Browse Articles

Identification and characterization of vasoactive intestinal peptide receptor antagonists with high-affinity and potent anti-leukemia activity

Nivolumab and ipilimumab maintenance therapy for advanced or metastatic urothelial carcinoma: Final results from SOGUG-VEXILLUM trial.

747 Background: The pioneering study was designed when platinum-based chemotherapy was the standard of care for advanced urothelial carcinoma and evaluated whether dual ICI (CTL4-PD1) could improve the benefit of maintenance therapy in this setting. Methods: This unique single-arm, multicentre study included patients with unresectable urothelial cancer that did not progress after first-line platinum-based CT (at least 4-6 cycles). The study treatment consisted of four cycles of ipilimumab (ipi) 3 mg/kg and nivo 1 mg/kg every 3 weeks (Q3W), followed by nivolumab (nivo) maintenance therapy (Q4W). The primary endpoint was progression-free survival (PFS) from the start of maintenance therapy in the overall and PD-L1 positive populations. Sample size was estimated using a Simon II stage design for the 4-months PFS rate (H0= 40%; H1= 60%; α = 0.05; β = 90%), requiring 25 patients in the 1st stage and up to 66 in total. Here, we report the final results of the study, which met the criteria to proceed to the second stage but was prematurely closed following the emergence of a new standard of care (enfortumab vedotin + pembrolizumab) in this setting. Results: From Sep 2022 to Apr 2024, 25 patients were included and received nivolumab and ipilimumab maintenance after first-line CT with gemcitabine combined with cisplatin in 14 patients (56%) or carboplatin in 11 (44%). The median age was 64 years (range: 53-79) and most were male (80%). At data cutoff, the median follow-up was 24 months (95% CI: 7-25.3), the 1- and 2-year PFS rates were 36% (95% CI: 21.4-60.7) and 28% (95% CI: 14.9-52.5), respectively, and the median PFS was 5.6 months (95% CI: 3.2-not reached [NR]). The median OS was 27.4 months (95% CI: 10.1-NR), with 64% (95% CI: 47.7-85.9) and 60% (95% CI: 43.6-82.6) patients alive at 1- and 2-years from the start of nivo/ipi, respectively. Five patients (20%) completed the scheduled 2 years of treatment. Nivo and ipi were permanently discontinued due to toxicity in 4 patients (16%). Grade ≥3 toxicities were observed in 10 patients (40%), with the most common being elevated ALT/AST (12%), immune-mediated hepatitis (8%), and diarrhea (8%). Conclusions: Despite the limited sample size, dual ICI maintenance with nivo plus ipi achieved durable disease control, with 60% of patients alive at 2 years, numerically exceeding historical outcomes from PD-1/PD-L1 monotherapy. The signal supports further exploration of dual ICI as a potential maintenance strategy in this disease. Comprehensive spatial transcriptomics and microbiome analyses are ongoing and will be presented. Clinical trial information: NCT05219435 .

Opening the black box: Biologic pathways underlying multimodal digital-pathology artificial intelligence in metastatic prostate cancer.

