Browse Articles

Mechanical and Optical Properties of Nanocluster‐Silica Metamaterials

ABSTRACT Nanostructured metamaterials with complex 3D geometries can be fabricated using two‐photon lithography but are typically limited to specific materials by the available photoresists. Here, we develop a two‐photon lithography photoresist for fabricating mechanically robust and optically active metamaterials. This photoresist consists of silver nanocluster photointiators in a polyhedral oligomeric silsequioxane (POSS) polymer matrix. Printed nanocomposites show a 216% increase in elastic modulus and 166% increase in energy absorption compared to structures made of POSS, while retaining 96% elastic recovery. Nanocomposite gyroid nanolattices reach 80% strain at failure. The nanolattice energy absorption is among the highest for lightweight nanoporous materials. Thermal annealing is used to convert the printed nanocomposites to nanoparticle‐embedded glass with 54% higher energy absorption than fused silica. The annealed gyroid nanolattices contain silver nanoparticles and exhibit plasmonic activity. Right and left‐handed chiral nanolattices result in different transmission spectra under linearly polarized light.

Chronological lifespan extension and nucleotide salvage inhibition in yeast by isonicotinamide supplementation

The application of 5.0-Tesla non-enhanced MRI in the preoperative assessment of renal tumors.

426 Background: To assess the utility of 5.0-Tesla non-enhanced magnetic resonance imaging (5T NE MRI) for preoperative evaluation of renal tumor patients, particularly with renal insufficiency, as an alternative to contrast-enhanced computed tomography (CECT). Methods: We enrolled participants in a sequential cohort based on their renal status. Initially, eighteen patients with renal insufficiency (glomerular filtration rate < 90 mL/min/1.73 m²) underwent a 5T NE MRI for preoperative assessment. Afterward, 68 patients with normal renal function underwent both 5T NE MRI and CECT preoperatively. Imaging diagnoses, tumor staging, and renal arterial visualization were evaluated. Results: In patients with renal insufficiency, 5T NE MRI correctly identified 16 of 17 (94.1%) renal cell carcinoma (RCC) cases and accurately staged 92.9% of T 1–2 stage RCC (13/14) and 100% of T 3–4 stage RCC (3/3). Among patients with normal renal function, 5T NE MRI demonstrated higher diagnostic accuracy for RCC than CECT (59/59, 100% versus 53/59, 89.8%, p = 0.031) and correctly diagnosed all lipid-poor angiomyolipoma cases (2/2 versus 0/2 on CT). 5T NE MRI provided superior accuracy for identifying 57/57 T 1–2 stage (100%) versus 50/57 (87.7%) on CECT (p = 0.016) with no overstaging, while CECT overstaged 7 cases. Both 5T NE MRI and CECT achieved 100% visualization of grade 3 renal arteries. Conclusions: 5T NE MRI offers high diagnostic accuracy and staging, additionally providing grade 3 vascular visualization. It yields excellent diagnostic performance for renal tumors comparable to CECT, without the need for nephrotoxic contrast or radiation. It is especially beneficial for patients with renal insufficiency as a promising alternative in preoperative evaluation. CECT, n/N (%) 5T NE MRI, n/N (%) P-value Diagnostic Accuracy  RCC 53/59 (89.8) 59/59 (100.0) 0.031  AML 7/9 (77.8) 9/9 (100.0) 0.500  Lipid-poor AML 0/2 2/2 T stage Accuracy  T 1-2 Accordance 50 57 0.016  T 3-4 Accordance 2 2 - Vessel Grade b  Grade ≤3 68 (100.0) 68 (100.0) -  Grade ≥4 61 (88.1) 46 (64.3) <0.001

Front-line (1L) treatment and recurrence patterns among patients with high-risk non–muscle-invasive bladder cancer (HR-NMIBC) with papillary carcinoma (PAP) or carcinoma in situ (CIS) following bacillus Calmette-Guérin (BCG) or other intravesical therapies (IVT).

