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PurposeMicroplastics have been widely reported to contaminate aquatic environments, particularly impacting marine organisms, but little is known of microplastic contamination of the soil environment. This study compared the distribution of microplastics in forest, urban, and agricultural soils, investigating the reasons for differences in abundance associated with land use.Materials and methodsWe analyzed distribution and abundance of microplastics in 100 soils, representing different land use types that include forest, urban (traffic and residence), and agriculture the environs of Yeoju City. Sampling plots were located on a systematic grid with 2.5 km × 2.5km spacing. Topsoil (0–5 cm) was collected with a hand auger and samples were pretreated by drying, density separation using ZnCl2 solution, organic matter digestion, and decompression filtration. Abundance of microplastics was measured by counting using a digital stereo microscope; microplastics were grouped by shapes (fragment, film, fiber, and sphere) and color (black, red, green, blue, yellow, white, and transparent). Fourier-transform infrared spectroscopy (FT-IR) analysis was used to identify polymer type of the microplastics.Results and discussionSoils of Yeoju contained an average 700 pieces·kg−1 of microplastics, but this greatly varied with land use types. Roadside soils had more microplastics (1108 pieces kg−1), mostly black styrene-butadiene rubber (SBR) fragments associated with tire dust. Unexpectedly, the largest amount of microplastics was detected not from urban soils but from an upland soil (3440 pieces kg−1). The mean abundance of microplastics in agricultural soil was 664 pieces kg−1, varying with farming types; the highest abundance was at orchard sites, followed by upland, greenhouse, and then paddy field sites. Polyethylene (PE) and polypropylene (PP) were identified from microplastics sampled at upland, greenhouse, and orchard sites, while SBR-derived microplastics were found more widely in all farmland soils, implicating that mulching film usage and farm machinery.ConclusionsSoil microplastic contamination is significant and widespread in urban and agricultural soils of Yeoju, but differs in form and distribution, according to the locality of traffic and farming. Atmospheric fallout to forest soils is quantified and found to be significantly impacted by microplastics. The use of mulching film as a source of PE and PP presents particular concern in terms of the effects of microplastic contamination on soil quality, health, and functionality in agroecosystems.

Plastic pollution is becoming a significant problem in urban areas due to excessive use and careless disposal. While studies on microplastics are increasingly being conducted across various environments, research on microplastics in soil is limited compared to other areas. Microplastics entering the soil through various routes can stay there for a long period of time, threatening soil organisms and eventually humans. Therefore, this study was carried out to investigate the distribution characteristics of microplastics according to types of land use. For this purpose, a total of 54 soil samples were collected from agricultural land, residential areas, roadsides, parks, and forests. The analysis of microplastics in the soil by stereo microscopy showed that the average numbers of microplastics (particles/kg) in agricultural land, residential areas, roadsides, parks, and forests were 5047, 3646, 4987, 2673, and 1097, respectively. Various colors (black, red, green, blue, yellow, white, and transparent) and shapes (fragment, fiber, film, and sphere) of microplastics were found in soils. The combination of black x fragment plastics showed the highest frequency. Microplastics in soil samples from agricultural land, roadside, and residential areas with sizes between 20 µm and 500 µm were determined using Fourier transform infrared spectrometer (FT-IR) and analyzed by MP finder. The number of microplastics detected in the soil with sizes ranging between 20 µm and 500 µm was in the order of roadside > residential areas > agricultural land, which was different from the results by stereomicroscopy. Polyethylene (PE), polypropylene (PP), and polymethyl methacrylate (PMMA) were detected in soils from roadsides. Polyurethane (PU), cellulose acetate (CA), polyethylene terephthalate (PET), PP, and polystyrene (PS) were detected in soils from residential areas, with PU being the most frequently detected.

Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of DNA copy numbers and DNA methylation. Transcriptomic deregulation by these aberrations plays key driver roles in heterogeneous progression of cancers. Here, we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes and the methylation-correlated expression (METcor) genes are co-regulated significantly. Multi-omics integration of the CNVcor and METcor genes reveal three prognostic subtypes of hepatocellular carcinoma, which can be validated by an independent data. The most aggressive subtype expressing stemness genes has frequent BAP1 mutations, implying its pivotal role in the aggressive tumor progression. In conclusion, our integrative analysis of genomic and epigenomic regulation provides new insights on the multi-layered pathobiology of hepatocellular carcinoma, which might be helpful in developing precision management for hepatocellular carcinoma patients. Hepatocellular carcinoma is known to harbour numerous genomic and epigenomic aberrations, driving transcriptomic deregulation. Here, the authors integrate genomic, epigenomic, and expression data to reveal three prognostic subtypes, providing insight to the pathobiology of hepatocellular carcinoma.

Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma. Functional cure rates are low with current treatment options (nucleos(t)ide analogs (NAs) and pegylated interferons). Bepirovirsen is an antisense oligonucleotide targeting all HBV messenger RNAs; in cell culture and animal models, bepirovirsen leads to reductions in HBV-derived RNAs, HBV DNA and viral proteins. This phase 2 double-blinded, randomized, placebo-controlled trial is the first evaluation of the safety and activity of an antisense oligonucleotide targeting HBV RNA in both treatment-naïve and virally suppressed individuals with chronic HBV infection. The primary objective was to assess the safety and tolerability of bepirovirsen in individuals with chronic hepatitis B (CHB) (NCT02981602). The secondary objective was to assess antiviral activity, including the change from baseline to day 29 in serum hepatitis B surface antigen (HBsAg) concentration. Participants with CHB infection ≥6 months and serum HBsAg ≥50 IU ml −1 were enrolled from seven centers across Hong Kong and the Republic of Korea and randomized (3:1 within each dose cohort) to receive bepirovirsen or placebo via subcutaneous injection twice weekly during weeks 1 and 2 (days 1, 4, 8 and 11) and once weekly during weeks 3 and 4 (days 15 and 22). Participants were then followed for 26 weeks. Twenty-four participants were treatment-naïve and seven were receiving stable NA therapy. Treatment-emergent adverse events were mostly mild/moderate (most commonly injection site reactions). Eleven (61.1%) and three (50.0%) treatment-naïve participants experienced one or more treatment-emergent adverse event in the bepirovirsen and placebo groups, respectively. In participants receiving NA therapy, the corresponding numbers were three (60.0%) and one (50.0%). Transient, self-resolving alanine aminotransferase flares (≥2× upper limit of normal) were observed in eight treatment-naïve participants and three participants on stable NA regimens in the bepirovirsen treatment arms. HBsAg reductions were observed and were significant versus placebo for treatment-naïve participants receiving bepirovirsen 300 mg ( P  = 0.001), but not for the bepirovirsen 150 mg group ( P  = 0.245) or participants receiving stable NA therapy ( P  = 0.762). Two participants in each of the 300 mg dose groups achieved HBsAg levels below the lower limit of quantitation by day 29 ( n  = 3) or day 36 ( n  = 1). Bepirovirsen had a favorable safety profile. These preliminary observations warrant further investigation of the safety and activity of bepirovirsen in a larger CHB patient population. A first-in-human study of an antisense oligonucleotide targeting hepatitis B virus (HBV) RNA provides initial insights into this potential new therapeutic modality for individuals with chronic HBV infection.

Although a robust association between metabolic dysfunction-associated fatty liver disease (MASLD) and cardiovascular disease (CVD) has been established, the impact of MASLD on CVD risk in young adults has not been fully evaluated. This population-based study included adults aged 20–39 years who underwent health screening examinations from 2009 to 2012 based on Korean National Health Insurance Service database. MASLD was defined as a fatty liver index ≥ 30 without any other cause of steatosis, and presence of one or more cardiometabolic risk factors. The primary outcome was newly developed CVD, including myocardial infarction, ischemic stroke, and congestive heart failure. During the median 10.6 years of follow-up, MASLD was observed in 1,435,659 (25.3%) of the 5,666,728 participants. Cumulative incidence of major adverse cardiovascular events was significantly higher in individuals with MASLD compared those without steatosis ( P  < 0.001). The adjusted hazard ratio (HR) for myocardial infarction was 1.23 [95% CI (confidence interval): 1.18–1.27] in individuals with MASLD compared to those without steatosis. The HR for ischemic stroke and congestive heart failure were higher in individuals with MASLD compared to those without steatosis (HR, 1.12; 95% CI, 1.07–1.17 and HR, 1.18; 95% CI, 1.15–1.21, respectively]. In the subgroup analysis, the elevated HR for CVD in the MASLD group was prominent among individuals who were female and obese. MASLD was associated with an increased risk of CVD in young adults. These findings highlight the need for early intervention in patients with MASLD before they reach middle to reduce the risk of CVD, particularly among young adults in South Korea.

