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Aim: Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD. Methods: Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods. Results: In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis‐4 performed similarly to alpha‐fetoprotein and ultrasound. In G2, Fibrosis‐4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87–0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95–1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis‐4 score. Conclusions: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis‐4 score in identifying individuals at high risk of HCC. [ABSTRACT FROM AUTHOR]

Aim: Epidermal growth factor receptor (EGFR) mutations are detected in non‐small cell lung cancer (NSCLC) and associated with responses to therapy with tyrosine kinase inhibitors (TKIs). We compared the analytical performances of two real‐time PCRs and droplet digital PCR (ddPCR) to detect EGFR mutations using plasma. Methods: Plasma EGFR tests were performed using 86 plasma samples from 75 prospectively enrolled NSCLC patients with early and advanced stages. Analytical performances of plasma‐using two real‐time PCR, Cobas EGFR mutation v2 and PANAMutyper, EGFR kit, and ddPCR were evaluated based on the tissue EGFR test results. The frequencies of EGFR mutations and acquired T790M mutation after TKI therapy were also assessed. Results: The incidence of all EGFR mutations was 52.3% (23/44) in tissue and was up to 43.2% (19/44) in plasma. The Cobas detection rates of three EGFR mutations (exon 19 deletions, L858R, and T790M) in plasma were similar to those in tissue. The Cobas showed a higher detection rate (76.7%) than that by the PANAMutyper (60.5%). Sensitivity for T790M mutation was lower than the sensitivity for the exon 19 deletions or L858R in both tests. Mutant allele frequency measured by ddPCR was significantly correlated with the semi‐quantitative values of the Cobas. Conclusions: Plasma EGFR tests showed similar detection rates for common EGFR mutations compared to the tissue EGFR tests. Cobas showed higher sensitivity in detection of EGFR mutations in body fluids than the PANAMutyper. Real‐time PCR using plasma or body fluids could be a suitable first test for the detection of EGFR mutations. [ABSTRACT FROM AUTHOR]

Peatlands at high latitudes have accumulated >400 Pg carbon (C) because saturated soil and cold temperatures suppress C decomposition. This substantial amount of C in Arctic and Boreal peatlands is potentially subject to increased decomposition if the water table (WT) decreases due to climate change, including permafrost thaw‐related drying. Here, we optimize a version of the Organizing Carbon and Hydrology In Dynamic Ecosystems model (ORCHIDEE‐PCH4) using site‐specific observations to investigate changes in CO2 and CH4 fluxes as well as C stock responses to an experimentally manipulated decrease of WT at six northern peatlands. The unmanipulated control peatlands, with the WT <20 cm on average (seasonal max up to 45 cm) below the surface, currently act as C sinks in most years (58 ± 34 g C m−2 year−1; including 6 ± 7 g C–CH4 m−2 year−1 emission). We found, however, that lowering the WT by 10 cm reduced the CO2 sink by 13 ± 15 g C m−2 year−1 and decreased CH4 emission by 4 ± 4 g CH4 m−2 year−1, thus accumulating less C over 100 years (0.2 ± 0.2 kg C m−2). Yet, the reduced emission of CH4, which has a larger greenhouse warming potential, resulted in a net decrease in greenhouse gas balance by 310 ± 360 g CO2‐eq m−2 year−1. Peatlands with the initial WT close to the soil surface were more vulnerable to C loss: Non‐permafrost peatlands lost >2 kg C m−2 over 100 years when WT is lowered by 50 cm, while permafrost peatlands temporally switched from C sinks to sources. These results highlight that reductions in C storage capacity in response to drying of northern peatlands are offset in part by reduced CH4 emissions, thus slightly reducing the positive carbon climate feedbacks of peatlands under a warmer and drier future climate scenario. [ABSTRACT FROM AUTHOR]

