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Background/Aims Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. Methods Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. Results The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P

In this study, the distinctive chemical fingerprints that contribute to the flavor characteristics of various protein materials, such as insects, plant-based protein, and livestock, were investigated. In edible-insects (Tenebrio molitor and Protaetia brevitarsis), aldehydes and cyclic volatile compounds were the predominant volatile components and had distinct flavor characteristics such as cheesy, sharp, green, floral, and sweet. In contrast, the relatively high levels of pyrazines and furans in plant-based protein materials, such as textured vegetable and pea protein. They included unique flavor properties characterized by sweet, fatty, grassy, creamy, and roasted. The primary volatile chemical group detected in livestock protein materials, such as a pork and a beef, was ketones. The pork sample showed specific flavors, such as alcoholic, green, and fruity, while a beef presented distinctive flavor, including creamy, fruity, and alcoholic. Based on the results, this research provided the understanding of the flavor aspects of diverse protein materials.

Background/Aim Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT). Methods We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1. Results A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74). Conclusion The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.

Abstract Citrus fruits are largely consumed due to their unique and pleasant aromas. Citrus hybrids have been developed to enhance their flavors and bioactivities. Citrus aroma depends on the composition of the volatile compounds in citrus essential oils (CEOs), which are mostly located in the peels. During the extraction of CEOs, a specific series of chemical reactions occurred depending on the extraction methods (CP, cold pressing; HD, hydrodistillation), leading to variations in the composition of volatile compounds. In this study, the orange and the tangor which is a hybrid between C. reticulata × C. sinensis were investigated to compare the changes in volatile compounds based on the extraction methods. Results showed that the CP‐specific volatile compounds were sesquiterpenes, oxygenated monoterpenes, and fatty acid derivatives, while the HD‐specific volatile compounds were terpinyl cation derivatives, limonene, and 4‐vinylguaiacol. On the other hand, the contents of some volatile compounds ((E)‐ocimene, α‐terpinene, and α‐terpinolene) were affected by the Citrus species rather than by the extraction methods. In particular, during HD, terpinene‐4‐ol and 4‐vinylguiacol, known as off‐flavor compounds in citrus juice, were formed more abundantly in the orange than in the tangor. In conclusion, these results provide comprehensive data on essential oils, especially those derived from oranges and tangors, for selecting the appropriate extraction method for obtaining a higher yield and quality of citrus flavor.

Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor associated with cancer metabolism and is regarded as a potent anticancer therapeutic strategy within the hypoxic microenvironment of cancer. In this study, stilbenoid derivatives were designed, synthesized, and assessed for their capacity to inhibit HIF-1α-associated cancer metabolism and evaluated for inhibition of cancer cell viability and HIF activation. Through the structure-activity relationship studies, compound 28e was identified as the most potent derivative. Specifically, under the hypoxic condition, 28e reduced the accumulation of HIF-1α protein and the expression of its target genes related to glucose metabolism without affecting the expression of HIF-1α mRNA. Furthermore, 28e inhibited glucose uptake, glycolytic metabolism, and mitochondrial respiration, decreasing cellular ATP production under hypoxic conditions. In addition, 28e displayed significant anti-tumor effects and effectively suppressed the accumulation of HIF-1α protein in tumor tissue in vivo xenograft model. These findings suggest that our stilbenoid derivatives exert their anticancer effects by targeting HIF-1α-centered cancer metabolism under hypoxic conditions.

Background & Aims: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue (NA) treatment and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) remains unclear. Here, we aimed to investigate the association of HBeAg seroclearance during potent NA treatment with the development of HCC and decompensated cirrhosis. Methods: Using a multicenter historical cohort including 2,392 non-cirrhotic adult patients with HBeAg-positive CHB who initiated NA treatment with tenofovir or entecavir, the risk of HCC and decompensated cirrhosis was compared between patients who achieved HBeAg seroclearance within 36 months of NA treatment (the HBeAg-loss group) and those who did not (the HBeAg-maintained group), using inverse probability of treatment weighting. Results: Over a median of 6.6 years of NA treatment, 1,077 patients achieved HBeAg seroclearance (HBeAg loss rate = 6.0 per 100 person-years), 64 patients developed HCC (HCC incidence rate = 0.39 per 100 person-years), and 46 patients developed decompensated cirrhosis (decompensation incidence rate = 0.28 per 100 person-years). The HBeAg-loss and HBeAg-maintained groups had a similar risk of developing HCC (hazard ratio 0.89; 95% CI 0.47–1.68; p = 0.72) and decompensated cirrhosis (hazard ratio 0.98; 95% CI 0.48–1.81; p = 0.91). Compared with delayed HBeAg seroclearance beyond 10 years of NA treatment, the risk of HCC was comparable in those who achieved earlier HBeAg seroclearance at any time point within 10 years, regardless of baseline age and fibrotic burden. Conclusions: Early HBeAg seroclearance during NA treatment was not associated with a reduced risk of development of HCC or decompensated cirrhosis in non-cirrhotic HBeAg-positive patients with CHB. Impact and implications: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue treatment and the risk of hepatocellular carcinoma in patients with chronic hepatitis B remains unclear. Our findings indicate that early on-treatment HBeAg seroclearance within 3 years was not associated with the development of hepatocellular carcinoma or decompensated cirrhosis. Achieving HBeAg seroclearance may not be an appropriate surrogate endpoint for preventing the development of liver-related outcomes in non-cirrhotic patients with HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues.

