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Effects of obesity on biphasic immune remodeling of CD45⁺ circulating cells during androgen deprivation therapy in prostate cancer.

216 Background: Androgen-deprivation therapy (ADT) is essential for advanced prostate cancer but linked to early inflammatory and cardiovascular events without clear immune mechanisms. Longitudinal immune-cell mapping during early ADT is limited. We profiled circulating CD45⁺ populations to define systemic immune shifts over 3 months of therapy. Methods: Forty-four blood samples from 19 men with treatment-naïve prostate cancer (median age 66 years; 11 Black, 8 White; 10 obese [BMI ≥ 30]) were collected at baseline (A), 1 month (B), and 3 months (C) after leuprolide. PBMC were analyzed by 45-marker CyTOF into CD4⁺/CD8⁺ T, B, NK, and plasmacytoid dendritic (pDC) cells, plus classical (cMo) and non-classical (nMo) monocytes. Mixed-effects models (participant random intercept; BMI covariate; FDR < 0.05) assessed log₂-fold-change (log₂-FC) vs baseline. Results: At baseline, CD4⁺ T cells (38 % [26–42]) dominated, followed by CD8⁺ T (22 % [17–26]), cMo (15 % [3–24]), and NK (10 % [9–15]). Non-obese men had higher cMo (20 % [16–29]) and nMo (4.8 % [2.7–7.6]), whereas obese men had greater CD4 (41 % [38–53]) and NK (12 % [10–17]) fractions (FDR ≈ 0.05 for CD4, cMo). ADT produced a biphasic pattern. At 1 month, cytotoxic clusters changed little overall (CD8 –0.06, NK –0.12 log₂-FC) but diverged by adiposity: non-obese men showed mild cytotoxic rises (CD8 +0.05, NK +0.07), whereas obese men displayed early innate gains (cMo +1.44, nMo +1.26, pDC +1.20). By 3 months, monocytes rebounded (cMo +1.08, nMo +1.48) with far greater amplitude in obese men (cMo +2.93 vs –1.14; nMo +1.89 vs +0.67). T cells contracted (CD4 –0.66, CD8 –0.37). No subset met FDR < 0.05 after correction. Conclusions: ADT drives a biphasic remodeling of circulating CD45⁺ immunity—an early, adiposity-modulated cytotoxic shift followed by an obesity-amplified monocyte rebound. These data highlight how metabolic state shapes immune plasticity under androgen deprivation and may inform cardio-oncologic risk. Baseline characteristics of men initiating ADT. Characteristic Total (n = 19) Non-obese (n = 9) Obese (n = 10) Age, years (median [IQR]) 66 (61–71) 65 (60–70) 67 (63–72) Race, n (%) Black / White 11 (58) / 8 (42) 5 (56) / 4 (44) 6 (60) / 4 (40) BMI, kg m⁻² (mean ± SD) 31.2 ± 4.6 27.0 ± 2.1 34.9 ± 3.1 Baseline CD45⁺ composition (median % [IQR]) – CD4 T cells 38 (26–42) 31 (21–34) 41 (38–53) – CD8 T cells 22 (17–26) 22 (16–23) 20 (18–27) – Classical monocytes (cMo) 15 (3–24) 20 (16–29) 3 (1–13) – Non-classical monocytes (nMo) 2 (2–6) 5 (3–8) 2 (1–2) – NK cells 10 (9–15) 9 (8–11) 12 (10–17) – Plasmacytoid DC (pDC) 0.24 (0.11–0.51) 0.34 (0.24–0.56) 0.13 (0.08–0.35) – B cells 3.8 (2.8–4.6) 4.4 (3.0–5.3) 3.4 (2.1–3.8) Abbreviations: BMI, body-mass index; IQR, interquartile range; PBMC, peripheral-blood mononuclear cells; DC, dendritic cells; cMo, classical monocytes; nMo, non-classical monocytes.

Survival outcomes with lutetium-177-PSMA-617 in metastatic castration-resistant prostate cancer patient according to baseline tumor characteristics.

