Browse Articles

Self‐Adaptive Mechanical Metasurface Enabling Zero‐Power‐Consumption Thermal Management of Electronic Devices (Adv. Mater. 14/2026)

Dual‐Gas Activation Nanodomains Enable Solar‐Powered Selective Methane Conversion

ABSTRACT Photocatalytic oxidation of methane to formaldehyde at concentrations compatible with direct fuel‐cell use remains a critical yet unmet challenge. Here we introduce a “dual‐gas coadsorption domain” architecture discovered through a high‐throughput screen of 37 earth‐abundant transition metals and their oxides. Reduced nickel oxide (NiO 1‐x ) emerged as the optimal co‐catalyst, decorating the pore edges of vacancy‐rich porous ZnO (pZnO). Oxygen vacancies in pZnO act as oxygen pumps, while adjacent NiO 1‐x nanoclusters chemisorb and polarize methane, lowering the C‐H activation barrier and steering the radical cascade toward methyl hydroperoxide instead of methanol. Methyl hydroperoxide quantitatively decomposes to formaldehyde, delivering 28.5 mmol g −1 (3 mM in solution, 88.5% selectivity). An outdoor reactor powered only by natural sunlight (peak 72.8 mW cm −2 ) produced 12.3 mmol g −1 formaldehyde in 6 h without detectable by‐products. The concentrated effluent feeds an alkaline formaldehyde fuel cell directly—no purification—co‐generating 0.2 kWh of electricity and valuable formate at a peak power density of 32.6 mW cm −2 . The work establishes a scalable, solar‐driven pathway for simultaneous methane valorization and on‐site energy conversion.

Diabetic retinopathy as a marker for renal cell carcinoma among patients with type 2 diabetes mellitus.

486 Background: Type 2 diabetes mellitus (T2DM) has been associated with increased risk of renal cell carcinoma (RCC). Animal studies indicate that glucose dysregulation and elevated insulin/IGF-1 signaling cascade accelerate renal tumorigenesis. Epidemiological studies suggest that greater severity of T2DM, defined by the number of complications and actively using glucose-lowering agents, is associated with higher RCC risk. Diabetic retinopathy (DR), readily detected during routine ophthalmology visits, can serve as a practical, objective marker of T2DM severity. However, few studies have directly examined the association between DR and RCC. In this study, we aim to evaluate whether the presence of DR increases the risk of RCC in patients with T2DM and to propose its potential as a clinical indicator for RCC screening. Methods: We conducted a case–control study using the All of Us Research Program Registered Tier v8 dataset. Adults with T2DM were identified by ICD-10 codes, excluding patients with RCC prior to T2DM diagnosis. DR was defined as non-proliferative and proliferative DR using ICD-10 codes. We fit multivariable logistic regression models to evaluate the association between DR to RCC status, adjusted for age, sex at birth, race, ethnicity, body mass index, and smoking status. Results: We identified 67,096 patients with T2DM. Among them, 7,320 (10.9%) had DR and 603 (0.9%) had RCC. Compared with patients without DR, those with DR were older (66.4 vs 64.4), more often male (49.6% vs 42.6%), and had lower smoking prevalence (43.6% vs 46.5%). RCC prevalence was 1.46% in the DR group vs 0.83% in the non-DR group. In multivariable analyses, DR was associated with higher odds of RCC (OR =1.58, 95% CI 1.27–1.98, p<0.001). In sex-stratified analyses, the association remained significant in both sex groups, with a slightly larger effect in men (male: OR =1.67, 95% CI 1.25-2.22, p<0.001; female: OR 1.60, 95% CI 1.10-2.33, p=0.015). Conclusions: DR was associated with higher odds of RCC compared with DM alone. These findings support considering RCC screening after DR diagnosis and the need for studies to evaluate the benefits, harms, and cost-effectiveness of DR-guided screening.

Structural classification of FOXA1 alterations and their association with clinical outcomes in prostate cancer patients: A multi-institutional retrospective analysis.

