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Background: With the prolongation of survival in recent years, the accumulation of toxic and side effects of therapeutic drugs and the concomitant drug-related adverse reactions were reported in recent years. However, myelodysplastic syndrome secondary to multiple myeloma is rare. Objective: To improve the understanding of myelodysplastic syndrome secondary to multiple myeloma. Methods: The clinical data of a patient with myelodysplastic syndrome secondary to multiple myeloma after treatment were analyzed, and the related literature was reviewed. Results: A 54-year-old male patient was diagnosed as multiple myeloma in February 2014. After three courses of first-line induction chemotherapy, he achieved complete remission and received two courses of consolidation treatment. After that, he continued to take thalidomide orally. The disease recurred 13 months after complete remission (CR) with 6q+ karyotype change in 37 months. 21q- karyotype change was found in 39 months. The patient was finally diagnosed as treatment-related secondary myelodysplastic syndrome. Due to the poor effect of chemotherapy, the disease continued to deteriorate. Conclusion: In the course of multiple drug treatment, clinicians should pay attention to the changes of molecular genetics and the treatment-related secondary tumor.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk for physical comorbidity. This study used a twin cohort to investigate the association between physical diseases and phenotypic variations of ADHD. A twin cohort enriched for ADHD and other neurodevelopmental conditions were analysed. The Attention Problems subscale of the Child Behavior Checklist/Adult Behavior Checklist (CBCL/ABCL-AP) was used to measure the participants’ severity of ADHD symptoms. Physical health issues were obtained with a validated questionnaire and were tested in relation to ADHD symptom severity in a co-twin control model. Neurological problems were significantly associated with a diagnosis of ADHD. A conditional model for the analysis of within-twin pair effects revealed an inverse association between digestive problems and the severity of ADHD symptoms, after adjusting for co-existing autism spectrum disorder and ADHD medications. Our findings suggest that individuals with ADHD are susceptible to neurological problems, why a thorough neurological check-up is indicated in clinical practice for this population. In addition, health conditions of digestive system could be considered as a non-shared environmental factor for behavioral phenotypes in ADHD. It supports the possible role of gut-brain axis in the underpinnings of ADHD symptoms, at least for a subgroup of individuals with certain genetic predisposition.

There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63–2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06–1.56), guanfacine (OR = 1.43, 95% CI = 1.12–1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09–1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.

This meta-analysis aims to determine whether autologous fat grafting (AFG) affects the risk of local-regional recurrence (LRR) in breast cancer patients. In pooled analyses of 11 eligible studies, AFG was not associated with increased LRR. Subgroup analyses showed that AFG did not increase the risk of LRR in patients undergoing breast-conserving surgery or mastectomy, in patients with in situ carcinomas or invasive carcinomas, or in patients undergoing postoperative radiotherapy.

Background Inconsistent associations between coffee consumption and bone mineral density (BMD) have been observed in epidemiological studies. Moreover, the relationship of bioactive components in coffee with BMD has not been studied. The aim of the current study is to identify coffee-associated metabolites and evaluate their association with BMD. Methods Two independent cohorts totaling 564 healthy community-dwelling adults from the Hong Kong Osteoporosis Study (HKOS) who visited in 2001–2010 (N = 329) and 2015–2016 (N = 235) were included. Coffee consumption was self-reported in an food frequency questionnaire. Untargeted metabolomic profiling on fasting serum samples was performed using liquid chromatography–mass spectrometry platforms. BMD at lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Multivariable linear regression and robust regression were used for the association analyses. Results 12 serum metabolites were positively correlated with coffee consumption after Bonferroni correction for multiple testing (P < 4.87 × 10–5), with quinate, 3-hydroxypyridine sulfate, and trigonelline (N’-methylnicotinate) showing the strongest association. Among these metabolites, 11 known metabolites were previously identified to be associated with coffee intake and 6 of them were related to caffeine metabolism. Habitual coffee intake was positively and significantly associated with BMD at the lumbar spine and femoral neck. The metabolite 5-acetylamino-6-formylamino-3-methyluracil (AFMU) (β = 0.012, SE = 0.005; P = 0.013) was significantly associated with BMD at the lumbar spine, whereas 3-hydroxyhippurate (β = 0.007, SE = 0.003, P = 0.027) and trigonelline (β = 0.007, SE = 0.004; P = 0.043) were significantly associated with BMD at the femoral neck. Conclusions 12 metabolites were significantly associated with coffee intake, including 6 caffeine metabolites. Three of them (AFMU, 3-hydroxyhippurate, and trigonelline) were further associated with BMD. These metabolites could be potential biomarkers of coffee consumption and affect bone health.

Phytosterols reduce intestinal cholesterol absorption and help to lower LDL-cholesterol. Many Chinese adults are lactose-intolerant and cannot tolerate bovine milk enriched with phytosterol. Soya-milk is a common beverage in Asia and it has beneficial effects on general health. We therefore conducted a randomized double-blind controlled trial to assess the effectiveness of a phytosterols-enriched soya drink in lowering serum LDL-cholesterol level (primary outcome) and other cardiovascular parameters (secondary outcomes). One hundred and fifty-nine normocholesterolaemic participants (85 men and 74 women; aged 19–79) were randomized to daily intake of one serving of phytosterols-enriched soya drink (N = 82), equivalent to 2 g of phytosterol per day, or a matched soya drink without phytosterols (N = 77) for 3 weeks. Adverse events, withdrawal and compliance were documented. Among the treatment group (N = 82), phytosterols-enriched soya drink significantly decreased LDL-cholesterol by 5.96% (SE 1.48, 95% CI − 8.91%, − 3.00%) with a median of 6.74% compared with baseline, resulting in a significant reduction of 4.70% (95% CI − 8.89%, − 0.51%; p = 0.028) with a median of 5.20% compared with placebo (N = 77). In contrast, there were no significant changes in other lipid parameters, blood glucose, blood pressure, body weight or waist circumference. Remarkably, 95% of the participants randomized to the fortified drink reported no adverse events at all. Daily consumption of a phytosterols-enriched soya drink may be a simple and cost-neutral means of lowering LDL-cholesterol in individuals in China, with massive population and rising incidence of coronary heart disease (ClinicalTrials.gov identifier: NCT02881658; date of registration: 14 Aug 2016).

