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Key Clinical Message This is the first case report in which computed tomography (CT) images of a patient with emphysematous pyelonephritis (EPN) capture the time course of emphysema from onset to resolution through conservative treatment. To re‐evaluate EPN, including refractory urinary tract infections, CT scans after 72 h might be helpful.

Maize is the staple food crop in Bhutan, which has not achieved national food self-sufficiency. On-farm assessment of yield variability would provide insights into the priorities for Bhutan's maize development program. Here, we conducted three studies in Bhutan: a household survey, on-station experiment, and on-farm monitoring. First, we interviewed 100 households and collected information on maize crop management options and farming characteristics. Second, we evaluated maize growth at two research stations in different elevation zones (640 and 1,700 ​m a.s.l.). Third, we harvested maize from 25 farm fields at low and high elevations. The gaps between potential yield (with the best management practices at the research stations) and average farm yield and between the best and average farm yields were 53% and 23%, respectively, at the low elevation, and 23% and 20%, respectively, at the high elevation. The classification and regression tree (CART) model showed that field location (distance from the farmer's home), seed source (certified vs. self-produced), and the number of household members involved in farming were the key farming characteristics that affected yield variability, and the manure application regime, urea application, sowing method, and weeding frequency were key management practices. Our results suggest that future research should clarify the most suitable sowing methods and nutrient and weed management regimes, and identify optimal cultivars for each elevation zone, with the goal of developing crop management guidelines for smallholder farmers in Bhutan.

Abstract 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.

Introduction Most congenital ureteral strictures occur at the ureteropelvic or ureterovesical junction in children. Mid‐ureteral stricture is very rare and can cause congenital hydronephrosis. Only a few studies have reported on coexisting mid‐ureteral stricture with ipsilateral atrophic kidney in young adults. Case presentation A 16‐year‐old girl presented with repeated urinary tract infection. Computed tomography revealed a right atrophic kidney and hydroureter. Retrograde pyelography showed a mid‐ureteral stricture. Laparoscopic nephroureterectomy was performed, and histological examination revealed mid‐ureteral stricture with hyperplasia of the fibrous connective tissue and an atrophic kidney. Conclusion Mid‐ureteral stricture in a young adult is extremely rare. Appropriate imaging studies including retrograde pyelography are necessary for accurate diagnosis of mid‐ureteral stricture.

ABSTRACTAcid sulfate soils in tropical coastal rice areas contain high Fe levels, and excess ferrous (Fe2+) ions are released during the early growth stage in the wet season. In such environments, Fe toxicity can cause significant yield losses. The objectives of this study were to evaluate the seedling growth of diverse rice germplasm (from japonica, aus and indica groups) under high-Fe conditions in hydroponic culture and to elucidate the growth characteristics of Fe toxicity tolerant genotypes. We calculated an Fe toxicity response index (FTRI) as a selection criterion that reflects both the response of shoot biomass to high Fe and the amount of Fe-induced leaf bronzing damage: higher FTRI values indicate greater tolerance to high Fe levels. We first compared Fe levels to determine the appropriate conditions for genotype selection, and then screened 2- to 3-week-old seedlings grown for 2 more weeks in hydroponic solution containing 500 mg Fe2+ L−1. Sixteen genotypes were screened, and for five of them, the differences in FTRI corresponded with previously reported yield performance in high-Fe fields. We identified Taichung65 (temperate japonica) as a promising donor, as it showed little bronzing damage and high relative (stress/control) biomass under high-Fe conditions, resulting in a high FTRI. Plant nutrient analyses of Taichung65 suggested that maintenance of low Fe concentration and low total Fe content in shoots despite high Fe concentration in the rhizosphere, through prevention of either root Fe uptake or Fe translocation from the root to the shoot, should be an important mechanism of Fe toxicity tolerance.

