Browse Articles

A Novel Design Strategy for Benzo[ <i>b</i> ]Thiophene Substituted Multiple Resonance Type Blue Fluorescent Dopant With Maximized Efficiency and Super‐Narrow FWHM

ABSTRACT Conventional blue fluorescent emitters suffer from low efficiency and broad full width at half maximum (FWHM), limiting their application in next‐generation organic light‐emitting diodes (OLEDs). In this work, we report a novel double boron‐based multi‐resonance‐type blue fluorescent emitter, v ‐DABNA‐BT by incorporating a benzo[ b ]thiophene unit into the v ‐DABNA core to address the efficiency and color purity issues of the blue OLEDs. The v ‐DABNA‐BT exhibited deep blue emission with a photoluminescence peak at 466 nm and an exceptionally narrow FWHM of 13.9 nm. As a pure blue fluorescent emitter, it delivered a high external quantum efficiency of 10.8%, FWHM of 15.6 nm, and color coordinate of (0.115, 0.138). In addition, the v ‐DABNA‐BT‐based hyperfluorescent (HF) OLEDs achieved a maximum external quantum efficiency of 28.7% with a FWHM of 18.2 nm, one of the best performances reported among HF systems employing pure fluorescent terminal emitters. This result underscores the potential of benzo[ b ] thiophene‐modified boron‐based MR‐type fluorescent emitters as promising candidates for high‐efficiency, high‐color‐purity OLED applications.

REJOICE-PanTumor01: A phase 2 signal-seeking study of raludotatug deruxtecan (R-DXd) in patients with advanced or metastatic gynecologic or genitourinary tumors.

TPS574 Background: Cadherin-6 (CDH6), a transmembrane protein involved in cell–cell adhesion and epithelial–mesenchymal transition, is overexpressed in many cancer types. R-DXd is an anti-CDH6 antibody–drug conjugate composed of a humanized CDH6 antibody covalently linked to a potent topoisomerase I inhibitor payload (DXd) via a plasma-stable linker. In an ongoing Phase 1 study (NCT04707248), a subgroup of patients with heavily pretreated ovarian cancer (OC) who received R-DXd 4.8–6.4 mg/kg, had an objective response rate (ORR) of 48.6% (95% confidence interval [CI], 31.9–65.6); median duration of response (DOR) was 11.2 months (95% CI, 3.1–not estimable), and progression-free survival (PFS) was 8.1 months (95% CI, 5.3–not estimable), irrespective of CDH6 expression level (data cut-off: July 14, 2023). The safety profile of R-DXd was manageable. In total, 11.1% of patients discontinued R-DXd due to treatment-emergent adverse events. These promising data warranted further investigation of R-DXd in REJOICE-Ovarian01 (NCT06161025), a Phase 2/3 study in patients with platinum-resistant high-grade serous OC (HGSOC), and in the REJOICE-PanTumor01 Phase 2 study, which is described here. Methods: REJOICE-PanTumor01 (NCT06660654) is a global, open-label Phase 2 study in patients with locally advanced or metastatic gynecologic (endometrial cancer [EC], cervical cancer, or non-HGSOC) or genitourinary (urothelial cancer [UC] or clear cell renal cell carcinoma [ccRCC]) tumors. Cohorts are tumor type–specific; patients in all cohorts must have relapsed or progressive disease after receiving ≥1 prior line (and ≤3 prior lines in the EC, UC, and ccRCC cohorts only) of standard treatment. Adult patients with ECOG performance status 0–1 are eligible; there is no selection for tumor CDH6 expression. Approximately 40 patients will be enrolled into each cohort to receive R-DXd 5.6 mg/kg IV every 3 weeks until disease progression per RECIST 1.1, unacceptable toxicity, death, or other reason per protocol. In each cohort, a nonbinding futility interim analysis will be conducted after 20 patients complete a minimum of 12 weeks of follow-up, the results of which may determine whether the remaining (~20) patients will be treated. Primary endpoints are ORR for the gynecological and UC cohorts, disease control rate (DCR) for the ccRCC cohort (both investigator-assessed), and safety and tolerability for all cohorts. Secondary endpoints are ORR (ccRCC cohort only), DCR (except ccRCC cohort), PFS, DOR, time to response (all investigator-assessed per RECIST 1.1), pharmacokinetics, and immunogenicity. Clinical trial information: NCT04707248 .

