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In this study, we conducted experiments to explore the potential of a low-power exploding foil initiator for accelerating microparticles through high-speed membrane deformation. This involved the use of a conductive layer with a conversion section known as a "bridge," which was positioned between the substrate and the cover layer. The application of pulsed electrical energy led to Joule heating at the bridge, while the vaporized gas generated impulsive loading, resulting in the deformation of the cover layer. According to the principles of energy conservation, 8.7% of the electrical input energy was converted into kinetic energy for the membrane. This deformation process achieved a velocity of 800 m/s, with a corresponding strain rate of 1.6 × 107 s−1. The applied impulse predominantly induced extension stresses in the cover layer rather than bending stresses. Under these conditions, a 17.5-µm radius polylactic acid bead was propelled and subsequently captured by a silicone gel layer, resembling human dermic skin. Considering factors such as particle clustering and deceleration due to air resistance during supersonic flight, assuming a normal incident angle, it was estimated that approximately half of the ejected particles could reach the human dermic layer, located 200 µm beneath the skin surface. These findings suggest that pulse discharge is a promising method for inducing high-speed membrane deformation, and the electrical microparticle accelerator holds potential for applications in needle-free drug delivery. [ABSTRACT FROM AUTHOR]

Osteoclasts are associated with certain diseases such as osteopetrosis. The development and functions of osteoclasts are controlled by the micro- and nano-surface roughness of biomaterials. However, the effect of fine micro/nano-patterns on osteoclastic differentiation remains poorly understood. In the present study, we investigated the effect of fine shape patterns at the nano-scale on osteoclastic differentiation. A hole pattern of 500 nm in diameter and 500 nm in height was prepared using nanoimprinting of a glycol-modified polyethylene terephthalate (G-PET) film for a basic topological study. RAW264.7 cells were used as an alternative basic model to primary cells. The result of a cell attachment assay showed that the average number of attached cells on the hole patterned-film was 1.5 times higher than that on the planar film. A cell differentiation assay showed that the average number of multinucleated osteoclasts on the hole patterned-film was approximately 1.9 times higher than that on the planar film. However, the patterning effects in this study were quite small (p> 0.05). Although the morphology of the cells was basically similar when observed under an optical microscope, the morphologies of the attached and differentiated cells were slightly different in terms of their cell shape and filopodia shape between the holed and planar films when observed under a scanning electron microscope. Differences in cell attachment and differentiation behaviors between holed and planar films would affect the functions of the osteoclasts. We suggest that fine nano-patterning of the substrate could be one factor to control osteoclastic differentiation and cell function. [ABSTRACT FROM AUTHOR]

(−)-Rotundone is an oxygenated sesquiterpene responsible for the peppery aroma in grapes, wines, herbs, and spices, and it was first identified in 'Syrah' wine from Australia. In this study, we demonstrated the expression profiles of genes related to (−)-rotundone biosynthesis during the maturation of 'Syrah' grapes from two different vineyards, namely, the Iwaimura and Johnohira vineyards in Japan. The α -guaiene and (−)-rotundone accumulation levels in the grape exocarp from the Johnohira vineyard, which has a cool climatic condition located at a high altitude, were extremely higher than those from the Iwaimura vineyard. Among the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway genes, the transcript levels of 1-deoxy-D-xylulose-5-phosphate synthase gene (DXS) in the grape exocarp from the Johnohira vineyard were higher than those from the Iwaimura vineyard after véraison. The expression levels of the mevalonate pathway genes, Vitis vinifera terpene synthase gene (VvTPS24) and cytochrome P450 gene (CYP71BE5) in the final step of (−)-rotundone biosynthesis were not significantly different between samples from the two vineyards during grape maturation. In contrast, the farnesyl diphosphate synthase gene (FPPS) expression level was considerably higher in the grape exocarp from the Johnohira vineyard than in that from the Iwaimura vineyard. Consistent with these observations, FPPS was constantly expressed at higher level in 'Syrah' grape exocarp compared with 'Merlot' grape which is a low-rotundone cultivar. These findings suggest that FPPS may play a key role in determining the accumulation level of (−)-rotundone, which can provide abundant substrates for VvTPS24 catalysis to produce α-guaiene as a precursor of (−)-rotundone. In addition, among the MEP pathway genes, DXS may have a regulatory role for a precursor supply from the plastids to (−)-rotundone biosynthesis. [ABSTRACT FROM AUTHOR]