Weed is a major biological factor causing declines in crop yield. However, widespread herbicide application and indiscriminate weeding with soil disturbance are of great concern because of their environmental impacts. Site-specific weed management (SSWM) refers to a weed management strategy for digital agriculture that results in low energy loss. Deep learning is crucial for developing SSWM, as it distinguishes crops from weeds and identifies weed species. However, this technique requires substantial annotated data, which necessitates expertise in weed science and agronomy. In this study, we present a channel attention mechanism-driven generative adversarial network (CA-GAN) that can generate realistic synthetic weed data. The performance of the model was evaluated using two datasets: the public segmented Plant Seedling Dataset (sPSD), featuring nine common broadleaf weeds from arable land, and the Institute for Sustainable Agro-ecosystem Services (ISAS) dataset, which includes five common summer weeds in Japan. Consequently, the synthetic dataset generated by the proposed CA-GAN obtained an 82.63% recognition accuracy on the sPSD and 93.46% on the ISAS dataset. The Fréchet inception distance (FID) score test measures the similarity between a synthetic and real dataset, and it has been shown to correlate well with human judgments of the quality of synthetic samples. The synthetic dataset achieved a low FID score (20.95 on the sPSD and 24.31 on the ISAS dataset). Overall, the experimental results demonstrated that the proposed method outperformed previous state-of-the-art GAN models in terms of image quality, diversity, and discriminability, making it a promising approach for synthetic agricultural data generation.

ABSTRACTDry direct seeding of rice (DDSR) is being increasingly used in water-scarce areas across Asia. When drought occurs, deep sowing may enable germinating seeds to utilize the residual moisture below the surface. Our objective was to examine the effects of different sowing depths on DDSR crop growth. Two yield experiments, one in the Philippines and the other in Japan, were established in rainfed lowlands, but drought did not occur. Across the experiments, sowing at a depth of 6 to 7 cm reduced the percentage of emergence compared with sowing at a depth of 1 to 2 cm (25% vs. 73%), which resulted in lower yield (3.5 vs. 4.4 t ha−1). The relative yield (deep-sowing/shallow-sowing) was positively correlated with the percentage emergence under deep sowing. Cultivars with no significant yield reduction under deep sowing maintained high emergence (>30%) under deep sowing. Seedling’s ability to emerge after deep sowing greatly differed among cultivars: the percentage emergence ranging from 0% to 18% from a depth of 8 to 10 cm, and from 11% to 44% from a depth of 6 to 7 cm. An ancillary field experiment was conducted under drought during the dry season in the Philippines: deep sowing increased the percentage emergence compared with shallow sowing (41% vs. 5%), when the soil surface was severely dry. Our results suggest that choosing cultivars that can tolerate deep sowing is a prerequisite for using deep sowing in DDSR, and that future breeding of DDSR should focus on this tolerance.

Abstract Maize is the world's most produced cereal crop, and the selection of maize cultivars with a high stem elastic modulus is an effective method to prevent cereal crop lodging. We developed an ultra-compact sensor array inspired by earthquake engineering and proposed a method for the high-throughput evaluation of the elastic modulus of maize cultivars. A natural vibration analysis based on the obtained Young’s modulus using finite element analysis (FEA) was performed and compared with the experimental results, which showed that the estimated Young’s modulus is representative of the individual Young’s modulus. FEA also showed the hotspot where the stalk was most deformed when the corn was vibrated by wind. The six tested cultivars were divided into two phenotypic groups based on the position and number of hotspots. In this study, we proposed a non-destructive high-throughput phenotyping technique for estimating the modulus of elasticity of maize stalks and successfully visualized which parts of the stalks should be improved for specific cultivars to prevent lodging.

Developing high-yielding rice varieties is critical to ensure global food security. To date, selection of promising genotypes is based on empirical evaluation for grain yield, but the relationship of agronomic traits to yield in tropical rice breeding is largely unknown. This study aimed to determine the extent of variation for 19 agronomic traits and interrelationships among traits in an irrigated rice breeding program at the International Rice Research Institute, Philippines. A large set of elite germplasm comprising advanced genotypes and varieties derived from the breeding pipeline was evaluated during dry and wet seasons. The broad-sense heritability ranged from 0.35 to 0.99 for all traits in both seasons. Grain yield for the whole plot (plot yield) was positively correlated with yield per plant, 1000 grain weight, and grain width in dry season, and yield per plant, 1000 grain weight, grain width, number of panicles per plant, and panicle exertion rate in wet season. Path analysis showed that the highest direct positive effect of traits on plot yield ranged from 0.25 to 0.45 in dry season and from 0.22 to 0.88 in wet season. Heat map bi-cluster analysis assigned genotypes into three main clusters in both seasons, while traits were grouped into three and five clusters in dry and wet seasons, respectively. The cluster analysis showed that spikelets per panicle, filled grains per plant, and yield per plant were key yield contributing traits. Identification of traits that were highly correlated with rice yield could be useful for developing new varieties adapted to tropical environments.

