Detection of atmospheric radon concentration anomalies and their potential for earthquake prediction using Random Forest analysis.

Various anomalies occurring before earthquakes are currently being studied to predict seismic events, with one of them being the radioactive element radon (222Rn). Radon concentrations in the soil, water, and atmosphere fluctuate in response to crustal movement. Recent research has statistically detected anomalies by analyzing the fluctuations in radon concentrations before earthquakes and conducting quantitative evaluations of radon. However, the method used to determine the parameters in the analysis was problematic. Therefore, in this study, we compared observed atmospheric radon concentration data with predicted values based on typical annual patterns using Random Forest analysis. We conducted a more objective analysis by employing this method and statistically determining anomalies using thresholds. This analysis was conducted using atmospheric radon concentration observation data obtained at Kobe Pharmaceutical University (KPU) before the 1995 Kobe Earthquake, and ionization currents emitted when radon decays were obtained at Fukushima Medical University (FMU) before the 2011 Tohoku-oki Earthquake. Consequently, before the major earthquakes occurred at both locations, the difference between the predicted and observed values exceeded the standard deviation by a factor of three. These results indicate the potential of Random Forest analysis to identify anomalies in atmospheric radon concentrations before earthquakes occur.

Quantitative Analysis of Nitrogen by Atom Probe Tomography Using Stoichiometric γ'-Fe4N Consisting of 15N Isotope.

The nitrogen deficiency in steels measured by atom probe tomography (APT) is considered to arise from the obscurement of singly charged dimer nitrogen ions (N2+) by the iron-dominant peak (56Fe2+) at 28 Da. To verify this by quantifying the amount of N2+ ions, γ'-Fe4N consisting of the 15N isotope was prepared on iron substrates by plasma nitriding using a nitrogen isotopic gas (15N2). Although considerable amounts of 15N2+ were observed at 30 Da without overlap with any iron peak, the observed nitrogen concentrations of γ'-Fe4N were clearly lower than the stoichiometric composition (19­20 at%), using both pulsed voltage and pulsed laser atom probes. The origin of the missing nitrogen, excluding nitrogen obscured by other ion species, was predicted to be the occurrence of neutral nitrogen or nitrogen gas molecules in field evaporation. The generation rate of iron nitride ions (FeN2+) for 15N was significantly lower than that for 14N in γ'-Fe4N, which affected the amount of the missing nitrogen. The isotope effect suggests that the isotopic ratio cannot always be determined from only one ion species among the multiple species observed in the APT analysis. We discuss the mechanism of the isotope effect in FeN2+ formation by field evaporation.

Preseismic atmospheric radon anomaly associated with 2018 Northern Osaka earthquake.

Despite the challenges in identifying earthquake precursors in intraplate (inland) earthquakes, various hydrological and geochemical measurements have been conducted to establish a possible link to seismic activities. Anomalous increases in radon (222Rn) concentration in soil, groundwater, and atmosphere have been reported prior to large earthquakes. Although the radon concentration in the atmosphere is lower than that in groundwater and soils, a recent statistical analysis has suggested that the average atmospheric concentration over a relatively wide area reflects crustal deformation. However, no study has sought to determine the underlying physico-chemical relationships between crustal deformation and anomalous atmospheric radon concentrations. Here, we show a significant decrease in the atmospheric radon concentration temporally linked to the seismic quiescence before the 2018 Northern Osaka earthquake occurring at a hidden fault with complex rupture dynamics. During seismic quiescence, deep-seated sedimentary layers in Osaka Basin, which might be the main sources of radon, become less damaged and fractured. The reduction in damage leads to a decrease in radon exhalation to the atmosphere near the fault, causing the preseismic radon decrease in the atmosphere. Herein, we highlight the necessity of continuous monitoring of the atmospheric radon concentration, combined with statistical anomaly detection method, to evaluate future seismic risks.

Predominant surface property of an anodized titanium that enhances the cell response.

