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Introduction Distant recurrence of non‐muscle invasive bladder cancer is a rare condition that is poorly understood and difficult to detect in follow‐up protocols. Case presentation A 73‐year‐old female with a history of T1N0M0 bladder cancer 8 years ago suffered from a left axillary tumor, a left lung tumor, left mediastinal lymph node swelling, and bilateral adrenal gland tumors. Initially, she was diagnosed with metastatic left breast cancer of the left accessory mamma by needle biopsy of an axillary tumor. Subsequent bronchoscopic biopsy of the mediastinal lymph node revealed metastatic urothelial carcinoma, although no recurrence was detected in the urinary tract. She underwent systemic therapy, and all regions shrank without reprogression. Conclusion Non‐muscle invasive bladder cancer should be managed considering distant metastasis. If the origin of the metastatic lesions is unknown, this disease should be considered as a possible origin, even in the absence of urinary tract recurrence.

Introduction Pelvic arteriovenous malformation is often a source of intraoperative bleeding. Here, we report our experience with a case of ureteral cancer with pelvic arteriovenous malformation treated using laparoscopic nephroureterectomy with temporary intraoperative occlusion of the internal iliac artery. Case presentation A 75‐year‐old man presented to our hospital with asymptomatic macro‐hematuria. Contrast‐enhanced computed tomography revealed right ureteral tumor with no apparent metastases, and right pelvic arteriovenous malformation. Three months later, multiple bladder cancers were identified and the patient underwent trans‐urethral resection of bladder tumor. The pathological diagnosis was urothelial carcinoma, pTa. We performed right laparoscopic nephroureterectomy with temporary intraoperative occlusion of the internal iliac artery. There was little intraoperative bleeding, and the surgery was safely completed. The pathological diagnosis was urothelial carcinoma, pT2 + Tis. Conclusion A patient showing ureteral cancer with pelvic arteriovenous malformation was safely treated using laparoscopic nephroureterectomy with temporary occlusion of the internal iliac artery.

Abstract Wildlife observation is a popular activity, and sightings of rare or difficult‐to‐find animals are often highly desired. However, predicting the sighting probabilities of these animals is a challenge for many observers, and it may only be possible by limited experts with intimate knowledge and skills. To tackle this difficulty, we developed user‐friendly forecast systems of the daily observation probabilities of a rare Arctic seabird (Ross's Gull Rhodostethia rosea) in a coastal area in northern Japan. Using a dataset gathered during 16 successive winters, we applied a machine learning technique of self‐organizing maps and explored how days with gull sightings were related to the meteorological pressure patterns over the Sea of Okhotsk (Method A). We also built a regression model that explains the relationship between gull sightings and local‐scale environmental factors (Method B). We then applied these methods with the operational global numerical weather prediction model (a computer simulation application about the fluid dynamics of Earth's atmosphere) to forecast the daily observation probabilities of our target. Method A demonstrated a strong dependence of gull sightings on the 16 representative weather patterns and forecasted stepwise observation probabilities ranging from 0% to 85.7%. Method B also showed that the strength of the northerly wind and the advancement of the season explained gull sightings and forecasted continuous observation probabilities ranging from 0% to 95.5%. Applying these two methods with the operational global numerical weather prediction model successfully forecasted the varied observation probabilities of Ross's Gull from 1 to 5 days ahead from November to February. A 2‐year follow‐up observation also validated both forecast systems to be effective for successful observation, especially when both systems forecasted higher observation probabilities. The developed forecast systems would therefore allow cost‐effective animal observation and may facilitate a better experience for a variety of wildlife observers.