Remodeling of the periprostatic adipose microenvironment in aggressive prostate cancer: Insights from a multi-institutional atlas-based geometric analysis.

389 Background: Periprostatic adipose tissue (PPAT) plays an increasingly recognized role in prostate cancer progression. Spatial and morphological features of the periprostatic fat envelope on biparametric prostate MRI (bpMRI) have been associated with tumor aggressiveness. However, prior studies have relied on manual measurements from regions of interest. This study employed voxel-wise analysis to characterize morphological differences in the PPAT between patients with and without clinically significant prostate cancer (csPCA). Methods: A total of 556 patients with bpMRI from four institutions were analyzed. Periprostatic fat (PPF) masks on T2-weighted images were manually generated for 245 patients by an expert radiologist (8 years of experience) and used to train an nnU-Net v2 model (validation DSC = 0.85); the remaining cases were automatically segmented. A template (A - ) was constructed from 100 T2w images with iterative affine and deformable registration. All subjects were rigidly registered to A - space with their PPF masks and signed distance functions were computed. Voxel-wise group differences were assessed using permutation testing with threshold-free cluster enhancement and family-wise error (FWE) correction. From significant regions, twelve shape descriptors were extracted and compared between groups using Mann–Whitney U tests. Results: The cohort included 415 patients with csPCA (Gleason score ≥7) and 141 with benign or indolent disease (Gleason Grade Group=1). Median PSA was 7.82 ng/mL (range: 0.5–107.8) and median age was 69 years (range: 48–93). Voxel-wise analysis identified 1,569 significant voxels (p &lt; 0.05, FWE-corrected), predominantly in the rectoprostatic region between the prostatic capsule and Denonvilliers' fascia. Three shape descriptors showed significant differences between groups. Patients with csPCA exhibited lower surface normal polar angle mean (0.683 vs. 0.787 rad, p = 0.007) and standard deviation (0.387 vs. 0.429 rad, p = 0.007), and lower mean curvature (0.0075 vs. 0.0094, p = 0.043). Conclusions: Patients with csPCA exhibited geometric differences in PPAT compared to those with benign or indolent prostate disease. Voxel-wise analysis identified these alterations in the adipose tissue between the prostatic capsule and Denonvilliers' fascia. These findings are consistent with studies indicating that PPAT is not merely a passive anatomical structure, but an active component of the tumor microenvironment. Significant radiomic shape descriptors of periprostatic fat. Feature What It Measures Benign/Indolent csPCA p-value θ mean Average tilt/orientation of fat surface around prostate 0.787 ± 0.428 0.683 ± 0.386 0.007 θ std Variability in fat surface orientation 0.429 ± 0.170 0.387 ± 0.162 0.007 κ mean Average curvature of fat boundary 0.009 ± 0.007 0.007 ± 0.007 0.043

Altered ciliary morphology reduces mechanosensation in a cystic kidney model as indicated by a mathematical model

Abstract This study investigates the biomechanical properties of primary cilia in healthy kidneys and an early-stage cystic kidney model (CKM), focusing on their role in flow-mediated mechanosensation. Morphological analysis showed that CKM cilia are longer, more curved, and exhibit disrupted axonemal integrity compared with normal cilia. To evaluate the effect of such structural changes on bending and stiffness, which may affect the drag force, shear stress and PC1/PC2 complex activation, we developed a mathematical model simulating urine-flow-induced drag. The model predicts that longer and curved cilia experience only one-fourth of the drag force of shorter and straight cilia under identical flow conditions. Remarkably, addition of 5% glucose to drinking water, which was reported to increase water intake, was predicted by the model to elevate urine flow to levels sufficient to partially normalize ciliary length and tubular morphology in CKM kidneys. These findings indicate that ciliary deformation impairs mechanosensation, contributing to cystogenesis, and that restoring mechanical stimulation may mitigate disease progression. Beyond estimating the urine volume required for therapeutic effect, the model offers a framework for developing interventions targeting ciliary mechanotransduction, which could be particularly useful when fluid-loading strategies are not feasible. This approach highlights the potential of combining morphological analysis, biophysical modeling, and mechanobiology to better understand and treat early cystic kidney disease.

