The multi-decade household humidifier disinfectant poisoning tragedy (HHDT) in South Korea highlights the importance of investigating government failures. This study aims to identify and discuss key failures and shortcomings in the South Korean authorities’ approach to regulating humidifier disinfectants (HDs) and monitoring cases of chemical poisoning. We reviewed both the HD risk prevention measures that the South Korean Ministry of Environment (KME) should have implemented under the Toxic Chemicals Control Act (TCCA) (1991–2013).Polyhexamethylene guanidine phosphate (PHMG), a new chemical, was approved for use as a disinfectant under the TCCA. KME declared PHMG non-hazardous based solely on preproduction documentation provided by the industry. In addition, the Korea Disease Control and Prevention Agency (KDCPA) failed to detect the HHDT that had accumulated each year for more than a decade. KME’s neglect of its responsibilities, coupled with KDCPA’s lack of chemical poisoning surveillance systems, led to the accumulation of widespread HHDT.

The multi-decade household humidifier disinfectant poisoning tragedy (HHDT) in South Korea highlights the importance of investigating government failures. This study aims to identify and discuss key failures and shortcomings in the South Korean authorities’ approach to regulating humidifier disinfectants (HDs) and monitoring cases of chemical poisoning. We reviewed both the HD risk prevention measures that the South Korean Ministry of Environment (KME) should have implemented under the Toxic Chemicals Control Act (TCCA) (1991–2013).Polyhexamethylene guanidine phosphate (PHMG), a new chemical, was approved for use as a disinfectant under the TCCA. KME declared PHMG non-hazardous based solely on preproduction documentation provided by the industry. In addition, the Korea Disease Control and Prevention Agency (KDCPA) failed to detect the HHDT that had accumulated each year for more than a decade. KME’s neglect of its responsibilities, coupled with KDCPA’s lack of chemical poisoning surveillance systems, led to the accumulation of widespread HHDT.

The multi-decade household humidifier disinfectant poisoning tragedy (HHDT) in South Korea highlights the importance of investigating government failures. This study aims to identify and discuss key failures and shortcomings in the South Korean authorities’ approach to regulating humidifier disinfectants (HDs) and monitoring cases of chemical poisoning. We reviewed both the HD risk prevention measures that the South Korean Ministry of Environment (KME) should have implemented under the Toxic Chemicals Control Act (TCCA) (1991–2013).Polyhexamethylene guanidine phosphate (PHMG), a new chemical, was approved for use as a disinfectant under the TCCA. KME declared PHMG non-hazardous based solely on preproduction documentation provided by the industry. In addition, the Korea Disease Control and Prevention Agency (KDCPA) failed to detect the HHDT that had accumulated each year for more than a decade. KME’s neglect of its responsibilities, coupled with KDCPA’s lack of chemical poisoning surveillance systems, led to the accumulation of widespread HHDT.

The multi-decade household humidifier disinfectant poisoning tragedy (HHDT) in South Korea highlights the importance of investigating government failures. This study aims to identify and discuss key failures and shortcomings in the South Korean authorities’ approach to regulating humidifier disinfectants (HDs) and monitoring cases of chemical poisoning. We reviewed both the HD risk prevention measures that the South Korean Ministry of Environment (KME) should have implemented under the Toxic Chemicals Control Act (TCCA) (1991–2013).Polyhexamethylene guanidine phosphate (PHMG), a new chemical, was approved for use as a disinfectant under the TCCA. KME declared PHMG non-hazardous based solely on preproduction documentation provided by the industry. In addition, the Korea Disease Control and Prevention Agency (KDCPA) failed to detect the HHDT that had accumulated each year for more than a decade. KME’s neglect of its responsibilities, coupled with KDCPA’s lack of chemical poisoning surveillance systems, led to the accumulation of widespread HHDT.

