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To expand the measurement target from that containing simple cylindrical-shaped components to complex-shaped components that have several directional tilted surfaces, we determined an issue in measuring the rough surfaces with laser distance measurement. The issue is that laser speckle causes measurement error, which amount, we found, can be determined by the diameter and irradiation angle of the measurement laser beam. We then developed two error-reduction techniques that are based on the optical properties of a detected waveform and power. We conducted a basic experiment and a feasibility study with actual samples, to evaluate the distance measurement performance of targets with various surface roughness and irradiation angles. The roughness and angle range of the evaluation was determined considering actual measurement needs in parts manufacturing. We confirmed that the measurement error, whose maximum value was nearly 80 μm, decreased to less than 20 μm using our proposed local-maximum-power-based technique.

OBJECTIVE To confirm if mirabegron 50 mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo. METHODS Post-hoc analyses were carried out using pooled data from a Japanese phase IIb and a phase III study. The primary efficacy end-point was baseline to end-of-treatment change in the mean number of micturitions/24 h. The secondary end-points were changes in the mean voided volume/micturition, mean number of urgency and incontinence episodes/24 h, and mean number of nocturia episodes/night. Other end-points were quality of life and incontinence normalization rates. RESULTS Women with urgency urinary incontinence (placebo n = 204, mirabegron n = 214) and mixed urinary incontinence (placebo n = 122, mirabegron n = 139) were included. Change in mean micturitions/24 h at end-of-treatment for mirabegron was statistically significant versus placebo in both populations; the effect size increased over time. For all secondary end-points, median changes for mirabegron were statistically significant versus placebo at end-of-treatment, except for nocturia for the urgency urinary incontinence population and urgency for the mixed urinary incontinence population. Mirabegron showed larger improvements versus placebo in all quality-of-life domains, except for general health perception in the urgency urinary incontinence population. Incontinence normalization rates for mirabegron were 47.2% and 49.6% in the urgency urinary incontinence and mixed urinary incontinence populations, respectively, versus 42.6% and 39.3% for placebo. CONCLUSIONS Mirabegron 50 mg significantly improved key overactive bladder symptoms versus placebo in women with urgency urinary incontinence, and it also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. These findings support the benefits of using mirabegron in the female overactive bladder wet population.

Leukocyte subtypes can be used to evaluate the severity of ulcerative colitis (UC). In this study, we examined the relationship between the lymphocyte-to-monocyte ratio (LMR) and the Mayo endoscopic score (MES) in assessing endoscopic activity in UC. Eighty-nine samples of leukocyte subtypes and biomarkers, including fecal calprotectin (FC), the fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP), from 71 patients with UC were retrospectively investigated, along with the MES. The MES was significantly correlated with the LMR, FC, the FIT, and CRP. There were significant differences in the LMR, FC, the FIT, and CRP between groups with an MES &lt, 1 and &gt, 2 (p = 0.001, p = 0.003, p &lt, 0.001, and p &lt, 0.001, respectively). In the receiver operating characteristic (ROC) analysis for predicting mucosal healing (MES 0 or 1), the areas under the curve (AUCs) for the LMR, FC, the FIT, and CRP, were 0.712, 0.860, 0.908, and 0.796, respectively. In the analysis of patients without immunomodulators, the correlation of the MES with the LMR and CRP was significant. The LMR can be used to assess endoscopic activity in UC, particularly in patients without immunomodulators.

Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as

Total body irradiation (TBI) with ovarian shielding is expected to preserve fertility among hematopoietic stem cell transplant (HSCT) patients with myeloablative TBI-based regimens. However, the radiation dose to the ovaries that preserves ovarian function in TBI remains poorly understood. Furthermore, it is uncertain whether the dose to the shielded organs is associated with relapse risk. Here, we retrospectively evaluated the relationship between fertility and the dose to the ovaries, and between relapse risk and the dose to the pelvic bones. A total of 20 patients (median age, 23 years) with standard-risk hematologic diseases were included. Median follow-up duration was 31.9 months. The TBI prescribed dose was 12 Gy in six fractions for three days. Patients’ ovaries were shielded with cylinder-type lead blocks. The dose–volume parameters (D98% and Dmean) in the ovaries and the pelvic bones were extracted from the dose–volume histogram (DVH). The mean ovary Dmean for all patients was 2.4 Gy, and 18 patients recovered menstruation (90%). The mean ovary Dmean for patients with menstrual recovery and without recovery were 2.4 Gy and 2.4 Gy, respectively, with no significant difference (P = 0.998). Hematological relapse was observed in five patients. The mean pelvis Dmean and pelvis D98% for relapse and non-relapse patients were 11.6 Gy and 11.7 Gy and 5.6 Gy and 5.3 Gy, respectively. Both parameters showed no significant difference (P = 0.827, 0.807). In conclusion, TBI with ovarian shielding reduced the radiation dose to the ovaries to 2.4 Gy, and preserved fertility without increasing the risk of relapse.

