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Abstract Purpose To assess the diagnostic performance of prostate MRI by estimating the proportion of clinically significant prostate cancer (csPCa) in patients without prostate pathology. Materials and methods This three-center retrospective study included prostate MRI examinations performed for clinical suspicion of csPCa (Grade group ≥ 2) between 2018 and 2022. Examinations were divided into two groups: pathological diagnosis within 1 year after the MRI (post-MRI pathology) is present and absent. Risk prediction models were developed using the extracted eleven common predictive variables from the patients with post-MRI pathology. Then, the csPCa proportion in the patients without post-MRI pathology was estimated by applying the model. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV/NPV) of prostate MRI in diagnosing csPCa were subsequently calculated for patients with and without post-MRI prostate pathology (estimated statistics) with a positive threshold of PI-RADS ≥ 3. Results Of 12,191 examinations enrolled (mean age, 65.7 years ± 8.4 [standard deviation]), PI-RADS 1–2 was most frequently assigned (55.4%) with the lowest pathological confirmation rate of 14.0–18.2%. Post-MRI prostate pathology was found in 5670 (46.5%) examinations. The estimated csPCa proportions across facilities were 12.6–15.3%, 18.4–31.4%, 45.7–69.9%, and 75.4–88.3% in PI-RADS scores of 1–2, 3, 4, and 5, respectively. The estimated (observed) performance statistics were as follows: AUC, 0.78–0.81 (0.76–0.79); sensitivity, 76.6–77.3%; specificity, 67.5–78.6%; PPV, 49.8–66.6% (52.0–67.7%); and NPV, 84.4–87.2% (82.4–86.6%). Conclusion We proposed a method to estimate the probabilities harboring csPCa for patients who underwent prostate MRI examinations, which allows us to understand the PI-RADS diagnostic performance with several metrics. Clinical relevance statement The reported estimated performance metrics are expected to aid in understanding the true diagnostic value of PI-RADS in the entire prostate MRI population performed with clinical suspicion of prostate cancer. Key Points Calculating performance metrics only from patients who underwent prostate biopsy may be biased due to biopsy selection criteria, especially in PI-RADS 1–2. The estimated area under the receiver operating characteristic curve of PI-RADS in the entire prostate MRI population ranged from 0.78 to 0.81 at three facilities. The estimated statistics are expected to help us understand the true PI-RADS performance and serve as a reference for future studies. Graphical Abstract

Abstract There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory cells. We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq). We also examined the effect of an anti-interleukin-1β (IL-1β) antibody in the murine AAD model. IL1B+ inflammatory macrophages and classical monocytes were increased in human AAD samples. Trajectory analysis demonstrated that IL1B+ inflammatory macrophages differentiated from S100A8/9/12+ classical monocytes uniquely observed in the aorta of AAD. We found increased infiltration of neutrophils and monocytes with the expression of inflammatory cytokines in the aorta and accumulation of inflammatory macrophages before the onset of macroscopic AAD in the murine AAD model. In blocking experiments using an anti-IL-1β antibody, it improved survival of murine AAD model by preventing elastin degradation. We observed the accumulation of inflammatory macrophages expressing IL-1β in both human AAD samples and in a murine AAD model. Anti-IL-1β antibody could improve the mortality rate in mice, suggesting that it may be a treatment option for AAD.

A coral reef aorta (CRA) is a rare aortic occlusive disease. Various less invasive approaches have been proposed for CRAs with extensive calcification of the entire aorta, but they are often technically difficult. A case of successful treatment of a patient with an extensive coral reef aorta by open thoracoabdominal aortic repair (TAAR) is reported. A 64-year-old man presented with a left foot ulcer with an infection following impaired wound healing. Computed tomography (CT) showed extensive CRA and lower extremity arterial disease (LEAD). Anatomic revascularization with open TAAR for extensive CRA and endovascular treatment for LEAD were performed. Although blood flow improved postoperatively, left lower limb amputation was required because of poor infection control. The clinical course after amputation was uneventful, and the patient was discharged on postoperative day 52. In conclusion, open TAAR for extensive CRA is challenging, but it should be considered in complicated cases.

