Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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Effect of Patient Clinical Variables in Osteoporosis Classification Using Hip X-rays in Deep Learning Analysis. International journal

Norio Yamamoto, Shintaro Sukegawa, Kazutaka Yamashita, Masaki Manabe, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Toshifumi Ozaki, Keisuke Kawasaki, Hitoshi Nagatsuka, Yoshihiko Furuki, Takashi Yorifuji

Medicina (Kaunas, Lithuania) 57 ( 8 ) 2021.8

Language：English Publishing type：Research paper (scientific journal)

Background and Objectives: A few deep learning studies have reported that combining image features with patient variables enhanced identification accuracy compared with image-only models. However, previous studies have not statistically reported the additional effect of patient variables on the image-only models. This study aimed to statistically evaluate the osteoporosis identification ability of deep learning by combining hip radiographs with patient variables. Materials andMethods: We collected a dataset containing 1699 images from patients who underwent skeletal-bone-mineral density measurements and hip radiography at a general hospital from 2014 to 2021. Osteoporosis was assessed from hip radiographs using convolutional neural network (CNN) models (ResNet18, 34, 50, 101, and 152). We also investigated ensemble models with patient clinical variables added to each CNN. Accuracy, precision, recall, specificity, F1 score, and area under the curve (AUC) were calculated as performance metrics. Furthermore, we statistically compared the accuracy of the image-only model with that of an ensemble model that included images plus patient factors, including effect size for each performance metric. Results: All metrics were improved in the ResNet34 ensemble model compared with the image-only model. The AUC score in the ensemble model was significantly improved compared with the image-only model (difference 0.004; 95% CI 0.002-0.0007; p = 0.0004, effect size: 0.871). Conclusions: This study revealed the additional effect of patient variables in identification of osteoporosis using deep CNNs with hip radiographs. Our results provided evidence that the patient variables had additive synergistic effects on the image in osteoporosis identification.

DOI： 10.3390/medicina57080846

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CSF1/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-cell Infiltration in the Sarcoma Microenvironment. International journal

Tomohiro Fujiwara, Mohamed A Yakoub, Andrew Chandler, Alexander B Christ, Guangli Yang, Ouathek Ouerfelli, Vinagolu K Rajasekhar, Aki Yoshida, Hiroya Kondo, Toshiaki Hata, Hiroshi Tazawa, Yildirim Dogan, Malcolm A S Moore, Toshiyoshi Fujiwara, Toshifumi Ozaki, Ed Purdue, John H Healey

Molecular cancer therapeutics 20 ( 8 ) 1388 - 1399 2021.8

Language：English Publishing type：Research paper (scientific journal)

Colony-stimulating factor 1 (CSF1) is a primary regulator of the survival, proliferation, and differentiation of monocyte/macrophage that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). Considering current advances in understanding the role of the inflammatory tumor microenvironment, targeting the components of the sarcoma microenvironment, such as TAMs, is a viable strategy. Here, we investigated the effect of PLX3397 (pexidartinib) as a potent inhibitor of the CSF1 receptor (CSF1R). PLX3397 was recently approved by the Food and Drug Administration (FDA) to treat tenosynovial giant cell tumor and reprogram TAMs whose infiltration correlates with unfavorable prognosis of sarcomas. First, we confirmed by cytokine arrays of tumor-conditioned media (TCM) that cytokines including CSF1 are secreted from LM8 osteosarcoma cells and NFSa fibrosarcoma cells. The TCM, like CSF1, stimulated ERK1/2 phosphorylation in bone marrow-derived macrophages (BMDMs), polarized BMDMs toward an M2 (TAM-like) phenotype, and strikingly promoted BMDM chemotaxis. In vitro administration of PLX3397 suppressed pERK1/2 stimulation by CSF1 or TCM, and reduced M2 polarization, survival, and chemotaxis in BMDMs. Systemic administration of PLX3397 to the osteosarcoma orthotopic xenograft model significantly suppressed the primary tumor growth and lung metastasis, and thus improved metastasis-free survival. PLX3397 treatment concurrently depleted TAMs and FOXP3+ regulatory T cells and, surprisingly, enhanced infiltration of CD8+ T cells into the microenvironments of both primary and metastatic osteosarcoma sites. Our preclinical results show that PLX3397 has strong macrophage- and T-cell-modulating effects that may translate into cancer immunotherapy for bone and soft-tissue sarcomas.

DOI： 10.1158/1535-7163.MCT-20-0591

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Induction and expansion of human PRRX1+ limb-bud-like mesenchymal cells from pluripotent stem cells. International journal

Daisuke Yamada, Masahiro Nakamura, Tomoka Takao, Shota Takihira, Aki Yoshida, Shunsuke Kawai, Akihiro Miura, Lu Ming, Hiroyuki Yoshitomi, Mai Gozu, Kumi Okamoto, Hironori Hojo, Naoyuki Kusaka, Ryosuke Iwai, Eiji Nakata, Toshifumi Ozaki, Junya Toguchida, Takeshi Takarada

Nature biomedical engineering 5 ( 8 ) 926 - 940 2021.8

Language：English Publishing type：Research paper (scientific journal)

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells' chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.

