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In patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), preoperative prediction of extraprostatic extension (EPE) can facilitate patient selection for nerve-sparing procedures. Since both multiparametric magnetic resonance imaging (mpMRI) and prostate health index (PHI) have shown promise for the diagnosis and prognostication of PCa, we investigated whether a combination of mpMRI and PHI evaluations can improve the prediction of EPE after RP.Patients diagnosed with PCa and treated with RP were prospectively enrolled between February 2017 and July 2019. Preoperative blood samples were analyzed for PHI (defined as [p2PSA/fPSA] × √tPSA), and mpMRI examinations were performed and interpreted by a single experienced uroradiologist retrospectively. The area under the receiver operating characteristic curve (ROC) was used to determine the performance of mpMRI, PHI, and their combination in predicting EPE after RP.A total of 163 patients were included for analysis. The pathological T stage was T3a or more in 59.5%. Overall staging accuracy of mpMRI for EPE was 72.4% (sensitivity and specificity: 73.2% and 71.2%, respectively). The area under the ROC of the combination of mpMRI and PHI in predicting EPE (0.785) was higher than those of mpMRI alone (0.717; p = 0.0007) and PHI alone (0.722; p = 0.0236). mpMRI showed false-negative non-EPE results in 26 patients (16%), and a PHI threshold of40 could avoid undiagnosed EPE before RP in 21 of these 26 patients.The combination of PHI and mpMRI may better predict the EPE preoperatively, facilitating preoperative counseling and tailoring the need for nerve-sparing RP.

SummaryMetastatic porocarcinomas (PC) have high mortality rates of 70%. PC is extremely rare, accounting for 0.01% of malignant cutaneous neoplasms, precluding the possibility of conducting clinical trials to evaluate treatment. Pathogenesis and clinical management of PC remain largely unknown Surgical resection of localized PC remains the mainstay of treatment. There are no effective agents for unresectable PC. Comprehensive genomic profiling did not yield any actionable genomic aberrations in our patient with metastatic PC.Ex vivodrug testing predicted pazopanib efficacy and treatment elicited remarkable clinicoradiological response. A functional precision medicine approach may be effective for the treatment of rare cancers.

There are limited real-world data to guide the sequencing of targeted therapies in patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to characterize real-world treatment patterns (primarily second line [2L]) after prior vascular endothelial growth factor (VEGF) targeted therapy in an unselected mRCC population from Taiwan between 2013 and 2017. Treatment-related adverse events (TRAEs) and their management were also evaluated (NCT03633579).This retrospective cohort study included patients who had received prior VEGF-targeted therapy and were treated at the National Taiwan University Hospital or the Taipei Veterans General Hospital between June 2013 and December 2017. Outcomes were characterized using descriptive statistics.Overall, 27 patients were included: 22 (81.5%) male; mean standard deviation (SD) age, 63.1 (11.1) years; 18 (66.7%) initiated targeted therapy during the year immediately following mRCC diagnosis. All patients received sunitinib as their first-line (1L) targeted therapy, with a median (range) treatment duration of 10 (1.8-65.8) months. The most common reason for discontinuing 1L sunitinib was disease progression (88.9% of patients). Everolimus was the most common 2L targeted therapy, in 23 patients (85.2%); 4 patients (14.8%) received 2L axitinib. Median (range) duration of 2L therapy was 4.0 (0.1-30.5) months for everolimus and 4.2 (0.5-9.2) months for axitinib. Ten TRAEs were reported among seven patients receiving 2L everolimus: hypertension (n = 5), hand-foot syndrome (n = 2), hyperglycemia (n = 1), renal failure (n = 1), and interstitial pneumonitis (n = 1). The majority (80%) of TRAEs were managed in the outpatient setting. No TRAEs were reported in the axitinib group.Real-world management of patients with mRCC in Taiwan broadly aligned with clinical guidelines and national reimbursement policy at the time of the study. These findings may be a useful reference for assessing the implications of evolving mRCC management approaches in Taiwan.

Figure S1: R1 does not affect contact inhibition during prostate cancer cell proliferation; Figure S2: R1 does not affect cell apoptosis in prostate cancer cells under both steady state and dynamic conditions; Figure S3: R1 promotes prostate cancer cell migration and invasion; Figure S4: R1/c-Myc physical interaction is not required for R1 regulation of c-Myc ubiquitination; Figure S5: R1 does not affect MIZ-1 and p53 protein expression in prostate cancer cells.

