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Exsolution‐Driven Layered Perovskites for Stable Thermal Carbon Capture and Utilization of Waste Streams

ABSTRACT Integrated carbon capture and utilization (ICCU) presents a sustainable route for simultaneous valorization of CO 2 and solid waste, yet maintaining cyclic stability under high‐temperature conditions remains challenging. Here, we construct dual‐functional materials based on Ni‐substituted layered perovskite Sr 2 TiO 4 , engineering to enhance Ni‐substrate interactions, thereby stabilizing ICCU reactions via in situ exsolution. Systematic experiments and characterizations reveal that gradual Ni exsolution from the Sr 2 TiO 4 /SrTiO 3 matrix during cyclic reactions yields well‐dispersed, surface‐anchored Ni nanoparticles. This dynamic process drives progressively increasing, then stabilized, CO 2 uptakes and syngas productions across cycles, contrasting sharply with the deactivation of predeposited Ni system. Moreover, electronic structure analysis reveals that CO emissions from exsolved Ni‐driven CO 2 splitting are both more kinetically unfavorable than Sr 2 TiO 4 carbonation and effectively suppressed by O 2 in the flue gas. These findings demonstrate a robust strategy for efficient co‐utilization of CO 2 and solid waste under demanding thermochemical conditions.

Large extracellular vesicles regulate endothelial angiogenic potential via paracrine and autocrine signaling

Comparison of multiparametric prostate MRI (mpMRI) vs. positive biopsy cores on risk of adverse pathologic outcomes after radical prostatectomy (RP) in Gleason grade group (GG) 2 prostate cancer.

320 Background: Current guidelines endorse prognostication with percentage of positive biopsy cores when deciding upon definitive treatment in intermediate risk prostate cancer. However, in the era of mpMRI, we hypothesize that Prostate Imaging Reporting and Data System (PI-RADS) scoring is more informative for predicting adverse pathologic outcomes after RP. Methods: A retrospective study was conducted of patients with GG 2 prostate cancer from a single institution who underwent RP from 2016-2025. Patients were included based on preoperative metrics, including percentage of positive biopsy cores (≥50% or <50%), mpMRI maximum lesion diameter (<15 mm or ≥15 mm), and PI-RADS score (<4 or ≥4). Multivariable logistic regression analyses identified significant predictors of postoperative upgrading and upstaging. Results: A total of 87 patients were included with a median preoperative PSA value of 7 ng/mL (IQR 5.65–9.90) and prostate volume of 59.14 mL (IQR 38.5–81.00). Of 87 patients, 41.4% were White and 41.4% were Black. In multivariable analysis including preoperative PSA value and prostate volume, high positive biopsy cores and high mpMRI lesion diameter were not associated with pathological upgrading, upstaging and adverse pathology. However, high PI-RADS score was independently associated with pathological upstaging (p = 0.02) and adverse pathology, including pT3-4 or pN1+ (p = 0.011). Conclusions: More accurate risk stratification is needed to guide treatment decisions for intermediate risk prostate cancer. Our findings highlight greater PI-RADS score as a predictive marker of adverse pathologic features at RP. While our analysis was limited by small cohort size, our results showed no significant association between percentage of positive biopsy cores and adverse pathologic findings. Therefore, consideration of mpMRI in future optimization of existing NCCN risk stratifications may be warranted. Future investigation is needed to confirm these findings. Multivariable logistic regression model for predicting postoperative pathological upgrading, pathological upstaging (pT3-4), and adverse pathology (pT3-4 or pN1+). Pathological Upgrading (GG ≥ 3) Pathological Upstaging(pT3-4) Adverse Pathology(pT3-4 or pN1+) Variables OR (95% CI) P OR (95% CI) P OR (95% CI) P Preoperative PSA 1.01 (0.89-1.25) 0.54 0.94 (0.82-1.08) 0.39 0.94 (0.81-1.08) 0.36 Prostate volume 1.00 (0.98-1.01) 0.66 1.00 (0.98-1.01) 0.47 0.99 (0.98-1.01) 0.39 Positive Biopsy Cores ≥ 50% 1.01 (0.44-2.31) 0.98 1.21 (0.66-2.24) 0.54 1.33 (0.71-2.48) 0.37 Max Lesion Diameter ≥ 15mm 1.01 (0.92-1.1) 0.91 1.00 (0.93-1.07) 0.89 0.99 (0.93-1.06) 0.85 PI-RADS ≥ 4 1.16 (0.47-2.88) 0.75 2.36 (1.15-4.83) 0.02 2.6 (1.25-5.42) 0.011

