LiF-Rich Solid Electrolyte Interphase Formation by Establishing Sacrificial Layer on the Separator.

The formation of a stable solid electrolyte interphase (SEI) layer is crucial for enhancing the safety and lifespan of Li metal batteries. Fundamentally, a homogeneous Li+ behavior by controlling the chemical reaction at the anode/electrolyte interface is the key to establishing a stable SEI layer. However, due to the highly reactive nature of Li metal anodes (LMAs), controlling the movement of Li+ at the anode/electrolyte interface remains challenging. Here, an advanced approach is proposed for coating a sacrificial layer called fluorinated self-assembled monolayer (FSL) on a boehmite-coated polyethylene (BPE) separator to form a stable SEI layer. By leveraging the strong affinity between the fluorine functional group and Li+, the rapid formation of a LiF-rich SEI layer in the cell production and early cycling stage is facilitated. This initial stable SEI formation promotes the subsequent homogeneous Li+ flux, thereby improving the LMA stability and yielding an enhanced battery lifespan. Further, the mechanism behind the stable SEI layer generation by controlling the Li+ dynamics through the FSL-treated BPE separator is comprehensively verified. Overall, this research offers significant contributions to the energy storage field by addressing challenges associated with LMAs, thus highlighting the importance of interfacial control in achieving a stable SEI layer.

Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

A rationally designed miniature of soluble methane monooxygenase enables rapid and high-yield methanol production in Escherichia coli.

Soluble methane monooxygenase (sMMO) oxidizes a wide range of carbon feedstocks (C1 to C8) directly using intracellular NADH and is a useful means in developing green routes for industrial manufacturing of chemicals. However, the high-throughput biosynthesis of active recombinant sMMO and the ensuing catalytic oxidation have so far been unsuccessful due to the structural and functional complexity of sMMO, comprised of three functionally complementary components, which remains a major challenge for its industrial applications. Here we develop a catalytically active miniature of sMMO (mini-sMMO), with a turnover frequency of 0.32 s-1, through an optimal reassembly of minimal and modified components of sMMO on catalytically inert and stable apoferritin scaffold. We characterise the molecular characteristics in detail through in silico and experimental analyses and verifications. Notably, in-situ methanol production in a high-cell-density culture of mini-sMMO-expressing recombinant Escherichia coli resulted in higher yield and productivity (~ 3.0 g/L and 0.11 g/L/h, respectively) compared to traditional methanotrophic production.

Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma.

BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.

Neural correlation of speech envelope tracking for background noise in normal hearing.

Everyday speech communication often occurs in environments with background noise, and the impact of noise on speech recognition can vary depending on factors such as noise type, noise intensity, and the listener's hearing ability. However, the extent to which neural mechanisms in speech understanding are influenced by different types and levels of noise remains unknown. This study aims to investigate whether individuals exhibit distinct neural responses and attention strategies depending on noise conditions. We recorded electroencephalography (EEG) data from 20 participants with normal hearing (13 males) and evaluated both neural tracking of speech envelopes and behavioral performance in speech understanding in the presence of varying types of background noise. Participants engaged in an EEG experiment consisting of two separate sessions. The first session involved listening to a 12-min story presented binaurally without any background noise. In the second session, speech understanding scores were measured using matrix sentences presented under speech-shaped noise (SSN) and Story noise background noise conditions at noise levels corresponding to sentence recognitions score (SRS). We observed differences in neural envelope correlation depending on noise type but not on its level. Interestingly, the impact of noise type on the variation in envelope tracking was more significant among participants with higher speech perception scores, while those with lower scores exhibited similarities in envelope correlation regardless of the noise condition. The findings suggest that even individuals with normal hearing could adopt different strategies to understand speech in challenging listening environments, depending on the type of noise.

A Pilot Study on the Validity and Reliability of Korean School Readiness Inventory on Children With Autism Spectrum Disorder.

OBJECTIVE: Successful transition to school is of great importance to children with autism spectrum disorder (ASD). The purpose of this study was to develop a school readiness inventory for Korean children with ASD, and demonstrate its content validity and reliability. METHODS: The Korean School Readiness Inventory (K-SRI) was developed to assess current levels of some fundamental skills needed for attending school for children with ASD. The K-SRI was comprised of four subscales and 16 test items: Self-help skills, Social and emotional development, School behavior, and Literacy and numeracy skills. For content validity, six experts rated the validity of the test items. Lawshe's Content Validity Ratio (CVR) was calculated. For reliability, parents of 22 children with ASD entering school completed the KSRI twice. Cronbach's alpha coefficient was calculated for internal consistency. The test-retest reliability was assessed using the intraclass correlation coefficient (ICC). RESULTS: All the items except two items in the literacy and numeracy skills did not show a CVR of 1. The two items were deleted resulting in a 14-item inventory. The Cronbach's alpha coefficient of the K-SRI was 0.93, showing good internal consistency reliability. The test- retest reliability results showed ICC value of 0.93 (p<0.001), which indicates good stability. CONCLUSION: A parent-rated, 14-item school readiness inventory for Korean children with ASD were developed and preliminary evidence of its content validity and reliability were demonstrated in this study. The present study provides a basis for future studies that would further help evaluate and promote school readiness of the children with ASD.

