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HSP-1-specific nanobodies alter chaperone function in vitro and in vivo

Metastatic lesion location and avidity on baseline PSMA PET/CT as predictor of duration of Lu177 treatment in men with metastatic castrate resistant prostate cancer.

188 Background: 177 Lu-PSMA-617 PSMA is a prostate-specific membrane antigen (PSMA) targeted radioligand therapy, which has been shown to improve progression-free survival in men with metastatic castrate-resistant prostate cancer (mCRPC). PSMA avidity on pretreatment PET/CT has been consistently linked to improved progression-free survival following treatment with Lu177, possibly translating to fewer required treatment cycles. In contrast, patients with low PSMA expression may need additional cycles to achieve therapeutic benefit or may require transition to alternative therapies due to inadequate response. This study seeks to clarify the predictive value of PSMA uptake on pretreatment PET/CT for determining treatment duration. Methods: We conducted a HIPAA-compliant, IRB-approved retrospective review of patients with mCRPC who received Lu-177 therapy between December 31, 2023, and February 29, 2024. Pretreatment PSMA PET scans were analyzed to identify sites of disease, and maximum and mean standardized uptake values (SUV) were measured for the most avid lesions in the viscera (liver and lung), lymph nodes, and bones using the SyngoVia VOI tool. Patients were stratified by treatment exposure (>3 vs. ≤3 Lu-177 cycles), and associations between SUV metrics and treatment duration were assessed using Fisher’s exact test. Results: 98 patients were included, with a median age of 73 years at Lu177 initiation. Disease distribution included lung (n=10), liver (n=16), lymph node (n=67), and bone (n=87). Due to limited sample sizes, analyses were restricted to lymph node and bone metastases. When PSMA uptake was analyzed by quartiles, mean SUV was not associated with the number of treatment cycles. However, a higher max SUV in bone and lymph node lesions correlated with a greater likelihood of patients completing more than three cycles (Table 1). Conclusions: Higher maximum SUV uptake in bone and lymph node metastases on pretreatment PSMA PET/CT was associated with a greater likelihood of prolonged treatment duration. These results suggest that tumors with high PSMA expression may derive increased benefit from extended Lu-177 therapy compared to tumors with low PSMA avidity. Lu177 treatment duration by PSMA avidity in lymph node and bone lesions. Number of Lu177 Cycles ≤3 >3 All p-value N % N % N % Lymph node SUV max  ≤14.22 13 25 4 8.7 17 17.35 0.0361  ≤33.17 9 17.31 7 15.22 16 16.33  ≤61.36 6 11.54 11 23.91 17 17.35  >61.36 5 9.62 11 23.91 16 16.33 Lymph node SUV mean  ≤20.0 9 17.31 7 15.22 16 16.33 0.0673  ≤37.8 6 11.54 10 21.74 16 16.33  ≤9.97 12 23.08 4 8.7 16 16.33  >37.85 5 9.62 11 23.91 16 16.33 Bone SUV Max  ≤20.49 13 25 8 17.39 21 21.43 0.047  ≤33.89 14 26.92 7 15.22 21 21.43  ≤64.8 13 25 9 19.57 22 22.45  >64.8 5 9.62 14 30.43 19 19.39 Bone SUV Mean  ≤12.29 13 25 8 17.39 21 21.43 0.1079  ≤19.33 13 25 7 15.22 20 20.41  ≤37.55 12 23.08 9 19.57 21 21.43  >37.55 6 11.54 14 30.43 20 20.41

National trends and disparities in bladder cancer mortality associated with tobacco use between 1999 and 2020.

