Background and Aim
Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) may reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). However, it is not clear whether there ...is difference in the on‐treatment HCC risks between ETV and TDF.
Methods
In this retrospective cohort study, we compared the on‐treatment HCC incidence of ETV and TDF in 1340 consecutive nucleos(t)ide analog‐naïve CHB patients by propensity score (PS) matching analysis. PS was calculated by using age, sex, drinking history, diabetes, liver cirrhosis, hepatitis B e antigen positivity, hepatitis B virus DNA, hepatitis B s antigen titer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha‐fetoprotein, albumin, bilirubin, prothrombin time, platelet count, and calendar year of treatment initiation as covariates. The HCC risk was assessed by Cox regression with death and liver transplantation as competing risks in the 1:1 PS‐matched cohorts (n = 596).
Results
TDF had higher cumulative virologic response (P = 0.027) whereas ETV showed higher AST and ALT normalization rates (P = 0.005 and < 0.001, respectively) in PS‐matched cohorts. HCC risk was similar between ETV and TDF, either by PS‐matching analysis (hazard ratio HR for TDF over ETV = 2.06, 95% confidence interval CI = 0.98–4.33, P = 0.058) or inverse probability of treatment weighting analysis (HR = 1.30, 95% CI = 0.81–2.10; P = 0.276).
Conclusions
ETV and TDF treatment was associated with similar risk for HCC development in CHB patients.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aconitum species (belonging to the Ranunculaceae) are well known herbaceous medicinal ingredients and have great economic value in Asian countries. However, there are still limited genomic resources ...available for Aconitum species. In this study, we sequenced the chloroplast (cp) genomes of two Aconitum species, A. coreanum and A. carmichaelii, using the MiSeq platform. The two Aconitum chloroplast genomes were 155,880 and 157,040 bp in length, respectively, and exhibited LSC and SSC regions separated by a pair of inverted repeat regions. Both cp genomes had 38% GC content and contained 131 unique functional genes including 86 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The gene order, content, and orientation of the two Aconitum cp genomes exhibited the general structure of angiosperms, and were similar to those of other Aconitum species. Comparison of the cp genome structure and gene order with that of other Aconitum species revealed general contraction and expansion of the inverted repeat regions and single copy boundary regions. Divergent regions were also identified. In phylogenetic analysis, Aconitum species positon among the Ranunculaceae was determined with other family cp genomes in the Ranunculales. We obtained a barcoding target sequence in a divergent region, ndhC-trnV, and successfully developed a SCAR (sequence characterized amplified region) marker for discrimination of A. coreanum. Our results provide useful genetic information and a specific barcode for discrimination of Aconitum species.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence ...(PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance.
Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers.
Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient's age, etiology and tumor invasiveness of HCC affected the performance of each marker.
AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition characterized by hepatic fat accumulation combined with underlying metabolic dysregulation. Having evolved from the ...previous term of nonalcoholic fatty liver disease (NAFLD), the term MAFLD more closely implicates the presence of overweight/obesity, type 2 diabetes, or metabolic dysregulation as essential pathogenic factors, leading to better identification of individuals with this metabolic liver disease. Low-grade inflammation, increased oxidative stress, mitochondrial dysfunction, and intestinal dysbiosis are also involved in its pathogenesis. MAFLD is not only associated with liver-related complications, but also with adverse cardiometabolic outcomes. Further studies are needed to assess whether the newly proposed definition of MAFLD is more accurate than the NAFLD in predicting the adverse liver-related and extrahepatic outcomes.
The term ‘nonalcoholic fatty liver disease’ (NAFLD) has several drawbacks; namely, an ambiguous overlap between simple steatosis and nonalcoholic steatohepatitis, and heterogeneity in interactions with other risk factors, making it difficult to predict its clinical effects.The new descriptor ‘metabolic dysfunction-associated fatty liver disease’ (MAFLD) is proposed to replace the term NAFLD, because it more closely implicates obesity and metabolic dysregulation, leading to better identification of individuals with metabolic liver disease.Metaflammation, oxidative stress, mitochondrial dysfunction, sarcopenia, and intestinal dysbiosis are also critically involved in the pathogenesis of MAFLD.To apply the term MAFLD in clinical practice, many challenging questions should be addressed in a holistic way through international cooperation between relevant medical specialists.Further research is needed to establish whether, and how, the proposed change to MAFLD impacts the risk of adverse hepatic and extrahepatic clinical outcomes.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Background and Aim
Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group ...remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS‐FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS‐FD.
Methods
Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5‐HTTLPR and ADRA2A 1291 G alleles and CCK‐1R intron 779T>C were assessed using a multivariate logistic regression model.
Results
A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS‐FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non‐overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS‐FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS‐FD overlap among FD patients. 5‐HTTLPR L/L was a risk factor for the co‐occurrence of IBS‐C among FD patients (OR: 12.47; 95% CI: 2.00–77.75; P = 0.007).
