LncRNA RUSC1-AS1 promotes the proliferation of hepatocellular carcinoma cells through modulating NOTCH signaling.

The long non-coding RNA (lncRNA) RUSC1-AS1 has been reported to be dysregulated in the progression of many cancers. Also, RUSC1-AS1 had been detected to be highly expressed in laryngeal squamous cell carcinoma and breast cancer cells, suggesting that RUSC1-AS1 may be a biomarker for cancers. However, the biological role and regulatory mechanism of RUSC1-AS1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we found that RUSC1-AS1 was upregulated in HCC tissues and cells, and predicted unfavorable prognosis of HCC patients. The function assays including colony formation, EdU, TUNEL assay revealed that RUSC1-AS1 facilitated HCC cell proliferation and inhibited HCC cell apoptosis. Furthermore, mechanism assays including luciferase reporter assay and RIP assay demonstrated that RUSC1-AS1 could directly bind to hsa-miR-7-5p. Besides, hsa-miR-7-5p targeted and negatively regulated NOTCH3 expression. Moreover, RUSC1-AS1 sponged hsa-miR-7-5p to upregulate NOTCH3 and to trigger the NOTCH signaling pathway. The rescue assays depicted that RUSC1-AS1 regulated HCC cell proliferation and apoptosis through modulating NOTCH signaling. In conclusion, lncRNA RUSC1-AS1 promoted the proliferation and reduced the apoptosis of HCC cells through activation of NOTCH signaling via hsa-miR-7-5p/NOTCH3 axis.

Predictive Value of Noncontrast Head CT with Negative Findings in the Emergency Department Setting.

BACKGROUND AND PURPOSE: Noncontrast head CTs are routinely acquired for patients with neurologic symptoms in the emergency department setting. Anecdotally, noncontrast head CTs performed in patients with prior negative findings with the same clinical indication are of low diagnostic yield. We hypothesized that the rate of acute findings in noncontrast head CTs performed in patients with a preceding study with negative findings would be lower compared with patients being imaged for the first time. MATERIALS AND METHODS: We retrospectively evaluated patients in the emergency department setting who underwent noncontrast head CTs at our institution during a 4-year period, recording whether the patient had undergone a prior noncontrast head CT, the clinical indication for the examination, and the examination outcome. Positive findings on examinations were defined as those that showed any intracranial abnormality that would necessitate a change in acute management, such as acute hemorrhage, hydrocephalus, herniation, or interval worsening of a prior finding. RESULTS: During the study period, 8160 patients in the emergency department setting underwent a total of 9593 noncontrast head CTs; 88.2% (7198/8160) had a single examination, and 11.8% (962/8160) had at least 1 repeat examination. The baseline positive rate of the "nonrepeat" group was 4.3% (308/7198). The 911 patients in the "repeat" group with negative findings on a baseline/first CT had a total of 1359 repeat noncontrast head CTs during the study period. The rate of positive findings for these repeat examinations was 1.8% (25/1359), significantly lower than the 4.3% baseline rate (P < .001). Of the repeat examinations that had positive findings, 80% (20/25) had a study indication that was discordant with that of the prior examination, compared with only 44% (593/1334) of the repeat examinations that had negative findings (P < .001). CONCLUSIONS: In a retrospective observational study based on approximately 10,000 examinations, we found that serial noncontrast head CT examinations in patients with prior negative findings with the same study indication are less likely to have positive findings compared with first-time examinations or examinations with a new indication. This finding suggests a negative predictive value of a prior noncontrast head CT examination with negative findings with the same clinical indication.

Is skeletal stability after bimaxillary surgery for skeletal class III deformity related to surgical occlusal contact?

A stable occlusion at the time of surgery is considered important for post-surgical stability after orthognathic surgery. The aim of this study was to determine whether skeletal stability after bimaxillary surgery using a surgery-first approach for skeletal class III deformity is related to the surgical occlusal contact or surgical change. Forty-two adult patients with a skeletal class III deformity corrected by Le Fort I osteotomy and bilateral sagittal split osteotomy with a surgery-first approach were studied. Dental models were set and used to measure the surgical occlusal contact, including contact distribution, contact number, and contact area. Cone beam computed tomography was used to measure the surgical change (amount and rotation) and post-surgical skeletal stability. The relationship between skeletal stability and surgical occlusal contact or surgical change was evaluated. No relationship was found between maxillary or mandibular stability and surgical occlusal contact. However, a significant relationship was found between maxillary and mandibular stability and the amount and rotation of surgical change. The results suggest that in the surgical-orthodontic correction of skeletal class III deformity with a surgery-first approach, the post-surgical skeletal stability is not related to the surgical occlusal contact but is related to the surgical change.

