Browse Articles

A composite biomarker approach to withhold neoadjuvant chemotherapy in select muscle-invasive bladder cancer patients.

841 Background: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) is recommended for muscle-invasive bladder cancer (MIBC). However, we propose a composite biomarker approach of circulating tumor cell status and gene expression to select patients in whom NAC may be omitted. Methods: Transurethral resection of bladder tumor (TURBT) samples were collected from patients with cT2-T4aN0-N1M0 MIBC who were included in the prospective CirGuidance study (NL3954), in which circulating tumor cells (CTC) were enumerated using the CELLSEARCH system. Expression profiling was performed using the validated Decipher Bladder genomic subtyping classifier to determine luminal and non-luminal molecular subtypes (Veracyte, Inc.). The luminal favorable subtype was determined using a lncRNA-based classifier (de Jong et al. 2019 & 2024). The primary endpoint was cancer-specific mortality (CSM), calculated from the date of study inclusion to the date of bladder cancer related death. Results: In the CirGuidance study (n = 231), most patients (n = 213; 92%) underwent RC without NAC, while (n = 18) received NAC plus RC. Among RC-only patients, CTCneg status (n = 172) was associated with a two-year CSM of 21% versus 41% in CTCpos patients (Gray’s test, p = 0.01). No significant differences were observed in the distribution of molecular subtypes between CTCpos or CTCneg patient subgroups. Within CTCneg patients treated with RC alone, 2-year CSM was 14% in luminal (n = 77, 36%) versus 25% in non-luminal (n = 136, 64%) whereas in CTCpos patients it was 38% and 44%, respectively. Among 18 NAC plus RC treated patients, non-luminal subtype (n = 10) had a two-year CSM of 11%, whereas in luminal subtype it was 27%, similar to outcomes when treated with RC alone. Importantly, the lncRNA-based luminal favorable classifier identified 26 patients with luminal favorable subtype among CTCneg patients with 0% CSM at two years (MVA p = 0.02) when treated with RC alone. Conclusions: We identified a biomarker-defined subgroup of MIBC with more favorable outcomes after RC alone. These findings support the future prospective validation of CTC and molecular subtyping as a tool to guide NAC selection.

Phase 1/2 study of an anti-PD-L1/IL-15 variant fusion protein (SIM0237) in BCG-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC).

764 Background: Treatment options for BCG-unresponsive (UR) NMIBC are limited. Anti-PD-1 monotherapy and IL-15 agonist in combination with BCG have shown clinical efficacy in BCG-UR carcinoma in situ (CIS) NMIBC. It remains unclear whether targeting both PD-(L)1 and IL-15 has synergistic effect in NMIBC. SIM0237 is an anti-PD-L1/IL-15 variant fusion protein. The single agent showed good safety profile and promising efficacy signal in patients with BCG-UR NMIBC in the dose escalation part. This abstract reported data from the dose escalation and expansion parts of SIM0237 monotherapy from the ongoing Phase 1/2 study (NCT06186414). Methods: Patients with BCG-UR high-risk NMIBC received intravesical SIM0237 following the standard induction/maintenance treatment schedule. A re-induction course was allowed if the patients had persistent CIS or high-grade Ta at Month 3. Key study endpoints included DLT, safety, tolerability, PK and efficacy [complete response (CR) rate and duration of CR for CIS NMIBC, disease-free survival (DFS) and DFS rate at specific time points for papillary-only NMIBC]. Results: From January 10, 2024 to the data cutoff date of August 8, 2025, a total of 43 patients (10 CIS with or without Ta/T1, 33 papillary-only) have received SIM0237 monotherapy, with 3, 10 and 30 patients at the dose levels of 75 mg, 150 mg and 300 mg, respectively. The median age was 62 years, with 81% male. The median number of prior BCG doses was 13. Of the 7 CIS patients who had at least 1 post-baseline tumor assessment, 6 achieved a best response of CR and 5 were maintaining the CR status. In the 33 papillary-only patients, the median follow-up duration was 4.57 months. The median DFS was immature, with a 12-month DFS rate of 75.4% (95% CI, 48.9%-89.4%). TEAEs occurred in 38 (88.4%) patients and 23 (53.5%) patients had TRAEs. The majority of TRAEs were Grade 1/2 and limited in the urinary system. Nine (20.9%) patients had Grade 3 TEAEs and 1 (2.3%) had Grade 3 TRAEs. No Grade 4 or 5 TEAEs were reported. Four (9.3%) patients had SAEs and 1 had TRSAEs of urinary bladder haemorrhage and prostatic haemorrhage. Ten (23.3%) patients had dose interruptions due to TEAEs, and 4 (9.3%) had dose interruptions due to TRAEs. No DLT, immune-related AE or AE leading to SIM0237 discontinuation. PK data showed undetectable systemic exposure of SIM0237 in all 29 patients with serum samples analyzed. Conclusions: Intravesical SIM0237 was safe and well tolerated with promising clinical efficacy in patients with BCG-UR high-risk NMIBC. The Phase 3 study of SIM0237 monotherapy in this patient population is under plan. Clinical trial information: NCT06186414 .