Cloud detection in remote sensing images is a challenging but significant task. Due to the variety and complexity of underlying surfaces, most of the current cloud detection methods have difficulty in detecting thin cloud regions. In fact, it is quite meaningful to distinguish thin clouds from thick clouds, especially in cloud removal and target detection tasks. Therefore, we propose a method based on multiscale features-convolutional neural network (MF-CNN) to detect thin cloud, thick cloud, and noncloud pixels of remote sensing images simultaneously. Landsat 8 satellite imagery with various levels of cloud coverage is used to demonstrate the effectiveness of our proposed MF-CNN model. We first stack visible, near-infrared, short-wave, cirrus, and thermal infrared bands of Landsat 8 imagery to obtain the combined spectral information. The MF-CNN model is then used to learn the multiscale global features of input images. The high-level semantic information obtained in the process of feature learning is integrated with low-level spatial information to classify the imagery into thick, thin and noncloud regions. The performance of our proposed model is compared to that of various commonly used cloud detection methods in both qualitative and quantitative aspects. Compared to other cloud detection methods, the experimental results show that our proposed method has a better performance not only in thick and thin clouds but also in the entire cloud regions.

Alcohol metabolism causes hepatocytes to release damage-associated molecular patterns (DAMPs). This includes mitochondrial DNA (mtDNA), which is generated and released from damaged hepatocytes and contributes to liver injury by producing proinflammatory cytokines. STING is a pattern recognition receptor of DAMPs known to control the induction of innate immunity in various pathological processes. However, the expression profile and functions of STING in the Gao binge ethanol model remain poorly understood. We demonstrated that STING is upregulated in the Gao binge ethanol model. STING functions as an mtDNA sensor in the Kupffer cells of the liver and induces STING-signaling pathway-dependent inflammation and further aggravates hepatocyte apoptosis in the Gao binge ethanol model. This study provides novel insights into predicting disease progression and developing targeted therapies for alcoholic liver injury.

Although highly heritable, environment also contributes to the etiology of autism spectrum disorder (ASD), with several specific environmental factors previously suggested. A registry-linked population-based twin cohort of 15,701 pairs (586 individuals with an ASD diagnosis), was established within the Child and Adolescent Twin Study in Sweden. Participants were evaluated for autistic symptoms at age 9 using the Autism-Tics, ADHD and other Comorbidities parental interview. A series of binary cut-offs indicated whether participants scored over various ASD symptom percentiles. Three early medical factors previously associated with ASD, beyond familial confounding (low birth weight, congenital malformations and perinatal hypoxia), were summed up creating an individual cumulative exposure load. A series of unconditional logistic regressions between all individuals and conditional regressions within twin pairs were performed for each outcome and exposure level. Between all individuals increasing cumulative early exposure loads were associated with increasing risk of ASD diagnosis (OR 3.33 (95%CI 1.79–6.20) for three exposures) and autistic symptoms (ranging from OR 2.12 (1.57–2.86) for three exposures at the 55th symptom percentile cut-off to OR 3.39 (2.2–5.24) at the 95th). Within twin pairs, the association between three exposures and an ASD diagnosis remained similar, but not statistically significant (OR 2.39 (0.62–9.24)). Having a higher load of early cumulative exposure was consistently associated with autistic symptoms after adjusting for familial confounding and sex (OR 3.45 (1.66–7.15) to OR 7.36 (1.99–27.18)). This study gives support to the cumulative stress hypothesis of ASD, and the dimensional model regarding environmental exposures, after adjustment for familial confounding.

Background The overall prognosis of hepatocellular carcinoma (HCC) is poor and novel prognostic biomarkers might better monitor the progression of HCC. Cell division cycle protein 45 (CDC45) plays a key role in DNA replication and considered to be involved in tumorigenesis. This study investigated CDC45 expression in tumour tissues and defined its prognostic value in HCC patients. Methods We used immunohistochemistry (IHC) staining to examine the expression of CDC45 in tumour tissue specimens and compare them with adjacent normal tissue specimens using a constructed tissue microarray (TMA) and analyzed how clinical features are related to HCC prognosis. Functional enrichment analyses were used to describe significantly involved hallmark pathways of differentially expressed genes (DEGs, which were screened out according to the high or low expression of CDC45 in tumour tissues). Results Our findings showed that the proteome expression of CDC45 was evidently downregulated in HCC tissues compared with matched normal tissues (P P = 0.046). Multivariate analysis indicated that CDC45 expression (P = 0.035) was an independent prognostic factor for the overall survival (OS) rate of HCC patients. Patients with CDC45 expression was positively correlated with OS rates among HCC patients (P Discussion Our findings showed that low proteomic level of CDC45 was associated with a poor prognosis in HCC patients, indicating that CDC45 might be a novel prognostic marker.

Objective This study aimed to compare the diagnostic performance of vital touch tissue quantification (VTQ) and virtual touch tissue imaging quantification (VTIQ) in diagnosing infants with biliary atresia (BA) from jaundiced infants. Methods In this study, 26 jaundiced infants with BA, 33 jaundiced infants without BA, and 40 normal infants were enrolled. The hepatic shear wave velocity (SWV) of each infant was determined by VTQ and VTIQ examinations, respectively. Then, the receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) and optimal cut-off values were calculated to evaluate the sensitivities and specificities of VTIQ and VTQ for BA. Results The mean values of SWV of the control group measured by VTQ and VTIQ were (1.09 ± 0.18) m/s and (1.36 ± 0.21) m/s, respectively. The mean values of SWV of the non-BA group measured by VTQ and VTIQ were (1.30 ± 0.28) m/s and (1.52 ± 0.29) m/s, respectively. The mean values of SWV of the BA group measured by VTQ and VTIQ were (2.36 ± 0.36) m/s and (2.43 ± 0.29) m/s, respectively. The diagnostic threshold of VTQ and VTIQ to diagnose BA was 1.77 and 1.92 m/s. The sensitivities of VTQ and VTIQ to diagnose BA were 90.9% and 95.5%. The specificities of VTQ and VTIQ to diagnose BA were 68.4% and 78.9%. Conclusion Vital touch tissue quantification and VTIQ could help distinguish infants with BA from jaundiced infants by measuring the liver SWV values. VTIQ has higher sensitivity and specificity than VTQ.

