Browse Articles

Prognostic value of neutrophil-to-eosinophil ratio (NER) in patients with metastatic renal-cell carcinoma treated with immunotherapy.

457 Background: Nivolumab, a monoclonal antibody against PD-1, improved clinical outcomes compared to everolimus in metastatic renal cell carcinoma (mRCC) following progression on antiangiogenic therapies. The objective of this cohort analysis was to explore the efficacy and safety of nivolumab in patients with mRCC treated at four Slovak cancer centers in 2016-2024, and to identify a prognostic value of NER. Methods: This study enrolled 149 patients (38 women), median age 62 years, who were treated with nivolumab following progression on at least one tyrosine kinase inhibitor (TKI). Clear-cell RCC (ccRCC) had 132 patients and non-clear-cell histology (non-ccRCC) 17 patients. Fifty-five patients had been previously treated with two lines of systemic therapy. Before nivolumab initiation, 27 patients had performance status ECOG≥2, anemia was present in 102 patients and hypercalcemia in 8 patients, LDH higher than 1.5 times the normal range had 19 patients. The NER was calculated as a ratio of neutrophils and eosinophils determined before nivolumab initiation. The study population was dichotomized by median NER into high (≥35.88) and low ( < 35.88) subgroups. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, with differences analyzed via a log-rank test. Results: At a median follow-up of 43.0 months, 127 patients progressed on nivolumab and 120 died. In this study population, median PFS was 9.7 months (95% CI 6.5–12.2) and median OS was 25.9 months (95% 20.6–32.2). The ORR was 31.5%. Serious immune-related adverse events (irAEs) were observed in 15.4% and the most common irAEs were hepatitis, arthritis, and nephritis. Patients with ECOG≥ 2 had shorter PFS and OS compared to ECOG 0–1 (p < 0.0001, HR 0.20 and p < 0.0001, HR 0.14, respectively), anemia was associated with worse OS (p < 0.0106, HR 0.56) and high LDH with shorter PFS and OS (p < 0.0015, HR 0.45 for PFS and p < 0.0006, HR 0.40 for OS). Patients with high NER versus low NER had declined PFS and OS (p < 0.0210, HR 0.67 and p < 0.0078, HR 0.59, respectively). Multivariate analysis showed the independent prognostic value of ECOG and LDH. Conclusions: This study confirmed that nivolumab represents an effective and safe treatment strategy. The NER determined before nivolumab initiation as the second or third line of systemic therapy has a prognostic value in metastatic RCC patients. Keywords: Metastatic renal-cell carcinoma, nivolumab, efficacy, safety, neutrophil-to-eosinophil ratio.

Intratumoral mature TLSs to predict response to ICI rechallenge in non–clear cell renal cell carcinoma.

450 Background: While immune checkpoint inhibitor (lCl)-based therapy has shown promising efficacy in patients with metastatic non-clear cell renal cell carcinoma (nccRCC) in the first-line setting, the optimal treatment following disease progression remains undefined. We aimed to investigate the efficacy, safety and predictive markers of ICl rechallenge in this population. Methods: Thirty-three patients with metastatic nccRCC who received ICI rechallenge were enrolled. Key outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Whole exome sequencing, bulk RNA sequencing and multiplex immunofluorescence were performed to further explore potential biomarker associated with efficacy of ICI-rechallenge among nccRCC. Results: Following ICI-rechallenge, the cohort demonstrated a median PFS of 11.8 months, an ORR of 16.7% and a DCR of 70%. Among clinicopathological variables, the FH-dRCC subtype was the only factor associated with the potential clinical benefit from ICI-rechallenge. Transcriptomic analysis revealed that an enrichment of B cells and central memory T cells signatures was associated with longer PFS (21.3 vs. 7.9 months). Notably, patients with a higher mature intratumoral tertiary lymphoid structure (m-iTLS) score assessed by mIF showed higher ORR (50% vs. 11%) and longer PFS (28.2 vs. 5.3 months) compared to those with a lower m-iTLS score. In terms of safety, ICI rechallenge was generally well tolerated, with no accumulation, or treatment-related deaths observed. Conclusions: ICI rechallenge may offer favorable clinical benefit and acceptable safety in patients with metastatic nccRCC. Higher density of mature intratumoral TLSs correlated with the efficacy of ICI-rechallenge but warrants further validation.