Abstract Background Accurate evaluation of tumor invasion depth is essential to determine the appropriate treatment strategy for patients with superficial esophageal cancer. The pretreatment tumor depth diagnosis currently relies on the magnifying endoscopic classification established by the Japan Esophageal Society (JES). However, the diagnostic accuracy of tumors involving the muscularis mucosa (MM) or those invading the upper third of the submucosal layer (SM1), which correspond to Type B2 vessels in the JES classification, remains insufficient. Previous retrospective studies have reported improved accuracy by considering additional findings, such as the size and macroscopic type of the Type B2 vessel area, in evaluating tumor invasion depth. Therefore, this study aimed to investigate whether incorporating the size and/or macroscopic type of the Type B2 vessel area improves the diagnostic accuracy of preoperative tumor invasion depth prediction based on the JES classification. Methods This multicenter prospective observational study will include patients diagnosed with MM/SM1 esophageal squamous cell carcinoma based on the Type B2 vessels of the JES classification. The tumor invasion depth will be evaluated using both the standard JES classification (standard-depth evaluation) and the JES classification with additional findings (hypothetical-depth evaluation) for the same set of patients. Data from both endoscopic depth evaluations will be electronically collected and stored in a cloud-based database before endoscopic resection or esophagectomy. This study’s primary endpoint is accuracy, defined as the proportion of cases in which the preoperative depth diagnosis matched the histological depth diagnosis after resection. Outcomes of standard- and hypothetical-depth evaluation will be compared. Discussion Collecting reliable prospective data on the JES classification, explicitly concerning the B2 vessel category, has the potential to provide valuable insights. Incorporating additional findings into the in-depth evaluation process may guide clinical decision-making and promote evidence-based medicine practices in managing superficial esophageal cancer. Trial registration This trial was registered in the Clinical Trials Registry of the University Hospital Medical Information Network (UMIN-CTR) under the identifier UMIN000051145, registered on 23/5/2023.

Abstract The Aira caldera, located in southern Kyushu, Japan, originally formed 100 ka, and its current shape reflects the more recent 30 ka caldera-forming eruptions (hereafter, called the AT eruptions). This study aimed to delineate the detailed two-dimensional (2D) seismic velocity structure of the Aira caldera down to approximately 15 km, by means of the travel-time tomography analysis of the seismic profile across the caldera acquired in 2017 and 2018. A substantial structural difference in thickness in the subsurface low-velocity areas in the Aira caldera between the eastern and western sides, suggest that the Aira caldera comprises at least two calderas, identified as the AT and Wakamiko calderas. The most interesting feature of the caldera structure is the existence of a substantial high-velocity zone (HVZ) with a velocity of more than 6.8 km/s at depths of about 6–11 km beneath the central area of the AT caldera. Because no high ratio of P- to S-wave velocity zones in the depth range were detected from the previous three-dimensional velocity model beneath the AT caldera region, we infer that the HVZ is not an active magma reservoir but comprises a solidified and cool remnant. In addition, a poorly resolved low-velocity zone around 15 km in depth suggests the existence of a deep active magma reservoir. By superimposing the distribution of the known pressure sources derived from the observed ground inflation and the volcanic earthquake distribution onto the 2D velocity model, the magma transportation path in the crust was imaged. This image suggested that the HVZ plays an important role in magma transportation in the upper crust. Moreover, we estimated that the AT magma reservoir in the 30 ka Aira caldera-forming eruptions has the total volume of 490 km3 DRE and is distributed in a depth range of 4–11 km. Graphical Abstract

Abstract Aim Hepatocellular carcinoma (HCC) with bile duct invasion (BDI) (BDIHCC) has a poor prognosis. Moreover, due to the paucity of reports, there is no consensus regarding optimal management of this clinical condition yet. The aim of this study was to clarify the efficacy and safety of proton beam therapy (PBT) for BDIHCC. Methods Between 2009 and 2018, 15 patients with BDIHCC underwent PBT at our institution. The overall survival (OS), local control (LC), and progression-free survival (PFS) curves were constructed using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria of Adverse Events version 4.0. Results The median follow-up time was 23.4 months (range, 7.9–54.3). The median age was 71 years (range, 58–90 years). Many patients were Child A (n = 8, 53.3%) and most had solitary tumors (n = 11, 73.3%). Additionally, most patients had central type BDI (n = 11, 73%). The median tumor size was 4.0 cm (range, 1.5–8.0 cm). The 1-, 2-, and 3-year OS rates were 80.0%, 58.7% and 40.2%, respectively, and the corresponding LC and PFS rates were 93.3%, 93.3%, and 74.7% and 72.7%, 9.7%, and 0.0%, respectively. Acute grade 1/2 dermatitis (n = 7, 46.7%), and grades 2 (n = 1, 6.7%) and 3 (n = 1, 6.7%) cholangitis were observed. Late toxicities such as grade 3 gastric hemorrhage and pleural effusion were observed. No toxicities of grade 4 or higher were observed. Conclusions PBT was feasible with tolerable toxicities for the treatment of BDIHCC.

