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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.

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.

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.

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.

Type 2 diabetes (T2D) is associated with severe mental illnesses (SMIs), such as schizophrenia, bipolar disorder, and depression. However, causal relationships between SMIs and T2D remain unclear owing to potential bias in observational studies. We aimed to characterize the causal effect of SMI liability on T2D using two-sample Mendelian randomization (MR). The causality between liability to SMI and T2D was investigated using the inverse-variance weighted (IVW), MR-Egger, MR-Egger with a simulation extrapolation, weighted median, and the MR pleiotropy residual sum and outlier method. Similarly, we performed additional MR which can detect the reverse causation effect by switching exposure and outcome for T2D liability for SMI. To further consider pleiotropic effects between SMIs, multivariable MR analysis was performed after accounting for the other traits. In the univariable IVW method, depression showed a causal effect on T2D (odds ratio [OR]: 1.128, 95% confidence interval [CI]: 1.024–1.245, P = 0.014). Multinomial MR more strongly supported these results (IVW OR: 1.197, 95% CI: 1.069, 1.340, P = 0.002; MR-Egger OR: 1.198, 95% CI: 1.062, 1.349, P = 0.003). Bidirectional MR showed reverse-causality absence between depression and T2D. However, causal relationship of bipolar and schizophrenia on T2D was not detected. Careful attention is needed for patients with depression regarding T2D prevention and treatment.

Accumulating data have highlighted the role of monocytes/macrophages in immune escape by generating immunologically “cold” tumors that do not respond to immunotherapy. CD244 (SLAMF4, 2B4), a member of the signaling lymphocyte activation molecule family, is expressed on myeloid cells, but its precise role has not been elucidated. Using monocyte lineage-specific CD244-deficient (LysM-cre+/-CD244fl/fl;cKO) mice challenged with B16F10 melanoma, we report for the first time that CD244 negatively regulates tumor immunity by inhibiting the differentiation and functional maturation of CD11b+Ly6ChiF4/80lomonocytes into CD11b+Ly6CloF4/80himacrophages within the tumor microenvironment. CD244-deficient macrophages more effectively activated antigen-specific T cell responses compared to WT macrophages, thus delaying tumor growth in the B16F10 melanoma model. Moreover, combinatorial intervention of anti-PD-L1 antibodies with CD244-KO BMDM markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with WT BMDM. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset (SCP398 from single-cell portal), revealed 221 differentially expressed genes of CD244-monocytes/macrophages were associated with phagocytosis, antigen presentation, and autophagy. Additionally, cell type deconvolution analysis within melanoma patients bulk RNA-seq datasets from TCGA database, revealed presence of CD244- monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. Hence, we proposed that CD244 serve as a critical immune checkpoint receptor on macrophages, and CD244-deficient macrophages may represent a novel therapeutic modality to convert immunologically “cold” tumors to “hot” tumors, which can function synergistically with checkpoint blockade therapies.

Objective This study investigated the effect of suicide prevention education on attitudes toward suicide among police officers.Methods We used an anonymous questionnaire for 518 officers and surveyed the demographic profiles and examined attitudes toward suicide utilizing the Attitudes Towards Suicide Scale (ATTS) (1=totally agree, 5=totally disagree). Our study divided participants into two groups, based on whether or not they had received suicide prevention education, and examined the differences in attitudes toward suicide between the groups.Results Of the total population, 247 (47.7%) officers had received suicide prevention education. The education group thought suicide as a predictable matter, disagreeing significantly more with the ATTS factor ‘suicide is unpredictable’ (3.36 vs. 3.35; p=0.001) compared with the no education group. Also, the education group more perceived suicide as a cry for help and at the same time disagreed more with the notion ‘suicidal thoughts will never disappear’ (2.08 vs. 2.26; p=0.025, 3.2 vs. 3.05; p=0.035, respectively).Conclusion Officers with experience in suicide prevention education showed more positive attitude toward suicide and suicide prevention. These findings suggest a need to organize more opportunities of suicide prevention educations, such as making the training mandatory for police officers.

