Browse Articles

The impact of neoadjuvant chemotherapy relative dose intensity on pathological complete response and survival in muscle-invasive urothelial cancer: A multicentric retrospective study.

760 Background: The Relative Dose Intensity (RDI) of neoadjuvant chemotherapy (NAC) is known to influence pathological response and survival in several solid tumours. However, its role in muscle-invasive urothelial carcinoma (MIUC) remains underexplored. This study aimed to evaluate the association between RDI of cisplatin-based (CB) NAC and pathological complete response (pCR), and its correlation with event-free survival (EFS) and overall survival (OS). Methods: We retrospectively collected data on 321 patients with cT2-cT4 ± N0-N+ MIUC of CB NAC followed by radical cystectomy across multiple centres in Italy and the UK between 2014 and 2025. RDI was defined as the ratio between the dose of chemotherapy administered and the planned dose, multiplied by the ratio between the planned duration and the actual duration of treatment, expressed as a percentage. The planned dose was 70 mg/m² of cisplatin per cycle over 4 cycles within 63 days. The primary endpoint was pCR (ypT0/ypTis); secondary endpoints included EFS and OS. To limit heterogeneity in drug delivery, only patients who received 3 or 4 cycles of NAC were included. Associations were analysed through χ² tests and Kaplan-Meier/log-rank methods. A multivariate logistic regression was performed including RDI, mEFS, mOS, cT stage, nodal status, Charlson Comorbidity Index, age, sex, performance status, nephrostomy, and histology. Results: Among 321 patients, 165 were included in the RDI-High (≥ 80%) and 156 in the RDI-Low ( < 80%) group. Median follow-up time was 26.6 months (95% CI, 23.7-29.9). Overall, 41 patients (12.8%) presented with node-positive disease and 280 (87.2%) were node-negative. The pCR rate was significantly higher in the RDI-High group compared with the RDI-Low group (47.9% vs 30.8%; p = 0.002). In multivariate logistic regression, RDI ≥80% remained an independent predictor of pCR (OR 2.68, 95% CI 1.48-4.84; p < 0.001). Similarly, RDI ≥80% was associated with a favourable trend toward improved EFS (HR 0.68, 95% CI 0.45–1.01; p = 0.057) and OS (HR 0.59, 95% CI 0.34-1.01; p = 0.055). Multivariate models were consistent with these findings. mEFS and mOS were not reached in either group. Achieving pCR was strongly associated with reduced risk of recurrence (EFS HR = 0.18, 95% CI: 0.11-0.31; p < 0.001) and death (OS HR = 0.30, 95% CI: 0.16-0.57; p < 0.001). Conclusions: These findings highlight the clinical relevance of maintaining adequate chemotherapy dose intensity to optimise neoadjuvant treatment efficacy in MIUC, given its strong association with higher pCR rates. This study demonstrates the essential impact of RDI on oncological outcomes and supports its inclusion as a stratification criterion in future neoadjuvant clinical trials.

Covalent Amorphous Alumina‐Hydrogenated Graphene Materials With Integrated Proton Radiation Shielding and Energy Storage Capability for Space Electronics

ABSTRACT The development of adaptive material platforms that integrate proton radiation shielding with energy storage capabilities is critical for achieving both miniaturization and cost‐effective reliability in space electronics. Here, we present an industrially viable technology for fabricating covalent amorphous alumina‐hydrogenated graphene (AHG) films that can attenuate energetic protons, store electrical energy, and adapt to downsizing. Specifically, the fabrication involves thermal‐driven precipitation and crystallization of carbon species into hydrogenated graphene layers, along with oxidation of aluminum into amorphous alumina, on a nickel‐copper alloy surface. AHG films exhibit effective attenuation of energetic protons (15.2 MeV, 4.3 × 10 12 p/cm 2 ), primarily attributed to proton trapping via C─H bond formation within the film matrix. Moreover, AHG films are laser‐scribed into interdigitated electrodes for constructing micro‐supercapacitors (µ‐SCs) with impressive energy (8.33 mWh/cm 3 ) and power (130 mW/cm 3 ) densities. Operando measurements of the AHG µ‐SCs demonstrate their dual functions in reducing the incident protons by ∼1.9 MeV in energy and ∼5.8 × 10 11 protons/cm 2 in fluence, while maintaining stable capacitive behavior with ∼93% capacitance retained after the severe irradiation. These findings suggest significant potential for developing single multifunctional products as a replacement for both traditional radiation shields and energy storage devices in next‐generation space electronics.