35 Background: To investigate cancer-control outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients receiving Lutetium-177 Prostate-Specific Membrane Antigen-617 (Lu-177-PSMA) radioligand therapy according to initial baseline tumor characteristics. Methods: We relied on the FRAMCAP (FRAnkfurt Metastatic Cancer database of the Prostate) database to assess progression-free survival (PFS) overall survival (OS) in patients receiving Lu-177-PSMA as first to seventh mCRPC line, according to initial time of metastasis (synchronous vs. metachronous), tumor grading (Gleason score [GS] 6-7 vs. 8-10) and M-stage (M1a vs. M1b vs. M1c) at initial metastatic hormone-sensitive prostate cancer (mHSPC). Kaplan-Meier curve analyses and multivariable Cox regression were applied. Results: Of 344 Lu-177-PSMA mCRPC patients, 198 (58%) had synchronous vs. 146 (42%) metachronous mHSPC, 87 (29%) vs. 107 (62%) GS 6-7 vs. 8-10 and 15 (10%) vs. 121 (81%) vs. 13 (9%) M1a vs. M1b vs. M1c mHSPC disease. Regarding cancer-control outcomes, no significant differences were observed in PFS (12.1 vs. 13.0 months) and OS (14.9 vs. 18.3 months) between synchronous and metachronous patients (both p≥0.1). Further, no differences were found in PFS (12.9 vs. 11.8 months) and OS (21.4 vs. 15.1 months) between GS 6-7 vs. GS 8-10 (both p≥0.3). Finally, in M-stage stratified analyses, M1a and M1b patients harbored more favorable survival outcomes compared to M1c in OS (17.9 vs. 17.7 vs. 9.0 months, p=0.01), but not for PFS (11.9 vs. 9.5 vs. 8.2 months, p=0.08). In multivariable Cox regression models adjusted additionally for ECOG status, neither initial time of metastasis, GS 8-10 nor M-stage were independently associated with worse PFS and OS outcomes. Conclusions: Lu-177-PSMA presents a viable therapeutic option providing favourable cancer-control outcomes in mCRPC patients across all subgroups of initially mHSPC patients, such as timing of metastatic disease, different tumor gradings and M-stage categories.

Y‐Doped PtFeNi Medium‐Entropy Nano‐Alloy with Engineered (111) Facets for Enhanced Oxygen Reduction Reaction

ABSTRACT The development of highly efficient and durable Pt‐based oxygen reduction reaction (ORR) catalysts is paramount for the widespread adoption of proton exchange membrane fuel cells (PEMFCs). Herein, we present a novel Y‐doped PtFeNi medium‐entropy alloy catalyst, PtFeNiY 8 (PFNY 8 , 8% Y doping), synthesized via a simple one‐pot method, achieving preferential exposure of the highly active (111) crystal facet. Systematic experiments and density functional theory calculations demonstrate that Y doping lowers surface energy to promote the formation of the (111) crystal facet, with an optimal doping level of 8% achieving the most stable electronic structure and the most favorable d ‐band center. The PFNY 8 /C catalyst demonstrates outstanding ORR performance, with a half‐wave potential ( E 1/2 ) of 0.93 V, mass activity (MA) of 3.00 A mg −1 Pt , and excellent durability (after 80,000 ADT cycles, the E 1/2 decreases by only 11 mV, and the MA retention is 73.4%). Furthermore, in PEMFCs, PFNY 8 /C demonstrates a peak power density of 1.75 W cm −2 under H 2 /O 2 conditions, outperforming commercial Pt/C. This study offers valuable insights into the role of Y doping in tailoring nanoparticle morphology and facet exposure, presenting a new strategy for designing high‐performance Pt‐based catalysts for next‐generation PEMFCs.

Wafer‐Scale Organic Neuromorphic Sensors for Programmable Displaying

ABSTRACT Conventional machine vision architectures suffer from intrinsic energy inefficiency and latency bottlenecks due to the physical segregation of sensing, memory, and processing units. Emerging organic neuromorphic devices offer a promising solution, yet concurrently achieving strong photoresponse, ultralow‐power operation, and reliable non‐volatile memory remains a critical challenge. Herein, we integrate a heterostructured dielectric layer, poly (amic acid) (PAA)/hafnium oxide, into wafer‐scale organic neuromorphic devices, significantly enhancing charge carrier mobility, photosensitivity, and memory performance. The optimized devices exhibit a suite of exceptional characteristics: high carrier mobility, ultralow light detection sensitivity (102 nW cm −2 ) with a fast response time (50 µs), minimal energy consumption (53 aJ per spike), long‐term memory retention (50 000 s), and robust endurance. We further demonstrate programmable organic thin‐film transistors (OTFTs) driving LED arrays, enabling repeatable light/mask‐induced pattern writing/erasing and integration of sensing‐memory‐display functions. Linear Dynamic Range Adjustment (LDRA) simulations reveal ultrahigh dynamic range and superior imaging capabilities of PAA‐optimized OTFTs. This hetero‐dielectric strategy establishes a universal platform for organic neuromorphic electronics, addressing key gaps in adaptive edge vision systems and human‐retina‐like interactive meta‐displays.

Hydrogen sulfide increases intracellular oxygen and inhibits the HIF response

Trial design and objectives for prostate cancer: Recommendations from the Prostate Cancer Clinical Trials Working Group 4 (PCWG4).

