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Validation of navigator-assisted hypofractionation (NAVAH) program surveys in African-American prostate cancer patients.

313 Background: Prostate cancer is a leading cause of malignancy and death in men. African-Americans have the highest overall cancer death rate and shortest survival time of any racial or ethnic group in the United States, with African-American prostate cancer patients having a morality rate 80% higher than White patients. The disparities in access to radiation therapy (RT), mortality rates, and treatment outcomes among African-American prostate cancer patients compared to other populations highlight the urgent need for targeted interventions. The Navigator-Assisted Hypofractionation (NAVAH) program, with its innovative patient navigation approach and culturally sensitive survey, aims to better identify the specific barriers faced by African-American patients with prostate cancer. This study is a report of the NAVAH program experience piloting a culturally sensitive survey in African -American prostate cancer patients. Methods: African-American patients with established prostate cancer having seen a Radiation Oncologist and consented to receive RT were recruited to participate in our ongoing Phase I trial (clinicaltrials.gov, NCT05978232); those enrolling on trial were administered surveys prior to receipt of RT. Survey information was assessed by topic category and survey responses were combined into a representative score for each category (outstanding, excellent, good, average, below average). Survey categories include availability (access to a medical center, coordinating care, and overall quality of care), accessibility (transportation, distance to care, and healthcare literacy), affordability (financial considerations, employment, and level of education), accommodation (access to internet, navigating transportation), acceptability (comfort and prejudice among interactions with the system), and cancer screening/cancer treatment. Results: Mean scores noted good availability (32 responses), excellent accessibility (20 responses), excellent affordability (22 responses), excellent accommodation (18 responses), average acceptability (44 responses), and average cancer screening/cancer treatment (40 responses). Patients noted neutral to positive interactions with doctors and nurses, but distrust of following the advice given to them at hospitals, and that the time interval from their first abnormal test to being informed of a cancer diagnosis was too long. Conclusions: Our findings indicate that this novel survey design is feasible in the African-American prostate cancer population. As more patients enroll in our ongoing Phase I trial, implementation of this survey will provide more definitive and comprehensive answers regarding additional topics, including financial challenges during treatment, access to accommodations, and perception of treatment during cancer care.

Impact of renal cell cancer histology on outcomes of microscopic positive surgical margins and implications on post-surgical follow-up.

519 Background: Positive surgical margins (PSM) are associated with worsened survival outcomes in Renal Cell Carcinoma (RCC). Current AUA guidelines recommend intensified post-surgical follow-up and clinical vigilance in patients with PSM. We sought to evaluate outcomes of different RCC-histologies with microscopic-PSM. Methods: We performed a retrospective analysis of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for RCC who had microscopic-PSM. The cohort was divided according to RCC-Histology [Chromophobe-RCC (chRCC); Clear Cell-RCC (ccRCC); Papillary-RCC (pRCC) for descriptive and survival analyses. Primary outcome was all-cause mortality (ACM)/overall survival (OS). Secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Cox proportional hazards multivariable analysis (MVA) was used to elucidate predictive factors for ACM and CSM. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year OSS and CSS. Results: A total of 8100 patients were analyzed, and we identified 312 patients with microscopic-PSM [26 (8.3%), 236 (75.6%), and 50 (16.0%) of patients had chRCC, ccRCC, and pRCC respectively]. Cox-regression revealed ccRCC to be associated with worsened ACM (versus chRCC [referent] HR=7.8, p=0.042), and worsened CSM (versus chRCC [referent] HR=2.97, p=0.033); pRCC did not demonstrate worsened ACM (p=0.148) and CSM (p=0.201). Comparing chRCC, ccRCC, and pRCC, KMA revealed a 5-year OS of 91%, 87%, and 63%, (p=0.024) and 5-year CSS of 93%, 86%, and 65%. KMA comparing microscopic-PSM versus negative surgical margins (NSM) noted no significant difference in 5-year OS for chRCC (85% vs. 86%, p=0.365) or pRCC (80% vs. 84%, p=0.952), but significantly lower 5-year OS in microscopic-PSM in ccRCC (77% vs. 85%, p<0.001). Conclusions: In patients with microscopic-PSM, we noted significant differences according to histology, with ccRCC being associated with significantly worsened survival and mortality outcomes when compared to chRCC and pRCC; microscopic-PSM was also associated with significantly worsened survival compared to NSM in ccRCC, but not chRCC and pRCC. Microscopic-PSM can be considered to represent a higher risk subgroup in ccRCC but not chRCC or pRCC. Intensified post-surgical follow up compared to NSM patient is appropriate in ccRCC, while microscopic-PSM in chRCC and pRCC can be followed similarly to NSM patients with the same histology.