Background/Aims Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. Methods This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. Results Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6–69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29–0.82, P=0.007) and after IPTW (aHR=0.42, 95% CI=0.26–0.70, P

Background. This study aimed to examine whether repeated measurements on noninvasive fibrosis scores during follow-up improve long-term nonalcoholic fatty liver disease (NAFLD) outcome prediction. Methods. A cohort study of 2,280 NAFLD patients diagnosed at the Seoul National University Hospital from 2001 to 2015 was conducted. Multivariable Cox regression models with baseline and designated time-point measurements of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were used to assess the association between these scores and overall mortality, liver-related outcomes, and cardiovascular events. Results. Higher baseline NFS (high versus low probability for advanced fibrosis groups) was associated with higher risk of mortality (adjusted hazard ratio (aHR), (95% confidence interval (CI)), 2.80, [1.39–5.63]) and liver-related outcomes (3.70, [1.27–10.78]). Similar findings were observed for the association of baseline FIB-4 with mortality (2.49, [1.46–4.24]) and liver-related outcomes (11.50, [6.17–21.44]). In models considering designated time-point measurements of the scores, stronger associations were noted. For NFS, a higher time-point measurement was associated with a significantly higher risk of mortality (3.01, [1.65–5.49]) and liver-related outcomes (6.69, [2.62–17.06]). For FIB-4, higher time-point measurements were associated with significantly higher mortality (3.01, [1.88–4.82]) and liver-related outcomes (13.26, [6.89–25.53]). An annual increase in FIB-4 (2.70, [1.79–4.05]) or NFS (4.68, [1.52–14.44]) was associated with an increased risk of liver-related outcomes. No association between NFS/FIB-4 and risk of cardiovascular events was observed in both models. Conclusions. Higher aHRs describing the associations of FIB-4/NFS with overall mortality and liver-related outcomes were observed in the models that included designated time-point measurements of the scores. In addition to the baseline measurement, a routine monitoring on these scores may be important in predicting prognosis of NAFLD patients.

Abstract Background Korea is expected to become a super-aged society in 2026, and improving nutritional status, which is directly related to health problems, is therefore important for increasing healthy life expectancy. Frailty is the most complex phenotype of aging, and leads to adverse health outcomes, disability, poor quality of life, hospitalization, and mortality. Malnutrition is a major risk factor for frailty syndrome. This study aimed to investigate the incidence of pre-frailty or frailty in the second wave (T2, 2018–2019) according to general characteristics and nutritional status in the first wave (T1, 2016–2017); and examine the longitudinal association of nutritional status in T1 and the incidence of pre-frailty or frailty in T2 among older adults living in a community. Methods A secondary data analysis was performed using the Korean Frailty and Aging Cohort Study (KFACS). Participants comprised 1125 community-dwelling older Korean adults aged 70–84 years (mean age: 75.03 ± 3.56 years; 53.8% males). Frailty was assessed using the Fried frailty index, and nutritional status was assessed using the Korean version of the Mini Nutritional Assessment Short-Form and blood nutritional biomarkers. Binary logistic regression was used to identify longitudinal associations between the nutritional status at T1 and pre-frailty or frailty at T2. Results Over the two-year follow-up period, 32.9% and 1.7% of the participants became pre-frail and frail, respectively. After the potential confounders were adjusted (sociodemographic, health behaviors, and health status characteristics), pre-frailty or frailty had a significant longitudinal association with severe anorexia (adjusted odds ratio [AOR], 4.17; 95% confidence interval [CI], 1.05–16.54), moderate anorexia (AOR, 2.31; 95% CI, 1.46–3.64), psychological stress or acute disease (AOR, 2.61; 95% CI, 1.26–5.39), and body mass index (BMI) less than 19 (AOR, 4.11; 95% CI, 1.20–14.04). Conclusions Anorexia, psychological stress, acute disease, and low BMI are the most significant longitudinal risk factors for pre-frailty or frailty in older adults. As nutritional risk factors may be preventable or modifiable, it is important to develop interventions targeting the same. Community-based health professionals in health-related fields should recognize and manage these indicators appropriately to prevent frailty among older adults living in the community.

Abstract This study was conducted to identify fall injury patterns, the transition from the baseline to follow-up, and the factors associated with the identified fall injury patterns using data obtained from the Korean Frailty and Aging Cohort Study. The participants were 566 community-dwelling older adults with fall experience. Three fall injury patterns were identified as the baseline and follow-up periods. The probability that the participant in the “fracture injury” pattern at Time 1 transitioned to the “fracture injury” pattern at Time 2 was 0.098. The factors associated with the “bruising and/or sprain injury” pattern were education level (relative risk ratio [RRR] = 0.55, p = 0.012), alcohol consumption (RRR = 0.50, p = 0.034), and balancing in tandem position (RRR = 2.77, p

Abstract Background As the life expectancy of people living with HIV increases with the advancements in antiretroviral treatment, the continuity of long-term therapy and health care for people living with HIV has gained more importance. However, the estimated proportion of people living with HIV who have access to treatment or are virally suppressed is unsatisfactory. Therefore, it is necessary to build strategies to improve treatment continuity by identifying the barriers and facilitators that affect the HIV care continuum. To enable this, we will conduct a scoping review to explore the barriers and facilitators related to the care continuum in high-income countries for adults living with HIV. Methods The review question will be identified based on the JBI guidelines for the development of scoping review protocols. Studies exploring the barriers to and facilitators of the HIV care continuum among adults living with HIV in high-income countries will be included in this review. A literature search will be conducted on the databases (platform) of MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (EBSCO), Embase (Ovid), and the Cochrane Central Register of Controlled Trials (Cochrane Library). Four researchers will screen articles for inclusion and subsequently build a charting form and collate the data to provide results. Discussion The results of this scoping review will provide comprehensive evidence for the barriers and facilitators to be considered in the care continuum of people living with HIV. Importantly, the results will provide insight for healthcare providers and researchers to develop interventions and research the continuity in caring for people living with HIV.

