Faster acquisition of magnetic resonance imaging sequences of the knee via deep learning reconstruction: a volunteer study.

AIM: To evaluate whether deep learning reconstruction (DLR) can accelerate the acquisition of magnetic resonance imaging (MRI) sequences of the knee for clinical use. MATERIALS AND METHODS: Using a 1.5-T MRI scanner, sagittal fat-suppressed T2-weighted imaging (fs-T2WI), coronal proton density-weighted imaging (PDWI), and coronal T1-weighted imaging (T1WI) were performed. DLR was applied to images with a number of signal averages (NSA) of 1 to obtain 1DLR images. Then 1NSA, 1DLR, and 4NSA images were compared subjectively, and by noise (standard deviation of intra-articular water or medial meniscus) and contrast-to-noise ratio between two anatomical structures or between an anatomical structure and intra-articular water. RESULTS: Twenty-seven healthy volunteers (age: 40.6 ± 11.9 years) were enrolled. Three 1DLR image sequences were obtained within 200 s (approximately 12 minutes for 4NSA image). According to objective evaluations, PDWI 1DLR images showed the smallest noise and significantly higher contrast than 1NSA and 4NSA images. For fs-T2WI, smaller noise and higher contrast were observed in the order of 4NSA, 1DLR, and 1NSA images. According to the subjective analysis, structure visibility, image noise, and overall image quality were significantly better for PDWI 1DLR than 1NSA images; moreover, the visibility of the meniscus and bone, image noise, and overall image quality were significantly better for 1DLR than 4NSA images. Fs-T2WI and T1WI 1DLR images showed no difference between 1DLR and 4NSA images. CONCLUSION: Compared to PDWI 4NSA images, PDWI 1DLR images were of higher quality, while the quality of fs-T2WI and T1WI 1DLR images was similar to that of 4NSA images.

Advancement of Photospheric Radius Expansion and Clocked Type-I X-Ray Burst Models with the New

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial.

BACKGROUND: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.

Differences in pain thresholds elicited by intraoral electrical stimuli between individuals with and without diabetes mellitus.

There is little evidence of sensation in individuals with diabetes mellitus (DM) in the dental research field. We investigated whether pain thresholds (PTs) differ between individuals with and without DM (non-DM; NDM). To this end, we assessed whether PTs obtained from the oral cavity, hands, and feet differed from each other and across groups, and whether PTs differed for the three current frequencies used for testing (2000 Hz, 250 Hz, and 5 Hz). Pain threshold measurements were obtained from the oral mucosa and the tips of the fingers and toes of 56 volunteers, including 21 individuals with DM (12 men and 9 women, average age: 72.1 ± 4.7 years) and 35 NDM individuals (17 males and 18 females, average age: 51.2 ± 23.9 years) using the Neurometer CPT/C® device to deliver electrical stimulation. A single operator obtained PT measurements from around the left greater palatine foramen and from the tip of the left first finger and of the left great toe. Individuals with DM had significantly lower PT values than those without DM. The PT values for the oral cavity, hands, and feet differed significantly from each other (foot > hand, foot > oral cavity, hand > oral cavity). Moreover, there was a significant difference in the PT values for 5 Hz and 2000 Hz, as well as for 250 Hz and 2000 Hz. This study concluded that PT values derived from DM participants are lower than those from NDM participants, although PT measurements varied across regions and with current frequency.

Efficiency of genomic selection for breeding population design and phenotype prediction in tomato.

Genomic selection (GS), which uses estimated genetic potential based on genome-wide genotype data for a breeding selection, is now widely accepted as an efficient method to improve genetically complex traits. We assessed the potential of GS for increasing soluble solids content and total fruit weight of tomato. A collection of big-fruited F1 varieties was used to construct the GS models, and the progeny from crosses was used to validate the models. The present study includes two experiments: a prediction of a parental combination that generates superior progeny and the prediction of progeny phenotypes. The GS models successfully predicted a better parent even if the phenotypic value did not vary substantially between candidates. The GS models also predicted phenotypes of progeny, although their efficiency varied depending on the parental cross combinations and the selected traits. Although further analyses are required to apply GS in an actual breeding situation, our results indicated that GS is a promising strategy for future tomato breeding design.

pulSED: pulsed sonoelectrodeposition of fractal nanoplatinum for enhancing amperometric biosensor performance.