AIMS To examine the safety and efficacy of vibegron, a new β3-adrenoceptor agonist, in patients aged ≥65 years, with a focus on the effects on cardiovascular system and overactive bladder (OAB) symptoms. METHODS A post-hoc subgroup analysis was performed of a randomized, placebo-controlled, double-blind comparative phase 3 study of vibegron, including those assigned to receive either vibegron 50 mg (V50), vibegron 100 mg (V100), or placebo for 12 weeks. Subjects were stratified into two subgroups based on age: a

Background/aim Copper metabolism MURR1 domain-containing 5 (COMMD5) is mainly expressed in renal tubules (RTs), where it facilitates re-differentiation of injured RTs. We reported that COMMD5 regulates the expression of epidermal growth factor receptor by participating in its endocytic membrane trafficking, thus inhibiting tumor growth. Here we aimed to determine the role of COMMD5 in malignant phenotypes of renal cell carcinoma (RCC). Materials and methods The associations between COMMD5 levels in RTs adjacent to RCC tumors in patients and their clinicopathologic characteristics were evaluated, and the effects of COMMD5 on cancer stemness in RCC cells were investigated. Results Low COMMD5 levels in RTs correlated with high tumorigenesis and poor patient outcomes. COMMD5 overexpression in RCC cells reduced the proportion of cancer stem cell-like cells and their malignant phenotypes, including proliferation, invasion and sphere formation. Secreted COMMD5 from RT cells also reduced malignant phenotypes. Conclusion COMMD5 might suppress malignant phenotypes of RCC, thus inhibiting tumor development and improving patient prognosis.

BACKGROUND. The Vesical Imaging Reporting and Data System (VI-RADS), based on multiparametric MRI (mpMRI), was developed to provide accurate information for the diagnosis of muscle-invasive bladder cancer (MIBC). OBJECTIVE. The purpose of our study was to evaluate the interobserver agreement and diagnostic performance of VI-RADS among readers with different levels of experience. METHODS. This retrospective study included 91 consecutive patients who underwent mpMRI before transurethral resection of bladder tumor (TURBT) from July 2010 through August 2018. After attending a training session, seven radiologists (five radiologists experienced in bladder MRI and two inexperienced radiologists) reviewed and scored all MRI examinations according to VI-RADS. The interobserver agreement was assessed by kappa statistics. ROC analysis was used to evaluate the diagnostic performance for MIBC. AUCs were estimated. RESULTS. Among 91 patients (72 men and 19 women; mean age ± SD, 73.2 ± 10.2 years), 48 (52.7%) had MIBC and 43 (47.3%) had non-muscle-invasive bladder cancer. Sixty-eight patients were treated with TURBT, and 23 were treated with radical cystectomy. Interobserver agreement was moderate to substantial (κ = 0.60-0.80) among the experienced readers, substantial (κ = 0.67) between the two inexperienced readers, and moderate to substantial (κ = 0.55-0.75) between the experienced and inexperienced readers. The pooled AUC was 0.88 (range, 0.82-0.91) for experienced readers and 0.84 (range, 0.83-0.85) for inexperienced readers, and 0.87 for all readers. Using a VI-RADS score of 4 or greater as the cutoff value for MIBC, the pooled sensitivity and specificity were 74.1% (range, 66.0-80.9%) and 94.1% (range, 88.6-97.7%) for experienced readers and 63.9% (range, 59.6-68.1%) and 86.4% (range, 84.1-88.6%) for inexperienced readers. Using a VI-RADS score of 3 or greater as the cutoff value, the pooled sensitivity and specificity were 83.4% (range, 80.9-85.1%) and 77.3% (range, 61.4-88.6%) for experienced readers and 82.0% (range, 80.9-83.0%) and 73.9% (range, 72.7-75.0%) for inexperienced readers. CONCLUSION. We observed moderate to substantial interobserver agreement and a pooled AUC of 0.87 among radiologists of different levels of expertise using VI-RADS. CLINICAL IMPACT. VI-RADS could help determine the depth and range of excision in TURBT, decreasing the risk of complications and enhancing the accuracy of pathologic diagnosis.

Surface microstructures impart various useful properties to objects, for example, improving optical characteristics, wettability, and sliding properties. It is well known that biomimicking relief structures are effective in making such properties arise and have been studied to be applied to various devices. Furthermore, they are expected to be utilized not only for improving a particular property but also for adding more complex functions on a device's surface by fabricating different multi-functional structures on a single surface in the future. However, to begin with, artificially fabricating such biomimicking special functional relief is difficult. One typical feature of biomimicking surfaces is the dual-scale structure, the smaller one of which is less than 200 nm. Moreover, in the case of realizing the more complex devices, it is necessary to fabricate various forms as changing process conditions dynamically. In this study, we proposed and developed a flexible evanescent wave interference lithography system as a novel fabrication method, which allows us to realize the fabrication of sub-half-wavelength complex relief structures. Firstly, we theoretically analyzed the fundamental behavior of the fabricated structure and found that the proposed concept has the potential to realize one of the target complex structures. Secondly, we developed the proposed system with high process flexibility, in which the number of beams, the azimuth angles, and the polarization can be simply manipulated. Finally, we validated the concept of the designed system by some experiments, where we fabricated dual-scale structures with 840-nm and 190-nm fringe patterns simultaneously.

