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Regulation of RNA-binding proteins by small biomolecules

Oriented Microstructured Scintillator for High‐Resolution X‐Ray Imaging

ABSTRACT The structured scintillator is regarded as the sole strategy for achieving high‐resolution X‐ray imaging. Unfortunately, the construction of large‐sized and uniform integrated candidates with oriented microstructure remains an insurmountable challenge. Herein, we propose and demonstrate a novel large‐scale, highly uniform integrated oriented microstructured glass composite scintillator by triggering the oriented crystallization habit of the metastable glass. It is featured by columnar microcrystalline arrays with a high refractive index embedded in the glass phase with a relatively low refractive index. This enables to form an intrinsic waveguide configuration with light confinement capabilities, in which the directional propagation of photons can be realized. As a result, an excellent scintillation performance with the X‐ray excited luminescence intensity of 5.67 times that of BGO can be realized. It also demonstrates the excellent environmental resistance because of the all‐oxide system. By using this oriented microstructured glass composite scintillator, the X‐ray imaging system is built, and an impressive imaging resolution of 30 lp mm −1 is successfully achieved. The progress represents a giant step toward high‐resolution X‐ray imaging with structured scintillators.

TORC2 coordinates MBF-dependent transcription and restrains oxidative stress responses during DNA replication stress in fission yeast

Real-world treatment transitions and healthcare resource utilization in patients with metastatic castration-resistant prostate cancer in Colombia.

49 Background: Although 10-20% PC patients in Latin America (LA) progress to mCRPC, real-world data describing mCRPC patient journey in LA is limited. This study examines treatment patterns, healthcare resource utilization (HRU), survival, and increased post-mCRPC treatment burden among mCRPC patients in Colombia. Methods: This non-interventional, multicenter, retrospective study included patients who progressed to mCRPC between Jan/2017 and Jun/2023 and received at least one line of systemic therapy in Colombia. Patients treated with PARP inhibitors or enrolled in clinical trials were excluded. The McNemar test was applied to assess the healthcare burden before and after mCRPC. Results: 369 mCRPC patients that received 1L treatment were included. The median OS was 34.5 months and median PFS was 13.6 months. The median age was 72y at mCRPC diagnosis. In the 1L, 66.1% received ARPI while 31.2% taxane-based chemotherapy. Among those who progressed after 1L (n=245;66.4%), treatment transitions occurred predominantly from ARPI→chemotherapy (46.1%), followed by chemotherapy→ARPI (18.0%) and ARPI→ARPI (11.8%). Less common sequences included chemotherapy→chemotherapy (9.8%) and ARPI→Radium-223 (3.3%). In terms of HRU, 24.7% required at least one emergency room visit (ERV) and 44.4% hospitalization due to cancer-related issues; 61.8% required radiation therapy, and 54.5% consulted with a palliative care specialist (PCS). ERV and hospitalizations increased from 7.6% to 17.1% and from 15.7% to 28.7% before and after mCRPC, respectively (p for ERV <0.01 and hospitalization <0.01). Conclusions: In this first multicenter Colombian real-world study of mCRPC patients, ARPI dominated 1L therapy and ≈50% switched to chemotherapy on progression. Patients with mCRPC experienced a higher burden of HRU, with 3x and 2x increase in ERV and hospitalizations compared to pre-mCRPC. These findings underscore not only the significant clinical deterioration observed in the resistant disease setting but also the critical implications for budget planning, the importance of maintaining patients in mHSPC for as long as possible. Healthcare resource utilization of patients with mCRPC. Healthcare resource n-(%)(N=369) Mean number of visits HRU before mCRPCn-(%)(N=369) HRU after mCRPCn-(%)(N=369) p-value (before vs. after mCRPC) Months from PC diagnosis to first reported event* Months from mCRPC diagnosis to first reported event* ERV 91–(24.7) 1.8(±1.4) 28-(30.8) 63- (69.2) <0.01 43.5 (18.1-107.8) 12.3 (4.4-27.0) Hospitalization 164–(44.4) 1.7(±1.0) 58-(35.4) 106-(64.6) <0.01 42.6 (19.6-94.7) 10.6 (4.2-23.6) Palliative Care specialist** 201–(54.5) 8.1(±9.5) 56-(27.9) 144-(71.6) <0.01 41.2 (12.7-89.3) 10.3 (2.5-24.2) *Median-Interquartile range. **In one patient, data on the time of first reported HRU was not available.

Impact of prior immune checkpoint inhibitor (ICI) and interval from ICI exposure on outcomes with enfortumab vedotin and pembrolizumab (EVP) in advanced urothelial carcinoma (aUC).

