Improved Mitigation of Cyber Threats in IIoT for Smart Cities: A New-Era Approach and Scheme.

Cybersecurity in Industrial Internet of Things (IIoT) has become critical as smart cities are becoming increasingly linked to industrial control systems (ICSs) used in critical infrastructure. Consequently, data-driven security systems for analyzing massive amounts of data generated by smart cities have become essential. A representative method for analyzing large-scale data is the game bot detection approach used in massively multiplayer online role-playing games. We reviewed the literature on bot detection methods to extend the anomaly detection approaches used in bot detection schemes to IIoT fields. Finally, we proposed a process wherein the data envelopment analysis (DEA) model was applied to identify features for efficiently detecting anomalous behavior in smart cities. Experimental results using random forest show that our extracted features based on a game bot can achieve an average F1-score of 0.99903 using 10-fold validation. We confirmed the applicability of the analyzed game-industry methodology to other fields and trained a random forest on the high-efficiency features identified by applying a DEA, obtaining an F1-score of 0.997 using the validation set approach. In this study, an anomaly detection method for analyzing massive smart city data based on a game industry methodology was presented and applied to the ICS dataset.

Novel Gastric Cancer Stem Cell-Related Marker LINGO2 Is Associated with Cancer Cell Phenotype and Patient Outcome.

The expression of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) has been reported in Parkinson's disease; however, its role in other diseases is unknown. Gastric cancer is the second leading cause of cancer death. Cancer stem cells (CSC) are a subpopulation of cancer cells that contribute to the initiation and invasion of cancer. We identified LINGO2 as a CSC-associated protein in gastric cancers both in vitro and in patient-derived tissues. We studied the effect of LINGO2 on cell motility, stemness, tumorigenicity, and angiogenic capacity using cells sorted based on LINGO2 expression and LINGO2-silenced cells. Tissue microarray analysis showed that LINGO2 expression was significantly elevated in advanced gastric cancers. The overall survival of patients expressing high LINGO2 was significantly shorter than that of patients with low LINGO2. Cells expressing high LINGO2 showed elevated cell motility, angiogenic capacity, and tumorigenicity, while LINGO2 silencing reversed these properties. Silencing LINGO2 reduced kinase B (AKT)/extracellular signal-regulated kinase (ERK)/ERK kinase (MEK) phosphorylation and decreased epithelial-mesenchymal transition (EMT)-associated markers-N-Cadherin and Vimentin and stemness-associated markers- POU class 5 homeobox 1 (OCT4) and Indian hedgehog (IHH), and markedly decreased the CD44⁺ population. These indicate the involvement of LINGO2 in gastric cancer initiation and progression by altering cell motility, stemness, and tumorigenicity, suggesting LINGO2 as a putative target for gastric cancer treatment.

Biomarkers Associated with Tumor Heterogeneity in Prostate Cancer.

BACKGROUND: Prostate cancers exhibit intratumor heterogeneity (ITH), like other cancer types. The ITH may affect diverse phenotypes such as treatment response, drug resistance, and clinical outcomes. It is crucial to consider ITH to understand tumorigenesis. METHODS: Genomic and transcriptomic profiles of prostate cancer patients were investigated to determine which markers are correlated with the degree of tumor heterogeneity. In addition, the correlation between the immune activity and clonality of tumors was examined. RESULTS: Tumor heterogeneity across all prostate cancer samples was variable. However, ITH events were dependent on genomic and clinical features. Interestingly, prostate-specific antigen score increased in tumors with multiple subclones, indicating high-grade tumor heterogeneity. On the other hand, CD8-positive T-cell activation decreased in highly heterogeneous tumors. Intriguingly, PTEN deletion was prominently enriched in high heterogeneity groups, with a strong association with heterozygous loss. Expression of major genes including PTEN, CDC42EP5, RNLS, GP2, NETO2, and AMPD3 was closely related to tumor heterogeneity in association with PTEN deletion. CONCLUSIONS: In prostate cancer, ITH, a potential factor affecting tumor progression, is associated with PTEN deletion and cytotoxic T cell inactivation.

The efficacy of endoscopic palliation of obstructive jaundice in hepatocellular carcinoma.