232 Background: Prostate cancer (PCa) spans indolent localized to lethal metastatic castration-resistant disease, underscoring the need for biologically grounded risk tools. ArteraAI multimodal artificial intelligence (MMAI), one of only two NCCN guideline–supported biomarkers for localized PCa and backed by Simon Level 1B evidence, has been validated as a prognostic marker across the spectrum of PCa. As an unsupervised AI model, MMAI remains non–human-interpretable limiting clinical trust as it is unknown what the AI is detecting. We therefore aimed to “open the black box”. For this unsupervised AI tool, “does biology matter?” If so, which pathways are important as mediators of metastatic progression that may be leveraged for novel therapeutic strategies. Methods: MMAI scores among patients with oligometastatic Pca were computed from digitized H&E images. A self-supervised model produced a 128- image-feature vector, which was used as input with clinical features (age, PSA, T stage) for MMAI scoring. Using the same prostate tissue, DNA panel and whole transcriptome sequencing (Tempus xT + xR) was performed. Pathogenic genomic alterations, differential gene expression, and gene set enrichment were analyzed across the MMAI spectrum. For select representative cases, AI attention heatmaps localized slide regions driving the MMAI score and were co-registered with spatial transcriptomic (ST) maps (10x Genomics Visium) to align heatmap foci with spatial gene-expression. Results: 181, 107, and 6 patients were included in DNA, RNA, and ST analyses, respectively. MMAI was positively correlated with MYC copy number gain. Association of transcriptomic profiles with increasing MMAI scores identified differential expression of ~1,000 genes. Higher MMAI was enriched for transcriptional signatures of tumor aggression related to ECM receptor interaction, EMT, E2F target, cell cycle, and DNA repair. MMAI score was positively associated with Hallmark gene sets including MYC targets, EMT, angiogenesis, and TGF-beta signaling. TME analysis highlighted positive association between the MMAI score and fibroblasts and a negative association with T and NK cells. ST assessment demonstrated higher proportions of fibroblasts and proliferative luminal epithelial cells with enrichment of transcriptional signatures related to DNA repair, MYC targets, oxidative phosphorylation, Wnt signaling, and interferon alpha/gamma signaling which corresponded to regions of high AI attention. Conclusions: MMAI aligns with core biologic drivers of omCSPC (cell-cycle, DNA-repair, MYC, EMT), providing the first evidence that this clinically-validated “black-box” AI is reading real tumor biology rather than spurious signals. Mapping these features improves interpretability, enhances clinical trust and suggests translational opportunities for novel therapeutic strategies.

Comparative evaluation and validation of rapid quantification methods for Mycoplasma hyopneumoniae: development of a PMA-based viability qPCR assay

Early monitoring of derived neutrophil-to-lymphocyte ratio (dNLR) as a predictive biomarker of benefit to immune checkpoint inhibitors (ICI) in advanced clear cell renal cell carcinoma (ccRCC).

562 Background: Baseline high derived neutrophil-to-lymphocyte ratio (dNLR>3) has been associated with poor outcomes to ICIs in several tumor types, including RCC. However, the clinical value of early and dynamic dNLR changes during treatment remains unclear. In the era of ICI–ICI and TKI–ICI combinations, exploring early dNLR as an accessible biomarker of benefit is clinically relevant. Methods: Patients with advanced ccRCC treated with ICIs between March 2023 and June 2025 were retrospectively analyzed, dNLR was calculated as neutrophils/(leukocytes−neutrophils), and evaluated at four timepoints: pre-baseline (≥1 month before C1), baseline (prior C1), preC2 (prior C2), and postC4 (after C4);a cutoff of dNLR >3 was used to define high-dNLR for all analyses, while in Cohort B (pretreated population) an additional cutoff of dNLR >2 was explored to define high-dNLR; progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: A total of 56 patients with advanced ccRCC were included. Cohort A comprised 25 patients treated with first-line ipilimumab plus nivolumab (I+N) (56% male; median age 67 years), ECOG PS ≥1 70%, and IMDC risk was intermediate in 56% and poor in 44%. Median follow-up was 13.3 months, with median PFS and OS of 6.6 months (95% CI, 4.1–19.6) and 13.3 months (95% CI, 4.8–21.2), respectively. High-dNLR at pre-baseline was seen in 8 patients, 25% of whom discontinued I+N due to early progression. High-dNLR at pre-baseline showed a trend toward poorer OS (HR 1.53, p=0.57), and at baseline toward shorter PFS and OS (HR 3.08, p=0.08; HR 2.3, p=0.24). PreC2 high-dNLR predicted worse OS (HR 4.83, p=0.026). Regarding dynamics, 5/8 pre-baseline high-dNLR remained high and 3 became low, while of 15 pre-baseline low, 2 became high. Between baseline and preC2, 7 patients were high; 3 changed to low and 1 died. Of 20 baseline low, 16 remained low and 3 became high. Two patients with high-dNLR at C4 developed grade 3 immune toxicity. Cohort B included 29 patients treated with nivolumab beyond first line (62% second-line, 34.5% third-line). Sixty-two percent were male, ECOG PS≥1 66%, and IMDC risk good/intermediate/poor in 31%/59%/7%.Median follow-up was 12 months, with median PFS and OS of 3.9 months (95% CI, 2.3–9.7) and 11.3 months (95% CI, 9.1–15.8), respectively. Only 3 patients showed high-dNLR at pre-baseline, all on prior-line treatment. With a lower cutoff (dNLR >2), 10 patients (34%) were high. PreC2 high-dNLR was linked to shorter PFS and OS (HR 7.33 and 2.50; p<0.005 and 0.12). Conclusions: Monitoring early changes in dNLR may provide insight into primary resistance to immunotherapy and early progression, supporting timely clinical intervention in selected patients.