Androgen receptor (AR) is the primary oncogenic driver of prostate cancer, including aggressive castration-resistant prostate cancer (CRPC). The molecular mechanisms controlling AR activation in general and AR reactivation in CRPC remain elusive. Here we report that monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines, reciprocally interacts with AR in prostate cancer. MAOA was induced by androgens through direct AR binding to a novel intronic androgen response element of the MAOA gene, which in turn promoted AR transcriptional activity via upregulation of Shh/Gli-YAP1 signaling to enhance nuclear YAP1–AR interactions. Silencing MAOA suppressed AR-mediated prostate cancer development and growth, including CRPC, in mice. MAOA expression was elevated and positively associated with AR and YAP1 in human CRPC. Finally, genetic or pharmacologic targeting of MAOA enhanced the growth-inhibition efficacy of enzalutamide, darolutamide, and apalutamide in both androgen-dependent and CRPC cells. Collectively, these findings identify and characterize an MAOA–AR reciprocal regulatory circuit with coamplified effects in prostate cancer. Moreover, they suggest that cotargeting this complex may be a viable therapeutic strategy to treat prostate cancer and CRPC.Significance:MAOA and AR comprise a positive feedback loop in androgen-dependent and CRPC, providing a mechanistic rationale for combining MAOA inhibition with AR-targeted therapies for prostate cancer treatment.

This file include 11 Supplementary Figures, Supplementary Materials and Methods, and Supplementary References.

Neuroendocrine prostate cancer (NEPC), a lethal subset of prostate cancer, is characterized by loss of AR signaling and resulting resistance to AR-targeted therapy during neuroendocrine transdifferentiation, for which the molecular mechanisms remain unclear. Here, we report that neuropilin 2 (NRP2) is upregulated in both de novo and therapy-induced NEPC, which induces neuroendocrine markers, neuroendocrine cell morphology, and NEPC cell aggressive behavior. NRP2 silencing restricted NEPC tumor xenograft growth. Mechanistically, NRP2 engages in reciprocal crosstalk with AR, where NRP2 is transcriptionally inhibited by AR, and in turn suppresses AR signaling by downregulating the AR transcriptional program and confers resistance to enzalutamide. Moreover, NRP2 physically interacts with VEGFR2 through the intracellular SEA domain to activate STAT3 phosphorylation and subsequently SOX2, thus driving NEPC differentiation and growth. Collectively, these results characterize NRP2 as a driver of NEPC and suggest NRP2 as a potential therapeutic target in NEPC.

Androgen receptor (AR) is the primary oncogenic driver of prostate cancer, including aggressive castration-resistant prostate cancer (CRPC). The molecular mechanisms controlling AR activation in general and AR reactivation in CRPC remain elusive. Here we report that monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines, reciprocally interacts with AR in prostate cancer. MAOA was induced by androgens through direct AR binding to a novel intronic androgen response element of the MAOA gene, which in turn promoted AR transcriptional activity via upregulation of Shh/Gli-YAP1 signaling to enhance nuclear YAP1–AR interactions. Silencing MAOA suppressed AR-mediated prostate cancer development and growth, including CRPC, in mice. MAOA expression was elevated and positively associated with AR and YAP1 in human CRPC. Finally, genetic or pharmacologic targeting of MAOA enhanced the growth-inhibition efficacy of enzalutamide, darolutamide, and apalutamide in both androgen-dependent and CRPC cells. Collectively, these findings identify and characterize an MAOA–AR reciprocal regulatory circuit with coamplified effects in prostate cancer. Moreover, they suggest that cotargeting this complex may be a viable therapeutic strategy to treat prostate cancer and CRPC. Significance: MAOA and AR comprise a positive feedback loop in androgen-dependent and CRPC, providing a mechanistic rationale for combining MAOA inhibition with AR-targeted therapies for prostate cancer treatment.