256 Background: FOXA1 is a transcription factor with gene alterations in 10-15% of prostate cancers. Due to its complex dynamics with the androgen receptor, the effects of mutations in the FOXA1 gene are variable, and clinical outcomes associated with FOXA1 alterations have been challenging to decipher. A recent classification system for FOXA1 alterations defined by mutational mechanism and orientation with respect to FOXA1 protein domains has been developed to inform clinical management for prostate cancer (Hwang J. CCR 2025). Here, we report consolidated multi-institutional patient outcomes associated with FOXA1 alteration classes in prostate cancer patients. Methods: We retrospectively analyzed 189 patients across 5 institutions by FOXA1 alteration class and calculated per-patient duration of exposure to androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPIs), and taxane chemotherapy. Associations of FOXA1 class and overall survival (OS) was examined by univariable Kaplan-Meier plot with log-rank test. Multivariable Cox proportional hazards models were fitted for OS related to FOXA1 alteration class and systemic treatment duration as independent predictors, adjusted for age, metastatic disease at diagnosis, and Gleason grade group as covariates, stratified by treating institution. Additional models were fitted to investigate for interaction effects between treatment exposures and FOXA1 mutation class. Baseline risk was defined by patients with FOXA1 Class 1B mutations. Results: Our final cohort included 9 patients with Class 1A, 94 with Class 1B, 19 with Class 1C, 3 with Class 2, 18 with Class 3A, 27 with Class 3B, and 19 with Class 4 alterations. FOXA1 Class 2 alterations correlated with decreased OS (HR 4.4, p=0.04). On multivariable analysis, improved OS was independently associated with longer treatment duration on ADT (HR 0.97 per month, p=0.03) and ARPIs (HR 0.89 per month, p<0.001). No significant association was found with duration of taxane. Interaction models showed treatment effect modification with ADT duration in Class 4 (β [Class4:ADT ] +0.07, p=0.003) and ARPI duration in Class 3B and 4 alterations (β [Class3B:ARPI] +0.10, p=0.05; β [Class4:ARPI] +0.09, p=0.03), suggesting modulation of the per-month survival benefit of treatment duration. Conclusions: Prior studies show that FOXA1 alterations produce distinct prostate cancer phenotypes. Here, we found that FOXA1 Class 2 alterations were significantly correlated with worse OS. Multivariable models suggest more OS benefit of ADT and/or ARPI duration in FOXA1 Class 1B, compared to 3B and 4 alterations. These findings emphasize the importance of structural subclassification of FOXA1 variants, rather than just their presence or absence, for prognostication and therapeutic selection for patients with prostate cancer.

Elucidating the mechanism of cefpodoxime-BSA interaction via a combination of multi-spectroscopic methods and molecular docking simulations

Abstract This research provides a comprehensive elucidation of the molecular interaction between cefpodoxime (CFP) and bovine serum albumin (BSA) through an integrated approach combining computational docking and a suite of spectroscopic methods. Initial evidence from UV-Vis absorption spectroscopy confirmed a ground-state complex formation between the drug and the protein. Subsequent fluorescence quenching studies established a static quenching mechanism, with a binding constant (Kb) of 3.99 × 10 4 L·mol −1 determined at 298 K, indicating moderate binding affinity. Analysis of the thermodynamic parameters, computed via the Van’t Hoff equation, revealed that the binding process is both spontaneous and endothermic. The positive entropy change (ΔS°) identified hydrophobic interactions as the predominant driving force for the complex formation. The binding site was precisely localized to subdomain IIA (Site I) of BSA, a finding consistently supported by two independent lines of evidence: competitive site-marker displacement assays and molecular docking simulations. Collectively, these insights into the binding affinity, forces, and specific location are fundamental for advancing the understanding of CFP’s pharmacokinetic profile. This knowledge is critical for predicting its distribution and elimination in vivo, thereby informing its safe clinical use and helping to mitigate potential adverse effects.

Patient (pt) preferences for treatment (tx) of non-metastatic hormone-sensitive prostate cancer (nmHSPC): A discrete choice experiment (DCE).

