Intraocular pressure changes during intravitreal aflibercept injection based on treat-and-extend regimen in Japanese patients with neovascular age-related macular degeneration and glaucoma.

PURPOSE: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2 mg/0.05 ml of aflibercept and followed for 52 weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52 weeks were recorded. RESULTS: The mean of aflibercept injections was 8.3 ± 1.9. The mean IOP at baseline was 14.0 ± 3.1 mmHg, and the mean IOP after aflibercept therapy was 13.0 ± 2.4 mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery. CONCLUSION: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma.

Achaete-scute family bHLH transcription factor 2 activation promotes hepatoblastoma progression.

Achaete-scute family bHLH transcription factor 2 (ASCL2) is highly expressed in hepatoblastoma (HB) tissues, but its role remains unclear. Thus, biological changes in the HB cell line HepG2 in response to induced ASCL2 expression were assessed. ASCL2 expression was induced in HepG2 cells using the Tet-On 3G system, which includes doxycycline. Cell viability, proliferation activity, mobility, and stemness were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation, migration, invasion, and sphere-formation assays. Quantitative reverse-transcription polymerase chain reaction was used to assess the expression of markers for proliferation (CCND1 and MYC), epithelial-mesenchymal transition (EMT; SNAI1, TWIST1, and ZEB1), mesenchymal-epithelial transition (CDH1), and stemness (KLF4, POU5F1, and SOX9). Compared with the non-induced HepG2 cells, cells with induced ASCL2 expression showed significant increases in viability, colony number, migration area (%), and sphere number on days 7, 14, 8, and 7, respectively, and invasion area (%) after 90 h. Furthermore, induction of ASCL2 expression significantly upregulated CCND1, MYC, POU5F1, SOX9, and KLF4 expression on days 2, 2, 3, 3, and 5, respectively, and increased the ratios of SNAI1, TWIST1, and ZEB1 to CDH1 on day 5. ASCL2 promoted the formation of malignant phenotypes in HepG2 cells, which may be correlated with the upregulation of the Wnt signaling pathway-, EMT-, and stemness-related genes. ASCL2 activation may therefore be involved in the progression of HB.

Complement activation products in tears of dry eye and meibomian gland dysfunction.

Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.

Urethral identification using three-dimensional magnetic resonance imaging and interfraction urethral motion evaluation for prostate stereotactic body radiotherapy.

Prostatic urethra identification is crucial in prostate stereotactic body radiotherapy (SBRT) to reduce the risk of urinary toxicity. Although computed tomography (CT) with a catheter is commonly employed, it is invasive, and catheter placement may displace the urethral position, resulting in possible planning inaccuracies. However, magnetic resonance imaging (MRI) can overcome these weaknesses. Accurate urethral identification and minimal daily variation could ensure a highly accurate SBRT. In this study, we investigated the usefulness of a three-dimensional (3D) T2-weighted (T2W) sequence for urethral identification, and the interfractional motion of the prostatic urethra on CT with a catheter and MRI without a catheter for implementing noninvasive SBRT. Thirty-two patients were divided into three groups. The first group underwent MRI without a catheter to evaluate urethral identification by two-dimensional (2D)- and 3D-T2W sequences using mean slice-wise Hausdorff distance (MSHD) and Dice similarity coefficient (DSC) of the contouring by two operators and using visual assessment. The second group provided 3-day MRI data without a catheter using 3D-T2W, and the third provided 3-day CT data with a catheter to evaluate the interfractional motion using MSHD, DSC, and displacement distance (Dd). The MSHD and DSC for the interoperator variability in urethral identification and visual assessment were superior in 3D-T2W than in 2D-T2W. Regarding interfractional motion, the Dd value for prostatic urethra was smaller in MRI than in CT. These findings indicate that the 3D-T2W yielded adequate prostatic urethral identification, and catheter-free MRI resulted in less interfractional motion, suggesting that 3D-T2W MRI without a catheter is a feasible noninvasive approach to performing prostate SBRT.

Shifting-field-of-view technique enhancing the inflow effect for identifying tumor/vessel boundaries in MRI for radiotherapy treatment planning.