All‐Solid Biomass Dual Network Ionic Conducting Elastomer with Multi Ion Synergy for Low‐Temperature Resistant Sensor and Triboelectric Nanogenerator

ABSTRACT Soft ionic conductors are ideal candidates for applications in wearable electronics, soft robotics, and human‐machine interfaces. However, achieving a balance between mechanical performance and ionic conductivity remains challenging. Besides, hydrogel‐based conductors typically fail at sub‐zero temperatures. To overcome these concurrent limitations, we report a fully solid‐state ionic conducting elastomer featuring a multi‐ionic (LiTFSI/ChCl) dual‐network derived from biomass. Molecular dynamics and density functional theory simulations verify synergistic Li─O coordination and hydrogen‐bonding networks, which enable a rare combination of mechanical strength (0.877  M Pa, 587% elongation) and high ionic conductivity (3.74 × 10 −3 S·m − 1 ). The strain sensors based on the elastomers enable stable motion sensing at −20°C and Morse code anti‐counterfeiting. Moreover, the elastomer serves as a stretchable triboelectric nanogenerator. At a resistance of 1 M Ω, the power density at −30°C increases to 290% of the value measured at room temperature, demonstrating its potential as a reliable and eco‐friendly alternative to conventional batteries in low‐temperature conditions. This work provides a novel design strategy for durable, high‐performance ionic conductors, paving the way for their use in extreme environment.

BMI1 represses G-quadruplex DNA formation to maintain genomic stability during replication

Role of urinary exosomal FAM153C-RPL19 in detection and risk stratification of prostate cancer: A multicentre Chinese cohort study.

374 Background: Serum PSA lacks specificity for prostate cancer (PCa), especially within the 4–10 ng/mL “grey zone,” leading to unnecessary biopsies and missed high-grade disease. Urinary exosomes concentrate tumour-derived RNAs and may improve non-invasive diagnosis. We evaluated a chimeric RNA, FAM153C-RPL19, in urinary exosomes as a diagnostic and prognostic marker for PCa.To determine the clinical performance of urinary exosomal FAM153C-RPL19 for PCa detection (overall and PSA grey zone), compare it with PSA and PCA3, test multi-marker models, and assess associations with grade, stage and progression-free survival (PFS). Methods: We analysed tissue, plasma and urine across three centres (Nanfang Hospital, Sun Yat-sen Memorial Hospital, Peking University People’s Hospital). Discovery used CPGEA and external validation cohorts; urinary/plasma exosomes were isolated by standardised SOPs (sequential centrifugation→TFF→ultracentrifugation). FAM153C-RPL19 was quantified by RT-qPCR with rigorous assay QC. Diagnostic performance was assessed by ROC/AUC; multivariable Cox tested prognostic value for PFS; multiple testing used Bonferroni/FDR where appropriate. Pre-specified subgroup analyses included PSA grey zone and Gleason/Stage strata. Results: Among 2,002 participants (PCa = 826; BPH = 396; non-PCa cancers = 352; healthy = 428), urinary exosomal FAM153C-RPL19 was significantly elevated in PCa versus all control groups and increased with higher Gleason score (≥7) and advanced stage (III–IV). Urine outperformed plasma for the same individuals. Diagnostic accuracy was high (AUC = 0.93) and remained robust in PSA grey-zone patients (AUC = 0.92); FAM153C-RPL19 outperformed PSA (AUC = 0.81) and PCA3 (AUC = 0.75). A combined model (FAM153C-RPL19 + PSA + PCA3) achieved AUC = 0.97, supporting multiplex testing. Prognostically, higher urinary exosomal FAM153C-RPL19 predicted shorter PFS (HR = 2.95, 95% CI 1.90–4.58). Findings were consistent across centres with harmonised pre-analytics. Conclusions: Urinary exosomal FAM153C-RPL19 provides accurate, non-invasive detection of PCa and clinically meaningful risk stratification, particularly within the PSA grey zone, and could reduce unnecessary biopsies. Incorporation into multi-marker urine assays further boosts performance and supports translation toward point-of-care liquid biopsy pathways. Prospective studies should evaluate its impact on biopsy decision-making and surveillance algorithms.

