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This article is linked to Chen et al papers. To view these articles, visit https://doi.org/10.1111/apt.17602 and https://doi.org/10.1111/apt.17767
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This article is linked to Papatheodoridis et al papers. To view these articles, visit https://doi.org/10.1111/apt.17093 and https://doi.org/10.1111/apt.17146
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer‐related deaths worldwide. Sarcomatoid HCC is a rare histological subtype of HCC with largely ...unclear clinical manifestations and outcomes. We evaluated the clinical manifestations and outcomes of patients with sarcomatoid HCC. We identified 5,047 patients with histologically proven HCC from the Cancer Registry Database (1996‐2016) of National Taiwan University Hospital. Among them, 40 patients with sarcomatoid HCC were identified from the pathology database of National Taiwan University Hospital. We included 160 patients with nonsarcomatoid HCC through propensity score matching according to sex, age, and Barcelona Clinic Liver Cancer stage. The majority of these patients with sarcomatoid HCC were men (75%); their median age was 58 years. Only 47.5% of the patients with sarcomatoid HCC presented with typical image patterns of HCC. The pathological grading of sarcomatoid HCC was more advanced compared with that of nonsarcomatoid HCC (42.5% vs. 23.8% in grade III and IV, P < 0.0001). The sarcomatoid group had significantly shorter median recurrence‐free (13.3 vs. 84.2 months, log‐rank P < 0.0001) and overall (8.3 vs. 69.3 months, log‐rank P < 0.0001) survival than did the nonsarcomatoid group. The results of the multivariable Cox proportional hazard model revealed histological sarcomatoid subtype as an independent factor for all‐cause mortality (hazard ratio HR, 6.47; 95% confidence interval CI, 3.12‐13.43; P < 0.0001) and tumor recurrence (HR, 4.08; 95% CI, 1.72‐9.66; P = 0.001). Conclusion: Compared with nonsarcomatoid HCC, sarcomatoid HCC was associated with more advanced histological grades and atypical image patterns. Histological sarcomatoid subtype is an independent predictor of tumor recurrence after curative treatment and all‐cause mortality in patients with HCC.
Linked ContentThis article is linked to Kuo et al and Huang et al papers. To view
these articles, visit https://doi.org/10.1111/apt.15053 and https://doi.org/10.1111/apt.15150.
•RNA editing of hepatitis delta virus genotype 2 and 4 involves the unbranched rod RNA•Editing rates are influenced by the base pairing surrounding of the editing site•Editing rates are controlled by ...the base pairing upstream of the editing core•The size of the upstream bulge of the editing site controls editing rates•Studying RNA editing across different genotypes offers insights into viral evolution
RNA editing of the hepatitis delta virus (HDV) is essential for generating the large delta antigen, which is crucial for virion assembly. In HDV genotype 1 (HDV-1), editing occurs within the context of the unbranched rod-like structure characteristic of HDV RNA, while RNA editing in HDV-3 requires a branched double-hairpin structure. The regulation of RNA editing in HDV-2 and HDV-4 remains uncertain. Based on predictions of the unbranched rod-like RNA structures of HDV-2 and HDV-4, the editing site occurs as an A.C mismatch pair, surrounded by four base pairs upstream and two base pairs downstream of the editing site, respectively. To investigate HDV-2 and HDV-4 RNA editing, cultured cells were transfected with non-replicating editing reporters carrying wild-type sequences or specific mutations. The results revealed that the editing rates observed for wild-type HDV-2 and HDV-4 were fairly similar, albeit lower than that of HDV-1. Like HDV-1, both HDV-2 and HDV-4 showed a reduction in editing rate when the A.C mismatch pair and the immediately upstream base-paired region were disturbed. Notably, extending the downstream base-paired region from two to three or four (forming a structure identical to that of HDV-1) base pairs increased editing rate. Furthermore, we presented novel evidence that indicates the importance of the first bulge's size, located upstream of the editing site, and the base-pairing length within 7–13 and 28-39 nucleotides downstream of the editing site in influencing the HDV-4 editing rate. To summarize, our analyses suggest that the unbranched rod-like structures surrounding the editing site of HDV-2 and HDV-4 play a crucial role in regulating their RNA editing rates.
Summary
Background
Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first‐line long‐term monotherapy for treatment of chronic hepatitis B (CHB) infection. High virological relapse rates ...are found after cessation of either ETV or TDF in CHB patients.
Aim
To compare hepatitis B virus (HBV) relapse rates in CHB patients without cirrhosis who discontinued ETV or TDF.
Methods
A retrospective‐prospective study was conducted in 342 CHB patients (108 hepatitis B e antigen (HBeAg)‐positive and 234 HBeAg‐negative) who received ETV and 165 (46 HBeAg‐positive, 119 HBeAg‐negative) who received TDF were recruited. All patients had post‐treatment follow‐up for at least 6 months. All fulfilled the stopping criteria of the Asia‐Pacific Association for the Study of the Liver of 2012.
Results
Patients who discontinued TDF had significantly higher rates and earlier times of virological and clinical relapse than those who discontinued ETV. This was also seen in propensity score (PS)‐matched HBeAg‐positive and HBeAg‐negative patients. Multivariate analysis showed that being in the TDF group was an independent factor for virological and clinical relapse in all patients and PS‐matched HBeAg‐positive and HBeAg‐negative patients. The rate of off‐therapy HBsAg loss was comparable between the ETV and TDF groups after 2‐3 years follow‐up. Clinical relapse tended to be more severe in the TDF group compared with the ETV group.
Conclusion
HBV relapse occurs sooner and is more severe after cessation of TDF than after cessation of ETV.
Herein, ruthenium (Ru) nanoparticles were anchored on carbon nanotubes (Ru/CNTs) functionalized as catalyst cathodes for non-aqueous Li–CO2 cells. For cycling tests through a low cut-off capacity ...(100 mA h g−1), the origin of battery deterioration resulted from the accumulation of Li2CO3 discharging products on catalytic surfaces, identical to the observations in previous studies. However, the Li–CO2 cells in this work showed a sudden death within several cycles of high cut-off capacity (500 mA h g−1), and no Li2CO3 residues were investigated on the cathode. In contrast, Li dendrites and passivation materials (LiOH and Li2CO3) were generated on Li anodes upon cycling at a limited capacity of 500 mA h g−1, which dominantly contributed to the battery degradation. A Li foil-replacement method was adopted to make the Ru/CNT cathode perform continuous 100 cycles under a cut-off capacity of 500 mA h g−1. These results indicate that not only Li2CO3 residues blocked on the active sites of the cathode but also Li dendrites and passivation materials produced on the anode caused Li–CO2 battery deterioration. Moreover, in the present work, a carbon thin film was deposited on Li metal (C/Li) by a sputtering system for suppressing the dendrite formation upon cycling and promoting the defense of the H2O attack from the electrolyte disintegration. The Li–CO2 cell with a Ru/CNT catalyst and a C/Li anode revealed an improved electrochemical stability of 115 cycles at a limited capacity of 500 mA h g−1. This proto strategy provided a significant research direction focusing on Li anodes for elevating the Li–CO2 battery durability.
Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and ...interpretation of pathway alteration patterns of individual patients.
We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets.
Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target.
Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between ...adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus
, family
, order
, and class
were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes
These results are different from research from western countries and could provide different targets for therapies by region.
Background: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in ...other regions.
Aim: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population.
Methodology: Data references were identified through indexed journals and non‐indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance.
Results: We estimated that 49.3–64.0 million adults in Asia, Australia and Egypt are anti‐HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria.
Conclusion: We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection.
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