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1. Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams

Author: Masashi Yagi, Shinichi Shimizu, Noriaki Hamatani, Takuto Miyoshi, Takuya Nomura, Takashi Toyoda, Mahoro Nakatani, Toshiro Tsubouchi, Masaki Shimizu, Yoshiaki Kuwana, Masumi Umezawa, Masaaki Takashina, Teiji Nishio, Masahiko Koizumi, Kazuhiko Ogawa, and Tatsuaki Kanai
Subjects: Medicine, Science
Abstract: Abstract The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8–12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.
Published: 2024
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2. Possible correlation between serum interleukin-8 levels and the activity of myositis in anti-NXP2 antibody-positive dermatomyositis

Author: Risa Konishi, Yuki Ichimura, Ryota Tanaka, Hanako Miyahara, Mari Okune, Masahide Miyamoto, Monami Hara, Atsushi Iwabuchi, Hidetoshi Takada, Yasuo Nakagishi, Mao Mizuta, Shuya Kaneko, Masaki Shimizu, Tomohiro Morio, Ichizo Nishino, Toshifumi Nomura, and Naoko Okiyama
Subjects: Dermatomyositis, nuclear matrix protein 2, interleukin-8, cytokine, Immunologic diseases. Allergy, RC581-607
Abstract: AbstractAnti-nuclear matrix protein 2 (NXP2) antibody-positive dermatomyositis (DM) is characterized by extensive and severe myositis. In this study, we evaluated which cytokines/chemokines involved with the activity of the myositis. We performed quantitative immunoassays using the MILLIPLEX® Multiplex Assays Using Luminex to evaluate serum levels of interferon-γ, interleukin (IL)-1β, IL-6, IL-8, IL-12p40, and tumor necrosis factor-α in samples collected over time from a 9-year-old female with anti-NXP2 antibody-positive DM. In our case, the serum level of IL-8 was elevated when the myositis worsened, and decreased in accordance with the improvement of myositis, suggesting that the serum IL-8 levels were correlated with the myositis activity. Serum levels of IL-8 in samples from five patients with anti-NXP2 antibody-positive DM and five patients with anti-transcriptional intermediary factor 1γ (TIF1γ) antibody-positive DM without both interstitial lung disease (ILD) and malignancy before starting treatments, along with five healthy controls, were also evaluate by an enzyme-linked immunosorbent assay. Serum IL-8 levels were significantly elevated in anti-NXP2 or anti-TIF1γ antibody-positive DM patients with myositis but not ILD, than healthy controls. It was suggested that serum levels of IL-8 correlate with the activity of myositis in DM including anti-NXP2 antibody-positive DM.
Published: 2024
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3. Successful treatment with tofacitinib for anti-melanoma differentiation-associated gene 5 antibody-positive juvenile dermatomyositis: case reports and review of the literature

Author: Susumu Yamazaki, Masaki Shimizu, Ayane Yakabe, Eisuke Inage, Keisuke Jimbo, Mitsuyoshi Suzuki, Futaba Miyaoka, Shuya Kaneko, Hitoshi Irabu, Asami Shimbo, Yoshiyuki Ohtomo, Masaaki Mori, Tomohiro Morio, and Toshiaki Shimizu
Subjects: Anti-melanoma differentiation-associated gene 5, Janus kinase inhibitors, juvenile dermatomyositis, immunosuppression therapy, tofacitinib, methylprednisolone, Immunologic diseases. Allergy, RC581-607
Abstract: AbstractAlthough the clinical efficacy of tofacitinib has been reported in adult patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (Ab+) dermatomyositis, data on its use in refractory juvenile dermatomyositis (JDM) are scarce. We describe two female Japanese patients with anti-MDA5 Ab + JDM and rapidly progressive interstitial lung disease who achieved remission by adding tofacitinib to existing immunosuppressive drugs and present a literature review. While both patients received various immunosuppressive or anti-inflammatory treatments for induction therapy, remission could not be achieved. Subsequently, tofacitinib was administered to reduce the Krebs von den Lungen-6 level 5 months after diagnosis in one patient; the other patient received tofacitinib 4 months after diagnosis to reduce ferritin levels and skin manifestations. Subsequently, both patients achieved remission, and prednisolone was withdrawn. Tofacitinib reduced the interferon signature associated with dermatomyositis/JDM disease progression and exerted a therapeutic effect on dermatomyositis/JDM. We found six published cases from five articles of tofacitinib for refractory anti-MDA5 Ab + JDM. Except for one case of herpes simplex meningitis, the other cases, including ours, had improved disease activity without severe adverse events, and steroids and immunosuppressive medicines could be tapered. Tofacitinib could be considered an available therapy for refractory anti-MDA5 Ab + JDM.
Published: 2024
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4. Asian Neonatal Network Collaboration (AsianNeo): a study protocol for international collaborative comparisons of health services and outcomes to improve quality of care for sick newborn infants in Asia – survey, cohort and quality improvement studies

Author: Yumi Kono, Hidehiko Nakanishi, Satoshi Kusuda, Hirokazu Arai, Maki Sato, Hiroaki Imamura, Takahide Yanagi, Moriharu Sugimoto, Hiroshi Matsumoto, Takashi Nakano, Satoshi Watanabe, Tomoaki Ioroi, Shigeharu Hosono, Makoto Nabetani, Osuke Iwata, Naho Morisaki, Bin Huey Quek, Kaoru Okazaki, Hideaki Harada, Masaki Kobayashi, Yuh-Jyh Lin, Yayoi Miyazono, Isamu Hokuto, Hiroshi Komatsu, Hiroshi Suzuki, Chayatat Ruangkit, Yuko Maruyama, Daisuke Nishi, Shanika Kosarat, Kapila Jayaratne, Tetsuya Isayama, Toshinori Nakashima, Tsutomu Ogata, Takashi Yamagami, Zubair Amin, Shinya Hirano, Seiji Yoshimoto, Chih-Cheng Chen, Yuji Ito, Rinawati Rohsiswatmo, Pertin Sianturi, Rocky Wilar, Dwi Hidayah, Risa Etika, Afifa Ramadanti, Pudji Andayani, Ema Alasiry, Ellen Sianipar, Yosuke Shima, Takashi Tachibana, Takahiro Okutani, Soon Min Lee, Hitoshi Yoda, Ichiro Morioka, Woei Bing Poon, Asao Yara, Akira Nishimura, Masato Ito, Tadayuki Kumagai, Hiroshi Yoshida, Takashi Okuno, Mei-Jy Jeng, Ee-Kyung Kim, Buranee Swatesutipun, Kei Inomata, Yuichi Kato, Kiyoaki Sumi, Atsushi Uchiyama, Narongsak Nakwan, Juyoung Lee, Keiji Goishi, Hiroshi Yamamoto, Hsiu-Ling Chen, Masahiro Kobayashi, Kazumasa Takahashi, Masayuki Ochiai, Fumihiko Ishida, Seok Chiong Chee, Siew Hong Neoh, Ee Lee Ang, Ann Cheng Wong, Masaru Shirai, Toru Ishioka, Toshihiko Mori, Toru Huchimukai, Kyone Ko, Akira Shimazaki, Tatsuya Yoda, Azusa Kobayashi, Yasushi Uchida, Mitsuhiro Ito, Kuniko Ieda, Toshiyuki Ono, Masashi Hayashi, Kanemasa Maki, Kozue Shiomi, Koji Nozaki, Taho Kim, Yasuyuki Tokunaga, Akihiro Takatera, Hiroshi Sumida, Yae Michinomae, Yoshio Kusumoto, Takeshi Morisawa, Tamaki Ohashi, Takahiko Saijo, Kosuke Koyano, Mikio Aoki, Koichi Iida, Mitsushi Goshi, Miho Sato, Hung-Yang Chang, Hironobu Tokumasu, Yoichi Kondo, Arif Budiman, Arief Budiman, Ken Nagaya, Fumihiko Namba, Yun Sil Chang, Masaru Yamakawa, Atsushi Nakao, Masaki Shimizu, Ming-Chih Lin, Jui-Hsing Chang, Shu-Chi Mu, Hung-Chih Lin, Fuyu Miyake, Rizalya Dewi, Yuri Ozawa, Seiichi Tomotaki, Ma Lourdes S Imperial, Belen Amparo E Velasco, Su Jin Cho, YoungAh Youn, Saman Kumara, Hsiang Yu Lin, Pracha Nuntnarumit, Sopapan Ngerncham, Chatchay Prempunpong, Pathaporn Prempraphan, Sarayut Supapannachart, Isra Firmansyah, Eny Yantri, Henri Azis, Ied Imelda, Mustarim , Benny Sana Putra, Leni Ervina Jumnalis, Andhika Tiurmaida Hutapea, Nadia Dwi Insani, Agnes Yunie Purwita Sari, Naomi Esthernita Dewanto, Thomas Harry Adoe, Tetty Yuniarti, Adhie Nur Radityo S, Tunjung Wibowo, Kartika Darma Handayani, Dina Djojo Husodo, Brigitta Ida Resita Vebrianti Corebima, Retno Wulandari, Made Sukmawati, I Ketut Adi Wirawan, Made Yuliari, James Thimoty, Sandra Bulan, Takashi Nasu, Yukiteru Tachibana, Ayumu Noro, Toshiya Saito, Yosuke Kaneshi, Nobuko Shiono, Nobuhiro Takahashi, Yusuke Ohkado, Tatsuro Satomi, Mika Nakajima, Eiki Nakamura, Tomofumi Ikeda, Genichiro Sotodate, Mari Ishii, Takahide Hosokawa, Rikio Suzuki, Masatoshi Sanjo, Michiya Kudo, Takushi Hanita, Satoshi Niwa, Masanari Kawamura, Yousuke Sudo, Tsutomu Ishii, Takashi Imamura, Yoshiya Yukitake, Goro Asada, Yasuaki Kobayashi, Yasushi Oki, Kenji Ichinomiya, Toru Fujiu, Hideaki Fukushima, Tetsuya Kunikata, Chika Morioka, Motoichiro Sakurai, Naoto Nishizaki, Satoshi Toishi, Harumi Otsuka, Masahiko Sato, Kenichiro Hirakawa, Kenichiro Hosoi, Hiromichi Shoji, Atsuo Miyazawa, Yuko Nagaoki, Naoki Ito, Ken Masunaga, Reiko Kushima, Sakae Kumasaka, Manabu Sugie, Daisuke Haruhara, Satsuki Kakiuchi, Riki Nishimura, Daisuke Ogata, Ayako Fukuyama, Kuriko Nakamura, Kanji Ogo, Masahiko Murase, Katsuaki Toyoshima, Maha Suzuki, Yoshio Shima, Atsushi Nemoto, Yukihide Miyosawa, Takehiko Hiroma, Gen Kuratsuji, Yoshihisa Nagayama, Tohei Usuda, Rei Kobayashi, Takeshi Hutani, Taketoshi Yoshida, Kazuhide Ohta, Shuya Nagaoki, Yasuhisa Ueno, Toru Ando, Ritsuyo Taguchi, Takeshi Arakawa, Shinji Usui, Tokuso Murabayashi, Shigeru Oki, Reiji Nakano, Taizo Ueno, Masami Shirai, Akira Oishi, Hikaru Yamamoto, Hiroshi Takeshita, Koji Takemoto, Masashi Miyata, Makoto Ohshiro, Masanori Kowaki, Osamu Shinohara, Yasunori Koyama, Takahiro Muramatsu, Akinobu Taniguchi, Naoki Kamata, Hiroshi Uchizono, Kenji Nakamura, Masahito Yamamoto, Jitsuko Ohira, Machiko Sawada, Ryosuke Araki, Daisuke Kinoshita, Ryuji Hasegawa, Shinsuke Adachi, Toru Yamakawa, Masahiko Kai, Hirotaka Minami, Kenji Mine, Reiko Negi, Satoru Ogawa, Ryoko Yoshinare, Atsushi Ogihara, Satoshi Onishi, Hiroyuki Ichiba, Misao Yoshii, Hitomi Okabe, Hiroshi Mizumoto, Masaaki Ueda, Kazumichi Fujioka, Takeshi Utsunomiya, Toshiya Nishikubo, Ken Kumagaya, Akiko Tamura, Masumi Miura, Yuki Hasegawa, Rie Kanai, Kei Takemoto, Koichi Tsukamoto, Misao Kageyama, Rie Fukuhara, Yutaka Nishimura, Seiichi Hayakawa, Yasuhiko Sera, Masahiro Tahara, Shinosuke Fukunaga, Keiko Hasegawa, Hiroshi Tateishi, Tomomasa Terada, Toru Kuboi, Osamu Matsuda, Shinosuke Akiyoshi, Takahiro Motoki, Yusei Nakata, Toshiharu Hikino, Shutaro Suga, Mitsuaki Unno, Hiroshi Kanda, Yasushi Takahata, Hiroyasu Kawano, Takayuki Kokubo, Toshimitsu Takayanagi, Muneichiro Sumi, Fumiko Kinoshita, Masanori Iwai, Naoki Fukushima, Yuki Kodama, Shuichi Yanagibe, Takuya Tokuhisa, Yoriko Kisato, Tatsuo Oshiro, Kazuhiko Nakasone, ChangWon Choi, Young-Ah Youn, Jae Won Shim, Jang Hoon Lee, Ga Won Jeon, Byong Sop Lee, Jin A Lee, Jae Woo Lim, Zuraidah Abdul Latif, Zainah Shaikh Hedra, Baizura Jamaluddin, Hasri Hafidz, Zainab Ishak, Geok Hoon Ngian, Chiong Hung Kiew, Mehala Devi Baskaran, Maslina Mohamad, Chee Sing Wong, Rozitah Razman, Maneet Kaur, Choo Hau Lim, Maizatul Akmar, Sheila Gopal Krishnan, Chae Hee Chieng, Chong Meng Choo, Eric Boon- Kuang Ang, AngShiau Chuen Diong, Angeline Seng- Lian Wan, Sharifah Huda Engku Alwi, Kwee Ching See, Rohani Abdul Jalil, Agnes Suganthi, Mei Ling Lee, Pauline Poh-Ling Choo, Lee Ser Chia, Azanna Ahmad Kamar, Anand Mohan A/L Mohana Lal, Agnes Huei- Hwen Foo, Abdul Nasir Mohamed Abdul Kadher, Ma. Lourdes Imperial, Belen Velasco, Ma. Esterlita V. Uy, Daisy Evangeline Garcia, Jacinto Blas Mantaring, Nethmini Thenuwara, Ming-Chou Chiang, Lan-Wan Wang, Xiao-Ping Wang, Yi-Li Hung, Yung Chieh Lin, Pen-Hua Su, Yung-Ning Yang, Po-Nein Tsao, Liang-Ti Huang, Yi-Yu Su, Shau-Ru Ho, Yan-Yan Ng, Kai-Ti Tseng, Yi-Yin Chen, Tsung-Yu Wu, Wei-Tse Chiu, Li-Jung Fang, Kao-Hsian Hsieh, Anavat Bupphachareonsuk, Anchalee Limrungsikul, Anita Luvira, Anucha Thatrimontrichai, Buranee Yangthara, Cholticha Laohajeeraphan, Hathitip Chaiprapa, Junya Jirapradittha, Kanmalee Jenjarat, Kannikar Booranavanich, Namtip Intub, Patcharin Thanomsingh, Pirarat Kotcharit, Piyawan Phummaphuti, Pornpimon Janyoungsak, Prapaiporn Chongkongkiat, Rapeephun Hansuebsai, Roongrawee Torbunsupachai, Santi Punnahitanan, Sommon Jindakul, Sopida Tanthawat, Sudarat Sirichaipornsak, Sudatip Kositamongkol, Supamas Supabanpot, Suparat Tipprasert, Tanin Pirunnet, Thanatda Siriporn, Usakorn Taesiri, Vasita Jirasakuldech, and Eleanor DR Cuarte
Subjects: Medicine
Abstract: Introduction Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants.Methods and analysis Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions).Ethics and dissemination The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020–244, 2022–156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.
Published: 2024
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5. Case Report: A neonatal case of cryopyrin-associated periodic syndrome with severe funisitis and neonatal asphyxia