704 Background: EVP is the preferred frontline regimen for patients (pts) with aUC. However, pivotal trials excluded pts with prior ICI exposure, while data on its impact on EVP outcomes are limited. We hypothesized that prior ICI exposure, but not the interval between prior ICI and EVP, would be associated with outcomes. Methods: Pts in the retrospective UNITE study treated with EVP were separated based on any prior ICI exposure vs no ICI exposure. Among ICI-exposed pts, additional assessed variables included interval from ICI completion to EVP start (ICI–EVP interval; analyzed as categorical variable at ≥3, ≥6, ≥12 mos), prior ICI therapy setting, prior pembrolizumab, and best response with prior ICI treatment in the metastatic setting. Potential associations between these factors and progression-free (PFS) and overall survival (OS) were evaluated using Kaplan–Meier and Cox regression, while associations with observed response rate (ORR) were analyzed using logistic regression in pts with scans after ≥1 EVP cycle. Results: Among 493 pts treated with EVP, 68 (21 adjuvant, 46 metastatic, 1 both) had prior ICI. Adjuvant ICI included nivolumab (n = 19), pembrolizumab (n = 1), and 1 unspecified regimen. ICI in metastatic setting included pembrolizumab (n = 26, 1 in combination without EV), switch maintenance avelumab (n = 12), other ICI regimens (n = 7), and 1 unknown. In this cohort, median age was 68 yrs, 68% male, 67% pure urothelial histology, 83% ECOG PS 0/1, 43% had visceral metastases (excluding bone). With a median follow-up of 16 mos from EVP start, median PFS and OS were 7 mos (95% CI 5.3–8.5) and 13 mos (95% CI 10.8–NR), respectively; ORR was 47% (28/59; 95% CI 34 – 61). Median ICI to EVP interval was 6 months (range 0.2 – 79.9). Pts with prior ICI had inferior survival compared to ICI-naive pts, and although the difference in ORR did not reach statistical significance, a trend toward lower ORR was observed in the prior-ICI cohort (Table). Among ICI-exposed pts, outcomes did not differ by ICI–EVP interval, prior pembrolizumab exposure, prior ICI setting, or progression on prior ICI. These findings were also consistent across adjuvant and metastatic ICI settings. Conclusions: In this multisite retrospective analysis, prior ICI exposure was associated with inferior survival with EVP in pts with aUC. The ICI–EVP interval was not associated with outcomes, suggesting that timing of EVP after prior ICI might not influence EVP efficacy. Prospective validation of our hypothesis-generating findings is warranted. ORR Median PFS Median OS Prior ICI (N=68) 47% (28/59)(95% CI 34 – 61) 6.7 mos(95% CI 5.3 – 8.5) 13.3 mos(95% CI 10.8 – NR) ICI-naive (N=425) 57% (211/369)(95% CI 52 – 62) 11.7 mos(95% CI 8.7 – 16.1) 21.9 mos(95% CI 18.6 – 47.8) Prior ICI vs ICI-naive OR: 0.68(95% CI 0.39 –1.18), p = 0.2 HR: 1.60(95% CI 1.16 –2.19), p = 0.02 HR: 1.53(95% CI 1.06 – 2.21), p = 0.003

Marking Techniques for Target Lymph Nodes in Node-Positive Breast Cancer Treated With Neoadjuvant Therapy in the AXSANA/EUBREAST-03/AGO-B-053 Study

PURPOSE Surgical axillary staging in patients with node-positive breast cancer (BC) who converted to clinical node negativity through neoadjuvant chemotherapy (NACT) has changed significantly in recent years. Targeted axillary dissection (TAD) and target lymph node (TLN) biopsy (TLNB) became increasingly popular. However, data comparing marking techniques for the TLN are limited. Here, we evaluate marking techniques in the largest prospective cohort worldwide. MATERIALS AND METHODS Among patients from the ongoing prospective multicenter AXSANA (EUBREAST-03) study who received TLN marking and TAD/TLNB, we evaluated different marking methods with respect to detection and removal rates and clinical performance. RESULTS Until January 6, 2025, 6,129 patients from 26 countries were enrolled. Of these patients, 2,596 had ≥1 TLN marked before NACT and completed surgery; 13.3% of the patients had ≥4 suspicious nodes at diagnosis. Pre-NACT TLN marking used a clip in 2,003 patients (77.2%), magnetic seed in 287 (11.1%), carbon ink in 192 (7.4%), radar marker in 119 (4.6%), radioactive seed in 18 (0.7%), radiofrequency identification device (RFID) in 12 (0.5%), or other methods in two (0.1%). One TLN was marked in 2,427 patients (93.5%), two TLNs in 138 (5.3%), and ≥3 in 27 patients (1%). Targeted removal of the TLN was planned in 2,100 patients (80.9%; TAD in 2,076 [80.0%] and TLNB in 24 [0.9%]). The TLN was detected and removed by TAD/TLNB in 1,915 patients (91.2%). TLN detection rate was the highest in patients whose TLNs were marked pre-NACT with markers suitable for probe-guided detection (96.6%; radioactive seed: 100%, magnetic seed: 96.9%, radar marker: 96.1%, RFID: 90%), followed by carbon ink (94.9%) and clip (89.6%; P < .001). CONCLUSION This large prospective analysis of patients with initially clinically node-positive BC receiving NACT demonstrates that probe-guided detection markers used to mark metastatic nodes before NACT provide superior detection rates.

