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Background: Tissue handling is one of the pivotal parts of surgical procedures. We aimed to elucidate the characteristics of experts' left-hand during laparoscopic tissue dissection. Methods: Participants performed tissue dissection around the porcine aorta. The grasping force/point of the grasping forceps were measured using custom-made sensor forceps, and the forceps location was also recorded by motion capture system (Mocap). According to the global operative assessment of laparoscopic skills (GOALS), two experts scored the recorded movies, and based on the mean scores, participants were divided into three groups: novice (

Abstract New technologies such as laparoscopic and robotic surgery are spreading, and there is a demand for physicians to keep up with novel methods. In contrast to the recent focus on healthcare professional burnout, the mental and physical costs during surgery are not well-understood. We aimed to quantify surgeons’ workloads in daily urological surgical practice and clarify potential background factors associated with such workloads. Urologists in Hokkaido, Japan, were invited to this study. Between December 2020 and December 2021, participants repeatedly reported workloads, which were assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX), after each surgery in conjunction with participants’ names, patients’ backgrounds, their roles (independent operator, operator under supervision, instructor, and 1st or 2nd assistant), and surgical outcomes, via SurveyMonkey®. Because of the heterogeneity among individuals, a linear mixed-effects model was utilized to analyze factors associated with NASA-TLX, calculating the parameter estimates (PE) of regression coefficients for each factor and their 95% confidence interval (CI). Sixty-five urologists (5 women) joined the study, and 2169 data were collected within 7 days after surgeries. A linear mixed-effects model revealed that female surgeons (PE + 15.56, 95% CI 2.36–28.77), urgent/emergency surgery (PE + 6.65, 95% CI 4.59–8.70), intraoperative complications (PE + 9.26, 95% CI 6.76–11.76), and near-miss incidents (PE + 3.81, 95% CI 2.27–5.36) were associated with higher workloads. Regarding the surgeons’ role, operator under supervision (PE + 12.46, 95% CI 9.86–15.06) showed the highest workloads. Surgeons’ workloads decreased as the number of previous cases of the same procedure increased. Surgeons’ workloads were associated with various factors. Given that the highest workloads were for operators under supervision, instructors should be aware of trainees’ high workloads and devise appropriate instructional interventions.

Abstract We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p

Purpose: To evaluate the utility of model-based deep learning reconstruction in prostate diffusion-weighted imaging (DWI). Methods: This retrospective study evaluated two prostate diffusion-weighted imaging (DWI) methods: deep learning reconstruction (DL-DWI) and traditional parallel imaging (PI-DWI). We examined 32 patients with radiologically diagnosed and histologically confirmed prostate cancer (PCa) lesions ≥10 mm. Image quality was evaluated both qualitatively (for overall quality, prostate conspicuity, and lesion conspicuity) and quantitatively, using the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) for prostate tissue. Results: In the qualitative evaluation, DL-DWI scored significantly higher than PI-DWI for all three parameters (p

Dual-polarization radars with parabolic dish antennas, which transmit horizontal and vertical waves, are widely used to measure precipitation. However, such radars cannot properly observe the convective storms developing at high altitudes in a short time because of the low spatiotemporal resolution of the data due to mechanical scanning at azimuth and elevation angles. In 2018, an X-band dual-polarized phased array weather radar (DP-PAWR) was developed in Japan. DP-PAWR provides polarimetric precipitation measurements via three dimensional (3D) volume scanning in 30 s using electronic scanning at elevation angles. This study investigated the relationship between the amount of full volume scan data (the radar reflectivity factor( $Z_{h}$ ), differential reflectivity( $Z_{dr}$ ), and specific differential phase( $K_{dp}$ )) above the freezing level and that of near-surface rainfall for three characteristically different summer convective storms in Japan. We also discussed the quantitative predictability of near-surface rainfall volume using the full volume scan data above the freezing level obtained from DP-PAWR. The results showed that the 30-s full volume scan data above the freezing level can quantitatively predict near-surface rainfall volume for various storms, including heavy convective storms multi-precipitation cores, as well as small-scale convective storms with 5 t 11.5 minutes of lead-time.