656 Background: Bladder Cancer is one of the most serious types of cancer that can lead to death, especially when it’s combined with tobacco use. We aim to assess the trends in bladder cancer mortality associated with tobacco use in the U.S. Methods: Nationwide mortality records were obtained from the CDC-WONDER database from 1999–2020 among U.S. adults > 25 years with bladder cancer (ICD-10 code: C67) and tobacco use (ICD-10 code: F17). Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) were calculated per 100,000 population and stratified by demographic variables. Joinpoint regression analysis was used to determine average and annual percent change (AAPC and APC). Results: From 1999 to 2020, a total of 50,560 deaths were reported among individuals aged 25 years and older with bladder cancer and tobacco use in the U.S. The AAMR significantly increased from 0.1 in 1999 to 1.45 in 2020 (AAPC: 15.85; p< 0.000001). Gender-stratified analysis revealed that men had a higher overall AAMR (1.87) with an AAPC: 16.0; p < 0.000001 than women (0.36) with an AAPC: 14.54; p < 0.000001. Regionally, the highest overall AAMR was noticed in the Midwest (1.36), followed by the Northeast (1.16). Racially, the highest overall AAMR was noticed in NH White (1.22) (AAPC: 16.69; 95% CI: 13.14 to 20.35; p > 0.000001) while the overall AAMR in Hispanics was (0.34) (AAPC: 5.13; 95% CI: 2.17 to 8.18; p = 0.0006. The non-metropolitan areas had a higher overall AAMR (1.4) compared to the metropolitan areas (0.99). Conclusions: Trends in bladder cancer associated with tobacco use in adults increased from 1999 to 2020. Higher trends were observed in men, the Northeast, NH White, and non-metropolitan areas, emphasizing the need for targeted interventions and specific management plans. Data for bladder cancer and tobacco use-related mortality in U.S. adults between 1999 and 2020. Variable Deaths (n) AAMR (95% CI) Overall 50,560 1.06 (1.05-1.07) Hispanics 1,024 0.3 (0.28-0.32) NH Blacks 2,456 0.56 (0.53-0.58) NH Whites 46,470 1.22 (1.21-1.23) Metropolitan Areas 38,617 0.99 (0.98-1.0) Non-Metropolitan Areas 11,943 1.4 (1.38-1.43) Men 40,156 2.02 (2.0-2.05) Women 10,404 0.38 (0.37- 0.38)

A multimodal data framework for motorcyclist injury severity on rural undivided roads

Clinical outcomes of pembrolizumab and enfortumab vedotin in variant histology urothelial carcinoma.

754 Background: Enfortumab vedotin (EV) in combination with pembrolizumab is an FDA-approved regimen for patients with locally advanced or metastatic urothelial carcinoma. However, its clinical benefit in the setting of variant histology remains uncertain. Methods: The Indiana University bladder cancer database was queried for patients diagnosed with variant histology treated with EV plus pembrolizumab between 2023 and 2025. Demographics, treatment line, metastatic sites, and histological variants were collected. We sought to evaluate clinical outcomes in patients with urothelial carcinoma harboring variant histology who received EV and pembrolizumab. Outcomes were stratified by degree of variant histology: ≥50% versus < 50% variant component on pathology. Kaplan-Meier estimates were used to evaluate progression-free survival (PFS) and overall survival (OS). The log rank test was used to compare groups. Results: A total of 32 patients were identified. Median age was 72 (range 49-89). EV plus pembrolizumab were administered as first-line therapy in 18 patients, second-line in 9, third-line in 4, and fourth-line in 1. Sites of metastasis included lymph nodes (n = 19), bone (n = 9), lung (n = 4), liver (n = 4), and adrenal glands (n = 2). Variant percentages were available for 26 patients; 10 demonstrated ≥50% variant histology. Common variants included squamous differentiation (n = 19), micropapillary (n = 9), plasmacytoid (n = 3), sarcomatoid (n = 1), pure squamous n = 1), and dedifferentiated urothelial carcinoma (n = 1). Six patients exhibited multiple variant patterns. Median follow-up was 10.1 months (range 1.6-20.3). Patients with ≥50% variant histology had a median PFS of 3.9 months (95% CI, 1.0-5.4), whereas those with < 50% variant component achieved a median PFS of 8.2 months (95% CI, 4.2-19.6) (p = 0.0355). For the entire cohort, median PFS was 5.8 months (95% CI, 4.3-15.5), median OS was 20.1 months (9.9-Not evaluable). Conclusions: EV combined with pembrolizumab demonstrated clinical activity in patients with variant histology urothelial carcinoma. Outcomes appeared more favorable in patients with a lower proportion of variant differentiation, suggesting that variant burden may influence response to therapy.

