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Phishing websites, mimicking legitimate counterparts, pose significant threats by stealing user information through deceptive Uniform Resource Locators (URLs). Traditional blacklists struggle to identify dynamic URLs, necessitating advanced detection mechanisms. In this study, we propose an effective approach utilizing residual pipelining for phishing URL detection. Our method extracts common URL features and sentiments, employing a residual pipeline comprising convolutional and inverted residual blocks. These resultant features are then fed into a Multi-Layer Perceptron (MLP) for classification. We evaluate the efficacy of our approach against traditional algorithms using a Kaggle dataset. Our results demonstrate superior accuracy, precision, F1 Score, and recall, showcasing its effectiveness in mitigating phishing threats. Utilizing a residual pipeline made up of convolutional and inverted residual blocks, we start our method by identifying similar URL features and sentiments. We also use domain age research to figure out how long URLs have been around. Additionally, the lexical study of URL structure makes our method more useful, resulting in impressive accuracy. With an accuracy of 98.29%, this research highlights the importance of innovative techniques in combating evolving cyber threats. Future research directions could focus on enhancing the model’s robustness against adversarial attacks and integrating real-time monitoring for proactive defense strategies.

ObjectiveStimulator of interferon genes (STING) is a key regulator in initiating innate immune response from sensing cytosolic DNA. Recent studies have revealed that the cGAS-STING signaling pathway has a crucial role in tumor development and progression across cancer types. Herein, we conducted a meta-analysis to explore the relationship between the immunoexpression of STING and the survival outcome of patients in various solid tumors. Studies relevant to the subject were searched from PubMed, Embase, and Web of Science.ResultsEleven studies including 2,345 patients were eligible for the analysis. STING expression in tumor cells was related to improved disease-free survival/recurrence-free survival (DFS/RFS) (HR = 0.656, 95% CI = 0.455–0.946, p = 0.024) but not with overall survival (OS) (HR = 0.779, 95% CI = 0.534–1.136, p = 0.194). STING expression in stromal cells, however, did not show significant correlation with DFS/RFS and OS (HR = 0.979, 95% CI = 0.565–1.697, p-value = 0.940 and HR = 1.295, 95% CI = 0.845–1.985, p = 0.235, respectively). In a subgroup analysis, STING expression in tumor cells was associated with better DFS (HR = 0.622, 95% CI = 0.428–0.903, p = 0.012). In tumor cells, favorable DFS/RFS were also related to studies from univariate analysis and the gastrointestinal system (HR = 0.667, 95% CI = 0.482–0.923, p = 0.015 and HR = 0.566, 95% CI = 0.330–0.971, p = 0.039).ConclusionsSTING expression in tumor cells is associated with favorable outcome in solid tumors.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, registration number: CRD42023427027

Apple (Malus domestica (Suckow) Borkh., 1803) is economically important horticultural fruit crop in the world. In this study, the complete chloroplast genome of Korean apple cultivar ‘Kamhong’ was characterized through the de novo assembly of Illumina sequencing data. The chloroplast genome is a circular molecule of 161,069 bp length with 36.55% GC content and has a total of 112 genes including 78 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. Phylogenetic analysis with protein-coding sequences of chloroplast genome revealed that ‘Kamhong’ was closely grouped with M. domestica cultivars reported in China. The genomic data generated in this study can extend a molecular basis for phylogenetic relationships of Korean cultivar ‘Kamhong’ with other M. domestica cultivars bred in other countries.

