Browse Articles

Invisible Hydrodynamic Sensing via Metamaterial Shells Optimized by Machine Learning

ABSTRACT Accurate flow‐field sensing is crucial for microfluidics, biomedicine, and environmental monitoring. However, conventional sensing devices inherently distort the flow due to permeability mismatch, leading to erroneous data. To overcome this fundamental limitation, we propose and validate a hydrodynamic sensing mechanism based on a rationally designed metamaterial shell that creates a protected sensing core while leaving the external flow almost undisturbed. Specifically, the shell restores the pressure field in the core region to the background pressure field that would exist in the absence of any obstacle, so that an actual sensor placed there would read the true undisturbed pressure, and at the same time suppresses the disturbance of the combined core–shell structure to the surrounding flow. This shell, with anisotropic permeability derived from scattering‐cancellation theory, thus renders the sensing core invisible to the background flow. Navigating the vast design space is achieved via a deep neural network, which inversely designs microstructures with exceptional accuracy (prediction error %). Our metashell‐enabled sensing scheme reduces pressure measurement errors by four to five orders of magnitude, achieving near‐perfect fidelity even under severe permeability contrasts. This theoretical–machine learning framework establishes a blueprint for distortion‐free hydrodynamic sensing, readily extendable to thermotics, acoustics, and electromagnetics.

Elasticization Enables Strain‐Tolerant Microstructure and Enhanced Performance in Stretchable Polymer Solar Cells

ABSTRACT The advancement of intrinsically stretchable photovoltaic films is essential for powering next‐generation wearable electronics through all‐polymer solar cells (APSCs). While blending with elastomeric materials has emerged as an effective strategy to enhance mechanical robustness, the fundamental microstructural evolution under strain remains poorly understood. Here we introduce and implement a synchrotron‐based in situ stretching X‐ray scattering technique to directly probe nanoscale morphological changes in real time. Incorporating a styrene‐isoprene‐styrene elastomer SIS induces enhanced π–π stacking intensity both parallel and perpendicular to the stretching direction. The resulting stretchable APSCs achieve a record‐high efficiency over 16% and exceptional mechanical stability, retaining over 80% of initial efficiency at 60% strain and 81% after 1000 stretching cycles at 40% strain. Furthermore, power output remains stable under strains of up to 60%, and the mechancial parameters are well predicted by the Coral‐Patel model. This study provides critical insights for elastomer selection and microstructure design in stretchable electronics.

Starvation of leukemic cells enhances DNA damage-induced apoptosis in vitro via ROS/p38 MAPK and prevents leukemia progression in fasting xenograft mice

Improving access to clinical trial participation among underrepresented kidney cancer patients.

430 Background: It is well-studied that multiple barriers exist to oncology clinical trial participation. Patient (pt)-related barriers include lack of education about clinical trials and increased financial burden. Literature is saturated with studies identifying barriers to oncology trial enrollment, but limited randomized studies exist addressing possible solutions. Our study addresses this educational gap, with an overall goal of increasing access to clinical trial participation. Methods: A clinical trial education program targeting kidney cancer patients was developed. By partnering with kidney cancer pts (N = 8) and using semi-structured interviews, information about their clinical trial knowledge was gathered. An in-person educational program and animated video covering varied topics pertaining to clinical trials were created. Pre/post program surveys captured participant demographics and current knowledge/perceptions about clinical trials. Wilcoxon signed-ranked test was used to compare the pre/post responses. Results: To date, 77 pts completed both surveys. Demographics included: Male (73.7%), Female (26.3%), < 60 years (23.7%), ≥ 60 years (76.3%), White (89.6%), Black (3.9%), American Indian (1.3%), Asian (2.6%), Other (1.3%), Hispanic/Latino (5.3%). Statistically significant improvements were observed in several domains between pre/post responses. Pts demonstrated increased understanding of placebo use in clinical trials (P = 0.0003), randomization (P = 0.0002), general knowledge of clinical trials (P < .0001), where to find cancer research studies (P < 0.0001) and improved perceptions regarding the cost and time to participate in clinical trials (P = 0.006). Conclusions: Previous research demonstrates the value of pt education in improving understanding and decision-making regarding clinical trial participation. Similarly, our study demonstrates statistically significant improvement in pt understanding of key clinical trial concepts following an educational intervention. Specifically, significant gains were observed in knowledge related to placebo use, randomization, general understanding of trials, and awareness of where to find cancer research studies. These results suggest that the educational program was effective in addressing common misconceptions and information gaps that may serve as barriers to trial participation. For non-statistically significant variables, such as understanding of the voluntary nature of trials, concerns about insurance coverage, timing of study offerings, and willingness to participate—it is possible that pts already possessed a strong baseline understanding. In summary, while our findings support the effectiveness of educational interventions in improving clinical trial literacy, further research is needed to determine whether education alone is sufficient to influence participation.