This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture-based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills.

In this paper, we propose a convex optimization-based estimation of sparse and smooth power spectral densities (PSDs) of complex-valued random processes from mixtures of realizations. While the PSDs are related to the magnitude of the frequency components of the realizations, it has been a major challenge to exploit the smoothness of the PSDs, because penalizing the difference of the magnitude of the frequency components results in a nonconvex optimization problem that is difficult to solve. To address this challenge, we design the proposed model that jointly estimates the complex-valued frequency components and the nonnegative PSDs, which are respectively regularized to be sparse and sparse-smooth. By penalizing the difference of the nonnegative variable that estimates the PSDs, the proposed model can enhance the smoothness of the PSDs via convex optimization. Numerical experiments on the phased array weather radar, an advanced weather radar system, demonstrate that the proposed model achieves superior estimation accuracy compared to existing sparse estimation models, regardless of whether they are combined with a smoothing technique as a post-processing step or not.

Abstract The Body Image Scale (BIS) is a 10-item tool that measures the body images of cancer patients. This study aims to validate the Japanese version of the BIS for bladder cancer patients. A multicenter cross-sectional survey was used to identify the participants, which included Japanese bladder cancer patients. The percentage of missing responses, internal consistency, and known-group validity were evaluated. The correlations between the BIS and two HRQOL instruments (the Bladder Cancer Index and the SF-12) were assessed to determine convergent validity. Among 397 patients, 221 patients were treated by transurethral resection of bladder tumor (TURBT) endoscopically, 49 patients underwent cystectomy with neobladder, and 127 patients underwent cystectomy involving stoma. The percentage of missing responses in the BIS ranged from 8.1 to 15.6%. Cronbach's α coefficient was 0.924. Higher BIS scores indicate negative body image, and the median BIS score for patients with native bladders after TURBT (0.5) was significantly lower than those of the patients with neobladder (4.0) and stoma formation (7.0), which indicated the discriminatory ability of the BIS. Each domain of the Bladder Cancer Index and the role summary score of the SF-12 correlated to the BIS scores, which confirmed the convergent validity. A range of BIS scores were identified among patients who reported similar physical summary scores and mental summary scores of the SF-12. This study confirmed the reliability and validity of the Japanese version of the BIS for bladder cancer patients.

We report a case of subarachnoid hemorrhage presenting with ischemic symptoms due to cerebral vasospasm. A 64-year-old woman with right facial paralysis was referred to our hospital for treatment because of bilateral middle cerebral artery aneurysms observed using magnetic resonance imaging. She had no headache episodes; however, contrast-enhanced magnetic resonance imaging showed contrast enhancement of the aneurysmal wall only on the left side. Therefore, she was considered to have a ruptured aneurysm and underwent craniotomy and aneurysmal neck clipping. The postoperative course was uneventful; however, she developed aphasia and dysphagia 9 months after the surgery and was readmitted. New cerebral infarction and subarachnoid hemorrhage were observed on the right side, and the patient exhibited marked vasospasm. Because of a headache episode one week earlier, coil embolization was performed after the vasospasm. She was discharged home with a modified Rankin scale score of 2 and planned rehabilitation. Aneurysms that enlarge and rupture in a short time period should be treated with caution. Vessel wall imaging was useful in identifying the ruptured aneurysm in the current case.

Abstract Introduction We report a case of laparoscopic adrenalectomy in a salvage setting after multiple chemotherapies for neuroendocrine carcinoma. Case presentation A 49‐year‐old man was diagnosed with unknown primary carcinoma with single brain metastasis, and right supraclavicular and mediastinal lymph node metastases. After stereotactic radiotherapy of the brain metastasis and systemic chemotherapy, lymphadanectomy was performed. The pathologic diagnosis was neuroendocrine carcinoma. At 11 months after surgery, computed tomography revealed right adrenal metastasis. Local radiotherapy initially resulted in complete remission. However, adrenal recurrence was noted 10 months later. Laparoscopic adrenalectomy was performed with curative intent. The patient is currently alive without recurrence at 20 months after the operation. Conclusion Adrenalectomy can become a treatment option if other metastases are well‐controlled with systemic therapy. Surgical elimination of oligometastases can offer long‐term disease control in selected patients as part of a multimodal approach.