162 Background: Clinical trial conduct in advanced prostate cancer has changed dramatically with the continued development of new imaging approaches, molecular phenotypes and genetic subtypes, prognosis assessments, and effective therapies across a range of disease states. This created a need to redefine terminology and best practices for clinical trials. Methods: We convened PCWG4, an international expert committee of multidisciplinary working groups, between 2016 and 2025 to update and expand PCWG2-3 recommendations based on emerging evidence and clinical trial data in an innovative biomarker and imaging context to provide guidance for clinical trial design, eligibility, and endpoint assessments. Results: PCWG4 redefines terminology around disease states and prior therapies in a patient-centric context, considering imaging modalities, with a particular focus on PET-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, imaging and non-imaging-based responses. We define delay/prevent endpoints including responses by pathology, ctDNA, circulating tumor cells, and PSA declines, and specify intervals for re-assessments including imaging, biomarker assessments, and patient reported outcomes. We propose new imaging-specific rPFS criteria including guidance with serial PSMA PET/CT imaging (Table). We provide recommendations in a biomarker-based context for the indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. Conclusions: PCWG4 expands guidance on patient and tumor profiling, as well as therapy development, to include both androgen deprivation therapy sensitive and resistant settings, reflecting today’s more heterogeneous and diverse patient population to optimize outcomes. PCWG4-defined radiographic progression by imaging modality for patients with metastatic disease. Pretreatment Scan On-treatment Scan #1(≥week 8) On-treatment Scan #2 All Subsequent Scans Bone scintigraphy Comparator Comparator for subsequent scansPOD never called here POD:PCWG3 criteria (2+2 additional new lesions) POD:≤5 new lesions: PCWG3 criteria 2 new lesions confirmed≥6 new lesions CT/MRI Any measurable disease Comparator PCWG3/RECIST PCWG3/RECIST PCWG3/RECIST PSMA PET Bones, and lymph nodes and lung metastases (non-RECIST qualifying by + on PET only) Comparator POD:≤5 new lesions: 2 new lesions confirmed on a subsequent scan≥6 new lesions Same as prior Same as prior Liver and non-pulmonary viscera Comparator POD:Any single new lesion that represents disease Same as prior Same as prior

A clinical, evidence-based risk estimator for individualizing benefit and response in oligometastatic prostate cancer (CEREBRO): A tool from the X-Met collaboration.

160 Background: To our knowledge, no tools are available to guide care in oligometastatic prostate cancer (omPC). Here, we leveraged individual patient-level data pooled from 8 randomized trials in the X-Met collaboration to construct CEREBRO, a tool for predicting patient-specific responses to various treatment scenarios. Methods: Patients with omPC from the STOMP, ORIOLE, SABR COMET, EXTEND continuous ADT, EXTEND intermittent ADT, ARTO, RADIOSA, and RAVENS trials were included. 6 patients (1%) with missing data were excluded. Treatment scenarios were defined as active surveillance (AS), metastasis-directed therapy (MDT), systemic therapy (ST), or MDT+ST. To account for varying baseline hazards, Weibull models were fit for overall survival (OS); progression-free survival (PFS); and castration-resistance free survival (CRFS) for patients with hormone-sensitive disease. Endpoint definitions were harmonized per X-Met framework. Results: Of 600 patients included (treatment scenarios: AS=50; MDT=153; ST=172; MDT+ST=225), 405 (67%) had hormone-sensitive omPC. With median follow-up of 38 months, median PFS, CRFS, and OS of all patients were 18, 70, and 84 months. In order of relative contribution, inputs for predicting outcomes were: treatment scenario, stage, prostate-specific antigen annotated by ADT status, metachronous vs synchronous presentation, imaging type, number of metastases, hormone sensitivity, and age. The model for each endpoint showed robust fit, calibration, superiority against the null model (per the likelihood ratio test), and risk stratification (Table). Median PFS times for model-defined low-, intermediate-, and high-risk strata were 46 months, 18 months, and 7 months ( p <0.0001). In addition, the PFS and OS models also showed strong discrimination via c index and a large interval of risk probabilities with additive clinical utility per decision-curve analysis (Table). A public webpage will be made available to facilitate prospective trial stratification, patient counseling for patient-specific outcome predictions for each potential treatment scenario, and forecasts comparing outcomes between treatment scenarios. Conclusions: CEREBRO is a high-performance tool, trained on robust prospective data from 8 randomized trials with routinely collected clinical variables, for predicting risk and treatment outcomes in omPC. Given the uncertainties in optimal timing of MDT and combination with ST, this tool has been built to facilitate current decision making. External validation is planned. Model summary. Endpoint C index (95% CI) Calibration Likelihood ratio p Risk strata p Net clinical utility observed between thresholds PFS 0.72 (0.70-0.75) 1.04 <0.0001 <0.0001 0.2-1.0 CRFS 0.63 (0.60-0.70) 1.01 0.02 0.004 0.2-0.5 OS 0.81 (0.76-0.86) 1.01 <0.0001 <0.0001 0.05-1.0

Real-world urinary detection of FGFR alterations to guide FGFR inhibitor therapy in bladder cancer.