Background Fusobacterium nucleatum has been identified to promote tumor progression in colorectal cancer (CRC). However, association between F. nucleatum and prognostic or clinicopathological features has been diverse among studies, which could be affected by type of biospecimen (formalin-fixed paraffin-embedded or fresh frozen [FF]). Methods Articles were systemically reviewed for studies that included the correlation between F. nucleatum and prognosis or clinicopathological features in CRC. Results Ten articles, eight studies with survival-related features involving 3,199 patients and nine studies with clinical features involving 2,655 patients, were eligible for the meta-analysis. Overall survival, disease-free survival, and cancer-specific survival were all associated with worse prognosis in F. nucleatum–high patients (p

Abstract Individual cell types of human tissues have their own CpG site methylation profiles, which might be utilized for the development of methylation markers to denote tumor-infiltrating lymphocytes (TILs). We aimed to develop DNA methylation markers that recapitulate the densities of TILs in gastric carcinoma (GC). Through genome-wide methylation profiling, NCOR2, PARK2, and ZSCAN12 were found to be highly methylated in CD3-positive and CD8-positive cells and rarely methylated in tumor cells. Scores of the three methylation markers were analyzed for their relationship with the overall survival and recurrence-free survival of patients with advanced GC (n = 471). The scores of three methylation markers were closely associated with densities of CD3-positive or CD8-positive cells at the tumor center or invasive front of GCs and found to be a significant prognostic factor in univariate analysis of overall survival and recurrence-free survival. In multivariate analysis, the highest score showed hazard ratios of 0.513 (CI 0.306–0.857) and 0.434 (CI 0.261–0.720) for overall survival and recurrence-free survival, respectively. The findings suggest that methylation markers signifying TILs might be utilized for the recapitulation of TIL density in GCs and serve as biomarkers for predicting prognosis in patients with GC.

Background Immunological contexture differs across malignancies, and understanding it in the tumor microenvironment (TME) is essential for development of new anticancer agents in order to achieve synergistic effects with anti-programmed cell death protein-1 (PD-1) therapy. TYRO3, AXL, and MERTK receptors are bi-expressed in both cancer and immune cells, and thus emerge as promising targets for therapeutic intervention. Whereas AXL and MERTK have been extensively studied, the role of TYRO3, in the TME, is still undetermined.Methods Here, we screened the TYRO3-focused chemical library consisting of 208 compounds and presented a potent and highly selective TYRO3 inhibitor, KRCT87. We explored the role of TYRO3 using mouse engrafting MC38 or 4T1 tumors. We validated the results using flow cytometry, RNA sequencing analysis, gene knockdown or overexpression, ex vivo immune cells isolation from mouse models, immunoblotting and quantitative PCR. Flow cytometry was used for the quantification of cell populations and immunophenotyping of macrophages and T cells. Co-cultures of macrophages and T cells were performed to verify the role of CCN1 in the tumors.Results TYRO3 blockade boosts antitumor immune responses in both the tumor-draining lymph nodes and tumors in MC38-syngeneic mice models. Moreover, the combination of KRCT87 and anti-PD-1 therapy exerts significant synergistic antitumor effects in anti-PD-1-non-responsive 4T1-syngeneic model. Mechanistically, we demonstrated that inhibition of TYRO3-driven CCN1 secretion fosters macrophages into M1-skewing phenotypes, thereby triggering antitumor T-cell responses. CCN1 overexpression in MC38 tumors diminishes responsiveness to anti-PD-1 therapy.Conclusions The activated TYRO3-CCN1 axis in cancer could dampen anti-PD-1 therapy responses. These findings highlight the potential of TYRO3 blockade to improve the clinical outcomes of anti-PD-1 therapy.

Abstract Background Triangular fibrocartilage complex (TFCC) has become an interest over the last few decades, discovering its understanding in anatomy, pathomechanism, biomechanics, and management in treatments. Currently, TFCC does not have a golden standard procedure, and not one surgical procedure is superior to the other. This study is to evaluate the comparative outcomes in TFCC patients that underwent either in all-inside arthroscopic suture anchors or the arthroscopic transosseous suture technique. Method From 2017 to 2019, 30 patients were analyzed. Eight patients were in an arthroscopic transosseous group and 22 patients were in an all-inside arthroscopic group. Comparison between patients’ flexion and extension range of motion (ROM), grip strength, and visual analog pain scale (VAS) preoperative and six-month follow-up were analyzed. Result There were significant increases in flexion ROM, extension ROM, and VAS between preoperative and postoperative in all-inside arthroscopic and arthroscopic transosseous. Only the all-inside arthroscopic group had a significant increase in grip strength. Postoperative flexion ROM had a significant difference between all-inside arthroscopic and arthroscopic transosseous. Conclusion Both the all-inside arthroscopic suture anchor technique and the arthroscopic transosseous suture technique are appropriate treatments to treat patients with TFCC. Both procedures have achieved the ultimate goal of improved longevity and optimal function. Level of evidence Level III; retrospective comparative cohort study.