Objective Young adults putting off marriage and having less children have become recent trends in many modern societies. Yet less is known about the psychological factors underlying the drastically low marriage and fertility rates. We hypothesized that childhood maltreatment experience may have a negative association with one’s marriage and childbearing intention.Methods A total of 1,004 college students (mean age of 20.8±2.3 years, 56.1% female) completed self-questionnaires including sociodemographic information, marriage and childbearing intention, Patient Health Questionnaire 9 (PHQ-9), and Childhood Trauma Questionnaire (CTQ). Multivariable logistic regression analyses were conducted to evaluate the effect of childhood trauma on marriage and childbearing intentions after controlling for sociodemographic variables and depression.Results 29.7% had no intention to get married and 40.4% had no intention to have children in the future. The prevalence of physical, sexual, and emotional abuse was 33.1%, 18.5%, and 22.3%, respectively. Multivariable logistic regression analyses revealed that female (p

Objective Subjective reports of patients with insomnia often show a discrepancy with their objective assessments of sleep. We aimed to assess subjective-objective sleep discrepancy in subjects with insomnia disorder as well as the psychological factors associated with the discrepancy.Methods This study is a secondary analysis of the baseline data of a randomized controlled study on 110 adults aged 18 years to 59 years with insomnia disorder. Subjective reports on sleep and the objective measures acquired by an overnight polysomnography were used to measure the sleep discrepancy. Smartphone Addiction Proneness Scale (SAPS), Center for Epidemiologic Studies Depression Scale (CES-D), beck anxiety inventory (BAI), and Global Assessment of Recent Stress (GARS) were used to evaluate the psychological factors associated with the sleep discrepancy.Results Mean total sleep time (TST) discrepancy of the participants was -81.65±97.41 minutes. Multivariable logistic regression analyses revealed that age (adjusted OR=1.07, 95% CI=1.01–1.13, p=0.027), years of education (adjusted OR=0.69, 95% CI=0.48–0.91, p=0.017), and smartphone addiction proneness (adjusted OR=1.14, 95% CI=1.04–1.27, p=0.008) were independent predictors of TST misperception. Mean sleep onset latency (SOL) discrepancy of the participants was 41.28±45.01 minutes. Only anxiety was an independent predictor of SOL misperception (adjusted OR=1.16, 95% CI=1.05–1.31, p=0.006).Conclusion The present study provides empirical evidence to increase our understanding of the various factors that are associated with subjective-objective sleep discrepancy. Screening insomnia patients with smartphone addiction proneness may help predict the potential discrepancy between the patients’ subjective reports and objective measures of sleep duration.

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.

Procalcitonin (PCT) (i.e. a precursor of calcitonin) attracts much attention as a reliable biomarker of bacterial infections because its concentration increases rapidly in the blood when bacterial infections occur in the body. Sepsis may occur due to indiscriminate and vigorous proliferation of infectious bacteria, and accordingly early diagnosis and treatment of bacterial infection are of crucial importance. However, current diagnostic methods for sepsis suffer from long assay time, multiple and complex assay steps, inaccuracy, and requirement of analytical equipments. The goal of this study is to develop an advanced one-step-immunoassay that enables quick and accurate diagnosis of sepsis through measuring the PCT concentration in patient sera, which is based on self-enhancement of optical detection signals from large gold particles (i.e. clusters of gold nanoparticles) that are formed on the agglomerates of PCT-bound 3-dimensional (3D) probes. The 3D probe is constructed through attaching polyclonal anti-PCT antibodies (IgGs) to the surface of a modified hepatitis B virus (HBV) capsid, where both tandem repeats of the B domain of Staphylococcal protein A (SPAB) and the hexa-histidine tag are inserted into each HBV core protein (i.e. subunit of HBV capsid). That is, anti-PCT IgGs are attached via strong interaction between the Fc region and surface-exposed SPAB. Furthermore, hook effect-free and PCT concentration-dependent optical signals were consistently generated by adding both bovine serum albumin (BSA) and nickel ions to patient sera and also by optimally adjusting the 3D probe concentration. Compared to conventional chemiluminescent microparticle immunoassay (CMIA) showing poor linearity of detection signals, this novel immunoassay accurately detected PCT with good linearity between PCT concentrations and optical signals in a wide range of PCT concentrations (0.05–200 ng mL−1) and also showed a sufficiently low limit of detection, resulting in 100% sensitivity and 100% specificity when tested with 30 sepsis patients and 30 healthy individuals.