Early relative dose intensity to predict survival outcomes in patients treated with enfortumab vedotin for metastatic urothelial carcinoma.

683 Background: Enfortumab vedotin (EV) is a standard therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy and immune checkpoint inhibitors. However, optimal early dosing strategies remain unclear in real-world practice. Maintaining relative dose intensity (RDI) may influence efficacy, yet the prognostic role of early RDI (eRDI) and its relationship with adverse event–related dose modification (AE-DM) are not well defined. Clarifying whether early dose modification affects outcomes is crucial for balancing efficacy and tolerability in EV therapy. Methods: We retrospectively analyzed 119 patients with mUC treated with EV monotherapy at multiple Japanese institutions from 2021 to 2024. Among them, 84 patients who underwent at least one post-baseline radiographic assessment and did not show early progressive disease (PD) were included in the efficacy analysis. Early RDI was defined as the mean RDI during the first three months. AE-DM was defined as any reduction, delay, or interruption due to toxicity. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared using the log-rank test, stratified by AE-DM status (positive or negative). Results: In the PD-excluded cohort, patients with eRDI ≥80% had significantly longer PFS and OS than those with eRDI <80% (median PFS: 8.5 vs 4.3 months, p=0.008; OS: not reached vs 11.2 months, p=0.012). Among AE-DM–negative patients, low eRDI predicted worse outcomes (median PFS: 11.7 vs 4.2 months, p=0.001; OS: not reached vs 13.8 months, p=0.021). Conversely, in AE-DM–positive patients, survival did not differ between eRDI groups, suggesting that clinically guided dose modification did not compromise efficacy. Conclusions: Early RDI predicted survival in patients who tolerated standard dosing without AE-DM, whereas dose modification for toxicity preserved efficacy. Maintaining early intensity is important for fit patients, while individualized dose modification may ensure safety and effectiveness in those with AE-DM. eRDI may serve as a practical early indicator in real-world EV therapy. Survival outcomes according to eRDI and AE-DM status. Cohort n Median PFS (months, eRDI ≥80% vs <80%) p-value Median OS (months, eRDI ≥80% vs <80%) p-value All PD-excluded 84 8.5 vs 4.3 0.008 NR vs 11.2 0.012 AE-DM (−) 49 11.7 vs 4.2 0.001 NR vs 13.8 0.021 AE-DM (+) 35 6.3 vs 6.1 0.67 15.1 vs 14.9 0.82 PFS, progression-free survival; OS, overall survival; eRDI, early relative dose intensity; PD, progressive disease; AE-DM, adverse event-related dose modification; NR, not reached.

Atomic‐Level Interactions Enable “Near‐Zero Strain” Cathodes for Ultra‐Stable Aqueous Magnesium‐Ion Batteries

ABSTRACT Aqueous magnesium‐ion batteries (AMIBs) are promising next‐generation energy storage devices owing to their high safety, theoretical capacity, and resource abundance. However, the strong electrostatic interactions between Mg‐ions and conventional cathodes usually lead to poor cycling stability and limited rate capability. Herein, we, for the first time, introduced “Near‐Zero Strain” engineering in AMIBs to developed the proof‐of‐the‐concept high entropy Prussian blue analog (HEPBA) cathodes materials with ultra‐stable cycling performance. The atomic‐level interactions and long‐range disordered lattice strain field enable HEPBA to spontaneously respond to ion intercalation‐induced stress with reversible changes in lattice structure, achieving one of the best long‐term stability among AMIBs (above 96.7% capacity retention after 20 000 cycles at a high current density of 5.0 A g − 1 ). Meanwhile, diverse metal atoms with overlapped d ‐band toward optimized HEPBA features efficient charge compensation with drastically enhanced rate capability (over 80.1 mAh g −1 at 5.0 A g − 1 ). Overall, the novel near‐zero strain engineering strategy toward cathode materials in this work revealed the enormous potentiality to improve multivalent‐ion batteries performance.

Mistletoe‐ and Mussel‐Inspired Fabrication of Hierarchically Structured Protein‐Cellulose Scaffolds From Biomolecular Condensates

ABSTRACT Nature's ability to produce hierarchical materials via biomolecular self‐assembly can inspire bioinspired avenues to advanced materials using biorenewable components and water as a solvent. Recent advances indicate that biomolecular condensates are important precursor phases for fabricating biological materials. Here, we leverage recent findings on the role of malleable biomolecular phases from both animal and plant systems to develop a synergistic mussel‐ and mistletoe‐inspired approach for fabricating protein‐cellulose composite scaffolds possessing tunable hierarchical structure. We demonstrate that recombinant mussel foot protein‐1 (rMfp‐1), undergoes controlled phase separation when mixed with surface‐functionalized anionic cellulose nanorods, forming condensates with characteristic core‐shell morphology. Using a facile approach based on freeze‐drying of suspensions, we produce freestanding protein‐cellulose composite scaffolds possessing tunable porous structures with potential as scaffolds for tissue engineering. Through a cross‐disciplinary approach combining various spectroscopic and imaging modalities, we gain mechanistic insights into the role of intermolecular interactions and physical processes in guiding this process. These findings highlight that hierarchically structured materials can be fabricated simply via multi‐component phase separation. This work establishes a framework for understanding and controlling bio‐inspired material fabrication, offering a strategy to engineer materials with tunable structure and properties that bridge biomaterials research and emerging directions in synthetic biology.