A phase III randomized trial of eribulin (E) with gemcitabine vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937—Updated design.

TPS894 Background: UC is the 2nd most common genitourinary cancer. Enfortumab vedotin (EV) + pembrolizumab became a SOC in 2023 in frontline mUC setting. There is no established standard of care for the subsequent lines of therapy limiting treatment options to platinum-based chemotherapy, docetaxel, paclitaxel, or gemcitabine. Erdafitinib remains an option for pts with FGFR3 alterations. A phase I/II CTEP study of eribulin (E) for mUC established the activity of E with an objective response rate (ORR) of 37.5%, median progression-free survival (PFS) of 4.1 months (mo), and median overall survival (OS) of 9.5 mo (N = 150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed an ORR of 50%, median OS of 11.9 mo, and median PFS of 5.3 mo (N = 24). The most common Grade 3-4 toxicities included neutropenia (63%), anemia and fatigue (29% each). Pts with liver metastases benefited from therapy with an ORR of 71% (n = 7) for GE vs. 24% for E (N = 49). Methods: This is an updated phase III, randomized trial comparing GE vs. SOC (docetaxel, paclitaxel, or gemcitabine monotherapy). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. Gemcitabine is added to E at 1000 mg/m2 on D 1 and D 8. SOC follows approved dosing. There is no limit to the number/sequence of prior regimens. Pts with bone only metastases are eligible. All pts must have: received systemic therapy with EV; received PD1/PDL1 Ab or been deemed ineligible for PD1/PDL1 Ab. The study seeks to find at least a 50% increase in the primary endpoint of OS (Hazard Ratio (HR) = 0.667). Secondary endpoints include ORR and PFS. This design has a power of 80% and a one-sided alpha of 0.05 to detect a HR = 0.667. We require 184 pts (92 in each arm) to yield a total of 168 eligible pts. Funding: National Institutes of Health/National Cancer Institute grants U10CA180888, U10CA180819. Eribulin is provided by Eisai. Clinical trial information: NCT04579224 .

Integrating 3D structural modelling and seismic interpretation to optimize hydrocarbon development in the Early Miocene Nukhul Formation, October Oil Field, Gulf of Suez, Egypt

Abstract This study presents an integrated 3D structural modelling workflow as a quantitative framework for applying advanced geological understanding to the spatial distribution of discrete and continuous reservoir properties of the underexplored, structurally complex Nukhul Formation in the October Oil Field. The updated 3D structural model was constructed by integrating high-resolution seismic interpretation with multidisciplinary subsurface datasets, including electric logs, detailed stratigraphic correlations, petrophysical evaluation, and production performance data from drilled wells. The current study specifically evaluates the structural controls on reservoir distribution and trapping styles within the field by combining 3D seismic interpretation with well-log and core-derived information. The refined model reveals a fault architecture dominated by a NNW–SSE (Clysmic) trend, with major faults dipping south-southwest (SSW) and horizons oriented northeast (NE), as determined from dipmeter data and seismic interpretation. The Nukhul reservoir is defined by a three-way dip closure, bounded by fault-dependent seals, where sealing capacity is governed by fault throw that juxtaposes permeable sand layers against impermeable lithologies. This configuration effectively inhibits cross-fault hydrocarbon migration, preserving attic accumulations. By integrating geological, geophysical, and petrophysical datasets, the new model significantly improves the delineation of attic targets, fault-bounded compartments, and reservoir–seal juxtapositions. Consequently, it provides refined well-placement recommendations, including high-potential attic infill drilling locations. Furthermore, the model establishes a technically robust basis for reservoir management and depletion planning, aiming to maximize recovery while minimizing water-handling risks. These outcomes demonstrate the value of incorporating new seismic and well datasets into legacy models and highlight their potential for reducing uncertainty in structurally complex syn-rift settings. Beyond the October Field, the updated structural modelling approach has broader implications for syn-rift petroleum systems in the Gulf of Suez and analogous rift basins, offering a predictive tool for fault-seal analysis, volumetric assessment, reservoir performance evaluation, and optimized drilling strategies.