Varices are a frequent complication of liver cirrhosis and a major cause of mortality in patients with liver cirrhosis. Patients with decompensated cirrhosis complications have a poor prognosis and require careful management. Portal hypertension is the most common complication of liver cirrhosis, which is the key determinant for varices development. Increased intrahepatic vascular resistance to portal flow leads to the development of portal hypertension. Collateral vessels develop at the communication site between the systemic and portal circulation with the progression of portal hypertension. Varices are the representative collaterals, develop gradually with the progression of portal hypertension and may eventually rupture. Variceal bleeding is a major consequence of portal hypertension and causes the death of cirrhotic patients. The present paper reviews the latest knowledge regarding the diagnosis and management of esophageal and gastric variceal bleeding.

IntroductionFavorable responses to the treatment including immune checkpoint inhibitors (ICIs) have been consistently reported in lung cancer with smoking history. As the tumor microenvironment (TME) may be involved in the treatment response to ICIs, we aimed to investigate the TME of lung cancer with different smoking status.MethodsLung adenocarcinoma (LUAD) tissue (Tu) and adjacent normal-appearing lung tissue (NL) from current and never smokers were investigated by single-cell RNA sequencing and immunofluorescence and immunohistochemical staining. The clinical implications of identified biomarkers were validated using open-source datasets.ResultsThe lungs of smokers had an increased proportion of innate immune cells in NL tissues, whereas Tu tissues had a lower proportion of these cells than those of non-smokers. Monocyte-derived macrophages (mono-Mc), CD163-LGMN macrophages, monocyte-derived dendritic cells (DCs), and plasmacytoid DCs (pDCs) were significantly enriched in smokers’ Tu. Among these clusters, pDCs, specifically enriched in the Tu of smokers. The expression of representative pDC markers, leukocyte immunoglobulin-like receptor A4 (LILRA4) and Toll-like receptor 9 (TLR9), was increased in the stromal cells of LUAD in patients with a smoking history. In an animal model of lung cancer, ionizing radiation induced robust TLR9 expressing immune cells in peritumoral area. Survival analysis using a TCGA-LUAD dataset indicated that patients overexpressing pDC markers exhibited superior clinical outcomes to age-, sex-, and smoking-matched control groups. Top 25% patients with high TLR9 expression exhibited significantly higher tumor mutational burden than that of low TLR9 expression group (bottom 25% patients) (5.81 mutations/Mb vs 4.36 mutations/Mb; P = 0.0059, Welch’s two-sample t-test).ConclusionThere is an increased pDC in the TME of smokers’ lung cancer, and the response of pDC to DNA damaging treatment would lead a conducive environment to ICIs containing regimens. These findings suggest that R&D that induces an increase in the activated pDC population is continuously required to enhance therapeutic effectiveness of ICIs-containing therapies in lung cancer.

IntroductionAlthough transarterial radioembolization (TARE) using yttrium-90 (90Y) is a treatment option for large hepatocellular carcinoma (HCC), a fraction of patients are ineligible for TARE due to high lung shunt fraction (LSF).MethodsWe evaluated if treatment with transarterial chemoembolization (TACE), owing to TARE ineligibility was associated with early HCC progression. Consecutive patients with HCC who were initially TARE candidates were included. Patients with vascular invasion or metastasis were excluded. Primary endpoints were time-to-progression (TTP) and overall survival (OS). The secondary endpoint was objective response rate.ResultsIn total, 175 patients were included: 144 underwent TARE (TARE-eligible group) and 31 underwent TACE due to high LSF (TARE-ineligible group). This latter group had larger tumors (13.8 cm vs. 7.8 cm, P

Treatment options for advanced hepatocellular carcinoma (HCC) have been rapidly evolving. Herein, we describe a patient with advanced HCC and portal vein tumor thrombosis (PVTT) who responded decisively to a multidisciplinary approach. The patient had an ill-defined infiltrative HCC (diffuse subtype), with several intrahepatic metastasis and tumor invasion of left portal vein. Concurrent use of transarterial radioembolization (TARE) and systemic therapeutics (atezolizumab + bevacizumab) ultimately proved successful. There was marked reduction in tumor volume after TARE and an additional three cycles of atezolizumab plus bevacizumab. This concurrent treatment was well tolerated, without adverse events during immunotherapy. The impressive results achieved suggest that concurrent TARE and combination atezolizumab/bevacizumab is a promising treatment approach for advanced HCC with PVTT.

Abstract Background/aim In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients. Methods This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child–Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response. Results After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2 months, p = 0.070) and PFS (4.6 vs 2.4 months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96–2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5 months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group. Conclusions Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC.

Owing to their unique properties and biological activities, ionic liquids (ILs) have attracted research interest in pharmaceutics and medicine. Hypoxia-inducible factor (HIF)− 1α is an attractive cancer drug target involved in cancer malignancy in the hypoxic tumor microenvironment. Herein, we report the inhibitory activity of ILs on the HIF-1α pathway and their mechanism of action. Substitution of a dimethylamino group on pyridinium reduced hypoxia-induced HIF-1α activation. It selectively inhibited the viability of the human colon cancer cell line HCT116, compared to that of the normal fibroblast cell line WI-38. These activities were enhanced by increasing the alkyl chain length in the pyridinium. Under hypoxic conditions, dimethylaminopyridinium reduced the accumulation of HIF-1α and its target genes without affecting the HIF1A mRNA level in cancer cells. It suppressed the oxygen consumption rate and ATP production by directly inhibiting electron transfer chain complex I, which led to enhanced intracellular oxygen content and oxygen-dependent degradation of HIF-1α under hypoxia. These results indicate that dimethylaminopyridinium suppresses the mitochondria and HIF-1α-dependent glucose metabolic pathway in hypoxic cancer cells. This study provides insights into the anticancer activity of pyridinium-based ILs through the regulation of cancer metabolism, making them promising candidates for cancer treatment.

