Hikikomori syndrome (HS), a phenomenon characterized by social withdrawal and isolation, has attracted significant attention in both academic and clinical settings. However, understanding the diverse nature of HS remains a challenge due to its multifaceted etiology and presentation. This paper aims to shed light on this phenomenon by examining three representative typologies of HS in clinical settings. Through detailed case analyses, we categorize HS into three main types: HS associated with neurodevelopmental disorders; HS triggered by the onset of mental illness; and HS emerging gradually with age-related challenges. By elucidating these typologies, we provide insights into the complex interplay of psychological, social, and developmental factors contributing to HS, thereby facilitating more tailored approaches for the evaluation of and intervention into this syndrome in clinical practice.

Background: Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype. Methods: An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study. Results: Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%). Conclusion CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.

Objective: This study compared the effects of preperitoneal pelvic packing (PPP) versus resuscitation alone, angioembolization, PPP with pelvic stabilization, resuscitative endovascular balloon occlusion of the aorta (REBOA) with PPP, pelvic stabilization, and REBOA. Methods: A comprehensive search was performed using multiple databases, trial registries, grey literature, and conference proceedings from inception until March 10, 2022. The risk of bias in non-randomized studies of intervention (ROBINS-I) and ROB 2.0 tools were used to assess the risk of bias for non-randomized studies and randomized controlled trials, respectively. The certainty of evidence was rated using the GRADE approach. Results: Twenty-two studies, including 1,762 participants, were retrieved. Based on randomized controlled trials, there was a high uncertainty regarding the effects of PPP versus angioembolization on improving the mortality rate (risk ratio [RR]=0.74; 95% confidence interval [CI] 0.22-2.49; very low certainty of evidence) and improving the hemorrhagic mortality rate (RR=0.19; 95% CI 0.01-3.72; very low certainty of evidence). Based on non-randomized studies, there was a high uncertainty regarding the effects of PPP versus angioembolization on improving the mortality rate (RR=0.76; 95% CI 0.48-1.21; I2=54%; very low certainty of evidence), improving the hemorrhagic mortality rate (RR=0.66; 95% CI 0.18-2.46; I2=75%; very low certainty of evidence), and reducing the post procedural complications (RR=0.76; 95% CI 0.39-1.48; I2=66%; very low certainty of evidence). Conclusion There is high uncertainty regarding the effects of PPP compared to resuscitation only, angioembolization, PPP with pelvic stabilization, REBOA following PPP, pelvic stabilization, and REBOA. (Registration No. CRD42022311628)

Objective: This study aimed to investigate the association between gaming time and problematic game use (PGU) within a large sample of Korean male gamers and to examine the potential moderating effects of loneliness, living alone, and household size. Methods: This study employed data from 743 male gamers from the National Mental Health Survey 2021, a nationally representative survey of mental illness conducted in South Korea. Self-reported data on the average gaming time per day, severity of PGU, loneliness, living alone, and household size were used. Results: Gaming time was positively associated with PGU and this relationship was significantly moderated by loneliness such that the positive effect of gaming time on PGU was greater when the levels of loneliness were high. The three-way interaction effect of gaming time, loneliness, and living alone was also significant, in that the moderating effect of loneliness on the relationship between gaming time and PGU was significant only in the living alone group. However, household size (i.e., number of housemates) did not moderate the interaction between gaming time and loneliness among gamers living with housemates. Conclusion These results suggest the importance of considering loneliness and living arrangements of male gamers, in addition to gaming time, in identifying and intervening with individuals at heightened risk of PGU.

Background: Ergothioneine (EGT) is a natural amino acid derivative in various animal organs and is a bioactive compound recognized as a food and medicine. Objectives: This study examined the effects of EGT supplementation during the in vitro maturation (IVM) period on porcine oocyte maturation and subsequent embryonic development competence after in vitro fertilization (IVF). Methods: Each EGT concentration (0, 10, 50, and 100 µM) was supplemented in the maturation medium during IVM. After IVM, nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels of oocytes were investigated. In addition, the genes related to cumulus function and antioxidant pathways in oocytes or cumulus cells were investigated. Finally, this study examined whether EGT could affect embryonic development after IVF. Results: After IVM, the EGT supplementation group showed significantly higher intracellular GSH levels and significantly lower intracellular ROS levels than the control group. Moreover, the expression levels of hyaluronan synthase 2 and Connexin 43 were significantly higher in the 10 µM EGT group than in the control group. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (NQO1) were significantly higher in the oocytes of the 10 µM EGT group than in the control group. In the assessment of subsequent embryonic development after IVF, the 10 µM EGT treatment group improved the cleavage and blastocyst rate significantly than the control group. Conclusions Supplementation of EGT improved oocyte maturation and embryonic development by reducing oxidative stress in IVM oocytes.