Objectives: ：Among the various risk factors for suicide, geographic factors have different effects on males and females. This study aimed to identify differences between genders in spatiotemporal dependence and spatiotemporal patterns of suicide mortality over the preceding decade. Methods: ：This research analyzed the age-adjusted suicide mortality rate per 100,000 population, spanning from 2012 to 2021, for intentional suicides across each administrative district (229 Si, Gun, Gu) in Korea. Data were sourced from the National Statistical Office of the Korean Statistical Information Service. The Moran’s I in-dex for spatial autocorrelation of the suicide mortality rates was computed. An emerging hot spot analysis was conducted to examine the community-level spatiotemporal distribution patterns, thus providing insight into the re-gional clustering characteristics that reflect the temporal-spatial clusters of suicide mortality rates. Results: ：TIn males, the Moran’s I indices were almost above 0 (p-value<0.05) for most years, indicating sig-nificant spatial autocorrelation. Conversely, no significant regional clustering was observed among females dur-ing the same period. The emerging hot spot analysis, focusing on the temporal trends in the spatial distributionof male suicide mortality rates from 2012 to 2021, identified two distinct time series patterns and a total of 12 hot spot areas: seven new spots and five sporadic spots. Conclusions ：This study is the first to intuitively demonstrate the disparities in spatiotemporal dependencies and patterns of suicide mortality rates in Korea between genders. The findings highlight the necessity for tailoredsuicide prevention strategies that are sensitive to gender differences.

Background: The persistent coronavirus disease 2019 (COVID-19) pandemic has had direct and indirect effects on mortality, making it essential to analyze excess mortality to fully understand the impact of the pandemic. In this study, we constructed a mathematical model using number of deaths from Statistics Korea and analyzed excess mortality between 2020 and 2022 according to age, sex, and dominant severe acute respiratory syndrome coronavirus 2 variant period. Methods: Number of all-cause deaths between 2010 and 2022 were obtained from the annual cause-of-death statistics provided by Statistics Korea. COVID-19 mortality data were acquired from the Korea Disease Control and Prevention Agency. A multivariate linear regression model with seasonal effect, stratified by sex and age, was used to estimate the number of deaths in the absence of COVID-19. The estimated excess mortality rate was calculated. Results: Excess mortality was not significant between January 2020 and October 2021.However, it started to increase monthly from November 2021 and reached its highest point during the omicron-dominant period. Specifically, in March and April 2022, during the omicron BA.1/BA.2-dominant period, the estimated median values for excess mortality were the highest at 17,634 and 11,379, respectively. Both COVID-19-related deaths and excess mortality increased with age. A notable increase in excess mortality was observed in individuals aged ≥ 65 years. In the context of excess mortality per 100,000 population based on the estimated median values in March 2022, the highest numbers were found among males and females aged ≥ 85 years at 1,048 and 910, respectively. Conclusion This study revealed that the prolonged COVID-19 pandemic coupled with its high transmissibility not only increased COVID-19-related deaths but also had a significant impact on overall mortality rates, especially in the elderly. Therefore, it is crucial to concentrate healthcare resources and services on the elderly and ensure continued access to healthcare services during pandemics. Establishing an excess mortality monitoring system in the early stages of a pandemic is necessary to understand the impact of infectious diseases on mortality and effectively evaluate pandemic response policies.

Background: The persistent coronavirus disease 2019 (COVID-19) pandemic has had direct and indirect effects on mortality, making it essential to analyze excess mortality to fully understand the impact of the pandemic. In this study, we constructed a mathematical model using number of deaths from Statistics Korea and analyzed excess mortality between 2020 and 2022 according to age, sex, and dominant severe acute respiratory syndrome coronavirus 2 variant period. Methods: Number of all-cause deaths between 2010 and 2022 were obtained from the annual cause-of-death statistics provided by Statistics Korea. COVID-19 mortality data were acquired from the Korea Disease Control and Prevention Agency. A multivariate linear regression model with seasonal effect, stratified by sex and age, was used to estimate the number of deaths in the absence of COVID-19. The estimated excess mortality rate was calculated. Results: Excess mortality was not significant between January 2020 and October 2021.However, it started to increase monthly from November 2021 and reached its highest point during the omicron-dominant period. Specifically, in March and April 2022, during the omicron BA.1/BA.2-dominant period, the estimated median values for excess mortality were the highest at 17,634 and 11,379, respectively. Both COVID-19-related deaths and excess mortality increased with age. A notable increase in excess mortality was observed in individuals aged ≥ 65 years. In the context of excess mortality per 100,000 population based on the estimated median values in March 2022, the highest numbers were found among males and females aged ≥ 85 years at 1,048 and 910, respectively. Conclusion This study revealed that the prolonged COVID-19 pandemic coupled with its high transmissibility not only increased COVID-19-related deaths but also had a significant impact on overall mortality rates, especially in the elderly. Therefore, it is crucial to concentrate healthcare resources and services on the elderly and ensure continued access to healthcare services during pandemics. Establishing an excess mortality monitoring system in the early stages of a pandemic is necessary to understand the impact of infectious diseases on mortality and effectively evaluate pandemic response policies.

