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Macroscopic Janus Transition Metal Dichalcogenide Single Crystals With Enhanced Piezoelectricity and Carrier Mobility

ABSTRACT Janus transition metal dichalcogenides (TMDCs), featuring intrinsic out‐of‐plane symmetry breaking and permanent electrical dipole moments, open novel avenues for atomic‐scale symmetry control. However, the absence of high‐quality, macroscopic single crystals has hindered the exploration of their predicted intriguing properties and practical applications. Herein, we demonstrate the synthesis of millimeter‐scale single‐crystal Janus TMDC monolayers, including MoSSe, WSSe, MoSeS, and WSeS. A combination of spectroscopic, microscopic, and electrical measurements confirms their exceptional crystallinity and spatial homogeneity over large areas. Notably, in contrast to conventional TMDC monolayers, the obtained Janus materials exhibit a strong out‐of‐plane piezoelectric response, with record experimental 𝑑 33 value of ∼2.06 pm/V for WSSe and ∼1.56 pm/V for MoSSe, representing an enhancement of over 15 times compared to previously reported experimental results. Moreover, field‐effect transistors (FETs) based on Janus MoSSe achieve an exceptional carrier mobility of ∼13 cm 2 ·V −1 ·s −1 , along with a device yield of 95% across an array of 100 devices. This work provides a feasible pathway for the scalable production of high‐quality, single‐crystal Janus materials and highlights their promise for integration into next‐generation electronic and optoelectronic devices.

Clinical utility of a urinary DNA methylation biomarker test in the diagnosis and surveillance of upper tract urothelial carcinoma: Results from a prospective trial.

822 Background: DNA methylation, an epigenetic modification frequently altered during tumorigenesis, has emerged as a promising diagnostic and prognostic biomarker for various cancers. However, data on patients with upper tract urothelial carcinoma (UTUC), particularly in the postoperative setting, remain limited. This study aims to evaluate the accuracy of a urine-based epigenetic test for the diagnosis and surveillance of UTUC. Methods: In this prospective clinical trial, urine samples were collected from primary UTUC patients prior to surgery with curative intent (radical nephroureterectomy/distal ureterectomy) and during follow-up visits (every 3 months) at two academic centers, the University of Southern California and Duke University, between April 2024 and July 2025. Samples were analyzed using Bladder CARE, a urine-based test that measures the methylation levels of three urothelial cancer-specific DNA biomarkers (tRNA-Cys, SIM2, and NKX1-1) in a single polymerase chain reaction (qPCR). Results were reported as Bladder CARE Index (BCI) scores and categorized into three groups: positive ( > 10), low-positive (2.5–10), and negative ( < 2.5). Preoperative results were compared to those from 1:1 sex- and age-matched cancer-free healthy controls. In addition, all pre- and post-op urine sample findings were correlated with clinical and follow-up data. Results: A total of 38 patients were included, of whom 14 had at least one follow-up sample. Final pathology showed stage Ta (n = 11), T1 (n = 5), T2 (n = 4), T3 (n = 15), and T4 (n = 3) UTUC. Most tumors were high-grade (34/36; 89%). Pre-surgery BCI results were positive in 29, low-positive in 3, and negative in 6 patients. Urine cytology was available for 26 patients, with 14 (54%) false negatives. Pre-surgery BCI was significantly higher than in controls (median 85.3 vs. 1.7, p < 0.001). The Bladder CARE test showed 84% sensitivity, 92% specificity, 91% positive predictive value, and 85% negative predictive value for UTUC detection. Median BCI was higher in pT2–T4 vs. pTa/T1 (112.8 vs. 39.4) and in high-grade vs. low-grade UTUC (112.8 vs. 1.2); however, these differences were not statistically significant (p = 0.8 and 0.1, respectively). Among 22 follow-up samples, a BCI cutoff of 10 showed 91% concordance with urothelial recurrence status. Conclusions: Bladder CARE is an accurate, non-invasive, urine-based epigenetic test for the diagnosis of UTUC. It may also aid in monitoring disease recurrence following surgery; however, a larger sample size and longer follow-up are needed to validate these findings. Clinical trial information: NCT06805630 .

An intra-patient contemporaneous comparison of ¹⁸ F-piflufolastat and ¹⁸ F-flotufolastat urinary radioactivity and local and pelvic region detection rates in men with low prostate-specific antigen biochemical recurrence of prostate cancer after radical prostatectomy.