From pluripotency to species conservation

Dual‐Scale‐Patterned Anion Exchange Membrane With Coupled Interface for Durable Water Electrolysis

ABSTRACT The widespread adoption of anion exchange membrane (AEM) water electrolysis is impeded by rapid performance decay, largely caused by catalyst layer detachment under low catalyst loading conditions. To overcome this, we present a structurally graded AEM design that establishes efficient transport pathways from the molecular level to the membrane/catalyst layer interface. At the bulk transport level, molecular dynamics simulations and experimental validation confirm that the designed polymer matrix, based on the C‐F backbone and flexible cationic side chains, promotes favorable microphase separation. This leads to well‐connected ionic nanochannels that facilitate superior bulk hydroxide conduction. At the membrane/catalyst interface, a biomimetic micro‐nano pattern, inspired by aquatic plants, is engineered onto the membrane surface via an industrially scalable embossing calendaring process. The resulting patterned interface optimizes interfacial contact, enhancing catalyst adhesion and mass transfer. By integrating these two scales of transport, a highly efficient membrane electrode assembly is realized, enabling synergistic management of ions, water, and gas bubbles. The resulting AEM achieves a record‐high hydroxide ion conductivity of 338.2 mS cm −1 at 80°C and exceptional ductility, with elongation of 162.0%, surpassing all previously reported AEMs. More importantly, the water electrolysis demonstrates markedly enhanced operational stability under various conditions.

Engineering Electronic Radial Effects for Fast Li ⁺ Transport in Solid‐State Electrolytes

ABSTRACT Achieving high Li + conductivity, near‐unity transference numbers, and stable interfaces in solid‐state electrolytes remains a major challenge for lithium‐metal batteries. Here we introduce a radial‐effect design principle: relativistic expansion and spin–orbit coupling of 5 d orbitals enhance s–d / p–d hybridization, weaken Li–anion interactions, and lower migration barriers. An entropy‐based descriptor, S d , trained and validated with machine learning across >10,000 oxides, sulfides, and halides captures this effect. Machine‐learning‐guided high‐throughput screening flags monoclinic HfO 2 , whose 5 d 2 radial expansion lowers migration barriers by ∼45% vs Sc 2 O 3 or Y 2 O 3 . Guided by this insight, we employ millisecond flash‐Joule heating to convert HfO 2 into nanosized single crystals, then embed them in a Li‐conductive binder to create sc‐HfO 2 @LCB, whose radial coupling yields interconnected Li + pathways (1.23 mS cm −1 , 30°C; t Li + = 0.82, 25°C) and a 4.8 V electrochemical window. Operando Raman/XANES confirms faster Li + transport. Consequently, 2 Ah LiNi 0.9 Co 0.05 Mn 0.05 O 2 ‖Li pouch cells deliver ∼472 Wh kg −1 (stack‐level), maintain superior rate capability over hundreds of cycles, and survive 150°C hot‐plate tests. These results establish radial‐effect engineering as a sophisticated strategy for high‐performance, thermally resilient solid‐state batteries.

Bacteriocin biophysics: From protein–protein interaction models to navigators of the bacterial cell envelope

Comparative treatment burden of BCG versus sequential gemcitabine and docetaxel for non-muscle-invasive bladder cancer: A time toxicity analysis.

730 Background: BCG shortages have necessitated alternative therapies for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). Sequential intravesical gemcitabine and docetaxel (Gem/Doce) has emerged as a promising alternative. However, the comparative treatment burden and resource utilization between these regimens remains unknown. Time toxicity is the total time that patients spend interacting with the healthcare system, which impacts patient’s quality of life. Herein, we aimed to calculate and compare the cumulative time toxicity of BCG and Gem/Doce. Methods: After IRB approval was obtained, we performed a retrospective analysis of patients with NMIBC treated with BCG or Gem/Doce between 2022 and 2025. Electronic medical records were reviewed to calculate time for intravesical therapy instillations, office visits including cystoscopies, transurethral resection of bladder tumor operations, and emergency department encounters. Time measurements were between facility arrival and discharge. Data was censored at the 5th-95th percentiles to minimize outlier impact. Continuous variables were compared using the Wilcoxon rank-sum test with Hodges–Lehmann estimates. Categorical variables were analyzed using chi-square or Fisher's exact tests. Sensitivity analyses assessed treatment-naïve patients. Results: There were 133 patients, of whom 86 received BCG (65%) and 47 received Gem/Doce (35%). Median age was 73 years for BCG and 74 years for Gem/Doce patients. There were 26% female patients. There were 47% of patients with T1, 28% with Ta and 24% with Tis disease. Sixty-six (77%) of BCG patients had treatment-naïve disease compared to 26 (55%) Gem/Doce patients (p = 0.016). The median time per instillation was 179 minutes for BCG compared to 192 minutes for Gem/Doce (Hodges-Lehmann shift +27 minutes, CI 4-57; p = 0.02). The median TURBT time per procedure was 431 minutes for BCG and 400 minutes for Gem/Doce (p = 0.071). The median office visit time was 82 minutes for BCG and 83 minutes for Gem/Doce (p = 0.44). Thirty-seven patients (28%) sought care at emergency departments during treatment, with similar rates between groups (p = 0.40). Treatment completion rates as defined by completion of at least 5 instillations were comparable: 91% BCG vs 96% Gem/Doce, p = 0.29. In standardized early treatment analysis (TURBT #1, office visit #1, and instillations 1-6), Gem/Doce added 284 minutes (+4.7 hours, p = 0.0008). Conclusions: To our knowledge, this is the first comparison of time toxicity between BCG and Gem/Doce. Gem/Doce is associated with increased instillation times and resultant increased patient time toxicity. This data can aid in tradeoff calculations. As available NMIBC therapies increase, time toxicity should be evaluated along with traditional oncologic and quality of life metrics.