Abstrac: Introduction: High-field Magnetic Resonance Imaging (MRI) installations are increasing, and there will be more opportunities to come into contact with higher-resolution images in the future. It is essential to understand how the whole normal brain is depicted in two or three dimensions, as high-resolution images may look different from conventional images. As there are currently limited examples of whole brain labeling on high-field, high-resolution MRI images, we have attempted to do so in this study. Materials and methods; We perform a detailed look at a whole brain 7 T MRI 100-µm slice published by Edlow et al. in 2019. We manually labeled the data in 2D and reconstructed each brain region in 3D. Result; We acquired 92 locations, including brain white matter and neuronal nuclei. Small areas, such as cranial nerves, could be identified in 2D slices, but detailed 3D structures could not be acquired. Discussion; This study is helpful because the very high-resolution 7 T MRI 100-µm imaging allows us to know which areas were identified and which were not and to compare the position and morphology of different brain regions simultaneously. Conclusion; It will be useful to understand high-resolution imaging in view of the findings of this study, which can be revealed from 7 T MRI 100-µm slice whole-brain images.

BackgroundTumor blood vessels play a key role in tumor metastasis. We have previously reported that tumor endothelial cells (TECs) exhibit abnormalities compared to normal endothelial cells. However, it is unclear how TECs acquire these abnormalities. Tumor cells secrete extracellular vesicles (EVs) to create a suitable environment for themselves. We have previously identified miR-1246 to be more abundant in high metastatic melanoma EVs than in low metastatic melanoma EVs. In the current study, we focused on miR-1246 as primarily responsible for acquiring abnormalities in TECs and examined whether the alteration of endothelial cell (EC) character by miR-1246 promotes cancer metastasis.MethodsWe analyzed the effect of miR-1246 in metastatic melanoma, A375SM-EVs, in vivo metastasis. The role of tumor EV-miR-1246 in the adhesion between ECs and tumor cells and the EC barrier was addressed. Changes in the expression of adhesion molecule and endothelial permeability were examined.ResultsIntravenous administration of A375SM-EVs induced tumor cell colonization in the lung resulting in lung metastasis. In contrast, miR-1246 knockdown in A375SM decreased lung metastasis in vivo. miR-1246 transfection in ECs increased the expression of adhesion molecule ICAM-1 via activation of STAT3, followed by increased tumor cell adhesion to ECs. Furthermore, the expression of VE-Cadherin was downregulated in miR-1246 overexpressed EC. A375SM-EV treatment enhanced endothelial permeability. VE-Cadherin was validated as the potential target gene of miR-1246 via the target gene prediction database and 3′ UTR assay.ConclusionmiR-1246 in high metastatic tumor EVs promotes lung metastasis by inducing the adhesion of tumor cells to ECs and destroying the EC barrier.

Introduction Granulocyte colony‐stimulating factor‐producing upper urinary tract urothelial carcinoma is rare, with a poor prognosis. Advanced urothelial carcinoma is currently treated with immune checkpoint inhibitors, whose efficacy for granulocyte colony‐stimulating factor‐producing upper urinary tract urothelial carcinoma remains unclear. Case presentation A 66‐year‐old male diagnosed with clinical stage T3N1M0 urothelial carcinoma of the right ureter with giant hydronephrosis underwent right radical nephroureterectomy. Local recurrence, leukocytosis, and elevated serum granulocyte colony‐stimulating factor levels were observed approximately 3 months after surgery. Chemotherapy was started but failed to control the disease. Therefore, pembrolizumab was chosen as the second‐line treatment. After this treatment, the blood leukocyte count rapidly normalized, and a clinically favorable response was achieved. There was no recurrence 10 months after the beginning of pembrolizumab treatment, which is still ongoing. Conclusion Pembrolizumab may be a treatment option for advanced granulocyte colony‐stimulating factor‐producing upper urinary tract urothelial carcinoma.