Switched networks require loop-avoidance protocols to avoid looping of broadcast and multicast Loop-avoidance protocols use a tree algorithm to construct a logical tree from one root such as rapid spanning tree protocol (RSTP). RSTP results in high convergence latency and heavily impaired network performance on root switch failures. Some protocols construct a logical tree from every switch resulting in high operational overhead. We propose the Meshed Tree Protocol (MTP) to designate the number of roots based on desired network uptime and computational overhead, where a meshed tree conceptually maintains multiple tree branches from a root. MTP based on multi meshed tree algorithm (MMTA), constructs and maintains multiple meshed trees from multiple designated roots. We compare a prototype of MTP based on MMTA against RSTP using switched networks in the Global Environment for Network Innovation (GENI) testbed. MTP's root failure recovery response is several magnitudes superior to RSTP.

Background and Objectives: The influence of age at diagnosis of breast cancer upon the prognosis of patients with different immunohistochemical (IHC)-defined subtypes is still incompletely defined. Our study aimed at examining the association of age at diagnosis and risk of breast cancer-specific mortality (BCSM).Methods: 172,179 eligible breast cancer patients were obtained for our study cohort using the Surveillance, Epidemiology, and End Results database from 2010 to 2015. Patients were classified into four IHC-defined subtypes according to their ER, PgR, and HER2 status. Kaplan–Meier plots were used to describe BCSM among patients in different age groups. A Cox proportional hazards model was used for multivariate analysis. A multivariable fractional polynomial model within the Cox proportional hazards model was used to evaluate the relationship between age at diagnosis and the risk of BCSM.Results: For the whole cohort, the median follow-up time was 43 months. Patients younger than 40 years and those older than 79 years presented with the worst BCSM (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.03–1.23, and HR 3.52, 95% CI 3.23–3.83, respectively, p < 0.01, with age 40–49 years as the reference). The log hazard ratios of hormone receptor (HoR)(+)/HER2(–) patients formed a quadratic relationship between age at diagnosis and BCSM, but not in the other three subtypes of breast cancer. In the HoR(+)/HER2(–) subtype, patients younger than 40 years had worse BCSM than those aged at 40–49 years (HR 1.26, 95% CI 1.10–1.45, and p < 0.01).Conclusions: Women diagnosed with HoR(+)/HER2(–) breast cancer younger than 40 years or older than 79 years of age suffer higher rates of cancer-specific mortality. Young age at diagnosis may be particularly prognostic in HoR(+)/HER2(–) breast cancer.

BACKGROUND: This study aimed to compare the diagnostic and predictive value of power Doppler ultrasonography (PDU) with Tc-99m dimercaptosuccinic acid (DMSA) renal scintigraphy in pediatric acute pyelonephritis (APN) using a semiquantitative analysis system. METHODS: A total of 92 children and infants (184 kidneys) were hospitalized with possible APN. All children were examined by PDU and DMSA scintigraphy within 72 hours of admission. An empiric 9-point semiquantitative analysis system was used to sort kidneys into four grades (grade 0–III). Patients with several episodes of APN and congenital structural anomalies were excluded. RESULTS: Of 184 kidneys, we found 68 abnormal (grade I–III) and 116 normal (Grade 0) with DMSA scintigraphy, and 84 abnormal and 100 normal with PDU. In all, 23 kidneys were shown to be diseased by PDU but normal on DMSA scintigraphy while 7 kidneys showed the opposite trend. The sensitivity and specificity of PDU for diagnosing APN was 89.7% and 80.2%, respectively (P

Background The outcomes of hepatocellular carcinoma (HCC) remain poor despite dramatic improvements in treatment, and novel prognostic biomarkers are urgently needed to ameliorate the situation. Cell division cycle protein 45 (CDC45) plays a key role in DNA replication, which is considered to be involved in tumorigenesis and has become a new prognostic marker. This study investigated CDC45 expression in tumour tissues and defined its prognostic value in HCC patients. Methods Differential transcriptional and proteomic expression profiles were obtained and validated using multiple datasets. We then used immunohistochemistry (IHC) staining to examine the expression of CDC45 in tumour tissue specimens and compare them with adjacent normal tissue specimens using a constructed tissue microarray (TMA) and analysed the relationship of clinical features and prognosis in HCC patients. Functional enrichment analyses were used to describe significantly involved hallmark pathways of differentially expressed genes (DEGs). Results Contrary to the transcriptome expression level in the database, our results showed that the proteome expression of CDC45 in was evidently downregulated in HCC compared with normal adjacent tissues (P

AIM: To estimate the prevalence of and risk factors for dry eye disease (DED) in young and middle-aged office employee in Xi'an. METHODS: This cross-sectional study of the prevalence of and risk factors for DED investigated 486 young and middle-aged Chinese office employee in Xi'an. DED symptoms and potential risk factors were assessed using the ocular surface disease index combined with a risk factors questionnaire, and tear function was evaluated using the tear film break-up time and Schirmer's test. Possible risk factors for DED were estimated by binary Logistic regression analysis. RESULTS: DED was diagnosed in 100 females and 96 males, giving a prevalence of 40.3% [95% confidence interval (CI)=36.0%-44.7%]. The multivariate binary Logistic regression model indicated that the possible risk factors for DED were being female (OR=1.592, 95%CI=1.034-2.451, P=0.035), being aged ≥40y (OR=1.593, 95%CI=1.034-2.454, P=0.035), using a VDT daily for >6h (OR=1.990, 95%CI=1.334-2.971, P=0.001), the presence of central air conditioning (OR=1.548, 95%CI=1.053-2.276, P=0.026), and self-reported dryness of the mouth and nose (OR=1.589, 95%CI=1.071-2.357, P=0.021). CONCLUSION: There is a high prevalence of clinically diagnosed DED in young and middle-aged video display terminal (VDT) users. Interventions against the modifiable risk factors should be taken to prevent the occurrence and development of DED in this population.