Ultrafast Programming of Large Curvature Based on Selenium‐Sulfur Dynamic Metathesis

ABSTRACT The construction and integration of curvature govern the structure and function of materials based on 2D sheets, yet achieving ultrafast and scalable curvature programming remains a major challenge. We rapidly generate large stress mismatches by combining an ultrafast stress‐relaxing diselenide‐containing polyurethane with an ultraslow stress‐relaxing disulfide‐containing polyurethane. Coupled with modular components and compression, this mismatch enables localized, directional loading of high stress with excellent scalability. Using this strategy, 2D polymer sheets achieve 180° bending within 10 s of UV irradiation, yielding a curvature‐programming rate 15‐fold faster than state‐of‐the‐art methods. Furthermore, origami modules, which display a 37‐fold enhancement in compressive performance, can be obtained through mass production and assembled into complex 3D architectures. This rapid, high‐curvature programming approach offers efficiency, mechanical robustness, and scalability, advancing the practical deployment of origami‐based metamaterials.

JBC reviews tribute to the memory of Dr William (Bill) Smith (1945–2024)

Investigation of the PORTOS gene expression signature and the benefit of docetaxel in the ECOG-ACRIN E3805 CHAARTED randomized trial.

212 Background: The CHAARTED trial randomized men with metastatic hormone-sensitive prostate cancer (mHSPC) to either Androgen Deprivation Therapy (ADT) alone or with docetaxel. The trial showed an overall survival benefit, more so in patients with high-volume disease. We have previously developed a prostate cancer radiation response signature (PORTOS) which has been validated in multiple randomized trials. Given the similarities in DNA damage, we hypothesized that PORTOS might predict the benefit of docetaxel in CHAARTED. Methods: FFPE tumor samples from the trial were profiled using the commercial Decipher gene expression platform (N=160), and PORTOS was calculated as previously described, and was dichotomized into high/low based on the median, as scores exhibited a bi-modal distribution. Results: There were no significant associations with clinicopathologic variables (age, performance status, tumor volume, PSA, etc.). In patients with high PORTOS, there was a significant benefit for the addition of docetaxel for clinical progression (CP), castration resistance (CR), and overall survival (OS), which were not significant in the low PORTOS patients. The univariable interaction between PORTOS (as a continuous variable) and treatment arm was statistically significant for CP and trended towards significance for CR and OS. When accounting for clinicopathologic variables on a multivariable analysis, the interaction P-values were similar. The predictive effect of PORTOS was present only in the high-volume patients (N=125), where high PORTOS had a significant benefit for the addition of docetaxel for CP, CR, and OS. Conclusions: These results suggest that PORTOS could be used to identify which patients benefit from docetaxel added to ADT in mHSPC, and provides additional information even in high-volume patients. In the era of ADT + ARPIs for mHSPC, studies of PORTOS in cohorts with ADT + ARPI ± docetaxel will be critical in fully evaluating its clinical potential. Patients: All High Volume All PORTOS: High Low High Low PORTOS:Arm Interaction sHR P sHR P sHR P sHR P UVA P MVA P Clinical Progression 0.31 <0.001 0.61 0.11 0.31 <0.001 0.69 0.25 0.04 0.04 Castration Resistance 0.36 <0.001 0.61 0.07 0.36 <0.001 0.59 0.07 0.06 0.06 Overall Survival 0.58 0.05 0.66 0.2 0.50 0.03 0.61 0.14 0.07 0.14