Abstract Together with rapid Arctic warming and sea ice decline, especially over the Barents–Kara seas (BKS), extreme cold winters have occurred frequently in mid-latitudes, particularly in Central Eurasia. A pattern with two distinct winter temperature anomalies centered over the BKS and Central Eurasia is known as the Warm Arctic–Cold Eurasia (WACE) pattern. The impacts of sea ice loss over the BKS and internal atmospheric variability on past WACE formation remain under discussion mainly due to the large internal atmospheric variability in the mid-latitudes. This study analyzed a large-ensemble historical experiment prescribing observed sea ice condition to investigate the role of internal atmospheric variability in the observed interannual variation of the WACE pattern. Comparison of ensemble members suggests that internal atmospheric variability is important for regulating the magnitude of the WACE pattern. Besides the strong effect of local sea ice loss, winter temperature over the BKS increases due to warm advection driven by the Ural blocking and positive phase of the North Atlantic Oscillation. A decrease in winter temperature over Central Eurasia is mainly attributable to the cold advection enhanced by Ural blocking rather than the remote effect of sea ice decline over the BKS. Our study reveals the importance of internal atmospheric variability in elucidating the observed interannual variation of the WACE pattern.

Abstract The responses of the East Asian summer monsoon (EASM) to the Indian summer monsoon (ISM) have been the subject of extensive investigation. Nevertheless, it remains uncertain whether the ISM can serve as a predictor for the EASM. Here, on the basis of both observations and a large-ensemble climate model experiment, we show that the subseasonal variability of abnormal diabatic heating over India enhances precipitation over central East China, the Korean Peninsula, and southern Japan in June. ISM heating triggers Rossby wave propagation along the subtropical jet, promoting southerly winds over East Asia. The southerly winds helps steer anomalous mid-tropospheric warm advection and lower-tropospheric moisture advection toward East Asia, providing conditions preferential for rainband formation. Cluster analysis shows that, depending on jet structures, ISM heating can serve as a trigger as well as a reinforcer of the rainband.

Glycosphingolipids (GSLs), mainly located in the cell membrane, play various roles in cancer cell function. GSLs have potential as renal cell carcinoma (RCC) biomarkers; however, their analysis in body fluids is challenging because of the complexity of numerous glycans and ceramides. Therefore, we applied wide-targeted lipidomics using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with selected reaction monitoring (SRM) based on theoretical mass to perform a comprehensive measurement of GSLs and evaluate their potency as urinary biomarkers. In semi-quantitative lipidomics, 240 SRM transitions were set based on the reported/speculated structures. We verified the feasibility of measuring GSLs in cells and medium and found that disialosyl globopentaosylceramide (DSGb5 (d18:1/16:0)) increased GSL in the ACHN medium. LC–MS/MS analysis of urine samples from clear cell RCC (ccRCC) patients and healthy controls showed a significant increase in the peak intensity of urinary DSGb5 (d18:1/16:0) in the ccRCC group compared with that in the control group. Receiver operating characteristic analysis indicated that urinary DSGb5 could serve as a sensitive and specific marker for RCC screening, with an AUC of 0.89. This study demonstrated the possibility of urinary screening using DSGb5 (d18:1/16:0). In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients.

Tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of advanced renal cell carcinoma (RCC). However, there is a lack of useful biomarkers for assessing treatment efficacy. Through urinary metabolite analysis, we identified the metabolites and pathways involved in TKI resistance and elucidated the mechanism of TKI resistance. To verify the involvement of the identified metabolites obtained from urine metabolite analysis, we established sunitinib-resistant RCC cells and elucidated the antitumor effects of controlling the identified metabolic pathways in sunitinib-resistant RCC cells. Through the analysis of VEGFR signaling, we aimed to explore the mechanisms underlying the antitumor effects of metabolic control. Glutamine metabolism has emerged as a significant pathway in urinary metabolite analyses. In vitro and in vivo studies have revealed the antitumor effects of sunitinib-resistant RCC cells via knockdown of glutamine transporters. Furthermore, this antitumor effect is mediated by the control of VEGFR signaling via PTEN. Our findings highlight the involvement of glutamine metabolism in the prognosis and sunitinib resistance in patients with advanced RCC. Additionally, the regulating glutamine metabolism resulted in antitumor effects through sunitinib re-sensitivity in sunitinib-resistant RCC. Our results are expected to contribute to the more effective utilization of TKIs with further improvements in prognosis through current drug therapies.

