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Background: Currently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines.Methods: Six BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated. Pan-RAF inhibitor (sorafenib or AZ628) and MEK inhibitor (selumetinib) or their combination were used in in vitro viability, video microscopy, immunoblot, cell cycle and TUNEL assays. The in vivo effects of the drugs were assessed in an orthotopic NSG mouse breast cancer model.Results: All cell lines showed a significant growth inhibition with synergism in the sorafenib/AZ628 and selumetinib combination. Combination treatment resulted in higher Erk1/2 inhibition and in increased induction of apoptosis when compared to single agent treatments. However, single selumetinib treatment could cause adverse therapeutic effects, like increased cell migration in certain cells, selumetinib and sorafenib combination treatment lowered migratory capacity in all the cell lines. Importantly, combination resulted in significantly increased tumor growth inhibition in orthotropic xenografts of MDAMB231 cells when compared to sorafenib - but not to selumetinib - treatment.Conclusions: Our data suggests that combined blocking of RAF and MEK may achieve increased therapeutic response in non-V600 BRAF mutant tumors. [ABSTRACT FROM AUTHOR]

Background: The International Prognostic Index (IPI) scoring system is the most widely used prognostic tool for diffuse large B-cell lymphoma (DLBCL); however, it fails to consistently identify patients with poor outcomes. This retrospective study was undertaken to confirm the clinical value of a new prognostic score and compare it with the IPI. Methods: The aim of this single-center study was to confirm the clinical value of a new prognostic score and its association with various clinical features, disease progression, and death in 70 patients with DLBCL who had undergone at least 6 cycles of chemotherapy. Results: The IPI and the new prognostic index were both associated with 3-year mortality (p ≤ 0.032); however, only the new prognostic index was associated with 3-year progression (p ≤ 0.036). Multivariate analysis showed that the new prognostic index was associated with 3-year progression but not overall survival. The new prognostic score also distinguished 3-year progression-free survival and overall survival in the low- and low-intermediate-risk groups as well as in the low-intermediate- and high-intermediate-risk groups. Conclusions: The new prognostic score represents a comprehensive prognostic model superior to the IPI. Prospective studies are necessary to explore whether treatment strategies may be adjusted using this new prognostic score. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is known to improve survival in selected patients with peritoneal metastasis. However, there is limited data supporting the role of CRS and HIPEC in elderly patients (≥65 years old). Methods: A retrospective review of a prospectively maintained database of patients who underwent CRS‐HIPEC between April 2001 and July 2015 from a single institution was performed. Patients were divided into two groups non‐elderly (<65 years old), and elderly (≥65 years old). Clinico‐ pathological parameters, morbidity and overall (OS) and disease‐free survival (DFS) of the patients were compared. Results: A total of 177 patients (median age 52, range 9–74) underwent CRS‐HIPEC with curative intent. There were 159 non‐elderly patients and 18 elderly patients. Median PCI scores were 12 (0–39) for the non‐ elderly patients and 11 (1–29) for the elderly patients (p=0.77). High‐grade complications occurred in 39 non‐elderly patients (24.5%) and 8 elderly patients (44.4%) (p=0.79), while 58 non‐elderly patients (38.7%) and 7 elderly patients (41.2%) stayed in ICU for more than 1 day (p=0.69). There was no difference in the 30‐day mortality between the two groups (0% vs. 0%, p=1). After a median follow‐up of 16 months for all patients, there was no difference in 5‐years OS (51.0% vs. 59.6%, p=0.88) and 5‐years DFS (23.3% vs. 53.3%, p=0.60) between non‐elderly and elderly patients. Conclusions: Surgical outcomes after CRS‐HIPEC do not differ significantly between non‐elderly and elderly patients. Hence, age should not be a contraindication in selecting patients for CRS and HIPEC. [ABSTRACT FROM AUTHOR]

Within mission-critical systems, the primary–backup scheme is a desirable approach for improving reliability and fault tolerance. It can be used to ensure a high mission success rate despite unexpected errors. However, it must cope with the need to maintain consistency between a primary and a backup whenever the primary encounters unexpected errors. We overcome this issue by introducing a platform that uses container-based light virtualization and an automatic build system to isolate an application so that it may then be deployed on different devices without manual intervention. We believe an advanced deployment procedure can retain the consistency of the primary–backup systems with low implementation complexity. Integrated with a cloud application, it can also manage mission-critical systems effectively, communicate with the redundant systems, and detect unexpected errors by using sophisticated fault-detection technologies. We demonstrate that the platform can improve the reliability of mission-critical systems through realistic experiment using a model electronic vehicle and can reduce hardware dependencies. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated.Methods: This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m2 on day 1 of each cycle. S-1 was administered at a dosage based on body surface area for 14 days in a 3-weekly cycle. The primary endpoint was progression-free survival (PFS).Results: A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1-10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3-4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%).Conclusion: Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC. [ABSTRACT FROM AUTHOR]

External beam radiotherapy (RT) has long played a crucial role in the treatment of glioblastoma. Over the past several decades, significant advances in RT treatment and image-guidance technology have led to enormous improvements in the ability to optimize definitive and salvage treatments. This review highlights several of the latest developments and controversies related to RT, including the treatment of elderly patients, who continue to be a fragile and vulnerable population; potential salvage options for recurrent disease including reirradiation with chemotherapy; the latest imaging techniques allowing for more accurate and precise delineation of treatment volumes to maximize the therapeutic ratio of conformal RT; the ongoing preclinical and clinical data regarding the combination of immunotherapy with RT; and the increasing evidence of cancer stem-cell niches in the subventricular zone which may provide a potential target for local therapies. Finally, continued development on many fronts have allowed for modestly improved outcomes while at the same time limiting toxicity. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer is a cancer of the digestive system with poor prognosis. Cell-free DNA has received much attention with its unique predominance, especially in colorectal cancer. Areas covered: This study has summarized recent advancements and challenges regarding cell-free DNA in predicting CRC prognosis. Furthermore, the authors make predictions on the potential developments concerning cell-free DNA in future prognosis prediction techniques. Expert commentary: Cell-free DNA has the value of predicting CRC prognosis as an important biomarke. Further clinical trials should be performed to promote translating cell-free DNA into clinical applications. [ABSTRACT FROM PUBLISHER]