In Situ Photoelectrochemical Chelation Programs Defect‐Resilient Coordination Microenvironments for Enhanced Water Oxidation

ABSTRACT Deep‐level defects function as non‐radiative recombination centers that throttle oxygen evolution reaction (OER) kinetics. Conventionally, static and pre‐deposited passivation layers often fail during operation, disconnecting defect suppression from the creation and sustained maintenance of catalytically competent sites. Here, we address this limitation with a photoelectrochemically‐driven microenvironment strategy that selectively manipulates the first coordination shell of surface Zn on ZnIn 2 S 4 . Under the in situ photoelectrochemical chelation process, hydroxyethylidene diphosphonic acid writes robust Zn–O–P motifs that subtly distort the Zn–S framework and convert deep traps into shallow states, thereby accelerating charge transfer while suppressing recombination. Density functional theory suggests that Zn–O–P lowers the OER overpotential and switches the rate‐determining step from O * →OOH * to OOH * →O 2 via stabilized * OOH intermediates. The optimized photoanode delivers a photocurrent density of 5.38 mA cm −2 at 1.23 V RHE , surpassing previously reported ZnIn 2 S 4 ‐based photoanodes. By unifying in situ deep‐trap management and active site construction along a single chemical pathway, this work establishes a modular and general route for dynamic defect engineering and active site reconfiguration, advancing defect‐tolerant innovations in energy conversion and storage.

Time-resolved Mn Kα emission reveals early redox dynamics in the S3 to S0 transition of the photosystem II Kok cycle

Carboplatin in patients with metastatic castration-resistant prostate cancer harboring somatic or germline homologous recombination repair gene mutations: Phase II single-arm trial (the CIPHER trial).

204 Background: Approximately one-fourth of patients with metastatic castration resistant prostate cancer (mCRPC) harbor mutations in homologous recombination repair (HRR) pathway genes. However, access to PARP inhibitors remains limited in LMICs. Carboplatin has been inadequately researched in such settings. Methods: We conducted a phase II single arm clinical trial at a tertiary care cancer centre in Northern India. Eligible patients harboring a mutation in the HRR pathway genes and previously treated with at least one androgen pathway receptor inhibitor, who did not have access to PARP inhibitors were treated with single agent carboplatin (dose: area under curve 5) every 3 weeks. The primary endpoint was PSA50 response, defined as a confirmed decline in serum levels of more than 50% from enrollment. Secondary endpoints included radiological response, and safety. Results: Of 213 patients with mCRPC screened for HRR mutations, 44 (20.6%) harbored a mutation in the HRR genes. Of these, 39 patients received carboplatin. The baseline characteristics are shown in the table. The primary end-point of PSA50 was observed in 41% patients. Among 30 evaluable patients for radiological responses, partial response occurred in 20.0%, and stable disease in 43.3%. The median duration of response was 6.2 months. In a multivariate analysis, patients with germline mutation were more likely to respond compared to those with somatic mutations (odds ratio, 6.76; P=0.05). Conclusions: In men with mCRPC harboring HRR mutations, carboplatin is associated with 41% PSA50 response rate, suggesting activity in this subset of patients. Patients with germline mutations are more likely to respond to carboplatin. In patients who do not have access to PARP inhibitors, use of carboplatin may be a reasonable option. Clinical trial information: CTRI/2023/04/051507 . Baseline characteristics (n=39). Characteristic Overall (N = 39) Age (years) median [min–max] 65 [52–81] PSA (ng/mL), median [min–max] 48.8 [2.3–1251.0] Family history Yes 11 (28.2%) ECOG Performance Status  0 12 (31.0%)  1 27 (69.0%) Volume*  High 33 (84.6%)  Low 6 (15.4%) Metastatic sites  Non regional Nodal involvement 26 (66.7%)  Visceral metastasis 7 (17.9%)  Lung metastasis 3 (7.7%)  Liver metastasis 5 (12.8%)  Skeletal metastasis 37 (94.9%) Pathology (Gleason score)  7 5 (12.8%)  8 18 (46.2%)  9 14 (35.9%)  10 2 (5.1%) Previous therapies  Abiraterone acetate (AA) 34 (87.2%)  Docetaxel (CSPC) 8 (20.5%)  Docetaxel (CRPC) 12 (30.8%)  Prior docetaxel (any) 20 (51.3%)  Enzalutamide 16 (41.0%)  Cabazitaxel 3 (7.7%)  Lu-177 PSMA therapy 3 (7.7%) Lines of prior systemic therapies  1 18 (46.2%)  2 15 (38.5%)  ≥ 3 6 (15.4%) Mutation type  Somatic mutation 23 (59.0%)  Germline mutation 16 (41.0%) HRR genes  BRCA2 11 (28.2%)  ATM 9 (23.1%)  BRCA1 6 (15.4%)  CDK12 3 (7.7%)  RAD54L 3 (7.7%)  BRIP1 2 (5.1%)  PALB2 2 (5.1%)  RAD51D 2 (5.1%)  AKT1 1 (2.6%)  BARD1 1 (2.6%)