Background Few prognostic factors have been proposed for patients with locally advanced renal cell carcinoma (RCC). This study aimed to investigate the possible predictive factors for disease-free survival (DFS) after curative surgery for RCC stage T3 or higher. Methods Patients with locally advanced RCC who underwent cure-intended partial or radical nephrectomy, with or without tumor thrombectomy, at our institution from April 1 st , 2005 to October 31 st , 2013 were retrospectively reviewed. Those undergoing cytoreductive nephrectomy were excluded. Preoperative data, including surgical and pathologic characteristics, were assessed for correlation with DFS. Chi-squared tests, multivariate Cox regression analysis, and Kaplan-Meier survival curve analyses were performed to determine potential predictive factors. A P-value less than 0.05 was considered statistically significant. Results A total of 159 patients were included for analysis. One hundred and nineteen (74.8%) patients remained disease-free during follow-up. Disease recurrence was found in 40 (25.2%) patients, and pathological T stage, capsule penetration, Fuhrman grade, thrombocytosis, and elevated serum alkaline phosphatase and γ-glutamyl transpeptidase levels were significantly associated with disease recurrence on univariate analysis. On multivariate analysis, capsule penetration (hazard ratio [HR] = 2.25, p = 0.038, 95% confidence interval [CI] = 1.05–4.85) and Fuhrman grade 3 or 4 (HR = 8.06, p = 0.003, 95% CI = 2.59–25.02) showed significant associations with DFS. Conclusions In patients with locally advanced RCC, capsule penetration and Fuhrman grade were associated with worse DFS after curative surgery. Urologists should closely monitor patients with capsule penetration and high Fuhrman grades, and adjuvant systemic treatments, other than targeted agents, should be considered.

Taiwan is located in a subtropical hot and humid climate, and there are many reasons for the Urban heat island(UHI) effect caused by the rising temperature in the city. For example, radiative heat, heat storage in buildings, and artificial heat dissipation affect microclimate changes to form a vicious cycle, which has a profound impact on climate and high-tempurature.In this study, Taichung City was selected as the study area, and after excluding the high-altitude jurisdictions and suburban areas, the characteristic factors were introduced into the analysis software in each administrative area to obtain effective research results. Previous studies on the relationship between urban climatic characteristics and temperature have been conducted by monitoring networks, building model analysis, and environmental climate simulations, with emphasis on data collection and simulation. Because of the diversity and complexity of the environmental characteristic factors, and the difficulty of predicting the target by the past analysis,this study uses the data collected by detection instruments to analyze data in the form of Decision Trees, which can effectively reduce excessive information collection and enhance the research efficiency and reduce the cost of equipment construction. Among the environmental characteristics, the factors with higher correlation to the target values were selected for data standardization and then analyzed by Artificial Neural Network(ANN)-K Nearest Neighbor(KNN) to achieve the prediction of the target values, in order to meet the expected results of this study.This study is dedicated to the analysis of the causes of UHI formation, and the analysis by Decision Tree research method reveals that the core area of Taichung City is affected by the surface factors of the high temperature area and the surrounding topographic conditions, resulting in microclimate hyperthermia. The results of the study showed that the percentages of the factors that affected the high temperature of the administrative area were as follows: Normalized Difference Vegetation Index (NVDI) was 24%, impervious area was 22%, building area density was 19%, and average building height and surface roughness were 16%. For the future application of the research results, an ANN model can be developed for the prediction of the selected high correlation factors, which can be used as a reference for the subsequent formulation of environmental regulations and the analysis of urban energy saving strategies.

In recent years, climate change and the urban heat island effect have caused extreme heat and thermal discomfort in the city. To adapt to this extreme condition, shading is one of the adaptation strategies. Effective shade can protect people from excessive solar radiation, improve outdoor thermal comfort and encourage people to engage in outdoor activities. Therefore, several countries have developed shading policies including constructing shading devices such as shaded walkways and increasing tree shades. For shading facilities, the orientation and dimensions are key factors affecting thermal comfort beneath them. However, it is rarely discussed in past studies and isn’t particularly specified in the government policies. Therefore, the objective of this research is to understand the relationship between the orientation and dimensions of outdoor shading devices and thermal comfort to provide references for policy-making and design.This research applies the Ladybug tool to calculate the physical equivalent temperature (PET) under various dimensions and orientations of two basic types of outdoor shading devices, the independent and the attached, during summer days. The effect of the dimensions on thermal comfort is evaluated with the effective aspect ratio.The results show that the lower the effective aspect ratio, the higher the average PET and the discomfort rate (the percentage of time with PET over 34℃) during summer days. The discomfort rate can be reduced to less than 5% when the effective ratio of shading devices is above 1.8. The orientation of shading devices also affects PET. For independent shading devices, the average PET and discomfort ratio in the N-S orientation is the highest and the E-W orientation is the lowest, while the attached type is the highest in the west and the lowest in the north. In addition, this study finds regression equations for the average PET of shading devices in summer with the effective aspect ratio as a parameter. Moreover, this study organizes the results into a reference table so users can easily understand the PET discomfort rate of shading devices in different dimensions and orientations.This research provides valuable information for the government to develop shading policies, assist designers to design comfort shading devices, and predicts thermal comfort levels under shading devices in various dimensions and orientation.

