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Yojiro Umezaki,1 Motoko Watanabe,2 Yukiko Shinohara,2 Shiori Sugawara,2 Kaoru Kawasaki,2 Trang TH Tu,2 Takeshi Watanabe,2 Takayuki Suga,2 Anna Miura,2 Miho Takenoshita,2 Yusuke Sato,3 Ichiro Minami,4 Jun Oyama,5 Akira Toriihara,5 Tatsuya Yoshikawa,2 Toru Naito,1 Haruhiko Motomura,2 Akira Toyofuku2 1Section of Geriatric Dentistry, Department of General Dentistry, Fukuoka Dental College, Fukuoka 814-0193, Japan; 2Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 3Department of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 4Department of Removable Partial Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 5Department of Diagnostic Radiology and Nuclear Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, JapanCorrespondence: Akira ToyofukuDepartment of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8548, JapanTel/Fax +81- 3-5803-5909Email toyoompm@tmd.ac.jpBackground: Phantom bite syndrome (PBS) is characterized by an uncomfortable sensation during occlusion without any evident abnormality. A recent case–control study with single-photon emission computed tomography (SPECT) using 99mTc-ethyl cysteinate dimer could not find the specific features of regional cerebral blood flow (rCBF), which might be due to the heterogeneity of PBS. We analyzed the brain images of PBS corresponding to the clinical features by studying PBS subgroups.Methods: This study contributes to elucidating the pathophysiology of PBS by evaluating regional brain perfusion on SPECT and its clinical features. We performed SPECT using 99mTc-ethyl cysteinate dimer in 44 patients with PBS. The SPECT images were analyzed qualitatively and quantitatively.Results: Asymmetrical rCBF patterns were detected, corresponding to symptom laterality. Patients with PBS with right-side symptoms showed right-side-predominant rCBF asymmetry in the parietal region and left-side-predominant rCBF asymmetry in the thalamus, and vice versa. Moreover, the analysis of the association between rCBF and patient behaviors revealed that patients who blamed their dentists for their symptoms tended to have a symmetrical rCBF pattern.Conclusion: Patients with PBS showed blood flow imbalance in the thalamus and parietal region corresponding to symptom laterality. There are two types of symmetrical and asymmetrical rCBF patterns in the pathophysiology of PBS despite similar clinical manifestations.Keywords: phantom bite syndrome, cerebral blood flow, single-photon emission computed tomography

Keitaro Shimozaki,1 Yasutaka Sukawa,1 Noriko Beppu,2 Isao Kurihara,3 Shigeaki Suzuki,4 Ryuichi Mizuno,5 Takeru Funakoshi,6 Shinnosuke Ikemura,7,8 Kai Tsugaru,1 Kazuhiro Togasaki,1 Kenta Kawasaki,1 Kenro Hirata,1 Hideyuki Hayashi,8 Yasuo Hamamoto,8 Hiromasa Takaishi,8 Takanori Kanai1 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Pharmacy, Keio University Hospital, Tokyo, Japan; 3Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; 4Department of Neurology, Keio University School of Medicine, Tokyo, Japan; 5Department of Urology, Keio University School of Medicine, Tokyo, Japan; 6Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; 7Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; 8Keio Cancer Center, Keio University School of Medicine, Tokyo, JapanCorrespondence: Yasutaka Sukawa Tel +81-3-3353-1211Fax +81-3-5363-6247Email sukawa@keio.jpPurpose: Immune checkpoint inhibitors (ICIs) have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in real-world practice.Patients and Methods: We conducted a retrospective study on patients with recurrent or metastatic non-small-cell lung cancer, malignant melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model and the shared frailty model.Results: Of 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. The median OS was significantly longer in the irAEs than in the no-irAE group (28.1 months vs 12.7 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.33– 0.73; P = 0.0004). Moreover, the OS of patients with multiple irAEs was significantly longer than that of patients with a single irAE (42.3 months vs 18.8 months; HR, 0.473; 95% CI, 0.346– 0.647; P < 0.0001).Conclusion: Our single-center retrospective study revealed a significant tendency associating the development of multiple irAEs with favorable prognoses.Keywords: immune checkpoint inhibitors, programmed cell death 1, prognosis