Disruptive mood dysregulation disorder (DMDD) is characterized by nonepisodic irritability and has a high rate of comorbidity with attention-deficit/hyperactivity disorder (ADHD). This is the first study to explore the effects of aripiprazole combined with methylphenidate on clinical symptoms and cognitive functions in patients with DMDD and ADHD.Patients with DMDD and ADHD (the DMDD-ADHD Group, n = 24; aged 7-17 years) completed a 6-week, open-label trial of aripiprazole and methylphenidate. The pre- and posttreatment outcome measures included the parent-rated Swanson, Nolan, and Pelham Scale-version IV, Child Behavior Checklist, and self-reported Beck Youth Inventories-II, as well as a neuropsychological battery composed of the Children's Color Trail Test and Conner's Continuous Performance Test. The comparison group consisting of patients with ADHD (the ADHD Group, n = 27) was recruited to investigate the differences in clinical and neuropsychological profiles between the two groups at baseline.The DMDD-ADHD Group showed worse irritability, disruptive behaviors, anxious/depressed symptoms, and social problems relative to the ADHD Group at baseline assessments. The combination treatment significantly improved irritability, externalizing symptoms, depression, anxiety, attention, social problems, and reaction time variability. The effect sizes of reductions in parent-rated irritability, oppositional defiant symptoms, and inattention were comparable (Cohen's d = 1.26, 1.11, and 1.40, respectively).This pilot study showed the tolerability of the aripiprazole/methylphenidate combination by patients with DMDD and ADHD and its efficaciousness for treating clinical symptoms and for improving cognitive function. Further randomized, controlled, cross-over studies are needed.

OBJECTIVE To investigate the improvement of cytotoxicity of autologous CIKs from patients with breast cancer to MCF-7 cells by suppressed PD-1 expression. METHODS The Lentiviral Vector/PD-1 carrying the gene that can suppressed PD-1 was transferred to CIK cells from patients with breast cancer to inhibit PD-1 expression. The PD-1 protein were detected by RT-PCR and Western blot. The positive PD-1 of CIKs and PD-L1 of MCF-7 cells were detected by FCM, and cytotoxicity of CIKs to MCF-7 was assayed by CCK-8. RESULTS The PD-1 positive CIKs with Lentiviral Vector/PD-1 transferred from patients with breast cancer were 16.02%, 14.36% and 14.64% at 14th, 21st and 28th day, obviously inhibited as compared to 50.54%, 74.50% and 73.36% in CIKs without transinfection (P< 0.05); the Lentiviral Vector/PD-1 decreased the PD-1 mRNA levels in CIK cells, and Lentiviral Vector/PD-1-transferred CIKs had lower PD-1 expression; CCK-8 detection showed that at 14th day, the cytotoxicity rates of CIKs with blank plasmids and those with PD-1 transfection to MCF-7 cells were 58.78% and 68.14%, respectively. CONCLUSION MCF-7 cells have a strong PD-L1 expression at its surface, and inhibition of PD-1 expression can improve the cytotoxicity of CIK cells.

Background Nausea and vomiting are the most common adverse reactions to chemotherapy. Aim To discuss the relationship between Helicobacter pylori and chemotherapy-induced nausea and vomiting (CINV). Methods A total of 112 patients with malignant tumours of the gastrointestinal tract was selected. Based on the 14C-urea breath test results, the patients were divided into H. pylori-positive (n = 59) and H. pylori-negative (n = 53) groups. Both groups received prophylactic antiemetic treatment during chemotherapy. The incidence of nausea and vomiting and their effects on the patients’ life functions was recorded using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemetic Tool (MAT) and the Functional Living Index Emesis (FLIE) from 0–120 h after chemotherapy. Records of the H. pylori-positive and H. pylori-negative groups were compared. Results The rates of nausea and vomiting remission were higher in the H. pylori -negative group than in the H. pylori -positive group. The proportions of no effect in daily life (NIDL) patients in the nausea and vomiting section were 73.4 and 75.5% in the H. pylori -negative group respectively. There was a higher proportion of NIDL patients in the H. pylori -negative group than in the H. pylori -positive group (P < 0.001, P = 0.046). A multivariate unconditional logistic regression analysis was performed, and the results showed that H. pylori infection was a factor affecting the nausea scores on the FLIE (odds ratio = 0.757, 95% confidence interval 0.597–0.960, P = 0.021). Conclusion H. pylori infection in patients with cancer may be a factor that increases CINV.

As machine learning is deployed in more settings, including in security-sensitive applications such as malware detection, the risks posed by adversarial examples that fool machine-learning classifiers have become magnified. Black-box attacks are especially dangerous, as they only require the attacker to have the ability to query the target model and observe the labels it returns, without knowing anything else about the model. Current black-box attacks either have low success rates, require a high number of queries, produce adversarial images that are easily distinguishable from their sources, or are not flexible in controlling the outcome of the attack. In this paper, we present AdversarialPSO, (Code available: https://github.com/rhm6501/AdversarialPSOImages) a black-box attack that uses few queries to create adversarial examples with high success rates. AdversarialPSO is based on Particle Swarm Optimization, a gradient-free evolutionary search algorithm, with special adaptations to make it effective for the black-box setting. It is flexible in balancing the number of queries submitted to the target against the quality of the adversarial examples. We evaluated AdversarialPSO on CIFAR-10, MNIST, and Imagenet, achieving success rates of 94.9%, 98.5%, and 96.9%, respectively, while submitting numbers of queries comparable to prior work. Our results show that black-box attacks can be adapted to favor fewer queries or higher quality adversarial images, while still maintaining high success rates.

Due to the development of electric vehicles (EVs), recently the research pays more attention to converters in the EV systems. Among the converters, the wide input voltage range converter implemented between the EV battery pack and the auxiliary circuits are discussed. The SiC-based wide input voltage range converter with boost function is implemented in the thesis. Moreover, the operating principles of the resonant converter are studied. In addition, the voltage stress on the resonant capacitor and the current stress through the resonant tank are also analyzed in detail. Finally, the laboratory prototype of wide input range full-bridge (FB) DC-to-DC resonant converter with active-boost rectifier based on SiC power transistors with the input voltage 200 - 400 V, output voltage 48 V, and rated power 1 kW is implemented. As the experimental results demonstrate, this converter can be operated in wide input voltage range, and the highest efficiency is 91.07%.