Author: Yuri Hayashida, Maho Hatano, Kazuyuki Ito, Manabu Sugie, Junko Kunieda, Masaki Shimizu, Tomohiro Morio, and Chikako Morioka
Subjects: cryopyrin-associated periodic fever syndrome, neonatal asphyxia, umbilical cord rupture, funisitis, CINCA syndrome/NOMID, Pediatrics, RJ1-570
Abstract: Cryopyrin-associated periodic syndrome (CAPS) is a genetic disorder and autoinflammatory disease characterized by chronic inflammation throughout the body. The most severe form of CAPS, Chronic Infantile Neurologic Cutaneous, and Articular (CINCA) syndrome, also known as Neonatal Onset Multisystem Inflammatory Disease (NOMID), has three main features: skin rash, CNS involvement, and joint symptoms. Although these symptoms are typically reported shortly after birth, there have been a few reports of prenatal inflammation. Here, we report our experience managing a case of a CAPS infant born in severe neonatal asphyxia due to a ruptured cord associated with severe funisitis. The baby was born at 38 weeks and 6 days of gestation, weighing 2,898 g, through an ultra-emergency Caesarian section prompted by variable deceleration. The Apgar score was 1 point at 1 min and 4 points at 5 min, necessitating intensive care due to hypoxic-ischemic encephalopathy. Upon delivery, it was observed that the umbilical cord had partially ruptured at the site of attachment to the baby, accompanied by arterial hemorrhage. Umbilical cord rupture was considered to be the cause of the sudden decrease in fetal heart rate. Pathological examination also showed that the inflammation of the cord was more severe on the side attached to the fetus and on the arterial side, suggesting that the inflammation had extended from the fetus. The father carried a genetic mutation associated with CINCA syndrome/NOMID (NLRP3 c.2068G>A p.Glu690Lys Hetero), which was also found in the child. Histopathologic examination of the placenta and umbilical cord can provide crucial insights into the intrauterine onset of inflammation, which is the first manifestation of CINCA syndrome/NOMID in newborns. It should be noted that births with a genetic predisposition to CAPS may have complications related to the placenta and umbilical cord.
Published: 2024
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6. Adenosine monophosphate deaminase in the endoplasmic reticulum–mitochondria interface promotes mitochondrial Ca2+ overload in type 2 diabetes rat hearts

Author: Arata Osanami, Tatsuya Sato, Yuki Toda, Masaki Shimizu, Atsushi Kuno, Hidemichi Kouzu, Toshiyuki Yano, Wataru Ohwada, Toshifumi Ogawa, Tetsuji Miura, and Masaya Tanno
Subjects: Adenosine monophosphate deaminase, Diabetic cardiomyopathy, Mitochondria‐associated endoplasmic reticulum membrane, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction We previously showed that upregulation of myocardial adenosine monophosphate deaminase (AMPD) is associated with pressure overload‐induced diastolic dysfunction in type 2 diabetes hearts. Here, we examined involvement of AMPD localized in the endoplasmic reticulum–mitochondria interface in mitochondrial Ca2+ overload and its pathological significance. Materials and Methods We used type 2 diabetes Otsuka Long–Evans Tokushima Fatty rats (OLETF) and non‐diabetes Long–Evans Tokushima Otsuka Fatty rats (LETO) as well as AMPD3‐overexpressing H9c2 cells and human embryonic kidney 293 cells. Results OLETF, but not LETO, showed diastolic dysfunction under the condition of phenylephrine‐induced pressure overload. The levels of 90‐kDa AMPD3 in outer mitochondrial membranes/endoplasmic reticulum and mitochondria‐associated endoplasmic reticulum membrane (MAM) fractions were significantly higher in OLETF than in LETO. The area of the MAM quantified by electron microscopic analysis was 57% larger, mitochondrial Ca2+ level under the condition of pressure overload was 47% higher and Ca2+ retention capacity in MAM‐containing crude mitochondria isolated before the pressure overloading was 21% lower in OLETF than in LETO (all P‐values
Published: 2023
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7. Nuclear translocation of MLKL enhances necroptosis by a RIP1/RIP3-independent mechanism in H9c2 cardiomyoblasts

Author: Shoya Ino, Toshiyuki Yano, Atsushi Kuno, Masaya Tanno, Hidemichi Kouzu, Tatsuya Sato, Tomohisa Yamashita, Wataru Ohwada, Arata Osanami, Toshifumi Ogawa, Yuki Toda, Masaki Shimizu, and Tetsuji Miura
Subjects: Necroptosis, Cardiomyocyte, MLKL, RIP1, RIP3, Therapeutics. Pharmacology, RM1-950
Abstract: Accumulating evidence suggests that necroptosis of cardiomyocytes contributes to cardiovascular diseases. Lethal disruption of the plasma membrane in necroptosis is induced by oligomers of mixed lineage kinase domain-like (MLKL) that is translocated to the membrane from the cytosol. However, the role played by cytoplasmic-nuclear shuttling of MLKL is unclear. Here, we tested the hypothesis that translocation of MLKL to the nucleus promotes the necroptosis of cardiomyocytes. Activation of the canonical necroptotic signaling pathway by a combination of TNF-α and zVAD (TNF/zVAD) increased nuclear MLKL levels in a RIP1-activity-dependent manner in H9c2 cells, a rat cardiomyoblast cell line. By use of site-directed mutagenesis, we found a nuclear export signal sequence in MLKL and prepared its mutant (MLKL-L280/283/284A), though a search for a nuclear import signal was unsuccessful. MLKL-L280/283/284A localized to both the cytosol and the nucleus. Expression of MLKL-L280/283/284A induced necroptotic cell death, which was attenuated by GppNHp, an inhibitor of Ran-mediated nuclear import, but not by inhibition of RIP1 activity or knockdown of RIP3 expression. GppNHp partly suppressed H9c2 cell death induced by TNF/zVAD treatment. These results suggest that MLKL that is translocated to the nucleus via RIP1-mediated necroptotic signaling enhances the necroptosis of cardiomyocytes through a RIP1-/RIP3-independent mechanism.
Published: 2023
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8. Fetal-onset malignant rhabdoid tumor: a case report

Author: Ryota Kobayashi, Wakako Sumiya, Toshiyuki Imanishi, Chika Kanno, Masayuki Kanno, Jun Unemoto, Ken Kawabata, Masami Kanno, and Masaki Shimizu
Subjects: Fetal diagnosis, Ex-utero intrapartum treatment, Malignant rhabdoid tumor, Fetal onset, Medicine
Abstract: Abstract Background A fetal-onset cervical mass may cause postnatal airway obstruction, and ex utero intrapartum treatment (EXIT) to secure the airway while maintaining fetal-placental circulation may be life-saving. Malignant rhabdoid tumors (MRT) are highly aggressive tumors, and when they develop in utero, the prognosis is even worse, with almost no reports of survival beyond the neonatal period. Herein, we report a case of a primary cervical MRT and describe our treatment using EXIT for securing the airway, wherein the infant’s life was saved. Case presentation A 40-year-old Japanese woman with no relevant medical or surgical history was diagnosed with a fetal left cervical mass and polyhydramnios during the third trimester. Fetal magnetic resonance imaging indicated the possibility of postnatal airway obstruction, and delivery using EXIT was planned. The infant was delivered by a planned cesarean section at 39 weeks and 5 days gestation, and tracheostomy was performed using EXIT. Postnatal contrast-enhanced computed tomography revealed suspected metastatic lesions in the subcutaneous tissue, lungs, and thymus, in addition to the mass in the left cervical region. MRT was diagnosed by biopsy of a subcutaneous mass in the left thigh, and chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide was initiated. The tumors regressed, and the infant was successfully weaned from artificial ventilation. After discharge from the hospital, she had a recurrent cervical mass and intracranial metastasis, and radiotherapy was initiated. Conclusions In our case, fetal diagnosis enabled advance planning of delivery using EXIT, thus saving the infant’s life. The use of chemotherapy for MRT, which has a poor prognosis, allowed tumor regression and enabled the infant to survive beyond the neonatal period.
Published: 2022
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9. Multimodal Imaging Findings in Retinopathy Associated with Facioscapulohumeral Muscular Dystrophy before and after Treatment with Intravitreal Aflibercept and Laser Photocoagulation

Author: Hiroshi Shimizu, Masaki Shimizu, Toshiya Nakano, Kousuke Noda, and Masaki Tanito
Subjects: facioscapulohumeral muscular dystrophy, aflibercept, laser photocoagulation, optical coherence tomography, optical coherence tomography angiography, Ophthalmology, RE1-994
Abstract: A 52-year-old man with a history of facioscapulohumeral dystrophy (FSHD) and hypertension presented with decreased vision in his left eye (OS) of several weeks’ duration. The best-corrected visual acuity was 1.0 in both eyes (OU), with fundus soft exudates in the right eye (OD) and exudative maculopathy OS. Optical coherence tomography (OCT) showed macular edema and hard exudates OS, and OCT angiography (OCTA) showed nonperfusion areas and arterial tortuosity OU and a capillary aneurysm OS. After photocoagulation of the nonperfusion areas OU and intravitreal injection of aflibercept OS, the macular edema OS decreased and subjective symptoms improved. However, the nonperfusion area OS was enlarged on OCTA. We report the OCTA findings before and after antivascular endothelial growth factor treatment in a patient with FSHD.
Published: 2022
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10. Side-Chain Labeling Strategy for Forming Self-Sorted Columnar Liquid Crystals from Binary Discotic Systems

Author: Tsuneaki Sakurai, Kenichi Kato, and Masaki Shimizu
Subjects: self-sort, segregated columns, binary mixture, amphiphilicity, homeotropic alignment, Crystallography, QD901-999
Abstract: The spontaneous formation of self-sorted columnar structures of electron-donating and accepting π-conjugated molecules is attractive for photoconducting and photovoltaic properties. However, the simple mixing of donor–acceptor discotic molecules usually results in the formation of mixed-stacked or alternating-stacked columns. As a new strategy for overcoming this problem, here, we report the “side-chain labeling” approach using binary discotic systems and realize the preferential formation of such self-sorted columnar structures in a thermodynamically stable phase. The demonstrated key strategy involves the use of hydrophobic and hydrophilic side chains. The prepared blend is composed of liquid crystalline phthalocyanine with branched alkyl chains (H2Pc) and perylenediimide (PDI) carrying alkyl chains at one side and triethyleneglycol (TEG) chains at the other side (PDIC12/TEG). To avoid the thermodynamically unfavorable contact among hydrophobic and hydrophilic chains, PDIC12/TEG self-assembles to stack up on top of each other and H2Pc as well, forming a homo-stacked pair of columns (self-sort). Importantly, H2Pc and PDIC12/TEG in the blend are macroscopically miscible and uniform, and mesoscopically segregated. The columnar liquid crystalline microdomains of H2Pc and PDIC12/TEG are homeotropically aligned in a glass sandwiched cell. The “labeling” strategy demonstrated here is potentially applicable to any binary discotic system and enables the preferential formation of self-sorted columnar structures.
Published: 2023
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11. Risk factors for hyperglycemia in extremely low birth weight infants during the first 14 days

Author: Yuka Inage, Daishi Hirano, Ai Nakagawa, Saya Yamada, Yuko Kotake, Naohiro Ikoma, Kensuke Kumazawa, Shion Hayashi, Yukitoshi Tanabe, Masahisa Kobayashi, and Masaki Shimizu
Subjects: bifidobacterium, hyperglycemia, infant, low birth weight, probiotics, Pediatrics, RJ1-570
Abstract: Background: There are limited data regarding the risk factors for hyperglycemia in extremely low birth weight infants (ELBWIs). The aim of this observational study was to investigate the incidence of hyperglycemia among ELBWIs during the first 14 days of life and identify independent risk factors for hyperglycemia development. Methods: We retrospectively evaluated 55 ELBWIs (32 male infants) between January 2015 and March 2020. Hyperglycemia was diagnosed when the glucose level was ≥180 mg/dL. Demographic and clinical data were extracted from the patients’ medical records. The risk factors associated with the onset of hyperglycemia were identified by Cox proportional hazards regression analysis with variables that had previously been identified as risk factors for hyperglycemia. Results: Hyperglycemia developed in 23 patients (41.8%) within the first 14 days of life. Gestational age, chorioamnionitis, postnatal intravenous glucocorticoids, and probiotic type were included in the analysis. The results indicated that hyperglycemia was significantly associated with gestational age (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48–0.87; P = 0.004). Further, Bifidobacterium breve (B. breve M-16V) use was related to hyperglycemia in ELBWIs (HR, 2.95; 95% CI, 1.10–7.87; P = 0.031). Conclusion: Hyperglycemia was strongly associated with lower gestational age and B. breve M-16V use in our study population. Although probiotic supplementation may be beneficial for preterm infants to reduce the incidence of necrotizing enterocolitis, the dextrin used as an excipient in B. breve M-16V may lead to an undesirable carbohydrate load in ELBWIs.
Published: 2022
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12. Downregulation of extramitochondrial BCKDH and its uncoupling from AMP deaminase in type 2 diabetic OLETF rat hearts

Author: Toshifumi Ogawa, Hidemichi Kouzu, Arata Osanami, Yuki Tatekoshi, Tatsuya Sato, Atsushi Kuno, Yugo Fujita, Shoya Ino, Masaki Shimizu, Yuki Toda, Wataru Ohwada, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, and Tetsuji Miura
Subjects: AMP deaminase, branched‐chain amino acids, branched‐chain α‐keto acid dehydrogenase, diabetic cardiomyopathy, Physiology, QP1-981
Abstract: Abstract Systemic branched‐chain amino acid (BCAA) metabolism is dysregulated in cardiometabolic diseases. We previously demonstrated that upregulated AMP deaminase 3 (AMPD3) impairs cardiac energetics in a rat model of obese type 2 diabetes, Otsuka Long‐Evans‐Tokushima fatty (OLETF). Here, we hypothesized that the cardiac BCAA levels and the activity of branched‐chain α‐keto acid dehydrogenase (BCKDH), a rate‐limiting enzyme in BCAA metabolism, are altered by type 2 diabetes (T2DM), and that upregulated AMPD3 expression is involved in the alteration. Performing proteomic analysis combined with immunoblotting, we discovered that BCKDH localizes not only to mitochondria but also to the endoplasmic reticulum (ER), where it interacts with AMPD3. Knocking down AMPD3 in neonatal rat cardiomyocytes (NRCMs) increased BCKDH activity, suggesting that AMPD3 negatively regulates BCKDH. Compared with control rats (Long‐Evans Tokushima Otsuka [LETO] rats), OLETF rats exhibited 49% higher cardiac BCAA levels and 49% lower BCKDH activity. In the cardiac ER of the OLETF rats, BCKDH‐E1α subunit expression was downregulated, while AMPD3 expression was upregulated, resulting in an 80% lower AMPD3‐E1α interaction compared to LETO rats. Knocking down E1α expression in NRCMs upregulated AMPD3 expression and recapitulated the imbalanced AMPD3‐BCKDH expressions observed in OLETF rat hearts. E1α knockdown in NRCMs inhibited glucose oxidation in response to insulin, palmitate oxidation, and lipid droplet biogenesis under oleate loading. Collectively, these data revealed previously unrecognized extramitochondrial localization of BCKDH in the heart and its reciprocal regulation with AMPD3 and imbalanced AMPD3‐BCKDH interactions in OLETF. Downregulation of BCKDH in cardiomyocytes induced profound metabolic changes that are observed in OLETF hearts, providing insight into mechanisms contributing to the development of diabetic cardiomyopathy.
Published: 2023
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13. Macrophage activation syndrome in systemic juvenile idiopathic arthritis