Biogenic amines (BAs), which are mainly generated by the microbial decarboxylation of amino acids, are important nitrogen compounds in fermented foods because of their toxicology. However, amino acids, the precursors of BAs, also play an important role in generating volatile and non-volatile metabolites, which are strongly associated with quality indicators for foods. Bacillus subtilis is one of dominant fermentative microorganism in various fermented foods and is well known as a BA-producing bacterium. In this study, B. subtilis strains which have different BAs-producing capacities, higher level of BAs production strain (BH) and lower level of BAs production strain (BL), were applied to compare the formations of volatile and non-volatile metabolite profiles according to cultivation times. In this study, histamine, putrescine, and spermidine were detected in all strains, however, 2-phenylethylamine was detected only in BH. Partial least squares discriminant analysis (PLS-DA) was applied to investigate the difference of metabolic profiles according to strains. In BH, some amino acids (phenylalanine, leucine, and threonine) and related volatile metabolites (3-methylbutanoic acid, pyrazines, styrene, and 1H-indole) were produced higher levels. On the other hand, BL produced significantly higher contents of metabolites associated with metabolism of fatty acids and nucleotides. It is necessary to consider the formation of metabolites in terms of quality as well as that of BAs during fermentation.

Hypoxia inducible factor (HIF)-1α is an important transcription factor regulating cancer metabolism in hypoxic environment. Capsaicin is known to inhibit hypoxia-induced HIF activity in lung cancer. Hence, in this study we tried to elucidate its inhibitory mechanism of action. In lung cancer cells, including H1299, H23, A549, and H2009 cells, capsaicin inhibited cell growth and HIF activation. Under hypoxic conditions, capsaicin reduced the accumulation of HIF-1α protein and the expression of its target genes, including pyruvate dehydrogenase kinase 1 (PDK1) and glucose transporter 1 (GLUT1), with no effect on overall HIF-1α mRNA levels in the H1299 cells. In addition, capsaicin increased intracellular oxygen levels by suppressing mitochondrial respiration, resulting in a reduction of HIF-1α accumulation. Furthermore, mitochondrial ATP production was reduced by capsaicin through the inhibition of mitochondrial respiration in the H1299, H23, A549, and H2009 cells. These results indicate that capsaicin potentially exhibits anticancer therapeutic effects in lung cancer under hypoxic conditions.

Background: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). Methods: We retrospectively included 284 samples with HBV DNA < 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, n = 239 and HBeAg-positive, n = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. Results: There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co]1.323; adjusted R2 = 0.8445; p < 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg 1.331; adjusted R2 = 0.7878; p < 0.001) in HBeAg-positive patients with qHBsAg titers of 14 × sqHBsAg [S/Co]−3.175; adjusted R2 = 0.6350; p < 0.001). Conclusions: There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL.

Hypoxia-inducible factor (HIF)-1 is an important regulator of the cellular response in the hypoxic tumor environment. While searching for HIF inhibitors derived from natural products that act as anticancer agents, we found that Glycyrrhiza uralensis exerts HIF-1 inhibitory activity in hypoxic cancer cells. Among the five components of G. uralensis, licochalcone A was found to potently suppress hypoxia-induced HIF-1α accumulation and expression of HIF-1α target genes, including GLUT1 and PDK1 in HCT116 cells. Licochalcone A also enhances intracellular oxygen content by directly inhibiting mitochondrial respiration, resulting in oxygen-dependent HIF-1α degradation. Hence, licochalcone A may effectively inhibit ATP production, primarily by reducing the mitochondrial respiration-mediated ATP production rate rather than the glycolysis-mediated ATP production rate. This effect subsequently suppresses cancer cell viability, including that of HCT116, H1299, and H322 cells. Consequently, these results suggest that licochalcone A has therapeutic potential in hypoxic cancer cells.

Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In wild-type (WT) mice injected AzA, GLP-1 plasma levels were elevated. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.

It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage. A total of 761 patients (RFA, n = 194; resection, n = 567) from Seoul National University Hospital (Seoul, South Korea) and 1277 patients (RFA, n = 352; resection, n = 925) from the Korean Primary Liver Cancer Registry were included in the hospital and nationwide cohorts, respectively. Primary and secondary endpoints were OS and recurrence-free survival (RFS), respectively. Additional analysis was performed when the history of the antiviral treatment and the type of prescribed nucleos(t)ide analogue were confirmed. The rate of complications was compared between the two treatment groups in the hospital cohort. Baseline characteristics were balanced, using inverse probability of treatment weighting (IPTW). In the hospital cohort, the RFA group had a smaller mean tumor size (1.7 vs. 3.9 cm) but a higher proportion of cirrhotic patients than the resection group (85.6% vs. 63.1%) (both p < 0.01). During 81.0 (interquartile range, 62.3–107.1) months of follow-up, there was no difference in OS (adjusted hazard ratio (aHR) = 0.870, 95% confidence interval (CI) = 0.400–1.897, p = 0.73) and RFA was associated with shorter RFS (aHR = 1.562, 95% CI = 1.099–2.219, p = 0.01) after employing IPTW. Antiviral treatment was independently associated with longer OS (aHR = 0.444, 95% CI = 0.251–0.786, p = 0.01) as well as RFS (aHR = 0.544, 95% CI = 0.391–0.757, p < 0.01) in the hospital cohort. In the nationwide cohort, there was no difference in OS (aHR = 0.981, 95% CI = 0.661–1.456, p = 0.92) between the two treatment groups when adjusted for antiviral treatment, which was a negative independent risk factor for mortality (aHR = 0.655, 95% CI = 0.451–0.952, p = 0.03) after IPTW. Among patients treated with tenofovir (n = 96) or entecavir (n = 184) in the hospital cohort, there was no difference in either OS (aHR = 0.522, 95% CI = 0.058–4.724, p = 0.56) or RFS (aHR = 1.116, 95% CI = 0.738–1.688, p = 0.60). The overall incidence of complications was higher in the resection group (26.3%) than in the RFA group (13.9%) (p < 0.01). RFA may provide comparable OS to resection in the treatment of very early or early HCC with a lower rate of complications, although RFS is marginally shorter than in the resection group after adjusting for antiviral treatment. Regardless of the type of NA, antiviral treatment in patients with HBV-related HCC is strongly associated with both OS and RFS.

