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Kawasaki disease (KD) typically occurs in children aged under 5 years and can cause coronary artery lesions (CALs). Early diagnosis and treatment with intravenous immunoglobulin can reduce the occurrence of CALs, therefore, identifying a good biomarker for diagnosing KD is essential. Here, using next-generation sequencing in patients with recurrent KD, those with viral infection, and healthy controls, we identified dysregulated circulating microRNAs as diagnostic biomarkers for KD. Pathway enrichment analysis illustrated the putative role of these miRNAs in KD progression. Their expression levels were validated using real-time polymerase chain reaction (qPCR). Fifteen dysregulated circulating miRNAs (fold changes &gt, 2 and &lt, 0.5) were differentially expressed in the recurrent KD group compared with the viral infection and control groups. These miRNAs were significantly involved in the transforming growth factor-β, epithelial–mesenchymal transition, and cell apoptosis signaling pathways. Notably, their expression levels were frequently restored after intravenous immunoglobulin treatment. Among the candidates, miR-24-3p expression level was significantly higher in patients with recurrent KD compared with healthy controls or viral infection controls (p &lt, 0.001). Receiver operating characteristic analysis revealed that high miR-24-3p expression levels may be a potential biomarker for KD diagnosis. In conclusion, we identified miR-24-3p significantly higher in KD patients, which may be a potential diagnostic biomarker for KD.

BACKGROUND Prescribing opioids for patients with chronic noncancer pain (CNCP) remains controversial. This study surveyed Taiwanese physicians who were clinically treating CNCP outpatients with long-term opioids. METHODS Anonymous questionnaires investigating the clinical practices, opioid knowledge, attitude, and barriers regarding the prescription of long-term opioids were delivered to 66 physicians treating CNCP outpatients who were officially registered and monitored by the Taiwan Food and Drug Administration in 2011. RESULTS All 66 (100%) physicians responded to the survey, comprising 41 (62%) board-certified pain specialists and 25 (38%) nonpain board-certified physicians. Pain specialists treated a greater number of CNCP outpatients and attended more CNCP training courses than nonpain board-certified physicians (97.6% vs. 56.0%, p < 0.001). Most of pain specialists stated that they were familiar with the Taiwan's narcotic regulations for CNCP patients (92.7% vs. 68.0%, p = 0.015). In addition, pain specialists were less likely to skip or reduce the dosage and duration of opioid prescriptions (22.0% vs. 36.0%, p < 0.001). By contrast, nonpain board-certified physicians had significantly less knowledge and a more negative attitude toward opioid prescription. The major perceived barriers were physician's reluctance to prescribe opioids (78% vs. 92%) and an inadequate knowledge of pain management (73% vs. 84%) among all physicians. CONCLUSION Among the Taiwanese physicians treating the officially registered CNCP patients, nonpain board-certified physicians had fewer patients, less knowledge, and an increased negative attitude toward long-term opioid prescriptions. Better education on chronic pain management is needed for improvement of clinical practice.

Cybercrimes are on a dramatic rise worldwide. The crime rate is growing day by day in every field or department which is directly or indirectly connected to the internet including Government, business or any individual. The main objective of this study is to evaluate the vulnerabilities in different software systems at the source code level by tracing their patch files. The authors have collected the source code of different types of vulnerabilities at a different level of granularities. They have proposed different ways to collect or trace the vulnerability code, which can be very helpful for security experts, organisations and software developers to maintain security measures. By following their proposed method, you can build your own vulnerability data-set and can detect vulnerabilities in any system by using suitable code clone detection technique. The study also includes a discussion of reasons for the rise in cybercrimes including zero-day exploits. A case study has been discussed with results and research questions to show the effectiveness of this study. This study concludes with the effective key findings of published and non-published vulnerabilities and the ways to prevent from different security attacks to overcome cybercrimes.

BACKGROUND Buccal mucosal squamous cell carcinoma (BMSCC) is an aggressive oral cancer. Moreover, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a well-known tumor suppressor in many cancers. Our aim was to investigate the association of RECK expression with prognosis in BMSCC patients with different clinicopathological features. MATERIALS AND METHODS The expression level of RECK was determined by immunohistochemistry using tissue microarrays containing specimens from 193 BMSCC patients. The association of RECK expression with outcomes in BMSCC patients stratified by different clinicopathological features was analyzed by Cox proportional hazards models. RESULTS The low expression level of RECK was associated with shorter disease-specific survival, especially in patients with age >40 years, moderate or poor cell differentiation, advanced pathological stage, and history of postoperative radiotherapy. However, the low expression level of RECK was not associated with poor disease-free survival, except in BMSCC patients with age ≦40 years, advanced pathological stage and lymph node metastasis. Furthermore, RECK-knockdowned cells showed higher cell viability and abilities of invasion/migration, indicating that RECK might be a tumor suppressor for tumor progression in oral cancer. CONCLUSION The low expression of RECK might be a potential prognostic biomarker for pathological outcome-dependent BMSCC patients.

Guanylate-binding protein 6 (GBP6) is a member of the guanylate-binding protein family, and its role in cancer has not yet been reported. We aimed to investigate the clinical significance of GBP6 in oral squamous cell carcinoma (OSCC). Next-generation sequencing was applied for analyzing differential gene expression profiling between corresponding tumor adjacent normal (CTAN) and tumor tissue from two paired OSCC patients. Real-time PCRs (RT-PCRs) were used to investigate the gene expression level of GBP6 of CTAN and tumor tissue samples from 14 TSCC patients. Immunohistochemistry was used to investigate the protein expression level of GBP6 in tumor tissues and paired CTAN tissues from 488 OSCC patients, including 183 buccal mucosa squamous cell carcinoma (BMSCC), 245 tongue squamous cell carcinoma (TSCC), and 60 lip squamous cell carcinoma (LSCC) patients. Compared with CTAN tissues of OSCC patients, GBP6 is identified as a downregulated gene using the NGS platform, which was confirmed in 14 OSCC patients by RT-PCR. Moreover, protein expression level of GBP6 in tumor tissues was lower than that in CTAN tissues and the low GBP6 expression was correlated with poor cell differentiation/lymph node metastasis in TSCC patients. In addition, TSCC patients with low expression levels of GBP6 had poor disease-specific survival rate. The low expression of GBP6 was associated with tumorigenesis and poor prognosis in OSCC patients, especially in TSCC patients. GBP6 may serve as a novel favorable diagnostic and prognostic biomarker in TSCC patients.