Trang TH Tu,1 Anna Miura,1 Yukiko Shinohara,1 Lou Mikuzuki,1 Kaoru Kawasaki,1 Shiori Sugawara,1 Takayuki Suga,1 Takeshi Watanabe,1 Yuma Aota,1 Yojiro Umezaki,2 Miho Takenoshita,1 Akira Toyofuku1 1Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 2Department of Geriatric Dentistry, Fukuoka Dental College, Fukuoka, Japan Objectives: There has been considerable research which has focused on clarifying the origin of pain in patients with atypical odontalgia (AO), also known as “idiopathic toothache”, and on identifying effective treatment, but there has been limited success so far. In this study, we assessed the outcomes of treatment and attempted to identify factors that could account for pain remission in patients with AO.Patients and methods: Data for 165 patients diagnosed with AO from June 2015 to August 2017 were retrospectively reviewed. The patients’ sex, age, duration of pain, and psychiatric history were collected, along with information on pain intensity, depressive status, and catastrophizing scores. Responses at 4 and 16 weeks from the start of treatment were observed. The associations between potentially associated factors and outcome were investigated using Bayesian model averaging.Results: A 30% reduction in pain was reported by 38 patients (46.3%) at 4 weeks and by 54 patients (65.9%) at 16 weeks. The pain intensity decreased as the depression and catastrophizing score improved; all of the changes were statistically significant (P

Yojiro Umezaki,1 Anna Miura,2 Yukiko Shinohara,2 Lou Mikuzuki,2 Shiori Sugawara,2 Kaoru Kawasaki,2 Trang TH Tu,2 Takeshi Watanabe,2 Takayuki Suga,2 Motoko Watanabe,3 Miho Takenoshita,2 Tatsuya Yoshikawa,2 Akihito Uezato,4 Toru Nishikawa,4 Ken Hoshiko,5 Toru Naito,1 Haruhiko Motomura,2 Akira Toyofuku2 1Section of Geriatric Dentistry, Department of General Dentistry, Fukuoka Dental College, Fukuoka, Japan; 2Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 3Department of Oral and Maxillofacial Radiology, Tokyo Dental College, Tokyo, Japan; 4Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 5Department of Pharmacy, Dental Hospital, Tokyo Medical and Dental University, Tokyo, Japan Objective: Oral cenesthopathy is characterized by foreign body sensations without medical and dental evidence for them. It is thought to be a rare disease in psychiatry, but many patients are visiting dental clinics seeking treatment to remove a foreign body. Even though the features of oral cenesthopathy might be different between a psychiatric clinic and a dental clinic, there has been no clinico-statistical study from dentists. In this study, we report a clinico-statistical study of patients with oral cenesthopathy in dentistry. Methods: This is a retrospective chart review of 606 outpatients with oral cenesthopathy in Tokyo Medical and Dental University from April 2010 through to March 2015. Results: A total of 159 male and 447 female patients were included in this study. The mean age was 62.08 years, and female patients were older than male patients. The trigger of the dental treatment and the acute phase of depression at the onset were significantly related (p=0.037). Only 128 patients (36%) had clinically significant improvement after 6 months of pharmacotherapy. No history of psychiatric disorders (odds ratio [OR] 0.479 [95% confidence interval {CI}: 0.262–0.875], p=0.017) and longer duration of illness (>18 months) (OR 2.626 [95% CI: 1.437–4.799], p=0.002) were significant factors for clinical outcomes. Conclusion: Patients with oral cenesthopathy in our clinic were predominantly elderly female patients. Dental treatment in the acute phase of depression might be a risk factor for oral cenesthopathy. Therefore, comprehending the situation of psychiatric disorder and obtaining adequate informed consent might be required to prevent the trouble concerning oral cenesthopathy. Keywords: oral cenesthopathy, delusional disorder somatic type, DDST, chart review, dentistry

Objectives: To identify the molecular etiology of distinct dental anomalies found in eight Thai patients and explore the mutational effects on cellular functions. Materials and Methods: Clinical and radiographic examinations were performed for eight patients. Whole exome sequencing, mutant protein modelling, qPCR, western blot analysis, scratch assays, immunofluorescence, confocal analysis, in situ hybridization, and scanning electron micrography of teeth were done. Results: All patients had molars with multiple supernumerary cusps, single‐cusped premolars, and a reduction in root number. Mutation analysis highlighted a heterozygous c.865A>G; p.Ile289Val mutation in CACNA1S in the patients. CACNA1S is a component of the slowly inactivating L‐type voltage‐dependent calcium channel. Mutant protein modeling suggested that the mutation might allow leakage of Ca2+ or other cations, or a tightening, to restrict calcium flow. Immunohistochemistry analysis showed expression of Cacna1s in the developing murine tooth epithelium during stages of crown and root morphogenesis. In cell culture, the mutation resulted in abnormal cell migration of transfected CHO cells compared to wildtype CACNA1S, with changes to the cytoskeleton and markers of focal adhesion. Conclusions: The malformations observed in our patients suggest a role for calcium signaling in organization of both cusps and roots, affecting cell dynamics within the dental epithelium. [ABSTRACT FROM AUTHOR]