High-density development has reduced greenery and water coverage, thus reducing the environment's ability to regulate temperature. Temperatures in urban areas are significantly higher than in suburban areas, resulting in severe heat island effects. The urban heat island intensity in many cities in Taiwan is generally higher than 2.5°C in summer. One of the causes is the poor ventilation of dense buildings. Therefore, the construction of wind corridor systems based on the current urban conditions is an excellent way to improve the quality of heat dissipation.The paper first reviews the definition of a wind corridor system and introduces the existing urban cases. Afterwards, the long-term climate data provided by the National Science and Technology Center for Disaster Reduction and the Taiwan Climate Change Projection Information and Adaptation Knowledge Platform, the High-Density Street-Level Air Temperature Observation Network data from the Building and Climate Laboratory of National Cheng Kung University, and the overlay of Landsat satellite computer visual and cadastral map data are used. The data were combined to investigate the appropriate hierarchical structure of the wind corridor systems in Taichung City.A Natural Wind Corridor is the long-term natural wind trend mapped from the data mentioned above. Then, based on the Natural Wind Corridor, the Urban Wind Corridor System at the height of 2 metres is constructed by the Least-Cost Path (LCP) analysis with roughness length grids. Implementing the Urban Wind Corridor at different scales, such as in urban and local areas, is discussed. We defined that wind passage is facilitated when the roughness length is less than 1 metre, and the path is allowed to deflect in advance when it encounters large areas of high roughness length (over 2 metres). The deflection angle should not exceed 30°. To define the Primary and Secondary Wind Corridor, we calculate the number of high-roughness-length grids that each route passes through. Wind corridors are classified as Type II when the grid amount of the route passing through, which contains greater than 1 metre in roughness length, is between 35% and 50% of the study domain. If this value is less than 35%, the wind corridor is classified as Type I.Besides, the Computational Fluid Dynamics (CFD) simulation was used to verify the effectiveness of the heat mitigation strategies and provide recommendations on implementation methods, such as limiting the minimum site ventilation ratio by area.We found that the LCP analysis has the advantage of being fast and less costly, but it also limits the results, e.g., the exclusive starting wind direction limits the interpretation. We suggest that supplementary conditions can be set for the difference in the nature of upwind and downwind areas.

Taiwan had become an aging society and its population ageing is increasing in recent years. It is estimated that Taiwan will become super-aged society by 2050. In view of demographic shift, raising temperature due to climate change, and elders are more sensitive to weather difference, elderly building is becoming a trend in building market and there are more researches focusing on elderly living environment and thermal comfort lately. Living environment should have good and comfortable space for the health of elderly. However, building design often lacks climate assessment. Previous studies have focused more on indoor spaces and less on outdoor thermal comfort. In this research, a new elderly housing was studied to explored the outdoor design suitable for elderly by analyzing outdoor thermal comfort.The new elderly housing under study is being built in Tainan city, Taiwan for people aged 55 or older, and is estimated to be completed in 2023. This project is supported by Taiwan Bureau of Energy, Ministry of Economic Affairs. Tainan city is located in south of Taiwan and has a hot and humid subtropical climate. The average annual temperature is around 24℃, and the average daytime temperature in July is about 33℃. This study used ENVI-met and Typical Meteorological Year, version 3 (TMY3) to simulate the outdoor thermal comfort. In addition, this study established three temperature and humidity measurement points within a 500m radius of the building site to record long term data, and also monitored microclimate on site during each season, including temperature, humidity, wind speed, wind direction and global radiation. The measured data were compared with the data from the Tainan meteorological station located in the city center, and thereafter the effects of different scenarios on outdoor thermal comfort were analyzed by simulating and comparing the data. The results showed that the temperature trend in the region is close to that of the Tainan meteorological station, but the average temperature is higher than 1-2℃. Physiological Equivalent Temperature (PET) is affected by the shadow of the building, and the result can be improved by 3-4℃ PET by adjusting the configuration. The result of this study suggested that outdoor space configuration should take building shading and climate into account during the design phase, and provide recommendations for outdoor thermal comfort for the elderly. In the future, user surveys could be conducted after the building is completed.