We study the emergence of agency from scratch by using Large Language Model (LLM)-based agents. In previous studies of LLM-based agents, each agent's characteristics, including personality and memory, have traditionally been predefined. We focused on how individuality, such as behavior, personality, and memory, can be differentiated from an undifferentiated state. The present LLM agents engage in cooperative communication within a group simulation, exchanging context-based messages in natural language. By analyzing this multi-agent simulation, we report valuable new insights into how social norms, cooperation, and personality traits can emerge spontaneously. This paper demonstrates that autonomously interacting LLM-powered agents generate hallucinations and hashtags to sustain communication, which, in turn, increases the diversity of words within their interactions. Each agent's emotions shift through communication, and as they form communities, the personalities of the agents emerge and evolve accordingly. This computational modeling approach and its findings will provide a new method for analyzing collective artificial intelligence.

CYP3A4 and CYP3A5 are the most abundant and important enzymes of the CYP3A subfamily, distributed in the liver, intestinal mucosa and kidney, and involved in tacrolimus metabolism. Here, we report a case of tacrolimus dosage refractoriness due to a genetic polymorphism of CYP3A5., Competing Interests: The authors state that the study was conducted without any commercial or financial relationships that could be interpreted as a conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction Decreased renal function after radical nephroureterectomy is one of the most important complications because it contributes to the decision to initiate adjuvant chemotherapy. This study aimed to investigate clinical factors associated with changes in renal function after radical nephroureterectomy in elderly patients. Methodology A total of 145 patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma were evaluated. The renal function was calculated preoperatively, postoperatively, and one month postoperatively, and the long-term change in renal function was investigated once a year. The association between clinical factors and changes in renal function following radical nephroureterectomy in univariate and multivariate analyses was stratified by age ≥75 years and <75 years. Results The median age of the patients was 71 years, with 94 patients (65%) aged <75 years and 51 patients (35%) aged ≥75 years. The median estimated glomerular filtration rates (eGFRs) were 57.1 (21.8-100) preoperatively, 36.1 (9.1-100) postoperatively, and 42.4 (19.5-100) in one month after radical nephroureterectomy. The median eGFRs in elderly patients were 50.8 (21.8-85.4) preoperatively. In the elderly group, only 8% had an eGFR of ≥50 as cisplatin-eligible at one month postoperatively. The long-term renal function in the elderly may decline further than during the stable postoperative periods. In the multivariate analysis, hydronephrosis (HN) was a significant predictor of decreased renal function in patients aged ≥75 years between the pre- and postoperative periods. Conclusions Elderly patients with HN who have upper tract urothelial carcinoma have a lower risk of decreased renal function after radical nephroureterectomy. This result may be useful in determining adjuvant therapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Iwate Medical University issued approval 2019-083. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kawamura et al.)