Prevalence of Attention Deficit Hyperactivity Disorder in Girls With Central Precocious Puberty.

OBJECTIVE: The purpose of the current study was to examine the prevalence of attention deficit hyperactivity disorder (ADHD) in girls with central precocious puberty. METHOD: Girls with central precocious puberty were prospectively recruited from the pediatric clinic. Screening was done with ADHD Rating Scale (ADHD-RS) and Child Behavior Checklist (CBCL). Those who screened positive on ADHD-RS were referred for the diagnostic evaluation which included a Computerized Performance Test (CPT) and a clinical interview conducted by a child adolescent psychiatrist. RESULTS: Among the 81 girls (mean age = 8.97 ± 0.91) who completed the study, 11 girls (13.58%) were diagnosed with ADHD: 5 of them were inattentive type and 6 of them were combined type. CONCLUSION: The present exploratory study showed that the prevalence of ADHD in girls with central precocious was higher than the known worldwide prevalence of ADHD in children.

Unrecognized comorbid autism spectrum disorder in children initially diagnosed with only attention deficit hyperactivity disorder.

The present study examined the prevalence of autism spectrum disorder (ASD) in intellectually capable children with attention deficit hyperactivity disorder (ADHD). Retrospective chart review on 103 children (mean age= 7.83 ± 1.72 years female=15.53%), without intellectual disability, who were diagnosed with only ADHD were done. Among the 103 children 27 children (26.21%) were later co-diagnosed with ASD. The results of the present study provide helpful insights in accurate recognition of co-occurring ASD in intellectually capable children diagnosed with ADHD. The potential for the coexistence of ASD should always be given careful consideration when examining children with ADHD.

A simple urine test by 3D-plus-3D immunoassay guides precise in vitro cancer diagnosis.

Although a variety of urinary cancer markers are available for in vitro diagnosis, inherent problems of urine environment-containing various inorganic/organic ions/molecules that vary in concentration over a 20-fold range or more and significantly attenuate antibody avidity for markers-render conventional immunoassays unsuitable, remaining unresolved and a major challenge. Here we developed a 3D-plus-3D (3p3) immunoassay method, based on a single-step urinary marker detection by 3D-antibody probes, which are free of steric hindrance and capable of omnidirectional capture of markers in a 3D solution. The 3p3 immunoassay showed an excellent performance in the diagnosis of prostate cancer (PCa) through detecting PCa-specific urinary engrailed-2 protein, demonstrating 100% sensitivity and 100% specificity with the urine specimens of PCa-related and other related disease patients and healthy individuals. This innovative approach holds a great potential in opening up a novel clinical route for precise in vitro cancer diagnosis and also pushing urine immunoassay closer to more widespread adoption.

Factors Affecting Stress and Mental Health During the COVID-19 Pandemic.

OBJECTIVE: This study examined the factors influencing the mental health and stress of individuals during the coronavirus disease-2019 (COVID-19) pandemic. METHODS: A total of 600 participants were enrolled in this anonymous questionnaire survey that included questions on their demographic profiles and experiences related to the COVID-19 pandemic. The COVID-19 Stress Scale for Korean People (CSSK), Warwick- Edinburgh Mental Wellbeing Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, and Multidimensional Scale of Perceived Social Support were used. Data were analyzed using multiple regression to identify the factors affecting the total CSSK scores and the scores of each of the three CSSK subscales. RESULTS: Multiple regression analyses revealed that the severity of insomnia, sex, degree of income decline, occupation, religion, education level, marital status, residential status, level of social support, and degree of depression and anxiety had significant relationships with COVID-19-related stress. CONCLUSION: We identified factors affecting stress and mental health in the general population during the COVID-19 pandemic. Our findings may be helpful in providing an individualized approach to managing the mental health of the public. We expect that the results of this study will be used to screen high-risk individuals vulnerable to stress and to establish policies related to the public health crisis.

Computerized Version of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS-COMP): Development and Validation of the Korean Clinician-Administered Version.