Topline results from BOND-003 cohort P: A multi-national, single-arm study of intravesical cretostimogene grenadenorepvec for treatment of high-risk, papillary only, BCG-unresponsive non-muscle invasive bladder cancer.

755 Background: Patients with High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer have limited treatment options. The US FDA approved treatments for BCG-UR patients with CIS, but additional bladder-sparing therapies are needed, especially for the BCG-UR papillary-only population. Cretostimogene is an oncolytic immunotherapy with dual mechanisms of action. It replicates in and lyses cancer cells with Rb-E2F pathway alterations. This releases tumor-specific antigens, initiating an anti-tumor immune response, further amplified by the GM-CSF transgene. The BOND-003 Cohort P study (NCT04452591) is a single-arm clinical trial assessing the efficacy and safety of intravesical cretostimogene in HR, papillary-only, BCG-UR NMIBC patients. Methods: Eligibility criteria include age ≥18 years, ECOG PS of 0-2, and histologically confirmed BCG-UR HG Ta/T1 papillary disease without CIS within 90 days of study enrollment as verified per central pathology review. Patients had no visible evidence of residual bladder cancer before treatment. Intravesical cretostimogene is instilled for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through Month 12, then every six months through Month 36. Re-induction is permitted at 3 months for patients with HG Ta or CIS. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and mandatory biopsy directed at prior tumor locations at Month 12, with centralized review of pathologic samples. Endpoints include HG-RFS, HG-EFS, PFS, and safety. The study has completed enrollment. Results: A total of 56 patients who received treatment with cretostimogene are evaluated based on data from September 1, 2025 cut off. At baseline, 76.7% of patients are 65 years or older, 21.4% are female, 64.3% have HG Ta, and 35.7% have HG T1 papillary NMIBC. Kaplan-Meier estimates of HG-RFS at 6- and 9-months are 84.6% (95% CI 73.1 - 96.1%) and 80.4% (95% CI 66.8-94.0%), respectively. No patients have undergone a radical cystectomy. One patient progressed to metastatic disease despite a clinical complete response in the bladder. Cretostimogene demonstrates a favorable safety profile, with most adverse events localized to low grade bladder symptoms. There are no serious treatment-related adverse events and no discontinuations related to cretostimogene. To date, no patients have required a dose delay or missed a dose due to a related adverse event. There have been no deaths related to study treatment. Further, updated data will be presented. Conclusions: These results demonstrate consistent efficacy and a well-tolerated safety profile. Mature data with longer term follow-up will build upon these promising findings and will inform future treatment approaches with cretostimogene. Clinical trial information: NCT04452591 .

Cardiovascular risk evaluation in men with prostate cancer study (CARE-PC): Pilot study to assess patient awareness and risk mitigation.

52 Background: Cardiovascular (CV) disease is a major cause of morbidity and mortality among patients (pts) with prostate cancer (PCa). Shared epidemiologic and androgen-deprivation therapy (ADT)-related factors may contribute to increased CV risk in pts with PCa. As there are limited clinically available tools to educate pts with PCa on CV health risks and CV risk mitigation strategies, CV risk factors are under-recognized and under-treated. We conducted a pilot study to evaluate the feasibility, data quality, and clinical impact of a patient-oriented, web-based application to directly inform PCa pts of their estimated CV risk and CV mitigation strategies (NCT06064149). Methods: Between 11/2023 and 4/2025, PCa patients (< 75 years) currently receiving or planned for ≥ 6 months ADT-based PCa therapy were enrolled. Pts were sent a website link for the CARE-PC application via the electronic medical record (EMR), and self-entered demographic, CV risk factor, CV disease and PCa medical history. Upon completion, CARE-PC immediately provided a personalized CV risk estimate and targeted, guideline-based CV risk reducing education. Primary endpoint was the application completion rate. Secondary endpoints included accuracy of patient-entered data (compared to EMR standard), prevalence of CV risk factors and disease, and cardiologist care access. Results: 82 pts met eligibility. The median age was 66 years, and 20% of pts had localized PCa and 80% had either biochemically recurrent or metastatic PCa. The CARE-PC application completion rate was 54% (44/82). Pts were more likely to complete the web-based tool if age ≥ 65 yrs (61% vs 42%), married (57% vs 46%), Caucasian (62% vs 14% African American), and recurrent or metastatic PCa (59% vs 31% localized PCa). Among 44 pts completing the web tool, 7% (3/44) of pts had diabetes and 61% (27/44) were using antihypertensives (both reported with a 98% (43/44) accuracy rate). 41 pts (93%) accurately reported their CV disease history; 16% (7/44) of pts had a confirmed history of ≥ 1 CV disease. 52% (23/44) of pts were currently followed by a cardiologist. 86% (38/44) accurately reported PCa clinical status (localized vs recurrent or metastatic). 70% (31/44) and 73% (32/44) of pts accurately reported prior PCa therapies and current PCa therapies, respectively. Conclusions: The CARE-PC web-based tool is feasible, but completion rates vary based on age, race, and marital status. Self-entered accuracy of CV risk factor and CV disease was high, with lower accuracy for prior/current PCa therapy. Ongoing analyses will evaluate pt engagement in CV care following CARE-PC participation. Further provider- and patient-oriented quality improvement initiatives are needed to increase awareness and mitigation of competing CV health risks within an individualized PCa clinical context. Clinical trial information: NCT06064149 .

