Browse Articles

Real-world clinical outcomes among patients with localized prostate cancer (LPC) undergoing radical prostatectomy (RP).

343 Background: RP is a curative option for LPC. While prognosis is generally favorable, patients with high-risk (HR) features face greater risk of recurrence and progression than those with low- or intermediate-risk (L/IR) disease. This study compared long-term outcomes of HR vs L/IR LPC patients treated with RP in the United States (US). Methods: This retrospective study used linked data from US community urology practices and administrative claims (PPS Analytics and Komodo Research Database; 1/1/2016–8/31/2024). The RP date served as the index date. Patients were stratified by HR vs L/IR status per NCCN guidelines based on TNM staging, Gleason score, and prostate-specific antigen level. Patients with metastasis, castration resistance, or advanced treatment before RP were excluded. Baseline characteristics (12 months pre-index) were balanced using inverse probability of treatment weighting. Outcomes including metastasis-free survival (time from index date to metastasis or death) and event-free survival (index date to biochemical recurrence, metastasis, or death) were compared via weighted Kaplan-Meier analyses and hazard ratios with 95% confidence intervals (CIs). Results: Overall, 18,971 patients with LPC were identified: 7,542 HR and 11,429 L/IR. After weighting, baseline characteristics were balanced between HR patients (mean age: 63.9 years, white: 52.6%, Medicare-insured: 46.8%, commercial-insured: 45.5%, median time from LPC diagnosis: 2.5 months, mean follow-up: 47.1 months) and L/IR patients (mean age: 63.6 years, white: 52.5%, Medicare-insured: 45.7%, commercial-insured: 46.7%, median time from LPC diagnosis: 2.8 months, mean follow-up 47.1 months). By 60 months, HR patients had a 3.59 greater rate of metastasis or death relative to L/IR patients (95% CI: 3.19, 4.04; p<0.001; Table). Rates of biochemical recurrence, metastasis, or death were also significantly higher in HR patients by 60 months (hazard ratio: 3.37; 95% CI: 3.18, 3.57; p<0.001). Conclusions: In this real-world analysis of patients with LPC treated with RP, those with HR disease had significantly worse metastasis-free and event-free survival than L/IR patients. These results highlight the greater clinical burden in HR LPC and the need for more effective treatment options. Clinical outcomes. Metastasis-free survival Event-free survival Kaplan-Meier rate High Risk Low/ Intermediate-risk High Risk Low/ Intermediate-risk 12 months 94.8% 98.9% 71.8% 92.0% HR (95% CI) 4.71 (3.86, 5.74); p<0.001 4.01 (3.71, 4.33); p<0.001 24 months 92.9% 98.2% 63.2% 88.1% HR (95% CI) 4.08 (3.46, 4.80); p<0.001 3.68 (3.45, 3.93); p<0.001 48 months 87.0% 96.4% 53.8% 82.9% HR (95% CI) 3.81 (3.35, 4.33); p<0.001 3.44 (3.24, 3.65); p<0.001 60 months 84.3% 95.1% 50.8% 80.7% HR (95% CI) 3.59 (3.19, 4.04); p<0.001 3.37 (3.18, 3.57); p<0.001 CI: confidence interval; HR: hazard ratio.

Association of a post-prostatectomy digital pathology–based multimodal artificial intelligence (MMAI) biomarker with nodal and extrapelvic metastasis on PET/CT at the time of biochemical recurrence and event-free survival following salvage radiotherapy.