Improving quality of life measures for use in shared decision-making in advanced prostate cancer.

50 Background: In advanced prostate cancer (aPC), understanding patient treatment goals is the cornerstone of shared decision-making (SDM); however, complex treatment choices make this difficult. Validated patient-reported outcome measures (PROMs) capture the patient’s perspective of their health and assess treatment impacts on their quality of life (QoL). Overall, current PROMs are overly general, not individualized, and imprecise in symptom assessment, which may limit their use in populations with mild symptom burden. Although common in trials, PROMs integration in clinical practice is used less in SDM due to low rates of patient completion and clinician–patient discussion following completion. A standardized approach to effectively incorporate patient-reported QoL measures in SDM for patients with aPC is needed. Methods: An international expert panel of clinicians specializing in oncology and urology was assembled to discuss ways to enhance the incorporation of QoL measures into SDM discussions in aPC. Results: Clinicians agreed that current PROMs are valuable but insufficiently address patients’ lived experiences and treatment goals. The panel emphasized the need for a standardized and validated tool that assesses QoL in aPC, leveraging the benefits of PROMs, to apply to SDM for patient-centered discussions. Initial criteria determined that data collection should be comprehensive, adaptive to bothersome symptoms, repeated to assess patient experience over time, and include underrepresented groups. The tool should adapt based on previous answers to identify changes in patient goals or circumstances, integrate into clinical infrastructure to reduce clinician workload, and address technological barriers to allow regular patient data entry. Moreover, it must be accessible and understandable, ensuring that clinicians and patients are well-informed during SDM. Proposed concepts included the use of Computer Adaptive Tests, pretreatment measures for patient goals and a QoL baseline, and specialized questions for patients with localized vs. advanced disease. Conclusions: The findings of this panel discussion indicate that, to optimize SDM in aPC, a new approach to assess QoL measures is needed for wider uptake and standardized use in clinic, ensuring that treatment strategies align with patient goals. This requires novel technologies that facilitate data acquisition, adapt to patient concerns, integrate into clinical systems, and make complex data understandable for patients.

Treatment (Rx) patterns and outcomes with second-line (2L) therapy in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) treated with cabozantinib plus nivolumab (cabo+nivo) or lenvatinib plus pembrolizumab (len+pem) in first-line (1L).