Prognostic and predictive impact of HER-2 expression in metastatic urothelial carcinoma: Results from the single-centre BLADDHER study.

805 Background: Identifying novel therapeutic targets is a relevant clinical need in metastatic urothelial carcinoma (mUC). HER-2 expression has been gaining increasing relevance after FDA's tumor-agnostic approval of Trastuzumab Deruxtecan (T-DxD) for HER2-positive non-breast malignancies after prior therapies. Prevalence and prognostic relevance of HER-2 expression in mUC is still poorly documented. Methods: HER-2 expression was retrospectively assessed in pathology samples of patients (pts) with mUC starting first line treatment at our Institution from 2021 to 2025. HER-2 expression was assessed by immunohistochemistry (IHC) and graded according to gastric tumor score. Clinical characteristics and outcomes in terms of response to systemic treatments were then compared between pts with HER-2 positive and negative tumors, respectively. Results: Eighty-eight pts were enrolled (74% male, median age 73). HER-2 positivity was found in 41% (23% 2+, 18% 3+), 53% were negative (26% 1+, 27% 0), and 6% not evaluable. FGFR mutations were detected in 14 patients (16%). No correlation was found between HER-2 expression and presence of histological variants, presence of FGFR mutations and sites of metastases (Table 1). Conversely, the HER-2 positive group had a higher rate of metastases at diagnosis (p = 0.047) and bladder primitive site (p = 0.005). After a median follow-up of 21.1 months (95% CI 14.9-28.8), HER-2 status was not associated with differences in first-line progression-free survival (PFS) (HR 1.01, 95% CI 0.53-1.91, p > 0.9), overall response rate (ORR) (OR 1.66, 95% CI 0.58-5.02,p = 0.4), or PFS on maintenance Avelumab (HR 1.10,95% CI 0.34-3.49, p = 0.9). Among 23 pts treated with Enfortumab Vedotin in 2nd/3rd line, ORR was not significantly different (OR 6.0, 95% CI 0.74-130, p = 0.14). Conclusions: In our cohort HER-2 positivity was found in 41% of mUC overall, and appeared to correlate with advanced disease at diagnosis and with bladder primitive site, but not with histological variants, sites of metastases and FGFR mutation. Response to cytotoxic and immunological therapies appeared comparable among HER-2 positive and HER-2 negative pts. The future availability of new HER-2 targeting agents will probably have a major impact on the outcomes of HER-2 positive pts. HER-2 positive (N=36) HER-2 negative (N=47) p-value FGFR statuswild typemutated 29 (81%)6 (17%) 35 (76%)8 (17%) 0.8 Histology variantabsentpresent 23 (64%)13 (36%) 29 (62%)18 (38%) 0.8 Metastasic disease at first diagnosis yesno 13 (36%)23 (64%) 8 (17%)39 (83%) 0.047 Primary tumor siteupper tractbladder 4 (11%)31 (89%) 18 (40%)27 (60%) 0.005 Only lymph nodes diseaseyesno 9 (25%)27 (75%) 21 (45%)26 (55%) 0.064 Liver metastasisyesno 5 (14%)31 (86%) 9 (19%)38 (81%) 0.5 Bone metastasisyesno 10 (28%)26 (72%) 6 (13%)41 (87%) 0.086

Customized Vertical Zn Deposition and Regulated Interfacial Kinetics via Anti‐Inflammatory Biomolecules for Ultra‐Stable Zn Metal Batteries