Permafrost thaw induces soil hydrological changes which in turn affects carbon cycle processes in the Arctic terrestrial ecosystems. However, hydrological impacts of thawing permafrost on microbial processes and greenhouse gas (GHG) dynamics are poorly understood. This study examined changes in microbial communities using gene and genome‐centric metagenomics on an Arctic floodplain subject to decadal drainage, and linked them to CO2 and CH4 flux and soil chemistry. Decadal drainage led to significant changes in the abundance, taxonomy, and functional potential of microbial communities, and these modifications well explained the changes in CO2 and CH4 fluxes between ecosystem and atmosphere—increased fungal abundances potentially increased net CO2 emission rates and highly reduced CH4 emissions in drained sites corroborated the marked decrease in the abundance of methanogens and methanotrophs. Interestingly, various microbial taxa disproportionately responded to drainage: Methanoregula, one of the key players in methanogenesis under saturated conditions, almost disappeared, and also Methylococcales methanotrophs were markedly reduced in response to drainage. Seven novel methanogen population genomes were recovered, and the metabolic reconstruction of highly correlated population genomes revealed novel syntrophic relationships between methanogenic archaea and syntrophic partners. These results provide a mechanistic view of microbial processes regulating GHG dynamics in the terrestrial carbon cycle, and disproportionate microbial responses to long‐term drainage provide key information for understanding the effects of warming‐induced soil drying on microbial processes in Arctic wetland ecosystems. [ABSTRACT FROM AUTHOR]

The sustainability of the vast Arctic permafrost carbon pool under climate change is of paramount importance for global climate trajectories. Accurate climate change forecasts, therefore, depend on a reliable representation of mechanisms governing Arctic carbon cycle processes, but this task is complicated by the complex interaction of multiple controls on Arctic ecosystem changes, linked through both positive and negative feedbacks. As a primary example, predicted Arctic warming can be substantially influenced by shifts in hydrologic regimes, linked to, for example, altered precipitation patterns or changes in topography following permafrost degradation. This study presents observational evidence how severe drainage, a scenario that may affect large Arctic areas with ice‐rich permafrost soils under future climate change, affects biogeochemical and biogeophysical processes within an Arctic floodplain. Our in situ data demonstrate reduced carbon losses and transfer of sensible heat to the atmosphere, and effects linked to drainage‐induced long‐term shifts in vegetation communities and soil thermal regimes largely counterbalanced the immediate drainage impact. Moreover, higher surface albedo in combination with low thermal conductivity cooled the permafrost soils. Accordingly, long‐term drainage effects linked to warming‐induced permafrost degradation hold the potential to alleviate positive feedbacks between permafrost carbon and Arctic warming, and to slow down permafrost degradation. Self‐stabilizing effects associated with ecosystem disturbance such as these drainage impacts are a key factor for predicting future feedbacks between Arctic permafrost and climate change, and, thus, neglect of these mechanisms will exaggerate the impacts of Arctic change on future global climate projections. [ABSTRACT FROM AUTHOR]

Warming temperatures are likely to accelerate permafrost thaw in the Arctic, potentially leading to the release of old carbon previously stored in deep frozen soil layers. Deeper thaw depths in combination with geomorphological changes due to the loss of ice structures in permafrost, may modify soil water distribution, creating wetter or drier soil conditions. Previous studies revealed higher ecosystem respiration rates under drier conditions, and this study investigated the cause of the increased ecosystem respiration rates using radiocarbon signatures of respired CO2 from two drying manipulation experiments: one in moist and the other in wet tundra. We demonstrate that higher contributions of CO2 from shallow soil layers (0–15 cm; modern soil carbon) drive the increased ecosystem respiration rates, while contributions from deeper soil (below 15 cm from surface and down to the permafrost table; old soil carbon) decreased. These changes can be attributed to more aerobic conditions in shallow soil layers, but also the soil temperature increases in shallow layers but decreases in deep layers, due to the altered thermal properties of organic soils. Decreased abundance of aerenchymatous plant species following drainage in wet tundra reduced old carbon release but increased aboveground plant biomass elevated contributions of autotrophic respiration to ecosystem respiration. The results of this study suggest that drier soils following drainage may accelerate decomposition of modern soil carbon in shallow layers but slow down decomposition of old soil carbon in deep layers, which may offset some of the old soil carbon loss from thawing permafrost. Warming thaws permafrost and the subsequent geomorphological changes re‐distribute surface water in the Arctic. Drying of tundra ecosystems increased autotrophic respiration and decomposition of modern soil carbon in shallow layers but decreased that of old soil carbon in deeper layers. These changes can be attributed to more aerobic soil conditions, but also soil temperature increases in shallow layers but decreases in deep layers, as well as shifts in plant communities. [ABSTRACT FROM AUTHOR]