A randomized phase 2 trial of nivolumab, relatlimab plus ipilimumab vs. nivolumab plus ipilimumab in first-line advanced renal cell carcinoma.

TPS580 Background: Ipilimumab plus nivolumab (ipi/nivo) is a standard of care for treatment-naïve, metastatic clear cell renal cell carcinoma (ccRCC). While durability of response may be superior to combination therapy with PD-1 inhibitors and agent tyrosine kinase inhibitors, ipi/nivo has a relatively low objective response rate (ORR) and relatively high progressive disease (PD) as best response. Building on the benefits of ipi/nivo through additional immune manipulation has biologic rationale and could expand the efficacy of this regimen. Lymphocyte-associated gene 3 (LAG3) is an inhibitory receptor on activated immune cells that plays a role in T cell exhaustion. LAG3 is expressed on T cells and is co-expressed with other inhibitory receptors such as PD-1. This co-expression induces the disfunction of T cells and thus limits the anti-tumor T cell response. Relatlimab is a human LAG-3-specific antibody that binds to the LAG-3 receptor with high affinity and blocks LAG-3 interactions with its canonical ligand, major histocompatibility complex (MHC) Class II, which is the peptide antigen presentation molecule recognized by CD4+ T cells. Relatlimab binding inhibits the negative regulatory function of LAG-3 in vitro. Relatlimab restores effector function of exhausted T cells. Combined LAG3 inhibition with relatlimab and PD-1 inhibition with nivolumab was recently demonstrated in the RELATIVITY-047 melanoma study. These compelling preclinical and clinical data have led to the hypothesis that adding relatlimab to ipilimumab plus nivolumab will increase objective response rate in patients with metastatic ccRCC. Methods: This is a phase 2 randomized, multicenter, study investigating the efficacy of nivolumab 480 mg every 4 weeks (Q4W), relatlimab 160 mg Q4W and ipilimumab 1 mg/kg every 8 weeks (Q8W) intravenous (IV) versus a doublet arm treating with nivolumab 480 mg Q3W and ipilimumab 1mg/kg Q3W IV followed by maintenance nivolumab in first-line advanced ccRCC. Co-primary endpoints include safety and ORR. Up to 60 patients with treatment naive, biopsy-proven ccRCC with adequate organ/marrow function with at least one evaluable lesion by RECIST 1.1 will be enrolled and randomized 2:1 to the experimental arm versus ipi/nivo. Ongoing safety and futility monitoring will employ a 2-arm Bayesian optimal phase 2 (BOP2) design. Sample size provides 64% power at a one-sided 0.15 significance level to detect a difference between the arms assuming the overall response rates are 40% vs. 60% for nivo/ipi vs. experimental arm, respectively. Secondary endpoints include progression free survival and OS. To explore the effects of the treatment on inducing activated T cell infiltration, biopsies and circulating immune cell subsets will be obtained for single cell analysis and spatial transcriptomic studies. Over 10 patients are enrolled at the time of submission. Clinical trial information: NCT06708949 .