32 Background: PET-based radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have become the mainstay of prostate cancer imaging; however, high urinary radioactivity from these primarily renally cleared compounds may obscure tumors in the prostate and peri-ureteric regions. We conducted the first intra-patient comparator study to assess the urinary radioactivity of two 18 F-labelled PSMA-PET radiopharmaceuticals, 18 F-piflufolastat and 18 F-flotufolastat. Methods: This multicenter, prospective, intra-patient comparator study (NCT06604442) enrolled men ≥ 18 years with low PSA (≤ 0.5 ng/mL) biochemical recurrence of prostate cancer ≥ 6 months after radical prostatectomy with undetectable PSA post-surgery, scheduled for a standard-of-care (SoC) 18 F-piflufolastat PET. Patients had a SoC PET/CT after IV 18 F-piflufolastat (target dose 333 MBq), and a second PET/CT 1–10 days later after IV 18 F-flotufolastat (target dose 296 MBq), both scans started approximately 60 min after administration and used the same scanner. The primary endpoint was the difference in urinary bladder radioactivity (mean standardized uptake value [SUV mean ]) between 18 F-piflufolastat PET and 18 F-flotufolastat PET. Secondary endpoints included patient and region-level detection rates (DR) for each radiopharmaceutical. Images were interpreted by two blinded central readers, with a third to resolve disagreements, allowing majority read results. Results: Between Oct 2024 and Jun 2025, 55 patients (mean PSA, 0.28 [range 0.09–0.50] ng/mL) were included in the primary efficacy analysis. Median bladder SUV mean was significantly higher with 18 F-piflufolastat (29.0; interquartile range [IQR], 18.9–40.8) than 18 F-flotufolastat (10.9; IQR, 6.0–18.5) with a median difference of 15.1 (IQR, 8.5–27.0; p<0.001 [Wilcoxon signed-rank test]). The patient-level DR was 27.3% (15/55) for 18 F-piflufolastat and 45.5% (25/55) for 18 F-flotufolastat (majority read). Among the 21 patients with very low PSA levels (≤ 0.2 ng/mL), 38.1% had a positive 18 F-piflufolastat scan compared with 52.4% for 18 F-flotufolastat scans (majority read). Regional and sub-regional DRs are shown in the table. Conclusions: In this intra-patient study, 18 F-flotufolastat showed significantly lower urinary radioactivity, and a higher overall DR than 18 F-piflufolastat indicating it may offer improved image assessment in regions close to the bladder. Clinical trial information: NCT06604442 . Region 18 F-Piflufolastat DR* n (%)N=55 18 F-Flotufolastat DR*n (%)N=55 Prostate bed 6 (10.9) 10 (18.2) Vesicourethral anastomosis 1 (1.8) 4 (7.3) Retrovesical 2 (3.6) 2 (3.6) Remnant seminal vesicles/ lateral surgical margin 2 (3.6) 4 (7.3) Pelvic lymph nodes 8 (14.5) 9 (16.4) Majority read. *≥ 1 PET positive lesion.

Determining individual preferences for gynecomastia avoidance among men with prostate cancer: A qualitative study.

TPS407 Background: Biochemical recurrence (BCR) affects 20–50% of men within 10 years of primary therapy for prostate cancer (PCa). The EMBARK trial demonstrated improved metastasis-free survival with Enzalutamide (ENZ), alone or in combination with ADT, compared with ADT alone. However, ENZ monotherapy introduces a side effect profile notably of gynaecomastia, nipple pain, and breast tenderness—occurring in approximately 45% of patients and causing treatment discontinuation in 16% of cases. Gynaecomastia may significantly affect men’s quality of life (QoL) due to changes in body image and associated discomfort. Previous qualitative work on breast-related symptoms in PCa is limited and largely focused on ADT-related, non-painful enlargement, without reflecting contemporary attitudes or the ENZ-specific side effect profile. As treatment options expand, understanding men’s perceptions of these side effects is critical to shared decision-making and aligning treatment strategies with patient preferences. Discrete choice experiments (DCEs) are an established method to quantify treatment preferences by identifying trade-offs between attributes such as efficacy, toxicity, and QoL. To inform a future DCE on treatment preferences, qualitative work is needed to explore men’s perceptions of breast-related side effects, their impact, and the acceptability of prophylactic measures such as tamoxifen. Methods: This qualitative study will use semi-structured interviews to explore men’s experiences and perceptions of gynaecomastia related to BCR PCa treatments, forming the basis for the development of DCE attributes and levels in a subsequent study. Purposive sampling will be used to recruit two groups: (1) men with BCR PCa without prior ADT/ENZ exposure, and (2) men with prior ADT/ARPI exposure who have experienced breast-related side effects. Approximately 10–12 participants per group (20–24 total) will be recruited, with final sample size determined by information power. Interviews will be conducted via telephone or videoconference, lasting approximately 30 minutes. Topics will include perceptions of QoL impacts, breast-related symptoms (hypothetical or experienced), attitudes towards prophylaxis, and the impact on body image and treatment decision-making. Interviews will be audio-recorded, transcribed verbatim, and analysed using NVivo. Demographic and clinical data (age, years since diagnosis, treatments received) will be collected. To mitigate risk of distress, participants will be informed of sensitive topics in advance, retain the right to skip questions or withdraw, and a distress protocol will be in place. Verbal informed consent will be recorded prior to interviews to minimise collection of identifying information. This study will generate foundational qualitative data to support patient-centred approaches to BCR PCa treatment decision-making. Clinical trial information: ACTRN12625001210460p.