Introduction: Tumor tissue sample is currently the gold standard for diagnosing gastrointestinal cancers, but also for genomic/immune component analyses that can help in the selection of therapy. However, this approach of studying a ‘representative’ sample of the tumor does not address inherent heterogeneity. Liquid biopsies, mainly represented by circulating tumor cells, circulating tumor DNA, tumor exosomes, and microRNAs, have the potential to assess various biomarkers for early detection of cancer, carrying out genomic/immune profiling for not only selection of appropriate therapy but also to monitor effect of therapy. Areas covered: This review summarizes the current evidence in the literature on liquid biopsies in gastrointestinal cancers concerning diagnosis, prognosis, and response to therapy. The following terms were used in PubMed: ‘esophageal’, ‘gastric’, ‘colorectal’, ‘cancer’, ‘circulating tumor cells’, ‘circulating tumor DNA’, microRNA’, ‘diagnosis’, ‘prognosis’, ‘response’, ‘resistance’. Expert commentary: Data increasingly supports the potential of liquid biopsies for early detection, selection of therapy, and monitoring response to therapy. One major question is whether assaying various components of the blood would accommodate considerable context-dependent heterogeneity of gastrointestinal tumors. There are many potential strategies to exploit liquid biopsy use. To put them in to perspective, well-designed and meticulous prospective studies will be needed to prove their usefulness. [ABSTRACT FROM PUBLISHER]

Background: Gene expression connectivity mapping has gained much popularity in recent years with a number of successful applications in biomedical research testifying its utility and promise. A major application of connectivity mapping is the identification of small molecule compounds capable of inhibiting a disease state. In this study, we are additionally interested in small molecule compounds that may enhance a disease state or increase the risk of developing that disease. Using breast cancer as a case study, we aim to develop and test a methodology for identifying commonly prescribed drugs that may have a suppressing or inducing effect on the target disease (breast cancer). Results: We obtained from public data repositories a collection of breast cancer gene expression datasets with over 7000 patients. An integrated meta-analysis approach to gene expression connectivity mapping was developed, which involved unified processing and normalization of raw gene expression data, systematic removal of batch effects, and multiple runs of balanced sampling for differential expression analysis. Differentially expressed genes stringently selected were used to construct multiple non-joint gene signatures representing the same biological state. Remarkably these non-joint gene signatures retrieved from connectivity mapping separate lists of candidate drugs with significant overlaps, providing high confidence in their predicted effects on breast cancers. Of particular note, among the top 26 compounds identified as inversely connected to the breast cancer gene signatures, 14 of them are known anti-cancer drugs. Conclusions: A few candidate drugs with potential to enhance breast cancer or increase the risk of the disease were also identified; further investigation on a large population is required to firmly establish their effects on breast cancer risks. This work thus provides a novel approach and an applicable example for identifying medications with potential to alter cancer risks through gene expression connectivity mapping. [ABSTRACT FROM AUTHOR]

This research focuses on the automatic provisioning of cloud resources by an intermediary enterprise. This enterprise provides a virtual private cloud for a single client enterprise by using resources from a public cloud. The intermediary cloud provider is controlled by a broker that uses techniques to dynamically control the number of resources used by the client enterprise. The research presents a hybrid auto-scaling technique based on a combination of a reactive approach and a proactive approach to scale resources based on user demand. The primary goal of this auto-scaling technique is to achieve a profit for the intermediary enterprise while maintaining a desired grade of service for the client enterprise. The second goal of the technique is to reduce costs for the single client enterprise. The technique supports both on-demand requests and requests with service level agreements (SLAs). This paper describes the auto-scaling algorithms associated with the hybrid technique and includes a discussion of system design and implementation experience for a prototype system. A detailed performance analysis based on simulations and measurements made based on the prototype is presented. [ABSTRACT FROM AUTHOR]

Objective: To assess the imaging features of peritoneal mesothelioma and identify key anatomical sites that aid patient selection for complete cytoreduction. Methods: Pre-operative imaging of 59 (32 males, 27 females) patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for histologically proven peritoneal mesothelioma [36 malignant peritoneal mesothelioma, 23 cystic mesothelioma were reviewed. Imaging findings were correlated with surgical outcome. Best imaging predictors of complete cytoreduction, n = 22 and major tumour debulking, n = 12 were assessed. Results: Most patients (88.9%) had diffuse peritoneal disease with mean radiological peritoneal cancer index of 18 ± 12 (range 2–39). Disease in the lesser omentum (n = 10), porta hepatis (n = 8), perigastric area (n = 5), mesentery (n = 25), small bowel (n = 17), hydronephrosis (n = 1), concurrent pleural disease (n = 2), lymph nodes (n = 1) and abdominal wall disease (n = 4) was considered unfavourable. While 78.9% of patients who underwent complete cytoreduction had no disease at unfavourable sites, 75% of those who underwent MTD did have disease at these sites. There was significant difference in the radiological peritoneal cancer index, severity of upper abdominal disease, small bowel and mesenteric involvement between patients who underwent complete cytoreduction and MTD for malignant peritoneal mesothelioma. Complete cytoreduction was not achieved in the presence of a rind of soft tissue around the small bowel (p = 0.016) and was unlikely in the presence of large volume upper abdominal disease (p = 0.06). Conclusion: Involvement of key anatomical sites such as small bowel serosa and large volume upper abdominal disease reduced the likelihood of achieving complete cytoreduction in patients with malignant peritoneal mesothelioma. [ABSTRACT FROM AUTHOR]

