Correction: Digital Phenotypes for Early Detection of Internet Gaming Disorder in Adolescent Students: Explorative Data-Driven Study.

[This corrects the article DOI: 10.2196/50259.].

Modification of microenvironmental pH of nanoparticles for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib.

This study aimed to develop a novel pH-modified nanoparticle with improved solubility and oral bioavailability of poorly water-soluble celecoxib by modifying the microenvironmental pH. After assessing the impact of hydrophilic polymers, surfactants and alkaline pH modifiers on the drug solubility, copovidone, sodium lauryl sulfate (SLS) and meglumine were chosen. The optimal formulation of solvent-evaporated, surface-attached and pH-modified nanoparticles composed of celecoxib/copovidone/SLS/meglumine at weight ratios of 1:1:0.2:0, 1:0.375:1.125:0 and 1:1:1:0.2:0.02, respectively, were manufactured using spray drying technique. Their physicochemical characteristics, solubility, dissolution and pharmacokinetics in rats were evaluated compared to the celecoxib powder. The solvent-evaporated and pH-modified nanoparticles converted a crystalline to an amorphous drug, resulting in a spherical shape with a reduced particle size compared to celecoxib powder. However, the surface-attached nanoparticles with insignificant particle size exhibited the unchangeable crystalline drug. All of them gave significantly higher solubility, dissolution, and oral bioavailability than celecoxib powder. Among them, the pH-modified nanoparticles demonstrated the most significant improvement in solubility (approximately 1600-fold) and oral bioavailability (approximately 4-fold) compared to the drug powder owing to the alkaline microenvironment formation effect of meglumine and the conversion to the amorphous drug. Thus, the pH-modified nanoparticle system would be a promising strategy for improving the solubility and oral bioavailability of poorly water-soluble and weakly acidic celecoxib.

Selective Enhancement of Viewing Angle Characteristics and Light Extraction Efficiency of Blue Thermally Activated Delayed Fluorescence Organic Light-Emitting Diodes through an Easily Tailorable Si3N4 Nanofiber Structure.

We selectively improved the viewing angle characteristics and light extraction efficiency of blue thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs) by tailoring a nanofiber-shaped Si3N4 layer, which was used as an internal scattering layer. The diameter of the polymer nanofibers changed according to the mass ratio of polyacrylonitrile (PAN) and poly(methyl methacrylate) (PMMA) in the polymer solution for electrospinning. The Si3N4 nanofiber (SNF) structure was fabricated by etching an Si3N4 film using the PAN/PMMA nanofiber as a mask, making it easier to adjust parameters, such as the diameter, open ratio, and height, even though the SNF structure was randomly shaped. The SNF structures exhibited lower transmittance and higher haze with increasing diameter, showing little correlation with their height. However, all the structures demonstrated a total transmittance of over 80%. Finally, by applying the SNF structures to the blue TADF OLEDs, the external quantum efficiency was increased by 15.6%. In addition, the current and power efficiencies were enhanced by 23.0% and 25.6%, respectively. The internal light-extracting SNF structure also exhibited a synergistic effect with the external light-extracting structure. Furthermore, when the viewing angle changed from 0° to 60°, the peak wavelength and CIE coordinate shift decreased from 20 to 6 nm and from 0.0561 to 0.0243, respectively. These trends were explained by the application of Snell's law to the light path and were ultimately validated through finite-difference time-domain simulations.

Digital Phenotypes for Early Detection of Internet Gaming Disorder in Adolescent Students: Explorative Data-Driven Study.