This study presents two cases of tumors in contact with the inferior vena cava during radiotherapy, and introduces a clinically useful technique for identifying tumor boundaries adjacent to blood vessels by adjusting the position of the field-of-view (FOV) to enhance the inflow effect in magnetic resonance imaging. We named this technique "Shifting-FOV." This method consists of three steps: (1) remove the upper and lower saturation pulses outside the FOV, (2) align the FOV to position the lower edge of the imaging slab as close to the tumor as possible, and (3) manually adjust the table position to locate the tumor at the center of the magnetic field. The proposed method allowed for accurate identification of the tumor/vessel boundaries in both cases. This is a useful technique that can be readily applied to other facilities. Furthermore, images obtained using this technique may enable accurate tumor contouring in radiotherapy treatment planning.

[Evaluation of Detectability in Clinical Practice of Metal Detectors, etc. for Magnetic Resonance Imaging].

PURPOSE: In order to prevent magnetic materials from being brought into the magnetic resonance imaging (MRI) examination room, many facilities have metal detectors, etc., but there are various types of equipment with different performance and characteristics. The purpose of this study was to evaluate each detector in actual clinical practice. METHODS: At multiple facilities, gate-type magnetic detectors, pole-type magnetic detectors, handy-type magnetic detectors, and handy-type metal detectors were used to identify 9 types of objects that may be brought into the MRI examination room. We performed evaluation of detection distance measurement assuming actual operation. RESULTS: The gate type was only able to detect objects with strong magnetism. With the pole type, the closer the measurement distance was to the pole, the more objects could be detected, and the lower the pole, the shorter the detection distance. With the handy type, there were many objects that could be detected when the device and the object were brought into close contact. CONCLUSION: The detectability of the instruments varied depending on the size and type of the object. It is important to understand the characteristics of each device and use it according to the purpose in carrying-in confirmation before the examination.

Tear fluid and complement activation products in tears after ocular surgery.

PURPOSE: Due to technological advancements, surgical invasiveness has been reduced. However, cataract surgery has been implicated in causing postoperative inflammation, including dry eye syndrome. The innate immune system may be involved in postoperative inflammation, and complement activation could potentially play a crucial role in defense against pathogens, homeostasis, and wound healing. To investigate changes in the tear film complement activation products (CAPs) and ocular surface after vitrectomy combined with cataract surgery. METHODS: Forty-three patients (23 women; median age, 69 years) were enrolled in this prospective study and underwent phacoemulsification and vitrectomy. We measured Schirmer's test (ST) and CAPs in the tears at baseline (the day before surgery), 4 days and 1 month after the surgery. Tears were collected in microtubes. The CAPs in the tear fluid were analyzed by cytometric bead array. RESULTS: The median ST (8.5 mm) at baseline increased to 16 mm at 4 days ( P < 0.001) and 10 mm at 1 month (P = 0.44). The C3a levels (1202 pg/ml) at baseline increased to 2753 pg/ml at 4 days (P < 0.001), and 1763 pg/ml at 1 month (P = 0.049). The C4a levels (476 pg/ml) at baseline increased to 880 pg/ml at 4 days (P < 0.001), and 657 pg/ml at 1 month (P = 0.013). The C5a levels (22.6 pg/ml) at baseline increased to 470.9 pg/ml at 4 days (P < 0.001), and 38.3 pg/ml at 1 month (P = 0.0048). The surgical eyes were divided into the short ST group (≦ 10 mm, n = 22) and long ST group (> 10 mm, n = 21) based on the preoperative ST values. At 1 month postoperatively, the C3a levels were 2194 pg/ml in the preoperative short ST group and 1391 pg/ml in the long ST group, with significantly higher C3a concentrations in the short ST group (P < 0.001). CONCLUSIONS: The CAPs levels in tears increased after vitrectomy combined with cataract surgery. A preoperative deficit in tear secretion might induce prolonged complement activation and delayed recovery of ocular surface parameters postoperatively.

Pirarubicin Combination Low-Dose Chemotherapy for Early Infantile Stage MS Neuroblastoma: Case Report.