Malignant hyperthermia (MH) may lead to metabolic crisis of skeletal muscle in susceptible individuals following exposure to triggering agents such as volatile anesthetics or depolarizing muscle relaxants. MH is a rare and a potentially lethal disease, which can lead to cardiac arrest. We report a case of severe MH, in which the rapidly evolving signs of hypermetabolism eventually resulted in cardiac arrest. Despite conventional treatments following cardiopulmonary resuscitation, the patient's vital signs did not improve. Therefore, we applied extracorporeal membrane oxygenation for providing hemodynamic support.

Anterior cervical osteophytes are commonly found in elderly patients, but rarely produce symptoms. When symptoms occur, they can range from mild symptoms of dysphagia, dysphonia, and foreign body sensation to severe symptoms of airway obstruction due to compression of the pharynx or larynx. We report the case of a 59-year-old man who underwent brain tumor surgery, and developed post-operative respiratory difficulty due to progressive pharyngo-laryngeal edema, requiring urgent endotracheal intubation, secondary to the presence of a previously asymptomatic anterior cervical osteophyte. It is paramount to recognize that asymptomatic anterior cervical osteophytes are a potential cause of life-threatening post-operative respiratory complications that can rapidly progress to life-threatening airway obstruction after surgeries in the prone position, especially in elderly patients.

This study investigated differences in the self-efficacy and clinical characteristics which were found relevant to addictive behaviors in young adults according to time spent gaming. To our knowledge, this is the first study to explore self-efficacy in casual gamers relative to patients with internet gaming disorder (IGD) and non-gamers. In total, 158 young adults participated in this study and were divided into three groups: excessive gamers, who were diagnosed with IGD based on the Diagnostic and Statistical Manual of Mental Disorder-fifth edition (DSM-5, n = 71); casual gamers, who played games regularly but did not meet the criteria for IGD (n = 37); and non-gamers/controls, who did not engage in gaming (n = 50). All participants completed self-administered questionnaires, including measures of self-efficacy and clinical features such as the Barratt Impulsiveness Scale, Beck Depression Inventory, Beck Anxiety Inventory, Behavioral Activation/Inhibition Systems, aggression, and psychosocial well-being. There were significant differences in the self-efficacy according to the extent of gaming (excessive gamers < casual gamers < non-gamers). In addition, aggression, impulsivity, depression, anxiety, level of stress, and behavioral inhibition system scores were significantly higher in excessive gamers than in casual gamers and non-gamers. These findings showed that individuals who spend more time playing games tend to have lower self-efficacy. Our study suggests that self-efficacy may protect against or constitute a risk of excessive gaming, particularly among casual gamers. It is necessary to pay attention to enhancing psychological well-being through self-efficacy to prevent addiction in young adult gamers.

Rice has been fermented to enhance its application in some foods. Although various microbes are involved in rice fermentation, their roles in the formation of volatile compounds, which are important to the characteristics of fermented rice, are not clear. In this study, diverse approaches, such as partial least squares-discriminant analysis (PLS-DA), metabolic pathway-based volatile compound formations, and correlation analysis between volatile compounds and microbes were applied to compare metabolic characteristics according to each microbe and determine microbe-specific metabolites in fermented rice inoculated by molds, yeasts, and lactic acid bacteria. Metabolic changes were relatively more activated in fermented rice inoculated by molds compared to other microbes. Volatile compound profiles were significantly changed depending on each microbe as well as the group of microbes. Regarding some metabolic pathways, such as carbohydrates, amino acids, and fatty acids, it could be observed that certain formation pathways of volatile compounds were closely linked with the type of microbes. Also, some volatile compounds were strongly correlated to specific microbes; for example, branched-chain volatiles were closely link to Aspergillus oryzae, while Lactobacillus plantarum had strong relationship with acetic acid in fermented rice. This study can provide an insight into the effects of fermentative microbes on the formation of volatile compounds in rice fermentation.

Introduction: Favorable responses to the treatment including immune checkpoint inhibitors (ICIs) have been consistently reported in lung cancer with smoking history. As the tumor microenvironment (TME) may be involved in the treatment response to ICIs, we aimed to investigate the TME of lung cancer with different smoking status. Methods: Lung adenocarcinoma (LUAD) tissue (Tu) and adjacent normalappearing lung tissue (NL) from current and never smokers were investigated by single-ce l l RNA sequencing and immunofluorescence and immunohistochemical staining. The clinical implications of identified biomarkers were validated using open-source datasets. Results: The lungs of smokers had an increased proportion of innate immune cells in NL tissues, whereas Tu tissues had a lower proportion of these cells than those of non-smokers. Monocyte-derived macrophages (mono-Mc), CD163-LGMN macrophages, monocyte-derived dendritic cells (DCs), and plasmacytoid DCs (pDCs) were significantly enriched in smokers' Tu. Among these clusters, pDCs, specifically enriched in the Tu of smokers. The expression of representative pDC markers, leukocyte immunoglobulin-like receptor A4 (LILRA4) and Toll-like receptor 9 (TLR9), was increased in the stromal cells of LUAD in patients with a smoking history. In an animal model of lung cancer, ionizing radiation induced robust TLR9 expressing immune cells in peritumoral area. Survival analysis using a TCGA-LUAD dataset indicated that patients overexpressing pDC markers exhibited superior clinical outcomes to age-, sex-, and smoking-matched control groups. Top 25% patients with high TLR9 expression exhibited significantly higher tumor mutational burden than that of low TLR9 expression group (bottom 25% patients) (5.81 mutations/Mb vs 4.36 mutations/Mb; P = 0.0059, Welch's two-sample t-test). Conclusion: There is an increased pDC in the TME of smokers' lung cancer, and the response of pDC to DNA damaging treatment would lead a conducive environment to ICIs containing regimens. These findings suggest that R&D that induces an increase in the activated pDC population is continuously required to enhance therapeutic effectiveness of ICIs-containing therapies in lung cancer. [ABSTRACT FROM AUTHOR]