Retinoic acid-induced 2 (RAI2) has been shown to be a putative suppressor of the early hematogenous dissemination of tumor cells to the bone marrow in breast cancer. Here, we investigated the associations of RAI2 mRNA and protein expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. Invasive breast cancer tissues (n = 604) were analyzed for RAI2 mRNA expression. We examined the associations of clinicopathological factors with the expression levels of RAI2 mRNA in these samples. We also analyzed RAI2 protein expression by immunohistochemistry in invasive breast cancer tissues (n = 422). We identified significant positive associations between low expression of RAI2 mRNA and shorter disease-free survival (DFS), breast-cancer-specific survival (BCSS), and overall survival (OS) in breast cancer patients. We also identified significant positive associations between negative for RAI2 protein expression and shorter DFS, BCSS, and OS in breast cancer patients. Low RAI2 mRNA and negative for RAI2 protein expression were positively associated with larger tumor size, higher tumor grade, and ERα-negativity. Multivariate analyses indicated that not only RAI2 mRNA but also RAI2 protein expression were independent risk factors for both DFS and BCSS in breast cancer patients. The median follow-up periods were 10.3 and 9.3 years for the RAI2 mRNA and protein expression analyses, respectively. Our findings suggest that RAI2 has a role in the metastasis of breast cancer, and that RAI2 expression could be a promising candidate biomarker of prognosis in breast cancer patients.

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post-micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is

In this paper, we propose an in-process measurement method of the diameter of micro-optical fiber such as a tapered optical fiber. The proposed technique is based on analyzing optically scattered light generated by standing wave illumination. The proposed method is significant in that it requires an only limited measurement range and does not require a high dynamic range sensor. These properties are suitable for in-process measurement. This experiment verified that the proposed method could measure a fiber diameter as stable as ± 0.01 μm under an air turbulence environment. As a result of comparing the measured diameter distribution with those by scanning electron microscopy, it was confirmed that the proposed method has a measurement accuracy better than several hundred nanometers.

For in-line surface inspection of microfluidic devices, optical measurement techniques with sub-micrometer resolution and a long working distance (W.D.) objective lens are needed. Structured illumination microscopy (SIM) is a good candidate to achieve high resolution. In micro-structured surface inspection, however, measurement needs to be carried out through coherent imaging, and thus conventional incoherent SIM cannot be applied directly due to interference of light from a sample. In this study, equations are reformulated by considering amplitude and phase of light waves. As a result, we found that higher spatial frequencies of samples can be derived even through coherent imaging by using multiple interference images. Based on this proposed coherent SIM, an optical measurement method with a long W.D. objective lens and sub-micrometer resolution for in-line surface inspection of sub-micro- and micro-structured surfaces is proposed. We analyzed resolution and performance of the proposed method from a theoretical and numerical perspective based on Fourier optics and imaging theory. The results verified that even with a long W.D. objective lens, the concept of the proposed method allows us to achieve sub-micrometer resolution in spite of non-fluorescence observation. This cannot be achieved by standard microscopy and the conventional incoherent SIM. We also conducted numerical analysis considering external disturbance that can occur in practical in-line inspection. The results revealed that the proposed method is capable to resolve two points with a distance less than half a micrometer with the maximum measurement error of no larger than 5%, under the condition where a maximal phase error of reference light is 2π/20 i.e., 20 nm error in length. These values are practical in in-line inspection.

著者人数: 16名, 形態: カラー図版あり, Number of Authors: 16, Physical characteristics: Original contains color illustrations, Accepted: 2020-12-18, 資料番号: PA2110024000

Objective To carry out an exploratory assessment of the efficacy and safety of TAS-303, a noradrenaline reuptake inhibitor, in women with stress urinary incontinence. Methods In a double-blind, placebo-controlled, early phase II study, women with stress urinary incontinence and stress urinary incontinence-predominant mixed urinary incontinence were randomized to a placebo or TAS-303 (3 or 6 mg) once daily for 8 weeks. The main efficacy end-points were mean percentage change in incontinence episode frequency per 24 h from baseline to week 8 (the primary end-point) and week 4. Results At week 8, the mean percentage change in incontinence episode frequency per 24 h was -34.73% in the TAS-303 3 mg group, -35.41% in the TAS-303 6 mg group and -28.07% in the placebo group (differences vs placebo, not significant). In patients with stress urinary incontinence, or incontinence episode frequency less than two episodes per 24 h at baseline, TAS-303 significantly reduced incontinence episode frequency versus placebo after 4 weeks; some secondary end-points also showed a tendency to improve in the same subgroups. No serious adverse events (e.g. central nervous system or cardiovascular effects) were observed; TAS-303 was well tolerated and had a favorable safety profile. Conclusion These findings suggest that TAS-303 is effective for improving stress urinary incontinence symptoms in some subgroups of patients with stress urinary incontinence. Therefore, further research is warranted.

Background Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80–90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos. Results There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups. Conclusions The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.

A 23-year-old man had epilepsy, mental retardation, and a stereotyped movement (figure 1 and video1), which was exacerbated by emotion. No abnormality was detected in the EEG during this movement. Array comparative genomic hybridization showed a Xq28 duplication: arr[GRCh37]Xq28(153032004_153406233)x2 (figure 2).

We present a successful case of percutaneous lymphatic embolization using N-butyl-2-cyanoacrylate (NBCA) for postoperative lymphorrhea in a patient with urothelial carcinoma of renal pelvis. A 75-year-old man with urothelial carcinoma of left renal pelvis with para-aortic lymph nodes metastases. The patient presented severe lymphorrhea after neo-adjuvant chemotherapy followed by laparoscopic total left nephroureterectomy and lymph nodes dissection. Since conservative treatments were ineffective, percutaneous lymphatic embolization using NBCA resulted in healing of the lymphorrhea without recurrence. Percutaneous lymphatic embolization using NBCA followed by intranodal lymphography is a powerful treatment option for intractable postoperative lymphorrhea after lymph nodes dissection.

