Search Results (2,673)

Background: Tumor-derived small extracellular vesicles (sEV), which we call TEX, carry a cargo of molecules that resembles the producer tumor cells. Circulating freely in body fluids, TEX potentially serve as a liquid tumor biopsy. TEX horizontally transfer their cargo to various recipient cells, imparting to them pro-tumor activity. Mechanisms of TEX-driven reprogramming might involve nucleic acids, especially double-stranded (ds)DNA. Methods: TEX isolated from supernatants of human tumor cells were identified as sEV, based on their size, endocytic origin and morphology. TEX treated with DNase/RNase cocktail were examined by transmission and cryo-electron microscopy and tested for biologic activity. DNA was extracted from enzyme-treated TEX, quantified by Qubit and analyzed for fragment sizes. The presence of genomic DNA in TEX was confirmed by PCR, and sequencing of the TP53 gene fragment for a mutational signature was performed. Results: Enzymatic and microscopic studies of TEX showed that nucleic acids are present in the biocorona on the outer surface. Their removal interfered with the biocorona integrity. A short TEX exposure to DNase/RNase altered their morphology without impairing vesicle functions; longer treatments induced TEX re-organization into smaller membrane-bound vesicles. The TEX lumen contained long fragments of protected genomic DNA with a mutational signature reflecting that of the tumor. Conclusions: Nucleic acids present on the TEX surface support the vesicular integrity. The TEX lumen contains membrane-protected large (ds)DNA fragments with the mutational signature of the parent tumor. The presence of surface and luminal nucleic acids in TEX, and especially their mutational signature, suggests that TEX may serve as highly promising cancer-specific biomarkers. Full article

Background: Contemporary models of parental burnout conceptualize it as an interplay between parental demands and insufficient resources. Though, research and current models remain sparse in their understanding of these demands and dynamics within the context of managing a child’s sleep wellness and related problems, which constitute a fundamental aspect in early parenting. The present work addresses this gap by examining this issue comprehensively. Methods: 2291 mother–child dyads were recruited from two sources: a random population sample (n = 1409) and a clinical sample (n = 882) of mothers seeking consultation for their child’s sleep issues (0–5 years old). Mothers completed an extensive panel of validated instruments and survey questions covering burnout and psychopathologies, sleep parameters, psychosocial, organizational, and demographic variables. Inferential analyses, regression modeling, cluster analysis, and mediation models were applied. Results: Two distinct profiles of parental burnout emerged: one associated with child sleep disturbances and the other with general parenting stress. The strongest-weighted risk factors pertained to maladaptive beliefs and perceptions (e.g., shame, “I am bad parent”, “My child cries because I do not meet his needs”), as well as additive stressors such as interparental tension and daytime child behavioral problems. The strongest protective factors involved resources that reduced parental demands or facilitated recovery including couple satisfaction, a consistent bedtime routine, greater capacity to take breaks (e.g., additional caregivers, father nighttime involvement, parental cohabitation, and child screen time). Conclusion: The identification of two distinct burnout profiles highlights the importance of incorporating, or placing more centrally, the management of young children’s insomnia in contemporary theoretical models of parental burnout. This research highlights the need for interventions on healthy self-beliefs and perceptions, effective daytime parenting strategies, positive couple dynamics, consistency in bedtime routines, and equitable distribution of caregiving responsibilities between parents to reduce the risk of parental burnout. Full article