Immune thrombocytopenia (ITP) is an autoimmune disorder in which its immune system destroys platelets and leads to haemorrhage symptom. Recent studies have found that regulatory T cells (Tregs) in peripheral blood, bone marrow, and spleen were reduced in ITP patients and recovered after effective ITP therapy. Low-dose Interleukin-2 (IL-2) has been reported recently to increase Tregs and used to treat autoimmune disease including graft-versus-host disease (GVHD) after organ transplantation and HCV-related autoimmune vasculitis. However, it is unknown whether IL-2 is able to treat ITP. We have used low-dose IL-2 (1.0 million IU/day) on 5 consecutive days per week for 4 weeks in a 36-year-old patient with ITP. The result has shown that low-dose IL-2 induces expansion of Tregs significantly and increase platelet count was gradually from 36 × 109 /L to maximum 85 × 109 /L. No side effects of IL-2 have been found. This result suggested that low-dose of IL-2 may have therapeutic potential for ITP. © 2016 International Clinical Cytometry Society.

AIM: To observe the therapeutic effect of corneal collagen cross-linking (CXL) in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS: New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each). The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM) at 4wk. RESULTS: A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (P

Exosomes can mediate intercellular communication by conveying various bioactive molecules. Plentiful evidence suggests that exosomes are involved in many liver diseases including hepatitis C virus infection, hepatitis B virus infection, hepatocellular carcinoma, liver fibrosis, cirrhosis, non-alcoholic fatty liver disease, and alcoholic liver disease. Moreover, exosomes are present in nearly all human body fluids. Therefore, exosomal miRNA or proteins have the potential to be novel biomarkers of liver diseases. In the treatment of liver diseases, exosomes could participate in adaptive immune response and mesenchymal stem cell-based therapy. Exosomes can also be used as vehicles for genetic materials and drug delivery.

Purpose The purpose of this paper is to examine issues academics at importing institutions face while delivering Australian degrees in Malaysia. Transnational higher education (TNE) has been widely researched. However, less widely researched is the area of understanding what academics at the offshore locations need to uphold the required academic standards of their partnered exporting universities. This area warrants close attention if Australian and other transnational education universities are to sustain their growth through a partnership model with offshore academics delivering a portion (often a substantial portion) of the teaching. Design/methodology/approach Two focus groups were conducted with a mix of long standing and newly recruited Malaysian lecturers who taught into an Australian degree through a partnership arrangement. The semi-structured questions which were used were derived from a preliminary literature review and previous internal institutional reports. Findings The findings from the focus groups indicate that TNE is largely “Australian-centric” when addressing the standard of academic quality and integrity. The findings pointed not so much to any sustained internationalisation of curriculum or administration or personnel but more as internationalisation as deemed required by the local academic. Originality/value To a greater extent, the findings highlighted that equivalent student outcomes do not necessarily equate to equivalent learning experiences or teaching workload. In fact, the frustration of the interviewees on the tension to fulfil the home institution curriculum and helping students to “comprehend” an Australian-centric curriculum translates to “additional and unrecognised workload” for the interviewees.

Planning for underground spaces has become an effective way to use central areas in cities given the steady economic growth in China. The development of underground spaces in mountainous cities has satisfied the needs of the diversification of the city commercial areas and pedestrian movement. Safety issues exist because these underground spaces were originally used for civil air defense. This study was based on the underground commercial street in Chongqing, which is a typical mountainous city. Based on the results of combined fieldwork and survey, this paper summarized current safety issues, which include the not-fully-open exit, the imbalanced exit location, blocked evacuation routes, and the poor awareness of the potential safety issues. This paper proposed a framework of the safety factors for the underground space and synopsized prevention strategies that are specific to potential disasters in the underground environment. The framework comprises ensuring that the exits are fully open, the underground corridors are kept unblocked, the open space on the street is increased for disaster prevention, and equipment security is maintained and managed. At last, This paper summarized disaster prevention strategies, which include ensuring unimpeded exits, balancing the locations of the exits, avoiding blocks, increasing the disaster prevention square area in the underground space, maintaining and managing the security of the equipment.

Purpose – The purpose of this paper is to determine the influence and interaction of social networks and personality traits on the self-disclosure behavior of social network site (SNS) users. According to social capital theory and the Big Five personality model, the authors hypothesized that social capital factors would affect the accuracy and amount of self-disclosure behavior and that personality traits would moderate this effect. Design/methodology/approach – A survey was conducted to collect data from 207 SNS users. The questionnaire was administered in university classrooms and libraries and via e-mail. The measurement model and structural model were examined by using LISREL 8.8 and SmartPLS 2.0. Findings – Based on the path analysis, the authors identified several interesting patterns to explain self-disclosure behavior on SNSs. First, the centrality of SNS users has a positive effect on their amount of self-disclosure. Moreover, people who are more extroverted disclose personal information that is more accurate with the level of the cognitive dimension held constant and disclose a greater amount of personal information with the level of the structural dimension held constant. From a practical perspective, the results may provide useful insight for companies operating SNSs. Originality/value – This study analyzed the influence of social capital factors on SNS users’ self-disclosure, as well as the interactions between personality and social capital factors. Specifically, the authors examined six important variables of social capital divided into three dimensions. This research complements current research on SNSs by focusing on SNS users’ motivation to disclose self-related information in addition to information sharing.