Correlation of adverse events (AEs) and clinical outcomes in first-line enfortumab vedotin–pembrolizumab (EVP) treatment for locally advanced or metastatic urothelial cancer (La/mUC).

717 Background: Neuropathy and rash are the most common AEs with EVP. Their association with clinical outcomes in standard-of-care settings remains unclear. We hypothesized that these AEs may be associated with improved survival. Methods: We reviewed our institutional database of patients with La/mUC treated with first-line EVP (March 2022–July 2025). AEs and grades were extracted from provider notes; missing grades were inferred per CTCAE v5. Kaplan–Meier and time-dependent Cox regression analyses were performed, modeling AEs as time-dependent variables to account for immortal-time bias and variable onset. OS was measured from EVP initiation to death or last follow-up. Results: Among 185 patients, 141 (76%) were male, and 95 (48%) had de novo metastatic disease. Urinary bladder primary and pure urothelial histology were seen in 129 (70%) and 123 (66%), respectively. Baseline details are listed in the Table. At a median follow up of 9.7 months (95%CI: 8.2-11.9), any grade of rash and neuropathy was reported in 71 (38%) and 51 (28%) patients, at median onset of 0.4 (IQR 0.2-0.9) months and 3.2 (IQR: 2.3-4.4) months respectively. Both were reported in 26 (14%) patients. Grade 3/4 rash and neuropathy were reported in 8 (4.3%) and 1 (0.5%) patient respectively. One Grade 5 rash was reported. All but one Grade ≥3 rash developed within 2 weeks of initiation. EV dose reduction occurred in 83 (45%), most commonly for neuropathy (25, 30.1%) and rash (17, 20.4%). Discontinuation of EV alone, P alone, and both drugs was seen in 30 (16%), 5 (2.7%), and 21 (11%), respectively. Median OS for the cohort was 36.5 months (17.5–not reached). OS was longer in patients with neuropathy vs no neuropathy (36.5 vs 17.6 months; HR 0.46, 95%CI 0.21–1.04; p = 0.06) and rash vs no rash (not reached vs 17.5 months; HR 0.34, 95%CI 0.17–0.68; p = 0.002). After adjusting for prior neuropathy (only for neuropathy analysis), liver metastases, ECOG, starting dose, and time on EV, neuropathy and rash were associated with OS HRs of 0.54 (95%CI 0.24–1.24; p = 0.14) and 0.42 (95%CI 0.20–0.86; p = 0.02), respectively. Conclusions: The prevalence and timing of neuropathy and rash observed in our cohort are consistent with major trials of EVP in La/mUC, underscoring the reproducibility of these safety findings. In first-line EVP-treated La/mUC, these hypothesis-generating findings suggest susceptibility to AEs may correlate with survival benefit. Alternative explanations include germline variation in payload metabolism. Limitations include small numbers, short follow-up, retrospective collection, and potential residual immortal-time bias despite modelling. n (%) (Total N=185) Baseline ECOG > 0 113 (61) Baseline neuropathy 38 (21) Liver Metastases 37 (20) Starting EV Dose- 1.25/1/0.75/0.5 mg/kg 145(78)/ 26(14)/ 13(7)/ 1(0.5) Median EV doses received 7 (IQR: 3-12)

Selective bladder preservation after neoadjuvant zanidatamab combined with tislelizumab and chemotherapy in patients with HER2-positive muscle-invasive bladder cancer (HARBOR): A multicenter study.