338 Background: Prostate cancer tx guidelines recommend androgen receptor pathway inhibitors (ARPI) ± androgen-deprivation therapy (ADT) as an effective alternative to ADT alone for pts with high-risk biochemically recurrent nmHSPC. ARPI ± ADT offers improved efficacy and a tolerable safety profile compared with ADT alone; however, understanding which attributes pts consider most when assessing tx options is important. This study quantified pt preferences for ARPIs ± ADT vs ADT alone in pts with nmHSPC across 9 countries, using a DCE method. Methods: Using convenience sampling, an online panel-based DCE survey was developed and administered to 374 pts with nmHSPC who had undergone definitive tx. The DCE included 14 choice cards, each presenting 2 hypothetical tx options with varying levels of efficacy (metastasis-free survival [MFS], tx suspension), tx-emergent adverse events (risk of fatigue, hot flashes, breast swelling), and sexual well-being (duration of interest in sex, duration of keeping erectile function). MFS was selected, as it served as a key efficacy endpoint in an nmHSPC study and is associated with overall survival. Pts were recruited from US (n = 56), Italy (n = 53), Germany (n = 52), UK (n = 43), Brazil (n = 40), France (n = 40), South Korea (n = 40), Spain (n = 40), and Australia (n = 10). Preference weights were estimated using a random parameter logit model. Relative attribute importance was derived from these weights and the corresponding attribute levels. EMBARK trial profiles for ARPI and ADT informed tx choice probabilities, and pts were assigned to the option with the highest predicted probability. Results: Median age was 66 years (IQR: 63.0–69.0). Of all pts, 245 (66%) were married/in a relationship and 109 (29%) were sexually active. Recurrence occurred in 157 (42%) pts after definitive tx. The most important attributes were 5-year MFS, risk of hot flashes, and duration of sexual interest relative to pre-tx baseline (Table). Among the pts, 363 (97%) selected ARPI ± ADT as their preferred tx option while 11 (3%) preferred ADT alone. Conclusions: In this DCE study, pts preferred ARPIs ± ADT vs ADT alone. MFS was the most significant driver of pt choices, followed by risk of hot flashes then interest in sex. These preferences suggest that ARPI-based txs may be viewed more favorably, which may reflect pts’ risk-benefit tradeoffs, favoring txs that balance clinical effectiveness, adverse events, and impact on sexual quality of life. Overall, the results support using personalized care plans for pts with nmHSPC. Attribute Relative importance, % (95% CI) 5-year MFS 28.9 (22.7, 35.2) Risk of hot flashes 18.6 (12.8, 24.5) Duration of sexual interest while on tx 17.4 (11.9, 22.9) Risk of breast swelling 11.7 (6.7, 16.8) Tx suspension 8.2 (1.5, 14.8) Duration of keeping erectile function while on tx 7.6 (2.6, 12.7) Risk of fatigue 7.5 (2.3, 12.6)

MajesTEC results with teclistamab in relapsed and/or refractory multiple myeloma

Portable Dosimeter With Ultralow Detection Limit Enabled by Large Size Solution Grown Inorganic Perovskite Single Crystal

ABSTRACT Inorganic perovskite CsPbCl 3 single crystals (SCs) grown via low‐cost solution methods typically achieve sizes smaller than 1 mm, primarily due to the low solubility of the raw materials in solvents. This limitation significantly constrains their viability for X‐ray detection applications. To address this challenge, an effective strategy is developed that not only increased the solubility of raw materials by 28 times but also significantly improved the crystallization matching between different components. This advance enabled the successful growth of high‐quality CsPbCl 3 ‐based SCs reaching 13 mm in size using a low‐temperature solution process. The solution‐grown SCs exhibit low trap density (∼10 8 cm −3 ), large resistivity (2.35 ×10 9 Ω cm), high µτ product (1.02 ×10 −3 cm 2 V −1 ), and superior uniformity. Therefore, X‐ray detectors fabricated on these SCs achieved a record‐high sensitivity of 2.19 ×10 5 µC Gy −1 cm −2 , a short response time of 307 µs, low noise current, and stable response output. Owing to these superior figures of merit, a prototype portable dosimeter assembled by the SC detector exhibited an extremely low detectable radiation of 0.07 nSv s −1 . Furthermore, the high‐definition X‐ray imaging of the SC detector is also demonstrated. This work provides an effective approach for the low‐cost manufacturing of high‐performance X‐ray detection systems.

Stable <i>P</i> ‐Type PbS Quantum Dot Ink for all‐Blade‐Coated Short‐Wavelength Infrared Photodiodes

ABSTRACT PbS colloidal quantum dots (CQDs) hold strong promise for short‐wave infrared (SWIR) optoelectronics. However, current photodetectors rely on p ‐type CQD layers fabricated via a laborious, defect‐prone layer‐by‐layer process. While robust n ‐type CQD inks have been realized, p ‐type inks remain challenging due to the absence of suitable ligands and solvents. An ideal solvent must ensure colloidal stability and be orthogonal to underlying layers. Here, we report a thiolate‐capped p ‐type PbS CQD ink using mercapto‐2‐propanol as the ligand and hexafluoro‐2‐propanol as the solvent. Stabilization arises from ligand–solvent hydrogen bonding, providing a shelf‐life exceeding six days. The solvent does not compromise pre‐deposited layers, enabling fully blade‐coated photodiodes in both n–p and p–n architectures. Devices fabricated with this ink exhibit a twofold increase in specific detectivity (2.55 × 10 12 Jones) and a 70% enhancement in bandwidth (155 kHz) compared to layer‐by‐layer controls, attributed to improved film morphology and charge transport.