The incidence of cancer is increasing at an alarming rate despite recent advances in prevention strategies, diagnostics and therapeutics for various types of cancer. The identification of novel biomarkers to aid in prognosis and treatment for cancer is urgently required. Uncontrolled proliferation and dysregulated apoptosis are characteristics exhibited by cancer cells in the initiation of various types of cancer. Notably, aberrant expression of crucial oncogenes or cancer suppressors is a defining event in cancer occurrence. Research has demonstrated that SAD1/UNC84 domain protein-2 (SUN2) serves a suppressive role in breast cancer, atypical teratoid/rhabdoid tumors and lung cancer progression. Furthermore, SUN2 inhibits cancer cell proliferation, migration and promotes apoptosis. Recent reports have also shown that SUN2 serves prominent roles in resistance to the excessive DNA damage that destabilizes the genome and promotes cancer development, and these functions of SUN2 are critical for evading initiation of cancer. Additionally, increasing evidence has demonstrated that SUN2 is involved in maintaining cell nuclear structure and appears to be a central component for organizing the natural nuclear architecture in cancer cells. The focus of the present review is to provide an overview on the pharmacological functions of SUN2 in cancers. These findings suggest that SUN2 may serve as a promising therapeutic target and novel predictive marker in various types of cancer.

Objectives: Methylphenidate (MPH) is highly effective in controlling the symptoms of attention-deficit/hyperactivity disorder (ADHD), but some children with ADHD either do not respond to, or do not tolerate, treatment. Dextromethorphan (DM) is a neuroprotective agent which has been used in the treatment of neuropsychiatric disorders. This clinical trial had examined the effect of DM on the use of MPH in the children with ADHD. Methods: This randomized double-blind clinical trial had evaluated 44 male outpatients, aged between 6 and 12 years, with a diagnosis of ADHD. The study subjects were randomly assigned into one of the two groups: receiving MPH alone (15-60 mg per day) or MPH plus DM (30-60 mg per day) for 8 weeks. Assessments, comprising the Chinese version of the Child Behavior Checklist (CBCL-C) scale and the Swanson, Nolan and Pelham Questionnaire (SNAP)-IV rating tests conducted by parents and the serum cytokines measured by microarray and enzyme-linked immunosorband assay (ELISA), were compared between groups at baseline and at 8 weeks after the medication was started. Results: There were a significant decrease at the mean scores of both CBCL-C and SNAP-IV scales after 8 weeks of treatment, but no significant differences between MPH and MPH+DM groups. Compared with the MPH-only group, the mean scores of some psychometric parameters reported on the CBCL-C and SNAP-IV scales regarding time effects as well as the attention problems on the CBCL-C scale regarding group effect were significantly higher in the DM+MPH group. Although there were no significant differences in the levels of various serum cytokines between groups, the subjects in the DM-MPH group had relatively fewer and lower levels of adverse effects. Significant interactions were found between the withdrawn/depression item reported on the CBCL-C scale and tumor necrosis factor α (ခTNF-α) (p = 0.027), as well as between thought problems item on the CBCL-C and TNF-α (p = 0.028) in subjects who had received DM+MPH treatment. Conclusion: Following the trial, DM+MPH was not superior to MPH alone for the treatment of children with ADHD, yet DM may potentially have negative effects on ADHD symptoms when combined with MPH. Clinical Trial Registration: Clinicaltrials.gov, trial number: NCT01787136.

Irritability is among the most bothersome emotional symptoms in children. It often leads to mental health services referral, significant impairment, and distress to their families. Although there is increasing scientific evidence supporting the existence of extreme irritability in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) diagnosis of disruptive mood dysregulation disorder, few studies have investigated the measurement of irritability in children. This pilot study aimed to examine the psychometric properties of the Chinese version of the Affective Reactivity Index (ARI) and the Aberrant Behavior Checklist (ABC)-irritability subscale. In addition, we investigated adaptive difficulties among children with irritability.A total of 97 children and adolescents 6 to 17 years of age (M = 10.20, SD = 2.70) were recruited from the psychiatric outpatient department of a university hospital in Taipei. The participants completed the Chinese version of the ARI self-report form and the Social Adjustment Inventory for Children and Adolescents (SAICA). Their parents completed the ARI parent report form, the Chinese version of the ABC-irritability subscale, and the Child Behavior Checklist. Diagnostic interviews were administered based on diagnostic criteria of DSM-5 to confirm the participants' psychiatric diagnoses.The Chinese ABC-irritability subscale and the parent and self-report scales of the Chinese ARI showed good test-retest reliability, internal consistency, and concurrent validity. Scores from the ABC-irritability subscale and two forms of the ARI were all significantly correlated with aggressive behaviors, anxious/depressed symptoms, and social problems. In addition, irritability among children was significantly associated with maladjustment in school, with peer problems, and with problems at home.Our findings suggest that irritability may be associated with impaired social adaptive functioning among children and adolescents. The Chinese version of the ARI and the ABC-irritability subscale are useful for measuring irritability in both clinical and research settings in the Chinese population.

The notable clinical success of cancer immunotherapy using checkpoint blockade suggests that it is likely to form the foundation of curative therapy for many malignancies. However, checkpoint blockades do not achieve sustained clinical response in most patients and thus amounts of problems needed to be figured out. Regarding these challenges, the 2017 Chinese Lung Cancer Summit expert panel organized a forum on the 14th Chinese Lung Cancer Summit to formally discuss these controversies. Five consensuses finally were reached to guide the application of checkpoint blockades.

Churn prediction is a major focus that all the companies need to concern. Many studies have shown that class imbalance has a significant impact on churn prediction, but there is still no consensus on which technique is the best to cope with this issue. Recently, active learning has proved to be effective for imbalance learning. We try to apply it to churn prediction in this paper. In order to verify its effectiveness, we carry out experiments on six real-world data sets from the telecommunication industry and compare its performance with the other three benchmark resampling methods. Besides using the AUC to measure the accuracy of classification, we take the profit-based measure --- expected maximum profit (EMP) into account which measures the real cost and benefit produced by the models. The experimental results show that active learning is a good choice in dealing with the class imbalance problem in churn prediction.