Introduction: Although transarterial radioembolization (TARE) using yttrium-90 ( 90Y) is a treatment option for large hepatocellular carcinoma (HCC), a fraction of patients are ineligible for TARE due to high lung shunt fraction (LSF). Methods: We evaluated if treatment with transarterial chemoembolization (TACE), owing to TARE ineligibility was associated with early HCC progression. Consecutive patients with HCC who were initially TARE candidates were included. Patients with vascular invasion or metastasis were excluded. Primary endpoints were time-to-progression (TTP) and overall survival (OS). The secondary endpoint was objective response rate. Results: In total, 175 patients were included: 144 underwent TARE (TARE-eligible group) and 31 underwent TACE due to high LSF (TARE-ineligible group). This latter group had larger tumors (13.8 cm vs. 7.8 cm, P<0.001) and higher MoRAL scores (1,385.8 vs. 413.3, P=0.002) than the TARE-eligible group. After balancing baseline characteristics with an inverse probability of treatment weighting (IPTW), the TAREineligible group showed shorter TTP [adjusted hazard ratio (aHR)=2.16, 95% confidence interval (CI)=1.14–4.07, P=0.02] and OS (aHR=1.80, 95% CI=0.85–3.80, P=0.12), although the latter was not statistically significant. The TARE-ineligible group had a significantly lower objective response rate than the TARE-eligible group (9.7% vs. 56.9%, P<0.001). Conclusion: TARE-ineligible patients had larger tumors and higher MoRAL scores than TARE-eligible patients. Treatment with TACE, owing to high LSF, was associated with a shorter TTP even after balancing tumor size and MoRAL scores. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate health behavior related to particulate matter (PM) in older adults and examine the factors affecting it. Methods: A cross-sectional survey design was used. Data were collected from 150 voluntary older adult participants from Songpa-gu in Seoul. The survey questions measured service perception and experience related to PM, risk perception related to PM, attitude toward risk of PM, and health behavior related to PM. Results: The average score for health behavior related to PM was 79.37, ranging from 51 to 115. There was a significant positive correlation between health behavior related to PM and risk perception related to PM (r=.58, p<.001) as well as between health behavior related to PM and attitude toward risk of PM (r=.70, p<.001). Multiple linear regression revealed that health behavior related to PM was predicted by levels of the existence of disease related to PM (β=.14, p=.019), service experience related to PM (b=.20, p=.021), risk perception related to PM (b=.20, p=.019), and attitude toward risk of PM (b=.44, p<.001). The model including these variables accounted for 47.0% of health behavior related to PM. Conclusion: Korean older adults have the low level of health behavior related to PM. The findings of this study emphasize that risk perception and attitude toward risk of PM should be evaluated, and the underlying diseases related to PM and their service experience should be considered in developing intervention to improve health behavior related to PM. [ABSTRACT FROM AUTHOR]

Background: Fat intake has been associated with certain cancers, including colorectal, breast, and prostate cancers. However, literature on dietary fat and skin cancer has been limited. Methods: We examined the association between fat intake and risk of skin cancer including cutaneous malignant melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) within two prospective studies: the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Dietary information on total, saturated, monounsaturated, polyunsaturated, omega-6, and omega-3 fat and cholesterol was repeatedly assessed generally every 4 years. Incident cases were identified by self-report. Diagnosis on melanoma and SCC was confirmed by pathologic records. Results: A total of 794 melanoma, 2,223 SCC, and 17,556 BCC in the NHS (1984-2012) and 736 melanoma, 1,756 SCC, and 13,092 BCC in the HPFS (1986-2012) were documented. Higher polyunsaturated fat intake was associated with risk of SCC [pooled HR for highest vs. lowest quintiles, 1.16; 95% confidence interval (CI), 1.05-1.28; Ptrend=0.001] and BCC (pooled HR, 1.06; 95% CI, 1.01-1.11; Ptrend=0.01). Higher omega-6 fat intake was associated with risks of SCC, BCC, and melanoma. Omega-3 fat intake was associated with risk of BCC, but not with SCC or melanoma. No other fats were associated with melanoma risk. The associations were similar in women and men and by other skin cancer risk factors. Conclusions: Polyunsaturated fat intake was modestly associated with skin cancer risk. [ABSTRACT FROM AUTHOR]

Fever (body temperature above 38°C) is relatively common during the first few days after general anesthesia. Postoperative fever is usually caused by the inflammation induced by surgery and resolves spontaneously; however, it can be a manifestation of a serious complication such as malignant hyperthermia. We report a case of postoperative hyperthermia (body temperature > 40°C) that was refractory to conventional anti-pyretic measures and finally resolved with dantrolene administration. [ABSTRACT FROM AUTHOR]

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations. [ABSTRACT FROM AUTHOR]

