Sphingomonas Immobilis sp. nov., and Sphingomonas natans sp. nov. bacteria isolated from soil.

Two novel strains of bacteria, CA1-15T and BIUV-7T, were isolated from soil samples gathered in Cheonan-si, Republic of Korea, and Inje-gun, Republic of Korea, respectively. These bacteria are Gram-negative, aerobic, and non-motile. Phylogenetic evaluations, using the sequence of the 16S rRNA gene, showed that strains CA1-15T and BIUV-7T belong to a distinctive clade within the family Sphingomonadaceae (order Sphingomonadales, class Alphaproteobacteria). The strains exhibited the highest similarity in their genetic makeup with representatives of the genus Sphingomonas. Strain CA1-15T was closely related to Sphingomonas echinoides NRRL B-3126T (97.8% similarity in 16S rRNA gene sequence), Sphingomonas oligophenolica JCM 12,082T (97.8%), Sphingomonas glacialis C16yT (97.6%) and Sphingomonas psychrolutea MDB1-AT (97.3%). Strain BIUV-7T was closely related to Sphingomonas nostoxanthinifaciens AK-PDB1-5T (97.0%), Sphingomonas vulcanisoli SN6-13T (96.3%), Sphingomonas naphthae DKC-5-1T (96.2%), and Sphingomonas prati W18RDT (95.7%). The optimal growth conditions for strains CA1-15T and BIUV-7T were determined to be at pH 7.0 and a temperature of 25 °C. Analysis of the cellular fatty acids of strain CA1-15T and BIUV-7T revealed that summed feature 8 (C18:1ω7c/C18:1ω6c) (60.4%), summed feature 8 (C18:1ω7c/C18:1ω6c) (62.9%) were the major component, respectively. Additionally, both strains exhibited ubiquinone Q-10 as their major respiratory quinone, and diphosphatidylglycerol (DPG), glycosphingolipid (SGL), and phosphatidylethanolamine (PE) as the major polar lipid. The genome of strain CA1-15T measures 4,133,944 bp, comprising 4,026 coding sequences (CDSs) and 46 tRNA genes. Similarly, the genome of strain BIUV-7T is 4,563,252 bp, characterized by 4,226 CDSs and 44 tRNA genes. The average nucleotide identity (ANI) analysis and digital DNA-DNA hybridization (dDDH) values between strain CA1-15T and other Sphingomonas species range from 73.2 to 79.9% and 19.4-22.9%, respectively. Comparatively, ANI and dDDH values between strain BIUV-7T and other Sphingomonas species are in the range of 72.9-76.5% and 19.3-20.9%, respectively. Based on the biochemical, chemotaxonomic, and phylogenetic analyses, it is evident that strains CA1-15T and BIUV-7T represent two novel bacterial species within the genus Sphingomonas. Accordingly, the names Sphingomonas immobilis sp. nov. and Sphingomonas natans sp. nov. are proposed. also, CA1-15T(= KCTC 92960T = NBRC 116547T) is the type strain of Sphingomonas immobilis and BIUV-7T(= KCTC 92961T = NBRC 116546T) is the type strain of Sphingomonas natans.

Testing the structural disconnection hypothesis: Myelin content correlates with memory in healthy aging.

INTRODUCTION: The "structural disconnection" hypothesis of cognitive aging suggests that deterioration of white matter (WM), especially myelin, results in cognitive decline, yet in vivo evidence is inconclusive. METHODS: We examined age differences in WM microstructure using Myelin Water Imaging and Diffusion Tensor Imaging in 141 healthy participants (age 20-79). We used the Virginia Cognitive Aging Project and the NIH Toolbox® to generate composites for memory, processing speed, and executive function. RESULTS: Voxel-wise analyses showed that lower myelin water fraction (MWF), predominantly in prefrontal WM, genu of the corpus callosum, and posterior limb of the internal capsule was associated with reduced memory performance after controlling for age, sex, and education. In structural equation modeling, MWF in the prefrontal white matter and genu of the corpus callosum significantly mediated the effect of age on memory, whereas fractional anisotropy (FA) did not. DISCUSSION: Our findings support the disconnection hypothesis, showing that myelin decline contributes to age-related memory loss and opens avenues for interventions targeting myelin health.