Colorectal cancer statistics, 2026

Abstract Colorectal cancer (CRC) is the second most common cancer‐related death in the United States and ranks first in adults younger than 50 years. Every 3 years, the American Cancer Society reports on CRC occurrence based on incidence from population‐based cancer registries and mortality from the National Center for Health Statistics. Overall, CRC incidence declined by 0.9% annually during 2013–2022 driven by decreases of 2.5% annually in adults aged 65 years and older. In sharp contrast, incidence rates increased by 3% annually in adults aged 20–49 years and by 0.4% annually in adults aged 50–64 years dominated by tumors in the distal colon and rectum. Consequently, overall rectal cancer incidence increased by 1% annually from 2018 to 2022 after decades of decline and now accounts for 32% of all CRC, up from 27% in the mid‐2000s. Increasing CRC incidence in adults aged 50–64 years was confined to regional and distant‐stage diagnosis (1.1%–1.3% annually during 2013–2022), likely contributing to an upturn in mortality in this age group of 1% annually since 2019 that was steepest (2.3% annually) in White individuals. Mortality has increased in adults younger than 50 years by 1% annually since 2004, whereas rates have decreased in adults 65 years and older by 2.3% annually since 2012. Despite steady progress for older adults, both CRC incidence and mortality are increasing in adults younger than 65 years who are in the prime of life, underscoring an urgent need for etiologic research to discover the cause of the rising trend. Meanwhile, morbidity and mortality could be mitigated with earlier diagnosis, through screening and educating clinicians and the general public about CRC symptoms, and greater attention to the unique needs of younger patients, including discussion about the preservation of fertility and sexual health.

Mind the Gap—Imaging Buried Interfaces in Twisted Oxide Moirés

ABSTRACT The ability to tune electronic structure in twisted stacks of layered, two‐dimensional (2D) materials has motivated the exploration of similar moiré physics with stacks of twisted oxide membranes. Due to the intrinsic three‐dimensional nature of bonding in many oxides, achieving atomic‐level coupling is significantly more challenging than in 2D materials. Although clean interfaces with atomic‐level proximity have been demonstrated in bulk ceramic bicrystals using high‐temperature and high‐pressure processing to facilitate atomic diffusion that flattens rough interfaces, such conditions are not readily accessible when bonding oxide membranes. This study shows how topographic mismatch from surface roughness of the membranes restricts atomic‐scale proximity at the interface to isolated patches even after contaminants and amorphous interlayers are eliminated. The reduced ability of 2D materials to conform to a membrane's step‐terrace topography also limits atomic‐scale contact. In all these material systems, the interface morphology is best characterized using cross‐sectional imaging and is necessary to corroborate investigations of interlayer coupling. When imaging the stacked membranes in projection, conventional through‐focal imaging is found to be insensitive to the buried interface, whereas electron ptychography reliably resolves structural variations on the order of a nanometer. These findings highlight interface roughness as a key challenge for oxide twistronics.

Directed Functionalization of Recombinant Spider Silk Nonwoven Membranes with Antibodies Using Non‐Canonical Amino Acids

ABSTRACT Natural spider silk fibers are recognized for their outstanding mechanical properties. The production of underlying recombinant spider silk proteins in scalable quantities unlocks their potential for technical and biomedical applications. The recombinant spider silk technology further enables the introduction of new functions via genetic encoding. In the present study, the non‐canonical amino acid L‐azidohomoalanine is incorporated into the engineered Araneus diadematus fibroin 4, eADF4(C16), at positions explicitly defined by methionine codons in an N‐terminal peptide tag. The azido‐functionalized eADF4(C16) is processed into particles, films, or electrospun into nanofibers. As functional entities, high molecular weight molecules, such as antibodies, are modified with bio‐orthogonal groups suitable for strain‐promoted cycloaddition to the exposed azido‐groups on the spider silk supports. The antibody‐activated spider silk nonwoven meshes exemplarily show their applicability as bio‐capturing membranes.

Are long-term remissions possible with hormonal therapy only? Post hoc analysis of EMBARK examining sustained prostate-specific antigen (PSA) <0.2 ng/mL despite testosterone (T) recovery after treatment (tx) suspension.

