Validation of the Utility of the Genetically Shared Regions of Chromosomes (GD-ICS) Measuring Method in Identifying Complicated Genetic Relatedness.

BACKGROUND: Relatives share more genomic regions than unrelated individuals, with closer relatives sharing more regions. This concept, paired with the increased availability of high-throughput single nucleotide polymorphism (SNP) genotyping technologies, has made it feasible to measure the shared chromosomal regions between individuals to assess their level of relation to each other. However, such techniques have remained in the conceptual rather than practical stages in terms of applying measures or indices. Recently, we developed an index called "genetic distance-based index of chromosomal sharing (GD-ICS)" utilizing large-scale SNP data from Korean family samples and demonstrated its potential for practical applications in kinship determination. In the current study, we present validation results from various real cases demonstrating the utility of this method in resolving complex familial relationships where information obtained from traditional short tandem repeats (STRs) or lineage markers is inconclusive. METHODS: We obtained large-scale SNP data through microarray analysis from Korean individuals involving 13 kinship cases and calculated GD-ICS values using the method described in our previous study. Based on the GD-ICS reference constructed for Korean families, each disputed kinship was evaluated and validated using a combination of traditional STRs and lineage markers. RESULTS: The cases comprised those A) that were found to be inconclusive using the traditional approach, B) for which it was difficult to apply traditional testing methods, and C) that were more conclusively resolved using the GD-ICS method. This method has overcome the limitations faced by traditional STRs in kinship testing, particularly in a paternity case with STR mutational events and in confirming distant kinship where the individual of interest is unavailable for testing. It has also been demonstrated to be effective in identifying various relationships without specific presumptions and in confirming a lack of genetic relatedness between individuals. CONCLUSION: This method has been proven effective in identifying familial relationships across diverse complex and practical scenarios. It is not only useful when traditional testing methods fail to provide conclusive results, but it also enhances the resolution of challenging kinship cases, which suggests its applicability in various types of practical casework.

ETV5 promotes lupus pathogenesis and follicular helper T cell differentiation by inducing osteopontin expression.

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.

Cytosolic N-terminal formyl-methionine deformylation derives cancer stem cell features and tumor progression.

Eukaryotic cells can synthesize formyl-methionine (fMet)-containing proteins not only in mitochondria but also in the cytosol to some extent. Our previous study revealed substantial upregulation of N-terminal (Nt)-fMet-containing proteins in the cytosol of SW480 colorectal cancer cells. However, the functional and pathophysiological implications remain unclear. Here, we demonstrated that removal of the Nt-formyl moiety of Nt-fMet-containing proteins (via expressing Escherichia coli PDF peptide deformylase) resulted in a dramatic increase in the proliferation of SW480 colorectal cancer cells. This proliferation coincided with the acquisition of cancer stem cell features, including reduced cell size, enhanced self-renewal capacity, and elevated levels of the cancer stem cell surface marker CD24 and pluripotent transcription factor SOX2. Furthermore, deformylation of Nt-fMet-containing proteins promoted the tumorigenicity of SW480 colorectal cancer cells in an in vivo xenograft mouse model. Taken together, these findings suggest that cytosolic deformylation has a tumor-enhancing effect, highlighting its therapeutic potential for cancer treatment.

Factors influencing stigma among college students with COVID-19 in South Korea: a descriptive study.

PURPOSE: This study is descriptive research aiming to identify factors influencing the stigma experienced by college students with coronavirus disease 2019 (COVID-19), focusing on COVID-19 pandemic stress, depression, and fear of negative evaluation as the main variables. METHODS: An online survey was administered to 175 college students who had been diagnosed with COVID-19 from January to May 2022 and were enrolled in universities in Seoul, Cheongju, and Daegu, South Korea. The survey collected data on pandemic stress, depression, fear of negative evaluation, and stigma. The data were analyzed using the t-test, ANOVA, the Scheffé test, Pearson's correlation coefficients, and stepwise multiple regression in SPSS/WIN 26.0. RESULTS: We analyzed differences in stigma scores based on general characteristics of the college students and found significant differences in stigma scores by age, major satisfaction, interpersonal satisfaction, date of COVID-19 confirmation, treatment modality, and recent subjective health condition. Factors influencing stigmatization were identified as COVID-19 pandemic stress, depression, date of COVID-19 confirmation, treatment modality, recent subjective health condition, and major satisfaction, with an overall explanatory power of 37.6%. CONCLUSION: This study is significant as it identifies emotional changes across various aspects of pandemic stress, depression, fear of negative evaluation, and stigma among college students who have been diagnosed with COVID-19. The findings of this study suggest the development of programs to reduce psychological distress and enhance mental health management skills among these students.

A novel approach of kinship determination based on the physical length of genetically shared regions of chromosomes.