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.

Climate change due to global warming is now affecting agricultural production worldwide. In rice, one of the most important crops, water limitation due to irregular rainfall in rainfed lowlands during crop growth limits yield. Dry direct-sowing has been proposed as a water-efficient approach to cope with water stress during rice growth, but poor seedling establishment due to drought during germination and emergence is a problem. Here, we germinated indica rice cultivars Rc348 (drought tolerant) and Rc10 (drought sensitive) under osmotic stress induced by PEG to elucidate mechanisms of germination under drought. Rc348 had higher germination rate and germination index under severe osmotic stress of −1.5 MPa, above those of Rc10. Rc348 showed up-regulated GA biosynthesis, down-regulated ABA catabolism, and up-regulated α-amylase gene expression in imbibed seeds under PEG treatment compared to that of Rc10. During germination, reactive oxygen species (ROS) play important roles in antagonism between gibberellic acid (GA) and abscisic acid (ABA). Embryo of Rc348 treated with PEG had significantly greater expression of NADPH oxidase genes and higher endogenous ROS levels, together with significantly increased endogenous GA1, GA4 and ABA contents compared to that of Rc10. In aleurone layers treated with exogenous GA, expression of α-amylase genes was higher in Rc348 than in Rc10, and expression of NADPH oxidase genes was enhanced with significantly higher ROS content in Rc348, suggesting higher sensitivity of GA to ROS production and starch degradation in aleurone cells of Rc348. These results suggest that the osmotic stress tolerance of Rc348 is due to enhancement of ROS production, GA biosynthesis, and GA sensitivity, resulting in a higher germination rate under osmotic stress.

On-farm food loss (i.e., grade-out vegetables) is a difficult challenge in sustainable agricultural systems. The simplest method to reduce the number of grade-out vegetables is to monitor and predict the size of all individuals in the vegetable field and determine the optimal harvest date with the smallest grade-out number and highest profit, which is not cost-effective by conventional methods. Here, we developed a full pipeline to accurately estimate and predict every broccoli head size (n > 3,000) automatically and nondestructively using drone remote sensing and image analysis. The individual sizes were fed to the temperature-based growth model and predicted the optimal harvesting date. Two years of field experiments revealed that our pipeline successfully estimated and predicted the head size of all broccolis with high accuracy. We also found that a deviation of only 1 to 2 days from the optimal date can considerably increase grade-out and reduce farmer's profits. This is an unequivocal demonstration of the utility of these approaches to economic crop optimization and minimization of food losses.

We report a case of alveolar rhabdomyosarcoma of the bladder which achieved complete response with neoadjuvant chemotherapy and surgery. A 58-year-old man was referred to our hospital due to bladder tumor discovered with urinary frequency and gross hematuria. Pathological diagnosis was alveolar rhabdomyosarcoma arising in the bladder which was an extremely rare type. Because the images showed no metastasis except for the right external iliac lymph node, curative treatment was performed consisting of cystectomy besides neoadjuvant chemotherapy using adriamycin and ifosfamide. No residual tumor was found in the extracted bladder specimen. He has been disease free at 12-month follow-up.

Abstract 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

Recent advances in rice breeding in tropical Asia led to the release of high-yielding drought-tolerant cultivars. Together with the use of these cultivars, improved nutrient management under drought should further increase rice productivity in rainfed lowland ecosystems. The objectives of this study were to evaluate cultivar differences in the responses of plant growth and grain yield to fertilizer application regimes. We compared 13 drought-tolerant rice cultivars with two irrigated rice cultivars under three nutrient management conditions in irrigated and rainfed lowlands in the Philippines during the wet seasons of 2014 and 2015. Drought stress was mild in both years, with a yield reduction of 11 to 12%, and there was no significant cultivar × nutrient management interaction in yield. The drought-tolerant cultivar NSIC Rc282 proved fertilizer-responsive, and had similar yield to those of the popular high-yielding cultivar NSIC Rc222 under all conditions. An ancillary experiment in 2016 confirmed that NSIC Rc282 was more drought-adapted than NSIC Rc222, with 11% to 37% higher yield under stress. In order to maximize the yield, NSIC Rc282 required N application only when the drought ended, whereas NSIC Rc222 required additional N during the drought. This shows that the details of drought-adaptive nutrient management differ between irrigated and drought-tolerant rice cultivars. We suggest that the introduction of high-yielding drought-tolerant rice cultivars will both improve productivity and increase the nutrient-use efficiency in rainfed environments.