189 Background: The phase 3 EMBARK trial (NCT02319837) assessed enzalutamide plus leuprolide (enza combo), leuprolide alone (LA), and enzalutamide monotherapy (enza mono) in patients (pts) with prostate cancer and high-risk biochemical recurrence. EMBARK demonstrated significant improvements for metastasis-free survival (enza combo and enza mono) and overall survival (enza combo). A key feature of EMBARK was tx suspension after 37 weeks in pts with PSA <0.2 ng/mL. We assessed the proportion of pts with sustained PSA <0.2 ng/mL despite T recovery. Methods: Pts were randomized 1:1:1 to receive enza combo, LA, or enza mono. Pts received tx for 36 weeks. This post hoc analysis evaluated proportions of pts with PSA <0.2 ng/mL and T recovery to baseline, 175 ng/dL, or 250 ng/dL after tx suspension of 12, 24, or 36 months. Results: During the entire 36 months after tx suspension, 9.3%, 3.4%, and 2.3% of pts in the enza combo (n=353), LA (n=354), and enza mono groups (n=354), respectively, maintained PSA <0.2 ng/mL; proportions during 12 and 24 months are shown (Table). During 36 months after tx suspension, among pts in the enza combo, LA, and enza mono groups, respectively, 3.7%, 1.4%, and 1.1% maintained PSA <0.2 ng/mL and achieved T recovery to >250 ng/dL. Results for T recovery to baseline and >175 ng/dL are shown (Table). Conclusions: Approximately 1 in 25 pts treated with enza combo for 9 months had PSA <0.2 ng/mL and normal T 3 years post therapy, demonstrating long-term “remissions” are possible after only 9 months of enza combo. Rates with LA and enza mono were not zero but were much lower than with enza combo (both 1%, vs 4% with enza combo). Clinical trial information: NCT02319837 . Pts with PSA <0.2 ng/mL and T recovery after tx suspension (safety population). 12 months 24 months 36 months Enza combo (n=353) LA (n=354) Enza mono (n=354) Enza combo (n=353) LA (n=354) Enza mono (n=354) Enza combo (n=353) LA (n=354) Enza mono (n=354) Pts with PSA <0.2 ng/mL during suspension, n (%) 127 (36.0) 53 (15.0) 33 (9.3) 58 (16.4) 24 (6.8) 15 (4.2) 33 (9.3) 12 (3.4) 8 (2.3) T >175 ng/dL † , n (%) 72 (20.4) 33 (9.3) 29 (8.2) 35 (9.9) 17 (4.8) 12 (3.4) 15 (4.2) 8 (2.3) 5 (1.4) T >250 ng/dL ‡ , n (%) 44 (12.5) 21 (5.9) 23 (6.5) 25 (7.1) 15 (4.2) 10 (2.8) 13 (3.7) 5 (1.4) 4 (1.1) T ≥baseline § , n (%) 21 (5.9) 11 (3.1) 18 (5.1) 16 (4.5) 10 (2.8) 10 (2.8) 9 (2.5) 3 (0.8) 4 (1.1) No T assessment, n (%) 6 (1.7) 5 (1.4) 2 (0.6) 8 (2.3) 3 (0.8) 1 (0.3) 5 (1.4) 1 (0.3) 1 (0.3) Data cutoff: January 31, 2023. The denominator for all percentages is the number of pts in the safety population. † T assessment at 12, 24, or 36 months ± 6-week window of recovery to >175 ng/dL. ‡ T assessment at 12, 24, or 36 months ± 6-week window of recovery to >250 ng/dL. § T assessment at 12, 24, or 36 months ± 6-week window of recovery to ≥baseline T.

Clinical outcomes and tolerability of ipilimumab/nivolumab in older (≥70 years) versus younger patients with metastatic clear cell RCC: A multi-institutional analysis of 514 patients.

444 Background: Ipilimumab plus nivolumab (I/N) is a standard first-line treatment for metastatic clear cell renal cell carcinoma (mccRCC), yet data in elderly patients remains less well characterized. Age-related immune changes, comorbidities, and polypharmacy may affect treatment tolerance and efficacy, yet data on discontinuation rates and outcomes by age are limited. We evaluated treatment tolerance, and outcomes of patients aged ≥70 versus < 70 years receiving first-line I/N for mccRCC. Methods: We conducted a retrospective study of patients with mccRCC treated with first-line I/N at Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center. Clinical data were extracted from electronic health records. Patients were stratified by age at treatment initiation (< 70 vs ≥70 years). Kaplan-Meier methods estimated time on treatment (first I/N dose to last dose of I/N or single-agent nivolumab), time to second-line therapy (TT2), and overall survival (OS); comparisons were made via log-rank tests. Rates of induction completion and discontinuation for adverse events (AEs) were compared using Fisher’s exact test. Results: Among 514 patients (median age 62 years; range 33–85); 98 (19%) were ≥70 years and 9 (1.7%) were ≥80 years. Baseline characteristics including gender, stage, IMDC risk, and metastatic sites were similar, though sarcomatoid/rhabdoid features were less frequent in older patients (20% vs 39%). Fewer older patients completed all four induction doses (53% vs 65%; p= 0.04), but median time on I/N regimen was comparable across the two cohorts (see table). AE-related discontinuation occurred more often in older adults (42% vs 25%, p < 0.001). Median TT2 was 27 months (95% CI, 13-NE) in older patients and 13 months (95% CI, 11-16) in younger patients (p=0.005). Median OS did not differ between groups with 5.0 months (95% CI 2.9-7.4) and 4.2 months (95% CI, 3.5-5.8), respectively (p= 0.85). Conclusions: Patients with mccRCC aged ≥70 vs. < 70 years achieved comparable time on treatment and OS with first-line I/N, despite lower rate of induction completion in the older group. These findings support the use of I/N in appropriately selected older adults, highlighting the importance of individualized treatment decisions. <70 years (n=416) ≥70 years (n=98) p-value Sarcomatoid or rhabdoid features, n (%)  160 (39%) 20 (20%) <0.001 Completion of four I/N doses, n (%)  268 (65%) 52 (53%) 0.04 AE-related discontinuation, n (%)  101 (25%) 41 (42%) <0.001 Median time on therapy, mo (95% CI)  5.3 (4.4, 6.1) 4.2 (2.8–8.0) 0.83 Median TT2, mo (95% CI)  13 (11–16) 27 (13–NE) 0.005 Median OS, years (95% CI)  4.2 (3.5–5.8) 5.0 (2.9–7.4) 0.85