ABSTRACT Controlling Zn (100) oriented deposition offers a promising route for highly reversible Zn anodes, yet the intrinsic susceptibility to parasitic reactions and unbalanced interfacial kinetics of this facet pose critical challenges. Herein, inspired by the biological regulation of inflammatory stress, sulfated polysaccharides are proposed as sustainable electrolyte additives. Specifically, dextran sulfate sodium (DSS) enables durable Zn (100) plating/stripping and balanced interfacial kinetics. The high‐density continuously grafted ─SO 3 − bonds in DSS can rebuild Zn 2+ solvation structure and construct a robust interfacial layer to mitigate parasitic reaction and dendrite formation. Preferred absorption of DSS on (100) facet through ─SO 3 − bonds restrict Zn growth along this facet and facilitate Zn 2+ diffusion from adjacent (002)/(101) facets, ultimately exposing Zn (100) texture. Multiple ─SO 3 − bonds enable fast desolvation and ionic transport kinetics, and steric hindrance of DSS ensures moderated Zn 2+ reduction kinetics, synergistically establishing a kinetics‐balanced interface for durable Zn (100) deposition. Consequently, the DSS‐modified electrolyte achieves exceptional cycling stability (10400 h at 1 mA cm −2 ) and high‐rate capability (1500 h at 20 mA cm −2 ) for (100)‐oriented Zn anodes. The broad compatibility with various cathodes underscores the practical promise of this strategy. This work highlights rational molecular design in regulating crystallographic orientation and interfacial kinetics for advanced Zn metal batteries.

Bioinspired Programmable Biaxial Rolling Gel Sheets for Complex 3D Morphing

ABSTRACT Shape‐morphing gels have shown promising applications in widespread fields, including soft robotics, flexible electronics, and smart medicine. The majority of efforts have been focused on rapid response and multi‐responsiveness of shape‐morphing materials with bilayer structure. However, achieving biaxial rolling with controllable curvature remains a critical challenge. Herein, inspired by the hygroscopic heterostructures in pine cone scale, we report a sinusoidal‐patterned hydrogel‐semi‐embedded‐organogel (HSEO) sheet constructed by wetting‐enabled 3D interfacial polymerization (WET‐DIP) strategy. The sinusoidal pattern serves as a programmable geometric template to redistribute anisotropic stress spatially. By tuning sinusoidal pattern parameters, we realize biaxial morphing and the modulation of longitudinal and transversal curvatures, consistent with the results of finite element analysis (FEA). The semi‐embedded heterostructure offers compressive force on the organogel to overcome isotropic stress limitations. Notably, this design leverages the sinusoidal periodic topology and semi‐embedded structure to precisely modulate stress distribution, enabling counterintuitive rolling behaviors and complex 3D transformations. This work pioneers a counterintuitive and programmable shape‐morphing mechanism for complex 3D architectures, offering a perspective for novel soft actuators.

Phosphoregulation of RAD51AP1 function in homology-directed repair

Real-world use of novel hormonal therapies in European and North American patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC).

86 Background: Androgen receptor pathway inhibitors (ARPIs) are essential for mHSPC treatment; however, global use may vary. Insights into real-world use of ARPIs by region are needed to understand differences in global treatment practices. Methods: This observational cohort study included newly diagnosed pts with mHSPC enrolled in the IRONMAN registry between June 2017 and March 2025 in Europe (EU) (Ireland, Norway, Spain, Sweden, Switzerland, UK) and North America (NA) (Canada, USA), with ≥3 months follow-up. Outcomes were the proportion of pts with mHSPC receiving initial ARPI (index date), Kaplan-Meier estimated ARPI discontinuation rate (DR), and physician-reported reasons for discontinuation. Results: 2545 pts with mHSPC were included (EU n=1129; NA n=1416). Median age was 71 years (range 43–94) in EU and 70 years (range 32–95) in NA. The majority of pts were White (EU: 74%; NA: 65%) and non-Hispanic (EU: 70%; NA: 79%). Median PSA levels at enrollment were 3.6 ng/mL in EU and 7.6 ng/mL in NA. Most pts had ECOG PS 0 (EU: 67%; NA: 56%). Median time from mHSPC diagnosis to index date was 2.2 months in EU and 1.9 in NA. Median follow-up was 24.0 months in both cohorts. The most common metastatic site was bone ± nodal (EU: 72%; NA: 66%), followed by visceral ± nodal or bone (EU:15%; NA: 22%), and nodal only (EU: 13%; NA: 12%). Initial chemotherapy use (including docetaxel [DOC] ± ADT and DOC + ADT + ARPI) was 19% of pts in EU and 11% in NA, while 67% of pts in each region used initial ARPI (Table). In EU, initial ARPI use increased from 0 pts in 2017 and 2018, to 20 (19%) in 2019, 97 (49%) in 2020, 152 (64%) in 2021, 170 (79%) in 2022, 205 (90%) in 2023, and 94 (84%) in 2024. Initial ARPI use was higher in NA from 2017 to 2021: 26 pts (79%) in 2017, 129 (58%) in 2018, 162 (59%) in 2019, 77 (71%) in 2020, 129 (71%) in 2021, 127 (73%) in 2022, 163 (71%) in 2023, and 113 (77%) in 2024. ARPI DR at 24 months was higher in NA (42%) vs EU (31%), with a similar distribution of discontinuation reasons. A small number of pts switched therapies, including to other ARPIs. Conclusions: In this real-world study, ARPI use increased over time, although EU lagged NA; initial chemotherapy use was higher in EU. A substantial proportion of patients discontinued ARPI within 24 months, particularly in NA, mainly due to progressive disease or adverse events. Further comparative studies are needed to guide optimal treatment decisions across regions, and whether to explore harmonization across regions. Clinical trial information: NCT03151629 . EU( n = 1129) NA ( n = 1416) Total ( N = 2545) Received initial ARPI, n (%) 756 (67) 949 (67) 1705 (67) Received initial chemotherapy, n (%) 209 (19) 158 (11) 367 (14) DR 24 months, n (%) 231 (31) 402 (42) 633 (37) Discontinuation reason, n (%)Progressive diseaseAdverse eventDeathPhysician decisionOther/unknown/lost to follow-up 88 (12)37 (5)38 (5)31 (4)37 (5) 109 (12)64 (7)48 (5)52 (6)129 (14) 197 (12)101 (6)86 (5)83 (5)166 (10)