Circulating tumor DNA (ctDNA) analysis in participants (pts) with advanced clear cell renal cell carcinoma (ccRCC) treated with first-line pembrolizumab (pembro) monotherapy from the phase 2 KEYNOTE-427 study.

541 Background: First-line pembro showed durable antitumor activity in pts with advanced ccRCC (cohort A) and non-ccRCC (cohort B) in the phase 2 KEYNOTE-427 study. We present an exploratory analysis of the association of ctDNA status with clinical outcomes from cohort A of KEYNOTE-427. Methods: Pts with advanced ccRCC and no prior systemic therapy received pembro 200 mg IV Q3W for ≤2 years. Whole exome sequencing (WES) of tumor tissue and plasma ctDNA were evaluated using Natera’s Signatera RUO 16-plex personalized ctDNA assay. Plasma samples with ≥2 variants (of 16 tested tumor-specific variants) detected above Signatera calling threshold were considered ctDNA positive. Continuous metrics of ctDNA burden (maximum somatic allele frequency [MSAF]) were explored. Primary objectives were to descriptively evaluate the association of baseline ctDNA status and ctDNA status change from baseline to cycle 2 day 1 (C2D1) with clinical outcomes (ORR, PFS, and OS). Secondary objectives included the association of MSAF and clinical outcomes and the association between ctDNA change at C2D1 with change in tumor size. No hypothesis testing was performed. Results: Of 110 pts with ccRCC, 72 had tumor tissue and plasma samples available for ctDNA testing; 58 had evaluable baseline ctDNA data, of whom 56 also had evaluable postbaseline ctDNA data. ctDNA was detected (ctDNA positive) at baseline in 39 pts (67%). At baseline, MSAF was not associated with ORR or change in tumor size (Spearman correlation -0.023). Pts with ctDNA positive status at baseline had shorter OS than those with negative status at baseline (median 30.5 mo [95% CI, 18.1-56.4] vs 53.7 mo [95% CI, 28.7-not reached (NR)]). ORR (28% vs 26%) and PFS (median 4.1 mo [95% CI, 2.7-12.6] vs 8.3 mo [95% CI, 6.9-NR]) were similar between pts with or without detectable ctDNA at baseline. ORR was higher in pts whose ctDNA status changed from positive at baseline to negative (pos-neg) at C2D1 (4/6; 67%) compared with pts who remained positive (pos-pos; 7/32; 22%), remained negative (neg-neg; 4/14; 29%), or changed from negative to positive (neg-pos; 1/4; 25%). Compared with the pos-pos group, pts in the pos-neg group had longer PFS (median 13.9 mo [95% CI, 12.4-NR] vs 2.8 mo [95% CI, 2.7-9.7]) and OS (median NR [95% CI, 28.2 mo-NR] vs 25.2 mo [95% CI, 14.2-40.7]). Larger C2D1 decrease in ctDNA burden relative to baseline was associated with improved ORR (AUC, 0.72 [95% CI, 0.52-0.92]). Conclusions: In pts with advanced ccRCC treated with pembro, ctDNA positivity at baseline may be associated with shorter OS and change from positive ctDNA status at baseline to negative during treatment may be associated with better ORR, PFS, and OS. Larger decreases in ctDNA burden at C2D1 were also associated with improved ORR. ctDNA as a treatment biomarker should be investigated in larger cohorts. Clinical trial information: NCT02853344 .