For the first time, we combine pulsed electrodeposition with out-of-phase pulsed sonication for controlled synthesis of fractal nanoplatinum structures as the transducer layer in electrochemical sensing. We develop and test this technique, called bimodal pulsed sonoelectrodeposition (pulSED), as a simple approach for creating highly conductive transducer nanometals for use in sensing and biosensing. We first compared the efficiency of pulSED nanoplatinum to other pulsed electrodeposition techniques, and then explored the effect of duty cycle and plating time on electroactive surface area and nanoparticle size/morphology. The developed pulSED nanoplatinum displayed fractal features with a relatively homogenous size distribution (26.31 ± 1.3 nm) and extremely high electroactive surface (0.28 ± 0.04 cm(2)) relative to other electroplating techniques (up to one order of magnitude higher). A high duty cycle (900 mHz) promotes formation of stable nanostructures (including fractal nanostructures) and reduces amorphous structure formation due to bubble cavitation and enhanced mass transport of metal ions to the electrode surface. To demonstrate the applicability of the pulSED technique, non-enzymatic and enzymatic sensors were developed for measuring hydrogen peroxide and glucose. The sensitivity for non-enzymatic peroxide sensing (3335 ± 305 µA cm(-2) mM(-1)), non-enzymatic glucose sensing (73 ± 14 µA cm(-2) mM(-1)) and enzymatic glucose biosensing (155 ± 25 µA cm(-2) mM(-1)) was higher than, or similar to, other nanomaterial-mediated amperometric sensors reported in the literature. The pulSED technique is a one pot method for tunable synthesis of nanometal structures as a transducer layer in electrochemical sensing and biosensing that requires no precursors or capping agents, and can be carried out at room temperature with inexpensive hardware.

Appendiceal orifice inflammation is associated with proximal extension of disease in patients with ulcerative colitis.

AIM: Ulcerative colitis (UC) is considered to be a disease of continuous mucosal inflammation extending proximally from the rectum. However, appendiceal orifice inflammation (AOI) is a skip lesion with segments of continuous involvement from the rectum. The aim of this study was to examine the clinical characteristics and clinical course, particularly focused on proximal extension, of UC in patients with AOI. METHOD: A retrospective evaluation of patients with UC who underwent total colonoscopy at the Department of Surgical Oncology, The University of Tokyo, from 2004 to 2014. The degree of AOI was graded endoscopically as follows: 0 (no inflammation); 1 (slight oedema); 2 (moderate inflammation); and 3 (marked inflammation). A total of 189 patient records were reviewed retrospectively. The presence of AOI was analysed with regard to the clinical information of each patient, and its association with proximal extension of proctitis or left-sided colitis was evaluated. RESULTS: Of 189 patients with UC who underwent total colonoscopy at our institution, 92 were diagnosed with pancolitis, 50 with left-sided colitis and 47 with proctitis. Endoscopic findings of AOI were observed in 26 patients, including 11 (12.0%) with pancolitis, six (12.0%) with left-sided colitis and nine (19.1%) with proctitis. During follow up, proximal extension of the disease occurred in all nine patients with proctitis AOI. CONCLUSION: AOI is more frequently observed in patients with proctitis. Our results showed correlations between AOI and subsequent proximal extension of mucosal inflammation in patients with proctitis.

Clinical pattern and progression of ulcerative proctitis in the Japanese population: a retrospective study of incidence and risk factors influencing progression.

AIM: The rate of extension of proctitis in Western countries has been reported, but no data regarding long-term follow-up have been described for the Japanese population. Additionally, patients with long-standing or extensive ulcerative colitis have an increased risk for developing colorectal cancer. This study evaluated both the rate of extension of the disease and the development of neoplasia among patients with an initial diagnosis of ulcerative proctitis. METHOD: We retrospectively investigated the medical charts of patients with proctitis from 1979 to 2014. The primary focus of this research was the extension of the inflammatory area. The secondary focus included risk factors for disease extension and the development of neoplasia. RESULTS: Sixty-six patients satisfied the inclusion criteria. Proximal extension of the disease occurred in 34 patients: 19 patients had left-sided colitis and 15 had pancolitis. According to a multivariate analysis, disease extension was significantly higher in patients with disease onset before 25 years of age (P-value = 0.043). The cumulative rates of disease extension at 10 and 20 years were 33.8% and 52.2%, respectively. Three patients were diagnosed with dysplasia during follow-up, all of whom experienced disease extension before the development of dysplasia. CONCLUSION: The rate of extension of ulcerative colitis in the Japanese population was comparable to that in Western countries. A younger age of disease onset was associated with disease extension. Extension of proctitis may be associated with an increased risk of colorectal cancer.

Dispersive and dissipative coupling in a micromechanical resonator embedded with a nanomechanical resonator.