Introduction: Post-sternotomy surgical site infection (SSI) is a serious complication of cardiovascular surgery. Here, we proposed a new clinical classification and reconstructive strategy for this condition. Methods: A retrospective study based on medical records was performed on 100 consecutive cases requiring wound management by plastic surgeons for post-sternotomy SSI at Kobe University Hospital between January 2009 and December 2021. We classified 100 cases into four categories according to the anatomical invasiveness of the infection (type 1, superficial SSI; type 2, sternal osteomyelitis; type 3, mediastinitis; and type 4, aortic graft infection). The standard treatment plan comprised initial debridement, negative pressure wound therapy with continuous irrigation, and reconstructive surgery. Reconstructive methods and their outcomes (in-hospital mortality rate, follow-up period, and infection recurrence rate) were investigated for each SSI category. Results: There were nine SSI cases in type 1, 28 in type 2, 25 in type 3, and 38 in type 4. The pectoralis major (PM) muscle advancement flap was mainly selected in types 1 and 2 (100 and 70.4%, respectively), while the omental flap or latissimus dorsi (LD) myocutaneous flaps were mainly selected in types 3 and 4 (77.3 and 81.8%, respectively) for reconstructive surgery. The in-hospital mortality rates for types 1, 2, 3, 4 were 44.4, 3.6, 12.0, and 15.8%, respectively. The mean follow-up periods for types 1, 2, 3, 4 were 542.8, 1514.5, 1154.5, and 831.1 days, respectively. Infection recurrence rates for types 1, 2, 3, 4 were 0, 11.5, 13.3, and 19.2%, respectively. All of these recurrent cases, except for 4 cases of type 4 that required surgical intervention, were treated with conservative wound management. Conclusion: A volume-rich flap (omental or LD flap) was required to fill the dead space after debridement in mediastinitis (type 3) or aortic graft infection (type 4), whereas superficial SSI (type 1) or sternal osteomyelitis (type 2) received a less-invasive flap (PM muscle advancement flap). Our new classification method was based on the anatomical invasiveness of the infection, providing both a simple and easy diagnosis and definitive treatment strategy.

Abstract Background We previously reported that high body weight was a risk factor affecting the onset of anti-epidermal growth factor receptor (EGFR) antibody drug-induced acneiform rash. The current study investigated the relationship between risk factors for anti-EGFR antibody drug-induced acneiform rash and survival probability in colorectal cancer patients, as well as effects of drug withdrawal, dose reduction, or treatment discontinuation on treatment continuation. Methods This retrospective study included 67 patients with unresectable advanced or recurrent colorectal cancer treated with anti-EGFR antibody drugs for the first time. Results The survival time and acneiform rash grade of patients with high body weight (≥ 67.2 kg) were significantly longer and higher than those of patients with low body weight (

Visible-wavelength GaN-based photonic-crystal surface-emitting lasers (PCSELs) have attracted attention for various applications, such as materials processing, high-brightness illuminations, and displays. In this letter, we demonstrate GaN-based PCSELs at green wavelengths. We formed a photonic crystal (PC) in p-GaN and filled holes of the PC with SiO _2 to ensure device stability. Through a current injection test under pulsed conditions and spectral analysis, we confirmed that the fabricated device possessed Γ-point single-mode oscillation at wavelengths above 505 nm. Our results have the potential to further expand the applications of PCSELs and semiconductor lasers in visible region.

Abstract Objectives Recent innovations in prophylactic treatment with steroids have overcome the issue of esophageal stricture after endoscopic submucosal dissection (ESD), except in entire circumferential esophageal squamous cell carcinoma (EC‐ESCC). Current Japanese guidelines weakly recommend performing ESD for clinical epithelial/lamina propria EC‐ESCC with a longitudinal extension

Abstract Background Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. Methods This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions. Results ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7–99.7%), specificity (95% CI) was 100% (92.7–100%), diagnostic accuracy (95% CI) was 98.9% (94.0–99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4–100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5–99.7%). Conclusions ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.

Abstract Background Although chemoradiotherapy (CRT) is one of the curative treatments for thoracic esophageal squamous cell carcinoma (ESCC) with submucosal invasion, the risk of local recurrence after CRT remains a clinical problem. This retrospective study aimed to analyze the predictive factors for local recurrence after CRT. Methods Ninety-one patients with clinical or pathological (c/p) T1bN0M0 thoracic ESCC who underwent CRT from 2004 to 2017 in our institution were analyzed retrospectively. Sixty-three patients were diagnosed with pathological T1b after undergoing initial endoscopic resection (ER) and treated with additional CRT; meanwhile, 28 patients were clinically diagnosed with T1b and underwent definitive CRT. We investigated the predictors of disease–specific survival (DSS) and local recurrence–free survival (LRFS) by performing univariate and multivariate analyses. Results The median observation period was 59.8 months. The 5-year DSS and LRFS rates were 84.3% (95% confidence interval [CI]: 76.1–92.5) and 87.1% (95% CI: 79.1–95.1), respectively. The multivariate analysis revealed no significant predictors associated with DSS. On the contrary, ER (hazard ratio [HR]: 0.11, 95% CI: 0.02–0.48, p = 0.003) and tumor length (HR: 6.78, 95% CI: 1.28–36.05, p = 0.025) were recognized as independent predictive factors for LRFS. During follow-up, recurrence was observed in 18 patients (19.8%). With regard to the patterns of relapse, local recurrence was the most common in 11 patients, and salvage ER was performed in 9 of 11 patients. Conclusions ER and tumor length were independent predictive factors for LRFS. Our study suggested that performance of ER prior to CRT improved the local control in patients with c/p T1bN0M0 ESCC. In addition, most of the patients who experienced local recurrence were treated with salvage ER, which contributed to preserving the organs.