Randomized trial of urinary tumor DNA (utDNA) testing-guided repeat transurethral resection (re-TURBT) in non-muscle-invasive bladder cancer (NMIBC): TRUCE-LB01.

TPS910 Background: Repeat transurethral resection of bladder tumor (re-TURBT) is a standard procedure for selected patients with non–muscle-invasive bladder cancer (NMIBC) to ensure complete tumor removal and accurate pathological staging. Although this approach improves diagnostic precision, a substantial proportion of patients are found to be tumor-free at re-TURBT, raising concerns about overtreatment. As an invasive intervention, re-TURBT is associated with bleeding, bladder perforation, and urinary tract infection, as well as psychological stress, hospitalization, and financial burden. These limitations emphasize the need for more precise and individualized strategies to identify patients who can safely omit re-TURBT. Liquid biopsy provides a dynamic and non-invasive means of detecting minimal residual disease. Because bladder tumors shed DNA directly into urine, urinary tumor DNA (utDNA) testing offers a sensitive and repeatable approach for assessing molecular residual disease after surgery. Incorporating utDNA testing to guide re-TURBT may help avoid unnecessary procedures while maintaining oncologic safety. The TRUCE-LB01 trial was initiated and is currently ongoing to evaluate the clinical utility, safety, and cost-effectiveness of utDNA-guided re-TURBT in patients with NMIBC. Methods: TRUCE-LB01 is an open-label, multicenter, randomized controlled trial assessing the role of utDNA testing in guiding repeat transurethral resection (re-TURBT) for NMIBC. Eligible participants are adults (≥18 years) with pathologically confirmed NMIBC, without evidence of muscle-invasive or metastatic disease, and meeting at least one indication for re-TURBT, such as incomplete initial TURBT, absence of detrusor muscle in the specimen (except for low-grade Ta or CIS), or stage T1 disease. A total of 196 patients are randomized 1:1 to either a standard re-TURBT arm, in which patients undergo re-TURBT within 2–6 weeks after the initial procedure, or a utDNA-guided arm, where re-TURBT is performed only if utDNA testing is positive and omitted when utDNA is negative. All patients receive standard intravesical therapy and follow-up per guideline recommendations. The primary endpoint is 2-year recurrence-free survival (RFS). Secondary endpoints include progression-free survival (PFS) and pathological outcomes of re-TURBT (residual tumor rate, upstaging, and CIS detection). Exploratory endpoints include diagnostic and prognostic performance of utDNA, patient compliance, cost-effectiveness, and patient-reported outcomes (PROs). The study is conducted in accordance with the Declaration of Helsinki and ICH-GCP guidelines. Patient enrollment is ongoing across multiple centers in China. Clinical trial information: NCT07187635 .

Androgen-receptor pathway inhibitors triplet therapy (ARAAT): Real-world outcomes in metastatic hormone-sensitive prostate cancer.