378 Background: Clinical prostate cancer variables have limited ability to predict patterns of recurrence or outcomes after radical prostatectomy (RP). In this analysis, we evaluated the performance of a digital pathology multimodal artificial intelligence (MMAI) algorithm in predicting patterns of recurrence at the time of post-RP biochemical recurrence (BCR) and oncologic outcomes following PET-guided salvage radiotherapy (RT). Methods: The EMPIRE-1 (NCT01666808) and -2 (NCT03762759) randomized trials evaluated the association of PET-guided salvage RT on event-free survival (EFS) in men experiencing BCR following RP. A subset of patients with available digitized histopathologic images from the prostatectomy specimen was identified. A locked MMAI model (post-RP MMAI v1.1), which uses digital histopathology images and routine clinical data, was applied to generate MMAI scores (continuous and categorized [high- vs. low-risk]). The primary aim was to evaluate the association of MMAI score with 18 F-fluciclovine or 68 Ga-PSMA-11 PET uptake (defined as prostate bed [PB], pelvic lymph node [PLN], or extrapelvic [EP] uptake) at the time of BCR. The secondary aim was to examine the association of MMAI score with EFS (defined as freedom from biochemical/clinical/radiographic recurrence or initiation of systemic therapy) following salvage RT in a contemporary cohort managed with PET/CT and early salvage therapy. Results: Of the 223 patients enrolled on EMPIRE-1 or 2 who underwent PET scan, 92 had digital prostatectomy histopathology images available for MMAI analysis. Median (IQR) PSA at the time of PET/CT was 0.3 (0.2-0.7) ng/mL. MMAI score (continuous or categorized) was not associated with PB uptake on PET. MMAI score was significantly associated with PLN uptake on PET (continuous score per 1 SD increase: OR 2.68, 95% CI 1.57-4.98, P<.001; high vs. low group: OR 4.05, 95% CI 1.37-15.03, P=0.02). MMAI score was significantly associated with EP uptake on PET (continuous score: OR 4.63, 95% CI 1.92-14.47, P=0.003), with EP PET positivity only observed in MMAI high patients. These associations remained significant after pN-stage adjustment. After a median follow-up of 2.0 years, n=15 patients experienced an EFS event following post-RP salvage RT. Among these patients, 12 (80%) had an MMAI-high score. Post-RP MMAI score was significantly associated with EFS (HR 1.80 per SD increase, 95% CI 1.02-3.19, P=0.04). Conclusions: MMAI score from a post-RP model is associated with pelvic lymph node and extrapelvic PET uptake at the time of BCR, even with a low PSA at the time of PET/CT. This MMAI model was also prognostic for EFS following PET-guided early salvage RT.

Aluminum-induced proteomic responses in Qualea dichotoma (Mart.) warm: a dataset descriptive analysis

Next-generation sequencing of bladder and upper tract micropapillary variant urothelial carcinoma patients and associated clinical outcomes.

828 Background: Micropapillary variant urothelial carcinoma (MPUC) is a histologically and genotypically defined variant of urothelial carcinoma (UC), with more aggressive disease course and presenting at a more advanced stage. Previous literature has revealed MPUC to have a distinct molecular and genetic profile which may be driving this disease, notably higher rates of ERBB2 mutations compared to UC. Our study investigated the relationship between MPUC tumor genetic changes and associated clinical and pathological outcomes. Methods: Retrospective chart review of the electronic medical record (EMR) at a single institution was performed for the years 2015 to 2025 to identify patients with a history of micropapillary variant urothelial carcinoma confirmed on surgical pathology. Patients with either tumor genomic profiling, or blood-based next-generation sequencing (NGS) were identified, and their NGS reports analyzed for specific genomic alterations, tumor mutational burden, and mutation type. Clinical and pathology data were retrieved from EMR. Statistical analysis was then performed using Cox-proportional hazards test and Chi squared analyses for univariate analysis, and Kaplan-Meir curves were generated for overall, progression-free, and recurrence-free survival. Results: A cohort of 192 men and 43 women were identified, 37 with NGS reports available. Most common gene mutations were TERT (81%), TP53 (62%), RB1 (35%), ARID1A (32%), and ERBB2 (27%). 69% of the cohort was alive at the time of review. Median overall survival and recurrence free survival were 55 months and 28.5 months respectively. There were no statistically significant differences in overall or recurrence free survival in patients with aberrant ERBB2 versus those without (p=0.99, p=0.98). Univariate analysis results are shown in Table 1- notably age at MPUC diagnosis, initial tumor stage, and both N and M stage at time of MPUC diagnosis were significant for increased risk of death. Conclusions: MPUC tumors harbor unique genetic profiles, distinct from UC and other variants possibly driving the shorter times to recurrence and overall survival. High levels of ERBB2 mutations are seen in MPUC patients, with potentially high levels of the downstream protein HER2 as a cause for this more aggressive phenotype. Further work is underway on the entire cohort using FISH staining for HER2 to examine the degree of activity and associated clinical outcomes in MPUC patients, as a potential for future drug target in this population. Baseline pathology and associated mortality. Variable Total Hazard Ratio 95% Confidence Interval P-value Age (Continuous) 235 1.03 1.01-1.06 0.01 Tumor stage 1.89 1.13-3.17 0.02  ≤ T1 95  ≥T2 140 Lymphovascular Invasion 1.39 0.86-2.23 0.17  Yes 89  No 146 Concomitant CIS 2.15 0.93-4.97 0.07  Yes 12  No 223 N-Stage 2.22 1.08-4.56 0.03  N0 188  N1+ 47 M-Stage 1.82 1.13-2.89 0.01  M0 153  M1+ 82