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant tumor. Sequestosome 1 (SQSTM1) serves as an adaptor of autophagy for degrading protein aggregates. The regulation of autophagy by EGFR and its clinical impacts are indicated in various types of cancer. However, the association of EGFR and SQSTM1 in OSCC is still unknown. Our results show that the expression levels of SQSTM1 and EGFR proteins are higher in tumor tissues than in the corresponding tumor-adjacent (CTAN) tissues of OSCC patients. The expression levels of SQSTM1 were positively associated with the EGFR expression level. High co-expression of SQSTM1 and EGFR is associated with poor prognosis in OSCC patients. Moreover, SQSTM1 expression is decreased in EGFR-knockdown cells. Cell growth and invasion/migration are also decreased in cells with single/combined knockdowns of EGFR and SQSTM1 or in SQSTM1-knockdown cells without EGFR kinase inhibitor Lapatinib treatment compared to that in scrambled cells. However, cell growth and invasion/metastasis were not significantly different between the scrambled cells and SQSTM1-knockdown cells in the presence of Lapatinib. This study is the first to indicate the biological roles and clinical significance of SQSTM1 regulation by EGFR in OSCC.

Simple Summary The survival rate of oral squamous cell carcinoma (OSCC) patients has not been improved in the past few decades, likely as a result of a lack of therapeutic targets. Through next generation sequencing for tumor tissues of OSCC patients, the gene expression level of guanylate binding protein 5(GBP5) was significantly elevated in tumor tissues compared with adjacent normal tissues and associated with poor prognosis in OSCC patients. Moreover, we found that GBP5 modulated cell cycle, invasion/migration, and cancer stemness in OSCC cells. Our study indicated that GBP5 might be a potential biomarker and therapeutic target for OSCC patients. Abstract Guanylate binding protein 5 (GBP5) is the interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) and is involved in pathogen defense. However, the role played by GBP5 in cancer development, especially in oral squamous cell carcinoma (OSCC), is still unknown. Herein, next-generation sequencing analysis showed that the gene expression levels of GBP5 were significantly higher in OSCC tissues compared with those found in corresponding tumor adjacent normal tissues (CTAN) from two pairs of OSCC patients. Higher gene expression levels of GBP5 were also found in tumor tissues of 23 buccal mucosal squamous cell carcinoma (BMSCC)/14 tongue squamous cell carcinoma (TSCC) patients and 30 oral cancer patients from The Cancer Genome Atlas (TCGA) database compared with those in CTAN tissues. Immunohistochemical results showed that protein expression levels of GBP5 were also higher in the tumor tissues of 353 OSCC patients including 117 BMSCC, 187 TSCC, and 49 lip squamous cell carcinoma patients. Moreover, TCGA database analysis indicated that high gene expression levels of GBP5 were associated with poor overall survival in oral cancer patients with moderate/poor cell differentiation, and associated with poor disease-free survival in oral cancer patients with moderate/poor cell differentiation and lymph node metastasis. Furthermore, GBP5-knockdowned cells exhibited decreased cell growth, arrest at G1 phase, and decreased invasion/migration. The gene expression of markers for epithelial−mesenchymal transition and cancer stemness was also reduced in GBP5-silenced oral cancer cells. Taken together, GBP5 might be a potential biomarker and therapeutic target for OSCC patients, especially for those with poor cell differentiation and lymph node metastasis.

Park-level integrated energy internet (PEI), a multiple energy coupling and obvious zoning system, is set up to meet the growing demand of energy consumption and improve the comprehensive utilization efficiency of multiple energy resources. Traditional distributed alternating direction method of multipliers (ADMM) algorithm with a control center holding all information is often used to solve the dispatch model of PEI, which may cause security problems. In this article, we use the parallel ADMM algorithm to solve the problem in a distributed way. Meanwhile, a completely distributed scheme based on the average-consensus parallel ADMM algorithm is designed to eliminate the computing center of the subregion. The simulation results verified the validity of the proposed method.

RSA public key cryptosystem is the “de-facto” standard, provides confidentiality and privacy security services over the internet. At Eurocrypt 1999, Boneh and Durfee proposed a polynomial time attacks on RSA small decryption key exponent. Their attacks worked by exploiting the lattice and sub lattice structure using lattice based Coppersmith's method to solve a modular polynomials, when $d and $d respectively. In this work, we propose a new attack on some special case of Boneh and Durfee's attack method with respect to large decryption exponent (i.e. $d=N^{\epsilon} > e=N^{\alpha}$ , where $\alpha$ and $\epsilon$ are the encryption and decryption exponents respectively) for some $\alpha\leq\epsilon$ . The condition $d > \phi(N)-N^{\epsilon}$ satisfies our devised attack and the experimental outcome certifies that an RSA cryptosystem with large decryption exponent successfully revealed the weak keys through lattice basis reduction method.