Gene therapy has started in the late 1980s as novel, clinically applicable therapeutic option. It revolutionized the treatment of genetic diseases with the initial intent to repair or replace defective genes. Gene therapy has been adapted for treatment of malignant diseases to improve the outcome of cancer patients. In fact, cancer gene therapy has rapidly gained great interest and evolved into a research field with highest proportion of research activities in gene therapy. In this context, cancer gene therapy has long entered translation into clinical trials and therefore more than two-thirds of all gene therapy trials worldwide are aiming at the treatment of cancer disease using different therapeutic strategies. During the decades in cancer gene therapy, tremendous knowledge has accumulated. This led to significant improvements in vector design, transgene repertoire, more targeted interventions, use of novel gene therapeutic technologies such as CRISPR/Cas, sleeping beauty vectors, and development of effective cancer immunogene therapies. In this chapter, a brief overview of current key developments in cancer gene therapy is provided to gain insights into the recent directions in research as well as in clinical application of cancer gene therapy., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Combined treatment modality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is emerging as an alternative option for colorectal peritoneal metastases, but there is ambiguity regarding patient selection, treatment protocols, and efficacy., Objective: To elaborate on the patient characteristics, hyperthermic intraperitoneal chemotherapy protocol and health outcomes in colorectal peritoneal metastases patients undergoing a combination of hyperthermic intraperitoneal chemotherapy and cytoreductive surgery and provide guidance for future studies., Data Sources: A Medline search for English language studies published between 2004 and 2019., Study Selection: Medical subject headings and key terms, including: hyperthermic intraperitoneal chemotherapy, colorectal peritoneal metastases, colorectal cancer and combinations thereof as per guidelines., Main Outcome Measures: Overall survival, disease-free survival, and morbidity and mortality rates., Results: Of the 26 included studies, 42% were published between 2016 and 2019. More than half of the studies were retrospective in nature and conducted in tertiary specialized centers outside of the United States. The median age range was 44 to 62 years. Mitomycin C-based therapy was seen in 50% of studies. Mean weighted median disease-free survival for 11 studies was 15 months (9 to 36 months). Median OS ranged from 12 to 63 months, with an average of 33.6 months among 20 studies. Overall morbidity varied from 11% to 56%, with a weighted mean of 29% in 18 studies. Mortality ranged from 0 to 34%, with a weighted mean of 4% in 15 studies., Limitations: Despite careful study selection, variability in methodology of the included studies can limit review findings., Conclusion: Due to study heterogeneity, and a recent large, randomized trial showing no overall benefit, use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in colorectal peritoneal metastases patients is highly controversial. Further standardized controlled studies can help uniformly define and build consensus among the medical community on patient eligibility and the optimal hyperthermic intraperitoneal chemotherapy techniques., Prospero: Registered on March 3, 2020, CRD42020146942., (Copyright © The ASCRS 2021.)

Purpose This study was conducted to investigate the neurocognitive functioning of children with intracranial germ cell tumor (IGCT) prior to receiving proton beam therapy (PBT), and to identify differential characteristics of their neurocognitive functioning depending on tumor location. As a secondary object of this study, neurocognitive functions were followed up at 1-2 years after PBT to examine early post-treatment changes. Materials and Methods Between 2008 and 2014, 34 children with IGCT treated who received PBT at National Cancer Center, Korea were enrolled in this study. Standardized neurocognitive tests of intelligence, memory, and executive functioning were performed with baseline psychological assessments using the Child Behavior Checklist (CBCL). Follow-up assessments after PBT were conducted in 20 patients (T2). The results were analyzed based on the locations of tumors, which included the suprasellar, pineal gland, basal ganglia, and bifocal regions. Results The neurocognitive function of IGCT patients was significantly lower than that of the normal population in performance intelligence quotient (p=0.041), processing speed (p=0.007), memory (p < 0.001), and executive functioning (p=0.010). Patients with basal ganglia tumors had significantly lower scores for most domains of neurocognitive functioning and higher scores for CBCL than both the normal population and patients with IGCT in other locations. There was no significant change in neurocognitive function between T1 and T2 for all types of IGCT patients in first 1-2 years after PBT. Conclusion Tumor location significantly affects the neuropsychological functioning in patients with IGCT. Neuropsychological functioning should be closely monitored from the time of diagnosis in IGCT patients. [ABSTRACT FROM AUTHOR]

Utilization of cloud computing resources has made a fast growth in e-business. Business and government agencies often need to handle large volume of service requests, the so-called instance-intensive business processes in a constrained period. On-time completion for instance-intensive business processes within the constrained time is a very important issue. In the past few years, traditional optimal task scheduling has been well researched and proven to be a nondeterministic polynomial (NP) time-complete problem. So many heuristic and metaheuristic algorithms are put forward to solve the issue with near-optimal solutions. However, most of them just treat a single workflow instance as a multistep task without considering that steps within a task can be different types of activities. To explain multistep features of business workflows, a typical motivating instance-intensive business example of security exchange and a multistep scheduling model for business workflows are introduced in this paper. Then our near-optimal dynamic priority scheduling (DPS) strategy is proposed on the basis of the idea of Min-Min heuristic algorithm and greedy philosophy. Compared to the first come first served and constrained Min-Min by makespan and standard deviation, DPS can make a more optimized choice in each round of scheduling towards overall outcome. To show the effectiveness of DPS, theoretical minimum execution time (METtheory) is used as a benchmark for evaluation based on simulation. The results show that the ratios between METtheory and DPS are more than 98.5% by scheduling different orders of magnitude tasks from 1000 to 1 000 000. In particular, the ratio between METtheory and DPS is nearly 99.9% with 1 000 000 tasks, which means that our DPS can get the near-optimal result when scheduling large number of tasks. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy.Methods: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS). Correlations of clinical response with smoking, rash, steady-state concentration of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite cotinine were performed.Results: The trial was terminated early for futility. Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and 95 days, respectively. Best response was stable disease (21%). There was a trend for improved PFS and OS in never smokers compared to current and past smokers (128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers had lower steady-state concentrations of erlotinib and OSI-420 compared to never smokers. There was evidence of recent smoking exposure in 30% of patients self-identified as past smokers. Rash was infrequent, with no cases of grade III/IV rash and it was not related to treatment outcomes.Conclusions: Overall, erlotinib monotherapy failed to improve outcomes compared to historical controls in patients with APC after 0-1 prior systemic therapies. There was a trend for improved PFS and OS in never smokers. [ABSTRACT FROM AUTHOR]

Background: Methylation plays an important role in the etiology and pathogenesis of colorectal cancer (CRC). This study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) and pathways in CRC by comprehensive bioinformatics analysis. Methods: Data of gene expression microarrays (GSE68468, GSE44076) and gene methylation microarrays (GSE29490, GSE17648) were downloaded from GEO database. Aberrantly methylated-DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. MCODE was used for module analysis of the PPI network. Results: Totally 411 hypomethylation-high expression genes were identified, which were enriched in biological processes of response to wounding or inflammation, cell proliferation and adhesion. Pathway enrichment showed cytokine-cytokine receptor interaction, p53 signaling and cell cycle. The top 5 hub genes of PPI network were CAD, CCND1, ATM, RB1 and MET. Additionally, 239 hypermethylation-low expression genes were identified, which demonstrated enrichment in biological processes including cell-cell signaling, nerve impulse transmission, etc. Pathway analysis indicated enrichment in calcium signaling, maturity onset diabetes of the young, cell adhesion molecules, etc. The top 5 hub genes of PPI network were EGFR, ACTA1, SST, ESR1 and DNM2. After validation in TCGA database, most hub genes still remained significant. Conclusion: In summary, our study indicated possible aberrantly methylated-differentially expressed genes and pathways in CRC by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of CRC. Hub genes including CAD, CCND1, ATM, RB1, MET, EGFR, ACTA1, SST, ESR1 and DNM2 might serve as aberrantly methylation-based biomarkers for precise diagnosis and treatment of CRC in the future. [ABSTRACT FROM AUTHOR]