Multi-stream deep learning framework integrating images and feature representations to predict mild cognitive impairment using the rey complex figure test

Population-level trends in radiation treatment of low-risk prostate cancer.

336 Background: Reducing overtreatment of localized prostate cancer remains a public health goal, particularly for patients with low-risk disease who are candidates for active surveillance. We evaluated population-level trends in disease risk among patients treated with radiation therapy for localized prostate cancer over the past fifteen years. Methods: Men with localized prostate cancer (N0M0) treated with external beam radiation or brachytherapy were identified from three distinct cohorts: the Surveillance, Epidemiology, and End Results (SEER) U.S. population registry (2010–2022, n=156,149); the Veterans Affairs (VA) integrated national health system (2010–2024, n=34,635); and the Michigan Radiation Oncology Quality Consortium (MROQC) statewide quality collaborative (2021–2025, n=2,348). The primary outcome was the proportion of radiation-treated patients classified as low-risk per guidelines (T1-2a, Grade Group 1, PSA <10 ng/mL) compared to those treated with intermediate- or high-risk disease. Patients receiving radiation more than one year after diagnosis were excluded to account for disease progression on active surveillance. Logistic regression adjusted for baseline covariates. Secondary analyses compared proportions across cohorts in overlapping years (2021–2022) using pairwise two-proportion z-tests. Results: The proportion of radiation-treated patients with low-risk disease declined from 33.7% to 7.6% (2010-2022) in SEER and from 22.9% to 2.0% (2010-2024) in the VA. Rates remained low in MROQC (2.8% to 4.2%, 2021-2025). In all cohorts, older age was associated with lower rates of radiation for low-risk disease (adjusted odds ratios [AOR] per 5 years: 0.70, 0.70, and 0.77; 95% CI: 0.70-0.71, 0.68-0.72, and 0.68-0.89, all p<0.001, in SEER, VA, MROQC respectively). Declines over time were statistically significant in SEER and the VA (AOR per 5 years: 0.46 and 0.44; 95% CI: 0.45-0.47 and 0.41-0.46, both p<0.001). In 2021 and 2022, the proportion of low-risk cases was lower in the VA and MROQC than in SEER (both p<0.01). Conclusions: Among men receiving radiation for localized prostate cancer, the proportion with low-risk disease has declined by more than 75% since 2010. Across all three cohorts (SEER, VA, MROQC), only 2-8% of patients treated with contemporary radiation therapy had low risk disease. This pattern parallels surgical trends and reflects improved diagnostic pathways and broader adoption of active surveillance for low-risk disease.

Engineering Heteroatomic Nanotraps in Vinyl‐Benzazole COFs: Record Capacity and 99% Selectivity for Photocatalytic Gold Recovery From E‐Waste

ABSTRACT The recovery of gold from electronic waste is a critical environmental and technological challenge for a circular and sustainable economy. Conventional methods for gold recovery often suffer from low efficiency, poor selectivity, and reliance on harsh chemicals. In this work, we engineered three vinyl‐azole‐bridged covalent organic frameworks (COFs), systematically controlling heteroatom motifs to elucidate the structure‐activity relationships behind gold ion adsorption and photocatalytic reduction. This strategic incorporation of azole‐based units yielded hydrogen‐bonded nanotraps along the pore walls, thereby maximizing active‐site density and enhancing electrostatic interactions for the selective capture of gold ions. We found that all these COFs show gold adsorption capacities exceeding 3600 mg g − 1 , with the thiazole‐containing COF—featuring both nitrogen and sulfur—exhibiting the highest binding affinity and photocatalytic efficiency to a record value of 4658.1 mg g − 1 under optimal conditions and a 99.2% efficiency for gold extraction. These results are confirmed by density functional theory (DFT) calculations, x‐ray photoelectron spectroscopy, and real e‐waste recovery experiments. The highly conjugated framework facilitates synergistic photoreduction of Au(III) to Au(0), exploiting the unique interplay between heteroatom chemistry, microenvironment engineering, and light‐driven redox processes. This work introduces a new class of COF photocatalysts engineered with heteroatomic nanotraps, achieving exceptional gold recovery efficiency.