TPS887 Background: Muscle-invasive bladder cancer (MIBC) is a highly aggressive malignancy commonly treated with radical cystectomy, which carries significant risks of complications and quality-of-life decline. Bladder-sparing strategies represent an important treatment approach, with neoadjuvant therapy playing a pivotal role in tumor downstaging, improving clinical complete response (cCR), and enabling selective bladder preservation. However, patients with HER2-positive MIBC generally have inferior outcomes, making the development of targeted approaches a pressing priority. Preclinical and early clinical studies have demonstrated that HER2-directed antibodies exert antitumor activity in urothelial carcinoma. Zanidatamab, a novel bispecific HER2 antibody, provides dual epitope binding, enhanced effector function including unique antibody-dependent cellular cytotoxicity (ADCC), and has shown robust activity in HER2-positive solid tumors. Combined with the PD-1 inhibitor tislelizumab and platinum-based chemotherapy, it may enable superior bladder-sparing efficacy in patients with HER2-positive MIBC. Methods: The ongoing HARBOR trial is a multicenter, open-label, single-arm, phase II study designed to evaluate the efficacy and safety of a selective bladder-preservation strategy following neoadjuvant zanidatamab plus tislelizumab and gemcitabine-cisplatin (GC) in patients with HER2-positive (immunohistochemistry 2+ or 3+) MIBC (cT2-4aN0-1M0). Twenty-five patients will receive four cycles of zanidatamab (1800 mg for weight < 70 kg or 2400 mg for weight ≥70 kg, IV, d1) + tislelizumab (200 mg, IV, d1) + gemcitabine (1,000 mg/m², IV, d1, d8) + cisplatin (70 mg/m², IV, d2). Post-treatment clinical reassessment determines subsequent management: patients achieving cCR undergo bladder-sparing treatment with zanidatamab plus tislelizumab; those without cCR may receive radiotherapy or partial cystectomy followed by zanidatamab plus tislelizumab, or proceed to radical cystectomy with adjuvant tislelizumab. The primary endpoint is cCR rate after neoadjuvant therapy. Key secondary endpoints include 1- and 2-year bladder-intact disease-free survival (BI-DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), safety, and patient-reported quality of life (QoL). Registration number: ChiCTR2500110562.

A Paradigm Shift in Anode‐Free Lithium Metal Battery: Pressure‐Activated Solid‐State Interfaces for High‐Rate Desolvated Cation Diffusion

ABSTRACT Anode‐free lithium metal batteries (AF‐LMBs) promise ultrahigh gravimetric/volumetric energy densities (> 400 Wh kg − 1 /1000 Wh L − 1 ) and simplified anode manufacturing as compared to conventional alkali‐ion batteries that rely on intercalation chemistry. However, their practical implementation remains plagued by dendritic protrusion from the substrate and rapid lithium inventory depletion, which further exacerbate in Ah‐scale pouch cells. Here, this study innovates a paradigm shift through a multiscale interfacial strategy addressing the core limitations of AF‐LMBs. Scalable cation‐exchange and mechanical exfoliation firstly produce few‐layer lithium montmorillonite nanosheets that integrated with polyacrylamide gel, which are functionalized onto the polyethylene separator (FMT‐Li/PAM‐PE). The composite separator thus reconciles high mechanical strength (204.4 MPa), thermal stability (< 2.5% shrinkage at 180°C), anion screening capability (t + = 0.78), and pressure‐activated adhesion to the substrate (peel strength > 3.4 N m − 1 via hydrogen bonding). Upon the formation cycle at stack pressure of 0.5 MPa, more crucially, the composite separator intimately attaches onto the Cu substrate modified with the recycled spent graphite rich in lithiophilic defects (SGR‐Cu), establishing the solid‐state Li + diffusion pathway at the separator‐anode interface and mitigating solvated Li + interaction. As assembled with a densely‐packed LiNi 0.8 Co 0.1 Mn 0.1 O 2 (3.6 mAh cm −2 ) cathode, the 1.0 Ah pouch cell achieves 81.1% capacity retention over 200 cycles, gravimetric/volumetric energy densities of 453.3 Wh kg − 1 / 1183.2 Wh L −1 and extreme power output of 1045.0 W kg − 1 . Beyond insights into multiscale ion regulation, this interfacial strategy also unlocks viability across diverse cell configurations (e.g., LiFePO 4 /Ni92||Cu), enabling the high‐rate cation diffusion for the commercial AF‐LMB prototyping.

