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Tailored Redox‐Active Catholytes Enabling High‐Rate and High‐Loading All‐Solid‐State Lithium‐Sulfur Batteries

ABSTRACT All‐solid‐state lithium‐sulfur batteries (ASSLSBs) hold great promise for next‐generation electrochemical energy storage due to sulfur's high theoretical specific capacity and low cost. However, sluggish sulfur conversion kinetics and severe volume variations during cycling, as well as poor ionic percolation in composite cathodes, limit their practical viability. To overcome these challenges, we herein introduce solid electrolytes of nominal composition Li 10.5− x Si 1.5 P 1.5 S 12− x I x (with x = 0, 0.2, 0.4), possessing high ionic conductivities of ≥ 7 mS cm −1 at room temperature. We show that increasing iodine content alters the phase composition and triggers reversible redox activity in these materials. If implemented as catholytes, this enables very fast sulfur conversion kinetics, ultimately leading to ASSLSBs with exceptional performance. The cells achieve 86% sulfur utilization at a rate of C/2 and at 45°C and offer high‐rate capability by delivering 1175 mAh g sulfur −1 at 5C and 590 mAh g sulfur −1 at 15C. Furthermore, the synergistic effects of ionic percolation and redox‐activity enable record areal capacities up to 14 mAh cm −2 with a sulfur loading of 10 mg cm −2 . Taken together, our findings provide new strategies for designing redox‐active catholytes for application in advanced ASSLSBs and further strengthen the redox‐mediating role of iodine therein.

The stress-activated kinase p38 mediates non-canonical activation of Src and tyrosine phosphorylation of the adapter protein TAB1

Liquid biopsy for detection of DDR gene alterations in metastatic prostate cancer (mPC): Diagnostic performance and clinical correlations.

218 Background: DNA-damage-repair (DDR) gene alterations, particularly those involving BRCA1/2 genes, are clinically relevant in the management of mPC. Tumor tissue remains the standard DNA source for molecular profiling, but sample availability and quality of retrieved DNA are limiting factors. Liquid biopsy (LB), based on circulating free DNA (cfDNA), offers a minimally invasive alternative for real-time monitoring of DDR gene alterations, especially in consideration of clonal heterogeneity. Methods: We conducted a retrospective study at the Veneto Institute of Oncology including a random sample of 50 mPC patients (pts) previously tested for DDR alterations on tumor tissue: 25 DDR-mutated (DDRmut) and 25 DDR wild-type (DDRwt). cfDNA was extracted from plasma and analysed with amplicon-based NGS (BRCA1/2) and capture-based NGS (16 DDR genes). Mutations found at LB were classified according to IARC/ACMG-AMP guidelines. Clinical variables, genomic findings, and outcomes were compared between DDRmut and DDRwt pts. The study was approved by local Ethics Committee and all pts signed the informed consent. Results: Median age at diagnosis was 68 years; 64% had high Gleason score (GS, 8 to 10), 56% had high-volume metastatic (HV) disease at diagnosis. DDRmut pts had higher PSA at the time of LB (0.76 vs. 0.08 ng/mL; p=0.004), longer time to castration resistance (29 vs. 7 months; p=0.002), and more frequent family history of cancer (56% vs 30%; p=0.044). Median cfDNA concentration was 5.27 ng/mL, higher in GS 8 to 10 vs 6 to 7 (5.57 vs. 4.51 ng/mL; p<0.001). No correlation was found with disease volume or PSA levels. cfDNA quantity and quality were adequate for NGS testing in all DDRmut and 18 DDRwt pts. LB detected the same DDR variants previously reported in tumor tissue analysis in 20/25 DDRmut pts. LB revealed six previously unknown DDR variants in 18 evaluable DDRwt pts involving BRCA2 gene (3pts, 2 Likely Pathogenic, 1 Not Present), ATM (2 pts, both Not Present) RAD51B (2 pts, both Not Present), and BRIP1 (1 pt, Not Present), with 2 pts bearing 2 concomitant variants. Median VAF ranged from 0.5 to 3.8%. All 6 pts had positive family history for tumors related to DDR mutations and were being treated with ARPi (androgen receptor pathway inhibitor) with undetectable or declining PSA. Overall concordance with archival tissue was 79% (κ=0.41). Conclusions: In this mPC cohort, cfDNA concentration correlated with Gleason score rather than PSA levels. LB demonstrated moderate concordance with tissue-based DDR profiling and revealed previously undetected but likely pathogenetic variants even in patients with biochemical response.. These findings support the potential role of LB in longitudinal monitoring of DDR alterations; however, methodological standardization and prospective validation are required before routine clinical implementation.