Ginseng polysaccharide has been known to have multiple immunomodulatory effects. In this study, we investigated whether Panax ginseng polysaccharide (GP) would have a preventive effect on influenza infection. Administration of mice with GP prior to infection was found to confer a survival benefit against infection with H1N1 (A/PR/8/34) and H3N2 (A/ Philippines/82) influenza viruses. Mice infected with the 2009 H1N1 virus suspended in GP solution showed moderately enhanced survival rates and lower levels of lung viral titers and the inflammatory cytokine (IL-6). Daily treatment of vaccinated mice with GP improved their survival against heterosubtypic lethal challenge. This study demonstrates the first evidence that GP can be used as a remedy against influenza viral infection. [ABSTRACT FROM AUTHOR]

Asian populations including Koreans are assumed to have a higher isoflavone intake due to the higher consumption of soybean. However, it is difficult to estimate isoflavone intake because there is no isoflavone database in Korea. In this study, an isoflavone database was established with systematic review. Literature with analytical values of Korean soybeans and its products were collected and evaluated to establish an isoflavone database. A total of 142 food items containing isoflavones were selected among 2,932 food items in the Korean Nutrient Database. Among these, only 25 food items were evaluated with analytical values and the remaining 98 items were replaced with adaptations or calculations from similar items. Dietary intake of isoflavones was assessed for 426 boys and 365 girls aged 8 to 11 years with 3-day food records. The daily mean isoflavone intake was 8.3 mg among boys and 7.2 mg among girls. More than 70% of subjects had a daily isoflavone intake below 10 mg. The most contributory food item to the isoflavone intake among adolescents was tofu in quantity and soybean sauce in frequency. This database could be used to estimate isoflavone intakes from dietary data among various populations and to evaluate the relationships between isoflavone intake and chronic disease. [ABSTRACT FROM AUTHOR]

The Nagoya Protocol is an international agreement adopted in 2010 (and entered into force in 2014) which governs access to genetic resources and the fair and equitable sharing of benefits from their utilisation. The agreement aims to prevent misappropriation of genetic resources and, through benefit sharing, create incentives for the conservation and sustainable use of biological diversity. While the equitable sharing of the benefits arising from the utilisation of genetic resources is a widely accepted concept, the way in which the provisions of the Nagoya Protocol are currently being implemented through national access and benefit-sharing legislation places significant logistical challenges on the control of transboundary livestock diseases such as foot-and-mouth disease (FMD). Delays to access FMD virus isolates from the field disrupt the production of new FMD vaccines and other tailored tools for research, surveillance and outbreak control. These concerns were raised within the FMD Reference Laboratory Network and were explored at a recent multistakeholder meeting hosted by the European Commission for the Control of FMD. The aim of this paper is to promote wider awareness of the Nagoya Protocol, and to highlight its impacts on the regular exchange and utilisation of biological materials collected from clinical cases which underpin FMD research activities, and work to develop new epidemiologically relevant vaccines and other diagnostic tools to control the disease.

Ecklonia cava, a brown seaweed native to the East Asian coast, is known for its unique composition, including polysaccharides, polyphenols, and phlorotannins. Fucoidan is a sulfated polysaccharide widely used as a functional ingredient in foods. This study obtained crude polysaccharides (ECC_CPS) from E. cava celluclast enzymatic hydrolysate using ethanol precipitation. ECC_CPS increased cell viability during the proliferation of Hanwoo muscle satellite cells (HMSCs). The effect of ECC_CPS on the expression of proliferation-related markers was confirmed as MYF5 and MYOD expression significantly increased, whereas PAX7 expression was maintained. The evaluation of cell migration activity has a major impact on cell proliferation and differentiation, and the cell migration index significantly increased with ECC_CPS treatment (p < 0.01). This was related to the HGF/MET pathway and FAK pathway. Treatment with ECC_CPS promoted differentiation at the cell differentiation stage, thereby increasing the expression of differentiation markers, such as MYH2, MYH7, and MYOG (p < 0.001 or p < 0.01). Therefore, our findings imply that crude polysaccharide obtained from E. cava can be an additive ingredient that enhances the proliferation and differentiation of muscle satellite cells used in the manufacture of cultured meat products.

The study was conducted to investigate the association between nutrient intakes and change of bone mineral contents (BMC) among early pubertal aged girls. Two hundred and thirty girls between 9 to 11 years of age participated in four surveys over 2 year period. During each survey, dietary intakes were collected with 3-day food records and BMC of left leg's calcaneus were measured PIXI(Lunar Ltd.). Body composition was measured by bioimpedance method. Mean values of BMC increased in consecutive measurements -- 1.48g, 1.54g, 1.61g and 1.66g. The change of BMC between the first and last measurements was significantly correlated with age, % body fat, BMC at the baseline and mean isoflavone intake (p<0.05). In stepwise regression of BMC change, protein, Vit.C, Fe and Vit.B6 were significant explanatory variables(R²=0.25, p<.001, F=14.89) after adjusting for age, % body fat and BMC at baseline. The results imply that the change of BMC among early pubertal aged girls may be affected by intakes of certain nutrients. [ABSTRACT FROM AUTHOR]