A Quasi‐Solid Ionic Liquid‐Polymer Hybrid Electrolyte for Shuttle‐Free and Dendrite‐Free Aqueous Zinc─Bromine Batteries

ABSTRACT Aqueous static zinc─bromine (Zn─Br) batteries hold promise for grid‐scale energy storage but still suffer from severe polybromide shuttling and poor Zn reversibility. Here, we develop a quasi‐solid ionic liquid‐polymer hybrid electrolyte by integrating a sulfonated polymer matrix with anchored 1‐butyl‐3‐methylimidazolium (BMI + ) cations. The fixed −SO 3 − groups construct highly Zn 2+ selective conduction channels, while BMI + forms strong electrostatic interactions with the polymer, generating immobilized ionic‐liquid domains that effectively capture polybromides. This hybrid design transforms BMI + from a soluble additive into a structural component of the quasi‐solid framework, thereby enabling simultaneous dendrite‐free Zn plating/stripping and shuttle suppression. With this multifunctional regulation, the Zn─Br batteries achieve a high initial capacity of 162.7 mAh g −1 , a discharge plateau of ∼1.78 V, and 25 000‐cycle durability at 20 C. Moreover, the pouch cell with high‐loading Br cathodes (∼14 mg KBr cm −2 ) retains 90.9% capacity after 1500 cycles. This work demonstrates that quasi‐solid ionic liquid‐polymer hybrid electrolytes can deliver shuttle‐free, long‐lasting Zn─Br batteries, pointing to a promising pathway for scalable and reliable aqueous energy storage.

Photodynamic activation of a KRAS RNA G-quadruplex–targeted photosensitizer induces ferroptosis in cisplatin-resistant non–small cell lung cancer

Opportunities for precision oncology: Real-world patterns and disparities in FGFR3 testing among US patients with advanced urothelial cancer.

682 Background: Activating fibroblast receptor growth factor-3 (FGFR3) genetic alterations occur in 15-20% of LA/mUC and biomarker directed therapy should be considered for patients with ≥1 prior lines of treatment. Genomic testing for FGFR3 at LA/mUC diagnosis is recommended; yet, real-world adherence to these recommendations and potential disparities in testing are poorly understood. Methods: The Flatiron Health Research Database (FHRD) was analyzed to identify adults diagnosed with LA/mUC between 1/2022 - 3/2025. FGFR3 testing was identified from structured genomic reports or physician documentation. Objectives included: 1) prevalence and timing of FGFR3 testing; 2) how often testing is repeated; and 3) clinical and demographic predictors of testing. Multivariable logistic regression (MLR) evaluated associations between testing and patient characteristics including age, gender, race, ECOG PS, and socioeconomic status; disease specific characteristics including primary tumor location, stage at initial diagnosis and maximum line of therapy (LOT) received; and practice type. Patients with FGFR3 alterations (excluding amplifications and variants of unknown significance) and 22 erdafitinib use were reported. Results: 3,661 patients with LA/mUC were identified. Overall, 41% (n=1495) of patients had ≥1 FGFR3 genomic test, among which 21% (n=319) had ≥2 tests. Of the 2,351 patients who received 1L, 28% (n=648) were tested prior to 1L with 75% (n=483/648) having results prior to initiating therapy. In MLR, significantly lower odds of testing were observed with increasing age (OR, 95% CI; 0.98, 0.98-0.99), Black race (0.66, 0.47-0.92), lower tract primary (0.60, 0.45-0.78), and initial diagnosis of non-metastatic disease (locally advanced [0.65, 0.54-0.78] or muscle invasive [0.67, 0.56-0.79]). Patients were less likely to be tested if treated in an academic setting (FHRD-defined). There was a greater likelihood of testing with each subsequent LOT (Table 1). Among tested patients with known results, 19% (n=274) had FGFR3 alterations. Among FGFR3+ patients with 2L+ (n=110), 46% received erdafitinib. Conclusions: FGFR3 testing in LA/mUC is often delayed or omitted with <50% of patients tested. Less than 30% were tested in the guideline-concordant window before 1L, and result availability was timely. Significant differences by age, race, disease stage, and primary site highlight gaps in precision oncology delivery for patients with LA/mUC. Interventions to promote timely and equitable testing are essential to expand access to targeted therapies and improve patient outcomes. Association between maximum LOT and FGFR3 testing. Maximum LOT  n  Odds Ratio (95% CI)  1L  1558  1.86 (1.57-2.21)*  2L  514  3.10 (2.48-3.89)*  3L  164  5.70 (3.93-8.36)*  4L+  115  7.49 (4.80-11.99)*  Referent group: No LOT (n=1310), *p-value<0.001.