708 Background: HR-NMIBC carries substantial burden and high recurrence risk. Guidelines recommend BCG as 1L therapy, with other IVTs for BCG-unresponsive patients. This study aimed to describe real-world patterns of 1L treatment and recurrence rates among patients with HR-NMIBC, with PAP or CIS, initiating BCG or other IVT in the United States. Methods: This retrospective cohort study using SEER-Medicare data (1/1/2007-12/31/2022) included treatment-naïve patients ≥65 years old with HR-NMIBC with PAP (T1 disease or high-grade Ta) or CIS (Tis staging or diagnosis code), who received ≥1 instillation of BCG (BCG cohort) or other IVT (IVT cohort; mitomycin, gemcitabine, valrubicin, docetaxel, epirubicin) as 1L treatment. Index date was the first instillation. Among BCG-treated patients with sufficient follow-up, induction and maintenance patterns were assessed. Recurrence was defined as reinitiation of the same therapy after a gap (BCG: ≥180-day gap; other IVT: ≥90-day gap), transurethral resection of bladder tumor (TURBT), biopsy, or initiation of a new treatment (i.e., alternative IVT, systemic chemotherapy, radiotherapy, cystectomy, immunotherapy [including pembrolizumab], hormonal therapy, or other antineoplastic therapy). Kaplan-Meier (KM) analyses assessed time to recurrence stratified by cohort, with censoring at the earliest of end of continuous enrollment, plan switch, death, or end of data. Results: Among 17,495 patients initiating 1L treatment, 12,792 (73%) received BCG (mean age: 76 years; 79% male; 91% White) and 861 (5%) other IVTs (mean age: 77 years; 76% male; 93% White). Of BCG-treated patients, 56% initiated within 3 months of diagnosis, 84% received adequate induction (≥5 instillations within 70 days), and 54% received adequate induction plus maintenance (≥7 installations within 274 days). Median time to recurrence was 7.8 months (95% confidence interval [CI]: 7.6, 8.1), with KM recurrence rates of 21% at 3 months, 43% at 6 months, 61% at 12 months, and 74% at 24 months. Among IVT-treated patients, most received mitomycin (64%) or gemcitabine (25%). Median time to recurrence was 5.8 months (95% CI: 5.1, 6.7), and KM recurrence rates were 30% at 3 months, 51% at 6 months, 65% at 12 months, and 72% at 24 months. Conclusions: In this real-world study of Medicare-insured patients with HR-NMIBC with PAP or CIS, over 60% experienced recurrence within 12 months of initiating 1L BCG or IVT. While most BCG-treated patients received adequate induction, just over half had adequate maintenance. Current intravesical options show limited durability, underscoring the need for more effective, bladder-sparing treatments. Without clinical measures available, recurrence estimates may be affected by claims-based definitions.

Expansion and characterization of tumor-infiltrating lymphocytes from primary and metastatic immune checkpoint inhibitor-exposed renal cell carcinoma tumors.