Neuroblastoma (NB) is a neural crest-derived malignant tumor which is diagnosed during infancy in approximately 40% of cases; spontaneous regressions are observed, but there are varying degrees of severity. Treatment is indicated if an infant's condition is at risk of deterioration. Herein, we report the case of a 42-day-old boy who presented with hepatomegaly and was diagnosed with stage MS NB. A pathological diagnosis of "poorly differentiated neuroblastoma with low mitosis-karyorrhexis index, favorable histology" was made; his tumor cells were hyperdiploid and MYCN was not amplified. Because he had respiratory distress caused by the rapidly evolving hepatomegaly, two cycles of chemotherapy containing vincristine and cyclophosphamide were administered in the second and fourth weeks of admission; however, his abdominal tumor did not shrink. In the sixth week of admission, chemotherapy was revised to pirarubicin and cyclophosphamide, and the tumor began to shrink. After discharge, there was no re-elevation of tumor markers; after 1 year, the hepatomegaly and liver metastases disappeared. During the 5-year follow-up, his growth and development were normal and he progressed without sequelae. A regimen that includes pirarubicin could merit further study in the treatment of early infants with stage MS low-risk NB who are at risk of complications.

[Effective therapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy with obinutuzumab for follicular lymphoma in leukemic phase].

The patient, a 56-year-old lady, also exhibited numerous lymphadenopathy, hepatosplenomegaly, hyperleukocytosis (167,200/µl, aberrant lymphocytes 91.5%), and fever. A lymph node biopsy revealed follicular lymphoma (FL), grade 1. Peripheral blood tumor cells did not express CD10, which was a distinctive characteristic of the lymph node specimen. To prevent tumor lysis syndrome (TLI), CHOP was delivered without an anti-CD20 antibody, but afterward, residual lymphoma cells were found in peripheral blood (>80%). As a result, obinutuzumab (Obi) was given on day 8 following the second round of CHOP, and the tumor cells in the peripheral blood vanished without any major side effects like TLI. She underwent six chemotherapy sessions before receiving maintenance therapy with Obi and achieving a full metabolic response. According to reports, leukemic FL exhibits negative CD10 expression in peripheral blood lymphoma cells, while leukemic mantle cell lymphoma also shows this trait. Therefore, it is important not to confuse the two types in diagnosis. Leukemic FL with significant leukocytosis is reportedly uncommon and has a bad prognosis. Our case indicates that CHOP with Obi would be a good alternative for cases like yours, however, there have been a few cases recorded. Further case accumulation or investigation is warranted.

MACULAR SENSITIVITY CHANGE AFTER COMPLEMENTARY LASER THERAPY AFTER RANIBIZUMAB INTRAVITREAL INJECTION IN BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: We examined the effect of ranibizumab with or without laser photocoagulation on retinal sensitivity in eyes with branch retinal vein occlusion. METHODS: Prospective randomized control study. Thirty patients with branch retinal vein occlusion received intravitreal injection of ranibizumab in a monthly pro re nata regimen. Fifteen patients received ranibizumab monotherapy alone (monotherapy group). The remaining 15 patients received rescue laser therapy at 3 or 9 months (combined group). The retinal sensitivity was measured at 32 points within central 8°, and the average of the main occlusion side among the 16 upper or 16 lower points was defined as the affected area sensitivity. RESULTS: In comparing the monotherapy group and the combined group, the number of injections during the 12 months was 5.4 versus 4.9, the change in retinal thickness ( µ m) was -254 versus -197, the ETDRS letters of improvement was +18.3 versus +19.6, and the change in the affected area sensitivity (dB) was +7.1 versus +4.6. At 12 months, all these results were significantly improved compared with their respective baselines, but none of the differences between the two groups reached statistical significance. CONCLUSION: Retinal sensitivity at 12 months improved in both the monotherapy group and the combined group. The additional laser did not reduce the number of injections or further improve visual acuity nor did it affect retinal sensitivity.

The Characteristics of Power Spectral Density in Bipolar Disorder at the Resting State.