National trends and predictors of inpatient palliative care utilization in metastatic prostate cancer.

71 Background: Men with metastatic prostate cancer (mPC) experience high symptom burden and often require intensive end-of-life care. Inpatient palliative care (IPC) utilization patterns, including the impact of epidural spinal cord compression (ESCC), are incompletely studied. Methods: We used the National Inpatient Sample database (2016–2022) to identify adult mPC hospitalizations with and without IPC using ICD-10 codes. We compared cohort demographics using t-tests and chi-square tests. We performed multivariate logistic models assessing predictors of IPC and mortality with IPC as the exposure, adjusting for age, race, primary payer, income quartile, hospital characteristics, and Elixhauser Comorbidity Index (ECI). We evaluated ESCC as a primary exposure for IPC use and mortality. p <0.05 was considered significant. Results: We identified 93,018 mPC hospitalizations; IPC occurred in 15,633 (16.8%). mPC admissions rose from 12,050 to 14,471 (APC 2.4%; p =0.019). IPC increased numerically from 1,812 to 2,742, without a significant APC. Versus non-IPC, IPC admissions more often involved age ≥60 (92.4% vs 91.4%; p <0.001), urban hospitals (93.6% vs 91.8%; p <0.001), teaching hospitals (76.4% vs 73.8%; p <0.001), higher comorbidity (ECI≥3: 89.2% vs 86.1%; p <0.001), longer LOS (7.33 vs 5.93 days; p <0.001), and higher unadjusted mortality (24.2% vs 3.3%; p <0.001). In adjusted models, higher IPC use was associated with age ≥60 (aOR 1.187; p <0.001), Black vs White race (aOR 1.09; p <0.001), and Medicaid, private insurance, and self-pay vs Medicare (all p <0.001); lower use occurred in the Midwest and West vs Northeast (aOR 0.87 each; p <0.001), rural vs urban hospitals (aOR 0.83; p <0.001), and non-teaching vs teaching hospitals (aOR 0.89; p <0.001). Larger hospitals had higher use (aOR 1.09; p <0.001). Higher comorbidity was associated with lower IPC (ECI Q3 aOR 0.91; p =0.0015; ECI Q4 aOR 0.92; p =0.009). ESCC independently predicted IPC use (aOR 1.17; p <0.001). In the mortality model, IPC was associated with higher in-hospital death (aOR 9.37; p <0.001). Additional mortality associations included age ≥60 (aOR 1.26; p <0.001), Asian/Pacific Islander race (aOR 1.30; p =0.002), private insurance (aOR 1.34; p <0.001), Midwest region (aOR 1.19; p <0.001), rural location (aOR 1.39; p <0.001), non-teaching hospitals (aOR 1.09; p =0.026) and higher ECI (Q3 aOR 1.24; Q4 aOR 1.55; both <0.001). ESCC was associated with lower inpatient mortality (aOR 0.71; p <0.001). Conclusions: IPC was used in ~1 in 6 mPC admissions, increased over time, and varied by age, race, payer, and hospital factors. ESCC was an independent predictor of IPC use, yet it was associated with lower in-hospital mortality. Geographic and institutional disparities may reflect differences in palliative care availability. The observed IPC use aligns with estimates of need among patients with advanced cancer.

Predicting the risk of prostate cancer metastasis at diagnosis in the VA Health Care System from H&E slides of the prostate needle biopsies.