82 Background: Darolutamide or abiraterone, in combination with androgen-deprivation therapy (ADT) and docetaxel (DOC) is recommended as a treatment strategy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). In this study (ARAAT), we report clinical outcomes in patients with mHSPC treated with triplet therapy consisting of darolutamide + ADT + DOC (DAR) or abiraterone + ADT + DOC (ABI). Methods: This retrospective cohort analysis used the ConcertAI Patient360 database, a geographically diverse US oncology electronic medical record dataset. Adult patients with mHSPC who initiated triplet therapy with DAR or ABI from January 2020 and January 2025 were included. Inverse probability of treatment weighting (IPTW) and multivariate Cox proportional hazard models were applied to account for baseline confounding factors. Endpoints were overall time to treatment discontinuation (TTD) due to any cause, time to castration-resistant progression-free survival (mCRPC or death), time to PSA <0.2 ng/mL (including Kaplan-Meier estimated rates of PSA <0.2 ng/mL), time to next treatment (TTNT), and overall survival. Results: A total of 592 pts with mHSPC initiated DAR (n=368) or ABI (n=224). Median baseline PSA was 53 ng/mL in the DAR cohort and 35 ng/mL in the ABI cohort. Median follow-up was 19 months in both the cohorts. In IPTW analysis, TTD (Hazard ratio [HR] 0.63), time to mCRPC or death (HR 0.73), TTNT (HR 0.54), and OS (HR 0.68) were significantly longer with DAR vs ABI (Table). The probability of PSA <0.2 ng/mL after 12 months was 61.6% (95% CI 55.2, 68.1) with DAR vs 52.6% (95% CI 43.7, 62.1) with ABI and 72.0% (95% CI 64.4, 79.2) with DAR vs 59.9% (95% CI 49.8, 70.2) with ABI after 24 months. Time to PSA <0.2 ng/mL was significantly shorter with DAR (HR 1.34; Table). The trend in results were consistent using multivariate Cox proportional hazard models (Table). Conclusions: In this real-world study, patients receiving darolutamide triplet therapy had significantly improved outcomes over abiraterone triplets, including TTD, time to mCRPC or death, TTNT, PSA response, and OS after adjustment for confounding factors. Endpoint (DAR vs ABI) IPTW modelHR (95% CI); P-value Multivariate Cox Proportional Hazard † HR (95% CI); P-value TTD 0.63 (0.53, 0.76); <0.001 0.65 (0.49, 0.85); 0.002 Time to mCRPC or death 0.73 (0.63, 0.86); <0.001 0.77 (0.60, 0.98); 0.033 TTNT 0.54 (0.44, 0.67); <0.001 0.57 (0.41, 0.79); <0.001 Time to PSA <0.2 ng/mL* 1.34 (1.10, 1.62); 0.003 1.46 (1.07, 1.99); 0.018 OS 0.68 (0.54, 0.86); 0.001 0.67 (0.48, 0.96); 0.026 *Model carried out in pts (DAR n=255; ABI n=143) with baseline PSA ≥1 and ≥1 PSA measurement during follow-up. † Directly adjusted model.

Multilevel Heterointerface Engineering Breaks the Trap‐Barrier Trade‐Off in High‐Energy‐Density Polymer Dielectrics

ABSTRACT The low energy density, inefficient operation, and thermal instability of polymer dielectrics hinder the deployment of film capacitors under harsh environmental conditions. Interface engineering has emerged as a powerful strategy to introduce charge traps or construct interfacial barriers, thereby regulating carrier dynamics and enhancing energy storage. Here, we propose a multilevel heterointerface engineering strategy that integrates boron nitride and barium niobate nanosheets through lattice interlocking. The large work‐function offset and bandgap contrast induce interfacial band bending and a built‐in electric field, forming a complementary trap‐barrier network that guides, blocks, and confines charge carriers. This design effectively suppresses charge injection and mobility, enhances interfacial polarization, and mitigates the propagation of breakdown pathways. Consequently, BNO@BN/PEI composites achieve exceptional energy storage performance, delivering 9.02 J cm −3 ( η = 92%) at room temperature and sustaining 6.1 J cm −3 ( η ≈ 90%) at 150°C, while still preserving 4.6 J cm −3 at 200°C. First‐principles calculations and finite element simulations further validate the structural and functional superiority of the multilevel heterointerface. This work establishes multilevel heterointerface engineering as a generalizable paradigm for breaking the trap‐barrier trade‐off in conventional dielectric design and paves the way for next‐generation high‐energy‐density and thermally robust polymer capacitors.

Sub‐5‐Min Ultrafast Growth of Millimeter‐Scale‐Length Tellurium Nanowires With Broadband Bulk Photovoltaic Response

ABSTRACT Bulk photovoltaic effect (BPVE) featured by polarization‐dependent photoresponse at zero external bias exhibits huge potential for exploiting next‐generation photodetectors. However, the BPVE is mainly limited in the wide‐bandgap ferroelectrics and complex van der Waals (vdW) heterostructures and scarcely demonstrated in narrow‐bandgap vdW semiconductors. Here we develop a surface self‐limiting diffusion driven growth strategy to rapidly synthesize millimeter‐scale‐length narrow‐bandgap tellurium (Te) single‐crystal nanowires with highly uniform non‐centrosymmetric structure. The sub‐5‐min ultrafast growth‐a feat not realized in prior Te synthesis arises from ultralow self‐limiting diffusion and nucleation barriers of H 2 Te precursors in a hydrogen‐assisted space‐confined environment. The fabricated photodetectors show broadband BPVE response from 520 nm to 4.6 µm, ultrahigh peak responsibility of 220 A/W and blackbody responsivity of 2.3 A/W, which are far superior to the state‐of‐the‐art self‐powered vdW devices. Furthermore, we demonstrate high‐resolution polarization imaging and BPVE detector arrays in a single Te nanowire. This work opens perspectives of ultralong Te nanowires with robust BPVE for the development of high‐performance on‐chip integrated multidimensional photodetection systems.