Li-ion storage characteristics and migration mechanisms of intrinsic, doped, and oxygen-deficient CeO2 and La2O3: A study using DFT+<i>U</i>

Rare-earth oxides (REOs) represented by CeO2 and La2O3 became a focal point in the study of Li-ion battery (LIB) electrode materials. However, leveraging defects to tune the intrinsic electronic structure of REO to enhance electrochemical performance, as well as understanding the underlying physical mechanisms at the atomic level, remained an open challenge. Density functional theory plus U calculations revealed that doping and oxygen vacancies not only regulated Li-ion insertion stability but also reduced the migration energy barriers in CeO2. Doping also decreased the volume change rate of CeO2 during Li-ion insertion. Oxygen vacancies lowered the Li-ion migration energy barrier in CeO2 from 1.516 to 0.903 eV. In comparison, Li-ion migration energy barriers in the La2O3 series structures were significantly lower than those in CeO2. Experimental results confirmed that the Li-ion diffusion coefficient of La2O3 was markedly higher than that of CeO2. Upon Li-ion insertion, the bandgap of CeO2 decreased from 2.18 to 1.60 eV, and density of states analysis revealed the profound impact of lithiation on the electronic structure. This comprehensive study enhances the understanding of the application potential of these typical rare-earth oxide materials in LIBs.

The effects of flight training on flying cadets’ brain structure

In recent years, the impact of professional training on brain structure has sparked extensive research interest. Research into pilots as a high-demand, high-load, and high-cost occupation holds significant academic and economic value. The aim of this study is to investigate the effects of flight training on the brain structure and cognitive functions of flying cadets. The structural magnetic resonance imaging (sMRI) data from 39 flying cadets and 37 general college students underwent analysis using voxel-based morphometry (VBM) and surface-based morphometry (SBM) methods to quantitatively detect and compute multiple indicators, including gray matter volume (GMV), curvature, mean curvature of the white matter surface (MC-WMS), the percentage of surface white matter gray matter (WM-GM percentage), surface Jacobi (S-Jacobi), and Gaussian curvature of white matter surface (GC-WMS). At the voxel level, the GMV in the left temporal pole: middle temporal gyrus region of flying cadets significantly decreased (Gaussian random field, GRF, P &lt; 0.05). At the surface level, there was a significant increase in curvature, MC-WMS, and S-Jacobi in the lateral occipital region of flight cadets (Monte Carlo block level correction, MCBLC, P&lt;0.05), a significant increase in WM-GM percentage in the cuneus region of flight cadets (MCBLC, P&lt;0.05), and a significant increase in GC-WMS in the middle temporal region of flight cadets (MCBLC, P&lt;0.05). In addition, these changes were correlated with behavioral tests. Research suggested that flight training might induce changes in certain brain regions of flying cadets, enabling them to adapt to evolving training content and environments, thereby enhancing their problem-solving and flight abilities. By analyzing multiple indicators at the voxel and surface levels in an integrated manner, it advances our understanding of brain structure, function, and plasticity, while also facilitating a more profound exploration of the neural mechanisms within the pilot’s brain.

Author Correction: Flow prediction in sound-based uroflowmetry

The prognostic impact of prostate-specific antigen at 6 months after post-prostatectomy radiotherapy: An individual patient data analysis of two NRG oncology randomized trials.