Mapping molecular sub-types in breast cancer (BC) tumours is a rapidly evolving area due to growing interest in, for example, targeted therapy and screening high-risk populations for early diagnosis. We report a new concept for profiling BC molecular sub-types based on volatile organic compounds (VOCs). For this purpose, breath samples were collected from 276 female volunteers, including healthy, benign conditions, ductal carcinoma in situ (DCIS) and malignant lesions. Breath samples were analysed by gas chromatography mass spectrometry (GC-MS) and artificially intelligent nanoarray technology. Applying the non-parametric Wilcoxon/Kruskal-Wallis test, GC-MS analysis found 23 compounds that were significantly different (p < 0.05) in breath samples of BC patients with different molecular sub-types. Discriminant function analysis (DFA) of the nanoarray identified unique volatolomic signatures between cancer and non-cancer cases (83% accuracy in blind testing), and for the different molecular sub-types with accuracies ranging from 82 to 87%, sensitivities of 81 to 88% and specificities of 76 to 96% in leave-one-out cross-validation. These results demonstrate the presence of detectable breath VOC patterns for accurately profiling molecular sub-types in BC, either through specific compound identification by GC-MS or by volatolomic signatures obtained through statistical analysis of the artificially intelligent nanoarray responses.

Summary Background Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. Methods For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18–70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0–1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624. Findings From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4–26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7–25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523–0·915; p non-inferiority superiority =0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16–9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76–7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [ vs one [ vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1–4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1–4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. Interpretation Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. Funding Shanghai Natural Science Foundation.

Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case–control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches conducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast cancer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confidence interval (CI) = 0.04–0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13–0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77–7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues respectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; therefore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis.

Objective To explore the role of Internet addiction in the development of self-harm/suicidal behavior among adolescents after 1-year of follow-up. Study design We conducted this 1-year, prospective cohort study of 1861 adolescents (mean age 15.93 years) attending a senior high school in Taiwan; 1735 respondents (93.2%) were classified as having no history of self-harm/suicidal attempts in the initial assessment and were referred to as the “noncase” cohort. The Chen Internet Addiction Scale was used to identify individuals with Internet addiction. The participants were evaluated for self-harm/suicidal behavior again 1 year later and the “noncase” cohort was selected for statistical analysis. To examine the relationship between Internet addiction and self-harm/suicidal behavior, multivariate logistic regression analysis was performed using Internet addiction at baseline as the predictor for newly developed self-harm/suicidal behavior in the next year, after adjustment for potential confounding variables. Results The prevalence rate of Internet addiction at baseline was 23.0%. There were 59 students (3.9%) who were identified as having developed new self-harm/suicidal behaviors on follow-up assessments. After controlling for the effects of potential confounders, the relative risk of newly emerging self-harm/suicidal behavior for participants who were classified as Internet addicted was 2.41 (95% CI 1.16-4.99, P = .018) when compared with those without Internet addiction. Conclusions Our findings indicate that Internet addiction is prospectively associated with the incidence of self-harm/suicidal behavior in adolescents.

Taking the underground street in Three Gorges Plaza in the Shapingba District, Chongqing, as an example, the present study focused on a densely populated underground street downtown in a mountainous city, in which the issue of emergency evacuation in case of fire was discussed. The total evacuation number could be worked out according to the 'method of trip generation rate'; the length of escape routes and the width of escape exits were counted, and the maximum capacity of people for each emergency exit was calculated according to the unit capacity. Based on the above data, the escape route was built by the iterative programming algorithm so as to check the safety of the current underground street in the mountainous city, in order that technical support can be provided for effective countermeasures. Thus, the emergency evacuation capability of a downtown underground street in a mountainous city can be enhanced. Keywords Civil air defense projects, escape routes, escape time, mountainous city, underground street. Language: en

We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data from 182 females, as follows: 48 females with OC, 48 tumor-free controls and 86 females with benign gynecological neoplasia. Analysis of the breath samples with gas chromatography linked with mass spectrometry shows that decanal, nonanal, styrene, 2-butanone and hexadecane could serve as potential volatile markers for OC. Analysis of the same samples with tailor-made nanoarrays shows good discrimination between females with OC and females that have either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity and specificity). Conversely, the nanoarray output shows excellent discrimination between the OC patients and the tumor-free controls (79% sensitivity, 100% specificity and 89% accuracy). These results suggest that the nanoarray approach might be useful to avoid unnecessary complicated or expensive tests for tumor-free females in case of a negative result. In the case of positive result, the test will indicate with high probability the presence of OC.

Hepatic fibrosis, a common pathological feature and leading cause of various chronic liver diseases, still lacks effective therapy. Hesperetin derivative (HD) is a derivative of Traditional Chinese Medicine monomer isolated from the fruit peel of Citrusaurantium L. (Rutaceae). In the present study, we revealed the anti-fibrotic effects of HD in CCl4-induced mouse hepatic fibrosis model and in TGF-β1-activated LX-2 cells, in vivo and in vitro. Results showed that HD prevented CCl4-induced liver injury and histological damage. Consistently, HD inhibited the up-regulation of liver fibrogenesis markers α-SMA, Col1α1, Col3α1 and TIMP-1 in primary hepatic stellate cells (HSCs) and suppressed inflammatory responses in primary liver macrophages from hepatic fibrosis mice. Furthermore, HD promoted the apoptosis of activated HSCs, a key step in the onset of fibrosis regression. Mechanistically, the Hedgehog pathway was involved in HD-treated hepatic fibrosis, and HD specifically contributed to attenuate the aberrant expression of Glioma associated oncogene-1 (Gli-1). Interestingly, blockade of Gli-1 removed the inhibitory effect of HD on activated HSCs, indicating that Gli-1 may play a pivotal role in mediating the anti-fibrotic effect of HD in hepatic fibrosis. Collectively, our results suggest that HD may be a potential anti-fibrotic Traditional Chinese Medicine monomer for the treatment of hepatic fibrosis.

This paper summarized the principles of urban road system planning from the aspects of traffic demand, comprehensive planning and emergency response. Then it analyzed framework system of disaster prevention and relief roads in Japan and Taiwan. It summarized the enlightenment of the experience of Japan and Taiwan to the establishment of the road system for disaster prevention and relief in China. It included the establishment of the road system for urban disaster prevention and relief theory, the standardization of the content of urban disaster prevention and relief planning, and the improvement of the road management system and mechanism for urban disaster prevention and relief. The theory of road system for disaster prevention and relief to guide the planning practice, so as to ensure the safe and sustainable development of China's cities.