848 Background: FGFR inhibitors have emerged as a promising therapeutic option for urothelial bladder cancer (UBC) patients harboring FGFR alterations ( FGFRalt ). While tissue-based testing is the gold standard for detecting FGFRalt , urinary tumor DNA (utDNA) analysis offers distinct advantages, including non-invasiveness and ease of sampling accessibility. Although utDNA testing has demonstrated potential in guiding clinical decision-making for FGFR inhibitor therapy, its implementation in real-world practice requires further evaluation to establish its reliability and utility. Methods: We performed longitudinal utDNA analysis on a real-world cohort of 155 UBC patients, utilizing 322 urine samples, with the well-established PredicineCARE assay, a capture-based next-generation sequencing platform. The study aimed to evaluate the utility of utDNA in patient selection, monitoring therapeutic efficacy, and detecting disease recurrence. Results: Our findings demonstrate high genomic concordance between utDNA and tissue DNA, supporting the reliability of utDNA as a diagnostic tool. Analysis of baseline urine samples from 155 patients using the PredicineCARE assay identified the five most frequently altered genes in utDNA: TP53 (56%), TERT (52%), FGFR3 (30%), PIK3CA (26%), and ARID1A (26%). These findings are consistent with mutation profiles reported in previous studies. Notably, we observed stage-specific differences in FGFRalt prevalence, with FGFR alterations detected in 51.9% of non-muscle-invasive bladder cancer (NMIBC) cases and 34.6% of muscle-invasive bladder cancer (MIBC) cases. Serial urine analyses revealed that a consistent decline in utDNA levels was associated with an objective response to treatment, while an early rise in utDNA levels predicted subsequent pathological evidence of recurrence. Conclusions: These results highlight the utility of utDNA analysis using the PredicineCARE assay in tailoring FGFR inhibitor therapy to improve patient outcomes. The use of utDNA as a biomarker has the potential to enhance precision medicine in UBC management, offering a non-invasive and accessible approach for real-world clinical practice.

Utility of circulating tumor DNA in patients with renal cell carcinoma at increased risk of recurrence after resection.

519 Background: Despite approval of adjuvant pembrolizumab for high-risk renal cell carcinoma (RCC), risk of disease recurrence persists for many patients after surgical resection, without proven biomarkers for minimal residual disease (MRD). Circulating tumor DNA (ctDNA) testing is utilized in other malignancies to identify MRD and monitor treatment response. Here we aim to investigate whether detection of ctDNA in patients with localized RCC after resection can predict disease recurrence and help guide patient management. Methods: We conducted a retrospective analysis of patients with localized RCC at high-risk for recurrence after resection from May 2022 to August 2025. Inclusion criteria was similar to Keynote-564, including pT2 with grade 4 or sarcomatoid features, pT3, pT4, or any pathological lymph node involvement. Post-nephrectomy and surveillance ctDNA testing were performed using tumor-informed, whole exosome sequencing-based Signatera assays. Disease-free survival (DFS) was performed using Kaplan-Meier and univariable Cox-regression analyses. Results: A cohort of 97 patients were included in the study, with median follow up 15.0 months. Of these, 92 (94.8%) patients had pT3 disease, 85 (87.6%) had clear cell RCC, and 39 (40.2%) received adjuvant therapy. Eleven (11.3%) patients had a positive initial post-operative ctDNA within 3 months of surgery; 12 (12.4%) had ctDNA conversion to positive outside of the 3-month window (median time from surgery to positive ctDNA was 3.5 months). ctDNA positivity has a sensitivity of 73.1% and a specificity of 94.4% for developing radiological progression. Median lead time from ctDNA positivity to radiographic progression was 3.5 (range: 0.9-7.9) months. Any positive ctDNA was associated with a significantly shorter DFS than ctDNA negative group (median 5.5m vs not reached, HR 15.0; 95%CI 5.2-43.5; p<0.0001). Of the 23 patients with ctDNA positivity, 19 had disease recurrence, with 8 on adjuvant therapy before progression. In ctDNA- group, receiving adjuvant therapy prior to progression has a trend towards longer DFS (HR of 0.24, 95%CI: 0.05-1.1). In the ctDNA+ group, early adjuvant treatment was not associated with significantly longer DFS (median 5.3m vs 8.8m, HR 0.45; 95%CI 0.18-1.1). Conclusions: Postoperative and surveillance ctDNA positivity is a significant predictor of disease recurrence for patients with localized RCC patients. Given the ctDNA+ cohort has early disease recurrence, this defines a high-risk population with MRD who may benefit from adjuvant treatment escalation. Prospective studies with longer follow up are necessary to validate the utility of postoperative ctDNA in predicting disease progression and informing clinical decision-making. Recurrence rates stratified by ctDNA positivity. Radiographic recurrence Radiographic NED ctDNA + (anytime) 19 (82.6%) 4 (17.4%) ctDNA - 7 (9.5%) 67 (90.5%)

Molecular Buffering Regulates Lattice Strain for Fatigue‐Resistant Perovskite Photovoltaics Under Cryogenic Thermal Cycling