The nucleotide exchange factor, GrpE, modulates substrate affinity by interaction of its N-terminal tails with the DnaK substrate–binding domain

Adjuvant pembrolizumab in non–clear cell renal cell carcinoma after nephrectomy: An international multicenter study.

473 Background: KEYNOTE-564 demonstrated that adjuvant pembrolizumab improves outcomes after nephrectomy for clear-cell renal cell carcinoma (RCC). Whether this benefit extends to non–clear cell RCC (nccRCC) remains uncertain. We evaluated the association between adjuvant pembrolizumab and outcomes in patients with nccRCC who underwent nephrectomy in a multicenter study. Methods: We conducted a retrospective multicenter cohort study at six international institutions. Eligible adults had nccRCC treated with nephrectomy and were classified by receipt of adjuvant pembrolizumab. The primary endpoints were disease-free survival (DFS), defined as the time from nephrectomy to the first radiographic or clinical recurrence, and overall survival (OS), defined as the time from diagnosis to death or last follow-up. Survival functions were estimated with the Kaplan–Meier method and compared between groups using the log-rank test. Estimates of median DFS and OS were calculated using the Kaplan–Meier method. Results: Patient characteristics are shown in Table 1. Among 90 patients, 15 (17%) received adjuvant pembrolizumab, and 75 (83%) were observed; age at diagnosis was 56.0 years (IQR 44.0–63.0; mean 52.9 ± 13.1) and 62.0 years (IQR 52.0–71.0; mean 59.6 ± 14.7) respectively. Recurrence occurred in 7/15 (46.7%) with pembrolizumab and 25/75 (44.6%) with observation. There was no significant difference in median DFS (p = 0.75) or OS (p = 0.89) between groups. Median DFS was 90.7 months (95% CI, 27.2–NR) with pembrolizumab vs 41.9 months (95% CI, 39.4–NR) with observation; median OS was not reached (95% CI, 65.1–NR) with pembrolizumab vs 52.4 months (95% CI, 44.4–NR) with observation. Conclusions: In this descriptive retrospective six-center cohort of nccRCC post-nephrectomy, adjuvant pembrolizumab did not demonstrate a DFS or OS advantage over observation. A larger multi-institutional cohort is in progress to refine effect estimates using richer clinical detail, with adjusted analyses and prespecified subgroup assessment. Baseline characteristics by treatment group. Characteristic Overall (n=90) Observation (n=75) Pembrolizumab (n=15) Sex (Male/Female), n (ratio) 58 / 32 (1.8:1) 48 / 27 (1.8:1) 10 / 5 (2:1) T1, n (%) 11 (12.2%) 10 (13.3%) 1 (6.7%) T2, n (%) 10 (11.1%) 10 (13.3%) 0 (0.0%) T3, n (%) 64 (71.1%) 52 (69.3%) 12 (80.0%) T4, n (%) 3 (3.3%) 2 (2.7%) 1 (6.7%) Papillary RCC, n (%) 41 (45.6%) 36 (48.0%) 5 (33.3%) Chromophobe RCC, n (%) 31 (34.4%) 27 (36.0%) 4 (26.7%) Unclassified RCC, n (%) 7 (7.8%) 6 (8.0%) 1 (6.7%) Xp11 translocation, n (%) 8 (8.9%) 4 (5.3%) 4 (26.7%)

Multimodal integration of VI-RADS, radiomics, and deep learning features for prediction of pathology and prognosis in bladder cancer.