BACKGROUND: Limited awareness, social stigma, and access to mental health professionals hinder early detection and intervention of internet gaming disorder (IGD), which has emerged as a significant concern among young individuals. Prevalence estimates vary between 0.7% and 15.6%, and its recognition in the International Classification of Diseases, 11th Revision and Diagnostic and Statistical Manual of Mental Disorders, 5th Edition underscores its impact on academic functioning, social isolation, and mental health challenges. OBJECTIVE: This study aimed to uncover digital phenotypes for the early detection of IGD among adolescents in learning settings. By leveraging sensor data collected from student tablets, the overarching objective is to incorporate these digital indicators into daily school activities to establish these markers as a mental health screening tool, facilitating the early identification and intervention for IGD cases. METHODS: A total of 168 voluntary participants were engaged, consisting of 85 students with IGD and 83 students without IGD. There were 53% (89/168) female and 47% (79/168) male individuals, all within the age range of 13-14 years. The individual students learned their Korean literature and mathematics lessons on their personal tablets, with sensor data being automatically collected. Multiple regression with bootstrapping and multivariate ANOVA were used, prioritizing interpretability over predictability, for cross-validation purposes. RESULTS: A negative correlation between IGD Scale (IGDS) scores and learning outcomes emerged (r166=-0.15; P=.047), suggesting that higher IGDS scores were associated with lower learning outcomes. Multiple regression identified 5 key indicators linked to IGD, explaining 23% of the IGDS score variance: stroke acceleration (ß=.33; P<.001), time interval between keys (ß=-0.26; P=.01), word spacing (ß=-0.25; P<.001), deletion (ß=-0.24; P<.001), and horizontal length of strokes (ß=0.21; P=.02). Multivariate ANOVA cross-validated these findings, revealing significant differences in digital phenotypes between potential IGD and non-IGD groups. The average effect size, measured by Cohen d, across the indicators was 0.40, indicating a moderate effect. Notable distinctions included faster stroke acceleration (Cohen d=0.68; P=<.001), reduced word spacing (Cohen d=.57; P=<.001), decreased deletion behavior (Cohen d=0.33; P=.04), and longer horizontal strokes (Cohen d=0.34; P=.03) in students with potential IGD compared to their counterparts without IGD. CONCLUSIONS: The aggregated findings show a negative correlation between IGD and learning performance, highlighting the effectiveness of digital markers in detecting IGD. This underscores the importance of digital phenotyping in advancing mental health care within educational settings. As schools adopt a 1-device-per-student framework, digital phenotyping emerges as a promising early detection method for IGD. This shift could transform clinical approaches from reactive to proactive measures.

Hollow Microcavity Electrode for Enhancing Light Extraction.

Luminous efficiency is a pivotal factor for assessing the performance of optoelectronic devices, wherein light loss caused by diverse factors is harvested and converted into the radiative mode. In this study, we demonstrate a nanoscale vacuum photonic crystal layer (nVPCL) for light extraction enhancement. A corrugated semi-transparent electrode incorporating a periodic hollow-structure array was designed through a simulation that utilizes finite-difference time-domain computational analysis. The corrugated profile, stemming from the periodic hollow structure, was fabricated using laser interference lithography, which allows the precise engineering of various geometrical parameters by controlling the process conditions. The semi-transparent electrode consisted of a 15 nm thick Ag film, which acted as the exit mirror and induced microcavity resonance. When applied to a conventional green organic light-emitting diode (OLED) structure, the optimized nVPCL-integrated device demonstrated a 21.5% enhancement in external quantum efficiency compared to the reference device. Further, the full width at half maximum exhibited a 27.5% reduction compared to that of the reference device, demonstrating improved color purity. This study presents a novel approach by applying a hybrid thin film electrode design to optoelectronic devices to enhance optical efficiency and color purity.

Hydrophobic surface induced pro-metastatic cancer cells for in vitro extravasation models.

In vitro vascularized cancer models utilizing microfluidics have emerged as a promising tool for mechanism study and drug screening. However, the lack of consideration and preparation methods for cancer cellular sources that are capable of adequately replicating the metastatic features of circulating tumor cells contributed to low relevancy with in vivo experimental results. Here, we show that the properties of cancer cellular sources have a considerable impact on the validity of the in vitro metastasis model. Notably, with a hydrophobic surface, we can create highly metastatic spheroids equipped with aggressive invasion, endothelium adhesion capabilities, and activated metabolic features. Combining these metastatic spheroids with the well-constructed microfluidic-based extravasation model, we validate that these metastatic spheroids exhibited a distinct extravasation response to epidermal growth factor (EGF) and normal human lung fibroblasts compared to the 2D cultured cancer cells, which is consistent with the previously reported results of in vivo experiments. Furthermore, the applicability of the developed model as a therapeutic screening platform for cancer extravasation is validated through profiling and inhibition of cytokines. We believe this model incorporating hydrophobic surface-cultured 3D cancer cells provides reliable experimental data in a clear and concise manner, bridging the gap between the conventional in vitro models and in vivo experiments.

Impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system and self nano-emulsifying granule system.