ABSTRACT Operational stability of perovskite solar cells (PSCs) under temperature fluctuations poses a critical challenge for their practical application in extreme environments such as polar and aerospace regions. Although they exhibit commendable low‐temperature performance, the operational degradation mechanism under cryogenic thermal cycling remains unknown. Here, we uncover a mechanochemical fatigue process wherein cycling between 173 and 298 K generates irreversible structural injury and deep‐level traps through cumulative lattice strain, rather than chemical decomposition. To address this, we design a π‐conjugated molecular buffer, (methylsulfonyl)benzamidine (MSMC), which dissipates cumulative lattice strain under cryogenic thermal cycling via a chemical bonding network while simultaneously healing crystallographic defects through bidentate lead coordination. This synergistic strategy endows p‐i‐n devices that achieve a record efficiency of 28.01% at 228 K (certified 25.94% at 298 K) and, critically, demonstrate unprecedented resilience to cryogenic thermal shocks, retaining 90% of their initial performance after 260 cycles, nearly threefold improvement over controls. The strategy also provides robust compatibility with standard ISOS protocols (light, heat, humidity), underscoring their broad operational resilience. This work establishes mechanochemical fatigue as a fundamental degradation mode and provides a molecular‐scale methodology for creating robust photovoltaics suitable for widespread applications.

High‐Throughput In Vivo Screening Using Barcoded mRNA Identifies Lipid Nanoparticles With Extrahepatic Tropism for In Situ Immunoengineering

ABSTRACT Interest continues to grow in the use of mRNA vaccines and therapeutics. While effective for immunization against infectious diseases, lipid nanoparticle (LNP) formulations used for other mRNA delivery applications suffer from off‐target accumulation, poor immune transfection, and reactogenicity, limiting their application to immunoengineering. Development of new mRNA LNPs is severely bottlenecked by the LNP discovery process, which is historically low‐throughput due to reliance on low‐plex measurements. Here, we develop a high‐throughput in vivo mRNA LNP screening platform based on barcoded mRNA (b‐mRNA). Using this b‐mRNA screening platform to simultaneously evaluate 122 LNPs, we identify novel LNP formulations capable of potent hepatic and extrahepatic transfection. We evaluate a lead LNP candidate for in situ immune modulation in a syngeneic mouse model of melanoma and demonstrate a significant reduction in tumor burden and extended survival compared to mice treated with a gold standard mRNA LNP formulation. We employ novel biochemical characterization techniques to analyze nanoparticle protein corona formation with single‐particle resolution and gain insight into the influence of protein adsorption on hepatic and splenic transfection. Together, our results demonstrate the value of advanced LNP screening and characterization techniques for the development of next‐generation mRNA LNPs for immunoengineering.

High-density lipoprotein mediates silica nanoparticle recognition by the multiligand receptor SR-B1

Membranous Nectin-4 expression to predict enfortumab vedotin response in metastatic urothelial carcinoma.

854 Background: Enfortumab vedotin (EV) is a standard of care for metastatic urothelial carcinoma (mUC), yet robust predictive biomarkers are lacking. Although its target, Nectin-4, is widely expressed, reported levels vary and the relative impact of membranous versus cytoplasmic localization remains unclear. While NECTIN4 amplification strongly predicts EV benefit, it occurs in only ~25% of cases, underscoring the need for refined biomarkers among the remaining ~75% non-amplified patients. We validated NECTIN4 amplification and systematically characterized subcellular Nectin-4 expression, developing a membranous scoring algorithm to enhance patient stratification. Methods: We retrospectively analyzed 183 pretreated mUC patients receiving EV (Nov 2019–Apr 2025, multicenter). NECTIN4 amplification was assessed by FISH and correlated with Nectin-4 immunohistochemistry (IHC). A four-tier membranous scoring system (0–3+), adapted from CAP HER2 gastric criteria, was benchmarked against H-scores. We further built an integrated model combining amplification and membranous staining categories to predict response. Results were compared with biomarker data from the EV-301 trial. Results: Membranous Nectin-4 expression (median H-score 160, IQR 70–240) was significantly lower than cytoplasmic (200, IQR 125–250; P < 0.001). Combined membranous + cytoplasmic scoring yielded higher values (median 250; 79.6% ≥150), consistent with EV-301 (median 250; 82.6% ≥150). A ≥150 cutoff enriched for EV response (our cohort: 52.6% vs. 29.2%; EV-301: 45.8% vs. 20%, P = 0.0014). High membranous expression (2+/3+) predicted superior ORR (59% vs. 21%, P < 0.001), PFS (8.8 vs. 2.6 mo; HR = 0.36, P < 0.001), and OS (13.0 vs. 8.3 mo; HR = 0.50, P = 0.005), whereas cytoplasmic staining was non-predictive. NECTIN4 amplification conferred excellent outcomes (ORR 77.5%; mPFS 17.0 mo; mOS 30.0 mo; all P < 0.001). The integrated model delineated three prognostic groups: amplified, non-amplified/high membranous (2+/3+), and non-amplified/low (0/1+) with ORRs of 77.5%, 45.6%, and 19.4%; mPFS 17.0, 5.5, and 2.6 months; mOS 30.0, 9.5, and 6.9 months (all P < 0.0001). Conclusions: Membranous, but not cytoplasmic, Nectin-4 independently predicts EV response in mUC. NECTIN4 amplification identifies long-term responders, while our novel membranous scoring system refines stratification among non-amplified patients. Comparison with EV-301 suggests that previously reported high expression levels likely reflected combined membranous and cytoplasmic staining, diluting the predictive power of membranous expression alone. These data establish NECTIN4 amplification and membranous Nectin-4 expression as complementary biomarkers to optimize EV patient selection.