10-Qubit Entanglement and Parallel Logic Operations with a Superconducting Circuit.

Here we report on the production and tomography of genuinely entangled Greenberger-Horne-Zeilinger states with up to ten qubits connecting to a bus resonator in a superconducting circuit, where the resonator-mediated qubit-qubit interactions are used to controllably entangle multiple qubits and to operate on different pairs of qubits in parallel. The resulting 10-qubit density matrix is probed by quantum state tomography, with a fidelity of 0.668±0.025. Our results demonstrate the largest entanglement created so far in solid-state architectures and pave the way to large-scale quantum computation.

Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression.

Tumor cells often produce high levels of reactive oxygen species (ROS) and display an increased ROS scavenging system. However, the molecular mechanism that balances antioxidative and oxidative stress in cancer cells is unclear. Here, we determined that oncogenic multiple copies in T-cell malignancy 1 (MCT-1) activity promotes the generation of intracellular ROS and mitochondrial superoxide. Overexpression of MCT-1 suppresses p53 accumulation but elevates the manganese-dependent superoxide dismutase (MnSOD) level via the YY1-EGFR signaling cascade, which protects cells against oxidative damage. Conversely, restricting ROS generation and/or targeting YY1 in lung cancer cells effectively inhibits the EGFR-MnSOD signaling pathway and cell invasiveness induced by MCT-1. Significantly, MCT-1 overexpression in lung cancer cells promotes tumor progression, necrosis and angiogenesis, and increases the number of tumor-promoting M2 macrophages and cancer-associated fibroblasts in the microenvironment. Clinical evidence further confirms that high expression of MCT-1 is associated with an increase in YY1, EGFR and MnSOD expression, accompanied by tumor recurrence, poor overall survival and EGFR mutation status in patients with lung cancers. Together, these data indicate that the MCT-1 oncogenic pathway is implicated in oxidative metabolism and lung carcinogenesis.

Self-adjustment and disintegration threshold of Langmuir solitons in inhomogeneous plasmas.

Dynamics of Langmuir solitons in the presence of a background density gradient is investigated numerically, including cases with steep gradients to the extent the solitons can disintegrate. The disintegration threshold is explained by regarding the electric field part of the soliton as a point mass moving along the self-generated potential well corresponding to the density cavity. On the other hand, it is demonstrated that the Langmuir solitons are robust when the density gradient is below the threshold. During the acceleration phase toward low density regions, Langmuir solitons adjust themselves to balance the electric field pressure and the negative plasma pressure by expelling the imbalanced portion as density cavities at the sound velocity. When the density gradient is below the disintegration threshold, the electric field part of the soliton bounces back and forth within the potential well suggesting the solitons have internal structures.

Comparison of different hypotensive anaesthesia techniques in orthognathic surgery with regard to intraoperative blood loss, quality of the surgical field, and postoperative nausea and vomiting.

Sixty-three consecutive patients undergoing bimaxillary surgery between June and August 2015 were included in this study. Twenty-one patients were included in each of three study groups. In group 1, sevoflurane was the sole maintenance anaesthesia agent used; in group 2, propofol was the predominant agent, in addition to a reduced amount of sevoflurane; in group 3, patients received sevoflurane until fixation was completed, at which point it was switched to propofol. The mean intraoperative blood loss (ml) was 707.14±290.74 in group 1, 917.62±380.30 in group 2, and 750.00±331.84 in group 3; the difference between groups 1 and 2 was significant (P=0.047). The mean score for the quality of surgical field assessment was 1.32±0.44 in group 1, 2.04±0.49 in group 2, and 1.45±0.53 in group 3 (P=0.003). The postoperative nausea and vomiting (PONV) rate was 28.6% in group 1, 9.5% in group 2, and 14.3% in group 3 (P=0.343). The quality of the surgical field was significantly better in groups 1 and 3 than in group 2. The average blood loss in group 1 was also significantly less than in group 2. The PONV rates were lower than those reported in other studies.

Pre-surgical regional blocks in orthognathic surgery: prospective study evaluating their influence on the intraoperative use of anaesthetics and blood pressure control.