The white ignimbrite layer on top of volcanic sequences in the Coastal Range is the youngest eruption of the northern Luzon Arc in the Taiwan region. A gabbroic enclave was coexisting with the andesitic ignimbrite in this sequence. This study reports the dating results, textural and petrographic descriptions, and geochemical characteristics of the gabbroic enclave and andesitic breccias in the ignimbrite. Both components erupted approximately at 4 Ma, and show enrichment in large ion lithophile elements and depletion in high field strength elements, which are important island arc characteristics. Major and trace elements indicated that the andesitic magma shows larger fractionation and lower degrees of partial melting than the basaltic magma which formed the gabbroic enclaves. We suggest that three sub-stages of magmatism occur during the youngest eruption of the northern Luzon Arc at ~4 Ma. In the first sub-stage, the basaltic magma generated by higher degrees of partial melting from the source rose to a shallow reservoir and cooled to build up the gabbroic wall rocks. Later, lower degrees of partial melting magma were injected into the shallow reservoir and fractionated to intermediate magma causing the second substage. The third sub-stage was activated by the recharged magma, which triggered the intermediate magma to rise along the earlier pathway and assimilated within the gabbroic wall rock. This magma eventually erupted to form the andesitic ignimbrite with gabbroic enclaves within.

Abstract Several studies have reported that the prognostic effect of KRAS mutations on colorectal cancers (CRCs) varies depending on the type of mutation. Considering the effect of KRAS mutations on tumor microenvironment, we analyzed the prognostic significance of KRAS mutation types after adjusting for the tumor-infiltrating lymphocytes (TIL) and tumor-stromal percentage (TSP) statuses. In two independent cohorts, KRAS mutations were analyzed by Sanger sequencing and/or next-generation sequencing. TIL density and the TSP were quantified from whole-slide immunohistochemical images. KRAS-mutant CRCs were divided into three subgroups (G12D/V, other codon 12 mutations and codon 13 mutations) to examine their differential effect on TIL density, the TSP and recurrence-free survival (RFS). Among the KRAS mutations, only the G12D/V subgroups showed significantly less TIL infiltration than the wild-type CRCs. According to survival analysis, G12D/V mutations were associated with short RFS; codon 13 mutations showed discordant trends in the two cohorts, and other codon 12 mutations showed no significant association. Multivariate analysis further supported the prognostic value of G12D/V mutations. This result is not only consistent with a recent study suggesting the immunosuppressive effect of mutant KRAS but also provides insight into the type-specific prognostic effect of KRAS mutations.

Abstract The copy number (CN) gain of protooncogenes is a frequent finding in gastric carcinoma (GC), but its prognostic implication remains elusive. The study aimed to characterize the clinicopathological features, including prognosis, of GCs with copy number gains in multiple protooncogenes. Three hundred thirty-three patients with advanced GC were analyzed for their gene ratios in EGFR, GATA6, IGF2, and SETDB1 using droplet dPCR (ddPCR) for an accurate assessment of CN changes in target genes. The number of GC patients with 3 or more genes with CN gain was 16 (4.8%). Compared with the GCs with 2 or less genes with CN gain, the GCs with 3 or more CN gains displayed more frequent venous invasion, a lower density of tumor-infiltrating lymphocytes, and lower methylation levels of L1 or SAT-alpha. Microsatellite instability-high tumors or Epstein–Barr virus-positive tumors were not found in the GCs with 3 or more genes with CN gain. Patients of this groups also showed the worst clinical outcomes for both overall survival and recurrence-free survival, which was persistent in the multivariate survival analyses. Our findings suggest that the ddPCR-based detection of multiple CN gain of protooncogenes might help to identify a subset of patients with poor prognosis.