Introduction Clear cell papillary renal cell carcinoma often develops in the context of the dialyzed kidney (end‐stage renal disease). However, the relationship between clear cell papillary renal cell carcinoma and microRNA expression in patients with end‐stage renal disease remains unclear. Case presentation A left renal tumor measuring 22 mm was detected and a radical nephrectomy was performed on a 50‐year‐old man who had received hemodialysis for the past 6 years. A pathological diagnosis of pT1aNxMx, clear cell papillary renal cell carcinoma was made. We studied the expression of miR‐155 in this case and compared it to the expression in nondialysis kidney tissue. The expression level of miR‐155 was upregulated in tumor tissue compared with expression levels in the renal cortex for the present case. The expression level of miR‐155 in the renal cortex was lower in the present case than in nondialysis kidney tissues. Conclusion We demonstrated upregulation of miR‐155 in a case of clear cell papillary renal cell carcinoma arising from end‐stage renal disease.

Introduction We report a rare case of renal cell carcinoma with vaginal metastasis that recurred with rapid progression and was resistant to sunitinib and nivolumab. Case presentation A 68‐year‐old woman presented with renal cell carcinoma and vaginal metastasis. Multiple lung metastasis appeared 3 months after simultaneous radical nephrectomy and hysterectomy with vaginal resection. Despite the treatment with sunitinib and nivolumab, the patient died 7 months after surgery. Immunohistochemical staining of primary and metastatic tumor specimens was CD8 and programmed death ligand‐1 negative. Conclusion Although vaginal metastasis of renal cell carcinoma is rare, lack of CD8 and programmed death ligand‐1 expression may cause nivolumab resistance and may be useful markers in patients with metastatic renal cell carcinoma.

Low oxygen concentrations in flooded paddy fields cause poor seedling establishment in wet direct seeded rice. We aimed to identify novel genomic regions associated with coleoptile elongation under anaerobic conditions in order to improve seedling establishment. Chromosome segment substitution lines (CSSLs), substituted with Koshihikari (Japonica-type) in the IR 64 genetic background (Indica-type) were evaluated. These lines were imbibed with a hydroponic solution containing Oxyrase to create a stable anaerobic condition and coleoptile lengths were measured six days after incubation at 30°C. Among the CSSLs, only SL2111 had a significantly longer coleoptile (23.9 mm) than that of IR 64 (14.3 mm). From genotype and phenotype analyses, a novel QTL, referred to as qACE3.1, for coleoptile elongation under anaerobic conditions was detected on chromosome 3. To explore the molecular mechanism of qACE3.1, the expression levels of genes encoding enzymes involved in starch degradation and fermentation were assessed. In SL2111 coleoptiles, the expression levels of pyruvate decarboxylase were significantly higher than in IR 64 coleoptiles whereas those of alcohol dehydrogenase were lower. In contrast, no differences were observed in the expression levels of genes associated with starch degradation. These results imply that qACE3.1 may specifically affect fermentative metabolism. In addition, we evaluated the impact of qACE3.1 on seedling establishment under flooded conditions in a paddy field.

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_view.cgi?recptno = R000041122 ).

Dry direct-seeded rice is widely practiced in drought-prone environments in tropical Asia where mechanized options for crop establishment are in great demand. The objective of this study is to identify the suitable design of a hand tractor-mounted multigrain seed drill under biophysical conditions in the Philippines. The prototype was newly designed and tested under field conditions in three provinces in 2015 and 2016. The results suggested that the prototype with tined furrow openers and an inclined circular seed plate in the hopper for seed metering driven by the ground wheel through the combination of chain and sprocket produced rice grain yield similar to the crop established from broadcasting. Field experiments also confirmed that the seed drill has a capacity of over 2 ha day−1 for rice and over 3 ha day−1 for mung bean, and thus, the prototype appears promising for rainfed lowlands in the Philippines. Abbreviations: BS: broadcast seeding; FS: furrow seeding; IRRI: International Rice Research Institute; MSD: Multigrain seed drill; PhilRice: Philippine Rice Research Institute