Introduction We report a rare case of primary renal leiomyosarcoma with a tumor thrombus in the inferior vena cava. Case presentation A 54‐year‐old woman presented with right flank pain and abdominal distension. Physical examination findings were unremarkable. Abdominal computed tomography revealed a heterogeneously enhancing right solid renal mass with a thrombus in the renal vein extending into the inferior vena cava. Magnetic resonance imaging demonstrated a renal tumor with a thrombus about 4 cm below the hepatic vein. Chest computed tomography and bone scintigraphy were negative. The patient underwent right radical nephrectomy and vena cava thrombectomy. Histophathologic evaluation of the resected tumor confirmed the diagnosis of leiomyosarcoma. She underwent no adjuvant therapy. Seven months after surgery, the patient died following a 2‐month history of multiple pulmonary and hepatic metastases. Conclusion This report highlights the importance of considering the possibility of renal leiomyosarcoma invasion to the inferior vena cava, similar to renal cell carcinoma.

Abstract The Martian Moons eXploration (MMX) mission will study the Martian moons Phobos and Deimos, Mars, and their environments. The mission scenario includes both landing on the surface of Phobos to collect samples and deploying a small rover for in situ observations. Engineering safeties and scientific planning for these operations require appropriate evaluations of the surface environment of Phobos. Thus, the mission team organized the Landing Operation Working Team (LOWT) and Surface Science and Geology Sub-Science Team (SSG-SST), whose view of the Phobos environment is summarized in this paper. While orbital and large-scale characteristics of Phobos are relatively well known, characteristics of the surface regolith, including the particle size-distributions, the packing density, and the mechanical properties, are difficult to constrain. Therefore, we developed several types of simulated soil materials (simulant), such as UTPS-TB (University of Tokyo Phobos Simulant, Tagish Lake based), UTPS-IB (Impact-hypothesis based), and UTPS-S (Simpler version) for engineering and scientific evaluation experiments.

Introduction Thyroid storm is a rare life‐threating condition. We report a case of thyroid storm after radical nephrectomy for renal cell carcinoma with inferior vena cava tumor thrombus. Case presentation A 76‐year‐old man with a left renal tumor and tumor thrombus extending into the inferior vena cava underwent left radical nephrectomy and thrombectomy. After the surgery, his postoperative course rapidly deteriorated, including central nervous system disturbance, fever, tachycardia, congestive heart failure, and hepatic manifestation. Thyroid function test revealed perioperative hyperthyroidism. Corticosteroids and inorganic iodide improved his condition, suggesting that he developed thyroid storm after surgery. He was discharged 5 months after surgery and has been free from disease recurrence for more than 2 years. Conclusion Thyroid storm after surgery is rare. However, this postoperative complication is important because it is fatal if not diagnosed and treated properly.

In December 2017, a dual-polarized (DP) phased-array weather radar (PAWR) was deployed to observe precipitation in Tokyo, Japan. The DP-PAWR has the following characteristics: high-temporal-resolution observations for a volume scan of 30 s in a 60 km range, high-density observations below a 15 km altitude, improved rain rate estimation using dual-polarimetric observations, and hydrometer classification abilities. To achieve high-temporal-resolution observations, wide transmitted waves with a beam width up to 5° are used for elevation angles. Although Fourier-domain digital beamforming can be used for receiving waves, the high sidelobe level of the antenna pattern using this type of beamforming results in substantial errors (e.g., overestimation of received power) because of ground clutter echoes. To solve this problem, an adaptive beamforming method based on the minimum mean square error (MMSE) was developed for a single-polarization phased-array radar. In this study, signal processing procedures, including the steering vector correction of real measurement data, are developed to apply the MMSE method to the DP-PAWR. The effect of phase errors and ground clutter on the dual-polarimetric parameters is evaluated via numerical simulations. Subsequently, the proposed method is applied to real measurement data of the DP-PAWR. Consequently, it is found that the clutter suppression achieved using the proposed method is clearly superior to that achieved using Fourier-domain digital beamforming.