Structural and mechanistic characterization of heparin interactions with tau fibrils

Overall survival (OS) in elderly, frail, or high comorbidity veterans receiving androgen receptor pathway inhibitors (ARPIs) with androgen-deprivation therapy (ADT) vs ADT alone for de novo metastatic castration-sensitive prostate cancer (mCSPC).

103 Background: Clinical trials and real-world analyses have shown that combining an ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide) + ADT improves survival vs ADT alone in patients with mCSPC. However, limited data exist on the impact of ARPI + ADT in patients who are elderly, frail, or who have a high comorbidity burden, since these patients are underrepresented in clinical trials. This real-world study evaluated characteristics and OS in this unique cohort of patients with de novo mCSPC. Methods: This observational cohort study used Veterans Health Administration electronic medical records to compare OS and patient characteristics in veterans with de novo mCSPC treated with ARPI + ADT vs ADT alone. Patients were ≥75 years of age, had a Veterans Affairs Frailty Index (VA-FI) score >0.2, or had a Charlson Comorbidity Index (CCI) score ≥3. Patients were indexed on their first claim for ADT between June 01, 2017, and December 31, 2022, and followed until censoring on June 01, 2025, or death. A multivariable, time-varying Cox model, adjusted for age, body mass index, CCI, and prostate-specific antigen (PSA) level, was used to estimate mortality risk and account for time between ADT and ARPI initiation. Results: Of 2398 total patients, 1037 (43.2%) received ARPI + ADT and 1361 (56.8%) received ADT alone. Median follow-up was 27.1 months. Compared to ADT alone, patients receiving ARPI + ADT were younger (median age 76.7 vs 81.2 years; SMD: -0.43), had a lower comorbidity burden (CCI ≥3: 49.0% vs 55.2%; SMD: 0.19), were less frail (VA-FI >0.2: 66.5% vs 71.5%; SMD: 0.11), and had a similar median PSA level (121.3 ng/mL vs 130.0 ng/mL; SMD: 0.02). ARPI + ADT was associated with a significantly lower risk of death (adjusted hazard ratio [aHR]: 0.81; 95% confidence interval [CI]: 0.74–0.90; P <0.001) vs ADT alone. Median OS was 33.0 months (95% CI: 30.2–35.9) for ARPI + ADT and 23.3 months (95% CI: 21.4–25.1) for ADT alone. Significant improvements in OS were consistent among age, CCI, and VA-FI subgroups (Table). Conclusions: In this real-world cohort of veterans with de novo mCSPC who were elderly, frail, or who had a high comorbidity burden, ARPI + ADT was associated with significantly longer OS in overall and subgroup analyses. These findings support the use of ARPI + ADT in this patient population. Subgroup ARPI + ADTMedian survival, months (95% CI), n ADT aloneMedian survival, months (95% CI), n aHR (95% CI) a , P value Age ≥75 years 33.1 (29.6–36.7),n = 645 22.7 (20.6–24.7),n = 995 0.85 (0.75–0.96), P <0.01 CCI score ≥3 29.0 (24.9–33.1),n = 508 19.6 (17.8–21.4),n = 751 0.75 (0.65–0.86), P <0.001 VA-FI score >0.2 27.1 (24.2–30.0),n = 690 19.7 (18.0–21.4),n = 973 0.81 (0.72–0.91), P <0.001 a ADT = reference group.

Stockholm3-MRI population-based screening: Two-year outcomes comparing Stockholm3 and PSA.

