Investigation of fetal right ventricular contraction using pressure driven fluid structure interaction modeling

Early adversity alters neurodevelopmental milestones in male and female rat pups and motor cortex morphology and gait in juveniles.

Goueta etal. (Journal of Child Psychology and Psychiatry, 2025, 66, 1209) utilized a Random Intercept Cross-Lagged Panel Model (RI-CLPM) to investigate reciprocal links between ADHD symptoms and adolescent risky behavior. Their finding that stable between-person differences, rather than within-person fluctuations, primarily drive this association challenges common clinical assumptions. While commending their methodological rigor, this commentary proposes five refinements to better capture the dynamic ADHD-risk nexus. First, aggregating diverse risk behaviors may mask distinct symptom-coupled fluctuations, requiring multivariate models to separate impulsivity from social deviance. Second, relying exclusively on parent reports introduces bias; future studies should incorporate multi-informant designs, ecological momentary assessment (EMA), and passive sensing. Third, standard time metrics overlook critical developmental milestones; event-contingent sampling around salient transitions can address process non-stationarity. Fourth, integrating time-varying mediators, such as sleep and parental monitoring, can reveal precise windows of heightened risk for targeted interventions. Finally, dimensional scoring might obscure non-linear threshold effects and pharmacological impacts. By addressing behavioral heterogeneity, reporter variance, developmental contexts, and non-linearities, future research can clarify exactly when, for whom, and under what conditions ADHD symptom fluctuations forecast adolescent risk.

Objective: To analyze the clinical and genetic characteristics of infantile-onset Pompe disease (IOPD) and evaluate the long-term efficacy of enzyme replacement therapy (ERT). Methods: A retrospective cohort study was conducted on 24 IOPD patients diagnosed and treated at the Children's Hospital, Zhejiang University School of Medicine, between December 2016 and June 2025. Clinical and genetic variation characteristics of patients were analyzed. According to the whether received alglucosidase α and gene therapy, patients were stratified into ERT group, non-ERT group and gene therapy group. Baseline characteristics, including gender, weight, age at symptom onset and diagnosis, degree of cardiac hypertrophy and gene coding for acid alpha-glucosidase (GAA)enzyme activity were compared among the three groups using Fisher exact test or the Kruskal-Wallis H test, as appropriate. Within the ERT group, Friedman test followed by Wilcoxon signed-rank tests were used to compare efficacy before treatment at 12 and 36 months of treatment. Kaplan-Meier method was performed for survival analysis. Results: Among the 24 patients, there were 13 males (54.2%) and 11 females (45.8%). The age of onset and diagnosis was 1.8 (0.9,3.0) and 4.8 (2.7,6.7) months, respectively. Significant differences were found among the ERT, no-ERT, and gene therapy groups in gender distribution and body weight (all P<0.05). However, no statistically significant differences were observed in age at onset, age at diagnosis, presence of muscle weakness, feeding difficulties, heart failure, degree of cardiac hypertrophy or GAA enzyme activity (all P>0.05). After 12 months of ERT, significant reductions were observed in interventricular septal thickness, left ventricular posterior wall thickness and left ventricular mass index (LVMI) (all P<0.05).​​ Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels showed significant differences at both the 12 and 36-month follow-up (P<0.05), whereas creatine kinase levels did not change significantly at these time points (P>0.05). Among the 5 patients in ERT group followed for 36 months, 4 patients achieved new motor developmental milestones, while 1 patient showed no significant motor improvement. Survival analysis revealed that all 8 patients in gene therapy group survived, 6 deaths in non-ERT group,and only 1 death in ERT group. The comparison of survival curves between ERT group and non-ERT group showed statistically significant difference (P=0.001). Univariable Firth Cox proportional hazards regression analysis demonstrated that ERT significantly decreased mortality risk (HR=0.04,95%CI 0.00-0.34,P=0.001). Regarding safety, only 1 mild allergic reaction occurred during 468 cumulative infusions in ERT group. Conclusion: ERT effectively prolongs survival and reverses cardiac hypertrophy in IOPD patients with a favorable safety profile, but its effect on improving skeletal muscle function remains limited.