Effects of steroid pretreatment on adverse events and overall survival during enfortumab vedotin in urothelial carcinoma.

731 Background: Enfortumab vedotin (EV) is a standard subsequent therapy for patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Although EV is effective, treatment-related adverse events (AEs), particularly the high incidence of skin toxicities, remain a major problem. Whether prophylactic steroid pretreatment can effectively reduce these toxicities is unknown. We aimed to evaluate the influence of steroid pretreatment on toxicity and survival outcomes in patients receiving EV monotherapy. Methods: We retrospectively analyzed 157 patients with la/mUC treated with EV monotherapy. Patients were stratified into those with prophylactic steroid pretreatment prior to EV initiation (pre-EV steroids, n = 20) and those without (no pre-EV steroids, n = 137). Clinical outcomes included the incidence and type of AEs, best objective response, disease-free survival (DFS), and overall survival (OS). Results: Steroid pretreatment was associated with a significantly lower incidence of skin AEs (10% vs. 62.7%, P < 0.001) and reduced number of cumulative AEs (median 1 vs. 2, P = 0.018). The incidence of grade ≥3 AEs was not significantly different between groups. Best objective response rates were comparable. However, patients with steroid pretreatment showed inferior OS compared to those without (median OS 10.3 vs. 17.4 months, P = 0.008), while DFS showed no significant difference. Multivariable analysis confirmed steroid pretreatment as an independent factor for reduced skin AEs (OR 0.08, P = 0.001) but worse OS (HR 1.99, P = 0.038). Conclusions: Steroid pretreatment during EV monotherapy mitigates skin toxicities but may compromise overall survival. Careful patient selection and judicious use of steroids are warranted to balance safety and efficacy in EV treatment for la/mUC.

Ultra-sensitive molecular residual disease detection via tumor-informed whole-genome sequencing-based ctDNA assay in resectable urothelial cancer in the MONSTAR-SCREEN-3 project.

810 Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for detecting molecular residual disease (MRD) and is increasingly integrated into both clinical practice and translational research in various cancers. Conventional methods often lack sensitivity for MRD, particularly in low-shedding tumors. To overcome this limitation, the MONSTAR-SCREEN-3 study is evaluating the utility of a tumor-informed whole-genome sequencing (WGS)-based MRD assay across more than a dozen cancer types. Here we report preliminary results from the urothelial cancer cohort, including upper tract urothelial cancer (UTUC) and bladder cancer (BC). Methods: MONSTAR-SCREEN-3 is a prospective, multicenter study enrolling 1,100 patients receiving curative-intent therapy in the definitive cohort. Personalized ctDNA panels were generated using a WGS-based tumor-informed platform incorporating up to 1,000 tumor-specific alterations. Serial plasma samples were collected at baseline, after neoadjuvant chemotherapy (if applicable), 1 month post-surgery, quarterly during the first year, and biannually thereafter for up to two years. Results: As of September 2025, 62 patients with resectable UTUC (n = 22) and BC (n = 40) had been enrolled. MRD results were available for 63 samples from 20 patients. Median age was 75 (range 50-90), and 70% were male. Among the 20 patients with available WGS data, a median of 20,081 panel-eligible alterations per patient were identified (range: 1,733-184,521). Nine patients received neoadjuvant chemotherapy and 11 had upfront surgery. Two patients also underwent transurethral resection of bladder tumor (TURBT). Seventeen patients underwent radical surgery, with pathological stages: pStage 0 (n = 4), I (n = 2), II (n = 5), III (n = 5), and IV (n = 1). ctDNA results were available for 18 patients at baseline, and ctDNA was detectable in 100% of evaluable cases (10/10 BC and 6/6 UTUC), with 18.8% (3/16) detected at ultra-sensitive levels (tumor fraction < 100 parts per million [ppm]; minimum: 2.9 ppm). The remaining two patients showed undetectable ctDNA at enrollment, consistent with prior TURBT. Post-surgery MRD positivity rates were 63% (10/16) at 1 month and 36% (5/14) at 3 months. One patient with 1-month post-surgery MRD positivity ( < 1 ppm) developed radiographic recurrence, with MRD detection preceding imaging findings by 1.7 months. One patient with intravesical recurrence was MRD-negative at 1-month post-surgery. Extended follow-up and longitudinal ctDNA dynamics will be presented. Conclusions: The WGS-based personalized ctDNA assay demonstrated technical feasibility in urothelial cancer highlighting the critical importance of ultra-sensitive platforms for low-shedding tumors.