Patient and trial design factors influencing participation in prospective bladder and kidney cancer clinical trials.

655 Background: Patients on clinical trials with renal cell carcinoma (RCC) or urothelial carcinoma (UC) have better outcomes than those receiving standard of care. However, some patients choose not to participate in trials. Overrepresentation of certain groups can bias trial results. Here, we explore the characteristics of patients who decline participation in RCC and UC trials. Methods: We retrospectively reviewed patients with RCC or UC who were referred to a single uro-oncology cancer centre, St Bartholomew’s Hospital, between January 2020 and December 2022. Each patient was followed until October 2024. We assessed associations between consent and patient characteristics (age, gender, ethnicity) and trial characteristics (randomisation, phase, comparator: placebo vs active treatment). Reasons for not starting screening were classified as patient preference, performance status, comorbidities, histology or others. Independent predictors of screening initiation were identified using multivariable logistic regression analysis (MVA). Results: A total of 406 patients (189 UC, 217 RCC) were included. Older age and non-white ethnicity were associated with lower consent rates (Table 1). Patient preference was the most common reason for non-screening (34% overall, 31% among non-white patients). Trial design characteristics also had an impact, with lower participation in randomised trials (48.1%) compared to non-randomised (73.7%) (p=0.032). The presence of a placebo arm was not significant in the MVA (p=0.293). Consent was higher in early phase than late phase trials on univariable analysis (p<0.001), with lower rates in phase 3 (42.6%) compared to early phase trials (86%). However, it was not an independent predictor in the MVA. Conclusions: Specific trial and patient characteristics predispose to non-clinical trial participation. Addressing these factors may result in a more broadly representative patient population in clinical trials. Multivariable logistic regression analysis. Variable OR 95% CI p value Age 0.96 0.93-0.98 0.0008 Ethnicity 0.27 0.11-0.63 0.0028 Randomisation 0.33 0.11-0.94 0.032 Phase 1 and 2 1.64e-7 1e-170 – 5e7 0.987 Phase 3 1.2e-8 NA – 7.4e20 0.985 Active treatment 1.80 0.02-1.56 0.127 Placebo 1.09 0.04-2.50 0.293

Treatment outcomes and associated factors among road traffic injury patients in emergency departments of public hospitals in Awi Zone Northwest Ethiopia

PSMA PET versus conventional imaging in metastatic prostate cancer: Evaluation of disease volume classification in a veteran cohort.

21 Background: Conventional imaging (CI), including CT and bone scans, has traditionally guided treatment decisions for patients with metastatic prostate cancer (mPCa). In the CHAARTED trial, a binary low/high-volume disease classification system was established using CI. However, the emergence of PSMA PET imaging, which can detect lesions previously unseen on CI, has complicated the use of disease volume classification to guide therapy. This study assessed the impact of PSMA PET on disease volume classification and treatment selection in mPCa patients at a single VA medical center. Methods: This retrospective study included veterans with mPCa who underwent PSMA PET imaging at the James J. Peters VA Medical Center. Metastatic disease was defined as ≥1 extra-pelvic PSMA-avid lesion. CHAARTED volume status was retrospectively assigned using both PSMA and CI data. Descriptive statistics and paired comparisons were conducted in R, and p<0.05 was considered significant. Results: A total of 75 patients were included (median age 77, IQR 15.5; 71% Black). Forty-two had CI within 3 months of PSMA PET, and 90% (38/42) had more lesions detected on PSMA. By CHAARTED criteria, 29% (12/42) were high-volume by CI, compared to 62% (26/42) by PSMA. Among CI low-volume patients, 50% (15/30) were upstaged by PSMA. Concordant high-volume patients demonstrated more advanced disease, with higher PSA (p=0.017) and lower 1-year survival (p=0.028) compared to concordant low-volume patients, while discordant cases (PSMA-high/CI-low) were intermediate. Chemotherapy use post-PSMA was low (8%), with androgen deprivation therapy (ADT) plus novel hormonal therapy (NHT) the most common treatment combination (31%). Conclusions: PSMA PET identified more metastatic lesions and more frequently classified disease as high-volume compared to CI. Concordant high-volume patients had the poorest outcomes, concordant low-volume the most favorable, and discordant patients were intermediate, suggesting that PSMA-informed classification may have improved prognostic value compared to CI. Despite more frequent upstaging, chemotherapy use remained uncommon, likely reflecting comorbidity burden and clinical preference for NHT. These findings, from a predominantly Black veteran cohort underrepresented in prostate cancer research, highlight the need for larger multi-institutional studies to validate the prognostic value of PSMA-guided disease stratification and ensure its generalizability across diverse populations. Clinical characteristics by CI–PSMA concordance. Variable Concordant High Discordant High (PSMA-high/CI-low) Concordant Low p-value N 11 15 15 - PSA, median (IQR) 246 (123–501) 86 (19.5–190) 28 (11.8–69.4) 0.017* Gleason, median (IQR) 9 (7.5–9) 8 (7–8.5) 7 (6.5–9) 0.926 1-year overall survival — % (95% CI) 45 (24–87) 53 (33–86) 87 (71–100) 0.028* *Indicates p < 0.05.