Encapsulated papillary carcinoma (EPC), a rare variant of papillary carcinoma of the breast, is regarded as a transition form between carcinoma in situ and invasive carcinoma. Here, we tried to identify differences in immunohistochemical phenotype between 10 EPCs with invasive properties (EPC with invasion) and 17 non-invasive EPCs (EPC). We immunohistochemically assessed the expression of hormone receptors, matrix metalloproteinase (MMP) 2 and MMP9, vascular endothelial growth factor (VEGF), CD31, and D2-40, markers of tumor-associated macrophages (CD163, CD206), Ki-67 and stem cell markers (CD44 and CD24). The frequency of MMP9-positive cases and the number of tumor-associated macrophages infiltrating into the fibrous capsule were significantly higher in EPC with invasion than in EPC. The expression of the standard form of CD44 (CD44s) was significantly stronger in EPC with invasion than in EPC (P = 0.0036) and was correlated with MMP2 expression and M2-like macrophage infiltration. A multivariate logistic model analysis showed that CD44s expression in tumor cell and infiltration of CD163 positive macrophage in EPC capsule showed an independent odds ratio for invasion of EPC. Thus, CD44s may be a potential marker predicting invasive potential of EPC and could play an important role in progression to the invasive phase of EPC.

Objectives The aim of this post hoc analysis from the Japanese mirabegron surveillance program was to investigate the safety and effectiveness of mirabegron in male patients with overactive bladder (OAB) symptoms with/without concomitant benign prostatic hyperplasia (BPH). Methods This 12‐week study included patients who were starting mirabegron treatment for the OAB symptoms of urinary urgency, daytime frequency, and urgency urinary incontinence. Patients were stratified according to BPH diagnosis, and patients with BPH were stratified into those who did/did not receive BPH‐specific treatment. Assessments included adverse drug reactions (ADRs), residual urine volume evaluations, and total Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score‐Quality of Life (IPSS‐QoL) measurements. Results Of 4540 male patients, 3176 (70.0%) had been diagnosed with BPH. Mean age was slightly higher in patients with BPH (74.7 ± 8.41 years) versus patients without BPH (71.0 ± 12.13 years). Overall, 66/1364 (4.84%), 170/2588 (6.57%), and 35/569 (6.15%) patients without BPH, with BPH + treatment, and with BPH + no treatment, respectively, experienced ≥1 ADR. No patients without BPH and 21/3176 (0.66%) patients with BPH experienced a urinary retention ADR. No significant changes from baseline to week 12 in residual volume were noted. Mirabegron was judged to be an effective treatment for 990/1296 (76.4%) patients without BPH, 1935/2491 (77.7%) patients with BPH + treatment, and 421/538 (78.3%) patients with BPH + no treatment. Significant decreases in total OABSS and IPSS‐QoL were observed for all groups. Conclusions Mirabegron was a well‐tolerated and effective treatment for patients with OAB symptoms with or without BPH in this post‐marketing study.

Focal segmental glomerulosclerosis (FSGS) is a common cause of steroid-resistant nephrotic syndrome. Spontaneous remission of FSGS is rare and steroid-resistant FSGS frequently progresses to renal failure. Many inheritable forms of FSGS have been described, caused by mutations in proteins that are important for podocyte function. Here, we show that a basic leucine zipper transcription factor, MafB, protects against FSGS. MAFB expression was found to be decreased in the podocytes of patients with FSGS. Moreover, conditional podocyte-specific MafB-knockout mice developed FSGS with massive proteinuria accompanied by depletion of the slit diaphragm-related proteins (Nphs1 and Magi2), and the podocyte-specific transcription factor Tcf21. These findings indicate that MafB plays a crucial role in the pathogenesis of FSGS. Consistent with this, adriamycin-induced FSGS and attendant proteinuria were ameliorated by MafB overexpression in the podocytes of MafB podocyte-specific transgenic mice. Thus, MafB could be a new therapeutic target for FSGS.

Non-alcoholic steatohepatitis (NASH) is a recognized risk factor for liver fibrosis and malignancies, and is associated with features of metabolic syndrome, such as obesity and insulin resistance (IR). We previously demonstrated that the disturbance of connexin 32 (Cx32), a gap junctional protein of hepatocytes, exacerbated NASH in Cx32 dominant-negative transgenic (Cx32ΔTg) rats fed methionine choline-deficient diet (MCDD). MCDD is well-established means of inducing NASH in rodents; however, the Cx32ΔTg-MCDD NASH model does not reproduce obesity and IR. In this study, we aimed to establish an improved NASH model. Eight-week-old male Cx32ΔTg and wild-type (Wt) rats received a high-fat diet (HFD) with dimethylnitrosamine (DMN) for 12 weeks. The HFD with DMN led to gains in body, liver, and visceral fat weights in both genotypes. IR was significantly greater in Cx32ΔTg than in Wt rats. Elevation of serum hepatic enzymes (AST, ALT), inflammatory cytokine expressions (Tnfα, Il-6, Tgf-β1, Il-1β, Timp2, and Col1a1), steatohepatitis, and fibrosis were significantly greater in Cx32ΔTg as compared with Wt rats. Regarding carcinogenesis, the number and area of glutathione S-transferase placental form (GST-P)-positive preneoplastic hepatic foci were significantly increased in Cx32ΔTg versus Wt rats. Moreover, activation of NF-κB and JNK contributed to the progression of NASH in Cx32ΔTg rats. These results suggest that Cx32 dysfunction promoted the progression of NASH, metabolic syndrome, and carcinogenesis. Therefore, the novel Cx32ΔTg–HFD–DMN NASH model may be a rapid and useful tool for evaluating the progression of NASH.

