Assessing the determinants of influenza and COVID-19 vaccine co-administration decisions in the elderly.

This research examines the low rate of co-administration of influenza and COVID-19 vaccines among seniors aged 65 and older in Korea, despite recommendations from authorities and academia worldwide. The study aimed to understand the influence of general characteristics and health beliefs on the vaccination choices of seniors, who were categorized into four groups based on their vaccination status: influenza only, COVID-19 only, both, or neither. A total of 400 participants, aged 65 and above, were selected through proportional stratified random sampling from five major Korean regions for a survey conducted between November 24th and December 15th, 2023. The results indicated no significant differences in general characteristics across these groups. However, regarding the health beliefs showed significant differences in perceived susceptibility and self-efficacy between the influenza-only and co-administration groups. Higher levels of perceived susceptibility and self-efficacy were associated with choosing co-administration. Contrary to previous studies focusing on safety concerns as a primary factor in vaccine hesitancy, this study highlights the role of individual health-related beliefs, particularly perceived susceptibility and self-efficacy, as critical in influencing the decision for co-administration among the elderly in Korea.

Twenty Years of Progress and the Way Forward: Immunization Registry Information System in Korea.

The National Immunization Program in The Republic of Korea offers mandatory and free vaccinations to children under 12, regulated by the Infectious Disease Prevention and Control Act. Tracking vaccination coverage is crucial for population protection and public health strategies. Since 2002, the Immunization Registry Information System (IRIS) has been used nationwide to capture vaccination data. This study reviewed documents related to IRIS's establishment and development. The Republic of Korea legally supports IRIS's construction and data collection, integrating vaccination data with the Ministry of the Interior and Safety's resident registration to minimize errors. This collaboration also facilitates cost reimbursement and digital registration, promoting wider vaccination coverage. IRIS manages expense claims once vaccination details are logged, and authorized medical institutions can access these records in real-time. Since 2015, the Korea Disease Control and Prevention Agency has been compiling annual data on national vaccination coverage. IRIS also sends automated reminders in 12 languages, reports adverse effects, and issues vaccination certificates. However, IRIS lacks integration between vaccine and disease registries, unlike countries such as England, Denmark, and the Netherlands. Improving integration capabilities could enhance IRIS's support for public health through an integrated information system.

Effect of the human papillomavirus vaccine on the risk of genital warts: a nationwide cohort study of Korean adolescent girls.

OBJECTIVES: The purpose of this study was to assess the effectiveness of human papillomavirus (HPV) vaccination administered to adolescent girls through Korea's National Immunization Program. METHODS: This retrospective cohort study included patients who were 12-13 years old, whether vaccinated or unvaccinated, between July 2016 and December 2017. The incidence of genital warts (GWs) was monitored through 2021. Time-stratified hazard ratios (HRs) were estimated, adjusting for birth year, socioeconomic status, and the level of urbanization of the region, and were presented with 95% confidence intervals (CIs). Data were sourced from the Immunization Registry Integration System, linked with the National Health Information Database. RESULTS: The study included 332,062 adolescent girls, with an average follow-up period of approximately 4.6 years. Except for the first year, the HRs for the vaccinated group were lower than those for the unvaccinated group. The HRs for specific cut-off years were as follows: year 2, 0.62 (95% CI, 0.31 to 1.13); year 3, 0.58 (95% CI, 0.35 to 0.96); and year 4 and beyond, 0.39 (95% CI, 0.28 to 0.52). CONCLUSIONS: Our findings indicate that HPV vaccination was associated with a reduction in the risk of GWs among adolescent girls. Notably, this reduction became significant as the incidence of GWs increased with age.

Genistein alleviates pulmonary fibrosis by inactivating lung fibroblasts.

Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybeanderived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-ß1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-ß1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis. [BMB Reports 2024; 57(3): 143-148].

JYNNEOS vaccine safety monitoring in the Republic of Korea, 2022: a cross-sectional study.