Financial independence, an important developmental milestone of emerging adulthood (ages 18-29), is critical to independent functioning in life. Examining whether financial independence in emerging adults with serious mental illness (SMI) is associated with self-stigma may inform ways to support achieving this milestone. Financial independence was investigated as a mediator between self-stigma and two of its harmful outcomes, lower self-esteem, and an increased "why try" effect. The "why try" effect was defined as a sense of futility about achieving life goals due to self-stigma. Self-stigma was expected to be associated with less financial independence, and less financial independence was expected to be related to reduced self-esteem and an increased "why try" effect. Emerging adult community mental health center clients who had an SMI (n = 239) were recruited to complete an electronic survey. Path analysis was used to analyze data. Consistent with previous research, self-stigma was associated with decreased self-esteem and an increased "why try" effect. Financial independence was associated with higher self-esteem and, unexpectedly, with an increased "why try" effect. Contrary to past findings among adults, self-stigma was associated with increased financial independence. Two indirect associations through financial independence were observed between (a) self-stigma and self-esteem and (b) self-stigma and the "why try" effect. Findings indicate that emerging adults with SMI may simultaneously experience self-stigma, financial independence, and the "why try" effect. Implications for psychiatric rehabilitation include increasing assistance with managing self-stigma among emerging adults with SMI pursuing financial independence. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

ART has transformed clinical practice but still face modest success rates, poorly defined implantation conditions, and persistent gaps in understanding early human development. At the same time, research in human reproductive biology remains strikingly underfunded relative to its medical and social impact. Over the last decade, advances in human pluripotent stem cell (PSC) biology have generated a suite of technologies that can recapitulate early stages of human development from blastocyst formation to early gastrulation in vitro. Here we review how such models can be harnessed to interrogate lineage specification, embryo-endometrium crosstalk, the origins of aneuploidy and implantation failure, and the developmental basis of placental and yolk sac disorders, with a focus on primates. We argue that integrating stem cell-derived embryo models into reproductive research agendas offers a tractable experimental framework to improve ART outcomes and address major unmet needs in human reproductive health.

Postnatal particulate matter exposure alters developmental milestones and brain gene expression in apoE transgenic mice in a sex- and genotype-dependent manner.

Long-term health outcomes of pediatric obstructive sleep apnea: A 10-year multicenter cohort study.

Developmental epileptic encephalopathy (DEE) is a severe neurodevelopmental disorder characterized by developmental delay, regression, and intractable seizures. Genetic testing plays a crucial role in identifying underlying pathogenic variants, guiding treatment, and improving patient outcomes, particularly in resource-limited settings. A one-and-a-half-year-old Sri Lankan boy was assessed due to global developmental regression. He exhibited motor delays, with developmental milestones around 9-12months, including the ability to form a pincer grasp and stand with support. He showed regression in speech and swallowing. By 15months, he could speak single words, which had reduced to monosyllable babbling by the time of presentation. He was born to healthy, non-consanguineous parents and had a healthy sibling. He had an uncomplicated antenatal and perinatal history and had no history of seizures. His paternal uncle also had developmental delay and epilepsy. He was found to have electrical status epilepticus in sleep (ESES) in the electroencephalogram (EEG) recording, and genetic testing revealed a CACNA1E loss-of-function mutation. He had a variable response to antiseizure medications, with a good response to acetazolamide and significant functional deterioration with topiramate. He also responded to treatment for ESES. Pathogenic variants of CACNA1E, particularly those causing either gain-of-function or loss-of-function effects, are linked to severe neurodevelopmental disorders. Clinically, CACNA1E mutations often present in early childhood with severe neurodevelopmental impairment, global developmental delay, autistic features, feeding difficulties, and self-injurious behaviors. The molecular mechanisms can explain the deterioration with topiramate and the improvement with acetazolamide, as the mutation causes a loss of function of the CACNA1E gene, which is potentially exacerbated by the blocking of the same channel by topiramate and improved by acetazolamide. This case exemplified the use of genetic diagnosis for precision treatment. It highlighted the need to look for modifiable conditions such as epileptic encephalopathy in children with developmental delay and regression, even in the absence of seizures. The CACNA1E mutation, EEG finding of ESES, and the responses to targeted treatment add to the literature of this rare disorder.