Rice technologies that are designed to reduce risks due to climate variations, improve productivity, or overcome labor scarcity are important in tropical Asia. The objective of this study was to evaluate mechanized options for dry direct-seeding of rice in terms of the productivity and production costs in rainfed lowlands. In a series of on-farm research trials over 3 years in Ubon Ratchathani province, Thailand, we compared seeding by seed drills mounted on two-wheel tractors with manual broadcast seeding. Demonstration trials of seed drills and site-specific nutrient management in 2017 with 11 of 26 participating farmers produced 2.50 t ha−1 of grain yield, but unexpected heavy storms forced the other 15 farmers to switch from dry to wet direct-seeding or manual transplanting. The seed drills produced 32% higher grain yield than manual broadcast seeding (3.3 vs. 2.5 t ha−1) in 2014, and 14–24% higher yield (3.3–3.6 vs. 2.9 t ha−1) in 2015. Mechanized seeding enabled seeding rate reduction by 50% in 2014 and by 52–61% in 2015, resulting in lower production costs than with manual seeding. Our results suggest that mechanized dry direct-seeding of rice with improved nutrient management can enhance farmer livelihoods in rainfed environments in northeastern Thailand. This approach can significantly reduce production costs compared with manual transplanting, while maintaining or increasing productivity compared with conventional manual broadcast seeding. Abbreviations: THB: Thai Baht

The increase in the number of tillers of rice significantly affects grain yield. However, this is measured only by the manual counting of emerging tillers, where the most common method is to count by hand touching. This study develops an efficient, non-destructive method for estimating the number of tillers during the vegetative and reproductive stages under flooded conditions. Unlike popular deep-learning-based approaches requiring training data and computational resources, we propose a simple image-processing pipeline following the empirical principles of synchronously emerging leaves and tillers in rice morphogenesis. Field images were taken by an unmanned aerial vehicle at a very low flying height for UAV imaging—1.5 to 3 m above the rice canopy. Subsequently, the proposed image-processing pipeline was used, which includes binarization, skeletonization, and leaf-tip detection, to count the number of long-growing leaves. The tiller number was estimated from the number of long-growing leaves. The estimated tiller number in a 1.1 m × 1.1 m area is significantly correlated with the actual number of tillers, with 60% of hills having an error of less than ±3 tillers. This study demonstrates the potential of the proposed image-sensing-based tiller-counting method to help agronomists with efficient, non-destructive field phenotyping.

Recent advances in unmanned aerial vehicle (UAV) remote sensing and image analysis provide large amounts of plant canopy data, but there is no method to integrate the large imagery datasets with the much smaller manually collected datasets. A simple geographic information system (GIS)-based analysis for a UAV-supported field study (GAUSS) analytical framework was developed to integrate these datasets. It has three steps: developing a model for predicting sample values from UAV imagery, field gridding and trait value prediction, and statistical testing of predicted values. A field cultivation experiment was conducted to examine the effectiveness of the GAUSS framework, using a soybean–wheat crop rotation as the model system Fourteen soybean cultivars and subsequently a single wheat cultivar were grown in the same field. The crop rotation benefits of the soybeans for wheat yield were examined using GAUSS. Combining manually sampled data (n = 143) and pixel-based UAV imagery indices produced a large amount of high-spatial-resolution predicted wheat yields (n = 8,756). Significant differences were detected among soybean cultivars in their effects on wheat yield, and soybean plant traits were associated with the increases. This is the first reported study that links traits of legume plants with rotational benefits to the subsequent crop. Although some limitations and challenges remain, the GAUSS approach can be applied to many types of field-based plant experimentation, and has potential for extensive use in future studies.

