Keyboard Data Protection Technique Using GAN in Password-Based User Authentication: Based on C/D Bit Vulnerability.

In computer systems, user authentication technology is required to identify users who use computers. In modern times, various user authentication technologies, including strong security features based on ownership, such as certificates and security cards, have been introduced. Nevertheless, password-based authentication technology is currently mainly used due to its convenience of use and ease of implementation. However, according to Verizon's "2022 Data Breach Investigations Report", among all security incidents, security incidents caused by password exposures accounted for 82%. Hence, the security of password authentication technology is important. Consequently, this article analyzes prior research on keyboard data attacks and defense techniques to draw the fundamental reasons for keyboard data attacks and derive countermeasures. The first prior research is about stealing keyboard data, an attack that uses machine learning to steal keyboard data to overcome the limitations of a C/D bit attack. The second prior research is an attack technique that steals keyboard data more efficiently by expanding the features of machine learning used in the first prior research. In this article, based on previous research findings, we proposed a keyboard data protection technique using GAN, a Generative Adversarial Network, and verified its feasibility. To summarize the results of performance evaluation with previous research, the machine learning-based keyboard data attack based on the prior research exhibited a 96.7% attack success rate, while the study's proposed method significantly decreased the attack success rate by approximately 13%. Notably, in all experiments, the average decrease in the keyboard data classification performance ranged from a minimum of -29% to a maximum of 52%. When evaluating performance based on maximum performance, all performance indicators were found to decrease by more than 50%.

A Mesoporous Tungsten Oxynitride Nanofibers/Graphite Felt Composite Electrode with High Catalytic Activity for the Cathode in Zn-Br Flow Battery.

High electrochemical polarization during a redox reaction in the electrode of aqueous zinc-bromine flow batteries largely limits its practical implementation as an effective energy storage system. This study demonstrates a rationally-designed composite electrode that exhibits a lower electrochemical polarization by providing a higher number of catalytically-active sites for faster bromine reaction, compared to a conventional graphite felt cathode. The composite electrode is composed of electrically-conductive graphite felt (GF) and highly active mesoporous tungsten oxynitride nanofibers (mWONNFs) that are prepared by electrospinning and simple heat treatments. Addition of the 1D mWONNFs to porous GF produces a web-like structure that significantly facilitates the reaction kinetics and ion diffusion. The cell performance achieves in this study demonstrated high energy efficiencies of 89% and 80% at current densities of 20 and 80 mA cm-2 , respectively. Furthermore, the cell can also be operated at a very high current density of 160 mA cm-2 , demonstrating an energy efficiency of 62%. These results demonstrate the effectiveness of the mWONNF/GF composite as the electrode material in zinc-bromine flow batteries.

Effective Ransomware Detection Using Entropy Estimation of Files for Cloud Services.

A variety of data-based services such as cloud services and big data-based services have emerged in recent times. These services store data and derive the value of the data. The reliability and integrity of the data must be ensured. Unfortunately, attackers have taken valuable data as hostage for money in attacks called ransomware. It is difficult to recover original data from files in systems infected by ransomware because they are encrypted and cannot be accessed without keys. There are cloud services to backup data; however, encrypted files are synchronized with the cloud service. Therefore, the original file cannot be restored even from the cloud when the victim systems are infected. Therefore, in this paper, we propose a method to effectively detect ransomware for cloud services. The proposed method detects infected files by estimating the entropy to synchronize files based on uniformity, one of the characteristics of encrypted files. For the experiment, files containing sensitive user information and system files for system operation were selected. In this study, we detected 100% of the infected files in all file formats, with no false positives or false negatives. We demonstrate that our proposed ransomware detection method was very effective compared to other existing methods. Based on the results of this paper, we expect that this detection method will not synchronize with a cloud server by detecting infected files even if the victim systems are infected with ransomware. In addition, we expect to restore the original files by backing up the files stored on the cloud server.

Neutralization Method of Ransomware Detection Technology Using Format Preserving Encryption.