CORE-008 cohort B: Evaluating intravesical cretostimogene grenadenorepvec in patients with high-risk, BCG-exposed non-muscle invasive bladder cancer.

TPS896 Background: Patients with High-Risk NMIBC whose disease trajectory falls outside the strict FDA guidance of BCG-Unresponsive represent a significant unmet need, often lacking access to clinical trials or evidence-based treatment options. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with dual mechanisms of action. It replicates in and lyses cancer cells with Retinoblastoma (Rb)-E2F pathway alterations, while simultaneously amplifying an anti-tumor immune response, further mediated by the GM-CSF transgene. The CORE-008 clinical trial (NCT06567743) is a Phase 2, multi-arm, multi-cohort trial to evaluate the efficacy and safety of cretostimogene in patients with HR NMIBC, across BCG-naïve, BCG-exposed, and BCG-unresponsive disease states. Here, we describe Cohort B of CORE-008, which examines the efficacy and safety of cretostimogene in BCG-exposed NMIBC. Methods: Cohort B eligibility criteria include pathologic confirmation of HR NMIBC, CIS containing and papillary only, as defined by the AUA/SUO guidelines, and recurrence after prior BCG. BCG-exposed NMIBC is defined as high-grade recurrence in patients who are BCG-resistant (recurrence after at least 5 of 6 induction doses), or who experience delayed relapse within 24 months following either adequate BCG (≥5 induction doses plus ≥2 reinduction or maintenance doses) but outside the defined BCG-Unresponsive window or following inadequate BCG (3–6 doses). Intravesical cretostimogene is instilled in combination with DDM, an excipient that enhances adenoviral delivery, for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through Month 12, then every six months through Month 36. Re-induction is permitted at Month 3, if persistent HG Ta or CIS is noted at biopsy. Response assessment includes serial cystoscopy with directed biopsy (as indicated), urine cytology, and CT/MR urogram. The primary endpoint for the CIS population is Complete Response (CR) at any time and HG-EFS for patients with papillary-only disease. Secondary endpoints include Duration of Response, all-cause Event-Free Survival, Bladder Cancer Specific Survival, Progression-Free Survival, Cystectomy-Free Survival, safety, and tolerability. Exploratory outcome measures consist of Health-Related Quality of Life, Overall Survival, and biomarker assessments. Cohort B is open for enrollment in collaboration with the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC). Clinical trial information: NCT06567743 .

Regeneration of Single‐Crystal with Repaired of the (003) Crystal Plane from Degraded Polycrystalline Ternary Cathode

ABSTRACT The direct regeneration of spent polycrystalline cathode materials into highly stable single‐crystal counterparts heralds a transformative shift in the recycling of spent lithium‐ion batteries (S‐LIBs). However, current direct recycling approaches, reliant on molten salt‐mediated single‐crystal transformation, remain constrained by operational complexity and a fragmented mechanistic understanding of defect repair on the (003) crystal plane. Herein, we unveil a streamlined one‐step regeneration strategy leveraging the LiNO 3 ‐LiOH·H 2 O‐Li 2 CO 3 system, enabling the conversion of polycrystalline S‐NCM523 to single‐crystal R‐NCM523 while simultaneously reconstructing (003) crystal plane. DFT and in situ analyses demonstrate that CO 3 2 − , NO 3 − , and OH − preferentially adsorb at the 3a sites within the lithium (Li) layer of the (003) plane. Their oxygen atoms hybridize with Li's 2s orbitals and TM's 3d orbitals, effectively suppressing rock‐salt phase formation via Li vacancy filling and Oxygen vacancy repair. A Two‐step sintering protocol drives particle single‐crystallization and active lithium replenishment. The resultant R‐NCM523 cathode significantly suppresses H2‐H3 phase transitions, delivering an initial half‐cell capacity of 165.80 mAh/g and retaining 81.0% of its discharge capacity after 1000 full‐cell cycles. This precursor‐free strategy achieves a molten salt recovery rate exceeding 90%, providing an industrially viable pathway for efficient, low‐energy S‐LIB regeneration.