The architectural design is heavily influenced by the base's climatic conditions, such as window opening, daylighting, ventilation, etc.In the past, weather information obtained from the existing climate data may be too far from the base, too wide a range of coverage, or too wide a difference in geographical features, making it difficult to obtain seasonal information.With the increasing degree of urbanization, the heat island effect has intensified, and considering Taiwan's fluctuating terrain, it is even more important to quickly obtain detailed and accurate environmental background information.The TMY3 standard meteorological year data available in Taiwan has been established for only eight out of 23 counties and cities in Taiwan.Taiwan's historical climate reconstruction data (TReAD) based on the Taiwan Climate Change Estimation Information and Adaptive Knowledge Platform (TCCIP) of the Ministry of Science and Technology (MOCT).The historical simulated climate data can show the climatic background of a location to some extent after verification by the present study and the Central Meteorological Administration of Meteorology.Based on the climate background data of the base, this study compares TReAD data to a health examination table: A microclimate health checklist is made to determine the climate background of a base based on the data of various meteorological parameters.A website on Taiwan's Historical Climate Map has also been set up to provide a convenient way for users to access climate information and to use it as a reference for architectural design and urban planning.Furthermore, the site may be expanded to understand the relationships and other applications of the various factors affecting the historical climate.Downscaling, close-knit climate data will help bring in the various stages of the architectural and urban life cycle as background data, such as open windows and airflow simulations.It is hoped that the link between urban and microclimate information can be further enhanced, creating a more pleasant architectural or urban environment, and effectively enhancing green architecture.

Sport has been such a popular issue that draws public concerns regarding the health and the better living quality for many years all over the world. With the unavoidable impacts from global warming and exacerbated extreme weather events, the tougher outdoor thermal condition and the arising heat stress risk were no doubt becoming essential tasks especially for outdoor sport events where many staffs, volunteers, athletes and audiences gathered at an open outdoor venue at the same period of time. For better understanding the thermal environment and thermal comfort especially for outdoor sports, 2021 National Intercollegiate Athletic Games held at Tainan, souther Taiwan, has been selected as the research target. And with the concerns related to the COVID-19 epidemic, the Game has been delayed from May to October, 2021. In this assessment, both Taiwan Climate Change Projection Information and Adaptation Knowledge Platform (TCCIP) Taiwan ReAnalysis Downscaling data (TReAD), and on site real-time environmental monitoring data (Temperature, Relative Humidity, Wind Speed, PM2.5, Sky View Factor), were applied in estimating mPET (modified Physiologically Equivalent Temperature) and WBGT (Wet-bulb Globe Temperature) for members participating the torch relay around Taiwan in April, and the delayed Game in October. In this study, we also collected questionnaires from the staffs, volunteers, athletes and audiences participating the Game for detailed analysis the connection between the environmental condition and physical sensation. The influences of the built environment and the strategies for heat mitigation are also discussed in this study.Keywords: 2021 Taiwan National Intercollegiate Athletic Games; Thermal Comfort; RayMan Pro; TReAD; mPET; WBGT; Thermal Risk Assessment; Hot-Humid Climate.

Urban Heat Island (UHI) is an evident phenomenon in Taiwan, especially the capital Taipei city, owing to the highly developed with numerous high-rise buildings and the basin terrain. Due to the problem above, a method to estimate the thermal stress possibility based on the urban pattern is necessary. In recent years, machine learning and deep learning developed quickly and achieved in many fields like image recognition, machine translation, and predicting environmental characteristics. With the excellent development of machine learning and deep learning, a novel method for estimating the thermal stress possibility was presented in this work. In this study, the average temperature distribution in Taipei at 1 pm in August 2021 was calculated based on the information from measurement points of the high-density street-level air temperature observation network (HiSAN) and the Central Weather Bureau (CWB). And the thermal condition was classified into three classes: the low, medium, and high possibility of thermal stress based on the median, upper quartile, and top 90% of the data. Simultaneously, Taipei city was classified with Local Climate Zone (LCZ) based on the satellite image from Landsat 8. And this study also collected the terrain data to correct the effect of altitude on temperature. The LCZ map and terrain were resampled into 100m spatial resolution for the subsequent work. Artificial Neural Network (ANN) and Deep Neural Network (DNN) were used and compared this work’s performances for estimating the thermal stress possibilities in Taipei city. The LCZ map and terrain data were reshaped as the images with 64 pixels to quantize pattern features within the areas of 800m2 and inputted into the models for training and predicting. Both ANN and DNN models have the same learning rate and training epochs which were 0.001 and 500 epochs. After the training processes of the models, ANN and DNN models were able to estimate the possibility of thermal stress for each area by LCZ map and terrain data. The results of ANN and DNN models proved the feasibility of using algorithms of machine learning and computer vision to assess microclimate conditions. Also, the novel method presented in this work can help estimate the thermal stress possible for the areas without measurement points.