Background and objective: Reduced lung function and high lipoprotein (a) (Lp(a)) levels are both recognized risk factors for cardiovascular disease. Few studies have investigated the association between serum Lp(a) and lung function in the general population. We evaluated the association between reduced lung function and high Lp(a) levels in healthy individuals without known medical disease diagnoses. Methods: We performed a cross‐sectional study on 64 082 Korean health screening examinees (33 049 males, 38 ± 7 years) who underwent a health examination in 2015. Results: The median Lp(a) level was 12 (6–25)mg/dL. The prevalence of high Lp(a) (defined as >30 mg/dL) was 19.5%. Subjects with a high Lp(a) had both lower values of measured forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC; L) than those with a low Lp(a) (P < 0.001). However, FEV1/FVC ratio was not significantly different between groups (P = 0.112). Comparison of the second, third and fourth measured FVC (L) quartiles with that of the lowest quartile (1Q) group (reference) on regression analysis revealed adjusted odd ratios (OR) for a high Lp(a) of 0.928 (95% CI: 0.876–0.982), 0.860 (0.808–0.916) and 0.895 (0.839–0.954), respectively (P for trend < 0.001). In addition, adjusted OR for high Lp(a) compared with reference was 0.894 (0.844–0.947), 0.857 (0.806–0.912) and 0.882 (0.8727–0.940) across the measured FEV1 (L) quartiles in increasing order (P for trend < 0.001). Conclusion: High Lp(a) levels were associated with reduced lung function in this cross‐sectional population study. Longitudinal follow‐up studies will be required to validate our findings. Reduced lung function and high Lp(a) levels are risk factors for cardiovascular disease (CVD). High Lp(a) levels were associated with reduced lung function in this large study. Thus, Lp(a) may be the link between increased CVD risk and reduced lung function. See relatedEditorial [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Low activity of natural killer (NK) cells is known to be associated with higher risk of cancer, especially with poor prognosis and the presence of colorectal cancer (CRC). We investigated whether NK cells activity differs between subjects with and without colorectal neoplasia (CRN). Methods: A cross‐sectional study was performed on 1818 asymptomatic examinees aged ≥ 30 years who underwent NK cell activity test (which quantitates the amount of interferon‐γ secreted into the plasma by NK cells) and a colonoscopy as part of a health checkup. Results: The mean age of the study population was 41.4 years. The proportion of overall CRN and advanced CRN was 13.5% (n = 246) and 0.7% (n = 13), respectively. Only one subject was diagnosed with CRC. The median level of NK cell activity was lower in subjects with CRN than in those without CRN (1205 vs 1515 pg/mL, P = 0.009). It was also lower in subjects with non‐advanced CRN than in those without CRN (1221 vs 1515 pg/mL; P = 0.036). Moreover, it was lower in subjects with advanced CRN than in those with non‐advanced CRN (480 vs 1221 pg/mL; P = 0.028). Subjects with low levels of NK cell activity (< 250 pg/mL) had a higher prevalence of overall CRN (19.0% vs 12.9%, P = 0.024) and advanced CRN (3.4% vs 0.4%, P = 0.001) than those who demonstrated higher level (≥ 250 pg/mL). Conclusions: Natural killer cell activity seemed to decrease along with CRC progression toward the later stages in the adenoma‐carcinoma sequence. Its activity may be depressed in relation to progression of neoplasia, even at precancerous stage. [ABSTRACT FROM AUTHOR]