640 Background: Recently, MRI-based assessments of bladder cancer using VI-RADS, radiomics, and deep learning models have been widely reported. However, it has not been known whether MRI-based approaches can comprehensively predict detailed pathological findings and survival outcomes. This study aimed to evaluate a multimodal approach integrating VI-RADS, radiomics, and deep learning features for predicting both pathology and survival outcomes. Methods: We retrospectively analyzed 106 patients with bladder cancer who underwent MRI and TURBT between August 2021 and July 2023. VI-RADS were assessed by two urologists. Tumors were manually segmented in 3D slicer, and radiomic features were extracted with PyRadiomics. Deep learning–derived features were obtained from cropped tumor images using EfficientNet-B7. Detailed pathological outcomes were modeled after feature selection with LASSO regression and cross-validation. For survival analysis, OS and PFS at 3 years were evaluated. Risk scores were derived from LASSO-selected features, and cutoff values were determined by ROC analysis to stratify patients into risk groups. Results: The multimodal approach showed favorable predictive performance. In this study, features selected by LASSO consisted of 85% from EfficientNet, 10% from VI-RADS, and 5% from radiomics. For pathological findings, neural boosting achieved high accuracy with AUCs of 0.995 for MIBC, 0.970 for T stage, 0.965 for high grade, 0.983 for necrosis, 0.891 for variant histology, and 0.917 for CIS. For survival outcomes, the risk score achieved AUCs of 0.835 for 3-year OS and 0.926 for 3-year PFS. Kaplan–Meier analysis demonstrated significantly poorer overall survival (HR = 13.99, 95% CI 3.84–50.58) and progression-free survival (HR = 18.79, 95% CI 4.11–85.79) in the high-risk group compared with the low-risk group. Conclusions: Integration of MRI-derived VI-RADS, radiomics, and deep learning features enables accurate prediction of pathology and prognosis in bladder cancer without additional clinical factors. This MRI-based multimodal risk score may support individualized patient stratification and treatment decision-making.

Patterns and predictors of online cancer information seeking among urological cancer survivors.

328 Background: Online health information seeking is linked to improved patient engagement, knowledge, and shared decision-making. We evaluated sociodemographic and clinical predictors of internet use for cancer information among survivors of urological malignancies. Methods: Data were obtained from the nationally representative US Health Information National Trends Survey (HINTS; years 2003-2024). Survivors of urological malignancies were identified by self-reported cancer history. The primary outcome was internet use for cancer information. Participants who reported searching for health information online were assumed to have sought cancer-related information. Survey-weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with age, education, income, marital status, rurality, insurance, self-rated health, and cancer type. Analyses were stratified by cancer type, with sensitivity analyses restricted to respondents diagnosed within ≤5 years. Results: A total of 1,078 unweighted survivors of urological malignancies, representing an estimated 38.2 million adults in the US population, were included (mean age, 71 years; 73.5% male). In multivariable analyses, participants aged ≥65 years were less likely to use the internet for cancer information than those aged <65 years (OR=0.21; 95% CIs, 0.12–0.36). Compared with bladder cancer survivors, those with prostate-only (OR=0.34; 95% CIs, 0.15–0.78) or other urological malignancies (OR=0.16; 95% CIs, 0.04–0.57) were less likely to report such use. Survivors who were married (OR=1.84; 95% CIs, 1.07–3.15), had a college education (OR=2.21; 95% CIs, 1.39–3.51), had household income ≥ $75,000 (OR=2.51; 95% CIs, 1.10-5.72), and had poor self-reported health (OR=4.14; 95% CIs, 1.14-15.11) were more likely to use the internet for cancer information. Stratified analyses yielded similar results across the three cancer types, except for race and self-rated health. Sensitivity analyses produced consistent findings. Conclusions: Nearly half of urological cancer survivors reported seeking cancer information online. Older age and lower socioeconomic status were associated with reduced engagement, demonstrating the need for targeted efforts to improve equitable digital access and support informed survivorship care. Internet use by survivor characteristics. Variable Yes (n = 503) No (n = 575) p-value Age, mean (SD) 68.6 (10.9) 73.0 (10.5) <0.001 Male sex, n 334 (66.4%) 459 (79.8%) <0.001 Married, n 347 (69.0%) 315 (54.8%) <0.001 College graduate, n 277 (55.1%) 182 (31.7%) <0.001 Household income ≥$50,000, n 321 (63.8%) 229 (39.8%) <0.001 Metro residence, n 420 (83.5%) 459 (79.8%) 0.12 Good/Very good self-rated health, n 336 (66.8%) 372 (64.7%) 0.43 Bladder cancer, n 44 (8.7%) 75 (13.0%) 0.089 Prostate cancer, n 360 (71.6%) 393 (68.3%) Renal cancer, n 57 (11.3%) 67 (11.7%)

Reconfigurable Vertical Schottky Photodiodes Based on Ferroelectric 2D Semiconductors for Perceptual‐Precision, Context‐Aware Neuromorphic Vision

ABSTRACT To realize in‐memory sensing and computing platforms, it is essential to integrate sensing, computation, and memory functionalities within a single device, enabling energy‐ and time‐efficient vision systems with high perceptual precision. However, achieving such multi‐functional processing capability within a compact device structure remains a major challenge. Here, a reconfigurable vertical photodiode based on α‐In 2 Se 3 is presented, a ferroelectric 2D semiconductor. Gradual and reversible modulation of built‐in electric fields at the top and bottom Schottky junctions is achieved through partial out‐of‐plane polarization switching of α‐In 2 Se 3 , enabling multi‐level, non‐volatile, and polarity‐tunable photoresponsivity. This allows analog programmability with a high degree of freedom in processing within a two‐terminal metal‐ferroelectric semiconductor‐metal (MFsM) structure, effectively resolving trade‐off between structural compactness and computing versatility. Leveraging these intrinsic characteristics, we demonstrate a versatile sensor‐level perceptual processing framework using a reconfigurable photodiode crossbar array. By exploiting the high‐density spatial integration capability, the system adaptively configures its spatial support to prioritize either suppressing environmental noise for robust feature extraction or preserving fine‐grained details for precise classification, depending on the task requirements. These results lay the foundation for highly scalable and energy‐efficient neuromorphic vision system with high perceptual precision.