254 Background: We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) within 6 months of completion of salvage radiotherapy (RT) in patients treated with RT with or without hormone therapy (HT). Methods: Individual patient data were obtained from 2 randomized trials (NRG’s RTOG 0534 and RTOG 9601) evaluating salvage RT with or without HT. HT was either androgen deprivation therapy (ADT) for 4-6 months or bicalutamide for 2 years. The lowest PSA recorded within 6 months after RT completion was identified and categorized as ≤ or &gt;0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox proportional hazards regression was used to estimate hazard ratio (HR) with 95% confidence intervals to characterize the association of PSA within 6 months post-RT completion with OS and MFS while adjusting for age, Gleason score, trial, and HT use. Five-year MFS and 10-year OS rates were estimated using the Kaplan-Meier method. Results: Among a total of 2,373 patients, 1833 (77%) patients achieved a nadir PSA ≤0.1 and 540 (23%) did not. Among patients who did not get HT, 50% did not reach the milestone compared to only 6% of patients who got HT. PSA ≤0.1 ng/mL was associated with better OS (HR 0.27 [95% CI 0.12-0.6], p=0.001) and better MFS (HR 0.25 [95% CI 0.13-0.47], p&lt;0.0001). The interaction test showed that the improved OS/MFS in patients who achieved the nadir was more prominent in those who did not receive HT compared to those who received HT. Five-year MFS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 94% vs 81%, 92% vs 87%, and 91% vs 93%, respectively, based on PSA ≤ vs &gt;0.1. Ten-year OS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 87% vs 76%, 84% vs 84%, and 82% vs 83%, respectively, based on PSA ≤ vs &gt;0.1. Conclusions: PSA &gt;0.1 ng/mL within 6 months was prognostic for OS and MFS in patients treated with salvage RT in the post-prostatectomy setting. This finding allows better patient counseling and can guide clinical trial design for treatment intensification or de-intensification in patients receiving salvage RT.

Molecular insights of low-PSA–expressing high-risk prostate cancer.

416 Background: Despite advances in molecular genetics and genome sequencing, identifying lethal and non-lethal forms of prostate cancer in the early stages of the disease remains challenging. A significant number of prostate cancer patients have high-risk tumors that produce low levels of prostate-specific antigen (PSA) at the time of diagnosis. There is an indication that the therapeutic outcome of these patients, may be considered unfavorable as they may not respond as well to ADT or androgen receptor pathway inhibitors (ARPI). Consequently, this type of high-risk prostate cancer with low PSA secretion may be associated with a unique subtype of the disease that has not been fully characterized. Methods: From 2013 to 2023, 3,619 patients diagnosed with prostate cancer underwent robotic-assisted radical prostatectomy (RARP) performed by a single experienced surgeon (AKT). The patients were classified into four groups based on their PSA levels: very low (&lt;2.5 ng/ml), low (2.6-5.0 ng/ml), medium (5.1-8.0 ng/ml), and high (&gt;8.0 ng/ml). We conducted an ANOVA analysis to compare various clinical characteristics across these groups. Additionally, we explored the gene expression profiles from the Cancer Genome Atlas (TCGA) prostate cancer cohort, specifically examining differential PSA/KLK3 mRNA expression within cancer cells. Furthermore, we selected and expanded single-cell clones from the LNCaP parental population to investigate the molecular landscape of low PSA expressing prostate tumor cells. Results: We observed that patients with high-risk prostate cancer and a very low PSA level (&lt;2.5 ng/ml) had higher rates of biochemical recurrence compared to those with high-grade cancer but PSA levels (&gt;2.5 ng/ml). Additionally, we noticed a significantly high presence of seminal vesicle (p= 1.058e-05) and neurovascular invasion (p=0.0047) in both the very low and high PSA groups compared to the other two groups. Importantly, the very low PSA group exhibited a higher rate of lymph node invasion (p= 0.00095) compared to the other three groups. Our transcriptomic analysis in the TCGA cohort revealed that genes which are upregulated in the very low PSA group compared to the high PSA group are significantly (p&lt;0.001) enriched in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, our study on LNCaP-derived clones revealed an increased migration potential and elevated expression of mesenchymal markers in LNCaP-PSA Low clones compared to the clones expressing high PSA. Conclusions: Our research identifies a distinct subtype of localized prostate cancer, demonstrating that low-PSA, high-risk prostate cancer is significantly invasive and leads to potentially lethal disease. This highlights the need for further investigation to better understand the biology of this poorly defined but aggressive subtype of localized prostate cancer.

Feasibility of surgical orchiectomy in prostate cancer patients on long term luteinizing hormone-releasing hormone (LHRH) agonist therapy.