Ransomware is one type of malware that involves restricting access to files by encrypting files stored on the victim's system and demanding money in return for file recovery. Although various ransomware detection technologies have been introduced, existing ransomware detection technologies have certain limitations and problems that affect their detection ability. Therefore, there is a need for new detection technologies that can overcome the problems of existing detection methods and minimize the damage from ransomware. A technology that can be used to detect files infected by ransomware and by measuring the entropy of files has been proposed. However, from an attacker's point of view, neutralization technology can bypass detection through neutralization using entropy. A representative neutralization method is one that involves decreasing the entropy of encrypted files by using an encoding technology such as base64. This technology also makes it possible to detect files that are infected by ransomware by measuring entropy after decoding the encoded files, which, in turn, means the failure of the ransomware detection-neutralization technology. Therefore, this paper derives three requirements for a more sophisticated ransomware detection-neutralization method from the perspective of an attacker for it to have novelty. These requirements are (1) it must not be decoded; (2) it must support encryption using secret information; and (3) the entropy of the generated ciphertext must be similar to that of plaintext. The proposed neutralization method satisfies these requirements, supports encryption without decoding, and applies format-preserving encryption that can adjust the input and output lengths. To overcome the limitations of neutralization technology using the encoding algorithm, we utilized format-preserving encryption, which could allow the attacker to manipulate the entropy of the ciphertext as desired by changing the expression range of numbers and controlling the input and output lengths in a very free manner. To apply format-preserving encryption, Byte Split, BinaryToASCII, and Radix Conversion methods were evaluated, and an optimal neutralization method was derived based on the experimental results of these three methods. As a result of the comparative analysis of the neutralization performance with existing studies, when the entropy threshold value was 0.5 in the Radix Conversion method, which was the optimal neutralization method derived from the proposed study, the neutralization accuracy was improved by 96% based on the PPTX file format. The results of this study provide clues for future studies to derive a plan to counter the technology that can neutralize ransomware detection technology.

Valgus Arthritic Knee Responds Better to Conservative Treatment than the Varus Arthritic Knee.

Background and Objectives: Clinically, it is beneficial to determine the knee osteoarthritis (OA) subtype that responds well to conservative treatments. Therefore, this study aimed to determine the differences between varus and valgus arthritic knees in the response to conservative treatment. We hypothesized that valgus arthritic knees would respond better to conservative treatment than varus arthritic knees. Materials and Methods: Medical records of 834 patients who received knee OA treatment were retrospectively reviewed. Patients with Kellgren-Lawrence grades III and IV were divided into two groups according to knee alignment (varus arthritic knee, hip-knee-ankle angle [HKA] > 0° or valgus arthritic knee, HKA < 0°). The Kaplan-Meier curve with total knee arthroplasty (TKA) as an endpoint was used to compare the survival probability between varus and valgus arthritic knees at one, two, three, four, and five years after the first visit. A receiver operating characteristic (ROC) curve was used to compare the HKA thresholds for TKA between varus and valgus arthritic knees. Results: Valgus arthritic knees responded better to conservative treatment than varus arthritic knees. With TKA as an endpoint, the survival probabilities for varus and valgus arthritic knees were 24.2% and 61.4%, respectively, at the 5-year follow-up (p < 0.001). The thresholds of HKA for varus and valgus arthritic knees for TKA were 4.9° and -8.1°, respectively (varus: area under the ROC curve [AUC] = 0.704, 95% confidence interval [CI] 0.666-0.741, p < 0.001, sensitivity = 0.870, specificity = 0.524; valgus: AUC = 0.753, 95% CI 0.693-0.807, p < 0.001, sensitivity = 0.753, specificity = 0.786). Conclusions: Conservative treatment is more effective for valgus than for varus arthritic knees. This should be considered when explaining the prognosis of conservative treatment for knees with varus and valgus arthritis.