548 Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has demonstrated efficacy in patients with immune checkpoint inhibitor (ICI)-refractory melanoma and non-small cell lung cancer. TIL expansion from treatment-naïve and ICI-exposed melanoma tumors has shown comparable feasibility; however, expansion feasibility from ICI-exposed renal cell carcinoma (RCC) tumors has not been established. Additionally, RCC metastases remain underexplored as a tissue source for viable TILs. We investigated TIL expansion from primary and metastatic ICI-exposed RCC tumors and characterized the phenotypic and functional properties to explore the potential for TIL-based ACT in ICI-refractory RCC. Methods: Following IRB approval, surgically resected specimens from 17 patients were collected and cultured with high-dose IL-2 (6000 IU/mL) for four weeks. All patients were treated with at least one cycle of immune checkpoint inhibitor therapy. TIL expansion success was defined as at least one fragment expanding to a minimum of 2 wells. TILs from 5 randomly selected metastatic tumor fragments from 3 different patients (2 adrenal tumor fragments and 3 lung tumor fragments) underwent rapid expansion protocol (REP) to assess the feasibility of therapeutic-scale manufacturing. Pre- and post-REP TIL phenotypes and reactivity to autologous tumor were analyzed with flow cytometry and co-culture assays. Results: 11 primary and 6 metastatic RCC tumor specimens (lung n = 4, adrenal n = 1, bone n = 1) were collected. TIL expansion was successful in 10/11 (90.9%) primary tumor specimens and 6/6 (100%) metastatic specimens. Primary TILs from both the primary and metastatic RCC tumors contained significantly higher proportions of T-cells versus NK cells (p = 0.002 and p < 0.0001, respectively), with no significant difference observed in CD4+ versus CD8+ T-cell populations in either group. In co-culture assays, Pre-REP TILs from 2/5 (40%) primary and 3/5 (60%) metastatic specimens demonstrated reactivity to autologous tumor. The mean fold expansion of TILs from metastatic samples following REP was 576.3-fold. The average post-REP TIL population consisted of 59.3% CD4⁺ and 29.3% CD8⁺ T cells. 3/5 (60%) post-REP TIL samples produced TNF-a and Granzyme B, and 2/5 (40%) produced IFN-g when co-cultured with autologous tumor. Conclusions: Tumor-reactive TILs can be successfully expanded from primary and metastatic ICI-exposed RCC tumors, with lymphocyte populations comprised predominantly of T-cells. Post-REP TILs from metastatic ICI-exposed RCC specimens exhibited retention of tumor-specific reactivity via cytokine production.

Biomimetic Urethra‐on‐a‐Chip Platform for Modelling Fibrosis: 3D‐Printing and Near‐Field Electrospinning in BAM‐Functionalized Microenvironment

ABSTRACT Urethral stricture, a prevalent urological disorder characterized by fibrosis of periurethral tissues, severely compromises urinary function and patient quality of life. Despite various clinical interventions, recurrence remains frequent, largely due to the lack of physiologically relevant in vitro models for mechanistic investigation and drug screening. Here, we present a biomimetic urethra‐on‐a‐chip platform that integrates microfluidics, three‐dimensional (3D) printing, and near‐field electrospinning to recapitulate the structural and biochemical complexity of the native urethra. The device features polydimethylsiloxane (PDMS) microchannels coupled with a multilayered polycaprolactone (PCL) membrane, functionalized using a bladder acellular matrix (BAM)–gelatin bioink to emulate the extracellular matrix (ECM) microenvironment. A bilayer microchamber configuration supports spatially organized coculture of fibroblasts and urothelial cells under dynamic perfusion, reproducing physiological shear stress and nutrient gradients. Under fibrotic stimulation by transforming growth factor beta 1 (TGF‐β1), the system faithfully mimicked fibroblast activation and epithelial injury, while rapamycin treatment effectively attenuated fibrotic responses, validating its potential for pharmacological testing. This urethra‐on‐a‐chip provides a robust, reproducible, and cost‐efficient platform for modeling urethral fibrosis and evaluating antifibrotic therapeutics. By bridging biofabrication, microfluidics, and tissue pathophysiology, this work establishes a versatile organ‐on‐a‐chip model with significant implications for translational research and personalized regenerative medicine.

Unlocking Built‐In Polarization via Single‐Atom Nickel Engineering in Hexagonal Cavities for Efficient Photoreforming of Biomass

ABSTRACT Rapid bulk charge recombination in crystalline semiconductors remains a critical bottleneck hindering the scalability of photocatalytic hydrogen generation. Here, we report that precise anchoring of single‐atom nickel into the hexagonal cavities of crystalline Zn 3 In 4 S 9 activates a strong built‐in polarization electric field (PEF), which dramatically enhances charge separation. The optimized Ni 0.4 ‐Zn 3 In 4 S 9 shows hydrogen production and benzaldehyde (BAD) generation rates of 48.14 and 44.72 mmol g −1 h −1 , respectively, corresponding to 22.3‐ and 17.4‐fold enhancements over the Zn 3 In 4 S 9 . It also exhibits a 42.9% apparent quantum yield at 420 nm and exceptional stability, maintaining over 94.2% (H 2 ) and 89.2% (BAD) activity after 48 h with 6.28‐ and 14.4‐fold stability enhancement for hydrogen and BAD production, respectively. This work proposes an atomic‐level design strategy for activating PEF in Zn 3 In 4 S 9 hexagonal cavities, enabling highly efficient photoreforming of biomass derivatives.