PURPOSE: Obstructive jaundice in patients with hepatocellular carcinoma (HCC) is uncommon (0.5-13%). Unlike other causes of obstructive jaundice, the role of endoscopic intervention in obstructive jaundice complicated by HCC has not been clearly defined. The aim of this study was to evaluate the clinical characteristics of obstructive jaundice caused by HCC and predictive factors for successful endoscopic intervention. MATERIALS AND METHODS: From 1999 to 2009, 54 patients with HCC who underwent endoscopic intervention to relieve obstructive jaundice were included. We defined endoscopic intervention as a clinical success when the obstructive jaundice was relieved within 4 weeks. RESULTS: Clinical success was achieved in 23 patients (42.6%). Patients in the clinical success group showed better Child-Pugh liver function (C-P grade A or B/C; 17/6 vs. 8/20), lower total bilirubin levels (8.1±5.3 mg/dL vs. 23.1±10.4 mg/dL) prior to the treatment, and no history of alcohol consumption. The only factor predictive of clinical success by multivariate analysis was low total bilirubin level at the time of endoscopic intervention, regardless of history of alcohol consumption [odds ratio 1.223 (95% confidence interval, 1.071-1.396), p=0.003]. The cut-off value of pre-endoscopic treatment total bilirubin level was 12.8 mg/dL for predicting the clinical prognosis. Median survival after endoscopic intervention in the clinical success group was notably longer than that in the clinical failure group (5.6 months vs. 1.5 months, p≤0.001). CONCLUSION: Before endoscopic intervention, liver function, especially total bilirubin level, should be checked to achieve the best clinical outcome. Endoscopic intervention can be helpful to relieve jaundice in well selected patients with HCC.

Investigation of SF6 injection during cyclic C2H2/SF6 flow for the formation of geometrically controlled carbon coils.

Carbon coils could be synthesized using C2H2/H2 as source gases along with SF6 as an incorporated additive gas using a thermal chemical vapor deposition (CVD) system. To obtain geometrically controlled carbon coils, a cyclic process, namely the turning on and off of C2H2 or SF6 flow during the initial reaction stage, was carried out. According to the different reaction processes, different interruption/injection times of C2H2 or SF6 flow and different injection sequences of the gas flow were investigated while maintaining the identical overall injection time of C2H2 and/or SF6 flow. The formation of carbon microcoils (CMCs) is favored by the lowest interruption/injection time ratio of SF6 flow within one cycle. In addition, the injection of SF6 flow prior to the injection of C2H2 flow promotes the formation of CMCs. Based on these results we revealed the role of the SF6 flow injection for the enhanced formation of geometrically controlled CMCs. The etching of materials, thereby promoting an increase in the number of nucleation sites for the survived growth species to form CMCs, by the increased fluorine concentration, originating from the dominant SF6 influx, is understood to be the main cause for the exclusive CMCs formation.

Phase II Trial of Erlotinib Plus Gemcitabine Chemotherapy in Korean Patients with Advanced Pancreatic Cancer and Prognostic Factors for Chemotherapeutic Response.

BACKGROUND/AIMS: Erlotinib and gemcitabine combined chemotherapy is becoming the treatment of choice in advanced pancreatic cancer. We evaluated the effectiveness of treatment with erlotinib plus gemcitabine and the prognostic factors for chemotherapeutic response in Korean pancreatic cancer patients. METHODS: Sixty-nine patients with advanced pancreatic cancer who were treated with daily erlotinib 100 mg orally and gemcitabine 1,000 mg/m(2)/30 min intravenous infusion on days 1, 8, and 15 of each 4-week cycle from 2006 to 2009 were included in this study. This study was a phase II single-center trial. RESULTS: All 69 patients with advanced pancreatic cancer were chemotherapy-naïve. The objective response rate was 18.8%, and the overall tumor-stabilization rate was 49.2%. The median overall survival was 7.7 months (95% confidence interval [CI], 6.0 to 9.4 months). The median progression-free survival was 1.9 months (95% CI, 1.4 to 2.5 months). Prognostic factors for good chemotherapeutic response were good performance status and the presence of skin rash during chemotherapy. Patients with lower performance scores showed worse chemotherapeutic responses (odds ratio [OR], 7.6; 95% CI, 2.4 to 24.8). Poor responses were predicted by the absence of skin rash during chemotherapy (OR, 3.0; 95% CI, 1.4 to 6.3). CONCLUSIONS: Erlotinib and gemcitabine chemotherapy is a tolerable treatment regimen and has a favorable therapeutic effect in Korean patients with advanced pancreatic cancer.

Radiotherapy prolongs biliary metal stent patency in malignant pancreatobiliary obstructions.