Adrenocortical tumors (ACTs) are rare in children and should be treated as malignant tumors. A 12-year-old female patient was referred to our institute for acute abdomen and hypovolemic shock. She had symptoms of virilization, including lowered voice, beard growth, and hirsutism. An elevated level of dehydroepiandrosterone sulfate was observed, and computed tomography scan showed a large left adrenal mass with massive hemorrhage. Emergency transcatheter arterial embolization was successfully performed using N-buthyl-2-cyanoacrylate as an embolic material. She underwent surgical resection on the following day. Histopathological analysis showed strong degeneration of the tumor and its necrosis, and the tumor was diagnosed as ACT of unknown grade. To our knowledge, this is the first case of a ruptured ACT treated with transcatheter arterial embolization in a pediatric patient.

Abstract The tectonic stress field was investigated in and around the aftershock area of the Hokkaido Eastern Iburi earthquake (M JMA = 6.7) occurred on 6 September 2018. We deployed 26 temporary seismic stations in the aftershock area for approximately 2 months and located 1785 aftershocks precisely. Among these aftershocks, 894 focal mechanism solutions were determined using the first-motion polarity of P wave from the temporary observation and the permanent seismic networks of Hokkaido University, Japan Meteorological Agency (JMA), and High Sensitivity Seismograph Network Japan (Hi-net). We found that (1) the reverse faulting and the strike-slip faulting are dominant in the aftershock area, (2) the average trend of P- and T-axes is 78° ± 33° and 352° ± 51°, respectively, and (3) the average plunge of P- and T-axes is 25° ± 16° and 44° ± 20°, respectively: the P-axis is close to be horizontal and the T-axis is more vertical than the average of the P-axes. We applied a stress inversion method to the focal mechanism solutions to estimate a stress field in the aftershock area. As a result, we found that the reverse fault type stress field is dominant in the aftershock area. An axis of the maximum principal stress (σ 1) has the trend of 72° ± 7° and the dipping eastward of 19° ± 4° and an axis of the intermediate principal stress (σ 2) has the trend of 131° ± 73° and the dipping southward of 10° ± 9°, indicating that both of σ 1- and σ 2-axes are close to be horizontal. An axis of the minimum principal stress (σ 3) has the dipping westward of 67° ± 6° that is close to be vertical. The results strongly suggest that the reverse-fault-type stress field is predominant as an average over the aftershock area which is in the western boundary of the Hidaka Collision Zone. The average of the stress ratio R = (σ 1 − σ 2)/(σ 1 − σ 3) is 0.61 ± 0.13 in the whole aftershock area. Although not statistically significant, we suggest that R decreases systematically as the depth is getting deep, which is modeled by a quadratic polynomial of depth.

Abstract The southwestern Kuril trench is seismically active due to the subduction of the Pacific plate. Great earthquakes in this zone have frequently induced fatal disasters. Seismic monitoring and hypocenter catalogs provide fundamental information on earthquake occurrence and disaster mitigation. Real-time hypocenter and magnitude estimates are extremely crucial data for tsunami warning systems. However, this region is located in the international border zone between Japan and Russia. The Japan Meteorological Agency and Russian Academy of Sciences have routinely determined hypocenters and issued earthquake information independently. Waveform data have not yet been exchanged internationally in real time. Here, we evaluated how a hypothetical Japan–Russia joint seismic network could potentially improve the hypocenter estimation accuracy. Experiments using numerical and observed data indicated that the joint network extended the distance over which hypocenters can be accurately determined over 100 km eastward compared to the Japan network only. This fact suggests that joint seismic data have the potential to improve the hypocenter accuracy in this region, which would provide improved performance in gathering disaster information at the moment of a tsunami warning.

Desbuquois dysplasia (DD) type 1 is a rare skeletal dysplasia characterized by a short stature, round face, progressive scoliosis, and joint laxity. The causative gene has been identified as calcium‐activated nucleotidase 1 (CANT1), which encodes a nucleotidase that preferentially hydrolyzes UDP to UMP and phosphate. In this study, we generated Cant1 KO mice using CRISPR/Cas9‐mediated genome editing. All F0 mice possessing frameshift deletions at both Cant1 alleles exhibited a dwarf phenotype. Germline transmission of the edited allele was confirmed in an F0 heterozygous mouse, and KO mice were generated by crossing of the heterozygous breeding pairs. Cant1 KO mice exhibited skeletal defects, including short stature, thoracic kyphosis, and delta phalanx, all of which are observed in DD type 1 patients. The glycosaminoglycan (GAG) content and extracellular matrix space were reduced in the growth plate cartilage of mutants, and proliferating chondrocytes lost their typical flat shape and became round. Chondrocyte differentiation, especially terminal differentiation to hypertrophic chondrocytes, was impaired in Cant1 KO mice. These findings indicate that CANT1 is involved in the synthesis of GAG and regulation of chondrocyte differentiation in the cartilage and contribute to a better understanding of the pathogenesis of DD type 1.