BACKGROUND: Determination of genetic relatedness between individuals plays a crucial role in resolving numerous civil cases involving familial relationships and in forensic investigation concerning missing persons. Short tandem repeats (STRs), known for their high degree of DNA polymorphism, have traditionally been the primary choice of DNA markers in genetic testing, but their application for kinships testing is limited to cases involving close kinship. SNPs have emerged as promising supplementary markers for kinship determination. Nevertheless, the challenging remains in discriminating between third-degree or more distant relatives, such as first cousins, using SNPs. OBJECTIVE: To investigate a kinship analysis method for distant degree of familial relationships using high-density SNP data. METHODS: A high-density SNP data from 337 individuals of Korean families using Affymetrix Axiom KORV1.0-96 Array was obtained for this study. SNPs were aligned by chromosomal positions, and identity-by-state (IBS) was determined, and then shared regions as consecutive SNPs with IBS of 1 or 2 were investigated. The physical lengths of these IBS segments were measured and summed them to create an Index, as a measure of kinship. RESULTS: The kinship was determined by the physical length of shared chromosomal regions that are distinguished by each kinship. Using this method, the relationship was able be distinguished up to the fourth degree of kinship, and non-relatives were clearly distinguished from true relatives. We also found a potential for this approach to be used universally, regardless of microarray platforms for SNP genotyping and populations. CONCLUSION: This method has a potential to determine the different degree of kinship between individuals and to distinguish non-relatives from true relatives, which can be of great help for practical applications in kinship determination.

Assessment of hair loss and skin changes during treatment in Asian breast cancer patients: A prospective cohort study.

With the increasing number of young breast cancer (BC) patients worldwide, concerns about hair loss and skin change persist among BC survivors. This study aimed to evaluate the hair loss and skin changes in Asian BC patients and to compare them according to the treatment regimens. This study enrolled 322 patients scheduled to undergo BC surgery. Hair loss and skin changes were assessed at the following two time points: one day before surgery and 6 months after surgery. Patients who had received systemic anticancer treatment before surgery were assigned to the neoadjuvant treatment group, while patients who were scheduled to receive systemic anticancer treatment were assigned to the adjuvant treatment group. In the adjuvant treatment group, patients with taxane-based chemotherapy had significantly higher odds of increased hair loss, a higher melanin index, and an increased volume of wrinkles (p < 0.0001, p = 0.0110, and p = 0.0371, respectively). In the neoadjuvant treatment group, hair loss was reversed in most patients at 6 months after surgery. Clinicians should inform BC patients about the potential for hair loss and skin changes and provide supportive care to mitigate the effects on the patients' quality of life.

Identifying subgroups of eating behavior traits unrelated to obesity using functional connectivity and feature representation learning.

Eating behavior is highly heterogeneous across individuals and cannot be fully explained using only the degree of obesity. We utilized unsupervised machine learning and functional connectivity measures to explore the heterogeneity of eating behaviors measured by a self-assessment instrument using 424 healthy adults (mean ± standard deviation [SD] age = 47.07 ± 18.89 years; 67% female). We generated low-dimensional representations of functional connectivity using resting-state functional magnetic resonance imaging and estimated latent features using the feature representation capabilities of an autoencoder by nonlinearly compressing the functional connectivity information. The clustering approaches applied to latent features identified three distinct subgroups. The subgroups exhibited different levels of hunger traits, while their body mass indices were comparable. The results were replicated in an independent dataset consisting of 212 participants (mean ± SD age = 38.97 ± 19.80 years; 35% female). The model interpretation technique of integrated gradients revealed that the between-group differences in the integrated gradient maps were associated with functional reorganization in heteromodal association and limbic cortices and reward-related subcortical structures such as the accumbens, amygdala, and caudate. The cognitive decoding analysis revealed that these systems are associated with reward- and emotion-related systems. Our findings provide insights into the macroscopic brain organization of eating behavior-related subgroups independent of obesity.

Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories.

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.

Experiences of Caring for Cohort-Isolated Patients among Nurses in Locked Psychiatric Units.

The aim of this study was to gain an understanding of the experiences of caring for cohorts of patients isolated due to coronavirus disease (COVID-19) among nurses in locked psychiatric units. A phenomenological approach was used to analyze data collected from 10 nurses with a minimum of one year of experience as a mental health nurse working in locked psychiatric units that were cohort-isolated due to COVID-19. Data collected using semi-structured one-to-one in-depth interviews were analyzed based on steps outlined by Colaizzi. Five themes and thirteen subthemes emerged. The five themes were as follows: "Challenges intensified by the nature of mental disorders", "Concerns regarding limited mental health care", "Escalating stress", "Bolstered identity as a mental health nurse", "Witnessing changes that have begun". Environmental and institutional measures need to be implemented to identify the potential phenomena that may affect locked psychiatric units during an infectious disease epidemic and ensure the safety of health care professionals and patients from the infectious disease.