Exploring the effect of corn starch/pea protein blending on the physicochemical and structural properties of biopolymer films and their aging resistance.

This study investigated the potential effect of blending corn starch and pea protein isolate in various ratios (100:0, 70:30, 50:50, 30:70, and 0:100) on the aging properties of biodegradable films. Unlike previous research, the focus was on the often-overlooked aspect of film aging. Fourier-transform infrared spectroscopy and X-ray diffraction demonstrated the physical blending of corn starch and pea protein, along with chemical bonding and conformational changes. The optical and microstructural properties showed the formation of smooth, homogeneous films with good compatibility between the polymers. The water resistance, barrier, and mechanical properties corresponding to the intrinsic nature of protein polymers showed a minimized fluctuations in film properties as film ages, with a reduction of at least twice when protein is added. Remarkably, the blend with a ratio of 30:70 demonstrated the most stable properties during aging. These results demonstrated that blending the pea protein isolate was favorable for delaying the retrogradation and recrystallization of corn starch films. Understanding how these blends influence the aging characteristics of films is not only a novel contribution to the scientific community but also holds practical significance, potentially opening a potential for applications in various industries.

Filling the gaps: leveraging large language models for temporal harmonization of clinical text across multiple medical visits for clinical prediction.

Electronic health records offer great promise for early disease detection, treatment evaluation, information discovery, and other important facets of precision health. Clinical notes, in particular, may contain nuanced information about a patient's condition, treatment plans, and history that structured data may not capture. As a result, and with advancements in natural language processing, clinical notes have been increasingly used in supervised prediction models. To predict long-term outcomes such as chronic disease and mortality, it is often advantageous to leverage data occurring at multiple time points in a patient's history. However, these data are often collected at irregular time intervals and varying frequencies, thus posing an analytical challenge. Here, we propose the use of large language models (LLMs) for robust temporal harmonization of clinical notes across multiple visits. We compare multiple state-of-the-art LLMs in their ability to generate useful information during time gaps, and evaluate performance in supervised deep learning models for clinical prediction.

Preface: Special issue: 14th International Conference on Brain Energy Metabolism: Energy substrates and microbiome govern brain bioenergetics and cognitive function with aging.

This Preface introduces the Special Issue entitled, "Energy Substrates and Microbiome Govern Brain Bioenergetics and Cognitive Function with Aging", which is comprised of manuscripts contributed by invited speakers and program/organizing committee members who participated in the 14th International Conference on Brain Energy Metabolism (ICBEM) held on October 24-27, 2022 in Santa Fe, New Mexico, USA. The conference covered the latest developments in research related to neuronal energetics, emerging roles for glycogen in higher brain functions, the impact of dietary intervention on aging, memory, and Alzheimer's disease, roles of the microbiome in gut-brain signaling, astrocyte-neuron interactions related to cognition and memory, novel roles for mitochondria and their metabolites, and metabolic neuroimaging in aging and neurodegeneration. The special issue contains 25 manuscripts on these topics plus three tributes to outstanding scientists who have made important contributions to brain energy metabolism and participated in numerous ICBEM conferences. In addition, two of the manuscripts describe important directions and the rationale for future research in many thematic areas covered by the conference.

Protocol for a single-arm, pilot trial of creatine monohydrate supplementation in patients with Alzheimer's disease.