Wood‐Structured Electrolyte for Ultra‐Stable Zinc‐Ion Batteries Under High Discharge Conditions

ABSTRACT Aqueous zinc‐ion batteries (AZIBs) operate stably at low depth of discharge (DOD) but suffer severe Zn 2+ transport imbalance, hydrogen evolution, and plating/stripping at high DOD (> 70%). Here, we present a radial wood‐based hierarchical heterogeneous interconnected structure (HHIS) electrolyte. HHIS is without low‐tortuosity channels, but during cycling, Zn 2+ predominantly migrates along laterally oriented vessels, fibers, and rays via pit coordination, ensuring uniform deposition. Leveraging these synergistic effects, HHIS stabilizes the Zn anode under high current, enabling > 9000 h of cycling and > 3300 h at 83.1% DOD, surpassing previous reports. This work directly converts wood into a high‐performance electrolyte and establishes a HHIS design strategy for addressing high‐DOD instability in AZIBs and advancing electrolyte commercialization.

Organic Radical Accelerates Charge Carrier Funneling in Quasi‐2D Perovskite LEDs

ABSTRACT Quasi‐2D metal halide perovskites (MHP) have emerged as promising candidates for light‐emitting diodes (PeLEDs) due to their intrinsic advantages in color purity, bandgap tunability, and stability. The prime working principle realizing high radiative emission in quasi‐2D MHP is the ultrafast, consecutive charge transfer (CT) process toward the low‐bandgap crystallites across multiple quantum wells, called charge carrier funneling. Ironically, such a key process is intrinsically limited in the quasi‐2D MHP by the molecular spacers, which have electronically insulating natures. To challenge this limit, herein, we explore the impact of a judiciously designed, stable, and conductive organic radical, (5H‐pyrido[3,2‐b]indole‐2,6‐dichlorophenyl)bis(2,4,6‐trichlorophenyl)methyl as a molecular additive in the MHP matrix. It is found that the spatially delocalized singly occupied molecular orbital offers an electronic bridge accelerating interfacial CT and the carrier funneling by surface adsorption, thus maximizing radiation recombination yield. As a result, the radical‐incorporating PeLEDs (peaking at ≈ 684 nm) achieve a remarkable external quantum efficiency of 26.8% with an operational half‐lifetime of ≈ 340 min, ranking among the best deep‐red devices reported to date. This work demonstrates that rational radical molecular design offers a powerful route to resolve intrinsic CT limitations in quasi‐2D MHP, unlocking both high efficiency and long‐term stability in next‐generation PeLEDs.

ARF6 controls VSMC phenotypic switching upon lipid stimulation to promote inflammatory signaling contributing to the progression of atherosclerosis

Real-world data on patients’ characteristics guiding physicians’ choice of first-line treatment for advanced urothelial carcinoma: Is there still a place for platinum-based chemotherapy?