Buccal mucosa squamous cell carcinoma (BMSCC) is one of major subsites of oral cancer and is associated with a high rate of metastasis and poor prognosis. Heat shock proteins (HSPs) act as potential prognostic biomarkers in many cancer types. However, the role of HSPD1 in oral cancer, especially in BMSCC, is still unknown. Through data analysis with The Cancer Genome Atlas (TCGA), we found the association of HSPD1 gene expression with tumorigenesis and poor prognosis in oral cancer patients. Our cohort study showed that higher HSPD1 protein level was associated with tumorigenesis and poor prognosis in BMSCC patients with lymph node invasion, suggesting that HSPD1 may be involved in tumor metastasis. Moreover, knockdown of HSPD1 induced E-cadherin expression and decreased the migration and invasion of BMSCC cells. In contrast, ectopic expression of HSPD1 diminished E-cadherin expression and promoted the migration/invasion of BMSCC cells. Further, HSPD1 regulated RelA activation to repress E-cadherin expression, enhancing the migration and invasion of BMSCC cells. Furthermore, HSPD1 protein level was inversely correlated with E-cadherin protein level in tumor tissues and co-expression of high HSPD1/low E-cadherin showed a significant association with poor prognosis in BMSCC patients. Taken together, HSPD1 might repress E-cadherin expression and promote metastatic characters of BMSCC cells for poor prognosis of BMSCC patients.

BACKGROUND/AIM Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC. MATERIALS AND METHODS This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method. RESULTS Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype. CONCLUSION We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect.

BACKGROUND Type V collagen (COL5), in the functional heterotrimer [α1(V)2 α2(V)] isoform, participates in the malignancies of various cancers. However, its role in tongue squamous cell carcinoma (TSCC) remains unclear. MATERIALS AND METHODS The expression levels of COL5A1 and COL5A2 polypeptide chains were examined using the tissue microarray from 245 TSCC patients with immunohistochemistry. Paired t test and Wilcoxon signed-rank test were performed for comparisons among the groups. Survival rates were estimated by using the Kaplan-Meier method and compared with log-rank tests. A Cox proportional hazards model was used to evaluate the impact of protein expression level on survival rate. RESULTS Expression level of COL5A1 was significantly increased in tumor tissues (P

C6orf141 (Chromosome 6 open reading frame 141) is a novel gene, and its role in oral cancer progression remains unclear. C6orf141 expression in oral squamous cell carcinoma (OSCC) and adjacent normal tissues from 428 patients was examined through immunohistochemistry (IHC). Our results revealed that C6orf141 expression was significantly reduced in OSCC compared with adjacent normal tissues. Low C6orf141 expression was significantly associated with a poor American Joint Committee on Cancer pathological stage (P P = 0.002), and pN stage (P = 0.032). Kaplan–Meier curves revealed that low C6orf141 expression was significantly associated with shorter disease-specific survival (DSS) in patients with OSCC (log-rank P = 0.007). Multivariate analysis indicated that low C6orf141 expression was an independent prognostic biomarker for DSS (adjusted hazard ratio = 1.34; 95% confidence interval = 1.10–1.81; P = 0.05). Additionally, ectopic C6orf141 expression could significantly suppress oral cancer cell proliferation, colony formation, and migratory and invasive abilities. Xenograft tumor growth assay revealed that C6orf141 could significantly suppress oral tumor growth in vivo. Our results suggest that C6orf141 plays a novel tumor-suppressive role in oral cancer cell growth and motility. Furthermore, C6orf141 dysfunction could be a potential prognostic biomarker for OSCC and provide new therapeutic strategies in the future.

In high efficiency and high-frequency applications, the soft-start methods for DC-DC converter with fast output voltage settling speed have attracted widespread attention. A novel soft-start circuit with controllable start-up time, high start-up speed, high stability, and no off-chip capacitor for a current mode DC-DC is proposed in this paper. The proposed soft-start circuit introduces a current-limiting feedback technique so that the inductor current during soft-start is controllable. The stability of the soft-start technique is verified theoretically in this paper. A Boost converter using this novel soft-start technique is fabricated in 0.35 μm BCD process. The soft-start time of the Boost converter is only 380 μs at the conditions of 45 V output voltage, 20 μF load capacitance, and 500 mA load current.

Ubiquitin-conjugating enzyme 2C (UBE2C) involves in numerous cellular processes and the tumor progression in many cancers. However, its role in oral squamous cell carcinoma (OSCC) is unclear. We aimed to investigate the role and clinical significance of UBE2C in OSCC. The expression levels of UBE2C were examined by immunohistochemistry in 185 buccal mucosa squamous cell carcinomas, 247 tongue squamous cell carcinomas (TSCCs) and 75 lip squamous cell carcinomas. The roles of UBE2C in cell growth, invasion/migration and cancer stemness were also examined in OSCC cells. The expression levels of UBE2C protein were higher in tumor tissues than they were in the corresponding tumor adjacent normal tissues from OSCC patients. Higher UBE2C expression was associated with poor cell differentiation and lymph node invasion in OSCC patients. High UBE2C expression was also correlated with shorter disease-specific survival in TSCC patients having poor cell differentiation, advanced pathological stages, lymph node metastasis as well as receiving radiation therapy. Compared to control cells, OSCC cells in which UBE2C was silenced showed decreased cell proliferation, migration/invasion and colony formation and they exhibited lower expression levels of the following cancer stemness markers&mdash, ALDH1/A2, CD44, CD166 and EpCAM. High co-expression levels of UBE2C/CD44, UBE2C/CD166 and UBE2C/EpCAM were associated with poor prognosis in oral cancer patients from The Cancer Genome Atlas database. Our findings indicated that UBE2C might be a potential biomarker for tumorigenesis and prognosis in TSCC.