Objective: The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer., Methods: Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx®. Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed., Results: Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149)., Conclusions: In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biomarkers that could detect the postoperative recurrence of upper tract urothelial carcinoma (UTUC) have not been established. In this prospective study, we aim to evaluate the utility of individualized circulating tumor DNA (ctDNA) monitoring using digital PCR (dPCR) as a tumor recurrence biomarker for UTUC in the perioperative period. Twenty-three patients who underwent radical nephroureterectomy (RNU) were included. In each patient, whole exome sequencing by next-generation sequencing and TERT promoter sequencing of tumor DNA were carried out. Case-specific gene mutations were selected from sequencing analysis to examine ctDNA by dPCR analysis. We also prospectively collected plasma and urine ctDNA from each patient. The longitudinal variant allele frequencies of ctDNA during the perioperative period were plotted. Case-specific gene mutations were detected in 22 cases (96%) from ctDNA in the preoperative samples. Frequently detected genes were TERT (39%), FGFR3 (26%), TP53 (22%), and HRAS (13%). In all cases, we obtained plasma and urine samples for 241 time points and undertook individualized ctDNA monitoring for 2 years after RNU. Ten patients with intravesical recurrence had case-specific ctDNA detected in urine at the time of recurrence. The mean lead time of urinary ctDNA in intravesical recurrence was 60 days (range, 0-202 days). Two patients with distal metastasis had case-specific ctDNA in plasma at the time of metastasis. In UTUC, tumor-specific gene mutations can be monitored postoperatively as ctDNA in plasma and urine. Individualized ctDNA might be a minimally invasive biomarker for the early detection of postoperative recurrence., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The progression of prostate cancer (PCa) relies on the activation of the androgen receptor (AR) by androgens. Despite efforts to block this pathway through androgen deprivation therapy, resistance can occur through several mechanisms, including the abnormal activation of AR, resulting in castration-resistant PCa following the introduction of treatment. Mutations, amplifications, and splicing variants in AR-related genes have garnered attention in this regard. Furthermore, recent large-scale next-generation sequencing analysis has revealed the critical roles of AR and AR-related genes, as well as the DNA repair, PI3K, and cell cycle pathways, in the onset and progression of PCa. Moreover, research on epigenomics and microRNA has increasingly become popular; however, it has not translated into the development of effective therapeutic strategies. Additionally, treatments targeting homologous recombination repair mutations and the PI3K/Akt pathway have been developed and are increasingly accessible, and multiple clinical trials have investigated the efficacy of immune checkpoint inhibitors. In this comprehensive review, we outline the status of PCa research in genomics and briefly explore potential future developments in the field of epigenetic modifications and microRNAs.

The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. We assessed the density of several immune cell types in pretreatment and posttreatment tissues via multiplex fluorescence immunohistochemical analysis. The median age was 67 years; 10 patients were male. Nine (75%) and 3 (25%) patients were cT2 and cT3, respectively. The 5-year progression-free and overall survivals were 90% and 100%, respectively. The densities of regulatory T cells (Treg; CD3 + CD4 + FoxP3 + cell) were significantly decreased and almost disappeared in the tumor microenvironment of posttreatment tissue compared with pretreatment tissue. Other immune cells, such as effector T cells or M2 macrophages, were not significantly changed between posttreatment and pretreatment tissues. In pathological complete response, Tregs in the tumor immune microenvironment were significantly decreased after platinum-based chemotherapy for muscle-invasive bladder cancer. The temporary arresting of immune response in the tumor microenvironment may reflect a favorable prognosis due to the decrease of Tregs with tumor shrinkage and improve the host tumor immune response., (© 2024. The Author(s).)

Matrix-assisted laser desorption/ionization (MALDI), surface-assisted laser desorption/ionization (SALDI), and time-of-flight mass spectrometry (TOFMS) imaging are used for visualizing the spatial distribution of analytes. Mass spectrometry (MS) imaging of a sample with a rough surface with a uniform distribution of an analyte does not provide uniform ion intensities in the image. A shift in the m/z value of the analyte ions is also observed. To resolve these issues, we proposed a normalization method for obtaining images based on the actual localization of an analyte. A platinum (Pt) film was used to facilitate ionization in SALDI. The Pt ions obtained from the film and copper(II)-phthalocyanine from a commercial blue pigment were used to evaluate the shift in the m/z values and ion intensities originating from the sample surface placed diagonally. The relationship between the shift in the m/z value and peak area in mass spectra was determined by analyzing the relationship between the shift and irradiated height position, as well as between the peak area and irradiated height position on the sample. The SALDI image can be obtained based on the actual location of the analyte to normalize the raw image data. Thus, the normalization of the ion intensities enables SALDI-MS imaging of samples with rough surfaces using high-resolution TOFMS. The proposed normalization method for SALDI-MS imaging enhances the accuracy and resolution of analyte localization on rough surfaces, benefiting applications in material science, biomedical research, forensic analysis, and industrial quality control., (Copyright © 2024 Riko Takata, Kotaro Hashimoto, Taichi Shimazaki, Kyosuke Kaneda, Shuhei Yamamoto, Shota Nakanishi, and Issey Osaka.)