Neoadjuvant treatment with disitamab vedotin plus perioperative toripalimab in patients with HER2-expressing muscle-invasive bladder cancer (MIBC) in the phase II RC48-C017 trial: Updated results.

766 Background: Disitamab vedotin (DV, a HER2-targeted antibody-drug conjugate with monomethyl auristatin E as the payload) in combination with toripalimab (a PD-1 inhibitor) has demonstrated significant and clinically meaningful improvement in both progression-free survival and overall survival (OS) in patients (pts) with untreated, HER2-expressing, advanced urothelial cancer (UC) in the phase III RC48-C016 study (Sheng, et al. NEJM 2025). However, its efficacy in the early-stage disease setting is not fully explored. The single-arm phase II RC48-C017 trial evaluated the efficacy and safety of the combination of DV and toripalimab in pts with HER2-expressing MIBC in the perioperative setting. The previous analysis showed a pathological complete response (pCR) rate of 63.6% in the surgical pts, and manageable safety (Sheng, et al. ASCO GU 2025). Methods: This study enrolled pts with previously untreated MIBC (cT2-4aN0-1M0) with locally confirmed HER2 expression (defined as immunohistochemistry [IHC] ≥1+). All pts must be eligible for and plan to undergo curative-intent radical cystectomy and pelvic lymph node dissection (RC+PLND). Eligible pts received 6 cycles of DV (2 mg/kg, once every 2 weeks [Q2W]) plus toripalimab (3 mg/kg Q2W) at the neoadjuvant phase. After RC+PLND, pts received 20 cycles of adjuvant toripalimab (3 mg/kg Q2W). The primary objective was to assess efficacy. We present the updated results, including event-free survival (EFS), OS, and safety, with a longer follow-up. The data cutoff (DCO) date for this analysis was August 14, 2025. Results: A total of 47 pts were enrolled and treated, with the majority (83.0%) at T2-4N0M0 stage. RC+PLND was performed in 33 pts. As of DCO, the median OS follow-up was 26.4 (95% CI: 24.4-28.2) months. The median EFS was not reached. At 12 and 18 months, the EFS rate was 93.2% (95% CI: 75.4-98.3) and 80.9% (54.4-92.9), respectively, in pts who underwent surgery, and was 91.0% (77.8-96.5) and 81.5% (64.3-90.9), respectively, in the total pts. The median OS was not reached; the 12- and 24-month OS rates were 95.7% (95% CI: 83.9-98.9) and 91.3% (95% CI: 78.6-96.7), respectively. No new safety signals were observed. Conclusions: These updated data demonstrated that the initial treatment response has translated into a durable long-term disease control and survival, as evidenced by the EFS and OS outcomes. This sustained treatment effect of neoadjuvant DV plus perioperative toripalimab in pts with HER2-expressing MIBC in the perioperative setting deserves further evaluation in pivotal clinical studies. Clinical trial information: NCT05297552 .

Ethical considerations of genetic and genomic testing in pediatric oncology: A narrative review

Abstract Genomics—and genomic testing in particular—has transformed oncology, facilitating both targeted therapies and personalized care. In pediatric oncology, unique clinical and ethical considerations arise. Compared with adults, children and adolescents are affected by more limited evidence regarding test performance, variant interpretation, and the clinical utility of genomically informed interventions. Nevertheless, genomic findings may have implications beyond the patient, affecting their parents, siblings, and other relatives and raising questions around consent, assent, privacy, and psychosocial impact. This narrative review examines how ethical dimensions of genetic and genomic testing evolve across the pediatric cancer continuum, from diagnosis and treatment through survivorship and transition to adult care. Attention is given to communication strategies, interdisciplinary support, and equity concerns that influence the responsible integration of genomic medicine. The authors also identify priority areas for future inquiry, including incorporation of children's perspectives, longitudinal approaches to recontact and reconsent, and better understanding of how genomic information affects treatment decision‐making. Pediatric genetic and genomic testing in oncology holds great promise, but its benefits can only be realized through thoughtfully developed and standardized communication practices, careful ethical deliberation, and equitable implementation. By proactively addressing these issues, pediatric oncologists can harness genomic advances in ways that respect and support children and their families.