The aim of this study is to evaluate the predominant material property that enhances the biocompatibility of an anodized titanium (Ti) implant. A Ti surface was anodized in an H3PO4 electrolyte with various voltages. Then, the cell responses involving attachment, proliferation, and differentiation were evaluated. Anodization using various voltages formed TiO2 layers with various surface morphologies. All the anodized surfaces showed enhanced cell responses; however, the performance differences depending on the surface morphologies were minimal. In addition, enhanced cell responses were not observed on the thermally oxidized Ti surface, although a TiO2 layer was formed; therefore, the beneficial effect was derived from the TiO2 layer fabricated via anodization. Based on these findings, the topmost surface structure of the TiO2 layer predominantly influenced the cell behaviors because this property governed the important surface functions, such as hydrophilicity.

Promotion of bone regeneration on titanium implants through a chemical treatment process using calcium phosphate slurry: Microscopic analysis, cellular response, and animal experiment.

The present study provides scientific evidence that a new chemical treatment process using calcium phosphate slurry promotes bone regeneration on titanium (Ti) implants. The material's surface modified by the treatment was analyzed using microscopic observation and the bone regeneration efficacy was evaluated both in vitro and in vivo. Formation of a thin hydroxyapatite layer with a thickness of about 50 nm and an increase of surface roughness were confirmed by microscopic observations. Histological evaluation of rat femora implanted with the specimens showed that the areas of the specimens directly attached to bone tissue were significantly more extensive than those implanted with control Ti at 2 and 8 weeks. Likewise, on the treated Ti, ALP activity, osteopontin, osteocalcin, and calcium contents of rat bone marrow stromal cells were significantly higher than on the control Ti. Furthermore, reverse transcription polymerase chain reaction showed greater expression of messenger ribonucleic acid encoding Cbfa1 and collagen type1 on the treated Ti at 2 weeks. Based on these results, we concluded that the new process was effective to enhance the osteoconductivity of Ti. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2716-2724, 2018.

Microstructures, mechanical properties and cytotoxicity of low cost beta Ti-Mn alloys for biomedical applications.

The microstructures, mechanical properties and biocompatibility of low cost ß-type Ti-(6-18)Mn alloys were investigated after solution treatment. Ti-9 Mn exhibits the best combination of tensile strength and elongation among the fabricated alloys, and its performance is comparable to or superior to those of Ti-6Al-4V ELI (Ti-64 ELI) in terms of every parameter evaluated. A hardness of 338 HV, a Young's modulus of 94 GPa, a 0.2% proof stress of 1023 MPa, an ultimate tensile strength of 1048 MPa and elongation of 19% were obtained for Ti-9 Mn. Furthermore, the cell viability and metallic ion release ratios are comparable to those of commercially pure titanium, making this alloy promising for biomedical applications. The Young's modulus is also lower than that of Ti-64 ELI (110 GPa), which can possibly reduce the stress shielding effect in implanted patients. STATEMENT OF SIGNIFICANCE: This study evaluates mechanical and biological performance of low cost solution treated ß-type Ti-(6, 9, 13 and 18 mass%)Mn alloys. It includes alloys containing a Mn content range higher than most previously published works (which is around or lower than 8 mass%). Furthermore, the effects of the ω phase and the ß phase stability of the alloys over some mechanical properties and microstructures are discussed. Ion release behavior under simulated body fluids and cell viability are also evaluated. For the case of the Ti-9 Mn, a mechanical and biological performance that is comparable to or superior than that of the widely used Ti-6Al-4V ELI and commercially pure Ti was observed.

Possible involvement of ΔNp63 downregulation in the invasion and metastasis of oral squamous cell carcinoma via induction of a mesenchymal phenotype.