BACKGROUND: Impaired brain bioenergetics is a pathological hallmark of Alzheimer's disease (AD) and is a compelling target for AD treatment. Patients with AD exhibit dysfunction in the brain creatine (Cr) system, which is integral in maintaining bioenergetic flux. Recent studies in AD mouse models suggest Cr supplementation improves brain mitochondrial function and may be protective of AD peptide pathology and cognition. AIMS: The Creatine to Augment Bioenergetics in Alzheimer's disease (CABA) study is designed to primarily assess the feasibility of supplementation with 20 g/day of creatine monohydrate (CrM) in patients with cognitive impairment due to AD. Secondary aims are designed to generate preliminary data investigating changes in brain Cr levels, cognition, peripheral and brain mitochondrial function, and muscle strength and size. METHODS: CABA is an 8-week, single-arm pilot study that will recruit 20 patients with cognitive impairment due to AD. Participants attend five in-person study visits: two visits at baseline to conduct screening and baseline assessments, a 4-week visit, and two 8-week visits. Outcomes assessment includes recruitment, retention, and compliance, cognitive testing, magnetic resonance spectroscopy of brain metabolites, platelet and lymphocyte mitochondrial function, and muscle strength and morphology at baseline and 8 weeks. DISCUSSION: CABA is the first study to investigate CrM as a potential treatment in patients with AD. The pilot data generated by this study are pertinent to inform the design of future large-scale efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05383833 , registered on 20 May 2022.

Seizure-induced LIN28A disrupts pattern separation via aberrant hippocampal neurogenesis.

Prolonged seizures can disrupt stem cell behavior in the adult hippocampus, an important brain structure for spatial memory. Here, using a mouse model of pilocarpine-induced status epilepticus (SE), we characterized spatiotemporal expression of Lin28a mRNA and proteins after SE. Unlike Lin28a transcripts, induction of LIN28A protein after SE was detected mainly in the subgranular zone, where immunoreactivity was found in progenitors, neuroblasts, and immature and mature granule neurons. To investigate roles of LIN28A in epilepsy, we generated Nestin-Cre:Lin28aloxP/loxP (conditional KO [cKO]) and Nestin-Cre:Lin28a+/+ (WT) mice to block LIN28A upregulation in all neuronal lineages after acute seizure. Adult-generated neuron- and hippocampus-associated cognitive impairments were absent in epileptic LIN28A-cKO mice, as evaluated by pattern separation and contextual fear conditioning tests, respectively, while sham-manipulated WT and cKO animals showed comparable memory function. Moreover, numbers of hilar PROX1-expressing ectopic granule cells (EGCs), together with PROX1+/NEUN+ mature EGCs, were significantly reduced in epileptic cKO mice. Transcriptomics analysis and IHC validation at 3 days after pilocarpine administration provided potential LIN28A downstream targets such as serotonin receptor 4. Collectively, our findings indicate that LIN28A is a potentially novel target for regulation of newborn neuron-associated memory dysfunction in epilepsy by modulating seizure-induced aberrant neurogenesis.

Correlates of axonal content in healthy adult span: Age, sex, myelin, and metabolic health.

As the emerging treatments that target grey matter pathology in Alzheimer's Disease have limited effectiveness, there is a critical need to identify new neural targets for treatments. White matter's (WM) metabolic vulnerability makes it a promising candidate for new interventions. This study examined the age and sex differences in estimates of axonal content, as well the associations of with highly prevalent modifiable health risk factors such as metabolic syndrome and adiposity. We estimated intra-axonal volume fraction (ICVF) using the Neurite Orientation Dispersion and Density Imaging (NODDI) in a sample of 89 cognitively and neurologically healthy adults (20-79 years). We showed that ICVF correlated positively with age and estimates of myelin content. The ICVF was also lower in women than men, across all ages, which difference was accounted for by intracranial volume. Finally, we found no association of metabolic risk or adiposity scores with the current estimates of ICVF. In addition, the previously observed adiposity-myelin associations (Burzynska et al., 2023) were independent of ICVF. Although our findings confirm the vulnerability of axons to aging, they suggest that metabolic dysfunction may selectively affect myelin content, at least in cognitively and neurologically healthy adults with low metabolic risk, and when using the specific MRI techniques. Future studies need to revisit our findings using larger samples and different MRI approaches, and identify modifiable factors that accelerate axonal deterioration as well as mechanisms linking peripheral metabolism with the health of myelin.