Conclusions
Bloating was a risk factor for IBS‐FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation‐dominant IBS.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Canine mammary gland tumor (CMT) is the most frequently diagnosed neoplasm in intact female dogs. As prognosis depends on the malignancy of tumors and metastasis levels, early and accurate diagnosis ...are crucial for prolongation of life expectancy. The genetic similarity of dogs with humans in addition to environmental and physiological similarities make them ideal models for the study of cancer. In this study, we analyzed differentially expressed microRNAs followed by RNA-Seq to investigate the alterations in mRNA levels based on the malignancy (benign, malignant) and the biopsy locations (tumors, surrounding normal tissues). We identified multiple breast cancer-related genes regardless of malignancy. We found cfa-miR-503 to be the only miRNA that showed altered expression in response to malignancy in CMTs. Although further validation is needed, cfa-miR-503 could be used as a potential diagnostic biomarker as well as a potential RNA-based anti-tumor drug in malignant CMTs.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of liver tumour that exhibits both hepatocytic and biliary differentiation within the same tumour. The histology and genomic ...alterations of recurrent/metastatic cHCC-CC are poorly understood. We selected six patients with cHCC-CC whose recurrent or metastatic tumours were histologically confirmed. Four patients with classic cHCC-CCs and two with intermediate cell carcinomas (ICs) were included. The clinicopathological features were evaluated, and next-generation sequencing was performed in 17 multiregional and longitudinal tumour samples. The histology of recurrent/metastatic lesions of classic cHCC-CCs was variable: hepatocellular carcinoma (HCC) was observed in one (25.0%) patient, cHCC-CC in one (25.0%) patient, and cholangiocarcinoma (CC) in two (50.0%) patients. Among 13 samples from four classic cHCC-CC patients, the most frequent pathological variants were TP53 (46.2%), TERT promoter (38.5%), ARID1A mutations (23.1%), and MET amplification (30.8%). In the sequencing analysis of each HCC and CC component, three (75.0%) of the four classic cHCC-CCs shared pathogenic variants. A large proportion of mutations, both pathogenic and those of undetermined significance, were shared by each HCC and CC component. Regarding ICs, the ATM mutation was detected in one patient. In conclusion, the histology of recurrent/metastatic cHCC-CCs was heterogeneous. Genomic profiling of classic cHCC-CCs revealed similar genomic alterations to those of HCC. Considerable overlapping genomic alterations in each HCC and CC component were observed, suggesting a monoclonal origin. Genetic alterations in ICs were different from those in either HCC or CC, suggesting the distinct nature of this tumour.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Apparently healthy individuals with elevated serum alpha-fetoprotein (AFP) levels (>7 ng/mL) for unknown causes visit clinics. We investigated their clinical characteristics, outcomes, and ...relationship with body fat deposition and muscle mass. The case group included asymptomatic 137 individuals with "elevated AFP level" (R772) diagnostic code from 2009 to 2018 in a tertiary hospital. The control group enrolled 274 age- and sex-matched patients with <5 cm hepatic hemangiomas. Hepatic, visceral, and psoas muscle adiposity and psoas muscle index (PMI) were measured in the subgroups of 45 cases and 90 controls with pre-contrast computed tomography (CT) images. The case group (mean age 47.5 years, male 35.8%) showed higher AFP levels (10.3 vs 2.5 ng/mL, p<0.001) and total bilirubin (0.8 vs 0.7 mg/dL, p<0.001), but a lower body mass index (22.2 vs 23.3 kg/m.sup.2, p = 0.011) and alanine aminotransferase levels (17.0 vs 19.0 IU/L, p = 0.047) than the controls. During 13 months of median follow-up, there was no cancer or liver disease development. The AFP levels were stable. In the subgroups with CT images, cases showed a lower proportion of hepatic steatosis (4.4% vs 18.9%, p = 0.023), higher psoas muscle attenuation (48.2 vs 43.8 Hounsfield units, p<0.001) and higher PMI (5.7 vs 4.2 cm.sup.2 /m.sup.2, p<0.001) than the controls. Elevated AFP levels in asymptomatic individuals may play a role in expressing a protective phenotype against hepatic steatosis, myosteatosis, and sarcopenia. AFP levels in patients with elevated AFP were stable during follow-up without liver injury or cancer development. Interaction between AFP expression and steatosis warrants further study.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dual clutch transmission (DCT) which can simultaneously improve acceleration performance and fuel efficiency compared to automatic transmissions (AT) and manual transmissions (MT) is one of the most ...noted studies in recent powertrain applications. However, much of energy consumption of clutch actuator reduces fuel efficiency of DCT-equipped vehicles. In order to reduce energy consumption of these actuators, a method of modifying mechanism and a method of improving it through control have been studied. However, the results of each study still use more energy or make the actuator less controllable. Thus, in this manuscript, we propose a ball-ramp DCT (BR-DCT) with a clutch actuator that changes mechanism to reduce power consumed by engagement and improve controllability. DCT is designed using the proposed structure and design parameter constraint selection method, and energy efficiency improvement effect of BR-DCT is verified through simulation. We also demonstrate effect of BR-DCT prototype on actuator energy saving through test bench experiment. As a result, clutch actuator of BR-DCT uses 84% less energy than conventional DCT and can improve vehicle fuel efficiency by 0.5%. In addition, since it has same characteristics as conventional DCT, it verifies that it can fully utilize controller developed previously.
PDF