Bioinspired Thermal Armor Enables Perovskite Meta‐Aerogels with Spectrally Tailored Luminescence up to 600 K

ABSTRACT High‐temperature flexible luminescent materials—enabling information transmission, safety monitoring, and operational reliability at extreme temperatures—have great potential for demanding applications such as metallurgy, petrochemical engineering, and fire protection. However, developing luminescent materials that integrate multicolor emission, high color purity, and mechanical flexibility at high temperatures remains an appealing yet formidable challenge. Herein, inspired by the multilevel architecture protecting pigments in the vividly colored butterfly's wing, we present a multiscale self‐confinement strategy to fabricate flexible perovskite luminescent nanofibrous meta‐aerogels with bioinspired thermal armor. Benefiting from multidimensional encapsulation to shield perovskite from extrinsic environmental perturbations and directional confinement to suppress ion migration and particle agglomeration, the biomimetic flexible meta‐aerogels achieve stable luminescence up to 600 K. The resulting meta‐aerogels exhibit tunable emission from blue to red and narrow‐band emission (full width at half maximum < 45 nm). Furthermore, the meta‐aerogels demonstrate excellent recovery after 500 compression cycles and temperature‐invariant superelasticity. These advancements highlight the significant potential of these materials for next‐generation flexible lighting and display applications under extreme conditions.

Dynamic Dipole Engineering Enables Ultrahigh Energy Storage with Minimal Losses

ABSTRACT Achieving high recoverable energy density ( W rec ) with near‐unity efficiency ( η ) in lead‐free dielectrics remains a major challenge for advanced pulse power capacitors, given their central role in emerging pulsed power systems and high‐voltage electronics. Here, we show that targeted engineering of dynamic dipole behavior provides an effective route to remarkable energy storage performance. Guided by phase‐field simulations, we design (Bi 0.5 Na 0.5 )TiO 3 (BNT)‐based multilayer ceramic capacitors that transform a continuous network of strongly correlated dipoles into discrete nano‐domains. Within each nano‐domain, dipoles retain strong local cooperativity, which maintains high polarization while markedly suppressing hysteresis losses. As a result, the optimized multilayer ceramic capacitors (MLCCs) achieve a recoverable energy density of 16.2 J cm −3 , an η of 98.5%, and a record‐high figure of merit ( W F ) of 1080 at 650 kV cm −1 . This moderate operating field also produces an ultrahigh energy storage strength ( ξ ) of 249 J kV −1 m −2 , highlighting the efficiency of the dipole‐regulation strategy. These findings demonstrate that weakly correlated and dynamic dipoles can be harnessed to advance high‐performance, lead‐free energy storage devices and offer a viable design principle for next‐generation capacitive technologies.

Unraveling the regioselectivity of Ophiostoma piceae sterol esterase as a case study for lipases with wide acyl-binding tunnel entrances

Head-to-head comparison of pembrolizumab-axitinib versus pembrolizumab-lenvatinib in metastatic RCC: Real world data from the Canadian Kidney Cancer Information System (CKCis) database.

