Retraction notice to "Gelatin scaffold combined with bone morphogenetic protein-4 induces odontoblast-like cell differentiation involving integrin profile changes, autophagy-related gene 10, and Wnt5 sequentially in human induced pluripotent stem cells" [Differentiation 93 (2017) 1-14].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors, with the approval of the Editor-in-Chief. The journal was initially contacted by the corresponding author to report the unavailability of the raw data of the results presented by the article, as well as the similarity between the Western blots from Figure 11A (MMP-3) and Figure 11C (MMP-3). Also, a significant amount of text has been reused from the articles that the authors have previously published in the Experimental Cell Research 341 (2016) 92-104 https://doi.org/10.1016/j.yexcr.2016.01.010 and the Journal of Biological Chemistry 289 (2014) 14380-14391 https://doi.org/10.1074/jbc.M113.526772. All of the authors except Nobuaki Ozeki and Taiki Hiyama have reportedly agreed to retract the article. N. Ozeki left Aichi Gakuin University in March 2018 and does not respond to co-authors inquiries, while T. Hiyama left Aichi Gakuin University and could not be reached. The authors deeply regret this error and any inconvenience it may have caused.

Cone-beam computed tomography classification of the mandibular second molar root morphology and its relationship to panoramic radiographic appearance.

OBJECTIVES: This study aimed to clarify the relationship between the panoramic radiographic appearance and the longitudinal cone-beam computed tomography (CBCT) classification of root configurations of the mandibular second molar. METHODS: Panoramic radiographs of 1058 mandibular second molars were classified into five types according to the number and configuration of the roots. These molars were also examined with CBCT at four levels between the pulp chamber and the root apex, and axial images perpendicular to the root axis were categorized into three patterns: single (fused root with small grooves on both buccal and lingual sides or a round root with one canal); double (two separate roots with a trabecular appearance between them); and C-shaped (root with a deep groove opening only on the lingual or buccal side relative to the opposite side). Based on these patterns and their scan levels, the CBCT root morphology appearance in each tooth unit was classified into seven groups. Relationships were investigated between these seven CBCT groups and the five panoramic root types. RESULTS: In panoramic types 1 and 2 (with separate roots), 85% had roots with a double pattern (groups II and III) on the CBCT images. In panoramic types 3 and 4 (with fused roots), 85% had C-shaped CBCT patterns at the lower scan levels. CONCLUSIONS: When panoramic images show fused root types, CBCT examinations should be planned to clarify the root canal configuration.

Correction: Interleukin-1 Receptor Antagonist Has a Novel Function in the Regulation of Matrix Metalloproteinase-13 Expression.

[This corrects the article DOI: 10.1371/journal.pone.0140942.].

Evaluation of an artificial intelligence system for detecting vertical root fracture on panoramic radiography.

OBJECTIVES: The aim of this study was to evaluate the use of a convolutional neural network (CNN) system for detecting vertical root fracture (VRF) on panoramic radiography. METHODS: Three hundred panoramic images containing a total of 330 VRF teeth with clearly visible fracture lines were selected from our hospital imaging database. Confirmation of VRF lines was performed by two radiologists and one endodontist. Eighty percent (240 images) of the 300 images were assigned to a training set and 20% (60 images) to a test set. A CNN-based deep learning model for the detection of VRFs was built using DetectNet with DIGITS version 5.0. To defend test data selection bias and increase reliability, fivefold cross-validation was performed. Diagnostic performance was evaluated using recall, precision, and F measure. RESULTS: Of the 330 VRFs, 267 were detected. Twenty teeth without fractures were falsely detected. Recall was 0.75, precision 0.93, and F measure 0.83. CONCLUSIONS: The CNN learning model has shown promise as a tool to detect VRFs on panoramic images and to function as a CAD tool.

A deep-learning artificial intelligence system for assessment of root morphology of the mandibular first molar on panoramic radiography.