Determinants of clinical outcomes of gastric cancer patients treated with neoadjuvant chemotherapy: a sub-analysis of the PRODIGY study.

BACKGROUND: In this post hoc analysis of the PRODIGY study, we aimed to investigate factors associated with survival outcomes and provide evidence for designing optimal perioperative treatment strategies for gastric cancer patients receiving neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 212 patients in the neoadjuvant chemotherapy group of the PRODIGY study were included as the study population. The prognostic impact of clinicopathologic factors, including the initial radiological clinical stage (cStage) and post-neoadjuvant chemotherapy pathological stage (ypStage), was analyzed. RESULTS: The median age was 58 years. The majority of patients (77.4%) had cStage III disease, and about 10% and 25% had ypStage 0 and I disease, respectively. According to the initial cStage, progression-free survival (PFS) and overall survival (OS) were significantly different (P < 0.01). PFS and OS were also different according to the ypStage (P < 0.01). In multivariate analyses, cStage IIIC disease (vs. cStage II) and ypStage II and III disease (vs. ypStage 0/I) were independent factors for poor survival outcomes. Based on the patterns of PFS and OS according to both cStage and ypStage, three patient groups were defined. These groups showed distinct PFS and OS (P < 0.01) with 5-year PFS rates of 95.7%, 77.9%, and 31.3% and 5-year OS rates of 95.7%, 82.4%, and 42.5%, respectively. CONCLUSIONS: Both initial cStage and ypStage were independent factors for survival outcomes of gastric cancer patients treated with neoadjuvant chemotherapy. Efforts should be made to develop optimal peri-operative treatment strategies for patients at different risks according to cStage and ypStage.

A Method for Neutralizing Entropy Measurement-Based Ransomware Detection Technologies Using Encoding Algorithms.

Ransomware consists of malicious codes that restrict users from accessing their own files while demanding a ransom payment. Since the advent of ransomware, new and variant ransomwares have caused critical damage around the world, thus prompting the study of detection and prevention technologies against ransomware. Ransomware encrypts files, and encrypted files have a characteristic of increasing entropy. Due to this characteristic, a defense technology has emerged for detecting ransomware-infected files by measuring the entropy of clean and encrypted files based on a derived entropy threshold. Accordingly, attackers have applied a method in which entropy does not increase even if the files are encrypted, such that the ransomware-infected files cannot be detected through changes in entropy. Therefore, if the attacker applies a base64 encoding algorithm to the encrypted files, files infected by ransomware will have a low entropy value. This can eventually neutralize the technology for detecting files infected from ransomware based on entropy measurement. Therefore, in this paper, we propose a method to neutralize ransomware detection technologies using a more sophisticated entropy measurement method by applying various encoding algorithms including base64 and various file formats. To this end, we analyze the limitations and problems of the existing entropy measurement-based ransomware detection technologies using the encoding algorithm, and we propose a more effective neutralization method of ransomware detection technologies based on the analysis results.

Expression of Cyr61 is associated with clinical course in patients with Crohn's disease.

BACKGROUNDS: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn's disease (CD). METHODS: Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients. RESULTS: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P < 0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P = 0.01). Cyr61 mRNA levels in inflamed mucosa were twofold higher than those in non-inflamed lesion (P > 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P < 0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend = 0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95% CI 0.20-0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P = 0.03). CONCLUSIONS: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.

Usefulness of cardiac magnetic resonance images for prediction of sudden cardiac arrest in patients with mitral valve prolapse: a multicenter retrospective cohort study.

BACKGROUND: An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. METHODS: MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. RESULTS: Of the 85 patients [age, 54.0 (41.0-65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65-148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02-1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08-1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. CONCLUSIONS: The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

Experimental evaluation of pseudo-sound in a parametric array.