In orthognathic surgery, maxillary (CNV2) and mandibular (CNV3) divisions of the trigeminal nerve can be blocked successfully prior to surgery. In this study, it was hypothesized that regional blocks (nerve block over a particular region: bilateral CNV2 and CNV3 divisions of the trigeminal nerve) would decrease the total requirement for intraoperative anaesthetic agents and facilitate the process of hypotensive anaesthesia. Local anaesthesia containing 1/100,000 epinephrine and 10ml 0.5% levobupivacaine was injected into the planned incisions in 50 patients. Twenty-five patients (group A) underwent orthognathic surgery without regional blocks and another 25 patients (group B) underwent surgery with regional blocks. The anaesthetic protocol was the same in both groups and administered by a single anaesthesiologist. The mean arterial pressure was recorded at several points throughout the operation, as well as all the medications used. The blood loss and the amounts of medications administered were lower in group B than in group A. In patients receiving regional blocks, the amounts of fentanyl and nicardipine required were significantly lower. The use of pre-emptive anaesthesia in orthognathic surgery may reduce the overall amounts of medications required for hypotensive anaesthesia, facilitate the intraoperative control of blood pressure, and decrease intraoperative blood loss.

Fibronectin induction abrogates the BRAF inhibitor response of BRAF V600E/PTEN-null melanoma cells.

The mechanisms by which some melanoma cells adapt to Serine/threonine-protein kinase B-Raf (BRAF) inhibitor therapy are incompletely understood. In the present study, we used mass spectrometry-based phosphoproteomics to determine how BRAF inhibition remodeled the signaling network of melanoma cell lines that were BRAF mutant and PTEN null. Short-term BRAF inhibition was associated with marked changes in fibronectin-based adhesion signaling that were PTEN dependent. These effects were recapitulated through BRAF siRNA knockdown and following treatment with chemotherapeutic drugs. Increased fibronectin expression was also observed in mouse xenograft models as well as specimens from melanoma patients undergoing BRAF inhibitor treatment. Analysis of a melanoma tissue microarray showed loss of PTEN expression to predict for a lower overall survival, with a trend for even lower survival being seen when loss of fibronectin was included in the analysis. Mechanistically, the induction of fibronectin limited the responses of these PTEN-null melanoma cell lines to vemurafenib, with enhanced cytotoxicity observed following the knockdown of either fibronectin or its receptor α5ß1 integrin. This in turn abrogated the cytotoxic response to BRAF inhibition via increased AKT signaling, which prevented the induction of cell death by maintaining the expression of the pro-survival protein Mcl-1. The protection conveyed by the induction of FN expression could be overcome through combined treatment with a BRAF and PI3K inhibitor.

NSD1 mutations generate a genome-wide DNA methylation signature.

Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase, NSD1. As layered epigenetic modifications are often interdependent, we propose that pathogenic NSD1 mutations have a genome-wide impact on the most stable epigenetic mark, DNA methylation (DNAm). By interrogating DNAm in SS patients, we identify a genome-wide, highly significant NSD1(+/-)-specific signature that differentiates pathogenic NSD1 mutations from controls, benign NSD1 variants and the clinically overlapping Weaver syndrome. Validation studies of independent cohorts of SS and controls assigned 100% of these samples correctly. This highly specific and sensitive NSD1(+/-) signature encompasses genes that function in cellular morphogenesis and neuronal differentiation, reflecting cardinal features of the SS phenotype. The identification of SS-specific genome-wide DNAm alterations will facilitate both the elucidation of the molecular pathophysiology of SS and the development of improved diagnostic testing.

Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS).

WHAT IS KNOWN AND OBJECTIVE: Febuxostat is recommended as an alternative drug for gouty patients with a history of allopurinol hypersensitivity or carrying the HLA-B*5801 allele. CASE SUMMARY: An 81-year-old man with the medical history of gout presented to our clinic with generalized rashes for 2 days. After taking febuxostat for 2 days, he developed generalized skin rash with high fever. Laboratory tests showed elevated liver enzymes and acute kidney injury. WHAT IS KNOWN AND OBJECTIVE: This is the first identified case of febuxostat-associated DRESS. Febuxostat should be withdrawn immediately when DRESS is observed to avoid further serious complications.

Modified maxillomandibular advancement for obstructive sleep apnoea: towards a better outcome for Asians.