Lattice Slot Waveguide for Terahertz Microfluidics Biomedical Trace Analysis

ABSTRACT Electromagnetic metasurface integrated microfluidic chips enable a real‐time, label‐free platform for terahertz trace analysis of volume‐limited biomedical samples with suppressed water absorption noise. However, conventional metal‐insulator‐metal (MIM) metasurface resonators exhibit inherently limited Q‐factor and sensitivity due to radiative leakage through open side boundaries. Here, a lattice slot waveguide based on MIM configuration is designed to effectively confine energy within the microfluidic channel and mitigate radiative loss. This trapped mode achieves enhanced sensitivity and Q‐factor through synergistic excitation of surface lattice resonance and guided mode resonance under propagation constant matching conditions. Leveraging this platform, an anisotropic detection strategy incorporating a patterned lattice structure is devised to achieve simultaneous polarization multiplexed responses, exhibiting a figure of merit of 135 in both polarizations. Experimental validation demonstrates a limit of detection of 625 pmol mL −1 and a Q‐factor of 189 for this polarization multiplexing microfluidic platform. This work offers a unique avenue for enhanced accuracy and efficiency in terahertz biomedical trace analyzing via multidimensional sensing capabilities.

From a single C-mannose to multiple C-mannosyltransferases

Real world outcomes comparing the use of GLP-1 agonists in patients with renal cell carcinoma (RCC) and comorbid obesity: A propensity score matched analysis from Global Federated Health Research Network.

484 Background: Renal cell carcinoma (RCC) is the most common type of urogenital cancer. Lifestyle and metabolic risk factors seem to play an important role in this rising incidence. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Emerging evidence suggests that these agents may have potential anti-tumor activity as GLP-1 signaling may influence pathways involved in cell proliferation and inflammation. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with RCC and comorbid obesity. Methods: A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with RCC and comorbid obesity were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, race, and common comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, myocardial infarction, heart failure, ischemic stroke, chronic kidney disease (CKD), metabolic dysfunction-associated steatotic liver disease (MASLD), and need for hemodialysis. Results: We identified 2232 patients with RCC and obesity who received GLP-1 receptor agonists, and 13090 patients with RCC and obesity who did not receive GLP-1 therapy. After propensity matching, each cohort consisted of 2231 patients with similar baseline characteristics. Our analysis found that over 5 years, patients with RCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of overall mortality (Hazard Ratio (HR): 0.493, 95% CI: 0.427 to 0.57, p-value < 0.001), myocardial infarction (Risk Difference: -2.239%, 95% CI: -3.836 to -0.642, p-value = 0.006), heart failure (Risk Difference: -4.213%, 95% CI: -6.876 to -1.551, p-value = 0.002), ischemic stroke (ischemic stroke: -2.111%, 95% CI: -3.44 to -0.781, p-value = 0.002), and CKD (Risk Difference: -8.526%, 95% CI: -11.441 to -5.611, p-value < 0.001). There was no statistically significant difference in the risk for MASLD and need for hemodialysis between the two subgroups. Conclusions: Our study revealed that patients with RCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of mortality, myocardial infarction, heart failure, CKD and ischemic stroke. Further longitudinal cohort studies are imperative to better understand these associations and guide evidence-based clinical practice in this population.

Adding metformin to androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): Quality of life (QoL) results from STAMPEDE.