314 Background: Diagnostic accuracy estimates for prostate cancer tests are often biased when biopsy verification depends on the index test. Using population registry follow-up, we compared two-year detection of clinically Grade Group 2 or higher (GG2) prostate cancer between PSA and a Stockholm3 pathway in the STHLM3-MRI trial. Methods: In the prospective STHLM3-MRI trial (NCT03377881), men aged 50-74 years provided blood for PSA and Stockholm3. Cancer diagnoses within 2 years of blood draw were ascertained by linkage to the Swedish National Cancer Registry; men alive and not emigrated at the end of the 2 years were considered for the analysis. The prespecified thresholds were PSA ≥ 3 ng/mL and Stockholm3 ≥ 11. Sensitivity, specificity, PPV, and NPV were estimated with 95% CIs; paired differences were tested with McNemar tests. Results: Among 12,670 men, 443 (3.5%) were diagnosed with GG2, including 40 interval cancers (men diagnosed after a negative test during follow-up). At Stockholm3 ≥ 11 the sensitivity was 90% (95% CI, 87–93), specificity 89% (95% CI, 89–90), PPV 24%, and NPV 99%. At PSA ≥ 3 ng/mL the sensitivity was 74% (95% CI, 69–78), specificity 90% (95% CI, 90–91), PPV 21%, and NPV 99%. Per 1000 men screened, Stockholm3 detected 31.6 GG2 prostate cancers vs. 25.8 with PSA (absolute difference 5.8/1000), with false positives 101.8 vs. 95 per 1000 and missed GG2 3.4 vs 9.2 per 1000. Differences in sensitivity were significant (p<0.001). Conclusions: In a population-based screening setting with registry follow-up that reduces verification bias, the Stockholm3 pathway detects more GG2 prostate cancers within 2 years than PSA while maintaining comparable specificity. Clinical trial information: NCT03377881 . Operating characteristics of Stockholm3 and PSA, reporting sensitivity, specificity, PPV, NPV and AUC for diagnosis of GG2 prostate cancer within the 2-year follow-up with 95% CI for Stockholm3 (≥11 and ≥15) and PSA ( ≥ 3 and ≥ 4 ng/mL). Metric Stockholm3 ≥ 11 Stockholm3 ≥ 15 PSA ≥ 3 PSA ≥ 4 Sensitivity 0.90 (0.87–0.93) 0.75 (0.71–0.79) 0.74 (0.69–0.78) 0.52 (0.47–0.57) Specificity 0.89 (0.89–0.90) 0.95 (0.94–0.95) 0.90 (0.90–0.91) 0.95 (0.94–0.95) PPV 0.24 (0.22–0.26) 0.33 (0.30–0.36) 0.21 (0.19–0.24) 0.26 (0.23–0.29) NPV 0.99 (0.99–0.99) 0.99 (0.99–0.99) 0.99 (0.99–0.99) 0.98 (0.98–0.98) AUC 0.96 (0.95–0.96) 0.96 (0.95–0.96) 0.93 (0.92–0.94) 0.93 (0.92–0.94)

Association of prior 5-α-reductase inhibitor exposure with ICI benefit in metastatic RCC: Multicentre cohort with single-cell immune profiling.

521 Background: Immune checkpoint inhibitors (ICIs) improve survival in metastatic renal cell carcinoma (mRCC), yet responses remain heterogeneous. Androgen-axis signalling can dampen CD8⁺ T-cell function; thus, prior exposure to 5-α-reductase inhibitors (5-ARIs; finasteride/dutasteride) may favour ICI efficacy by reshaping the tumour immune microenvironment. Methods: Design, Setting, and Participants: Multicentre retrospective cohort of 185 mRCC patients receiving ICIs (2015–2020) at three tertiary hospitals. Patients were stratified by documented continuous 5-ARI use ≥12 months before ICI initiation; propensity score matching (PSM) balanced baseline covariates. A subset of fresh tumours underwent scRNA-seq. Intervention: ICIs alone or in standard combinations; prior finasteride/dutasteride exposure as the key variable of interest. Outcome Measurements and Statistical Analysis: Primary endpoints: progression-free survival (PFS) and overall survival (OS) by Kaplan–Meier and multivariable Cox models. Secondary endpoints: objective response rate (ORR), disease control rate (DCR), time to response, duration of response, and safety. Subgroup/sensitivity analyses were pre-specified; scRNA-seq profiled immune cell states and PD-1 expression. Results: After PSM, groups were well balanced. Prior 5-ARI exposure associated with higher ORR (59.8% vs 39.8%, p=0.0075) and numerically higher DCR (87.0% vs 78.7%). Survival favoured the 5-ARI group (PFS HR 0.64, 95%CI 0.47–0.86, p=0.0085; OS HR 0.65, 95%CI 0.47–0.90, p=0.0271), with 3-year OS 31.2% vs 15.0%. Responses occurred earlier (median TTR 2.8 vs 4.05 months) and lasted longer (DoR 7.5 vs 1.8 months; both p<0.001). Grade ≥III adverse events were not increased. scRNA-seq showed reduced Tregs, lower CD8⁺ T-cell exhaustion and decreased PD-1 expression within exhausted CD8⁺ subsets among 5-ARI-exposed patients, suggesting an immunologically favourable milieu. Benefits were generally consistent across age, IMDC risk, PD-L1 status and metastatic burden. Conclusions: Pre-treatment exposure to 5-ARIs correlates with meaningfully improved ICI effectiveness and favourable immune reprogramming in mRCC. These findings support prospective trials testing androgen-axis modulation as an inexpensive, scalable adjunct to immunotherapy and warrant evaluation of 5-ARI history as a readily available clinical stratifier.

OMAHA-004: Phase 3 trial of CYP11A1 inhibitor opevesostat versus androgen receptor pathway inhibitor (ARPI) switch in participants with metastatic castration-resistant prostate cancer (mCRPC) after a prior ARPI.