Matrix-assisted laser desorption ionization (MALDI) and surface-assisted laser desorption ionization (SALDI) mass spectrometry (MS), which can detect biomolecules and polymers, are widely used in biochemistry and material science. Some compounds that are difficult to ionize using MALDI can be ionized using SALDI. However, it is difficult to obtain high ion yields using SALDI/MS. In this study, a fabricated platinum (Pt) film with nanostructures on the sample surface using a sputtering method was evaluated to determine the optimal metal film for ion yield in SALDI. The surface morphology of the Pt film was analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray reflectivity (XRR), and ultraviolet-visible-near-infrared (UV-Vis-NIR) reflectance spectroscopy. The SEM, AFM, and TEM images of the Pt film showed the deposited metal film giving high ion yields of polyethylene glycol (PEG) in SALDI/MS with a Pt film (Pt-SALDI) that had a rough surface. The densities and reflectivity of films were analyzed by XRR and UV-Vis-NIR. The higher ion yields of PEG were obtained by Pt-SALDI with the Pt films with lower densities and reflectivity. This indicates that the deposition conditions for the Pt films significantly improved the ion yield in Pt-SALDI/MS. The Pt-SALDI has ionization capabilities different from those of MALDI. Therefore, optimization of Pt film for SALDI/MS and the MS imaging allows more compounds to be detected with higher sensitivity., (Copyright © 2024 Kotaro Hashimoto, Kyosuke Kaneda, Taichi Shimazaki, Chouma Kurihashi, Shuhei Yamamoto, Riko Takata, Shota Nakanishi, and Issey Osaka.)

Introduction: Patients with translocation renal cell carcinoma (tRCC) have a poor prognosis without standardized treatment., Case Presentation: The first case was of a 72-year-old woman who underwent robot-assisted partial nephrectomy for a left renal tumor and was pathologically diagnosed with tRCC. Recurrence was observed in the left retroperitoneal soft tissue. After treatment with avelumab-axitinib, continued progression-free survival was confirmed at the 90-week follow-up. The second case was of a 41-year-old woman referred to our hospital and presented with translocation renal cell carcinoma metastasis to a para-aortic lymph node. After treatment with avelumab-axitinib, continued progression-free survival was confirmed at the 43-week follow-up., Conclusion: The outcomes of these cases indicate that avelumab-axitinib therapy has a long-term antitumor effect in some patients with tRCC., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background: Prostate cancer in the anterior region may be missed on a transrectal systematic biopsy (SBx). Therefore, this study aimed to evaluate the performance of magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TBx) in detecting anterior region cancer in patients with a history of SBxs., Methods: Prostate biopsies were performed in 224 patients after multiparametric MRI, among whom 119 patients with prostate imaging reporting and data system (PI-RADS version 2) scores of 3 to 5 underwent MRI-TRUS fusion TBxs. Afterward, cancer detection rates (CDRs) and TBx-positive core regions were compared by categorizing patients into those with or without a history of SBxs., Results: Total CDR was 68.8% (44/64 cases) in the initial biopsy group (Initial-Bx group) and 47.3% (26/55 cases) in the previous-negative-systematic biopsy group (Pre-Neg-SBx group) ( P  = 0.018). Interestingly, both TBx- and SBx-core positive cases were more common in the Initial-Bx group than in the Pre-Neg-SBx group (Initial-Bx group: 75% [33/44 cases] vs. Pre-Neg-SBx group: 42.3% [11/26 cases], P  = 0.006). However, only TBx-core positive cases were more common in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 11.4% [5/44 cases] vs. Pre-Neg-SBx group: 30.8% [8/26 cases], P  = 0.043). In addition, the proportion of anterior lesions detected by TBx cores was higher in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 26.3% [10/38 cases] vs. Pre-Neg-SBx group: 52.6% [10/19 cases], P  = 0.049)., Conclusion: Using MRI-TRUS fusion TBx in the evaluation of previously negative SBx cases improved the detection rate of anterior lesions, which might have been missed in previous SBxs. Especially in patients with a history of SBxs mpMRI should be performed to screen for anterior lesions., (© 2023 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