265 Background: Androgen deprivation, achieved through surgical or medical castration, is central to metastatic prostate cancer (PCa) treatment. Life-long castration is thought to be critical to the management of patients with metastatic disease. Orchiectomy offers an alternative, more convenient, and cheaper alternative for permanent castration, but is under-utilized, in part due to patient reluctance. We hypothesized that patients on long term medical castration therapy would be willing to accept surgical castration as an alternative to repeated LHRH agonist injections. Methods: Men ≥18 years with metastatic PCa, on LHRH agonists for ≥1 year and ≤2 prior systemic therapies, were eligible. Participants first provided consent for an educational session on orchiectomy, followed by the collection of demographic and disease characteristics. Those providing further consent completed the PROMIS sexual function and satisfaction measures v2.0 and the Hopwood body image surveys, with a urology consult offered. At 6 months, patients completed the same surveys, and those undergoing orchiectomy also completed the decision regret scale. 100 patients agreeing to the educational session were required to provide a 10% confidence interval on an estimated 30-50% of patients undergoing an orchiectomy. Results: Of the 130 patients approached, 101 signed the first consent form (education), 58 signed the second (surveys), and 27 agreed to meet with the urology team. Patients agreeing to the educational session had a median age of 71 years (IQR 65-75), 46% were Black and 48% White, 48% completed college or an advanced degree, 36% had annual income &gt; $80K, 58% were married and 64% received systemic therapy other than LHRH agonists. Fourteen patients underwent bilateral orchiectomy (one subcapsular). No association was found between orchiectomy and race, education, annual income, or marital status. While ~75% of all patients were dissatisfied with their sexual life, the vast majority had no body image concerns. Decision regret was low, with 13/14 patients satisfied with their choice of orchiectomy. Pathology revealed testicular atrophy in all cases. Conclusions: Only 11% of patients approached, and 14% of patients who participated in an educational session on orchiectomy proceeded with the procedure, suggesting limited feasibility for surgical castration in patients on long-term LHRH agonists. Testicular atrophy suggests that discontinuing medical castration may be an alternative cost-effective strategy to maintain castration in prostate cancer patients with metastatic disease. Clinical trial information: NCT04705038 .

Trends and demographic disparities in the preferred place of death for bladder cancer patients in the United States (2000–2020): An analysis from the CDC database.

747 Background: Understanding trends in end-of-life care for bladder cancer patients, particularly their preferred place of death (PPOD), is essential for improving palliative care planning. Despite being a leading cause of mortality in the U.S., there is limited insight into how preferences for end-of-life settings have evolved over time, or how they vary across demographic groups. Identifying these trends can help enhance care quality and address disparities in access to hospice and home-based care. This study aims to provide a comprehensive analysis of PPOD trends for bladder cancer patients from 2000 to 2020. Methods: Data from the CDC WONDER database were used to analyze bladder cancer mortality trends between 2000 and 2020. Deaths were categorized by place of death (home, hospice, medical facility, nursing home), age, race, census region, and year. Descriptive statistics summarized mortality trends, and chi-square tests assessed associations between demographic characteristics and place of death. Logistic regression identified factors associated with hospice utilization, adjusting for age, race, and region. The analysis also examined the impact of the COVID-19 pandemic on end-of-life care in 2020. Results: Between 2000 and 2020, there were 293,906 bladder cancer deaths in the U.S., with the South accounting for the highest proportion (35.6%). Home was the most common place of death (41.6%), followed by medical facilities (24.4%), nursing homes (19.5%), and hospice facilities (9.0%). Significant associations were found between place of death and age, race, and region (p &lt; 0.001). Logistic regression showed younger individuals (under 85) had higher odds of dying in hospice, while Black individuals were less likely to use hospice than White individuals (OR = 0.699, p &lt; 0.001). Hospice utilization increased over time (OR = 1.134 per year, p &lt; 0.001). In 2020, home and hospice deaths increased, with a decline in medical facility deaths, likely due to the COVID-19 pandemic. Conclusions: Hospice care and home-based end-of-life care have become more prominent, though disparities in access persist, particularly among racial and regional groups. These findings highlight the need for more inclusive palliative care strategies to ensure equitable access to compassionate end-of-life care for all patients. Logistic regression results for factors influencing hospice utilization. Variable B S.E. p-value Odds Ratio 35-44 years -18.100 1742.864 0.992 0.000 45-54 years 0.309 0.041 &lt;0.001 1.362 55-64 years 0.291 0.023 &lt;0.001 1.338 65-74 years 0.207 0.018 &lt;0.001 1.230 75-84 years 0.121 0.017 &lt;0.001 1.128 Asian or Pacific Islander -19.165 946.130 0.984 0.000 Black or African American -0.358 0.031 &lt;0.001 0.699 Year (2000-2020) 0.126 0.001 &lt;0.001 1.134

Polarization-insensitive microwave power receiving composite array based on reflection phase gradient metasurfaces

