Inter- and intra-subject variability pose a major challenge to decoding human brain activity in brain-computer interfaces (BCIs) based on non-invasive electroencephalogram (EEG). Conventionally, a ...time-consuming and laborious training procedure is performed on each new user to collect sufficient individualized data, hindering the applications of BCIs on monitoring brain states (e.g. drowsiness) in real-world settings. This study proposes applying hierarchical clustering to assess the inter- and intra-subject variability within a large-scale dataset of EEG collected in a simulated driving task, and validates the feasibility of transferring EEG-based drowsiness-detection models across subjects. A subject-transfer framework is thus developed for detecting drowsiness based on a large-scale model pool from other subjects and a small amount of alert baseline calibration data from a new user. The model pool ensures the availability of positive model transferring, whereas the alert baseline data serve as a selector of decoding models in the pool. Compared with the conventional within-subject approach, the proposed framework remarkably reduced the required calibration time for a new user by 90% (18.00 min–1.72 ± 0.36 min) without compromising performance (p = 0.0910) when sufficient existing data are available. These findings suggest a practical pathway toward plug-and-play drowsiness detection and can ignite numerous real-world BCI applications.
•A novel subject-transfer framework for reducing calibration time in brain state decoding.•Feasibility of cross-subject model transferring inferred from hierarchical clustering.•Robust decoding performance supported by large-scale existing data.•Significant decrease in calibration time using baseline brain activity.
MicroRNA miR-31 is implicated in the neoplastic process of various malignancies including oral squamous cell carcinoma (OSCC). Silent information regulator 3 (Sirtuin3 or SIRT3) is a NAD-dependent ...deacetylase that regulates metabolic process. Suppressor role of SIRT3 has been found in neoplasms. This study investigates the disruptions of miR-31-SIRT3 cascade to explore their potential association with metabolic change in OSCC. We identified that miR-31 directly targeted SIRT3 in OSCC cells, and a reverse correlation between miR-31 expression and SIRT3 expression was noted in OSCC tumors. SIRT3 expression attenuated the miR-31 enhanced tumor cell migration and invasion. It also reduced the tumorigenic potential of FaDu cell line. miR-31-SIRT3 impaired the mitochondrial membrane potential and structural integrity. The dis-regulation of this axis also contributed to the genesis of oxidative stress. In addition, miR-31 switched tumor cells from aerobic metabolism to glycolytic metabolism. This study provides novel evidences demonstrating the presence of miR-31-mediated post-transcriptional regulation of SIRT3 in OSCC. The disruption of miR-31-SIRT3 cascade and the consequential metabolic aberrances are involved in OSCC progression.
•miR-31 targets SIRT3 to drive OSCC invasion.•OSCC tumors exhibit miR-31 upregulation and SIRT3 downregulation.•miR-31-SIRT3 disruption underlies the mitochondrial disturbance.•miR-31-SIRT3 cascade induces ROS, glycolytic metabolism and lactate production.
Drowsy driving is one of the major causes that lead to fatal accidents worldwide. For the past two decades, many studies have explored the feasibility and practicality of drowsiness detection using ...electroencephalogram (EEG)based brain-computer interface (BCI) systems. However, on the pathway of transitioning laboratory-oriented BCI into real-world environments, one chief challenge is to obtain high-quality EEG with convenience and long-term wearing comfort. Recently, acquiring EEG from non-hair-bearing (NHB) scalp areas has been proposed as an alternative solution to avoid many of the technical limitations resulted from the interference of hair between electrodes and the skin. Furthermore, our pilot study has shown that informative drowsiness-related EEG features are accessible from the NHB areas. This study extends the previous work to quantitatively evaluate the performance of drowsiness detection using cross-session validation with widely studied machine-learning classifiers. The offline results showed no significant difference between the accuracy of drowsiness detection using the NHB EEG and the whole-scalp EEG across all subjects (p = 0.31). The findings of this study demonstrate the efficacy and practicality of the NHB EEG for drowsiness detection and could catalyze explorations and developments of many other real-world BCI applications.
To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC).
This was a matched-pair ...study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4-5 fractions over 4-5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses.
The median follow-up time was 14 months for all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size (≤4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable.
SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.
A recent trend in tourism research involves the application of high technology in marketing practices such as virtual reality (VR), cell phone apps, and new media. Among these, VR is the most novel. ...In 2016, Discovery Travel created TRVLR, which includes all seven continents. Even earlier, specific tourist destinations were providing VR content about their respective locales. These venues expose potential tourists to tourist locations by immersing them in a visceral, 360-degree storytelling setting. However, while VR has gradually grown in popularity in the tourism industry, the marketing effects have been infrequently studied by academia. This research asked participants to view a VR presentation of a famous 700-year-old Chinese painting, and investigated viewers' nostalgia and ST travel intentions. Information was collected from 308 samples at certain popular tourist destinations around Fuzhou in the Fujian Province of China, and Taipei and Taoyuan in Taiwan. Structural equation modeling was then used to analyze the collected data and test the hypotheses. The findings indicate that VR is a very useful tool for encouraging respondents to travel to Jinan in a slower and more intensely observational manner, significantly arousing their sense of nostalgia and leading to a strong intention to ST to Jinan. This research provides important insights into how this new technology might function as a tool for marketing Jinan, a tier-two but historically important destination in China. The implications of these findings are important to understanding the associations for potential tourists among VR use, destination marketing, and travel intention, particularly when the object city is relatively unknown.
•VR is a very useful tool for encouraging travel to Jinan in a slower and more intensely observational manner.•VR marketing for a tier-two city in China.•Build the model to understanding the associations for potential tourists among destination image, VR effects, nostalgia, destination marketing, and travel intention.
Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide. This study clarified the oncogenic role of miR‐134 in OSCC. Reporter assays, using both wild‐type and mutant constructs, ...confirmed that Programmed Cell Death 7 (PDCD7) gene was a potential target of miR‐134. The OSCC cells exogenously expressed miR‐134 exhibited reduced PDCD7 expression. As expected, exogenous miRZip‐134 expression increased PDCD7 expression in the OSCC cells; additionally, PDCD7 expression suppressed the oncogenicity of the OSCC cells. By contrast, PDCD7 knockout through gene editing increased in vitro oncogenicity and neck nodal metastasis in mice, and reduced E‐cadherin (E‐cad) expression. PDCD7 transactivated E‐cad expression via the GC‐box in the promoter. Moreover, miR‐134‐associated cellular transformation and E‐cad downregulation was attenuated by PDCD7. Downregulation of both PDCD7 and E‐cad and high levels miR‐134 expression was observed in OSCC tumor tissues. Activation of the miR‐134‐PDCD7‐E‐cad pathogenesis cascade occurred early during the human and murine oral carcinogenesis process. In conclusion, the oncogenic effect of miR‐134 in oral carcinoma is mediated by reducing PDCD7 and E‐cad expression.
What's new?
The functional roles of miR‐134 in malignant transformation are complicated and controversial to date. This study clarifies that miR‐134 targets Programmed Cell Death (PDCD) 7 to drive oncogenicity in oral squamous cell carcinoma. PDCD7 transactivates the expression of E‐cadherin, a head and neck squamous cell carcinoma progression marker, for oral carcinoma suppression. Knockout of PDCD7 increases the nodal metastasis of oral carcinoma xenografts in mouse model. The activation of miR‐134–PDCD7–E‐cad regulatory axis occurs in the early stage of oral carcinogenesis. This work shows the potential of miR‐134 inhibition and PDCD7 induction for oral carcinoma abrogation.
Splicing, a key step in the eukaryotic gene-expression pathway, converts precursor messenger RNA (pre-mRNA) into mRNA by excising introns and ligating exons. This task is accomplished by the ...spliceosome, a macromolecular machine that must undergo sequential conformational changes to establish its active site. Each of these major changes requires a dedicated DExD/H-box ATPase, but how these enzymes are activated remain obscure. Here we show that Prp28, a yeast DEAD-box ATPase, transiently interacts with the conserved 5' splice-site (5'SS) GU dinucleotide and makes splicing-dependent contacts with the U1 snRNP protein U1C, and U4/U6.U5 tri-snRNP proteins, Prp8, Brr2, and Snu114. We further show that Prp28's ATPase activity is potentiated by the phosphorylated Npl3, but not the unphosphorylated Npl3, thus suggesting a strategy for regulating DExD/H-box ATPases. We propose that Npl3 is a functional counterpart of the metazoan-specific Prp28 N-terminal region, which can be phosphorylated and serves as an anchor to human spliceosome.
Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of ...the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies. However, the following questions are still poorly understood: (i) how does metabolic reprogramming occur during HNSCC development? (ii) how does the tumorous milieu contribute to HNSCC tumourigenesis? and (iii) at the molecular level, how do various metabolic cues interact with each other to control the oncogenicity and therapeutic sensitivity of HNSCC? In this review article, the regulatory roles of different metabolic pathways in HNSCC and its microenvironment in controlling the malignancy are therefore discussed in the hope of providing a systemic overview regarding what we knew and how cancer metabolism could be translated for the development of anti-cancer therapeutic reagents.
Background
Bariatric surgery may be beneficial in mildly obese patients with poorly controlled diabetes. The optimal procedure to achieve diabetes remission is unknown. In 2011, we published the ...short-term results of a pilot study designed to evaluate the efficacy of diabetic control and the role of duodenal exclusion in mildly obese diabetic patients undergoing laparoscopic sleeve gastrectomy (SG) vs. a laparoscopic single anastomosis (mini-) gastric bypass (SAGB). This study analyzes the 5-year results and evaluates the incretin effect.
Methods
A double-blind randomized trial included 60 participants with a hemoglobin A1c (HbA1c) level higher than 7.5 %, a body mass index (BMI) between 25 and 35 Kg/m
2
, a C-peptide level ≥1.0 ng/mL, and a diagnosis of type 2 diabetes mellitus (T2DM) for at least 6 months. A SAGB with duodenal exclusion or a SG without duodenal exclusion was performed.
Results
The 5-year results of the primary outcome were as an intention-to-treat analysis for HbA1c ≤6.5 % without glycemic therapy. Assessments of the incretin effect and β cell function were performed at baseline and between 36 and 60 months. The patients were randomly assigned to SAGB (
n
= 30) and SG (
n
= 30). At 60 months, 18 participants (60 %; 95 % confidence interval (CI), 42 to 78 %) in the SAGB group and nine participants (30 %; 95 % CI, 13 to 47 %) in the SG group achieved the primary end points (odds ratio (OR), 0.3; 95 % CI, 0.1 to 0.8 %). The participants assigned to the SAGB procedure had a similar percentage of weight loss as the SG patients (22.8 ± 5.9 vs. 20.1 ± 5.3 %;
p
> 0.05) but achieved a lower level of HbA1c (6.1 ± 0.7 vs. 7.1 ± 1.2 %;
p
< 0.05) than the SG patients. There was a significant increase in the incretin effect before and after surgery in both groups, but the SAGB group had a higher incretin effect than the SG group at 5 years.
Conclusions
In mildly obese patients with T2DM, SG is effective at improving glycemic control at 5 years, but SAGB was more likely to achieve better glycemic control than SG and had a higher incretin effect compared to SG.
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