We report the case of a 68-year-old man who developed a sigmoidorectal fistula after marked response to enfortumab vedotin for advanced bladder cancer. The patient had undergone radical cystectomy with ileal conduit after neoadjuvant chemotherapy. Six months after surgery, local recurrence in the pelvic cavity and multiple lung metastases were found, and the patient was administered pembrolizumab as second-line therapy. Due to worsening local recurrence and suspected invasion of the sigmoid colon and rectum, enfortumab vedotin was initiated as third-line therapy and comprehensive genomic profiling was simultaneously performed. Enfortumab vedotin was remarkably effective, the lung metastases disappeared, and the local recurrent lesion shrank in volume although a sigmoidorectal fistula was found to form through the tumor cavity. Immunohistochemical analysis of the tumor specimens exhibited increased nectin-4 expression. This rare case of metastatic bladder cancer with sigmoidorectal fistula associated with effective enfortumab vedotin therapy suggests that nectin-4 expression and comprehensive genomic profiling might be useful in predicting treatment response to enfortumab vedotin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tamada, Ikarashi, Yanagawa, Toyoshima, Takahashi, Matsuura, Maekawa, Kato, Kanehira, Takata and Obara.)

Patients with end-stage renal disease (ESRD) or receiving dialysis have a much higher risk for renal cell carcinoma (RCC), but carcinogenic mechanisms and genomic features remain little explored and undefined. This study's goal was to identify the genomic features of ESRD RCC and characterize them for associations with tumor histology and dialysis exposure. In this study, we obtained 33 RCCs, with various histological subtypes, that developed in ESRD patients receiving dialysis and performed whole-genome sequencing and transcriptome analyses. Driver events, copy-number alteration (CNA) analysis and mutational signature profiling were performed using an analysis pipeline that integrated data from germline and somatic SNVs, Indels and structural variants as well as CNAs, while transcriptome data were analyzed for differentially expressed genes and through gene set enrichment analysis. ESRD related clear cell RCCs' driver genes and mutations mirrored those in sporadic ccRCCs. Longer dialysis periods significantly correlated with a rare mutational signature SBS23, whose etiology is unknown, and increased mitochondrial copy number. All acquired cystic disease (ACD)-RCCs, which developed specifically in ESRD patients, showed chromosome 16q amplification. Gene expression analysis suggests similarity between certain ACD-RCCs and papillary RCCs and in TCGA papillary RCCs with chromosome 16 gain identified enrichment for genes related to DNA repair, as well as pathways related to reactive oxygen species, oxidative phosphorylation and targets of Myc. This analysis suggests that ESRD or dialysis could induce types of cellular stress that impact some specific types of genomic damage leading to oncogenesis., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background/aim: Surgical treatment of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is associated with high morbidity and mortality rates, therefore presurgical systemic therapies are required in order to improve the safety and feasibility of the surgical procedure by decreasing the thrombus level and burden. The efficacy of presurgical combination therapy of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) for advanced renal cell carcinoma with IVC thrombus remains unclear., Case Report: We report a case of a 69-year-old male with cT3bN0M0 locally advanced RCC. We successfully performed a less invasive nephrectomy with thrombectomy, because nivolumab plus cabozantinib administration remarkably reduced the primary tumor and IVC thrombus, resulting in complete pathological response, as assessed with perioperative immunohistochemistry., Conclusion: To the best of our knowledge, this is the first report showing that nephrectomy could be safely performed for RCC with IVC thrombus after presurgical nivolumab plus cabozantinib therapy, leading to pathological complete response., Competing Interests: The Authors declare no conflicts of interest., (Copyright 2023, International Institute of Anticancer Research.)