Pathogenic variants in Transcription Factor 12 (TCF12) have been identified as genetic causes of craniosynostosis. The phenotypic spectrum of TCF12-related craniosynostosis is broad and remains incompletely understood. Herein, we report a case of a 2-month old male with a heterozygous pathogenic variant of TCF12 (c.1267C > T; pArg423*) and bicoronal craniosynostosis. He underwent bicoronal suturectomy at 4months of age, followed by post-operative molding helmet therapy. He returned at 2years of age with developmental regression including loss of expressive language and fine motor skills. Shortly after he developed clinical findings of elevated intracranial pressure (ICP) and was found to have synostosis of the sagittal and bilateral lambdoid sutures, and a Galassi III left middle fossa arachnoid cyst with significant midline shift, requiring surgical fenestration. Post-operatively, the cyst decreased in size with resolution of midline shift. The patient did not regain any developmental milestones and continued to demonstrate deficits in language, social communication, and fine motor function despite resolution of other preoperative signs and symptoms of elevated ICP. To our knowledge, this is the first reported case of TCF12-associated craniosynostosis with a co-occurring arachnoid cyst. Furthermore, there is limited literature describing the long-term neurodevelopmental outcomes of children with TCF12 pathogenic variants. Thus, this case offers expanded insight into the broad phenotypic spectrum of TCF-12 related craniosynostosis and its potential clinical sequelae.

Rare deleterious variants in SHANK3 are established causes of autism spectrum disorder (ASD), but the extent to which they define a phenotypically and genetically coherent ASD subgroup remains unclear. Using the SPARK cohort, we identified 132 SHANK3 variant carriers; 108 had phenotype data and were compared with 47,555 non-carrier ASD cases. SHANK3 damaging variant carriers showed lower cognitive ability, poorer motor coordination, and delayed developmental milestones. Protein-truncating variant and deletion carriers showed similarly severe phenotypic profiles, whereas duplication carriers did not differ from non-carriers. A combined threshold of intelligence quotient (IQ) < 70 and impaired motor coordination (DCDQ total score) < 35 defined a discriminative cognitive-motor phenotype among cases meeting this cognitive-motor phenotype. Beyond SHANK3 , SLC6A1 was the only additional gene reaching false discovery rate significance, while pathway analyses implicated synaptic and chromatin-related processes. Phenotype-meeting cases did not show elevated ASD polygenic risk, supporting a rare-variant-enriched cognitive-motor subgroup within ASD.

The development of the functional cortical hierarchy, spanning sensorimotor to association systems, is exclusively studied as a function of age. During adolescence, this overlooks puberty as a major neurodevelopmental driver and source of variability. We studied sensorimotor-association axis refinement longitudinally (6323 observations across 4919 subjects), leveraging individual differences to disentangle chronological age from pubertal effects. We derived low dimensional features of sensorimotor-association axis development from resting-state functional connectomes, revealing substantial inter-individual heterogeneity in maturational trajectories that challenge group-level developmental trends and milestones. Then, we demonstrate independent effects of age and pubertal stage on sensorimotor-association axis refinement through the polarization of the cortical hierarchy. We further show that coordinated system-level shifts in network topology reflect an ongoing specialization of functional connectivity profiles across all major functional networks. Our findings frame adolescent hierarchical functional cortical maturation as an individualized, multifactorial phenomenon shaped by distinct chronological age and pubertal processes.

Hereditary spastic paraplegia type 4 (SPG4), caused by variants in SPAST, is the most common form of HSP and exhibits a remarkable phenotypic heterogeneity ranging from late-onset pure presentations to severe, early-onset complex disease. Robust genotype-phenotype correlations and detailed natural history data are lacking, limiting clinical trial readiness. We analyzed 206 patients with genetically confirmed SPG4 enrolled across seven international centers, complemented by high-quality literature-derived cases. Deep phenotyping included standardized motor scales, spasticity ratings, developmental milestones, and patient-reported outcomes. We developed an extended essentiality-mapping framework to classify SPAST missense variants by integrating in silico pathogenicity predictions, evolutionary constraint, physicochemical residue connectivity, and variant enrichment within the human spastin hexamer structure. Plasma neurofilament light chain (pNfL) using was quantified using Simoa in 26 patients and 101 controls. We identified 136 distinct SPAST variants, including 10 novel variants. Variant class segregated strongly by inheritance, with de novo cases enriched for missense variants and inherited cases showing a variety of variant classes with enrichment for truncating variants. Longitudinal analysis revealed two latent trajectories: a rapidly progressive severe subgroup enriched for de novo missense variants, and a biphasic moderate subgroup enriched for inherited truncating variants. Patient stratification integrating spastin essentiality mapping (missense variants affecting essential, neutral, or context-dependent residues) with established genetic modifiers (biallelic pathogenic variants or modifier variants in trans) classified patients into predicted severe and moderate subgroups with divergent age at onset and clinical disease progression. The severe subgroup showed early developmental delays, rapid loss of ambulation, and declining quality of life, while the moderate subgroup displayed delayed but accelerating disease progression. pNfL levels were elevated in both subgroups, most pronounced in severe early disease. This study provides the most detailed natural history of SPG4 to date and introduces a biologically informed stratification framework that links variant class and location to divergent clinical trajectories. These data establish clinically meaningful benchmarks and offer a genotype-based framework to improve anticipatory care and optimize trial design for SPG4.

