Decision-making deficits in obsessive-compulsive disorder are associated with abnormality of recency and response consistency parameter in prospect valence learning model.

Background: Patients with obsessive-compulsive disorder (OCD) have deficits in decision-making in the Iowa Gambling Task (IGT). However, no study has investigated the parameters of the prospect valence learning (PVL) model in the IGT for OCD. Aims: This study aimed to investigate deficits in decision-making in OCD using the PVL model and identify whether the parameters of the PVL model were associated with obsessive-compulsive severity. Methods: Forty-seven medication-free patients with OCD were compared with 47 healthy controls (HCs). Decision-making was measured using the total net and block net scores of the IGT. A PVL model with a decay-reinforcement learning rule (PVL-DecayRI) was used to investigate the parameters of the model. Correlation analysis was conducted between each parameter of the PVL-DecayRL and obsessive-compulsive symptoms. Results: The total net score of patients with OCD was significantly lower than that of the HCs. The block net scores of the OCD group did not differ across the five blocks, whereas in the HCs, the fifth block net score was significantly higher than the block net scores of the first and second blocks. The values of the recency and response consistency parameters of the PVL-DecayRI in patients with OCD were significantly lower than those in HCs. The recency parameter positively correlated with the Y-BOCS obsessive score. Meanwhile, there was no correlation between consistency parameter values and symptom severity in OCD. Conclusion: Our detailed analysis of the decision-making deficit in OCD suggests that the most recent outcome has a small influence on the expectancy of prospect valence, as indicated by the lower recency parameter, and is characterized by more impulsive choices, as indicated by the lower consistency parameter.

Possible intermediate quantum spin liquid phase in α-RuCl3 under high magnetic fields up to 100 T.

Pursuing the exotic quantum spin liquid (QSL) state in the Kitaev material α-RuCl3 has intrigued great research interest recently. A fascinating question is on the possible existence of a field-induced QSL phase in this compound. Here we perform high-field magnetization measurements of α-RuCl3 up to 102 T employing the non-destructive and destructive pulsed magnets. Under the out-of-plane field along the c* axis (i.e., perpendicular to the honeycomb plane), two quantum phase transitions are uncovered at respectively 35 T and about 83 T, between which lies an intermediate phase as the predicted QSL. This is in sharp contrast to the case with in-plane fields, where a single transition is found at around 7 T and the intermediate QSL phase is absent instead. By measuring the magnetization data with fields tilted from the c* axis up to 90° (i.e., in-plane direction), we obtain the field-angle phase diagram that contains the zigzag, paramagnetic, and QSL phases. Based on the K-J-Γ-[Formula: see text] model for α-RuCl3 with a large Kitaev term we perform density matrix renormalization group simulations and reproduce the quantum phase diagram in excellent agreement with experiments.

High-Speed Tracking with Mutual Assistance of Feature Filters and Detectors.

Object detection and tracking in camera images is a fundamental technology for computer vision and is used in various applications. In particular, object tracking using high-speed cameras is expected to be applied to real-time control in robotics. Therefore, it is required to increase tracking speed and detection accuracy. Currently, however, it is difficult to achieve both of those things simultaneously. In this paper, we propose a tracking method that combines multiple methods: correlation filter-based object tracking, deep learning-based object detection, and motion detection with background subtraction. The algorithms work in parallel and assist each other's processing to improve the overall performance of the system. We named it the "Mutual Assist tracker of feature Filters and Detectors (MAFiD method)". This method aims to achieve both high-speed tracking of moving objects and high detection accuracy. Experiments were conducted to verify the detection performance and processing speed by tracking a transparent capsule moving at high speed. The results show that the tracking speed was 618 frames per second (FPS) and the accuracy was 86% for Intersection over Union (IoU). The detection latency was 3.48 ms. These experimental scores are higher than those of conventional methods, indicating that the MAFiD method achieved fast object tracking while maintaining high detection performance. This proposal will contribute to the improvement of object-tracking technology.

Posterior cingulate cortex spontaneous activity associated with motor response inhibition in patients with obsessive-compulsive disorder: A resting-state fMRI study.