Abstract Thymic atrophy in sepsis is a critical disadvantage because it induces immunosuppression and increases the mortality rate as the disease progresses. However, the exact mechanism of thymic atrophy has not been fully elucidated. In this study, we discovered a novel role for VSIG4-positive peritoneal macrophages (V4(+) cells) as the principal cells that induce thymic atrophy and thymocyte apoptosis. In CLP-induced mice, V4(+) cells were activated after ingestion of invading microbes, and the majority of these cells migrated into the thymus. Furthermore, these cells underwent a phenotypic shift from V4(+) to V4(−) and from MHC II(low) to MHC II(+). In coculture with thymocytes, V4(+) cells mainly induced apoptosis in DP thymocytes via the secretion of TNF-α. However, there was little effect on CD4 or CD8 SP and DN thymocytes. V4(−) cells showed low levels of activity compared to V4(+) cells. Thymic atrophy in CLP-induced V4(KO) mice was much less severe than that in CLP-induced wild-type mice. In addition, V4(KO) peritoneal macrophages also showed similar activity to V4(−) cells. Taken together, the current study demonstrates that V4(+) cells play important roles in inducing immunosuppression via thymic atrophy in the context of severe infection. These data also suggest that controlling the function of V4(+) cells may play a crucial role in the development of new therapies to prevent thymocyte apoptosis in sepsis.

Background The prognostic potential of Crohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) has been investigated through the assessment of different criteria. Methods The prognostic impact of CLR was investigated in 636 CRC patients to compare methods from previously published articles. These methods included CLR measured by number of lymphoid aggregates (LAs) (CLR count), LA size greater than or equal to 1 mm (CLR size), CLR density with a cutoff value of 0.38, and subjective criteria as defined by intense CLR. Results In univariate survival analysis, CLR-positive CRC as defined by the four aforementioned methods was associated with better overall survival (OS) (hazard ratio [HR], 0.463; 95% confidence interval [CI], 0.305 to 0.702; p < .001; HR, 0.656; 95% CI, 0.411 to 1.046; p = .077; HR, 0.363; 95% CI, 0.197 to 0.669; p = .001; and HR, 0.433; 95% CI, 0.271 to 0.690; p < .001, respectively) and disease-free survival (DFS) (HR, 0.411; 95% CI, 0.304 to 0.639; p < .001; HR, 0.528; 95% CI, 0.340 to 0.821; p = .004; HR, 0.382; 95% CI, 0.226 to 0.645, p = .004; and HR, 0.501; 95% CI, 0.339 to 0.741; p < .001, respectively) than CLR-negative CRC, regardless of criteria with the exception of OS for CLR density. In multivariate analysis, two objective criteria (CLR count and CLR density) and one subjective criterion (intense CLR) for defining CLR were considered independent prognostic factors of OS and DFS in CRC patients. Conclusions CLR has similar traits regardless of criteria, but CLR-positivity should be defined by objective criteria for better reproducibility and prognostic value.

A safety margin must always be maintained between trains. To this end, position data of all trains must be provided to the railway system in real time. Basically, this data has been provided based on the infrastructure installed on the railway. However, enormous costs are required to install the infrastructure, and continuous maintenance is required. In addition, cases of accidents due to un-detection or false-detection of trains are being reported as news. Due to these problems, researches on infra-less navigation system for trains have been conducted. Taking into account the blocking phenomenon of Global Positioning System (GPS)/Global Navigation Satellite System (GNSS) signals in tunnels, the navigation system for trains should constitute an integrated navigation system. However, the accuracy and reliability of navigation solution provided by the integrated navigation system are not always satisfied. And this can lead to instability of the railway system. Therefore, the navigation solution for trains must have high accuracy and also the reliability information of the corresponding navigation solution must be provided. In this article, we construct an Inertial Navigation System (INS)/GPS/Non-Holonomic Constraints (NHC) integrated navigation system for trains with NHC motion. A simulation trajectory is generated considering the real trajectory, and the accuracy and reliability of the navigation information according to the trajectory and measurements are analyzed together. And based on this information, we propose a method to calculate the safety margin between trains. The performance of the proposed technology is verified through a real trajectory-based Monte Carlo simulation.