460 Background: Immune checkpoint inhibitor-tyrosine kinase inhibitor (IO-TKI) combinations have transformed first-line treatment for metastatic renal cell carcinoma (mRCC). Pembrolizumab-axitinib (PA) and pembrolizumab-lenvatinib (PL) have each demonstrated efficacy in randomized trials, but real-world comparative data remain limited. Methods: We conducted a retrospective cohort study using the CKCis registry. Patients with confirmed mRCC who received first-line PA or PL were included. Primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and safety. Results: A total of 632 patients were identified (median age 66; 73.5% male), including 516 (81.6%) with clear cell and 116 (18.4%) with non-clear cell histology. Of these, 549 (86.9%) received PA and 83 (13.1%) received PL. Median follow-up was 28.9 months. Baseline characteristics were generally comparable between groups, although differences were observed in histology, performance status and the distribution of brain and lung metastases. At 12 months, the PFS rate was higher with PL compared with PA (75.9% vs. 57.1%); 5-year PFS was 36.2% vs. 25.9%, respectively (P < 0.01). 12-month OS was 93.9% for PL and 85.2% for PA; 5-year OS was 65.9% vs. 51.4% (P = 0.0172). For non-clear cell histology, 12-month OS was 91.6% for PL and 78% for PA (P = 0.0335). Among clear cell histology, 12-month OS was 94.9% for PL and 86.6% for PA (P = 0.0884). In the IMDC favourable-risk group, 12-month OS rate was 100% with PL and 95.2% with PA (P = 0.5994). For intermediate/poor IMDC risk, 12-month OS rate was 92% with PL and 82.3% with PA (P = 0.0145). Multivariable Cox analysis adjusting for age and IMDC risk showed that PA was associated with an increased risk of death compared with PL (HR = 2.15; 95% CI, 1.14-4.06; P = 0.019). IMDC risk was an independent predictor of OS, with patients in the intermediate/poor-risk group demonstrating a 94% higher hazard of death relative to those in the favourable-risk group (HR = 1.94; 95% CI, 1.32–2.87; P = 0.001). Dose reductions of the TKI occurred more frequent with PL (50%) than with PA (35.3%). Both regimens were associated with manageable but frequent toxicities. Fatigue, diarrhea, and anorexia were commonly observed with PA. PL showed a similar overall profile but a higher rate of Grade 3 proteinuria. No Grade 5 events occurred. Conclusions: In this real-world mRCC cohort, treatment with PL was associated with better PFS and OS compared to PA, but higher dose modification rates. These findings align with outcomes observed in pivotal trials and suggest that PL may offer a clinically meaningful benefit in routine practice. Prospective studies are needed to validate these results and to further explore the balance between efficacy and tolerability among first-line IO-TKI combinations.

Prostate cancer screening uptake and predictors of elevated prostate-specific antigen levels in Southwestern Nigeria.

403 Background: Prostate cancer is the most commonly diagnosed malignancy among men in Nigeria, yet uptake of prostate-specific antigen (PSA) testing remains low, contributing to late-stage diagnosis and poor outcomes. There is limited community-based data on screening uptake and factors influencing PSA levels among Nigerian men. This study aims to assess the uptake of PSA testing, identify factors influencing screening uptake, and evaluate risk factors associated with elevated PSA levels in a Nigerian community. Methods: We conducted a community-based cross-sectional study in Ilesa West, Osun State, Nigeria, among men aged 40 years and above. Participants completed a questionnaire, and blood samples were collected for PSA testing. PSA levels of ≥ 4.0 ng/mL were considered elevated. We used Chi-square tests and Pearson correlation for analysis. Results: Among 81 participants (55.30 ± 11.02 years), only 2.5% had ever undergone PSA testing, while 11.1% were aware of prostate cancer. Awareness of PSA testing was significantly associated with prior PSA testing (p<0.05). Findings also indicated that employment status (p=0.011) and marital status (p=0.033) were significantly associated with prior PSA testing. Elevated PSA levels (≥4 ng/mL) were observed in 21% of the participants. About just 17.3% had a past surgical history, 33.3% had lower urinary tract symptoms (LUTS), and 45.7% had at least a co-existing chronic disease. LUTS were significantly (p<0.05) associated with PSA levels. Furthermore, PSA levels showed a significant positive correlation with age (r=0.408, p<0.01). Conclusions: PSA testing uptake in this Nigerian community is alarmingly low despite a notable proportion of men having elevated PSA levels. Older age and LUTS were significant predictors of elevated PSA, highlighting opportunities for targeted screening. Interventions incorporating health education, integration of prostate cancer screening into primary care, and subsidized services are urgently needed to improve early detection and reduce prostate cancer mortality in Nigeria.

Adaptive lateral constraint-driven POCS interpolation method

Abstract The Projection onto Convex Sets (POCS) interpolation algorithm is widely adopted in seismic data processing, benefiting from its low computational complexity and strong data adaptability. However, the conventional POCS method fails to fully explore the inter-trace correlation information of seismic data, which leads to interpolation results with poor lateral continuity and high interpolation noise. To address this issue, this paper takes the traditional alternating projection framework for biconvex sets as the foundation, introduces a laterally constrained convex set, and thus effectively improves the interpolation quality of seismic data in terms of lateral continuity, signal-to-noise ratio (SNR) and interpolation accuracy. The specific research work is outlined as follows: First, the triple convex sets are defined in detail, the projection formula of the lateral constrained set is derived, and the triple convex set interpolation workflow is established. Second, the convergence of the new algorithm is theoretically proven, and its computational efficiency is compared and analyzed, which provides a reliable theoretical foundation for the stability of the algorithm. Finally, to verify the effectiveness of the proposed method, experiments are conducted on both synthetic seismic data and field seismic data, with a quantitative comparison of the interpolation accuracy between the two algorithms. The results demonstrate that the proposed algorithm significantly enhances interpolation accuracy while ensuring reconstruction efficiency, and therefore possesses excellent practical value.