135 Background: ADT, the standard treatment for mHSPC, induces metabolic side effects that impact QoL. In the STAMPEDE trial, metformin improved metabolic parameters, and had a signal for oncological benefit in high-volume disease. Its potential to enhance QoL remains clinically relevant. Methods: Men with mHSPC were randomly allocated 1:1 to standard of care (SOC: ADT ± docetaxel ± radiotherapy) ± metformin. Diabetic patients were ineligible. Patients completed EORTC QLQ-C30 and PR25 questionnaires at baseline and regular intervals for up to two years. The primary analysis assessed longitudinal global QoL using linear mixed models with a time-by-treatment interaction, adjusting for baseline. Cross-sectional analyses were conducted at predefined timepoints. A between-arm difference ≥ 4 points on the transformed 0–100 scale defined clinical relevance for our primary outcome. Functional domains and symptom scores were also compared. Results: A total of 996 men completed baseline and at least one further QoL assessment up to 24 months (SOC: 443; SOC + metformin: 553). Clinical characteristics were well balanced across groups. Global QoL over two years did not differ between arms (mean difference = +1.1 [95% CI –0.7 to 3.0]; p = 0.24, favouring metformin). Functional domains were similar: small improvements in emotional (+2.2; p = 0.008) and cognitive (+2.2; p = 0.007) function were evident but this did not reach clinical significance. Physical and social functioning were similar, as were fatigue, and pain. Diarrhoea was more frequent with metformin (+5.8; p < 0.001). Treatment-related symptoms (PR25 composite) favoured metformin (–2.4; p < 0.001) but were below the threshold for clinical significance. Findings in men with high-volume disease were consistent with the primary analysis, showing non-significant improvements in global QoL with metformin. Conclusions: Metformin is safe, inexpensive, and well tolerated in men with mHSPC receiving standard therapy. Overall QoL was maintained, with no deterioration across functional domains and only a modest, manageable increase in diarrhoea. Small improvements in emotional, cognitive, and treatment-related symptoms were observed, supporting metformin’s favourable tolerability profile alongside its known metabolic benefits. Clinical trial information: NCT00268476 .

Differential enrichment of key bacterial taxa in the rhizosphere of naturally growing and artificially restored Kandelia obovata forests

Abstract The structure of the soil bacterial community is crucial for maintaining ecosystem balance and facilitating material transformation in mangrove ecosystems. The large-scale destruction of mangroves directly impacts soil bacterial processes, potentially leading to ecosystem degradation. This study employed Illumina NovaSeq high-throughput sequencing to investigate the rhizosphere bacterial community of Kandelia obovata seedlings in both natural and artificially restored forests. Although alpha and beta diversity analyses revealed that the overall bacterial community structure was not significantly altered by artificial restoration, significant shifts in the abundance of specific bacterial genera were identified. A substantial proportion (86.1%-92.6%) of bacterial sequences remained unclassified at the genus level. Distinct dominant genera were observed across different groups: the well-grown artificial group (treat-k) was enriched with Sulfurovum , Actibacter , and Desulfatiglans (5.09%, 2.18%, and 1.82%, respectively), while the poorly-grown artificial group (treat-s) was characterized by Ignavibacterium , Prolixibacter , and Woeseia (2.10%, 1.21%, and 1.06%, respectively). The natural group was dominated by Woeseia , Desulfatiglans , and Halioglobus (1.56%, 1.53%, and 1.11%). Statistical analysis further confirmed that the abundance of several genera, including Ignavibacterium , Prolixibacter , and Haliangium differed significantly ( p  < 0.05) between the poorly-grown group (treat-s) and the better-grown groups (treat-k and natural). In conclusion, while artificial restoration did not restructure the rhizosphere bacterial community at a global level, it selectively shaped the microbial assemblage by enriching specific bacterial taxa, which might play a crucial role in determining the growth status of Kandelia obovata during restoration.

Toward noninvasive genomic profiling in muscle-invasive bladder cancer using quantitative CT texture analysis.

825 Background: Urothelial bladder cancer exhibits substantial pathological, molecular, and clinical heterogeneity. Genomic and transcriptomic profiling of muscle-invasive bladder cancer (MIBC) has identified recurrent alterations that inform classification and therapeutic targets. However, evolving mutational landscapes and the infrastructure required for testing limit routine clinical applicability. Computed tomography (CT), used routinely for staging and surveillance, may offer a noninvasive method to infer tumor biology. Radiomics - the extraction of quantitative imaging features - may help link phenotypic imaging signatures to underlying molecular alterations. Methods: We integrated genomics data from The Cancer Genome Atlas with CT data from The Cancer Imaging Archive in 89 patients with biopsy-proven MIBC to create models for prediction of DNA mutations, Tumor Mutational Burden (TMB), and mRNA expression. An in-house developed CT-based radiomics pipeline was used to compute 488 texture metrics for the segmented images and quantify visual characteristics such as brightness distribution, pixel relationships, and periodic structural patterns. Three machine learning classifiers - Random Forest, Extreme Gradient Boosting, and Elastic Net - were trained on the radiomics data and evaluated with 10-fold cross-validation using area under the receiver-operator curve (AUC) as a balanced performance measure. Results: Among 15 DNA mutations found in at least 10% of the cohort, EP300, FGFR3, and ARID1A were predicted most reliably, with AUCs of 0.77 and 0.76, and 0.75 respectively. The models also predicted tumors with high TMB (AUC = 0.61), transcriptomic patterns associated with poor prognosis by two mRNA panels (AUC = 0.73, AUC = 0.65), and transcriptional levels of key cell cycle (CDKN1A, AUC = 0.78) and apoptotic (CASP3, AUC = 0.71) genes. Finally, the model could frequently discriminate the luminal infiltrated molecular subtype from other variants (AUC = 0.69). Conclusions: Our study demonstrates that CT-derived radiomics features can capture biologically and clinically relevant information in muscle-invasive bladder cancer. These findings support the potential utility of radiomics as a noninvasive, scalable adjunct to genomic profiling in MIBC.