Intercellular Communication‐Driven Mitochondrial Transfer via CXCR4‐Engineered Macrophages Reprograms Bone Marrow Metabolism for Osteoporosis Therapy

ABSTRACT Osteoporosis is characterized by impaired bone formation and disrupted bone marrow homeostasis, largely driven by mitochondrial dysfunction in bone marrow mesenchymal stem cells (BMSCs). To address this, a live mitochondrial delivery system composed of CXCR4‐engineered macrophages loaded with nanozyme‐functionalized mitochondria (CM‐MTBM). This system integrates bone‐targeted migration, reactive oxygen species scavenging, and communication‐mediated mitochondrial transfer. CM‐MTBM restores mitochondrial respiration, enhances osteogenic differentiation, and alleviates oxidative apoptosis in BMSCs, thereby promoting metabolic recovery and redox balance. In osteoporotic mice, CM‐MTBM treatment markedly improved the trabecular bone microarchitecture and promoted osteogenic repair. Single‐cell transcriptomic analysis further revealed the enrichment of osteogenic BMSC subpopulations and functional reprogramming of the bone marrow immune–metabolic microenvironment. Mechanistically, CM‐MTBM activated mitochondrial oxidative metabolism while suppressing inflammation and senescence‐associated signaling, achieving coordinated metabolic and osteogenic activation. Collectively, this work established a communication‐driven mitochondrial transfer paradigm that reframes mitochondrial therapy from passive structural supplementation to communication‐driven metabolic reprogramming, establishing a conceptual and technological framework for precision treatment of metabolic bone disorders.

Writers and readers of sialylation in immunoregulation in cancer

Real-world evaluation of olaparib combined with novel hormone therapy in metastatic castration-resistant prostate cancer with intraductal adenocarcinoma.

213 Background: Intraductal adenocarcinoma of the prostate (IDC-P) is an aggressive histological variant of prostate cancer and was reported harboring increased homologous recombination repair deficiency (HRD). Our aim was to explore the predictive value of IDC-P on the efficacy of novel hormone therapy (NHT) in combination with olaparib in the metastatic castration-resistant prostate cancer (mCRPC) after progression on NHT. Methods: This study included 64 consecutive patients receiving olaparib plus NHT (abiraterone (59), enzalutamide (3), darolutamide (2)) after progression on NHT: 33 IDC-P and 31 prostate adenocarcinoma (PAC) were identified. Prostate-specific antigen (PSA) progression-free survival (PSA-PFS), treatment change-free survival (TFS), and overall survival (OS) were compared between IDC-P and PAC using the Kaplan-Meier method. Cox proportional-hazards models were employed to evaluate the predictive value of IDC-P for PSA-PFS, TFS, and OS. PSA response, subgroup analysis, and adverse events (AEs) were also evaluated. Results: The median follow-up for the total cohort was 35 months. Patients with IDC-P presented longer PSA-PFS and TFS compared to those with PAC (PSA-PFS: 6.2 months (IDC-P) vs. 3.0 months (PAC), p < 0.01; TFS: 10.0 months (IDC-P) vs. 6.3 months (PAC), p < 0.01). The PSA response rate was comparable (45.2% (IDC-P) vs. 35.7% (PAC), p = 0.60). In patients with BRCA 1/2 variants, IDC-P was associated with a significantly longer PSA-PFS and TFS (PSA-PFS: 9.8 months (IDC-P) vs. 3.0 months (PAC), p < 0.01; TFS: 11.3 months (IDC-P) vs. 10.2 months (PAC), p = 0.04). In the BRCA 1/2 wild-type/unknown subgroup, patients with IDC-P showed comparable PSA-PFS and TFS (PSA-PFS: 3.7 months (IDC-P) vs. 3.0 months (PAC), p = 0.27; TFS: 4.0 months (IDC-P) vs. 5.2 months (PAC), p = 0.20). Multivariate Cox regression analysis demonstrated IDC-P to be a predictor for better PSA-PFS and TFS independent of BRCA 1/2 variation. OS was comparable in the total cohort but displayed benefits in IDC-P when no further treatments were administered following olaparib plus NHT (14.0 months (IDC-P) vs. 10.2 months (PAC), p = 0.035). AE rates were comparable between IDC-P and PAC. Conclusions: IDC-P predicted better efficacy of olaparib plus NHT in previously NHT-treated mCRPC independent of BRCA1/2 mutation status. The results identifies a population who may benefit from poly ADP-ribose polymerase inhibitors combined with NHT without using genomic testing.

SWOG 2427: Single arm phase II study of bladder preservation with immunoradiotherapy after a clinically meaningful response to neoadjuvant therapy in patients with muscle invasive bladder cancer (BRIGHT).

TPS913 Background: A subset of patients with MIBC who receive neoadjuvant therapy (NAT) prior to radical cystectomy (RC) have a pathologic complete response (pCR) at the time of RC. With pCR rates of 22-42% in patients with MIBC following NAT (+/- ICI), whether a subset of patients with good clinical response to NAT can avoid RC is an important unanswered question, especially with the development of more active systemic therapies. HCRN 16-257 evaluated maintenance nivolumab in lieu of cystectomy in patients with MIBC who experienced clinical complete response (cCR) following neoadjuvant GC and nivolumab. The cCR rate was 48%, but 8/33 (24%) patients who elected bladder preservation subsequently underwent cystectomy for local disease recurrence. The RETAIN trial also evaluated omission of local therapy following neoadjuvant therapy with a 2-year bladder preservation rate in patients with ≤T1 disease following NAC of 54% (22/41). Of the 9/25 (36%) patients on that trial developed metastatic disease, 8/9 developed localized disease before metastasizing. These data illustrate the critical role that local therapy plays in patients with MIBC. For this reason, we believe that radiotherapy to the bladder combined with ICI will improve bladder intact event-free survival (BI-EFS). This trial also allows for patients to opt for bladder preservation based on a good clinical response to NAT. Methods: This is a single arm, phase 2 trial (NCT07061964) evaluating risk-adapted bladder preservation therapy for patients with MIBC following NAT. NAT consists of any NCCN guideline concordant therapy for MIBC. Patients with cT2-T4aN0M0 MIBC who complete NAT will be eligible if they have ≤T1 disease on post-NAT TURBT, confirmed by biopsies of prior tumor sites and systematic sampling (left/right lateral walls, dome, posterior wall, trigone). Patients will receive 55 Gray (Gy) in 20 fractions of radiotherapy (RT) to the bladder with 1 year of pembrolizumab. The primary objective is to evaluate whether 3-year BI-EFS is at least 70% in participants with < = T1 (without multifocal CIS) following NAT and RT with 1 year of pembrolizumab. Secondary objectives include local muscle invasive recurrence-free survival, metastasis-free survival (MFS), overall survival (OS), the rate of salvage cystectomy, and evaluation of the frequency and severity of toxicities in participants who receive RT and pembrolizumab. Plasma and urine will be banked for future correlative studies. S2427 was activated in September 2025 with an accrual goal of 111 patients. Clinical trial information: NCT07061964 .

Shaking and withering intensity from oolong tea processing alters the chemical and sensory quality of tobacco

Evaluation of toxicity profiles of next-generation androgen receptor pathway inhibitors in the geriatric population: Analysis of the FAERS (FDA Adverse Event Reporting System) database.

206 Background: The use of next-generation ARPIs in combination with ADT has revolutionized the treatment of prostate cancer. However, toxicity data remain limited, particularly in the geriatric population. The aim of this study was to evaluate the age-related toxicity profile of ARPIs to guide personalized treatment selection. Methods: This retrospective study was conducted using data from the FAERS (2015–2025). After deduplication per FDA guidance, 14,526,785 unique reports were retained. Male prostate cancer cases aged ≥18 years in which an ARPIs —enzalutamide, apalutamide, darolutamide, abiraterone— was listed as the primary suspect drug were included (n = 33,076). Adverse events were classified using Standardised MedDRA Queries (SMQs, MedDRA v28.1), which group clinically related preferred terms into hierarchical categories. Malignancy-related SMQs were excluded to avoid indication bias. Disproportionality analyses were performed using Reporting Odds Ratios (RORs) to detect significant positive signals (lower 95% CI >1). SMQs meeting this threshold were further assessed by univariate logistic regression for age-specific risk (% of events for total population, <70 vs ≥70 years: OR, p), analyzed separately for each drug (R v4.3.1). Results: FAERS included 33,076 prostate cancer cases (enzalutamide: 19,105; abiraterone: 9,775; apalutamide: 2,981; darolutamide: 1,215).For abiraterone, hepatic disorders were less frequent in older individuals (5.6%, OR: 0.78, p=0.007), whereas hypokalaemia (3.6%, OR: 1.33, p=0.026), cardiac arrhythmias (2.6%, OR: 1.68, p = 0.001), cardiac failure (2.2%, OR: 2.32, p<0.0001), and non-infectious encephalopathy/delirium (0.4%, OR: 2.23, p=0.07) were more frequent with increasing age. For enzalutamide, gastrointestinal dysfunctions (18.4%, OR: 0.91, p=0.026) were less frequent in older men, whereas the incidence of convulsions (1.7%, OR: 1.30, p=0.068), psychotic disorders (1.1%, OR: 1.47, p = 0.029), and dementia (0.5%, OR: 33.01, p<0.001) increased with age. Apalutamide was linked to increased hypersensitivity (20.7%, OR: 1.46, p=0.001), lower hepatic disorders (3.4%, OR: 0.53, p=0.003), and a possible rise in interstitial lung disease (2.7%, OR: 1.80, p=0.064). For darolutamide, no specific toxicity was found to increase with age. Conclusions: In the geriatric population, ARPI selection should be individualized based on the toxicity profiles of the agents.

Performance Constraints of All‐Perovskite Tandem Solar Cells in Low‐Intensity, Low‐Temperature Environments

Abstract All‐perovskite tandem solar cells (2J‐PSCs) reach the highest power‐to‐weight ratios, making them promising candidates for space applications. To determine their potential for future deep space missions, this study assesses the performance of 2J‐PSCs under low‐intensity and low‐temperature (LILT) conditions, akin to those found near Saturn, the Asteroid belt, or in eclipse. Temperature‐dependent current density‐voltage ( J – V ) measurements under varying solar intensities (AM0, 0.1 AM0, 0.01 AM0) reveal that the 2J‐PSCs, comprising 1.80 eV high‐bandgap and 1.27 eV low‐bandgap perovskites, exhibit significant efficiency losses at lower temperatures and low light levels. In contrast, 1.54 eV single‐junction PSCs (1J‐PSCs) exhibit resilient performance, maintaining or even increasing their power conversion efficiency at low temperatures. The main performance problem of the 2J‐PSCs is then identified as a demixing of the 1.80 eV perovskite due to its high Br ratio at temperatures below 250 K. This demixing at low temperatures leads to a significant increase in ion‐induced performance losses as well as current imbalances between the two subcells in the monolithic tandem. Together, this causes severe S‐shapes in solar cell operation and impedes the operation of the monolithic interconnected tandem solar cells. Notably, these limitations vanish upon heating, leading to a recovery of performance.

Deregulated translation of the transcription factor Myt3 predisposes islet β cells to dysfunction under obesity-induced metabolic stress

Regional variations in bladder cancer (BC) clinical trial availability within the United States (US).

652 Background: Geographic disparities of phase I-III cancer clinical trials in the US are well described (Gu et al., JMCP 2024), but specific patterns for BC remain unexplored. We evaluated BC trial availability across US counties, interrogating associations with epidemiologic and socioeconomic factors. Methods: We queried ClinicalTrials.gov for adult, interventional BC trials from June 1, 2019 to June 1, 2025, and mapped the US site ZIP codes to counties using US Postal Service data. County-level age-adjusted incidence and mortality, and Social Vulnerability Index (SVI) were obtained from the CDC, NCI, and Agency for Toxic Substances and Disease Registry. The SVI reflects 16 socioeconomic and demographic variables. Trial characteristics were summarized descriptively. To assess geographic factors linked to trial availability, we modeled the number of trials available per county using a zero-inflated negative binomial (ZINB) regression—a model that accounts for the many counties without trials and estimates how county characteristics relate to the trial rate. The model was adjusted for county size, effectively analyzing the rate of trials per household. Results are expressed as incidence rate ratios (IRRs), where IRR > 1 indicates a higher trial rate as the predictor increases. Analyses used R 4.4.3. Results: We identified 436 eligible trials with active sites across 713 US counties; 77.3% of counties had no trials. Trials were mostly sponsored by pharmaceutical companies (48.4%) followed by academia (39%). Most trials focused on drug therapy (80.2%) over surgery (6.4%) or radiation (4.6%); and most were early phase (I/II, 72%). Using the ZINB model, higher BC incidence was associated with slightly higher trial rate per household (IRR 1.033, 95% CI 1.003–1.063). Notably, higher BC mortality was associated with fewer trials (IRR 0.80, 95% CI 0.73–0.88). Compared with high-SVI (most socially vulnerable) counties, less vulnerable counties had higher trial rates: lower-middle SVI (IRR 1.57, 95% CI 1.18–2.08), middle-high SVI (IRR 1.60, 95% CI 1.22–2.11), and low-SVI counties (IRR 2.53, 95% CI 1.89–3.38). Of 7,091 trial sites in the US, 657 (9.3%) were in counties with the highest quintile (Q5) for BC incidence. However, only 225 (3.2%) sites were in Q5 counties for BC mortality. Metastatic and non-metastatic trials were similarly represented across mortality quintiles. While most trials were early phase overall, high mortality counties had proportionally less early phase trial sites (56.4% Q5 vs. 63.8% Q1). Conclusions: Most US counties lacked a BC trial. Trial availability was higher where disease is diagnosed, not where patients most often die from it. Research access is concentrated in counties with high BC incidence and low social vulnerability. Expanding trial sites to high mortality or high-SVI counties may be an actionable step for investigators to improve equitable trial access nationwide.

Circulating tumor DNA response adapted treatment de-escalation in metastatic urothelial carcinoma (CT-READ).

TPS907 Background: Metastatic urothelial carcinoma (mUC) remains a lethal disease remains an aggressive malignancy with a 5-year survival rate below 10% despite recent therapeutic advances. The phase III EV-302 trials established the combination of pembrolizumab (P) and enfortumab vedotin (EV) as the first-line (1L) standard of care, demonstrating a median overall survival (OS) of 31.5 months and progression-free survival (PFS) of 12.5 months. However, ≥Grade 3 treatment-related adverse events (TRAEs) occur in more than half of treated patients, frequently necessitating dose interruptions or discontinuations. Notably, sustained clinical benefit is often observed following EV discontinuation, suggesting that some patients may achieve durable disease control with reduced treatment intensity. Circulating tumor DNA (ctDNA) represents a dynamic, minimally invasive biomarker of tumor burden and treatment response. Retrospective longitudinal analyses in patients with mUC treated with P+EV have demonstrated the prognostic and predictive value of ctDNA dynamics. (6) Specifically, ≥50% reductions in ctDNA levels have been independently associated with improved PFS and OS, supporting ctDNA as a robust, real-time biomarker to inform response-adapted, biomarker-driven therapeutic de-escalation strategies. Methods: This single-institution, single-arm, open-label, phase II pilot trial (NCT06313666) evaluates ctDNA-guided PEV de-escalation in patients with untreated mUC. Eligible Patients will receive standard 1L PEV for 8 cycles. Plasma ctDNA is measured every 12 weeks using a tumor-informed multiplex PCR assay. Patients achieving ≥50% ctDNA reduction at 6 months and without radiographic progression discontinue EV and continue pembrolizumab monotherapy every 6 weeks until progression or toxicity. EV rechallenge is permitted at progression. Primary endpoints are 3- and 6-month PFS post-de-escalation. A Simon two-stage minimax design (n = 30; 21 expected to de-escalate) will be used; the study will be considered positive if ≥7 patients remain progression-free at 3 months. Secondary and correlative endpoints include correlation of ctDNA dynamics with imaging-based response and clinical outcomes, ctDNA clearance kinetics, and neuropathy evaluation. Clinical trial information: NCT06313666 .

Analysis of the resistance of small peptides from Periplaneta americana to H2O2-induced apoptosis in KGN Cells based on miRNA-seq

Blind Spots in REZILIENT-1: Does Post-Platinum Zipalertinib Address Needs in Epidermal Growth Factor Receptor ex20ins+ Non–Small Cell Lung Cancer?

Sensitive Shortwave Infrared Organic Photodetectors Enabled by Nonfullerene Acceptor Featuring an Ultralow Optical Bandgap of Less than 1.0 eV

ABSTRACT Shortwave infrared (SWIR) photodetectors are in high demand in modern applications, including night surveillance, biological imaging, and optical communication. Emerging organic semiconductors, featuring a tailorable spectral response and solution processability, open new avenues for SWIR light detection. However, SWIR organic photodetectors (OPDs) suffer from a scarcity of ultralow‐bandgap organic semiconductors and low responsivity above 1000 nm. Here, we report a new electron‐rich building block, thieno[3′,2′:4,5]cyclopenta[1,2‐ b ]thieno[2,3‐ d ]pyrrole (SNCS), that exhibits strong electron‐donating ability. By applying acceptor–donor–acceptor and acceptor‐quinoidal‐donor‐quinoidal‐acceptor strategy, we developed two new nonfullerene acceptors: SNCS‐4F and SNCSTT‐4F. The latter, with thieno[3,4‐ b ]thiophene moiety, exhibits strong SWIR absorption up to 1400 nm in thin films. The best‐performing PTB7‐Th:SNCSTT‐4F‐based OPD exhibits a record external quantum efficiency of 50.2%, a responsivity of 0.49 A W −1 and remarkable specific detectivity of 4.47 × 10 12 Jones at 1200 nm under zero bias. This is the highest performance among reported SWIR organic photodiodes and is comparable with commercial InGaAs photodetectors. Ultraviolet photoelectron spectra, Mott–Schottky analysis and trap density of states analysis were applied to evaluate the OPDs’ performances. Finally, we demonstrate that the OPDs can detect SWIR light with high sensitivity in photoplethysmography measurements and infrared audio communication applications.

Atomic Eu‐Mediated Acetonitrile Adsorption Configuration Switch Drives Long‐Term and Ampere‐Level Electrosynthesis of Ethylamine in AEM Electrolyzer

ABSTRACT Electrocatalytic hydrogenation of acetonitrile (AN‐ECH) offers a sustainable pathway for ethylamine (EA) synthesis. However, achieving high selectivity in AN‐ECH necessitates carefully balancing proton availability to suppress the hydrogen evolution reaction (HER), which often conflicts with the proton supply requirements under industrial‐grade current densities. Herein, we design and develop a novel and effective AN‐ECH catalyst consisting of rare‐earth Eu atoms modified on Cu 2 O nanoneedles to drive efficient and durable AN‐ECH at ampere‐level currents. The optimized Eu‐Cu 2 O catalyst achieves a high EA Faradaic efficiency of 98.1 % and an exceptional production rate of 2253.2 µmol h −1 cm −2 compared with pure Cu 2 O. Notably, the Eu‐Cu 2 O can continuously operate 420 h at 2 A in an anion‐exchange membrane electrolyzer for AN‐ECH, representing the longest reported stability under the industrial‐current conditions to date. Operando characterization and theoretical calculations elucidate that the Eu incorporation tailors the electronic structure of Cu sites, thus switching the adsorption configuration of AN from the flat‐lying multi‐site π‐adsorption to vertical N‐end adsorption. This reconfiguration of the adsorption site lowers the energy barrier for the imine hydrogenation step, dictating the ideal proton addition pathway while enhancing the proton addition kinetics to suppress the HER. This work provides fundamental insights into rare‐earth tuning of AN hydrogenation mechanisms and represents a critical advancement toward ampere‐scale electrosynthesis of EA.