Age as modifier of early proteomic remodeling after androgen deprivation therapy (ADT) in prostate cancer: Influence of innate immune/complement–ECM pathways.

246 Background: ADT is standard for advanced prostate cancer (PC) but increases cardiometabolic risk. The proteomic mechanisms, and whether they differ by age, remain poorly defined. We profiled longitudinal plasma proteomes around ADT initiation to test for age-modified effects. Methods: Men with PC starting ADT (n = 14; baseline, 1, 3 months) underwent Olink Explore profiling (2,874 proteins). Standardized NPX changes were modeled with linear mixed-effects (random intercepts; fixed effects for visit and age &lt;70 vs ≥70) and FDR control. Age×time interactions, baseline traits, and pathway enrichments were analyzed. Results: Median age 65.5 years (IQR 64–72.8); 43% African American; BMI 30.4; 50% diabetes; 79% hypertension; 50% metastatic; median Gleason 8.5. Nine proteins changed over 3 months (FDR q&lt;0.05): Upregulated: ITIH4 (acute-phase/complement), MDGA1. Downregulated: KLK3/PSA (on-target), INSL3 (Leydig), EDDM3B, galanin, PI3 (elafin), SPINT3, ENDOU. Most trajectories were consistent across ages except PI3, which declined only in &lt;70 (β −0.71, FDR &lt;10⁻⁴) and was unchanged in ≥70 (β −0.003, FDR 0.99; interaction q = 0.025). Galanin and ENDOU were significant only in younger men. ITIH4, INSL3, KLK3, EDDM3B, SPINT3, and MDGA1 changed in both (≥70 q ≤ 0.05). Baseline clustering revealed two proteomic phenotypes without differential response. Two deaths occurred (non-significant). Conclusions: ADT induces rapid, multisystem proteomic remodeling with suppression of androgen-linked and activation of innate immune/complement–ECM pathways. Age modifies anti-inflammatory protease regulation (PI3), suggesting divergent inflammatory and matrix-remodeling responses after ADT in younger vs older men. These findings link ADT to early complement–ECM biology underlying cardiometabolic risk and highlight age and select proteins as candidates for biomarker-guided monitoring. Larger, outcome-linked cohorts are needed for validation. Age stratified 3 month effects (standardized NPX β) and FDR q-values. Protein (biology) Direction β (&lt;70y) q (&lt;70y) β (≥70y) q (≥70y) Age×time q ITIH4 (acute-phase/complement-linked) Up +0.42 0.0016 +0.56 0.0218 0.65 MDGA1 (neuronal glycoprotein) Up +0.41 0.0009 +0.56 0.0501 0.65 KLK3/PSA (on-target) Down −4.20 2.9×10⁻⁵ −5.10 0.0167 0.53 INSL3 (Leydig function) Down −5.89 7×10⁻⁶ −5.09 0.0115 0.65 EDDM3B (reproductive) Down −1.55 7×10⁻⁶ −1.87 0.0167 0.65 Galanin (neuroendocrine) Down −1.35 0.00029 −0.76 0.168 0.65 PI3 / Elafin (anti-inflammatory) Down −0.71 9×10⁻⁶ −0.003 0.987 0.025 SPINT3 (serine protease inhibitor) Down −4.48 2.9×10⁻⁵ −4.65 0.0115 0.65 ENDOU (RNA processing) Down −0.72 0.00029 −0.48 0.123 0.65 β = standardized effect (baseline→3 mo); FDR = Benjamini–Hochberg; interaction q from mixed-effects age×time term.

Leveraging large language models (LLM) to guide adjuvant treatment recommendations for renal cell carcinoma (RCC) after nephrectomy.