Author: Masaki Shimizu
Subjects: macrophage activation syndrome, interleukin-6, interleukin-18, interferon-γ, hemophagocytic lymphohistiocytosis, Immunologic diseases. Allergy, RC581-607
Abstract: Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of systemic juvenile idiopathic arthritis (s-JIA). An immunological feature is the excessive activation and proliferation of T lymphocytes and macrophages. Massive hypercytokinemia is strongly associated with its pathogenesis, particularly the overproduction of interleukin (IL)-1, IL-6 and IL-18; interferon (IFN)-γ; and tumor necrosis factor (TNF)-α. Furthermore, heterozygous mutations in causative genes for primary hemophagocytic lymphohistiocytosis and in vivo exposure to highly elevated levels of IL-6 and IL-18 might induce natural killer cell dysfunction and decrease their numbers, respectively. A proper diagnosis is important to begin appropriate therapeutic interventions and change an unfavorable prognosis. The 2016 ACR/EULAR classification criteria for MAS have a high diagnostic performance; however, the diagnostic sensitivity for onset is relatively low. Therefore, careful monitoring of laboratory values during the course of MAS is necessary to diagnose it early in s-JIA. Further studies on the diagnosis and monitoring of disease activity using serum cytokine profile and a targeted cytokine strategy are required.
Published: 2021
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14. Case report: Optimized ruxolitinib-based therapy in an infant with familial hemophagocytic lymphohistiocytosis type 3

Author: Daiki Niizato, Takeshi Isoda, Noriko Mitsuiki, Shuya Kaneko, Dan Tomomasa, Takahiro Kamiya, Masatoshi Takagi, Kohsuke Imai, Michiko Kajiwara, Masaki Shimizu, Tomohiro Morio, and Hirokazu Kanegane
Subjects: cytokine, familial hemophagocytic lymphohistiocytosis (FHL), HLH, hematopoietic cell transplantation (HCT), janus kinase, ruxolitinib, Immunologic diseases. Allergy, RC581-607
Abstract: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare and fatal autosomal recessive immune disorder characterized by uncontrolled activation of T and NK cells, macrophages, and overproduction of inflammatory cytokines. Early hematopoietic cell transplantation (HCT) is required for long-term survival. Current therapy is based on the HLH-94/2004 protocol, but is insufficient to fully control disease activity. This case report describes an infant with FHL type 3 who, despite initial therapy with dexamethasone and etoposide, showed aberrant cytokine levels, including interleukin-18 (IL-18), chemokine ligand 9 (CXCL9), soluble interleukin-2 receptor (sIL-2R), and soluble tumor necrosis factor receptor type II (sTNF-RII). The Janus kinase inhibitor ruxolitinib was therefore coadministered. The patient was treated with dose-adjusted ruxolitinib guided by cytokine profiles, and was successfully prepared for HCT. The results demonstrate the effectiveness and safety of dose-adjusted ruxolitinib as a bridging therapy for FHL, and the value of monitoring cytokine levels, especially IL-18, CXCL9, sIL-2R, and sTNF-RII, as disease-activity markers for FHL.
Published: 2022
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15. Rationale and design of a multicenter, double-blinded, randomized, placebo-controlled trial to investigate the effects of naldemedine on opioid-induced constipation for patients with cancer pain: A study protocol

Author: Takahiro Higashibata, Jun Hamano, Takaomi Kessoku, Shinya Kajiura, Mami Hirakawa, Yoshiki Horie, Masaki Shimizu, Shunsuke Oyamada, Keisuke Ariyoshi, Kota Kihara, Yohei Yamanaka, Kumi Konishi, Kosuke Doki, Yasuyuki Takashima, Manabu Horiuchi, Masato Homma, Takeshi Yamada, Yoshiyuki Yamamoto, Toshikazu Moriwaki, Tatsuya Morita, Atsushi Nakajima, and Hiroka Nagaoka
Subjects: Opioid-induced constipation, Naldemedine, Prevention, Randomized controlled trial, Medicine (General), R5-920
Abstract: Background: It is unclear which laxatives are appropriate to prevent opioid-induced constipation (OIC). This study will evaluate whether prophylactic use of naldemedine prevents OIC in patients with cancer who start opioid administration. Methods: This study is a multicenter, double-blinded, randomized, placebo-controlled trial. Patients who meet the eligibility criteria and give consent will be randomly assigned to the naldemedine or placebo group. Both groups will take each drug once a day after breakfast for 14 days. Results: The primary endpoint is the proportion of patients with a Bowel Function Index of less than 28.8 on Day 14. The secondary endpoints include assessment scales of the impact of constipation on comprehensive quality of life. Conclusions: This is the first study proposed to assess the superiority of naldemedine over placebo in the prevention of OIC. If naldemedine is found to be effective in reducing OIC compared with the placebo, it will be regarded as a new standard for OIC prophylaxis at opioid initiation. Trial registration: jRCT identifier: jRCTs031200397. Registered March 5, 2021, https://rctportal.niph.go.jp/en/detail?trial_id=jRCTs031200397.
Published: 2022
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16. Pathogenic roles and diagnostic utility of interleukin-18 in autoinflammatory diseases

Author: Masaki Shimizu, Syuji Takei, Masaaki Mori, and Akihiro Yachie
Subjects: IL-18, systemic juvenile idiopathic arthritis, adult Still's disease, inflammasomes, NLRC4, pyogenic sterile arthritis, Immunologic diseases. Allergy, RC581-607
Abstract: Interleukin (IL)-18 is a pleiotropic, pro-inflammatory cytokine involved in the regulation of innate and adaptive immune responses. IL-18 has attracted increasing attention as a key mediator in autoinflammatory diseases associated with the development of macrophage activation syndrome (MAS) including systemic juvenile idiopathic arthritis and adult-onset Still’s disease. In these diseases, dysregulation of inflammasome activity and overproduction of IL-18 might be associated with the development of MAS by inducing natural killer cell dysfunction. Serum IL-18 levels are high in patients with these diseases and therefore are useful for the diagnosis and monitoring of disease activity. In contrast, a recent study revealed the overproduction of IL-18 was present in cases of autoinflammation without susceptibility to MAS such as pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. The pathogenic and causative roles of IL-18 remain unclear in these autoinflammatory diseases. Further investigations are necessary to clarify the role of IL-18 and its importance as a therapeutic target in the pathogenesis of autoinflammatory diseases.
Published: 2022
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17. Assessment of type I interferon signatures in undifferentiated inflammatory diseases: A Japanese multicenter experience

Author: Takayuki Miyamoto, Yoshitaka Honda, Kazushi Izawa, Nobuo Kanazawa, Saori Kadowaki, Hidenori Ohnishi, Masakazu Fujimoto, Naotomo Kambe, Naoya Kase, Takeshi Shiba, Yasuo Nakagishi, Shuji Akizuki, Kosaku Murakami, Masahiro Bamba, Yutaka Nishida, Ayano Inui, Tomoo Fujisawa, Daisuke Nishida, Naomi Iwata, Yoshikazu Otsubo, Shingo Ishimori, Momoko Nishikori, Kiminobu Tanizawa, Tomoyuki Nakamura, Takeshi Ueda, Yoko Ohwada, Yu Tsuyusaki, Masaki Shimizu, Takasuke Ebato, Kousho Iwao, Akiharu Kubo, Toshinao Kawai, Tadashi Matsubayashi, Tatsuhiko Miyazaki, Tomohiro Kanayama, Masahiko Nishitani-Isa, Hiroshi Nihira, Junya Abe, Takayuki Tanaka, Eitaro Hiejima, Satoshi Okada, Osamu Ohara, Megumu K. Saito, Junko Takita, Ryuta Nishikomori, and Takahiro Yasumi
Subjects: interferon, interferon signature, interferonopathy, autoinflammation, A20 haploinsufficiency, pulmonary hemosiderosis, Immunologic diseases. Allergy, RC581-607
Abstract: PurposeUpregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature.MethodsThe type I IFN signature was measured in patients’ whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature.ResultsA total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling.ConclusionsHalf of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.
Published: 2022
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18. Does renin‐angiotensin system inhibition have impacts on muscle mass and bone mineral density in heart failure patients?

Author: Satoshi Katano, Toshiyuki Yano, Masaki Shimizu, Katsuhiko Ohori, Hidemichi Kouzu, Masayuki Koyama, Ryohei Nagaoka, Takuya Inoue, Yuhei Takamura, Tomoyuki Ishigo, Hiroyuki Takashima, Masaki Katayose, Hirofumi Ohnishi, and Tetsuji Miura
Subjects: Heart failure, Renin‐angiotensin system, Sarcopenia, Skeletal muscle, Osteoporosis, Propensity score matching, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Aims Results of experimental studies have indicated the possibility of muscle and bone mass being negatively regulated by renin‐angiotensin system (RAS) activation, but that possibility has not been analysed in patients with heart failure (HF). Methods and results Data for HF patients who received a dual‐energy X‐ray absorptiometry scan in our hospital were reviewed. Propensity scores for the use of RAS inhibitors (RASIs) were calculated using a multivariate logistic regression model to minimize selection bias. One hundred sixty pairs of patients were extracted. Plasma aldosterone concentration was significantly lower in the RASIs group than in the no‐RASIs group (119 [IQR 71–185] vs. 94 [IQR 60–131] pg/mL, P = 0.003), confirming RAS inhibition in the RASIs group. Skeletal muscle mass index tended to be higher in the RASIs group than in the non‐RASIs group (15.6 [IQR 14.0–17.2] vs. 15.0 [IQR 13.3–16.6] pg/mL, P = 0.065). The proportion of patients with muscle wasting, defined as appendicular skeletal muscle mass indexes of
Published: 2021
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19. Childhood‐onset systemic lupus erythematosus with trisomy X and the increased risk for bone complications: a case report

Author: Susumu Yamazaki, Yuko Akutsu, Asami Shimbo, Masaki Shimizu, Yuko Segawa, and Masaaki Mori
Subjects: Trisomy X, Systematic lupus erythematosus, Corticosteroids, Avascular necrosis, Osteoporosis, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Systemic lupus erythematosus is a multi-organ inflammatory autoimmune disease; immune complexes are part of the pathogenesis, but not entirely responsible. Trisomy X is the most common female chromosomal abnormality and the role of an additional X chromosome in the development of systemic lupus erythematosus is well recognized. However, the potential complications and optimal management of childhood lupus with trisomy X remain unclear. Herein, we describe a case of childhood-onset systemic lupus erythematosus associated with severe bone complications presumably secondary to trisomy X. Case presentation A 16-year-old Japanese girl was diagnosed with childhood-onset systemic lupus erythematosus and trisomy X. A chromosomal abnormality (47, XXX) was incidentally identified on bone marrow examination initially done to determine the cause of pancytopenia. She had a persistent headache, fever for six days, diffuse hair loss, mucosal ulcers, butterfly eruptions, and palmar erythema. Furthermore, thrombocytopenia, anemia, and erythrocyte fragmentation were detected, suggesting secondary thrombotic microangiopathy. She was initially treated with intravenous methylprednisolone pulse therapy and prescribed monthly cyclophosphamide for severe disease activity, prednisolone, mycophenolate mofetil, and hydroxychloroquine as remission maintenance drugs. She developed generalized extremity pain that had been worsening throughout the disease. Extremity magnetic resonance imaging performed 12 months after the treatment onset revealed multifocal avascular necrosis, and dual-energy X-ray absorptiometry revealed further decreased bone mineral density. High plasma levels of factor VIII were detected by additional tests for coagulation functions, and we suspected the possibility that factor VIII might cause avascular necrosis due to thrombosis. Currently, she is being treated with prednisolone and MMF for SLE. However, her extremity pain has not been managed effectively even under the administration of non-steroidal anti-inflammatory drugs and pregabalin. Conclusions An additional X chromosome has been reported to be associated with factor VIII and osteoporosis. Additionally, elevated plasma levels of FVIII is the risk factors for thrombosis, which leads to the risk of avascular necrosis. Patients with systemic lupus erythematosus complicated by trisomy X might be at a higher risk of avascular necrosis and osteoporosis that can also manifest in childhood systemic lupus erythematosus.
Published: 2021
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20. Serum insulin-like growth factor-binding protein 2 levels as an indicator for disease severity in enterohemorrhagic Escherichia coli induced hemolytic uremic syndrome

Author: Yuko Tasaki, Natsumi Inoue, Masaki Shimizu, Naotoshi Sugimoto, Sayaka Ishikawa, Mao Mizuta, Tadafumi Yokoyama, Mondo Kuroda, Kazuhide Ohta, Akihiro Yachie, and Taizo Wada
Subjects: insulin-like growth factor-binding protein 2, enterohemorrhagic escherichia coli, hemolytic uremic syndrome, biomarker, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Background Insulin-like growth factor-binding protein (IGFBP) 2 plays an important role in the regulation of cell adhesion, migration, growth, and apoptosis. This study aimed to investigate the clinical significance of serum IGFBP2 as a biomarker for disease activity and severity in hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli (EHEC). Methods IGFBP2 production by human renal glomerular endothelial cells (RGECs) after exposure to Shiga toxin 2 (Stx-2) was investigated in vitro. Serum IGFBP2 levels in blood samples obtained from 22 patients with HUS and 10 healthy controls (HCs) were quantified using an enzyme-linked immunosorbent assay. The results were compared to the clinical features of HUS and serum tau and cytokine levels. Results Stx-2 induced the production of IGFBP2 in RGECs in a dose-dependent manner. Serum IGFBP2 levels were significantly higher in patients with HUS than in HCs and correlated with disease severity. Additionally, serum IGFBP2 levels were significantly higher in patients with encephalopathy than in those without encephalopathy. A serum IGFBP2 level above 3585 pg/mL was associated with a high risk of encephalopathy. Furthermore, serum IGFBP2 levels significantly correlated with serum levels of tau and inflammatory cytokines associated with the development of HUS. Conclusions Correlation of serum IGFBP2 level with disease activity in patients with HUS suggests that IGFBP2 may be considered as a possible indicator for disease activity and severity in HUS. Larger studies and additional experiments using various cells in central nervous system should elucidate the true value of IGFBP2 as a clinical diagnostic marker. Abbreviations IGFBP: insulin-like growth factor-binding protein; HUS: hemolytic uremic syndrome; EHEC: enterohemorrhagic Escherichia coli; RGECs: renal glomerular endothelial cells; STx-2: Shiga toxin 2; HCs: healthy controls; LPS: lipopolysaccharide; ROC: receiver operating characteristic; sTNFR: soluble tumor necrosis factor receptor.
Published: 2021
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21. Organic fluorophores that emit ultraviolet light in the aggregated state

Author: Masaki Shimizu and Tsuneaki Sakurai
Subjects: conjugation, light‐emitting materials, molecular design, solid‐state emission, UV OLEDs, Chemistry, QD1-999, Biology (General), QH301-705.5
Abstract: Abstract Ultraviolet (UV)‐emissive organic light‐emitting diodes (OLEDs) have attracted growing attention as future UV‐lighting sources following UV‐LED. The design and development of highly efficient UV‐emissive organic solids are essential for the advancement of UV‐OLEDs. Reviewed herein are organic small molecules and polymers that exhibit UV emission in the aggregated state such as crystal, powder, and amorphous film. The UV‐emissive molecules are in principle limited to those whose photoluminescence (PL) maxima are less than 400 nm and whose PL quantum yields in the aggregated state, which are useful for evaluating the potential of solid‐state emitters, are reported. In cases that electroluminescence (EL) studies are demonstrated, the emission maxima and external quantum efficiencies with the device structures are also shown. Some exceptions are also included whose PL quantum yields are not reported, but UV‐EL with an emission maximum of less than 400 nm is demonstrated.
Published: 2022
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22. Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Author: Masaki Shimizu, Mao Mizuta, Nami Okamoto, Takahiro Yasumi, Naomi Iwata, Hiroaki Umebayashi, Yuka Okura, Noriko Kinjo, Tomohiro Kubota, Yasuo Nakagishi, Kenichi Nishimura, Mariko Mohri, Masato Yashiro, Junko Yasumura, Hiroyuki Wakiguchi, and Masaaki Mori
Subjects: Macrophage activation syndrome, Systemic juvenile idiopathic arthritis, Tocilizumab, Classification criteria, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background This study aimed to determine the influence of tocilizumab (TCZ) in modifying the clinical and laboratory features of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Furthermore, we assessed the performance of the 2016 MAS classification criteria for patients with s-JIA-associated MAS while treated with TCZ. Methods A panel of 15 pediatric rheumatologists conducted a combination of expert consensus and analysis of real patient data. Clinical and laboratory features of s-JIA-associated MAS in 12 TCZ-treated patients and 18 untreated patients were evaluated. Possible MAS was defined as having characteristic laboratory features but lack of clinical features of MAS, or atypical MAS, or early treatment that prevented full-blown MAS. Results Clinically, the TCZ-treated patients with s-JIA-associated MAS were less likely febrile and had significantly lower ferritin, triglyceride, and CRP levels than the untreated patients with s-JIA-associated MAS. Other laboratory features of MAS including lower platelet counts and lower fibrinogen were more pronounced in TCZ-treated patients. The TCZ-treated patients with s-JIA-associated MAS were less likely to be classified as MAS based on the MAS classification criteria (25% vs 83.3%, p
Published: 2020
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23. Bedside Ultrasonography in Evaluating Mediastinum Leakage in an Extremely-Low-Birth-Weight Infant with Esophageal Perforation