In a number of large clinical studies, concurrent administration of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with cytotoxic chemotherapy has failed to improve the survival rate in unselected patients with advanced non-small cell lung cancer (NSCLC). The purpose of the current study was to investigate the antitumor effects of gefitinib in combination with docetaxel in EGFR-TKI-sensitive, primary resistant and acquired resistant human lung cancer cell lines and the associated molecular mechanisms. EGFR-TKI-sensitive and EGFR-TKI-resistant human lung cancer cell lines were exposed to gefitinib or docetaxel alone, or in combination. Cell viability was assessed using the MTT assay. Cell cycle distribution and apoptosis were measured by flow cytometry and alterations in signaling pathways were examined by immunoblotting. The cytotoxic interaction between docetaxel and gefitinib was determined by combination index (CI) analysis. Coadministration of gefitinib and docetaxel was observed to result in superior inhibition of tumor cell proliferation, however, increased rates of apoptosis were only observed in EGFR-TKI-sensitive cells, whereas, antagonistic activity was observed in the EGFR-TKI-resistant cell lines. Gefitinib arrested the cell cycle at the G1 phase, whereas docetaxel arrested the cell cycle at the S phase. In addition, in cells exhibiting a synergistic interaction between gefitinib and docetaxel, an increase in p-EGFR and p-AKT was observed following chemotherapy exposure. By contrast, in cells exhibiting no change or a decrease in p-EGFR and p-AKT following docetaxel treatment, an antagonistic interaction between the two agents was observed. In conclusion, the combination of docetaxel and gefitinib generated synergistic effects in EGFR-TKI-sensitive cells and antagonistic effects in EGFR-TKI-primary and acquired resistant cells, suggesting that EGFR-TKIs, combined with docetaxel, may be beneficial to NSCLC patients with EGFR mutations. The results also indicate that the interactions between gefitinib and docetaxel may be associated with the effect of docetaxel on EGFR phosphorylation.

Part 5: Malware Forensics; International audience; Malware is the fastest growing threat to information technology systems. Although a single absolute solution for defeating malware is improbable, a stacked arsenal against malicious software enhances the ability to maintain security and privacy. This research attempts to reinforce the anti-malware arsenal by studying a behavioral activity common to software – the use of handles. The characteristics of handle usage by benign and malicious software are extracted and exploited in an effort to distinguish between the two classes. An automated malware detection mechanism is presented that utilizes memory forensics, information retrieval and machine learning techniques. Experimentation with a malware dataset yields a malware detection rate of 91.4% with precision and recall of 89.8% and 91.1%, respectively.

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

// Wei Wang 1, * , Wei-Dong Jia 2 , Bing Hu 1 , Yue-Yin Pan 1, * 1 Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, PR China 2 Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, PR China * These authors contributed equally to this work Correspondence to: Wei Wang, email: whouwei@gmail.com Yue-Yin Pan, email: yueyinpan1965@163.com Keywords: RAB10, hepatocellular carcinoma, oncogene, biomarker, therapeutic target Received: December 08, 2016 Accepted: February 07, 2017 Published: February 19, 2017 ABSTRACT Hepatocellular carcinoma (HCC), one of the most common and lethal cancers worldwide, has a high recurrence rate with current treatment modalities. Identifying biomarkers for early diagnosis and discovering new sufficient molecular targets for the development of targeted therapies are urgently needed. RAB10, a member of the RAS family, has been shown to be highly expressed in HCC. However, the function of RAB10 in HCC is less studied. Here we report that RAB10 acts as an oncogene in HCC. The shRNA-mediated knockdown of RAB10 significantly reduced the proliferation of HCC cells and colony formation, induced cell cycle arrest at G0/G1 phase and increased apoptosis in vitro . In addition, RAB10 knockdown suppressed HCC growth in nude mice. Moreover, RAB10 silencing decreased the phosphorylation of InsR, Met/HGFR, Ron/MST1R, Ret, c-Kit/SCFR, EphA3, EphB4, Tyro3/Dtk, Axl, Tie2/TEK, VEGFR2/KDR, Akt/PKB/Rac, S6 Ribosomal Protein and c-Abl, while the phosphorylation of HSP27, p38 MAPK, Chk2 and TAK1 increased significantly. These results suggest that RAB10 regulates cell survival and proliferation through multiple oncogenic, cell stress and apoptosis pathways. More importantly, high RAB10 expression levels in HCC cells correlated with a poor prognosis in HCC patients. Therefore, our findings revealed an oncogenic role for RAB10 in the pathogenesis of HCC and that RAB10 is a potential molecular target or a biomarker for HCC.

Objective: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Methods: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. Results: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI

Sorafenib is a highly selective multi-targeted agent and has been reported to have potent antitumor effects against various tumors, including human non-small cell lung cancer (NSCLC). In the present study, we explored the antitumor effect and associated molecular mechanisms of sorafenib against human lung cancer cell lines in vitro. We also investigated the efficacy of concurrent and sequential administration of sorafenib and gemcitabine in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-sensitive and EGFR-TKI-resistant NSCLC cell lines. The PC-9 (EGFR-TKI-sensitive, EGFR-mutated) and A549 (EGFR-TKI-resistant, K-Ras-mutated) NSCLC cell lines were treated with sorafenib and gemcitabine, alone, in combination or with different schedules. Cytotoxicity was assessed by MTT assay, cell cycle distribution was analyzed by flow cytometry and alterations in signaling pathways were analyzed by western blotting. We found that sorafenib exhibited dose-dependent growth inhibition in the EGFR-TKI-sensitive and EGFR-TKI-resistant NSCLC cell lines, and the sequence gemcitabine→sorafenib exhibited the strongest synergism. Sorafenib arrested the cell cycle at G1 phase, whereas gemcitabine caused arrest at S phase. The molecular mechanism of this synergism is that the downstream signaling pathways that were initially activated by gemcitabine exposure were efficiently suppressed by the subsequent exposure to sorafenib. By contrast, the reverse of this sequential administration resulted in antagonism, which may be due to differential effects on cell cycle arrest. The results suggest that sorafenib as a single agent exhibits anti-proliferative effects in vitro in NSCLC cell lines with EGFR and K-Ras mutations and that the sequential administration of gemcitabine followed by sorafenib is superior to sorafenib followed by gemcitabine and concurrent administration.