This paper presents a polarization-insensitive microwave power receiving composite metasurface array. The composite array consists of a reflection phase gradient metasurface array and a horizontal omnidirectional antenna, with a central operating frequency of 5.8 GHz. The reflection phase gradient metasurface array elements are insensitive to the polarization of the incident wave and are arranged radially around the array center. This configuration creates a radial reflection phase gradient that efficiently converts incident plane waves of different polarizations into surface waves converging toward the center. The surface wave energy is then extracted by the horizontal omnidirectional antenna and converted into direct current (DC) by a rectifier. Numerical simulations demonstrate that the composite array maintains effective surface wave excitation and propagation toward the center for both circularly polarized and various horizontally polarized plane waves, achieving a plane wave-to-surface wave conversion efficiency of 74.89%. Experimental validation shows that the proposed array achieves a maximum energy collection efficiency of 62.23% and an RF-DC conversion efficiency of 39.96% over a broad frequency range of 5.6–6.0 GHz. This study achieves polarization insensitivity while simultaneously enhancing the operational efficiency of microwave energy receivers. The results offer a valuable design reference for leveraging reflection phase gradient arrays in wireless power transfer applications.

Addressing imbalanced data classification with Cluster-Based Reduced Noise SMOTE

In recent years, the challenge of imbalanced data has become increasingly prominent in machine learning, affecting the performance of classification algorithms. This study proposes a novel data-level oversampling method called Cluster-Based Reduced Noise SMOTE (CRN-SMOTE) to address this issue. CRN-SMOTE combines SMOTE for oversampling minority classes with a novel cluster-based noise reduction technique. In this cluster-based noise reduction approach, it is crucial that samples from each category form one or two clusters, a feature that conventional noise reduction methods do not achieve. The proposed method is evaluated on four imbalanced datasets (ILPD, QSAR, Blood, and Maternal Health Risk) using five metrics: Cohen’s kappa, Matthew’s correlation coefficient (MCC), F1-score, precision, and recall. Results demonstrate that CRN-SMOTE consistently outperformed the state-of-the-art Reduced Noise SMOTE (RN-SMOTE), SMOTE-Tomek Link, and SMOTE-ENN methods across all datasets, with particularly notable improvements observed in the QSAR and Maternal Health Risk datasets, indicating its effectiveness in enhancing imbalanced classification performance. Overall, the experimental findings indicate that CRN-SMOTE outperformed RN-SMOTE in 100% of the cases, achieving average improvements of 6.6% in Kappa, 4.01% in MCC, 1.87% in F1-score, 1.7% in precision, and 2.05% in recall, with setting SMOTE’s neighbors’ number to 5.

Host plant flooding stress in soybeans differentially impacts avirulent and virulent soybean aphid (Aphis glycines) biotypes

Defining subgroups of patients with intermediate risk prostate cancer for whom active surveillance is safe.

393 Background: A number of guideline groups recommend active surveillance (AS) for patients with low risk prostate cancer as well as selected patients with intermediate-risk prostate cancer (IRPC) – these groups are not well defined. Our group has previously shown that some patients with IRPC have high rates of progression to advanced disease. The goal of this study was to determine a subset of patients with IRPC where AS is safe. Methods: This single-institution, phase II study enrolled men with low-risk and selected IRPC patients since 1995. Patients were followed with PSA every 3-6 months, DRE every 6 months with repeat systematic biopsies at 1 year and every 3 years. Since 2013, MRI staging was done every 2 years with targeted and systematic biopsies done for new or growing lesions. Patients were followed until death or withdrawn consent. Time to treatment, metastasis-free survival (MFS), cause-specific survival (CSS) and overall survival were calculated from date of registration biopsy. Results: 1409 men were analyzed with a median follow-up of 11.0 years (range 1.2 – 26.4 years). Median age and PSA at registration biopsy were 67 years and 5.03 ng/ml. 86.4%, 11.8% and 1.7% had GG1, GG2 and GG3 disease. 72.9%, 5.8%, 7.3% and 13.6% had low, GG1 favourable IRPC (FIR), GG2 FIR and unfavourable risk ds (UIR). 996 men had at least one repeat biopsy, 768 reclassified, 604 underwent treatment, 166 had biochemical failure, 64 developed metastases and 41 died of prostate cancer. 10 year MFS was 97.4%. Absolute percentage pattern 4/5 (APP4) at baseline had a sensitivity of 36%, specificity of 86% and AUC of 64% with an optimal cutpoint of &gt;0.30 for predicting MFS. Multivariable analysis (MVA) revealed APP4 (HR 2.86) at baseline and at repeat biopsy (vs baseline) of high risk vs UIR (HR 5.61) and high risk vs GG2 FIR (HR 10.4) were independent predictors of MFS. 10 year CSS was 98.5%. MVA revealed APP4 (&gt;0.7, AUC 67%; HR 3.13) and high risk vs UIR (HR 34.4) were independent predictors of CSS. Conclusions: Patients with GG1 prostate cancer and those with GG2 FIR and APP4 &lt; 0.30 appear to have very low risk of metastases and prostate cancer death and are suitable for active surveillance.