A micromechanical resonator embedded with a nanomechanical resonator is developed whose dynamics can be captured by the coupled-Van der Pol-Duffing equations. Activating the nanomechanical resonator can dispersively shift the micromechanical resonance by more than 100 times its bandwidth and concurrently increase its energy dissipation rate to the point where it can even be deactivated. The coupled-Van der Pol-Duffing equations also suggest the possibility of self-oscillations. In the limit of strong excitation for the nanomechanical resonator, the dissipation in the micromechanical resonator can not only be reduced, resulting in a quality factor of >3× 10(6), it can even be eliminated entirely resulting in the micromechanical resonator spontaneously vibrating.

A comparative study of graphene-hydrogel hybrid bionanocomposites for biosensing.

Hydrogels have become increasingly popular as immobilization materials for cells, enzymes and proteins for biosensing applications. Enzymatic biosensors that utilize hydrogel as an encapsulant have shown improvements over other immobilization techniques such as cross linking and covalent bonding. However, to date there are no studies which directly compare multiple hydrogel-graphene nanocomposites using the same enzyme and test conditions. This study compares the performance of four different hydrogels used as protein encapsulants in a mediator-free biosensor based on graphene-nanometal-enzyme composites. Alcohol oxidase (AOx) was encapsulated in chitosan poly-N-isopropylacrylamide (PNIPAAM), silk fibroin or cellulose nanocrystals (CNC) hydrogels, and then spin coated onto a nanoplatinum-graphene modified electrode. The transduction mechanism for the biosensor was based on AOx-catalyzed oxidation of methanol to produce hydrogen peroxide. To isolate the effect(s) of stimulus response on biosensor behavior, all experiments were conducted at 25 °C and pH 7.10. Electroactive surface area (ESA), electrochemical impedance spectroscopy (EIS), sensitivity to methanol, response time, limit of detection, and shelf life were measured for each bionanocomposite. Chitosan and PNIPAAM had the highest sensitivity (0.46 ± 0.2 and 0.3 ± 0.1 µA mM(-1), respectively) and electroactive surface area (0.2 ± 0.06 and 0.2 ± 0.02 cm(2), respectively), as well as the fastest response time (4.3 ± 0.8 and 4.8 ± 1.1 s, respectively). Silk and CNC demonstrated lower sensitivity (0.09 ± 0.02 and 0.15 ± 0.03 µA mM(-1), respectively), lower electroactive surface area (0.12 ± 0.02 and 0.09 ± 0.03 cm(2), respectively), and longer response time (8.9 ± 2.1 and 6.3 ± 0.8 s, respectively). The high porosity of chitosan, PNIPAAM, and silk gels led to excellent transport, which was significantly better than CNC bionanocomposites. Electrochemical performance of CNC bionanocomposites were relatively poor, which may be linked to poor gel stability. The differences between the Chitosan/PNIPAAM group and the Silk/CNC group were statistically significant (p < 0.05) based on ANOVA. Each of these composites was within the range of other published devices in the literature, while some attributes were significantly improved (namely response time and shelf life). The main advantages of these hydrogel composites over other devices is that only one enzyme is required, all materials are non-toxic, the sensor does not require mediators/cofactors, and the shelf life and response time are significantly improved over other devices.

A hybridisation-dependent membrane-insertable amphiphilic DNA.

We synthesised a novel membrane-insertable amphiphilic DNA. The amphiphilic DNA had a nine-nucleotide hydrophobic region at one end consisting of octyl phosphotriester linkages. The amphiphilic DNA bound to the lipid membrane by inserting the hydrophobic region; this process was facilitated by the presence of the complementary DNA strand.

IL-1ß-induced matrix metalloproteinase-3 regulates cell proliferation in rat dental pulp cells.

OBJECTIVE: We previously reported that matrix metalloproteinase-3(MMP-3) accelerates wound healing following dental pulp injury. In this study, we tested the hypothesis that induction of MMP-3 activity by interleukin-1ß would promote proliferation and apoptosis of dental pulp cells. MATERIALS AND METHODS: Dental pulp cells were isolated from rat incisors and subjected to interleukin-1ß. Matrix metalloproteinase-3 mRNA and protein expression were assessed using reverse transcription-polymerase chain reaction and Western blotting, respectively. Matrix metalloproteinase-3 activity was measured using fluorescence. Dental pulp cell proliferation and apoptosis were determined using enzyme-linked immunosorbent assays (ELISA) for BrdU and DNA fragmentation, respectively. siRNA was used to reduce MMP-3 transcripts in these cells. RESULTS: Treatment with interleukin-1ß increased MMP-3 mRNA and protein levels as well as its activity in dental pulp cells. Cell proliferation was also markedly increased, with no changes in apoptosis observed. Treatment with siRNA against MMP-3 potently suppressed this interleukin-1ß-induced increase in MMP-3 expression and activity, and also suppressed cell proliferation but unexpectedly increased apoptosis in these cells (P < 0.05). This siRNA-mediated increase in apoptosis could be reversed with exogenous MMP-3 stimulation (P < 0.05). CONCLUSIONS: Interleukin-1ß induces MMP-3-regulated cell proliferation and suppresses apoptosis in dental pulp cells.