BACKGROUND/AIM Breast cancer is a common type of cancer in women, and metastasis frequently leads to therapy failure. Using next-generation sequencing (NGS), we aspired to identify the optimal differentially expressed genes (DEGs) for use as prognostic biomarkers for breast cancer. MATERIALS AND METHODS NGS was used to determine transcriptome profiles in breast cancer tissues and their corresponding adjacent normal tissues from three patients with breast cancer. RESULTS Herein, 15 DEGs (fold change >4 and

Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer death worldwide due to the limited availability of biomarkers and therapeutic targets. Autophagy related protease 4B (ATG4B) is an essential protease for the autophagy machinery, and ATG4B phosphorylation at Ser383/392 increases its proteolytic activity. ATG4B expression and activation are crucial for cancer cell proliferation and invasion. However, the clinical relevance of ATG4B and phospho-Ser383/392-ATG4B for OSCC remains unknown, particularly in buccal mucosal SCC (BMSCC) and tongue SCC (TSCC). With a tissue microarray comprising specimens from 498 OSCC patients, including 179 BMSCC and 249 TSCC patients, we found that the protein levels of ATG4B and phospho-Ser383/392-ATG4B were elevated in the tumor tissues of BMSCC and TSCC compared with those in adjacent normal tissues. High protein levels of ATG4B were significantly associated with worse disease-specific survival (DSS) in OSCC patients, particularly in patients with tumors at advanced stages. In contrast, phospho-Ser383/392-ATG4B expression was correlated with poor disease-free survival (DFS) in TSCC patients. Moreover, ATG4B protein expression was positively correlated with phospho-Ser383/392-ATG4B expression in both BMSCC and TSCC. However, high coexpression levels of ATG4B and phospho-Ser383/392-ATG4B were associated with poor DFS only in TSCC patients, whereas they had no significant association with DSS in BMSCC and TSCC patients. In addition, silencing ATG4B with an antisense oligonucleotide (ASO) or small interfering RNA (siRNA) diminished cell proliferation of TW2.6 and SAS oral cancer cells. Further, knockdown of ATG4B reduced cell migration and invasion of oral cancer cells. Taken together, these findings suggest that ATG4B might be a biomarker for diagnosis/prognosis of OSCC and a potential therapeutic target for OSCC patients.

Background High Snail expression is known as a poor prognostic factor in breast cancer. However, its prognostic impact for breast cancer with different molecular subtypes is still controversial. Methods Snail expression was examined by immunohistochemistry in tissue microarray slides of 85 corresponding tumor-adjacent normal (CTAN) and 247 breast invasive ductal carcinoma (IDC) tissues. Multivariable Cox regression analysis was used to assess the impact of Snail expression on survival rate by different molecular subtypes of breast IDC patients. Results The level of Snail expression in IDC tumor tissues was significantly higher than that in CTAN tissues. Moreover, high Snail expression had direct impacts on poor disease specific survival (DSS) and disease-free survival (DFS) in breast IDC patients with human epidermal growth factor receptor 2 (HER2)-positive and human epidermal growth factor receptor (EGFR)-positive statuses as well as the HER2 intrinsic subtype. Additionally, breast IDC patients with a combination of three prognostic factors, including high Snail expression and HER2-positive and EGFR-positive statuses, had much poor DSS and DFS with a statistically significant linear trend. Conclusion High Snail expression could predict a poor prognosis for breast IDC patients with HER2/EGFR-positive subtypes.

The aim of this study was to investigate the associations among the immunoexpression levels of manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) in lip squamous cell carcinoma (LSCC) tissues and the clinicopathological characteristics, and prognostic factors in patients with LSCC. The immunoexpression levels of Mn-SOD, GPx, and MPO were examined in 76 LSCC tissue samples using immunohistochemical staining on tissue microarray slides, and compared to those in normal lip mucosa adjacent to venous lakes (normal controls), normal tissue adjacent to corresponding tumors (NTACT), and recurrent tumors. Associations between immunoexpression levels and clinicopathological characteristics were analyzed using the Student's t-test. The prognostic factors were analyzed using Cox regression. The immunoexpression levels of Mn-SOD, GPx, and MPO were significantly different among the normal controls, NTACTs, tumors, and recurrent tumors (Mn-SOD: p = 0.001, GPx: p

Background The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. Methods In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion. Results The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08–2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32–4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39–4.50; p = 0.002) in patients with breast cancer. Conclusion Our findings revealed that a IDH1low/Snailhigh molecular signature could serve as an independent biomarker for poor prognosis in breast cancer Electronic supplementary material The online version of this article (10.1186/s13058-018-0953-7) contains supplementary material, which is available to authorized users.

Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.

// Jer-Shyung Huang 1, 2, * , Cheng-Mei Yang 3, 4, * , Jyh-Seng Wang 5 , Huei-Han Liou 6 , I-Chien Hsieh 5 , Guan-Cheng Li 6 , Sin-Jhih Huang 6 , Chih-Wen Shu 6 , Ting-Ying Fu 5 , Yun-Chung Lin 7 , Luo-Ping Ger 6, 8 and Pei-Feng Liu 6, 9 1 Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 2 National Yang-Ming University School of Medicine, Taipei, Taiwan 3 Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 4 Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan 5 Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 6 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 7 Department of Pathology, China Medical University Hospital, Taichung, Taiwan 8 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Optometry, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Luo-Ping Ger, email: lpger@vghks.gov.tw Pei-Feng Liu, email: pfliu@vghks.gov.tw Keywords: buccal mucosa squamous cell carcinoma, caspase-3, cleaved caspase-3, tumorigenesis, prognosis Received: June 04, 2017 Accepted: July 26, 2017 Published: August 24, 2017 ABSTRACT Buccal mucosa squamous cell carcinoma (BMSCC) is the most common oral cancer in Southeast Asia. Caspase-3, a key molecule in regulating apoptosis, promotes the malignancy of various cancers. However, its role in BMSCC is unknown. Herein, we evaluated the association of caspase-3 expression with tumorigenesis and prognosis in BMSCC patients. Immunohistochemical staining indicated that the expression levels of cleaved caspase-3 ( p

Background/purpose Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids. Methods An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine. Results For 210 of 328 outpatients (64.0%), the median pain duration was 96 months and opioid treatment duration was 57 months. The median morphine equivalent dose was 150 mg/d, with 30.5% of patients exceeding the daily watchful dose, defined as 200 mg of morphine equivalent dose. Pain reduction after taking opioids was ∼50% in the past week. The top three diagnoses were chronic pancreatitis, spinal cord injury, and neuralgia. The leading side effects were constipation (46.7%), and decreased sexual desire (69.5%) and satisfaction (57.9%). Depression was currently diagnosed in 55.2% of patients. Twenty patients (9.5%) displayed at least one aberrant behavior in the past month. Only 76 (36.2%) patients had ever received nerve block procedures, and 118 (56.2%) tried complementary and alternative medicine. Conclusion This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose.