567 Background: Selecting adjuvant therapy after nephrectomy for renal cell carcinoma (RCC) requires reviewing scattered electronic health records (EHR) and performing accurate eligibility and risk assessments. Large Language Models (LLMs) may assist physicians by extracting key clinical data and generating evidence-based recommendations between active surveillance and adjuvant pembrolizumab. Methods: We selected RCC patients who underwent nephrectomy at Mayo Clinic in Arizona, Florida, and Minnesota between December 2021 and September 2025. Data extraction from EHRs was performed by a HIPAA-compliant LLM (GPT-5 and Gemini 2.0-Flash-001) and compared to human labels. Data on patients’ demographics, medical history, pathology, laboratory results, and imaging were collected. GPT-5 generated treatment recommendations using a structured prompt that incorporated patients’ features and relevant clinical information that is available to clinicians. Concordance between the human labels and LLM was evaluated for extraction. For treatment recommendations, agreement between the LLM’s output and physician’s documented recommendation in clinical notes was assessed, with disagreements reviewed independently by two blinded genitourinary oncologists. Results: The dataset included 85 patients, median (range) age of 65 (34-84) years; 24.7% were females. Patients who declined adjuvant treatment for personal reasons were excluded. LLM achieved an extraction accuracy of 95% for presenting symptoms, 97% for BMI and ECOG, and &gt; 99% for pathology variables. Concordance between LLM and physician treatment recommendations was 84.7% (72/85). Among 13 discrepant cases, one oncologist agreed with the LLM in 9 cases and the other in 8. The main reasons for disagreement between the physicians and the LLM were that the LLM favored active surveillance for patients with declining renal function, whereas physicians still considered adjuvant pembrolizumab appropriate in such cases. Additionally, the LLM demonstrated hesitancy to recommend pembrolizumab for patients with low performance status. Overall, the 13 discrepant cases were nuanced and challenging, with disagreement observed between the two oncologists themselves in three instances. Conclusions: LLMs demonstrated high accuracy in extracting clinically relevant variables and generating objective, evidence-based adjuvant treatment recommendations for RCC after nephrectomy. Importantly, LLM did not generate any inappropriate or potentially harmful recommendations. Our pipeline can serve as a supportive decision tool to enhance consistency in post-nephrectomy management and assist physicians in choosing between active surveillance and adjuvant pembrolizumab. However, final treatment decisions should remain the responsibility of the treating physician after comprehensive patient evaluation.

A deep reinforcement learning framework for influence maximization problem on large-scale social networks

Real-world effectiveness and safety of first-line (1L) avelumab + axitinib (ave + axi) in patients with advanced renal cell carcinoma (aRCC): Final analysis of the prospective AVION study.

438 Background: In the JAVELIN Renal 101 phase 3 trial, 1L Ave + Axi significantly prolonged progression-free survival (PFS) and increased the objective response rate (ORR) vs sunitinib in patients with aRCC, with an acceptable safety profile. At the final analysis, the 12- and 24-month overall survival (OS) rates for Ave + Axi were 85.7% and 68.8%, respectively. The AVION study evaluated patients with aRCC receiving 1L Ave + Axi in routine clinical practice in various European countries. Results from the primary analysis showed the real-world effectiveness and acceptable safety of Ave + Axi in a heterogeneous population. We report the final analysis. Methods: AVION (NCT04941768) was a prospective noninterventional study of patients with aRCC treated with 1L Ave + Axi in Germany, Greece, Belgium, or Russia. Patients were observed for 24 months. The primary objective was OS rate at 12 months. Secondary objectives included OS rate at 24 months; median OS and PFS; ORR; duration of response (DOR); safety; and health-related quality of life (HRQOL; NCCN/NFKSI-19). Results: By data cutoff (July 23, 2025), 104 patients were included. Median age was 70 years (range, 37-87), and 70.2% were male. International Metastatic RCC Database Consortium risk group was favorable, intermediate, poor, or not reported in 26.0%, 45.2%, 12.5%, and 16.3%, respectively. Tumor histology was clear cell, sarcomatoid, and other in 89.4%, 3.8%, and 6.7%, respectively. Median duration of Ave or Axi treatment was 9.8 and 8.8 months, respectively. Median OS was not reached (95% CI, not estimable [NE]-NE), and 12- and 24-month OS rates (95% CI) were 81.8% (72.6%-88.1%) and 69.2% (58.4%-77.8%), respectively. Median PFS was 11.1 months (95% CI, 6.9-18.1), and 12- and 24-month PFS rates (95% CI) were 47.3% (36.6%-57.2%) and 31.1% (20.2%-42.6%), respectively. In patients evaluable for response (n = 91), ORR was 48.4% (95% CI, 37.7-59.1), and disease control rate was 80.2% (95% CI, 70.6-87.8); median DOR was not reached (95% CI, NE; range, 0-23.9 months). Treatment-related adverse events (TRAEs) of any grade occurred in 68.3% and were grade ≥3 in 19.2% and serious in 13.5%. TRAEs led to permanent discontinuation of Ave or Axi in 3.8% or 10.6%, respectively, and led to death in 1 patient (immune-mediated myocarditis). The most common TRAEs of any grade were diarrhea (27.9%), fatigue (14.4%), hypertension (10.6%), dysphonia (8.7%), and nausea (8.6%); the most common grade ≥3 TRAE was diarrhea (4.8%). HRQOL scores were generally stable during treatment, including total score and subscales. Conclusions: The final analysis of AVION confirms the real-world effectiveness, acceptable safety, and favorable tolerability with maintained HRQOL of 1L Ave + Axi treatment in a heterogeneous real-world population with aRCC in Europe, consistent with earlier results and previous studies. Clinical trial information: NCT04941768 .

