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Background: Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. Data regarding the predictive significance of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Thus, this study analyzed ctDNA during osimertinib administration as a second-line or greater setting to examine the association between EGFR mutation levels and clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC).Methods: Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were enrolled. Plasma samples were obtained at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed using digital polymerase chain reaction.Results: The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib treatment than at pretreatment and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. There was no statistically significant difference in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD.T790M detection at PD after osimertinib initiation was a significant independent prognostic factor for predicting worse prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely associated with shorter survival after osimertinib initiation.Conclusion: Molecular testing based on ctDNA is useful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment.

Novel amorphous iron hydrides (AIHs) are synthesized for the first time under ambient conditions by employing novel “quiescent reaction”, without stirring for mixing solutions, during a conventional aqueous reduction-precipitation process. The kind and morphology of AIHs are dependent on the processing condition, where two types are found, with one form consisting of a tangle of uniform nanowires and the other being granular in nature. Both AIHs undergo transformation to crystalline α-Fe by heat treatment at 600 °C. The nanowire AIH exhibits the hydrogen content of 0.10 wt%, while the granular AIH of 0.22 wt%. Their magnetic and thermal properties are accordingly different, and the non-diffusive hydrogen contributes to stability of AIHs. It is strongly suggested that, by use of quiescent reaction, iron-hydrogen clusters are formed and preserved at an early stage of precipitation reaction, and subsequently aggregated into novel AIHs, preventing α-Fe crystallization. Hence, the AIHs would be categorized as metastable hydrides stabilized with iron-hydrogen clusters. In addition, newly discovered quiescent reaction in aqueous solution, from which unprecedented AIHs are derived, sheds new light on fundamental and essential aqueous reaction.

Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody-positive and age at onset ≥60 years are poor prognosis factors in polymyositis (PM) and dermatomyositis (DM) associated with interstitial lung disease (ILD) among Japanese patients. However, the influence of age on the clinical features of anti-MDA5 autoantibody-positive patients with DM remains unclear.We retrospectively examined 40 patients with DM and anti-MDA5 autoantibodies according to age. We compared patients aged60 and ≥60 years with respect to clinical features including laboratory test findings, high-resolution lung computed tomography data, treatment content, and complications such as infections and prognosis. We also examined clinical features between surviving and deceased patients in the older patient group.Of 40 enrolled patients, 13 were classified as old and 27 as young. Older patients had significantly fewer clinical symptoms including arthralgia/arthritis (Clinical features and mortality of anti-MDA5 autoantibody-positive DM patients were influenced by age. Patients aged ≥60 years had a worse prognosis, and combination immunosuppressive therapy was often ineffective for RP-ILD in older patients.

Dermatomyositis (DM) with autoantibody against melanoma differentiation-associated gene-5 (MDA5) is characterized by elevated risk of rapidly progressive interstitial lung disease (RP-ILD) with a potentially fatal course. Pneumomediastinum (PNM) is a common pulmonary manifestation which accompanies ILD. However, the clinical features of the patients with anti-MDA5 antibody-positive DM who develop PNM remain unclear.We retrospectively examined 31 patients with DM having anti-MDA5 antibody and compared the clinical features between patients with PNM (PMN(+)) (n = 11) and those without (PNM(-) (n = 20). In addition, we evaluated the treatment-related prognoses in PNM(+) group.CT score (total ground-glass opacity (GGO) score, P = 0.02; total fibrosis score, P = 0.02) before treatment, and mortality (P = 0.04) were significantly higher in PNM(+) group. The cumulative survival rate as assessed by Kaplan-Meier method was significantly lower for the PNM(+) group (P = 0.02). Among 11 PMN(+) patients, 9 patients (9/11, 81.8%) underwent intensive immunosuppression therapy for RP-ILD, and 5 patients (5/11, 45.5%) did not respond to it and died from the respiratory failure. At the time of diagnosis of PNM, nonsurvivors had worse liver function (ALT, P = 0.03; LDH, P = 0.01), worse respiratory status (A-aDO2, P = 0.01), and worse CT score (total GGO score, P 0.01).A subgroup of patients with DM having anti-MDA5 antibody complicated by PNM as well as RP-ILD did respond to intensive immunosuppression therapy. Initial aggressive immunosuppressive therapy should be considered for these patients.Key Points• This study clearly demonstrate the presence of PNM was associated with elevated risk of death due to respiratory failure from RP-ILD among patients with DM having circulating anti-MDA5-antibody.•This study demonstrate evaluation of CT image may be helpful to find patients with better response to the intense immunosuppression therapy for the patients with DM having circulating anti-MDA5-antibody and PNM.

Anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) occurs in elderly people, and patients with anti-myeloperoxidase autoantibodies (MPO-ANCA)-positive AAV are often complicated with interstitial lung disease (ILD). This study aimed to evaluate the age-related clinical features of elderly patients with MPO-ANCA-positive AAV-ILD. This study retrospectively investigated 63 patients with MPO-ANCA-positive AAV-ILD, all of whom were 65 years or older at diagnosis. Clinical characteristics, causes of death and survival rates among three groups stratified by age (65–74 years, n = 29; 75–79 years, n = 18; over 80 years, n = 16) were compared. This study also examined the association with severe infections in these patients. Among the three age groups, there were significant differences in sex (P = 0.032), serum Krebs von den Lungen-6 (P

Background Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies have been identified as myositis-specific autoantibodies that are often associated with clinically amyopathic dermatomyositis (CADM) and a poor prognosis due to rapidly progressive interstitial lung disease (RP-ILD) in East Asian patients. Besides anti-MDA5 autoantibodies, patients with CADM may have myositis-associated autoantibodies (MAAs), which characterize other connective tissue diseases such as rheumatoid arthritis and Sjogren's syndrome. However, the clinical significance of the coexistence of anti-MDA5 autoantibodies and MAAs in patients with CADM remains unclear. Methods We retrospectively analyzed 24 patients with CADM who had anti-MDA5 autoantibodies. Their clinical phenotypes including laboratory test results, high-resolution lung computed tomography data, response to therapy, and prognosis were compared between those who were positive and negative for MAAs, such as antinuclear antibody (ANA), anti-cyclic citrullinated peptide (CCP), anti-SSA, and anti-SSB antibodies. Results Among 24 patients, 9 (37.5%) additionally had at least one of the MAAs examined in this study: 1 patient was positive for ANA, 5 for anti-CCP, 5 for either anti-SSA or anti-SSB, 1 for anti-cardiolipin, and 1 for anti-Scl-70. Although all anti-MDA5-positive patients with CADM had ILD, the MAA-positive patients showed a lower risk of developing RP-ILD (p = 0.03), a more favorable response to combination therapy of corticosteroids and immunosuppressive agents, and a lower mortality rate than patients with no MAAs (p = 0.03). Conclusions Our data suggest that anti-MDA5-positive patients with CADM who also have MAAs have a better prognosis than those without MAAs; thus, anti-MDA5 autoantibodies by themselves may not be strong predictors of worse clinical outcomes in patients with CADM. Coexistent MAAs could be biomarkers for a favorable prognosis in anti-MDA5-positive patients with CADM.

This study evaluated the effect of zirconia framework design on fracture load of implant-supported zirconia-based prostheses after thermal cycling and mechanical loading. Three different zirconia framework designs were investigated: uniform-thickness (UNI), anatomic (ANA), and supported anatomic (SUP) designs. Each framework was layered with feldspathic porcelain (ZAC group) or indirect composite material (ZIC group). The specimens then underwent fracture load testing after thermal cycling and cyclic loading. In the ZAC group, mean fracture load was significantly lower for UNI design specimens than for the other framework designs. In the ZIC group, there was no significant difference in mean fracture load between ANA design specimens and either UNI or SUP design specimens. To improve fracture resistance of implant-supported zirconia-based prostheses after artificial aging, uniformly thick layering material and appropriate lingual support with zirconia frameworks should be provided.

Objectives To evaluate the effects of framework design and layering material on the fracture strength of implant-supported zirconia-based molar crowns. Material and methods Sixty-six titanium abutments (GingiHue Post) were tightened onto dental implants (Implant Lab Analog). These abutment-implant complexes were randomly divided into three groups (n = 22) according to the design of the zirconia framework (Katana), namely, uniform-thickness (UNI), anatomic (ANA), and supported anatomic (SUP) designs. The specimens in each design group were further divided into two subgroups (n = 11): zirconia-based all-ceramic restorations (ZAC group) and zirconia-based restorations with an indirect composite material (Estenia C&B) layered onto the zirconia framework (ZIC group). All crowns were cemented on implant abutments, after which the specimens were tested for fracture resistance. The data were analyzed with the Kruskal-Wallis test and the Mann-Whitney U-test with the Bonferroni correction (α = 0.05). Results The following mean fracture strength values (kN) were obtained in UNI design, ANA design, and SUP design, respectively: Group ZAC, 3.78, 6.01, 6.50 and Group ZIC, 3.15, 5.65, 5.83. In both the ZAC and ZIC groups, fracture strength was significantly lower for the UNI design than the other two framework designs (P = 0.001). Fracture strength did not significantly differ (P > 0.420) between identical framework designs in the ZAC and ZIC groups. Conclusions A framework design with standardized layer thickness and adequate support of veneer by zirconia frameworks, as in the ANA and SUP designs, increases fracture resistance in implant-supported zirconia-based restorations under conditions of chewing attrition. Indirect composite material and porcelain perform similarly as layering materials on zirconia frameworks.