The purpose of this study was to investigate the impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system (SNEDDS) and self nano-emulsifying granule system (SEGS). The mesoporous calcium silicate (Ca-silicate) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) were utilised as hydrophobic carrier and hydrophilic carrier, respectively. The liquid SNEDDS formulation, composed of Tween80/Kollipohr EL/corn oil (35/50/15%) with 31% (w/w) dexibuprofen, was spray-dried and fluid-bed granulated together with Avicel using Ca-silicate or HP- ß-CD as a solid carrier, producing four different solid SNEDDS and SEGS formulations. Unlike the Ca-silicate-based systems, spherical shape and aggregated particles were shown in HP-ß-CD-based solid SNEDDS and SEGS, respectively. Molecular interaction was detected between Ca-silicate and the drug; though, none was shown between HP-ß-CD and the drug. Each system prepared with either carrier gave no significant differences in micromeritic properties, crystallinity, droplet morphology, size, dissolution and oral bioavailability in rats. However, the HP-ß-CD-based system more significantly improved the drug solubility than did the Ca-silicate-based system. Therefore, both carriers hardly affected the properties of both solid SNEDDS and SEGS; though, there were differences in the aspect of appearance, molecular interaction and solubility.

Heterogenization of Molecular Electrocatalytic Active Sites through Reticular Chemistry.

The electrochemical conversion of small molecules, such as CO2 , O2 , and H2 O, has received significant attention as a potential engine for sustainable life. Metal-organic frameworks (MOFs) are a promising class of electrocatalytic materials for such processes. An attractive aspect of utilizing this class of materials as electrocatalysts is that well-known molecular active sites can be introduced to well-defined crystalline heterogeneous catalytic systems with high tunability. This review offers strategic insights into recent studies on MOF-based electrocatalysts by discussing the notable active sites that have been utilized in both homogeneous and heterogeneous catalysts, while highlighting instances where such active sites have been introduced into MOFs. In addition, material design principles enabling the integration of electrochemically active components with the MOF platform are outlined. Viewpoints on the viability of MOFs as an alternative to currently used electrocatalysts are also discussed. Finally, the future direction of MOF-based electrocatalysis research is established.

Hydroxypropyl-ß-cyclodextrin-based solid dispersed granules: A prospective alternative to conventional solid dispersion.

The purpose of the present study was to develop hydroxypropyl-ß-cyclodextrin (HP-ß-CD)-based solid dispersed granules as a superior system to solid dispersion. The solid dispersed granules and solid dispersion were compared in terms of powder property improvement, solubility increment and oral bioavailability enhancement of poorly water-soluble dexibuprofen. Solid dispersion (drug/HP-ß-CD/Tween80 = 1:7:0.1, weight ratio) and solid dispersed granules (drug/HP-ß-CD/Tween80/Microcrystalline cellulose = 1:7:0.1:4) were fabricated using a spray-dryer and fluid bed granulator, respectively. The HP-ß-CD-based solid dispersed granules significantly improved solubility, dissolution profile and oral bioavailability of dexibuprofen compared to pure drug powder. Moreover, the solid dispersed granules maximised the oral bioavailability of dexibuprofen to the same extent as the solid dispersion. However, considerable improvements of powder and tablet properties were observed in solid dispersed granules as compared with solid dispersion. Therefore, HP-ß-CD-based solid dispersed granules would be a prospective alternative to solid dispersion.

Mitochondrial double-stranded RNAs as a pivotal mediator in the pathogenesis of SjÓ§gren's syndrome.

SjÓ§gren's syndrome (SS) is a systemic autoimmune disease that targets the exocrine glands, resulting in impaired saliva and tear secretion. To date, type I interferons (I-IFNs) are increasingly recognized as pivotal mediators in SS, but their endogenous drivers have not been elucidated. Here, we investigate the role of mitochondrial double-stranded RNAs (mt-dsRNAs) in regulating I-IFNs and other glandular phenotypes of SS. We find that mt-dsRNAs are elevated in the saliva and tears of SS patients (n = 73 for saliva and n = 16 for tears) and in salivary glands of non-obese diabetic mice with salivary dysfunction. Using the in-house-developed 3D culture of immortalized human salivary gland cells, we show that stimulation by exogenous dsRNAs increase mt-dsRNAs, activate the innate immune system, trigger I-IFNs, and promote glandular phenotypes. These responses are mediated via the Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT) pathway. Indeed, a small chemical inhibitor of JAK1 attenuates mtRNA elevation and immune activation. We further show that muscarinic receptor ligand acetylcholine ameliorates autoimmune characteristics by preventing mt-dsRNA-mediated immune activation. Last, direct suppression of mt-dsRNAs reverses the glandular phenotypes of SS. Altogether, our study underscores the significance of mt-dsRNA upregulation in the pathogenesis of SS and suggests mt-dsRNAs as propagators of a pseudo-viral signal in the SS target tissue.

Engineering of Surface Energy of Cell-Culture Platform to Enhance the Growth and Differentiation of Dendritic Cells via Vapor-Phase Synthesized Functional Polymer Films.