BACKGROUND/AIMS: Biliary stenting is the most effective decompressive method for treating malignant biliary obstructive jaundice. Although the main cause of stent occlusion is tumor growth, few studies have investigated whether stent patency is affected by the combination of cancer-treatment modalities. The aim of this study was to evaluate the effects of local radiotherapy on metal-stent patency in patients with malignant biliary obstruction. METHODS: Patients who underwent self-expandable biliary metallic stenting for malignant biliary obstruction from 1999 to 2007 were included. Forty patients received chemotherapy and radiation therapy (radiation group, RG), and 31 patients received only chemotherapy (nonradiation group, NRG). RESULTS: The cumulative median stent patency was significantly longer in the RG than in the NRG (17.7 months; 95% confidence interval [CI], 1.8 to 33.6 months vs 8.7 months; 95% CI, 4.9 to 12.5 months; p=0.025). Stent occlusion caused by tumor growth or stent migration occurred in two (5%) and three (7.5%) cases in the RG and in six (19.3%) and two (6.5%) cases in the NRG, respectively. CONCLUSIONS: The patency of biliary metal stents in pancreatobiliary cancer patients who receive chemoradiation therapy is significantly longer than that in patients who do not receive radiotherapy, which suggests that local cancer control significantly affects stent patency.

Binding interaction of HMGB4 with cisplatin-modified DNA.

Proteins in the HMG family are important transcription factors. They recognize cisplatin-damaged DNA lesions with a structure-specific preference and account for more than 70% of all proteins that interact with the cisplatin 1,2-intrastrand d(GpG) cross-link. HMGB4, a new member of the mammalian HMGB protein family expressed preferentially in the testis, was generated recombinantly, and its interactions with cisplatin-modified DNA were investigated in vitro. The binding affinities of the two individual DNA-binding domains of HMGB4 to DNA carrying a cisplatin 1,2-intrastrand d(GpG) cross-link are weaker than those of the DNA-binding domains of HMGB1. Full-length HMGB4, however, has a 28-fold stronger binding affinity (K(d) = 4.35 nM) for the platinated adduct compared to that of HMGB1 (K(d) = 120 nM), presumably because the former lacks a C-terminal acidic tail. The residue Phe37 plays a critical role in stabilizing the binding complex of HMGB4 with the cisplatin-modified DNA, as it does for HMGB1. Hydroxyl radical footprinting analysis of the HMGB4/platinated DNA complex reveals a footprinting pattern very different from that of HMGB1, however, revealing very little binding asymmetry with respect to the platinated lesion. An in vitro repair assay revealed that HMGB4, at 1 µM, interferes with repair of cisplatin 1,2-intrastrand cross-link damage by >90% compared to control, whereas HMGB1 at the same concentration inhibits repair by 45%. This repair inhibition capability is highly dependent on both the binding affinity and the size of the proteins. The putative role of HMGB4 in the mechanism of action of cisplatin, and especially its potential relevance to the hypersensitivity of testicular germ cell tumors to cisplatin, are discussed.

Redox state-dependent interaction of HMGB1 and cisplatin-modified DNA.

HMGB1, one of the most abundant nuclear proteins, has a strong binding affinity for cisplatin-modified DNA. It has been proposed that HMGB1 enhances the anticancer efficacy of cisplatin by shielding platinated DNA lesions from repair. Two cysteine residues in HMGB1 domain A form a reversible disulfide bond under mildly oxidizing conditions. The reduced domain A protein binds to a 25-bp DNA probe containing a central 1,2-d(GpG) intrastrand cross-link, the major platinum-DNA adduct, with a 10-fold greater binding affinity than the oxidized domain A. The binding affinities of singly and doubly mutated HMGB1 domain A, respectively deficient in one or both cysteine residues that form the disulfide bond, are unaffected by changes in external redox conditions. The redox-dependent nature of the binding of HMGB1 domain A to cisplatin-modified DNA suggests that formation of the intradomain disulfide bond induces a conformational change that disfavors binding to cisplatin-modified DNA. Hydroxyl radical footprinting analyses of wild-type domain A bound to platinated DNA under different redox conditions revealed identical cleavage patterns, implying that the asymmetric binding mode of the protein across from the platinated lesion is conserved irrespective of the redox state. The results of this study reveal that the cellular redox environment can influence the interaction of HMGB1 with the platinated DNA and suggest that the redox state of the A domain is a potential factor in regulating the role of the protein in modulating the activity of cisplatin as an anticancer drug.

A Pilot Study of Sequential Capsule Endoscopy Using MiroCam and PillCam SB Devices with Different Transmission Technologies.