Surgical stress response after colorectal resection: a comparison of robotic, laparoscopic, and open surgery.

BACKGROUND: The perioperative immune status of colorectal robotic surgery (RS), laparoscopic surgery (LS), and open surgery (OS) patients has not been compared. Our aim was to evaluate perioperative stress and immune response after RS, LS and OS. METHODS: This prospective study included 46 colorectal surgery patients from the Department of Surgical Oncology of the University of Tokyo Hospital. Peripheral venous blood samples were obtained preoperatively and on postoperative days 1, 3, and 6. We evaluated expression of HLA-DR (marker of immune competence), C-reactive protein (CRP) levels, and lymphocyte subset counts (natural killers, cytotoxic T cells and helper T cells). RESULTS: Fifteen, 23, and 8 patients underwent RS, LS and OS, respectively. HLA-DR expression was the lowest on day 1 and gradually increased on days 3 and 6 in all the groups. There was no significant difference in postoperative HLA-DR expression between the RS and LS group. However, on day 3, HLA-DR expression in the RS group was significantly higher than in the OS group (p = 0.04). On day 1, CRP levels in the LS group were significantly lower than in the RS group (p = 0.038). There were no significant perioperative changes in the lymphocyte subset cell count between the three groups. CONCLUSIONS: Perioperative surgical stress, as evaluated by immunological parameters, was comparable between robotic and laparoscopic surgery and higher with open surgery. Robotic surgery may be an alternative to laparoscopic surgery, as a minimally invasive surgery option for colorectal cancer.

Preliminary results of proton-beam therapy for stage III non-small-cell lung cancer.

BACKGROUND: We conducted a preliminary retrospective evaluation of the efficacy and toxicity of proton-beam therapy (pbt) for stage iii non-small-cell lung cancer. METHODS: Between January 2009 and August 2013, 27 patients (26 men, 1 woman) with stage iii non-small-cell lung cancer underwent pbt. The relative biologic effectiveness value of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned such that the 90% isodose volume of the prescribed dose encompassed the planning target volume. Of the 27 patients, 11 underwent neoadjuvant chemotherapy. Cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events. RESULTS: Median age of the patients was 72 years (range: 57-91 years), and median follow-up was 15.4 months (range: 7.8-36.9 months). Clinical stage was iiia in 14 patients (52%) and iiib in 13 (48%). The median dose of pbt was 77 GyE (range: 66-86.4 GyE). The overall survival rate in the cohort was 92.3% at 1 year and 51.1% at 2 years. Locoregional failure occurred in 7 patients, and distant metastasis, in 10. In 2 patients, initial failure was both locoregional and distant. The 1-year and 2-year rates of local control were 68.1% and 36.4% respectively. The 1-year and 2-year rates of progression-free survival were 39.9% and 21.4% respectively. Two patients experienced grade 3 pneumonitis. CONCLUSIONS: For patients with stage iii non-small-cell lung cancer, pbt can be an effective and safe treatment option.

Two-mode thermal-noise squeezing in an electromechanical resonator.

An electromechanical resonator is developed in which mechanical nonlinearities can be dynamically engineered to emulate the nondegenerate parametric down-conversion interaction. In this configuration, phonons are simultaneously generated in pairs in two macroscopic vibration modes, resulting in the amplification of their motion. In parallel, two-mode thermal squeezed states are also created, which exhibit fluctuations below the thermal motion of their constituent modes as well as harboring correlations between the modes that become almost perfect as their amplification is increased. The existence of correlations between two massive phonon ensembles paves the way towards an entangled macroscopic mechanical system at the single phonon level.

Serum milk fat globule epidermal growth factor 8 elevation may subdivide systemic lupus erythematosus into two pathophysiologically distinct subsets.