Material‐Level Integration of Magnetic Actuation and Triboelectric Sensing for Adaptive Soft Robotic Platforms

Abstract The seamless integration of actuation and sensing within materials is essential for developing compact, autonomous, and adaptive robotic systems. However, existing approaches often rely on modular assemblies or multilayer structures, leading to increased bulk, fabrication complexity, and limited integration density. Herein, a magnetically augmented structural platform is introduced for triboelectric‐nanogenerator sensing and actuation (MASTA) that combines magnetic‐field‐induced actuation with enhanced triboelectric tactile sensing through physically distinct mechanisms. It employs a high concentration of neodymium‐based magnetic particles embedded in an elastomer matrix, which enhances the triboelectric output through increased dielectric constant, magnetoelectric coupling, and magnetizing currents while enabling programmable magnetic actuation. The experimental results demonstrate significant improvements in the triboelectric performance, achieving a 325% voltage increase compared with pristine systems, while exhibiting substantial magnetic actuation capability. Three soft robotic applications validate the multifunctionality of MASTA: shape morphing with self‐sensing of motion and ground contact, reconfigurable locomotion and surface adaptation through a kirigami‐based auxetic design under distributed magnetic fields, and origami‐inspired environmental interactions through droplet‐triggered transformations. Overall, MASTA is a versatile, self‐sensing, and magnetically programmable platform that advances the design of intelligent soft robotic materials, enabling real‐time perception, adaptive behavior, and integrated multifunctionality without the need for additional actuation or sensing components.

Time-dependent changes in meibum lipid composition and progression of dry eye following disruption of the fatty acid elongase Elovl1

External validation of AI age discrepancy as a measure of frailty in kidney tumor patients.

427 Background: Our team previously introduced AI Age Discrepancy, a novel parameter for quantifying frailty and postoperative risk in kidney cancer patients undergoing nephrectomy. AI Age discrepancy was found to be a significant predictor of shorter overall survival and longer length of hospital stays post nephrectomy, independent of established factors. This work presents a replication of the previous study using a larger cohort from a different health system, along with an external validation. Methods: This retrospective study included 1800 patients treated at a single large health system for internal validation and 590 patients from an external validation dataset, all of whom had contrast-enhanced CT imaging and underwent partial or radical nephrectomy for suspected renal malignancy. Only patients over the age of 18 were included. A ResNet-50 neural network was fine-tuned on the primary institution patients' CT images to predict age as a continuous variable. 5-fold cross-validation was performed to obtain predictions for all patients. The ensemble of models was then used to predict age for the external validation cohort, with the final prediction being the average of the 5 models. The AI Age Discrepancy was calculated as the difference between the predicted age and the true age at nephrectomy. Multivariate Cox proportional-hazards regression was used to evaluate AI Age Discrepancy as a predictor of Length of Hospital Stay (LOS) and Overall Survival (OS) with established factors as model covariates. Results: The model age predictions showed a significant and high correlation to the true age for both the primary institution and external validation cohorts, with Pearson correlation coefficients of 0.75 (p = 1.86e-321) and 0.71 (p = 2.81e-91), respectively. For the primary institution, the AI Age discrepancy was a significant predictor of OS with a hazard ratio (HR) of 1.021 (p = 0.013). AI Age discrepancy was not a significant predictor of LOS for this cohort. For the external validation cohort, AI Age Discrepancy was a significant predictor of both OS and LOS, with HR of 1.073 (p = 0.023) and 0.985 (p = 0.015), respectively. Conclusions: This study confirms that the AI Age Discrepancy parameter is a significant predictor of overall survival for kidney tumor patients undergoing nephrectomy. The model demonstrated significant predictive power on both the primary institution and the external validation cohorts, demonstrating its generalizability. However, the association with length of hospital stay was not significant in the primary institution, suggesting that institutional factors may influence this relationship. These findings support the potential integration of AI Age Discrepancy into preoperative risk stratification to improve individualized patient management.