690 Background: The treatment landscape for patients with advanced urothelial carcinoma (mUC) has evolved rapidly in recent years. Current guidelines recommend enfortumab vedotin plus pembrolizumab (EV/P) combination as preferred 1L standard of care (SOC), but platinum-based chemotherapy (PBC) followed by avelumab as switch-maintenance strategy is still considered as another SOC. The availability of several treatment options creates the potential for individualized treatment and arises the question of patients’ selection for each option. We performed an international retrospective study to identify patients’ characteristics who guide physicians’ choice for each option. Methods: This international study was conducted from November 2024 to February 2025 in France, Germany, Japan and USA. We included 606 patients with mUC starting a 1l-treatment. Anonymous patient charts from medical oncologists were analyzed. The analysis included comprehensive clinical data collection including patient characteristics (age, gender, comorbidities, ECOG, CDDP eligibility), disease characteristics (tumor burden, metastatic sites, symptomatology, PDL1 status, FGFR status) and treatment patterns. Results: From the 606 enrolled patients, 71,5% were male, median age was 67.2 years (65.8 – 71.7) and 85.3% of the patients were ECOG 0-1. The high majority of patients (77%) had at least one comorbidity, mostly Hypertension (50%), controlled diabetes (20%) and cardiovascular disease (13.5%). A total of 424 patients were CDDP eligible (70%) and 182 CDDP ineligible (30%). At start of 1L treatment, 51 % of pts had a symptomatic disease, 18.2% had a high tumor burden. Most frequent metastatic sites were lung (44.6%) followed by bone (32.7%) and liver (19.2%) respectively. About 19% of pts had a lymph node only disease. A total of 201 pts was treated with EV/P and 223 with PBC, respectively. Patients treated with EV/P had a higher tumor burden (21 vs 14%, p 0.18) and were more often symptomatic (59% vs 42.6%, p 0.51). In CDDP eligible pts groups EV/P treated pts were younger (median age 66.8 vs 67.9), had a higher tumor burden, more symptomatic disease (47% vs 25%) and had more visceral metastatic sites. No pts comorbidities are relevant in this subgroup. In the CDDP ineligible population EV/P treated pts had less comorbidities and less visceral disease. Conclusions: Our RWD suggest that patients with a high tumor burden, symptomatic disease and visceral metastases were more likely to receive EV/P combination especially in a “fit” population. Further prospective RW studies are warranted to help physician to individualize 1 st line therapy in mUC.

DB-1311/BNT324 (a novel B7H3 ADC) in patients with heavily pretreated mCRPC from a phase 1/2 study: Analyses according to prior treatment with lutetium 177 (177Lu)-PSMA-617.

176 Background: 177Lu-PSMA-617 (Lu 177) has reported improved outcomes in metastatic hormone sensitive and castration resistant prostate cancer (mHSPC/mCRPC); however, there is still a high unmet need, particularly for patients (pts) with mCRPC. Moreover, data on clinical outcomes following Lu 177 is limited. DB-1311/BNT324 is an investigational B7H3 ADC with encouraging activity in pts with heavily pretreated mCRPC (ASCO 2025 #5015). Herein we present new clinical results with a focus on pts with mCRPC who received Lu 177 treatment. Methods: In the dose optimization cohort of this phase 1/2 study (NCT05914116), pts with previously treated mCRPC received DB-1311/BNT324 6 mg/kg or 9 mg/kg Q3W, while in the dose expansion cohorts (post Lu 177 mCRPC and taxane-naïve mCRPC), pts received 6 mg/kg Q3W until progression or unacceptable toxicity. The primary endpoints were objective response rate (ORR, using PCWG3-modified RECIST v1.1) and safety. Secondary endpoints included disease control rate (DCR), duration of response (DOR), radiographic progression-free survival (rPFS), overall survival (OS), PSA response and PSA DOR. Results: At data cut-off (05 Sept, 2025) 104 pts with mCRPC had been treated (6 mg/kg n=68; 9 mg/kg n=34) with 52 pts (50%) still on treatment after a median follow-up of 9.2 mos (range 0.1–19.4). Median age was 70 yrs (range 45–90); 71% enrolled in US/AUS, 29% in China; 53% were White, 31% Asian, 13% Black; median prior lines was 4 (range 1–14). Among 58 response-evaluable pts (measurable disease at baseline per RECIST 1.1), unconfirmed ORR was 41.4% (95% CI 28.6, 55.1), confirmed ORR (cORR) was 34.5%, and DCR was 87.9% (95% CI 76.7, 95.0). Median DOR was 10.2 mos (95% CI 7.2, ne). Median rPFS (N=82) was 11.3 mos (95% CI 7.2, ne) with 6-mo rPFS rate of 72.0% and 9-mo rPFS rate of 63.0%. OS was immature at data cut-off, but encouraging 6-mo (91.7%) and 9-mo OS (88.2%) rates were observed. PSA 50 response rate was 35.4% and median PSA DOR was 8.4 mos (95% CI 4.4, NE). Safety data were in line with previous report at ASCO 2025, with nausea and hematological events, primarily Grade 1–2, being most common. Thirty-four (33%) pts received prior Lu 177 (median age: 69 yrs [range 55–84]; 65% White, 15% Asian, 15% Black; median prior lines: 5 [range 2–14]) with 24 (71%) still on treatment. Outcomes were similar in pts who received prior Lu 177 and pts who did not (Table). Conclusions: DB-1311/BNT324 showed encouraging durable efficacy in heavily pretreated mCRPC including patients who were previously treated with 177Lu-PSMA-617 with no new safety signals reported. Further development of DB-1311/BNT324 in mCRPC is warranted. Clinical trial information: NCT05914116 . Post Lu 177 No prior Lu 177 Response evaluable, n 10 48 cORR, % 30.0 35.4 DCR, % 100 85.4 Efficacy evaluable, n 23 59 Median rPFS, months 11.3 NE 9-month rPFS rate, % 61.1 63.7 9-month OS rate, % 86.2 88.5 PSA 50 response rate, % 30.4 37.3