Bipolar disorder (BD) is a common psychiatric disorder, but its pathophysiology is not fully elucidated. The current study focused on its electrophysiological characteristics, especially power spectral density (PSD). Resting state with eyes opened magnetoencephalography data were collected from 21 patients with BD and 22 healthy controls. The whole brain's PSD was calculated from source reconstructed waveforms at each frequency band (delta: 1-3 Hz, theta: 4-7 Hz, alpha: 8-12 Hz, low beta: 13-19 Hz, high beta: 20-29 Hz, and gamma: 30-80 Hz). We compared PSD values on the marked vertices at each frequency band between healthy and patient groups using a Mann-Whitney rank test to examine the relationship between significantly different PSD and clinical measures. The PSD in patients with BD was significantly decreased in lower frequency bands, mainly in the default mode network (DMN) areas (bilateral medial prefrontal cortex, bilateral precuneus, left inferior parietal lobe, and right temporal cortex in the alpha band) and salience network areas (SAL; left anterior insula [AI] at the delta band, anterior cingulate cortex at the theta band, and right AI at the alpha band). No significant differences in PSD were observed at low beta and high beta. PSD was not correlated with age or other clinical scales. Altered PSDs of the DMN and SAL were observed in the delta, theta, and alpha bands. These alterations contribute to the vulnerability of BD through the disturbance of self-referential mental activity and switching between the default mode and frontoparietal networks.

Pitfalls of Using T2-contrast Enhancement Techniques in 3D-FLAIR to Detect Endolymphatic Hydrops.

PURPOSE: To determine whether T2-contrast enhancement techniques can be used to diagnose endolymphatic hydrops, we compared fluid signal artifacts with and without T2-contrast enhancement techniques in 3D fluid-attenuated inversion recovery (3D-FLAIR). METHODS: We prepared a custom-made phantom consisting of eight tubes half-filled with saline. Images were obtained using four 3D-FLAIR: without T2-contrast enhancement (Normal), with non-selective T2-inversion recovery (T2-IR), and two with non-selective T2 preparation IR (T2-prep). Scans were performed with and without rice covering the phantom to simulate minimal and severe B0-inhomogeneity conditions. The average signal intensity (SI) values of eight saline tubes were compared between the four sequences and between each other. Comparisons were performed for all measurement slices and the central 10 slices. The images using T2-contrast enhancement technique were obtained from a volunteer and a patient suspected of Meniere's disease. RESULTS: The Normal sequence SI for all slices was significantly lower than that for the other sequences, with smaller standard deviation (SD) and no outliers. Several outliers were detected in the other sequences. The SDs and outliers were larger without rice than with rice. When the central 10 slices with rice, the T2-IR had a significantly higher SI with more outliers compared with the Normal sequence. The T2-prep had no outliers and SIs that were comparable to those of the Normal sequence. However, without rice, the T2-IR and T2-prep sequences had significantly higher SIs with outliers and larger SDs compared to the Normal sequence. In the corresponding images, the Normal sequence achieved excellent fluid suppression, whereas the T2-IR and T2-prep sequences showed high-signal artifacts. Imperfect fluid suppressions were observed in the volunteer image and the endolymphatic hydrops on the post-gadolinium image differed in size and shape in the non-injected T2-IR in the patient image. CONCLUSION: T2-contrast enhancement techniques should be used with caution in 3D-FLAIR for diagnosing endolymphatic hydrops.

Stereotactic radiotherapy for ventricular tachycardia: A study protocol.

Background: Currently, the standard curative treatment for ventricular tachycardia (VT) and ventricular fibrillation (VF) is radiofrequency catheter ablation. However, when the VT circuit is deep in the myocardium, the catheter may not be delivered, and a new, minimally invasive treatment using different energies is desired. Methods: This is a protocol paper for a feasibility study designed to provide stereotactic radiotherapy for refractory VT not cured by catheter ablation after at least one catheter ablation. The primary end point is to evaluate the short-term safety of this treatment and the secondary endpoint is to evaluate its efficacy as assessed by the reduction in VT episode. Cyberknife M6 radiosurgery system will be used for treatment, and the prescribed dose to the target will be 25Gy in one fraction. The study will be conducted on three patients. Conclusion: Since catheter ablation is the only treatment option for VT that is covered by insurance in Japan, there is currently no other treatment for VT/VF that cannot be cured by catheter ablation. We hope that this feasibility study will provide hope for patients who are currently under the stress of ICD activation. Trial registration: The study has been registered in the Japan Registry of Clinical Trials (jRCTs042230030).