Author: Mitsuhiro Haga, Yumiko Sato, Tomo Kakihara, Wakako Sumiya, Masayuki Kanno, Tetsuya Ishimaru, Masaki Shimizu, and Hiroshi Kawashima
Subjects: esophageal perforation, mediastinum leakage, ultrasonography, extremely-low-birth-weight infant, Gynecology and obstetrics, RG1-991
Abstract: Esophageal perforation in premature infants is a life-threatening condition that requires prompt treatment. Contrast-enhanced computed tomography (CECT) is recommended for diagnosis. However, it is difficult to obtain CECT images in premature infants because of their unstable conditions. We encountered a case of esophageal perforation in an extremely-low-birth-weight female infant. Bedside ultrasonography was useful in the diagnosis and follow-up evaluation of leakage in the mediastinum. Ultrasonography can be a useful modality for the evaluation of perforation of the lower part of the esophagus in premature infants.
Published: 2022
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24. Utility and safety of tocilizumab in Takayasu arteritis with severe heart failure and muscle wasting

Author: Toshiyuki Yano, Arata Osanami, Masaki Shimizu, Satoshi Katano, Nobutaka Nagano, Hidemichi Kouzu, Masayuki Koyama, Atsuko Muranaka, Ryo Harada, Hirosato Doi, Nobuyoshi Kawaharada, and Tetsuji Miura
Subjects: Takayasu arteritis, Tocilizumab, Interleukin‐6, Heart failure, Aortic regurgitation, Sarcopenia, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Takayasu arteritis (TA) is a large vessel vasculitis of unknown aetiology characterized by chronic inflammatory changes of the aorta and its major branches. We report the active TA case who had severe heart failure due to acute myocardial infarction and aortic regurgitation. Bentall procedure was successfully performed, but he had severely depressed left ventricular function and muscle wasting together with vascular inflammation. The treatment with tocilizumab, an interleukin‐6 receptor monoclonal antibody, in addition to prednisolone and standard heart failure therapy led to prompt remission of TA activity and improvement of left ventricular function and muscle wasting. Taken together with possible involvement of interleukin‐6 in the pathogenesis of heart failure and muscle wasting, inhibition of interleukin‐6 receptor signalling by tocilizumab may be a safe and reasonable approach in the treatment of active TA with heart failure and muscle wasting.
Published: 2019
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25. Clinical features and characteristics of uveitis associated with juvenile idiopathic arthritis in Japan: first report of the pediatric rheumatology association of Japan (PRAJ)

Author: Junko Yasumura, Masato Yashiro, Nami Okamoto, Kosuke Shabana, Hiroaki Umebayashi, Naomi Iwata, Yuka Okura, Tomohiro Kubota, Masaki Shimizu, Minako Tomiita, Yasuo Nakagishi, Kenichi Nishimura, Ryoki Hara, Mao Mizuta, Takahiro Yasumi, Fumiya Yamaide, Hiroyuki Wakiguchi, Masao Kobayashi, and Masaaki Mori
Subjects: Juvenile idiopathic arthritis, Uveitis, Epidemiology, Asian, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Although there are many reports on Juvenile Idiopathic arthritis-associated uveitis (JIA-U) from various countries, especially from Europe and North America, there are few reports from Asia. Our aim was to investigate the epidemiology, characteristics and predictors of JIA-U in Japan. Methods Data were retrospectively collected on 726 patients with JIA from medical records as of April 2016 at 15 medical centers specialized in pediatric rheumatic diseases. Of these, patients with uveitis were further investigated for the specific characteristics of this manifestation. Results The prevalence of uveitis was 6.1% in the 726 JIA patients examined. Incidence of uveitis was significantly higher in patients with an earlier arthritis onset (2.6-vs.-5.8 years, P
Published: 2019
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26. Clinical Significance of Serum Soluble TNF Receptor I/II Ratio for the Differential Diagnosis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome From Other Autoinflammatory Diseases

Author: Junko Yasumura, Masaki Shimizu, Tomoko Toma, Masato Yashiro, Akihiro Yachie, and Satoshi Okada
Subjects: familial Mediterranean fever, Kawasaki disease (KD), soluble tumor necrosis factor receptor, systemic juvenile idiopathic arthritis (sJIA), tumor necrosis factor receptor associated periodic syndrome (TRAPS), Immunologic diseases. Allergy, RC581-607
Abstract: Objectives: Genetic analysis of TNFRSF1A can confirm the diagnosis of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), but interpretation of the pathogenesis of variants of unknown significance is sometimes required. The aim of this study was to evaluate the clinical significance of serum soluble tumor necrosis factor receptor type I (sTNFR-I)/II ratio to differentiate TRAPS from other autoinflammatory diseases.Methods: Serum sTNFR-I and sTNFR-II levels were measured using an enzyme-linked immunosorbent assay in patients with TRAPS (n = 5), familial Mediterranean fever (FMF) (n = 14), systemic juvenile idiopathic arthritis (s-JIA) (n = 90), and Kawasaki disease (KD) (n = 37) in the active and inactive phase, along with healthy controls (HCs) (n = 18).Results: In the active phase, the serum sTNFR-I/II ratio in patients with s-JIA, KD, and FMF was significantly elevated compared with that in HCs, whereas it was not elevated in patients with TRAPS. In the inactive phase, the serum sTNFR-I/II ratio in patients with s-JIA and FMF was significantly higher compared with that in HCs, and the ratio was lower in TRAPS patients than in patients with s-JIA and FMF.Conclusions: Low serum sTNFR-I/II ratio in the active and inactive phase might be useful for the differential diagnosis of TRAPS and other autoinflammatory diseases.
Published: 2020
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27. Lipiodol lymphangiography in a very low birth weight premature infant

Author: Mitsuhiro Haga, MD, Motoi Kato, Masami Kanno, Masaki Shimizu, and Shoji Watanabe
Subjects: Chylothorax, Lipiodol lymphangiography, Very-low-birth-weight infant, Pediatrics, RJ1-570, Surgery, RD1-811
Abstract: The efficacy and safety of therapeutic lipiodol lymphangiography have been reported by several studies. However, to our knowledge, no study has reported the use of this procedure in very-low-birth-weight infants. We present a case of an extremely-low-birth-weight infant girl who developed chylothorax on day 34 that was refractory to medical treatment. We performed therapeutic lipiodol lymphangiography on day 59 when her body weight was 800 g. Six days after the procedure, her pleural effusion suddenly decreased, and the chest tube was removed on day 67. No complications occurred.
Published: 2020
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28. Clinical Significance of Serum Galactose-Deficient IgA1 Level in Children with IgA Nephropathy

Author: Hitoshi Irabu, Masaki Shimizu, Shuya Kaneko, Natsumi Inoue, Mao Mizuta, Kazuhide Ohta, and Akihiro Yachie
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: This study was aimed at investigating the clinical significance of serum galactose-deficient IgA1 (Gd-IgA1) levels measured by a novel lectin-independent enzyme-linked immunosorbent assay (ELISA) using an anti-Gd-IgA1 monoclonal antibody (KM55) as a disease-specific biomarker for IgA nephropathy (IgAN) in children. Thirty-three children with IgAN, 40 with non-IgA glomerular diseases, and 38 age-matched healthy controls (HCs) were enrolled. Serum Gd-IgA1 levels were quantified by ELISA using KM55. Results were statistically compared with clinical features and pathological findings of IgAN. Serum Gd-IgA1 levels were significantly elevated in children with IgAN compared with children with non-IgA glomerular diseases and HCs. Serum Gd-IgA1 levels in children with IgAN were positively correlated with serum total IgA levels. However, the serum Gd-IgA1/total IgA ratio (Gd-IgA1/IgA) was also significantly elevated in children with IgAN. Serum Gd-IgA1 levels in children with IgAN increased in an age-dependent manner. The cutoff value of serum Gd-IgA1 levels for differentiating IgAN from non-IgA glomerular diseases was 3236 in children
Published: 2020
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29. Kawasaki Disease with an Initial Manifestation Mimicking Bacterial Inguinal Cellulitis

Author: Tsukasa Tanaka, Masaki Shimizu, Oshi Tokuda, Hiroko Yamamoto, Natsuki Matsunoshita, Kanae Takenaka, and Keiichiro Kawasaki
Subjects: Pediatrics, RJ1-570
Abstract: Background. Kawasaki disease (KD) is typically characterized by fever, oral cavity erythematous changes, bilateral bulbar conjunctival injection, skin rash, erythema and edema of the hands and feet, and cervical lymphadenopathy. Some atypical patients with KD initially develop cervical and pharyngeal cellulitis; however, an initial presentation with inguinal cellulitis is extremely rare. In addition, to our knowledge, no report has documented the cytokine profile in a KD patient with cellulitis. Case presentation. A previously healthy 8-year-old Japanese girl was hospitalized following a 2-day history of fever and a 5-day history of pain and erythema in the left inguinal region. She was diagnosed with bacterial inguinal cellulitis and was administered antibiotics. The next day, a polymorphous rash emerged on her trunk. After 3 days of antibiotics, however, her fever continued and the cellulitis had spread over the entire lower abdomen. Simultaneously, the bilateral bulbar conjunctival injection without exudate became more prominent and her lips became erythematous. In addition, erythematous changes on her palms appeared a few hours later, which led to the diagnosis of KD. Since she had a high risk score that predicted no response to initial intravenous immunoglobulin (IVIG) at the initiation of treatment, she was treated with IVIG, intravenous prednisolone (PSL), and oral aspirin. The KD symptoms improved the next day, but the cellulitis did not completely resolve until 2 months after discharge. The patient’s serum cytokine profile at admission had an IL-6 dominant pattern which was consistent with that of patients with KD despite her initial lack of KD symptoms, and the pattern observed at admission was sustained until IVIG and PSL administration. Conclusion. KD should be included in the differential diagnosis for patients presenting with inguinal cellulitis who are unresponsive to initial empiric antibiotics.
Published: 2020
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30. Remarkable Increase of Fluorescence Quantum Efficiency by Cyano Substitution on an ESIPT Molecule 2-(2-Hydroxyphenyl)benzothiazole: A Highly Photoluminescent Liquid Crystal Dopant

Author: Tsuneaki Sakurai, Masaya Kobayashi, Hiroyuki Yoshida, and Masaki Shimizu
Subjects: cyano group, ESIPT, fluorescence, host–guest liquid crystal, luminescent liquid crystal, Crystallography, QD901-999
Abstract: Fluorescent molecules with excited-state intramolecular proton transfer (ESIPT) character allow the efficient solid-state luminescence with large Stokes shift that is important for various applications, such as organic electronics, photonics, and bio-imaging fields. However, the lower fluorescence quantum yields (ΦFL) in the solution or viscous media, due to their structural relaxations in the excited state to reach the S0/S1 conical intersection, shackle further applications of ESIPT-active luminophores. Here we report that the introduction of a cyano group (-CN) into the phenyl group of 2-(2-hydroxyphenyl)benzothiazole (HBT), a representative ESIPT compound, remarkably increase its fluorescence quantum yield (ΦFL) from 0.01 (without -CN) to 0.49 (with -CN) in CH2Cl2, without disturbing its high ΦFL (=0.52) in the solid state. The large increase of the solution-state ΦFL of the cyano-substituted HBT (CN-HBT) is remarkable, comparing with our previously reported ΦFL values of 0.05 (with 4-pentylphenyl), 0.07 (with 1-hexynyl), and 0.15 (with 4-pentylphenylethynyl). Of interest, the newly-synthesized compound, CN-HBT, is miscible in a conventional room-temperature nematic liquid crystal (LC), 4-pentyl-4′-cyano biphenyl (5CB), up to 1 wt% (~1 mol%), and exhibits a large ΦFL of 0.57 in the viscous LC medium. A similar ΦFL value of ΦFL = 0.53 was also recorded in another room-temperature LC, trans-4-(4-pentylcyclohexyl)benzonitrile (PCH5), with a doping ratio of 0.5 wt% (~0.5 mol%). These 5CB/CN-HBT and PCH5/CN-HBT mixtures serve as light-emitting room-temperature LCs, and show anisotropic fluorescence with the dichroic ratio of 3.1 upon polarized excitation, as well as electric field response of luminescence intensity changes.
Published: 2021
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31. Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part one