TPS299 Background: Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), a catalyst of the first and rate-limiting step of steroid biosynthesis. Opevesostat showed antitumor activity in participants with heavily pretreated mCRPC in the phase 1/2 CYPIDES trial. The randomized, open-label, phase 3 OMAHA-004 trial (NCT06136650) is designed to evaluate the efficacy and safety of opevesostat in participants with mCRPC after a prior ARPI. Methods: Eligible participants have mCRPC that progressed during androgen deprivation therapy ≤6 months before screening and on or after 1 ARPI for metastatic or nonmetastatic hormone-sensitive prostate cancer (HSPC) or CRPC for ≥8 weeks (≥14 weeks with bone progression). Prior ARPI plus docetaxel for HSPC is permitted if participants received no more than 6 cycles of docetaxel without radiographic disease progression. Approximately 1314 participants will be randomized 1:1 to opevesostat 5 mg orally twice-daily plus dexamethasone 1.5 mg and fludrocortisone 0.1 mg orally once daily or abiraterone acetate 1000 mg orally once daily plus prednisone 5 mg orally twice daily (if prior enzalutamide, darolutamide, or apalutamide) or enzalutamide 160 mg orally once-daily (if prior abiraterone). Stratification factors are metastatic site (bone only vs liver vs other), androgen receptor ligand binding mutation (AR-LBDm) status (positive vs negative), and prior docetaxel treatment for HSPC (yes vs no). Once the predefined enrollment threshold for participants with either mutation status (AR-LBDm-positive, ~400 participants or AR-LBDm-negative, ~914 participants) is met, no additional participants with that mutation status will be permitted to enroll. The protocol was amended to use radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 by blinded independent central review (BICR), analyzed separately in participants with AR-LBDm–positive and –negative disease, as the primary end point and overall survival as a key secondary end point. Other secondary end points include time to initiation of first subsequent anticancer therapy or death, objective response rate and duration of response per PCWG3-modified RECIST v1.1 by BICR, time to pain progression; time to prostate-specific antigen (PSA) progression, PSA response rate, time to first symptomatic skeletal-related event, and safety and tolerability. Enrollment is ongoing. Clinical trial information: NCT06136650 .

Quantum Dots Encapsulated in Porous Matrices for Artificial Photosynthesis: From H ₂ Evolution to CO ₂ Reduction and Beyond

ABSTRACT Semiconductor quantum dots (QDs) have emerged as promising materials for artificial photosynthesis, owing to their exceptional light‐harvesting capabilities, efficient exciton generation, and tunable surface properties. However, challenges still remain in enhancing their solar‐to‐chemical conversion efficiency, reaction selectivity, long‐term stability, and diversification of redox reactions. A promising strategy to address these limitations involves the precise confinement of QDs within porous matrices (either flexible or rigid frameworks), which offers new opportunities for advanced artificial photosynthetic systems. Furthermore, recent progress in nanomaterial synthesis and advanced characterization techniques has enabled innovative approaches for encapsulating QDs in porous matrices. This review systematically summarizes recent advancements in this field, covering fabrication strategies, charge carrier dynamics, and emerging functionalities. First, the predominant synthetic approaches is discussed, including “ship‐in‐a‐bottle” and “bottle‐around‐the‐ship” methods, along with the benefits and challenges of QD encapsulation in porous matrices. Next, key applications is highlighted, such as photocatalytic H 2 evolution, CO 2 photoreduction, and organic photoredox catalysis, providing mechanistic insights and performance comparisons. Finally, current challenges is outlined and future study directions to inspire the rational design of QD/porous material composites for large‐scale, practical photochemical applications and beyond.

Sustainable Continuous Scale Synthesis of Positive Material for High‐performance Wearable Aqueous Zn Metal Batteries

ABSTRACT One factor limiting the development of wearable, aqueous zinc metal batteries has been the inability to continuously synthesize high‐performance positive electrodes quickly, efficiently, and sustainably. In this work, a continuous and scalable synthesis of high‐performance positive electrodes at room temperature by situ electrochemical synthesis and activation of MOF materials on flexible current collectors was developed. The process avoids the time‐consuming, material‐consuming, energy‐intensive, and hazardous ‘one pot’ solvothermal method commonly used, and yields flexible positive electrodes (Ni 0.7 Co 0.3 (HBTC)(4,4′‐bipy) based double hydroxide on flexible substrates) with good performance. After matching with a negative electrode made out of zinc, the energy densities of the whole wearable devices reach ∼319 Wh L −1 for fiber batteries and ∼264 Wh L −1 for planar batteries, respectively. This advancement can provide an effective method to narrow the gap between lab and industrial production and promote the practical application of wearable aqueous zinc metal batteries.