Patterns of neoadjuvant chemotherapy (NAC) use in stage II-III bladder cancer: A California Cancer Registry (CCR) analysis.

647 Background: NAC followed by radical cystectomy (RC) improves survival compared to RC alone in patients with muscle invasive bladder cancer (MIBC), yet real-world uptake has lagged. Adjuvant chemotherapy (AC) for those not receiving NAC has been employed though survival benefit has not been established. With evolving perioperative regimens involving immunotherapy changing the treatment landscape, understanding patterns of treatment over time is important. Methods: We evaluated patients with Stage II-III bladder cancer aged > 20, diagnosed from 2004-2022 in the CCR, who underwent RC to assess receipt of both systemic and surgical treatment. Descriptive statistics summarized characteristics of the study population by receipt of NAC + RC, RC + AC, or RC alone among patients. Multivariable logistic regression models identified factors associated with receipt of NAC + RC vs those receiving either RC + AC or RC alone. Results: Among 6749 eligible patients, 2724 (40.4%) received NAC + RC, 438 (6.5%) received RC + AC, and 3587 (53.1%) underwent RC alone. Receipt of NAC was significantly associated with more recent diagnosis (2014-2022 vs 2004-2013): odds ratio [OR] 7.50, 95% CI 6.6.3-8.48), higher neighborhood socioeconomic status (SES) (OR 1.33, 95% CI 1.14-1.56, highest vs lowest tertile), male sex (OR 1.17, 95% CI 1.02-1.34) and care at an NCI-designated Cancer Center (OR 1.40, 95% CI 1.25-1.57). Significantly lower odds of NAC use were observed for those aged > 80 (vs age 20-49; OR 0.31, 95% CI 0.22-0.43), with a Charlson comorbidity score > 1 (vs 0, OR: 0.65, 95% CI 0.57-0.75), and Hispanic individuals (vs non-Hispanic White; OR 0.82, 95% CI 0.69-0.99). Conclusions: NAC use has increased over time, but utilization is lower among older individuals, women, those living in lower SES neighborhoods, Hispanic individuals and those with more comorbidities. These results can help to shape future intervention and optimize treatment utilization as perioperative approaches with broader eligibility criteria emerge.

Parallel liquid biopsy analysis of miR-371a-3p and cell-free DNA in testicular germ cell tumors.

614 Background: miR-371a-3p has emerged as a novel biomarker in testicular germ cell tumors (TGCTs), showing strong potential to improve diagnosis and disease monitoring. Despite robust supporting data, miRNA testing has not yet been implemented in routine clinical practice. Cell-free DNA (cfDNA) represents another promising liquid biopsy biomarker that may provide complementary molecular information and enhance the clinical utility of miR-371a-3p. Methods: Prospectively collected samples from a representative unselected cohort of TGCT patients treated at a single center were evaluated for both miR-371a-3p and cfDNA levels. In total, 109 patient samples were analyzed: 48 at diagnosis, 6 at relapse, 33 during follow-up, and 22 during the disease and treatment course. Controls included 11 healthy adult donors. cfDNA concentrations were measured by qPCR using albumin as the housekeeping gene. miR-371a-3p was detected by an optimized commercial assay and normalized to miR-30b-5p as a control. Results: miR-30b-5p was detectable in 102 of 109 (94%) patient samples, which were then further analyzed for miR-371a-3p. miR-371a-3p was present in 19 of these 102 (19%) samples. It was significantly more frequently detected in patients with clinically manifest disease (15 of 38 samples, 39%) than in those without clinical evidence of disease (4 of 64 samples, 6%), p = 0.0001, representing the sensitivity of 39% and specificity of 94%, with ROC AUC 0.67. There was no difference in miR-371a-3p positivity between patients with seminomas vs. non-seminomas, but it was more frequently found in patients with elevated conventional serum tumor markers (10 of 29 samples, 34%) than in those with normal markers (9 of 73 samples, 12%), p < 0.01. Although cfDNA levels were also elevated in patients with advanced disease and positive serum markers as previously reported (Boublikova et al , Urol Oncol 2022), there was no correlation between cfDNA concentration and miR-371a-3p relative expression (p > 0.05). Conclusions: miR-371a-3p was associated with active or metastatic TGCT and was largely undetectable during remission. Despite its strong potential as a universal biomarker for TGCT—with the exception of mature teratoma—a considerable number of false-negative and false-positive results remain. Detailed analysis of these outliers may help identify biological factors underlying discordant results and guide further refinement of the assay. The lack of association between cfDNA concentration and miR-371a-3p relative expression suggests that levels of these biomarkers may provide independent information on TGCT biology.

Predictors of early termination in phase 2–3 genitourinary oncology trials: A two-decade analysis of clinicaltrials.gov.

331 Background: Early termination of clinical trials delays progress and wastes resources. Predictors of such discontinuation remain poorly characterized. We analyzed two decades of genitourinary (GU) oncology trials to identify trial-level factors associated with completion versus early termination. Methods: Interventional Phase 2–3 GU oncology trials (prostate, bladder, kidney) registered on ClinicalTrials.gov between 2005–2025 were included if conducted in U.S. adults and listed as Completed or Terminated. Withdrawn, suspended, and observational studies were excluded. The primary outcome was trial completion (Completed vs. Terminated). Predictors included trial design (phase, randomization, and masking), primary sponsor type (large pharmaceutical company vs. small/non-industry), intervention category, geographic scope (multisite vs. multinational), and presence of a Data Monitoring Committee (DMC). Associations were evaluated using multivariable logistic regression with robust standard errors. Results: Among 1,597 Phase 2–3 GU oncology trials (445 [27.9%] terminated; 1,152 [72.1%] completed), the leading causes of termination were poor accrual (41.8%), unknown/other (21.6%), and sponsor cancellation (8.5%). On multivariable analysis, prostate cancer trials were more likely to complete than bladder studies (OR 1.84, 95% CI 1.29–2.61, p<0.001). Higher completion odds were also observed for multisite (OR 1.58, 95% CI 1.19–2.10, p=0.002), multinational (OR 1.73, 95% CI 1.16–2.56, p=0.006), and large pharma–sponsored trials (OR 1.67, 95% CI 1.01–2.75, p=0.045). Conversely, randomized designs (OR 0.67, 95% CI 0.52–0.88, p=0.002) and trials with a DMC (OR 0.69, 95% CI 0.53–0.90, p=0.008) were linked to early termination. Trial phase, disease stage, masking, intervention type, line of therapy, and number of arms were not significantly correlated with completion. Conclusions: About one-quarter of Phase 2–3 GU oncology trials end prematurely. Prostate, multisite, multinational, and large industry-sponsored studies are more likely to be completed, whereas randomized designs with DMC oversight are at higher risk of early termination. These findings highlight modifiable design and operational factors to improve feasibility and success in future GU oncology trials. Trial characteristics by completion status (N = 1,597). Characteristic, n (%) Total Terminated Completed Disease site  Bladder 274 (17.2) 91 (20.4) 183 (15.9)  Kidney 354 (22.2) 109 (24.5) 245 (21.3)  Prostate 969 (60.7) 245 (55.1) 724 (62.8) Phase 3 (vs 2) 262 (16.4) 58 (13.0) 204 (17.7) Randomized 844 (52.8) 244 (54.8) 600 (52.1) Large Pharma primary sponsor 194 (12.1) 30 (6.7) 164 (14.2) Multisite (>1 site) 960 (60.1) 233 (52.4) 727 (63.1) Multinational 346 (21.7) 68 (15.3) 278 (24.1) DMC present 816 (51.1) 261 (58.7) 555 (48.2) Drug-based intervention 1,417 (88.7) 406 (91.2) 1,011 (87.8)

Defect‐Elimination Strategies for Fabricating High‐Strength and Highly Conductive MXene Fibers

ABSTRACT Two‐dimensional (2D) transition metal carbides and nitrides (MXenes) nanosheets exhibit outstanding mechanical, electrical, electrochemical, and photothermal conversion properties, along with good solution processability, making them highly promising for the fabrication of high‐performance conductive MXene fibers. However, issues such as weak interfacial interactions, structural disorder, and nanosheet wrinkling often result in void defects, which hinder both load and electron transfer, thereby limiting the performance of macroscopic MXene fibers. This review systematically summarizes the recent progress in the defect‐elimination strategies for the fabrication of high‐strength and highly conductive MXene fibers, with a focus on performance and applications, from the perspectives of structure and interfacial design. Particular attention is given to strategies aimed at performance enhancement, especially those focused on strengthening interfacial interactions, improving alignment of MXene nanosheets, and eliminating voids, which are critical factors in assembling high‐performance conductive MXene fibers. Meanwhile, this review highlights the diverse multifunctional applications of MXene fibers in wearable electronic textiles. Finally, we conclude by discussing the key advantages and persistent challenges associated with various assembly structures, and present an outlook on the future design and development of high‐performance conductive MXene fibers, offering valuable insights for advancing research and practical applications of MXene fibers.