Cyto-KIK: A phase II trial of cytoreductive surgery in kidney cancer plus immunotherapy (nivolumab) and targeted kinase inhibition (cabozantinib).

513 Background: Despite recent therapeutic advancements in metastatic clear cell renal cell carcinoma (mccRCC), only about 10% of patients will achieve a complete response (CR) to therapy. Cytoreductive nephrectomy (CN) removes a large portion of the tumor burden which may be a source of immunosuppression. Improved outcomes with neoadjuvant compared to adjuvant immune checkpoint inhibitors has been demonstrated in several tumor types including melanoma. In 2020, CheckMate9ER established cabozantinib (cabo) and nivolumab (nivo) as a first-line treatment regimen in mccRCC. We hypothesized that if tumor-specific immune responses to immunotherapy are greatest prior to nephrectomy, then treatment with cabo+nivo prior to CN will lead to maximal peripheral and intra-tumoral specific immune responses and higher rates of CR during treatment. Methods: This is an open label phase II, single arm, multicenter trial of combination cabo+nivo prior to and after CN in patients with mccRCC. 38 treatment-naïve subjects were enrolled with the primary endpoint of CR rate according to RECIST version 1.1. Subjects received cabo (40mg) daily and nivo (480mg) every 4 weeks for 12 weeks prior to nephrectomy and a 3+3 design was used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabo and nephrectomy. Post-operatively, subjects resumed treatment with cabo+nivo until evidence of disease progression. Secondary endpoints include median size reduction of the primary tumor, response rate, surgical outcomes using the Clavien-Dindo classification system, PFS and OS. Results: Between June 2020 and April 2025, 38 patients were enrolled. 71% of subjects were male and 29% were female with median age 64 years at time of enrollment. 74% of patients had IMDC intermediate-risk disease and 26% of patients had IMDC poor- risk disease. The first 5 subjects were enrolled in cohort 1 and the subsequent 33 subjects enrolled in cohort 2 with a 14-day interval of discontinuation between cabo and CN. All subjects received at least one dose of the study drugs, however, 6 subjects did not complete CN. Out of 35 subjects, 22% experienced a partial response and 77% had stable disease prior to nephrectomy. The ORR was 50% (3CRs, 13 PRs) for 32 subjects post-CN. 6/13 PRs had RECIST responses ≥95%. Median size reduction of the primary tumor was 19%. There were no path CRs reported but 5 subjects experienced near path CRs, > 90% tumor necrosis. There was one Grade IIIa Clavien-Dindo surgical complication related to the study. All subjects experienced a grade 1-2 AE and 11% of subjects experienced a grade 3 or higher AE. There were no new safety signals. Conclusions: This novel phase II trial of cabo+nivo prior to cytoreductive nephrectomy demonstrates safety and feasibility of CN in the current IO+TKI era. The complete response rate was 9% in this high risk de-novo metastatic population. Clinical trial information: NCT04322955 .

Microcrystalline‐Infused Peptide Hydrogel Enables Sustained Tacrolimus Delivery to Prolong Survival and Prevent Rejection in Kidney Transplantation

