Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free ...form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3
cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and is highly correlated with hepatitis virus infection. Our previous report shows that a DEAD box RNA helicase, ...DDX3, is targeted and regulated by hepatitis C virus (HCV) core protein, which implicates the involvement of DDX3 in HCV-related HCC development. In this study, the potential role of DDX3 in hepatocarcinogenesis is investigated by examining its expression in surgically excised human HCC specimens. Here we report the differential deregulation of DDX3 expression in hepatitis virus-associated HCC. A significant downregulation of DDX3 expression is found in HCCs from hepatitis B virus (HBV)-positive patients, but not from HCV-positive ones, compared to the corresponding nontumor tissues. The expression of DDX3 is differentially regulated by the gender and, moreover, there is a tendency that the downregulation of DDX3 expression in HCCs is more frequent in males than in females. Genetic knockdown of DDX3 with small interfering RNAs (siRNA) in a nontransformed mouse fibroblast cell line, NIH-3T3, results in a premature entry to S phase and an enhancement of cell growth. This enhanced cell cycle progression is linked to the upregulation of cyclin D1 and the downregulation of p21(WAF1) in the DDX3 knockdown cells. In addition, constitutive reduction of DDX3 expression increases the resistance of NIH-3T3 cells to serum depletion-induced apoptosis and enhances the ras-induced anchorage-independent growth, indicating the involvement of DDX3 in cell growth control. These findings together with the previous study suggest that the deregulation of DDX3, a DEAD box RNA helicase with cell growth-regulatory functions, is involved in HBV- and HCV-associated pathogenesis.
The Internet of things (IoT) combines different sources of collected data which are processed and analyzed to support smart city applications. Machine learning and deep learning algorithms play a ...vital role in edge intelligence by minimizing the amount of irrelevant data collected from multiple sources to facilitate these smart city applications. However, the data collected by IoT sensors can often be noisy, redundant, and even empty, which can negatively impact the performance of these algorithms. To address this issue, it is essential to develop effective methods for detecting and eliminating irrelevant data to improve the performance of intelligent IoT applications. One approach to achieving this goal is using data cleaning techniques, which can help identify and remove noisy, redundant, or empty data from the collected sensor data. This paper proposes a deep reinforcement learning (deep RL) framework for IoT sensor data cleaning. The proposed system utilizes a deep Q-network (DQN) agent to classify sensor data into three categories: empty, garbage, and normal. The DQN agent receives input from three received signal strength (RSS) values, indicating the current and two previous sensor data points, and receives reward feedback based on its predicted actions. Our experiments demonstrate that the proposed system outperforms a common time-series-based fully connected neural network (FCDQN) solution, with an accuracy of around 96% after the exploration mode. The use of deep RL for IoT sensor data cleaning is significant because it has the potential to improve the performance of intelligent IoT applications by eliminating irrelevant and harmful data.
Summary
Background
Controversy exists regarding glucocorticoids therapy and the risk of peptic ulcer bleeding (PUB).
Aim
The present study was undertaken to determine whether short‐term use ...of glucocorticoids is associated with the occurrence of peptic ulcer bleeding.
Methods
The records of adult patients hospitalised for newly diagnosed peptic ulcer bleeding from 2000 to 2012 were retrieved from the Taiwan National Health Insurance Research Database, a nationwide population‐based registry system. The association between systemic glucocorticoids usage and peptic ulcer bleeding was determined with a conditional logistic regression model comparing cases and controls during time windows of 7, 14 and 28 days using a case‐crossover design.
Results
Of the 8894 enrolled patients, the adjusted self‐matched odds ratios for peptic ulcer bleeding after exposure to the glucocorticoids were 1.37 (95% CI: 1.12–1.68, P = 0.003) for the 7‐day window, 1.66 (95% CI: 1.38–2.00, P < 0.001) for the 14‐day window and 1.84 (95% CI: 1.57–2.16, P < 0.001) for the 28‐day window. Moderate to high, but not low dose glucocorticoids (methylprednisolone <4 mg/day or its equivalence) were associated with an increased risk of peptic ulcer bleeding. Concomitant use of a nonselective nonsteroidal anti‐inflammatory drug (NSAID) or aspirin further elevated the risk. However, it does not eliminate the effect of underlying diseases flare‐up that may have placed the patients at risk for peptic ulcer bleeding in this kind of study design.