FLT4 as a marker for predicting prognostic risk of refractory acute myeloid leukemia.

Treating patients with refractory acute myeloid leukemia (AML) remains challenging. Currently there is no effective treatment for refractory AML. Increasing evidence has demonstrated that refractory/relapsed AML is associated with leukemic blasts which can confer resistance to anticancer drugs. We have previously reported that high expression of Fms-related tyrosine kinase 4 (FLT4) is associated with increased cancer activity in AML. However, the functional role of FLT4 in leukemic blasts remains unknown. Here, we explored the significance of FLT4 expression in leukemic blasts of refractory patients and mechanisms involved in the survival of AML blasts. Inhibition or absence of FLT4 in AML blasts suppressed homing to bone marrow of immunocompromised mice and blocked engraftment of AML blasts. Moreover, FLT4 inhibition by MAZ51, an antagonist, effectively reduced the number of leukemic cell-derived colony-forming units and increased apoptosis of blasts derived from refractory patients when it was co-treated with cytosine arabinoside under vascular endothelial growth factor C, its ligand. AML patients who expressed high cytosolic FLT4 were linked to an AML-refractory status by internalization mechanism. In conclusion, FLT4 has a biological function in leukemogenesis and refractoriness. This novel insight will be useful for targeted therapy and prognostic stratification of AML.

Workplace Violence Experienced by Community Mental Health Workers.

A cross-sectional online survey was conducted to 1) investigate the prevalence of workplace violence and workers' emotional distress, 2) explore factors associated with workplace violence, and 3) assess workers' needs for preventive measures. A total of 763 community mental health workers participated in Korea. Among them, 85.85% of workers experienced workplace violence, including verbal (74.31%), emotional (66.45%), infectious (47.44%), informational (42.60%), sexual (32.50%), and physical (23.72%) abuse. Binary logistic regression analysis indicated that sex, occupation, certification, and working institution were significantly associated with workplace violence. Workplace violence affects workers' depression, anger, and anxiety negatively. The most-needed preventive measure is a two-person home visit.

A Case of Cowden Syndrome Presenting with Diverse Cutaneous Manifestations.

Cowden syndrome is caused by mutations in the phosphatase and tensin homolog (PTEN) gene and is part of the PTEN hamartoma tumor syndrome. Skin lesions including trichilemmomas, acral keratosis, mucocunateous neuromas and oral paillomas are the most prevalent feature found in patients with Cowden syndrome. It also possesses an increased risk of developing malignancies including breast, thyroid, endometrial, and colorectal cancers. Due to the increased risk of cancer, early diagnosis and regular surveillance are important for Cowden syndrome patients. Herein, we report a case of Cowden syndrome with diverse cutaneous manifestations and thyroid cancer.

Factors Affecting COVID-19 Preventive Behaviors of Young Adults based on eHealth Literacy and the Health Belief Model: A Cross-Sectional Study.

Following the COVID-19 pandemic, disease prevention and preventive behaviors have become crucial for public health. In young adults, the internet is a popular source of health information. However, research that explores the factors associated with disease preventive behaviors based on the eHealth literacy (eHL) and the Health Belief Model (HBM) in young adults is lacking. A cross-sectional study design was used. Snowball sampling was used to recruit the participants through social network services. Proportionate stratified sampling was applied according to age, sex, and education level to mitigate sampling bias. The URL link for the online survey was provided via their mobile phones. A total of 324 participants, aged 20 to 39, completed the structured questionnaires (response rate = 98.2%). Frequency and descriptive statistical analyses, independent t-tests, one-way analyses of variance, Pearson's correlation coefficients, and multiple linear regression analyses were performed. Factors associated with COVID-19 preventive behaviors were COVID-19-related eHL (ß = .376, P < .001) and self-efficacy (ß = .221, P < .001), which were positively associated with COVID-19 preventive behaviors. Boosting self-efficacy and the ability to find, evaluate, and apply health information with sufficient evidence from the Internet can improve COVID-19 preventive behaviors. The government and healthcare personnel should consider psychological factors such as self-efficacy when developing COVID-19 disease prevention behavioral guidelines for the Internet.

Effects of Emotional Regulation, Resilience, and Distress Disclosure on Post-Traumatic Growth in Nursing Students.