Text Extraction and Standardization System Development for Pathological Records in the Korea Biobank Network.

In Korea, the Korea Centers for Disease Control and Prevention operates the Korea BioBank Network (KBN). KBN has pathological records that collected in Korea and it is useful dataset for research. In this study, we established system that time efficient and reduced error by step-by-step data extraction process from KBN pathological records. We tested the extraction process by 769 lung cancer cohorts and 1292 breast cancer cohorts and accuracy is 91%. We expect this system can be used to efficiently process data from multiple institutions, including Korea BioBank Network.

Increases in anterograde axoplasmic transport in neurons of the hyper-glutamatergic, glutamate dehydrogenase 1 (Glud1) transgenic mouse: Effects of glutamate receptors on transport.

The excitatory neurotransmitter glutamate has a role in neuronal migration and process elongation in the central nervous system (CNS). The effects of chronic glutamate hyperactivity on vesicular and protein transport within CNS neurons, that is, processes necessary for neurite growth, have not been examined previously. In this study, we measured the effects of lifelong hyperactivity of glutamate neurotransmission on axoplasmic transport in CNS neurons. We compared wild-type (wt) to transgenic (Tg) mice over-expressing the glutamate dehydrogenase gene Glud1 in CNS neurons and exhibiting increases in glutamate transmitter formation, release, and synaptic activation in brain throughout the lifespan. We found that Glud1 Tg as compared with wt mice exhibited increases in the rate of anterograde axoplasmic transport in neurons of the hippocampus measured in brain slices ex vivo, and in olfactory neurons measured in vivo. We also showed that the in vitro pharmacologic activation of glutamate synapses in wt mice led to moderate increases in axoplasmic transport, while exposure to selective inhibitors of ion channel forming glutamate receptors very significantly suppressed anterograde transport, suggesting a link between synaptic glutamate receptor activation and axoplasmic transport. Finally, axoplasmic transport in olfactory neurons of Tg mice in vivo was partially inhibited following 14-day intake of ethanol, a known suppressor of axoplasmic transport and of glutamate neurotransmission. The same was true for transport in hippocampal neurons in slices from Glud1 Tg mice exposed to ethanol for 2 h ex vivo. In conclusion, endogenous activity at glutamate synapses regulates and glutamate synaptic hyperactivity increases intraneuronal transport rates in CNS neurons.

Non-invasive in vivo measurements of metabolic alterations in the type 2 diabetic brain by 1 H magnetic resonance spectroscopy.

Type 2 diabetes (T2D) is a complex chronic metabolic disorder characterized by hyperglycemia because of insulin resistance. Diabetes with chronic hyperglycemia may alter brain metabolism, including brain glucose and neurotransmitter levels; however, detailed, longitudinal studies of metabolic alterations in T2D are lacking. To shed insight, here, we characterized the consequences of poorly controlled hyperglycemia on neurochemical profiles that reflect metabolic alterations of the brain in both humans and animal models of T2D. Using in vivo 1 H magnetic resonance spectroscopy, we quantified 12 metabolites cross-sectionally in T2D patients and 20 metabolites longitudinally in T2D db/db mice versus db+ controls. We found significantly elevated brain glucose (91%, p < 0.001), taurine (22%, p = 0.02), glucose+taurine (56%, p < 0.001), myo-inositol (12%, p = 0.02), and choline-containing compounds (10%, p = 0.01) in T2D patients versus age- and sex-matched controls, findings consistent with measures in T2D db/db versus control db+ littermates. In mice, hippocampal and striatal neurochemical alterations in brain glucose, ascorbate, creatine, phosphocreatine, γ-aminobutyric acid, glutamate, glutamine, glutathione, glycerophosphoryl-choline, lactate, myo-inositol, and taurine persisted in db/db mice with chronic disease progression from 16 to 48 weeks of age, which were distinct from control db+ mice. Overall, our study demonstrates the utility of 1 H magnetic resonance spectroscopy as a non-invasive tool for characterizing and monitoring brain metabolic changes with T2D progression.