Efficient Photocatalytic CO ₂ Reduction to C ₂₊ Products with Pt _1‐ <i> _x </i> Pd <i> _x </i> Sn ₄ Dirac Nodal Arc Semimetal

ABSTRACT The photochemical CO 2 reduction reaction (CRR) represents a zero‐carbon pathway for converting CO 2 into value‐added chemicals, yet its industrial implementation has been constrained by low selectivity and product diversity. Dirac nodal arc semimetals characterized by ultrahigh carrier mobility (&gt;25 000 cm 2 ·V −1 ·s −1 ) offer a promising platform to search for efficient catalysts for CO 2 conversion. Herein, we demonstrate that strategic Pt incorporation into PdSn 4 optimizes the electronic structure and carrier dynamics of this Dirac semimetal. Experimental and theoretical analyses reveal that the resulting Pd─Sn─Pt local electronic structure redistributes charge density around Pd and Pt atoms, which facilitates C─C coupling via *OC─COH and *OC─CHOH intermediates and enhances carrier mobility by 40% versus the pristine PdSn 4 single crystal. The optimized Pd 0.4 Pt 0.6 Sn 4 single crystal achieves C 2 H 4 i) formation rate of 328 µmol∙g −1 ∙h −1 ; ii) product selectivity of 73.1%; iii) electron‐based selectivity of 89%. This work establishes electronic‐structure‐tunable Dirac semimetals as a new paradigm for multi‐carbon photochemical CO 2 reduction, providing a design strategy for next‐generation photocatalysts.

Bisecting βGlcNAc: MA’AT analysis of 13C-labeled oligosaccharides containing βGlcNAc-(1→4)-βMan O-glycosidic linkages

Prospective monitoring of biochemically recurrent prostate cancer (BCR) using prostate specific membrane antigen (PSMA) imaging: 21-month follow-up.

37 Background: The use of PSMA imaging is impacting the management of BCR, but it remains unclear if treatment escalation is required for PSMA+ BCR. While patients (pts) at the highest risk of death from prostate cancer (e.g. PSA Doubling Time (DT) less than 6 months) may benefit from therapy, the majority of BCR pts will not die of prostate cancer. Longitudinal data pf PSMA+ BCR is required to better understand risk stratification for PSMA+ BCR. Methods: NCT05588128 enrolls BCR pts after definitive therapy +/- salvage options. Pts are required to have a PSA&gt;0.5 ng/ml, negative bone scan and computed tomography (CT; lymph nodes (LNs) up to 1.5 cm are permitted.) Prior therapies are permitted as long as testosterone&gt;100 ng/dL. If initial PSMA scan is positive, PSMA scan is repeated every 6 months, but annually if negative. While on-study, patients may have systemic therapy for less than 6 month intervals and radiation (RT) is permitted. Results: 129 patients are evaluable with a median potential follow-up of 21.75 months (mos). Median baseline age=71 years, PSA=2.3 ng/ml and PSA DT=11.0 mos but 35% have PSA DT &lt;6 mos. At baseline 23 pts (18%) had negative PSMA, 22 (17%) had prostate only findings, 24 (19%) had 1 LN, 9 (7%) had 2-3 LNs and 33 (26%) had 4+ LNs. Also, 19 pts (15%) had bone findings, 4 (3%) had PSMA+ serosal lesions and 1pt had PSMA+ pulmonary nodule. During the course of follow-up, 28 pts elected androgen deprivation therapy (ADT)-sparing NCI protocols, 1 pt had ADT, 1 pt had salvage RT, and 7 had RT to PSMA+ finding(s). Of 107 pts with PSMA+ findings, only 4 (3.7%) had developed metastasis on CT/bone scan with a median f/u of 21.75 mos. Conclusions: Most patients with BCR will not die of prostate cancer and it remains unclear how PSMA imaging will help risk stratify pts. This ongoing study demonstrates that with nearly 2 years of median follow-up, the risk of metastatic progression on CT or bone scan remains low even if patients have PSMA+ findings at baseline. These data do not support using PSMA imaging as the sole criteria to initiate therapy for BCR pts including those with numerous PSMA findings. This study continues to accrue patients at the National Cancer Institute, Bethesda, MD. Clinical trial information: NCT05588128 .