Recent evidence suggests that broad brain regions, not limited to the fronto-striato-thalamo-cortical circuit, play an important role in motor response inhibition. However, it is still unclear which specific key brain region is responsible for impaired motor response inhibition observed in obsessive-compulsive disorder (OCD). We calculated the fractional amplitude of low-frequency fluctuations (fALFF) and measured response inhibition ability using the stop-signal task in 41 medication-free patients with OCD and 49 healthy control (HC) participants. We explored the brain region that shows different association between the fALFF and the ability of motor response inhibition. Significant differences in fALFF associated with the ability of motor response inhibition were identified in dorsal posterior cingulate cortex (PCC). There was a positive correlation between increased fALFF in the dorsal PCC and impaired motor response inhibition in OCD. In the HC group, there was a negative correlation between the two variables. Our results suggest that the magnitude of resting-state blood oxygen level-dependent oscillation of the dorsal PCC is a key brain region for the underlying mechanisms of impaired motor response inhibition in OCD. Future studies should examine whether this characteristic of dorsal PCC affects other large-scale networks responsible for motor response inhibition of OCD.

GLUT9 as a potential drug target for chronic kidney disease: Drug target validation by a Mendelian randomization study.

Although chronic kidney disease (CKD) is recognized as a major public health concern, effective treatment strategies have yet to be developed. Identification and validation of drug targets are key issues in the development of therapeutic agents for CKD. Uric acid (UA), a major risk factor for gout, has also been suggested to be a risk factor for CKD, but the efficacy of existing urate-lowering therapies for CKD is controversial. We focused on five uric acid transporters (ABCG2, SLC17A1, SLC22A11, SLC22A12, SLC2A9) as potential drug targets and evaluated the causal association between serum UA levels and estimated glomerular filtration rate (eGFR) using single-SNP Mendelian Randomization. The results showed a causal association between genetically predicted changes in serum UA levels and eGFR when genetic variants were selected from the SLC2A9 locus. Estimation based on a loss-of-function mutation (rs16890979) showed that the changes in eGFR per unit increase in serum UA level was -0.0082 ml/min/1.73 m2 (95% CI -0.014 to -0.0025, P = 0.0051). These results indicate that SLC2A9 may be a novel drug target for CKD that preserves renal function through its urate-lowering effect.

Multicellular dynamics on structured surfaces: Stress concentration is a key to controlling complex microtissue morphology on engineered scaffolds.

Tissue engineers have utilised a variety of three-dimensional (3D) scaffolds for controlling multicellular dynamics and the resulting tissue microstructures. In particular, cutting-edge microfabrication technologies, such as 3D bioprinting, provide increasingly complex structures. However, unpredictable microtissue detachment from scaffolds, which ruins desired tissue structures, is becoming an evident problem. To overcome this issue, we elucidated the mechanism underlying collective cellular detachment by combining a new computational simulation method with quantitative tissue-culture experiments. We first quantified the stochastic processes of cellular detachment shown by vascular smooth muscle cells on model curved scaffolds and found that microtissue morphologies vary drastically depending on cell contractility, substrate curvature, and cell-substrate adhesion strength. To explore this mechanism, we developed a new particle-based model that explicitly describes stochastic processes of multicellular dynamics, such as adhesion, rupture, and large deformation of microtissues on structured surfaces. Computational simulations using the developed model successfully reproduced characteristic detachment processes observed in experiments. Crucially, simulations revealed that cellular contractility-induced stress is locally concentrated at the cell-substrate interface, subsequently inducing a catastrophic process of collective cellular detachment, which can be suppressed by modulating cell contractility, substrate curvature, and cell-substrate adhesion. These results show that the developed computational method is useful for predicting engineered tissue dynamics as a platform for prediction-guided scaffold design. STATEMENT OF SIGNIFICANCE: Microfabrication technologies aiming to control multicellular dynamics by engineering 3D scaffolds are attracting increasing attention for modelling in cell biology and regenerative medicine. However, obtaining microtissues with the desired 3D structures is made considerably more difficult by microtissue detachments from scaffolds. This study reveals a key mechanism behind this detachment by developing a novel computational method for simulating multicellular dynamics on designed scaffolds. This method enabled us to predict microtissue dynamics on structured surfaces, based on cell mechanics, substrate geometry, and cell-substrate interaction. This study provides a platform for the physics-based design of micro-engineered scaffolds and thus contributes to prediction-guided biomaterials design in the future.