ABSTRACT Tacrolimus (TAC) is essential in post‐kidney transplantation immunosuppressive therapy but is hindered by its narrow therapeutic window and patient long‐term adherence challenges, leading to severe side effects in recipients. To address this, we developed an injectable self‐assembling peptide hydrogel that encapsulates TAC within a microcrystalline phase via a novel multiphase assembly strategy. This hydrogel enables sustained TAC release, maintaining therapeutic blood concentrations (5–15 ng/mL) for seven days post‐injection. In a vascularized composite allotransplant model, TAC‐loaded hydrogel preserves skin integrity on day 7 with vessel sutures, highlighting its potential for tissue preservation. In a life‐sustaining kidney transplantation model, rats receiving a single injection of TAC‐loaded hydrogel exhibited significantly improved survival (∼68 days) compared to the oral administration group (∼21 days). Histopathological and blood analysis confirmed minimal inflammation and intact tissue architecture in hydrogel‐treated grafts, alongside no systemic toxicity in major organs. These findings highlight multiphase assembly as a novel, effective strategy for controlled TAC release, offering a promising approach to improve patient outcomes in organ transplantation.

Dynamic Electron–Hole Shuttle at Atomic Interfaces for Solar‐Driven H ₂ O ₂ and Benzaldehyde Coproduction

ABSTRACT Harnessing solar energy to produce value‐added chemicals simultaneously requires the critical step of spatially separating redox processes. However, conventional photocatalysts remain fundamentally constrained by sluggish charge dynamics and irreversible recombination. Here, we propose an atomic‐level interfacial shuttle mechanism in sub‐nanometer gold cluster‐anchored nickel manganite (H‐NiMn 2 O 4‐β /Au 0.5 NCs), which couples dynamic electron–hole separation with Ni 3+ /Ni 2+ redox cycling. Ultrafast transient absorption spectroscopy indicates electron transfer occurring within 3.06 ps, mediated by an Au–O–Ni coordination interface. In this system, Ni 3+ functions as a transient electron trap, undergoing rapid reduction to Ni 2+ and subsequently transferring electrons to adjacent Au clusters, accelerating charge kinetics by 22.16‐fold. This atomic‐scale electron relay selectively steers 2e − oxygen reduction by balancing *OOH intermediate stabilization and desorption, yielding H 2 O 2 at 1.00 mmol g −1 h −1 . Simultaneously, hole accumulation on lattice oxygen drives α–H abstraction, enabling photooxidation of benzyl alcohol to benzaldehyde (14.59 mmol g −1 h −1 ). This work presents a dynamic dual‐site catalysis model, offering atomic‐level insight into interfacial charge management for solar‐driven redox transformations.

A conformation-dependent hydrophobic degron determines Rab9a-mediated vesicular trafficking

Representation of Latin American oncologists in oral sessions at the ASCO Genitourinary Cancers symposium: A five-year review (2021–2025).

44 Background: Latin American (LATAM) investigators contribute substantially to global genitourinary (GU) cancer research through participation in multinational studies. However, their representation as speakers in leading international forums remains uncertain. This study evaluated LATAM participation as oral presenters and as co-authors of abstracts presented in oral and rapid-oral sessions at the ASCO Genitourinary Cancers Symposium over a five-year period. Methods: A retrospective descriptive review was performed using the official programs of ASCO GU meetings held between 2021 and 2025. Session types analyzed included oral abstract, rapid-oral, and case-based discussions. Author affiliations were examined to identify LATAM representation. For each session, the total number of speakers, the number of LATAM-affiliated speakers, and LATAM co-authors of abstracts presented in oral or rapid-oral sessions were recorded. Results: Across 94 sessions (65 oral/rapid-oral and 29 case-based or educational), more than 500 invited speakers were identified. Only four LATAM speakers appeared during the study period (2025 n = 1; 2024 n = 2; 2023 n = 1; 2021–2022 n = 0). In contrast, 48 LATAM authors were listed among abstracts presented in oral or rapid-oral sessions, originating primarily from Brazil, Argentina, Chile, Mexico, and Colombia. Notably, only one of these appearances resulted from a direct invitation by conference scientific organization, whereas the remaining participations were linked to investigator roles within multinational clinical trials. Despite recurrent authorship in pivotal studies, such as those evaluating novel hormonal agents, immune checkpoint inhibitors, and targeted therapies, LATAM investigators seldom served as the designated presenters of their collaborative work. Conclusions: From 2021 to 2025, Latin American oncologists accounted for <0.5% of all ASCO GU speakers despite frequent authorship in major oral abstracts. The findings reveal a persistent gap between scientific contribution and visibility, emphasizing the importance of intentional strategies by international societies to promote equitable regional representation and recognition in global oncology.