Prognostic value of quantitative PSMA-PET parameters during chemotherapy in prostate cancer.

33 Background: PSMA-PET/CT is increasingly being used to monitor chemotherapy in prostate cancer and shows promise for predicting outcomes and improving response evaluation. This retrospective study aimed to determine the prognostic value of quantitative tumor burden parameters derived from PSMA-PET/CT for overall survival (OS) during taxane-based chemotherapy. Methods: Databases from 6 institutions were screened for patients who underwent[ 68 Ga]Ga-PSMA11-PET and serum PSA measurements at baseline and within three months after last taxane based chemotherapy dose. Tumor segmentation was performed using DeepPSMA software and PSMA-PET whole-body quantitative parameters were obtained: PSMA-positive tumor volume (PSMA-VOL) and maximum/average standardized uptake value (SUV max , SUV mean ). Univariate Cox-regression analyses by hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate association of whole-body quantitative PSMA parameters and PSA levels with OS. Harrell’s concordance index (C-index) was used to determine prognostic accuracy. Optimal cut points were determined by maximizing the log-rank statistic. Results: A total of 128 patients were included, of whom 62/128 (48%) had castration-sensitive prostate cancer and 66/128 (52%) castration-resistant prostate cancer. At baseline, PSMA-VOL numerically reached the highest prognostic value for OS (C-index: 0.88) followed by PSA (C-index: 0.80, p = 0.85), while the percentage change in PSA levels had the highest prognostic value during treatment (C-index: 0.94) significantly higher than percentage change in PSMA-VOL (C-index: 0.85, p = 0.02), (complete data shown in Table 1). Conclusions: Baseline and post-therapeutic PSMA-PET/CT quantitative parameters are prognostic for OS after taxane-based chemotherapy in prostate cancer. Baseline PSMA-VOL had the highest prognostic value for OS, while changes in PSA levels outperformed changes in quantitative PSMA-PET parameters during treatment. Parameter Cut point HR (95% CI) P-value C-index (95% CI) PSMA vol , baseline &gt; 28 ml 5.59 (2.77 – 11.27) &lt; 0.001 0.88 (0.81 – 0.96) SUV mean , baseline &lt; 13.2 2.00 (0.96 – 4.15) 0.06 0.29 (0.13 – 0.45) SUV max , baseline &gt; 71 2.18 (1.23 – 3.86) 0.007 0.69 (0.57 – 0.82) PSA, baseline &gt; 3.9 ng/ml 3.53 (1.75 – 7.13) &lt; 0.001 0.80 (0.69 – 0.92) PSMA vol , relative change &gt; -21 % 4.48 (2.80 – 7.17) &lt; 0.001 0.85 (0.78 – 0.91) SUV max , relative change &gt; -70 % 2.42 (1.50 – 3.82) &lt; 0.001 0.76 (0.67 – 0.86) SUV mean , relative change &gt; -44 % 5.98 (2.57 – 13.88) &lt; 0.001 0.85 (0.73 – 0.98) PSA, relative change &gt; -97 % 7.03 (3.20 – 15.43) &lt; 0.001 0.94 (0.88 – 0.99)

PSA response to Lu177-PSMA-617 in patients experiencing xerostomia and ocular dryness in metastatic castration resistant prostate cancer.