Epithelial-to-mesenchymal transition (EMT), an essential developmental program, is involved in tumor progression. ΔNp63, a homolog of p53, is associated with the EMT program, but the detailed mechanism remains to be elucidated. In this study, we investigated the role of ΔNp63 in EMT during progression of oral squamous cell carcinoma (OSCC). Five OSCC cell lines and specimens from 78 patients with OSCC were used. The expressions of ΔNp63, p63α, p63ß and epithelial markers (cytokeratins 5 and 14) was detected in the OSCC cells, but not in SQUU-B cells (high metastatic potential). E-cadherin was expressed in all OSCC cells. Mesenchymal markers were strongly expressed in the SQUU-B cells. Knockdown of endogenous ΔNp63 in HSC-2 cells induced morphological changes to the spindle shape, decreased the expression of epithelial markers, increased the expression of mesenchymal markers, increased migration and reduced proliferation. By contrast, SQUU-B cells overexpressing ΔNp63ß showed changed their morphology from stromal cell-like to epithelial cells. However, E-cadherin expression was not affected by ΔNp63 knockdown or overexpression. Immunohistochemical staining revealed that cancer cells expressing vimentin were found at the invasive front in the OSCC specimens. The intensity of ΔNp63 expression was also decreased in these cells. Interestingly, the vimentin positivity or decreased intensity of ΔNp63 was positively associated with metastases and poor prognosis in the OSCC patients. These results indicated that ΔNp63 downregulation in cancer cells induces a mesenchymal phenotype that is related to tumor progression of OSCC.

Response of osteoblast-like MC3T3-E1 cells on bioactive titanium fabricated by a chemical treatment process using a calcium-phosphate slurry.

We recently developed a chemical treatment process using a calcium-phosphate slurry for fabricating new layers consisting of hydroxyapatite and titanium dioxide (TiO2) on titanium (Ti) substrate. In this study, the response of osteoblast-like MC3T3-E1 cells on Ti substrate treated with a calcium-phosphate slurry was investigated to elucidate its behavior in a biological environment. The cellular adhesiveness and proliferation capacity did not differ significantly between the treated and untreated Ti substrates, suggesting that the slurry treatment did not cause cytotoxicity. The slurry treatment did not affect the increase in alkaline phosphatase activity after the induction of cell differentiation, whereas it was found to be significantly advantageous for the calcification behavior on the slurry-treated Ti substrate. In consequence, the hard-tissue compatibility of Ti is expected to be improved by the chemical treatment process using a calcium-phosphate slurry.

Immunohistochemical location of the p75 neurotrophin receptor (p75NTR) in oral leukoplakia and oral squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that the p75 neurotrophin receptor (p75NTR) is a useful marker of keratinocyte stem cells. Although the stem cell markers of original normal tissue have been used to identify cancer stem cells in a variety of cancers, the expression and function of p75NTR have been poorly understood in oral squamous cell carcinoma (OSCC). The objective of this study is, thus, to examine p75NTR expression immunohistochemically in oral leukoplakia (OL), the most frequent precancerous lesion, and OSCC, and to reveal the usefulness of p75NTR as a marker for undifferentiated cancer cells and a novel prognostic factor for OSCC patients. METHODS: In this study immunohistochemical expression of p75NTR, Ki-67, cytokeratin (CK) 5, and CK14 was examined in 112 cases of OL and 81 of OSCC. The labeling indices (LIs) of p75NTR and Ki-67 were calculated, and the association of these LIs with histopathologic characteristics was then evaluated. RESULTS: In the normal oral epithelium and OL, p75NTR was expressed only in the basal layer, and its LI was invariant, irrespective of the extent of epithelial dysplasia. In OSCC, however, p75NTR-LI was significantly increased in association with upgrading of histologic grade and mode of tumor invasion. Furthermore, the prognosis of the high p75NTR-LI group (LI ≥ 53.1%) was poorer than that of the low p75NTR-LI group (LI < 53.1%). CONCLUSIONS: These results suggest that p75NTR is expressed in undifferentiated cell populations in OL and OSCC. Furthermore, p75NTR is possibly involved in invasion and poor prognosis in OSCC.

Association of cytokeratin 17 expression with differentiation in oral squamous cell carcinoma.