Next-generation photo-Fenton treatment using MIL-100(Fe) synthesized through a green route for sustainable remediation of pharmaceutical wastewater

Abstract The photocatalytic Fenton oxidation reaction of paracetamol (PCT), as a widely used pharmaceutical and persistent water contaminant, was investigated using RTG-MIL-100(Fe) framework, prepared via a KI-assisted, solvent free, room temperature synthesis, in the presence of H₂O₂ under UV irradiation. The mild conditions synthesis of RTG-MIL-100(Fe) is investigated, and the material is comprehensively assessed through characterized using X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Brunauer–Emmett–Teller (BET), and X-ray Photoelectron Spectroscopy (XPS). The catalytic system is introduced as a source of photo-Fenton-like reaction and demonstrated a dual mechanistic pathway involving both semiconductor-like photoexcitation and open metal site (OMS) activation. The operating Fenton parameters are optimized and the experimental research revealed that the reaction is working at the room temperature using 400 ppm H₂O₂, 20 mg/L of RTG-MIL-100(Fe)at natural pH of wastewater (5.5) and the PCT reached almost complete removal 99.6%. The synergistic interaction of photogenerated charge carriers and OMS-driven Fenton-like processes resulted in efficient oxidative mineralization of PCT to CO₂ and H₂O. Furthermore, the reaction is endothermic in nature and following the first order reaction kinetics. These findings highlight the potential of KI-modified MOF-based photo-Fenton catalysts as sustainable and robust materials for the treatment of pharmaceutical wastewater.

End-of-life treatment patterns in patients (pts) with metastatic renal cell carcinoma (mRCC).

466 Background: The treatment landscape of mRCC has rapidly evolved in recent years, particularly with the introduction of tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 inhibitors (PD-1i). However, therapeutic options after progression on these agents remain limited, and data on how treatment decisions are made near the end of life are lacking. Herein, we sought to assess treatment patterns in relation to the time of death in real-world pts with mRCC. Methods: This study used the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: pts with mRCC who initiated first-line (1L) therapy and had a recorded date of death. The data cutoff was 10/31/2024. Pts were categorized into two groups: treatment-free, if no systemic therapy was administered during the last 3 months of life, or on-treatment, if systemic therapy was received within 3 months preceding death. Demographic and clinical variables at their last line of therapy (LOT) initiation, including age, race, region, socioeconomic status, practice type, and insurance, were summarized using medians (IQR) or proportions. Comparisons were performed using Wilcoxon rank-sum or chi-squared tests. Results: Among 13,909 pts with mRCC diagnosed between 1/1/2011 and 7/18/2024, 7,179 initiated 1L therapy, had a recorded date of death, and were eligible and included in our analysis. Of these, 4,731 (65.9%) received systemic therapy within 3 months of death (on-treatment), while 2,448 (34.1%) did not (treatment-free). At the time of their last LOT initiation, patients in the treatment-free group were older with a median age 70 years (IQR 62 – 77), as compared to 68 years (IQR 60 – 75) in on-treatment group (p < 0.001). Patients in the on-treatment group were more likely to be treated in community practice (p < 0.001), and to have commercial health plan (p < 0.001). The most common last treatments within 3 month of death were TKIs (42%), followed by single agent PD-1i (15%), and PD-1i + TKI (12%). Additional baseline characteristics and treatment patterns will be presented at the meeting. Conclusions: In this large real-world cohort, most pts with mRCC remained on systemic therapy within 3 months of death, most commonly TKIs or PD-1i. These results highlight the need to better define appropriate end-of-life care and optimize treatment decision-making for pts with mRCC to balance therapeutic benefit with quality of life. Limitations include retrospective nature of study and possible data missingness.