Cardio-kidney-metabolic syndrome and prostate cancer: Prognostic significance of higher stages for cardiovascular morbidity and mortality.

358 Background: Patients with prostate cancer (PC) face a significant burden of cardiovascular disease (CVD). The newly established Cardio-kidney-metabolic syndrome (CKMS) integrates a multitude of comorbidities and risk factors that shape the pathophysiology of CVD. This study aims to evaluate the association between CKMS and cardiovascular (CV) outcomes and mortality in patients with PC. We hypothesized that higher stages of CKMS are associated with higher risk of CV events (CVE), CV mortality (CVm), PC specific mortality (PCsm) and all-cause mortality. Methods: In this retrospective study, we utilized the SEER-Medicare linkage to identify patients with localized or metastatic PC ≥ 65 years of age. The chronic conditions files were subsequently used to classify patients into three CKMS groups as follows: stages 0-1 (excess/dysfunctional adiposity and no CKMS risk factors), stages 2-3 (metabolic risk factors, chronic kidney disease (CKD), or subclinical CVD), and stage 4 (clinical CVD in CKMS). Multivariable Fine-Gray competing risk models were used to evaluate CVE, CVm, and PCsm. The CVE composite included myocardial infarction, heart failure, atrial fibrillation, ischemic stroke, and peripheral artery disease post cancer diagnosis. We assessed all-cause mortality using Cox proportional hazard models. All statistical models adjusted for age, race, marital status, education level, socioeconomic position, PC grade, PC stage, rurality, surgery, radiation, chemotherapy, and androgen deprivation therapy (ADT). Results: A total of 104,400 patients met our inclusion criteria, with CKMS stages 0-1 having 17,028, stages 2-3 having 35,353, and stage 4 having 52,019 patients. There was a significant increase in CVE incidence in patients with CKMS stages 2-3 when compared to stages 0-1 (sHR 1.38; 95%CI 1.32-1.43, p&lt;0.001), with a decrease in PCsm (0.92; 95% CI 0.85-0.99, p=0.035). Compared to CKMS stages 0-1, stage 4 showed a greater increase in CVE incidence (sHR 2.94; 95%CI 2.83-3.05, p&lt;0.001), with a significant increase in CVm (sHR 2.64; 95%CI 2.36-2.96, p&lt;0.001), and all-cause mortality (sHR 1.69; 95%CI 1.62-1.78, p&lt;0.001) (Table). Conclusions: Higher CKMS stages are associated with worse CV outcomes in patients with PC. These findings show the critical need for proper diagnosis and management of CKMS in PC patients. Fine-Gray competing risk and Cox proportional hazards regression for the various outcomes using the fully adjusted model. Stage CVE CVm PCsm All-cause mortality CKMS 0-1 Reference Reference Reference Reference CKMS 2-3 1.375 (1.322-1.430, p&lt;0.001) 1.051 (0.92-1.18, p=0.43) 0.920 (0.851-0.99, p=0.035) 1.00 (0.95-1.06, p=0.801) CKS 4 2.939 (2.832-3.051, p&lt;0.001) 2.64 (2.36-2.96, p&lt;0.001) 1.0 (0.933-1.08, p=0.91) 1.69 (1.617-1.783, p&lt;0.001) Overall Population, Competing Risk = (All-Cause Mortality), sHR (95% CI, p-value).

The actionable transcriptome: a framework for incorporating RNA sequencing into precision oncology

Hydrogel Thermostat Inspired by Photoprotective Foliage Using Latent and Radiative Heat Control (Adv. Mater. 17/2026)

Sheath‐Inspired Durable Semi‐Convertible Hydrogel Enabled Controllable Lubrication and Contractibility