Optical phased arrays (OPAs), which manipulate an optical beam by controlling the phase of light, are optical devices characterized by high speed, small size, light weight, and high reliability that make various applications possible. In this study, an eight-channel-waveguide OPA using an electro-optic (EO) polymer for phase control was fabricated. Very high-speed optical beam scanning with a frequency of 2 MHz was demonstrated by applying a driving waveform superimposing sinusoidal and rectangular-wave voltages. Furthermore, the EO polymer OPA can be operated with a low total-operation power consumption of 0.38 mW at a scanning speed of 500 kHz.

Background: Virtual reality simulators allow trainees to perform repeated practice and provide objective dexterity metrics regarding their performance, which means that virtual reality–based surgical training is becoming a vital part of initial learning of basic laparoscopic surgical skills. However, its educational role in learning advanced procedures remains undetermined. We evaluated the validity of the laparoscopic radical nephrectomy module of the LapVision virtual reality simulator. Methods: Urologists, medical students, and a junior resident voluntarily participated in the present study, and they performed training with a laparoscopic left radical nephrectomy module. For construct validation, dexterity metrics calculated in the simulator and the mean score of Global Operative Assessment of Laparoscopic Skills evaluated by 2 experts' video review were compared according to the certification of Japanese Endoscopic Surgical Skill Qualification or previous surgical experience. Results: Ten experts (≥50 laparoscopic surgeries), 9 intermediates (11-49), and 14 novices (0-10) voluntarily participated in the present study. Regarding the construct validity, there was a significant difference in the total number of errors, blood loss, and Global Operative Assessment of Laparoscopic Skills score among the groups for both the Endoscopic Surgical Skill Qualification status and previous surgical experience. Conclusion: The present study demonstrated good construct validity for the LapVision nephrectomy module. Furthermore, global skill assessment was possible by experts' reviews, which indicates the usefulness of the virtual reality procedural module as a skill assessment tool. Virtual reality–based procedural simulation has marked potential to become a vital part of integrated laparoscopic training programs.

BackgroundThe quality of transurethral resection of bladder tumor (TURBT) markedly varies among surgeons and may have a considerable impact on treatment outcomes. The importance of a surgical checklist for TURBT has been suggested in order to standardize the procedure and improve surgical and oncological outcomes. In the present study, we verified the usefulness of a checklist for managing patients with non-muscle-invasive bladder cancer (NMIBC).MethodsThis retrospective study included 201 NMIBC patients diagnosed with Ta, T1, or Tis between October 2011 and February 2021. After September 2016, TURBT was performed with a checklist. We analyzed the intravesical recurrence-free survival (RFS) rate and the presence or absence of the detrusor muscle in resected specimens before and after the introduction of the checklist. Survival rates were compared using the Log-rank test. A multivariate analysis with Cox proportional hazards modeling was performed to verify risk factors for intravesical recurrence.ResultsNinety-nine patients who underwent TURBT with the checklist (checklist group) were compared with 102 patients who underwent TURBT without the checklist (non-checklist group). When the analysis was narrowed down to 9 critical items, we observed a mean number of 9 documented items per operative report (98.0% completion) after implementation of the checklist. Two-year intravesical RFS rates in the checklist and non-checklist groups were 76.7 and 69.5%, respectively (p = 0.1059). The Cox proportional multivariate analysis showed that the rate of intravesical recurrence was slightly lower in the checklist group (hazard ratio 0.7376, 95% CI 0.4064-1.3388, P = 0.3170).ConclusionThe introduction of a checklist is recommended for the standardization of TURBT and increasing the quality of operative reporting, and it may also improve oncological outcomes.