There has recently been a rapid progress in computational methods for determining protein targets of small molecule drugs, which will be termed as compound protein interaction (CPI). In this review, we comprehensively review topics related to computational prediction of CPI. Data for CPI has been accumulated and curated significantly both in quantity and quality. Computational methods have become powerful ever to analyze such complex the data. Thus, recent successes in the improved quality of CPI prediction are due to use of both sophisticated computational techniques and higher quality information in the databases. The goal of this article is to provide reviews of topics related to CPI, such as data, format, representation, to computational models, so that researchers can take full advantages of these resources to develop novel prediction methods. Chemical compounds and protein data from various resources were discussed in terms of data formats and encoding schemes. For the CPI methods, we grouped prediction methods into five categories from traditional machine learning techniques to state-of-the-art deep learning techniques. In closing, we discussed emerging machine learning topics to help both experimental and computational scientists leverage the current knowledge and strategies to develop more powerful and accurate CPI prediction methods.

Background/Aims: Epigenetic change is one of the mechanisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigenetic changes of miR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication. Methods: The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mucosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori -eradication and H. pylori -persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the methylation levels. Results: In the GC cell lines, the level of miR- 200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order. In the H. pylori -persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methylation decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group. Conclusions: Epigenetic alterations of miR-200a/b may be implicated in H. pylori -induced gastric carcinogenesis. This field defect for cancerization is suggested to be improved by H. pylori eradication.

Objectives In this pandemic situation caused by a novel coronavirus disease in 2019 (COVID-19), an electronic support system that can rapidly and accurately perform epidemic investigations, is needed. It would systematically secure and analyze patients’ data (who have been confirmed to have the infection), location information, and credit card usage. Methods The “Infectious Disease Prevention and Control Act” in South Korea, established a legal basis for the securement, handling procedure, and disclosure of information required for epidemic investigations. The Epidemic Investigation Support System (EISS) was developed as an application platform on the Smart City data platform. Results The EISS performed the function of inter-institutional communication which reduced the processing period of patients’ data in comparison to other methods. This system automatically marked confirmed cases’ tracking data on a map and hot-spot analysis which lead to the prediction of areas where people may be vulnerable to infection. Conclusion The EISS was designed and implemented for use during an epidemic investigation to prevent the spread of an infectious disease, by specifically tracking confirmed cases of infection.

IPIN 2019 Competition, sixth in a series of IPIN competitions, was held at the CNR Research Area of Pisa (IT), integrated into the program of the IPIN 2019 Conference. It included two on-site real-time Tracks and three off-site Tracks. The four Tracks presented in this paper were set in the same environment, made of two buildings close together for a total usable area of 1000 m2 outdoors and and 6000 m2 indoors over three floors, with a total path length exceeding 500 m. IPIN competitions, based on the EvAAL framework, have aimed at comparing the accuracy performance of personal positioning systems in fair and realistic conditions: past editions of the competition were carried in big conference settings, university campuses and a shopping mall. Positioning accuracy is computed while the person carrying the system under test walks at normal walking speed, uses lifts and goes up and down stairs or briefly stops at given points. Results presented here are a showcase of state-of-the-art systems tested side by side in real-world settings as part of the on-site real-time competition Tracks. Results for off-site Tracks allow a detailed and reproducible comparison of the most recent positioning and tracking algorithms in the same environment as the on-site Tracks.