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been widely used for analyses of biomolecules and industrial materials. Surface-assisted laser desorption/ionization (SALDI) is studied to complement the ionization ability for the MALDI/MS. In this study, lab-made mist chemical vapor deposition (mist CVD) system was used to produce metal films as ionization assistance materials for SALDI/MS. The system could give Ag film from inexpensive silver trifluoroacetate solution rapidly and simply under atmospheric pressure. Phosphatidylcholines could be detected high sensitively and diacylglycerols (DAGs) could not be detected in MALDI/MS. In the SALDI/MS and the MS imaging with Ag film by mist CVD, both the phosphatidylcholines and the DAGs could be detected and the localized images. In the Ag film-SALDI/MS of lipids, not only Ag-adducted ions but also Na- and K-adducted ions were detected. The Ag film formed by the mist CVD to act as an ionization-assistance material and a cationization agent in SALDI would be useful in MS imaging of biological tissue sections., (Copyright © 2023 Riko Takata, Yuji Nakabayashi, Kotaro Hashimoto, Akio Miyazato, and Issey Osaka.)

Aldosterone-producing adenomas (APAs) have different steroid profiles in serum, depending on the causative genetic mutation. Ion mobility is a separation technique for gas-phase ions based on their m / z values, shapes, and sizes. Human serum (100 µL) was purified by liquid-liquid extraction using tert -butyl methyl ether/ethyl acetate at 1/1 ( v / v ) and mixed with deuterium-labeled steroids as the internal standard. The separated supernatant was dried, re-dissolved in water containing 20% methanol, and injected into a liquid chromatography-ion mobility-mass spectrometer (LC/IM/MS). We established a highly sensitive assay system by separating 20 steroids based on their retention time, m / z value, and drift time. Twenty steroids were measured in the serum of patients with primary aldosteronism, essential hypertension, and healthy subjects and were clearly classified using principal component analysis. This method was also able to detect phosphatidylcholine and phosphatidylethanolamine, which were not targeted. LC/IM/MS has a high selectivity for known compounds and has the potential to provide information on unknown compounds. This analytical method has the potential to elucidate the pathogenesis of APA and identify unknown steroids that could serve as biomarkers for APA with different genetic mutations.