17O-labeled water distribution in the human inner ear: Insights into lymphatic dynamics and vestibular function.

We evaluated the inner ear distribution of 17O-labeled saline administered to the human tympanic cavity. Magnetic resonance imaging was performed after intratympanic administration in five healthy volunteers and one patient with cochlear endolymphatic hydrops. In all volunteers, 17O-labeled water permeated the cochlear basal turn and vestibule at 30 min and disappeared gradually within 2-4 h. All participants experienced positional vertigo lasting a few hours to a few days. Visualization of 17O-labeled water distribution in the endolymphatic space of the posterior ampulla showed indistinct separation of endolymph and perilymph in the cochlea and most of the vestibule in all participants. Intralabyrinthine distribution of 17O-labeled water differed from that in previous reports of intratympanically administered gadolinium-based contrast agent. 17O-labeled water in the endolymphatic space may cause heavier endolymph and positional vertigo. These results of this study may add new insights for investigating the distribution and the effects of molecules in the inner ear after the intratympanic administration in living humans.

Recombinant human soluble thrombomodulin and danaparoid combination anticoagulant therapy for disseminated intravascular coagulation in a child with streptococcal toxic shock syndrome: A case report.

Disseminated intravascular coagulation (DIC) is a common and morbid complication of streptococcal toxic shock syndrome (STSS). Because DIC with STSS progresses rapidly, prompt and proper care is critical. The present report describes the case of a 10-year-old boy who survived STSS with DIC without sequelae after treatment with combination anticoagulant therapy of recombinant human soluble thrombomodulin (rhTM) and danaparoid. RhTM and antithrombin-III were administered on day 1. RhTM administration was continued. Despite this, on day 2, his general condition remained poor, his fever persisted and his DIC score increased from an initial 5 points upon admission to 9 points. Therefore, danaparoid was additionally administered from day 2 onwards. The patient recovered without serious complications. Combination anticoagulant therapy of rhTM and danaparoid for DIC in a child with STSS was effective and safe. Therefore, this combination therapy could be used as an option for managing high-risk, rapidly progressing disease states, which predispose to morbid sequelae and death, such as DIC with STSS. RhTM and danaparoid therapy may reduce the risk of serious complications, such as organ failure, and improve the prognosis not only in STSS but also in other conditions with infection and DIC concurrence, such as sepsis.

Age-Related Maculopathy Susceptibility 2 and Complement Factor H Polymorphism and Intraocular Complement Activation in Neovascular Age-Related Macular Degeneration.

Purpose: To investigate the association of risk alleles in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) with complement activation products in the aqueous humor in eyes with neovascular age-related macular degeneration (nAMD) including polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and pachychoroid neovasculopathy (PNV). Design: Prospective, comparative, observational study. Participants: Treatment-naïve patients with nAMD and cataract patients as controls. Methods: The study included 236 eyes of 236 patients with nAMD and 49 control eyes of 49 patients. Aqueous humor samples were collected from 67 eyes with drusen-associated nAMD, 72 eyes with PCV, 26 eyes with RAP, and 71 eyes with PNV before intravitreal anti-VEGF injection and cataract surgery in the 49 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, and C5a using a bead-based immunoassay. Genotyping of the ARMS2 A69S (rs10490924), CFH I62V (rs800292), and CFH Y402H (rs1061170) was performed using TaqMan genotyping. Main Outcome Measures: The levels of complement activation products (C3a, C4a, and C5a) in the aqueous humor in each genotype of ARMS2 and CFH. Results: The C3a level in the aqueous humor was significantly elevated (P = 0.006) in patients with nAMD and the ARMS2 A69S risk allele, whereas the levels of the complement activation products were not associated with CFH I62V and Y402H genotypes. Among the control eyes, no significant differences were seen in any complement activation products for all genetic polymorphisms. The levels of the complement activation products in the aqueous humor of eyes with the nAMD subtypes for each genetic polymorphism did not show significant differences. Conclusions: The C3a concentration in the aqueous humor was significantly higher in Japanese nAMD patients with the ARMS2 A69S risk allele, whereas it was not elevated in the patients with CFH I62V. Age-related maculopathy susceptibility 2 A69S polymorphism is strongly associated with local complement activation in nAMD patients.