Abstract Rapid Arctic warming has altered the regional hydrological cycle through reduction in Arctic sea ice. Observational and modeling efforts provided evidence that the enhanced evaporation from the Arctic Ocean could increase snowfall over high latitude terrestrial zones. However, questions remain regarding the amount of equatorward moisture transport and its change over the decadal timescale. Here we show that the transport of atmospheric moisture to Siberia that originated from Arctic Ocean evaporation has increased significantly in autumn to early winter during 1981–2019 when substantial sea ice retreat was observed. The enhanced Arctic moisture content is found in western Siberia in September, consistent with the observed increase in snow cover investigated in earlier studies. Meanwhile, the annual maximum daily amount of Arctic moisture shows a sharp increase in eastern Siberia during October–December associated with cyclonic activities along coastal regions. Our results suggest the importance of monitoring equatorward moisture transport during snow accumulation seasons because it could enhance local snowstorms as evaporation from the Arctic Ocean increases in the near future.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Increasing food loss and waste (FLW) is a global problem, and efforts are being made to use waste food as potential livestock feed material. The amount of self-supplied feed is lower in Japan than in other countries, and the government recommends FLW use for animal feed. Sake (Japanese rice wine) is a traditional alcoholic beverage. During the sake manufacturing process, large amounts of squeezed solids or “lees” (sake lees) are generated. Sake lees are nutritious and functional, but are prone to spoilage. In this study, we investigated whether sake lees should be mixed with animal feed immediately or after drying. To assess the usefulness of sake lees as a poultry feed ingredient and determine the effect of sake lees on intestinal immunity, we performed a feeding trial with three treatments: a raw sake lees (RSL) diet, dried sake lees (DSL) diet, and control diet. Three-week-old broilers were fed these diets (n＝8 per group) for two weeks. We then calculated feed efficiency and performed RT-qPCR to assess the effects of diet on intestinal immunity. The growth performance in the RSL diet group was equivalent to that in the control diet group. The DSL diet became difficult for broilers to eat, resulting in decreased growth performance. In the ileum of RSL-diet broilers, the mRNA expression levels of TGF-β1 and avian β-defensin (AvBD)12 were significantly increased compared to those of control diet broilers (p

Abstract The role of the diurnal atmospheric circulation cycle around the eastern Indian subcontinent, leeward of the monsoon westerlies, on the hydroclimate of South Asia remains unknown. Here, we reveal that low‐level moist southerlies are greatly enhanced at night parallel to the coastline over the western Bay of Bengal (BoB), and then flow onto the Gangetic Plain enhancing onshore moisture flux and nocturnal precipitation over the Himalayas and the Meghalaya Plateau. This nocturnal surge is strongly controlled by the diurnal cycle of dynamic and thermodynamic effects around the subcontinent. At night, nocturnal westerly low‐level jets appear over the subcontinent. Strong low‐level southwesterly flow with a low‐level jet structure also appears parallel to the coastline over the western BoB, extending from the west of Sri Lanka. The low‐level westerlies from the subcontinent and the low‐level southwesterlies merge into a single strong southwesterly flow, forming the low‐level moist surge.

Abstract The intensity of extreme precipitation has been projected to increase with increasing air temperature according to the thermodynamic Clausius–Clapeyron (C-C) relation. Over the last decade, observational studies have succeeded in demonstrating the scaling relationship between extreme precipitation and temperature to understand the projected changes. In mid-latitude coastal regions, intense precipitation is strongly influenced by synoptic patterns and a particular characteristic is the long-lasting heavy precipitation driven by abundant moisture transport. However, the effect of synoptic patterns on the scaling relationship remains unclear. Here we conduct an event-based analysis using long-term historical records in Japan, to distinguish extreme precipitation arising from different synoptic patterns. We find that event peak intensity increases more sharply in persistent precipitation events, which lasted more than 10 h, sustained by atmospheric river-like circulation patterns. The long duration-accumulated precipitation extremes also increase with temperature at a rate considerably above the C-C rate at higher temperatures. Our result suggests that long-lasting precipitation events respond more to warming compared with short-duration events. This greatly increases the risks of future floods and landslides in the mid-latitude coastal regions.

In the original publication [...]