The purpose of this study was to characterize the motion features of surgical devices associated with laparoscopic surgical competency and build an automatic skill-credential system in porcine cadaver organ simulation training. Participants performed tissue dissection around the aorta, dividing vascular pedicles after applying Hem-o-lok (tissue dissection task) and parenchymal closure of the kidney (suturing task). Movements of surgical devices were tracked by a motion capture (Mocap) system, and Mocap-metrics were compared according to the level of surgical experience (experts: ≥50 laparoscopic surgeries, intermediates: 10–49, novices: 0–9), using the Kruskal-Wallis test and principal component analysis (PCA). Three machine-learning algorithms: support vector machine (SVM), PCA-SVM, and gradient boosting decision tree (GBDT), were utilized for discrimination of the surgical experience level. The accuracy of each model was evaluated by nested and repeated k-fold cross-validation. A total of 32 experts, 18 intermediates, and 20 novices participated in the present study. PCA revealed that efficiency-related metrics (e.g., path length) significantly contributed to PC 1 in both tasks. Regarding PC 2, speed-related metrics (e.g., velocity, acceleration, jerk) of right-hand devices largely contributed to the tissue dissection task, while those of left-hand devices did in the suturing task. Regarding the three-group discrimination, in the tissue dissection task, the GBDT method was superior to the other methods (median accuracy: 68.6%). In the suturing task, SVM and PCA-SVM methods were superior to the GBDT method (57.4 and 58.4%, respectively). Regarding the two-group discrimination (experts vs. intermediates/novices), the GBDT method resulted in a median accuracy of 72.9% in the tissue dissection task, and, in the suturing task, the PCA-SVM method resulted in a median accuracy of 69.2%. Overall, the mocap-based credential system using machine-learning classifiers provides a correct judgment rate of around 70% (two-group discrimination). Together with motion analysis and wet-lab training, simulation training could be a practical method for objectively assessing the surgical competence of trainees.

Background Immune checkpoint inhibitors (ICIs) are increasingly being used to treat malignancies. Some patients experience immune-related adverse events (irAEs), which may affect any organ/tissue. IrAEs are occasionally fatal and usually have nonspecific symptoms. We developed a three-step application (https://irae-search.com/) to provide healthcare professionals with information on the diagnosis, treatment options, and published reports for 38 categories of irAEs encountered in clinical practice. Methods IrAEs reported in ≥5 cases were identified from articles published between October 2018 and August 2020 by searching Japanese (SELIMIC, JAPIC-Q Service, and JMED Plus) and international (MEDLINE, EMBASE, Derwent Drug File) databases. The cases’ symptoms were entered into the application to identify irAEs, which were verified using the reported diagnosis, to evaluate the application’s sensitivity and specificity. Results Overall, 1209 cases (1067 reports) were analyzed. The three most common categories of irAEs were pituitary or adrenal disorders (14% of cases), skin disorders (13%), and diabetes mellitus (10%). The top three primary diseases were lung cancer (364 cases), melanoma (286 cases), and renal cell carcinoma (218 cases). The average sensitivity was 90.8% (range 44.4%–100.0%) initially, and improved to 94.8% (range 83.3%–100.0%) after incorporating the symptoms reported in published cases into the application’s logic for two irAE categories. The average specificity was 79.3% (range 59.1% [thyroid disorders]–98.2% [arthritis]). Conclusion irAE Search is an easy-to-use application designed to help healthcare professionals identify potential irAEs in ICI-treated patients in a timely manner to facilitate prompt management/treatment. The application showed high sensitivity and moderate-to-high specificity for detecting irAEs.