As surface temperatures are expected to rise in the future, ice-rich permafrost may thaw, altering soil topography and hydrology and creating a mosaic of wet and dry soil surfaces in the Arctic. Arctic wetlands are large sources of CH4, and investigating effects of soil hydrology on CH4 fluxes is of great importance for predicting ecosystem feedback in response to climate change. In this study, we investigate how a decade-long drying manipulation on an Arctic floodplain influences CH4-associated microorganisms, soil thermal regimes, and plant communities. Moreover, we examine how these drainage-induced changes may then modify CH4 fluxes in the growing and nongrowing seasons. This study shows that drainage substantially lowered the abundance of methanogens along with methanotrophic bacteria, which may have reduced CH4 cycling. Soil temperatures of the drained areas were lower in deep, anoxic soil layers (below 30 cm), but higher in oxic topsoil layers (0-15 cm) compared to the control wet areas. This pattern of soil temperatures may have reduced the rates of methanogenesis while elevating those of CH4 oxidation, thereby decreasing net CH4 fluxes. The abundance of Eriophorum angustifolium, an aerenchymatous plant species, diminished significantly in the drained areas. Due to this decrease, a higher fraction of CH4 was alternatively emitted to the atmosphere by diffusion, possibly increasing the potential for CH4 oxidation and leading to a decrease in net CH4 fluxes compared to a control site. Drainage lowered CH4 fluxes by a factor of 20 during the growing season, with postdrainage changes in microbial communities, soil temperatures, and plant communities also contributing to this reduction. In contrast, we observed CH4 emissions increased by 10% in the drained areas during the nongrowing season, although this difference was insignificant given the small magnitudes of fluxes. This study showed that long-term drainage considerably reduced CH4 fluxes through modified ecosystem properties. [ABSTRACT FROM AUTHOR]

The cervical cancer screening guidelines suggest that early detection of HPV16 and HPV18 is helpful for identifying women with cervical intraepithelial neoplasia (CIN) grade two or higher. We comparatively evaluated three HPV DNA assays, Roche Cobas HPV, RFMP HPV PapilloTyper, and Hybrid Capture 2 (HC2). A total of 861 cervical swab samples from women over 30 years of age were classified into two groups, that is, high grade squamous intraepithelial lesion (HSIL) and non-HSIL, according to cervical cytology results and analyzed by three assays. The results of direct sequencing or Linear array HPV genotyping test were considered true when the three assays presented discrepancies. The concordance rates between Roche Cobas HPV versus RFMP HPV PapilloTyper, RFMP HPV PapilloTyper versus HC2, and Roche Cobas versus HC2 were 94.5%, 94.3%, and 95.9%, respectively. For detection of HPV16 and HPV18, Roche Cobas HPV showed the concordance rates of 98.3% (κ = 0.73) and 99.4% (κ = 0.40) with the confirmation tests, respectively; and RFMP HPV PapilloTyper showed the concordance rates of 99.5% (κ = 0.92) and 100.0% (κ = 1.00), respectively. In conclusion, Roche Cobas HPV, RFMP HPV PapilloTyper, and HC2 showed high agreement rates. Roche Cobas HPV and RFMP HPV PapilloTyper are particularly useful, since both provide HPV specific genotypes, HPV16 and HPV18. J. Med. Virol. 87:1587-1593, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND Dermatophagoides farinae and Tyrophagus putrescentiae are recognised as an important source of allergens. An assessment was made of the toxicity of hiba, Thujopsis dolabrata var. hondai, oil and 13 organic compounds and the control efficacy of four experimental spray formulations containing the oil (5-30 g L−1 spray) against both mite species. RESULTS In a contact + fumigant mortality bioassay, (−)-thujopsene was the most toxic constituent against D. farinae and T. putrescentiae (24 h LC50 9.82 and 10.92 µg cm−2), and the toxicity of the compound was nearly identical to that of benzyl benzoate (9.33 and 10.14 µg cm−2). The toxicity was more pronounced in carvacrol, (+)-terpinen-4-ol, β-thujaplicin, (−)-terpinen-4-ol, cedrol and α-terpineol (LC50 12.05-15.20 and 12.74-16.48 µg cm−2) than in N, N-diethyl-3-methylbenzamide (LC50 35.53 and 38.42 µg cm−2) against both mite species. The hiba oil 30 g L−1 spray and commercial permethrin ( cis: trans 25:75) 2.5 g L−1 spray treatment resulted in 100 and 11% mortality against the two mite species respectively. In vapour-phase mortality tests, the two compounds were consistently more toxic in closed versus open containers, indicating that toxicity was achieved mainly through the action of vapour. CONCLUSION Reasonable mite control in indoor environments can be achieved by a spray formulation containing the 30 g L−1 hiba oil as a potential contact-action fumigant. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to examine an impact of body mass index (BMI) and weight change on the risk of diabetes according to metabolic health status. Methods Cohort study of 34,999 Korean men and women 30-59 years of age free of diabetes at baseline were followed-up annually or biennially for an average of 5.1 years. Being metabolically healthy was defined as not having any metabolic syndrome component. Results During 176,878.6 person-years of follow-up, 889 participants developed diabetes (incidence rate 5.0 per 1000 person-years). Compared to metabolically healthy normal-weight individuals, the adjusted hazard ratios for diabetes in metabolically unhealthy obese and in metabolically healthy obese were 13.7 (95% confidence interval [CI] 9.8-19.0) and 2.7 (95% CI: 1.7-4.3), respectively. The aHR (95% CI) for incident diabetes for weight changes of <−0.9, 0.5 to 2.0, and ≥2.1 kg compared to a weight change of −0.9 to 0.4 kg (reference) were 0.80 (0.66-0.97), 0.99 (0.82-1.20), and 1.24 (1.02-1.49), respectively ( P-trend<0.001). Conclusions In this large cohort of young and middle age Koreans, metabolic health status, obesity, and weight change were all independently associated with increased incidence of diabetes over 5 years of follow-up. [ABSTRACT FROM AUTHOR]