Acanthamoeba keratitis (AK) is an infectious ocular disease which is difficult to diagnose correctly and cure. Development of an effective and safe therapeutic drug for AK is needed. Our preliminary screening of more than 200 extracts from wild plants collected in Korea suggested the potential amoebicidal activity of Phragmites australis (Cav.) Trin. ex Steud. extract (PAE) against Acanthamoeba species. Here, we aimed to analyze the amoebicidal activity of PAE on Acanthamoeba and its underlying amoebicidal mechanism. PAE induced amoebicidal activity against both A. castellanii and A. polyphaga trophozoites, while it showed low cytotoxicity in human corneal epithelial cells (HCE-2) and human retinal pigment epithelial cells (ARPE-19). Transmission electron microscopy analysis showed subcellular morphological changes, such as increased granules, abnormal mitochondria, and atypical cyst wall formation, in the PAE-treated A. castellanii. Fluorometric apoptosis assay and TUNEL assay revealed apoptosis-like programmed cell death (PCD) in the PAE-treated A. castellanii. The PAE treatment increased reactive oxygen species production and reduced mitochondrial membrane potential in the amoeba. The enhanced expression of autophagy-associated genes was also detected. These results suggested that PAE exerted a promising amoebicidal effect on A. castellanii trophozoites via the PCD pathway. PAE could be a potential candidate for developing a therapeutic drug for AK.

Background Ultrasound-guided greater occipital nerve (GON) block has been frequently used to treat various types of headaches, and botulinum toxin has recently begun to be used in patients with headache. Our study presents the long-term effect of botulinum toxin on GON block using ultrasound in patients with chronic headache in occipital area. Methods Patients with occipital headache were divided into two groups (bupivacaine: BUP group [n = 27], botulinum toxin: BTX group [n = 27]), and ultrasound-guided GON block was performed at the C2 level. GON was detected with ultrasound and distance from GON to midline, from the skin surface to GON, and size of GON were measured in both groups. Visual analogue scale (VAS) scores and Likert scale were assessed at pretreatment and at 1, 4, 8, and 24 weeks after treatment in both groups. Results The distance from GON to midline was 18.9 ± 4.4 mm (right) and 17.3 ± 3.8 mm (left). The depth from the skin was 12.9 ± 1.5 mm (right) and 13.4 ± 1.6 mm (left). GON size was 3.1 mm on both sides. The VAS score and patient satisfaction score (Likert scale) in 4, 8, and 24 weeks after injection were superior for the BTX than the BUP group. Conclusions Ultrasound-guided GON block using BTX is effective in reducing short-term and long-term pain in patients with chronic headache in the occipital area.

Background SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC. Methods We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs. Results A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancer-specific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022). Conclusions We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.

Background Although colorectal sessile serrated adenomas/polyps (SSA/Ps) with morphologic dysplasia are regarded as definite high-risk premalignant lesions, no reliable grading or risk-stratifying system exists for non-dysplastic SSA/Ps. The accumulation of CpG island methylation is a molecular hallmark of progression of SSA/Ps. Thus, we decided to classify non-dysplastic SSA/Ps into risk subgroups based on the extent of CpG island methylation. Methods The CpG island methylator phenotype (CIMP) status of 132 non-dysplastic SSA/Ps was determined using eight CIMP-specific promoter markers. SSA/Ps with CIMP-high and/or MLH1 promoter methylation were regarded as a high-risk subgroup. Results Based on the CIMP analysis results, methylation frequency of each CIMP marker suggested a sequential pattern of CpG island methylation during progression of SSA/P, indicating MLH1 as a late-methylated marker. Among the 132 non-dysplastic SSA/Ps, 34 (26%) were determined to be high-risk lesions (33 CIMP-high and 8 MLH1-methylated cases; seven cases overlapped). All 34 high-risk SSA/Ps were located exclusively in the proximal colon (100%, p = .001) and were significantly associated with older age (≥ 50 years, 100%; p = .003) and a larger histologically measured lesion size (> 5 mm, 100%; p = .004). In addition, the high-risk SSA/Ps were characterized by a relatively higher number of typical base-dilated serrated crypts. Conclusions Both CIMP-high and MLH1 methylation are late-step molecular events during progression of SSA/Ps and rarely occur in SSA/Ps of young patients. Comprehensive consideration of age (≥ 50), location (proximal colon), and histologic size (> 5 mm) may be important for the prediction of high-risk lesions among non-dysplastic SSA/Ps.

