MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the ...miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.
Background
Although jaw asymmetry is commonly seen in skeletal Class III patients, its correlation with occlusal function and masticatory muscle activity has not been fully elucidated.
Objectives
The ...purpose of this study was to investigate the occlusal function and masticatory muscle activity in skeletal Class III patients with various patterns of mandibular asymmetry.
Methods
Forty‐two patients and 10 normal participants were examined. The patients were categorised into three groups. Groups 1 and 2 exhibited menton and ramus deviation to the same side. Menton deviation was larger than ramus deviation in Group 1, whereas Group 2 showed the inverse relation. Group 3 patients showed menton and ramus deviation in opposite directions. Occlusal contact area (OCA), relative bite force (RBF), and temporalis anterior (TA) and masseter muscle (MM) activity at maximum clenching were measured using T‐Scan Novus system and Bio‐EMG‐III. Statistical analysis was performed using the t‐test, one‐way analysis of variance with Bonferroni correction and Spearman correlation (α = .05).
Results
Compared with normal participants, the patients had smaller OCA and greater asymmetry in the distribution of masticatory muscle activity. Greater ramus deviation was associated with smaller OCA in Group 1 but with larger OCA in Group 3. In Group 1, greater menton deviation was related to stronger TA activity on the non‐deviation side. In Group 2, greater ramus deviation was related to stronger MM activity on the deviation side.
Conclusion
Deviation of the menton and ramus was individually related to OCA and masticatory muscle activity, and this relationship varied according to the pattern of mandibular asymmetry.
Skeletal Class III patients with jaw asymmetry had smaller occlusal contact and more imbalanced masticatory muscle activity. In various patterns of asymmetry, deviations of menton and ramus differentially correlated with occlusal contact and muscle activity.
Aspirin has been found to lower the occurrence rates of some cancers through the inhibition of the cyclooxygenase enzyme. For example, there is a well-known association between aspirin use and the ...occurrence of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers. However, the association, if any, between aspirin use and HCC in hepatitis C virus (HCV) carriers is unknown. Therefore, this study compared the occurrence rates of HCC in HCV carriers treated with or without aspirin.
The participants in this retrospective cohort study consisted of people newly diagnosed with HCV in Taiwan from 2000 to 2012. Those who were treated with aspirin were defined as the control group, whereas those not treated with aspirin were defined as the comparison cohort. We used a 1:1 propensity score matching by age, sex, comorbidities, drugs, diagnosis year, and index year with covariate assessment.
Our study sample consisted of 2980 aspirin-treated HCV carriers and 7771 non-aspirin-treated HCV carriers. After propensity score matching, each cohort consisted of 1911 HCV carriers. The adjusted hazard ratio (aHR) of HCC incidence in the aspirin users (aHR = 0.56, 95% CI = 0.43-0.72, p < 0.001) was significantly lower than that in the non-aspirin users. A Kaplan-Meier analysis showed that among the HCV carriers, the aspirin users had a lower cumulative incidence rate of HCC over the first 10 years of aspirin treatment (p < 0.0001).
The HCC incidence rate was lower in the aspirin-using HCV carriers than in the non- aspirin-using HCV carriers, indicating that the effects of aspirin might occur through inhibition of the cyclooxygenase enzyme pathway. Moreover, protection from HCC was provided by less than a year of aspirin treatment, while treatment with aspirin for 1 to 2 years exhibited the greatest protective effect. We therefore encourage aspirin treatment to prevent HCC in HCV carriers.
Using 7-hydroxy-1-indanone as a prototype (I), which exhibits excited-state intramolecular proton transfer (ESIPT), chemical modification has been performed at C(2)–C(3) positions by fusing benzene ...(molecule II) and naphthalene rings, (molecule III). I undergoes an ultrafast rate of ESIPT, resulting in a unique tautomer emission (λmax ∼530 nm), whereas excited-state equilibrium is established for both II and III, as supported by the dual emission and the associated relaxation dynamics. The forward ESIPT (normal to proton-transfer tautomer species) rates for II and III are deduced to be (30 ps)−1 and (22 ps)−1, respectively, while the backward ESIPT rates are (11 ps)−1 and (48 ps)−1. The ESIPT equilibrium constants are thus calculated to be 0.37 and 2.2 for II and III, respectively, giving a corresponding free energy change of 0.59 and −0.47 kcal/mol between normal and tautomer species. For III, normal and tautomer emissions in solid are maximized at 435 and 580 nm, respectively, achieving a white light generation with Commission Internationale de l’Eclairage (CIE) (0.30, 0.27). An organic light-emitting diode based on III is also successfully fabricated with maximum brightness of 665 cd m–2 at 20 V (885 mA cm–2) and the CIE coordinates of (0.26, 0.35). The results provide the proof of concept that the white light generation can be achieved in a single ESIPT system.