Additive Manufacturing of Molecular Architecture Encoded Stretchable Polyethylene Glycol Hydrogels and Elastomers (Adv. Mater. 15/2026)

Cold, Rapid, and Scalable Stamping of Aramid‐Networked Viscoelastic h‐BN Doughs for Complex Thermal Architectures

ABSTRACT Extensive efforts have been made to fabricate complex 3D thermal management materials from hexagonal boron nitride (h‐BN) using 3D printing and templating. However, these techniques are often energy‐intensive, time‐consuming, and inherently limited in scalability, owing to prolonged processing times and low throughput. Herein, we report a cold, rapid, and scalable stamping approach for constructing intricate, large‐area h‐BN‐based thermal architectures. This strategy relies on forming highly viscoelastic h‐BN doughs achieved through developing a para‐aramid ( p ‐aramid) fiber network and densification via a bimodal alumina mixture. The p ‐aramid network maximizes viscoelasticity with a minimal binder content (5.1 wt.%), enabling the doughs to exhibit pronounced plasticity during stamping while maintaining solid‐like behavior after relaxation. Consequently, the doughs conform precisely to complex stamp geometries within 2 s under ambient conditions, preserving their high structural integrity. Scalability is demonstrated by stamping various 3D geometries exceeding 10 cm, including cubes, cylinders, annular sectors, and honeycombs. Furthermore, the fiber‐reinforced structures exhibit enhanced thermal conductivity (TC) and fatigue resistance under extreme temperatures (− 50°C and 200°C). Notably, the resulting architectures substantially improve the TC of the polymer composites when used as internal frameworks. This low‐energy stamping strategy represents a paradigm shift in the processing of advanced thermal materials.

Multifunctional Fluidic Units for Emergent, Responsive Robotic Behaviors

Abstract Fluidic circuits have shown significant promise in enabling complex functionality in soft robots with a minimal number of input signals. However, implementing complex behaviors typically involves numerous specialized components, resulting in intricate and nonversatile circuits. To address this challenge, a multifunctional fluidic unit designed to operate flexibly as a valve, sensor, or actuator is introduced. This unit provides an extensive design space that allows precise tuning to achieve the desired functionality. In particular, one configuration integrates all three functions simultaneously, resulting in a self‐sensing oscillating actuator. By assembling multiple units—each customized for specific roles—complex robotic behaviors can be realized. The versatility and effectiveness of this modular approach are demonstrated by creating several robotic systems, including a controlled shaker, a multimodal hopper, and a crawler capable of sensing environmental boundaries. Furthermore, when these units are mechanically coupled via a shared body, it exhibit emergent passive behaviors, such as self‐synchronization—a behavior that is elucidated with a Kuramoto model of networks of oscillators. This study highlights the potential of multifunctionality as a powerful and efficient strategy for realizing embodied intelligence in fluidic robotic systems.

Deferred cytoreductive nephrectomy in patients with advanced RCC treated with first-line nivolumab plus ipilimumab: A propensity score-matched analysis from the RENOIR study (KCSG GU22-13).

439 Background: Despite limited supporting evidence, deferred cytoreductive nephrectomy (dCN) has been regarded a useful therapeutic option in selected patients, particularly those demonstrating a favorable response to upfront systemic therapy in the era of immune-oncology. In this context, present study evaluated the clinical characteristics and role of dCN in patients with advanced renal cell carcinoma (aRCC) treated with 1 st -line nivolumab plus ipilimumab (NI) therapy. Methods: Patients with aRCC who underwent dCN during 1 st -line NI were identified from the Korean Cancer Study Group study (KCSG GU22-13), a retrospective cohort of 466 patients treated between 2018 and 2022 across 21 centers in Korea. To adjust for baseline differences between the dCN and NI-only groups, 1:3 nearest-neighbor propensity score matching was conducted. Covariates included age, sex, and International Metastatic RCC Database Consortium risk group. The primary endpoint was time to treatment failure (TTF); secondary endpoints included overall survival (OS) and clinical characteristics of patients undergoing dCN. Results: Twenty-four dCN patients were identified. Most had one or two metastatic sites (lung 70.8%, lymph node 66.7%). The median time from NI initiation to dCN was 5.3 months (mo), and the median number of treatment cycles was 20 (range, 2–85). The objective response rate (ORR) was 70.8%, while 12.5% demonstrated initial disease progression, primarily in the kidneys. Most patients underwent dCN for palliation, particularly to control gross hematuria, but one-third (n = 7) were curatively intended based on near complete response (CR) in extrarenal metastatic sites. Two patients discontinued NI postoperatively due to achieving CR. Notably, patients who achieved objective response before dCN showed significantly more favorable survival from the date of dCN (not reached vs. 25.7 mo, p = 0.01), whereas dCN performed in cases of initial progression failed to confer meaningful survival benefits. After matching, 96 patients (24 dCN; 72 NI-only) were analyzed. Compared with NI-only, dCN patients had larger primary tumors (≥7.5 cm; 75.0% vs. 50.0%, p = 0.03), fewer liver metastases (0% vs. 16.7%, p = 0.03), and higher completion of 4 NI induction cycles and ORR (83.3% vs. 56.9%, p = 0.02 and 70.8% vs. 51.4%, p = 0.09). With a median follow-up of 26.2 months, median TTF was longer in the dCN group (49.4 vs. 6.4 mo; p = 0.09), though not statistically significant. Median OS did not differ significantly (not reached vs. 42.8 mo; p = 0.22). Conclusions: In aRCC treated with 1st-line NI, response before dCN predicted post-dCN survival. After matching, dCN showed a trend toward longer TTF, suggesting potential benefit in selected responders.