O-GlcNAcase promotes dendritic spine morphogenesis while downregulating their GluA2-containing AMPA receptors

A phase 1 study of docetaxel in combination with 177-lutetium-PSMA-I&T in patients with metastatic castration-resistant prostate cancer.

TPS281 Background: Radioligand therapy targeting prostate-specific membrane antigen (PSMA) with 177-Lutetium-labeled ligands has demonstrated meaningful antitumor activity and a manageable safety profile in patients with mCRPC. Preclinical and clinical data support combining 177-Lutetium-PSMA with other systemic agents to enhance efficacy through complementary mechanisms. Docetaxel remains a standard first-line chemotherapy for mCRPC, and the ongoing DORA trial is evaluating its combination with the alpha-emitter radium-223, highlighting the clinical interest in integrating chemotherapy with radiopharmaceuticals. However, the optimal and safe dose of docetaxel when combined with beta-emitting agents such as 177-Lutetium-PSMA-I&T has not yet been established. Methods: This investigator-initiated, single-center, open-label phase 1 study is evaluating the safety and tolerability of docetaxel in combination with 177-Lutetium-PSMA-I&T in chemotherapy-naïve patients with mCRPC. A standard 3+3 dose-escalation design is used to determine the recommended phase 2 dose (RP2D) of docetaxel. Patients receive fixed-dose 177-Lutetium-PSMA-I&T (7.4 GBq IV every 6 weeks, up to 4 cycles) combined with escalating docetaxel doses (50, 60, and 75 mg/m² IV every 3 weeks, up to 10 cycles). Continuous androgen deprivation therapy is required. Eligible patients must have histologically confirmed prostate adenocarcinoma, metastatic disease on conventional imaging, castration resistance (testosterone <50 ng/dL), ECOG performance status 0–1, and high PSMA uptake on 68-Galium-PSMA PET/CT (SUVmax ≥20 in ≥1 lesion and >10 in other lesions). Key exclusion criteria include prior chemotherapy or radiopharmaceuticals in the castration-resistant setting, neuroendocrine histology, discordant lesions on 18F-FDG PET/CT, or active secondary malignancies. The primary endpoint is determination of the RP2D of docetaxel in combination with 177-Lutetium-PSMA-I&T. Secondary endpoints include incidence of dose-limiting toxicities (DLTs), treatment completion rates, and late toxicities up to 24 weeks after therapy completion. Exploratory endpoints include PSA decline ≥50%, radiographic progression-free survival per PCWG3, and metabolic response by PERCIST on PSMA PET/CT. Planned enrollment is 2–15 patients, accounting for an estimated 30% screening failure rate.

Post-chemotherapy retroperitoneal lymph node dissection for patients with metastatic pure seminoma.