Cloud computing provides a way to coordinate and share relevant information and data on real-time basis over an organization. The adoption of cloud services is one of the most emerging technological advances in the practice of current competitive business environment. The research done in this article is based on the analysis of the data obtained from the semiconductor sector. Cloud adoption would most likely be the best answer for them. However, because of various types of complexities, semiconductor industries may have to confront with a few trust issues while receiving cloud services. This article aims to identify the trust factors in the adoption of cloud services in semiconductor industries. Further, the moderating effect of these trust elements related to the technological, organizational, and environmental success factors has been discussed here. On the basis of literature survey, a hypothetical model has been developed, and the relationships among the latent variables have been studied by using structural equations. The study reveals that while trust factors moderate the technology and environment-related success factors, there is not much moderating effect of the trust issues on the organization-related success factors in the adoption of cloud services in semiconductor industries. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is an essential regulator and biomarker of several types of cancer. However, the association between its expression and prognosis in patients with resected T3 stage gastric adenocarcinoma (RT3-GA) remains to be determined. In total, 683 patients with resectable T3-GA who underwent surgery were retrospectively included in the present study, and their immunohistochemical data for EGFR expression were collected. The associations between the patients' clinicopathologic characteristics and EGFR immunohistochemistry data were analyzed by multiple statistical methods. Annexin V apoptosis and MTT cell viability assays were performed to explore the effect of EGFR on AGS gastric adenocarcinoma cell survival. EGFR expression levels were categorized into two groups: low (406 cases) and high (277 cases). High EGFR was demonstrated to be significantly associated with distant metastasis (P=0.043) and severely decreased median overall survival time (MOST) and recurrence-free survival time (MRFST). MOST and MRFST in the low EGFR group were 39 and 37 months, respectively; whereas in the high EGFR group these values were only 18 and 13 months (P=3.10x10-9 and P=6.74x10-8, respectively). Multivariate analysis confirmed that high EGFR expression levels were associated with poor survival, which was associated with significantly increased recurrence risk and ∼2-fold elevation in mortality risk [hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.43-2.10; P=2.37x10-8 and HR, 1.80; 95% CI, 1.50-2.17; P=3.80x10-10]. Inhibiting EGFR with AG1478 suppressed its effect on promoting AGS cell survival. These results suggest that high EGFR expression indicates poor survival in patients with RT3-GA, which may be correlated with EGFR promoting GA cell survival. [ABSTRACT FROM AUTHOR]

Background: Aberrant DNA methylation profiles are a characteristic of all known cancer types, epitomized by the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Hypermethylation has been observed at CpG islands throughout the genome, but it is unclear which factors determine whether an individual island becomes methylated in cancer.Methods: DNA methylation in CRC was analysed using the Illumina HumanMethylation450K array. Differentially methylated loci were identified using Significance Analysis of Microarrays (SAM) and the Wilcoxon Signed Rank (WSR) test. Unsupervised hierarchical clustering was used to identify methylation subtypes in CRC.Results: In this study we characterized the DNA methylation profiles of 94 CRC tissues and their matched normal counterparts. Consistent with previous studies, unsupervized hierarchical clustering of genome-wide methylation data identified three subtypes within the tumour samples, designated CIMP-H, CIMP-L and CIMP-N, that showed high, low and very low methylation levels, respectively. Differential methylation between normal and tumour samples was analysed at the individual CpG level, and at the gene level. The distribution of hypermethylation in CIMP-N tumours showed high inter-tumour variability and appeared to be highly stochastic in nature, whereas CIMP-H tumours exhibited consistent hypermethylation at a subset of genes, in addition to a highly variable background of hypermethylated genes. EYA4, TFPI2 and TLX1 were hypermethylated in more than 90% of all tumours examined. One-hundred thirty-two genes were hypermethylated in 100% of CIMP-H tumours studied and these were highly enriched for functions relating to skeletal system development (Bonferroni adjusted p value =2.88E-15), segment specification (adjusted p value =9.62E-11), embryonic development (adjusted p value =1.52E-04), mesoderm development (adjusted p value =1.14E-20), and ectoderm development (adjusted p value =7.94E-16).Conclusions: Our genome-wide characterization of DNA methylation in colorectal cancer has identified 132 genes hypermethylated in 100% of CIMP-H samples. Three genes, EYA4, TLX1 and TFPI2 are hypermethylated in >90% of all tumour samples, regardless of CIMP subtype. [ABSTRACT FROM AUTHOR]

The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

In ocean transportation, detecting vessel delays in advance or in real time is important for fourth-party logistics (4PL) in order to fulfill the expectations of customers and to help customers reduce delay costs. However, the early detection of vessel delays faces the challenges of numerous uncertainties, including weather conditions, port congestion, booking issues, and route selection. Recently, 4PLs have adopted advanced tracking technologies such as satellite-based automatic identification systems (S-AISs) that produce a vast amount of real-time vessel tracking information, thus providing new opportunities to enhance the early detection of vessel delays. This paper proposes a data-driven method for the early detection of vessel delays: in our new framework of refined case-based reasoning (CBR), real-time S-AIS vessel tracking data are utilized in combination with historical shipping data. The proposed method also provides a process of analyzing the causes of delays by matching the tracking patterns of real-time shipments with those of historical shipping data. Real data examples from a logistics company demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Information-centric sensor networks (ICSNs) are a paradigm of wireless sensor networks that focus on delivering information from the network based on user requirements, rather than serving as a point-to-point data communication network. Introducing learning in such networks can help to dynamically identify good data delivery paths by correlating past actions and results, make intelligent adaptations to improve the network lifetime, and also improve the quality of information delivered by the network to the user. However, there are several factors and limitations that must be considered while choosing a learning strategy. In this paper, we identify some of these factors and explore various learning techniques that have been applied to sensor networks and other applications with similar requirements in the past. We provide our recommendation on the learning strategy based on how well it complements the needs of ICSNs, while keeping in mind the cost, computation, and operational overhead limitations. [ABSTRACT FROM AUTHOR]