ABSTRACT The dynamic lubrication of sheath surrounding the tendon is significant to the motion of limbs. The sheath‐inspired hydrogels for soft actuator and transplantable substitutes primarily focus on high toughness and intrinsic lubricating ability, it remains a significant challenge to design the hydrogels with secreting lubricants capability for continuous lubrication like sheath. In this work, a sheath‐inspired semi‐convertible hydrogel is designed by cooperating responsive supramolecular networks (gelatin and polydopamine particles) into covalent polymer network (polyvinyl alcohol/poly(N‐isopropylacrylamide)). The interpenetrating covalent networks provide the high mechanical strength of 1.73 MPa and reversible contracting capability. The non‐covalent disassembly of gelatin network under near‐infrared light irradiation endows photothermal‐responsive dynamic lubricating function, which could reach superlubricity level (coefficient of friction of 0.007) by introducing hydrophosphatidylcholine in the hydrogel. The synergy of well‐lubricating capability and mechanical property of the hydrogel endows excellent durable property, which presents well elasticity after 15 000 compression cycles; and extreme low wear even after 100 000 shearing cycles. The developed hydrogel in this work is further processed into smart lubrication platform and photothermal regulation switch, which can broaden the application of smart responsive and interfacial lubricating materials.

Plasma cell-free DNA methylation as a predictive biomarker for hormonal therapy response in advanced prostate cancer.

235 Background: Androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitors (ARPI) is standard for advanced prostate cancer (PCa), but progression is inevitable and early biomarkers are lacking. Cell-free DNA (cfDNA) methylation offers a potential minimally invasive approach to monitor tumor and systemic responses. Methods: We conducted a prospective study of 48 men with advanced PCa: 10 with castration-resistant (CRPC) and 38 with metastatic hormone-sensitive disease (mHSPC), all receiving ADT+ARPI. Plasma was collected at baseline and 3 mo (CRPC) or 7 mo (mHSPC). cfDNA was profiled by enzymatic methylation sequencing of 3.98M cytosine-phosphate-guanine motifs (CpGs). Kaplan-Meier and Cox regression tested associations of baseline PSA and CpG methylation with progression-free survival (PFS). Landmark analyses assessed change in CpG from baseline. Differentially methylated regions (DMRs) were identified using a fixed-effect model with gene and tissue-of-origin annotation. Results: Median age was 75 y (CRPC) and 67 y (mHSPC); 90% and 71% were white. Median PFS was 12.3 mo (95% CI, 5.3–NR) for CRPC and 48.4 mo (95% CI, 17.3–NR) for mHSPC. Global methylation shifts were greater in CRPC, suggesting more extensive epigenetic remodeling. At the CpG level, 33,958 differentially methylated CpGs (DMCs) were identified in CRPC vs 1,621 in mHSPC (max ∆β ≤0.8 vs ≤0.55); 15% and 12% reached p&lt;0.01. DMR analysis identified 450 regions in CRPC and 601 in mHSPC (p&lt;0.01), with only 29 genes overlapping, underscoring stage-specific programs. Pathway enrichment was largely driven by normal tissue cfDNA: CRPC showed cardiovascular-associated loci (HSPA12B hypomethylation), aligning with ARPI-related CV toxicity, while mHSPC showed neural loci (AOX1 hypomethylation), consistent with docetaxel neuropathy. Notably, 30–40% of DMRs localized to promoters and 30–50% to CpG islands, highlighting many changes occurring in regions critical for transcriptional regulation. Tissue-of-origin deconvolution confirmed negligible prostate cfDNA in CRPC, consistent with tumor apoptosis evasion. Immune-derived cfDNA showed the strongest changes (4,638 DMCTs in CRPC vs 474 in mHSPC, p&lt;0.01), reflecting immune activation under therapy. Normal tissue cfDNA also revealed systemic off-target effects, paralleling known ARPI- and docetaxel-related cardiovascular and neuropathic toxicities. Conclusions: cfDNA methylation profiling revealed stage- and tissue-specific epigenetic changes linked to PFS, integrating tumor, immune, and normal tissue signals. These data support cfDNA methylation as a minimally invasive biomarker to track therapeutic response and systemic toxicities in advanced PCa.

ARTEMIS-003: A phase 2 study of HS-20093 (GSK5764227) in patients with metastatic castration-resistant prostate cancer (mCRPC).