127 Background: Lu177-PSMA-617 (PSMA Lu177) therapy can cause dry mouth and/or eyes, as prostate specific membrane antigen (PSMA) is expressed in salivary and lacrimal glands. We evaluate the PSA response in pts with metastatic castration resistant prostate cancer (mCRPC) receiving PSMA-Lu177 who experienced dry mouth/eyes. Methods: The Indiana University Prostate Cancer database was queried for pts with mCRPC who were treated with PSMA Lu177. Adverse Events were documented throughout the course of treatment. PSA30 and PSA50 response were analyzed among subgroups of patients who had presence/absence of xerostomia and ocular dryness. Comparisons between the groups were based on the Chi Square test, or Fisher’s Exact test, if more appropriate. Results: 144 pts with mCRPC were treated with PSMA Lu177 between November 2022 and October 2024. Included pts received at least 2 doses. Median age was 74 (53, 91). 126 pts had metastatic disease in bone, 80 in pelvic lymph nodes, 27 lungs, 20 liver, and 5 brain. 58 pts had 1 prior ARPI, 86 pts had ≥2 prior ARPI. 28 pts had no prior taxane regimen, 116 had at least 1 prior taxane. 23 pts had prior PARP inhibitor. Median follow-up from start of PSMA Lu177 was 9.77 months (1.38-26.9). 62 (43.1%) pts experienced dry mouth, 15 (10.4%) experienced dry eyes, and 13 (9%) experienced both. 92 (63.9%) pts achieved PSA30 response, and 81 (56.3%) achieved PSA 50 response. Conclusions: Patients with mCRPC treated with PSMA Lu177 who reported dry mouth were more likely to experience PSA responses. Number and % of Pts Achieving PSA30 and PSA50 Response Characteristic (N) PSA30 response, N (%) PSA30 p-value PSA50 response, N (%) PSA50 p-value Dry mouth Present (N=62) Absent (N=82) 49 (79%)43 (52.4%) 0.0010 41 (66.1%)40 (48.8%) 0.0377 Dry eyes Present (N=15) Absent (N=129) 11 (73.3%)81 (62.8%) 0.4211 8 (53.3%)73 (56.6%) 0.8099 Dry eyes and/or dry mouth Present (N=64) Absent (N=80) 51 (79.7%)41 (51.3%) 0.0004 43 (67.2%)38 (47.5%) 0.0180

Relationship of spatial transcriptomic analyses with distance-associated transcriptomic spectrum and morphology-specific signatures of localized prostate cancer.

422 Background: Current clinical management and classification of prostate cancer is dependent upon specimen morphology assessment. Limited studies have focused on identifying and mapping transcriptomic signatures within morphological variants. Additionally, the impact of transcriptomic distance-relationship between benign and tumor glands has yet to be identified. In this analysis, we profiled and derived signature gene sets for morphological variants and assessed the spatial impact of distance from the adjacent tumor areas on surrounding benign tissues. Methods: Four (three African American and one European ancestry) formalin fixed paraffin embedded prostate cancer samples were obtained via radical prostatectomy and underwent the GeoMx DSP workflow with gene expression level counts. The four patients each had different dominant morphologic features on the slide used, with one patient with extensive foamy gland morphology, one with extensive atrophic morphology, one with extensive mucinous morphology, and one with extensive Gleason pattern 5 carcinoma. Other regions of interest (ROIs) were benign (including benign glands, benign stromal) or mixed tumor/benign. Transcriptomic analysis was performed on these ROIs to derive the morphology-specific gene signatures. Additionally, distance-based spectrum of proximity of benign ROIs to tumor ROIs was constructed to identify genes that are significantly associated with distance to the nearest tumor ROI. Results: 96 ROIs from four patients (denoted by the dominant morphological tumor features) were annotated. In total, 95 ROIs and 8,102 genes passed quality control for analyses. A distance-based spectrum analysis revealed that benign ROIs that are closer to tumor ROIs were highly enriched in transcriptomic androgen signature and MYC signature and endothelial or club-like features were enriched in benign ROIs further from tumor ROIs. Moreover, distinct gene set signatures were established for each morphological feature. Conclusions: Benign ROIs closer to the tumor are more tumor-like and enriched in androgen receptor pathways and MYC signatures. We identified transcriptomic differences among the morphological tumor features that demonstrate inter-patient and intra-patient tumor heterogeneity.

Resonant-type multifunctional device using organic piezoelectrics for detecting differential pressure and acceleration

In this study, a multifunctional device was developed using the organic piezoelectric material polyvinylidene fluoride (PVDF) to detect mechanical operations. This device utilizes a mechanism in which the resonance of the element structure is excited and detected using PVDF. This enabled the proposal of a device principle that can allow detection of various physical quantities, such as differential pressure and acceleration. The device can detect low pressures of up to 1.5 kPa with a sensitivity of −0.19 Hz/Pa. Additionally, it can measure acceleration with output linearity and cross-axis sensitivity. This device is advantageous because it can evaluate both pressure and acceleration using a common sensor structure and measurement methods, and it can be manufactured at room temperature using inexpensive materials. It holds potential for applications in the maintenance of various industrial machinery and monitoring of natural disasters.