First Report of Powdery Mildew Caused by Golovinomyces ambrosiae on Xanthium orientale in Korea.

Xanthium orientale L. (syn. Xanthium canadense Mill., Asteraceae), known as cocklebur, is an annual weed native to North America, which is now a neophyte distributed throughout the world. This plant was accidentally introduced to Korea in the late 1970s ( So et al. 2008) and is considered a problematic exotic weed in orchards, for which many herbicides are ineffective (Kim et al. 2020). In September 2018, powdery mildew was observed on X. orientale in Jeju, Korea. The disease incidence ranged from 40 to 60%. Voucher specimens were deposited in the Korea University Herbarium (Accession No. KUS-F30795) and Kunsan National University Herbarium (KSNUH1988). Symptoms appeared as round to irregular white patches with abundant hyphal growth on the leaf surface. Hyphal appressoria were nipple-shaped, and 3 to 6 µm diam. Conidiophores (n = 30) were 145 to 206 × 9 to 11.6 µm and produced 2 to 5 immature conidia in chains with a sinuate outline. Foot-cells of the conidiophores were straight, cylindrical, and 43 to 100.9 µm long. Conidia (n = 30) were ellipsoid-ovoid, doliiform to somewhat limoniform, 25.2 to 31.8 × 13.6 to 16.8 µm (l/w 1.6 to 2.1), and devoid of distinct fibrosin bodies. The morphological characteristics corresponded to those of Golovinomyces ambrosiae (Schwein.) U. Braun & R.T.A. Cook (Braun and Cook 2012, under Golovinomyces spadiceus (Beck. & M.A. Curtis) U. Braun; Qiu et al. 2020). To confirm the identity of the causal fungus, the internal transcribed spacer (ITS), large subunit (LSU) (Bradshaw and Tobin 2020), the intergenic spacer (IGS) of rDNA, and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene (Bradshaw et al. 2022) were amplified for a herbarium specimen (KUS-F30795). A BLASTn search of these sequences revealed 100% identity with reference sequences of G. ambrosiae on diverse Asteraceae plants (AB077644 for ITS, AB077643 for LSU, ON361171 for IGS, and ON075648 for GAPDH). However, there was a single nucleotide difference on both the IGS and GAPDH sequences when compared to the closely related species Golovinomyces latisporus. The sequences were deposited in GenBank (Accession No. OQ165157 (ITS), OQ165164 (LSU), OR050524 (IGS), and OR086076 (GAPDH)). Phylogenetic analyses of ITS, LSU, IGS, and GAPDH sequences revealed the Korean sample formed a well-supported group with other G. ambrosiae sequences, confirming its identity. A pathogenicity test was performed through inoculation by gently pressing diseased leaves onto the leaves of five healthy plants. Five non-inoculated plants served as controls. All plants were maintained in a greenhouse at 25±2°C. Powdery mildew colonies developed on the inoculated plants after ten days, whereas the control plants remained symptomless. The fungus present on the inoculated leaves was morphologically identical to that observed on the initially diseased leaves, fulfilling Koch's postulates. Powdery mildew on X. orientale has previously been reported as Golovinomyces cichoracearum (≡ Erysiphe cichoracearum) sensu lato in the USA, G. ambrosiae (= G. spadiceus) throughout all continents, and Podosphaera fusca sensu lato (now P. xanthii) in Korea (Braun and Cook 2012; Farr and Rossman 2023). To date, powdery mildew in Korea has been reported only on Xanthium strumarium as G. cichoracearum s. lat. and Podosphaera xanthii (KSPP 2022). To our knowledge, this is the first report of powdery mildew caused by G. ambrosiae on X. orientale in Korea.