Abstract The cellulose δ18O of plant tissues in peat is a potential climate proxy. However, understanding what is driving the shifts in δ18O of cellulose is required for its application. Here, we analyzed the δ18O values of Sphagnum and vascular plant cellulose, as well as the δ18O and δD values of pore water, in a 4‐m‐long peat core from the Bekanbeushi ombrotrophic bog to understand paleoclimatic changes in northern Japan over the past 2,000 years. The cellulose δ18O values of Sphagnum were lower than those of vascular plant tissues, although both draw water from the same layer. Whereas the cellulose δ18O values of Sphagnum more directly reflect those of precipitation, those of vascular plants become enriched through transpiration. Thus, the difference between vascular plants and Sphagnum (Δδ18Ovp–sp) is a potential proxy for relative humidity. Cellulose δ18O of Sphagnum revealed centennial variations with maxima around 800, 1300, and 1500 CE and minima around 500, 1000, 1700, and 1900 CE. The Δδ18Ovp–sp was inversely correlated with Sphagnum cellulose δ18O, indicating that the axis of summer westerlies was more frequently located to the north and the climate was moist in the former periods, whereas the axis of summer westerlies was generally located to the south and the climate was dry in the latter periods. These results suggest a warm and moist climate during the former periods due to frequent rainy summers driven by strong East Asian summer monsoon activity, and the opposite conditions in the latter periods.

The connection between Arctic sea ice loss and mid-latitude cooling in Eurasia has been widely debated. Here, model experiments reveal that the persistence of sea ice loss-related snow and soil temperature anomalies in Eurasia may lead to further cooling in the following winters.

Abstract In summer 2002, abnormally high-temperature events and associated low soil moisture conditions were observed in Northeast Eurasia. In this study, two regional climate model experiments, one with and the other without soil moisture–atmosphere interaction, were conducted to investigate the role of soil moisture in surface air temperature and precipitation in Northeast Eurasia utilizing the Weather Research and Forecasting (WRF) model. In the experiment without interaction, satellite-based soil moisture was prescribed. Under the persistent mid-tropospheric ridge pattern with prolonged clear skies, both experiments captured the magnitude of the extreme surface air temperature events. A comparison of the model experiments demonstrated that the mid-tropospheric ridge pattern was intensified by dry soil moisture conditions that further increase the surface air temperature. The temporal variability of surface air temperature for the experiments with and without soil moisture–atmosphere interaction reveals the strong coupling of soil moisture to surface air temperature in June–August, raising the possibility that extreme hot temperature events in Northeast Eurasia were strengthened by the soil moisture anomaly. These results also indicate that the impact of soil moisture–atmosphere coupling on surface air temperature varies spatially and temporally, having higher importance for the predictability of extreme high-temperature events in Northeast Eurasia during mid-summer. This also suggests that the performance of the land surface model in simulating appropriate land–atmosphere coupling intensity is a key to evaluating the impact of climate change on extreme heat events in this region.

The coastal area of Bangladesh is highly vulnerable to extreme sea levels because of high population exposure in the low-lying deltaic coast. Since the area lies in the monsoon region, abundant precipitation and the resultant increase in river discharge have raised a flood risk for the coastal area. Although the effects of atmospheric forces have been investigated intensively, the influence of precipitation on extreme sea levels in this area remains unknown. In this study, the influence of precipitation on extreme sea levels for three different stations were investigated by multivariate regression using the meteorological drivers of precipitation, sea level pressure, and wind. The prediction of sea levels considering precipitation effects outperformed predictions without precipitation. The benefit of incorporating precipitation was greater at Cox’s Bazar than at Charchanga and Khepupara, reflecting the hilly landscape at Cox’s Bazar. The improved prediction skill was mainly confirmed during the monsoon season, when strong precipitation events occur. It was also revealed that the precipitation over the Bangladesh area is insensitive to the El Niño-Southern Oscillation and Indian Ocean Dipole mode. The precipitation over northern Bangladesh tended to be high in the year of a high sea surface temperature over the Bay of Bengal, which may have contributed to the variation in sea level. The findings suggest that the effect of precipitation plays an essential role in enhancing sea levels during many extreme events. Therefore, incorporating the effect of terrestrial precipitation is essential for the better prediction of extreme sea levels, which helps coastal management and reduction of hazards.