The COVID-19 pandemic raised concerns regarding the effects of maternal SARS-CoV-2 infection during pregnancy on infant growth and neurodevelopment. Prior evidence has been inconsistent, limited by small sample sizes, short follow-up, and confounding by prematurity. We evaluated growth and developmental outcomes through 24 months among term-born children exposed in utero to maternal SARS-CoV-2 infection compared with unexposed controls. We conducted a nationwide retrospective matched cohort study including 66,285 term infants born in Israel between March 2020 and March 2022. Maternal SARS-CoV-2 infection during pregnancy defined exposure, with exposed infants (n=22,096) matched to unexposed controls by delivery date. National registries provided standardized growth and developmental data. Outcomes included infant growth and attainment of 31 developmental milestones up to 24 months, analyzed using adjusted stratified Cox regression models. Infant growth trajectories, developmental milestone attainment, and referral rates were similar between exposed and unexposed children. Findings were consistent across sub-analyses by sex, trimester of infection, maternal disease severity, and during the pre-vaccine period. This large nationwide study did not identify a significant association between maternal SARS-CoV-2 infection during pregnancy and early childhood growth or development among term neonates. Based on nationwide data with two-year follow-up, these findings offer reassuring evidence regarding outcomes.

Attrition of new therapies is a major concern in oncology drug development. Little is known about subsequent drug development milestones once an oncology agent has entered clinical testing in children and adolescents. This study identified 191 cancer drugs that first entered clinical trials between 2005 and 2020 and for which patients <18 years were eligible. The authors tracked subsequent drug development and regulatory milestones through 2025. They calculated Kaplan-Meier cumulative incidence rates of reaching each milestone, and they calculated Cox hazard rates according to features of the drug and trial characteristics. The majority (62.8%) of the 191 identified drugs were small molecule inhibitors. The majority of trials evaluated single agents (66.5%) and were multicenter trials (77.9%). At 10 years from first pediatric-eligible trials, the cumulative incidence rates of subsequent phase 1, phase 2, and phase 3 trials were 56.1%, 63.0%, and 17.7%, respectively. Of 191 drugs, 71 (37.2%) had no new trials that allowed patients <18 years of age for 5 or more years from first pediatric-eligible trial. For drugs not already approved at time of initial pediatric-eligible trial, the 10-year cumulative incidence rates for subsequent pediatric Food and Drug Administration and European Medicines Agency approval were 12.0% and 5.6%, respectively. Initial trial phase and drug regulatory status at time of initial pediatric-eligible trial were the most consistent determinants of achieving subsequent drug development milestones. Oncology drugs entering testing in children and adolescents are at high risk of attrition, including low rates of subsequent late phase trials and pediatric regulatory approvals.

Transcriptomic reprogramming underlies perfluorobutanoic acid (PFBA)-induced hormesis in the fall armyworm, Spodoptera frugiperda.

ABSTRACTIncreasing evidence suggests that interactive feeding is an important variable in language development, with early disruptions in feeding potentially having long‐term consequences. This longitudinal experiment characterized early patterns of feeding difficulties and language development in full‐term, typically‐developing infants across the developmental milestones of 8, 12, 18, 24, and 54 months. Parent‐directed assessments were used to assess feeding difficulties and language abilities between 8 and 24 months and a clinical language assessment was administered at 54 months. Results revealed that certain feeding difficulties, such as poor saliva control at 18 months, correlate negatively with expressive vocabulary size and may signal co‐occurring and later occurring less developmentally advanced language skills at 18 and 24 months. Others, such as food selectivity, are characteristic of children with less developmentally advanced language skills at 24 months. Together, these findings suggest that feeding difficulties may reduce opportunities for language stimulation and/or reflect underlying oral‐motor developmental vulnerabilities that also affect language development.