Influence of acetylation and chemical interaction on edible film properties and different processing methods for food application.

This study developed sweet potato starch (SPS) based edible films and investigated several methods (acetylation, amidated pectin (AP), and CaCl2 use) to improve the edibility and different processing methods (casting and extruding) to package food possible in commercial use. Starch acetylation was conducted with up to 8 mL of acetic acid (A8) and improved the stretchability and solubility of the film. The AP addition [∼30 wt% (P3)] enhanced the film strength, further increasing solubility. CaCl2 addition [∼150 mg/g of AP (C3)] also positively influenced the film solubility and water barrier properties of the films. The SPS-A8P3C3 film showed 3.41 times higher solubility than the native SPS film. Both casted and extruded SPS-A8P3C3 films drastically dissolved in high-temperature water. When applied to oil packaging, two films could delay the lipid oxidation of the packaged samples. These results demonstrate the usability of edible packaging and extruded film for commercial use.

A dual stimuli-responsive smart soft carrier using multi-material 4D printing.

This paper proposes a 4D printed smart soft carrier with a hemispherical hollow and openable lid. The soft carrier is composed of a lid with a slot (with a shape of 4 legs), a border, and a hemisphere. The soft carrier is fabricated by 4D printing using smart hydrogels. Specifically, the lid, border, and hemisphere are fabricated using a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel, a non-responsive polyethylene glycol (PEG) hydrogel with superparamagnetic iron oxide nanoparticles (SPIONs), and a PEG hydrogel, respectively. Since the SPIONs are included in the border, the slot in the center of the lid is opened and closed according to the temperature change caused by near-infrared (NIR) irradiation, and the proposed soft carrier is magnetically driven by an external magnetic field. The hemisphere enables the storage and transport of cargo. The proposed soft carrier can control the opening and closing of the slot and movement to a desired position in water. Several cargo delivery experiments were conducted using various shapes and numbers of cargo. In addition, the proposed soft carrier can successfully handle small living marine organisms. This soft carrier can be manufactured by 4D printing and operated by dual stimuli (NIR and magnetic field) and can safely deliver various types of cargo and delicate organisms without leakage or damage. The flexibility of 4D printing enables the size of the soft carrier to be tailored to the specific physical attributes of various objects, making it an adaptable and versatile delivery approach.

Erysiphe lonicerigena sp. nov., a Powdery Mildew Species Found on Lonicera harae.

A powdery mildew (Erysiphaceae) has been continuously collected on the leaves of Lonicera harae in the southern part of the Korean Peninsula, where this shrub is indigenous. Microscopic examination of the asexual morphs revealed that the current collections are differentiated from the all known Erysiphe species on Lonicera spp. by its longer conidiophores and longer conidia. Although the morphology of the chasmothecia is reminiscent of Erysiphe ehrenbergii and E. lonicerae, the specimens on L. harae differ from them in having smaller ascospores. A phylogenetic tree generated from a combined dataset of the internal transcribed spacer region and 28S rDNA gene sequences demonstrates that sequences obtained from three powdery mildew collections on L. harae clustered together as an independent species clade with high bootstrap values distant from other Erysiphe species on Lonicera, representing a species of its own. Based on morphological differences and molecular-phylogenetic results, the powdery mildew on L. harae is proposed as a new species, Erysiphe lonicerigena, and the holomorph of the fungus is described and illustrated in this study.

Text Extraction and Standardization System Development for Pathological Records in the Korea Biobank Network.

In Korea, the Korea Centers for Disease Control and Prevention operates the Korea BioBank Network (KBN). KBN has pathological records that collected in Korea and it is useful dataset for research. In this study, we established system that time efficient and reduced error by step-by-step data extraction process from KBN pathological records. We tested the extraction process by 769 lung cancer cohorts and 1292 breast cancer cohorts and accuracy is 91%. We expect this system can be used to efficiently process data from multiple institutions, including Korea BioBank Network.