This study aimed to identify novel prognostic biomarker for advanced renal cell carcinoma (RCC) patients treated with anti-PD-1 therapy, using quantitative multi-immunofluorescence (IF) analysis of tumor immunity. Twenty-five consecutive patients who had metastatic or unresectable RCC treated with anti-PD-1 therapy were studied. The patients were divided into a responder group (n = 12) and a non-responder group (n = 13). Quantitative multi-IF staining was performed on biopsy or surgical kidney samples using a panel of antibodies. Sections were scanned using a Mantra microscope, and the images were analyzed with inForm™ software. Responders had significantly higher rate of TIM3-positive tumor (100% versus 53.9%, p < 0.01) than non-responders. Multi-IF analysis showed that TIM3 expression on tumor cells was most strongly related to response to anti-PD-1 therapy, while some of the known immune-related prognostic factors in RCC (CD45RO, FOXP3, VEGF, PD-L1, PD-L2, CD163) had no significant association. Patients with TIM3-positive tumor showed significantly longer overall survival (not reached median time versus 6.0 months, p < 0.01) and progression-free survival (18.9 versus 1.1 months, p < 0.01) than those with TIM3-negative tumor. Immunohistochemistry study using samples obtained after anti-PD-1 therapy showed infiltration of CD163 macrophages and release of HMGB1, a ligand of TIM3, in necrotic tumor area. In conclusion, our study found clinical correlation between TIM3 expression on tumor cells and response to anti-PD-1 therapy. Further studies are warranted to verify whether TIM3 expression on tumor cells before systemic therapy predicts the efficacy of anti-PD-1 therapy for RCC in the clinical setting.

The (pro)renin receptor is a multifunctional protein with roles in angiotensin-II-dependent and -independent intracellular cell signaling and roles as an intracellular accessory protein for the vacuolar H+-ATPase, including hormone secretion. While (pro)renin receptor mRNA is widely expressed in various human tissues, localization of (pro)renin receptor protein expression has not yet been systemically determined. Therefore, this study localized (pro)renin receptor protein expression in human organs. Systemic immunohistochemical examination of (pro)renin receptor expression was performed in whole body organs of autopsy cases. (Pro)renin receptor immunostaining was observed in the cytoplasm of cells in almost all human organs. It was observed in thyroid follicular epithelial cells, hepatic cells, pancreatic duct epithelial cells, zona glomerulosa and zona reticularis of the cortex and medulla of the adrenal gland, proximal and distal tubules and collecting ducts of the kidney, cardiomyocytes, and skeletal muscle cells. In the brain, (pro)renin receptor staining was detected in neurons throughout all areas, especially in the medulla oblongata, paraventricular nucleus and supraoptic nucleus of the hypothalamus, cerebrum, granular layer of the hippocampus, Purkinje cell layer of the cerebellum, and the pituitary anterior and posterior lobes. In the anterior lobe of the pituitary gland, all types of anterior pituitary hormone-positive cells showed double staining with (pro)renin receptor. These data showed that (pro)renin receptor protein was expressed in almost all organs of the human body. Its expression pattern was not uniform, and cell-specific expression pattern was observed, supporting the notion that (pro)renin receptor plays numerous physiological roles in each human organ.

We aimed to identify the clinical characteristics related to increased nivolumab exposure in Japanese patients with renal cell carcinoma (RCC) in real-world clinical setting. Eleven patients were treated with the originally approved nivolumab dosing regimen of 3 mg/kg every 2 weeks (Q2W) (3-mg/kg group) and 8 patients with a flat dose of 240 mg Q2W (flat dosing group). Trough concentrations (Cmin) until the fifth cycle were measured by sandwich enzyme-linked immunosorbent assay using anti-nivolumab monoclonal antibody established by the Autonomously Diversifying Library system. Mean Cmin at four cycles of nivolumab were significantly higher in the flat dosing group than in the 3-mg/kg group. In an analysis of covariates related to nivolumab concentration, serum albumin (Alb) was significantly lower in the 3-mg/kg group than in the flat dose group. Cmin correlated significantly with serum Alb at all cycles. In conclusion, serum Alb was a potential clinically relevant covariate for nivolumab pharmacokinetics in Japanese RCC patients. Further studies should verify whether serum Alb affects nivolumab efficacy and toxicity.

The (pro)renin receptor [(P)RR] is a multifunctioning protein playing roles in various pathological conditions. A soluble form of (P)RR [s(P)RR] has been considered a biomarker for (P)RR expression in tissues. Expression of (P)RR has been described in aldosterone-producing adenoma (APA), but the roles of (P)RR have yet to be fully determined. This study investigated the significance of (P)RR and serum s(P)RR concentrations in patients with APA. We evaluated associations between (P)RR expression and expression of CYP11B2, an aldosterone synthase, and aldosterone production by the adrenal glands and assessed the relationships between serum s(P)RR concentration and background factors. (P)RR colocalized with CYP11B2 and expression levels of (P)RR were positively associated with those of CYP11B2 in APA tissues. (P)RR immunoreactivity in these tissues correlated positively with plasma aldosterone concentrations (PAC) and urinary aldosterone excretion. Also, in APA, (P)RR mRNA abundance was positively correlated with β-catenin mRNA abundance. Significant positive correlations were identified between serum s(P)RR concentration and plasma glucose, hemoglobin A1c, and serum creatinine levels, but not with PAC (in either peripheral vein or adrenal vein) or adrenal (P)RR expression level. This study showed that (P)RR expression level correlates with CYP11B2 expression in APA tissues and PAC and urinary aldosterone excretion, suggesting that (P)RR expression may contribute to aldosterone synthesis via CYP11B2 activation in APAs, although serum s(P)RR concentration failed to show any significant relationship with adrenal (P)RR expression. Adrenal (P)RR activity might offer a therapeutic target in the treatment of PA, although this issue needs to be investigated in future studies.