BACKGROUND: With the recent global mpox outbreak, the JYNNEOS vaccine (Modified Vaccinia Ankara-Bavarian Nordic) was developed as a third-generation smallpox vaccine and initially favored for mpox immunization. Vaccine-associated side effects contribute to vaccine hesitancy. Consequently, tracking adverse events post-immunization is crucial for safety management. This study used data from the national active vaccine safety surveillance conducted in Korea from August 25 to November 24, 2022 to detect potential safety signals and adverse events. METHODS: Data on health conditions following vaccination were gathered from web-based surveys and reported via active surveillance through the Immunization Registry Information System. This follow-up system functioned via a text message link, surveying adverse events and health conditions beginning on the second day post-vaccination. Information about specific adverse events, including both local and systemic reactions, was collected. RESULTS: The study included 86 healthcare workers who had received at least 1 dose of the JYNNEOS vaccine. Among the respondents, 79.1% reported experiencing at least 1 adverse event, with the majority being local reactions at the injection site. The incidence of adverse events was higher following the first dose (67.9%) than after the second dose (34.4%). The most frequently reported adverse event for both doses was mild pain at the injection site. CONCLUSION: The study provides crucial information on the safety of the JYNNEOS vaccine, demonstrating that most adverse events were manageable and predominantly localized to the injection site. Nonetheless, additional research is needed on the safety of various vaccine administration techniques and the vaccine's effects on broader demographics.

Fatty acid amides as potential circulating biomarkers for sarcopenia.

BACKGROUND: Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics. METHODS: Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated. RESULTS: Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all Ps < 0.01). Consistent with these results in human plasma, targeted metabolome profiling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle tissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted metabolome profiling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma (P = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia parameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (P = 0.001, P = 0.001, respectively). The area under the receiver-operating characteristic curve (AUC) for DHA EA level ≤ 4.60 fmol/µL for sarcopenia was 0.618 (95% confidence interval [CI]: 0.532-0.698). DHA EA level ≤ 4.60 fmol/µL was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03-4.30), independent of HGS. The addition of DHA EA level to age and HGS significantly improved the AUC from 0.620 to 0.691 (P = 0.0497). CONCLUSIONS: Our study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with sarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key metabolite to become a reliable metabolic biomarker for sarcopenia. Further research on fatty acid amides will provide insights into the metabolomic changes relevant to sarcopenia from an aging perspective.

Why school is crucial to increase vaccination coverage for children: Evaluation of school vaccination check program in South Korea 2021-2022.

The School Vaccination Check Program (SVCP) is a public health measure that aims to achieve high levels of National Immunization Program (NIP) vaccination coverage for children by checking the completion of the vaccination schedule for students when they enter elementary or middle school. Due to the COVID-19 pandemic, the SVCP was stopped in 2020 and 2021, and restarted in June-August 2022. In this study, we examined and quantified the relationship with SVCP and the vaccination uptake by comparing the vaccination coverage of 2021 and 2022. Based on the standard schedule, the vaccination records of DTaP5, IPV4, MMR2 and IJEV4 were evaluated for elementary school students. The Tdap6, IJEV5 and HPV1 were evaluated for the students from middle school. Using a difference-in-difference study design and national level big data, the study compared vaccination coverage as of August 2021 and 2022. The study found that the SVCP was effective in increasing vaccination coverage for targeted vaccinations such as DTaP5, IPV4, MMR2 and IJEV4 for elementary school students, and Tdap6, IJEV5 for middle school students. However, the SVCP did not show a statistically significant effect on increasing vaccination coverage on HPV1 for middle school students. School can play an important role to improve vaccination coverage. Therefore, close collaboration with health and education authority is crucial to accomplish successful vaccination program reducing vaccine preventable disease outbreaks in schools.

Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics. Methods: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0. Results: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment. Conclusions: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.

Proteomic analysis for the effects of non-saponin fraction with rich polysaccharide from Korean Red Ginseng on Alzheimer's disease in a mouse model.