BACKGROUND/AIMS: Studies have investigated the use of different types of radiofrequency capsules for comparison or sequential capsule endoscopy, but none have compared the MiroCam device - which utilizes a novel data transmission technology - with other capsules. This study compared the feasibility of sequential capsule endoscopy using the MiroCam and PillCam SB devices, which employ different transmission technologies. METHODS: Patients with diseases requiring capsule endoscopy were enrolled. After a 12-hour fast, one randomly selected capsule was swallowed. The second capsule was swallowed once fluoroscopy had indicated that the first capsule had migrated below the gastric outlet. RESULTS: The total operating time in 24 patients was 702+/-60 min (mean+/-SD) for the MiroCam and 446+/-28 min for the PillCam SB (p<0.0001). The rate of a complete examination to the cecum was 83.3% for the MiroCam and 58.3% for the PillCam SB (p=0.031). Diagnostic yields for the MiroCam, PillCam SB, and sequential capsule endoscopy were 45.8%, 41.7%, and 50.0%, respectively. The agreement rate between the two capsules was 87.5%, with a kappa value of 0.74. Electrical interference in data transmission between the two capsules was not observed, but temporary visual interferences were observed in seven patients (29.2%). CONCLUSIONS: Sequential capsule endoscopy with the MiroCam and PillCam SB produced slight but nonsignificant increases in the diagnostic yield, and the two capsules did not exhibit electrical interference. A larger trial is necessary for elucidating the usefulness of sequential capsule endoscopy.

Comparison of efficacies between stents for malignant colorectal obstruction: a randomized, prospective study.

BACKGROUND: Colonoscopic insertion of a self-expandable metallic stent (SEMS) has been widely performed for the treatment of malignant colorectal obstruction. Different types of stents could influence the efficacy and complication rate of stent use. OBJECTIVE: To compare the efficacy and complication rates between two SEMSs, the uncovered WallFlex stent and the covered Comvi stent. DESIGN: A prospective, randomized study. SETTING: Tertiary-care academic medical center. PATIENTS: Between 2007 and 2009, a total of 151 patients with malignant colorectal obstruction were enrolled. INTERVENTION: Two types of colorectal SEMSs (the uncovered WallFlex stent by Boston Scientific Corp and the newly developed covered Comvi stent by Taewoong Medical Co) were inserted. MAIN OUTCOME MEASUREMENTS: Technical success, clinical success, stent patency, and complication rate according to stent type. RESULTS: Technical failure occurred in 2 patients (1.3%); one was in the WallFlex group and the other in the Comvi group. Clinical failure developed in 9 patients (6.0%): 6 patients from the WallFlex group and 3 from the Comvi group. Complications because of cancer infiltration occurred more frequently in the WallFlex group (14.5% vs 3.8%). However, the rate of stent migration was higher in the Comvi group (21.1% vs 1.8%). The mean patency of the stent did not differ between the two groups (P = .50). LIMITATIONS: This was a single-center study. CONCLUSION: Both uncovered WallFlex and covered Comvi stents were suitable for relieving malignant colorectal obstruction. Tumor ingrowth was more common in the WallFlex group, but stent migration was more common in the Comvi group.

Active locomotion of a paddling-based capsule endoscope in an in vitro and in vivo experiment (with videos).

BACKGROUND: Capsule endoscopy that could actively move and approach a specific site might be more valuable for the diagnosis or treatment of GI diseases. OBJECTIVE: We tested the performance of active locomotion of a novel wired capsule endoscope with a paddling-based locomotion mechanism, using 3 models: a silicone tube, an extracted porcine colon, and a living pig. DESIGN: In vitro, ex vivo, and in vivo experiments in a pig model. SETTING: Study in an animal laboratory. INTERVENTIONS: For the in vitro test, the locomotive capsule was controlled to actively move from one side of a silicone tube to the other by a controller-operated automatic traveling program. The velocity was calculated by following a video recording. We performed ex vivo tests by using an extracted porcine colon in the same manner we performed the in vitro test. In in vivo experiments, the capsule was inserted into the rectum of a living pig under anesthesia, and was controlled to move automatically forward. After 8 consecutive trials, the velocity was calculated. MAIN OUTCOME MEASUREMENTS: Elapsed time, velocity, and mucosal damage. RESULTS: The locomotive capsule showed stable and active movement inside the lumen both in vitro and ex vivo. The velocity was 60 cm/min in the silicone tube, and 36.8 and 37.5 cm/min in the extracted porcine colon. In the in vivo experiments, the capsule stably moved forward inside the colon of a living pig without any serious complications. The mean velocity was 17 cm/min over 40 cm length. We noted pinpoint erythematous mucosal injuries in the colon. LIMITATION: Porcine model experiments, wired capsule endoscope. CONCLUSIONS: The novel paddling-based locomotive capsule endoscope performed fast and stable movement in a living pig colon with consistent velocity. Further investigation is necessary for practical use in humans.