Objectives: This study aims to investigate whether a cribriform pattern on prostate biopsy may be a factor in suspicion of intraductal carcinoma of the prostate after radical prostatectomy., Methods: This retrospective study assessed 100 men who underwent prostatectomy from 2015 to 2019. Participants were grouped as 76 patients with Gleason pattern 4 and 24 patients without this pattern. All 100 participants underwent retrograde radical prostatectomy and limited lymph node dissection. The same pathologist evaluated all specimens. The cribriform pattern was evaluated with haematoxylin and eosin counterstaining, and intraductal carcinoma of the prostate was evaluated with immunohistochemical analysis of cytokeratin 34βE12., Results: Patients with intraductal carcinoma of the prostate on immunohistochemical analysis showed a significant tendency to relapse in the postoperative period, and those with the cribriform pattern on biopsy had a significant recurrence rate. In univariate and multivariate analyses, intraductal carcinoma of the prostate confirmed in biopsy tissue was an independent predictor of biochemical recurrence after prostatectomy. The rate of intraductal carcinoma of the prostate confirmation was 28% of cases with a cribriform pattern in biopsy tissue, which was increased to 62% in prostatectomy tissues., Conclusion: The cribriform pattern in the biopsy tissue may be a predictor for intraductal carcinoma of the prostate., Competing Interests: We declare that we have no conflicts of interest.Approval of the research protocol by an Institutional Reviewer Board and the approval number: R2‐24. Informed consent: NA. Registry and the registration no. of the study/trial: NA. Animal studies: NA., (© 2022 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Introduction: Immunotherapy-based combinations have become the standard first-line therapy for metastatic renal cell carcinoma. However, combined immunotherapy for renal collecting duct carcinoma had been reported, but its therapeutic efficacy had been unclear., Case Presentation: The first case was a 62-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with multiple bone metastases. After 7 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. The second case was a 71-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with lymph node and lung metastases. After 9 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. In both cases, the tumor cell expression of programmed death ligand-1 was negative, and CD4 + and CD8 + cells were observed in the tumor., Conclusion: Combined immunotherapy with pembrolizumab and axitinib may be effective for metastatic renal collecting duct carcinoma., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Introduction: Aggressive angiomyxoma is a rare mesenchymal tumor in females of reproductive age that occurs in the pelvis and perineal zone with a high risk of local infiltration and recurrence. Male aggressive angiomyxoma in perineal zone is very rare., Case Presentation: A 63-year old male presented to our hospital with chief complaint of perineal mass. He was diagnosed with perineal lipoma by needle biopsy 3 years before. Computed tomography revealed a 16 cm perineal tumor without lymph node or distal metastasis. As the tumor had gradually increased, we performed tumor resection. The histological diagnosis of tumor using immunohistochemistry was aggressive angiomyxoma with complete resection. Moreover, expressions of both estrogen and progesterone receptors were recognized. No recurrence was seen 9 months after surgery., Conclusion: Male aggressive angiomyxoma is a very rare tumor, which has expressions of female hormone receptors. Hormonal therapy might be effective for perioperative therapy or recurrence., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy., Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity., Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants., Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings., (© The Author(s) 2022. Published by Oxford University Press.)

Background: A virtual reality (VR) simulator is utilized as an inexpensive tool for gaining basic technical competence in robotic-assisted surgery (RAS). We evaluated operator 3D motion sickness while using a VR simulator and assessed whether it can be reduced by repeating the training., Methods: This prospective observational study was conducted at the Department of Urology, Iwate Medical University, a tertiary training hospital in an urban setting. A total of 30 undergraduate medical students participated in the study. We compared whether the VR simulator improved the students' skills in operating the da Vinci robot. Fifteen students underwent training with a VR simulator for 4 h a day for 5 days. Then, motion sickness was determined using the Visual Analog Scale and Simulator Sickness Questionnaire (SSQ) before and after the training., Results: Manipulation time significantly improved after training compared to before training (293.9 ± 72.4 versus 143.6 ± 18.4 s; p < 0.001). Although motion sickness worsened after each training session, it gradually improved with continuous practice with the VR simulator. SSQ subscores showed that the VR simulator induced nausea, disorientation, and oculomotor strain, and oculomotor strain was significantly improved with repeated training., Conclusions: In undergraduate students, practice with the VR simulator improved RAS skills and operator 3D motion sickness caused by 3D manipulation of the da Vinci robot., (© 2021. The Author(s).)

Objective: To investigate if the use of therapeutic agents for dysuria is a risk factor for the primary recurrence of non-muscle invasive bladder cancer (NMIBC)., Methods: First, patients with NMIBC were divided into two groups: the non-recurrence group and the recurrence group. Patient characteristics were compared between both groups. The risk factors of recurrence that were statistically different between the two groups were identified by multivariate analysis. Second, we divided the patients into risk and non-risk groups, and differences in the recurrence-free survival (RFS) between the two groups were analyzed before and after propensity score matching (PSM)., Results: A total of 162 patients were included, with 84 patients in the non-recurrence group and 78 patients in the recurrence group. In the multivariate analysis, the intake of dysuria agents and bacillus Calmette-Guérin (BCG) therapy were independent factors. The RFS results in terms of the intake of dysuria agents were statistically significant before and after PSM analysis, but no factors were significantly different between the BCG and non-BCG groups after PSM., Conclusions: Therapeutic agents for dysuria might be at an independent risk factor for NMIBC recurrence. This trial is registered with the UMIN Clinical Trials Registry under the number UMIN000036097 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno = R000041122).