Fine-Scale Spatial Prediction on the Risk of Plasmodium vivax Infection in the Republic of Korea.

BACKGROUND: Malaria elimination strategies in the Republic of Korea (ROK) have decreased malaria incidence but face challenges due to delayed case detection and response. To improve this, machine learning models for predicting malaria, focusing on high-risk areas, have been developed. METHODS: The study targeted the northern region of ROK, near the demilitarized zone, using a 1-km grid to identify areas for prediction. Grid cells without residential buildings were excluded, leaving 8,425 cells. The prediction was based on whether at least one malaria case was reported in each grid cell per month, using spatial data of patient locations. Four algorithms were used: gradient boosted (GBM), generalized linear (GLM), extreme gradient boosted (XGB), and ensemble models, incorporating environmental, sociodemographic, and meteorological data as predictors. The models were trained with data from May to October (2019-2021) and tested with data from May to October 2022. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The AUROC of the prediction models performed excellently (GBM = 0.9243, GLM = 0.9060, XGB = 0.9180, and ensemble model = 0.9301). Previous malaria risk, population size, and meteorological factors influenced the model most in GBM and XGB. CONCLUSION: Machine-learning models with properly preprocessed malaria case data can provide reliable predictions. Additional predictors, such as mosquito density, should be included in future studies to improve the performance of models.

Factors associated with the timely diagnosis of malaria and the utilization of types of healthcare facilities: a retrospective study in the Republic of Korea.

BACKGROUND: This study aimed to analyze trends in the timely diagnosis of malaria cases over the past 10 years in relation to the utilization of different types of healthcare facilities. METHODS: The study included 3,697 confirmed and suspected cases of malaria reported between January 1, 2013, and December 31, 2022, in the national integrative disease and healthcare management system. Some cases lacking a case report or with information missing from the case report were excluded from the analysis. A generalized linear model with a Poisson distribution was constructed to estimate risk ratios and 95% confidence intervals adjusted for other variables, such as distance. RESULTS: When cases involving diagnosis >5 days after symptom onset in confirmed patients (5DD) were examined according to the type of healthcare facility, the risk ratio of 5DD cases was found to be higher for tertiary hospitals than for public health facilities. Specifically, the risk ratio was higher when the diagnosis was established at a tertiary hospital, even after a participant had visited primary or secondary hospitals. In an analysis adjusted for the distance to each participant's healthcare facility, the results did not differ substantially from the results of the crude analysis. CONCLUSION: It is imperative to improve the diagnostic capabilities of public facilities and raise awareness of malaria at primary healthcare facilities for effective prevention and control.

Helicobacter pylori promotes epithelial-to-mesenchymal transition by downregulating CK2ß in gastric cancer cells.

Strains of Helicobacter pylori that are positive for the oncoprotein CagA (cytotoxin-associated gene A) are associated with gastric cancer and might be related to the epithelial-to-mesenchymal transition (EMT). Casein kinase 2 (CK2) is a serine/threonine protein kinase that plays a major role in tumorigenesis through signaling pathways related to the EMT. However, the role played by the interaction between CagA and CK2 in gastric carcinogenesis is poorly understood. Although CK2α protein expression remained unchanged during H. pylori infection, we found that CK2α kinase activity was increased in gastric epithelial cells. We also found that the CK2ß protein level decreased in H. pylori-infected gastric cancer cells in CagA-dependent manner and demonstrated that CagA induced CK2ß degradation via HDM2 (human double minute 2; its murine equivalent is MDM2). We observed that CagA induced HDM2 protein phosphorylation and that p53 levels were decreased in H. pylori-infected gastric cancer cells. In addition, downregulation of CK2ß induced AKT Ser473 phosphorylation and decreased the AKT Ser129 phosphorylation level in gastric cancer cells. We also found that the downregulation of CK2ß triggered the upregulation of Snail levels in gastric cancer cells. Furthermore, our in vivo experiments and functional assays of migration and colony formation suggest that CK2ß downregulation is a major factor responsible for the EMT in gastric cancer. Therefore, CK2 could be a key mediator of the EMT in H. pylori-infected gastric cancer and could serve as a molecular target for gastric cancer treatment.

Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. DESIGN: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. RESULTS: The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. CONCLUSION: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

AK-1, a SIRT2 inhibitor, destabilizes HIF-1α and diminishes its transcriptional activity during hypoxia.

Sirtuin family proteins are involved in the regulation of hypoxic responses which are primarily dependent on a hypoxia-inducible factor (HIF). However, few studies have examined the use of sirtuin inhibitors to regulate HIF. The present study examined the effect of a SIRT2-specific inhibitor, AK-1, on hypoxic responses. Under hypoxic conditions, AK-1 increased the ubiquitination of HIF-1α in a VHL-dependent manner, leading to the degradation of HIF-1α via a proteasomal pathway. Downregulation of HIF-1α expression reduced its transcriptional activity and, eventually, reduced the expression of BNIP3, one of HIF-1 target genes, in AK-1-treated cells. These data demonstrate that SIRT2 inhibition attenuates hypoxic responses, and that SIRT2 inhibitors may have potential as treatments for hypoxia-associated pathological conditions.

Regulatory roles of ganglioside GQ1b in neuronal cell differentiation of mouse embryonic stem cells.

Gangliosides play an important role in neuronal differentiation processes. The regulation of ganglioside levels is related to the induction of neuronal cell differentiation. In this study, the ST8Sia5 gene was transfected into mESCs and then differentiated into neuronal cells. Interestingly, ST8Sia5 gene transfected mESCs expressed GQ1b by HPTLC and immunofluorescence analysis. To investigate the effects of GQ1b over-expression in neurogenesis, neuronal cells were differentiated from GQ1b expressing mESCs in the presence of retinoic acid. In GQ1b expressing mESCs, increased EBs formation was observed. After 4 days, EBs were co-localized with GQ1b and nestin, and GFAP. Moreover, GQ1b co-localized with MAP-2 expressing cells in GQ1b expressing mESCs in 7-day-old EBs. Furthermore, GQ1b expressing mESCs increased the ERK1/2 MAP kinase pathway. These results suggest that the ST8Sia5 gene increases ganglioside GQ1b and improves neuronal differentiation via the ERK1/2 MAP kinase pathway.

A community-based case-control study of behavioral factors associated with scrub typhus during the autumn epidemic season in South Korea.

A community-based, case-control study was carried out to investigate risk factors for scrub typhus in South Korea. Cases (n = 299) were defined as persons who were diagnosed serologically within the past two weeks. Two neighborhood control subjects were selected by matching for sex, age, and occupation. Taking a rest directly on the grass, working in short sleeves, working with bare hands, and squatting to defecate or urinate posed the highest risks, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of 1.7 (1.2-2.3), 1.6 (1.1-2.4), 1.7 (1.2-2.4), and 2.0 (1.4-2.9), respectively. Wearing a long-sleeved shirt while working, keeping work clothes off the grass, and always using a mat to rest outdoors showed protective associations, with aORs and 95% CIs of 0.5 (0.3-0.9), 0.6 (0.4-0.9), and 0.7 (0.5-0.9), respectively. These results might be useful in the establishment of a detailed control strategy for scrub typhus.