Parametric arrays have been widely investigated due to their high directivity in the low-frequency region when measuring the acoustic characteristics of materials, such as sound transmission and reflection properties, in the limited space of acoustic water tanks. Because a parametric array utilizes nonlinear interaction across the frequency components, nonlinear phenomena arise in both the acoustic medium and the hydrophone system. The unwanted nonlinear sound generated in the hydrophone and instrumentation is termed pseudo-sound. This study devised an experiment to measure the pseudo-sound without a truncator to assess the effect of the pseudo-sound in the near field. In order to separately measure the pseudo-sound, the hydrophone was placed close to the projector so that the pseudo-sound was dominantly generated. The method is based on the fact that, if we can suppress a parametric signal by minimizing the propagation path length in the medium, the resulting measured signal can be attributed to the pseudo-sound. The resultant signal levels were matched to the levels at corresponding distances based on the primary levels of a (separately conducted) distance-varying experiment. Finally, the suitability of the proposed technique was evaluated by comparing its results with the pseudo-sound levels measured using a truncator.

Comparative Experimental Investigation on Optimal Parametric Array Types.

As a sound transmitting device that relies on the nonlinearity of a medium, a parametric array (PA) can generate high-directivity low-frequency signals using a small aperture transducer and high-frequency signals. Despite their relatively low source level, the PA is frequently used to measure the acoustic properties of materials in low-frequency regions owing to their high directivity in confined acoustic water tanks. Therefore, methods for improving the source level of secondary signals are of interest. Currently, there are two driving methods for PA: the dual-frequency PA and the broadband PA with amplitude modulation. In this study, we share the results of an elaborate and comparative experimental investigation of these two driving methods. Comparisons are made and discussed in terms of the intensity of the generated secondary signal and its characteristics in the frequency domain. Based on these factors, we confirmed that the broadband PA was more suitable as the sound source of the low-frequency characteristic measurement system of acoustic materials.

Effect of Intermittent Hypoxia on Metabolic Syndrome and Insulin Resistance in the General Male Population.

Background and objectives: Obstructive sleep apnea (OSA) is closely associated with insulin resistance (IR) and is an independent risk factor for incident type 2 diabetes mellitus (T2DM). Most studies evaluate the correlation between OSA and IR in only obese or T2DM patients. Therefore, we tried to investigate the effect of OSA on metabolic syndrome and IR in the general healthy male population. Materials and Methods: 184 subjects who visited a preventive health examination program were recruited for this study. All subjects received overnight polysomnography by a portable device (Watch-PAT 200). We examined several metabolic parameters and a homeostasis model of assessment for insulin resistance index (HOMA-IR). The subjects were divided into three groups by AHI (Apnea-hyponea index): normal group (AHI < 5), mild OSA group (5 ≤ AHI < 15), and moderate-severe OSA group (AHI ≥ 15). They were also divided into two groups according to minimum oxygen saturation: low group, Min-SpO2 < 88%; and high group, Min-SpO2 ≥ 88%. Results: Parameters of metabolic syndrome, including waist circumference, systolic and diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol showed significant differences among the AHI groups. Furthermore, HOMA-IR showed significant differences among the AHI groups. Those parameters, including metabolic syndrome and HOMA-IR, also showed differences between Min-SpO2 groups. Conclusions: In summary, this study helps confirm that AHI is associated with HOMA-IR in the general male population. Furthermore, the severity of AHI correlated with the parameters of metabolic syndrome. Therefore, AHI might be an indicator for evaluating both T2DM and metabolic syndrome, even in the general male population.

Effectiveness of Simulated Horseback Riding for Patients With Chronic Low Back Pain: A Randomized Controlled Trial.