Targeting NAT10 alleviates colonic senescence and elderly-onset colitis by disrupting N4-acetylation of DYRK1A

Rational Design of 3D Morphable Color‐shifting Mesosurfaces Using Bioinspired Janus Micro‐ and Nanolattices

Abstract Morphable 3D mesosurfaces with tunable optical properties present unique opportunities for adaptive, multifunctional systems such as next‐generation displays, intelligent camouflage, and visual‐based mechanical sensing. Directly embedding nanoscale optical features onto morphable, curved 3D mesosurfaces remains challenging, due to the extreme mismatch in length scales and material limitations. 3D assembly methods offer alternative routes to the fabrication of morphable 3D color‐shifting mesosurfaces, but the synergetic design/control of visible optical performance and complex 3D shapes has rarely been explored. Inspired by the biological construction of hierarchical micro‐ and nanopores in diatom cell walls, novel design strategies of 3D morphable color‐shifting mesosurfaces with rationally engineered Janus micro‐ and nanolattices are proposed. A double‐sided patterning method, combining top‐down lithography and nanomolding, enables precise integration of Janus lattices onto thin‐film 2D precursor structures, which are then transformed into target 3D mesosurfaces through buckling‐guided 3D assembly. Synergetic designs of micro‐ and nanolattice patterns allow the customization of 3D optical mesosurfaces with desired shapes and reflectance distributions, guided by a theoretical mechanics model and experimentally measured reflectance spectra. Leveraging angle‐dependent reflectance, morphable ribbon‐shaped surfaces whose color changes gradually during in‐plane stretching and out‐of‐plane compression are demonstrated, suggesting potential applications in power‐free, visual‐based strain and pressure sensing.

Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?

Neoadjuvant tislelizumab in combination with disitamab vedotin (RC48) followed by distal ureterectomy for patients with HER-2 expressing lower segment ureteral carcinoma (LSUC): A single-arm, phase II, single-center study.

765 Background: As a special subtype of upper tract urothelial carcinoma (UTUC), lower segment ureteral carcinoma (LSUC) is common. Its unique location makes it resectable via distal ureterectomy (DU) while preserving the kidney. However, the high recurrence rate of UTUC makes this treatment strategy potentially risky. Nevertheless, programmed death receptor-1 immune checkpoint inhibitors is becoming a potential option for UTUC. Moreover, given frequent HER-2 expression in UTUC, combining anti-HER-2 antibody–drug conjugates (ADC) with PD-1 ICIs may achieve better treatment efficacy and outcomes. Therefore, to explore efficacy and safety of the new kidney-sparing strategy that neoadjuvant tislelizumab, a type of PD-1 ICIs, combined with Disitamab Vedotin (RC48), a kind of anti-HER-2 ADC, followed by DU for pts with LSUC, we evaluated it in the single-arm, phase II, single-center TRUCE-UTUC01 trial. Methods: In this study, pts with HER-2 expressing (IHC 2+/3+ at baseline pathological specimen) cT1-4N0-2M0 LSUC were enrolled and received 2-3 cycles of neoadjuvant RC48 2.0mg/kg and Tislelizumab 200mg intravenously on days 1, Q3W, followed by distal ureterectomy (DU). The primary endpoint is pathological complete response (pCR, defined as no residual lesions found in the pathological specimen from DU). Secondary endpoints include objective response (OR, including CR and PR according to RECIST 1.1), overall survival (OS), relapse-free survival (RFS), and progress-free survival (PFS). Treatment-related adverse events (TRAEs) are evaluated according to CTCAE v5.0. This trial is registered with ClinicalTrials.gov number, NCT05837806, and is ongoing. Results: 10 pts were enrolled, comprising 7(70%) males, with a median age of 71(IQR 65-77) years. Baseline Her-2 expression was 2+ in 7 (70%) pts, and 3+ in 3 (30%) pts. 1 pts withdrew from the study for refusing surgery. All pts have received no less than 2 cycles of treatment, then completed imaging evaluation, while 9 pts completed pathological assessment. 4 of 9 (44%) pts achieved pCR, 4 of 10 pts achieved ICR, and 7 of 10 pts achieved IOR. The median follow-up time was 51.6 weeks as of October 2025, with no deaths reported. Only 1 pts suffered recurrence and progression. The median RFS/PFS has not yet been reached. The TRAEs of any grade with the highest incidence were alopecia (50%), pruritus (40%) and fatigue (30%). Only 1 (10%) pts experienced grade 3 TRAEs, including fatigue and alanine aminotransferase increase. Conclusions: The neoadjuvant tislelizumab + RC48 followed by DU demonstrates favourable efficacy in HER-2 expressing LSUC with acceptable TRAEs. Our approach indicates that this kidney-sparing strategy for LSUC is feasible and holds potential. Clinical trial information: NCT05837806 .