Circulating tumor DNA kinetics as a biomarker of response to enfortumab-pembrolizumab in advanced urothelial carcinoma.

703 Background: The association of circulating tumor DNA (ctDNA) reduction with treatment response has been investigated across multiple malignancies. This study aims to assess the impact of ctDNA response on survival outcomes in patients receiving enfortumab-pembrolizumab (EV-P). Methods: We identified 32 patients with advanced urothelial carcinoma who received EV-P and had ≥2 ctDNA assessments with ≥1 detectable level. Deep molecular response was defined as >2-log reduction from highest ctDNA detection. Radiographic progression was determined from radiology reports documenting progression by RECIST criteria. Kaplan Meier analyses were performed to compute Hazard Ratios (HR) with 95% confidence intervals (CI) for radiographic progression free survival (rPFS), defined as time from treatment start to radiographic progression or death and overall survival (OS) defined as time from treatment start to death were computed. Log-rank tests were performed to compare PFS and OS in patients with deep molecular response to those without response. A p-value <0.05 indicated a statistically significant association with response. Results: Thirty-two patients were included (median age 71 years; range 39–90). Median follow-up was 10.6 months. At cutoff (10/1/2025), 26 patients were alive and 6 had died. Seventeen (53%) achieved a ≥2-log ctDNA reduction (responders), while 15 (47%) did not (non-responders). Progression-free survival was significantly longer in responders (log-rank P < 0.001); median PFS was 5.9 months (95% CI 2.4–NR) in non-responders and not reached in responders (HR 0.09, 95% CI 0.02–0.44; P = 0.0026). Median overall survival was 12.7 months (95% CI 10.0–NR) in non-responders versus not reached in responders (log-rank P = 0.011; HR 0.11, 95% CI 0.01–0.88; P = 0.037). At cutoff, 94% of responders and 67% of non-responders were alive. Conclusions: Achieving a >2-log decrease in ctDNA during EV + Pembrolizumab therapy was significantly associated with improved progression free and overall survival. These findings support ctDNA kinetics as a potential early biomarker of response warranting prospective validation. Clinical outcomes by >2-log ctDNA reduction status. Endpoint > 2-log drop (n = 17 ≤ 2-log drop (n = 15) Log-rank p Median (mo) ≤ 2-log > 2-log HR (95% CI) P C-index PFS 2 events (12%) 10 events (67%) 0.0002 5.9 (2.4–NA) NR 0.09 (0.02–0.44) 0.0026 0.77 OS 1 event (6%) 6 events (40%) 0.011 12.7 (10.0–NA) NR 0.11 (0.01–0.88) 0.037 0.73

PoseShot: hybrid CNN–BiLSTM transformer model for free throw action recognition via pose analysis

Abstract The evaluation of basketball free throw techniques has traditionally relied on subjective assessments, which introduces inherent biases and inconsistencies in performance analysis. This study presents PoseShot, a novel dual channel hybrid CNN-BiLSTM-Transformer Model that facilitates the comprehensive analysis of free throw mechanics with data-driven insights. Unlike conventional human activity recognition that focuses on coarse activity labels, PoseShot is designed to analyze fine-grained, phase-dependent mechanics within a single basketball free throw motion. The proposed framework integrates training footage with precise body posture angle calculations via a dual-channel deep learning architecture to enable the capture of subtle technical variations. Our innovative approach synthesizes convolutional neural networks (CNN) for spatial feature extraction, bidirectional long short-term memory (BiLSTM) for temporal sequence processing, and a transformer encoder for enhanced contextual understanding of motion dynamics. The model demonstrates exceptional performance, achieving an F 1 -score of 95.76%, precision of 95.72%, and recall of 95.80%. These metrics surpass the performance of established architectures, including DenseNet, Swin Transformer, and Vision Transformer, particularly for the analysis of complex throwing motions. By incorporating both spatial features and postural dynamics, PoseShot provides accuracy in motion analysis. Empirical evaluation reveals PoseShot’s capacity to identify crucial biomechanical determinants of successful free throws, thus offering quantifiable insights for performance enhancement. Since the model’s analysis elucidates the intricate relationship between posture optimization and action consistency, it can provide actionable guidance for athletes and coaches. This research bridges the gap between subjective evaluation methods and advanced motion analytics, establishing PoseShot as a transformative tool in sports performance analysis. The findings demonstrate the potential for data-driven approaches to revolutionize basketball training methodologies through precise, objective assessment criteria.