As urbanization expands, the urban heat island (UHI) effect caused by high temperatures is becoming obvious increasingly. Previous researches have shown that urban types and anthropogenic heat emission are the main influencing factors. However, the differences in the types of urban areas lead to different UHI intensity between regions. In this context, more and more studies begin to explore the impact of meteorological data on building energy consumption. The temperature of the air conditioner setting and the time of use account for a large percentage of the total building energy consumption. Cooling degree hours (CDH) is the cumulative value of the temperature difference between the outside air temperature and the base temperature of the cooled room. This study was used the ASHRAE standard cold room temperature of 23°C. Information such as climate data, building morphology, zoning and building electricity collection can be integrated through the Geographic Information System (GIS). This study used existing electricity consumption data and GIS maps to estimate energy consumption information in Taichung, and combine the historical climate reconstruction data of Taiwan from The Taiwan Climate Change Projection and Information Platform Project (TCCIP) to analyze the relationship between urban high temperature and residential energy consumption.The study area is Taichung City, Taiwan, excluding the mountainous areas with low temperature. This study divided Taichung into 500×500 m2 grids, and analyzed the estimated residential energy consumption with climate data. The highest average temperature in Taiwan is in July, so this study collects temperature data for July 2021 in Taichung. According to the analysis, it can calculate the Taichung average temperature from July is between 26-28°C and the average RH is 80-85%. CDH in the suburbs below 80°C -hour. City center CDH is between 105-180°C -hour. After integrating building form and land use with GIS, the average residential energy consumption of the grid was calculated. The average residential energy consumption of Taichung is about 3,000MWh.Get rid of the grid without building and compare the energy consumption of the building, CDH increases as the energy consumption increases. However, when the energy consumption exceeds 4,000 MWh, the CDH approaches 50°C-hour. Based on this result, the energy consumption below 1,000MWh is the slope maximum. The energy consumption between 1,000 MWh and 3,000 MWh is smaller slope value. The slope of energy consumption above 3,000 MWh tends to be nearly 0, revealing that the energy consumption was less affected by the increasing CDH. The results can be used in future urban energy planning to develop regional improvement strategies for areas with higher energy consumption.

Background Lineage plasticity is recognized as a treatment-induced resistance mechanism in prostate cancer (PCa) and contributes to the development of neuroendocrine prostate cancer (NEPC), a lethal variant of castration-resistant prostate cancer (CRPC), that is increasing in the era of second-generation anti-hormonal therapy. At present, there are no effective treatments for NEPC. Conclusions and perspectives Following our long-standing interest in studying RE1-silencing transcription factor (REST), a pivotal repressor of neuroendocrine differentiation (NED), we conducted a siRNA screening targeting 147 REST-repressing long non-coding RNAs (lncRNAs) and identified prostate cancer transcript-neuroendocrine 1 (PCAT-NE1) as a novel lncRNA that induces NED through activating autophagy signaling, crucial for NED of prostate adenocarcinoma cell. Analyses of clinical data and samples indicate that PCAT-NE1 is elevated in NEPC. Through gain- and loss-of-function experiments, we find that PCAT-NE1 promotes NED. Mechanistically, PCAT-NE1 acts as a competing endogenous RNA (ceRNA) that sponge hsa-miR-6889-3p, leading to the up-regulation of autophagy-related gene VPS13A and autophagy activation. These findings provide new insight into lncRNA-mediated mechanism for autophagy activation in NEPC and suggest PCAT-NE1 as a potential diagnostic biomarker and therapeutic target for NEPC.