Ultrathin, Stretchable, and 3D‐Printable Complementary Nanotubes–Polymer Composites for Multimodal Radiation Shielding in Extreme Environments

ABSTRACT A novel material system capable of simultaneously attenuating electromagnetic interference (EMI) and neutron radiation, while retaining multifunctionality such as lightweight and mechanical stretchability, is urgently needed for versatile passivation platforms in advanced aerospace, defense, medical, and next‐generation electronic applications operating under extreme environments. Here, we report (1) a neat composite comprising complementary nanotubes (boron nitride nanotubes, BNNTs, and single‐walled carbon nanotubes, SWCNTs) for dual‐mode attenuation that includes EMI and neutron shielding, and (2) its extension into a 3D‐printed architecture using an intrinsically stretchable polydimethylsiloxane (PDMS) matrix, which altogether enables a robust and conformable shielding architecture for emerging applications. Utilizing direct ink writing, we achieve scalable fabrication of structurally complex geometries (e.g., freestanding honeycomb lattices) with tunable mechanical and shielding properties. The resulting neat composites demonstrate EMI shielding effectiveness exceeding 50 dB and neutron attenuation coefficient of 1.27 mm −1 (equivalent to ∼72% attenuation at a mm thickness) at thicknesses on the order of tens of micrometers, where the polymer composites exhibit the shielding effectiveness up to 23 dB at sub‐millimeter thicknesses while maintaining mechanical resilience under cyclic strain and thermal extremes (–196°C to 250°C). These findings present a lightweight and robust shielding strategy for next‐generation electronics in harsh environments.

Recent Progress in BiFeO ₃ ‐Based Sensor Technologies: Fundamentals, Performance Metrics, and Diverse Applications

ABSTRACT Bismuth ferrite (BiFeO 3 , BFO) is a prototypical multiferroic perovskite that simultaneously exhibits ferroelectricity, antiferromagnetism, piezoelectricity, and strong visible‐light absorption due to its relatively narrow band gap. The interplay among lattice distortions, defect chemistry, and orbital hybridization not only underpins these multifunctional responses but also renders them highly tunable through defect‐dipole modulation, band‐gap engineering, and interface or surface control. Owing to the unique coupling between ferroic and electronic functionalities, BFO has emerged as a versatile platform for next‐generation sensing technologies, including optoelectronic, pressure, gas, humidity, and biosensors. This review systematically examines the structure–property relationships in BFO, recent advances in synthesis and modification strategies, and their implications for sensor performance across diverse domains. Special emphasis is placed on the microscopic mechanisms governing its sensing behavior, including band‐structure modulation, defect‐mediated charge transport, and surface adsorption‐driven chemistry, as well as on strategies to leverage these mechanisms for sensing performance optimization. Finally, we outline the opportunities and challenges in harnessing BFO's multifunctionality for practical sensing applications in environmental, healthcare, industrial, and energy‐related fields.

Polypharmacy and potential drug–drug interactions with novel androgen receptor signaling inhibitors (ARSIs) in patients (pts) with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) in a real-world setting.

346 Background: Patients (pts) with nmCRPC are typically elderly, with comorbidities often leading to polypharmacy and a higher risk of drug–drug interactions (DDIs). Efficacy and safety of ARPIs may be compromised by DDIs. We aimed to evaluate the prevalence and relevance of polypharmacy and potential DDIs involving ARPIs in a real-world setting. Methods: We conducted a retrospective cohort (March 2009 to July 2023) at a tertiary cancer center. Patients with high-risk nmCRPC were defined by ≥3 consecutive PSA rises and a PSA doubling time (PSADT) <10 months, with no metastasis on conventional imaging (CT and bone scans), as per criteria from pivotal trials (SPARTAN, PROSPER, ARAMIS). DDIs were assessed using Drugs.com and Lexicomp. Polypharmacy was defined as >4 concomitant drugs. Overall survival (OS), prostate cancer–specific survival (PCSS), and metastasis-free survival (MFS) were estimated from nmCRPC diagnosis by the Kaplan–Meier method and analyzed with univariate Cox models. Results: A total of 1,234 pts with prostate cancer (ICD-10 C61) were screened, and 96 had high-risk nmCRPC. Median age was 73 years (IQR 69–80), PSA 3.0 ng/mL (IQR 1.1–8.5), PSADT 3.3 months (IQR 1.8–5.6), and Charlson Comorbidity Index 5 (IQR 5–7). Most patients (97%) used at least 1 concomitant medication, with a median of 4 (IQR 3–6). Polypharmacy occurred in 43% and was associated with a trend to shorter OS (3.6 vs 4.5 y; HR 1.53, 95% CI 0.93–2.47, p = 0.08) and PCSS (3.6 vs 5.1 y; HR 1.52, 95% CI 0.95–2.47, p = 0.09), but not MFS (2.1 vs 2.9 y, p = 0.64). Potential DDIs were more frequent with enzalutamide and apalutamide (Table). Amlodipine (18%) was the most common major interaction in the Drugs.com database; omeprazole (18%) was most associated with prohibitive interactions (risk rating X) in Lexicomp. Cross-database inconsistencies were identified: 1 major and 15 moderate interactions reported only in Drugs.com, and 6 Lexicomp category C interactions not listed in Drugs.com. Conclusions: Polypharmacy and potential DDIs with ARPIs are common in nmCRPC. Although darolutamide was associated with fewer interactions, some major or X-rated DDIs were observed, reinforcing the need for individualized management and database cross-checking. Potential DDIs with ARPIs in different databases. Drugs.com – n (%) Minor Moderate Major Enzalutamide 1 (1%) 83 (86.4%) 28 (29.1%) Apalutamide 1 (1%) 82 (85.4%) 28 (29.1%) Darolutamide 27 (28.1%) 20 (20.1%) 2 (2.1%) Lexicomp – n (%) C D X Enzalutamide 60 (62.5%) 9 (9.37%) 1 (1%) Apalutamide 49 (51%) 7 (7.3%) 20 (20.8%) Darolutamide 40 (41.6%) 1 (1%) 1 (1%)