A tribute to Sebastián Cerdán and his key contributions to brain metabolism.

This is a tribute to Sebastián Cerdán, a brilliant and innovative NMR spectroscopist whose studies contributed greatly to the fundamental information to the understanding of brain metabolism, particularly in regard to multinuclear magnetic resonance spectroscopy (MRS) techniques. Sebastián Cerdán sadly passed away in May 2022. He was a wonderful mentor and colleague who will be greatly missed.

Comparison of chitosan and gelatin-based films and application to antimicrobial coatings enriched with grapefruit seed extract for cherry tomato preservation.

Bio-based single, composite, and bilayer edible films were developed based on chitosan and gelatin, including grapefruit seed extract (GSE) as an antimicrobial agent. The physicochemical and antimicrobial properties of films were analyzed, and it was found that compounding and laminating two polymers could enhance their physicochemical properties. The composite film was strong, endurable, and flexible compared with the single ones. In addition, the composite and bilayer films had lower water vapor permeability than the single ones. Edible films and coatings with GSE presented a greater bactericidal effect than the inactive ones. In addition, the hardness, weight, and color changes of the coated cherry tomatoes during 7-day storage did not differ, whereas a bacterial reduction against Salmonella Typhimurium was revealed. Taken together, composite and bilayer films with CH and GL and enriched with GSE were developed for food packaging applications, and it showed improved mechanical, water barrier, and antimicrobial properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01254-9.

Characteristics and Potential Challenges of Digital-Based Interventions for Children and Young People: Scoping Review.

BACKGROUND: Digital health technologies are becoming increasingly available to children and young people and their families. However, there are no scoping reviews that provide both an overview of the characteristics of digital interventions for children and young people and potential challenges to be considered when developing and implementing them. OBJECTIVE: This study aimed to systematically review scientific publications to identify the current characteristics and potential complications of digital interventions for children and young people. METHODS: This scoping review was conducted using the framework of Arksey and O'Malley and adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews. A search of 5 databases (PubMed, Scopus, Embase, MEDLINE, and CINAHL) and Google Scholar was performed for eligible clinical trials published between January 1, 2018, and August 19, 2022. RESULTS: The initial search of the 5 databases yielded 3775 citations; duplicates and those not meeting the inclusion criteria were eliminated. In total, 34 articles were included in the final review and relevant information, such as the descriptive characteristics and potential challenges, were classified. Mental health (26/34, 76%) was the most common target for the digital intervention for children and young people, exceeding physical health (8/34, 24%) by more than 3 times. In addition, a substantial number of digital interventions were dedicated solely to children and young people. Digital interventions for children and young people were more likely to be delivered via computers (17/34, 50%) rather than smartphones (13/34, 38%). More than one-third of the studies (13/34, 38%) applied cognitive behavioral theory as the theory of digital interventions. The duration of the digital intervention for children and young people was more likely to vary depending on the target user rather than the target disease. Intervention components were classified into 5 categories: guidance, task and activity, reminder and monitoring, supportive feedback, and reward system. Potential challenges were subcategorized into ethical, interpersonal, and societal challenges. For ethical challenges, the consent of children and young people or caregivers, potential risk of adverse events, and data privacy issues were considered. For interpersonal challenges, the engagement of children and young people was affected by the preference or barrier of caregivers to participate in studies. For societal challenges, restricted ethnicity in recruitment, limited availability of digital technology, differences in internet use patterns between girls and boys, unified clinical settings, and language barriers were described. CONCLUSIONS: We identified potential challenges and provided suggestions about ethical, interpersonal, and societal aspects to consider when developing and deploying digital-based interventions for children and young people. Our findings provide a thorough overview of the published literature and may serve as a comprehensive, informative foundation for the development and implementation of digital-based interventions for children and young people.