OBJECTIVE: The purpose of the present study was to develop and validate the Korean version of the clinician-administered KSADSCOMP, which is the recently updated, web-based computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia for school-age children (KSADS). METHODS: A total of 71 participants (mean age=12.04±3.86 years, female=29.57%) participated in the study. A child-adolescent psychiatrist established a diagnosis for the participant after a thorough psychiatric interview with the participant and the parent. Researchers who were blind to the diagnoses administered the clinician-administered KSADS-COMP to the parents and participants. The gold-standard diagnoses made by child-adolescent psychiatrists were compared to the current diagnoses generated by the clinician-administered KSADS-COMP. Percent agreement, Cohen's Kappa, Gwet's first-order agreement coefficient (AC1), sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Gwet's AC1, our preferred measure of agreement, showed excellent range between 0.78 and 1. Sensitivity, specificity, positive predicted value and negative predictive value also showed high scores. CONCLUSION: The current study demonstrated excellent criterion validity of the Korean version of the clinician-administered KSADSCOMP, though the small sample size could be a limitation. The current study was the first study to examine the criterion validity of the KSADS-COMP. Due to its readily usable format and efficient and accurate diagnostic process, widely-use of KSADS-COMP is expected.

Safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression: the ASSURE study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation. METHODS: We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings. RESULTS: The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25-0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups. CONCLUSION: The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

Surface Oxygen Vacancy Inducing Li-Ion-Conducting Percolation Network in Composite Solid Electrolytes for All-Solid-State Lithium-Metal Batteries.

Composite solid electrolytes (CSEs) are newly emerging components for all-solid-state Li-metal batteries owing to their excellent processability and compatibility with the electrodes. Moreover, the ionic conductivity of the CSEs is one order of magnitude higher than the solid polymer electrolytes (SPEs) by incorporation of inorganic fillers into SPEs. However, their advancement has come to a standstill owing to unclear Li-ion conduction mechanism and pathway. Herein, the dominating effect of the oxygen vacancy (Ovac ) in the inorganic filler on the ionic conductivity of CSEs is demonstrated via Li-ion-conducting percolation network model. Based on density functional theory, indium tin oxide nanoparticles (ITO NPs) are selected as inorganic filler to determine the effect of Ovac on the ionic conductivity of the CSEs. Owing to the fast Li-ion conduction through the Ovac inducing percolation network on ITO NP-polymer interface, LiFePO4 /CSE/Li cells using CSEs exhibit a remarkable capacity in long-term cycling (154 mAh g-1 at 0.5C after 700 cycles). Moreover, by modifying the Ovac concentration of ITO NPs via UV-ozone oxygen-vacancy modification, the ionic conductivity dependence of the CSEs on the surface Ovac from the inorganic filler is directly verified.

Validation of the Korean self-administered computerized versions of the kiddie schedule for affective disorders and schizophrenia for school-age children (KSADS-COMP).

The purpose of the present study was to examine the validity of the Korean version of the parent and youth self-administered versions of the KSADS-COMP (The Kiddie Schedule for Affective Disorders and Schizophrenia for school-age children). To assess the criterion validity of the KSADS-COMP, diagnoses made by the selfadministered KSADS-COMP were compared to the gold-standard diagnoses made by the child-adolescent psychiatrists in 41 participants (mean age=14.93 ± 2.16 years, female=41.46 %). Gwet's first order agreement coefficient (AC1) concordance ratings showed moderate to good range. The present study shows promising validity of the Korean self-administered versions of the KSADS-COMP in Korean youths.

Long-term methylphenidate use for children and adolescents with attention deficit hyperactivity disorder and risk for depression, conduct disorder, and psychotic disorder: a nationwide longitudinal cohort study in South Korea.

BACKGROUND: Methylphenidate (MPH) is the most frequently prescribed medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the safety of its long-term use remain unclear. In particular, real-world evidence of long-term MPH treatment regarding the risk of depression, conduct disorders, and psychotic disorders in children and adolescents is needed. This study aimed to compare the risks of depression, conduct disorder, and psychotic disorder between long- and short-term MPH treatments in children and adolescents. METHODS: This population-based cohort study used a nationwide claims database of all patients with ADHD in South Korea. Patients aged less than 18 years who were prescribed MPH were included in the study. Long- and short-term MPH were defined as > 1 year, and < 1 year, respectively. Overall, the risk of developing depressive disorder, conduct disorder and oppositional defiant disorder (ODD), and psychotic disorder were investigated. A 1:2 propensity score matching was used to balance the cohorts, and the Cox proportional hazards model was used to evaluate the safety of MPH. RESULTS: We identified 1309 long-term and 2199 short-term MPH users. Long-term MPH use was associated with a significantly lower risk of depressive (hazard ratio [HR], 0.70 [95% confidence interval [CI] 0.55-0.88]) and conduct disorders and ODD (HR, 0.52 [95% CI 0.38-0.73]) than short-term MPH use. Psychotic disorder was not significantly associated with long-term MPH use (hazard ratio [HR], 0.83 [95% confidence interval [CI] 0.52-1.32]). CONCLUSIONS: Our findings suggest that long-term MPH use may be associated with a decreased risk of depression, conduct disorders and ODD. Moreover, the long-term use of MPH does not increase the risk of psychotic disorders. Long-term MPH administration may be considered as a favourable treatment strategy for children and adolescents with ADHD regarding depressive, conduct, and psychotic disorders.