Hydrophobic interactions determine the optimum temperature of a housekeeping enzyme

SPPADE symptom burden and ePRO-based outcome prediction in patients with mCRPC treated with ¹⁷⁷ Lu-PSMA-617 (LuPSMA).

142 Background: LuPSMA is a life-prolonging radioligand therapy that is widely considered to have favorable tolerability. SPPADE symptoms (Sleep disturbance, Pain, Physical dysfunction, Anxiety, Depression, low Energy) are common in prostate cancer, yet data on patient-reported outcomes with LuPSMA in real-world settings remain limited. Methods: The E2C2 study (NCT03892967) evaluates the impact of a collaborative care intervention on patient-centered outcomes and healthcare utilization. This analysis includes mCRPC patients who initiated LuPSMA at Mayo Clinic (June 2022-July 2023) and completed at least one symptom survey within 6 weeks before or 2 weeks after the first LuPSMA treatment (baseline survey). SPPADE symptoms were rated on 0-10 scales; scores of 4-6 indicate moderate and 7-10 severe burden. A composite z-score was derived by standardizing each SPPADE domain to the cohort mean and averaging z-scores across domains per patient. Patients were stratified by composite symptom burden using cohort median and upper-tertile cutoffs. Associations with PSA50 response and overall survival (OS, from start of LuPSMA) were assessed using chi-square and Kaplan-Meier methods. In a longitudinal subgroup of patients completing a baseline survey plus at least one additional PRO survey while receiving LuPSMA (≥2 surveys), scores were compared from baseline to best during-treatment using Wilcoxon and Mann-Whitney U tests. Results: Of 373 patients starting LuPSMA, 51 patients met inclusion criteria. Median age was 71 years, 31% had visceral metastases, and median baseline PSA was 42.1 ng/mL. Overall, 85% of patients reported at least one moderate symptom and 46% at least one severe symptom. The most common moderate-to-severe symptoms were low energy (58%), pain (52%), and sleep disturbance (49%). Using an upper-tertile cutoff of the composite SPPADE score, 17 patients had high and 34 had low/moderate symptom burden prior to LuPSMA. PSA50 response was achieved in 17.6% of patients with high vs 47.1% with low/moderate composite symptom scores (p = 0.08). Median OS was 9.2 vs 16.7 months for high vs low symptom groups (p = 0.15, median split). The longitudinal subgroup included 24 patients with serial ePRO assessments while on LuPSMA. Composite SPPADE scores improved from baseline to the best during-treatment assessment in both PSA50 responders (n=10) and non-responders (n=14), with median composite z-score Δ of 0.35 vs 0.20, respectively (p = 0.68). Conclusions: Among patients with mCRPC receiving LuPSMA, baseline SPPADE symptom burden was high. Though not statistically significant in this underpowered cohort, PSA response and OS were numerically inferior in those with higher baseline burden. These findings suggest that ePRO-captured symptom burden may provide prognostic and patient-centered insights beyond traditional clinical variables. Clinical trial information: NCT03892967 .

Inferring optimal MTAP homozygous loss (homozygous deletion) detection in urothelial cancer: Prevalence and co-alterations based upon treatment exposure and anatomical location.