Alcohol and diabetes are known risk factors for hepatocellular carcinoma (HCC); however, it is unclear whether the association between alcohol consumption and HCC risk differs by fasting serum glucose level and diabetes. We investigated the dose-response relationship between alcohol consumption and the risk of HCC according to glycemic status. This population-based observational cohort study included patients who underwent general health checkups in 2009 using the Korean National Health Insurance Service Database. The primary outcome was HCC incidence, and Cox proportional hazard regression analysis was performed to estimate the relationship between alcohol consumption and HCC risk according to glycemic status. A total of 34,321 patients newly diagnosed with HCC were observed in the median follow-up period of 8.3 years. In the multivariable model, we adjusted for age, sex, smoking, regular exercise, income, hypertension, dyslipidemia, and body mass index. Mild-to-moderate alcohol consumption increased the risk of HCC in all glycemic statuses (normoglycemia: hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02 to 1.10; prediabetes: HR, 1.19; 95% CI, 1.14 to 1.24; and diabetes: HR, 2.02; 95% CI, 1.93 to 2.11) compared to normoglycemic nondrinking. Heavy alcohol consumption also increased the risk of HCC in all glycemic statuses (normoglycemia: HR, 1.39; 95% CI, 1.32 to 1.46; prediabetes: HR, 1.67; 95% CI, 1.58 to 1.77; and diabetes: HR, 3.29; 95% CI, 3.11 to 3.49) compared to normoglycemic nondrinking. Since alcohol consumption information in this study was based on a self-administered questionnaire, there may be a possibility of underestimation. Although we excluded patients with a history of viral hepatitis using diagnosis codes, we could not obtain information on hepatitis B or hepatitis C serum markers. Both mild-to-moderate and heavy alcohol consumption was associated with an increased risk of HCC in all glycemic statuses. The increased risk of HCC according to alcohol consumption was the highest in the diabetes group, suggesting that more intensive alcohol abstinence is required for patients with diabetes.

Background External beam radiation therapy (RT) has shown promising effects for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) in recent studies. However, there is still a lack of consensus on the optimal RT scheme for PVTT treatment. We evaluated the efficacy and safety of image-guided 10-fraction hypofractionated RT in these patients. Methods Between January 2016 and March 2022, a total of 95 HCC patients with PVTT received 10-fraction hypofractionated image-guided radiation therapy (IGRT) at two institutes, and 69 patients were analyzed. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein, and Vp4 = main portal vein. Response evaluation was performed using Response Evaluation Criteria in Solid Tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT. Results The median prescribed dose of 50 Gy (range: 40-50 Gy; biologically effective dose [BED]: 56-75Gy 10 ) was delivered in 10 fractions. In this cohort, 4.3% of patients had Vp1, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. Median Planning target volume was 105.3 cc (interquartile range [IQR], 74.1–179.4 cc). Fifty-two (75.4%) patients received 50 Gy. With a median follow-up of 10.2 months (IQR, 6–21 months), the median OS was 20.3 months, and 1-year FFLP, PFS, and OS rates were 88.7%, 26.9%, and 62.2%, respectively. At 3 months follow-up, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, alpha-fetoprotein level ≥ 600 IU/ml (hazard ratio [HR] 2.06, p  = 0.03), Child–Pugh Class B or C (HR 2.30, p  = 0.02), and stage IVA or IVB (4.05, p  = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.9%) cases of grade ≥ 3 toxicity: grade 3 liver enzyme elevation ( n  = 1), and acute cholangitis ( n  = 1). Conclusions Hypofractionated RT demonstrated promising local PVTT control and OS rates with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56–75 Gy 10 ) is a feasible treatment option for PVTT in HCC patients.