Rainbow Photonic Crystals: Self‐Assembly of Carbohydrate Bottlebrushes Block Copolymers

Abstract Tunable and responsive photonic crystal systems are the subject of great research interest owing to their ability to actively respond to chemical, physical, biological, and other external stimuli. In this study, a new series of well‐defined and novel carbohydrate‐based bottlebrush copolymers are introduced, exhibiting narrow molecular weight (M n ) distributions in the range of 823.5 to 1455.0 kDa. These bottlebrushes self‐assemble into 1D photonic crystals (1D‐PCs), and their self‐assembly in lamellae structures is investigated using a wide range of techniques. The 1D‐PCs formed from different bottlebrushes display a full spectrum of colors, ranging from colorless to rainbow colors, including blue, green, orange, and red, effectively spanning the entire UV–vis range. Remarkably, a very fast (a few seconds) change in the color is obtained simply by different solvent, a consequence of the lamellae domain swelling. This demonstrates the impressive tunability, fast responsiveness, and reversibility of these systems. Furthermore, by mixing the bottlebrushes with small carbohydrates, their optical properties can be further modified, achieving a red shift in reflective colors from orange to red. This approach provides a flexible strategy for tailoring the optical characteristics of photonic crystals without the need for synthesizing new carbohydrate‐based bottlebrushes, thus offering a versatile platform for controlling their properties.

Target validation uncouples mitochondrial translocator protein from 19-Atriol-mediated inhibition of steroidogenesis and identifies enzymatic targets

Real-world darolutamide safety and effectiveness in nonmetastatic castration-resistant prostate cancer (nmCRPC) by lipid-modifying agent use: Post hoc analyses of DAROL interim analysis 4 (IA4).

99 Background: Darolutamide is approved for nmCRPC based on significant metastasis-free survival (MFS) and overall survival (OS) benefits vs placebo and favorable safety in the phase 3 ARAMIS study. DAROL is assessing real-world outcomes with darolutamide in patients with nmCRPC. In this elderly population, many patients are receiving lipid-modifying agent (LMA) therapy. We assess the impact of the darolutamide + LMA combination on safety and effectiveness of darolutamide. Methods: DAROL is an ongoing, international, multicenter, prospective, open-label, single-arm, noninterventional study in patients with nmCRPC treated with darolutamide according to local practice. The primary endpoint is safety. OS and MFS are secondary endpoints. Concomitant LMA use was defined as LMA starting before darolutamide and continuing during darolutamide therapy. Using inverse probability of treatment weighting adjusting for baseline factors, the LMA subgroup was compared with all other patients (No LMA). Results: IA4 was conducted when 799 patients had received ≥12 months of treatment. Of these, 258 (32%) were receiving LMAs at baseline: statin n=251, non-statin n=35 (some patients received >1 LMA). Prostate cancer characteristics were similar between LMA and No LMA subgroups; however, there were important differences in medical history, including more metabolic (91% vs 39%), vascular (84% vs 66%), and cardiac (46% vs 21%) disorders in the LMA vs No LMA subgroup; fatigue incidence was 4% vs 2% at baseline; 7% in each subgroup had a medical history of hepatic disorders. Darolutamide maintained OS in patients with concomitant LMA with no difference vs the No LMA subgroup (adjusted HR 1.01, 95% CI 0.73–1.39); MFS slightly favored the No LMA subgroup (adjusted HR 1.39, 95% CI 1.09–1.77). The LMA vs No LMA subgroup had more treatment-emergent adverse events (TEAEs; 74% vs 55%) and grade 3/4 TEAEs (28% vs 12%), but fewer discontinuations due to TEAEs (7% vs 10%); darolutamide discontinuations due to disease progression were similar in the LMA and No LMA subgroups (17% each). The most frequent TEAEs showed <5% difference between the LMA and No LMA subgroups except for fatigue (16% difference: 27% vs 11% incidence), which may be related to comorbidity burden. Cardiac TEAEs occurred in 8% and 4%, respectively. TEAEs associated with LMAs, including liver abnormalities (LMA 3%, No LMA 2%), did not appear to be increased with concomitant darolutamide. Further effectiveness analyses and data comparing the LMA subgroup with other patients with cardiovascular disease but no LMA therapy will be reported. Conclusions: Darolutamide was well tolerated, with no new safety signals observed in the LMA vs no LMA subgroup. Darolutamide is a standard of care option for nmCRPC in patients irrespective of concomitant LMA use. Clinical trial information: NCT04122976 .

Homologous recombination deficiency signature (HRDsig) in adenocarcinoma of the bladder (ACB): Implications for PARP inhibitor (PARPi) treatment.