Abstract An abnormal collection of air in the thorax is one of the most common life-threatening events that occurs in the intensive care unit. Patient management differs depending on the location of the air collection; therefore, detecting abnormal air collection and identifying its exact location on supine chest radiographs is essential for early treatment and positive patient outcomes. Thoracic abnormal air collects in multiple thoracic spaces, including the pleural cavity, chest wall, mediastinum, pericardium, and lung. Pneumothorax in the supine position shows different radiographic findings depending on the location. Many conditions, such as skin folds, interlobar fissure, bullae in the apices, and air collection in the intrathoracic extrapleural space, mimic pneumothorax on radiographs. Additionally, pneumopericardium may resemble pneumomediastinum and needs to be differentiated. Further, some conditions such as inferior pulmonary ligament air collection versus a pneumatocele or pneumothorax in the posteromedial space require a differential diagnosis based on radiographs. Computed tomography (CT) is required to localize the air and delineate potential etiologies when a diagnosis by radiography is difficult. The purposes of this article are to review the anatomy of the potential spaces in the chest where abnormal air can collect, explain characteristic radiographic findings of the abnormal air collection in supine patients with illustrations and correlated CT images, and describe the distinguishing features of conditions that require a differential diagnosis. Since management differs based on the location of the air collection, radiologists should try to accurately detect and identify the location of air collection on supine radiographs.

Abstract Six wells were continuously monitored in Hokkaido, northern Japan, to relate groundwater level changes to regional seismic activity. Groundwater level changes following the 2018 Hokkaido Eastern Iburi earthquake were detected in three of the six wells, even though they are located hundreds of kilometers from the epicenter. The groundwater level changes are qualitatively consistent with the volumetric strain induced by the earthquake. We analyzed groundwater level responses to the M2 tidal constituent before and after the earthquake, but related changes in amplitude and phase shifts remained within the usual variation. Observed coseismic change was explained by the response to the M2 tidal constituent component and the calculated volumetric strain for one of the wells, where groundwater level decreased. The observed change in the other two was found to be much greater than the corresponding estimates of the volumetric strain.

Abstract Background It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). Methods Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. Results Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. Conclusions Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

PurposeTo compare the inter-observer variability of apparent diffusion coefficient (ADC) values of prostate lesions measured by 2D-region of interest (ROI) with and without specific measurement instruction.MethodsForty lesions in 40 patients who underwent prostate MR followed by targeted prostate biopsy were evaluated. A multi-reader study (10 readers) was performed to assess the agreement of ADC values between 2D-ROI without specific instruction and 2D-ROI with specific instruction to place a 9-pixel size 2D-ROI covering the lowest ADC area. The computer script generated multiple overlapping 9-pixel 2D-ROIs within a 3D-ROI encompassing the entire lesion placed by a single reader. The lowest mean ADC values from each 2D-small-ROI were used as reference values. Inter-observer agreement was assessed using the Bland-Altman plot. Intraclass correlation coefficient (ICC) was assessed between ADC values measured by 10 readers and the computer-calculated reference values.ResultsTen lesions were benign, 6 were Gleason score 6 prostate carcinoma (PCa), and 24 were clinically significant PCa. The mean±SD ADC reference value by 9-pixel-ROI was 733 ± 186 (10-6 mm2/s). The 95% limits of agreement of ADC values among readers were better with specific instruction (±112) than those without (±205). ICC between reader-measured ADC values and computer-calculated reference values ranged from 0.736-0.949 with specific instruction and 0.349-0.919 without specific instruction.ConclusionInterobserver agreement of ADC values can be improved by indicating a measurement method (use of a specific ROI size covering the lowest ADC area).

Abstract The present location of the tectonic boundary and the convergence rate between the Amur and Okhotsk plates in northern Hokkaido, Japan, were herein estimated from the velocity field using data from a continuous GNSS network. The observed velocity profiles are in agreement with the theoretical ones calculated from a tectonic block collision model. The estimated kinematic boundary agrees with both geological and seismic boundaries. Overall, this indicates that the geological boundary acts like a mechanical one. The calculated convergence velocity of 14.0–16.5 mm/year is consistent with predictions from regional plate motion models and suggests that a considerable amount of interplate convergence is in progress along this boundary. Deep crustal seismicity is also in agreement with the estimated elastic thickness of 20.5–25.5 km. The non-occurrence of large earthquakes during the past several centuries, and the estimated convergence velocity suggest that there is a high potential for a large event in the near future.