Extracellular vesicles (EVs) and circulating tumor DNA (ctDNA) as potential biomarkers of response to ¹⁷⁷ Lu-PSMA-617.

214 Background: 177 Lu-PSMA-617 (LuPSMA) has revolutionized care for patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC), but only half achieves PSA decline ≥50%. Biomarkers are urgently needed to improve pt selection. EVs and ctDNA released by cancer cells into the blood are emerging biomarkers to estimate overall tumor burden and capture tumor heterogeneity in mCRPC. Here, we analyzed pre-treatment plasma levels of tumor EVs and ctDNA in a pilot cohort of 35 pts with mCRPC treated with LuPSMA. Methods: Blood samples were collected pre-cycle 1 of LuPSMA at Tulane Cancer Center between 12/2018-1/2025. Plasma-derived small and large EVs were incubated with fluorescently conjugated antibodies and enumerated using nanoscale flow cytometry. ctDNA fraction was estimated from plasma cfDNA methylation WGS (∼10×) with ichorCNA. We also analyzed EVs from blood samples of male healthy donors (HD) and pts with localized prostate cancer (LPC) collected 1 day to 8 months after radical prostatectomy (post-RP) from 6/2020-8/2024 at Mayo Clinic as controls. Results: Median age at collection for 10 HD was 55 yrs and for 36 pts with LPC post-RP was 65 yrs. Median PSMA+ EV level was 2.0 x 10 6 /mL for post-RP and 1.4 x 10 6 /mL for HD. For 35 pts with mCRPC, 25 pts had complete data for analysis. Median PSMA+ EV level was 1.4 x 10 7 /mL, significantly higher than post-RP (p<0.001) and HD (p<0.001). At LuPSMA start, median age was 69 yrs (range 54-83), PSA was 82 ng/mL (range 0.8-503), median time from CRPC diagnosis to start was 50 months (range 6.9-285), median time from plasma collection to treatment initiation was 0.5 months (range 0-7.3). Median number of prior lines of life-extending therapy was 4 (range 1-11), including 100% androgen receptor pathway inhibitor and 75% docetaxel. Pts received median 4 cycles of LuPSMA. Median ctDNA fraction was 14.0% (range 0-51.1). Median time to reach nadir PSA for pts with any decline was 2.6 months. 15 pts (60%) achieved PSA40 (defined ≥40% decline in PSA from start to nadir) (range -99% to -42%) compared to 10 pts (40%) who did not (range -16% to rise), which predicted better median overall survival (OS) after LuPSMA start (40.7 v 6.0 months; HR 0.23, 95% CI, 0.07-0.71; p=0.0001). Pts were classified as LuPSMA responders using PSA40. Responders had a lower ratio of large to small PSMA+ EVs (0.30 v 0.53, p=0.0042) with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% CI, 0.68-0.99), and a lower median ctDNA fraction (6.1% v 26.2%, p=0.0044) with an AUC of 0.83 (95% CI, 0.68-1.00). Incorporating both PSMA+ EV and ctDNA fraction together predicted PSA40 response with an AUC of 0.93 (95% CI, 0.84-1.00, p=0.0003). Conclusions: Using pre-LuPSMA plasma samples from a heavily pre-treated historical cohort, we integrated non-invasive liquid biopsy methods to successfully predict response to LuPSMA using PSA decline. Prospective validation is underway.

Peripheral blood correlates of outcomes with adjuvant tremelimumab plus durvalumab for patients with renal cell carcinoma at high or intermediate risk of relapse: Initial results from the TransRAMPART study.