Association of enriched <i>YES1</i> tumor expression at the stromal interface with overall survival in clear cell renal cell carcinoma when treated with first-line immune checkpoint blockade.

522 Background: Immune checkpoint blockade (ICB) has improved response rates for patients with advanced clear cell renal cell carcinoma (ccRCC). However, most ccRCC patients develop resistance. Prior studies have shown YES1 expression is upregulated in malignant cells at the tumor-stromal interface of treatment resistant primary tumors. Our objective was to validate YES1 upregulation in an expanded cohort of ICB and tyrosine kinase inhibitor (TKI) exposed patients, develop a bulk RNA sequencing (RNAseq) gene signature, and test for overall survival (OS) in the Oncology Research Information Exchange Network’s (ORIEN) multi-institutional molecular database of patients treated with ICB. Methods: Tissue microarrays were constructed using one-millimeter cores from the tumor-stromal interface of surgically excised primary ccRCC tumors and normal controls. Single-cell spatial transcriptomics (scST) was obtained using a 6,000 gene panel. Malignant cell YES1 expression was compared between treatment-naïve and treatment-exposed samples. Genes of known related proteins to YES1 were tested for correlation within tumor cells, and also compared between the two groups. Same patient RNAseq data were used to construct a signature using genes that correlated with YES1 expression on scST. We tested OS in treatment-naïve patients with a metastatic diagnosis who received any systemic therapy and a subgroup of patients who received a first-line ICB regimen in the multi-institutional ORIEN cohort. Optimal cut off was determined using the survminer package in R, and rank sum test was performed on Kaplan-Meier curves. Cox regression was also performed and YES1 score was treated as a continuous variable. Results: 209,255 cells were analyzed from 21 treatment-naïve and 11 treatment-exposed patients (ICB only, TKI only, or ICB/TKI). On linear mixed effect modeling, YES1 expression was higher in ICB-exposed patients but not TKI-exposed patients (p = 0.001 and p = 0.634). In ORIEN, significantly elevated YES1 score was associated with worse OS in 130 patients with treatment naïve metastatic ccRCC who received systemic therapy (rank sum p-value 0.047). In the subgroup of 69 patients who received first line ICB, elevated YES1 score was associated with worse OS (p = 0.019), but not in the 69 patients who received first line TKI therapy (p = 0.296). Seven genes of proteins known to interact with YES1 were correlated within tumor cells and expressed at higher levels within ICB-exposed patients in both the single-cell and bulk RNA sequencing data ( GRB2, CRK, PAK2, MAPK1, NCK1, MAPK14, and NRAS ). Conclusions: We found that a spatially informed bulk RNA gene signature associated with malignant YES1 upregulation at the tumor-stromal interface was associated with worse OS in a cohort of patients who received first-line ICB treatment.

Design, synthesis, characterization, pharmacological evaluation and in silico ADMET and molecular docking and dynamics simulations of a novel series of N-substituted pyrazole from chalcone derivatives

Abstract A novel series of N -pyrazolyl-thienopyrimidine and pyridopyrimidine hybrids was synthesized and characterized using spectroscopic methods. Compounds 4c , 5c , and 12 exhibited superior antibacterial potency compared to Levofloxacin, with molecular docking revealing strong binding to key bacterial targets (e.g., DNA gyrase, Neuraminidase). In-silico ADMET analysis confirmed favorable drug-like properties and low toxicity for 4c , supported by stable molecular dynamics interactions. Additionally, 5c and 12 demonstrated potent anti-inflammatory activity surpassing Celecoxib, with reduced ulcerogenicity. These findings introduce a promising new class of dual-action agents for antibacterial and anti-inflammatory drug development.