150 Background: B7 homolog 3 protein (B7-H3) is a promising therapeutic target in solid tumors including prostate cancer. This multicenter, open label, phase 2 study aimed to evaluate the efficacy and safety of HS-20093 (GSK5764227), a novel B7-H3 targeted antibody–drug conjugate (ADC) with topoisomerase 1 inhibitor payload, in patients (pts) with mCRPC (registration number: NCT06001255). Methods: Pts who had progressed after at least first-line standard therapy were enrolled and received HS-20093 8.0 mg/kg every 3 weeks intravenously. The primary endpoint was confirmed objective response rate (cORR) as assessed per RECIST 1.1 and PCWG3 criteria in pts with target lesion at baseline. Safety and other efficacy endpoints were analyzed in pts who received ≥1 dose of HS-20093. Results: As of July 20th, 2025, a total of 50 Chinese adult pts were enrolled and all received ≥1 dose of HS-20093. The median follow-up time was 8.7 (range: 0.1, 16.7) months. Median age was 68 (range: 49, 79) years old and 72.0% of the pts had ECOG PS 1. All pts had been pretreated with novel hormonal therapy and 72.0% had received prior taxane-based chemotherapy. The median number of prior therapies was 2 (range:1, 8). Of 33 pts with target lesion, the cORR was 33.3% (95% CI: 18.0, 51.8) and disease control rate was 87.9% (95% CI: 71.8, 96.6). The median duration of response was not reached. A total of 16 pts showed at least 50% decrease on prostate specific antigen (PSA 50 ), with a confirmed PSA 50 response rate of 32.0%. The median radiological progression free survival (rPFS) was not reached and the rate of rPFS at 9 months was 55.7% (95% CI: 34.3, 72.5). HS-20093 showed anti-tumor activity in both taxane-naïve and taxane-treated pts (Table 1). Treatment-related adverse events (TRAEs) were observed in 49 patients (98.0%), of which 54.0% were Grade ≥3 and 20.0% were serious adverse events. The most frequent TRAEs were hematologic toxicity and gastrointestinal toxicity, in line with previously reported safety profile. One Grade 2 interstitial lung disease event occurred. Conclusions: HS-20093 monotherapy showed encouraging anti-tumor activity and was generally well-tolerated with a manageable safety profile in pts with mCRPC. Clinical trial information: NCT06001255 . Efficacy. Population TotalN=50 Taxane-naïve in mCRPC settingN=22 Taxane-treated in mCRPC setting N=28 cORRn (%) (95% CI) N*=3311 (33.3) (18.0, 51.8) N*=134 (30.8) (9.1, 61.4) N*=207 (35.0) (15.4, 59.2) cPSA 50 n (%) (95% CI) 16 (32.0) (19.5, 46.7) 5 (22.7) (7.8, 45.4) 11 (39.3) (21.5, 59.4) 9-month rPFS rate% (95% CI) 55.7 (34.3, 72.5) 62.9 (26.4, 85.1) 50.3 (24.1, 71.7) *Patients had target lesion at baseline. c, confirmed; CI, confidence interval; PSA 50 , at least 50% decrease on prostate specific antigen; rPFS, radiological progression free survival.

Thiolutin extends replicative lifespan by rewiring yeast transcription and metabolism

Abstract Transcription is a major cellular energy sink tightly coupled to growth, metabolism, and aging. Thiolutin, a widely used RNA polymerase inhibitor in yeast, has unclear long-term effects on aging. We show that thiolutin oppositely affects replicative and chronological aging in Saccharomyces cerevisiae by remodeling transcription, metabolism, and proteostasis. Thiolutin extends replicative lifespan, increasing reproductive potential and prolonging the mitotic phase, despite slower growth and lower ATP. This longevity is linked to global transcriptional repression, including reduced ribosome biogenesis, translation, and mitochondrial oxidative phosphorylation, and dampening of TOR1-dependent growth programs. In parallel, thiolutin triggers a selective adaptive response with activation of RPN4-mediated proteasome remodeling and redox-responsive genes, without HOG1 induction. Conversely, thiolutin accelerates early chronological aging: post-mitotic survival drops alongside repression of reserve carbohydrate genes (GPH1, GSY2, TSL1), suggesting impaired adaptation when entering stationary phase. FT-Raman spectroscopy confirms coordinated depletion of RNA, proteins, lipids, and carbohydrates. Thus, thiolutin promotes a low-energy, stress-adaptive state that benefits budding yeast cells but compromises early survival of non-budding populations, underscoring transcription–energy coupling in aging trajectories.