611 Background: Post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) for metastatic testicular seminoma is reserved for highly select cases and can be associated with significant morbidity. We report contemporary outcomes of pcRPLND in patients with metastatic pure seminoma with the goal of better defining patient selection for surgery and exploring gaps in diagnostic staging. Methods: Patients who underwent pcRPLND after ≥1-line of chemotherapy for metastatic pure seminoma at our institution between 2000-2024 were included. Clinicopathologic, radiographic, perioperative, oncologic, and survival outcomes are reported. Results: 52 patients underwent pcRPLND for metastatic pure seminoma during the study period. Most patients (67%) received ≥2 lines of chemotherapy prior to surgery. Eight patients (15%) harbored residual viable seminoma at pcRPLND (Table), 38% and 6% following first-line and ≥2-lines of chemotherapy, respectively. None of the patients that received high-dose chemotherapy (TI-CE) had viable disease at surgery. Over a median follow up of 50-months, 5 (10%) patients relapsed after pcRPLND, all of whom had viable residual seminoma at pcRPLND. Of the 8 patients with residual seminoma at pcRPLND, 2 were cured with pcRPLND alone, 3 with pcRPLND plus additional chemotherapy, and 3 died from progressive disease. Conclusions: The risk of finding viable residual seminoma at pcRPLND varied based on prior chemotherapy received. These data underscore the importance of careful patient selection given the competing risks of morbidity associated with pcRPLND, the high likelihood of cure with high-dose chemotherapy, and the need for better diagnostics to guide surgical decision-making in this setting. Patients with residual seminoma at pcRPLND (N=8). ID Age a CS IGCCCG risk Chemo. PET/CT (pre-pcRPLND) No. (+) nodes Pathologic node size (cm) Adjuvant chemo. Time to relapse (mo.) Relapse location b Salvage therapy Survival I 40 III Intermediate BEPx3 Negative 1 7.3 EPx2 12.8 Unk. Unk. DOD II 49 II Good EPx4 Positive>3cm 1 0.8 No 4.2 SH, SR TIPx4 NED III 33 II Good EPx4 - 2 0.4 No - - No NED IV 36 I Good EPx4 Positive<3cm 1 2.1 No 12.1 SH TIPx4 NED V 42 II Good BEPx3 Positive<3cm 1 2.2 TIPx4 - - No NED VI 25 I Good EPx4 Positive<3cm 1 3.1 No - - No NED VII 49 III Good EPx4→TIPx4 - 1 5.5 No 5.6 SH GOx4, RT DOD VIII 21 II Good EPx4→TIPx4 Negative 1 - No 2.6 PC, P TI-CE DOD Acronyms: CS, clinical stage; IGCCCG, International Germ Cell Cancer Collaborative GroupPET/CT, positron emission tomography CT; FU, follow-up; EP, etoposide, cisplatin; BEP, bleomycin, etoposide, cisplatin; TIP, paclitaxel, ifosfamide, cisplatin; GO, gemcitabine, oxaliplatin; RT, radiation therapy; DOD, dead of disease; NED, no evidence of disease. Dashes (-) represent unknown values. a Age at diagnosis. b Relapse was based on radiographic +/- biopsy findings. SH, suprahilar; SR, suprarenal; PC, peritoneal carcinomatosis; P, pelvic.

Influence of pore structure on grain bulk modulus of underground rock masses under hydro-mechanical conditions

Characterizing frailty and its drivers in bladder cancer using machine learning-derived vulnerability and resource phenotypes.

724 Background: Frailty predicts surgical complications and mortality in bladder cancer. Guidelines endorse evaluating for frailty, ideally via Comprehensive Geriatric Assessment (CGA) prior to determining a treatment plan. The objective of this study was to apply artificial intelligence to prospectively collected CGA data to not only quantify frailty but also to characterize its drivers in a clinically interpretable framework that can inform management. Methods: Urothelial cancer patients enrolled from a multidisciplinary bladder cancer clinic (9/2020–7/2021) completed a CGA incorporating validated assessments of functional status, multimorbidity, nutrition, cognition, and mental health, augmented with CT-derived body composition assessments. A random forest classifier was trained to identify predictive features of frailty. These predictive features were then transformed into positive (resources) and negative (vulnerabilities) scores and analyzed both individually and by domain. A principal component analysis (PCA) biplot was generated to provide an interpretable visualization of frailty phenotypes, with quadrants corresponding to distinct vulnerability domains. A Cox proportional hazards model was constructed using patient death and follow-up time as outcomes, adjusted for pathological stage, to assess prognostic significance. Results: The cohort included 67 patients (median age 71, 16.4% female), the majority with muscle-invasive disease (77.6%). Random forest modeling identified comorbidity burden, ECOG status, grip strength, and psychosocial resilience factors among the most strongly associated features. The PCA biplot stratified patients into distinct vulnerability/resource phenotypes, with physical performance and comorbidity burden mapping to vulnerability quadrants, and psychosocial resilience features (hope, optimism, self-kindness) mapping to resource quadrants. In Cox modeling, comorbidity score was associated with increased mortality risk (HR 1.15, p =0.04), whereas demographic resource score was protective (HR 0.78, p =0.024), independent of pathological stage (C-index 0.71). Conclusions: In this prospective observational cohort study, we leveraged machine learning to generate a paradigm on which an individual's personalized vulnerability versus resource profile can be mapped that highlight actionable drivers of frailty that may be targeted with interventions to mitigate those drivers or buttress resources prior to anticipated medical or surgical interventions. The resultant frailty atlas offers a novel, interpretable framework that distinguishes physical, psychosocial, and multimorbidity-related vulnerabilities, with demonstrated prognostic significance. This approach moves beyond simple frailty classification to provide clinically relevant, data-driven insights that can inform personalized prehabilitation and treatment planning in bladder cancer. Findings also provide proof of concept of the complex heterogeneity of patient frailty.