From detection to direction: ctDNA-guided personalized therapy for muscle-invasive bladder cancer

Isotopically Selected Co‐Doping of ¹²¹ Sb and ¹²³ Sb Pairs in Silicon

ABSTRACT A reliable route to the deterministic fabrication of impurity ion donors in silicon is required to advance quantum computing architectures based upon such systems. This paper reports the ability to dope isotopically‐defined unique ( 121 Sb 123 Sb) 2+ molecular ions into silicon with measured detection efficiencies of 94% being obtained. Atomically resolved imaging of the doped Sb ions reveals substitutionally incorporated atoms with a Sb‐to‐Sb separation of ≈2 nm post‐implantation, thus indicating suitability to form coupled qudit systems. Molecular dynamics simulations support the preference for doped Sb atoms to occupy lattice sites, driven by fast (≈1s) re‐crystallization of localized ion implantation induced damage at 300 K. The Sb doping method used is fully compatible with integration into processing that includes pre‐enrichment of the silicon host to sub‐3 ppm 29 Si levels. As such, we present a potential pathway to the creation of scaled qudit arrays within silicon platforms for quantum computing.

Stable Glycerol Electrooxidation to Glycerate Over 1000 Hours on a Hydroxyl‐Modulated PdNiMo Alloy

ABSTRACT The electrochemical upgrading of glycerol into a single, valuable C 3 product remains a long‐standing challenge, constrained by the limitations of insufficient activity, low selectivity, and poor stability. Here, we report a ternary PdNiMo alloy catalyst that synergistically modulates the electronic structure and optimizes the surface *OH coverage for efficient and stable glycerol‐to‐glycerate conversion. Combined experimental and theoretical studies reveal that Mo incorporation downshifts the d‐band center and weakens *OH binding, while Ni introduction optimizes the balance between *OH‐covered and free Pd sites. The resulting PdNiMo catalyst exhibits exceptional GEOR performance, achieving a high current density of 171 mA cm −2 at 0.8 V vs. RHE and a superior glycerate selectivity of 67.5%. More impressively, in a membrane electrode assembly electrolyzer, the catalyst demonstrates outstanding durability, maintaining a current density of over 50 mA cm −2 for more than 1000 h at a cell voltage of 1.2 V cell . This work elucidates the critical role of tailored hydroxyl coverage in selective oxidation and provides a design principle for advanced electrocatalysts in renewable energy‐powered electrosynthesis.

Association between genomic classifier scores and initial management of localized prostate cancer in a population-based cohort in the United States.