A phase 2 study of gemcitabine plus carboplatin as second-line therapy after prior enfortumab vedotin and pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma.

TPS901 Background: Urothelial carcinoma (UC) is a common malignancy of older adults, associated with poor survival once metastatic. Enfortumab vedotin plus pembrolizumab (EVP) is now the first-line standard of care for locally advanced and metastatic UC based on the landmark EV-302 trial, supplanting platinum-based chemotherapy. However, the optimal treatment following EVP progression remains critically undefined. Gemcitabine plus carboplatin (GC) is an active and well-tolerated regimen in cisplatin-ineligible patients. We hypothesize GC will become the de facto second-line therapy in this setting and propose a phase 2 study to prospectively evaluate its efficacy and establish a benchmark for future later line trials. Methods: This is a non-randomized, single-arm, open-label phase 2 study using a Simon two-stage design to assess GC efficacy and safety following EVP progression. Eligible patients have locally advanced or metastatic UC, prior EVP exposure, ECOG PS 0-2, and adequate organ function. Treatment consists of gemcitabine 1,000 mg/m² IV on days 1 and 8 plus carboplatin AUC 5 on day 1 every 3 weeks for up to 6 cycles or until progression or unacceptable toxicity. Tumor response will be assessed every 9 weeks per RECIST v1.1. The primary objective is overall response rate (ORR), including confirmed complete and partial responses. A Simon two-stage design will be utilized. If 3 (16%) or fewer of 19 patients enrolled in the first stage have a CR or PR, enrollment will stop for futility. The second stage will enroll an additional 36 patients. We will test the alternative hypothesis that ORR ≥ 0.3 against the null hypothesis that ORR ≤ 0.15 with 80% power and one-sided type-I error of 4.8%. Secondary objectives include progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. Key exploratory objectives will focus on unique factors affecting the older subpopulation of adults (≥65 years) receiving GC. Multifaceted geriatric assessments (GA) and a novel battery of biomarkers of molecular aging—including telomere length and epigenetic clocks, will be collected at specific timepoints and correlated to risk of treatment related toxicity and clinical outcomes. A predictive model, based on a composite of these variables, will be built for future validation studies and to optimize care delivery for older patients with cancer. Clinical trial information: NCT07043972 .

Prediction of socioeconomic disadvantage using AI analysis of CT imaging in kidney cancer patients.

428 Background: Socioeconomic status (SES) has been linked to higher rates of mortality after major urologic surgery; however, SES is difficult to assess at the individual level with current measures assessed at the neighborhood level. Artificial intelligence (AI) provides the ability to appreciate additional clinical information from vast amounts of data to make clinical inferences and predictions. For example, AI powered image analysis has shown that predicted “biologic age” is a stronger predictor of survival and chemotherapy tolerance than chronological age in kidney cancer patients. This finding suggests that AI-derived analysis can indicate frailty or advanced biologic age that is not reflected in actual age. In this study, our objective was to apply AI image analysis to predict Area Deprivation Index (ADI) score. Methods: Retrospectively, patients who underwent nephrectomy and had preoperative contrast-enhanced abdominal CT imaging available from 10/2009 to 7/2024. ADI, a validated metric for SES, was obtained from the Neighborhood Atlas. A ResNet-50 neural network was fine-tuned to predict ADI from CT image inputs. 5-fold cross validation was used to obtain predictions for all patients. Predicted ADI was compared to actual ADI with linear regression. Results: A total of 1349 nephrectomy patients had available imaging and ADI. Predicted ADI was correlated with actual ADI (r = 0.18, p = 1.79x10-11, y = 0.0552 * x + 0.4661). Predicted ADI was not associated with oncologic or survival outcomes following nephrectomy. Conclusions: In a preliminary analysis of a computer-vision based AI model, we demonstrated the ability to predict Area Deprivation Index from CT images in kidney cancer patients, suggesting socioeconomic status may be embedded within medical imaging data. Further refinement of the model is needed. A robust model for SES prediction may provide a better and more personalized estimation of SES exposures and may offer critical insights into how these exposures impact clinical outcomes in patients afflicted by oncologic diseases.