Background: There is little evidence for the use of early postoperative intraperitoneal chemotherapy (EPIC) in patients with low-grade appendiceal mucinous neoplasms (LAMNs) with pseudomyxoma peritonei (PMP). This study aims to assess the outcomes regarding the use of EPIC in a large cohort of patients with LAMNs with PMP uniformly treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC), all of whom received hyperthermic intraperitoneal chemotherapy (HIPEC), and most of whom also received EPIC. Methods: This was a retrospective study of prospectively collected data of consecutive patients with peritoneal carcinomatosis of appendiceal origin who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia, between January 1996 and November 2015. Subgroup analyses were performed for patients with a high Peritoneal Cancer Index (PCI) >20 and also based on histopathological subtypes of LAMNs. Results: A total of 250 patients formed the cohort of this study. No significant differences were observed in terms of hospital mortality ( p = 0.153), major morbidity rate (i.e., grade III/IV; p = 0.593), intensive care unit stay ( p = 0.764), and total hospital stay ( p = 0.927); however, patients who received HIPEC + EPIC had a significantly longer stay in the high dependency unit. Multivariate analysis showed combined HIPEC with EPIC is an independent prognostic factor for better survival outcomes (hazard ratio 0.30, 95 % confidence interval 0.12-0.74; p = 0.009), adjusted for age, PCI, and histopathological subtypes. Conclusions: The combination of HIPEC + EPIC can provide additional survival benefits for patients with LAMNs with PMP compared with HIPEC alone, without increasing postoperative morbidity and mortality. EPIC should be considered following CRS and HIPEC for patients with LAMNs with PMP. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB., Method: Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence., Results: At a median follow-up of 18.6 months (95% CI 15.9-21.2), PFS and OS were 7.5 (95% CI 6.7-8.3) and 13.9 (95% CI 10.9-16.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048)., Conclusions: Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is becoming accepted treatment for peritoneal carcinomatosis (PC) from colorectal cancer. Quality of life (QoL) for patients after surgery is still a concern amongst physicians despite studies that show that QoL recovers after surgery. We conducted a prospective QoL study on patients undergoing CRS and HIPEC and attempt to identify factors that affect the QoL. Methods: Patients who underwent CRS and HIPEC for PC from colorectal cancer from March 2012 to January 2015 were included. The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and the colorectal module (QLQ-CR29) were administered prior to surgery and thereafter at 3, 6, and 12 months. Results: Twenty-three patients underwent 25 procedures. Median disease-free survival was 12.9 months [95 % confidence interval (CI) 2.5-19.3]. Physical and role functioning scores decreased at 3 months but returned to baseline at 6 months. There were significant increases in emotional and social functioning scores at 6-12 months and improvements in all symptoms scales at 6-12 months, especially the fatigue and appetite scores. A higher PCI score, longer duration of surgery, the presence of a stoma, and recurrence within 3 months were associated with a poorer QoL. Conclusions: QoL after CRS and HIPEC improved or returned to baseline in all categories by 6-12 months after surgery. Patient selection is important not only for improved survival but also for improved QoL. [ABSTRACT FROM AUTHOR]

It has been realized that shrimp cell immortalization may not be accomplished without in vitro transformation by expressing immortalizing gene in cells. In this process, efficiency of transgene expression is confined to the ability of vectors to transmit gene of interests to the genome. Over the years, unavailability of such vectors has been hampering application of such a strategy in shrimp cells. We report the use of recombinant baculovirus mediated transduction using hybrid promoter system for transgene expression in lymphoid cells of Penaeus monodon. Two recombinant baculovirus vectors with shrimp viral promoters (WSSV-Ie1 and IHHNV-P2) were constructed (BacIe1-GFP and BacP2-GFP) and green fluorescent protein (GFP) used as the transgene. The GFP expression in cells under the control of hybrid promoters, PH-Ie1 or PH-P2, were analyzed and confirmed in shrimp cells. The results indicate that the recombinant baculovirus with shrimp specific viral promoters (hybrid) can be employed for delivery of foreign genes to shrimp cells for in vitro transformation. [ABSTRACT FROM AUTHOR]

This paper addresses the problem of efficient federation formation by the cloud providers (CPs) with an aim to fulfill the dynamic resource demands of users for supporting data-intensive workloads. Existing works only focus on forming federations based on the highest profit gained by each of the CPs in a federation. Therefore, these approaches often suffer from the risk of selecting unreliable CPs in the federation resulting in additional penalty cost and loss of CPs's reputation due to service level agreement violation between the users and the federation. In contrast, we argue that a trust model is necessary to find the most promising cloud collaborators. Accordingly, we propose a novel cloud federation formation mechanism by utilizing a trust-based cooperative game theory, which enables the CPs to dynamically form a federation based on profit maximization and penalty cost minimization as a result of selecting the trustworthy CPs. Simulation results show that the cloud federation formed by the proposed mechanism is stable, satisfies the fairness property, and yields higher profit for the participating CPs in the long run without incurring penalty cost as compared with the state-of-the-art approaches. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Vehicular ad-hoc network (VANET) is becoming a promising technology for improving the efficiency and the safety of intelligent transportation systems by deploying a wide variety of applications. Smart vehicles are expected to continuously exchange a huge amount of data either through safety or non-safety messages dedicated for road safety or infotainment and passenger comfort applications, respectively. One of the main challenges posed by the study of VANET is the data dissemination design by which messages have to be efficiently disseminated in a high vehicular speed, intermittent connectivity, and highly dynamic topology. In particular, broadcast mechanism should guarantee fast and reliable data delivery within a limited wireless bandwidth in order to fit the real time applications' requirements. In this work, we propose a simple and efficient adaptive data dissemination protocol called 'SEAD'. On the one hand, the originality of this work lies in its simplicity and efficiency regardless the application's type. Simplicity is achieved through a beaconless strategy adopted to take into account the surrounding vehicles' density. Thanks to a metric locally measured, each vehicle is able to dynamically define an appropriate probability of rebroadcast to mitigate the broadcast storm problem. Efficiency is manifested by reducing excessive retransmitted messages and hence promoting the network capacity and the transmission delay. The simulation results show that the proposed protocol offers very low packet drop ratio and network load while still maintaining a low end-to-end delay and a high packet delivery. On the other hand, SEAD protocol presents a robust data dissemination mechanism which is suitable either for safety applications or for other kinds of application. This mechanism is able to adapt the protocol performance in terms of packet delivery ratio to the application's requirements. [ABSTRACT FROM AUTHOR]