OBJECTIVES:: The distal root of the mandibular first molar occasionally has an extra root, which can directly affect the outcome of endodontic therapy. In this study, we examined the diagnostic performance of a deep learning system for classification of the root morphology of mandibular first molars on panoramic radiographs. Dental cone-beam CT (CBCT) was used as the gold standard. METHODS:: CBCT images and panoramic radiographs of 760 mandibular first molars from 400 patients who had not undergone root canal treatments were analyzed. Distal roots were examined on CBCT images to determine the presence of a single or extra root. Image patches of the roots were segmented from panoramic radiographs and applied to a deep learning system, and its diagnostic performance in the classification of root morphplogy was examined. RESULTS:: Extra roots were observed in 21.4% of distal roots on CBCT images. The deep learning system had diagnostic accuracy of 86.9% for the determination of whether distal roots were single or had extra roots. CONCLUSIONS:: The deep learning system showed high accuracy in the differential diagnosis of a single or extra root in the distal roots of mandibular first molars.

Randomized Phase II Trial of CapOX plus Bevacizumab and CapIRI plus Bevacizumab as First-Line Treatment for Japanese Patients with Metastatic Colorectal Cancer (CCOG-1201 Study).

PURPOSE: The aim of this randomized, multicenter, noncomparative, phase II trial was to investigate the efficacy and safety of two potential first-line treatments, capecitabine and oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine and irinotecan (CapIRI) plus bevacizumab, in Japanese patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with untreated mCRC were randomly assigned to receive either CapOX plus bevacizumab (CapOX/BEV arm: bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 2,000 mg/m2 on days 1-14, every 3 weeks) or CapIRI plus bevacizumab (CapIRI/BEV arm: bevacizumab 7.5 mg/kg and irinotecan 200 mg/m2 on day 1 and capecitabine 1,600 mg/m2 on days 1-14, every 3 weeks). The primary endpoint was overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 107 patients were enrolled. The intent-to-treat population comprised 54 patients in the CapOX/BEV arm and 53 patients in the CapIRI/BEV arm. The median follow-up period was 35.5 months. ORR was 56% in the CapOX/BEV arm and 55% in the CapIRI/BEV arm. Median PFS and OS were 12.4 and 26.7 months in the CapOX/BEV arm and 11.5 and 28.7 months in the CapIRI/BEV arm, respectively. The frequencies of hematological and nonhematological adverse events above grade 3 were 13% and 30% in the CapOX/BEV arm and 25% and 23% in the CapIRI/BEV arm, respectively. CONCLUSION: CapOX plus bevacizumab and CapIRI plus bevacizumab are equally effective and feasible as the first-line treatments in Japanese patients with mCRC. IMPLICATIONS FOR PRACTICE: The CCOG-1201 study was designed to evaluate the efficacy and safety of capecitabine and oxaliplatin plus bevacizumab and capecitabine and irinotecan plus bevacizumab as a first-line treatment in Japanese patients with metastatic colorectal cancer. This article reports on the trial and efforts to define the role of these regimens, including the effect of KRAS status and UGT1A1 polymorphisms in metastatic colorectal cancer.

Energy dispersive spectroscopy-scanning transmission electron microscope observations of free radical production in human polymorphonuclear leukocytes phagocytosing non-opsonized Tannerella forsythia.

We investigated the association between human polymorphonuclear leukocytes (PMNs) and non-opsonized Tannerella forsythia ATCC 43037 displaying a serum-resistant surface layer (S-layer). When PMNs were mixed with T. forsythia in suspension, the cells phagocytosed T. forsythia cells. Nitro blue tetrazolium (NBT) reduction, indicative of O2- production, was observed by light microscopy; cerium (Ce) perhydroxide deposition, indicative of H2 O2 production, was observed by electron microscopy. We examined the relationship between high-molecular-weight proteins of the S-layer and Ce reaction (for T. forsythia phagocytosis) using electron microscopic immunolabeling. Immunogold particles were localized within the PMNs and on cell surfaces, labelling at the same Ce-reacted sites where the S-layer was present. We then used energy dispersive spectroscopy (EDS)-scanning transmission electron microscope (STEM) to perform Ce and nitrogen (N) (for S-layer immunocytochemistry) elemental analysis on the phagocytosed cells. That is, the elemental mapping and analysis of N by EDS appeared to reflect the presence of the same moieties detected by the 3,3'-diaminobenzidine-tetrahydrochloride (DAB) reaction with horseradish peroxidase (HRP)-conjugated secondary antibodies, instead of immunogold labeling. We focused on the use of EDS-STEM to visualize the presence of N resulting from the DAB reaction. In a parallel set of experiments, we used EDS-STEM to perform Ce and gold (Au; from immunogold labeling of the S-layer) elemental analysis on the same phagocytosing cells.