641 Background: Validated homozygous loss detection is becoming increasingly important in clinical practice, with prostate NCCN guideline inclusion of BRCA1/2 loss (portending durable benefit from PARP inhibitor) and multi-tumor trials of PRMT5 and MAT2A inhibitors ongoing (biomarker: MTAP deletion). Homozygous losses are challenging to detect and require intentional NGS assay design and validations. Using a well-validated test, we sought to evaluate the most common losses in metastatic urothelial cancer tissue samples, evaluate their prognostic associations on standard of care regimens, prevalence before and after standard of care regimens, and overlap with other biomarkers. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Urothelial Cancer clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (~800 sites of care). Patients with metastatic urothelial cancer and tissue tumor genomic testing by FoundationOne CDx were eligible for analysis. Prevalence of alterations was compared between non-sequential groups of specimens obtained from patients who were naïve or exposed to immune checkpoint inhibitors (ICI) or chemo. Outcome analyses were adjusted for: ECOG performance score, age, and socioeconomic status. Results: 1446 specimens from 1446 unique patients met criteria for assessment. Only three genes featured homozygous losses with a prevalence greater than 3%: CDKN2A (36.5%), CDKN2B (34.6%), and MTAP (28.8%). Prevalence of each of these alterations was similar in specimens from patients who were naïve to ICI or chemo compared to those exposed to ICI or chemo. Multivariable models did not suggest associations with outcome on ICI, chemo, or enfortumab vedotin. In 401 cases (27.7%) MTAP , CDKN2A and CDKN2B genes were co-lost, with 97 (6.7%) of cases where CDKN2A and CDKN2B were lost but not MTAP . MTAP loss without CDKN2A/B loss was very rare (n = 15, 1.04%). In multivariable models adjusting for ICI and chemo exposure, upper tract urothelial carcinoma had significantly higher prevalence of MTAP loss (OR: 2.53, p < 0.0001) with a prevalence of 48.3%. RB1 mutations were strongly inversely associated with MTAP loss (OR: 0.037, p < 0.0001) and FGFR3 mutations were strongly associated with MTAP loss (OR: 2.46, p < 0.0001). Conclusions: MTAP loss prevalence in urothelial cancer is about 29% via an assay and algorithm designed to detect homozygous losses, with higher prevalence in upper tract urothelial carcinoma. Our results are consistent with a model of MTAP loss in bladder cancer as a bystander effect of CDKN2A/B loss, and that it is a truncal event, inferring that both archival or contemporaneous tissue specimens are valid for assessment of MTAP loss for patient enrollment into clinical trials for PRMT5 and MAT2A inhibitors.

Use of spatial transcriptomics to analyze the molecular landscape of tuberous sclerosis complex–associated angiomyolipoma: Implications for diagnosis and therapeutic targeting.

517 Background: Tuberous sclerosis complex–associated angiomyolipoma (TSC-AML) is often bilateral, multifocal, and sometimes massive or familial, with increased rupture/hemorrhage risk, complicating management vs sporadic AML. mTOR inhibitors are available but with limited efficacy, so deeper molecular understanding may guide therapy selection and new targeted approaches. We performed a pilot, hypothesis-generating spatial transcriptomic comparison of TSC-AML, sporadic AML, and renal cell carcinoma (RCC) to contextualize its biology. Methods: Formalin-fixed paraffin-embedded sections from one case each of TSC-AML, sporadic AML, and RCC underwent spatial gene expression profiling (CytAssist Visium). Unsupervised clustering and pathway analysis defined cell-type–specific programs and candidate targets. Results: Both TSC-AML and sporadic AML showed triphasic architecture (vascular, smooth muscle, adipose) and PEC markers (PMEL, MLANA, ACTB, DES). TSC-AML had TSC1/2 downregulation without significant mTOR, MLST8, or RPTOR upregulation, suggesting post-translational mTORC1 activation. RCC showed broad mTORC1 pathway upregulation. Vascular regions enriched angiogenesis/ECM remodeling (Wnt, NABA matrisome), adipose regions activated lipid metabolism (PPAR signaling, triglyceride synthesis). Comparative profiling found 42 genes uniquely upregulated in TSC-AML, including immune modulators (IL33, ABCC8), metabolic regulators (FABP4, APOC1), muscle genes (LDB3, SYNM), and neuronal genes (GRIA2, ASTN1), suggesting candidate biomarkers and therapeutic targets. Conclusions: This pilot study maps the spatial transcriptome of TSC-AML, identifies candidate biomarkers for precision diagnostics, and highlights angiogenic, ECM, and metabolic pathways as therapeutic targets. Comparative profiling vs RCC and sporadic AML revealed distinct pathway activation, underscoring TSC-AML’s unique biology. These findings warrant validation in larger cohorts and could inform clinical management. Forty-two genes upregulated in TSC-associated angiomyolipoma. Lipid metabolism / Adipogenesis FABP4, APOC1, ADIPOQ, PLIN1, CES1 Immune regulation / Inflammation IL33, APOBEC3C, IGSF21, LGALS1 Muscle structure / Cytoskeleton LDB3, SYNM, PGAM2, TPM2, PLN, MRVI1, ADRA1A Neuronal / Synaptic function GRIA2, ASTN1, SNCG, CELF2, AFF2, C14orf180, TRARG1 Metabolism / Stress response PDK1, STEAP4, NDRG4, DUOX2, NMNAT2 Other / Unclassified IGFN1, TMEM132C, ADGRL3, ABCC8, KCNQ4, PDE1B, PIL5