This study examines the perceived impact of sensory and interactive architectural design in inclusive learning environments on the sensory–emotional responses and behavioral–academic outcomes of children with neurodevelopmental disorders—namely Autism Spectrum Disorder, Down Syndrome, and Attention-Deficit/Hyperactivity Disorder—during early childhood within the Egyptian educational context. Adopting a perception-based, non-causal analytical perspective, a descriptive–analytical, survey-based design was implemented using a validated questionnaire developed from an architectural–educational conceptual framework grounded in relevant literature. The study involved (N = 202) parents, teachers, therapists, and caregivers who evaluated the perceived influence of environmental design elements on children’s sensory responses, behavior, social interaction, and academic performance, based on observational and experiential assessments rather than objective environmental performance measurements. The results indicated high perceived impacts on sensory–emotional responses (84.8%) and behavioral–academic outcomes (82.0%). Movement–spatial attributes showed the strongest influence, followed by balanced natural lighting, calming colors, natural materials, and low-noise acoustic conditions, while natural elements and sensory gardens played a regulatory role in supporting emotional stability and social interaction. The study concludes that sensory- and emotionally responsive architectural design, when understood as a supportive component of the educational experience rather than an independent causal factor, and integrated with appropriate pedagogical practices, contributes to inclusive learning environments accommodating neurodevelopmental diversity, while informing the development of an applied, evidence-informed architectural design framework that translates perceptual–correlational findings into structured and operational design guidelines adaptable to the Egyptian educational context. Full article

Parental educational involvement is a pivotal factor associated with an individual’s academic development; however, its specific association with academic delay of gratification and the underlying mechanisms remain not fully understood. Drawing upon ecosystem theory, this study examined a serial mediation model to explore the links between parental educational involvement and academic delay of gratification, focusing on the mediating roles of self-control and consideration of future consequences. A cross-sectional design was employed, involving 726 junior high school students. Data were collected using the Parental Educational Involvement Scale, Academic Delay of Gratification Scale, Self-Control Scale, and Consideration of Future Consequences Scale, with statistical analyses performed via SPSS 26.0 and the PROCESS macro. The results indicated that: (1) parental educational involvement, academic delay of gratification, self-control, and consideration of future consequences were positively correlated with each other in a pairwise manner; (2) academic delay of gratification was significantly predicted by parental educational involvement (β = 0.117, p < 0.001); (3) self-control and consideration of future consequences play a mediating role in the relationship between parental education involvement and academic delay of gratification. There are three mediating pathways involved in this process: the individual mediating role of self-control (β = 0.092, 95% CI [0.054, 0.133]), the individual mediating role of consideration of future consequences (β = 0.030, 95% CI [0.015, 0.050]) and the chain mediating role of self-control and consideration of future consequences (β = 0.015, 95% CI [0.008, 0.024]). This study examined the internal mechanism between parental educational involvement and academic delay of gratification, which is helpful in improving junior middle school students’ ability to engage in academic delay of gratification. Full article

Background: In countries lacking donor registries, related donors, including haploidentical ones, often serve as the main option. This research aimed to examine the feasibility of locating donors for allogeneic hematopoietic stem cell transplants and to assess the outcomes associated with various donor types. Methods: Between 2019 and 2024, a retrospective observational study was carried out, involving 520 patients and 824 potential stem cell donors. Of these patients, 155 successfully identified a suitable donor and underwent allogeneic stem cell transplantation using mobilized peripheral blood stem cells. The study tracked overall and event-free survival over a five-year period to assess outcomes based on different donor types. Results: With alternative related donors (ARDs), 91% of patients were able to find at least one suitable donor for transplantation. The chances of identifying an appropriate donor increase with a larger pool of potential donors. Transplantation outcomes using ARDs, such as siblings, children, or parents, were similar to those with matched sibling donors. Other relatives could be considered as potential haploidentical donors, but the results with these donors were less favorable compared to those of others. Conclusions: The use of ARDs has significantly expanded the availability of related donors, with promising outcomes. Full article