Background This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy. Methods F. nucleatum DNA was quantitatively measured in a total of 593 CRC tissues retrospectively collected from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative. Results No significant differences in survival were observed between the F.nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses according to tumor location demonstrated that disease-free survival was significantly better in F.nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal, ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariate analysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoid colon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore, the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not in a MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor location and MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treated with adjuvant chemotherapy. Conclusions Intratumoral F. nucleatum load is a potential prognostic factor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treated with oxaliplatin-based adjuvant chemotherapy.

In the Long Term Evolution (LTE) system, the Signal Propagation Model (SPM) and the location information of the base stations are required for positioning a smartphone. To this end, this paper proposes a technique for estimating the SPM and the location of the base station at the same time using location-based Reference Signal Received Power (RSRP) information acquired in a limited area. In the proposed technique, multiple Virtual Locations (VLs) for a base station are set within the service area. Signal propagation modelling is performed based on the assumptions that a base station is in each VL and the RSRP measurements are obtained from the corresponding base station. The residuals between the outputs of the estimated SPM and the RSRP measurements are then calculated. The VL with the minimum sum of the squared residuals is determined as the location of the base station. At the same time, the SPM estimated based on the corresponding VL is selected as the SPM of the base station. As a result of the experiment in Seoul, it was confirmed that the positions of seven base stations were estimated with an average accuracy of 40.2 m.

In the present study, we developed a computational method and panel markers to assess microsatellite instability (MSI) using a targeted next-generation sequencing (NGS) platform and compared the performance of our computational method, mSILICO, with that of mSINGS to detect MSI in CRCs. We evaluated 13 CRC cell lines, 84 fresh and 119 formalin-fixed CRC tissues (including 61 MSI-high CRCs and 155 microsatellite-stable CRCs) and tested the classification performance of the two methods on 23, 230, and 3,154 microsatellite markers. For the fresh tissue and cell line samples, mSILICO showed a sensitivity of 100% and a specificity of 100%, regardless of the number of panel markers, whereas for the formalin-fixed tissue samples, mSILICO exhibited a sensitivity of up to 100% and a specificity of up to 100% with three differently sized panels ranging from 23 to 3154. These results were similar to those of mSINGS. With the application of mSILICO, the small panel of 23 markers had a sensitivity of ≥95% and a specificity of 100% in cell lines/fresh tissues and formalin-fixed tissues of CRC. In conclusion, we developed a new computational method and microsatellite marker panels for the determination of MSI that does not require paired normal tissues. A small panel could be integrated into the targeted NGS panel for the concurrent analysis of single nucleotide variations and MSI.

Clonorchiasis caused by Clonorchis sinensis is endemic in East Asia; approximately 15 million people have been infected thus far. To diagnose the infection, serodiagnostic tests with excellent functionality should be performed. First, 607 expressed sequence tags encoding polypeptides with a secretory signal were expressed into recombinant proteins using an in vitro translation system. By protein array-based screening using C. sinensis-infected sera, 18 antigen candidate proteins were selected and assayed for cross-reactivity against Opisthorchis viverrini-infected sera. Of the six antigenic proteins selected, four were synthesized on large scale in vitro and evaluated for antigenicity against the flukes-infected human sera using ELISA. CsAg17 antigen showed the highest sensitivity (77.1%) and specificity (71.2%). The sensitivity and specificity of the bacterially produced CsAg17-28GST fusion antigen was similar to those of CsAg17 antigen. CsAg17 antigen can be used to develop point-of-care serodiagnostic tests for clonorchiasis.