Abstract Purpose We investigated that preoperative membranous urethral length (MUL) would be associated with the recovery of urinary continence after robot-assisted laparoscopic prostatectomy (RALP). Patients and methods We studied 204 patients who underwent RALP between May 2013 and March 2016. All patients underwent pelvic magnetic resonance imaging (MRI) preoperatively to measure MUL. Urinary continence was defined as the use of one pad or less (safety pad). The 204 patients were divided into two groups: continence group, those who achieved recovery of continence at 3, 6, and 12 months after RALP, and incontinence group, those who did not. We retrospectively analyzed the patients in terms of preoperative clinical factors including age, body mass index (BMI), estimated prostate volume, neurovascular bundle salvage, history of preoperative hormonal therapy, and MUL. Results The safety pad use rate was 69.6%, 86.9%, and 91.1% at 3, 6, and 12 months, respectively. On univariate and multivariate analyses, MUL were significant factors in every term of recovery of urinary continence in both groups. According to the receiver operating characteristic (ROC) curve analysis, the preoperative MUL that could best predict early recovery of urinary continence at 3 months after RALP was 12 mm. Conclusions We suggest that preoperative MUL > 12 mm would be a predictor of early recovery of urinary continence after RALP.

Abstract Background Reduced port laparoscopic surgery (RPLS) is comparable to conventional multiport laparoscopic surgery and has the potential to provide improved cosmesis and decreased pain; as such, it satisfies a growing demand for less invasive surgical procedures. Moreover, a zigzag incision of the umbilicus results in a less visible scar in plastic surgery. Here we report a series of two cases with bilateral organ tumors treated by single-stage RPLS using a combination of a transumbilical approach and a zigzag incision. Case presentation Case 1: A 63-year-old man was diagnosed with right renal cell carcinoma (RCC) (clear cell carcinoma, pT1a, venous invasion (−)) and a splenic tumor (cavernous hemangioma). Case 2: An 84-year-old woman was diagnosed with concurrent left RCC (clear cell carcinoma, pT1b, 65 × 65 mm, venous invasion (+)) and ascending colon cancer (adenocarcinoma pT3 with no nodal involvement (0/48)). The perioperative course was uneventful in both cases. However, an additional incision was required in Case 2 for specimen excision. Therefore, the scars were more obvious in Case 2 than in Case 1. Conclusions Although more cases are required to evaluate the superiority of this technique, this novel procedure could be considered for patients with bilateral lesions.

Unmanned aerial vehicle (UAV) and structure from motion (SfM) photogrammetry techniques are widely used for field-based, high-throughput plant phenotyping nowadays, but some of the intermediate processes throughout the workflow remain manual. For example, geographic information system (GIS) software is used to manually assess the 2D/3D field reconstruction quality and cropping region of interests (ROIs) from the whole field. In addition, extracting phenotypic traits from raw UAV images is more competitive than directly from the digital orthomosaic (DOM). Currently, no easy-to-use tools are available to implement previous tasks for commonly used commercial SfM software, such as Pix4D and Agisoft Metashape. Hence, an open source software package called easy intermediate data processor (EasyIDP; MIT license) was developed to decrease the workload in intermediate data processing mentioned above. The functions of the proposed package include (1) an ROI cropping module, assisting in reconstruction quality assessment and cropping ROIs from the whole field, and (2) an ROI reversing module, projecting ROIs to relative raw images. The result showed that both cropping and reversing modules work as expected. Moreover, the effects of ROI height selection and reversed ROI position on raw images to reverse calculation were discussed. This tool shows great potential for decreasing workload in data annotation for machine learning applications.

