON and Cdh12ΔSCON alleles caused unintended skipping of the exon downstream of the insertion site, culminating in a frameshift and PTC. Consequently, the Cdh12SCON allele led to a ~ 25% reduction in mRNA expression, indicating that it was not transcriptionally inert as designed. Despite unintended exon skipping, the Cdh12ΔSCON allele still effectively suppressed mRNA expression. These findings highlight the importance of transcript-level characterization of engineered alleles prior to functional studies, as artefactual splicing events may occur across multiple gene-targeting strategies, including artificial intron-based conditional alleles as shown here.
The Clinical Genome Resource (ClinGen) Von Hippel-Lindau (VHL) Variant Curation Expert Panel (VCEP) has created variant classification specifications tailored to the VHL gene, including phenotype-driven and evidence-based criteria, utilizing somatic and germline mutational hotspots, along with functional and in-silico data. Using the American College of Medical Genetics and Genomics (ACMG) guidance and the ClinGen Sequence Variant Interpretation (SVI) recommendations, the VCEP made substantial modifications to 8 evidence codes (PVS1, PS3, PS4, PM1, BS2, BS3, BS4, BP5), while 14 had minor changes, and 6 were not used (PM3, PP2, BP1, PP4, PP5/BP6). The VHL VCEP applied two literature sets of over >428 papers in Clinical Interpretations of Variants in Cancer (CIViC) and >8700 structured annotations using Hypothesis. From 31 pilot variants, 15 remained pathogenic/likely pathogenic, 9 resolved to benign through the stand-alone benign evidence code while 7 variants with initial uncertain classifications lacking additional evidence, remained uncertain. The versioned VHL VCEP specifications are publicly available in the ClinGen Criteria Specifications Registry and will enhance the transparency and consistency of variant classifications for this highly sequenced hereditary cancer gene.
Patients with Down Syndrome (DS) are characterized by dysfunction of several organs, including the liver, brain, heart defects, gastrointestinal anomalies, and lethal immune hypersensitivity. A person with DS is also susceptible to various inflammatory diseases, including hepatic autoimmune diseases. The Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is known to trigger the stimulator of interferon genes (STING) and downstream proinflammatory factors. In this work, we hypothesized that oxidative stress-associated DNA damage triggers activation of the cGAS-STING signaling pathway and promotes liver inflammation in DS. Here, we investigated the role of reactive oxygen species (ROS) associated DNA damage and the cGAS-STING signaling pathway in the pathogenesis of hepatic inflammation in the DS model. Our results showed that DS cells harbor excessive ROS and DNA damage in DS fibroblasts and DS mouse liver. Further, DS cells accumulate micronuclei that likely serve as a source of cytoplasmic DNA to stimulate cGAS-STING activation. In addition, RNA-seq analysis results showed enhanced expression of key type I interferon factors in cGAS-STING pathways in DS liver and inflammatory responses and elevated liver enzymes such as alanine transaminase (ALT) that indicate a hepatocellular liver injury in DS. The results of this study opened the opportunity to connect endogenous DNA damage triggers innate immune response, which may contribute to the upregulation of the cGAS-STING signaling to exacerbate hepatic inflammation in DS.