128 Background: Men diagnosed with high-grade prostate cancer harbor increased rates of occult metastatic disease. We propose that features of the cancer in H&E stained tissue sections from prostate needle biopsies can be used to predict metastatic disease at diagnosis. Methods: We analyzed 168 high-risk cases from the Greater Los Angeles VA (GLA VA), equally divided into non-metastatic with at least five years of follow-up after diagnosis (M0) or synchronous metastatic cases (M1), and 38 cases with metachronous metastases (M0-P). From each case we analyzed all available images of H&E biopsies. Biases in the data were mitigated through supervised stratification and novel color augmentation strategies. Features were extracted from high-grade cancer tiles using 9 Foundation models. These embeddings served as input to a DTFT multiple instance learning (MIL) aggregator model that was trained de-novo to provide a metastatic risk (MR) score. The MR scores were combined with race, age and PSA clinical variables as a covariate in a linear regression or in a super learner to examine the contribution of each variable for the M1 prediction. Performance was assessed using 5-fold nested cross-validation. Results: The AUCs for prediction of metastasis at diagnosis ranged from 0.82 – 0.85. Addition of PSA and race further increased the AUC. A principle component analysis revealed explainable differences in the embeddings of M0 and M1 cases. Tiles used for M0/M1 discrimination by the aggregator model were further examined by analyzing the model’s attention on cancer and stroma regions. While the majority of the attention was in the cancer region in M0 cases, the attention in M1 cases was primarily in the stroma. Conclusions: We demonstrate that digital pathology slides from diagnostic prostate needle biopsies contain information for prostate cancer staging at diagnosis in a small, real-world cohort at VA. Using state-of-the-art Foundation models as feature extractors improves the accuracy of staging, in particular when the number of cases for training is small. Explainability of the feature embedding and classification tasks allows to examine what the models are learning and increases the confidence in the AI-generated results. Accuracy of metastasis prediction in VA cohort. Foundation model architecture MIL model MIL Model *AUC *Balanced Accuracy CONCH 80.86 ± 7.91 76.48 ± 5.77 HIBOU-B 85.82 ± 6.10 81.07 ± 6.20 MoCo v3 ResNetS0 80.36 ± 7.44 78.76 ± 5.81 Phikon 85.45 ± 5.70 80.59 ± 4.85 Phikon-v2 85.26 ± 6.25 80.83 ± 3.59 GigaPath (Prov-GigaPath) 85.17 ± 6.31 80.30 ± 4.21 UNI 86.03 ± 5.44 81.48 ± 4.33 UNl2-H 85.50 ± 7.45 82.02 ± 6.30 Virchow (1280d) 84.99 ± 6.51 83.12 ± 5.91 Virchow2 (1280d) 84.11 ± 6.87 78.64 ± 7.26 *Classification performance AUC and balanced accuracy (mean and std, %) using case-level bags on final tiles with a fixed feature setting and dino cls keep=4. Best result per column in bold.

Interfacial Modulation for Anti‐Disproportionation in Zr‐Nb‐Fe‐Ni Based Hydrogen Isotope Storage Alloys Driven by Product Destabilization Strategy

ABSTRACT Thermal/hydrogen‐induced disproportionation is one of the most fatal obstacles for practical Zr 2 Fe‐based hydrogen isotope storage alloys. Here, an interfacial transport inhibition effect at the disproportionation interface is revealed, in which theoretical screening from a product‐destabilization perspective identifies minor Nb substitution as an effective route to developing a disproportionation‐resistant Zr 1.9 Nb 0.1 Fe 0.7 Ni 0.3 alloy. This composition preserves an ultralow equilibrium hydrogen pressure and accelerated hydrogen absorption kinetics, while simultaneously delivering markedly enhanced resistance to disproportionation and outstanding cycling stability under harsh conditions. By integrating experimental results with thermodynamic and kinetic analyses, this work directs modification studies toward the viewpoint of interfacial transport kinetics for disproportionation. Combined density functional theory analyses and Ab initio molecular dynamics simulations systematically reveal that dispersed substitutional Nb atoms act as interfacial pinning centers at the hydride/disproportionation interfaces, effectively inhibiting detrimental interfacial phase transformation, closely related to weakened interfacial bonding strength, charge transfer, and orbital hybridization. Consequently, disproportionation‐related atomic rearrangement as well as the nucleation and growth of ZrH 2 are kinetically retarded. For the first time, these findings demonstrated that targeted interfacial kinetic engineering constitutes an effective strategy for suppressing disproportionation in Zr 2 Fe‐based hydrogen storage systems.

Single‐Site‐Directed Unidirectional Epitaxy of Large‐Scale 2D Materials

ABSTRACT Large‐scale synthesis of van der Waals (vdW) layered 2D materials remain a major challenge for their integration into high‐performance electronics and optoelectronics. Although the multi‐grain coalescence method provides a promising route to large‐area growth, its success critically depends on achieving uniform crystallographic orientation across all nucleated domains, a challenge that has not yet been fully resolved. Here, we present an effective strategy for realizing unidirectional epitaxial growth of 2D materials by controllably introducing single active sites on flat terraces. Using the heteroepitaxy of MoSe 2 on Au(111) as a model system, we combine molecular beam epitaxy with first‐principles calculations to validate this mechanism. We show that Se adsorption disrupts the intrinsic herringbone reconstruction of Au(111), releasing surface Au atoms that aggregate into stable dimers. These dimers act as symmetry‐breaking nucleation centers, guiding the unidirectional alignment of MoSe 2 domains. From the perspective of interfacial interactions, we further clarify how substrate surface activation enhances the epitaxial quality of 2D materials. This work establishes a scalable pathway toward large‐scale single‐crystal 2D films and provides a conceptual framework for advancing the epitaxial growth of 2D materials.

Electromotility can be disassociated from gating charge movement in outer hair cells of conditional alpha2 spectrin knockout mice