Abstract Background Tumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood. Methodology The metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The expressions of pH regulators in TECs and NECs were determined by quantitative reverse transcription-PCR. Cell proliferation was measured by the MTS assay. Western blotting and ELISA were used to validate monocarboxylate transporter 1 and carbonic anhydrase 2 (CAII) protein expression within the cells, respectively. Human tumor xenograft models were used to access the effect of CA inhibition on tumor angiogenesis. Immunohistochemical staining was used to observe CAII expression, quantify tumor microvasculature, microvessel pericyte coverage, and hypoxia. Results The present study shows that, unlike NECs, TECs proliferate in lactic acidic. TECs showed an upregulated CAII expression both in vitro and in vivo. CAII knockdown decreased TEC survival under lactic acidosis and nutrient-replete conditions. Vascular endothelial growth factor A and vascular endothelial growth factor receptor signaling induced CAII expression in NECs. CAII inhibition with acetazolamide minimally reduced tumor angiogenesis in vivo. However, matured blood vessel number increased after acetazolamide treatment, similar to bevacizumab treatment. Additionally, acetazolamide-treated mice showed decreased lung metastasis. Conclusion These findings suggest that due to their effect on blood vessel maturity, pH regulators like CAII are promising targets of antiangiogenic therapy. Video Abstract Graphical abstract

In this study, we report atmospheric electric field (AEF) anomalies observed around the time of earthquakes (EQs) in Japan. Using a newly developed AEF observation network with three spatially separated stations in Japan (Chofu, Kakioka, and Iwaki), we conducted a study for two EQs that occurred within a few 100 km from the EQ epicenter under relatively good local weather conditions as shown by a local all-sky camera and weather information. Time series and wavelet analyses of the AEF indicate that fluctuation anomalies in the AEF with periods of 10–60 min and larger than 70 min were observed from a few hours before up to a few hours after the occurrence of the EQs. The lag in the onset time increased with increasing distance from the EQ epicenter to the field site. The above-mentioned characteristics of these AEF fluctuation anomalies were similar among the three stations, and therefore the observed AEF anomalies were considered to be an imminent precursor of EQs. The observed AEF anomalies were likely to be caused by internal gravity waves (IGWs) generated around the EQ epicenter a few hours before the EQ, passing over the field site while changing the AEF by changing the space charge density in the surface layer of the atmosphere.

The aim of present study was to enhance the nutraceutical properties of ginger extract (GE) by employing supersaturable self-emulsifying drug delivery systems (S-SEDDS). SEDDS of GE (SEDDS/GE), consisting of medium-chain triglyceride, lysolecithin and glycerin, was produced. To prepare S-SEDDS of GE (S-SEDDS/GE), hydroxypropyl methylcellulose was added to the SEDDS/GE as a precipitation inhibitor. Physicochemical, pharmacokinetic, and hepatoprotective properties of GE formulations were characterized. Both formulations improved the dissolution behavior of GE due to the formation of fine micelles with a median diameter of ca. 110 nm. After oral administration of GE samples in rats, the relative bioavailabilities of 6-gingerol and 8-gingerol in the S-SEDDS/GE-treated group were ca. 3-fold higher than those of GE-treated group, respectively. Repeated oral administration of GE/S-SEDDS (100 mg-GE/kg) provided a hepatoprotective effect in a rat model of carbon tetrachloride-induced hepatotoxicity. From these observations, the S-SEDDS approach might be efficacious for enhancing the nutraceutical properties of GE.

Going from bench to bedside is a simplified description of translational research, with the ultimate goal being to improve the health status of mankind. Tumor endothelial cells (TECs) perform angiogenesis to support the growth, establishment, and dissemination of tumors to distant organs. TECs have various features that distinguish them from normal endothelial cells, which include alterations in gene expression patterns, higher angiogenic and metabolic activities, and drug resistance tendencies. The special characteristics of TECs enhance the vulnerability of tumor blood vessels toward antiangiogenic therapeutic strategies. Therefore, apart from being a viable therapeutic target, TECs would act as a better mediator between the bench (i.e., angiogenesis research) and the bedside (i.e., clinical application of drugs discovered through research). Exploitation of TEC characteristics could reveal unidentified strategies of enhancing and monitoring antiangiogenic therapy in the treatment of cancer, which are discussed in this review.