Excluding tracheostomy, maxillomandibular advancement (MMA) is the most effective surgical treatment for obstructive sleep apnoea (OSA). However, the anticipated facial changes may prevent acceptance of this procedure by patients with bimaxillary protrusion, a common feature of Asian faces. We therefore developed a modified MMA technique for such cases, consisting of anterior segmental osteotomies together with standard Le Fort I and bilateral sagittal split osteotomies. A prospective study of 20 consecutive Taiwanese adults with moderate-to-severe OSA who underwent modified MMA and postsurgical orthodontics was undertaken to evaluate the efficacy with regard to OSA and the postoperative facial appearance and dental occlusion. After modified MMA, the mean apnoea-hypopnoea index decreased from 41.6±19.2 n/h to 5.3±4.0 n/h (P<0.001). All patients had a successful outcome. No patient was dissatisfied with their postoperative facial appearance. The mean Peer Assessment Rating score decreased from 21.9±14.3 to 1.7±1.6 (P=0.001). The data suggest that the modified MMA is effective in treating patients with moderate-to-severe OSA without negatively affecting facial appearance or dental occlusion. To achieve a better outcome, surgical-orthodontic integration is warranted. The surgery-first approach can achieve early improvement.

Does Ethnic Variability Exist in the Systemic Exposures of OATP1A2 Substrates-Fexofenadine in Taiwanese?

The aim of this study was to investigate differences in organic anion transporting polypeptide 1A2 activity among the Taiwanese population via an analysis of 3 pharmacokinetic studies completed in a total of 103 healthy male Taiwanese subjects. The pharmacokinetics of fexofenadine was measured as an indicator of organic anion transporting polypeptide 1A2 activity. Using the Kolmogorov-Smirnov test and quantile plots, the frequency distributions of area under the concentration-time curve and concentration were shown to be tri-modal and to represent 3 pharmacokinetic phenotypes. In a comparison with published data, the mean area under the concentration-time curve of fexofenadine in the Taiwanese subjects was similar to that in American, German, and Indian subjects, but significantly different from that in some Asian populations, including Korean and Japanese ethnic groups. These results suggested that Taiwanese subjects showed genetic variation in fexofenadine pharmacokinetics that was associated with differences in organic anion transporting polypeptide 1A2 activity.

MCT-1 expression and PTEN deficiency synergistically promote neoplastic multinucleation through the Src/p190B signaling activation.

Multinucleation is associated with malignant neoplasms; however, the molecular mechanism underlying the nuclear abnormality remains unclear. Loss or mutation of PTEN promotes the development of malignant tumors. We now demonstrate that increased expression of the oncogene MCT-1 (multiple copies in T-cell malignancy 1) antagonizes PTEN gene presentation, PTEN protein stability and PTEN functional activity, thereby further promoting phosphoinositide 3 kinase/AKT signaling, survival rate and malignancies of the PTEN-deficient cells. In the PTEN-null cancer cells, MCT-1 interacts with p190B and Src in vivo, supporting that they are in proximity of the signaling complexes. MCT-1 overexpression and PTEN loss synergistically augments the Src/p190B signaling function that leads to inhibition of RhoA activity. Under such a condition, the incidence of mitotic catastrophes including spindle multipolarity and cytokinesis failure is enhanced, driving an Src/p190B/RhoA-dependent neoplastic multinucleation. Targeting MCT-1 by the short hairpin RNA markedly represses the Src/p190B function, improves nuclear structures and suppresses xenograft tumorigenicity of the PTEN-null breast cancer cells. Consistent with the oncogenic effects in vitro, clinical evidence has confirmed that MCT-1 gene stimulation is correlated with p190B gene promotion and PTEN gene suppression in human breast cancer. Accordingly, MCT-1 gene induction is recognized as a potential biomarker of breast tumor development. Abrogating MCT-1 function may be a promising stratagem for management of breast cancer involving Src hyperactivation and/or PTEN dysfunction.

Tobacco control in Vietnam.