Summary Objective To investigate thyroid-stimulating hormone receptor ( TSHR) and thyroid peroxidase ( TPO) mutations in Korean patients with primary congenital hypothyroidism (CH). Context Congenital hypothyroidism is a common genetic disorder in which the majority of mutations occur in the TSHR and TPO genes. Design We examined the frequencies of TSHR and TPO mutations among Korean patients with primary CH. Furthermore, we explored the relationships between imaging findings and mutation status. Patients A total of 193 paediatric patients with nonsyndromic CH were enrolled in the present study. Measurements Patients with decreased 99mTc uptake were screened for TSHR mutations using Sanger sequencing, and those with increased uptake were screened for TPO mutations. The relationships between scintigraphic and ultrasonographic findings and mutation status were analysed. Results Thirteen (16·5%) of 79 patients with decreased 99mTc uptake were found to harbour TSHR mutations including G132R, G245S, R450H, R519C and F525S. The R450H mutation was present in 13 (72·2%) of 18 disease alleles. Seven (10·3%) of 68 patients with increased 99mTc uptake harboured TPO mutations including R189Q, K439E, G493S, C808LfsX72, A863T, R875Hfs and P883S. The TSHR and TPO mutations were observed only in patients with normal to slightly enlarged thyroid glands. Conclusions This study identified underlying TSHR and TPO mutations in Korean patients with CH and revealed a possible relationship between imaging findings and mutation status. In addition, the low rate of mutation positivity suggests significant genetic heterogeneity of CH in the Korean population. [ABSTRACT FROM AUTHOR]

Plate-like osteoma cutis ( PLOC) is a dermatological disorder characterized by superficial ossification and rarely occurs without any underlying tissue abnormalities or pre-existing calcification. The hereditary form of PLOC is mainly due to inactivating mutation in the GNAS gene. Inactivating mutation of the GNAS gene is associated with several diseases, which commonly manifest heterotopic ossification and hormonal resistance; however, the development of malignant neoplasm has never been reported. Herein, we report a case of a patient with a novel nonsense mutation in the GNAS gene, who presented with concurrent PLOC and medulloblastoma. [ABSTRACT FROM AUTHOR]