Introductions: The COVID-19 pandemic has profoundly impacted many aspects of life, with especially severe effects on social interactions. Quarantine and social distancing measures, while essential for controlling viral spread, imposed unprecedented restrictions on social engagement, intensifying feelings of isolation and stress. This study aims to investigate the short- and long-term effects of the pandemic on youth mental health, a population for whom peer interactions are vital for developmental milestones and overall well-being. Methods: A literature review was conducted, analyzing scientific articles published between 2020 and 2024 that focused on the mental health of youth during and after the COVID-19 pandemic. Results: Evidence indicates a notable increase in depression, anxiety, and other mental health disorders among adolescents and youth during the pandemic. Prolonged periods of home confinement have led to increased feelings of loneliness, which have been linked to elevated risks of depression and suicidal ideation. Furthermore, persistent mental health challenges have been associated with excessive internet use and decreased physical activity during this period—behaviors that continue to adversely affect youth mental health as pandemic restrictions ease. Conclusions: The COVID-19 pandemic has had a significant and lasting impact on youth mental health, largely due to the critical role of social interactions and peer relationships in this age group. Social isolation remains a key factor contributing to ongoing mental health issues even after the pandemic. Given the long-term implications, increased attention and intervention efforts are urgently needed to support youth mental health, especially as this area remains under-researched.

Cobalamin C (cblC) deficiency is one of the most common congenital vitamin B12 metabolic abnormalities, and may cause severe neurologic symptoms, gastrointestinal and nephritic symptoms. A 9-month-old boy presented with a 10-day history of progressive dyspnea and weak cough, accompanied by moaning, perioral cyanosis, and poor feeding. The parents also reported significant developmental regression and delay, characterized by an inability to raise his head, sit independently, or vocalize "dada" and "mama": milestones typically achieved by this age. The patient was diagnosed with cblCdeficiency, complicated by combined methylmalonic acidemia and homocystinuria, based on clinical manifestations (developmental regression, cyanosis, pulmonary arterial hypertension (PAH)) and confirmatory genetic testing (compound heterozygous variants in the methylmalonic aciduria cobalamin deficiency type C with homocystinuria gene: c.567dupT and c.80A > G). Following admission, the patient received multifaceted treatment. Metabolic therapy included hydroxocobalamin, folic acid, betaine, and L-carnitine to address the methylmalonic acidemia and homocystinuria. Antibiotic therapy with cefotaxime was administered for concurrent pneumonia. Additionally, bosentan (64 mg/day) was initiated for the management of PAH. At discharge, the patient exhibited stable vital signs, improved developmental milestones, reduced pulmonary artery systolic pressure, normal renal function, and no evidence of hydrocephalus progression. Genetic analysis revealed a genotype-phenotype correlation: the c.567dupT variant was associated with neurodevelopmental disorders and early-onset severe disease, whereas the c.80A > G variant correlated with PAH and renal dysfunction. This report highlights the diverse clinical manifestations of cblC deficiency based on specific methylmalonic aciduria cobalamin deficiency type C with homocystinuria mutations. A review of the literature supports these genotype-phenotype associations, aiding in prognostic stratification and targeted management.

Decades of research have established links between speech input and children's vocabulary growth. However, it is unclear if input also facilitates phonological development. Phonology has a strong biological component-implicating fine motor development-so language socialization factors like speech input may matter less. Further complicating matters, children in many cultures are exposed to vastly different amounts of speech input, and yet these children still reach many major language development milestones on age-appropriate timelines. How does speech input relate to infant phonological development in the first years of life? We estimated infants' (1) speech input and (2) vocal maturity using daylong audio recordings taken in an Indigenous Quechua- and Spanish-speaking community in Bolivia (n = 10, M age = 12 months, 5 females, 5 males) and an immigrant Spanish- and English-speaking community in the United States (n = 10, M age = 9 months, 4 females, 6 males; all Hispanic or Latino). Although we found no differences in the overall amount of speech input to adults and children between communities, infants in the United States were 2.5× more likely to hear speech directed to them than the infants in Bolivia. When child-directed speech (CDS) was instead characterized to include all speech directed to any child within the infants' vicinity, there were no differences between communities. When employing these different definitions of CDS, we found positive relationships between quantity of speech input and different metrics of the Bolivian infants' vocal maturity. These results paint a nuanced picture showing that directed speech input, even when less common, is related to early phonological development, and that by expanding the definition of speech input to accommodate diverse cultural settings we can understand how infants' language development is resilient to differences in speech input.