The article presents a clinical case involving a patient with presumptive coexistence of two hereditary disorders, confirmed by molecular genetic analyses. Clinical evaluation of the proband, a 9-year-old girl, revealed features characteristic of Kabuki syndrome, including a typical “Kabuki makeup” facial phenotype, short stature, intracranial hypertension, and diffuse muscular hypotonia. Additional clinical findings included chronic right-sided otitis media, conjunctivitis, recurrent pneumonia, bilateral conductive hearing loss, astigmatism, and primary adenitis. Clinical assessment and molecular genetic testing were performed. High-throughput sequencing identified a previously reported pathogenic heterozygous variant in the KMT2D gene, NM_003482.4:c.15142C>T p.Arg5048Cys, and two known heterozygous variants in the CFTR gene: NM_000492.4:c.1521_1523delCTT p.Phe508del and c.3454G>C p.Asp1152His, classified as pathogenic and of variable clinical significance, respectively. Segregation analysis demonstrated that the KMT2D variant most likely arose in the proband de novo, whereas the CFTR variants were inherited from each of the parents. Notably, the proband’s clinically unaffected elder sister carried the same CFTR genotype. Based on the clinical presentation and molecular genetic findings, the diagnosis of Kabuki syndrome type 1 was conclusively established in the patient. Functional assessment of CFTR demonstrated its preserved function, which did not support a diagnosis of CF or CFTR-related disorders. Full article

In recent years, an ion-adsorption type REE deposit has been discovered for the first time in the weathering crust of epimetamorphic rocks in Ningdu County, Jiangxi Province, which provides a new idea for the exploration of ion-adsorption-type REE deposits. However, most previous studies on the ore-forming parent rocks of ion-adsorption-type REE deposits have focused on granites and volcanic rocks, while studies on epimetamorphic rocks remain extremely scarce. In this paper, petrographic analysis of epimetamorphic rocks, LA-ICP-MS U–Pb dating and trace element analysis of zircon and apatite were conducted on the metamorphic tuff from the Kuli Formation in Ningdu County, Jiangxi Province, so as to constrain the formation age and tectonic dynamic setting of the rock mass, investigate the petrogenesis and material source of the rock mass, and reveal the metallogenic potential of the rock mass. The results of zircon and apatite U–Pb dating show that the protolith of the metamorphic tuff from the Kuli Formation formed at ca. 770 Ma, representing a product of mid-Neoproterozoic magmatic activity. The protolith restoration of metamorphic rocks suggests that the protolith of the metamorphic tuff from the Kuli Formation is magmatic rock. The estimated results of zircon Ti thermometry indicate that the magmatic crystallization temperature ranges from 623 to 723 °C, with an average value of approximately 696 °C, and the calculated zircon oxygen fugacity values vary from −18.7 to −9.4, with an average of −13.8, implying that the rock formed under conditions of relatively low temperature and high oxygen fugacity. The correlation diagrams of trace elements and element ratios in zircon and apatite reveal that the magmatic evolution involved extensive fractional crystallization of minerals such as zircon, monazite, apatite, titanite, rutile, and plagioclase during the formation of the rock mass. The discrimination diagrams of trace elements in zircon and apatite demonstrate that the metamorphic tuff from the Kuli Formation was formed in a continental margin arc or arc-related orogenic belt, and the magmatic source is characterized by crust–mantle mixing. Combined with previous research findings on regional tectonic-magmatic activities, it can be concluded that the metamorphic tuff from the Kuli Formation was formed in a tectonic setting of back-arc extension and intra-arc rifting caused by the rollback of the subducting oceanic slab. The upwelling of the asthenospheric mantle induced the partial melting of arc-derived sediments in the continental crust, which was subsequently mixed with mantle-derived magma, ultimately generating the parent magma of the metamorphic tuff. The metamorphic tuff from the Kuli Formation in Ningdu County, Jiangxi Province, has high REE abundance and relatively easily weathered REE mineral assemblages, which can provide sufficient material sources for ion-adsorption REE mineralization and have a great metallogenic potential for ion-adsorption REE deposits. Full article