Proteins are fundamentally the most important macromolecules for biochemical, mechanical, and structural functions in living organisms. Therefore, they provide us with diverse structural building blocks for constructing various types of biomaterials, including an important class of such materials, hydrogels. Since natural peptides and proteins are biocompatible and biodegradable, they have features advantageous for their use as the building blocks of hydrogels for biomedical applications. They display constitutional and mechanical similarities with the native extracellular matrix (ECM), and can be easily bio-functionalized via genetic and chemical engineering with features such as bio-recognition, specific stimulus-reactivity, and controlled degradation. This review aims to give an overview of hydrogels made up of recombinant proteins or synthetic peptides as the structural elements building the polymer network. A wide variety of hydrogels composed of protein or peptide building blocks with different origins and compositions - including β-hairpin peptides, α-helical coiled coil peptides, elastin-like peptides, silk fibroin, and resilin - have been designed to date. In this review, the structures and characteristics of these natural proteins and peptides, with each of their gelation mechanisms, and the physical, chemical, and mechanical properties as well as biocompatibility of the resulting hydrogels are described. In addition, this review discusses the potential of using protein- or peptide-based hydrogels in the field of biomedical sciences, especially tissue engineering.

As recent advancements in the chimeric antigen receptor-T cells have revolutionized the way blood cancers are handled, potential benefits from producing off-the-shelf, standardized immune cells entail the need for development of allogeneic immune cell therapy. However, host rejection driven by HLA disparity in adoptively transferred allogeneic T cells remains a key obstacle to the universal donor T cell therapy. To evade donor HLA-mediated immune rejection, we attempted to eliminate T cell’s HLA through the CRISPR/Cas9 gene editing system. First, we screened 60 gRNAs targeting B2M and multiple sets of gRNA each targeting α chains of HLA-II (DPA, DQA and DRA, respectively) using web-based design tools, and identified specific gRNA sequences highly efficient for target deletion without carrying off-target effects. Multiplex genome editing of primary human T cells achieved by the newly discovered gRNAs yielded HLA-I- or HLA-I/II-deficient T cells that were phenotypically unaltered and functionally intact. The overnight mixed lymphocyte reactions demonstrated the HLA-I-negative cells induced decreased production of IFN-γ and TNF-α in alloreactive T cells, and deficiency of HLA-I/II in T cells further dampened the inflammatory responses. Taken together, our approach will provide an efficacious pathway toward the universal donor cell generation by manipulating HLA expression in therapeutic T cells.

Nano-biomaterial hybridization is a promising strategy to generate unique and advanced material properties that are not available with nano- or biomaterials alone. In particular, the surface stabil...

The aim of the present study was to evaluate the prevalence and characteristics of subjects with obstructive sleep apnea (OSA) among adults with insomnia disorder. Among 105 participants (mean age = 40.61 ± 11.62, male = 53.3%) diagnosed with insomnia disorder who reported that they do not snore loudly, the prevalence of OSA was 35.2%. Despite the high Apnea-Hypopnea Index, longer lighter stages of sleep, and more numbers of total arousal in the polysomnography, subjects with OSA had a lesser tendency to overestimate their sleep onset latency compared to those without OSA. This study highlights the importance of examining insomnia patients for OSA even when the patients do not report loud snoring. Future studies are needed to identify the specific clinical features of patients with co-existing OSA and insomnia.

Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum.

The purpose of the present study was to examine the severity of suicidal ideation of the older adults according to the amount of involvement in grandchild care. Data for this research were drawn from a cross-sectional study conducted on community-dwelling adults aged 65 years or older. The 922 participants were divided into three groups according to their involvement in grandchild care: 18.5% had provided daily care, 12.4% had provided occasional care, and 69.1% had never cared for their grandchildren. ANCOVA analysis showed that the scores for depression was significantly lower in the group which took care of their grandchildren occasionally compared to the other two groups. The scores for suicidal ideation was significantly higher in the group which had never taken care of their grandchildren compared to the other two groups. Current study suggests that grandparenting may have a positive effect on suicidal ideation of the older adults.

Methane monooxygenase (MMO), which exists in particulate (pMMO) or soluble forms (sMMO) in methanotrophic bacteria, is an industrially promising enzyme that catalyses oxidation of low-reactive methane and other carbon feedstocks into methanol and their corresponding oxidation products. However, the simple, fast and high-yield production of functionally active MMO, which has so far been unsuccessful despite diverse approaches based on either native methanotroph culture or recombinant expression systems, remains a major challenge for its industrial applications. Here we developed pMMO-mimetic catalytic protein constructs by genetically encoding the beneficial reassembly of catalytic domains of pMMO on apoferritin as a biosynthetic scaffold. This approach resulted in high-yield synthesis of stable and soluble protein constructs in Escherichia coli, which successfully retain enzymatic activity for methanol production with a turnover number comparable to that of native pMMO. Methane monooxygenase (MMO)—a protein of high biotechnological interest for the selective and mild conversion of methane to methanol—lacks a high-throughput production system. Now, the authors report the efficient production of particulate MMO-mimics for catalysis in solution and hydrogels.