Purpose: We report two cases of retinal dystrophy with high myopia associated with a novel retinitis pigmentosa 2 (RP2) exon1 deletion and a simultaneous transforming growth factor β-induced (TGFBI) point mutation.Case summary: The patients were two male siblings previously diagnosed with retinitis pigmentosa. They had a maternal family history of granular corneal dystrophy, and both presented with high myopia of ≥ -7.00 diopters (D). On ophthalmologic imaging, they displayed identical symmetric diffuse retinal dystrophy with hyperpigmented bony spicules in both eyes. Optical coherence tomography revealed diffuse thinning of the neurosensory retina and disruption of the ellipsoid zone. Full-field electroretinography showed nearly flattened cone and rod responses. Although targeted next-generation sequencing did not reveal any mutations in either case, whole-exome sequencing confirmed the existence of a single heterozygous TGFBI point mutation (c.371G>A(p.(Arg124His))) in both patients. Subsequent whole genome sequencing (WGS) confirmed novel RP2 exon1 deletion (c.-37_c.102+581del (720bp)). Conclusions In this case of familial hereditary granular corneal dystrophy, there were difficulties diagnosing and interpreting the genetic test results because of the very rare RP2 deletion. Prior to WGS, it was thought that retinal dystrophy could be attributed to an atypical clinical feature associated with the TGFBI mutation and high myopia. Retinal specialists who diagnose and manage these patients are advised to compile plans that consider appropriate genetic testing and interpretation of the outcomes.

Purpose: Over the past decade, interest in exosomes as therapeutics has surged. In particular, stem-cell–derived exosomes may be more effective as a treatment for liver disease than the stem cells themselves. We have previously developed human chemically derived hepatic progenitors (hCdHs) from human hepatocytes. hCdHs can differentiate into hepatocytes and cholangiocytes, regenerating the liver in mouse models. In this study, we evaluated the mitigating effects of hCdHs-derived exosomes (hCdHs-exo) on liver damage and compared them with those of exosomes from bone marrow mesenchymal stem cells (BMMSCs-exo). Methods: Exosomes were isolated from hCdHs and BMMSCs by culturing cells in large quantities and separating the exosomes from the culture medium using ultracentrifugation. Isolated exosomes were characterized by various methods before experimental use. In vitro, the ability of exosomes to inhibit activation of hepatic stellate cells (HSCs) by transforming growth factor beta 1 was evaluated. In vivo, exosomes were injected into mice with carbon tetrachloride (CCl4 )-induced liver damage, and their effectiveness in mitigating liver damage was assessed by histological staining and biochemical analysis. Results: The analyses confirmed the successful isolation of exosomes from both cell types. In vitro, hCdHs-exo significantly reduced the levels of transcription factors and activation markers in induced HSCs. In vivo, hCdHs-exo effectively alleviated liver damage caused by CCl4 . Furthermore, both in vitro and in vivo studies confirmed that hCdHs-exo had a greater effect in alleviating liver damage than did BMMSCs-exo. Conclusion These results demonstrate that hCdHs-exo, similarly to hCdHs, have superior efficacy in alleviating liver damage compared with BMMSCs-exo.

Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.