Structural Modulation Enables Bright and Efficient Cs–Cu–Cl Electroluminescence

ABSTRACT Cesium–copper–halide (Cs–Cu–X) perovskites are potential substitutes to lead‐halide perovskites for broadband electroluminescence (EL) in white light‐emitting diodes (LED) due to their non‐toxicity and unique self‐trapped exciton (STE) characters. Many efforts have been devoted to pushing up EL efficiencies of Cs–Cu–I LED devices, while there is no report of EL based on their Cl‐based counterparts yet. In this work, the EL of the Cs–Cu–Cl nanocrystals (NCs) was first demonstrated by a holistic structural modulation, whose champion device reached an external quantum efficiency of 2.02% and a high luminance of 3345 cd m −2 . The efficient bluish‐white EL was explored to collectively derive from the smooth film morphology, exciton inter‐band transition, triplet STE behavior, and promising electron transport ability of the Cs–Cu–Cl NC film. Additionally, the potential photophysical process for the broadband emission was proposed, collectively expanding the Cu‐based perovskite EL family for displays and lighting applications.

Motif V is an allosteric couple between the SARS-CoV-2 nsp13 nucleotide triphosphatase and helicase active sites

Association of serum kidney injury molecule-1 with treatment response and survival in metastatic renal cell carcinoma.

534 Background: First-line immune checkpoint inhibitor (IO)-based therapies have improved the prognosis of patients with metastatic renal cell carcinoma (mRCC). However, reliable blood-based biomarkers predicting treatment response and survival are lacking. Kidney Injury Molecule-1 (KIM-1) is a tubular injury marker overexpressed in RCC and detectable in serum. We investigated the association between baseline and on-treatment serum KIM-1 levels and clinical outcomes in mRCC patients receiving IO-based therapy. Methods: We retrospectively analyzed 73 patients with mRCC who received first-line IO+IO (n=36) or IO+TKI (n=37) between 2018 and 2024. Serum KIM-1 was measured at baseline in all patients and at 3 weeks in 63 patients. Patients were stratified into tertiles according to baseline KIM-1 values. Clinical characteristics, objective response rate (ORR), and progression-free survival (PFS) were compared among groups. Kaplan–Meier curves and Cox regression models were used for survival analysis. Subgroup analyses were performed according to primary tumor status. Results: Higher baseline KIM-1 was associated with adverse outcomes. Kaplan–Meier analysis showed significantly shorter PFS in the high KIM-1 group compared with the low/intermediate groups (HR 2.18, 95% CI 1.15–4.16, p=0.017). In multivariable Cox regression adjusted for IMDC risk, baseline high KIM-1 was not an independent predictor but showed a trend toward worse PFS (HR 2.01, 95% CI 0.98–4.12, p=0.056). Subgroup analysis by primary tumor status showed that in patients without primary tumors, high baseline KIM-1 was significantly associated with shorter PFS (HR 2.80, 95% CI 1.15–6.81, p=0.023), whereas in those with primary tumors, baseline KIM-1 levels did not significantly affect PFS. Among 63 patients with paired samples, responders showed a greater KIM-1 decrease than non-responders (median decrease 754 vs 258 pg/mL, p=0.018). Patients with a KIM-1 decrease had higher ORR, although PFS did not differ significantly between the increase and decrease groups. Conclusions: These findings support serum KIM-1 as a promising biomarker for predicting therapeutic efficacy in mRCC. Results of multivariate analysis for progression-free survival. Varieble Univariate analysis 　 Multivariate analysis 　 HR(95%CI) p HR(95%CI) p Age 0.94(0.20-4.64) 0.9346 1.01(0.40-2.53) 0.9038 Sex(male) 1.27(0.53-3.07) 0.5824 1.14(0.59-2.20) 0.7371 IMDC risk 1.47(0.78-2.79) 0.1231 1.33(0.68-2.61) 0.4307 pKIM1 5.22(1.25-16.97) 0.0115 2.01(0.98-4.12) 0.056

Acute and chronic GU/GI toxicity after conventional versus hypofractionated radiotherapy (HFRT) with concurrent chemotherapy for muscle-invasive bladder cancer: A multi-institutional analysis by CURE-BC - Consortium for Urothelial Radiation Excellence – Bladder Cancer.