Abstract Extremely heavy precipitation affects human society and the natural environment, and its behaviour under a warming climate needs to be elucidated. Recent studies have demonstrated that observed extreme precipitation increases with surface air temperature (SAT) at approximately the Clausius–Clapeyron (CC) rate, suggesting that atmospheric water vapour content can explain the relationship between extreme precipitation and SAT. However, the relationship between atmospheric water vapour content and SAT is poorly understood due to the lack of reliable observations with sufficient spatial and temporal coverage for statistical analyses. Here, we analyse the relationship between atmospheric water vapour content and SAT using precipitable water vapour (PWV) derived from global positioning system satellites. A super-CC rate appears in hourly PWV when the SAT is below 16 °C, whereas the rate decreases at high SAT, which is different from the precipitation-SAT relationship. The effects of upper air temperature and water vapour can consistently explain the super-CC rate of PWV relative to SAT. The difference between moist and dry adiabatic lapse rates increases with SAT, in consequence of more ability to hold water vapour in the free atmosphere under higher SAT conditions; therefore, attainable PWV increases more rapidly than the CC rate as SAT increases.

Wind energy development has been limited by concerns associated to the varying features in wind speed which tends to destabilize the power system. This study aims to clarify the variability of winds within a day in the Philippines, specifically the hourly changes of onshore horizontal winds at 100-m hub-heights. A whole one-year experiment using the Weather Research and Forecasting model shows that onshore wind speeds decrease during the transitional hours between land breeze and sea breeze. The decreases in wind speed are most significant over coastal regions with high sloping topography. The extreme decreases in wind speed during morning hours, due to the natural processes, are found to often occur at the same time as the extreme electricity undersupply caused by the morning increase in energy demand. This result warns that the power system stability in the Philippines may become more sensitive to the variability of wind as the share of wind energy generation increases in the future. The findings of this study can contribute to promote sustainability in the operation of existing wind-reliant power systems and planning of future wind energy developments.

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells.

We report a histologically pure stage 1 seminoma with an elevated human chorionic gonadotropin (hCG). A 38 year-old man was referred for the evaluation of the left testicular swelling. He showed an elevated serum hCG level of 25,265 mIU/ml with normal a fetoprotein and lactate dehydrogenase. Imaging showed heterogeneous tumor without any metastatic lesions. We conducted 4 courses of chemotherapy before detecting hCG nadir. The final pathological report showed pure seminoma with syncytiotrophoblastic cells but no choriocarcinoma components. The patient remains disease free until present time. The case raised several questions regarding diagnosis and treatment strategy for bulky testicular seminoma.

It has recently been proposed that microrefugia played an important role in species survival during past climate change events. However, the current distributions of microrefugia remain largely unknown. Wind-hole sites are areas affected by preferential flows of cool air generated in interstitial spaces created by rock fragments or colluvia. Alpine plant species occurring in lowland wind-hole sites isolated from alpine zones may be relicts of the last glacial period. Hokkaido, northern Japan, is known to contain many wind-hole sites in which alpine plant species can occur. Here we surveyed 55 wind-hole sites in the Kitami region, eastern Hokkaido, and observed two alpine plant species (lingonberry, Vaccinium vitis-idaea, and Labrador tea, Rhododendron groenlandicum ssp. diversipilosum var. diversipilosum) in 14 wind-hole sites. Statistical modeling showed that wind-hole sites are likely to occur in areas with high maximum slope angles and volcanic rock cover, and concave surfaces. Our predictions of wind-hole site distributions suggest that such topographic conditions are common in our study area, and that many undiscovered wind-hole sites exist. Ignoring microhabitats may greatly underestimate species distributions in topographically complex regions, and dispersed cool spots may also function as stepping stones and temporal habitats for cold-adapted species. Because these localized unique habitats usually occur in economically unproductive sites, identifying and protecting potential microrefugia (cool spots) would be a robust and cost-effective mitigation of climate change impacts.