Background: The first interim analysis of the KEYNOTE-564 study showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery in patients with clear cell renal cell carcinoma at an increased risk of recurrence. The analysis reported here, with an additional 6 months of follow-up, was designed to assess longer-term efficacy and safety of pembrolizumab versus placebo, as well as additional secondary and exploratory endpoints. Methods: In the multicentre, randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-564 trial, adults aged 18 years or older with clear cell renal cell carcinoma with an increased risk of recurrence were enrolled at 213 hospitals and cancer centres in North America, South America, Europe, Asia, and Australia. Eligible participants had an Eastern Cooperative Oncology Group performance status of 0 or 1, had undergone nephrectomy 12 weeks or less before randomisation, and had not received previous systemic therapy for advanced renal cell carcinoma. Participants were randomly assigned (1:1) via central permuted block randomisation (block size of four) to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 17 cycles. Randomisation was stratified by metastatic disease status (M0 vs M1), and the M0 group was further stratified by ECOG performance status and geographical region. All participants and investigators involved in study treatment administration were masked to the treatment group assignment. The primary endpoint was disease-free survival by investigator assessment in the intention-to-treat population (all participants randomly assigned to a treatment). Safety was assessed in the safety population, comprising all participants who received at least one dose of pembrolizumab or placebo. As the primary endpoint was met at the first interim analysis, updated data are reported without p values. This study is ongoing, but no longer recruiting, and is registered with ClinicalTrials.gov, NCT03142334. Findings: Between June 30, 2017, and Sept 20, 2019, 994 participants were assigned to receive pembrolizumab (n=496) or placebo (n=498). Median follow-up, defined as the time from randomisation to data cutoff (June 14, 2021), was 30·1 months (IQR 25·7–36·7). Disease-free survival was better with pembrolizumab compared with placebo (HR 0·63 [95% CI 0·50–0·80]). Median disease-free survival was not reached in either group. The most common all-cause grade 3–4 adverse events were hypertension (in 14 [3%] of 496 participants) and increased alanine aminotransferase (in 11 [2%]) in the pembrolizumab group, and hypertension (in 13 [3%] of 498 participants) in the placebo group. Serious adverse events attributed to study treatment occurred in 59 (12%) participants in the pembrolizumab group and one (

Whether epidural anesthesia and analgesia (EA) is beneficial for postoperative cancer outcomes remains controversial and we conducted this historical cohort study to evaluate the association between EA and long-term outcomes following surgery for renal cell carcinoma (RCC). We collected patients receiving RCC surgery from 2011 to 2017 and followed up them until February 2020. Patient attributes, surgical factors and pathological features were gathered through electronic medical chart review. The association between EA and recurrence-free and overall survival after surgery was evaluated using Cox regression models with inverse probability of treatment weighting (IPTW) to balance the observed covariates. The median follow-up time for the 725 included patients was 50 months (interquartile range: 25.3–66.5) and 145 of them (20%) received perioperative EA. We demonstrated EA use was associated with better recurrence-free survival [IPTW adjusted hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.49–0.83, p < 0.001] and overall survival [IPTW adjusted HR: 0.66, 95% CI: 0.49–0.89, p = 0.006] in patients receiving surgical resection for RCC. More prospective studies are needed to verify this connection between EA and superior cancer outcomes after RCC surgery.

Background: Renal cell carcinoma (RCC) is the most common neoplasm in kidneys, and surgical resection remains the mainstay treatment. Few studies have investigated how the postoperative pain changes over time and what has affected its trajectory. This study aimed to characterize the variations in postoperative pain over time and investigate associated factors after RCC surgery. Methods: This retrospective study was conducted in a single medical center in Taiwan, where maximal pain scores in a numeric rating scale were recorded daily in the first five postoperative days (PODs) after RCC surgery. Latent curve models were developed, using two latent variables, intercept and slope, which represented the baseline pain and rate of pain resolution. These models explain the variations in postoperative pain scores over time. A predictive model for postoperative pain trajectories was also constructed. Results: There were 861 patients with 3850 pain observations included in the analysis. Latent curve analysis identified that female patients and those with advanced cancer (stage III and IV) tended to have increased baseline pain scores (p = 0.028 and 0.012, respectively). Furthermore, patients over 60 years, without PCA use (both p < 0.001), and with more surgical blood loss (p = 0.001) tended to have slower pain resolution. The final predictive model fit the collected data acceptably (RMSEA = 0.06, CFI = 0.95). Conclusion: Latent curve analysis identified influential factors of acute pain trajectories after RCC surgery. This study may also help elucidate the complex relationships between the variations in pain intensity over time and their determinants, and guide personalized pain management after surgery for RCC.

Background This study aimed to evaluate the association of asymptomatic pyuria before ureterorenoscopic lithotripsy (URSL) with postoperative febrile urinary tract infection (UTI). Methods This observational case–control study identified the patients undergoing URSL for ureteral stones between May 2011 and October 2015. The included patients were classified into two groups: the asymptomatic pyuria group (6–50 white blood cells [WBCs]/high-power field [HPF]) and the non-pyuria group (≤ 5 WBCs/HPF). All data were collected by reviewing medical records. Postoperative outcomes were collected in terms of febrile UTI, emergency visits, and stone-free rate. Results A total of 232 patients were included, 101 in the pyuria group, 131 in the non-pyuria group. Two (0.9%) patients developed febrile UTI after URSL and 12 (5.2%) patients visited emergency department for URSL-related symptoms. The overall stone-free rate was 90.9%. There was no significant difference between the pyuria and non-pyuria groups regarding febrile UTI, emergency visits, and stone-free rate. Multivariate analysis revealed that pyuria was neither significantly associated with postoperative febrile UTI (OR = 1.03, 95% CI = 0.06–18.10, P = 0.98), nor with emergency visits (OR = 0.48, 95% CI = 0.13–1.85, P = 0.29). Conclusions Compared to the patients with sterile urine prior to URSL, those with asymptomatic pyuria were not prone to develop febrile UTI after URSL.