Objectives The objective of this in vitro study was to investigate fracture loads of screw-retained zirconia-based molar restorations (hybrid abutment crown) fabricated with different restorative materials and designs. Material and methods Forty-four screw-retained zirconia-based molar restorations were fabricated on dental implants and divided into four groups (n = 11): porcelain-layered zirconia-based restorations (PLZ), indirect composite-layered zirconia-based restorations (ILZ), metal–ceramic restorations (MC), and monolithic zirconia restorations (MONO). The zirconia-based restorations in the PLZ, ILZ, and MONO groups were adhesively bonded on implant abutments with a dual-polymerized resin material. All restorations were tightened on implant bodies with titanium screws and were tested for fracture resistance. The Kruskal–Wallis test and Steel–Dwass test were used to evaluate differences in fracture loads (α = 0.05). Results As compared with the other groups, the MONO specimens had a significantly higher mean fracture resistance (7.54 kN); no significant differences were found among the PLZ (1.96 kN), ILZ (1.80 kN), and MC (1.45 kN) groups (P > 0.05). For the PLZ, ILZ, and MC groups, all specimens fractured within the layering materials. In contrast, the fracture mode for the MONO group was complete fracture of the restorations. Conclusions All restorations withstood the masticatory forces. Fracture loads were significantly higher for screw-retained implant-supported monolithic zirconia restorations than for screw-retained bilayered restorations. For the screw-retained bilayered zirconia-based restorations, the fracture resistance of ILZ restorations was comparable to that of PLZ restorations and MC restorations.

To evaluate shear bond strength of a gingiva-colored indirect composite to three implant framework materials, before and after thermocycling, and verify the effect of surface pre-treatment for each framework.Commercially pure titanium (CP-Ti), American Dental Association (ADA) type 4 casting gold alloy (Type IV) and zirconia ceramics (Zirconia) were assessed. For each substrate, 96 disks were divided into six groups and primed with one of the following primers: Alloy Primer (ALP), Clearfil Photo Bond (CPB), Clearfil Photo Bond with Clearfil Porcelain Bond Activator (CPB+Activator), Estenia Opaque Primer (EOP), Metal Link (MLP) and V-Primer (VPR). The specimens were then bonded to a gingiva-colored indirect composite (Ceramage Concentrate GUM-D). Shear bond strengths were measured at 0 and 20 000 thermocycles and data were analyzed with the Steel-Dwass test and Mann-Whitney U-test.Shear bond strengths were significantly lower after thermocycling, with the exception of Type IV specimens primed with CPB (p = 0.092) or MLP (p = 0.112). For CP-Ti and Zirconia specimens, priming with CPB or CPB+Activator produced significantly higher bond strengths at 0 and 20 000 thermocycles, as compared with the other groups. For Type IV specimens, priming with ALP or MLP produced higher bond strengths at 0 and 20 000 thermocycles.Shear bond strength of a gingiva-colored indirect composite to CP-Ti, gold alloy and zirconia ceramics was generally lower after thermocycling. Application of a hydrophobic phosphate monomer and polymerization initiator was effective in maintaining bond strength of CP-Ti and zirconia ceramics. Combined use of a thione monomer and phosphoric monomer enhanced the durable bond strength of gold alloy.