Crowd sensing networks can be used for large scale sensing of the physical world or other information service by leveraging the available sensors on the phones. The collector hopes to collect as much as sensed data at relatively low cost. However, the sensing participants want to earn much money at low cost. This paper examines the evolutionary process among participants sensing networks and proposes an evolutionary game model to depict collaborative game phenomenon in the crowd sensing networks based on the principles of game theory in economics. A effectively incentive mechanism is established through corrected the penalty function of the game model accordance with the cooperation rates of the participant, and corrected the game times in accordance with it's payoff. The collector controls the process of game by adjusting the price function. We find that the proposed incentive game based evolutionary model can help decision makers simulate evolutionary process under various scenarios. The crowd sensing networks structure significantly influence cooperation ratio and the total number of participant involved in the game, and the distribution of population with different game strategy. Through evolutionary game model, the manager can select an optimal price to facilitate the system reach equilibrium state quickly, and get the number of participants involved in the game. The incentive game based evolutionary model in crowd sensing networks provides valuable decision-making support to managers. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P=0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3-4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically. [ABSTRACT FROM AUTHOR]

Aim Improved methods for early detection of colorectal cancer ( CRC) are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. Biochemical methods have improved in recent years, and several hypermethylated genes that are sensitive and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed. Method A systematic literature search was performed using the Medline, Web of Science and Embase databases. Studies were included if they analysed hypermethylated genes from stool or blood samples in correlation with CRC. Studies in languages other than English and those based on animal models or cell lines were excluded. Results The literature search yielded 74 articles, including 43 addressing blood samples and 31 addressing stool samples. In blood samples, hypermethylated ALX4, FBN2, HLTF, P16, TMEFF1 and VIM were associated with poor prognosis, hypermethylated APC, NEUROG1, RASSF1A, RASSF2A, SDC2, SEPT9, TAC1 and THBD were detected in early stage CRC and hypermethylated P16 and TFPI2 were associated with CRC recurrence. In stool samples, hypermethylated BMP3, PHACTR3, SFRP2, SPG20, TFPI2 and TMEFF2 were associated with early stage CRC. Conclusion Hypermethylation of the promoters of specific genes measured in blood or stool samples could be used as a CRC biomarker and provide prognostic information. The majority of studies, however, include only a few patients with poorly defined control groups. Further studies are therefore needed before hypermethylated DNA can be widely applied as a clinical biomarker for CRC detection and prognosis. [ABSTRACT FROM AUTHOR]

We consider infrastructure-based mobile networks that are assisted by a single relay transmission where both the downstream destination and relay nodes are mobile. Selecting the optimal transmission path for a destination node requires up-to-date link quality estimates of all relevant links. If the relay selection is based on link quality measurements, the number of links to update grows quadratically with the number of nodes, and measurements need to be updated frequently when nodes are mobile. In this paper, we consider a location-based relay selection scheme where link qualities are estimated from node positions; in the scenario of a node-based location system such as GPS, the location-based approach reduces signaling overhead, which in this case only grows linearly with the number of nodes. This paper studies these two relay selection approaches and investigates how they are affected with varying information update interval, node mobility, location inaccuracy, and inaccurate propagation model parameters. Our results show that location-based relay selection performs better than SNR-based relay selection at typical levels of location error when medium-scale fading can be neglected or accurately predicted. [ABSTRACT FROM AUTHOR]

We propose a new recognition task in the area of computational paralinguistics: automatic recognition of eating conditions in speech, i. e., whether people are eating while speaking, and what they are eating. To this end, we introduce the audio-visual iHEARu-EAT database featuring 1.6 k utterances of 30 subjects (mean age: 26.1 years, standard deviation: 2.66 years, gender balanced, German speakers), six types of food (Apple, Nectarine, Banana, Haribo Smurfs, Biscuit, and Crisps), and read as well as spontaneous speech, which is made publicly available for research purposes. We start with demonstrating that for automatic speech recognition (ASR), it pays off to know whether speakers are eating or not. We also propose automatic classification both by brute-forcing of low-level acoustic features as well as higher-level features related to intelligibility, obtained from an Automatic Speech Recogniser. Prediction of the eating condition was performed with a Support Vector Machine (SVM) classifier employed in a leave-one-speaker-out evaluation framework. Results show that the binary prediction of eating condition (i. e., eating or not eating) can be easily solved independently of the speaking condition; the obtained average recalls are all above 90%. Low-level acoustic features provide the best performance on spontaneous speech, which reaches up to 62.3% average recall for multi-way classification of the eating condition, i. e., discriminating the six types of food, as well as not eating. The early fusion of features related to intelligibility with the brute-forced acoustic feature set improves the performance on read speech, reaching a 66.4% average recall for the multi-way classification task. Analysing features and classifier errors leads to a suitable ordinal scale for eating conditions, on which automatic regression can be performed with up to 56.2% determination coefficient. [ABSTRACT FROM AUTHOR]

Grid computing has emerged a new field, distinguished from conventional distributed computing. It focuses on large-scale resource sharing, innovative applications and in some cases, high performance orientation. The Grid serves as a comprehensive and complete system for organizations by which the maximum utilization of resources is achieved. The load balancing is a process which involves the resource management and an effective load distribution among the resources. Therefore, it is considered to be very important in Grid systems. For a Grid, a dynamic, distributed load balancing scheme provides deadline control for tasks. Due to the condition of deadline failure, developing, deploying, and executing long running applications over the grid remains a challenge. So, deadline failure recovery is an essential factor for Grid computing. In this paper, we propose a dynamic distributed load-balancing technique called 'Enhanced GridSim with Load balancing based on Deadline Failure Recovery' (EGDFR) for computational Grids with heterogeneous resources. The proposed algorithm EGDFR is an improved version of the existing EGDC in which we perform load balancing by providing a scheduling system which includes the mechanism of recovery from deadline failure of the Gridlets. Extensive simulation experiments are conducted to quantify the performance of the proposed load-balancing strategy on the GridSim platform. Experiments have shown that the proposed system can considerably improve Grid performance in terms of total execution time, percentage gain in execution time, average response time, resubmitted time and throughput. The proposed load-balancing technique gives 7 % better performance than EGDC in case of constant number of resources, whereas in case of constant number of Gridlets, it gives 11 % better performance than EGDC. [ABSTRACT FROM AUTHOR]