442 Background: Cabo+Nivo and Len+Pem are very effective and approved 1L Rx for pts with mccRCC [PMID:33657295, 33616314]. However, after progression on these Rx, outcomes with 2L agents are not well established. Herein, we present Rx patterns and outcomes with 2L therapy after 1L Cabo+Nivo or Len+Pem in pts with mccRCC. Methods: This study used pt-level data from the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility criteria: diagnosis of mccRCC, receipt of Cabo+Nivo (cohort 1) or Len+Pem (cohort 2) in 1L and documentation of 2L Rx. For both cohorts the data cut-off date was 10/31/2024. The primary endpoints were real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS) from the start of 2L Rx and were summarized using median survival and 95% confidence interval (CI) via the Kaplan-Meier method. Results: Cohort 1 consisted of 238 pts treated with 1L Cabo+Nivo of which 66 who received 2L met eligibility and included in the analysis. These pts were diagnosed with mccRCC between 9/1/2012 – 10/5/2023, and initiated 2L from 8/23/2018 - 9/23/2024. Median age was 65 years (IQR 58, 76), 67% were White non-Hispanic and 71% were male. Cohort 2 consisted of 145 pts treated with 1L Len+Pem of which 37 received 2L and met eligibility and included in the analysis. These pts were diagnosed with mccRCC between 11/14/2014 – 2/2/2024 and initiated 2L from 6/29/2021 – 9/9/2024. Median age was 71 years (IQR 64, 76), 78% were White non-Hispanic and 68% were male. Rx patterns and survival outcomes summarized in Table. Conclusions: These data present Rx patterns after Cabo+Nivo or Len+Pem. 2L Rx in this setting retain modest activity. These findings underscore the limited efficacy of current 2L options in the post-Cabo+Nivo or Len+Pem setting, highlight the urgent need for novel therapies in this setting and provide survival estimates for future trial design and patient counseling. Rx patterns and survival outcomes of pts in cohort 1 and cohort 2. Rx in 2L Cohort 1 n(%) Cohort 1 median rwTTNT (mo) (95% CI) Cohort 1 median rwOS (mo) (95% CI) Cohort 2 n(%) Cohort 2 median rwTTNT (mo) (95% CI) Cohort 2 median rwOS (mo) (95% CI) TKI 21 (31.82%) 5.8 (3.0, —) 36 (5.0, —) 17 (45.95%) 4.6 (2.9, —) 14 (5.1, —) TKI + PD-1i 14 (21.21%) 12 (8.5, —) 19 (18, —) 10 (27.03%) 7.5 (5.2, —) 8.6 (5.2, —) CTLA-4i + PD-1i 12 (18.18%) 6.3 (2.6, —) 17 (9.1, —) 0 NA NA Single PD-1i 9 (13.64%) 18 (18, —) — (18, —) 3 (8.11%) — (2.1, —) — (—, —) HIF 2 (3.03%) 8.1 (7.4, —) — (—, —) 1 (2.70%) 3.1 (—, —) 3.1 (—, —) Other 8 (12.12%) 2.3 (1.4, —) — (3.5, —) 6 (16.22%) 4.9 (4.6, —) 6.5 (4.8, —) i = inhibitor.

Neoadjuvant combined chemotherapy and immunotherapy for upper tract urothelial carcinoma: Final results from a phase II study.

775 Background: Upper tract urothelial carcinoma (UTUC) carries a poor prognosis even after radical nephroureterectomy (RNU).The efficacy of neoadjuvant chemotherapy for UTUC remains uncertain due to limited and mainly retrospective evidence.This phase II study aims to investigate the efficacy and safety of combining chemotherapy (Gemcitabine/Cisplatin/ Carboplatin) with a PD-1 inhibitor (Toripalimab /Tislelizumab/Nivolumab/Pembrolizumab) as neoadjuvant treatment (NT) in UTUC. Methods: This single-arm, phase II trial enrolled 33 patients with high-grade cT1N0M0 or cT2–3N0M0 UTUC, confirmed by ureterorenoscopic biopsy and cross-sectional imaging. Patients received 2–4 cycles of neoadjuvant therapy consisting of gemcitabine (800 mg/m² , days 1 and 8), cisplatin or carboplatin (60 mg/m² on day 1), and a PD-1 inhibitor (240 mg on day 1) every 21 days, followed by RNU with pelvic lymphadenectomy. The primary endpoint was pathological complete response (pCR) rate; secondary endpoints included safety, compliance, and surgical feasibility. Results: All 33 patients completed treatment and were included in the analysis.The median age was 65.0 years; 54.5 % were male.Most had unifocal tumors, with a median maximum diameter of 3.0 cm (0.7-7.5). All patients experienced obstructed hydronephrosis. Clinical T staging was confirmed by multi-parameter MRI, indicating nine T2 and twenty-four T3 patients. Ureterorenoscopy biopsy revealed thirty high-grade and three low-grade urothelial carcinoma patients. All patients were classified as high-risk UTUC. Twenty-four patients completed 4 cycles, seven underwent 3 cycles and two underwent 2 cycles. The median interval time from initiation of NT to RNU and from the end of NT to RNU was 18.3 (10-34) weeks and 6.7 (2.3-29) weeks respectively. Operative time was slightly longer than for patients undergoing upfront surgery. The pCR rate was 27.3% (9/33), the ≤pT1 rate was 69.7% (23/33), and the DCR was 100%. No grade 5 chemotherapy-related adverse events were recorded, but 39.4% (13/33) experienced grade 2 myelosuppression, 24.2% (8/33) grade 3, and 6% (2/33) grade 4. Five patients experienced immune-related adverse events after 4 cycles, including hypothyroidism (grade 2) and adrenal insufficiency (grade 2). No serious surgery-related complications or readmissions within one month were reported. With a median follow-up of 22.1 months, all patients remained alive and tumor-free. Conclusions: The combination of chemotherapy and a PD-1 inhibitor as neoadjuvant therapy showed promising efficacy with acceptable safety in high-risk UTUC. This approach may offer a new therapeutic option for improving pathological responses before surgery. Clinical trial information: NCT04099589 .

Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease

Harnessing Direct Oxo Coupling for Durable Water Oxidation via Atomic‐Level Strain Engineering

ABSTRACT Iridium oxides are the state‐of‐the‐art oxygen evolution reaction (OER) catalysts in proton exchange membrane water electrolysis (PEMWE). However, its activity is still hampered by the high thermodynamic barrier of *OOH intermediates in the conventional adsorbate evolution mechanism (AEM). To resolve this challenge, we present an atomic‐level compressive strain‐engineering strategy to modulate reaction pathways by incorporating erbium (Er 3 + ) into the IrO 2 (Er‐IrO x ) framework. The large ionic radius of Er 3 + shortens the Ir–Ir distance and optimizes the electronic structure of active sites. This strain‐induced reconfiguration shifts the OER pathway from AEM to the direct oxo coupling mechanism (OPM), where O─O formation occurs through radical coupling, bypassing the high‐energy *OOH intermediate. The resulting Er‐IrO x catalyst reaches a small Tafel slope of 70.55 mV dec − 1 and a remarkably low overpotential of 209 mV at 10 mA cm −2 . More importantly, when configured into a practical PEMWE, it delivers a high current density of 6 A cm −2 at a low voltage of 1.899 V and maintains durable operation for over 400 h. This work offers a generalized approach for breaking activity‐stability trade‐offs in Ir‐based catalysts, promoting the commercial implementation of green hydrogen production.

Long non-coding RNA LINC00607 epigenetically regulates endothelial TSPAN18 to promote hypoxia-induced thromboinflammation

Real-world effects of sodium-glucose cotransporter 2 inhibitor use on renal cell carcinoma.

480 Background: The Warburg effect has long been recognized as a key driver of cancer cell metabolism. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce cellular glucose uptake, thereby limiting the substrate for this pathway. We evaluated the incidence of renal cell carcinoma (RCC) among SGLT2i users, using dipeptidyl peptidase-4 inhibitor (DPP4i) users as a controls. Among patients with RCC, we further compared survival outcomes between users of these two drug classes. Methods: In this retrospective study, de-identified patient data was pooled from over 72 healthcare networks across the US using the TriNetX database. Adult patients ( > 18 years old) were propensity-score matched for age at index event, sex, race and ethnicity in all stages of this study. In the first stage, patients with type 2 diabetes (ICD 10 E.11) with no history of urological cancers (C64, C65, C66, C67, C68) were divided into cohorts based on the use of SGLT2i (ATC A10BK) or DPP-4i (ATC A10BH) within the past 3 years. Metformin use (RxNorm 6809) was excluded from all groups to avoid confounding. They were further matched for factors increasing risk of RCC: hypertension, acute kidney failure or chronic kidney disease, tobacco use, chronic viral hepatitis, calculus of kidney and ureters, BMI, serum creatinine, and HbA1c. A total of 71,442 patients in each group were compared for association with RCC (C64) incidence. In the second stage, patients with RCC and no prior urological malignancy were divided into SGLT2i and DPP4i users based on use within the past 3 years and matched for comorbidities (hypertension, ischemic heart disease, atherosclerosis, cerebrovascular diseases, type 2 diabetes, acute kidney failure or chronic kidney disease, diseases of the liver, chronic lower respiratory diseases), TNM staging and labs (serum creatinine, hemoglobin, total bilirubin, total protein, serum LDL, triglycerides, NT-pro BNP, ejection fraction, HbA1c, BMI). After propensity-score matching, 1,159 patients per group were compared for death as an outcome, and Kaplan–Meier (KM) analysis was used to estimate survival probability. Results: SGLT2i users had a lower incidence of renal cell carcinoma over 3 years when compared to DPP4i users (RR: 0.746, 95% CI 0.655 - 0.849, p < 0.0001). SGLT2i users with RCC had a lower risk of mortality when compared to DPP4i users (RR: 0.64, 95% CI 0.507 - 0.808, p = 0.0001). On KM analysis, SGLT2i users had a 83.209% survival probability (compared to 74.47% in control) at the end of time window, with median survival not being reached at most recent follow up in both groups. Conclusions: Prior studies have reported high levels of SGLT2 expression on RCC cells. This could explain the above findings, as well as make RCC a suitable target for cancer risk modification using SGLT2 inhibition. Further prospective studies are needed to validate this.