DOI： 10.1038/s41551-021-00778-x

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Letter regarding "Clinical outcomes and trans-syndesmotic screw frequency after posterior malleolar fracture osteosynthesis". International journal

Norio Yamamoto, Yosuke Tomita, Tomoyuki Noda, Kohei Iwamoto, Toshifumi Ozaki

Injury 52 ( 8 ) 2479 - 2480 2021.8

Two simple stitches for medial meniscus posterior root repair prevents the progression of meniscal extrusion and reduces intrameniscal signal intensity better than modified Mason-Allen sutures. International journal

Yuki Okazaki, Takayuki Furumatsu, Takaaki Hiranaka, Yuya Kodama, Yusuke Kamatsuki, Keisuke Kintaka, Toshifumi Ozaki

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 31 ( 6 ) 1005 - 1013 2021.8

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Medial meniscus posterior root tears (MMPRTs) can cause severe medial extrusion of the medial meniscus (MMME) and the progression of knee degenerative changes, inducing a high signal intensity of the meniscus on magnetic resonance imaging (MRI). Although MMME and intrameniscal signal intensity (IMSI) reportedly decreased within 3 months after MMPRT repair, no previous studies have reported these changes after a 1-year follow-up. This study aimed to investigate the 1-year postoperative changes in MMME and IMSI on MRI after using different suture techniques. METHODS: Overall, 33 patients with MMPRT were evaluated, 22 underwent FasT-Fix-dependent modified Mason-Allen suture (F-MMA) repair, and 11 underwent two simple stitches (TSS) repair. MRI examinations were performed preoperatively and 1 year postoperatively. MMME and IMSI were determined using MRI. RESULTS: A significant decrease in postoperative MMME was observed in the TSS group (4.1 ± 1.0) relative to that in the F-MMA group (5.1 ± 1.4, P = 0.03). A significant decrease in postoperative IMSI (0.75 ± 0.14) was observed relative to preoperative IMSI in the TSS group (P < 0.01), whereas postoperative IMSI (0.94 ± 0.25) was similar to preoperative IMSI in the F-MMA group (P = 0.06). Furthermore, a significant decrease in postoperative IMSI was observed in the TSS group relative to that in the F-MMA group (P < 0.01). CONCLUSIONS: The most important finding of this study is that TSS repair yielded a greater decrease in MMME and IMSI than F-MMA repair in patients with MMPRT. These results suggest that TSS repair is more useful for restoring loading stress to the posterior horn of the medial meniscus.

DOI： 10.1007/s00590-020-02830-z

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Medial meniscus posterior root repair using a modified Mason-Allen suture can prevent the progression of cartilage degeneration on the loading surface of the medial compartment: a second-look arthroscopic evaluation

Takihira S, Furumatsu T, Okazaki Yuki, Hiranaka T, Kintaka K, Kodama Y, Kamatsuki Y, Miyazawa S, Ozaki T

Acta Med Okayama 75 ( 4 ) 423 - 430 2021.8

Assessment of the concordance rate between intraoperative pathological diagnosis and the final pathological diagnosis of spinal cord tumors

Muraoka S, Yamane K, Misawa H, Takigawa T, Tetsunaga T, Oda Y, Nakanishi K, Ozaki T, Tanaka T

Acta Med Okayama 75 ( 4 ) 455 - 460 2021.8

Language：English Publishing type：Research paper (scientific journal)

The intraoperative pathological diagnosis (IPD) plays an important role in determining the optimal surgical treatment for spinal cord tumors. The final pathological diagnosis (FPD) is sometimes different from the IPD. Here, we sought to identify the accuracy of the IPD of spinal cord tumors compared to the FPD. We retrospec-tively analyzed the cases of 108 patients with spinal cord tumors treated surgically in our institute; the IPD, FPD, mismatched cases, and concordance rate between the IPD and FPD were investigated. Five cases involved a mismatch between the IPD and FPD. The overall concordance rate was 95.4%, with 90.9% for extra-dural lesions, 98.5% for intradural extramedullary lesions, 84.2% for intramedullary lesions, and 100% for dumbbell-type tumors. The concordance rate of intramedullary lesions tended to be lower than that of other lesions (p = 0.096). A lower concordance rate was revealed for intramedullary lesions compared to the other lesions. Despite the IPD clearly remaining a valuable tool during operative procedures, surgeons should recog-nize the limitations of IPDs and make comprehensive decisions about surgical treatments.

DOI： 10.18926/AMO/62397

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変形性肩関節症とCCN3発現上昇との相関について

廣瀬一樹, 中田英二, 服部高子, 鉄永智紀, 山田和希, 佐藤嘉洋, 桑原実穂, 滝川正春, 久保田聡, 尾崎敏文

日本整形外科学会雑誌 95 ( 8 ) S1506 - S1506 2021.8