Author: F. De Benedetti, J. Anton, M. Gattorno, H. Lachmann, I. Kone-Paut, S. Ozen, J. Frenkel, A. Simon, A. Zeft, E. Ben-Chetrit, H. M. Hoffman, Y. Joubert, K. Lheritier, A. Speziale, J. Guido, Roberta Caorsi, Federica Penco, Alice Grossi, Antonella Insalaco, Maria Alessio, Giovanni Conti, Federico Marchetti, Alberto Tommasini, Silvana Martino, Romina Gallizzi, Annalisa Salis, Francesca Schena, Francesco Caroli, Alberto Martini, Gianluca Damonte, Isabella Ceccherini, Marco Gattorno, Marie-Louise Frémond, Carolina Uggenti, Lien Van Eyck, Isabelle Melki, Darragh Duffy, Vincent Bondet, Yoann Rose, Bénédicte Neven, Yanick Crow, Mathieu P. Rodero, Yvonne Kusche, Johannes Roth, Katarzyna Barczyk-Kahlert, Giovanna Ferrara, Annalisa Chiocchetti, Silvio Polizzi, Josef Vuch, Diego Vozzi, Anna Mondino, Erica Valencic, Serena Pastore, Andrea Taddio, Flavio Faletra, Umberto Dianzani, Ugo Ramenghi, Qing Zhou, Xiaomin Yu, Erkan Demirkaya, Natalie Deuitch, Deborah Stone, Wanxia Tsai, Amanda Ombrello, Tina Romeo, Elaine F. Remmers, JaeJin Chae, Massimo Gadina, Steven Welch, Seza Ozen, Rezan Topaloglu, Mario Abinun, Daniel L. Kastner, Ivona Aksentijevich, Donatella Vairo, Rosalba Monica Ferraro, Giulia Zani, Jessica Galli, Micaela De Simone, Marco Cattalini, Elisa Fazzi, Silvia Giliani, Ebun Omoyinmi, Ariane Standing, Dorota Rowczenio, Annette Keylock, Sonia Melo Gomes, Fiona Price-Kuehne, Sira Nanthapisal, Claire Murphy, Thomas Cullup, Lucy Jenkins, Kimberly Gilmour, Despina Eleftheriou, Helen Lachmann, Philip Hawkins, Nigel Klein, Paul Brogan, Anita Dhanrajani, Mercedes Chan, Stephanie Pau, Janet Ellsworth, Jaime Guzman, Florence A. Aeschlimann, Marinka Twilt, Simon W. Eng, Shehla Sheikh, Ronald M. Laxer, Diane Hebert, Damien Noone, Christian Pagnoux, Susanne M. Benseler, Rae S. Yeung, Christoph Kessel, Katrin Lippitz, Toni Weinhage, Claas Hinze, Helmut Wittkowski, Dirk Holzinger, Niklas Grün, Dirk Föll, Pieter Van Dijkhuizen, Federica Del Chierico, Clara Malattia, Alessandra Russo, Denise Pires Marafon, Nienke M. ter Haar, Silvia Magni-Manzoni, Sebastiaan J. Vastert, Bruno Dallapiccola, Berent Prakken, Fabrizio De Benedetti, Lorenza Putignani, Berna Eren Fidanci, Kenan Barut, Serap Arıcı, Dogan Simsek, Mustafa Cakan, Ezgi D. Batu, Sezgin Şahin, Ayşenur Kısaarslan, Ebru Yilmaz, Özge Basaran, Ferhat Demir, Kubra Ozturk, Zübeyde Gunduz, Betül Sozeri, Balahan Makay, Nuray Ayaz, Onder Yavascan, Ozlem Aydog, Yelda Bilginer, Zelal Ekinci, Dilek Yıldız, Faysal Gök, Muferret Erguven, Erbil Unsal, Ozgur Kasapcopur, For the FMF Arthritis Vasculitis and Orphan Disease Research in Paediatric Rheumatology (FAVOR), Hafize E. Sönmez, Betül Sözeri, Yonatan Butbul, Seza Özen, Claudia Bracaglia, Giusi Prencipe, Manuela Pardeo, Geneviève Lapeyre, Emiliano Marasco, Walter Ferlin, Robert Nelson, Cristina de Min, N. Ruperto, H. I. Brunner, P. Quartier, T. Constantin, E. Alexeeva, K. Marzan, N. Wulffraat, R. Schneider, S. Padeh, V. Chasnyk, C. Wouters, J. B. Kuemmerle-Deschner, T. Kallinich, B. Lauwerys, E. Haddad, E. Nasonov, M. Trachana, O. Vougiouka, K. Leon, E. Vritzali, A. Martini, D. Lovell, PRINTO/PRCSG, Stefano Volpi, Claudia Pastorino, Francesca Kalli, Alessia Omenetti, Sabrina Chiesa, Arinna Bertoni, Paolo Picco, Gilberto Filaci, Elisabetta Traggiai, Marie-Louise Fremond, Naoki Kitabayashi, Olivero Sacco, Isabelle Meyts, Marie-Anne Morren, Carine Wouters, Eric Legius, Isabelle Callebaut, Christine Bodemer, Frederic Rieux-Laucat, Mathieu Rodero, Nadia Jeremiah, Alexandre Belot, Eric Jeziorski, Didier Bessis, Guilhem Cros, Gillian I. Rice, Bruno Charbit, Anne Hulin, Nihel Khoudour, Consuelo Modesto Caballero, Monique Fabre, Laureline Berteloot, Muriel Le Bourgeois, Philippe Reix, Thierry Walzer, Despina Moshous, Stéphane Blanche, Alain Fischer, Brigitte Bader-Meunier, Frédéric Rieux-Laucat, K. Annink, N. ter Haar, S. Al-Mayouf, G. Amaryan, K. Barron, S. Benseler, P. Brogan, L. Cantarini, M. Cattalini, A. Cochino, F. Dedeoglu, A. De Jesus, O. Dellacasa, E. Demirkaya, P. Dolezalova, K. Durrant, G. Fabio, R. Gallizzi, R. Goldbach-Mansky, E. Hachulla, V. Hentgen, T. Herlin, M. Hofer, H. Hoffman, A. Insalaco, A. Jansson, I. Koné-Paut, A. Kozlova, J. Kuemmerle-Deschner, R. Laxer, S. Nielsen, I. Nikishina, A. Ombrello, E. Papadopoulou-Alataki, A. Ravelli, D. Rigante, R. Russo, Y. Uziel, Nienke ter Haar, Jerold Jeyaratnam, Anna Simon, Matteo Doglio, Jordi Anton, Consuelo Modesto, Pierre Quartier, Esther Hoppenreijs, Luca Cantarini, Loredana Lepore, Inmaculada Calvo Penades, Christina Boros, Rita Consolini, Donato Rigante, Ricardo Russo, Jana Pachlopnik Schmid, Thirusha Lane, Nicolino Ruperto, Joost Frenkel, Chiara Passarelli, Elisa Pisaneschi, Virginia Messia, Antonio Novelli, Fabrizio Debenedetti, P. A. Brogan, X. Wei, Martina Finetti, Francesca Orlando, Elisabetta Cortis, Angela Miniaci, Nicola Ruperto, Charlotte Eijkelboom, Pavla Dolezalova, Isabelle Koné-Paut, Marija Jelusic-Drazic, Liliana Bezrodnik, Mari Carmen Pinedo, Valda Stanevicha, Marielle van Gijn, Silvia Federici, Hermann Girschick, Gerd Ganser, Susan Nielsen, Troels Herlin, Sulaiman Mohammed Al-Mayouf, Michael Hofer, Jasmin Kuemmerle-Deschner, Susanne Schalm, Annette Jansson, on behalf of PRINTO and Eurofever registry, Marta Marchi, Chiara Marini, Angelo Ravelli, Alberto Garaventa, Sonia Carta, Enrica Balza, Patrizia Castellani, Caterina Pellecchia, Silvia Borghini, Maria Libera Trotta, Anna Rubartelli, Andrew Henrey, Thomas Loughin, Roberta Berard, Natalie Shiff, Roman Jurencak, Susanne Benseler, Lori Tucker, on behalf of ReACCh-Out Investigators, Charalampia Papadopoulou, Ying Hong, Petra Krol, Yiannis Ioannou, Clarissa Pilkington, Hema Chaplin, Stephania Simou, Marietta Charakida, Lucy Wedderburn, Lynn R. Spiegel, Sara Ahola Kohut, Jennifer Stinson, Paula Forgeron, Miriam Kaufman, Nadia Luca, Khush Amaria, Mary Bell, J Swart, F. Boris, E. Castagnola, A. Groll, G. Giancane, G. Horneff, H. I. Huppertz, T. Wolfs, E. Alekseeva, V. Panaviene, F. Uettwiller, V. Stanevicha, L. M. Ailioaie, E. Tsitami, S. Kamphuis, G. Susic, F. Sztajnbok, B. Flato, A. Pistorio, Stephanie J. W. Shoop, Suzanne M. M. Verstappen, Janet E. McDonagh, Wendy Thomson, Kimme L. Hyrich, CAPS, Maarit Tarkiainen, Pirjo Tynjala, Pekka Lahdenne, Janne Martikainen, Acute-JIA Study Group, Meredyth Wilkinson, Christopher Piper, Georg Otto, Claire T. Deakin, Stefanie Dowle, Stefania Simou, Daniel Kelberman, Claudia Mauri, Elizabeth Jury, David Isenberg, Lucy R. Wedderburn, Kiran Nistala, I. Foeldvari, D. J. Lovell, G. Simonini, M. Bereswill, J. Kalabic, Kiem Oen, Brian M. Feldman, Brenden Dufault, Jennifer Lee, Karen Watanabe Duffy, Ciaran Duffy, ReACCh-Out Investigators, N. Tzaribachev, G. Vega-Cornejo, I. Louw, A. Berman, I. Calvo, R. Cuttica, F. Avila-Zapata, R. Cimaz, E. Solau-Gervais, R. Joos, G. Espada, X. Li, M. Nys, R. Wong, S. Banerjee, For Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology Collaborative Study Group (PRCSG), Rebecca Nicolai, Margherita Verardo, Adele D’Amico, Luisa Bracci-Laudiero, Gian Marco Moneta, Gillian Rice, Anne-Laure Mathieu, Sulliman O. Omarjee, Tracy A. Briggs, James O’Sullivan, Simon Williams, Rolando Cimaz, Eve Smith, Michael W. Beresford, Yanick J. Crow, GENIAL Investigators, UK JSLE Study Group, Madeleine Rooney, Nick Bishop, joyce davidson, Clarissa pilkington, Michael Beresford, Jacqui Clinch, Rangaraj Satyapal, Helen Foster, Janet Gardner Medwin, Janet McDonagh, Sue Wyatt, On Behalf of the British Society for Paediatric and Adolescent Rheumatology, Valentina Litta Modignani, Francesco Baldo, Stefano Lanni, Alessandro Consolaro, Giovanni Filocamo, Helen J. Lachmann, on behalf of Eurofever Registry, Gianmarco Moneta, Camilla Celani, Bilade Cherqaoui, Linda Rossi-Semerano, Perrine Dusser, Véronique Hentgen, Claire Grimwood, Linda Rossi, Isabelle Kone Paut, Veronique Hentgen, Denise Lasigliè, Denise Ferrera, Giulia Amico, Marco Di Duca, Laura Obici, Roberto Ravazzolo, Ryuta Nishikomori, Juan Arostegui, Andrea Petretto, Chiara Lavarello, Elvira Inglese, Federica Vanoni, Michaël Hofer, on behalf of EUROFEVER PROJECT, P. N. Hawkins, T. van der Poll, U. A. Walker, H. H. Tilson, Pascal N. Tyrrell, Raphaela Goldbach-Mansky, Norbert Blank, Hal M. Hoffman, Elisabeth Weissbarth-Riedel, Boris Huegle, Tilmann Kallinich, Ahmet Gul, Marlen Oswald, Fatma Dedeoglu, Aki Hanaya, Takako Miyamae, Manabu Kawamoto, Yumi Tani, Takuma Hara, Yasushi Kawaguchi, Satoru Nagata, Hisashi Yamanaka, Almira Ćosićkić, Fahrija Skokić, Belkisa Čolić, Sanimir Suljendić, Anna Kozlova, Irina Mersiyanova, Mariya Panina, Lily Hachtryan, Vasiliy Burlakov, Elena Raikina, Alexey Maschan, Anna Shcherbina, Banu Acar, Meryem Albayrak, Betul Sozeri, Sezgin Sahin, Amra Adrovic, Nese Inan, Serhan Sevgi, Caroline M. Andreasen, Anne Grethe Jurik, Mia B. Glerup, Christian Høst, Birgitte T. Mahler, Ellen-Margrethe Hauge, Cecilia Lazea, Laura Damian, Calin Lazar, Rodica Manasia, Chloe M. Stephenson, Vimal Prajapati, Paivi M. Miettunen, Dilek Yılmaz, Yavuz Tokgöz, Yasin Bulut, Harun Çakmak, Ferah Sönmez, Elif Comak, Gülşah Kaya Aksoy, Mustafa Koyun, Sema Akman, Yunus Arıkan, Ender Terzioğlu, Osman Nidai Özdeş, İbrahim Keser, Hüseyin Koçak, Ayşen Bingöl, Aygen Yılmaz, Reha Artan, X. Xu, Fatemeh F. Mehregan, Vahid Ziaee, Mohammad H. Moradinejad, Francesco La Torre, Clotilde Alizzi, Pio D’Adamo, G. Junge, J. Gregson, Hasmik Sargsyan, Hulya Zengin, Berna E. Fidanci, Cagla Kaymakamgil, Dilek Konukbay, Dilek Yildiz, Faysal Gok, Iris Stoler, Judith Freytag, Banu Orak, Christine Seib, Lars Esmann, Eva Seipelt, Faekah Gohar, Dirk Foell, Ismail Dursun, Sebahat Tulpar, Sibel Yel, Demet Kartal, Murat Borlu, Funda Bastug, Hakan Poyrazoglu, Zubeyde Gunduz, Kader Kose, Mehmet E. Yuksel, Abdullah Calıskan, Ahmet B. Cekgeloglu, Ruhan Dusunsel, Katerina Bouchalova, Jana Franova, Marcel Schuller, Marie Macku, Katerina Theodoropoulou, Raffaella Carlomagno, Annette von Scheven-Gête, Claudia Poloni, Laura O. Damian, Dan Cosma, Amanda Radulescu, Dan Vasilescu, Liliana Rogojan, Simona Rednic, Mihaela Lupse, Lien De Somer, Pierre Moens, Rocio Galindo Zavala, Laura Martín Pedraz, Esmeralda Núñez Cuadros, Gisela Díaz-Cordovés Rego, Antonio L. Urda Cardona, Ilaria Dal Forno, Sara Pieropan, Ombretta Viapiana, Davide Gatti, Gloria Dallagiacoma, Paola Caramaschi, Domenico Biasi, Daniel Windschall, Ralf Trauzeddel, Hartwig Lehmann, Rainer Berendes, Maria Haller, Manuela Krumrey-Langkammerer, Antje Nimtz-Talaska, Philipp Schoof, Ralf Felix Trauzeddel, Christine Nirschl, Estefania Quesada-Masachs, Carla Aguilar Blancafort, Sara Marsal Barril, Francisca Aguiar, Rita Fonseca, Duarte Alves, Ana Vieira, Alberto Vieira, Jorge A. Dias, Iva Brito, Gordana Susic, Vera Milic, Goran Radunovic, Ivan Boricic, Pauline Marteau, Catherine Adamsbaum, Michel De Bandt, Irène Lemelle, Chantal Deslandre, Tu Anh Tran, Anne Lohse, Elisabeth Solau-Gervais, Pascal Pillet, Julien Wipff, Cécile Gaujoux-Viala, Sylvain Breton, Valérie Devauchelle-Pensec, Sandra Gran, Olesja Fehler, Stefanie Zenker, Michael Schäfers, Thomas Vogl, Severine Guillaume Czitrom, EH Pieter Van Dijkhuizen, Silvia Magni Manzoni, Francesca Magnaguagno, Laura Tanturri de Horatio, Nienke M. Ter Haar, Annemieke S. Littooij, Vitor A. Teixeira, Raquel Campanilho-Marques, Ana F. Mourão, Filipa O. Ramos, Manuela Costa, Wafa A. Madan, Orla G. Killeen, Adriana Rodriguez Vidal, Diana Sueiro Delgado, Maria Isabel Gonzalez Fernandez, Berta Lopez Montesinos, Aleksey Kozhevnikov, Nina Pozdeeva, Mikhail Konev, Evgeniy Melchenko, Vladimir Kenis, Gennadiy Novik, Aysenur Pac Kısaarslan, Butsabong Lerkvaleekul, Suphaneewan Jaovisidha, Witaya Sungkarat, Niyata