AIMS To investigate the effect of anagliptin (Ana), a dipeptidyl peptidase-4 (DPP-4) inhibitor, on acute ischemia-induced bladder dysfunction in rats. METHODS Eight-week-old female Wistar-ST rats were randomly assigned into four groups: (a) sham; (b) ligation (Lig); (c) Lig + Ana; and (d) Lig + Liraglutide (a glucagon-like peptide-1 [GLP-1] receptor agonist; Lira). Rats in the Lig, Lig + Ana, and Lig + Lira groups underwent ligature of the bilateral internal iliac arteries. Ana was orally administered mixed with the CE-2 diet. Lira was subcutaneously administered once a day. Blood glucose levels, plasma dipeptidyl peptidase 4 (DPP-4) activity, GLP-1 levels, and bladder function were measured in all groups. Bladder blood flow was measured in the sham, Lig, and Lig + Ana groups, 4 weeks postsurgery. RESULTS No differences in blood glucose levels among the groups were observed. DPP-4 activity decreased in the Lig + Ana group (P

Objectives Despite just a 4-year interval from the last version (2015) of the Clinical Practice Guidelines for Bladder Cancer, several dramatic paradigm shifts have occurred in the latest clinical practice regarding both the diagnosis and treatment of bladder cancer. Herein, we updated the 2019 version of the Clinical Practice Guidelines for Bladder Cancer under the instruction of the Japanese Urological Association. Methods We previously reported in a revision working position paper for Clinical Practice Guidelines for Bladder Cancer 2019 edition and described the methods of revision detail. Results The major points of change in the 2019 version are presented and explanations are given as follows: (i) introduction of the new reference assessment system; (ii) modification of the risk classification for non-muscle-invasive bladder cancer; (iii) addition of clinical questions for the new tumor-visible techniques in non-muscle-invasive bladder cancer; (iv) inclusion of minimally invasive surgeries for muscle-invasive bladder cancer and immune checkpoint inhibitors for locally advanced/metastatic muscle-invasive bladder cancer; (v) overview chapter of the histological variant of urothelial cancer and rare cancers of the bladder; and (vi) recommendation of follow up in non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Conclusions Guidelines should be updated based on the current evidence and updates carried out without delay. The hope is that this guidelines will be assessed by many urologists and will be the cornerstone for the next revision.

Background Gastric cancer (GC) patients frequently develop peritoneal metastasis; however, the underlying mechanism remains unknown. We hypothesised that omental adipocytes (OmAd) trigger GC cells towards malignant activity to induce peritoneal metastasis. Methods We analysed interactions among human GC cells, endothelial cells and OmAd using a 3D co-culture system. We also employed a multipronged animal study, including subcutaneous and orthotopic tumours, and humanised omental adipose tissue models. Urinary levels of CXCL2 were analysed in human GC patients with and without peritoneal metastasis. Results Conditioned media derived from OmAd (OmAd-CM) promoted the proliferation, migration and capacity to induce angiogenesis of GC cells through AKT phosphorylation and VEGFA overexpression, whereas silencing CXCL2 in OmAd cancelled OmAd-induced effects. In an orthotopic tumour model using SCID mice, omentectomy suppressed GC growth and peritoneal dissemination, and reduced serum levels of CXCL2. OmAd promoted GC growth in a humanised omental adipose tissue model using NSG mice, but silencing CXCL2 in OmAd cancelled OmAd-induced tumour growth. Finally, urinary levels of CXCL2 were significantly higher in GC patients with peritoneal metastasis than in those without. Conclusion Omental adipocytes trigger GC cells to an aggressive phenotype through CXCL2 secretion, which induces angiogenesis followed by cell growth and peritoneal metastasis.

Background Immune checkpoint inhibitors (ICIs) have been used to treat many cancers, but ICIs are rarely administered for malignant tumours coexisting with inflammatory bowel disease. Methods and results We report a 77-year-old man experiencing an ulcerative colitis (UC) flare-up after receiving nivolumab as third-line therapy for multiple metastases of renal cell carcinoma. Mild UC (proctitis form) had been diagnosed at age 59 years and remission was maintained for 17 years with only a low dose of 5-ASA. After nivolumab treatment, the patient developed diarrhoea, bloody stools and was hospitalised. Computed tomography revealed inflammation involving the entire colon and endoscopy revealed severe UC exacerbation. Histological analysis showed UC findings and also increased crypt apoptosis which is unusual for inflammatory bowel diseases, while being typical of ICI-induced colitis. As with ICI-induced colitis, this exacerbation was strongly suggested to have been caused by nivolumab, although remission was achieved by increasing the 5-ASA dose to 4000 mg without prednisolone. Conclusion The administration of ICI for UC is not as yet sufficiently safe and further research is required.