Coating seed particles of 53 to 210 µm with clayey particles was carried out by means of a tumbling fluidized bed in order to enlarge and reuse the clayey particles wasted in producing a carrier for driftless dust formulation. The influence of operating factors on the coating efficiency η and on the growth rate of seed particles was investigated. η varied depending upon thermal operating factors but was not influenced much by mechanical ones. It was found that η was related roughly to RW defined as the ratio of the feed rate of water fed as slurry droplets to the maximum theoretical evaporation rate of water in a coating chamber. η increased with RW. The relationship between η and RW varied with the additive ratio of binder PVA to clayey particles, Cb, and η became high with increasing Cb. The growth rate of seed particles was explained well by an equation derived on the basis of the mass balance of clayey particles in a coating chamber.† This report was originally printed in J. Soc. Powder Technology, Japan, 22(5), 278-287 (1985) in Japanese, before being translated into English by KONA Editorial Committee with the permission of the editorial committee of the Soc. Powder Technology, Japan.

Tumor angiogenesis research and antiangiogenic drug development make use of cultured endothelial cells (ECs) including the human microvascular ECs among others. However, it has been reported that tumor ECs (TECs) are different from normal ECs (NECs). To functionally validate antiangiogenic drugs, cultured TECs are indispensable tools, but are not commercially available. Primary human TECs are available only in small quantities from surgical specimens and have a short life span in vitro due to their cellular senescence. We established immortalized human TECs (h-imTECs) and their normal counterparts (h-imNECs) by infection with lentivirus producing simian virus 40 large T antigen and human telomerase reverse transcriptase to overcome the replication barriers. These ECs exhibited an extended life span and retained their characteristic endothelial morphology, expression of endothelial marker, and ability of tube formation. Furthermore, h-imTECs showed their specific characteristics as TECs, such as increased proliferation and upregulation of TEC markers. Treatment with bevacizumab, an antiangiogenic drug, dramatically decreased h-imTEC survival, whereas the same treatment failed to alter immortalized NEC survival. Hence, these h-imTECs could be a valuable tool for drug screening to develop novel therapeutic agents specific to TECs or functional biological assays in tumor angiogenesis research.

The etiology of Cronkhite-Canada syndrome (CCS) remains unknown and many cases are refractory to treatment. Therefore, new therapies are urgently needed. Furthermore, a number of CCS cases with gastrointestinal carcinoma have been reported. Our patient had rapid onset of CCS and early development of colon carcinoma associated with adenomas. High anterior resection of the sigmoid colon and ileostomy were performed, and her symptoms and endoscopic and histological findings improved. Helicobacter pylori eradication was carried out 2 years later, surgical closure of an ileal fistula the following year. After 4 months, upper gastrointestinal endoscopy and colonoscopy showed that the CCS lesions had completely disappeared, and biopsies confirmed a normal stomach, duodenum, ileum and colon histologically. The patient has maintained remission for 2 years. The clinical course of this case, showing complete regression of CCS lesions following abdominal colectomy and H. pylori eradication, suggests the significance of H. pylori infection in the treatment of CCS.

The Global Lightning and Sprite Measurements on the Japanese Experiment Module (JEM-GLIMS) started continuous nadir observations of lightning and transient luminous events (TLEs) at the International Space Station (ISS) in November 2012 and completed the observations in August 2015. As JEM-GLIMS uses the nadir observation technique, the JEM-GLIMS optical instruments simultaneously measure both incomparably intense lightning emissions and weak sprite emissions. We adopted combined data analytical methods to distinguish between these two types of emissions: (1) a subtraction of the wideband LSI-1 image from the narrowband LSI-2 image, (2) a calculation of the intensity ratio between different photometer channels, and (3) an estimation of the charge moment change (CMC) of the suspected sprite-producing CG discharge. This report presents as a case study one sprite event detected at 19:50:40.30580 UT on 28 September 2013 and identified using the above analytical methods. From the results derived from detailed data analyses, we judged that the optical emission measured by LSI-2 is a sprite emission. We carried out the geometry conversion toward the LSI-1 and subtracted images and found that the sprite emission location shifts by 3.5 km from the peak lightning emission location, which agree with the previous reports. The detailed horizontal distributions of sprites and the relationship between the sprite location and the parent lightning location are quantitatively revealed for the first time.