On the hedge and safe-haven abilities of bitcoin and gold against blue economy and green finance assets during global crises: Evidence from the DCC, ADCC and GO-GARCH models

This paper investigates the diversification, hedging, and safe-haven capabilities of Bitcoin and gold against blue economy and green finance assets using three different MGARCH models (DCC, ADCC, and GO-GARCH) during adverse events such as the COVID-19 health crisis and the 2022 Russia-Ukraine conflict. Blue economy assets, which refer to sectors that sustainably utilize ocean resources, are a key focus alongside green finance assets. The findings reveal that during crises, Bitcoin demonstrates robust safe-haven characteristics, particularly against blue economy assets like BJLE and OCEN. Conversely, gold exhibits pronounced safe-haven properties against specific blue economy and green finance assets such as BJLE and FAN. The GO-GARCH model highlights gold’s strong diversification and safe-haven roles, especially against BJLE. Bitcoin, on the other hand, is more effective as a diversifier for PIO. Moreover, the GO-GARCH model consistently outperforms the DCC and ADCC models in terms of hedging effectiveness, showing that gold is the preferred hedging instrument for GNR and TAN, while Bitcoin is more effective for other blue and green assets. The results underscore the distinct roles of Bitcoin and gold in portfolio management strategies, offering insights for investors navigating market uncertainties in the context of sustainable investments.

Integrated visual and text-based analysis of ophthalmology clinical cases using a large language model

A phase 2, randomized, open-label study of gemcitabine/cisplatin plus cemiplimab (REGN2810, anti-PD-1) with or without fianlimab (REGN3767, anti-LAG-3) for organ preservation in patients with localized muscle-invasive bladder cancer (NeoSTOP-IT).

TPS882 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) remains the standard of care for muscle-invasive bladder cancer (MIBC) – a disease with a median diagnosis age of 73 years old. While curative, RC negatively impacts quality of life and conveys significant rates of morbidity (60%) and mortality (5%), highlighting the need for bladder preservation. Several trials have shown the curative potential of NAC (Grossman, NEJM 2003), immunotherapy (Necchi, JCO 2018), and chemoimmunotherapy (Galsky, Nat Med 2023) (Powles, NEJM 2024) in patients with MIBC. LAG-3 is an immune checkpoint receptor that is highly expressed in exhausted tumor-infiltrating lymphocytes within bladder cancer contributing to increased tumor tolerance and a poor overall prognosis. Fianlimab (anti-LAG-3) in combination with cemiplimab (anti-PD-1) has been previously shown to be both tolerable and effective in patients with solid tumors. Methods: Neo-STOPIT is a phase 2, open-label, randomized trial with continuous Bayesian toxicity monitoring. Eligible patients must have histologically confirmed MIBC (T2-T3 N0 M0). Mixed histology is permitted if there is a urothelial component. Upper tract disease, prior immunotherapy, and/or bladder chemoradiation is not permitted. Patients will undergo maximal transurethral resection of bladder tumor (TURBT) followed by gemcitabine and cisplatin (21 day cycles). Patients will be randomized 2:1 to receive concomitant cemiplimab (350 mg IV q3w) + fianlimab (1600 mg IV q3w) or cemiplimab. Patients will then repeat TURBT and imaging. Patients with clinical complete response (cCR) may defer RC and continue maintenance immunotherapy for 13 more cycles with surveillance urinary cytology/cystoscopy, imaging, and circulating tumor DNA. Patients without a cCR will undergo RC. The primary endpoint of cCR is defined as the absence of: residual tumor on cystoscopy, metastatic disease on cross-sectional imaging, and positive urine cytology. Secondary endpoints include bladder-intact survival, recurrence free survival, overall survival, and safety/tolerability. Translational exploratory endpoints, including organoid establishment, are planned. We will enroll 36 patients (24 patients in C+F arm). We hypothesize that 70% patients in the C+F arm will achieve cCR compared to 43% (historical control). At least 21 patients will give us 80% power for a one-sided Z-test at a significance of 0.05. To ensure patient safety, toxicity will be monitored using the Bayesian method of Thall et. al. The study will be stopped, at any time during the study, if we observe 70% or more probability that the serious treatment-related adverse event rate is &gt;30%. Recruitment will begin January 2025. Clinical trial information: NCT06571708 .