In stationary camera sensor networks (CSNs), when the deployment characteristics and sensing models are defined, the coverage can be deduced and remain unchanged over time. However, in the maritime environment, the rough and random sea condition can move CSN from the initial location. We envisage that camera sensors are mounted on quasi-mobile platforms such as buoys. Hence, it is important to understand the effect of realistic sea surface movements in achieving full-view coverage because in full-view coverage, target's facing direction is taken into account to judge whether a target is guaranteed to be captured because image shot at the frontal viewpoint of a given target considerably increases the possibility to detect and recognize the target. To accurately emulate the maritime environment, the movement of the buoy, which is attached with a cable that is nailed at the sea floor, has been characterized based on the sea wave that is created by the wind, and it is limited by the cable. The average percentage of full-view coverage has been evaluated based on different parameters such as equilateral triangle grid length, sensing radius of camera, wind speed and wave height. Furthermore, a method to improve the target detection and recognition has been proposed in the presence of poor link quality using cooperative transmission with low power consumption. In some parameter scenario, the cooperative transmission method has achieved around 70 % improvement in the average percentage of full-view coverage of a given target and total reduction of around 13 % for the total transmission power PTotal( Q). Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The phosphoinositide 3-kinase/Akt ppathway activation commonly occurs in various types of human cancer and has an important role in chemoresistance. Combination of traditional chemotherapy drugs and molecular-targeted agents is a promising strategy for cancer therapy, which has shown enhanced cytotoxicity and lower drug resistance. The present study found that the Akt inhibitor, MK-2206, can increase the effect of cisplatin in the gastric cancer cell line AGS, which has higher Akt phosphorylation, but exhibited a poor combination effect in MKN-45 and MGC-803 cells, which have limited Akt activation . The MTT assay demonstrated that sequential treatment of cisplatin, followed by the Akt inhibitor, MK-2206, caused a synergistic effect of proliferation inhibition, and the apoptosis assay by propidium iodide/fluorescein isothiocyanate staining also showed that combination treatment induced more apoptosis compared to the monotherapy groups. Using western blot analysis, MK-2206 was shown to significantly suppress the phosphorylation of Akt (Ser473), however, the expression of total Akt remained the same, and the combination treatment also increased the expression of cleaved poly adenosine diphosphate ribose polymerase, which contributed to apoptosis . [ABSTRACT FROM AUTHOR]

Cancer is the leading cause of death in Singapore, comprising almost 30% of annual deaths. The incidence and prevalence continue to rise, resulting in Singapore having the highest age-standardized rate of cancer in southeast Asia. A review of national health policies in 1992 resulted in the creation of a National Cancer Centre Singapore (NCCS) in 1999. The current NCCS, with its three pillars of clinical service, research and education, manages about 70% of all new cancer cases in the countries public healthcare system. As it outgrows its current outfit and looks to the new NCCS building in 2020, the goal must be for strategic planning to attract and retain the best minds and heart in the field of cancer if it were to continue to be successful in achieving its vision and mission. This article chronicles the NCCS's history and details the foundation of its strategic plans. [ABSTRACT FROM AUTHOR]

Glioblastoma, the most common and most malignant type of primary brain tumor, is associated with poor prognosis, even when treated using combined therapies, including surgery followed by concomitant radiotherapy with temozolomide-based chemotherapy. The invasive nature of this type of tumor is a major reason underlying treatment failure. The tumor-tropic ability of neural and mesenchymal stem cells offers an alternative therapeutic approach, where these cells may be used as vehicles for the invasion of tumors. Stem cell-based therapy is particularly attractive due to its tumor selectivity, meaning that the stem cells are able to target tumor cells without harming healthy brain tissue, as well as the extensive tumor tropism of stem cells when delivering anti-tumor substances, even to distant tumor microsatellites. Stem cells have previously been used to deliver cytokine genes, suicide genes and oncolytic viruses. The present review will summarize current trends in experimental studies of stem cell-based gene therapy against gliomas, and discuss the potential concerns for translating these promising strategies into clinical use. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have investigated the risk factors in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) who die within 3 months of undergoing surgical intervention and systemic chemotherapy. This study aimed to identify the risk factors associated with the post-treatment 3-month mortality rate. Methods: Retrospectively collected data from Hiroshima University were analyzed for patients presenting with synchronous PC from CRC between 1992 and 2012. The clinical, histological and survival data were evaluated and correlated with the overall survival rate at 3 months after surgical intervention. Results: In patients who underwent surgical intervention with systemic chemotherapy for synchronous PC from CRC ( N = 65), a Kaplan-Meier analysis and the log-rank test revealed that systemic chemotherapy ( P = 0.023) and the modified Glasgow Prognostic Score (mGPS) ( P = 0.00001) were associated with the 3-month mortality rate. Multivariate analyses using these two factors revealed that the mGPS (0/1, 2) (odds ratio 8.087; 95 % CI 1.512-43.25; P = 0.015) was an independent risk factor for the 3-month mortality rate. Conclusion: The mGPS is an important independent predictor of the 3-month mortality rate in patients who undergo surgical intervention with systemic chemotherapy for synchronous PC from CRC. The mGPS could aid surgeons in choosing the appropriate treatment strategy and best care for patients. [ABSTRACT FROM AUTHOR]

Wireless sensor network (WSN) consists of a large number of sensors and sink nodes which are used to monitor events or environmental parameters, such as movement, temperature, humidity, etc. Reinforcement learning (RL) has been applied in a wide range of schemes in WSNs, such as cooperative communication, routing and rate control, so that the sensors and sink nodes are able to observe and carry out optimal actions on their respective operating environment for network and application performance enhancements. This article provides an extensive review on the application of RL to WSNs. This covers many components and features of RL, such as state, action and reward. This article presents how most schemes in WSNs have been approached using the traditional and enhanced RL models and algorithms. It also presents performance enhancements brought about by the RL algorithms, and open issues associated with the application of RL in WSNs. This article aims to establish a foundation in order to spark new research interests in this area. Our discussion has been presented in a tutorial manner so that it is comprehensive and applicable to readers outside the specialty of both RL and WSNs. [ABSTRACT FROM AUTHOR]