Temporal and racial patterns in prostate cancer stage migration following USPSTF PSA screening policy changes: A SEER 2005–2022 analysis.

42 Background: The U.S. Preventive Services Task Force (USPSTF) revised its prostate-specific antigen (PSA) screening recommendations in 2012 (Grade D, advising against routine screening) and again in 2018 (Grade C, encouraging individualized decision-making for men aged 55–69). Earlier studies showed a rise in metastatic disease after 2012, but most stopped before 2018 and lacked racial detail. Using the latest SEER data through 2022, we evaluated how prostate cancer stage at diagnosis changed across screening eras and racial groups, capturing the effect of both guideline shifts. Methods: We identified men with malignant prostate cancer (ICD-O-3 C61.9) in the SEER 17 Registries (2000–2022, November 2024 submission). Screening eras were defined as pre-2012 (Grade A/B), post-2012 (Grade D), and post-2018 (Grade C). SEER Summary Stage 2000 was grouped as localized, regional, or distant. Race and ethnicity were classified as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), American Indian/Alaska Native (NHAIAN), Asian or Pacific Islander (NHAPI), and Hispanic. Stage distributions were compared across eras and races. Results: Among 997,000 cases, localized-stage disease declined from 70.9 % before 2012 to 66.8 % after 2012 and 64.2 % after 2018, while distant-stage disease rose from 5.5 % to 6.9 % to 8.6 %. The steepest drop in localized disease occurred among NHW men (from 73 % in 2006–2007 to 62 % in 2022). NHB men had persistently higher rates of distant disease (≈ 16 %) across all eras, with minimal change following the 2018 Grade C update. Hispanic and NHAPI men showed smaller but parallel shifts. The inflection point began soon after 2012 and only partially stabilized after 2018. Conclusions: Following the 2012 USPSTF Grade D recommendation, localized prostate cancer diagnoses declined while distant-stage presentations increased across all racial groups. The 2018 Grade C revision led to only partial stabilization, and disparities—particularly among Black men—persisted. These findings underscore the long-term influence of national screening policies and support more nuanced, risk-adapted approaches to PSA screening. Temporal changes in prostate cancer stage at diagnosis by race and screening era (SEER 2005–2022). Localized (%) Distant (%) Ethnicity Pre-2012 Post-2012 Post-2018 Pre-2012 Post-2012 Post-2018 Overall 70.9 66.8 64.2 5.5 6.9 8.6 NH White 70.9 66.8 64.2 6.5 7 7.6 NH Black 13.5 15.1 15.5 16.5 15.9 16 Hispanic 9.2 10.4 10.7 11.1 11.8 13.3 NHAPI 4.9 5.2 5.7 5.8 6.2 6.9 NH: non-hispanic; NHAPI: Non-Hispanic Asian or Pacific Islander.

Advances in the management of localized bladder cancers

Recent Progress in Contact Force Sensing Techniques for Cardiovascular Interventional Procedures (Adv. Mater. 17/2026)

Nanolaminate Ferroelectric Transistor Enabling Wide‐Reservoir In Sensor Neuromorphic Vision

ABSTRACT This work reports a hardware‐oriented hybrid reservoir computing (HRC) system based on a nanolaminate ferroelectric thin‐film transistor (FeTFT) that unifies volatile and nonvolatile functions in a single three‐terminal device. The HZO/HfO 2 /HZO gate stack modulates grain size and suppresses ferroelectric variability, enabling precise multilevel control and highly linear weight updates via the incremental step pulse with verify algorithm (ISPVA). Electrical input induces long‐term memory, while optical excitation yields short‐term memory, allowing dual‐mode operation. Light‐driven 4‐bit reservoirs operate at picoampere currents (∼10 pW/device) and emulate nociceptive neuron behavior. Combining three wavelength‐dependent reservoirs (405, 450, 532 nm) expands the feature space and improves classification accuracy. Using ISPVA‐linearized readout, the system achieves 93.1% and 85.1% accuracies on MNIST and Fashion‐MNIST, respectively exceeding prior FeTFT/memristor‐based RC systems. This approach establishes a scalable, energy‐efficient route toward multifunctional in‐sensor neuromorphic computing based on a unified ferroelectric platform.