Background: Juvenile Idiopathic Arthritis (JIA) is the most prevalent rheumatological disease in childhood. It is classified into seven subtypes, each with specific clinical features. The pathogenesis of JIA involves an increased inflammatory response. Treatment options include pharmacological therapy, patient education, physical therapy, and rehabilitation. Methods: Patients received IAC injections and were subsequently divided into two groups: one group underwent HKT, while the other did not. The effects of HKT were assessed before treatment and one month after the IAC injections and initiation of HKT, using the Child Health Assessment Questionnaire (CHAQ), Visual Analogue Scale (VAS), and the Child Health Questionnaire—Parent Form 50 (CHQ-PF50). Results: Data were analyzed using the t-test. The HKT group showed non-statistically significant improvements in CHAQ and VAS scores compared to the non-HKT group. However, statistically significant differences were observed in the CHQ-PF50, particularly in the self-esteem and pain subscales. Conclusions: Although global differences between groups were not statistically significant, the group that underwent HKT demonstrated better scores, suggesting that HKT may reduce pain and contribute to improved quality of life in children with JIA. Full article

Background: Motivation is widely recognized as a key factor influencing learning and rehabilitation outcomes in children with cerebral palsy (CP). Despite its acknowledged relevance, motivation is rarely assessed systematically in pediatric neurorehabilitation, and there is limited consensus regarding appropriate outcome measures. Objectives: This systematic mapping review aimed to examine how motivation-related constructs are assessed in rehabilitation studies involving children with CP, identifying the instruments used and evaluating the extent to which motivation is explicitly measured across different rehabilitation contexts. Methods: The review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420250651843). PubMed and Scopus were searched for studies published between 2013 and 2025. Eligible studies included rehabilitation interventions for children with CP that incorporated a clearly defined motivation-related outcome. Study quality and risk of bias were assessed using Joanna Briggs Institute tools and the RoB 2 tool. Results: Nine studies met the inclusion criteria, including 109 subjects, comprising randomized controlled trials and case series. Most studies involved children with mild to moderate motor impairment (GMFCS or MACS levels I–II). Motivation was assessed through heterogeneous approaches, including self-efficacy, mastery motivation, participation, adherence, and intrinsic motivation, with data collected from children, parents, therapists, or dyads. Conclusions: Although motivation is frequently cited as a critical component of effective rehabilitation in children with CP, its assessment remains inconsistent and methodologically fragmented. This mapping review, based on a limited and heterogeneous evidence base, highlights the need for standardized, validated, and developmentally appropriate tools to measure motivation-related constructs in pediatric CP rehabilitation. Full article

Low-temperature stress during germination is a major constraint for lettuce establishment in temperate and early-season production systems, causing delayed emergence, poor stand uniformity, and reduced yield. Cold germination represents an adaptive trait that enables seeds to initiate growth under suboptimal temperatures, but its genetic basis in lettuce remains poorly understood. Here, we investigated genetic architecture underlying cold germination using a biparental recombinant inbred line population derived from a cross between Lactuca sativa cv. Salinas and Lactuca serriola (wild lettuce). Phenotypic evaluations revealed substantial variation in germination performance at low temperatures, with cultivated lettuce exhibiting superior cold germination compared with the wild parent. Estimates of heritability indicated that genetic factors accounted for a large proportion of the observed phenotypic variation, demonstrating strong potential for selection. Quantitative trait locus (QTL) analysis identified two genomic regions significantly associated with cold germination ability, together explaining a substantial fraction of phenotypic variance (35%). These regions contained candidate genes involved in hormone signaling, membrane stability, and stress-responsive transcriptional regulation, including components of abscisic acid (ABA), gibberellic acid (GA), and ethylene pathways known to modulate germination under adverse conditions. Together, these results indicate that cold germination is a genetically complex trait that has likely been shaped through domestication and breeding. By elucidating the genetic basis of cold germination in lettuce, this study provides valuable targets for marker-assisted breeding aimed at improving seedling establishment and extending lettuce production into cooler environments. Full article