718 Background: HFRT is increasingly used as a bladder-preserving regimen for muscle-invasive bladder cancer (MIBC), although comparative data on acute and late genitourinary (GU) and gastrointestinal (GI) toxicity versus conventional fractionation (CFRT), particularly with pelvic nodal fields or concurrent cisplatin or gemcitabine, remain limited. Methods: We conducted a multi-institutional retrospective analysis of patients with MIBC treated with definitive radiotherapy between January 2010 to March 2024. Patients were categorized based on fractionation schedule (CFRT 1.8-2 Gy/fraction, mean dose 6300 cGy vs. HFRT 2.25-2.75 Gy/fraction, mean dose 5500 cGy), nodal treatment (pelvic RT vs bladder-only), receipt of neoadjuvant chemotherapy (NAC), and concurrent chemotherapy. Acute (≤6 months of RT) and chronic physician documented GU and GI toxicities were graded per CTCAE v5.0. Statistical comparisons were done using chi-square. Results: A total of 174 patients from 3 institutions were included: 59 received HFRT, (6 received NAC, 7 had pelvic RT); 115 received CFRT, (22 received NAC, 56 had pelvic RT). Overall, 160 patients received concurrent chemotherapy—39 cisplatin, 77 gemcitabine, and 32 5FU/MMC. The incidence of acute ≥Grade 2 GU toxicity was 52.5% vs 52.2% (p = 0.9634), chronic ≥Grade 2 GU 16.9% vs 28.7% (p = 0.089), acute ≥Grade 2 GI 30.5% vs 18.3% (p = 0.0667), and chronic ≥Grade 2 GI 3.4% vs 6.9% (p = 0.3386), in HFRT vs CFRT groups respectively. Subset analysis showed HFRT vs CFRT patients had no difference in toxicity within those treated with any of the three chemotherapy agents, or with pelvic RT or with neoadjuvant chemotherapy. Paradoxically, there were fewer acute GU/GI and chronic GU toxicities in those treated with pelvic RT vs. bladder only and fewer acute GU and chronic GU/GI toxicities in those treated with NAC, likely reflecting selection bias. In the HFRT subgroup, gemcitabine (17/41) was associated with worse acute ≥Grade 2 GI toxicity, 41.5% vs. 0% with cisplatin (0/8), (p = 0.0242) while acute ≥Grade 2 GU and chronic ≥Grade 2 GU/GI toxicities were not statistically different. Conclusions: In this large multi-institutional cohort, hypofractionated radiotherapy demonstrated comparable acute and chronic toxicity outcomes relative to conventional fractionation in MIBC. Trends toward increased chronic ≥Grade 2 GU toxicity in those treated with CFRT and acute GI toxicity with HFRT, especially when given with gemcitabine warrant further study.

Prospective multicenter development and external validation of a narrow-band imaging based prediction model for malignancy risk in bladder lesions.