Gyrification of the medial and lateral orbitofrontal cortex in first-degree relatives of patients with obsessive-compulsive disorder.

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset.

Simultaneous measurement of specific heat and thermal conductivity in pulsed magnetic fields.

We report an experimental setup for simultaneously measuring specific heat and thermal conductivity in feedback-controlled pulsed magnetic fields of 50 ms duration at cryogenic temperatures. A stabilized magnetic field pulse obtained by the feedback control, which dramatically improves the thermal stability of the setup and sample, is used in combination with the flash method to obtain absolute values of thermal properties up to 37.2 T in the 22-16 K temperature range. We describe the experimental setup and demonstrate the performance of the present method with measurements on single-crystal samples of the geometrically frustrated quantum spin-dimer system SrCu2(BO3)2. Our proof-of-principle results show excellent agreement with data taken using a standard steady-state method, confirming the validity and convenience of the present approach.

Functional connectivity between pre-supplementary motor area and inferior parietal lobule associated with impaired motor response inhibition in first-degree relatives of patients with obsessive-compulsive disorder.

Previous studies have suggested that specific fronto-striatal circuits are associated with impaired motor response inhibition in patients with obsessive-compulsive disorder (OCD) and their relatives. However, no study has investigated the underlying resting-state network associated with motor response inhibition in the unaffected first-degree relatives of patients with OCD. We measured motor response inhibition using stop-signal task, and obtained resting-state fMRI in 23 first-degree relatives and 52 healthy control participants. We explored the group differences in the functional network from seed regions-of-interest (ROIs) associated with motor response inhibition abilities. We used the inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) as seed-ROIs. A significant group difference was observed in functional connectivity between the pre-SMA and inferior parietal lobule. In the relative group, reduced functional connectivity between these areas was associated with a longer stop-signal reaction time. Additionally, relatives showed significantly greater functional connectivity between the IFG and SMA, precentral, and postcentral areas. Our results could provide new insights into the resting-state neural activity of the pre-SMA underlying impaired motor response inhibition of unaffected first-degree relatives. In addition, our results suggested that relatives have an altered connectivity of the sensorimotor region, similar to that of patients with OCD shown in previous literature.

Heterogeneous expression and role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in small cell lung cancer.

The present study investigated the expression and role of ROR2 in small cell lung cancer (SCLC). To examine the expression of ROR2, 27 surgically resected SCLC tissue samples were immunostained for ROR2. Sixteen tissue samples were positive and some showed intratumor heterogeneity in staining intensity. The heterogeneity of ROR2 expression was also observed in tumor tissues from a PDX model of SCLC, in which there were cells with high ROR2 expression (ROR2high cells) and without its expression (ROR2low cells). These cells were subjected to a RNA sequence analysis. GSEA was performed and the results obtained revealed the enrichment of molecules such as G2M checkpoint, mitotic spindle, and E2F targets in ROR2high cells. The rate of EdU incorporation was significantly higher in ROR2high cells than ROR2low cells from the PDX model and the SCLC cell lines. Cell proliferation was suppressed in ROR2 KO SBC3 cells in vitro and in vivo. Comparisons of down-regulated differentially expressed genes in ROR2 KO SBC3 cells with up-regulated DEG in ROR2high cells from the PDX model revealed 135 common genes. After a Metascape analysis of these genes, we focused on Aurora kinases. In SCLC cell lines, the knockdown of ROR2 suppressed Aurora kinases. Therefore, ROR2 appears to regulate the cell cycle through Aurora kinases. The present results reveal a role for ROR2 in SCLC and afford a candidate system (ROR2-Aurora kinase) accompanying tumor heterogeneity in SCLC.

Pulmonary Neuroendocrine Cells and Small Cell Lung Carcinoma: Immunohistochemical Study Focusing on Mechanisms of Neuroendocrine Differentiation.