Background: MicroRNAs (miRNA) are frequently dysregulated in clear cell renal cell carcinoma (ccRCC).Objective: This study aimed to elucidate the role of miRNA expression patterns in renal carcinogenesis and to identify the specific miRNAs that exhibit expression patterns closely associated with patient outcomes.Methods: We examined the expression patterns of selected miRNAs, including miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p, miRNA-210-3p, miRNA-141-3p, miRNA-200c-3p, miRNA-135a-5p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p, in 96 samples of ccRCCs using the TaqMan real-time PCR method. In addition, cluster analysis was performed to stratify expression patterns of multiple miRNAs.Results: In the present study, three distinct subgroups could be clearly stratified in ccRCCs. Subgroup 1 was characterized by upregulation of miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p and miRNA-210-3p. Subgroup 2 was closely associated with downregulation of miRNA-141-3p, miRNA200c-3p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p. Moreover, significant lower expression of miRNA-135a-5p was a distinctive feature of subgroup 3, which was correlated with metachronous metastasis. Among the individual markers in subgroup 3, miRNA-135a-5p was retained in multivariate analysis. The cutoff value of miRNA-135a-5p expression to identify the association of an altered level of miRNA-135a-5p with metachronous metastasis in ccRCCs was determined and showed excellent specificity.Conclusion: We suggest that the expression pattern of the chosen miRNAs is useful to identify renal carcinogenesis and to help identify the association of such expression patterns with metachronous metastasis in ccRCCs. In addition, miRNA-135a-5p was an excellent marker for prediction of metachronous metastasis.

Here we report a case of 57-year-old woman with renal angiomyolipoma associated with tuberous sclerosis complex involving inferior vena cava thrombus. We could perform less invasive nephrectomy with thrombectomy because everolimus administration reduced the inferior vena cava thrombus. To the best of our knowledge, this is the first report the use of everolimus before performing surgery to treat renal angiomyolipoma with inferior vena cava thrombus.

Objectives: Adenocarcinoma is known to be associated with ulcerative colitis, but the diagnosis is sometimes challenging, both clinically and pathologically. Methods and Results: We present a case of extremely well-differentiated adenocarcinoma associated with ulcerative colitis, in which preoperative diagnosis was not possible. Glands in biopsy specimens showed a serrated appearance that looked like low-grade dysplasia or regenerative mucosa. After an operation due to severe symptoms of stenosis, carcinoma was diagnosed. Tumor cells, especially in invasive glands, tended to show stronger immunoreactivity against anti-CK7, TNF-α and Aurora B antibodies compared to cells of mucosal lesion. Interestingly, CD44v6, one of the adhesion molecules, was less expressed in invasive glands, while those glands exhibited stronger expression of a disintegrin and metalloproteinase 17 (ADAM 17), one of the sheddases that cleaves an extracellular domain of CD44. Conclusions: These observations appear interesting to consider the pathogenesis and to diagnose extremely well-differentiated adenocarcinoma in ulcerative colitis, although further investigation is needed.

Aerobic culture is a water-saving technique for direct-seeded rice cultivation. Growing rice under continuously unsaturated soil conditions can maximize water-use efficiency and minimize both labor requirements and greenhouse-gas emissions. Under a temperate climate, aerobic culture can produce a rice yield greater than 9 t ha–1 especially in central Japan (11.4 t ha–1). Aerobic culture using large-scale center-pivot sprinklers is being established in the central United States, where yields can surpass 10 t ha–1. However, yields remain at less than 8 t ha–1 in the tropics. The high yield of Japanese aerobic culture is mainly attributed to vigorous nitrogen uptake during the reproductive stage, which allows rice plants to produce more spikelets and biomass. Fertilizer management for aerobic culture must satisfy both the nitrogen demand and control spikelet density to achieve an appropriate sink–source balance. Unfortunately, the poor development of the root system in rice limits its water uptake from unsaturated soil. Adaptive responses such as adventitious root emergence, lateral root branching, and deep root penetration would protect the plants against dehydration stress in aerobic culture. Intermediate plant height with a few large tillers rather than semi-dwarf stature with profuse tillering should be a suitable plant type for aerobic culture, and plants should show leaf expansion despite fluctuations of soil moisture. The development and identification of suitable genotypes and crop management options are underway worldwide for more resource-use efficient and productive aerobic rice culture.