Overall survival in men with metastatic castration-resistant prostate cancer treated with olaparib or lutetium-177-PSMA-617 following prior systemic therapy.

202 Background: Both olaparib and lutetium-177-PSMA-617 have been approved for post-taxane and post-ARPI (androgen receptor pathway inhibitor) metastatic castration-resistant prostate cancer (mCRPC). However, optimal sequencing or superior selection between the two agents to maximize clinical outcomes and survival is unclear. Here, we compare the overall survival (OS) among patients who received either agent following prior systemic therapy, comparing regimens that included androgen receptor targeted therapy with or without chemotherapy. Methods: A retrospective analysis using the TriNetX database identified patients diagnosed with prostate cancer from 2000–2024. Patients were grouped by treatment with docetaxel (doc), enzalutamide (enz), or abiraterone (abi) alone or in combination, followed by either olaparib or lutetium-177-PSMA-617. Overall (OS) and 1-year survival were estimated via Kaplan-Meier analysis, with group differences assessed by log-rank test yielding hazard ratios (HR) and 95% confidence intervals. Incidence of anemia and neutropenia at 180 days was also compared. Results: A total of 1,832 patients who met the inclusion criteria were identified, and 1,238 after matching. Propensity matching was performed between groups that ultimately received either olaparib or lutetium-177-PSMA-617; of these, a combined 190 received doc+abi, 104 received doc+enz, 354 received doc+abi+enz, 212 received enz+abi, 212 received abi, and 166 received enz. There was a statistically significant difference in OS when comparing Olaparib vs lutetium-177-PSMA-617 after receiving doc+abi of 10.1 vs 15.9 months (HR = 1.43; 95% CI 0.98 - 2.10), as well as after enz (18.1 months vs time not reached for lutetium-177-PSMA-617, HR = 2.03; 95% CI 1.17 – 3.51). Comparisons done between post-taxane and post-ARPI groups also saw lower 1-year survival post-ARPI with olaparib vs lutetium-177-PSMA-617 of 60.6% vs 67.0% (HR = 1.34; 95% CI 1.01 – 1.79). Olaparib used was also associated with higher rates of anemia with doc+abi (HR = 1.47; 95% CI 1.05 - 2.06), doc+abi+enz (HR = 1.34; 95% CI 1.05 – 1.71), and enz (HR = 1.71; 95% CI 1.12 – 2.60). No significant differences were observed for neutropenia. Conclusions: This real-world study potentially suggests superior OS in men with metastatic prostate cancer receiving lutetium-177-PSMA-617 over Olaparib, particularly when given post-ARPI. Further prospective studies are needed to confirm these findings. Group Median OS (months) p HR (95% CI) doc + abi 10.1 vs 15.9 0.064 1.43 (0.98–2.10) doc + enz 14.2 vs 11.7 0.588 1.15 (0.69–1.93) doc+abi+enz 12.9 vs 15.4 0.168 1.20 (0.92–1.57) enz+abi 15.1 vs 17.6 0.124 1.36 (0.92–2.00) abi 18.8 vs NR 0.355 1.24 (0.78–1.97) enz 18.1 vs NR 0.01 2.03 (1.17–3.51) All groups compare Olaparib vs lutetium-177-PSMA-617 after the listed medications in any order.