Neuroendocrine (NE) differentiation has been histochemically detected in normal and cancer tissues and cells. Immunohistochemical analyses have provided a more detailed understanding of NE biology and pathology. Pulmonary NE cells are a rare lung epithelial type, and small cell carcinoma of the lung (SCLC) is a high-grade NE tumor. Pulmonary NE and SCLC cells share common mechanisms for NE differentiation. Neural or NE cell lineage-specific transcription factors, such as achaete-scute homologue 1 (Ascl1) and insulinoma-associated protein 1 (INSM1), are crucial for the development of pulmonary NE cells, and NE differentiation is influenced by the balance between Ascl1 and the suppressive neural transcription factor, hairy-enhancer of split 1, a representative target molecule of the Notch signaling pathway. In this review, we discuss the importance of Ascl1 and INSM1 in identifying pulmonary NE and SCLC cells and introduce Ascl1-related molecules detected by comparative RNA-sequence analyses. The molecular classification of SCLC based on the expression of lineage-specific transcription or co-transcription factors, including ASCL1, NEUROD1, POU2F3, and YAP1, was recently proposed. We attempted to characterize these 4 SCLC subtypes using integrated immunohistochemical studies, which will provide insights into the molecular characteristics of these subtypes and clarify the inter- and intratumor heterogeneities of SCLC.

Inverse Association Between Resting-State Putamen Activity and Iowa Gambling Task Performance in Patients With Obsessive-Compulsive Disorder and Control Subjects.

Background: Symptoms of obsessive-compulsive disorder (OCD) have been conceptualized as manifestations of decision-making deficits. Patients with OCD exhibit impairment during the decision-making process, as assessed by the Iowa Gambling Task (IGT). This impairment is independent of clinical severity and disease progression. However, the association between the decision-making deficit and resting-state brain activity of patients with OCD has not been examined. Methods: Fifty unmedicated patients with OCD and 55 matched control subjects completed IGT. Resting-state brain activity was examined using the fractional amplitude of low-frequency fluctuations (fALFFs). fALFF analysis focused on the slow-4 and 5 bands. Group comparisons were performed to determine the association between IGT performance and fALFFs. Results: There was a significant group difference in the association between the IGT total net score and slow-4 fALFFs in the left putamen (voxel height threshold of p < 0.001; cluster size threshold of p < 0.05; family wise error-corrected). Higher putamen slow-4 fALFFs were correlated with lower IGT scores for OCD patients (r = -0.485; p < 0.0005) and higher IGT scores for control subjects (r = 0.402; p < 0.005). There was no group difference in the association between the IGT total net score and slow-5 fALFFs. Conclusions: These findings in unmedicated patients demonstrate the importance of resting-state putamen activity for decision-making deficit associated with OCD, as measured by IGT. The inverse correlation may be explained by the hypersensitive response of the putamen in patients with OCD.

Alterations of default mode and cingulo-opercular salience network and frontostriatal circuit: A candidate endophenotype of obsessive-compulsive disorder.

Background It is gradually becoming clear that obsessive-compulsive disorder (OCD) patients have aberrant resting-state large-scale intrinsic networks of cingulo-opercular salience (SN), default mode (DMN), and front-parietal network (FPN). However, it remains unknown whether unaffected first-degree relatives of OCD patients have these alterations as a vulnerability marker to the disorder. Methods We performed resting-state functional magnetic resonance imaging (rsfMRI) scans of 47 medication-free OCD patients, 21 unaffected healthy first-degree relatives of OCD patients, and 62 healthy control (HC) participants. We explored differences between the three groups in the functional connectivity from SN (seeds: anterior-insula (AI) and dorsal anterior cingulate cortex (dACC)), DMN (seeds: medial prefrontal cortex (MPFC) and posterior parietal cortex (PCC)), and FPN (seeds: dorsolateral prefrontal cortex (DLPFC)). Results Compared to HC, both OCD patients and first-degree relatives showed significantly greater functional connectivity between AI and PCC and between DLPFC and the thalamus. Compared to first-degree relatives and HC, OCD patients showed reduced functional connectivity between PCC and DLPFC, and this altered functional connectivity was negatively correlated with anxiety and depressive symptom within OCD group. Conclusions OCD patients and unaffected first-degree relatives of OCD patients showed overlapping alterations in resting state functional connectivity between the regions of SN and DMN and between DLPFC and the thalamus. Our results suggested that alterations between large-scale intrinsic networks and within the dorsal cognitive cortico-striato-thalamo-cortical (CSTC) circuit could represent endophenotype markers of OCD.