Population-based data regarding the prognostic implication of gamma-glutamyl transferase (GGT) have been inconsistent. We examined the association of GGT with all-cause and disease-specific mortality. Using the Korean nationwide database, we included 9,687,066 subjects without viral hepatitis or cirrhosis who underwent a health examination in 2009. Subjects were classified into three groups by sex-specific tertile of serum GGT levels. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases codes. During the median follow-up period of 8.3 years, 460,699 deaths were identified. All-cause mortality increased as serum GGT levels became higher (hazard ratio [HR], 95% confidence interval [CI] 1.05, 1.04–1.05 in the middle tertile, and 1.33, 1.32–1.34 in the high tertile) compared to the low tertile of serum GGT levels. Similar trends were observed for cardiovascular disease (CVD) (HR, 95% CI 1.07, 1.05–1.09 in the middle tertile, 1.29, 1.26–1.31 in the high tertile), cancer (HR, 95% CI 1.08, 1.07–1.10 in the middle tertile, 1.38, 1.36–1.39 in the high tertile), respiratory disease (HR, 95% CI 1.10, 1.08–1.13 in the middle tertile, 1.39, 1.35–1.43 in the high tertile), and liver disease mortality (HR, 95% CI 1.74, 1.66–1.83 in the middle tertile, 6.73, 6.46–7.01 in the high tertile). Regardless of smoking, alcohol consumption and history of previous CVD and cancer, a higher serum GGT levels were associated with a higher risk of mortality. Serum GGT levels may be useful for risk assessment of all-cause and disease-specific mortality in general population.

Background Metabolic-associated fatty liver disease (MAFLD) encompasses diverse disease groups with potentially heterogeneous clinical outcomes. We investigated the risk of all-cause and disease-specific mortality in MAFLD subgroups. Methods Using the Korean National Health Insurance Service database, participants were divided into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Hazard ratios (HRs) and 95% confidence interval (CI) values for all-cause and disease-specific mortality according to MAFLD subgroups were analyzed using Cox proportional hazards models. Results Among 9,935,314 participants, those with MAFLD-diabetes showed the highest risk of all-cause and disease-specific mortality. The HRs (95% CI) for all-cause mortality were 1.61 (1.59–1.63), 1.36 (1.34–1.38), and 1.19 (1.18–1.20) in the MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obese groups, respectively. The magnitude of cardiovascular disease and cancer-related risk showed the same pattern. The risk of liver-related mortality in the MAFLD-lean group (HR: 2.84, 95% CI: 2.72–2.97) was comparable with that in the MAFLD-diabetes group (HR: 2.85, 95% CI: 2.75–2.95). When stratified by body mass index, liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03, 95% CI: 4.23–5.97). Conclusions The MAFLD-lean and MAFLD-diabetes groups had a higher risk of all-cause and disease-specific mortality than did the MAFLD-overweight/obese group. Classifying MAFLD subgroups based on metabolic phenotypes might help risk stratification of patients with MAFLD.

Background The association between nonalcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been inconsistent, and the impact of hepatic fibrosis on this relationship remains uncertain. We investigated the association between NAFLD and the risk of new-onset AF across different age groups. Methods A total of 3,179,582 participants from the 2009 Korean National Health Screening Program were divided into five groups based on NAFLD status: no NAFLD (fatty liver index [FLI] < 30); grade 1 NAFLD without advanced fibrosis (FLI 30–59 & BARD < 2); grade 1 NAFLD with advanced fibrosis (FLI 30–59 & BARD ≥ 2); grade 2 NAFLD without advanced fibrosis (FLI ≥ 60 & BARD < 2); and grade 2 NAFLD with advanced fibrosis (FLI ≥ 60 & BARD ≥ 2). The primary outcome was incident AF. Results During the median follow-up of 9.3 years, 62,542 patients were diagnosed with new-onset AF. In the age- and sex-adjusted model, the risk of new-onset AF increased across NAFLD grades and fibrosis categories: grade 1 NAFLD without advanced fibrosis (hazard ratio [HR] 1.120, 95% confidence interval [CI]: 1.081–1.161); grade 1 NAFLD with advanced fibrosis (HR 1.275, 95% CI 1.251–1.300); grade 2 NAFLD without advanced fibrosis (HR 1.305, 95% CI: 1.252–1.360); and grade 2 NAFLD with advanced fibrosis (HR 1.627, 95% CI: 1.586–1.670). In the multivariate model, the excess risk of AF in patients with NAFLD and advanced fibrosis remained significant, even in participants aged 20–39 years. Conclusion Patients with NAFLD had a higher risk of new-onset AF, which increased progressively with NAFLD severity, particularly in those aged 20–29 years.