Hybridization is considered an important process in plant evolution, especially in the origins of domesticated plant taxa, with many crop species being the result of interspecific hybridization events. There are several unidentified lineages of Spondias in the northeastern region of Brazil known only by vernacular names such as ‘cajaguela’, ‘umbu-cajá’, and ‘umbuguela’. These taxa are often regarded as being of hybrid origin, based on supposedly intermediate morphological features. However, the morphology-based hypotheses of hybrid origin and parentage of these Spondias taxa remain largely untested experimentally. We collected 355 accessions of Spondias, including S. bahiensis, other putative hybrid taxa, and both native (S. mombin, S. tuberosa, and S. venulosa) and introduced (S. purpurea) species believed to be the parental taxa. We then reconstructed phylogenies of plastid and nuclear markers and haplotype networks in order to ascertain the genetic affinities between putative hybrids and other Spondias species. All taxa with intermediate morphology were confirmed as hybrids between their putative parental species. All hybrids involving S. purpurea (native to Mexico) appear to be F₁ generation. The recently described S. bahiensis is shown to have originated from hybridization between S. tuberosa and S. venulosa. The other ‘umbu-cajá’ taxon found in Northeastern Brazil is revealed to be the result of hybridization between S. mombin and S. tuberosa. Both the northern ‘umbu-cajá’ taxon and S. bahiensis appear to be well-established hybrid lineages and not early-generation hybrids. Additionally, some introgression and backcrossing processes between S. bahiensis and one of the parents was also observed. Our findings confirm the hybrid origins of the domesticated Spondias taxa found in Northeastern Brazil. Full article

Cancer cachexia is a multifactorial metabolic syndrome that profoundly impairs treatment tolerance and prognosis; however, how tumor-intrinsic transcriptional programs contribute to cachexia induction and shape responses to chemotherapeutic stress remains poorly understood. In this study, we analyzed a paired human duodenal neuroendocrine carcinoma cell-line model consisting of the non-cachexia-inducing parental line TCC-NECT-2 and its cachexia-inducing derivative AkuNEC. Bulk RNA sequencing was performed under baseline conditions and after doxorubicin treatment (10 μM, 24 h), and transcriptomic differences were assessed using log2 fold-change–based analyses to characterize baseline reprogramming, drug-induced responses, and differential stress adaptation. Despite comparable morphology and similar levels of doxorubicin-induced acute cytotoxicity, AkuNEC cells exhibited extensive baseline transcriptional reprogramming relative to TCC-NECT-2, including coordinated upregulation of inflammatory, secretory, and metabolic regulators previously implicated in cancer cachexia, together with suppression of structural and homeostatic programs. Following doxorubicin exposure, AkuNEC cells showed a distinct transcriptional response characterized by selective reorganization of proliferation-, metabolism-, and stress-related pathways, indicating enhanced transcriptional plasticity rather than uniform stress suppression. Differential response analyses further revealed preferential induction of genes involved in cell cycle control, DNA replication, and metabolic adaptation in AkuNEC under chemotherapeutic stress. These findings indicate that cachexia-inducing capacity is embedded within tumor-intrinsic transcriptional states and is amplified by stress-induced plasticity, supporting a network-level model of cancer cachexia that links systemic host effects with tumor adaptation to therapy. The TCC-NECT-2/AkuNEC model provides a tractable framework for dissecting these tumor-intrinsic mechanisms and their relevance to cachexia-associated cancer biology. Full article

Background/Objectives: Sleep plays a crucial role in children’s cognitive, emotional, and physical development. Although sleep practices and perceptions are shaped significantly by cultural and familial contexts, most sleep recommendations are developed by Western countries. This qualitative study explores primary school children’s perceptions of sleep, examining how cultural contexts, family environments, and technology influence sleep practices. Methods: Two cross studies were conducted: Study 1, in India, involved 15 children aged 8–12 years, and Study 2, in the UK, involved 12 children aged 8–10 years. Semi-structured group interviews and thematic analysis were used. Results: Both studies revealed common themes, including perceived sleep benefits, consequences of poor sleep, factors affecting sleep quality, and the role of technology. Study 1 showed that Indian children identified clear benefits of sleep, such as physical and emotional well-being, while highlighting significant barriers, including late bedtime routines, stress related to academic performance, and extensive use of social media and digital media devices. Cultural and religious practices were commonly mentioned as sleep aids. Study 2’s results from the UK revealed similar recognition of sleep benefits, notably recovery and growth. UK children emphasised environmental barriers such as noise pollution, sibling disturbances, and uncomfortable sleeping conditions. Technology usage was acknowledged as both a barrier and an occasional aid, with stricter parental controls on bedtime and device usage. Conclusions: This research highlights the importance of culturally sensitive sleep education programmes and recommendations to enhance children’s sleep health globally. Full article