Spontaneous cholesterol embolization is thought to be due to aortic plaque-derived shower emboli; however, flowing cholesterol crystals have not been detected. Free multilayer cholesterol crystals obtained from the femoral artery were observed using polarized light microscopy. Detection of these crystals may indicate the occurrence of spontaneous shower emboli. (Level of Difficulty: Intermediate.), Graphical abstract, Spontaneous cholesterol embolization is thought to be due to aortic plaque-derived shower emboli; however, flowing cholesterol crystals have not been…

Recent advances in non-obstructive general angioscopy (NOGA) have enabled the detection of aortic atherosclerosis. The incidence of spontaneous ruptured aortic plaques (SRAPs) and aortic injuries was found to be high in patients diagnosed with or suspected of having coronary artery disease. These facts may result in a paradigm shift for diseases such as aging and acute aortic syndrome because the incidence of systemic embolic diseases and aortic disease are assumed be high. Aortic thromboembolism has been thought to be mainly iatrogenic and is referred to as "cholesterol embolization syndrome" or "cholesterol crystal embolization", although the cholesterol crystals (CCs) were not demonstrated routinely as real images. Atheromatous materials, fibrins, calcifications, macrophages, and a mixture of such substances are released through a puff or puff-chandelier rupture. Among atheromatous materials, CCs can be easily detected clinically in sampled blood via polarized light microscopy. Atheromatous materials include rich CCs and free monolayers, and multilayer CCs are released when the atheromatous materials from vulnerable plaques break into pieces, such as in puff or puff-chandelier rupture. Released SRAPs seem to be asymptomatic; however, accumulation of SRAPs referred to as accumulated spontaneous asymptomatic plaques may cause aging through systemic "embolic" processes, such as mechanical obstruction and an inflammasome pathway. Unique findings in "atherosclerotic" acute aortic syndrome, such as a clear boundary between the dissected lesion and the normal lesion, fissure/fissure bleeding suggesting an entry or a reentry, and subintimal blood flow detected through NOGA are reported. Fissure/fissure bleeding and subintimal blood flow may be the first or last triggers of "atherosclerotic" acute aortic syndrome. Pre-emptive diagnosis and risk stratification of acute "atherosclerotic" aortic dissection and feedback for endovascular therapy may be enabled through the use of NOGA in the future.

Pancreatic serous cystic neoplasms (SCNs), such as serous cystadenoma (SCA), are generally recognized as benign because malignant counterparts of SCNs have been extremely rare. In clinical practice, pancreatic cystic neoplasms diagnosed as SCNs have been managed by conservative observation, as long as the patients remained asymptomatic. We herein report a case of metachronous ductal adenocarcinoma that was discovered during long-term follow-up of SCN and review the related literature. To our knowledge, this was the first reported case of the local presence of ductal adenocarcinoma adjacent to SCA that was preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

To investigate the application of the multi-beam angle sensor (MBAS) to high-precision optical aspheric and freeform surfaces, which are critical components in optical systems, we present a method of using an MBAS to reconstruct an aspheric surface from angle data. The MBAS is based on a multi-autocollimator system with a microlens array, which can split the beam into several spots and can convert centroid detection of the light intensity into an angle measurement. The MBAS is designed to address the curvature-range problem via a circumferential scan better than other methods and automatically eliminates the tilt error caused by rotation of a workpiece. Using a tracking technique, the MBAS can automatically determine focal spot positions from the centroid measurement of the light intensity. This is directly related to the accuracy of the angular difference measurement. The experimental results confirm the feasibility of using an MBAS for 3D surface profile measurements of cylindrical surfaces.

Antiangiogenic agents, such as ramucirumab, should be cautiously administered along with radiotherapy because of the enhanced risk of adverse events.

OBJECTIVE To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P

We report a rare case of extraskeletal Ewing’s sarcoma originating from the larynx. This report describes a 20-year-old man with a large laryngeal tumor extending to the left hypopharynx. This was confirmed to be Ewing’s sarcoma based on biopsy and fluorescence in situ hybridization (FISH) findings. Surgery was considered to be inappropriate due to the large tumor size. He received one course of VDC-IE (vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide) chemotherapy, but this proved to be ineffective. Radiotherapy at a total dose of 68.4 Gy/38 fractions resulted in marked shrinkage of the tumor. The patient is alive 20 months after treatment with no sign of recurrence or metastasis. The highlights of this report are that FISH is important for the early confirmation of a suspected Ewing’s sarcoma diagnosis and that the treatment provided is effective for prolonging the survival of a patient with Ewing’s sarcoma.

We propose a new method of inspecting a surface for fine defects that combines the optical inspection method with observation of the physical behavior of a liquid. A liquid thin film on a substrate behaves as a near-field physical probe that autonomously captures nano-particulate defects. Optical observation of the interfacial behavior of the liquid thin film is used to detect minute defects. This method combines the characteristics of optical detection (i.e., detection from a remote field and simultaneous detectability on a plane) and the high sensitivity of a physical near-field probe. We examined the basic principles of the proposed method through numerical calculation and applied it in experiments to detect fine particulate defects on a silicon substrate for semiconductor manufacturing to demonstrate the validity of the basic concept of the proposed method.