Conclusions
Short‐term (7–28 days) exposure to glucocorticoids is significantly associated with peptic ulcer bleeding; this risk seems dose‐dependent and is higher when nonselective NSAIDs or aspirin are used concurrently.
MicroRNA-224 (miR-224) is frequently over-expressed in liver and colorectal cancers. We and others have previously described the role of miR-224 over-expression in cell proliferation in vitro but we ...have yet to identify the relevant miR-224 direct target. In this study, we further demonstrated that miR-224 up-regulation promotes cell proliferation using both in vitro assays and in vivo tumor growth models. We systematically screened for high confidence miR-224 targets by overlapping in silico predicted targets from multiple algorithms and significantly down-regulated genes in miR-224-expressing cells from whole genome expression microarrays. A total of 72 high confidence miR-224 targets were identified and found to be enriched in various cancer-related processes. SMAD family member 4 (SMAD4) is experimentally validated as the direct cellular target through which miR-224 promotes cell proliferation. The clinical relevance of our experimental observations was supported by a statistically significant inverse correlation between miR-224 and SMAD4 transcript expression in tumor versus paired adjacent non-tumorous tissues from HCC patients (p<0.001, r= -0.45, R(2) =0.122). Furthermore, miR-224 up-regulation and SMAD4 down-regulation is significantly associated with poorer patient survival (p<0.05). In summary, miR-224/SMAD4 pathway is a clinically relevant pathway to provide new insights in understanding HCC. (191 words).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Evidence of false-positive galactomannan enzyme immunoassay (GM-EIA) results associated with intravenous immunoglobulin (IVIG) administration is scarce. Here, we aimed to determine the false-positive ...rate of GM-EIA after IVIG administration and to identify the related factors.
Standard GM-EIA was performed using diluted and pure human IVIG samples with and without heat treatment. We also included adult patients who had at least one GM-EIA result within 1 week of IVIG administration for analysis. Those who had prior invasive aspergillosis within 1 year before IVIG therapy were excluded. The clinical characteristics and galactomannan index (GMI) kinetics between patients with false-positive and true-positive GMI were compared.
All diluted and pure IVIG samples tested positive for GM. Heat treatment resulted in the considerable elevation of GMI. Of 48 patients with positive GM-EIA results within 1 week of IVIG administration, 22 (45.8%) were considered to have false-positive antigenaemia (false-positive group, FPG). After the completion of IVIG administration, a decline in GMI was observed in all FPG patients but in only 18 out of 26 patients (69.2%) with true-positive results (true-positive group, TPG). By 7, 14, and 18 days of IVIG administration, GMI reverted to negative values in 7/15 (46.7%), 18/20 (90%) and 22/22 (100%) FPG patients, respectively, and 6/24 (25%), 14/24 (58.3%), and 16/26 (61.5%) of TPG patients, respectively. The TPG was more likely to have two or more consecutively positive GMIs after IVIG administration than the FPG (adjusted odds ratio, 9.01; 95% confidence interval, 1.99–40.9).
IVIG treatment may produce false-positive GM-EIA results. A positive GMI among patients receiving human IVIG should be interpreted with caution.
Aims
The concept of using specific dietary components to selectively modulate the gut microbiota to confer a health benefit, defined as prebiotics, originated in 1995. In 2018, a group of scientists ...met at the International Scientific Association for Probiotics and Prebiotics annual meeting in Singapore to discuss advances in the prebiotic field, focussing on issues affecting functionality, research methodology and geographical differences.
Methods and Results
The discussion ranged from examining scientific literature supporting the efficacy of established prebiotics, to the prospects for establishing health benefits associated with novel compounds, isolated from different sources.
Conclusions
While many promising candidate prebiotics from across the globe have been highlighted in preliminary research, there are a limited number with both demonstrated mechanism of action and defined health benefits as required to meet the prebiotic definition. Prebiotics are part of a food industry with increasing market sales, yet there are great disparities in regulations in different countries. Identification and commercialization of new prebiotics with unique health benefits means that regulation must improve and remain up‐to‐date so as not to risk stifling research with potential health benefits for humans and other animals.