644 Background: White-light cystoscopy lacks specificity, driving unnecessary resections. NBI improves visibility but raises false positives and lacks a thresholded aid. We externally validated an NBI rule-in nomogram for real-time use. Methods: Prospective, seven-center, lesion-level study (11/2021–06/2024). Consecutive adults undergoing cystoscopy were scored in vivo under NBI with a standardized atlas for morphology (smooth/cauliflower/patchy) and vascular patterns (dotted/thick-branching); lesion size and routine covariates were recorded on harmonized CRFs; uniform Olympus CYF-VHA across sites. Histopathology after resection/biopsy was the reference. A prespecified logistic nomogram was trained and validated with centers held out. Analyses (R v4.2) included AUC (DeLong), calibration (intercept/slope/Brier/HL), decision-curve per-100 translation, and ≤10/≤5-mm subgroups. Results: Seven-center study (n = 1,404 lesions; 843 patients) showed a prespecified 7-feature NBI nomogram, at fixed threshold 0.537, with external performance specificity 0.918 and sensitivity 0.861. Multivariable effects (OR, 95% CI) aligned with endoscopic heuristics: cauliflower-like 10.83 (4.79–26.00); dotted 6.77 (3.27–14.67); thick-branching 4.14 (2.17–8.18); gross hematuria 3.19 (1.55–6.77); boundary-clear 2.17 (1.11–4.32); male 2.16 (1.09–4.33); patchy 0.13 (0.02–0.53). Diagnostic transforms supported rule-in use (LR⁺ 10.47, Youden’s J 0.779). Per 100 cystoscopies, ~38.8 benign resections avoided and ~8 cancers missed; training/internal showed similar magnitudes (~32.4/~66.7 avoided; ~6.4/~5.3 missed), concordant with net benefit at the same threshold (external ~31.6 fewer unnecessary interventions per 100). Discrimination was high: AUC 0.93 (95% CI 0.91–0.95) training, 0.98 (0.96–0.99) internal, 0.95 (0.93–0.97) external. Training/internal threshold performance is consistent across cohorts (sensitivity 0.827–0.896, specificity 0.841–0.958; LR⁺ 5.63–19.68) and centers. Calibration: validation Brier 0.06–0.10, Hosmer–Lemeshow p > 0.05 across cohorts, supporting the cut-point. Performance was preserved in challenging strata: ≤10 mm lesions AUC 0.927 (0.906–0.948) with sensitivity/specificity 0.846/0.888; ≤5 mm AUC 0.925 (0.892–0.957) with 0.878/0.893. EPV≈60 mitigated overfitting; all inputs are immediately observable under NBI. Conclusions: An externally validated, multicenter NBI-based prediction model converts familiar endoscopic cues into a prespecified, scope-ready rule-in decision that curbs unnecessary interventions while maintaining clinical safety, even in sub-centimeter lesions. Inputs are directly observable, computation is immediate, and calibration/validation support transportable use across operators and sites; a prospective implementation study is warranted.

Novel Antimicrobial Nano Bacteriocin: Lactic Acid Bacteria‐Derived, Self‐Assembled, and Enhanced for Superior Antimicrobial Activity

ABSTRACT As antimicrobial resistance emerges as a critical global health threat, food‐grade bacteriocin, a kind of antimicrobial peptide (AMPs), offers promising new therapies but is hampered by poor stability and water solubility. To address this, we engineered a carrier‐free self‐assembly strategy: a novel bacteriocin from lactic acid bacteria in fermented food was modified to increase its hydrophobicity, enabling spontaneous formation of nano‐antimicrobial bacteriocins (NAMBs) in TSB, LB, and MH media. These NAMBs exhibit a broader antimicrobial spectrum and enhanced potency against both Gram‐positive and Gram‐negative pathogens, including Listeria monocytogenes , Acinetobacter baumannii , and Vibrio parahaemolyticus , as evidenced by markedly reduced minimum inhibitory concentrations in vitro and superior therapeutic efficacy in infected mice in vivo. Mechanistic investigations reveal targeted disruption of cell envelope metabolism: in L. monocytogenes , NAMBs fortify the peptidoglycan layer while depleting wall teichoic acids and lipoteichoic acids, impairing carbohydrate metabolism and membrane transport; in A. baumannii , they downregulate fatty acid synthesis, disorder phospholipid composition, and weaken lipopolysaccharide integrity, culminating in membrane destabilization and cell death. These dual actions—disordering metabolic processes and remodeling bacterial cell walls or membranes—highlight the versatility of NAMBs. Our carrier‐free self‐assembly approach thus overcomes AMP stability and solubility limitations and paves the way for next‐generation antimicrobial therapies.

F2,6BP restores mitochondrial genome integrity in Huntington’s disease

Final Silence

A physician confronts the burden of silence in the care of the dying.