Gender and menopause influence the severity and development manner of nonalcoholic steatohepatitis (NASH). Male p62/Sqstm1 and nuclear factor E2-related factor-2 (p62 and Nrf2) double-knockout (DKO) mice exhibit severe steatohepatitis caused by hyperphagia-induced obesity, overload of lipopolysaccharide (LPS) into the liver, and potentiation of the inflammatory response in Kupffer cells. However, the pathogenetic phenotype of steatohepatitis in female DKO mice remains unknown. Phenotypic changes of steatohepatitis in DKO mice were compared in terms of gender differences. Compared with DKO male mice, DKO female mice exhibited later onset of steatohepatitis with obesity after 30 weeks of age, as well as milder severity of hepatic inflammation and fibrosis. Serum estradiol was higher in female than male mice, with levels increasing up to 30 weeks of age before decreasing until 50 weeks of age (corresponding to the post-menopausal period). Fecal and serum LPS were lower in female mice than male mice, and inflammatory signaling in the liver was attenuated in female compared with male mice. Correlating with LPS levels, the composition of intestinal microbiota in female mice was different from male mice. Gender differences were observed for the development of steatohepatitis in DKO mice. Low-grade inflammatory hit in the liver under in vivo conditions of high estradiol may be attributable to the milder pathological features of steatohepatitis in female mice.

A method for absolute distance measurement is developed here that uses a Fizeau-type spectroscopic interferometer with a Fabry−Perot etalon and a rotating diffraction grating. The integral multiple of the free spectral range (FSR) can be measured using a fiber-type etalon. When the range of length is greater than half of the FSR, the absolute distance can be determined with arbitrary ranges. Moreover, the limited position can be measured over a long distance. Instead of calibrating the wavelength, we use the Fabry−Perot etalon as a standard to determine the absolute position and calibrate the system. Two diffraction gratings increase the spectroscopic resolution to considerably extend the effective range of measurement. Experiments to test the proposed method indicate that it can be used to measure absolute distance with arbitrary ranges of length of up to 120 mm, with repeatability between 0.23 μm (0.0272%) and 0.77 μm (0.0619%), and can measure distances up to 1200 mm.

Background Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. Methods The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. Results Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM. Conclusions Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

We analyzed the ERG gene status using fluorescence in situ hybridization (FISH) in two chemotherapy-naive cases with metastatic castration-resistant prostate cancer (mCRPC) in which abiraterone demonstrated a long-term durable complete response. FISH identified Class 1 Edel and Class 2+ Edel in case 1, and Class 1 Edel in case 2. Our experience suggests that abiraterone may be effective in cases with mCRPC and ERG gene abnormalities, particularly Class 2+ Edel or Class 1 Edel. This is the first report of two cases with mCRPC that simultaneously investigated the ERG gene status and clinical aspects, including image evaluations and pathology.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by peripheral airways inflammation and emphysema. Emerging evidence indicates a contribution of both innate and adaptive immune cells to the development of COPD. Transcription factor T-bet modulates the function of immune cells and therefore might be involved in the pathogenesis of COPD. To elucidate the role for T-bet in elastase-induced emphysema, pathological phenotypes were compared between wild-type and T-bet-/- mice. T-bet-/- mice demonstrated enhanced emphysema development on histological analyses, with higher values of mean linear intercept and dynamic compliance relative to wild-type mice. The number of neutrophils in BAL fluids, lung IL-6 and IL-17 expression, and the proportion of CD4+ T cells positive for IL-17 or retinoic acid receptor-related orphan receptor-γt were higher in T-bet-/- mice than in wild-type mice. Although T-bet downregulates cytokine expression in bone marrow-derived macrophages and MH-S cells, a murine alveolar cell line, depending on the surrounding environment, IL-6 expression in alveolar macrophages isolated from elastase-treated mice was not dependent on T-bet. Coculture of bone marrow-derived macrophages and CD4+ T cells revealed that T-bet regulation of IL-17 expression was dependent on CD4+ T cells. Neutralizing antibodies against IL-6R or IL-17 ameliorated the development of emphysema in T-bet-/- mice. In conclusion, we demonstrate that T-bet ameliorates elastase-induced emphysema formation by modulating the host immune response in the lungs.

Purpose This study was performed to clarify the clinical features of Japanese patients with PRRT2 mutations. Methods The PRRT2 gene was analyzed in 135 patients with benign infantile epilepsy (BIE) or paroxysmal kinesigenic dyskinesia (PKD) using a direct sequencing method: 92 patients had BIE alone, 25 had both BIE and PKD, and 18 had PKD alone. Of the cases, 105 were familial, and 30 were sporadic. Clinical information was collected using a structured questionnaire. Results PRRT2 mutations were identified in 104 patients. Among the familial cases, PRRT2 mutations were found in at least one individual in 21 of 28 families with BIE alone, in 26 of 27 families with infantile convulsions and choreoathetosis, and in 2 of 3 families with PKD alone. Among the sporadic cases, PRRT2 mutations were observed in 7 of 25 patients with BIE alone, in 1 of 1 patient with BIE and PKD, and in 3 of 4 patients with PKD alone. The c.649dupC mutation was the most frequent, followed by the c.981C > G mutation. Among the patients with epilepsy, the median age at BIE onset was 5 months, the median age at the last seizure was 6 months, and the median number of seizures was 5. Conclusion PRRT2 mutations were found in 68% of Japanese probands with BIE or PKD. The phenotypes of BIE associated with PRRT2 mutations were consistent with those of BIE diagnosed clinically.