Significance and Impact of Study
This summary of the workshop discussions indicates potential avenues for expanding the range of prebiotic substrates, delivery methods to enhance health benefits for the end consumer and guidance to better elucidate their activities in human studies.
Purpose
Medial patellofemoral ligament (MPFL) reconstruction is often performed using gracilis autografts, which may be associated with donor site morbidity and complications. The use of a synthetic ...material can circumvent a harvest operation and has previously been demonstrated to be effective in other types of reconstructive procedures and may be effective in MPFL reconstruction. This study reports the clinical result with the use of a modern ultra-high molecular weight polyethylene with a braided jacket of polyester tape (FT) in MPFL reconstruction compared to using standard autografts.
Methods
Data were collected prospectively in 50 MPFL reconstructions. The first 27 underwent reconstruction using gracilis tendon (GT) autograft; the following 23 patients were treated with FT. All patients were clinically and radiologically assessed and underwent pre- and post-operative scoring using the Kujala score, Bartlett score, Tegner activity rating scale, SF-12 score and Lysholm score. Statistical significance was tested between groups using ANOVA with repeated measures.
Results
There were no significant differences in the pre-operative scores between the FT and GT groups (n.s.). Both groups showed significant improvements across all scoring modalities between pre- and post-operative periods 12, 24 and 48 months of follow-up (
p
< 0.05). There were no significant differences in knee function scores between the GT and FT groups.
Conclusion
The use of FiberTape in MPFL reconstruction is safe and effective, and it significantly improves patient’s quality of life and related post-operative outcome measures. There were no significant differences in all knee scores compared to GT autografts. Using this technique for MPFL reconstruction, tendon harvesting is unnecessary and hence eliminates donor site morbidity-associated complications.
Level of evidence
II.
Chronic hepatitis B virus (HBV) infection is epidemiologically associated with hepatocellular carcinoma (HCC), but its role in HCC remains poorly understood due to technological limitations. In this ...study, we systematically characterize HBV in HCC patients. HBV sequences were enriched from 48 HCC patients using an oligo-bead-based strategy, pooled together and sequenced using the FLX-Genome-Sequencer. In the tumors, preferential integration of HBV into promoters of genes (P < 0.001) and significant enrichment of integration into chromosome 10 (P < 0.01) were observed. Integration into chromosome 10 was significantly associated with poorly differentiated tumors (P < 0.05). Notably, in the tumors, recurrent integration into the promoter of the human telomerase reverse transcriptase (TERT) gene was found to correlate with increased TERT expression. The preferred region within the HBV genome involved in integration and viral structural alteration is at the 3'-end of hepatitis B virus X protein (HBx), where viral replication/transcription initiates. Upon integration, the 3'-end of the HBx is often deleted. HBx-human chimeric transcripts, the most common type of chimeric transcripts, can be expressed as chimeric proteins. Sequence variation resulting in non-conservative amino acid substitutions are commonly observed in HBV genome. This study highlights HBV as highly mutable in HCC patients with preferential regions within the host and virus genome for HBV integration/structural alterations.
Hypoxia-inducible factor 1 (HIF-1), a transcription factor that is critical for tumor adaptation to microenvironmental stimuli, represents an attractive chemotherapeutic target. YC-1 is a novel ...antitumor agent that inhibits HIF-1 through previously unexplained mechanisms. In the present study, YC-1 was found to prevent HIF-1α and HIF-1β accumulation in response to hypoxia or mitogen treatment in PC-3 prostate cancer cells. Neither HIF-1α protein half-life nor mRNA level was affected by YC-1. However, YC-1 was found to suppress the PI3K/Akt/mTOR/4E-BP pathway, which serves to regulate HIF-1α expression at the translational step. We demonstrated that YC-1 also inhibited hypoxia-induced activation of nuclear factor (NF)-κB, a downstream target of Akt. Two modulators of the Akt/NF-κB pathway, caffeic acid phenethyl ester and evodiamine, were observed to decrease HIF-1α expression. Additionally, overexpression of NF-κB partly reversed the ability of wortmannin to inhibit HIF-1α-dependent transcriptional activity, suggesting that NF-κB contributes to Akt-mediated HIF-1α accumulation during hypoxia. Overall, we identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1 expression.
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