PURPOSE: The aim of this study was to confirm the expression profile of cytokeratin (CK)17 in comparison with that of CK13 in oral squamous cell carcinoma (OSCC) and leukoplakia and to clarify an association of CK17 with the OSCC differentiation. MATERIALS: The expression of CK17 and CK13 was immunohistochemically examined in 105 patients with OSCC and 108 patients with leukoplakia. A correlation of CK expression with clinicopathological variables was carried out. The over-expression levels of CK17 mRNA were analyzed by real-time RT-PCR in 5 OSCC cell lines (HSC-2, HSC-3, SAS, SQUU-A, SQUU-B). RESULTS: CK17 and CK13 were detected in 101 (96.2 %) and three (2.9 %) of the 105 OSCCs, respectively. CK17 was significantly expressed in well-differentiated OSCC compared to moderately/poorly differentiated OSCC (p < 0.01). As detected in 19 of the 34 dysplastic leukoplakias (55.9 %) and 36 of the 74 hyperplastic leukoplakias (48.6 %), CK17 was significantly expressed in dysplastic leukoplakias (p < 0.01). As detected in 11 of the 34 dysplastic (32.4 %) and 52 of the 74 hyperplastic leukoplakias (70.3 %), CK13 was significantly expressed in hyperplastic leukoplakias (p < 0.01). The relative expression of CK17 mRNA in HSC-2 was significantly higher than in HSC-3 and SAS (p < 0.05). Moreover, the relative expression of CK17 mRNA in SQUU-A was significantly higher than in SQUU-B (p < 0.05). CONCLUSION: CK17 expression could be associated with the differentiation and the malignancy of OSCC. A combination pattern of CK17/CK13 might be a suitable marker of malignant transformation.

Clinical significance of combined assessment of the maximum standardized uptake value of F-18 FDG PET with nodal size in the diagnosis of cervical lymph node metastasis of oral squamous cell carcinoma.

RATIONALE AND OBJECTIVES: This study aimed to elucidate the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for nodal involvement in oral squamous cell carcinoma (OSCC), and to reveal clinically useful factors to distinguish between true-positive (TP) and false-positive (FP) nodes. MATERIALS AND METHODS: Thirty-eight patients with primary OSCC who underwent neck dissection were assessed. The diagnostic accuracy of F-18 FDG PET/CT was evaluated, and then compared with that of CT/ultrasonography (US). Furthermore, the association of the maximum standardized uptake value (SUVmax) and nodal size with the histopathologic findings was examined. RESULTS: Sensitivity and specificity using F-18 FDG PET/CT were 77.1% and 97.3%, and those using CT/US were 72.9% and 98.9%, respectively. The SUVmax of TP nodes was significantly higher than that of FP nodes. Nodes with SUVmax >4.5 were pathologically confirmed as metastasis. Nodes with SUVmax ≤4.5 were further discriminated between TP and FP nodes by using the long axis diameters or the ratios of long to short axis diameter as clinical parameters. Positive correlation between the SUVmax and the short-axis diameter was found in TP nodes. The AUC obtained from the ROC curves of the SUVmax alone (AUC, 0.804) was improved by combination with the long-axis diameter (AUC, 0.867) or the short-axis diameter (AUC, 0.846), although no significant difference was found. CONCLUSIONS: These results indicated that F-18 FDG PET/CT was potentially useful in diagnosing preoperative nodal state. Furthermore, combined assessment of SUVmax with nodal size could be significant in the identification of metastatic lymph nodes in OSCC patients.

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma.

This study examined immunohistochemical expression of ΔNp63, a keratinocyte stem cell marker, in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) and then to elucidate usefulness of ΔNp63 as a marker for diagnosis and prognosis. One-hundred and twelve cases of OL and 81 cases of OSCC were analyzed by immunohistochemical staining for ΔNp63, Ki-67, and cytokeratin 14. These labeling indices (LIs) were calculated, and the association of these LIs with clinicopathologic characteristics in the OL and OSCC was evaluated. In the OL, these LIs increased significantly according to the severity of epithelial dysplasia (p<0.0001). ΔNp63-LI in the OL with malignant transformation was significantly higher than that in the OL without (49.3 vs. 34.2%; p<0.01). In the OSCC, the LIs increased significantly in association with the histologic grade (p<0.0001). A significant difference between the high and low ΔNp63-LI groups was found in the incidence of cervical lymph node and distant metastasis (p<0.05). The prognosis of the high ΔNp63-LI (mean value >73.8%) group is poorer than that of the low ΔNp63-LI (mean value ≤73.8%) group (p<0.05). These results suggested that increased ΔNp63 expression is involved in malignant transformation in epithelial dysplasia and poor prognosis in OSCC.