Foot and mouth disease was the first disease for which, in 1996, the World Organisation for Animal Health (WOAH; founded as OIE) established an official list of disease-free territories, which has helped to facilitate the trade of animals and animal products from those territories. Since that year, there have been a number of suspensions of FMD-free status which have impacted the livestock industry of the territories affected. The objective of this study is to identify factors associated with the time taken to recover FMD-free status after suspension. Historical applications submitted (between 1996 and the first semester of 2020) by WOAH Members for recognition and recovery of FMD-free status were used as the main source of data. Only FMD-free status suspensions caused by outbreaks were considered. Data on the Member's socio-economic characteristics, livestock production systems, FMD outbreak characteristics, and control strategies were targeted for the analysis. The period of time taken to recover FMD-free status was estimated using Kaplan–Meier survival curves. A Cox proportional hazard model was used to identify factors associated with the time taken to recover FMD-free status after suspension. A total of 163 territories were granted official FMD-free status during the study period. The study sample consisted of 45 FMD-free status suspensions. Africa and the Americas accounted for over 50% of FMD-free status suspensions, while over 70% of these occurred in formerly FMD-free territories where vaccination was not practiced. The study noted that implementing a stamping-out or vaccination and remove policy shortened the time to recover FMD-free status, compared with a vaccination and retain policy. Other variables associated with the outcome were the income level of the Member, Veterinary Service capacity, time taken to implement control measures, time taken until the disposal of the last FMD case, whether the territory bordered FMD-infected territories, and time elapsed since FMD freedom. This analysis will contribute toward the understanding of the main determinants affecting the time to recover the FMD free status of WOAH Members and policy processes for FMD control and elimination.

Polyphenols and other compounds with antioxidant properties are found in plants and are one of the main antioxidants proven to reduce body weight and the risk of insulin resistance. Still, the mechanism behind the protective effects against obesity remains unclear. Thus, the study aims to assess the impact of flavonoid-rich arriheuk extract, a purple wheat extract, on mitochondrial function using 3T3-L1 adipocytes and investigate the molecular mechanism behind its protective effects against adipogenesis and lipolysis. The study findings strongly indicate that arriheuk significantly suppressed triglyceride levels and inhibited the expression of transcription factors like C/EBPα and PPARγ in 3T3-L1 adipocytes. Furthermore, treatment with arriheuk suppressed the expression of SREBP1c and FAS proteins linked to lipogenesis. In addition, treatment with arriheuk extract decreased the mRNA levels of adipogenic transcription factors, increased glycerol release, and inhibited adipocyte differentiation. Interestingly, the arriheuk-mediated PGC-1α expression triggered mitochondrial biogenesis by promoting the AMPK phosphorylation and SIRT1 expression in adipocytes. Also, arriheuk suppressed adipogenesis and elicited browning through the AMPK- and SIRT1-associated pathways. Collectively, these findings strongly suggest that arriheuk extract regulates browning in 3T3-L1 white adipocytes by triggering the AMPK/SIRT1 pathway, indicating the prospective applications of arriheuk as a functional food to control obesity.

Welsh onion (Allium fistulosum L.) is widely used in diverse Asian cuisines, especially in stir-fried and deep-fried foods. This study investigated the effects of different temperatures (140, 165, and 190 °C) and types of the vegetable frying oil (soybean, corn, canola, and palm oils) on the formation of volatile profiles and hazardous compounds [polycyclic aromatic hydrocarbons (PAHs) and acrylamide] in Welsh onion. Specific volatile chemical groups such as aldehydes, sulfur-containing compounds, and furans/furanones were major volatiles in Welsh onion fried (WOF). The composition of aldehydes and sulfur-containing compounds decreased, while those of furans/furanones increased when WOF samples were exposed to higher temperatures. At 190 °C, PAHs were detected at lower than the EU maximum tolerable limit (the sum of 4 PAHs,

Bacillus subtilis is often exposed to diverse culture conditions with the aim of improving hygiene or food quality. This can lead to changes in the volatile metabolite profiles related to the quality of fermented foods. To comprehensively interpret the associated metabolic expressions, changes in intracellular primary and extracellular secondary volatile metabolites were investigated by exposing B. subtilis to an alkaline pH (BP, pH 8.0) and a high salt concentration (BS, 1 M). In particular, B. subtilis was cultured in a leucine-enriched medium to investigate the formation of leucine-derived volatile metabolites. This study observed metabolic changes in several metabolic pathways, including carbohydrate metabolism, amino acid metabolism, fatty acid metabolism, and leucine degradation. The formation of proline (an osmolyte), furans, pyrrole, and monosaccharide sugars (glucose, galactose, and fructose) was enhanced in BS, whereas fatty acid derivatives (ketones and alcohols) increased in BP. In the case of leucine degradation, 3-methyl-butanal and 3-methylbutanol could be salt-specific metabolites, while the contents of 3-methylbutanoic acid and 3-methylbutylacetate increased in BP. These results show culture condition-specific metabolic changes, especially secondary volatile metabolites related to the sensory property of foods, in B. subtilis.

Background: The purpose of this study was to evaluate the prevalence of velamentous cord insertion (VCI) and the actual association between pathologically confirmed VCI and perinatal outcomes in twins based on the chorionicity. Methods: All twin pregnancies that received prenatal care at a specialty clinic for multiple pregnancies, from less than 12 weeks of gestation until delivery in a single institution between 2015 and 2018 were included in this retrospective cohort study. Results: A total of 941 twins were included in the study. The prevalence of VCI in dichorionic (DC) twins and monochorionic diamniotic (MCDA) twins was 5.8% and 7.8%, respectively (p = 0.251). In all study population, the prevalence of vasa previa and placenta accreta spectrum was higher in VCI group than that of non-VCI group (p = 0.008 and 0.022). In MCDA twins with VCI, birth weight, 1 and 5-min Apgar score were lower than DC twins with VCI (p = 0.010, 0.002 and 0.000). There was no significant association between VCI and selective fetal growth restriction (p = 0.486), twin-to-twin transfusion syndrome (p = 0.400), and birth-weight discordance (>20% and >25%) (p = 0.378 and 0.161) in MCDA twins. Conclusion: There was no difference in the incidence of VCI in twins based on the chorionicity. Moreover, VCI was not a risk factor for adverse perinatal outcomes excepting vasa previa and placenta accreta spectrum, which had a high incidence in twins with VCI.