Abstract We investigated the cause of destructive ground motion during the 2018 Hokkaido eastern Iburi earthquake. We conducted strong motion observations of aftershocks and microtremors and the surface wave method in the damaged areas of the town of Mukawa, Hokkaido prefecture, Japan. The ground accelerations were continuously recorded during a period of approximately 3 months after the main shock on September 6, 2018. The heavily damaged buildings were mainly situated around the strong motion station (HKD126) in Mukawa town. Such concentration of damage can be explained by the strong power that was observed in the 1–2 s period of the response spectrum at this station. We estimated the S-wave velocity profiles of this station site and a temporary station site that was installed on a nearby hill. The estimated S-wave velocity, which was inverted from phase velocity structures with the microtremor array and the surface wave method observations explained the difference in the SH-wave amplification characteristics between the two sites. An analysis of HKD126 and the temporarily observed records clearly indicates the strong effects of the local geological conditions on the heavily damaged area of Mukawa. The strong ground motion power generated during the main shock in Mukawa for 1–2 s period was mainly amplified by this shallow underground velocity structure.

Abstract The Hokkaido Eastern Iburi earthquake (M JMA = 6.7) occurred on September 6, 2018, in the Hokkaido corner region where the Kurile and northeastern Japan island arcs meet. We relocated aftershocks of this intraplate earthquake immediately after the main shock by using data from a permanent local seismic network and found that aftershock depths were concentrated from 20 to 40 km, which is extraordinarily deep compared with other shallow intraplate earthquakes in the inland area of Honshu and Kyushu, Japan. Further, we found that the aftershock area consists of three segments. The first segment is located in the northern part of the aftershock area, the second segment lies in the southern part, and the third segment forms a stepover between the other two segments. The hypocenter of the main shock, from which the rupture initiated, is located on the stepover segment. The centroid moment tensor solution for the main shock indicates a reverse faulting, whereas the focal mechanism solution determined by using the first-motion polarity of the P wave indicates strike-slip faulting. To explain this discrepancy qualitatively, we present a model in which the rupture started as a small strike-slip fault in the stepover segment of the aftershock area, followed by two large reverse faulting ruptures in the northern and southern segments.

Abstract Based on analyses of global navigation satellite system data since 1996, we investigate the spatiotemporal strain field around the Ishikari-Teichi-Toen fault zone, which is a major active fault zone close to the epicenter of the 2018 Eastern Iburi earthquake in Hokkaido, Japan. Strain rates during almost whole periods, except for the timings of two distant large interplate earthquakes and following several years show an E–W to ESE–WNW contraction of ~ 0.1 ppm/year. This strain rate is approximately an order of magnitude larger than that of the surrounding area. Strain rate disturbances due to large earthquakes diminish within several years and return to the original level, suggesting that there is a uniform strain accumulation along this fault zone. Strain rate profiles that traverse the fault zone are characterized by a major contraction, corresponding to the Ishikari lowlands where a significantly thick low seismic velocity layer exists. A relatively high strain rate around this fault zone may reflect some amount of inelastic strain accumulation in addition to the elastic strain accumulation along the faults originating from complex fault and crustal structures.

We derived a new GPS site velocity field by integrating the data of ten newly built stations across the Liupan Shan Fault, in the northeastern margin of the Tibetan Plateau and those of pre-existing sites in this area for the period of 1999 - 2015. The GPS velocity field in a Eurasian plate-fixed frame shows a clockwise rotation around the Ordos cratonic block. Relative to the Ordos block, GPS sites generally move northeastward. The inferred GPS velocity profile across the Liupan Shan Fault shows that fault-normal velocities decrease from west to east from 5.4 ± 0.9 mm yr-1, at the central of the Lanzhou block to 0.1 ± 0.8 mm yr-1 at the western Ordos craton. We estimated the locking degree and the slip deficit rate on the Liupan Shan Fault using the tectonic elastic block model. Modeling results show that the Liupan Shan Fault is characteristic of segmentation in terms of locking degree and slip deficit rate. The southern segment has the largest locking degree, with complete locking to the depth of 13 - 15 km; the locking degree in the central segment is smaller than that of the northern and southern segments. On average, the slip deficit rate at the northern segment is larger than that of the Southern and central segments. We estimate the maximum magnitude of an expected earthquake based on the moment budget since the last large earthquake of M 6.7 in 1921. If the accumulated energy was completely released by a single earthquake, the expected maximum magnitude would be Mw 6.7. The model prediction suggests a high potential for seismic hazard in the Liupan Shan area.

Molecular mechanisms underlying the nephrotoxicity associated with bevacizumab are unclear. Endothelin-1 (ET-1) is involved in podocyte injury and proteinuria, and its level increases in most cases of kidney disorders. Forkhead box protein O1 (FoxO1), a transcription factor, is a major determinant of ET-1 promoter activation and is regulated by protein kinase B (Akt) phosphorylation-dependent nuclear exclusion. We evaluated the effect of bevacizumab on ET-1 production in human glomerular microvascular endothelial cells (hGECs). We analyzed the changes in the mRNA and protein levels of ET-1 in hGECs treated with bevacizumab using real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Changes in the protein levels and phosphorylation status of Akt and FoxO1 in hGECs treated with bevacizumab were analyzed by western blotting. After cell lysis, FoxO1 protein was isolated from the cytoplasmic and nuclear fractions. We also investigated the effects of AS1842856 (a FoxO1 inhibitor) on bevacizumab-induced ET-1 production. Bevacizumab significantly and dose-dependently increased the mRNA and protein levels of ET-1 in hGECs (p