Efficacy and safety of Lu-177-DGUL in a phase 2 study of patients with metastatic castration-resistant prostate cancer (mCRPC).

209 Background: Prostate-specific membrane antigen (PSMA) is an integral membrane protein highly specific to the prostate. The prevalence of PSMA expression is more than 90% in prostate cancers. Lutetium (177Lu) DGUL is a radiopharmaceutical developed for the treatment of prostate cancer patients. DGUL is a small molecule with high binding affinity to PSMA, and while it selectively binds to prostate cancer cells upon labeling with Lu-177 and emits β-rays to cause damage, it minimizes damage to normal cells. Methods: This was an open-label, single-arm, multi-center, phase 1/2 study (NCT05547061). Key eligibility criteria included patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed after treatment with an androgen receptor pathway inhibitor (ARPI) with or without docetaxel, had at least one PSMA-positive lesion on baseline imaging using Ga-68-NGUL, and an ECOG performance status of ≤ 2. Patients received Lu-177-DGUL intravenously every 6 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Key secondary endpoints were disease control rate (DCR), prostate-specific antigen (PSA) response, and the incidence of adverse events. Results: In the phase 2 study, 121 patients were screened, of whom 91 were enrolled and treated with Lu-177-DGUL. The confirmed objective response rate (ORR) was 35.9% (7 complete responses, 21 partial responses), and the disease control rate (DCR) was 60.3%. The proportions of patients with a confirmed decrease in the PSA level of at least 50% and 80% from baseline were 66.7% (52/78) and 39.7% (31/78), respectively. In a subgroup analysis, the ORR was 41.9% (13/31) in pre-taxane patients and 31.9% (15/47) in post-taxane patients. Regarding safety, the most common treatment-emergent adverse events (occurring in ≥10% of patients) were anaemia (31.9%), dry mouth (13.2%), decreased appetite (12.1%), and nausea (11.0%). Conclusions: Lu-177-DGUL demonstrated promising anti-tumor activity and a manageable safety profile in PSMA-positive mCRPC. The consistent anti-tumor activity observed across subgroups, including pre- and post-taxane, highlights its potential as a robust treatment for mCRPC. Clinical trial information: NCT05547061 .

Association between prostate cancer and mental health: A comparison across cancer types using the Medical Expenditure Panel Survey, 2017–2022.

132 Background: Mental health is a critical yet often underrecognized dimension of cancer survivorship, influencing quality of life, treatment adherence, and long-term outcomes. This study evaluated whether men with prostate cancer (PCa) experience better mental health outcomes than those with other major cancers or no cancer, using nationally representative data. Methods: We conducted a repeated cross-sectional study using Medical Expenditure Panel Survey Household Component data (2017–2022). Respondents were categorized into three groups: PCa, other malignancies, and no history of cancer. The primary outcome was fair/poor self-rated mental health. Secondary outcomes included major depressive symptoms (PHQ-2 ≥ 3) and serious psychological distress (K6 ≥ 13). Multivariable logistic regression was employed to estimate adjusted odds ratios (aORs) with 95% confidence intervals, controlling for sociodemographic and health-related covariates. Results: Among 31,706 respondents (mean age 62.2 ± 10.9 years), most were non-Hispanic White (60.5%). Overall, 5.3% had PCa, 5.1% other cancers, and 89.6% no cancer (Table 1). In the primary analysis, 41.0% reported less-than-good self-rated mental health: 42.1% among PCa survivors, 40.4% among those without cancer, and 47.2% among individuals with other malignancies (p &lt; 0.001). Compared with PCa, men without cancer had similar odds (aOR 0.96, 95% CI 0.85–1.09), while those with other cancers had higher odds (aOR 1.24, 95% CI 1.05–1.46), driven mainly by colorectal cancer (aOR 1.37, 95% CI 1.03–1.81). In secondary analyses, depressive symptoms (PHQ-2 ≥ 3) were reported by 7.3% of PCa survivors, 7.4% without cancer (aOR 0.98, 95% CI 0.76–1.27), and 8.6% with other cancers (aOR 1.21, 95% CI 0.87–1.68; p = 0.31). On the K6 scale, serious psychological distress was observed in 3.0% of PCa survivors and 3.7% of other groups (p = 0.47); colorectal cancer showed lower odds (aOR 0.12, 95% CI 0.02–0.86) and lymphoma higher (aOR 2.34, 95% CI 0.98–5.59). Conclusions: Mental health outcomes among PCa survivors were comparable to men without cancer and more favorable than in other malignancies. Nonetheless, over 40% reported suboptimal well-being, underscoring the need for integrated mental health screening and support across cancer populations. Mental health measures by cancer history. No history of cancer Prostate Non-prostate cancer Total Test N 28,405 (90.7) 1,690 (5.4) 1,611(5.1) 31,706(100.0) Overall Mental Health Status Below 'Good', n (%)  No 16,931(59.6) 978 (57.9) 850(52.8) 18,759(59.2) &lt;0.001  Yes 11,474(40.4) 712 (42.1) 761(47.2) 12,947(40.8) K6 Score 13 or higher, n (%)  No 20,564(96.3) 1,255 (97.0) 1,192(96.3) 23,011(96.4) 0.473  Yes 782(3.7) 39 (3.0) 46(3.7) 867(3.6) Having Depression Symptom, n (%)  No 20,004(92.6) 1,218 (92.7) 1,154(91.4) 22,376 (92.5) 0.308  Yes 1,599(7.4) 96 (7.3) 108(8.6) 1,803 (7.5)