Gastropericardial fistula as a complication in a refractory gastric ulcer after esophagogastrostomy with gastric pull-up.

A gastropericardial fistula, defined as penetration of a gastric lesion into the pericardium, is a rare occurrence. Such a fistula is usually associated with a huge ulcer in the gastric fundus, an ulcer within a hiatus hernia, a history of esophagogastric surgery, the concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs), or Zollinger-Ellison syndrome. The patient in this case presented with shoulder pain and melena, caused by a gastropericardial fistula that had occurred as a late complication of postoperative esophagogastrostomy and a refractory gastric ulcer. Despite the severity of the condition, the patient showed great improvement after medical treatment and the fistula was cured at the end.

Benefits of recurrent colonic stent insertion in a patient with advanced gastric cancer with carcinomatosis causing colonic obstruction.

Malignant obstruction develops frequently in advanced gastric cancer. Although it is primarily the gastric outlet that is obstructed, there are occasional reports of colonic obstruction. Treating intestinal obstruction usually requires emergency surgery or stent insertion. There are several kinds of complications with stent insertion, such as bowel perforation, stent migration, bleeding, abdominal pain and reobstruction. Nevertheless, endoscopic stent insertion could be a better treatment than emergency surgery in cases of malignant bowel obstruction in cancer patients with poor performance status. We report a case of advanced gastric cancer with carcinomatosis in which a recurrent colonic stent was inserted at the same site because of cancer growth into the stent. The patient maintained a good condition for chemotherapy, thus improving their chances for survival.

[Efficacy of endoscopic resection for small rectal carcinoid: a retrospective study].

BACKGROUND/AIMS: Well differentiated rectal carcinoid tumors which are less than 1cm in diameter can be treated by endoscopic resection. We aimed to evaluate the efficacy of endoscopic resection in treating small sized rectal carcinoids. METHODS: Medical records of 30 rectal carcinoid cases treated by endoscopic resection in Yonsei University College of Medicine, Severance Hospital between January 1995 and March 2007 were reviewed retrospectively. RESULTS: Mean age was 49.7 years and male to female ratio was 1:0.88. Mean size of tumor was 6.29+/-3.06 mm and 25 out of 30 patients (83.3%) had tumors of diameter less than 10 mm. Twenty-two out of 30 patients treated by conventional polypectomy, 6 by endoscopic mucosal resection using a transparent cap (EMR-C) and 2 by endoscopic submucosal dissection (ESD). Histological examination revealed that 9 patients had resection margin positive for tumor; 7 (31.8%) were in polypectomy group, 1 (16.7%) in EMR-C group, and 1 (50%) in ESD group (p=0.868). Five patients underwent transanal excision to remove residual tumor. No residual tumor was found in additionally resected tissue. Mean follow-up duration was 19. 3 months (range 0-122), and there were no recurrence. CONCLUSIONS: Endoscopic resection is an effective method in the treatment of small rectal carcinoids. However, long-term outcome remains to be elucidated by a large scaled prospective study.

Denaturing gradient gel electrophoresis analysis of bacterial community profiles in the rhizosphere of cry1AC-carrying Brassica rapa subsp. pekinensis.

The effect of genetically modified (GM) Brassica rapa subsp. pekinensis (Chinese cabbage) expressing Bt toxin gene (cry1AC) to the rhizosphere bacterial community was examined using the denaturing gradient gel electrophoresis (DGGE) fingerprinting method. From the visual comparison of the DGGE profiles, there were no significant differences between the profiles of Bt and control rhizosphere in both Suwon and Yesan samples. From the sequence analysis of the individual bands, Sphingomonas sp. of Alphaproteobacteria and several actinobacterial members were identified as the main bacterial taxa in both Suwon and Yesan samples. In the multiple correspondence analysis, no clear separation between Bt and control rhizosphere was seen in both Suwon and Yesan datasets. The profiles of bulk soils were separated from those of rhizosphere. The DGGE fingerprinting analyses indicated that Bt crops did not significantly alter the genetic composition of rhizosphere bacterial communities.