MicroRNA-211 and autophagy-related gene 14 signaling regulate osteoblast-like cell differentiation of human induced pluripotent stem cells.

MicroRNAs (miRNAs) have been the subject of recent attention as key regulatory factors in cell differentiation. In the current study, to explore the early signaling cascade of osteogenic differentiation of human induced pluripotent stem (hiPS) cells, we investigated miR-211 regulation and autophagy-related gene (Atg) signaling in osteogenic differentiation. In addition to reciprocal strong induction of miR-211 expression in differentiated cells following osteogenic differentiation, we found abundant Argonaute 3 bound to miR-211. There were also dramatic increases in the mRNA and protein levels of Atg14 together with increases in the amount of autophagosomes as well as autophagic fluxes. While transfection of a miR-211 inhibitor abrogated the induction of Atg14, autophagy events, osteoblast differentiation markers, and induction of calcification were suppressed markedly. Treatment with small interfering RNAs against Atg14 also suppressed the osteogenic differentiation medium (ODM)-induced increase in osteogenic differentiation. The osteogenic phenotype was inhibited by chloroquine (an autophagy inhibitor), but increased after treatment with rapamycin (an autophagy inducer). Taken together with our previous findings, we have revealed a unique sequential cascade involving miR-211 and Atg14 in ODM-induced differentiation of hiPS cells into osteoblast-like cells at a relatively early stage.

Gelatin scaffold combined with bone morphogenetic protein-4 induces odontoblast-like cell differentiation involving integrin profile changes, autophagy-related gene 10, and Wnt5 sequentially in human induced pluripotent stem cells.

While human induced pluripotent stem (hiPS) cells have potential use in regenerative medicine, there are no reports on odontoblastic differentiation of hiPS cells. In the current study, to examine integrin profiles and explore the early signaling cascade of odontoblastic differentiation in hiPS cells, we investigated the regulation of autophagy-related gene (Atg) and wingless/int1 (Wnt) signaling in gelatin scaffold (GS) combined with bone morphogenetic protein (BMP)-4 (GS/BMP-4)-mediated odontoblastic differentiation. Following GS/BMP-4 treatment, there was a dramatic loss of α3 and α6 integrins, and reciprocal strong induction of α1 integrin expression in the differentiated cells. GS/BMP-4 increased the mRNA and protein levels of Atg10, Lrp5/Fzd9 (an Atg10 receptor), and Wnt5 together with the amount of autophagosomes and autophagic fluxes. Treatment with siRNAs against Atg10 and Wnt5a individually suppressed the GS/BMP-4-induced increase in odontoblastic differentiation. The odontoblastic phenotype was inhibited by chloroquine, but increased after treatment with rapamycin (an autophagy enhancer). Taken together with our previous findings, we have replicated our results from the rodent system in a novel human system. We have revealed a unique sequential cascade involving Atg10, Wnt5a, α1 integrin, and matrix metalloproteinase-3 in GS/BMP-4-induced differentiation of hiPS cells into odontoblast-like cells at a relatively early stage.

Polyphosphate-induced matrix metalloproteinase-13 is required for osteoblast-like cell differentiation in human adipose tissue derived mesenchymal stem cells.

Inorganic polyphosphate [Poly(P)] induces differentiation of osteoblastic cells. In this study, matrix metalloproteinase (MMP)-13 small interfering RNA (siRNA) was transfected into human adipose tissue-derived mesenchymal stem cells (hAT-MSC) to investigate whether MMP-13 activity induced by Poly(P) is associated with osteogenic differentiation. Real-time quantitative polymerase chain reaction, Western blotting, and an MMP-13 activity assay were used in this study. Poly(P) enhanced expression of mature osteoblast markers, such as osteocalcin (BGLAP) and osteopontin (SPP1), osterix (OSX), and bone sialoprotein (BSP), and increased alkaline phosphatase (ALP) activity and calcification capacity in hAT-MSCs. These cells also developed an osteogenic phenotype with increased expression of Poly(P)-induced expression of MMP-13 mRNA and protein, and increased MMP-13 activity. MMP-13 siRNA potently suppressed the expression of osteogenic biomarkers BGLAP, SPP1, OSX, BSP, and ALP, and blocked osteogenic calcification. Taken together, Poly(P)-induced MMP-13 regulates differentiation of osteogenic cells from hAT-MSCs.