Objective To investigate the relationships between two single-nucleotide polymorphisms at miR-146a C > G (rs2910164) and miR-1269b G > C (rs7210937) and the risk of developing oral premalignant lesions (OPLs), oral squamous cell carcinoma (OSCC), pharyngeal SCC (PSCC), and oral and pharyngeal SCC (OPSCC). Design Genotyping of miR-146a C > G and miR-1269b G > C was performed in two case-control studies using the TaqMan assay. A total of 197 healthy control subjects, 241 OPLs patients, and 188 OPSCC patients who habitually chewed betel quid (BQ) were recruited into one case-control study. Additionally, 668 cancer-free control subjects and 658 OPSCC patients were recruited into the other case-control study. Results The G/G genotype at miR-146a C > G was associated with the decreased risk of OSCC [adjusted odds ratio (AOR) = 0.66, P = 0.040], PSCC (AOR = 0.42, P = 0.013), and OPSCC (AOR = 0.63, P = 0.020). Additionally, the C allelic type and C/C genotype at miR-1269b G > C decreased the risk of BQ-related oral leukoplakia (C vs. G: AOR = 0.68, P = 0.012; C/C vs. G/G: AOR = 0.43, P = 0.009), BQ-related OPLs (C vs. G: AOR = 0.69, P = 0.008; C/C vs. G/G: AOR = 0.44, P = 0.005), and BQ-related OPSCC (C vs. G: AOR = 0.65, P = 0.003; C/C vs. G/G: AOR = 0.47, P = 0.011). In OPSCC patients, the G/G genotype of miR-146a was correlated with well-differentiated cells (P = 0.041), and the G/C and C/C genotypes of miR-1269b were correlated with the absence of lymph node involvement (P = 0.031), especially in OSCC patients (P = 0.038 and P = 0.007, respectively). Conclusion The genetic variants of miR-146a and miR-1269b are biomarkers against the development of OPLs and OPSCC.

// Ting-Ying Fu 1, 2, * , Chao-Nan Wu 3, 4, * , Huei-Cin Sie 1 , Jiin-Tsuey Cheng 5 , Yaoh-Shiang Lin 6 , Huei-Han Liou 7 , Yu-Kai Tseng 8, 9 , Chih-Wen Shu 7 , Kuo-Wang Tsai 7, 10 , Leing-Ming Yen 1 , Hui-Wen Tseng 11, 12 , Ching-Jiunn Tseng 7, 13, 14, 15 , Luo-Ping Ger 7, 16 , Pei-Feng Liu 7, 17 1 Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 2 Department of Optometry, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan 3 Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 4 Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan 5 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 6 Department of Otorhinolaryngology-Head & Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 7 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 8 Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan 9 Department of Orthopedics, National Cheng Kung University Hospital, Tainan, Taiwan 10 Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan 11 Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 12 Department of Nursing, Meiho University, Pingtung, Taiwan 13 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 14 Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan 15 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 16 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 17 Department of Biotechnology, Fooyin University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Luo-Ping Ger, email: lpger@vghks.gov.tw Pei-Feng Liu, email: pfliu@vghks.gov.tw Keywords: DDX60, oral cancer, subsite-specific, tumorigenesis, prognosis Received: April 14, 2016 Accepted: October 28, 2016 Published: November 08, 2016 ABSTRACT The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues. However, its association with tumorigenesis was specific to the oral cavity subsite after the stratification of betel quid chewing, smoking, and drinking. Among OSCC patients, higher levels of DDX60 expression were associated with the male gender, a well-differentiated tumor, advanced stage of disease, and a large tumor size with subsite specific features. LSCC patients with high DDX60 expression levels showed shorter disease-specific survival, particularly those with moderately or poorly differentiated tumors. Additionally, TSCC or OSCC patients with high DDX60 expression showed a poor disease-free survival (DFS), particularly those with moderately or poorly differentiated tumors. Therefore, DDX60 is a novel and unfavorable biomarker for tumorigenesis and prognosis of OSCC in a subsite-specific manner.

Authentication is the fundamental security service used in almost all remote applications. All such sensitive applications over an open network need authentication mechanism that should be delivered in a trusted way. In this paper, we design an RSA based authentication system for smart IoT environment over the air network using state-of-the-art industry standards. Our system provide security services including X.509 certificate, RSA based Public Key Infrastructure (PKI), challenge/response protocols with the help of proxy induced security service provider. We describe an innovative system model, protocol design, system architecture and evaluation against known threats. Also the implemented solution designed as an add on service for multiple other sensitive applications (smart city apps, cyber physical systems etc.) which needs the support of X.509 certificate based on hard tokens to populate other security services including confidentiality, integrity, non-repudiation, privacy and anonymity of the identities. The proposed scheme is evaluated against known vulnerabilities and given detail comparisons with popular known authentication schemes. The result shows that our proposed scheme mitigate all the known security risks and provide highest level assurance to smart gadgets.