Safety and efficacy of pasritamig (PAS) + docetaxel (DOCE) in participants with metastatic castration-resistant prostate cancer (mcrPc): Initial results of a phase 1b study.

171 Background: DOCE is a standard of care for pts with mCPRC after androgen receptor pathway inhibitor (ARPI) failure, but more effective regimens are needed. PAS is a first-in-class, bispecific T-cell engaging antibody that binds to the CD3 receptor complex on T cells and to human kallikrein 2 (KLK2), which is highly and specifically expressed in prostate tissue and PC cells. PAS was well tolerated (Grade 1 cytokine release syndrome [CRS] <10%) with Q6W outpatient dosing and promising single-agent activity in a first-in-human phase 1 study in heavily pretreated mCRPC (Stein, J Clin Oncol 2025;43:2515-26). Methods: The primary objective of this open-label, Phase 1b study in mCRPC (NCT05818683) was to determine the recommended phase 2 regimen of PAS + DOCE based on safety. PAS was administered at RP2R (300 mg IV Q6W, with step-up doses of 3.5 mg on day 1 and 18 mg on day 8) in combination with DOCE (fixed dose 75 mg/m 2 IV Q3W starting on day 15) in an outpatient setting. Corticosteroids were not administered except as premedication for DOCE. Hematopoietic growth factor support was allowed. Results: As of 28 August 2025, 51 pts (median [range] age 70y [55–84], visceral metastases 33.0%) had received ≥1 dose of PAS + DOCE (median duration to date: combo, 3.5 months, PAS, 4.9 months); 31/51 pts remain on therapy (20 on combo, 11 on PAS only). Pts were heavily pretreated with a median of 3 (range 1–9) prior therapies, including ARPI (100%), DOCE (43.1%), cabazitaxel (21.6%), Lutetium-177 vipivotide tetraxetan (19.6%). PAS and DOCE were readily combinable at their full monotherapy doses with no observed dose-limiting toxicities. Treatment-related adverse events (TRAEs) were consistent with DOCE in mCRPC (Table); frequent (>20%) TRAEs included fatigue (58.8%), alopecia (41.2%), diarrhea and nausea (31.4% each), peripheral edema (25.5%), dysgeusia (21.6%). 58.8% of pts had PAS-related TRAEs. PAS TRAEs (>10%) included fatigue (29.4%) and diarrhea (11.8%). No pts had CRS of any grade. Grade ≥3 TRAEs occurred in 27.5% of pts, related serious AE in 13.7%, and TRAE leading to treatment discontinuation in 13.7% (PAS-related, n=1 each). There were no fatal TRAEs. Confirmed PSA50 was 64.7% (75.0% in taxane-naïve). Confirmed PSA90 was 35.3% (46.4% in taxane-naïve). Conclusions: PAS was readily combinable with DOCE, demonstrating a safety profile consistent with DOCE alone, no CRS, and promising anti-tumor activity in heavily pretreated patients post-ARPI/taxanes. A confirmatory phase 3 trial is planned. Clinical trial information: NCT05818683 . SAFETY Overall (N=51) PAS-related DOCE-related ≥1 TRAE, n (%) 50 (98.0) 30 (58.8) 49 (96.1) Grade ≥3 TRAE, n (%) 14 (27.5) 1 (2.0) 14 (27.5) TEAE leading to discontinuation, n (%) 7 (13.7) 1 (2.0) 7 (13.7) CRS, n (%) 0 0 0 EFFICACY Overall (N=51) Taxane-naïve pts (n=28) Confirmed PSA50, n (%) 33 (64.7) 21 (75.0) Confirmed PSA90, n (%) 18 (35.3) 13 (46.4)

Touch‐Driven Bi‐Chiral Superstructures for Nested Encryption of Multiplexed Optical Information (Adv. Mater. 13/2026)