Morphometrics in three dimensional choroidal vessel models constructed from swept-source optical coherence tomography images.

We created three types of vessel models: vessel volume, surface, and line models from swept-source optical coherence tomography images and tested experimentally calculated three-dimensional (3D) biomarkers. The choroidal volume (CVolume), surface area (VSurface), and vessel length-associated index (VLI) were measured. The calculated 3D parameters were the mean choroidal thickness, choroidal vascularity index (CVI), vessel length density index (VLDI), vessel length to the stromal (VL-S) ratio, surface-to-volume ratio (S-V ratio), and vessel diameter index (VDI). Cluster analysis showed that the parameters were classified into two clusters: one was represented by the VVolume including the CVolume, VSurface, CVI, S-V ratio, VLI, VDI, and subfoveal choroidal thickness and the other by the VL-S ratio including the VLDI. Regarding the regional distribution, the VVolume, CVolume, VSurface, CVI, VLI, VL-S ratio, and VDI at the foveal center were higher than at the parafovea (P < 0.01). Although the VVolume decreased with age and axial length (AL) elongation, the association of the 3D parameters with age and AL elongation differed. The VLI, VLDI, VL-S ratio, and CVI decreased with age (P < 0.01) but not with AL elongation. The results suggested a structural difference in the choroidal vessel volume reduction between aging and AL elongation. The 3D parameters may provide additional information about the choroidal vasculature.

The Impact of System-Related Magnetic Resonance Imaging Geometric Distortion in Stereotactic Radiotherapy: A Case Report.

Magnetic resonance imaging (MRI) is now essential in stereotactic radiotherapy (SRT) planning for brain tumors because of its excellence in soft-tissue contrast and high spatial resolution. However, MRI distortion is sometimes difficult to recognize, and it may cause large misalignments in radiotherapy planning. In this case report, we will show how much difference in the dose distribution of SRT can be made by using MRI without distortion correction.

Disrupted local beta band networks in schizophrenia revealed through graph analysis: A magnetoencephalography study.

AIMS: Schizophrenia (SZ) is characterized by psychotic symptoms and cognitive impairment, and is hypothesized to be a 'dysconnection' syndrome due to abnormal neural network formation. Although numerous studies have helped elucidate the pathophysiology of SZ, many aspects of the mechanism underlying psychotic symptoms remain unknown. This study used graph theory analysis to evaluate the characteristics of the resting-state network (RSN) in terms of microscale and macroscale indices, and to identify candidates as potential biomarkers of SZ. Specifically, we discriminated topological characteristics in the frequency domain and investigated them in the context of psychotic symptoms in patients with SZ. METHODS: We performed graph theory analysis of electrophysiological RSN data using magnetoencephalography to compare topological characteristics represented by microscale (degree centrality and clustering coefficient) and macroscale (global efficiency, local efficiency, and small-worldness) indices in 29 patients with SZ and 38 healthy controls. In addition, we investigated the aberrant topological characteristics of the RSN in patients with SZ and their relationship with SZ symptoms. RESULTS: SZ was associated with a decreased clustering coefficient, local efficiency, and small-worldness, especially in the high beta band. In addition, macroscale changes in the low beta band are closely associated with negative symptoms. CONCLUSIONS: The local networks of patients with SZ may disintegrate at both the microscale and macroscale levels, mainly in the beta band. Adopting an electrophysiological perspective of SZ as a failure to form local networks in the beta band will provide deeper insights into the pathophysiology of SZ as a 'dysconnection' syndrome.