Background: Adolescent football players are exposed to substantial psychological demands, and psychosocial support within family and sport environments has been shown to influence motivational climate, stress responses, and emotional well-being. However, the comparative effects of coordinated multi-source psychosocial support from parents and coaches versus single-source support on psychological outcomes remain insufficiently examined. Aims: to examine the effects of a multi-component psychosocial program involving parents and coaches on depression, anxiety, stress, and self-regulation in adolescent football players. Methods: A total of 60 male adolescent soccer players were recruited and randomly assigned to four groups: combined supportive communication from both parents and coaches (SCCP; n = 15), supportive communication from coaches only (SCC; n = 15), supportive communication from parents only (SCP; n = 15), and a control group (CG; n = 15). Over a 12-week intervention period, participants attended 12 sessions incorporating structured supportive communication and related psychosocial strategies. Mental health outcomes were assessed using the Depression Anxiety Stress Scale (DASS-21), while self-regulation was measured with the Self-Regulation Questionnaire (SRQ). Results: The SCCP group demonstrated the largest improvements across outcomes, with reductions observed in anxiety, depression, and stress, and significant time effects for all mental health parameters. For depression, the time effect showed a (p < 0.001; η²p = 0.93 [Very large]; −45.77%). Anxiety scores also indicated a significant time effect (p < 0.001; η²p = 0.81 [Very large]; −46.55%). Stress demonstrated an exceptionally significant time effect (p < 0.001; η²p = 0.98 [Very large]; −48.29%). Additionally, the self-regulation outcomes showed significant improvements, with a time effect for the Planning subscale of the SRQ indicating (p < 0.001; η²p = 0.86 [Very large]; +66.38%). Conclusion: The findings provide preliminary evidence that a multi-component program involving parents and coaches is associated with improvements in depression, anxiety, stress, and self-regulation among adolescent football players. These results suggest that coordinated psychosocial support across family and sport environments may contribute to adolescent athletes’ psychological well-being, although replication in other cultural and sporting contexts is required. Full article

Stickler syndrome is a monogenic connective tissue disorder primarily caused by pathogenic variants in collagen-related genes, most commonly COL2A1. Prenatal diagnosis remains challenging, particularly in healthcare systems with limited access to molecular genetic testing. We report a prenatal case of suspected craniofacial anomaly detected on second-trimester ultrasound. Fetal DNA obtained by amniocentesis underwent next-generation sequencing. Parental testing was performed to assess inheritance. It was confirmed that autosomal dominant Stickler syndrome type I (ORPHA:90653) was caused by a heterozygous pathogenic frameshift variant in COL2A1 (c.3137del) that was inherited from the mother and identified in the fetus. Micrognathia was identified during prenatal ultrasound, and postnatal evaluation revealed characteristics that were consistent with Pierre Robin sequence and connective tissue involvement. The molecular discoveries elucidated the observed phenotype and facilitated multidisciplinary perinatal management. This case underscores the indispensable function of molecular diagnostics in the prenatal identification of monogenic disorders, including Stickler syndrome, in cases where conventional karyotyping is inadequate. Targeted clinical surveillance and family counseling are facilitated by early genetic confirmation. The report also emphasizes the necessity of incorporating molecular diagnostics into routine prenatal care for rare genetic diseases and the systemic limitations in access to genomic testing. Although the identified variant has been previously reported, this case highlights the clinical and diagnostic value of prenatal molecular confirmation in a resource-limited healthcare setting. Full article