Spin-glass transition in the spin-orbit-entangled Jeff = 0 Mott insulating double-perovskite ruthenate.

We have successfully synthesized new Ru4+ double perovskite oxides SrLaInRuO6 and SrLaGaRuO6, which are expected to be a spin-orbit coupled Jeff = 0 Mott insulating ground state. Their magnetic susceptibility is much significant than that expected for a single Ru4+ ion for which exchange coupling with other ions is negligible. Their isothermal magnetization process suggests that there are about 20 percent isolated spins. These origins would be the Ru3+/Ru5+ magnetic defects, while the regular Ru4+ sites remain nonmagnetic. Moreover, SrLaGaRuO6 shows a spin-glass-like magnetic transition at low temperatures, probably caused by isolated spins. The observed spin-glass can be interpreted by the analogy of a dilute magnetic alloy, which can be seen as a precursor to the mobile Jeff = 1 exciton as a dispersive mode as predicted.

The role of YAP1 in small cell lung cancer.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1) are core downstream effectors of the Hippo pathway, which is involved in diverse biological processes. The oncogenic effects of YAP and TAZ in non-small cell lung cancer (NSCLC) have recently been reported; however, their roles in SCLC remain unclear. Immunohistochemistry (IHC) on lung cancer tissues and Western blotting (WB) on lung cancer cell lines were performed to examine the expression of YAP1. Genome editing using CRISPR/Cas9 was then used to knockout the YAP1 gene in the H69AR cell line. An RNA-sequence analysis, gene ontology (GO) analysis, WB, cell counting assay, invasion assays, and xenograft studies were conducted on these cells to investigate the biological roles of YAP1. IHC revealed that insulinoma-associated protein 1 was expressed in most cases (28 out of 32 cases), while only four cases expressed YAP1. The knockout of YAP1 in H69AR cells, a chemically induced SCLC-Y subtype, reduced cell proliferation and invasion capacity and restored drug sensitivity. Xenograft assays revealed that the knockout of YAP1 suppressed cell proliferation. Tumor tissues showed the expression of neuroendocrine markers and a low Ki-67 index. In SCLC, YAP1 plays an important role in biological functions, such as cell proliferation, EMT, drug sensitivity, and neuroendocrine differentiation.

ZMYM3 May Promote Cell Proliferation in Small Cell Lung Carcinoma.

Zinc finger, myeloproliferative, and mental retardation-type containing 3 (ZMYM3) is a highly conserved protein among vertebrates. Although it promotes DNA repair and moderate histone acetylation, the other functions of ZMYM3 remain unclear. We herein examined the physiological functions of ZMYM3 in human lung cancer using a ZMYM3-knockdown small cell lung cancer (SCLC) cell line. ZMYM3-knockdown SCLC cells grew slowly and the Ki-67 labeling index was lower in ZMYM3-knockdown cells than in mock cells. The subcutaneous tumors that formed after xenotransplantation into immunodeficient mice were slightly smaller in the ZMYM3-knockdown group than in the mock group. Furthermore, public RNA-sequencing data analyses showed similar RNA profiles between ZMYM3 and some cell proliferation markers. These results indicate that ZMYM3 promotes cell proliferation in human lung carcinomas, particularly SCLC.

High-resolution calorimetry in pulsed magnetic fields.

We have developed a new calorimeter for measuring the thermodynamic properties in pulsed magnetic fields. Instrumental design is described along with the instrument construction details, including the sensitivity of a RuO2 thermometer. Operation of the calorimeter is demonstrated by measuring the heat capacity of three samples: pure germanium, CeCu2Ge2, and κ-(BEDT-TTF)2Cu[N(CN)2]Br, in pulsed fields up to 43.5 T. Obtaining field stability is key in measuring high-resolution heat capacity under pulsed fields. We also examine the performance of the calorimeter by employing two measurement techniques: the quasi-adiabatic and dual-slope techniques. We demonstrate that the calorimeter developed in this study is capable of performing high-resolution calorimetry in pulsed magnetic fields, which opens the door to new opportunities for high-field thermodynamic studies.