As trust becomes increasingly important in the software domain. Due to its complex composite concept, people face great challenges, especially in today's dynamic and constantly changing internet technology. In addition, measuring the software trustworthiness correctly and effectively plays a significant role in gaining users trust in choosing different software. In the context of security, trust is previously measured based on the vulnerability time occurrence to predict the total number of vulnerabilities or their future occurrence time. In this study, we proposed a new unified index called "loss speed index" that integrates the most important variables of software security such as vulnerability occurrence time, number and severity loss, which are used to evaluate the overall software trust measurement. Based on this new definition, a new model called software trustworthy security growth model (STSGM) has been proposed. This paper also aims at filling the gap by addressing the severity of vulnerabilities and proposed a vulnerability severity prediction model, the results are further evaluated by STSGM to estimate the future loss speed index. Our work has several features such as: (1) It is used to predict the vulnerability severity/type in future, (2) Unlike traditional evaluation methods like expert scoring, our model uses historical data to predict the future loss speed of software, (3) The loss metric value is used to evaluate the risk associated with different software, which has a direct impact on software trustworthiness. Experiments performed on real software vulnerability datasets and its results are analyzed to check the correctness and effectiveness of the proposed model.

Buccal mucosa squamous cell carcinoma (BMSCC) is one of major subsites of oral cancer and is associated with a high rate of metastasis and poor prognosis. Heat shock proteins (HSPs) act as potential prognostic biomarkers in many cancer types. However, the role of HSPD1 in oral cancer, especially in BMSCC, is still unknown. Through data analysis with The Cancer Genome Atlas (TCGA), we found the association of HSPD1 gene expression with tumorigenesis and poor prognosis in oral cancer patients. Our cohort study showed that higher HSPD1 protein level was associated with tumorigenesis and poor prognosis in BMSCC patients with lymph node invasion, suggesting that HSPD1 may be involved in tumor metastasis. Moreover, knockdown of HSPD1 induced E-cadherin expression and decreased the migration and invasion of BMSCC cells. In contrast, ectopic expression of HSPD1 diminished E-cadherin expression and promoted the migration/invasion of BMSCC cells. Further, HSPD1 regulated RelA activation to repress E-cadherin expression, enhancing the migration and invasion of BMSCC cells. Furthermore, HSPD1 protein level was inversely correlated with E-cadherin protein level in tumor tissues and co-expression of high HSPD1/low E-cadherin showed a significant association with poor prognosis in BMSCC patients. Taken together, HSPD1 might repress E-cadherin expression and promote metastatic characters of BMSCC cells for poor prognosis of BMSCC patients.

This paper takes the parametric modeling technology of ancient buildings on the Southern Silk Road as the research object, and conducts a more in-depth analysis of the types, forms, advantages, and shortcomings of parametric modeling in ancient building modeling with a wealth of cases to demonstrate profound theories in simple language. The parametric modeling of the dwellings of Bai ethnic group in Dali was used as a case for verification. This paper is a more in-depth research paper on the digital modeling of ancient buildings, which has positive reference significance for this kind of research and production.

In this study, we revisit the RSA public key cryptosystem in some special case of Boneh and Durfee's attack when the private key d assumes to be larger than the public key e. The attack in this study is the variation of an approach adopted by Luo et al. (2009) based on large decryption exponent. They had chosen a large private key (d > e) and found the weak keys in some specific range between N0.258 ≤ e ≤ N0.857. We highlight the shortcomings and new improvements in our study with more refined bound analysis up to the range between N0.104 ≤ e ≤ N0.923. Our experimental results revealed more refined bounds using lattice-based Coppersmith's method. In our experimental yield, we find the small roots of the devised polynomial, which helps to factorise the RSA modulus of size up to 1,024-bits. We also measure the probability of a specific range of weak keys, which further certify our results about weak keys in an RSA constrained secret key environment.

Compared with the household air-conditioning, central air-conditioning has larger rated capacity and more concentrated operating period. These characteristics of the central air-conditioning make it a high quality resource that can be participated in the centralized load regulation. Firstly, the equivalent thermal parameters model of central air-conditioning and the thermal comfort model of human body are established, and then the aggregation strategy of central air-conditioning loads is proposed to minimize the operation fees of load aggregator under the constraints of the minimum aggregated load requirement, adjustment time period and users' comfort index. The particle swarm optimization algorithm is adopted to solve the optimal problem in this paper. Finally, the aggregated central air-conditioning loads are used to smooth the wind power fluctuation in the wind farm, and the optimal dispatch costs are compared with the investment cost of energy storage equipment needed to compensate the power fluctuation. The analysis results show that the load aggregation strategy of central air-conditioning is more economical than the configuration of traditional energy storage equipment.

Background The ageing population and the expected increase in the number of elderly patients make an evidence-based assessment of Extracorporeal Membrane Oxygenation (ECMO) therapy in old patients progressively more important. Veno-arterial (VA) ECMO results for patient aged

Background Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20–30% pathologic complete response. Because miRNAs are frequently dysregulated in breast cancer and have broad tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. Understanding the role and mechanism of dysregulated miRNAs in TNBC may help to develop novel diagnostic and prognostic strategy for TNBC patients. Methods The miRNA array profiles of 1299 breast cancer patients were collected from the Metabric database and subjected to analysis of the altered miRNAs between TNBC and non-TNBC. In Student’s t-test and Kaplan-Meier analysis, four upregulated miRNAs correlated with poor survival in TNBC but not in non-TNBC. Four miRNAs were manipulated in multiple cell lines to investigate their functional role in carcinogenesis. From these results, we studied miR-105 and miR-93-3p in greater detail. The level of miR-105 and miR-93-3p were evaluated in 25 breast cancer tumor tissues. In addition, the diagnostic utility of circulating miR-105 and miR-93-3p were examined in 12 normal and 118 breast cancer plasma samples by ROC curve construction. Results miR-105 and miR-93-3p were upregulated and correlated with poor survival in TNBC patients. Both miR-105 and miR-93-3p were found to activate Wnt/β-catenin signaling by downregulation of SFPR1. By this action, stemness, chemoresistance, and metastasis were promoted. Importantly, the combination of circulating miR-105/93-3p may serve as a powerful biomarker for TNBC, even in early-stage disease. Conclusions miR-105/93-3p activates Wnt/β-catenin signaling by downregulating SFRP1 and thereby promotes stemness, chemoresistance, and metastasis in TNBC cells. Most importantly, combined circulating miR-105/93-3p levels represent a prime candidate for development into a diagnostic biomarker for both early- and late-stage TNBC. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0918-2) contains supplementary material, which is available to authorized users.