Impact of FGFR3 alterations on first-line platinum based chemotherapy in patients with metastatic or locally advanced urothelial carcinoma: The retrospective IFUCA study.

735 Background: FGFR3 alterations are observed in 10–15% of patients with advanced urothelial carcinoma (UC). While targeted therapies are emerging, the prognostic and predictive value of FGFR3 alterations in the context of first-line platinum-based chemotherapy (PBC) remains unclear. Methods: We conducted a multicenter retrospective cohort study including patients (pts) with histologically confirmed UC treated in first line with PBC (carboplatin or cisplatin), with or without immune checkpoint inhibitor (ICI) as maintenance or second line. Only patients with known FGFR3 status on baseline tumor tissue, locally assessed were included. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), objective response rates (ORR), and PFS with ICI, stratified by FGFR3 status. Results: Between 2016 and 2022, 191 pts were included, of whom 58 (30.4%) had FGFR3-altered tumors (FGFR3^alt). Baseline characteristics were well balanced, although FGFR3^alt patients had more de novo metastatic disease and fewer prior local treatments (HR = 0.65; p = 0.01). After a median follow-up of 32 months, median PFS with PBC was 6.6 months in both FGFR3^alt and wild-type groups (HR = 1.27; p = 0.15) respectively. Median OS was 22.1 vs. 20.8 months (HR = 0.91; p = 0.658), and ORR in 133 pts were similar across subgroups (70.7% vs. 69.2% respectively). ICI was administered to 65 (34%) of patients and no difference in PFS was observed between groups with 4.4 vs 2.9 months (HR = 0.86 ; p = 0.5868) respectively. In multivariate analysis, FGFR3 status was not associated with survival. Conclusions: FGFR3 status did not significantly impact response to PBC in first-line treatment or ICI. These findings underscore that the presence of an FGFR3 alteration does not guide the choice of platinum-based treatment, and the need for prospective biomarker-driven trials to identify best treatment sequences in advanced UC.

Primary urethral squamous cell carcinoma: Insights and outcomes from a 27-year institutional experience.

627 Background: Primary urethral cancer is one of the rarest cancers worldwide, resulting in limited data and ongoing debates about the optimal standard of care. This study aimed to share our institutional experience in treating primary squamous cell carcinoma (SCC) of the urethra, the most common histologic subtype of urethral carcinoma. Methods: Utilizing an IRB-approved urethral cancer database, we conducted a retrospective review, identifying patients diagnosed with primary urethral carcinoma based on International Classification of Diseases codes (ICD-10: C-68 and ICD-9: 189.3). Codes related to “Secondary malignant neoplasm of other urinary organs” were also examined to ensure comprehensive patient identification. Data on patient demographics, baseline characteristics, treatments, and outcomes were extracted and analyzed. Results: We identified 68 patients with primary urethral cancer from August 1997 to September 2023, of whom 35 (51.5%) had primary SCC of the urethra. Baseline characteristics are summarized in Table 1. Among the 35 patients, 16 (45.7%) received neoadjuvant chemotherapy, with gemcitabine-based regimens being the most common (N=8), followed by TIP (paclitaxel, ifosfamide, and cisplatin) in 6 patients. Urethrectomy (N=12) was the most frequent surgical procedure, followed by penectomy and radical cystectomy. The median follow-up time was 2.4 years. Seventeen (48.6%) patients received adjuvant chemotherapy or immunotherapy, most commonly the TIP regimen (N=5, 29.4%) and pembrolizumab (N= 4, 23.5%). Additionally, 12 (34.3%) underwent adjuvant radiotherapy. The 5- year recurrence free survival and overall survival rates were 56.8%, and 93.8%, respectively. Of the 15 patients who developed secondary metastases, lymph nodes and regional genitourinary sites were the most frequent (each N=6), followed by the lungs (N=2) and bone (N=1). Conclusions: Our findings indicate that while the overall survival of primary urethral SCC patients is relatively favorable, there remains a lack of consensus regarding the standard of care for this malignancy. Additionally, despite the extended timeline of our study, the median follow-up duration was relatively short. These results highlight the need for larger multi-institutional studies with longer follow-up periods to establish a clearer standard of care for primary urethral cancer. Demographics and perioperative characteristics of the patients. Age (yrs.) 63.2 ± 13.4 Gender (Male) 26 (74.3%) Surgery of primary disease (N=31) Urethrectomy 12 (34.3%) Penectomy 8 (22.9%) Radical cystectomy 7 (20.0%) Other (mass excision, urethroplasty) 4 (11.4%) Primary Pathological staging (N=34) &lt; (y) pT2N0 6 (20.0%) ≥ (y) pT2N0 17 (48.6%) pN+ 9 (25.7%) Metastatic 2 (5.7%)