Although the dendritic cell (DC)-based modulation of immune responses has emerged as a promising therapeutic strategy for tumors, infections, and autoimmune diseases, basic research and therapeutic applications of DCs are hampered by expensive growth factors and sophisticated culture procedures. Furthermore, the platform to drive the differentiation of a certain DC subset without any additional biochemical manipulations has not yet been developed. Here, five types of polymer films with different hydrophobicity via an initiated chemical vapor deposition (iCVD) process to modulate the interactions related to cell-substrate adhesion are introduced. Especially, poly(cyclohexyl methacrylate) (pCHMA) substantially enhances the expansion and differentiation of conventional type 1 DCs (cDC1s), the prime DC subset for antigen cross-presentation, and CD8+ T cell activation, by 4.8-fold compared to the conventional protocol. The cDC1s generated from the pCHMA-coated plates retain the bona fide DC functions including the expression of co-stimulatory molecules, cytokine secretion, antigen uptake and processing, T cell activation, and induction of antitumor immune responses. To the authors' knowledge, this is the first report highlighting that the modulation of surface hydrophobicity of the culture plate can be an incisive approach to construct an advanced DC culture platform with high efficiency, which potentially facilitates basic research and the development of immunotherapy employing DCs.

A Versatile Surface Modification Method via Vapor-phase Deposited Functional Polymer Films for Biomedical Device Applications.

For last two decades, the demand for precisely engineered three-dimensional structures has increased continuously for the developments of biomaterials. With the recent advances in micro- and nano-fabrication techniques, various devices with complex surface geometries have been devised and produced in the pharmaceutical and medical fields for various biomedical applications including drug delivery and biosensors. These advanced biomaterials have been designed to mimic the natural environments of tissues more closely and to enhance the performance for their corresponding biomedical applications. One of the important aspects in the rational design of biomaterials is how to configure the surface of the biomedical devices for better control of the chemical and physical properties of the bioactive surfaces without compromising their bulk characteristics. In this viewpoint, it of critical importance to secure a versatile method to modify the surface of various biomedical devices. Recently, a vapor phase method, termed initiated chemical vapor deposition (iCVD) has emerged as damage-free method highly beneficial for the conformal deposition of various functional polymer films onto many kinds of micro- and nano-structured surfaces without restrictions on the substrate material or geometry, which is not trivial to achieve by conventional solution-based surface functionalization methods. With proper structural design, the functional polymer thin film via iCVD can impart required functionality to the biomaterial surfaces while maintaining the fine structure thereon. We believe the iCVD technique can be not only a valuable approach towards fundamental cell-material studies, but also of great importance as a platform technology to extend to other prospective biomaterial designs and material interface modifications for biomedical applications.

A cyclic manipulation of cage isomers via anion exchange and thermal isomerism.

A cyclic manipulation of peanut cage isomers has been achieved via anion exchange and unusual cage isomerism.

Clinical and Radiologic Features of Osteoporotic Spine Fracture with Delayed Neurologic Compromises.

OBJECTIVES: Osteoporotic spine fractures (OSFs) with delayed neurologic compromises (NCs) have been increasingly reported. Although several studies have addressed that the pathologic mechanism of NC involves nonunion and segmental instability, the risk factors remain unclear. Therefore, the purpose of this study was to assess the radiologic and clinical features of OSFs with delayed NC. METHODS: Thirty patients with delayed NC (group 1) were matched in a 1-to-1 format with 30 patients without delayed NC (group 2) by age, bone mineral density, body mass index, and medical treatment for osteoporosis. Clinical and radiologic parameters were assessed to determine the risk factors related to delayed NC. Clinical outcomes were also compared between the 2 groups. RESULTS: Neurologic compromises were presented as myelopathy in 20 patients and radiculopathy in 10 patients. Initial kyphotic angle (KA) and height loss (HL) were significantly greater in group 1 (21.6 ± 12.9 degrees vs. 10.5 ± 8.6 degrees, P = 0.0001 for KA; 55.8% ± 15.2% vs. 19.9% ± 10.9%, P = 0.0001 for HL). Fracture instability with intravertebral cleft, posterior wall involvement, midportion type of magnetic resonance classification, thoracolumbar level, and aortic calcification were significantly correlated with delayed NC. In multivariate analysis, initial HL (hazard ratio = 1.24; P = 0.012) and midportion-type fracture (hazard ratio = 14.9: P = 0.03) were the independent risk factors related to delayed NC. In addition, clinical outcomes at the last follow-up were significantly better in group 2. CONCLUSIONS: Initial HL and midportion-type fracture were correlated with delayed NC following OSFs. Moreover, pre-existing stenotic lesions might be associated with delayed NC.