CONTEXT: A simulated horseback riding (SHR) exercise is effective for improvement of pain and functional disability, but its comparative effectiveness with the other is unknown. OBJECTIVE: The authors aimed to demonstrate the effect of a SHR exercise in people with chronic low back pain. DESIGN: A randomized controlled trial. SETTINGS: Community and university campus. PARTICIPANTS: A total of 48 participants with chronic low back pain were divided into 2 groups, and SHR exercises (n = 24) or stabilization (STB) exercises (n = 24) were performed. INTERVENTIONS: The exercises were performed for 30 minutes, 2 days per week for 8 weeks. MAIN OUTCOME MEASURES: Numeric rating scale, functional disabilities (Oswestry disability index and Roland-Morris disability), and fear-avoidance beliefs questionnaire (FABQ) scores were measured at baseline and at 4 weeks, 8 weeks, and 6 months. RESULTS: A 2-way repeated analysis of variance identified that between-group comparisons showed significant differences in the FABQ related to work scale (F = 21.422; P = .01). There were no significant differences in the numeric rating scale (F = 1.696; P = .21), Oswestry disability index (F = 1.848; P = .20), Roland-Morris disability (F = 0.069; P = .80), and FABQ related to physical scale (F = 1.579; P = .24). In within-group comparisons, both groups presented significant differences in numeric rating scale (both SHR and STB after 4 wk), Oswestry disability index (both SHR and STB after 6 mo), and Roland-Morris disability (SHR after 6 mo and STB after 8 wk) compared with baseline values. In FABQ-related physical (SHR after 4 wk) and work scales (SHR after 6 mo), there were only significant differences in the SHR compared with baseline values. CONCLUSIONS: SHR exercise for 8 weeks had a greater effect than STB exercise for reducing work-related FABQ. The SHR exercise performed in a seated position could substantially decrease pain-related fear disability in young adults with chronic low back pain.

Combining Hyperpolarized Real-Time Metabolic Imaging and NMR Spectroscopy To Identify Metabolic Biomarkers in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that progresses without any symptom, and oftentimes, it is detected at an advanced stage. The lack of prior symptoms and effective treatments have created a knowledge gap in the management of this lethal disease. This issue can be addressed by developing novel noninvasive imaging-based biomarkers in PDAC. We explored in vivo hyperpolarized (HP) 13C MRS of pyruvate to lactate conversion and ex vivo 1H NMR spectroscopy in a panel of well-annotated patient-derived PDAC xenograft (PDXs) model and investigated the correlation between aberrant glycolytic metabolism and aggressiveness of the tumor. Real-time metabolic imaging data demonstrate the immediate intracellular conversion of HP 13C pyruvate to lactate after intravenous injection interrogating upregulated lactate dehydrogenase (LDH) activity in aggressive PDXs. Total ex vivo lactate measurement by 1H NMR spectroscopy showed a direct correlation with in vivo dynamic pyruvate-to-lactate conversion and demonstrated the potential of dynamic metabolic flux as a biomarker of total lactate concentration and aggressiveness of the tumor. Furthermore, the metabolite concentrations were very distinct among all four tumor types analyzed in this study. Overexpression of LDH-A and hypoxia-inducible factor (HIF-1α) plays a significant role in the conversion kinetics of HP pyruvate-to-lactate in tumors. Collectively, these data identified aberrant metabolic characteristics of pancreatic cancer PDXs and could potentially delineate metabolic targets for therapeutic intervention. Metabolic imaging with HP pyruvate and NMR metabolomics may enable identification and classification of aggressive subtypes of patient-derived xenografts. Translation of this real-time metabolic technique to the clinic may have the potential to improve the management of patients at high risk of developing pancreatic diseases.

Caveolin-1 enhances brain metastasis of non-small cell lung cancer, potentially in association with the epithelial-mesenchymal transition marker SNAIL.