Since the early 2000's, much attention has been paid to human thermal assessment in urban outdoor environments in different climatic zones. Some previous studies have argued that an absence of an agreed protocol for outdoor human bio-meteorological research causes complexity in comparing the studies' results for several reasons: An abundance of human thermal indices, a variety of interpretations of bio-meteorological terms, an array of procedures for data collection and a lack of agreed methods in determining thermal comfort ranges and index modifications. This study aims to review strategies and methods for human bio-meteorological research and to examine their suitability for thermal perception assessment. From 2001 to 2021, 254 case studies assessed human thermal perception by investigating in-situ thermal conditions versus subjective thermal perception, relying on protocols such as ASHRAE Standard 55 and EN ISO 10551 that were originally developed for indoor environments. Fifty-four cases determined different ranges for thermal comfort. Although 43 studies tried to modify indices to various climatic zones, only 13 studies modified the nine PET physiological stress categories and 4 studies modified the ten UTCI stress categories). Thus, comparisons between the studies' results become complicated. Our review points to three main reasons for the complexity: first, the 7-point TSV scales, does not always fit the scales of the applied thermal index; second, measurement procedures do not always represent the local climate conditions; third, certain methods for modifying thermal index scale thresholds are not capable of modifying the entire index scale. On the basis of our findings, we suggest a framework for bio-meteorological research, with attention to measurement procedure, appropriate questionnaire design, careful data control and suitable methods to enable modification of thermal indices. This study recommends applying systematic and objective statistical methods like linear regression and discriminant analysis in order to successfully modify the entire index scale.

INTRODUCTION AND OBJECTIVE:Renal artery pseudoaneurysm (RAP) after partial nephrectomy is uncommon but a potential life-threatening complication. The aim of the study is to investigate the incidenc...

INTRODUCTION AND OBJECTIVE:To investigate the additional value of phi in predicting csPCa in Asian men with elevated PSA and MRI prostate performed.METHODS:This is a multicentre evaluation of prosp...

Background There are models to predict pathological outcomes based on established clinical and prostate-specific antigen (PSA)-derived parameters; however, they are not satisfactory. p2PSA and its derived biomarkers have shown promise for the diagnosis and prognosis of prostate cancer (PCa). The aim of this study was to investigate whether p2PSA-derived biomarkers can assist in the prediction of aggressive pathological outcomes after radical prostatectomy (RP). Methods We prospectively enrolled patients who were diagnosed with PCa and treated with RP between February 2017 and December 2018. Preoperative blood samples were analyzed for tPSA, free PSA (fPSA), percentage of fPSA (%fPSA), [-2]proPSA (p2PSA), and percentage of p2PSA (%p2PSA). Prostate health index (PHI) was calculated as (p2PSA/fPSA) × √tPSA. Prostate volume was determined by transrectal ultrasound using the ellipsoid formula, and PHI density was calculated as PHI/prostate volume. The areas under the receiver operating characteristic curve were estimated for various PSA/p2PSA derivatives. Aggressive pathological outcomes measured after RP were defined as pathological T3 or a Gleason score (GS) >6 as determined in RP specimens. Results One hundred and forty-four patients were included for analysis. Postoperative GS was >6 in 86.1% of the patients, and pT stage was T3a or more in 54.2%. Among all PSA- and p2PSA-derived biomarkers, PHI density was the best biomarker to predict aggressive pathological outcomes after RP. The odds ratio of having an aggressive pathological outcome of RP was 8.796 (p = 0.001). In multivariate analysis, adding %fPSA to base model did not improve the accuracy (area under curve), but adding PHI and PHI density to base model improved the accuracy by 2% and 16%, respectively, in predicting pT3 stage or GS ≥ 7. The risk of pT3 stage or GS ≥ 7 was 20.8% for PHI density 1.125 (sensitivity: 74.6% and specificity: 88.9%). Conclusion PHI density may further aid in predicting aggressive pathological outcomes after RP. This biomarker may be useful in preoperative counseling and may have potential in decision making when choosing between definitive treatment and active surveillance of newly diagnosed PCa.