Nursing students, who need to reflect on self, secure their identity, and be prepared as would-be nurses, can make a good use of post-traumatic growth (PTG) that can function as a catalyst for positive change even amidst this COVID-19 crisis. Emotional regulation strategies in traumatic events are key factors for successful growth, resilience is positively associated with PTG, and distress disclosure is an important factor for stress reduction. In this context, this study is a descriptive research study to identify factors influencing the PTG of nursing students, using emotional regulation, resilience, and distress disclosure as the main variables. Data were collected from 231 junior and senior students of the nursing departments of two universities, and the collected data were analyzed using the t-test, the Mann-Whitney U test, ANOVA, the Scheffé test, Pearson's correlation coefficients, and stepwise multiple regression in SPSS/WIN 26.0. Analysis of the PTG scores of the nursing students by general characteristics revealed significant differences in PTG according to the transfer status, perceived health status, and levels of satisfaction with major, hybrid-learning class, interpersonal relationship satisfaction, and clinical practice. Factors influencing PTG were identified to be resilience, reappraisal among emotional regulation strategies, satisfaction with clinical practice, and transfer, with the overall explanatory power calculated at 44%. Based on the results of this study, it is necessary to consider resilience and reappraisal, which is a sub-variable of emotional regulation strategies, in order to develop programs designed to promote PTG of nursing students in the future.

Corrigendum: A Double-Blind, Split-Face, Randomized Study on the Effects and Safety of Intradermal Injection of Botulinum Toxin Type A 150 kD Neurotoxin in the Cheek.

This corrects the article on p. 442 in vol. 34, PMID: 36478426.

Virtual simulation and problem-based learning enhance perceived clinical and cultural competence of nursing students in Asia: A randomized controlled cross-over study.

BACKGROUND: Both clinical and cultural competencies are of paramount importance in ensuring patients' safety and high-quality care. While problem-based learning (PBL) is a widely applied pedagogy in nursing education, an emerging technology-based pedagogy, virtual simulation provides a realistic clinical learning experience for students. It can be an effective solution for continuing clinical and cultural learning across countries in the era of the pandemic. OBJECTIVES: This study aimed to compare the effectiveness of virtual simulation and PBL on the perceived clinical and cultural competence for nursing students. DESIGN: A randomized controlled cross-over study design was used. SETTINGS AND PARTICIPANTS: Sixty-one undergraduate and postgraduate nursing students from five Asian regions were selected for participation. METHODS: Participants were randomized to receive either virtual simulation (group A) or PBL (group B) for one day, followed by another intervention on the second day. Three self-reported questionnaires were used: Clinical Competence Questionnaire (CCQ), Inventory for Assessing the Process of Cultural Competence among Healthcare Professionals-Student Version (IAPCC-SV), and demographic questionnaire. RESULTS: The results revealed that students in both arms had significant improvements in CCQ total score (A: d = 21.500, P < 0.001; B: d = 16.710, P = 0.001), nursing professional behavior (A: d = 8.233, P < 0.001; B: d = 6.323, P < 0.001), and advanced nursing skills (A: d = 2.533, P = 0.008; B: d = 2.129, P = 0.029) after two interventions. In addition, both arms demonstrated significant improvements in IAPCC-SV total score (A: d = 3.467, P = 0.037; B: d = 4.032, P = 0.010) and cultural skills (A: d = 0.767, P = 0.012; B: d = 1.000, P = 0.001). No significant differences were observed between the two arms. CONCLUSIONS: The findings indicated that both virtual simulation and PBL were effective in promoting students' perceived clinical and cultural competence. As both education modes have their own uniqueness and effectiveness in both outcomes, the combination of both could enhance the variability of learning modalities. Notably, the use of virtual simulation first could engage students better in learning and achieve better educational outcomes.

A Double-Blind, Split-Face, Randomized Study on the Effects and Safety of Intradermal Injection of Botulinum Toxin A (Incobotulinum Toxin A) in the Cheek.

BACKGROUND: Intradermal injection of botulinum toxin A (BTXA) is used for cosmetic purposes without strong evidence for clinical use, as opposed to intramuscular injection. OBJECTIVE: To evaluate the efficacy and safety of intradermal injection of incobotulinum toxin A (iBTXA) in the cheeks. METHODS: We conducted a study with 18 volunteers who received intradermal injection of iBTXA into one cheek and normal saline into the contralateral side as a control. Volunteers visited the clinic at weeks 2, 4, 8, and 12 after injection. At each visit, pores and wrinkles were evaluated by a facial analyzer, sebum secretion by a sebumeter, skin texture by both volunteers and clinicians, and wrinkles of the nasolabial fold were graded with photographic reviews. RESULTS: There were no significant effects on the wrinkles of the infraorbital area and sebum secretion. However, there were significant improvements in the wrinkles of the nasolabial fold and skin texture on the iBTXA injected side. The effects on the wrinkles of the nasolabial fold lasted 12 weeks, and those on skin texture lasted 8 weeks. Improvement in the pore size was observed only at week 2. No serious adverse events were reported except one volunteer who complained of facial palsy after the injection of 30 units of iBTXA in one cheek. However, injection of 20 units of iBTXA in one cheek was not associated with any adverse events. CONCLUSION: Intradermal injection of iBTXA, could provide clinical benefits for skin texture and wrinkles overcoming the skin prick effect without obvious side effects.

The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians.

Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases.