Browse Articles

Circulating KIM-1 and ctDNA as prognostic markers in oligometastatic clear cell renal cell carcinoma (ccRCC): The K-COMPASS model.

537 Background: Biomarkers do not yet exist to triage patients with oligometastatic ccRCC for de-escalation strategies. Two promising biomarkers are kidney injury molecule-1 (KIM-1) and circulating tumor DNA (ctDNA). Methods: Patients with ccRCC and ≤5 metastases were enrolled on a single-arm phase 2 trial of metastasis-directed therapy (MDT) without systemic therapy (NCT03575611), powered for the primary endpoint of systemic therapy–free survival (STFS). Plasma samples for ctDNA and KIM-1 measurement were collected at baseline and 3-month follow-up. Personalized ctDNA detection panels (≤2000 somatic variants) were constructed from tumor whole-genome sequencing (Myriad Genetics). To create the Kidney Cancer OligoMetastasis Prognostic Assessment Systemic Score (K-COMPASS), we screened 24 candidate variables by elastic net-penalized Cox regression with 5-fold cross-validation repeated 100 times, with performance assessed by C-index. Predictors with nonzero coefficients were refit with Weibull regression for STFS. Results: Among 112 patients with KIM-1 measurements available, median baseline KIM-1 level was 127.0 pg/mL (IQR 71.5–228.0). KIM-1 and ctDNA were associated with STFS at baseline and 3 months in univariable and multivariable analyses (table). Progression-free survival (PFS) and overall survival (OS) were also associated with KIM-1 at baseline (PFS: HR=2.2, 95% CI 1.5–3.3; OS: HR=5.1, 95% CI 2.5–10.2, P <0.001) and at 3 months (PFS: HR=3.5, 95% CI 2.2–5.5; OS: HR=5.0, 95% CI 2.3–10.9) (all P <0.001). K-COMPASS construction selected baseline KIM-1, baseline ctDNA MRD, and 4 clinical variables (prior systemic therapy lines, ECOG performance status, number of metastatic lesions, time from diagnosis to metastasis). The complete model showed strong discrimination (C-index=0.76) and excellent calibration (slope=1). A user-facing K-COMPASS tool is available online (www.trialdesign.org). Conclusions: To our knowledge, this is the first evaluation of KIM-1 in oligometastatic ccRCC and the first to analyze KIM-1 and ctDNA in tandem for RCC. Both biomarkers were strongly and independently associated with outcomes in patients receiving MDT without systemic therapy. Integrating KIM-1 and ctDNA with clinical factors (K-COMPASS) yielded a well-calibrated model with high discrimination to support risk-adapted decision-making. External validation is planned. Univariable and multivariable association of baseline KIM-1 and ctDNA MRD status with systemic therapy free survival. HR (95% CI) Baseline 3-Month Follow-Up Univariable Multivariable Univariable Multivariable KIM-1(per log10[pg/mL]) 2.5 (1.5–4.1) P <0.001 1.9 (1.0–3.6) P =0.041 3.2 (1.9–5.4) P< 0.001 2.2 (1.1–4.5) P =0.028 ctDNA (MRD+ vs MRD–) 2.8 (1.3–5.9) P =0.0089 2.5 (1.1–5.6) P =0.032 4.4 (2.1–9.5) P< 0.001 2.7 (1.1–6.7) P =0.032

Phase 2 trial of pembrolizumab (P) with response-guided bladder-sparing in patients with muscle-invasive bladder cancer (MIBC; HCRN GU 20-444).

737 Background: Many pts with MIBC are not candidates for radical cystectomy (RC) and/or favor bladder-sparing alternatives. Neoadjuvant chemotherapy (NAC) following TURBT leads to a pathologic complete response (pCR) in a subset of pts, suggesting that RC is not universally required to achieve cure. We previously showed that TURBT followed by cisplatin-based NAC plus PD-1 blockade yielded a stringently defined clinical CR (cCR) in 43% of pts and ~2/3 of such pts omitting upfront RC experienced durable bladder-intact survival (Galsky, Nat Med, 2023). However, ~50% of pts with MIBC are ineligible for cisplatin, and neoadjuvant PD-1 blockade monotherapy can produce pCR rates of 30-40%. HCRN GU 20-444 evaluated TURBT followed by P monotherapy with response-guided bladder-sparing for pts with MIBC. Methods: Eligible pts had cT2-3N0M0 urothelial cancer and were cisplatin-declining or -ineligible. Following maximal TURBT, pts received 2 cycles of P (q6 week dosing) followed by clinical restaging with MRI/CT, urine cytology, and cystoscopy with biopsies. Pts with a cCR omitted definitive local therapy and received up to 7 additional cycles of P. Pts without a cCR received definitive local therapy (RC or chemoradiation). ctDNA was serially evaluated through WGS of tumor and plasma coupled with artificial intelligence-based pattern recognition for ultrasensitive detection of residual disease (TrueMRD, Veracyte). The primary endpoint was cCR rate. Key secondary and exploratory endpoints included 2-year MFS, OS, and ctDNA status. Results: From 7/2022 to 12/2024, 46 pts were enrolled; the median age was 74 (24% were ≥80). cCR was achieved in 43% (95% CI 29%-59%) of pts. Median follow-up was 11 months (range 2.4-33.5). Among pts achieving a cCR, all proceeded without upfront RC, none developed metastatic disease; 1/20 had a delayed cystoprostatectomy due to a new prostate cancer (bladder cancer pT0N0); 2/20 died due to non-cancer causes. Adverse events were consistent with the toxicity profile of P. Cycle 1 (C1) ctDNA was undetectable in 90% and 55% of pts with and without a cCR, respectively (Mann-Whitney P = 0.01). Undetectable C1 ctDNA was associated with improved MFS (HR 11.2, 95% CI 2.2-57, log-rank P = 0.0003) and OS (HR 11.4, 95% CI 1.3-103, P = 0.007). C2 ctDNA was undetectable in 100% pts with a cCR. Among pts without a cCR, undetectable C2 ctDNA was associated with improved MFS (HR 14.8, 95% CI 1.4-2000, P = 0.02). Conclusions: TURBT plus P monotherapy yields promising bladder-intact metastasis-free survival in pts achieving a stringently defined cCR. Pts with C1 or C2 undetectable ctDNA have an extremely low risk of metastatic recurrence, even when omitting RC. ctDNA status after only 6 weeks of P distinguishes outcomes in pts without a cCR. These findings highlight the potential of cCR status coupled with ctDNA to redefine response-guided individualized treatment pathways in MIBC. Clinical trial information: NCT05406713 .

Pathologic response after neoadjuvant therapy in renal cell carcinoma using irRVT criteria.

549 Background: Pathologic response after neoadjuvant therapy for renal cell carcinoma (RCC) lacks a standardized system that correlates with outcomes and captures immune-related histologic effects. This study evaluated clinical impact and pathologic response using immune-related residual viable tumor (irRVT) criteria—validated in other malignancies—among patients undergoing surgery for localized or metastatic RCC. Methods: A prospectively maintained RCC database was queried for patients undergoing surgery after systemic therapy. Pathology was re-reviewed to quantify %irRVT, defined as the proportion of residual viable tumor within the entire tumor bed, distinct from nonspecific necrosis and the regression bed consisting of immune-mediated cell death and immune activation components. Treatment details and clinical outcomes were reported based on degree of pathologic response. Survival in metastatic cases was estimated using the Kaplan-Meier method. Results: Thirty-seven patients were identified, with median follow-up of 21.7 mo after surgery. Early recurrence (≤6 mo) occurred in 11 patients (10 initially cM1), all demonstrating a tumor bed necrosis-to-regression ratio ≥1, a previously undescribed pattern. Radiographic and pathologic responses were significantly associated (p=0.015), though several cases showed discordance (Table 1). Partial nephrectomy was performed in 6 patients (one cM1) without positive margins or high-grade complications; median GFR declined from 56 to 47 mL/min/1.73 m². Localized RCC comprised 38% of the cohort (50% cT3–4). Patients received a median of 17 wk of IO and 14 wk of TKI; 43% achieved major pathologic response (irRVT < 10%). None progressed preoperatively or received adjuvant therapy; one recurred postoperatively. Among 23 metastatic cases, 48% demonstrated poor pathologic response (irRVT ≥ 50%), associated with shorter median post-operative PFS versus others (15.0 mo vs 31.7 mo, p = 0.048). Conclusions: irRVT criteria capture immune-related pathologic responses not reflected by radiographic or conventional pathologic criteria. Poor pathologic response correlated with shorter PFS. Neoadjuvant therapy was oncologically safe in localized RCC and preserved renal function. Further validation of irRVT as a prognostic marker is warranted. Degree of pathologic response based on immune-related residual viable tumor (irRVT) criteria. Radiographic response by RECIST 1.1 criteria. Major (<10%)n=13 Partial (10-49%) n=6 Poor (≥50%)n=18 Radiographic Response Partial Stable Progression 9 (69%)4 (31%)0 2 (33%)4 (67%)0 2 (11%)14 (78%)2 (11%) Progression after surgery None ≤6 months >6 months 9 (69%)1 (7.7%)3 (23%) 2 (33%)3 (50%)1 (17%) 9 (50%)7 (39%)2 (11%) Treatment Duration (m), (Med (Q1-Q3)) Immunotherapy Targeted Therapy (TKI) 4.9 (4.3-7.9)5.3 (3.2-7.0) 3.2 (2.3-8.2)4.1 (0.8-8.6) 5.8 (4.4-8.3)3.5 (1.8-6.0)

Real-world patient characteristics and treatment patterns among patients with metastatic castration-resistant prostate cancer treated with talazoparib plus enzalutamide in the US.

121 Background: Talazoparib plus enzalutamide (tala+enza) was approved by FDA in June 2023 for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC), based on statistically significant radiographic progression-free survival from the TALAPRO-2 (TP-2) study. 8% of patients in TP-2 cohort 2 (HRR-selected) received prior abiraterone treatment during the enrollment period from 2018 to 2022. The current study evaluated HRR gene testing, clinical characteristics, and treatment patterns of patients receiving tala+enza in a real world setting. Methods: A non-interventional, retrospective cohort study of US patients with mCRPC was conducted using Flatiron Health’s electronic health record database. Adult patients were included if they initiated tala+enza between June 20, 2023 to February 28, 2025. Gene clustering hierarchy was defined as any BRCA1/BRCA2 alteration ( BRCA cluster), then any PALB2 ( PALB2 cluster), next any CDK12 ( CDK12 cluster), then any ATM ( ATM cluster). Descriptive statistics were used to summarize clinical characteristics, HRR gene testing, and treatment patterns. Results: A total of 192 adult patients with mCRPC treated with tala+enza were included. The median age was 73 years, with the majority of patients being White (62.0%) and from the South (52.1%). Nearly half (47.9%) had a Gleason score of 9-10. The median follow-up from initiation of tala+enza was 8.2 months. Of the 192 patients, 54.2% received androgen receptor pathway inhibitors (ARPi), 10.9% received apalutamide, 21.9% received enzalutamide, 29.7% received abiraterone, and 5.2% received darolutamide prior to mCRPC diagnosis. Additionally, 10.9% of patients received docetaxel prior to mCRPC diagnosis. Tala+enza was initiated during 1L for mCRPC for 39.1%, 2L for 28.6%, and 3L+ for 32.2% of patients. Of those that initiated tala+enza, 76.0% started at 0.5mg dose and 22.9% of patients had at least one dose reduction during the follow up. While 97.4% had documented HRR mutation testing during the study period, only 41.1% had a documented test prior to their mCRPC diagnosis. The most frequent HRR biomarker clusters prior to initiation of tala+enza diagnosis were ATM (27.6%), BRCA (27.1%), CDK12 (13.5%), other cluster (13.5%), PALB2 (3.1%) and 15.1% had no documented mutation or test. Conclusions: This study highlights heterogeneous treatment and HRR testing patterns among patients with mCRPC receiving tala+enza. In this real-world dataset, over half of patients had received ARPi treatment prior to mCRPC. Despite limited follow-up, these findings offer early insights into real-world use and future evaluations should investigate real world clinical outcomes.

Quantitative 3D Real‐Space Analysis of Photonic Supraparticles

ABSTRACT Supraparticles (SPs) are assemblies of smaller particles, and they form an interesting material class. One way through which these structures can be formed is self‐assembly (SA) in spherical confinement, and what makes them unique is that they combine the properties of the smaller particles with collective properties arising from the length scale on which these smaller particles are ordered. Additionally, the limited number of particles in an SP enables them to form structures that are not found in bulk systems. An example of this is icosahedral symmetry, which is the equilibrium structure for SPs up to several hundreds of thousands of particles. Although these icosahedral structures have been investigated through computer simulations and several experimental techniques have been used to analyze them in 3D, the number of experimental datasets published is so limited that no statistically relevant conclusions have been drawn so far. The experimental technique most commonly applied to study them is scanning electron microscopy (SEM), but with this, only quantitative information about the surface of the SPs can be obtained. By using a combination of 3D confocal and stimulated emission depletion (STED) microscopy on extremely well‐index‐matched (within 0.002) fluorescent core‐shell, colloidal silica spheres (of 442–478 nm in diameter with polydispersities below 1%), we obtained full 3D real‐space datasets of tens of SPs within several hours. The structures were classified based on bond order parameters and deviations from local centrosymmetry, using an unsupervised machine learning model. From this, we are able to correctly classify structures that are commonly misidentified using SEM. Additionally, the quantitative real‐space analysis gave experimental insights into the SA pathway and defect formation mechanisms of mostly icosahedral SPs.

Phase Transition Regulation Mechanisms in P2‐Type Oxide Cathodes

ABSTRACT Layered sodium transition metal oxides (Na x TMO 2 ) are one of the promising cathodes for sodium ion batteries due to the high energy density and advantages of large‐scale manufacturing. Recently, P2‐type oxides cathodes, as an important family of Na x TMO 2 , has been paid much attention because the oxygen redox chemistry can further boost the energy density of the cathodes through the special configurations of “Na−O−Li” or “Na−O−Mg”. However, these materials suffer the phase transition due to highly depleting Na + in the structure, when the oxygen redox chemistry is triggered. Past of the decade has witnessed the effective strategies to cope with the phase transition issues through elements doping, but the universal rule behind the elements doping strategies is still a mystery, which is essential to provide guidance to design the advanced cathodes. In this perspective, we present a discussion on phase transitions during charge/discharge process in P2‐type oxides, drawing from the research within our group and recent publications. Phase transition process in P2‐type cathodes is analyzed through the lens of structural geometry evolution toward intrinsic physical/chemical properties. Governing principles and regulation mechanisms of phase transition are elucidated as well, which can give contributions to the rational design of high‐performance P2‐type oxide cathodes.

IMGeS study: A prospective, multicentre, phase II trial of sequential intravesical mitomycin-C and gemcitabine therapy in BCG-unresponsive high-risk NMIBC ineligible for or declining radical cystectomy.

TPS904 Background: High-risk non-muscle-invasive bladder cancer (HR-NMIBC) unresponsive to adequate Bacillus Calmette-Guérin (BCG) has a high risk of recurrence and progression. Although several novel bladder-preserving approaches such as immune checkpoint inhibitors, viral gene therapy, and cytokine-based regimens, are under investigation, their efficacy remains limited, financial toxicity is a concern, and current FDA approvals are restricted to carcinoma in situ (CIS). Radical cystectomy (RC) therefore remains the standard of care, but many patients are ineligible or decline surgery. Both intravesical mitomycin-C (MMC) and gemcitabine (GEM) have demonstrated efficacy in NMIBC, and sequential administration may offer synergistic benefit. No prospective data exist. Methods: The IMGeS study is an investigator-initiated, prospective, open-label, multicentre, single-arm phase II trial evaluating the efficacy and safety of sequential intravesical MMC and GEM in BCG-unresponsive HR-NMIBC. Eighty-two patients will be enrolled from eight Korean centres over 24 months, with 12 months of follow-up. Eligible patients have histologically confirmed BCG-unresponsive high-risk NMIBC per AUA criteria, including refractory or relapsing disease within 6–9 months of adequate BCG, and are unsuitable for or refuse RC. Key exclusions include muscle-invasive or metastatic disease, upper tract urothelial carcinoma, prior intravesical MMC or GEM within 2 years (except a single immediate postop dose), and other predominant histology. Following TURBT, patients receive induction with MMC 40 mg/20 mL intravesically retained for 1–2 hours, immediately followed by gemcitabine 2 g/50 mL retained for 1–2 hours, weekly for 6 weeks. Patients without recurrence at 3-month cystoscopy receive monthly maintenance instillations for 12 months. The primary endpoint is 1-year high-risk recurrence-free survival (HRFS); secondary endpoints include progression-free, cystectomy-free, cancer-specific, and overall survival, as well as safety and tolerability. Exploratory endpoints include biomarker analyses from tumor, urine, and blood. Clinical trial information: NCT06388720 .

Evaluating frailty and quality of life in low-income, uninsured men with prostate cancer.

334 Background: We evaluated frailty across multiple domains and examined its association with prostate cancer (PCa)-specific health-related quality of life (HRQoL) outcomes in low-income, uninsured men enrolled in the Improving Access, Counseling and Treatment for Californians with Prostate Cancer (IMPACT) Program. Methods: We retrospectively assessed frailty using a deficit accumulation frailty index, derived from the RAND SF-12v2 (12-Item Short Form Survey, version 2), California Health Interview Survey (CHIS), and Total Illness Burden Index for Prostate Cancer (TIBI-CaP). PCa-specific HRQoL was measured at IMPACT enrollment, using the UCLA Prostate Cancer Index (PCI), which covers urinary, sexual, and bowel function and bother. We analyzed associations between frailty status and PCI domains using multivariable logistic regression. Results: Among 358 participants (mean age 60; 68% Hispanic), 25% were frail, 45% were pre-frail, and 30% were non-frail. Across all PCI domains, PCa-specific HRQoL was significantly worse in the pre-frail and frail groups. Sexual function demonstrated the greatest impairment (mean ± SD: non-frail 54.1 ± 33.9 vs pre-frail 38.2 ± 31.3 vs frail group 24.6 ± 28.9, p<0.0001). After covariate adjustment, frailty remained independently associated with worse PCa-specific HRQoL across all PCI domains, while pre-frailty showed clinically significant worse urinary bother (estimate (SE): -12.5 (5.1), p=0.0151), sexual function (-14.8 (4.4), p=0.0009), and sexual bother (-22.2 (5.8), p<0.0001) compared with non-frailty. Conclusions: Frailty is significantly associated with poorer PCa-specific HRQoL in low-income, uninsured men. These findings suggest that comprehensive frailty assessment has a role in stratifying risk of HRQoL reduction and guiding personalized interventions to improve genitourinary dysfunction and bother in men with PCa. Frailty group comparison of adjusted PCI estimates (N=358). (non-frail group estimate used as reference) PCI Domain Estimate (SE) Urinary Function Urinary Bother Sexual Function Sexual Bother Bowel Function Bowel Bother Frail -15.8 (4.2) -29.1 (6.1) -29.0 (5.3) -27.2 (6.8) -15.8 (3.0) -23.4 (4.8) p-value a p=0.0002 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 Pre-frail -7.4 (3.6) -12.5 (5.1) -14.8 (4.4) -22.2 (5.8) -4.1 (2.5) -8.5 (4.1) p-value a p=0.0391 p=0.0151 p=0.0009 p=0.0001 p=0.1011 p=0.0385 a p-value < .0083 is significant after Bonferroni correction.

Association of pre-operative circulating tumor DNA (ctDNA) status with clinicopathologic characteristics in patients (pts) with localized renal cell carcinoma (RCC).

532 Background: Clinicopathologic nomograms, such as UISS, Leibovich, and SSIGN models, are used to estimate recurrence risk in localized RCC. However, these tools demonstrate limited predictive accuracy as they were developed in retrospective cohorts and lack integration of molecular or immune biomarkers. There is growing interest in ctDNA as a biomarker for risk stratification in RCC. Pre-operative ctDNA positivity has been associated with clinical features linked to worse outcomes, underscoring its utility in detecting aggressive disease pre-surgery. Here, we present preliminary analyses on correlation between ctDNA status and clinicopathologic characteristics in an institutional cohort of RCC. Methods: Of the 92 pts with available tissue specimens and pre-operative plasma collected between March 2023 and December 2024, five with metastatic disease at the time of nephrectomy were excluded. ctDNA in plasma samples was detected using a personalized, tumor-informed 16-plex mPCR-NGS assay (Signatera, Natera, Inc.). Ridge penalized multivariable logistic regression was performed to identify association between pre-operative ctDNA status and other clinical characteristics. Results: Of the 87 pts included in the study, clinical data (clinical stage, ISUP nucleolar grade, histology, tumor size) and pre-operative ctDNA results were available for 79 pts, (71% male, 90% clear cell). At the time of this analysis, median follow-up was 12 months (range: 1 –27.4 months). Before nephrectomy, 39.2% (31/79) tested positive, and 60.7% (48/79) were ctDNA-negative. Multivariate analyses revealed that pre-operative ctDNA-positivity was associated with a significantly larger mean tumor size compared to ctDNA-negativity (6.2 cm vs. 4.0 cm; OR: 1.38, 95% CI: 1.04 – 1.85, p=0.026). Additionally, ctDNA-positivity was significantly associated with advanced disease stage (stage III/IV [pT1-T2 with N or pT3 or pT4 and/or N1]; OR: 4.60, 95% CI: 1.58 – 14.42, p 0.005) when compared to pts with early stage disease (stage I/II, pT1 or pT2), but not with higher grade (grade III-IV vs. lower grade I-II; OR: 1.01 95% CI: 0.37 – 2.72, p=0.988). In the 31 pts who tested ctDNA positive pre-operatively, 26 had follow-up post-operative ctDNA collected. Two of these pts remained persistently positive post-operatively and presented with metastatic disease within 6 months. Conclusions: Pre-nephrectomy ctDNA positivity correlates with tumor size and stage, suggesting that ctDNA reflects underlying tumor burden and biology. Ongoing analyses will assess clearance with nephrectomy and post-operative longitudinal testing to define prognostic and clinical utility of ctDNA. Integrating ctDNA with tumor features in large contemporary datasets may refine current risk models and enable ctDNA-guided adaptive perioperative trials in localized RCC.

Bridging the Gap: Transforming Total Neoadjuvant Therapy: NEOTERIC Signals a Step Forward in the Treatment of Locally Advanced Rectal Cancer

Wafer‐Scale Synthesis of Molecularly Engineered 2D Covalent Organic Framework Films for Highly‐Sensitive and Rapid‐Response Humidity Sensing

ABSTRACT Covalent organic frameworks (COFs) hold exceptional potential for humidity sensing due to their tunable chemical structure and high porosity, yet their uncontrolled relationships between molecular design, nanoscale architecture, and sensing performance have hindered their practical applications. Here, we report the rational molecular engineering of wafer‐scale, ultrathin 2D imine‐linked COF films via interfacial polymerization, illustrating precise control over electronic band structure, nanoscale porosity, and hygroscopicity for exceptional humidity sensing, thus unveiling the underlying structural‐property correlations. By simultaneously incorporating triazine and multi‐hydroxyl groups, the humidity sensor based on 2D COF TPT‐THTA exhibits a high sensitivity (66 124% per %RH), fast response/recovery times (0.12/0.40 s), and minimal hysteresis (ΔRH ≈ 1.0%), due to a synergistic effect of high structural polarity, excellent hydrophilicity, and the nanoscale confined crystalline pore framework. The nanometer‐scale thickness and ultrasmooth surface facilitate efficient charge transport and water adsorption kinetics. Leveraging these properties, we further demonstrate a prototypical wearable sensor for real‐time respiratory monitoring, which is capable of accurately tracking physiological states and detecting pathological patterns (asthma, apnea). This work establishes a fundamental molecular engineering paradigm for 2D COF film‐based sensors, bridging the gap between programmable materials and next‐generation high‐performance health diagnostics.

Combinatorial Assembly of Biomimetic Janus Membrane with Multiscale Architectures for Guided Bone Regeneration

ABSTRACT Guided bone regeneration (GBR) has gained significant attention in the field of bone tissue engineering. However, designing an effective barrier membrane that simultaneously meets the mechanical and biological requirements at the soft–hard tissue interface remains a considerable challenge. Herein, we introduce a combinatorial assembly strategy to construct a continuous Janus membrane with multiscale architectural features inspired by biological materials. Structurally, the membrane features an asymmetric design, comprising a compact layer with a Bouligand architecture that incorporates amorphous calcium phosphate (ACP) to enhance mechanical strength and prevent soft tissue infiltration, and a porous layer that recapitulates the trabecular structure of cancellous bone, enriched with hydroxyapatite (HAp) crystals to promote cellular adhesion and osteoinduction. Subsequent in vitro and in vivo results show that the membrane not only exhibits excellent biocompatibility and barrier function but also significantly enhances osteogenic differentiation and bone regeneration in a cranial defect model. This work demonstrates that integrating diverse fabrication techniques enables the creation of functionally efficient GBR membranes with hierarchical structures, offering a promising pathway toward multifunctional regenerative materials.

Light‐Driven Reconfigurable Logic in a Monolithic Perovskite Device via Nonlinear Photoresponse Switching

Abstract Modulating nonlinear carrier dynamics in a single‐layer device is essential for achieving complex logic operations with minimal power consumption; however, it remains challenging due to inherently linear charge transport and unipolar photoresponses. Here, a multifunctional optoelectronic logic gate (OELG) based on a bias‐free, single‐layer perovskite device is reported that exhibits light intensity‐dependent polarity switching. Incorporation of poly‐L‐lysine into MAPbI 3 enables trap‐state engineering for nonlinear response modulation. An asymmetric dual‐photogate architecture allows spatially controlled charge transport by tuning the position of incident light. This configuration enables the realization of all eight fundamental logic gate functions, including XOR and XNOR, in a single material and device. Additionally, the device independently handles two channels, amplitude inputs, and temporal modulation inputs. It performs logic operations not by pixel‐level imaging, but by applying a scenario‐based conceptual modulation map to the device, with the outputs derived from experimentally recorded photovoltage responses. These findings establish a promising platform for compact, energy‐efficient, light‐driven logic systems with potential applications in light fidelity (Li‐Fi) communication and on‐device artificial intelligence.

Assistance of a large language model–based AI agent in preoperative communication for reduction of prostate cancer patients' anxiety and clinicians' burden: A prospective, randomized, single-blinded, phase II trial.

56 Background: Preoperative communication is crucial in reducing patients' anxiety but demands considerable effort from clinicians. While large language models offer potential for addressing medical inquiries, their use in preoperative communication lacks sufficient clinical validation. Methods: We developed an AI agent using DeepSeek-R1 for preoperative communication, based on clinical guidelines and our institute's experience. Patients with newly diagnosed prostate cancer scheduled for radical surgery at our center were enrolled, excluding those with severe mental illness or cognitive dysfunction. Upon admission, patients were randomized at the ward level into control and AI agent-assisted groups. Both groups immediately received baseline emotional and cognitive assessments such as GAD-7 and B-IPQ. Specific questions of the two groups were collected via our AI agent. The AI agent-assisted group then received personalized responses from our AI agent, validated for scientific accuracy before delivery. Both groups then received preoperative communication from clinicians blinded to group assignments and underwent emotional and cognitive assessments again. Clinicians' workload was assessed using NASA-TLX. Primary endpoints were GAD-7 scores and NASA-TLX results. Secondary endpoints included other emotional (VAS-A, I-PANAS-SF), disease cognition scales (APAIS, B-IPQ), patient satisfaction, and communication time for clinicians. Sample size determination assumed 50% of patients would achieve a GAD-7 score below 4 with AI agent. With a two-sided significance level of 0.05 and power of 0.95, 100 patients per group are needed at least. Non-parametric rank-sum tests compared variables. All p values were two-sided (α = 0.05). Results: From Feb to Aug 2025, a total of 245 patients were randomized into control (n=124) and AI agent-assisted (n=121) groups. The two groups of patients totally asked 3,294 questions, averaging 13.94 questions per patient. These questions covered various aspects of surgery, including anesthesia, perioperative care, and management. Patients in the AI agent-assisted group experienced notably lower anxiety levels compared with the control group, with decrease in GAD-7 scores (median (IQR): 3.5 (2.0-5.0) vs. 7.5 (6.5-9.0), P<0.001). Clinician workload was notably reduced in the AI agent-assisted group, with lower NASA-TLX scores (median (IQR): 38.0 (24.5-52.5) vs. 57.0 (37.0-77.5), P<0.001) and remarkable nearly half the communication time compared to the control group (9.78 mins vs. 17.91 mins, P<0.001). Conclusions: AI-assisted preoperative communication significantly reduces patient anxiety, enhances disease perception, and decreases clinician workload, identifying previously unaddressed patient concerns. Clinical trial information: 07082049.

P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for individuals aged 11-50 years with intermediate and poor-risk metastatic germ cell tumours (GCTs).

TPS623 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 is standard first-line chemotherapy for intermediate and poor-risk metastatic GCT. Acceleration of standard chemotherapy regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP is the first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. It aims to determine the superiority of accelerated BEP versus standard BEP in this setting. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2 stages. The primary endpoint for stage 1 (n = 150) was favourable response; and for stage 2 (n = 500) is progression free survival (PFS). These sample sizes provide > 80% power with a two-sided type I error rate of 5% to detect absolute improvements of 21% in the favourable response rate (stage 1), and of 7% in PFS rates at 2 years (stage 2). The target population is males and females aged 11 to 50 with intermediate-risk or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (3-weekly) or accelerated BEP (2-weekly) with cisplatin 20mg/m 2 D1-5, etoposide 100mg/m 2 D1-5, bleomycin 30,000 IU/m 2 weekly x 12, and pegylated G-CSF 6mg D6 or filgrastim daily. Study assessments occur at 30 days after completing chemotherapy, 6 months from randomization, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies. As of 25 September 2025, 380 participants have been recruited from 22 ANZ sites, 18 UK sites (led by Cambridge Clinical Trials Unit), and 167 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n = 76) identified no safety concerns. The stage 1 analysis of safety and activity (response rate) for the first 150 patients was reviewed by the Independent Data Safety Monitoring Committee, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .

Oncological outcomes of primary retroperitoneal lymph node dissection in patients with clinical stage IIB seminoma: A binational retrospective analysis.

609 Background: Primary retroperitoneal lymph node dissection (pRPLND) is emerging as a first-line treatment option for stage IIA/B seminoma, aiming to avoid long-term toxicities of chemo- and radiotherapy for long-term survivors. However, current evidence mainly involves small-volume disease (<3cm), and data for stage IIB remain limited. This study assessed oncological outcomes and recurrence predictors in patients with stage IIB seminoma undergoing pRPLND. Methods: A retrospective binational analysis was performed at two high-volume centers in Germany and the United States. Forty patients (Cologne n=20; USC n=20) treated between 2016–2025 were included. Inclusion criteria were pure seminoma, negative serum tumor markers, and clinical stage IIB. No patients received adjuvant chemotherapy. Statistical analyses identified predictors of recurrence. Results: Median (range) age was 35 years (22–67) with a median follow-up of 27 months (1–110). Preoperative imaging showed a median lymph node size of 2.5 cm (2–4.5). Median blood loss and operative time were 100mL and 154 min, respectively. Nerve-sparing was achieved in 97.5%. The median number of resected nodes was 23 (6–49), with a median of 1 (0–17) positive node and a median size of 3.05 cm (0.9–7.7). Pathology showed pN0 in 5%, pN1 in 2.5%, pN2 in 80%, and pN3 in 12.5%. Extranodal extension was present in 52.5%. Nine patients (22.5%) recurred after a median of 10 months (3–36), including 5 in-field and 4 outfield. The median size of the initial positive node in this subgroup was 4.6 cm (2.1–7.7). On univariable analysis, size of positive lymph node was the only significant predictor of recurrence (OR 2.3, 95% CI 1.21–4.7; p=0.002). Conclusions: pRPLND provides a curative option for most stage IIB seminoma patients with favorable oncological outcomes. Larger nodal disease may be less suitable for surgical management due to the increased recurrence risk, potentially warranting adjuvant or alternative therapies. Patients presenting with clinical stage IIC disease should not undergo primary surgery. Histopathological results. Median (range) number of resected lymph nodes 22.5 (6–49) Median (range) Positive lymph nodes 1 (0–17) Median (range) size of positive lymph nodes [cm] 3.05 (0.9–7.7) Nerve sparing (n, %) 39 (97.5) pN0 (n, %) 2 (5) pN1 (n, %) 1 (2.5) pN2 (n, %) 32 (80) pN3 (n, %) 5 (12.5) Extranodal extension (n, %) 21 (52.5) Recurrence (n, %) 9 (22.5) Median (range) time to recurrence [months] 10 (3–36) Infield // Outfield (n, %) 5 (55.5) // 4 (45.5) Median (range) size of initial positive lymph node [cm] 4.6 (2.1-7.7)

Cardiovascular toxicity with androgen-receptor pathway inhibitors in metastatic prostate cancer: A meta-analysis of randomized trials.