Background Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). Conclusions Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer’s tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

Objectives: Cerebral white matter lesions (WMLs) are regarded to be subclinical ischemic changes of the cerebral parenchyma. Many previous studies have shown that baseline blood pressure (BP) is one of the most important factors for WMLs, but the relation between exercise BP and WMLs has not been fully evaluated. So, we sought to investigate the relationships between cerebral WMLs and peak exercise BP. Methods: Brain magnetic resonance imaging scan and treadmill testing were performed simultaneously in 130 consecutive subjects without history of stroke or transient ischemic stroke. Results: Among 130 subjects, 42 individuals (32%) presented WMLs. Individuals with WMLs were older than those without WMLs, and baseline systolic BP and pulse pressure were higher in subjects with WMLs. During treadmill test, peak exercise systolic BP was more significantly elevated in subjects with WMLs. In multivariable logistic regression analysis, elevated baseline systolic BP, not peak exercise systolic BP, was associated with the presence of WMLs, independently of age. However, in multivariable logistic regression analysis of 88 normotensive subjects, elevated peak systolic BP during exercise was the only determinant for the presence of WMLs. Conclusions: Elevated peak systolic BP during exercise is significantly related with WMLs, subclinical small vessel disease of brain, especially in normotensive subjects.

Background: Patent ductus arteriosus (PDA) ligation is usually performed by congenital cardiac surgeons. However, due to the uneven distribution of congenital cardiac surgeons in South Korea, many institutions depend solely on adult cardiac surgeons for congenital cardiac diseases. We report the outcomes of PDA ligations performed by adult cardiac surgeons at our institution. Methods: The electronic medical records of 852 neonates at Chung-Ang University Hospital, Seoul, South Korea from November 2010 to May 2014 were reviewed to identify patients with PDA. Results: Of the 111 neonates with a diagnosis of PDA, 26 (23%) underwent PDA ligation. PDAs were ligated within 28 days of birth (mean, 14.5±7.8 days), and the mean gestational age of these patients was 30.3±4.6 weeks (range, 26 to 40 weeks) with a mean birth weight of 1,292.5±703.5 g (range, 480 to 3,020 g). No residual shunts through the PDA were found on postoperative echocardiography. There was 1 case of 30-day mortality (3.8%) due to pneumonia, and 6 cases of in-hospital mortality (23.1%) after 30 days, which is comparable to results from other centers with congenital cardiac surgery programs. Conclusion: Although our outcomes may not be generalizable to all hospital settings without a congenital cardiac surgery program, in select centers, PDA ligations can be performed safely by adult cardiac surgeons if no congenital cardiac surgery program is available.

Abstract Background DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5′ untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. Methods A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival. Results Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter. Conclusions Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.

Background Tumor microenvironment has recently drawn attention in that it is related with tumor prognosis. Cancer-associated fibroblast also plays a critical role in cancer invasiveness and progression in colorectal cancers. Periostin (POSTN), originally identified to be expressed in osteoblasts and osteoblast-derived cells, is expressed in cancer-associated fibroblasts in several tissue types of cancer. Recent studies suggest an association between stromal overexpression of POSTN and poor prognosis of cancer patients. Methods We analyzed colorectal cancer cases for their expression status of POSTN in tumor stroma using immunohistochemistry and correlated the expression status with clinicopathological and molecular features. Results High level of POSTN expression in tumor stroma was closely associated with tumor location in proximal colon, infiltrative growth pattern, undifferentiated histology, tumor budding, luminal necrosis, and higher TNM stage. High expression status of POSTN in tumor stroma was found to be an independent prognostic parameter implicating poor 5-year cancer-specific survival and 5-year progression-free survival. Conclusions Our findings suggest that POSTN overexpression in tumor stroma of colorectal cancers could be a possible candidate marker for predicting poor prognosis in patients with colorectal cancers.