This study explores a novel area-selective passivation bonding technology utilizing gold, a crucial facilitator for heterogeneous integration, which fulfills the urgent demand for high-performance ...computing (HPC). This mask-free patterning bonding technology allows for chip bonding at ambient temperatures under 120 °C within a short timeframe, successfully mitigating copper oxidation and post-chemical mechanical polishing (CMP) dishing issues without additional high-cost lithography. The technology, with its area-selective features, proves versatile for a variety of bonding structures, such as copper pillars, interconnect Cu-Cu, and Cu/SiO2 bonding, circumventing lithography issues and streamlining the traditional metal passivation bonding process. Our investigation confirms the superior quality and robustness of these area-selective films, together with the robust electrical performance of both interconnect Cu-Cu and Cu/SiO2 hybrid bonding devices.
Background
Programmed death‐ligand 1 (PD‐L1) expression is associated with clinical outcomes of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (ADC) treated with tyrosine kinase ...inhibitors (TKIs). However, whether PD‐L1 expression plays a role in anaplastic lymphoma kinase (ALK)‐positive lung ADC is unknown. We aimed to evaluate the impact of PD‐L1 in patients with ALK‐positive lung ADC receiving crizotinib.
Materials and Methods
PD‐L1 expression was identified by immunohistochemistry (IHC). Reverse transcriptase‐polymerase chain reaction was used for ALK variant detection, and immunofluorescence‐based multiplex staining was applied for exploring immune cells in tumor microenvironments.
Results
A total of 78 patients with ALK‐positive advanced ADC were enrolled in our study, of whom 52 received crizotinib. Compared with EGFR/ALK wild‐type tumors, PD‐L1 expression was lower in ALK‐positive ADC. ALK fusion variants were identified in 32 patients, and those with variant 3 and 5 (short variants) had higher PD‐L1 expression than those with other variants. The crizotinib objective response rate (ORR) and progression‐free survival (PFS) was better in tumors with negative PD‐L1 expression (ORR/PFS in PD‐L1 0% vs. 1%–49% vs. 50%–100%: 60.7%/11.8 months vs. 38.5%/6.5 months vs. 36.4%/4.0 months, p = .007/.022). The multivariate Cox proportional hazards model revealed that PD‐L1 0% (vs. ≥1%) was an independent factor for longer PFS (adjusted hazard ratio 0.322, 95% confidence interval 0.160–0.650, p = .002). Multiplex IHC in three cases showed a varied extent of immune cell infiltrations in tumors with different PD‐L1 expression.
Conclusion
Positive PD‐L1 expression was associated with unfavorable clinical outcomes in patients with ALK‐positive lung ADC receiving crizotinib.
Implications for Practice
Not all lung adenocarcinoma with sensitizing driver mutations experienced durable responses to small‐molecule tyrosine kinase inhibitors (TKIs). Similar to the negative impact of programmed death‐ligand 1 (PD‐L1) in epidermal growth factor receptor mutant tumors treated with TKIs, this study demonstrated that positive PD‐L1 expression was also associated with worse response rate and shorter progression‐free survival of anaplastic lymphoma kinase (ALK)‐positive adenocarcinoma treated with crizotinib. Among different ALK fusion partners, tumors with short variants (V3 and V5) had higher PD‐L1 compared with long variants (V1, V2, and V6). Testing PD‐L1 before initiating crizotinib for ALK‐positive lung cancer could be a simple method to provide important prognostic information.
This article focuses on the effect of PD‐L1 on ALK‐positive lung adenocarcinoma and examines the association of pretreatment tumor PD‐L1 and clinical outcomes of patients receiving the first approved ALK inhibitor, crizotinib.
It is unclear whether dysbiosis in hepatitis C virus (HCV) infected patients results from the viral infection per se or develops as a result of hepatic dysfunction. We aimed to characterize ...compositions in gut microbiome before and shortly after HCV clearance. In this prospective cohort study, adult patients with confirmed HCV viremia were screened before receiving direct antiviral agents. Those with recent exposure to antibiotics or probiotics (within one month), prior abdominal surgery, or any malignancy were ineligible. Stool was collected before antiviral therapy started and at 12 weeks after the treatment completed. From the extracted bacterial DNA, 16 s rRNA gene was amplified and sequenced. Each patient was matched 1:2 in age and sex with uninfected controls. A total of 126 individuals were enrolled into analysis. The gut microbiome was significantly different between HCV-infected patients (n = 42), with or without cirrhosis, and their age-and sex-matched controls (n = 84) from the levels of phylum to amplicon sequence variant (all p values < 0.01 by principal coordinates analysis). All patients achieved viral eradication and exhibited no significant changes in the overall composition of gut microbiome following viral eradication (all p values > 0.5), also without significant difference in alpha diversity (all p values > 0.5). For the purpose of exploration, we also reported bacteria found differently abundant before and after HCV eradication, including Coriobacteriaceae, Peptostreptococcaceae, Staphylococcaceae, Morganellaceae, Pasteurellaceae, Succinivibrionaceae, and Moraxellaceae. Gut microbiota is altered in HCV-infected patients as compared with uninfected controls, but the overall microbial compositions do not significantly change shortly after HCV eradication.
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