Partial nephrectomy (PN) versus ablative therapies (AT) for T1a clear cell renal cell carcinoma (ccRCC): Analysis of 2,161 patients.

459 Background: PN is considered the standard treatment for T1a ccRCC, whereas AT have been increasingly utilized as minimally invasive alternatives, particularly in patients with high surgical risk or impaired kidney function. However, comparative data on oncologic and kidney outcomes between these two strategies are limited. Methods: This retrospective study included 2,161 patients with clinical T1a ccRCC who underwent either PN (N = 2,045) or AT (N = 116) between January 2006 and December 2024. Baseline characteristics, survival outcomes, and renal functional preservation were evaluated in both the overall cohort and the propensity score–matched cohort to adjust for confounders. Kidney outcome events were defined as declines of ≥30%, ≥40%, or ≥50% in estimated glomerular filtration rate (eGFR) from baseline, respectively. Results: Before matching, patients in the PN group were younger (mean age 55.1 vs. 63.9 years, P < 0.001) and had higher body mass index (BMI) (mean BMI 25.3 vs. 24.4 kg/m², P = 0.004), whereas the AT group had a lower baseline eGFR level (84.7 vs. 90.6 mL/min/1.73 m², P = 0.014) and were more likely to have underlying hypertension (57.8% vs. 42.0%, P < 0.001) and diabetes (33.6% vs. 24.2%, P = 0.022). During the median follow–up duration of 66.3 months (95% confidence interval [CI] 64.0–68.5), locoregional recurrence (hazard ratio [HR] and 95% CI: not estimable, P < 0.001), distant recurrence (HR: 0.189, 95% CI: 0.072–0.500, P < 0.001), death (HR: 0.141, 95% CI: 0.085–0.235, P < 0.001) and kidney function decline (≥30% [HR: 0.220, 95% CI: 0.111–0.433, P < 0.001], ≥40% [HR: 0.124, 95% CI: 0.058–0.264, P < 0.001], or ≥50% [HR: 0.141, 95% CI: 0.052–0.383, P < 0.001] decline in eGFR from baseline) were significantly superior in the PN group compared to AT group. The superior oncologic outcomes and kidney function preservation of PN were consistently observed in the propensity score–matched cohort (n = 605; 489 treated with PN and 116 with AT): locoregional recurrence (HR and 95% CI: not estimable, P < 0.001), distant recurrence (HR: 0.186, 95% CI: 0.059–0.584, P = 0.004), death (HR: 0.275, 95% CI: 0.162–0.468, P < 0.001), and kidney function decline (≥30% [HR: 0.383, 95% CI: 0.196–0.748, P = 0.005], ≥40% [HR: 0.230, 95% CI: 0.101–0.525, P < 0.001], or ≥50% [HR: 0.164, 95% CI: 0.049–0.548, P = 0.003]). Conclusions: PN demonstrated superior oncologic control and kidney function preservation compared with AT in patients with T1a ccRCC. These findings strongly support that PN should be prioritized as the curative treatment approach whenever clinically feasible.

Erratum: Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial

Tissue expansion-enhanced mass-spectrometry imaging decodes biomolecular landscapes

Crystal Engineering of Reticular Materials for Gas‐ and Liquid‐Phase Hydrocarbon Separation

ABSTRACT Crystal engineering focuses upon the design, properties, and applications of crystals, whereas reticular chemistry involves linking molecular building blocks to create network structures. The intersection of these areas is evident in the number of systematic studies of structure/function relationships concerning porous coordination networks (PCNs) and covalent organic frameworks (COFs). PCNs and COFs are inherently modular in nature and therefore amenable to systematic fine‐tuning of both pore size and chemistry in a manner that is infeasible for other classes of porous solid. This review highlights how this exquisite control over pore size and chemistry has enabled the development of a new generation of physisorbents that are effective in the context of industrially relevant hydrocarbon (HC) separations. The motivation behind such reticular sorbents is the need to replace today's energy‐intensive HC separation methods with more sustainable alternatives. Physisorbents are attractive in this context as they can offer the high selectivity needed for trace removal of impurities along with relatively low energy of recycling. This review details how crystal engineering strategies offer precise control of pore size and chemistry to enable HC selectivity to reach hitherto unprecedented levels. Nevertheless, despite these property advances, challenges remain to be addressed before commercial adoption becomes feasible.