High‐Valence‐Cation‐Induced Lattice Expansion for Activating Li ₂ S Cathode in All‐Solid‐State Lithium‐Sulfur Batteries

ABSTRACT The practical deployment of lithium sulfide (Li 2 S) cathodes in all‐solid‐state lithium‐sulfur batteries (ASSLSBs) is challenged by their poor innate conductivities and high activation barriers. Here, we demonstrate a lattice engineering strategy using Zr 4+ substitution to fundamentally activate Li 2 S. The introduced Zr 4 + expands the lattice, creating lithium vacancies that enhance ionic conductivity by two orders of magnitude. Simultaneously, Zr─S orbital hybridization narrows the bandgap for superior electronic conductivity and weakens Li─S bonds to lower the activation energy. This synergistic effect enables a highly reversible solid‐state sulfur conversion. As a result, our ASSLSB delivers an ultrahigh energy density of 996.2 Wh kg −1 based on the cathode with a record 65 wt.% electrode‐level Li 2 S content and maintains stability for over 100 cycles, far exceeding the conventional configuration of ∼40 wt.% loading. This strategy establishes a viable pathway toward practical high‐energy‐density ASSLSBs by fundamentally activating Li 2 S electrochemistry.

Tuning Cu–Cu Spacing in Single‐Atomic Layer Cu Catalysts for Efficient and Stable CO ₂ ‐To‐C ₂ H ₄ Electroreduction

ABSTRACT The transition to sustainable energy relies on the efficient conversion of CO 2 into specific multi‐carbon (C 2+ ) products, yet this process is severely hindered by the slow kinetics of C─C coupling and uncertain product selectivity. Single‐atom catalysts (SACs) exhibit promising catalytic performance but suffer from a fundamental limitation: their lack of contiguous active sites impedes C─C coupling. Herein, we report an innovative isotropic 2D Cu single‐atomic‐layer catalyst anchored on amorphous carbon substrate, designed to enhance C─C coupling and C 2+ selectivity. By stabilizing Cu δ + species and precisely tuning the Cu–Cu spacing to 2.35 Å‐matching the C─C bond length of ethylene (C 2 H 4 ), which significantly promotes C 2 H 4 production. The catalyst achieved a remarkable Faradaic efficiency of 78.6% for C 2 H 4 at −0.8 V versus the reversible hydrogen electrode, accompanied with high stability over 120 h. These findings not only elucidate the profound impact of spatially controlled active sites in complex multi‐step reactions but also represent a significant leap forward in CO 2 conversion technologies, offering great potential for sustainable carbon utilization and addressing global energy transition challenges.

AHCY: A metabolic gatekeeper at the interface of methylation, redox balance, and cellular stress response