Hearing Aid Fitting Orientation and the APSO Standard.

The Audiology Practice Standards Organization (APSO) which was formed in 2017 set out to compile basic services that audiologists within the field should adhere to in their practice. The second standard of the APSO is the Hearing Aid Fitting Standard for Adult and Geriatric Patients. Among the services outlined for an adult hearing aid fitting, orientation is discussed. A hearing aid fitting orientation needs to be device- and patient-centered while also covering various aspects of hearing aid orientation that supports patient's success during the process. This article discusses APSO Standard 12 regarding hearing aid orientation and details how this standard can be implemented in the clinic.

An Optimally Fabricated Platform Guides Cancer-Specific Activation of Chemotherapeutic Drugs and Toxicity-Free Cancer Treatment.

Cancer chemotherapeutic drugs such as doxorubicin, mitomycin C, and gemcitabine, which are mostly small synthetic molecules, are still clinically useful for cancer treatment. However, despite considerable therapeutic efficacy, severe toxicity-associated problems, which are mainly caused by the non-specific mode of action such as chromosomal DNA damage and interference in the DNA replication even in normal cells, remain unresolved and a major challenge for safer and thus more widespread adoption of chemotherapy. Herein, an innovative platform is developed through beneficially integrating core peptide units into highly-ordered, stable, and flexibly guest-adaptable structure of apoferritin, which simultaneously fulfills high-capacity loading of chemotherapeutic drugs compared with the case of FDA-approved antibody-drug conjugates, efficient drug targeting to cancer cells, and cancer cell-specific drug release and activation. This approach dramatically reduces drug toxicity to normal cells, significantly enhances efficacy in in vivo cancer treatment without toxicity to normal organs of mice, and thus is expected to open up a novel clinical route to break through the limits of current cancer chemotherapy.

Synthetic pro-peptide design to enhance the secretion of heterologous proteins by Saccharomyces cerevisiae.

Heterologous protein production in Saccharomyces cerevisiae is a useful and effective strategy with many advantages, including the secretion of proteins that require posttranslational processing. However, heterologous proteins in S. cerevisiae are often secreted at comparatively low levels. To improve the production of the heterologous protein, human granulocyte colony-stimulating factor (hG-CSF) in S. cerevisiae, a secretion-enhancing peptide cassette including an hIL-1ß-derived pro-peptide, was added and used as a secretion enhancer to alleviate specific bottlenecks in the yeast secretory pathway. The effects of three key parameters-N-glycosylation, net negative charge balance, and glycine-rich flexible linker-were investigated in batch cultures of S. cerevisiae. Using a three-stage design involving screening, selection, and optimization, the production and secretion of hG-CSF by S. cerevisiae were significantly increased. The amount of extracellular mature hG-CSF produced by the optimized pro-peptide after the final stage increased by 190% compared to that of the original pro-peptide. Although hG-CSF was used as the model protein in the current study, this strategy is applicable to the enhanced production of other heterologous proteins, using S. cerevisiae as the host.

Effects of anxiety on sedation among pediatric patients undergoing esophagogastroduodenoscopy.

We investigated whether the severity of anxiety among children undergoing endoscopy could affect sedation. We prospectively recruited patients under 18 years of age who were scheduled to undergo esophagogastroduodenoscopy (EGD). Baseline anxiety was evaluated using the Spence Children's Anxiety Scale (SCAS). Our analysis considered the type and dose of sedative drugs, degree of sedation, and complications associated with sedation according to the scale score. The mean total SCAS T-scores and each subscale score were significantly higher in the 6-12-year age group. The mean T-score among patients who exhibited irritability during EGD was higher than that among other patients, with significant differences in the Total, Obsessive Disorder, Panic Agoraphobia and General Anxiety subscales. The midazolam doses of children exhibiting irritability were more likely to need higher (p = 0.006). Other sedation-related complications were not associated with the T-scores in each subscale. Total sleep time was not associated with any T-score subscales. Anxiety levels were significantly higher among 6-12-year-olds and children exhibiting irritability. Anxiety was often associated with irritability, difficulties achieving adequate sedation during EGD, and additional sedative drug administration. We recommend higher doses or more potent drugs to facilitate endoscopy for children with high anxiety levels.