The age and genesis of Michigan's world-class native copper deposits are poorly constrained. The copper is hosted by basaltic flow tops and conglomeratic interbeds of the 1095 [+ or -] 2 Ma Keweenawan Portage Lake Formation. Progressive thermal demagnetization isolates stable hematite remanent magnetization components at 28 paleomagnetic sites. Paleomagnetic tilt tests show that magnetite in massive flow interiors is primary (1095 [+ or -] 2 Ma) and that hematite throughout the formation is syntectonic. The altered cupriferous deposits contain primary ~1095 Ma and secondary ~1053 Ma hematite in various proportions. The Caledonia Mine's basaltic mineralization carries the ~1053 Ma hematite dominantly whereas the Delaware Mine's conglomeratic interbed mineralization carries the ~1095 Ma hematite dominantly. The ~1095 Ma hematite is attributed mostly to magnetite exsolution during flow extrusion and to weathering oxidation between extrusion events. An infusion of epigenetic hydrothermal fluids emplaced the native copper with additional hematite and polarity self-reversing titanohematite at 1053 [+ or -] 7 Ma. Importantly, paleomagnetic evidence supports a 1053 [+ or -] 7 Ma age also for the White Pine stratiform sedimentary copper mineralization, for the oxidation of the Oronto Group clastic rocks to red beds, and for the time limits of major tectonic uplift and deformation on the Keweenaw Peninsula. Key words: paleomagnetism, native copper mineralization, Keweenawan Supergroup, North America, Proterozoic. L'age et la genese des gisements de cuivre natif de classe mondiale du Michigan ne sont pas bien etablis. Le cuivre occupe le sommet de coulees basaltiques et des interlits conglomeratiques de la Formation keweenawienne de Portage Lake de 1095 [+ or -] 2 Ma. Une demagnetisation thermique progressive isole des elements d'hematite a magnetisation remanente stable dans 28 sites paleomagnetiques. Des tests d'inclinaison paleomagnetique montrent que la magnetite dans la partie interne de coulees massives est primaire (1095 [+ or -] 2 Ma) et que l'hematite dans toute la formation est syntectonique. Les gisements cupriferes alteres contiennent des proportions variables d'hematite primaire de ~1095 Ma et secondaire de ~1053 Ma. Dans la mineralisation basaltique a la mine Caledonia, l'hematite de ~1053 Ma domine, alors que, dans la mineralisation dans des interlits conglomeratiques de la mine Delaware, l'hematite de ~1095 Ma est dominante. L'hematite de ~1095 Ma est principalement attribuee a l'exsolution de magnetite durant l'extrusion des coulees et l'oxydation associee a la meteorisation entre les episodes d'extrusion. L'infusion de fluides hydrothermaux epigenetiques a mis en place le cuivre natif avec d'autre hematite et de la titanohematite a polarite autoinversee a 1053 [+ or -] 7 Ma. Fait a noter, les observations paleomagnetiques appuient aussi un age de 1053 [+ or -] 7 Ma pour la mineralisation cuprifere sedimentaire stratiforme de White Pine, pour l'oxydation des roches clastiques du Groupe d'Oronto en des couches rouges et pour les limites temporelles d'importants episodes de soulevement tectonique et de deformation dans la peninsule Keweenaw. [Traduit par la Redaction] Mots-cles: paleomagnetisme, mineralisation de cuivre natif, Supergroupe de Keweenawan, Amerique du Nord, Proterozoique., Introduction The Mesoproterozoic Keweenawan strata on the northwestern side of the Keweenaw Peninsula in northern Michigan host two world-class copper mining districts (Fig. 1). The native copper lode (NCL) district, [...]