Chitrapazt, Praman Fuangfa, Thumanoon Ruangchaijatuporn, Soamarat Vilaiyuk, Dan Ø. Pradsgaard, Arne Hørlyck, Anne H. Spannow, Carsten W. Heuck, Talia Diaz, Fernando Garcia, Lorenia De La Cruz, Nadina Rubio, Joanna Świdrowska-Jaros, Elzbieta Smolewska, Mirta Lamot, Lovro Lamot, Mandica Vidovic, Edi Paleka Bosak, Ivana Rados, Miroslav Harjacek, Nikolay Tzaribachev, Polymnia Louka, Romiesa Hagoug, Chiara Trentin, Olga Kubassova, Mark Hinton, Mikael Boesen, Olena A. Oshlianska, Illya A. Chaikovsky, G. Mjasnikov, A. Kazmirchyk, Umberto Garagiola, Irene Borzani, Paolo Cressoni, Fabrizia Corona, Eszter Dzsida, Giampietro Farronato, Antonella Petaccia, Alenka Gagro, Agneza Marija Pasini, Goran Roic, Ozren Vrdoljak, Lucija Lujic, Matija Zutelija-Fattorini, Monika M. Esser, Deepthi R. Abraham, Craig Kinnear, Glenda Durrheim, Mike Urban, Eileen Hoal, Victoria B. Nikolayenko, Kubilay Şahin, Yasar Karaaslan, Adele Civino, Giovanni Alighieri, Sergio Davì, Roberto Rondelli, Andrea Magnolato, Francesca Ricci, Alma Olivieri, Valeria Gerloni, Bianca Lattanzi, Francesca Soscia, Alessandro De Fanti, Stefania Citiso, Lorenzo Quartulli, Maria Cristina Maggio, Manuela Marsili, Maria Antonietta Pelagatti, Valentino Conter, Franca Fagioli, Andrea Pession, Marco Garrone, Mariangela Rinaldi, Jaime De Inocencio, Stella Garay, Daniel J. Lovell, Berit Flato, EPOCA Study Group, Angela Aquilani, Simona Cascioli, Ivan Caiello, Denise Pires-Marafón, Rita Carsetti, Emily Robinson, Salvatore Albani, Wilco de Jager, Sytze de Roock, Trang Duong, Justine Ellis, Kimme Hyrich, Laetitia Jervis, Daniel Lovell, Lucy Marshall, Elizabeth D. Mellins, Kirsten Minden, Jane Munro, Peter A. Nigrovic, Jason Palman, Sunil Sampath, Laura E. Schanberg, Susan D. Thompson, Richard Vesely, Chris Wallace, Chris Williams, Qiong Wu, Nico Wulffraat, Rae S. M. Yeung, M. B. Seyger, D. Arikan, J. K. Anderson, A. Lazar, D. A. Williams, C. Wang, R. Tarzynski-Potempa, J. S. Hymans, Gabriele Simonini, Erika Scoccimarro, Irene Pontikaki, Teresa Giani, Alessandro Ventura, Pier Luigi Meroni, Gaetana Minnone, Marzia Soligo, Luigi Manni, Luisa Bracci Laudiero, Noortje Groot, I. Grein, N. M. Wulffraat, R. Schepp, G. Berbers, C. C. Barbosa Sandoval de Souza, V. Paes Leme Ferriani, G. Pileggi, S. de Roock, Ingrid H. R. Grein, Silvia Scala, Elisa Patrone, Casper Schoemaker, on behalf of Dutch JIA patient organization, Wendy Costello, on behalf of ENCA, Suzanne Parsons, Jean-David Cohen, Damien Bentayou, Marc-Antoine Bernard Brunel, Sonia Trope, Jens Klotsche, Miriam Listing, Martina Niewerth, Gerd Horneff, Angelika Thon, Hans-Iko Huppertz, Kirsten Mönkemöller, Ivan Foeldvari, ICON study group, Achille Marino, Stefano Stagi, Niccolò Carli, Federico Bertini, Adriana S. Díaz-Maldonado, Sally Pino, Pilar Guarnizo, Alfonso Ragnar Torres-Jimenez, Berenice Sanchez-Jara, Eunice Solis-Vallejo, Adriana Ivonne Cespedes-Cruz, Maritza Zeferino-Cruz, Julia Veronica Ramirez-Miramontes, Ankur Kumar, Anju Gupta, Deepti Suri, Amit Rawat, Nandita Kakkar, Surjit Singh, Özge A. Gücenmez, Erbil Ünsal, Bo Magnusson, Karina Mördrup, Anna Vermé, Christina Peterson, Board of the Swedish Pediatric Rheumatology Registry, Caroline Freychet, Jean Louis Stephan, Cathryn E. Harkness, Leanne Foster, Emma Henry, Pauline Taggart, Coskun F. Ozkececi, Esra Kurt, Gokalp Basbozkurt, Daiva Gorczyca, Jacek Postępski, Aleksandra Czajkowska, Bogumiła Szponar, Mariola Paściak, Anna Gruenpeter, Iwona Lachór-Motyka, Daria Augustyniak, Edyta Olesińska, Emediong S. Asuka, Tatyana Golovko, Samuel U. Aliejim, Emilio Inarejos Clemente, Estibaliz Iglesias Jimenez, Joan Calzada Hernandez, Sergi Borlan Fernandez, Clara Gimenez Roca, David Moreno Romo, Natalia Rodriguez Nieva, Juan Manuel Mosquera Angarita, Jordi Anton Lopez, Esmeralda Nuñez-Cuadros, Gisela Diaz-Cordovés, Rocío Galindo-Zavala, Antonio Urda-Cardona, Antonio Fernández-Nebro, Daniel Álvarez de la Sierra, Marina Garcia Prat, Mónica Martínez Gallo, Ricardo Pujol Borrell, Ana M. Marín Sánchez, Etienne Merlin, Sylvie Fraitag, Jean-Louis Stephan, Federico Annoni, Giancarla Di Landro, Sofia Torreggiani, Marta Torcoletti, Georgina Tiller, Jo Buckle, Angela Cox, Peter Gowdie, Roger C. Allen, Jonathan D. Akikusa, Hayde G. Hernández-Huirache, Edel R. Rodea-Montero, William Fahy, Christelle Sordet, Karin B. Berggren, Johanna T. Kembe, Joyce Bos, Wineke Armbrust, Marco van Brussel, Jeanette Cappon, Pieter Dijkstra, Jan Geertzen, Elizabeth Legger, Marion van Rossum, Pieter Sauer, Otto Lelieveld, Levent Buluc, Gur Akansel, Bahar Muezzinoglu, Ljubov Rychkova, Tatyana Knyazeva, Anna Pogodina, Tatyana Belova, Tamara Mandzyak, Ekaterina Kulesh, Alessandro Cafarotti, Cosimo Giannini, Roberta Salvatore, Giuseppe Lapergola, Caterina Di Battista, Maria Loredana Marcovecchio, Raffaella Basilico, Piernicola Pelliccia, Francesco Chiarelli, Luciana Breda, Beverley Almeida, Sarah Tansley, Harsha Gunawardena, Neil McHugh, Juvenile Dermatomyositis Research Group (JDRG), Jessie Aouizerate, Marie De Antonio, Christine Barnerias, Guillaume Bassez, Isabelle Desguerre, Romain Gherardi, Jean-Luc Charuel, François-Jérôme Authier, Cyril Gitiaux, C. H. Spencer, Rabheh Abdul Aziz, Chack-Yung Yu, Brent Adler, Sharon Bout-Tabaku, Katherine Lintner, Melissa Moore-Clingenpeel, Liza McCann, Nicola Ambrose, Mario Cortina-Borja, Juvenile Dermatomyositis Cohort and Biomarker Study (JCDBS), Prasad T. Oommen, Fabian Speth, Johannes-Peter Haas, Working Group “Juvenile Dermatomyositis” of the German Society for Paediatric and Adolescent Rheumatology (GKJR), Claudio Lavarello, Gabriella Giancane, Angela Pistorio, Lisa Rider, Rohit Aggarwal, Sheila K. Oliveira, Ruben Cuttica, Michel Fischbach, Gary Sterba, Karine Brochard, Frank Dressler, Patrizia Barone, Ruben Burgos-Vargas, Elizabeth Candell Chalom, Marine Desjonqueres, Graciela Espada, Anders Fasth, Stella Maris Garay, Rose-Marie Herbigneaux, Claire Hoyoux, Chantal Job Deslandre, Frederick W. Miller, Jiri Vencovsky, Erdal Sag, Gulsev Kale, Haluk Topaloglu, Beril Talim, Francesco Zulian, Tadej Avcin, Roberto Marini, Anne Pagnier, Michel Rodiere, Christine Soler, Rebecca Ten Cate, Yosef Uziel, Jelena Vojinovic, Ana V. Villarreal, Nydia Acevedo, Yuridiana Ramirez, Enrique Faugier, Rocio Maldonado, Bita Arabshahi, John H. Lee, Ian Leibowitz, Lawrence O. Okong’o, Jo Wilmshurst, Monika Esser, Christiaan Scott, Ezgi Deniz Batu, Nagehan Emiroglu, Hafize Emine Sonmez, Gokcen Dilsa Tugcu, Zehra Serap Arici, Ebru Yalcin, Deniz Dogru, Ugur Ozcelik, Mithat Haliloglu, Nural Kiper, Masato Yashiro, Mutsuko Yamada, Toshihiko Yabuuchi, Tomonobu Kikkawa, Nobuyuki Nosaka, Yosuke Fujii, Yukie Saito, Hirokazu Tsukahara, Sulaiman M. Al-Mayouf, Nora AlMutiari, Mohammed Muzaffer, Rawiah shehata, Adel Al-Wahadneh, Reem Abdwani, Safia Al-Abrawi, Mohammed Abu-shukair, Zeyad El-Habahbeh, Abdullah Alsonbul, Aleksandra Szabat, Monika Chęć, Violetta Opoka-Winiarska, Biman Saikia, Ranjana W. Minz, Christine Arango, Clara Malagon, Maria D. P. Gomez, Angela C. Mosquera, Ricardo Yepez, Tatiana Gonzalez, Camilo Vargas, GRIP study group, Marta Balzarin, Biagio Castaldi, Elena Reffo, Francesca Sperotto, Giorgia Martini, Alessandra Meneghel, Ornella Milanesi, Ozgur Kasapçopur, Maria Teresa Terreri, Ekaterina Alexeeva, Maria Katsicas, Mikhail Kostik, Thomas Lehman, W.-Alberto Sifuentes-Giraldo, Vanessa Smith, Flavio Sztajnbok, Tadey Avcin, Maria Jose Santos, Dana Nemcova, Cristina Battagliotti, Liora Harel, Mahesh Janarthanan, Kathryn Torok, Nicola Helmus, Eileen Baildem, Michael Blakley, Kim Fligelstone, Antonia Kienast, Clare Pain, Amanda Saracino, Gabriele Simoni, Lisa Weibel, Maria K. Osminina, Nathalia A. Geppe, Olga V. Niconorova, Olesya V. Karashtina, Oksana V. Abbyasova, Olga V. Shpitonkova, Sinem Durmus, Hafize Uzun, Angela Mauro, Eleonora Fanti, Fabio Voller, Franca Rusconi, Fernando Garcia-Rodriguez, Ana V. Villarreal-Treviño, Angel J. Flores-Pineda, Paola B. Lara-Herrea, Diego R. Salinas-Encinas, Talia Diaz-Prieto, Maria R. Maldonado-Velazquez, Sarbelio Moreno-Espinosa, Enrique Faugier-Fuentes, Mirella Crapanzano, Ilaria Parissenti, Man S. Parihar, Pandiarajan Vignesh, ManojKumar Rohit, Kavitha Gopalan, Savita V. Attri, Alan Salama, David Jayne, Mark Little, Yulia Kostina, Galina Lyskina, Olga Shpitonkova, Alena Torbyak, Olga Shirinsky, Maria Francesca Gicchino, Maria Cristina Smaldone, Mario Diplomatico, Alma Nunzia Olivieri, C H. Spencer, Richard McClead, Hiren Patel, Chung-Yung Yu, Dita Cebecauerová, Tomáš Dallos, Edita Kabíčková, Martin Kynčl, Daniela Chroustová, Jozef Hoza, Dana Němcová, Vladimír Tesař, Pavla Doležalová, Tuncay Hazirolan, Fatih Ozaltin, Fabiola Almeida, Isabela H. Faria de Paula, Maíra M. Sampaio, Fernando N. Arita, Andressa G. Alves, Maria Carolina Santos, Eunice M. Okuda, Silvana B. Sacchetti, Fernanda Falcini, Marini Francesca, Gemma Lepri, Marco Matucci-Cerinic, Maria Luisa Brandi, Hakan Kisaoglu, Sema Misir, Selim Demir, Yuksel Aliyazicioglu, Mukaddes Kalyoncu, Carlos Eduardo Ramalho, Fabiola D. Almeida, Joan Calzada-Hernández, Rosa Bou, Estíbaliz Iglesias, Judith Sánchez-Manubens, Fredy Hermógenes Prada Martínez, Clara Giménez Roca, Sergi Borlan Fernández, Marek Bohm, Kamran Mahmood, Valentina Leone, Mark Wood, Ken-Ichi Yamaguchi, Satoshi Fujikawa, Working Group of Behçet’s Disease, Pediatric Rheumatology Association of Japan (PRAJ), Kyu Yeun Kim, Do Young Kim, Dong Soo Kim, Maka Ioseliani, Ivane Chkhaidze, Maia Lekishvili, Nana Tskhakaia, Shorena Tvalabeishvili, Aleksandre Kajrishvili, Maiko Takakura, Masaki Shimizu, Natsumi Inoue, Mao Mizuta, Akihiro Yachie, Giovanni Corsello, Maryam Piram, Carla Maldini, Sandra Biscardi, Nathalie Desuremain, Catherine Orzechowski, Emilie Georget, Delphine Regnard, Isabelle Kone-Paut, Alfred Mahr, Mihaela Sparchez, Zeno Sparchez, Nydia Acevedo Silva, Ana V. Villarreal Treviño, Yuridiana Ramirez Loyola, Talia Diaz Prieto, Enrique Faugier Fuentes, Maria D. R. Maldonado Velazquez, Pilar Perez, Sagar Bhattad, Ranjana Minz, Jitendra Shandilya, Pediatric Allergy and Immunology Unit, PGIMER, Chandigarh, Ana Villarreal, Yuridiana Ramírez, Zeynep Birsin Özçakar, Suat Fitoz, Fatos Yalcinkaya, Annacarin Horne, Francesca Minoia, Francesca Bovis, Sergio Davi, Priyankar Pal, Kimo Stein, Sandra Enciso, Michael Jeng, Despoina Maritsi, Randy C. Cron, Anne Thorwarth, Sae Lim von Stuckrad, Angela Rösen-Wolff, Hella Luksch, Patrick Hundsdoerfer, Peter Krawitz, Nuray Aktay Ayaz, Doğan Simsek, Şebnem Sara Kılıc, Emine Sonmez, Aysenur Pac Kisaarslan, Ozge Altug Gucenmez, Z. Serap Arıcı, Fatih Kelesoglu, Zelal Ekinci Ekinci, Maria Miranda-Garcia, Carolin Pretzer, Michael Frosch, F. Gohar, Angela McArdle, Niamh Callan, Belinda Hernandez, Miha Lavric, Oliver FitzGerald, Stephen R. Pennington, Joachim Peitz, Joern Kekow, Ariane Klein, Anna C. Schulz, Frank Weller-Heinemann, Anton Hospach, J-Peter Haas, BIKER collaborative group, Karen Put, Jessica Vandenhaute, Anneleen Avau, Annemarie van Nieuwenhuijze, Ellen Brisse, Tim Dierckx, Omer Rutgeerts, Josselyn E. Garcia-Perez, Jaan Toelen, Mark Waer, Georges Leclercq, An Goris, Johan Van Weyenbergh, Adrian Liston, Patrick Matthys, Carine H. Wouters, Yasuo Nakagishi, Michael J. Ombrello, Victoria Arthur, Anne Hinks, Patricia Woo, International Childhood Arthritis Genetics (INCHARGE) Consortium, Barbara Stanimirovic, Biljana Djurdjevic-Banjac, Olivera Ljuboja, Boris Hugle, MArgarita Onoufriou, Olga Vougiouka, Kenza Bouayed, Sanae El Hani, Imane Hafid, Nabiha Mikou, Nunu Shelia, Mari Laan, Jaanika Ilisson, and Chris Pruunsild
Subjects: Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Published: 2017
Full Text: View/download PDF

32. Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part two

Author: Olga Lomakina, Ekaterina Alekseeva, Sania Valieva, Tatiana Bzarova, Irina Nikishina, Elena Zholobova, Svetlana Rodionovskaya, Maria Kaleda, Yasuo Nakagishi, Masaki Shimizu, Mao Mizuta, Akihiro Yachie, Yuko Sugita, Nami Okamoto, Kousuke Shabana, Takuji Murata, Hiroshi Tamai, Eve M. Smith, Peng Yin, Andrea L. Jorgensen, Michael W. Beresford, on behalf of On behalf of the UK JSLE Cohort Study, Antonio Eleuteri, Beatrice Goilav, Laura Lewandowski, Angel Phuti, Dawn Wahezi, Tamar Rubinstein, Caroline Jones, Paul Newland, Stephen Marks, Rachel Corkhill, Diana Ekdawy, Clarissa Pilkington, Kjell Tullus, Chaim Putterman, Chris Scott, Antony C. Fisher, Andrea Jorgensen, Ezgi Deniz Batu, Can Kosukcu, Ekim Taskiran, Sema Akman, Kubra Ozturk, Betul Sozeri, Erbil Unsal, Zelal Ekinci, Yelda Bilginer, Mehmet Alikasifoglu, Seza Ozen, Hanna Lythgoe, Hermine I. Brunner, Gaurav Gulati, Jordan T. Jones, Mekibib Altaye, Jamie Eaton, Mark Difrancesco, Joo Guan Yeo, Jingyao Leong, Loshinidevi D/O Thana Bathi, Thaschawee Arkachaisri, Salvatore Albani, Nagla Abdelrahman, Michael W Beresford, Valentina Leone, UK JSLE study group supported by the National Institute of Health Research Clinical Research Network, Noortje Groot, D. Shaikhani, I. E. M. Bultink, M. Bijl, R. J. E. M. Dolhain, Y. K. O. Teng, E. Zirkzee, K. de Leeuw, R. Fritsch-Stork, S. S. M. Kamphuis, Rachael D. Wright, Reem Abdawani, Laila Al Shaqshi, Ibrahim Al Zakwani, Natali W. Gormezano, David Kern, Oriany L. Pereira, Gladys C. C. Esteves, Adriana M. Sallum, Nadia E. Aikawa, Rosa M. Pereira, Clovis A. Silva, Eloisa Bonfa, Jessica Beckmann, Nora Bartholomä, Nils Venhoff, Philipp Henneke, Ulrich Salzer, Ales Janda, Alina Lucica Boteanu, Sandra Garrote Corral, Alberto Sifuentes Giraldo, Mariluz Gámir Gámir, Antonio Zea Mendoza, Amra Adrovic, Reyhan Dedeoglu, Sezgin Sahin, Kenan Barut, Aida Koka, Funda Oztunc, Ozgur Kasapcopur, Ana Luisa Rodriguez-Lozano, Francisco Rivas-Larrauri, Silvestre García de la Puente, Andressa G. F. Alves, Maria F. D. A. Giacomin, Juliana Farhat, Alfésio L. F. Braga, Adriana M. E. Sallum, Lúcia M. D. A. Campos, Luiz A. A. Pereira, Ana J. D. F. C. Lichtenfels, Clóvis A. Silva, Sylvia C. L. Farhat, Banu Acar, Z. Birsin Ozcakar, Nilgün Çakar, Nermin Uncu, Gökçe Gür, Semanur Özdel, Fatoş Yalçınkaya, Christiaan Scott, Nicky Brice, Peter Nourse, Christine Arango, Angela C. Mosquera, Clara Malagon, Ana P. Sakamoto, Marco F. C. D. Silva, Ananadreia S. Lopes, Gleice C. S. Russo, Adriana E. M. Sallum, Katia Kozu, Eloisa Bonfá, Claudia Saad-Magalhães, Rosa M. R. Pereira, Claudio A. Len, Maria T. Terreri, Deepti Suri, Siyaram Didel, Amit Rawat, Surjit Singh, Despoina Maritsi, MArgarita Onoufriou, Olga Vougiouka, Maria Tsolia, Edi Paleka Bosak, Mandica Vidović, Mirta Lamot, Lovro Lamot, Miroslav Harjaček, Erika Van Nieuwenhove, Adrian Liston, Carine Wouters, Fatemeh Tahghighi, Vahid Ziaee, Seid-Reza Raeeskarami, Francisca Aguiar, Sandra Pereira, Mariana Rodrigues, Cláudia Moura, Gustavo Rocha, Hercília Guimarães, Iva Brito, Rita Fonseca, Gerd Horneff, Ariane Klein, Kirsten Minden, Hans-Iko Huppertz, Frank Weller-Heinemann, Jasmin Kuemmerle-Deschner, J-Peter Haas, Anton Hospach, BIKER collaborative group, Ricardo Menendez-Castro, Boris Huegle, Johannes-Peter Haas, Joost Swart, Gabriella Giancane, Francesca Bovis, Elio Castagnola, Andreas Groll, Daniel J. Lovell, Tom Wolfs, Michael Hofer, Violeta Panaviene, Susan Nielsen, Jordi Anton, Florence Uettwiller, Valda Stanevicha, Maria Trachana, Denise Pires Marafon, Constantin Ailioaie, Elena Tsitsami, Sylvia Kamphuis, Troels Herlin, Pavla Doležalová, Gordana Susic, Berit Flatø, Flavio Sztajnbok, Angela Pistorio, Alberto Martini, Nico Wulffraat, Nicolino Ruperto, Marco Gattorno, Antonio Brucato, Martina Finetti, George Lazaros, Silvia Maestroni, Mara Carraro, Davide Cumetti, Alessandra Carobbio, Monia Lorini, Alessandro Rimini, Renzo Marcolongo, Anna Valenti, Gian Luca Erre, Riccardo Belli, Fiorenzo Gaita, Maria Pia Sormani, Massimo Imazio, Mario Abinun, Nicola Smith, Tim Rapley, Flora McErlane, Lianne Kearsley-Fleet, Kimme L. Hyrich, Helen Foster, Nikolay Tzaribachev, Andrew Zeft, Rolando Cimaz, John Bohnsack, Thomas Griffin, Ruy Carrasco, Jason Dare, Ivan Foeldvari, Richard Vehe, Teresa Simon, Hermine Brunner, S. Verazza, S. Davì, A. Consolaro, A. Insalaco, V. Gerloni, R. Cimaz, F. Zulian, S. Pastore, F. Corona, G. Conti, P. Barone, M. Cattalini, E. Cortis, L. Breda, A. N. Olivieri, A. Civino, R. Podda, D. Rigante, F. La Torre, G. D’Angelo, M. Jorini, R. Gallizzi, M. C. Maggio, R. Consolini, A. De Fanti, M. G. Alpigiani, A. Martini, A. Ravelli, on behalf of Italian Pediatric Rheumatology Study Group, Aysenur Pac Kısaarslan, Zubeyde Gunduz, Ruhan Dusunsel, Ismail Dursun, Hakan Poyrazoglu, Ekaterina Kuchinskaya, Farida Abduragimova, Mikhail Kostik, Erik Sundberg, Soley Omarsdottir, Lena Klevenvall, Helena Erlandsson-Harris, Gokalp Basbozkurt, Ozge Erdemli, Dogan Simsek, Fatih Yazici, Yildirim Karsioglu, Aysen Tezcaner, Dilek Keskin, Huseyin Ozkan, Cengizhan Acikel, Erkan Demirkaya, Ilonka Orbán, Krisztina Sevcic, Valentin Brodszky, Emese Kiss, Ismaiel A. Tekko, Madeleine Rooney, James McElnay, Cliff Taggart, Helen McCarthy, Ryan F. Donnelly, Drug Delivery Group, Mary Slatter, Zohreh Nademi, Mark Friswell, Sharmila Jandial, Terence Flood, Sophie Hambleton, Andrew Gennery, Andrew Cant, Phoi-Ngoc Duong, Isabelle Koné-Paut, Giovanni Filocamo, María Luz Gamir, Helga Sanner, Laura Carenini, Mesut Topdemir, Yildirim Karslioglu, Faysal Gok, Nadezhda Tsurikova, Elena Ligostaeva, Navdha R. Ramchurn, O. Kostareva, I. Nikishina, S. Arsenyeva, S. Rodionovskaya, M. Kaleda, D. Alexeev, Ismail Dursun Dursun, Sara Murias, Estefania Barral, Rosa Alcobendas, Eugenia Enriquez, Agustin Remesal, Jaime de Inocencio, Tania M. Castro, Simone A. Lotufo, Tatjana Freye, Raffaella Carlomagno, Thomas Zumbrunn, Jan Bonhoeffer, Elvira Cannizzaro Schneider, Daniela Kaiser, Michaël Hofer, Véronique Hentgen, Andreas Woerner, Juvenile Inflammatory Rheumatism (JIR) Cohort, Tobias Schwarz, Jens Klotsche, Martina Niewerth, Gerd Ganser, ICON study group, Jerold Jeyaratnam, Nienke ter Haar, Donato Rigante, Fatma Dedeoglu, Ezgi Baris, Sebastiaan Vastert, Joost Frenkel, Jonathan S. Hausmann, Kathleen G. Lomax, Ari Shapiro, Karen L. Durrant, P. A. Brogan, M. Hofer, J. B. Kuemmerle-Deschner, B. Lauwerys, A. Speziale, K. Leon, X. Wei, R. M. Laxer, Sara Signa, Marta Rusmini, Elena Campione, Sabrina Chiesa, Alice Grossi, Alessia Omenetti, Roberta Caorsi, Gianmaria Viglizzo, Isabella Ceccherini, Silvia Federici, Helen Lachmann, Nicola Ruperto, on behalf of PRINTO and Eurofever Registry, Federica Vanoni, on behalf of PRINTO and Eurofever Project, Sonia Melo Gomes, Ebun Omoyinmi, Juan I. Arostegui, Eva Gonzalez-Roca, Despina Eleftheriou, Nigel Klein, Paul Brogan, Stefano Volpi, Elettra Santori, Paolo Picco, Claudia Pastorino, Gillian Rice, Alessandra Tesser, Yanick Crow, Fabio Candotti, Ada B. Sinoplu, Gozde Yucel, Gizem Pamuk, Laura O. Damian, Cecilia Lazea, Mihaela Sparchez, Paulina Vele, Laura Muntean, Adriana Albu, Simona Rednic, Calin Lazar, Leonardo O. Mendonça, Alessandra Pontillo, Jorge Kalil, Fabio M. Castro, Myrthes T. Barros, Manuela Pardeo, Virginia Messia, Fabrizio De Benedetti, Antonella Insalaco, Giorgia Malighetti, Chiara Gorio, Francesca Ricci, Ilaria Parissenti, Paola Montesano, Barbara Bonafini, Veronica Medeghini, Marco Cattalini, Lucio Giordano, Giulia Zani, Rosalba Ferraro, Donatella Vairo, Silvia Giliani, Maria Cristina Maggio, Girolamo Luppino, Giovanni Corsello, Maria Isabel Gonzalez Fernandez, Berta Lopez Montesinos, Adriana Rodriguez Vidal, Juan I. Arostegui Gorospe, Inmaculada Calvo Penades, Nadia K. Rafiq, Karen Wynne, Khalid Hussain, Paul A. Brogan, Elizabeth Ang, Nicholas Ng, Ayla Kacar, Ozge Altug Gucenmez, Balahan Makay, Sevket Erbil Unsal, Yasin Sahin, Tufan Kutlu, Fugen Cullu-Cokugras, Hasret Ayyildiz-Civan, Tulay Erkan, Sana Al Zuhbi, Eiman Abdalla, Ricardo A. Russo, María M. Katsicas, Francesca Minoia, Angelo Ravelli, Sagar Bhattad, Anju Gupta, Vignesh Pandiarajan, Ritambhra Nada, Kaara Tiewsoh, Philip Hawkins, Dorota Rowczenio, Sarka Fingerhutova, Jana Franova, Leona Prochazkova, Eva Hlavackova, Pavla Dolezalova, Havva Evrengül, Selçuk Yüksel, Mustafa Doğan, Dolunay Gürses, Harun Evrengül, Silvia De Pauli, Serena Pastore, Anna Monica Bianco, Giovanni Maria Severini, Andrea Taddio, Alberto Tommasini, Svetlana O. Salugina, Evgeny Fedorov, Elena Kamenets, Ekaterina Zaharova, Tatiana Sleptsova, Ekaterina Alexeeva, Kirill Savostyanov, Alexander Pushkov, Tatyana Bzarova, Saniya Valieva, Rina Denisova, Kseniya Isayeva, Evgeniya Chistyakova, Margarita Soloshenko, Elena Kaschenko, Utako Kaneko, Chihaya Imai, Akihiko Saitoh, Vitor A. Teixeira, Filipa O. Ramos, Manuela Costa, Yonatan Butbul Aviel, Shafe Fahoum, Riva Brik, Zeynep Birsin Özçakar, Banu Acar Celikel, Fatos Yalcinkaya, Benedetta Schiappapietra, Sergio Davi’, Federica Mongini, Luisa Giannone, Cecilia Bava, Maria Giannina Alpigiani, Alessandro Consolaro, Dragana S. Lazarevic, Jelena Vojinovic, Jelena Basic, Valentina Muratore, Valentina Marzetti, Neus Quilis, Belen Serrano Benavente, Alessandra Alongi, Adele Civino, Lorenzo Quartulli, Giedre Januskeviciute, Pieter van Dijkhuizen, N. Groot, W. van Dijk, A. Kardolus, Raul Gutiérrez Suárez, Ellen B. Nordal, Veronika G. Rypdal, Lillemor Berntson, Maria Ekelund, Kristiina Aalto, Suvi Peltoniemi, Marek Zak, Mia Glerup, Ellen D. Arnstad, Anders Fasth, Marite Rygg, the Nordic Study Group of Pediatric Rheumatology (NoSPeR), Ana Catarina Duarte, Sandra Sousa, Lídia Teixeira, Ana Cordeiro, Mª José Santos, Ana Filipa Mourão, Maria José Santos, Mónica Eusébio, Ana Lopes, Filipa Oliveira-Ramos, Manuel Salgado, Paula Estanqueiro, José Melo-Gomes, Fernando Martins, José Costa, Carolina Furtado, Ricardo Figueira, Jaime C. Branco, João E. Fonseca, Helena Canhão, Ana F. Mourão, Maria Jose Santos, Andrea Coda, Samuel Cassidy, Kerry West, Gordon Hendry, Debra Grech, Julie Jones, Fiona Hawke, Davinder Singh Grewal, Charlene Foley, Orla Killeen, Emma MacDermott, Douglas Veale, Ursula Fearon, Dilek Konukbay, Ela Tarakci, Nilay Arman, Sezgin Şahin, Jane Munro, Esi Morgan, Meredith Riebschleger, Jennifer Horonjeff, Vibeke Strand, Clifton Bingham, Ma. Theresa M. Collante, Margarita Ganeva, Stefan Stefanov, Albena Telcharova, Dimitrina Mihaylova, Radoslava Saraeva, Reni Tzveova, Radka Kaneva, Adelina Tsakova, Katya Temelkova, GRANT Medical University, Sofia 68/, Maria Mercedes C. Picarelli, Luiz C. Danzmann, Florencia Barbé-Tuana, Lucas K. Grun, Marcus H. Jones, Marijan Frković, Karla Ištuk, Ika Birkić, Saša Sršen, Marija Jelušić, Alan Easton, Rachael Quarmby, Raju Khubchandani, Mercedes Chan, Radoslav Srp, Katerina Kobrova, Dana Nemcova, Jozef Hoza, Michal Uher, Melania Saifridova, Lenka Linkova, Sirirat Charuvanij, Isree Leelayuwattanakul, Thita Pacharapakornpong, Sakda A.-O. Vallipakorn, Butsabong Lerkvaleekul, Soamarat Vilaiyuk, Stefano Lanni, Sergio Davì, Randy Q. Cron, Chiara Passarelli, Elisa Pisaneschi, Antonio Novelli, Claudia Bracaglia, Ivan Caiello, Kathy de Graaf, Florence Guilhot, Walter Ferlin, Grant Schulert, Alexi A. Grom, Robert Nelson, Cristina de Min, Dirk Holzinger, Christoph Kessel, Ndate Fall, Alexei Grom, Wilco de Jager, Raffaele Strippoli, Anna Horne, Stephan Ehl, Sandra Ammann, Kai Lehmberg, Karin Beutel, Dirk Foell, AnnaCarin Horne, Laura Pagani, Graciela Espada, Yi-jin Gao, Susan Shenoi, Sheila Weitzman, Giusi Prencipe, Antonia Pascarella, Walter G. Ferlin, Laurence Chatel, Philippe Jacqmin, Kathy De Graaf, Maria Ballabio, Zoë Johnson, Geneviève Lapeyre, Fabrizio de Benedetti, de Min Cristina, Hiroyuki Wakiguchi, Shunji Hasegawa, Reiji Hirano, Fumiko Okazaki, Tamaki Nakamura, Hidenobu Kaneyasu, Shouichi Ohga, Kazuko Yamazaki, Tomo Nozawa, Taichi Kanetaka, Shuichi Ito, Shumpei Yokota, Kirsty McLellan, Ishbel MacGregor, Neil Martin, Joyce Davidson, Sandra Hansmann, Andreas Eikelberg, Iris Haug, Sabrina Schuller, Susanne M. Benseler, Single Hub and Access point for paediatric Rheumatology in Europe (SHARE), Liliia S. Nazarova, Kseniia V. Danilko, Viktor A. Malievsky, Tatiana V. Viktorova, Angela Mauro, Angela Barnicoat, Jane Hurst, Nathalie Canham, Sandrine Lacassagne, Anastasia Wiener, Boris Hügle, Bernd Denecke, Ivan Costa-Filho, Johannes Peter Haas, Klaus Tenbrock, David Popp, Arjan Boltjes, Frank Rühle, Stefanie Herresthal, Femke van Wijk, Joachim Schultze, Monika Stoll, Luisa Klotz, Thomas Vogl, Johannes Roth, Estefania Quesada-Masachs, Daniel Álvarez de la Sierra, Marina Garcia Prat, Ana M. Marín Sánchez, Ricardo Pujol Borrell, Sara Marsal Barril, Mónica Martínez Gallo, Consuelo Modesto Caballero, Iryna Chyzheuskaya, Lyudmyla M. Byelyaeva, Rostislav M. Filonovich, Helena K. Khrustaleva, Larisa I. Zajtseva, Tamara M. Yuraga, Thomas Giner, Lukas Hackl, Julia Albrecht, Reinhard Würzner, Juergen Brunner, Marta Minute, Fulvio Parentin, Agostino Nocerino, Mette Nørgaard, Mikel Alberdi-Saugstrup, Marek S. Zak, Susan M. Nielsen, Ellen Nordal, Klaus G. Müller, Nordic Study Group of Pediatric Rheumatology (NoSPeR), Mojca Zajc Avramovič, Vita Dolžan, Nataša Toplak, Tadej Avčin, N. Ruperto, D. J. Lovell, C. Wallace, M. Toth, I. Foeldvari, J. Bohnsack, D. Milojevic, C. Rabinovich, D. Kingsbury, K. Marzan, P. Quartier, K. Minden, E. Chalom, G. Horneff, R. M. Kuester, J. Dare, M. Heinrich, H. Kupper, J. Kalabic, H. I. Brunner, on behalf of PRINTO and PRCSG, Ruben Burgos-Vargas, Tamas Constantin, Joke Dehoorne, Valda Stanevica, Katarzyna Kobusinska, Zbigniew Zuber, Richard Mouy, Ingrida Rumba-Rozenfelde, Chantal Job-Deslandre, Ronald Pederson, Jack Bukowski, Tina Hinnershitz, Bonnie Vlahos, Paula Keskitalo, Salla Kangas, Paula Vähäsalo, Raul A. Chavez Valencia, David Martino, Anne-Louise Ponsonby, Rachel Chiaroni-Clarke, Braydon Meyer, Roger C. Allen, Jonathan D. Akikusa, Jeffrey M. Craig, Richard Saffrey, Justine A. Ellis, Carol Wallace, Yosef Uziel, Gary Sterba, Rayfel Schneider, Ricardo Russo, Athimalaipet V. Ramanan, Jana Pachlopnik Schmid, Kim E Nichols, Paivi Miettunen, Toshiyuki Kitoh, Norman T. Ilowite, Jan-Inge Henter, Alexei A Grom, Edward M. Behrens, Tadej Avcin, Maurizio Aricò, Sriharsha Grevich, Peggy Lee, Sarah Ringold, Brian Leroux, Hannah Leahey, Megan Yuasa, Jessica Foster, Jeremy Sokolove, Lauren Lahey, William Robinson, Joshua Newson, Anne Stevens, Stephanie J. W. Shoop, Suzanne M. M. Verstappen, Wendy Thomson, Janet E. McDonagh, CAPS, Timothy Beukelman, Yuki Kimura, Marc Natter, Norm Ilowite, Kelly Mieszkalski, Grendel Burrell, Brian Best, Helen Bristow, Shannon Carr, Anne Dennos, Rachel Kaufmann, Laura Schanberg, for the CARRA Registry Investigators, Gabriele Simonini, Francesca Lancini, Margaux Gerbaux, Phu-Quoc Lê, Laurence Goffin, Valérie Badot, Céline La, Laure Caspers, François Willermain, Alina Ferster, Maria Ceci, Francesco Licciardi, Marco Turco, Francesca Santarelli, Davide Montin, Claudia Toppino, Clotilde Alizzi, Bruno Papia, Beatrice Vergara, Umberto Corpora, Luca Messina, Maria Tsinti, Vasiliko Dermentzoglou, Panagiotis Tziavas, Marija Perica, Lana Tambić Bukovac, Mustafa Çakan, Nuray Aktay Ayaz, Gonca Keskindemirci, Michael Lang, Catherine Laing, Susanne Benseler, Tommy Gerschman, Nadia Luca, Heinrike Schmeling, Anastasia Dropol, Jaymi Taiani, Nicole Johnson, Brian Rusted, Panagiota Nalbanti, Polyxeni Pratsidou, Grigoris Pardalos, Vasiliki Tzimouli, Anna Taparkou, Maria Stavrakidou, Fotios Papachristou, Florence Kanakoudi-Tsakalidou, Peter Bale, Emily Robinson, Jason Palman, Elizabeth Ralph, Kimberly Gilmour, Clare Heard, Lucy R. Wedderburn, Yara Barrense-Dias, Antonarakis Gregory, Dhouib Amira, Scolozzi Paolo, Hanquinet Sylviane, Hofer Michaël, Nataliya Panko, Salah Shokry, Liudmila Rakovska, Sally Pino, Adriana Diaz-Maldonado, Pilar Guarnizo, Sofia Torreggiani, Paolo Cressoni, Umberto Garagiola, Giancarla Di Landro, Giampietro Farronato, Fabrizia Corona, Samantha Bell, Parveen Bhatti, Lee Nelson, Beth A. Mueller, T. A. Simon, A. Baheti, N. Ray, Z. Guo, Anasuya Hazra, Thomas Stock, Ronnie Wang, Charles Mebus, Christine Alvey, Manisha Lamba, Sriram Krishnaswami, Umberto Conte, Min Wang, Daniel Kingsbury, Elena Koskova, Elzbieta Smolewska, Richard K. Vehe, Daniel Lovell, Tomohiro Kubota, Junko Yasumura, Toshitaka Kizawa, Masato Yashiro, Tsuyoshi Yamatou, Yuichi Yamasaki, Syuji Takei, Yoshifumi Kawano, Ulrika Järpemo Nykvist, Bo Magnusson, Rikard Wicksell, Karin Palmblad, Gunnar L. Olsson, Mohammadreza Modaressi, Mohammad-Hassan Moradinejad, Valentina Seraya, Alisa Vitebskaya, Veronica Moshe, Gil Amarilyo, Liora Harel, Phillip J Hashkes, Amir Mendelson, Noa Rabinowicz, Yonit Reis, Zane Dāvidsone, Arina Lazareva, Ruta Šantere, Dace Bērziņa, Valda Staņēviča, Giulia Camilla Varnier, Susan Maillard, Cristina Ferrari, Silvia Zaffarano, Juvenile Dermatomyositis Research Group and European Federation of Immunological Societies, Judith Wienke, Felicitas Bellutti Enders, Lucas L. van den Hoogen, Jorre S. Mertens, Timothy R. Radstake, Henny G. Hotten, Ruth Fritsch, Lucy Wedderburn, Kiran Nistala, Berent Prakken, Annet van Royen-Kerkhof, Mohammad Alhemairi, Mohammed Muzaffer, Pieter Van Dijkhuizen, Claire T. Deakin, Stefania Simou, Maria De Iorio, Qiong Wu, Tania Amin, Lee Dossetter, Juvenile Dermatomyositis Research Group (JDRG), Raquel Campanilho-Marques, Claire Deakin, Clarissa A. Pilkington, on behalf of Juvenile Dermatomyositis Research Group (JDRG), Silvia Rosina, Sirisucha Soponkanaporn, on behalf of the UK Juvenile Dermatomyositis Research Group (JDRG), Zehra S. Arıcı, Gökçen D. Tuğcu, Ezgi D. Batu, Hafize E. Sönmez, Deniz Doğru-Ersöz, Beril Talim, Nural Kiper, Seza Özen, Alexander Solyom, Ezgi Batu, John Mitchell, Ariana Kariminejad, Fatemeh Hadipour, Zahra Hadipour, Marta Torcoletti, Carlo Agostoni, Maja Di Rocco, Pranoot Tanpaiboon, Andrea Superti-Furga, Luisa Bonafé, Nur Arslan, Norberto Guelbert, Karoline Ehlert, Giedre Grigelioniene, Ratna Puri, Edward Schuchman, Pilar Gomez, Tatiana Gonzalez, Ricardo Yepez, Camilo Vargas, GRIP study group, Falcini Fernanda, Gemma Lepri, Alessandra Ferrari, Marco Matucci-Cerinic, Antonella Meini, Gian Marco Moneta, Emiliano Marasco, Rebecca Nicolai, Luisa Bracci-Laudiero, Olga Kopchak, Alexander Mushkin, Alexey Maletin, Catalina Mosquera, Rita A. Amorim, Juliana Molina, Gustavo Moreira, Flávia H. Santos, Melissa Fraga, Livia Keppeke, Vanessa M. Silva, Camila Hirotsu, Sergio Tufik, Maria Teresa Terreri, Vinícius L. Braga, Maria Beatriz Fonseca, Vania Schinzel, Maria Teresa R. Terreri, Liliana Jorge, Liana Guerra, Edson Amaro Junior, Maria Cristina Castiglione, Alessandra Tricarico, Emily Boulter, Andre Schultz, Kevin Murray, Fernanda Falcini, Stefano Stagi, Eleonora Bellucci, Ingrid H. R. Grein, Gecilmara Pileggi, Natália B. F. Pinto, Aline L. de Oliveira, Lyudmila Belyaeva, Rostislav Filonovich, Helena Khrustaleva, Larisa Zajtseva, Jaanika Ilisson, Chris Pruunsild, Olivier Gilliaux, Francis Corazza, Christophe Lelubre, on behalf of PANLAR Pediatric Rheumatology Study Group, Zoilo Morel, Claudia Saad-Magalhães C, Luis Lira, Mabel Ladino, Ruth Eraso, Ivonne Arroyo, Clovis Silva, Carlos Rose, and PANLAR Pediatric Rheumatology Study Group
Subjects: Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Published: 2017
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33. Serum Leucine-Rich α2-Glycoprotein as a Biomarker for Monitoring Disease Activity in Patients with Systemic Juvenile Idiopathic Arthritis