350 Background: Tissue-based gene expression assays provide prognostic information in prostate cancer, but their independent clinical value, particularly in guiding the use of initial treatment versus active surveillance (AS), remains uncertain. We evaluated the association between results of a 22-gene genomic classifier (GC) and initial management in a novel, population-based sample linking genomic and clinical data. Methods: We leveraged the Surveillance, Epidemiology, and End Results – Decipher linked database, which integrates incident prostate cancer diagnoses during 2010-2018 with Decipher Prostate GC test orders and results. Patients included in our analysis had low-risk or favorable intermediate-risk prostate cancer, underwent biopsy-based GC testing, and had complete demographic and clinical data (PSA, Gleason grade group, stage, NCCN risk category). First-course management was classified as immediate therapy (surgical or radiation) versus AS. GC scores were categorized based on commonly used thresholds: low (&lt;0.45), intermediate (0.45–0.60), or high (&gt;0.60). We used multivariable logistic regression to assess the association between the receipt of AS versus immediate treatment and GC scores, adjusting for demographic, clinical, and pathological covariates, with stratification by clinical risk group (low- or intermediate-risk). Results: Among 2,547 men with low- or favorable intermediate-risk prostate cancer, 744 (72.2%) with low-risk disease and 404 (26.6%) with intermediate-risk disease were managed initially with AS. In those with low NCCN risk disease, the proportion managed with initial AS was higher in those with low GC scores (419/527 [79.5%]), compared to 218/304 (71.7%) with intermediate GC scores and 107/199 (53.8%) with high GC scores (p&lt;0.001). Similarly, among those with intermediate-risk disease, AS was more common in those with low GC scores (239/562 [42.5%]) compared to 103/425 (24.2%) with intermediate GC scores and 62/530 (11.7%) with high GC scores, p&lt;0.001 (Figure). In the low-risk group, higher GC scores were independently associated with lower odds of AS versus treatment (compared to low GC, intermediate GC: odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.49–0.97, p=0.033; high GC: OR=0.29, 95% CI: 0.20–0.43, p&lt;0.001). In the intermediate-risk group, the associations were of greater magnitude (intermediate GC: OR=0.42, 95% CI: 0.31–0.57, p&lt;0.001; high GC: OR=0.19, 95% CI: 0.14–0.27, p&lt;0.001). Conclusions: In this analysis of the first publicly available population-based linkage of genomic and clinical data, higher GC scores were independently associated with lower odds of AS among men with low- or intermediate-risk prostate cancer in the United States.

ECOG ACRIN EA8192 cohort C: A phase II trial of neoadjuvant gemcitabine/durvalumab in patients (pts) with high grade (HG) upper tract urothelial carcinoma (UTUC) ineligible for cisplatin-based chemotherapy.

749 Background: There is mounting data for neoadjuvant chemotherapy use in HG UTUC, but the role of neoadjuvant chemoimmunotherapy remains less clear, including in cisplatin-ineligible pts, representing an unmet need in this population. Our multicenter trial evaluated the efficacy and safety of neoadjuvant gemcitabine/durvalumab (GD) in pts with HG UTUC. Methods: Cisplatin-ineligible pts with localized cN0 HG UTUC planned for radical nephroureterectomy (NU) were assigned to 4 GD cycles. Primary endpoint was pCR (ypT0N0/x); accrual goal was 29 pts; 18% pCR was considered worthy of further study, while 4% pCR would not justify further pursuit. Simon’s two stage design was used and if ≥1 out of the first 14 pts (13 evaluable) had pCR in stage I, another 15 pts (14 evaluable) would be accrued. With 27 evaluable (eligible and treated) pts, success was defined as ≥3 pCRs. Secondary endpoints included safety/tolerability, event-free survival (EFS) and overall survival (OS) both measured from registration and disease-free survival (DFS) measured from NU. Results: From 2022–2025, 31 pts enrolled (19 men) with median age 79 (44-88), including 15 renal pelvis, 15 ureteral, and 1 multifocal tumor; 5 with sessile appearance. Thirty pts were eligible and received ≥ 1 therapy dose and 23 completed all 4 planned cycles. Three patients achieved pCR (10%; 90%CI: 3.0 - 25.2%), 10 achieved pathologic stage &lt; ypT2N0/x (33%, 90%CI: 19.3 – 49.9%). All 30 pts experienced treatment-related adverse events (TRAEs), 13 experienced G3-4 TRAEs (most common were anemia and neutropenia: 4 pts each), with no G5 TRAE. Among pts who underwent NU, median time from last neoadjuvant dose to NU was 10 weeks (range 5-22 weeks); 6 pts did not have lymph node dissection; 5 treated pts did not undergo NU: 1 due to progression before NU, 1 due to unresectable tumor, 1 due to cancer-related death, 1 due to refusal of further intervention, 1 due to deconditioning. With median follow-up of 11 months, the estimated 1-year EFS was 77.4% (60.9 – 98.3%). Conclusions: Neoadjuvant GD was feasible and relatively well tolerated in pts with HG UTUC; associated with 10% pCR, 33% &lt; ypT2N0/x and promising 1-year EFS. Follow-up continues to further assess EFS, DFS, OS, while biomarker analysis is planned. Lymph node dissection for pts with HG UTUC is standard of care. The addition of durvalumab to accelerated MVAC chemotherapy is being evaluated in the randomized phase 3 part of this trial for cisplatin eligible patients (cohort A vs B; NCT04628767). Clinical trial information: NCT04628767 .