527 Background: Despite optimal surgery, approximately 1/3 of patients with renal cell carcinoma (RCC) develop incurable relapse. Adjuvant pembrolizumab reduces the risk of relapse in patients with clear cell RCC and is considered standard care. Post nephrectomy plasma KIM-1 levels have been shown to be prognostic in RCC in the ASSURE & IMmotion010 trials. RAMPART (NCT03288532) is an investigator-led, international randomized phase III study, that enrolled patients with RCC at intermediate and high risk of relapse. Patients were randomized to placebo (Arm A), durvalumab (Arm B), durvalumab + tremelimumab (Arm C). A DFS benefit has recently been reported for Arm C compared to the control Arm A (DFS at 3 years 81% vs. 73%, HR 0.65, 95% CI 0.45 to 0.93, p = 0.009). Methods: TransRAMPART collected longitudinal blood, tissue and urine samples in parallel to the main study. The aims included understanding prognostic or predictive markers for adjuvant treatment. A total of 187 patients were recruited. Samples were collected at baseline, 16 weeks, 32 weeks, and at later timepoints up to 5 years. Blood samples were profiled by MSD cytokine array (plasma), and by high resolution flow cytometry (PBMCs) by IMU Biosciences. Here we report the initial results of these exploratory blood-based analyses for Arm A and Arm C. Results: High baseline KIM-1 levels ( > 86 pg/mL, as used in analysis of the IMmotion010 trial) were associated with worse DFS outcomes in the combined A+C population (p = 0.0075, HR = 3.4, 95% CI 1.3-8.9, n = 77). Analyzing the patients by arm, KIM-1 remained negatively prognostic in the control Arm A (p = 0.0015, HR = 8.0, 95% CI 1.7-37, n = 45), however the effect was no longer seen with adjuvant combination immunotherapy in arm C (p = 0.72, HR = 1.3, 95% CI 0.31-5.1, n = 32). Peripheral immune profiling revealed an immune profile associated with Arm C treatment which returned toward baseline following the treatment period (64 patients in Arm A, 50 patients in Arm C). KIM-1 levels did not correlate with immune changes; instead, various immune cell lineages showed differential phenotypic enrichment according to baseline KIM-1. Tracking these phenotypes through the treatment period revealed divergence between Arm A and Arm C patients. Conclusions: We confirm that baseline KIM-1 levels are prognostic in RCC in an independent population. Although this exploratory analysis only assessed a subset of the whole trial population, this prognostic effect seems to be negated by adjuvant immunotherapy. There is an immune signature associated with KIM-1 levels distinct from the impact of treatment, suggesting an interplay between KIM-1 and immune activity in the postoperative period. Deeper characterization of these immune changes is ongoing. Clinical trial information: NCT03288532 .

Radiotherapy followed by adjuvant temozolomide improves survival for patients with aggressive <i>IDH</i> ‐mutated anaplastic glioma

Disulfide‐Mediated Confinement Assembly Enabling Thermal‐Hyperhardening Hydrogels via Phase Evolution

ABSTRACT In a continuous material life cycle, driving multi‐step, autonomous phase evolution–from physical assembly to chemical reconfiguration, and ultimately achieving a leapfrog improvement of macroscopic material properties represents a critical challenge in developing next‐generation adaptive materials. Herein, we propose a dynamic covalent disulfide‐mediated confinement assembly strategy, wherein thioctate is integrated into poly(acrylic acid) networks to demonstrate the biomimetic phase evolution process. The resultant polymer exhibits thermal‐induced hyperhardening transition from a soft hydrogel to a rigid glassy material, with a record‐breaking 27 000‐fold increase in modulus, from 8 × 10 −4 to 22 MPa. The significant mechanical reinforcement is attributed to thermal‐driven hydrophobic aggregation of 1,2‐dithiolane motifs. The local concentrated monomers further trigger the disulfide‐mediate ring‐opening polymerization into covalently crosslinked microspheres, which effectively reinforce poly(acrylic acid) backbones via dynamic reconstruction of calcium (II) ‐carboxyl coordination. The potential application of soft actuators featuring composite architectures is demonstrated by integrating the rapid hyperhardening transition and prolonged mechanical stability of the hydrogels, as well as robust interfacial bonding capability via disulfide exchange. This universal phase evolution strategy based on dynamic covalent chemistry establishes an ideal material platform for developing multi‐mode, on‐demand regulation of high‐performance adaptive materials.

Charge Carrier and Spin Transport Properties in Diketopyrrolopyrrole‐Based Polymers

ABSTRACT The organic active layer in organic spin‐valves (OSVs) plays a vital role in regulating the device's performance, and the variations in molecular structure can significantly modulate their physicochemical properties. Herein, we synthesized two diketopyrrolopyrrole‐based donor‐acceptor copolymers with distinct alkyl side chains, namely DPP‐BTCN‐C1 (with side‐chain branching points closer to the conjugated skeleton) and DPP‐BTCN‐C3. To evaluate the charge carrier transport properties, a polymer field‐effect transistor and space charge limited current method based on the two molecules were conducted. The experimental results demonstrated that the DPP‐BTCN‐C1 materials had a higher electron transport mobility. Moreover, the spin transport properties were also revealed by fabricating OSVs devices. In the OSVs with a 50 nm interlayer, DPP‐BTCN‐C1 exhibited a higher magnetoresistance (RM) value of up to 24.6 %. By fitting the polymer thickness dependence of the MR value at 10 K, a longer spin diffusion length and higher spin polarization injection efficiency were achieved for the DPP‐BTCN‐C1 structure. We attributed the differences in charge and spin transport performance to the modulation of the film microstructure and energy levels by the alkyl side chains. This work studied the structure‐property relationship of polymer OSVs from the perspective of side‐chain engineering, providing valuable insights for the design of polymers with enhanced spin properties.