The present study evaluated the effect of various surface treatments for zirconia ceramics on shear bond strength between an indirect composite material and zirconia ceramics. In addition, we investigated the durability of shear bond strength by using artificial aging (20,000 thermocycles). A total of 176 Katana zirconia disks were randomly divided into eight groups according to surface treatment, as follows: group CON (as-milled); group GRD (wet-ground with 600-grit silicon carbide abrasive paper); groups 0.05, 0.1, 0.2, 0.4, and 0.6 MPa (airborne-particle abrasion at 0.05, 0.1, 0.2, 0.4, and 0.6 MPa, respectively); and group HF (9.5% hydrofluoric acid etching). Shear bond strength was measured at 0 thermocycles in half the specimens after 24-h immersion. The remaining specimens were subjected to 20,000 thermocycles before shear bond strength testing. Among the eight groups, the 0.1, 0.2, 0.4, and 0.6 MPa airborne-particle abraded groups had significantly higher bond strengths before and after thermocycling. The Mann-Whitney U-test revealed no significant difference in shear bond strength between 0 and 20,000 thermocycles, except in the 0.2 MPa group (P = 0.013). From the results of this study, use of airborne-particle abrasion at a pressure of 0.1 MPa or higher increases initial and durable bond strength between an indirect composite material and zirconia ceramics.

This study aims to evaluate the effect of both feldspathic porcelain coating of zirconia frameworks and priming agents on shear bond strength between an indirect composite material and zirconia frameworks. A total of 462 airborne-particle-abraded zirconia disks were divided into three groups: untreated disks (ZR–AB), airborne-particle-abraded zirconia disks coated with feldspathic porcelain, (ZR–PO–AB), and hydrofluoric acid-etched zirconia disks coated with feldspathic porcelain (ZR–PO–HF). Indirect composite (Estenia C&B) was bonded to zirconia specimens with no (CON) or one of four priming agents—Clearfil Photo Bond (CPB), Clearfil Photo Bond with Clearfil Porcelain Bond Activator (CPB + activator), Estenia Opaque primer, or Porcelain Liner M Liquid B (PLB)—with or without an opaque material (Estenia C&B Opaque). All specimens were tested for shear bond strength before and after 20,000 thermocycles. The Steel–Dwass test and Mann–Whitney U test were used to compare shear bond strength. In ZR–AB specimens, the initial bond strength of the CPB and CPB + Activator groups was significantly higher as compared with the other three groups (P

The purpose of the present study was to evaluate the durability of bond strength between an indirect composite material and zirconia ceramics after thermocycling (100 000 cycles) and to assess the effect of various priming agents for zirconia surface treatments.A CAD/CAM system (Katana, Noritake Dental Supply) was used to fabricate 96 zirconia disks as a bonding substrate. The specimens were randomly divided into six groups (n = 16) and treated with one of the following acidic priming agents: Alloy Primer (ALP, Kuraray), Clearfil Ceramic Primer (CCP, Kuraray), Clearfil Photo Bond (CPB, Kuraray), Clearfil Photo Bond with Clearfil Porcelain Bond Activator (CPB + Activator, Kuraray), Estenia Opaque Primer (EOP, Kuraray) and Porcelain Liner M Liquid A (PLA, Sun Medical). The specimens were bonded with an indirect composite material (Estenia CB Dentin, Kuraray). Shear bond strengths were tested before and after 100 000 thermocycles and the data were analyzed by using the Steel-Dwass test and Mann-Whitney U-test.After 100 000 thermocycles, the PLA group showed the lowest bond strength (p = 0.010), whereas the CPB + Activator (23.9 MPa; p0.014) and CPB (22.7 MPa; p0.028) groups had significantly higher bond strengths than the other groups. The Mann-Whitney U-test revealed that bond strengths did not significantly decrease after thermocycling, except for specimens in the PLA (p = 0.038) and CCP (p = 0.028) groups.Application of a combination of hydrophobic phosphate monomer (MDP) and initiator results in a durable long-term bond between Katana zirconia and Estenia CB composite material.

Objectives This study evaluated the fracture resistance of single-tooth implant-supported zirconia-based indirect composite-layered molar restorations. Material and methods Forty-four titanium abutments (GingiHue Post) were placed on dental implants (Osseotite Implant). Standardized single-tooth cement-retained implant-supported mandibular molar restorations were fabricated for each of four test groups (n = 11) as follows: porcelain-fused-to-metal crowns (PFM), zirconia-based all-ceramic crowns (ZAC), zirconia-based indirect composite-layered crowns primed with Estenia Opaque Primer for zirconia frameworks (ZIC-E), and zirconia-based indirect composite-layered crowns (ZIC). The crowns were luted with a glass-ionomer cement (Ketac Cem Easymix). Fracture resistance (N) was determined by force application of a perpendicular load to the crowns with a universal testing machine. One-way analysis of variance (ANOVA) and the Tukey's HSD test were used to assess differences in fracture resistance values (α = 0.05). Results Mean fracture resistances (SD) were 3.09 (0.22) kN, 3.11 (0.34) kN, 2.84 (0.21) kN, and 2.50 (0.36) kN for the PFM, ZAC, ZIC-E, and ZIC groups, respectively. Fracture resistance in the ZIC specimens was significantly lower (P