(Bi0.5Na0.5)TiO3 [BNT] is expected as one of candidate lead-free materials because these ceramics show relatively good high-power piezoelectric properties. In this study, we tried to understand the bending strength and fracture behavior of the BNT-based ceramics. To measure the bending strength, a three-point bending test on the basis of JIS was conducted using 12.0 × 4.0 × 1.0 mm3 specimens. An average bending strength, σA, of pure BNT ceramics sintered at 1100 °C for 2, 12 and 24 h were 217, 195 and 187 MPa, respectively. It is cleared that the σA increased with decreasing the sintering time, (grain size and pore size). We also investigated the bending strength of Nb2O5 doped BNT ceramics [BNT-Nb x, x = 0.05 ∼ 1.5 wt%] and MnCO3 doped BNT ceramics [BNT-Mn x, x = 0.5 and 1.0 wt%]. Values of the σA of BNT-Nb 0.5 and BNT-Mn 0.5 were 222, and 188 MPa, respectively. It is clarified that soft dopants (Nb) can improve the bending strength of BNT-based ceramics. Additionally, hot-pressed BNT [HP-BNT] were sintered at 1050 °C for 5 h, and the σA of HP-BNT was 245 MPa.

Congenital dermoid fistulas of the anterior chest regions (CDFACRs) consist of a skin orifice at the anterior border of the sternocleidomastoid muscle with fistulas extending caudally in the subcutaneous tissue near the sternoclavicular joint. We report 2 pediatric CDFACR cases with pathognomonic sonography findings. By using sonography, we could diagnose the fistulas as CDFACRs by focusing on their location and direction and could reveal the distal side for complete resection. We suggest that sonography, which does not involve radiation or require sedation, is a better choice for the initial examination of CDFACRs than computed tomography or MRI.

Global Navigation Satellite Systems have been extensively used to investigate the ionosphere response to various natural and man-made phenomena for the last three decades. However, ionospheric reaction to volcano eruptions is still insufficiently studied and understood. In this work we analyzed the ionospheric response to the 11–16 June 2009 VEI class 4 Sarychev Peak volcano eruption by using surrounding Russian and Japanese GPS networks. Prominent covolcanictotal electron content (TEC)ionospheric disturbances (CVIDs) with amplitudes and periods ranged between 0.03–0.15 TECU and 2.5–4.5 min were discovered for the three eruptive events occurred at 18:51 UT, 14 June; at 01:15 and 09:18 UT, 15 June 2009. The estimates of apparent CVIDs velocities vary within 700–1000 m/s in the far-field zone (300–900 km to the southwest from the volcano) and 1300–1800 m/s in close proximity toSarychev Peak. The characteristics of the observed TEC variations allow us to attribute them to acoustic mode. The south-southwestward direction is preferred for CVIDs propagation. We concluded that the ionospheric response to a volcano eruption is mainly determined by a ratio between explosion strength and background ionization level. Some evidence of secondary (F2-layer) CVIDs’ source eccentric location were obtained.

Background: Sorafenib has been used in the treatment of advanced hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Sorafenib-associated organ reduction have been reported on imaging, such as thyroid, pancreas and muscle, but there has been no research on prostate volume reduction (PVR). Methods: We retrospectively analyzed 26 patients (twenty with HCC and six patients with RCC) who underwent sorafenib therapy for 31 to 1225 days (median, 100 days). PVR was estimated by two independent readers using CT volumetry. Results: The sum of all prostate volumes measured by reader 1 was 24.2 ± 13.8 cm3 on the baseline CT and 20.4 ± 10.6 cm3 on the follow-up CT (p < 0.001), and that measured by reader 2 was 22.3 ± 13.9 cm3 on the baseline CT and 19.2 ± 10.6 cm3 on the follow-up CT (p < 0.001). The concordance correlation coefficient for the prostate volume measured by the two readers was 0.95 on the baseline CT scans and 0.94 on the follow-up CT scans. Sorafenib-associated PVR demonstrated slight dependence to the exposure time (r = –0.23). One patient with benign prostatic hyperplasia (BPH) showed PVR (from 80.4 to 61.5 cm3 [reader 1]; 83.4 to 61.6 cm3 [reader 2]) after sorafenib administration. Sorafenib-associated PVR occurred in patients both with and without underlying liver dysfunction with relative prostate volume changes of 86.7 ± 12.0% and 85.0 ± 9.0%, respectively. Conclusion: Our study demonstrated significant PVR with sorafenib treatment in patients regardless of the presence of BPH and underlying liver dysfunction.