Software reliability is one of the key features of software quality assurance. It is primarily associated with the defects of software, which indicates a major factor in software development. Software has become an indispensable investment for an organization. The users are more concerned about accurate and efficient failure prediction model. Early fault prediction model can reduce the cost of the test, increase reliability and improve the quality of software. Precise prediction is desired from the every model but no model has proved to be successful at efficiently and accurately developing software reliability model. In this paper, the authors have combined two most popular reliability prediction models and get the most accurate output from them by using Markov method based on their residual errors. Furthermore, experiment analysis and comparison carried out on U.S. Navy Tactical Data System, which shows the accuracy of the hybrid approach.

To evaluate the clinicopathological characteristics, high-risk lifestyle factors (HRLF: chronic exposure to sun, betel quid, alcohol, and tobacco), and prognostic factors of lip cancer. The hospital records of patients with pathologically confirmed lip squamous cell carcinoma (LSCC, n = 112) and lip basal cell carcinoma (LBCC, n = 21) were reviewed. Differences in clinicopathological characteristics between LSCC and LBCC, upper and lower lip, and status of second primary tumors were compared by chi-square test and logistic regression. The prognostic factors for LSCC were analyzed by Cox regression. Compared with LBCC patients, LSCC patients were men-predominant (p 0.001), had younger ages at onset (p 0.001), and higher rates of lower lips involvement (p 0.001) and HRLFs. Patients with second primary tumors were highly associated with lower lip cancer involvement (adjusted odds ratio = 2.91, p = 0.03). Patients with lower lip cancer had more HRLFs with an increasing linear trend (p = 0.004). The poorer prognostic factors of LSCC for disease-specific survival were advanced stage III/IV [crude hazard ratio (CHR) = 11.16, p 0.001], tumor dimension 4 cm (CHR = 8.19, p = 0.006), lymph node involvement (CHR = 11.48, p 0.001), and recurrence (CHR = 3.96, p = 0.01); whereas for disease-free survival were moderately to poorly differentiated LSCC (CHR = 4.97, p = 0.002) and alcohol consumption (CHR = 3.13, p = 0.04). LSCC and lower lip cancer were highly associated with HRLFs.

Apoptosis plays a dual role in cancer development and malignancy. The role of apoptosis-related caspases in cancer remains controversial, particularly in oral tongue squamous cell carcinoma (OTSCC). In this study, we examined the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue microarrays consisting of samples from 246 OTSCC patients by immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were significantly higher compared to those in adjacent normal tissues (all p

Backgrounds Diabetes mellitus (DM) is a common endocrine disorder and an increasing epidemic worldwide. Proportional diabetic patients eventually develop cutaneous diseases. Objectives This study determined the statistical association of cutaneous manifestations and DM as well as the DM-associated cutaneous manifestations in elderly male residents. Methods A cross-sectional study was conducted in a Veterans Home in Taiwan. The cutaneous manifestations and major systemic diseases of the residents were recorded separately. Univariate logistic regression and multivariate analysis after adjustment for age, body mass index and significant major systemic diseases provided odds ratios and P values for the statistical association. Results A total of 313 male residents (age ≥65 years) were recruited, including 70 (22.4%) with DM. Their most common cutaneous manifestations included fungal infection (77%) and brown spots on the legs (38.3%). Chronic ulcers adjusted odds ratios (AOR 4.90, 95%CI: 1.82–13.19; P = 0.002), brown spots on the legs (AOR 6.82, 95%CI: 3.60–12.89; P

Background The effect of maternal exposure to essential minerals and heavy metals on fetus is an important issue, which affects women around the world. Few data are available on the concentration of both essential minerals and heavy metals in maternal/fetal medicine. The aims of this study were to (1) assess the correlation of mercury (Hg), manganese (Mn), iron (Fe), and copper (Cu) in paired maternal/fetal blood samples, and (2) study potential confounding factors during pregnancy. Methods Our study recruited 145 healthy pregnant women with a mean age of 28.06 years, gathering information by collecting interviewer-administered questionnaires. Paired maternal/fetal blood samples were collected by delivery. Results There was a positive correlation of Hg ( r = 0.78, p r = 0.31, p r = 0.17, p = 0.038), and Cu ( r = 0.21, p = 0.010) in paired maternal/fetal samples. Prenatal vitamin use (>3 times/wk) was significantly associated with lower maternal Hg (adjusted odds ratio 0.272, p = 0.005) and lower maternal Cu (adjusted odds ratio 0.267, p = 0.004) levels. Median fetal Hg, Mn, and Fe levels were higher than corresponding maternal levels, while median fetal Cu level was lower than maternal Cu level. Conclusion There was a positive correlation of Hg, Fe, Cu, and Mn in paired maternal/fetal samples in this series. Our findings have raised the possibility of reducing maternal Hg and Cu by way of prenatal vitamin supplementation.

Objectives This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)–related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). Study Design In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. Results The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction Conclusions BQ chewers carrying the T allele or C/T + T/T genotypes in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC.