Background: The most common type of dementia, Alzheimer's disease (AD), is marked by the formation of extracellular amyloid beta (Aß) plaques. The impairments of axons and synapses appear in the process of Aß plaques formation, and this damage could cause neurodegeneration. We previously reported that non-saponin fraction with rich polysaccharide (NFP) from Korean Red Ginseng (KRG) showed neuroprotective effects in AD. However, precise molecular mechanism of the therapeutic effects of NFP from KRG in AD still remains elusive. Methods: To investigate the therapeutic mechanisms of NFP from KRG on AD, we conducted proteomic analysis for frontal cortex from vehicle-treated wild-type, vehicle-treated 5XFAD mice, and NFP-treated 5XFAD mice by using nano-LC-ESI-MS/MS. Metabolic network analysis was additionally performed as the effects of NFP appeared to be associated with metabolism according to the proteome analysis. Results: Starting from 5,470 proteins, 2,636 proteins were selected for hierarchical clustering analysis, and finally 111 proteins were further selected for protein-protein interaction network analysis. A series of these analyses revealed that proteins associated with synapse and mitochondria might be linked to the therapeutic mechanism of NFP. Subsequent metabolic network analysis via genome-scale metabolic models that represent the three mouse groups showed that there were significant changes in metabolic fluxes of mitochondrial carnitine shuttle pathway and mitochondrial beta-oxidation of polyunsaturated fatty acids. Conclusion: Our results suggested that the therapeutic effects of NFP on AD were associated with synaptic- and mitochondrial-related pathways, and they provided targets for further rigorous studies on precise understanding of the molecular mechanism of NFP.

Identification of genetic variants associated with diabetic kidney disease in multiple Korean cohorts via a genome-wide association study mega-analysis.

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex, involving metabolic and hemodynamic factors. Although DKD has been established as a heritable disorder and several genetic studies have been conducted, the identification of unique genetic variants for DKD is limited by its multiplex classification based on the phenotypes of diabetes mellitus (DM) and chronic kidney disease (CKD). Thus, we aimed to identify the genetic variants related to DKD that differentiate it from type 2 DM and CKD. METHODS: We conducted a large-scale genome-wide association study mega-analysis, combining Korean multi-cohorts using multinomial logistic regression. A total of 33,879 patients were classified into four groups-normal, DM without CKD, CKD without DM, and DKD-and were further analyzed to identify novel single-nucleotide polymorphisms (SNPs) associated with DKD. Additionally, fine-mapping analysis was conducted to investigate whether the variants of interest contribute to a trait. Conditional analyses adjusting for the effect of type 1 DM (T1D)-associated HLA variants were also performed to remove confounding factors of genetic association with T1D. Moreover, analysis of expression quantitative trait loci (eQTL) was performed using the Genotype-Tissue Expression project. Differentially expressed genes (DEGs) were analyzed using the Gene Expression Omnibus database (GSE30529). The significant eQTL DEGs were used to explore the predicted interaction networks using search tools for the retrieval of interacting genes and proteins. RESULTS: We identified three novel SNPs [rs3128852 (P = 8.21×10-25), rs117744700 (P = 8.28×10-10), and rs28366355 (P = 2.04×10-8)] associated with DKD. Moreover, the fine-mapping study validated the causal relationship between rs3128852 and DKD. rs3128852 is an eQTL for TRIM27 in whole blood tissues and HLA-A in adipose-subcutaneous tissues. rs28366355 is an eQTL for HLA-group genes present in most tissues. CONCLUSIONS: We successfully identified SNPs (rs3128852, rs117744700, and rs28366355) associated with DKD and verified the causal association between rs3128852 and DKD. According to the in silico analysis, TRIM27 and HLA-A can define DKD pathophysiology and are associated with immune response and autophagy. However, further research is necessary to understand the mechanism of immunity and autophagy in the pathophysiology of DKD and to prevent and treat DKD.

Monkeypox Vaccination in the Republic of Korea: Identifying the High-Risk Target Group.

In June 2022, the first monkeypox case was reported as imported into Korea. The general public asked whether they should get vaccinated against monkeypox because of the recent COVID-19 vaccination experience. As of the current monkeypox outbreak situation, a ring vaccination strategy for the high-risk group is more appropriate than the mass population vaccination with smallpox vaccines. Therefore, identifying the proper target group by available vaccines based on the risk and benefit analysis is a key issue of the vaccination program. In addition, the target group should be reviewed by the epidemiological situation of the jurisdiction along with the updated evidence of the monkeypox virus on transmission dynamics, severity, and fatality.

Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts.

Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. As the genetic biomarkers for sarcopenia are not yet well characterised, this study aimed to investigate the genetic variations related to sarcopenia in a relatively aged cohort, using genome-wide association study (GWAS) meta-analyses of lean body mass (LBM) in 6961 subjects. Two Korean cohorts were analysed, and subgroup GWAS was conducted for appendicular skeletal muscle mass (ASM) and skeletal muscle index. The effects of significant single nucleotide polymorphisms (SNPs) on gene expression were also investigated using multiple expression quantitative trait loci datasets, differentially expressed gene analysis, and gene ontology analyses. Novel genetic biomarkers were identified for LBM (rs1187118; rs3768582) and ASM (rs6772958). Their related genes, including RPS10, NUDT3, NCF2, SMG7, and ARPC5, were differently expressed in skeletal muscle tissue, while GPD1L was not. Furthermore, the 'mRNA destabilisation' biological process was enriched for sarcopenia. Our study identified RPS10, NUDT3, and GPD1L as significant genetic biomarkers for sarcopenia. These genetic loci were related to lipid and energy metabolism, suggesting that genes involved in metabolic dysregulation may lead to the pathogenesis of age-related sarcopenia.

COVID-19 vaccination program in South Korea: A long journey toward a new normal.

Objectives: This article presents an overview of South Korea's COVID-19 vaccination program and describes the key measures the country enacted to overcome the initial vaccine shortage and expand the vaccinated population. Methods: Review of official government documents, international and local databases, and media reports regarding the COVID-19 vaccination program. Results: South Korea overcame the early phase of vaccine shortage and quickly expanded vaccination coverage by evidence-based priority setting and transparent information sharing using innovative technologies. Conclusions: It was important to secure effective and safe vaccines as early as possible to fight against COVID-19, yet the delayed start did not equate to failure. Persistent innovation and rapid adaptation to changing circumstances allowed South Korea to expand its vaccination coverage despite the initial delay in procuring vaccine doses. However, the emergence of virus variants and the waning effect of the vaccines require that Korea initiate a new vaccination program that includes booster shots. Public Interest Summary: Vaccination is a safe and effective way to fight against COVID-19. However, acquiring adequate vaccine supply and administering doses safely and effectively are difficult tasks. South Korea accomplished this mission initially using innovative technologies and rapidly adapting to changing circumstances. However, new variants and decreasing vaccine efficacy induce the Korean government to begin another vaccination program that includes booster shots.

Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study.

BACKGROUND: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). METHODS: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. RESULTS: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. CONCLUSION: The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Hypermethylation of the interferon regulatory factor 5 promoter in Epstein-Barr virus-associated gastric carcinoma.

Interferon regulatory factor-5 (IRF-5), a member of the mammalian IRF transcription factor family, is regulated by p53, type I interferon and virus infection. IRF-5 participates in virus-induced TLR-mediated innate immune responses and may play a role as a tumor suppressor. It was suppressed in various EBV-infected transformed cells, thus it is valuable to identify the suppression mechanism. We focused on a promoter CpG islands methylation, a kind of epigenetic regulation in EBV-associated Burkitt's lymphomas (BLs) and gastric carcinomas. IRF-5 is not detected in most of EBV-infected BL cell lines due to hypermethylation of IRF-5 distal promoter (promoter-A), which was restored by a demethylating agent, 5-aza-2'-deoxycytidine. Hypomethylation of CpG islands in promoter-A was observed only in EBV type III latent infected BL cell lines (LCL and Mutu III). Similarly, during EBV infection to Akata-4E3 cells, IRF-5 was observed at early time periods (2 days to 8 weeks), concomitant unmethylation of promoter-A, but suppressed in later infection periods as observed in latency I BL cell lines. Moreover, hypermethylation in IRF-5 promoter-A region was also observed in EBV-associated gastric carcinoma (EBVaGC) cell lines or primary gastric carcinoma tissues, which show type I latent infection. In summary, IRF-5 is suppressed by hypermethylation of its promoter-A in most of EBV-infected transformed cells, especially BLs and EBVaGC. EBV-induced carcinogenesis takes an advantage of proliferative effects of TLR signaling, while limiting IRF-5 mediated negative effects in the establishment of EBVaGCs.

Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signaling pathway.