Background: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). Methods: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. Results: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. Conclusion VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

Objective: To propose standardized MRI-proton density fat fraction (PDFF) cutoff values for diagnosing hepatic steatosis, evaluated using contemporary PDFF measuring methods in a large population of healthy adults, using histologic fat fraction (HFF) as the reference standard. Materials and Methods: A retrospective search of electronic medical records between 2015 and 2018 identified 1063 adult donor candidates for liver transplantation who had undergone liver MRI and liver biopsy within a 7-day interval. Patients with a history of liver disease or significant alcohol consumption were excluded. Chemical shift imaging-based MRI (CS-MRI) PDFF and high-speed T2-corrected multi-echo MR spectroscopy (HISTO-MRS) PDFF data were obtained. By temporal splitting, the total population was divided into development and validation sets. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the MRI-PDFF method. Two cutoff values with sensitivity > 90% and specificity > 90% were selected to rule-out and rule-in, respectively, hepatic steatosis with reference to HFF ≥ 5% in the development set. The diagnostic performance was assessed using the validation set. Results: Of 921 final participants (624 male; mean age ± standard deviation, 31.5 ± 9.0 years), the development and validation sets comprised 497 and 424 patients, respectively. In the development set, the areas under the ROC curve for diagnosing hepatic steatosis were 0.920 for CS-MRI-PDFF and 0.915 for HISTO-MRS-PDFF. For ruling-out hepatic steatosis, the CS-MRI-PDFF cutoff was 2.3% (sensitivity, 92.4%; specificity, 63.0%) and the HISTO-MRI-PDFF cutoff was 2.6% (sensitivity, 88.8%; specificity, 70.1%). For ruling-in hepatic steatosis, the CS-MRI-PDFF cutoff was 3.5% (sensitivity, 73.5%; specificity, 88.6%) and the HISTO-MRI-PDFF cutoff was 4.0% (sensitivity, 74.7%; specificity, 90.6%). Conclusion In a large population of healthy adults, our study suggests diagnostic thresholds for ruling-out and ruling-in hepatic steatosis defined as HFF ≥ 5% by contemporary PDFF measurement methods.

BACKGROUND/OBJECTIVES: The objective of this study was to describe the development process of the Korean Healthy Eating Index (KHEI) based on the Korea National Health and Nutrition Examination Survey (KNHANES). SUBJECTS/METHODS: The components of KHEI were selected based on Dietary Guidelines for Koreans, domestic and overseas dietary quality indices, and results of the analysis of association with chronic diseases. The standards for scoring of KHEI were selected based on the 2015 Dietary Reference Intakes for Koreans (KDRI). The KHEI scores of Korean adults were calculated using a 1-day 24-h recall data in the 2013–2015 KNHANES. RESULTS: The KHEI included eight adequacy components evaluating the proper intake of recommended foods such as fruit, vegetable, and milk and three moderation components evaluating the consumption of food that limit intake such as sodium and saturated fatty acid. In addition, three balance components assessing the balance of energy intake were included. The KHEI score was defined to range from the minimum of 0 point to the maximum of 100 points. Among Korean adults, the total KHEI score was 63.2 out of 100. Gender and age differences were found in the average of total KHEI scores. Women showed higher score than men (61.7 in men and 64.7 in women, respectively). By age group, 20s and 30s showed the lowest scores with 57.4 and 61.1 respectively, and the scores increased with age by peaking at 67.8 in ages 60–69 and slowed down again in ages 70 or over. CONCLUSIONS The KHEI can be useful for establishing and assessing national nutritional policies and in epidemiological studies to assess the relationship between overall dietary quality and chronic diseases. KHEI will need to be continuously updated to reflect changes in dietary guidelines and the KDRI.

Background: Reference intervals defined for adults or children of other ethnicities cannot be applied in the evaluation of Korean pediatric patients. Pediatric reference intervals are difficult to establish because children are in their growing stage and their physiology changes continuously. We aimed to establish reference intervals for routine laboratory tests for Korean pediatric patients through retrospective multicenter data analysis. Methods: Preoperative laboratory test results from 1,031 pediatric patients aged 0 month–18 years who underwent minor surgeries in four university hospitals were collected. Age- and sex-specific reference intervals for routine laboratory tests were defined based on the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. Results: The pediatric reference intervals determined in this study were different from existing adult reference intervals and pediatric reference intervals for other ethnicities. Most tests required age-specific partitioning, and some of those required sex-specific partitioning for at least one age-partitioned subgroup. Erythrocyte sedimentation rate, monocyte percentage, basophil percentage, activated partial thromboplastin time, glucose, cholesterol, albumin, bilirubin, chloride, and C-reactive protein did not show any difference between age- or sex-partitioned subgroups. Conclusions We determined Korean pediatric reference intervals for hematology, coagulation, and chemistry tests by indirect sampling based on medical record data from multiple institutions. These reference intervals would be valuable for clinical evaluations in the Korean pediatric population.

Objective: We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. Methods: A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. Results: Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. Conclusion Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.