BACKGROUND:Parameters reported in pathologic reviews have been failing to assess exactly the malignant potential of gastrointestinal cancers. We hypothesized that malignant potential could be defined by common latent variables (hypothesis I), but there are substantial differences in the associations between malignant potential and pathologic parameters according to the origin of gastrointestinal cancers (hypothesis II). We shed light on these issues by structural equation modeling. MATERIALS AND METHODS:We conducted a cross-sectional survey of 217 esophageal, 192 gastric, and 175 colorectal cancer patients who consecutively underwent curative surgery for their pathologic stage I cancers at Keiyukai Sapporo Hospital. Latent variables identified by factor analysis and seven conventional pathologic parameters were introduced in the structural equation modeling analysis. RESULTS:Because latent variables were disparate except for their number, 'three' in the examined gastrointestinal cancers, the first hypothesis was rejected. Because configural invariance across gastrointestinal cancers was not approved, the second hypothesis was verified. We could trace the three significant paths on the causal graph from latent variables to lymph node metastasis, which were mediated through depth, lymphatic invasion, and matrilysin expression in esophageal cancer, whereas only one significant path could be traced in both gastric and colorectal cancer. Two of the three latent variables were exogenous in esophageal cancer, whereas one factor was exogenous in the other gastrointestinal cancers. Cancer stemness promoted viability in esophageal cancer, but it was suppressed in others. CONCLUSION:These results reflect the malignant potential of esophageal cancer is higher than that of the other gastrointestinal cancers. Such information might contribute to refining clinical treatments for gastrointestinal cancers.

During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein β (C/EBPβ) expression levels. The effect of C/EBPβ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPβ transgenic mice to investigate the relationship between C/EBPβ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPβ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPβ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPβ transgenic mice decreased C/EBPβ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPβ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure.

PURPOSE: To evaluate the pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs (NSAIDs) in the retinochoroidal tissues of rabbits. METHODS: The cyclooxygenase (COX) inhibitory activity of diclofenac, bromfenac, and amfenac, an active metabolite of nepafenac, were determined using human-derived COX-1 and COX-2. Each of the three NSAIDs was applied topically to rabbits, and after 0.5 to 8 hrs, the concentration of each drug in the aqueous humor and the retinochoroidal tissues was measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetics of the drugs in the tissues after repeated doses as is done on patients was calculated by a simulation software. The inhibitory effect of each NSAID on the breakdown of the blood-retinal barrier was assessed by the vitreous protein concentration on concanavalin A-induced retinochoroidal inflammation in rabbits. RESULTS: The half-maximal inhibitory concentration (IC50) of diclofenac, bromfenac, and amfenac was 55.5, 5.56, and 15.3 nM for human COX-1, and 30.7, 7.45, and 20.4 nM for human COX-2, respectively. The three NSAIDs were detected in the aqueous humor and the retinochoroidal tissue at all-time points. Simulated pharmacokinetics showed that the levels of the three NSAIDs were continuously higher than the IC50 of COX-2, as an index of efficacy, in the aqueous humor, whereas only the bromfenac concentration was continuously higher than the IC50 at its trough level in the retinochoroidal tissues. The intravitreous concentration of proteins was significantly reduced in rabbits that received topical bromfenac (P = 0.026) but not the other two NSAIDs. CONCLUSIONS: Topical bromfenac can penetrate into the retinochoroidal tissues in high enough concentrations to inhibit COX-2 and exerts its inhibitory effect on the blood-retinal barrier breakdown in an experimental retinochoroidal inflammation in rabbits. Topical bromfenac may have a better therapeutic benefit than diclofenac and nepafenac for retinochoroidal inflammatory diseases.

We surveyed hospital and community pharmacists about their educational experience regarding generic medicines (GE) during their pharmacy school years and after they started working and explored whether there were differences in their knowledge and perceptions of GE based on whether they were educated or not. The anonymous survey was conducted between December 1, 2019, and January 31, 2020. A total of 805 pharmacists completed the questionnaire: 535 who worked in insurance pharmacies and 270 in hospital pharmacies. Only 13.4% (n=108/805) of pharmacists received education on GE both as pharmacy students and after becoming a pharmacist. Conversely, a significant 25.2% (n=203/805) of pharmacists did not receive any associated education. Pharmacists who received education both as pharmacy students and after working as pharmacists had considerably greater knowledge of the "relevance of generic names and therapeutic areas" and "advantages (e.g., better dosing feel) of GE" than those who received no education at all. In addition, there were substantially lower negative perceptions on the quality and effectiveness of GE and considerably higher positive perceptions toward promoting GE use. According to the results of present survey, pharmacists have limited learning experience on GE, and education improves their GE knowledge and their perceptions of its effectiveness and quality, which would promote GE use. In particular, educational experiences regarding GE during their pharmacy school years would have a positive effect on their knowledge regarding GE and their perceptions. Pharmacists over 40 years of age had lower GE knowledge and perceptions than pharmacists under 39 years of age. [ABSTRACT FROM AUTHOR]