BACKGROUND: Zinc, an essential trace element, inhibits osteoclast differentiation in vitro and in vivo. The molecular mechanism for the inhibitory effect of zinc, however, is poorly understood. The purpose of this study was to investigate the effect of zinc and determine its molecular mechanism on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in mouse bone marrow-derived monocyte cells (BMMs) and RAW264.7 cells. RESULTS: In BMMs, zinc treatment during osteoclast differentiation decreased RANKL-induced osteoclast formation in a dose-dependent manner. We show that zinc suppressed the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1). Zinc also accumulated phospho-Nfatc1 (p-Nfatc1) in the cytosol in a dose-dependent manner and inhibited the translocation of Nfatc1 to the nucleus in RAW264.7 cells. Zinc suppressed the activities of Nfatc1 in the nucleus without changing the activities of NF-κB in RAW264.7 cells. In contrast, calcineurin activity decreased in response to zinc but its protein level was unchanged. RANKL-induced Ca2+ oscillations were inhibited by zinc treatment, but phospho-phospholipase Cγ1 (p-PLCγ1), the upstream signaling molecule of Ca2+ oscillations, was unaffected. Moreover, a constitutively active form of Nfatc1 obviously rescued suppression of osteoclastogenesis by zinc. CONCLUSIONS: Taken together, these results demonstrate for the first time that the inhibitory effect of zinc during osteoclastogesis is caused by suppressing the Ca2+-Calcineurin-NFATc1 signaling pathway. Thus, zinc may be a useful therapeutic candidate for the prevention of bone loss caused by NFATc1 activation in osteoclasts.

LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients.

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study.

OBJECTIVES: There is a wide variation in risk factors for intrahepatic cholangiocarcinoma (ICC) among various populations. Several studies have suggested that hepatitis C virus (HCV) infection may play a role in the development of ICC, whereas the role of hepatitis B virus (HBV) infection is less clear. METHODS: To determine whether HBV or HCV infection is a risk factor of ICC, we compared baseline demographic and clinical factors in 622 patients diagnosed between 2000 and 2004 with histologically confirmed ICC and 2,488 healthy controls, matched 4:1 with ICC patients for sex and year of birth. RESULTS: HBV infection (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.6-3.3), but not HCV infection, was significantly related to ICC. Other significant risk factors for ICC included liver cirrhosis (OR 13.6), heavy alcohol consumption (OR 6.6), diabetes (OR 3.2), Clonorchis sinensis infection (OR 13.6), hepatolithiasis (OR 50.0), and choledochal cysts (OR 10.7). CONCLUSIONS: Our results indicate that development of ICC seems to be more closely related to HBV infection than to HCV infection in Korea, where both HBV and ICC are endemic.

Is pancreatic core biopsy sufficient to diagnose autoimmune chronic pancreatitis?

OBJECTIVES: This study aimed to evaluate the adequacy of pancreatic core biopsy in histological diagnosis of autoimmune chronic pancreatitis (AIP). METHODS: Histopathologic study as well as immunohistochemical staining using anti-IgG4 antibody was done with pancreatic tissue specimens of 26 AIP patients (19 transabdominal ultrasound (US)-guided core biopsies, 3 intraoperative wedge biopsies, and 4 surgical resections). Eight patients with alcoholic chronic pancreatitis and 10 patients with pancreatic cancer served as controls. RESULTS: Lymphoplasmacytic sclerosing pancreatitis (LPSP) histology was observed in 26% (5/19) of US-guided core biopsy specimens, 33% (1/3) of open biopsy specimens, and all 4 resection specimens in AIP patients. None of the patients in the control group showed the full spectrum of changes of LPSP. Abundant IgG4-positive cells (>10 cells/high-power field) in the pancreas were observed in 21% (4/19) of AIP patients with US-guided core biopsy specimen. Abundant IgG4-positive cells in the pancreas were also observed in 2 of 8 patients with chronic alcoholic pancreatitis and 1 of 10 patients with pancreatic cancer. CONCLUSIONS: Transabdominal US-guided pancreatic core biopsy may not provide enough tissue to evaluate characteristic histopathologic features of AIP that include LPSP or abundant IgG4-positive cell infiltration. The LPSP histology may be specific to AIP, but abundant IgG4-positive cells in the pancreas may not.