Author: Masaki Shimizu, Natsumi Inoue, Mao Mizuta, Yasuo Nakagishi, and Akihiro Yachie
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: To investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are useful as a marker of disease activity in systemic juvenile idiopathic arthritis (s-JIA), we determined serum LRG levels in fifty-nine s-JIA patients, 15 with other subtypes of JIA, 7 with Kawasaki disease (KD), 7 with influenza A infection (flu), 7 with enterohemorrhagic Escherichia coli (EHEC) infection, and 20 healthy controls (HC). Results were compared with the clinical features of s-JIA and serum cytokine levels including interleukin- (IL-) 6, IL-18, and soluble tumor necrosis factor receptors I and II. Serum LRG levels in active s-JIA were higher compared to those in other subtypes of JIA, EHEC, flu patients, and HC. Serum LRG levels were normalized in the inactive s-JIA phase after treatment. Serum LRG levels were positively correlated with serum C-reactive protein and ferritin levels. Serum LRG levels reflected s-JIA disease activity and thus may be useful for monitoring s-JIA disease activity.
Published: 2019
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34. Transitional Channel Flow: A Minimal Stochastic Model

Author: Paul Manneville and Masaki Shimizu
Subjects: transition to/from turbulence, wall-bounded shear flow, plane Poiseuille flow, spatiotemporal intermittency, directed percolation, critical phenomena, Science, Astrophysics, QB460-466, Physics, QC1-999
Abstract: In line with Pomeau’s conjecture about the relevance of directed percolation (DP) to turbulence onset/decay in wall-bounded flows, we propose a minimal stochastic model dedicated to the interpretation of the spatially intermittent regimes observed in channel flow before its return to laminar flow. Numerical simulations show that a regime with bands obliquely drifting in two stream-wise symmetrical directions bifurcates into an asymmetrical regime, before ultimately decaying to laminar flow. The model is expressed in terms of a probabilistic cellular automaton of evolving von Neumann neighborhoods with probabilities educed from a close examination of simulation results. It implements band propagation and the two main local processes: longitudinal splitting involving bands with the same orientation, and transversal splitting giving birth to a daughter band with an orientation opposite to that of its mother. The ultimate decay stage observed to display one-dimensional DP properties in a two-dimensional geometry is interpreted as resulting from the irrelevance of lateral spreading in the single-orientation regime. The model also reproduces the bifurcation restoring the symmetry upon variation of the probability attached to transversal splitting, which opens the way to a study of the critical properties of that bifurcation, in analogy with thermodynamic phase transitions.
Published: 2020
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35. Relation among the knee, sagittal spinal alignment, and the spinal range of motion: Investigation in local medical check-ups using the SpinalMouse

Author: Shinya Yanagisawa, Naoki Sato, Masaki Shimizu, Kenichi Saito, Atsushi Yamamoto, and Kenji Takagishi
Subjects: knee, sagittal spinal alignment, SpinalMouse, spinal range of motion, Sports medicine, RC1200-1245
Abstract: Background: This study was designed as an investigation in a local population to assess the relation between the knee joint and spinal alignment in a population-based study using the SpinalMouse. Methods: Medical check-ups were conducted for residents of a mountain village in Japan. The study population included 107 men and 157 women (528 knees) with a mean age of 71.1 ± 6.8 years (range, 60–87 years). A questionnaire dealing with any current symptoms involving the knees was administered, and physical examinations dealing with the range of motion (ROM) of knee were conducted. The SpinalMouse was used to measure sagittal spinal alignment and spinal ROM. The parameters considered were thoracic kyphosis angle, lumbar lordosis angle (LLA), sacral inclination angle (SIA), and trunk angle of inclination (INC). The patients were divided into a group with knee flexion contracture (FC group) and a group without knee FC (non-FC group) to conduct a comparative study of both groups. Results: With regard to static spinal alignment, LLA and SIA decreased significantly in the FC group (p
Published: 2015
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36. Mitochondrial Disease as a Cause of Neonatal Hemophagocytic Lymphohistiocytosis

Author: Kazumasa Fuwa, Mitsuru Kubota, Masami Kanno, Hiroshi Miyabayashi, Ken Kawabata, Keiichi Kanno, and Masaki Shimizu
Subjects: Pediatrics, RJ1-570
Abstract: Diagnosis of mitochondrial respiratory chain disorder (MRCD) is often difficult. Its pathogenesis is still unclear. We diagnosed MRCD by measuring the activity of the mitochondrial respiratory chain enzyme, and the patient also had hemophagocytic lymphohistiocytosis (HLH). A preterm female infant was born at 34 weeks of gestation. On day 6, HLH was revealed by bone marrow aspiration. She died on day 10 due to uncontrollable HLH. An autopsy was performed, and we measured the activity of the mitochondrial respiratory chain enzyme in the liver, muscle, and heart. The activity of complex I was decreased in all tissues. As we could not prove another origin of the HLH, she was diagnosed as having HLH caused by MRCD. It is useful to measure the activity of the mitochondrial respiratory chain enzyme for diagnosing MRCD. MRCD, which has a severe clinical course, may be related to HLH.
Published: 2016
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37. Successful Treatment of Primary Sclerosing Cholangitis with a Steroid and a Probiotic

Author: Masaki Shimizu, Hidenori Iwasaki, Shintaro Mase, and Akihiro Yachie
Subjects: Primary sclerosing cholangitis, Inflammatory bowel disease, Probiotics, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Primary sclerosing cholangitis (PSC) is a serious disease that not only affects quality of life but can also have a significant effect on patient survival. The treatment for PSC is primarily supportive with the aim of controlling cholestatic symptoms and preventing complications. Ursodeoxycholic acid may induce biochemical improvements in affected patients; however, long-term pediatric studies to determine its possible benefits in young patients are lacking. Thus, the treatment of pediatric PSC remains a significant clinical challenge. We describe a patient with PSC and undetermined colitis who was treated with a combination of a steroid, salazosulfapyridine, and a probiotic. This treatment provided benefits both for PSC and the undetermined colitis. These findings suggest that bacterial flora and gut inflammation are closely associated with the pathogenesis of inflammatory bowel disease-related PSC. Suppression of bowel inflammation and maintenance of bacterial homeostasis may be important for treating PSC.
Published: 2012
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38. 1,1,3,3-Tetrakis(alkylthio)-1,3-dilithio-2-silapropanes: Useful reagents for the synthesis of polysilacycloalkanes via dianionic ring formation

Author: Masaki Shimizu, Masayuki Iwakubo, Yasushi Nishihara, Katsunari Oda, and Tamejiro Hiyama
Subjects: Organic chemistry, QD241-441
Published: 2006
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