Background: Despite accurate preoperative imaging assessment, optimal cytoreductive surgery with hyperthermic intraperitoneal chemotherapy remains unfeasible in many patients with peritoneal carcinomatosis at the time of surgery. The aim of this study was to evaluate the role of diagnostic laparoscopy in the selection of candidates., Methods: Prospectively collected data of all patients undergoing diagnostic laparoscopy in our Department were retrospectively analyzed. Demographics and perioperative features as well as operative details and outcome were evaluated., Results: The study included 744 consecutive patients. Primary ovarian tumors were the most common indications, followed by gastric tumors and recurrent colorectal cancers. The procedure was successfully completed in 99.73% of cases. Approximately two thirds of them (68%) had undergone previous surgical procedures. The presence of ascites was recorded in 482 patients (64.78%). A total of 374 (50.3%) patients were excluded from surgical exploration. Among those who eventually underwent surgery, CC0 resection was obtained in 64.6% (239) of cases. Understaging of peritoneal carcinomatosis was observed in 11 patients (1.48%). Postoperative mortality was null and 5 (0.8%) complications were observed. Three (0.4%) port-site metastases were recorded at the beginning of the experience., Conclusion: Diagnostic laparosocopy is a safe and feasible tool able to improve the selection of patients eligible for cytoreduction with hyperthermic intraperitoneal chemotherapy, at the same time allowing avoiding a significant number of unnecessary laparotomies.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors., Methods: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm 3 ), neutropenia (absolute neutrophils < 2000/mm 3 ), and thrombocytopenia (platelets < 140 000/mm 3 )., Results: Two hundred and thirty-five CRS-HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0-16 days), 0 day (0-2 days), and 1 day (1-2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1-3 days), 1 day (1-2days), and 3 days (range 0-16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105-0.502], P < .001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P = .010) were independent risk factors for thrombocytopenia on multivariable logistic regression., Conclusion: Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS-HIPEC., (© 2019 John Wiley & Sons Australia, Ltd.)

In recent days, due to the rapid technological advancements, the grid computing has become an important area of research in distributed systems. The load balancing is a very important and complex problem in grid computing. In this paper, we propose a dynamic-distributed load-balancing technique called the improved load balancing on enhanced GridSim with deadline control (IEGDC) for computational grids. Here, we provide a new mechanism of scheduling to enhance the utilization of the resources and to prevent the resource overloading. A selection method for scheduling by considering the state of resource bandwidth and capacity of various resources is presented. We simulate the proposed load-balancing strategy on the GridSim platform. The proposed mechanism on comparison is found to outperform the existing schemes in terms of response time, resubmitted time, finished and unfinished Gridlets. The simulation results are presented. [ABSTRACT FROM AUTHOR]

Malignant glioma is among the most challenging of all cancers to treat successfully. Despite recent advances in surgery, radiotherapy and chemotherapy, current treatment regimens have only a marginal impact on patient survival. In this study, we constructed a novel nanoparticle containing neuritin peptide with grp170. The nanoparticle could elicit a neuritin-specific cytotoxic T lymphocyte response to lyse glioma cells in vitro. In addition, the nanoparticle could inhibit tumor growth and improve the lifespan of tumor-bearing mice in vivo. Taken together, the results demonstrated that the nanoparticle can inhibit tumor growth and represents a promising therapy for glioma. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we planned to assess if adult stem cell-based suicide gene therapy can efficiently eliminate glioblastoma cells in vivo. We investigated the therapeutic potential of mouse Oct4- bone marrow multipotent adult progenitor cells (mOct4- BM-MAPCs) in a mouse glioblastoma model, guided by multimodal in vivo imaging methods to identify therapeutic windows. Methods: Magnetic resonance imaging (MRI) of animals, wherein 5 × 105 syngeneic enhanced green fluorescent protein-firefly luciferase-herpes simplex virus thymidine kinase (eGFP-fLuc-HSV-TK) expressing and superparamagnetic iron oxide nanoparticle labeled (1% or 10%) mOct4- BM-MAPCs were grafted in glioblastoma (GL261)-bearing animals, showed that labeled mOct4- BM-MAPCs were located in and in close proximity to the tumor. Subsequently, ganciclovir (GCV) treatment was commenced and the fate of both the MAPCs and the tumor were followed by multimodal imaging (MRI and bioluminescence imaging). Results: In the majority of GCV-treated, but not phosphate-buffered saline-treated animals, a significant difference was found in mOct4- BM-MAPC viability and tumor size at the end of treatment. Noteworthy, in some phosphatebuffered saline-treated animals (33%), a significant decrease in tumor size was seen compared to sham-operated animals, which could potentially also be caused by a synergistic effect of the immune-modulatory stem cells. Conclusions: Suicide gene therapy using mOct4- BM-MAPCs as cellular carriers was effective in reducing the tumor size in the majority of the GCV-treated animals leading to a longer progression-free survival compared to sham-operated animals. This treatment could be followed and guided noninvasively in vivo by MRI and bioluminescence imaging. Noninvasive imaging is of particular interest for a rapid and efficient validation of stem cell-based therapeutic approaches for glioblastoma and hereby contributes to a better understanding and optimization of a promising therapeutic approach for glioblastoma patients. [ABSTRACT FROM AUTHOR]

To program in distributed computing environments such as grids and clouds, workflow is adopted as an attractive paradigm for its powerful ability in expressing a wide range of applications, including scientific computing, multi-tier Web, and big data processing applications. With the development of cloud technology and extensive deployment of cloud platform, the problem of workflow scheduling in cloud becomes an important research topic. The challenges of the problem lie in: NP-hard nature of task-resource mapping; diverse QoS requirements; on-demand resource provisioning; performance fluctuation and failure handling; hybrid resource scheduling; data storage and transmission optimization. Consequently, a number of studies, focusing on different aspects, emerged in the literature. In this paper, we firstly conduct taxonomy and comparative review on workflow scheduling algorithms. Then, we make a comprehensive survey of workflow scheduling in cloud environment in a problem-solution manner. Based on the analysis, we also highlight some research directions for future investigation. [ABSTRACT FROM AUTHOR]