BACKGROUND: Caveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investigated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM). METHODS: Cav-1 expression was investigated in a series of 102 BM samples and 49 paired primary NSCLC samples, as well as 162 unpaired primary NSCLC samples with (63 cases) or without (99 cases) metastasis to distant organs. Human lung cancer cell lines were used for in vitro functional analysis. RESULTS: High Cav-1 expression in tumor cells was observed in 52% (38/73) of squamous cell carcinomas (SQCs) and 33% (45/138) of non-SQCs. In SQC, high Cav-1 expression was increased after BM in both paired and unpaired samples of lung primary tumors and BM (53% vs. 84% in paired samples, P = 0.034; 52% vs. 78% in unpaired samples, P = 0.020). Although the difference in median overall survival in patients NSCLC was not statistically significant, high Cav-1 expression in tumor cells (P = 0.005, hazard ratio 1.715, 95% confidence index 1.175-2.502) was independent prognostic factors of overall survival on multivariate Cox regression analyses, in addition to the presence of BM and non-SQC type. In vitro assays revealed that Cav-1 knockdown inhibited the invasion and migration of lung cancer cells. Genetic modulation of Cav-1 was consistently associated with SNAIL up- and down-regulation. These findings were supported by increased SNAIL and Cav-1 expression in BM samples of SQC. CONCLUSIONS: Cav-1 plays an important role in the BM of NSCLC, especially in SQC. The mechanism may be linked to SNAIL regulation.

The Role Played by SLUG, an Epithelial-Mesenchymal Transition Factor, in Invasion and Therapeutic Resistance of Malignant Glioma.

In malignant gliomas, invasive phenotype and cancer stemness promoting resurgence of residual tumor cells render treatment very difficult. Hence, identification of epithelial-mesenchymal transition (EMT) factors associated with invasion and stemness of glioma cells is critical. To address the issue, we investigated several EMT factors in hypermotile U87MG and U251 cells, orthotopic mouse glioma model, and human glioma samples. Of several EMT markers, SLUG expression was notably increased at the invasive fronts of gliomas, both in mouse tumor grafts and human glioma samples. The biological role played by SLUG was investigated using a colony-forming assay after chemotherapy and irradiation, and by employing a neurosphere culture assay. The effect of SLUG on glioma progression was examined in our patient cohort and samples, and compared to large public data from the REMBRANDT and TCGA. Genetic upregulation of SLUG was associated with increased levels of stemness factors and enhanced resistance to radiation and temozolomide. In our cohort, patients exhibiting lower-level SLUG expression evidenced longer progression-free survival (P = 0.042). Also, in the REMBRANDT dataset, a group in which SLUG was downregulated exhibited a significant survival benefit (P < 0.001). Although paired glioblastoma samples from our patients did not show a significant increase of SLUG expression, increased mRNA levels of SLUG were found in recurrent glioblastoma from TCGA (P = 0.052), and in temozolomide-treated glioma cells and mouse tumor grafts. SLUG may contribute to glioma progression by controlling invasion at infiltrating margins, associated with increased stemness and therapeutic resistance.

Real-Time Interrogation of Aspirin Reactivity, Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy.

Hyperpolarized magnetic resonance spectroscopy enables quantitative, non-radioactive, real-time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single- and double-13 C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T1 ) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13 C-NMR spectroscopy. Hyperpolarized, double-labeled aspirin was well tolerated in mice and could be observed by both 13 C-MR imaging and 13 C-NMR spectroscopy in vivo.

Sporadic Early-Onset Diffuse Gastric Cancers Have High Frequency of Somatic CDH1 Alterations, but Low Frequency of Somatic RHOA Mutations Compared With Late-Onset Cancers.