853 Background: Pure and predominant non-urachal adenocarcinoma histologies in primary bladder carcinomas are uncommon. Given the interest in expanding the clinical utility of PARPi to new tumor types, we conducted a study of ACB to evaluate their genomic landscape stratified on HRDsig status. Methods: 328 clinically advanced ACB underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of genomic alterations (GA). All patients had clinically advanced disease and were confirmed by central pathology review to be either pure or predominant adenocarcinoma histology at the time of CGP. Genomic ancestry, microsatellite instability (MSI) status, tumor mutational burden (TMB), HRDsig and cosmic trinucleotide signature were analyzed from the CGP data. PD-L1 expression was determined at percentage of tumor proportion score (%TPS) using the Dako 22C3 system. Statistical analysis utilized the Fisher Exact system with the False discovery rate (FDR) corrected using the Benjamini/Hochberg adjustment. Results: Of the 328 ACB cases, 13 (4.0%) were HRDsig-positive (HRDsig+), while 315 (96.0%) were HRDsig-negative (HRDsig-). There were more men with HRDsig+ ACB (92.3% vs 59.7%; NS) and the median age was relatively similar between the groups (median 63 vs 67). Genomic ancestry distribution was similar with a trend towards higher frequencies of EUR ancestry in the HRDsig+ ACB (84.6% vs 66.2%; NS) and AFR ancestry in the HRDsig- ACB (19.7% vs 7.7%; NS). MSI high status was extremely rare in both groups (0.0% vs 1.3%) and the median TMB levels were also similar (3.8 vs 3.5 mutations/Mb) in HRDsig+ and HRDsig-, respectively. An MMR signature was more frequent in the HRDsig+ ACB (15.4% vs 5.4%; NS). HRDsig- ACB over-expressed PD-L1 more frequently than HRDsig+ ACB (15.2% vs 0.0%; NS). Higher frequencies of GA associated with HRDsig+ status were identified in the HRDsig+ ACB but did not reach statistical significance: ATM (15.4% vs 6.0%), BRCA1 (7.7%vs 1.0%), BRCA2 (7.7% vs 1.9%), RAD21 (10.0% vs 4.8%), RAD51C (7.7% vs 0.0%). ERBB2 were uncommon (7.6% in HRDsig- and 0.0% in HRDsig+; NS). KRAS (28.9% vs 0.0%) and TP53 (81.3% vs 76.9%) GA were more frequent in the HRDsig- ACB (NS), whereas GA in PTEN (23.1% vs 4.8%) and MET (7.7% vs 2.2%) were more frequent in the HRDsig+ ACB. Conclusions: At a 4.0% frequency, HRDsig+ status is uncommon in ACB but associated with trends towards particular genomic features, which have the potential to guide future clinical trial designs testing PARPi and other agents in this challenging histology. Limitations include the retrospective nature, lack of clinical outcomes annotation, selection and confounding biases.

Implementing evidence-based first-line therapy for metastatic urothelial carcinoma: A quality improvement initiative in community oncology.

664 Background: First-line (1L) novel combination regimens have transformed outcomes for pts with locally advanced or metastatic urothelial carcinoma (LA/mUC). Community-based healthcare professionals (HCPs) face unique challenges with evolving guidelines and toxicity management. This initiative sought to address these gaps by equipping clinicians with evidence-based tools and strategies to improve care and outcomes. Methods: In Oct–Nov 2024, 31 HCPs from urban community clinics serving underserved populations were surveyed and chart audits were conducted (n = 150; 12% Stage 4, with treatment initiation after Dec 2023) to assess practice patterns and gaps in treatment. In live audit-feedback (AF) sessions, HCPs reviewed findings and developed action plans. Following implementation of action plans, including integration of a bladder cancer management pocket guide, HCPs participated in a PDSA workshop with an expert to review progress and refine processes. Follow-up surveys and chart audits evaluated practice change 6 months post-intervention. Results: Key barriers to evidence-based integration of 1L combination therapies included formulary restrictions (45%), limited evidence or guideline support (42%), and access/insurance barriers (39%). Few HCPs reported performing biomarker testing in every pt (3%). In choosing 1L systemic therapy, HCPs prioritized response rates (45%), pt medical factors (36%), toxicity (32%), and regimen familiarity (32%). Although 52% estimated most of their pts received enfortumab vedotin/pembrolizumab (E/P), chart audits showed only 32% of eligible pts initiated E/P, while 68% received single-agent (SA) immunotherapy (IO). Reasons for non-use included pt preference (58%), toxicity concerns (48%), and pt medical factors (36%), most commonly autoimmune disease (58%) or uncontrolled diabetes (23%). Chart audits revealed adverse events (AE) (52%) was the top reason for 1L treatment discontinuation. Following action plan implementation, HCPs reported making updates to clinical pathways, improvements in biomarker testing, and AE management through pt education and use of the pocket guide. System-level changes included standardized testing, enhanced workflows, and chart audit tracking to sustain practice improvement. Additional follow-up data will be presented. Conclusions: This QI initiative identified gaps in evidence-based integration of 1L combination therapy and biomarker testing for LA/mUC in community settings. Through AF, action planning, and use of a pocket guide, providers improved evidence-based treatment, biomarker testing, shared decision-making, and AE management. These findings highlight the need to strengthen workflows, standardize testing, and support under-resourced clinics, providing a scalable framework to improve LA/mUC care across diverse practice settings.

Clinical characteristics and survival outcomes in veterans receiving radium-223 for metastatic castration-resistant prostate cancer.