Self‐Assembled Ruthenium Complexes With Sonobleaching Ligand for Enhanced Tumor Penetration and Immunogenic Sonotherapy

ABSTRACT Ruthenium complexes, which can be activated with precise light‐induced spatiotemporal control, are recognized as promising candidates for cancer therapy. However, the inadequate tumor penetration and their dependence on light activation present challenges to deeper clinical application. Herein, we introduce a charge‐reversal strategy to enhance tumor penetration and cellular uptake of RuIR783, a self‐assembled metalloprodrug activated by ultrasound, thereby enabling deep tissue penetration. RuIR783 is synthesized by coordinating a Ru(II) polypyridyl complex with a heptamethine cyanine dye bearing two hydrophilic sulfonic groups. The cyanine dye component serves as both the ultrasound antenna and the self‐assembly motif. RuIR783 self‐assembles into large nanoparticles with negatively charged surfaces, facilitating their circulation in the bloodstream and accumulation at tumor sites. Upon ultrasound irradiation, the cyanine scaffold within the accumulated RuIR783 nanoparticles undergoes rapid sonobleaching, resulting in their transformation into smaller nanofragments with cationic surface charges. This transformation enhanced tumor penetration by 6.5‐fold and cellular internalization by 4.2‐fold. The generation of singlet oxygen and monocationic anticancer Ru complexes enhances the efficacy of immunogenic cell death through mitochondrial damage, achieving a 90.5% tumor inhibition rate. This study demonstrates the first ultrasound‐mediated activation of metalloprodrugs for immunogenic tumor treatment through morphological transformation and charge reversal.

Hepatic management of toxic sterols after acute deletion of Cyp51 from cholesterol synthesis

Patterns of management and multidisciplinary care in high/very high and intermediate risk localized prostate cancer: A population-based study in Ontario, Canada.

333 Background: Patients with high- or very high-risk (H/vHR) localized prostate cancer (LPC) are at significantly increased risk of recurrence, metastasis, and mortality than those with intermediate risk (IR) LPC. Multidisciplinary management involving urologists, radiation oncologists, and medical oncologists is vital to optimize treatment outcomes. Understanding real-world care patterns is essential to identify gaps and guide improvement in care delivery. This study aims to characterize current management practices and multidisciplinary care patterns among patients with H/vHR and IR LPC in Ontario, Canada. The focus is on evaluating consultation rates, treatment approaches, and coordination of care during the initial diagnosis and the first-year post-diagnosis. Methods: A retrospective, population-based cohort study was conducted using province-wide linked administrative data from Ontario. The study included 12,939 patients diagnosed with H/vHR PCa and 16,650 with IR disease between 2010 and 2021. Descriptive analyses summarized consultation patterns with urology, radiation oncology, and medical oncology, both prior to treatment and within the first year after diagnosis. Comparisons between groups were performed using standardized differences and p-values. Results: Most patients in both groups visited a urologist (H/vHR: 97.8%; IR: 94%; p<0.001). However, fewer high-risk patients had radiation oncology consultations before treatment (H/vHR: 41.2%; IR: 62.5%; p<0.001). Among those undergoing radical prostatectomy, about 40% had prior radiation oncologist consultations, with no significant difference across risk groups. Medical oncology consultations were rare (~2%) in both groups. Within the first year, approximately one-third of patients were seen only by a urologist, whereas over 65% consulted both urologists and radiation oncologists. Notably, multidisciplinary care involving all three specialties was uncommon (H/vHR: 40%; IR: 32%). Conclusions: Despite the recognized importance of multidisciplinary management, significant gaps remain in the coordination of care for prostate cancer patients, especially among high-risk groups. Strengthening collaborative approaches is crucial to enhance treatment decision-making and improve clinical outcomes. Future efforts should prioritize optimizing multidisciplinary pathways to ensure comprehensive, patient-centered care.