A novel methodology to study the release of fragmented fibres, including microplastics, in laboratory washing conditions

Abstract Fragmented fibres, including fibrous microplastics, are increasingly recognised as a major pollutant originating from textile laundering. While many studies have quantified fibre release, the mechanisms underlying fibre fragmentation and detachment remain poorly understood, partly due to the lack of techniques to capture fibre–flow interactions under controlled conditions. This study introduces a novel methodology for the simultaneous characterisation of turbulent flow and textile fibre dynamics under simulated washing conditions. The approach combines a Von Kármán Swirling Flow apparatus, which generates reproducible shear and turbulence, with dual high-speed imaging to record both the fluid, analysed using Particle Image Velocimetry, and the fibres, analysed using optical flow. Proof-of-concept experiments with polyester and cotton yarns demonstrate that the method can capture fibre motion, deformation, and protrusion in synchrony with surrounding flow fields. A Reynolds number definition for top- and front-loading washing machines is also proposed, providing a basis for comparing washing conditions. This reproducible, non-invasive framework establishes a foundation for systematic investigations of fibre behaviour during laundering by providing mechanistic insight into fibre breakage and release processes that underpin textile-derived pollution, which is not covered by existing gravimetric methods that quantify mass release from textiles.

Sasanlimab plus bacillus Calmette-Guérin in BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC): Exploratory biomarker analysis of the phase 3 CREST trial.

806 Background: The primary analysis of the phase 3 CREST trial (NCT04165317), evaluating sasanlimab, a PD-1 inhibitor, combined with BCG induction and maintenance (I+M) showed statistically significant and clinically meaningful improvement in event-free survival (EFS) vs BCG-I+M alone in patients (pts) with BCG-naive, high risk, non-muscle invasive bladder cancer (NMIBC). A trend toward improved EFS was noted in pts with high PD-L1 expression treated with sasanlimab and BCG-I+M. We present additional exploratory analyses examining associations between tumor microenvironment (TME)-related features and response to sasanlimab plus BCG-I+M. Methods: Pre-treatment tumor biopsies were assessed for CD8 + T-cell infiltration by immunohistochemistry (IHC) (N = 609), tumor mutational burden (TMB) by whole exome sequencing (WES) (N = 543), and gene expression by whole transcriptome sequencing (WTS) (N = 534). Exploratory analyses were performed correlating these features with EFS using Cox proportional hazards models. Results: Neither baseline tumor-infiltrating CD8⁺ T cells nor TMB was associated with improved EFS with sasanlimab in combination with BCG I+M versus BCG I+M alone. This observation, coupled with our previously reported PD-L1 data (Powles, ASCO, 2025), suggested that single biomarkers may not adequately reflect the complexity of the TME and we therefore focused on transcriptomic analyses. Transcriptomic profiling revealed that inflammatory and immune signatures (effector and inhibitory signatures) were associated with inferior EFS in the BCG monotherapy arm, but not in the sasanlimab plus BCG-I+M arm. Consistent with these findings, bladder cancer transcriptomic subtypes known to be heavily immune infiltrated, such as UROMOL class 2b and TCGA luminal infiltrated, were associated with poor EFS with BCG-I+M but demonstrated improved EFS with sasanlimab+BCG-I+M (HR = 0.41 [95% CI, 0.23-0.75], P &lt; 0.01; HR = 0.46 [95% CI, 0.25-0.86], P = 0.01 respectively). Importantly, such immunobiological features were present in subsets of tumors across NMIBC stages, underscoring that stage alone does not reflect the biological heterogeneity captured by transcriptomic profiling. Conclusions: These findings demonstrate that pre-treatment NMIBC TMEs characterized by high immune infiltration are associated with poor outcomes with BCG monotherapy, potentially due to BCG promoting further upregulation of inhibitory molecules and adaptive immune resistance. The addition of sasanlimab to BCG-I-M may help overcome this resistance, offering a promising therapeutic strategy for pts with immune-infiltrated high-risk NMIBC. This combination has the potential to address a critical unmet need in the management of high-risk NMIBC, particularly within molecular subgroups associated with poor outcomes with BCG monotherapy. Clinical trial information: NCT04165317 .