Industrial‐Scale High‐Selectivity Plastic Upgrading with Stability Exceeding 1000 h over Distorted PtPdTe Nanosheets

ABSTRACT The electrocatalytic ethylene glycol (EG) oxidation to value‐added chemicals is highly desirable for profitable resource utilization, yet encounters a low yield rate and poor durability. Herein, a class of highly distorted PtPdTe nanosheets (PtPdTe‐a) with modulated electronic states and oxophilicity is prepared by reconstructing layered PtPdTe dichalcogenide and delivers a record mass activity (11.78 A mg Pt+Pd −1 ) toward EG oxidation reaction with high glycolic acid (GA) Faradaic efficiency (96.7%). Mechanistic investigations reveal that PtPdTe‐a features a strong p‐d coupling effect for facilitating the formation and adsorption of hydroxyl adspecies to accelerate the oxidation of carbonyl intermediates, thereby avoiding over‐oxidation and switching the pathway toward desired C2 direction. We further demonstrate the unprecedented stability of PtPdTe‐a‐based electrolyzer for over 1000 h (> 150 mA cm −2 ). The scale‐up electrolyzer can achieve GA electrosynthesis with a record yield rate of 5.04 mmol cm −2 h −1 and a very high initial current density of over 800 mA cm −2 from the upgrading of PET. Our new strategy can produce 422.36 g of terephthalic acid, 904.08 g of Na 2 SO 4 , and 112.69 g of GA from 500 g of PET with a profit of about $880.23 ton −1 PET. Besides, PtPdTe‐a is highly efficient for ethanol oxidation into acetic acid with excellent selectivity.

ATGL-catalyzed biosynthesis mediates the upregulation of fatty acid hydroxy fatty acids (FAHFA) levels in white adipose tissue with fasting

Association between preoperative glycemic control and outcomes after radical prostatectomy.

345 Background: Elevated hemoglobin A1c (A1c) levels are often thought to contribute to adverse perioperative outcomes in diabetic patients. However, data supporting this is limited and conflicting, particularly among patients undergoing radical prostatectomy (RP) for prostate cancer. While some institutions delay surgery in patients with elevated A1c levels, evidence supporting strict thresholds is limited. We evaluated whether preoperative A1c ≥ 8% independently predicts adverse short-term outcomes following RP. Methods: We analyzed the 2023 ACS-NSQIP participant use file with targeted prostatectomy variables. Patients undergoing radical prostatectomy were stratified by preoperative A1c levels (< 8% versus ≥ 8%) measured within 180 days of surgery. Univariate analysis compared 30-day operative outcomes including major, minor, and procedure-specific complications. Multivariate logistic regression adjusted for confounders on significant endpoints, as well as overall complications, readmissions, reoperations, and mortality. Results: Among 7,162 patients undergoing radical prostatectomy, 110 (1.5%) had preoperative A1c ≥ 8%. Patients with elevated A1c demonstrated significantly higher BMI (31.15 vs 29.14 kg/m², p < 0.0001) and increased comorbidities including CHF and hypertension (p < 0.0001). Univariate analysis revealed significant associations between A1c ≥ 8% and wound dehiscence (0.91% vs 0.11%, p = 0.019), anastomotic leak (5.97% vs 1.29%, p = 0.001), and cerebrovascular events (0.91% vs 0.03%, p < 0.0001). However, following multivariable adjustment, these associations were attenuated and no longer significant. No significant differences were observed in rates of major complications, minor complications, infectious complications, procedure-specific complications, readmissions, or reoperations. Conclusions: This multi-institutional analysis demonstrates that while A1c ≥ 8% correlates with select complications in univariate analysis, it does not independently predict adverse outcomes after adjustment for comorbidity burden. Elevated A1c appears to serve as a marker of medical complexity rather than a direct contributor to perioperative morbidity. Although preoperative optimization remains prudent, A1c ≥ 8% is not associated with adverse perioperative outcomes during radical prostatectomy in appropriate surgical candidates. Clinical decision-making should incorporate comprehensive patient assessment rather than relying solely on glycemic thresholds. Radical prostatectomy patient outcomes. HbA1c <8 or No Diabetes Dx N = 7052 HbA1c ≥8 N= 110 P-value Minor Complications 406 (5.76%) 9 (8.18%) 0.2801 Major Complications 405 (5.74%) 9 (8.18%) 0.2768 Urological Complications 378 (5.36%) 7 (6.36%) 0.6433 Return to operating room 58 (0.82%) 2 (1.82%) 0.2556 Readmission 293 (4.15%) 7 (6.36%) 0.2512 Death 4 (0.06%) 0 (0%) 0.8027