112 Background: Radium-223 is an alpha-emitting radiopharmaceutical that selectively targets bone metastases while minimizing damage to surrounding tissue. It is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC), where it improves survival and reduces skeletal-related events. However, the real-world effectiveness of radium-223 and the influence of tumor suppressor gene (TSG) alterations on clinical outcomes remain unclear. Evaluating patient characteristics and survival outcomes in a national veteran population may help identify factors associated with treatment benefit and inform clinical decision-making. Methods: This retrospective cohort study included veterans with mCRPC who initiated radium-223 therapy within the Veterans Health Administration. Demographic and clinical characteristics at treatment initiation included age, BMI, race, PSA within 3 months, and number of radium-223 doses received. Overall survival (OS) was defined from the first radium-223 dose to death, with survivors censored at last follow-up. Kaplan–Meier methods estimated survival outcomes, and subgroup analyses compared OS by TSG alteration status ( PTEN, TP53, RB1 ). Cox regression explored associations between clinical variables and OS. Results: Among 661 veterans, mean age at treatment start was 73 years, mean BMI was 29, and 70% were White, 24% Black, and 6% other race. Each 10-year increase in age was associated with a 19% higher risk of death (HR = 1.19, 95% CI: 1.07–1.31, p =0.001). Race and BMI were not significantly associated with survival. Median baseline PSA was 50 ng/mL (IQR 11–155), and baseline PSA was not significantly associated with survival. Patients received a median of four (IQR 2-6) radium doses, with 38% completing six. Median OS was 11.2 months (95% CI: 10.2–12.1). Among 185 veterans with sequencing data, 49% had PTEN, TP53, or RB1 alterations. OS was similar between TSG-altered (14.2 months) and unaltered (13.1 months) groups. Conclusions: Veterans treated with radium-223 for mCRPC had a median OS of 11.2 months. TSG alterations and baseline PSA were not significantly associated with survival, whereas increasing age was linked to higher mortality risk. Race and BMI showed no significant associations with outcomes. These findings provide real-world benchmarks for radium-223 outcomes in veterans and underscore the need to identify factors that support treatment and optimize survival.

Printable Deep‐Blue Fluorescent Light‐Emitting π‐Conjugated Polymers for All‐Organic RGB Visible Light Communication

ABSTRACT All‐organic red‐green‐blue (RGB) visible light communication (VLC) systems hold significant promise for future wireless communications because they can be readily integrated with existing lighting infrastructures. However, the stability, efficiency, and exciton decay times of printed deep‐blue organic light‐emitting diodes (OLEDs) currently fall short of the high bandwidth, rapid response, and swift data transmission requirements of VLC systems. Herein, two printable deep‐blue fluorescent light‐emitting π‐conjugated polymers (LπCPs) were fabricated based on a multi‐dimensional self‐encapsulation strategy for application in all‐OLED RGB VLC systems. The printed fluorescent films displayed remarkably fast decay life‐times of ∼0.30 ns, enabling high bandwidth and fast response. The deep‐blue OLEDs presented a CIE coordinate of (0.15, 0.06), narrow deep‐blue emission with a full width at half maximum (FWHM) of 21 nm, high external quantum efficiency (EQE) of 1.94%, and high brightness of 6698 cd/m 2 with remarkable durability. Finally, preliminary printed all‐OLED RGB VLC systems were successfully established, and through efficient energy transfer, demonstrated the transmission of pseudo‐random binary sequence (PRBS) signals and audio data at a rate of 1 Mbps. The fast response times, on the order of microseconds, highlight the potential of these all‐OLED VLC systems for high‐speed data transmission.

Dealloying Engineering and Interfacial Catalyzing toward Long‐Lifespan Anode‐Free Sodium Metal Battery

ABSTRACT Anode‐free Na metal batteries are acclaimed for their high energy densities achieved through current collectors in situ plated with Na metal in the absence of active negative materials. However, realizing high reversible Na plating/stripping on a bare current collector and stable electrolyte chemistry is challenging. Herein, we report a dealloying strategy to treat a Chinese paktong current collector, controlling its crystal orientation and surface properties in situ. The dealloyed foil (D‐CNZ) with (220) orientation and high Ni content provides high‐affinity nucleation sites that initiate and sustain a uniform Na metal deposition, and catalytic active sites to form a propitious solid electrolyte interphase layer. Dealloying treatment enables a highly reversible Na plating/stripping for 10 000 h (1 mA cm −2 /1 mAh cm −2 ), significantly outperforming current collectors reported in the literature. The present anode‐free Na metal battery (AFSMB) prototype, comprised of D‐CNZ current collector, Na 3 V 2 (PO 4 ) 3 cathode, and ether electrolyte can operate for over 200 cycles at 1C, and 100 cycles at 10C. In addition, the NVP||D‐CNZ anode‐free pouch cell delivers 102 mAh g −1 at 0.5C and maintains 97% capacity over 120 cycles. Our superior AFSMB enabled by the D‐CNZ enlightens an arena toward large‐scale energy storage applications.