The role of skin mechanics in contact force variation under different friction conditions

Abstract When grasping objects, humans actively adjust grip force in response to surface slipperiness and motion. Previous studies have showed that corrective actions occur after tactile afferents signal surface friction or slip events. However, the influence of the mechanical behavior of the skin on the development of contact forces is poorly understood. In this study, using contact kinematics derived from a natural reach-and-grasp task, we applied a glass surface onto restrained fingers via a robotic manipulator under low- and high-friction conditions. Contact forces were measured with a force sensor, and skin deformations were captured using a high-speed camera. As expected, the normal force remained unaffected by friction, however, interestingly the tangential force rose more slowly and peaked lower under low friction. This resulted in a higher normal-to-tangential force ratio, resembling friction-dependent scaling of grip-to-load force ratio observed in active grasping. The skin partially slipped throughout contact development, with the proportion of the slipped area first decreasing and then increasing. The time course of tangential force correlated with the extent of skin slip, both varying with friction. The findings demonstrate that skin mechanics potentially influences the grip stabilization during the initial phase of object handling, which doesn’t involve feedback-driven grip force adjustments.

Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma.

440 Background: To retrospectively evaluate the differential efficacy of immuno-oncology (IO)-IO and IO-tyrosine kinase inhibitor (TKI) combination therapies based on metastatic site in patients with metastatic renal cell carcinoma. Methods: This retrospective analysis used data from a multicenter study conducted by the JK-FOOT Study Group. A total of 579 patients with mRCC who treated with first-line combination immunotherapy between September 2018 and December 2024 were included in the study. Patients with metastases in the lymph nodes, lung, bone, liver, brain, and other distant sites were analyzed for progression-free survival (PFS) and overall survival (OS) according to metastatic site. Only patients with intermediate- or poor-risk disease, as defined by the International Metastatic RCC Database Consortium (IMDC) risk group, were included. The primary outcomes were PFS and OS, and the secondary outcome was objective response rate (ORR), with a comparison between the IO-IO and IO-TKI groups. Results: In patients with lymph node metastases (n = 38), lung metastases (n = 141), and brain metastases (n = 18), there were no significant differences in overall survival (OS) or progression-free survival (PFS) between the IO-IO and IO-TKI groups. In patients with bone metastases (n = 85), there was a trend toward improved OS in the IO-TKI group compared to the IO-IO group (P = 0.053), while in patients with liver metastases (n = 24), OS was significantly longer in the IO-TKI group (P = 0.011). Conclusions: For patients with metastatic renal cell carcinoma and bone or liver metastases, IO-TKI combination therapy is a more appropriate treatment option than IO-IO therapy.

Vebreltinib effective in MET-amplified NSCLC