Treatment outcomes of patients (pts) with small cell or neuroendocrine carcinoma (SC/NE) of the prostate: A single-institution experience.

111 Background: Neuroendocrine carcinoma of the prostate, including the small cell subset, is aggressive with poor prognosis. Most reported series are from large databases (e.g. Surveillance, Epidemiology, and End Results) which lack granular details on clinical history. We examine our institution’s 58 pt series with SC/NE of the prostate. Methods: We identified pts with SC/NE of the prostate treated with platinum-based chemotherapy. Pts must have had biopsy-proven SC/NE histology. Pt history, including whether it was de novo or treatment-emergent SC/NE (t-SC/NE) disease, stage at SC/NE diagnosis, and treatment history were recorded. For localized SC/NE treated with definitive intent, disease-free survival (DFS) was measured from SC/NE diagnosis to relapse or death. For metastatic SC/NE, systemic therapies were noted. Overall survival (OS) was defined from SC/NE diagnosis to death, estimated by Kaplan-Meier method and compared by log-rank test. Results: Fifty-eight pts with SC/NE were identified (median age 66). Nineteen (32.8%) had de novo SC/NE, while the rest had t-SC/NE. Forty-four (75.9%) pts had metastatic disease at SC/NE diagnosis. Most had pure small cell (n=15) or neuroendocrine (n=21) histology, with the remaining (n=22) having a mixed component (e.g. adenocarcinoma). Of 14 pts without distant metastases at SC/NE diagnosis, 10 received definitive local therapy: most commonly chemotherapy followed by radiation (n=3), chemotherapy followed by surgery (n=3), or surgery alone (n=2). Median DFS for pts treated with definitive local therapy was 11.7 months (mos). For all pts, OS was longer for de novo vs treatment-emergent SC/NE (26.5 vs 10.9 mos, p=0.0001) and mixed vs pure SC/NE histology (21.0 vs 11.0 mos, p=0.0002). Among 45 pts treated with first line (1L) carboplatin and etoposide (Table 1) for metastatic SC/NE, OS did not differ between those receiving maintenance immunotherapy (IO) vs not (12.5 vs 11.0 mos, p=0.9). Conclusions: In one of the largest non-database series of SC/NE prostate cancer pts, OS was longer for de novo SC/NE and mixed histology. Maintenance IO after carboplatin + etoposide was not associated with improved OS. Treated with 1L carboplatin + etoposide for metastatic SC/NE (n=45) Number of patients Maintenance IO 18 No maintenance IO 27 Best response to carboplatin + etoposide (with or without maintenance IO)  Complete response 3  Partial response 20  Stable disease 8  Progressive disease 5  Not evaluable 9

Embedding Fe‐Based Redox Chemistry Into Low‐Cost Oxyhalide Solid Electrolytes for High‐Performance All‐Solid‐State Batteries

ABSTRACT Halide solid electrolytes (SEs) with excellent ionic conductivity and wide electrochemical stability windows are promising for next‐generation all‐solid‐state batteries (ASSBs). However, their intrinsic electrochemical inertness and high cost significantly constrain the attainable energy density and large‐scale applicability of ASSBs. Here, we integrate Fe 2 O 3 into Li 2 ZrCl 6 (LZC) to construct an electrochemically active and cost‐effective oxyhalide SE (Li 1.6 ZrFe 0.8 O 1.2 Cl 5.6 , denoted LiZrFeOCl‐1604), which enables Fe‐based redox chemistry while preserving cost‐effectiveness. Benefiting from its amorphous framework comprising interconnected Zr─O/Cl, Fe─O/Cl, and Li─Cln ( n ≤ 6) polyhedra,LiZrFeOCl‐1604 exhibits a high ionic conductivity of 2.55 mS cm −1 and a pronounced reversible capacity of 163 mAh g −1 . Coupled with LiFePO 4 (LFP) cathode, the composite electrode delivers a high capacity of 321.6 mAh g −1 and an energy density of 982.1 Wh kg −1 (based on LFP mass), representing a 101.8% enhancement over electrochemically inactive LZC. Moreover, the ASSBs retain 92.7% of its initial capacity (205.7 mAh g −1 ) over 800 cycles at 1C rate. Notably, this asynchronous charge–discharge behavior not only boosts the practical energy density but also mitigates safety risks associated with overcharge and overdischarge of ASSBs.