A wireless power transfer system using multilayer flat spiral coils is constructed in this paper. The multilayer flat spiral coil can deliver power highly efficiently, being used in the resonator coupling WPT system. Thus, three structures of inductive coil are displayed in order to compare the benefits of the multilayer flat spiral coil. The second part describes three structures of the coils and the basic system. Moreover, the system with these pairs of coils is simulated by the MAXWELL and SIMPLORER. And the results show the advantages of the multilayer flat spiral coil directly which can bring high transfer efficiency and stable transfer.

Akt activation has been implicated broadly in tumorigenesis, but the basis for its dysregulation in cancer cells is incompletely understood. In this study, we sought to clarify a regulatory role for the Akt-binding carboxy-terminal modulator protein (CTMP), which has been controversial. In evaluating CTMP expression in paired normal–tumor specimens of 198 patients with breast cancer, we found that CTMP was upregulated in breast tumors, where it was associated with poor patient survival. Notably, CTMP expression also correlated positively with Akt phosphorylation in breast cancer clinical specimens and cell lines. Furthermore, ectopic expression of CTMP promoted cell proliferation and enhanced the tumorigenic properties of estrogen-dependent breast cancer cells. This effect was correlated with increased sensitivity to insulin-induced Akt phosphorylation, which is mediated primarily by the phosphoinositide 3-kinase–Akt pathway. In contrast, short hairpin RNA-mediated silencing of endogenous CTMP decreased the proliferation of estrogen-dependent or estrogen-independent breast cancer cells. Mechanistic investigations defined the N-terminal domain of CTMP at amino acids 1 to 64 as responsible for Akt binding. Taken together, our results firmly corroborate the concept that CTMP promotes Akt phosphorylation and functions as an oncogenic molecule in breast cancer. Cancer Res; 73(20); 6194–205. ©2013 AACR.

Shaft fault is the most common fault for hydraulic machinery. In this paper, wavelet packet energy spectrum analysis method was used for multi frequency bands division of shaft monitoring signals. The variable bands frequency energy can construct feature vectors needed for fault diagnosis based on support vector machine, by integrating the procedure of wavelet packet analysis method and online monitoring technology, feature can be extracted in real time, and it make possible for real-time fault diagnosis and prediction of hydraulic machine.

Objective The present study investigated the relationship between the expression of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase (GPx), and myeloperoxidase (MPO) in buccal mucosal squamous cell carcinoma (SCC), and the risk of second primary tumors (SPTs). Study design Immunohistochemistry was performed to examine the expression of MnSOD, GPx, catalase, and MPO in tissue microarray slides of 173 male patients with buccal mucosal SCC who had undergone potentially curative resections. Results Forty-five (26.01%) patients developed SPTs. The prevalent subsites of SPTs were buccal mucosa (48.89%), tongue (13.33%), and lip (11.11%). High expression level of MPO was correlated with an increased risk of SPTs, even after adjustment for development of clinicopathologic parameters (high vs. low expression, adjusted hazard ratio = 3.89; 95% confidence interval, 1.33-11.41; P = .013). Conclusions SPTs are common in male buccal mucosal SCC patients. Higher MPO expression in buccal mucosal SCC is a risk factor for SPTs.

Modern low-power system on a chip needs direct current converter with dynamic voltage scaling (DVS) ability for core power supply. The converter output should be accurate voltage across the full load current and voltage scaling range. An integrated buck converter for DVS application is proposed in this brief. Voltage mode phase lead compensation is implemented in the converter, with much smaller passive components than conventional type-III compensation. To improve accuracy, the output voltage error accompanied with load current and reference voltage caused by finite loop gain in analog control loop is corrected by the digital error corrector. The output voltage is compared by two comparators whose threshold voltage is about 10 mV above and below the reference voltage, respectively. The duty cycle is slightly adjusted by finite state machine according to outputs of the two comparators. Experimental results show that the converter is well regulated over an output range of 0.7-1.8 V, with step voltage of 25 mV. When load current suddenly changes between 170 and 500 mA, the overshoot and undershoot voltage are 32 and 50 mV, respectively. Load regulation is maintained about 1% throughout the full load range. The voltage error is within ±10 mV in the voltage scaling range.

Background Interleukin-18 (IL-18) plays an important role in mediating cytokine cascade leading to coronary artery lesions (CALs) in Kawasaki disease (KD). However, our research suggested that the literature regarding IL-18 and KD is limited. Consequently, this study aimed to evaluate the correlation between IL-18 and CALs in patients with KD. Methods In this prospective study of 14 children with KD (seven without and seven with CALs in the acute phase), we obtained patient measurements of a series of serum IL-18 levels in the acute, subacute, and convalescent phases. Serum IL-18 levels were measured with a Bio-Plex cytokine assay. Control samples were obtained from 18 febrile children with viral infection. Results Compared with febrile controls, patients with acute-stage CALs [postintravenous immunoglobulin (post-IVIG) period] had a significantly higher IL-18 level (88.4 ± 20.7 vs 56.0 ± 35.0 pg/mL, p = 0.006). However, those without acute-stage CALs (post-IVIG period) lacked similarly elevated IL-18 level readings (62.0 ± 40.6 vs 56.0 ± 35.0 pg/mL, p = 0.762). The IL-18 level of patients with acute-stage CALs did not decrease significantly until the convalescent phase (97.4 ± 55.8 vs 38.7 ± 22.6 pg/mL, p = 0.018), but for those without CALs, it decreased significantly in the subacute phase (60.2 ± 37.4 vs 23.6 ± 13.8 pg/mL, p = 0.018). In the subacute stage, there was a significant difference of IL-18 level between patients with and without acute-stage CALs ( p = 0.048). Conclusion Our data show that IL-18 levels were elevated in the acute phase of KD and might be related to the formation of CALs.