Ultrahigh-energy density (UHED) states greater than 1 Gbar pressure are typically observed under extreme conditions, such as in the core of an inertial confinement fusion implosion. A novel alternative approach for generating volumetric UHED states is to use nanowire arrays irradiated with a femtosecond ultrahigh-intensity laser. In this paper, we present an experimental investigation on laser absorption and energy transport in nanowire arrays irradiated with a picosecond kilojoule petawatt laser. The laser–target interactions were studied by measuring the x-ray emission and escaping hot electrons from a bare Cu foil and a foil with a nanowire array grown on its surface. The measured Cu-Kα and He-α emissions from the nanowire array were higher than those from the flat foil. In addition, hot electrons observed from the front surface of the nanowire array were enhanced. On the other hand, despite the stronger Kα emission from the nanowire array and the enhancement of hot electrons escaping from the front surface of the nanowire array, the number of hot electrons observed from the rear side of the flat foil target was slightly lower than that of the flat foil. A comparison of the experimental results with the results of a two-dimensional particle-in-cell simulation code suggested that the magnetic fields generated around the periodic nanowire array trap hot electrons, improving the electron-to-target energy coupling and efficiently producing UHED states. [ABSTRACT FROM AUTHOR]

The Cantung tungsten-copper (W-Cu) skarn orebodies are hosted by Proterozoic and Lower Cambrian metasedimentary rocks next to the Cretaceous 'Mine Stock' monzogranite. Paleomagnetic analyses of 283 specimens from the Open Pit scheelitechalcopyrite orebody (17 sites) and from adjacent host rocks including the aplite dikes (11 sites) isolated a stable characteristic remanent magnetization (ChRM), mostly by alternating field and then thermal step demagnetization. The step demagnetization results along with rock magnetic analyses of the W concentrate show that the main remanence carriers are single- or pseudosingle-domain pyrrhotite, titanomagnetite, and (or) magnetite. There is no statistically significant difference at 95% confidence between the site mean ChRM directions for the W-Cu ore, the host rock, or the aplite dikes populations. This result indicates that the intrusion of the Mine Stock is coeval with the genesis of the scheelite skarn ore and with dike emplacement to give an overall mean ChRM direction of declination 342.9°, inclination 82.0° (N =22 sites, radius of cone of 95% confidence [α.sub.95] = 4.2°, precision parameter k = 54.7) that defines a paleopole at 76.2°N latitude, 212.2°E longitude (radius of cone of 95% confidence [A.sub.95] = 8.1°). This paleopole is concordant with the coeval 98 Ma North American paleopole at 92% confidence, which provides strong evidence that the eastern Selwyn Basin has been an autochthonous part of North America since the mid- Cretaceous. Les gisements de skarns a tungstene-cuivre (W-Cu) de Cantung sont encaisses dans des roches metasedimentaires datant du Proterozoique et du Cambrien inferieur, a proximite du stock intrusif de monzogranite << Mine Stock >> datant du Cretace. Des analyses paleomagnetiques sur 283 echantillons provenant du gisement nomme << Open Pit >> de scheelitechalcopyrite (17 sites) et des roches encaissantes adjacentes, incluant des dykes d'aplite (11 sites), ont permis d'isoler une aimantation remanente caracteristique stable (ChRM), principalement par alternance des champs puis par desaimantation thermique par etapes. Les resultats de la desaimantation par etapes, jumeles aux analyses magnetiques du concentre W, montrent que les principaux porteurs de la remanence sont une pyrrhotite, une titano-magnetite et/ou une magnetite, a domaine unique ou pseudo-unique. Il n'y a pas de difference statistique significative, au niveau de confiance de 95 %, entre les directions moyennes de la ChRM pour le minerai W-Cu, la roche encaissante ou les populations de dykes d'aplite. Selon ce resultat, l'intrusion du<>est contemporaine de la genese du minerai de skarns de scheelite et de la mise en place des dykes pour donner une direction moyenne generale de declinaison de la ChRM de 342,9 °, d'inclinaison de 82,0 ° (N = 22 sites, rayon du cone de confiance a 95 % [α.sub.95] = 4,2 °, parametre de precision k = 54,7) definissant un paleopole a une latitude de 76,2 °N et a une longitude de 212,2 °E (rayon du cone de confiance a 95 % [A.sub.95] = 8,1 °). Ce paleopole concorde avec le paleopole nord-americain contemporain de 98 Ma avec un niveau de confiance de 92 %, ce qui fournit de fortes indications que le bassin Selwyn oriental forme une partie autochtone de l'Amerique du Nord depuis le Cretace moyen. [Traduit par la Redaction], Introduction The 98-95 Ma Tungsten plutonic suite in the eastern Selwyn Basin forms an ~ 300 km long northwest-trending belt of plutons in the western Northwest Territories (NWT) and eastern [...]