JTZ-951 (enarodustat), a hypoxia-inducible factor prolyl hydroxylase inhibitor, improves iron utilization and anemia of inflammation: Comparative study against recombinant erythropoietin in rat.

Anemia with inflammation-induced defective iron utilization is a pathological condition observed in patients suffering from chronic kidney disease (CKD) or chronic inflammatory disease. There is no reasonable treatment for these conditions, because the effects of erythropoiesis stimulating agents (ESAs) or iron supplementation in the treatment of anemia are insufficient. JTZ-951 (enarodustat) has been characterized as a novel, orally bioavailable inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), and has been developed as a novel therapeutic agent for anemia with CKD. In this study, the effects of JTZ-951 on iron utilization during erythropoiesis and on anemia of inflammation were compared with those of recombinant human erythropoietin (rHuEPO) using normal rat and rat model of anemia of inflammation. In normal rats, under conditions in which JTZ-951 and rHuEPO showed similar erythropoietic effect, repeated doses of JTZ-951 induced erythropoiesis while retaining the hemoglobin content in red blood cells, while administration of rHuEPO resulted in decrease in some erythrocyte-related parameters. As for iron-related parameters during erythropoiesis, JTZ-951 exhibited more efficient iron utilization compared to rHuEPO. A single dose of JTZ-951 resulted in decrease in hepcidin expression observed within 24 h after administration, but a single dose of rHuEPO did not. In a rat model of anemia of inflammation (also known as a model with functional iron-deficiency), JTZ-951 showed erythropoietic effect, in contrast with rHuEPO. These results suggest that, unlike rHuEPO, JTZ-951 stimulates erythropoiesis by increasing iron utilization, and improves anemia of inflammation.

Ligand dependent magnetism of theJeff= 3/2 Mott insulator Cs2MX6(M= Ta, Nb,X= Br, Cl).

Magnetic and structural properties of double perovskite type bromides Cs2MBr6(M= Ta, Nb), where Ta4+(5d1) and Nb4+(4d1) ions form the face centered cubic lattice, are investigated and compared with chlorides Cs2MCl6. Cs2TaBr6exhibits the effective magnetic moment of 0.24µB, which is much smaller than the spin only value of ad1ion, 1.73µB, and comparable to 0.25µBin Cs2TaCl6. On the other hand, the effective magnetic moment of Cs2NbBr6is 0.7µBand is substantially smaller than 1.0µBin Cs2NbCl6. On cooling, successive structural and magnetic phase transitions accompanying the release of electronic entropy approximatelyRln 4 in total as expected for theJeff= 3/2 state are observed. The type of the ligand changes the temperature dependence of magnetic susceptibility at low temperature as well as its magnitude. The role of the ligands on the magnetism ofJeff= 3/2 Mott insulators are discussed in the light of metal-ligand hybridization and the electron-lattice coupling.

Significant cases of central cusps, enamel pits, and oral fibromas in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which benign nodular tumors form in the cerebral cortex, cerebellum, and throughout the body causing various symptoms. In this study, we summarized the incidence of dental findings in patients with TSC at our hospital and its association with diseases in various organs. Patients diagnosed with TSC at our hospital between January 2013 and September 2017, and who were examined in the dental and oral surgery department were included in this study. The presence of intraoral manifestations (central cusps, enamel pits, oral fibromas) was examined by means of visual inspection, intraoral photography, and X-ray photography. In addition, the relationship with associated diseases (neurological, cutaneous, cardiac, renal, and pulmonary) according to organ and disease severity was examined. The mean age (± SD) of the 42 TSC patients (19 men and 23 women) was 27.8 ± 14.6 years, of which 24 patients (11 men and 13 women) presented with oral manifestations. Of these patients, seven had central cusps, 10 had enamel pits, and 17 had oral fibromas. The group with central cusps had significantly higher neurological issues in the relationship between intraoral manifestations and associated disease based on the involved organ. The prevalence of central cusps in TSC was 16.7%, which is significantly higher than the 2.6% reported in healthy Japanese subjects. The central cusp is a diagnostic factor alongside the presence of enamel pits and oral fibromas, which can aid in the early diagnosis of TSC by dentists.