145 Background: Multiple trials have demonstrated addition of androgen-receptor pathway inhibitors (ARPIs) improve survival in patients with metastatic prostate cancer but there is a need to quantify cardiovascular toxicity. Understanding the nature and extent of ARPI-associated cardiovascular adverse events across disease states and toxicity grades is critical to inform treatment decisions and long-term patient safety. Methods: MEDLINE, and EMBASE were systematically searched from database inception through August 30, 2025, for phase III randomized controlled trials evaluating abiraterone, enzalutamide, apalutamide, darolutamide, orteronel in metastatic prostate cancer. Trials were included if they reported CVS toxicity. Meta-analysis using a random-effects model was performed to assess the difference of all-cause and treatment-emergent cardiovascular adverse events between ARPI+ADT and ADT alone. Summary effects were expressed as relative risk (RR) with associated 95% confidence intervals. Results: A total of 21 trials (45 references) with 25,576 patients (mCSPC: 12,537, mCRPC: 13,039) were included in this meta-analysis. Compared to ADT alone, ARPI+ADT significantly increased the risk of all cause, all grade hypertension in both mCSPC (RR 1.60, 1.22–2.10) and mCRPC (RR 1.61, 1.20–2.16) as well as grade ≥ 3 hypertension (RR 1.71, 1.17–2.48) in mCRPC setting. There was an increased risk of all-cause, all grade acute coronary syndrome (RR 2.21, 1.09–4.49) and AV nodal disease (RR 2.53, 1.18–5.43) with ARPI+ADT compared to ADT alone in mCSPC setting. There was increased risk of all cause, all grade, any cardiac events (RR 1.30, 1.10–1.54) as well as grade ≥ 3 any cardiac events (RR 1.70, 1.20–2.42) in mCRPC setting. Risk of all cause, all grade hot flashes (RR 1.47, 1.16–1.85) was also significantly increased with ARPI+ADT when compared to ADT alone. In terms of treatment-emergent adverse effects, a significant increase was observed only for pulmonary embolism with ARPI+ADT when compared to ADT alone (RR 1.66, 1.06–2.60) in mCRPC setting. Conclusions: Current evidence indicates potentially increased risk of hypertension, venous thromboembolic, and ischemic cardiac events with ARPI therapy in metastatic prostate cancer. Proactive CV risk assessment, particularly in patients with preexisting comorbidities or prolonged ARPI exposure, may optimize outcomes and minimize treatment interruptions. All cause adverse events. Adverse Event Disease State All Grade Grade ≥3 Any Cardiac Event mCSPC 0.81 (0.37–1.76) 0.88 (0.16–4.64) mCRPC 1.30 (1.10–1.54) 1.70 (1.20–2.42) Hypertension mCSPC 1.60 (1.22–2.10) 1.43 (0.82–2.52) mCRPC 1.61 (1.20–2.16) 1.71 (1.17–2.48) ACS mCSPC 2.21 (1.09–4.49) 1.77 (0.86–3.61) mCRPC – – Hot Flashes mCSPC – – mCRPC 1.47 (1.16–1.85) 1.46 (0.21–9.97)

Thermal and mechanical behavior of plasma-synthesized, nanometer scale aluminum fluoride passivation layers

Aluminum is highly valued in ultraviolet (UV) optics for its exceptional reflectivity at wavelengths as short as 90 nm, but its effectiveness is compromised by rapid formation of a native oxide layer that reduces its UV reflectivity. To mitigate this issue, fluorine-containing protective layers, such as aluminum fluoride, are applied to inhibit oxidation while maintaining high transmission rates. Additionally, an aluminum fluoride layer serves as an effective barrier coating in advanced lithium-ion battery designs, preventing failures like significant temperature increases and thermal runaway. Despite these important applications, the thermal and mechanical properties of aluminum fluoride thin films have not been thoroughly investigated. In this study, optical pump–probe techniques are used to measure the thermal conductivity and elastic moduli of aluminum fluoride passivation layers with thicknesses ranging from 4 to 48 nm. The passivation layers are produced using a plasma-based process that removes the native oxide while converting the aluminum into aluminum fluoride. The results show that both thermal conductivity and elastic moduli increase with film thickness, indicating a thickness-dependent change in physico-chemical composition. Energy-dispersive x-ray spectroscopy reveals that thicker layers contain a higher proportion of fluorine relative to aluminum. Moreover, x-ray photoelectron spectroscopy and infrared variable-angle spectroscopic ellipsometry indicate that the chemical structure stabilizes in thicker samples, confirming the formation of AlF3. These findings provide valuable insights into the process–structure–property relationships of plasma-produced fluorinated layers, which are critical for optimizing UV optical coatings and enhancing lithium-ion battery safety.

Spatial and temporal variability of supraglacial algae on an Alpine glacier (Forni Glacier, Italy)

Excimer-laser-annealing-induced crystallization and atomic ordering of Co2Mn0.5Fe0.5Ge Heusler alloy thin films for spintronic applications

Magnetic Heusler alloys are highly attractive for spintronics; however, realizing their full potential requires high-temperature annealing, which is often incompatible with practical device fabrication. Excimer laser annealing (ELA) potentially addresses this temperature constraint by making use of the short annealing time and temperature gradient along the depth direction. We investigated the effect of ELA on Co2Mn0.5Fe0.5Ge half-metallic Heusler-alloy thin films and demonstrated that ELA successfully induces crystallization and B2 atomic ordering. Optimized ELA condition using low fluence with a high number of laser irradiations achieved reduced resistivity and negative anisotropic magnetoresistance, indicating improved atomic ordering and high spin polarization, while maintaining flatness of the films. These findings establish ELA as a viable annealing method for integrating high-performance Heusler alloys into the device structure with strict thermal budget. Moreover, ELA offers additional advantages such as enhanced throughput and selective area annealing, thereby broadening the scope of Heusler-alloy applications in spintronic devices.