The study goal was to establish a standard industrial procedure for the measurement of thermal effusivity by a thermal microscope (TM), using a periodic heating method with a thermoreflectance (TR) technique. To accomplish this goal, a working group was organized that included four research institutes. Each institute followed the same procedure: a molybdenum (Mo) film was sputtered on the surface of Pyrex, yttria-stabilized zirconia (YSZ), alumina (Al2O3), Germanium (Ge), and silicon (Si) samples, and then the phase lag of the laser intensity modulation was measured by the resultant surface temperature. A procedure was proposed to calibrate the effect of 3D heat flow, based on the analytical solution of the heat conduction equation, and thermal effusivity was measured. The derived values show good agreement with literature values. As a result, the TM calibration procedure can be recommended for practical use in measuring the thermal effusivity in a small region of the materials.

We studied the structural and photoluminescence (PL) characteristics of InAs quantum dots (QDs) grown on nitrogen (N) δ-doped GaAs(001). The emission wavelength for low-density N-δ doping exhibited a blueshift with respect to that for undoped GaAs and was redshifted with increasing N-sheet density. This behavior corresponded to the variation in the In composition of the QDs. N-δ doping has two opposite and competing effects on the incorporation of Ga atoms from the underlying layer into the QDs during the QD growth. One is the enhancement of Ga incorporation induced by the lattice strain, which is due to the smaller radius of N atoms. The other is an effect blocking for Ga incorporation, which is due to the large bonding energy of Ga-N or In-N. At a low N-sheet density, the lattice-strain effect was dominant, while the blocking effect became larger with increasing N-sheet density. Therefore, the incorporation of Ga from the underlying layer depended on the N-sheet density. Since the In-Ga intermixing betw...

γ-Titanium aluminide (TiAl) is well known to have excellent potential for high temperature structural applications. The self propagating high-temperature synthesis (SHS) process has been expected to provide new fabrication routes for intermetallic materials. In recent years, considerable research on the reactive sintering process has been carried out for near-net shaping of intermetallics. In this study, we present a new fabrication route based on a combination of pseudoHIP and SHS to produce TiAl intermetallic compounds with the controlled microstructure and improved deformability. Reactive bonding of TiAl compounds also can be achieved by the SHS process, in particular, by use of pseudoHIP-SHS. It should be emphasized that the combination of pseudoHIP and SHS is effective in utilizing the heat release and transient liquid phase involved in SHS to obtain near-net shape products of TiAl intermetallic compounds with a high material density.

Dendritic cells (DCs) are antigen-presenting cells that initiate and modulate immune responses, including tumor immunity. In this study we examined, immunohistochemically, the distribution of DC subsets in the primary tumor, adjacent tissue and regional lymph nodes (RLNs) of patients with oral squamous cell carcinoma (OSCC). The numbers of S100+ and CD1a+ DCs in tissue adjacent to the primary tumor were greater in patients without metastasis to RLNs (PN- cases), compared with those with metastasis (PN+ cases), while greater numbers of CD83+ DCs in the primary tumors were found in PN+ cases. In the RLNs, the numbers of S100+ and CD1a+ DCs were less in PN+ cases than in PN- cases, while the numbers of CD83+ DCs were greater in PN+ cases compared with those in PN- cases. These results suggest that the distribution of DC subsets in OSCC may reflect the degree of tumor immunity induced in the host bearing OSCC.

We have fabricated oriented copper-phthalocyanine (CuPc) films by vacuum deposition on rubbed polyimide (PI) alignment layers. It was found that the b-axis of α-type CuPc microcrystals changes its direction depending on the thickness of PI layers, namely, the b-axis is perpendicular to the rubbing direction on a thin rubbed PI layer but is almost perfectly aligned to the rubbing direction on a thick rubbed PI layer. The oriented structure on a thick PI layer was confirmed by a high dichroic ratio of about 4, which is expected in the optical absorption of α-type CuPc, and by highly oriented needle-shaped microcrystals observed by atomic force microscopy.