OBJECTIVES: To investigate the use of tobacco in Vietnam. STUDY DESIGN: Review study. METHODS: Data were collected through a review of tobacco-related literature in Vietnam. Grey literature and web content from agencies such as the World Health Organization and the US Centers for Disease Control and Prevention were consulted. RESULTS: Tobacco smoking is still common in Vietnam, although numerous policies have been issued and implemented over the last two decades. Based on the most recent data (2010), the prevalence of smoking among adults aged >15 years was 23.8%, with a higher percentage among males (47.4%) than females (1.4%). The prevalence of smoking among students aged 13-15 was 3.8% (2007), with a similar gender pattern. The prevalence of exposure to secondhand smoke is of concern, with 73.1% and 55.9% of adults reporting exposure to secondhand smoke at home and at work or other places, respectively. Of the adult respondents, 55.5% believed that smoking may cause lung cancer, stroke and heart disease. Most students (93.4%) and adults (91.6%) had seen anti-smoking media messages. Of the students, 56.4% had seen pro-cigarette advertisements on billboards, 36.9% had seen pro-cigarette advertisements in newspapers or magazines, and 8.2% had been offered free cigarettes by tobacco company representatives. The price of cigarettes decreased by approximately 5% between 1995 and 2006, whereas gross domestic product per capita increased by more than 150%. On average, smokers smoked 13.5 cigarettes per day, and spent US$86 on cigarettes per year. Despite such high levels of tobacco exposure in Vietnam, the total tax on cigarettes remains at 45% of the retail price. Furthermore, only 29.7% of smokers had been advised to quit by a healthcare provider in the past 12 months. CONCLUSION: Strong enforcement and evidence-based regulations which rounded on MPOWER are needed to help protect current smokers and non-smokers from the devastating effects of tobacco.

The role of the occipital artery in the diagnosis of intracranial dural arteriovenous fistula using duplex sonography.

BACKGROUND AND PURPOSE: The occipital artery is usually a main feeding artery of an intracranial dural arteriovenous fistula. The aim of this study was to establish the role of the OA in the diagnosis of DAVFs by using duplex sonography. MATERIALS AND METHODS: We first compared the clinical features between patients with DAVFs having and not having the OA as one of feeding arteries in 181 consecutive patients with DAVFs. Second, we investigated the OA by using duplex sonography in 60 control subjects to test the accessibility. Finally, we studied 24 DAVF and 60 non-DAVF patients to validate the diagnostic performances of duplex sonography. Hemodynamic parameters, including the resistance index and flow velocity, were analyzed. RESULTS: Half of the DAVFs (51%) had the OA as one of feeding arteries. DAVFs with the OA as one of the feeders were more likely located at noncavernous sinuses; to belong to types IIb, IIa+b, III, IV, or V; and to be associated with aggressive manifestations compared with DAVFs without the OA as a feeder (P < .05). Accessibility of the OA by using duplex sonography was 100%. The resistance index was lower and flow velocity was higher in the OA among patients with DAVFs compared with control subjects (P < .001). An OA resistance index <0.76 yielded a sensitivity and specificity of 96% and 97%, respectively, for the diagnosis of a DAVF. CONCLUSIONS: The OA resistance index can be used to screen for DAVFs having the OA as one of feeding arteries, and this kind of DAVF was usually associated with nonbenign clinical courses.

Experimental realization of plaquette resonating valence-bond states with ultracold atoms in optical superlattices.

The concept of valence-bond resonance plays a fundamental role in the theory of the chemical bond and is believed to lie at the heart of many-body quantum physical phenomena. Here we show direct experimental evidence of a time-resolved valence-bond quantum resonance with ultracold bosonic atoms in an optical lattice. By means of a superlattice structure we create a three-dimensional array of independent four-site plaquettes, which we can fully control and manipulate in parallel. Moreover, we show how small-scale plaquette resonating valence-bond (RVB) states with s- and d-wave symmetry can be created and characterized. We anticipate our findings to open the path towards the creation and analysis of many-body RVB states in ultracold atomic gases.

TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death.

Self-aggregation of transforming growth factor ß (TGF-ß)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid ß (Aß) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aß in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aß aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aß. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aß formation. TIAF1 is known to suppress SMAD-regulated promoter activation. Intriguingly, without p53, self-aggregating TIAF1 spontaneously activated the SMAD-regulated promoter. TIAF1 was essential for p53-, WOX1- and dominant-negative JNK1-induced cell death. TIAF1, p53 and WOX1 acted synergistically in suppressing anchorage-independent growth, blocking cell migration and causing apoptosis. Together, TIAF1 shows an aggregation-dependent control of tumor progression and metastasis, and regulation of cell death.

Landau-Zener sweeps and sudden quenches in coupled Bose-Hubbard chains.

We simulate numerically the dynamics of strongly correlated bosons in a two-leg ladder subject to a time-dependent energy bias between the two chains. When all atoms are initially in the leg with higher energy, we find a drastic reduction of the interchain particle transfer for slow linear sweeps, in quantitative agreement with recent experiments. This effect is preceded by a rapid broadening of the quasimomentum distribution of atoms, signaling the presence of a bath of low-energy excitations in the chains. We further investigate the scenario of quantum quenches to fixed values of the energy bias. We find that for a large enough density the momentum distribution relaxes to that of an equilibrium thermal state with the same energy.