BACKGROUND & AIMS: Early-onset gastric cancer, which develops in patients younger than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea. Patients with pathogenic germline mutations in CDH1, TP53, and ATM were excluded from the onset of this analysis, given our focus on somatic alterations. We used MutSig2CV to evaluate the significance of mutated genes. We recruited 29 additional early-onset Korean DGC samples and performed SNP6.0 array and targeted sequencing analyses of these 109 early-onset DGC samples (54.1% female, median age, 38 years). We compared the SNP6.0 array and targeted sequencing data of the 109 early-onset DGC samples with those from diffuse-type stomach tumor samples collected from 115 patients in Korea who were 46 years or older (late onset) at the time of diagnosis (controls; 29.6% female, median age, 67 years). We compared patient survival times among tumors from different subgroups and with different somatic mutations. We performed gene silencing of RHOA or CDH1 in DGC cells with small interfering RNAs for cell-based assays. RESULTS: We identified somatic mutations in the following genes in a significant number of early-onset DGCs: the cadherin 1 gene (CDH1), TP53, ARID1A, KRAS, PIK3CA, ERBB3, TGFBR1, FBXW7, RHOA, and MAP2K1. None of 109 early-onset DGC cases had pathogenic germline CDH1 mutations. A higher proportion of early-onset DGCs had mutations in CDH1 (42.2%) or TGFBR1 (7.3%) compared with control DGCs (17.4% and 0.9%, respectively) (P < .001 and P = .014 for CDH1 and TGFBR1, respectively). In contrast, a smaller proportion of early-onset DGCs contained mutations in RHOA (9.2%) than control DGCs (19.1%) (P = .033). Late-onset DGCs in The Cancer Genome Atlas also contained less frequent mutations in CDH1 and TGFBR1 and more frequent RHOA mutations, compared with early-onset DGCs. Early-onset DGCs from women contained significantly more mutations in CDH1 or TGFBR1 than early-onset DGCs from men. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times in patients with early-onset DGCs (hazard ratio, 3.4; 95% confidence interval, 1.5-7.7). RHOA activity was reduced by an R5W substitution-the RHOA mutation most frequently detected in early-onset DGCs. Silencing of CDH1, but not RHOA, increased migratory activity of DGC cells. CONCLUSIONS: In an integrative genomic analysis, we found higher proportions of early-onset DGCs to contain somatic mutations in CDH1 or TGFBR1 compared with late-onset DGCs. However, a smaller proportion of early-onset DGCs contained somatic mutations in RHOA than late-onset DGCs. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times of patients, which might account for the aggressive clinical course of early-onset gastric cancer. Female predominance in early-onset gastric cancer may be related to relatively high rates of somatic CDH1 and TGFBR1 mutations in this population.

Lower expression of endogenous intestinal alkaline phosphatase may predict worse prognosis in patients with Crohn's disease.

BACKGROUNDS: Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn's disease (CD). METHODS: A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. RESULTS: Median age of patients was 22.5 years (range, 15-49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months-54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). CONCLUSION: Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib by Using Hyperpolarized 13C-Pyruvate MR Spectroscopy and 18F-FDG PET/CT Imaging in a Mouse Model.

Purpose To assess in a mouse model whether early or late components of glucose metabolism, exemplified by fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and hyperpolarized carbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy, can serve as indicators of response in ovarian cancer to multityrosine kinase inhibitor pazopanib. Materials and Methods In this Animal Care and Use Committee approved study, 17 days after the injection of 2 × 106 human ovarian SKOV3 tumors cells into 14 female nude mice, treatment with vehicle or pazopanib (2.5 mg per mouse peroral every other day) was initiated. Longitudinal T2-weighted MR imaging, dynamic MR spectroscopy of hyperpolarized pyruvate, and 18F-FDG PET/computed tomographic (CT) imaging were performed before treatment, 2 days after treatment, and 2 weeks after treatment. Results Pazopanib inhibited ovarian tumor growth compared with control (0.054 g ± 0.041 vs 0.223 g ± 0.112, respectively; six mice were treated with pazopanib and seven were control mice; P < .05). Significantly higher pyruvate-to-lactate conversion (lactate/pyruvate + lactate ratio) was found 2 days after treatment with pazopanib than before treatment (0.46 ± 0.07 vs 0.31 ± 0.14, respectively; P < .05; six tumors after treatment, seven tumors before treatment). This was not observed with the control group or with 18F-FDG PET/CT imaging. Conclusion The findings suggest that hyperpolarized 13C-pyruvate MR spectroscopy may serve as an early indicator of response to tyrosine kinase (angiogenesis) inhibitors such as pazopanib in ovarian cancer even when 18F-FDG PET/CT does not indicate a response. © RSNA, 2017 Online supplemental material is available for this article.