Water-guided laser processing have been widely used because of low heat affected zone and high aspect ratio processing. However, its processing point is not determined and must be measured with several μm accuracy. For this purpose, in-process measurement method was proposed. Measurement beam of optical comb is coaxially introduced to processing beam so that absolute distance of optical path in water-guide is measured with using optical comb tandem pulsed interferometer in water. To verify the principle of proposed method, in-water absolute distance measurement was evaluated. Repeatability of in-water measurement was under 100 nm and 1.0 mm displacement of target mirror in water was properly measured with under 1 μm error from reference displacement sensor. From these results, it is confirmed that proposed method properly works in-water environment.

Microstructures are widely used in the manufacture of functional surfaces. An optical-based in-process and non-invasive method is preferred for the depth measurement of the fine microgroove structure. A dark-field method is proposed using the features of polarization based on the waveguide theory. According to the numerical simulation based on the FDTD method and Fourier optics, the proposed method allows depth measurement for fine microgroove having an aperture size of less than several hundred nanometers with an aspect ratio (width/depth) of larger than one, even under the far-field measurement.

Lethal giant larvae homolog 2 (LLGL2) and solute carrier family 7 member 5 (SLC7A5) have been reported to be involved in resistance to endocrine therapy. This study aimed to assess the effects of LLGL2/SLC7A5 co-expression in predicting prognosis and response to endocrine therapy in ERα-positive breast cancer patients by using LLGL2/SLC7A5 mRNA and protein expression in long-term follow-up invasive breast cancer tissues. We identified that low LLGL2/SLC7A5 mRNA co-expression (LLGL2low/SLC7A5low) was associated with disease-free survival (DFS) compared with other combination groups in all breast cancer patients. In ERα-positive breast cancer patients, LLGL2low/SLC7A5low showed longer DFS and overall survival (OS) compared with LLGL2high/SLC7A5high and a positive trend of longer survival compared with other combination groups. We also observed that LLGL2low/SLC7A5low showed longer survival compared with LLGL2high/SLC7A5high in ERα-positive breast cancer patients receiving adjuvant tamoxifen therapy. Multivariate analysis demonstrated that LLGL2low/SLC7A5low was an independent favorable prognostic factor of both DFS and OS, not only in all breast cancer patients, but also in ERα-positive breast cancer patients. High co-expression of LLGL2 and SLC7A5 protein showed a positive trend of shorter survival. Our study showed that co-expression of LLGL2 and SLC7A5 mRNA is a promising candidate biomarker in early breast cancer patients.

Tapered fibers with a diameter of sub-micrometer to several micrometer show various optical characteristics, and the diameter is the most important parameter. To guarantee their functions, it is necessary to measure the fiber diameter with high precision during manufacturing. In this research, we propose an in-process measurement method of the diameter of sub-micro-optical fiber. The proposed technique is based on analyzing optically scattered light generated by standing wave illumination. First, we show the scattering characteristics of sub-microfibers using numerical simulation based on finite element method (FEM). From the result of simulation, it was revealed that the optical fiber of 100 nm in diameter can be evaluated with the standing wave illumination.

The optical-based super-resolution, non-invasive method is preferred for the inspection of surfaces with massive microstructures widely applied in functional surfaces. The Structured Illumination Microscopy (SIM) uses standing-wave illumination to reach optical super-resolution. Recently, coherent SIM is being studied. It can obtain both the super-resolved intensity distribution and the phase and amplitude distribution from the sample surface. By analysis of the phase-depth dependency, the depth measurement for microgroove structures with coherent SIM is expected. FDTD analysis is applied for observing the near-field response of microgroove narrower than the diffraction limit under the standing-wave illumination. The near-field phase shows depth dependency in this analysis.

Background: The aim of this study was to optimize the scan range and timing in postoperative CT imaging follow-up for ovarian cancer (OC) patients based on the recurrence pattern in CT imaging and clinical findings. Methods: The subjects were 194 consecutive patients with primary OC treated at our hospital between 2014 and 2019. Recurrence patterns on chest and abdominopelvic CT images obtained for routine postoperative follow-up were evaluated retrospectively to optimize scan range. Medical records were reviewed to determine whether clinical signs and symptoms (patient-reported symptoms and transvaginal ultrasound findings) and tumor markers levels can be sufficiently reliable indicators of recurrence to optimize timing. Results: A total of 890 CT examinations were performed for the 194 patients. Data from the 146 patients with no residual disease at the first CT after standard treatment were analyzed. Recurrence was detected by CT in 15 patients: abdominopelvic recurrence alone in 12 patients, and concurrent chest and abdominopelvic recurrence in 3 patients (2.1%). Abdominopelvic recurrence preceded chest recurrence in all cases. At the time of CT-based recurrence, 13 patients (87%) had medical examination findings and/or elevated tumor markers, while the remaining 2 patients had neither. Conclusions: Regular medical examination and tumor markers were useful for detecting recurrence, but overlooked 13% of patients with recurrence. This indicates that routine abdominopelvic CT is essential for follow-up. However, routine chest CT may not be necessary unless abdominopelvic recurrence is detected first.