OBJECTIVE: Impaired clearance of apoptotic cells is a potential trigger of systemic lupus erythematosus (SLE). Milk fat globule epidermal growth factor 8 (MFG-E8) plays an important role in the clearance of dying cells. Previously, we reported serum MFG-E8 was elevated in some SLE patients. Here we further investigated the prevalence of MFG-E8 in active SLE and other autoimmune diseases and also tried to clarify the characteristics of MFG-E8-positive and -negative SLE. METHODS: Serum MFG-E8 was measured in 40 active non-treated SLE patients, 104 disease controls and 104 healthy controls by ELISA. Clinical characteristics and serum cytokine profiles were compared between MFG-E8-positive and MFG-E8-negative SLE patients. RESULTS: Prevalence of MFG-E8 was significantly higher in SLE patients (40%) than in various controls (p < 0.05). MFG-E8 level became negative after treatment, and increased again upon relapse. When compared, MFG-E8-positive SLE patients showed higher immune complex (p = 0.021) and lower complement (p = 0.004 for CH50). In contrast, MFG-E8-negative SLE patients tended to show higher CRP (p = 0.094). There was a positive correlation between MFG-E8 level and immune complex level (r s = 0.49, p = 0.049). TNF-α (p = 0.019), IFN-γ (p = 0.031) and IL-10 (p = 0.013) were significantly higher in MFG-E8-positive SLE. CONCLUSION: MFG-E8-positive SLE and -negative SLE may have different clinical features, the one with stronger immunological response and the other with stronger inflammatory response, and those two groups may be two distinct subtypes of SLE driven by different mechanisms. Further, MFG-E8 could be used as a biomarker for diagnosis and monitoring of disease activity in certain SLE patients.

Cytokines induce MMP-3-regulated proliferation of embryonic stem cell-derived odontoblast-like cells.

OBJECTIVES: Matrix metalloproteinase (MMP)-3 expression increases after pulpectomy and accelerates angiogenesis in rat dental pulp by an uncharacterised mechanism. Odontoblasts, a major component of dental pulp, could represent a therapeutic target. We investigated whether MMP-3 activity is induced by cytokines and/or is associated with cell proliferation and apoptosis in embryonic stem cell-derived odontoblast-like cells. MATERIALS AND METHODS: We used reverse transcriptase polymerase chain reaction, western blotting, an MMP-3 activity assay, a BrdU-cell proliferation enzyme-linked immunosorbent assay and DNA fragmentation analysis to evaluate siRNA-mediated downregulation of MMP-3 expression and activity, and any changes in the proliferative and apoptotic responses associated with this reduced expression. RESULTS: Pro-inflammatory cytokines (interleukin-1ß, tumour necrosis factor-α and interferon-γ, at relatively low concentrations) induced MMP-3 mRNA and protein expression, and increased MMP-3 activity and cell proliferation, but not apoptosis. MMP-3 silencing produced a potent and significant suppression of cytokine-induced MMP-3 expression and activity, decreased cell proliferation and increased apoptosis. These effects were rescued by application of exogenous MMP-3. CONCLUSIONS: Our results suggest that pro-inflammatory cytokines induce MMP-3-regulated cell proliferation and anti-apoptosis effects in odontoblast-like cells derived from embryonic stem cells, in addition to their well-documented destructive role in inflammation.

Mouse ES cells have a potential to differentiate into odontoblast-like cells using hanging drop method.

OBJECTIVES: We examined whether mouse embryonic stem (ES) cells can differentiate into odontoblast-like cells without epithelial-mesenchymal interaction. MATERIALS AND METHODS: Cells were cultured by the 'hanging drop' method using a collagen type-I scaffold (CS) combined with bone morphogenetic protein (BMP)-4 (CS/BMP-4). Expression of odontoblast-related mRNA and protein, and cell proliferation were performed by reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence staining and WST-1 assay, respectively. RESULTS: Cells potently expressed odontoblast-related cell marker mRNAs following induction of odontoblastic differentiation. Dentin sialophosphoprotein, a marker of mature odontoblasts, was strongly expressed in differentiated ES cells. The cells also acquired an odontoblast-like functional phenotype, as evidenced by the appearance of alkaline phosphatase activity and calcification. The cell-surface expression of α2, α6, αV and αVß3 integrin proteins was rapidly upregulated in differentiated cells. Finally, anti-α2 integrin antibody suppressed the expression of odontoblastic markers in cells grown using this culture system, suggesting that α2 integrin expression in ES cells triggers their differentiation into odontoblast-like cells. CONCLUSIONS: Mouse ES cells cultured by the 'hanging drop' method are able to differentiate into cells with odontoblast-specific physiological functions and cell-surface integrin protein expression.