Intismeran autogene (V940/mRNA-4157) plus bacillus Calmette-Guérin (BCG) versus BCG alone for high-risk non–muscle-invasive bladder cancer: The phase 2 INTerpath-011 study.

TPS882 Background: Transurethral resection of a bladder tumor (TURBT) followed by intravesical BCG is the standard of care for patients with treatment-naive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC). However, many patients develop disease recurrence and progression, and novel therapies are needed to improve outcomes. Intismeran autogene (intismeran) is an individualized neoantigen therapy being evaluated for the treatment of several solid tumor types, including muscle-invasive bladder cancer. Intismeran is hypothesized to enhance the antitumor activity of BCG by eliciting endogenous antitumor T cell responses directed at the unique neoantigens of the tumor. INTerpath-011 (NCT06833073) is a randomized, multicohort, open-label, phase 2 study evaluating efficacy and safety of intismeran plus BCG versus BCG alone (cohort A) and intismeran alone (cohort B; exploratory) in participants with HR NMIBC. Methods: Eligible participants are adults with BCG-naive HR NMIBC (high-grade [HG] Ta, T1, and/or carcinoma in situ [CIS]; cohort A) or BCG-naive or BCG-exposed HR NMIBC (CIS with or without papillary tumors [HG Ta or T1]) who are ineligible for or refuse intravesical therapy (cohort B). BCG naive is defined as either not receiving BCG or having received BCG > 2 years before HR NMIBC recurrence. BCG exposed is defined as having not received adequate BCG dosing and HR NMIBC recurrence within 2 years of the last BCG dose. Participants must undergo TURBT ≤12 weeks before enrollment and provide tumor tissue and blood samples for next-generation sequencing and intismeran production and blood for ctDNA testing. In cohort A, approximately 278 participants will be randomly assigned 1:1 to receive 50 mg intravesical BCG (induction: Q1W for 6 weeks; maintenance: Q1W for 3 weeks at weeks 13, 25, 49, and 73) with or without intismeran 1 mg intramuscularly Q3W for 9 doses. In cohort B, approximately 30 participants will receive intismeran 1 mg intramuscularly Q3W for 9 doses. Disease assessment (urine cytology by blinded independent central review [BICR] and cystoscopy) will occur Q12W (and ≥4 weeks after last BCG dose in cohort A) for the first 2 years and Q24W for years 3-5. Computed tomography urography or magnetic resonance urography will occur Q72W for the first 2 years and Q104W for years 3-5. Primary end points are event-free survival (cohort A) and complete response rate (CRR; cohort B) by BICR. Secondary end points include relapse-free survival, disease-specific survival, overall survival, time to cystectomy, and safety (both cohorts). Additional secondary end points include CRR by BICR and duration of response (DOR) in participants with CIS at baseline treated in cohort A, and DOR in cohort B. Enrollment is ongoing. Previously presented at ESMO Congress 2025, FPN: 3135eTiP, Petros Grivas et al. – Reused with permission. Clinical trial information: NCT06833073 .

Aetiology of acute respiratory infection in Vientiane, Lao PDR, from a case–control study

Abstract Acute respiratory infections (ARI) remain a major cause of child mortality in low- and middle-income countries. However, the risk factors for ARI are poorly understood in low-income settings, and ARI aetiology is changing, driven by vaccination. There are very limited data from Lao PDR (Laos) on ARI aetiology and risk factors to support health policy decisions. This study aimed to investigate the aetiology of hospitalised ARI, and describe risk factors associated with hospitalised ARI, in children under 5 years of age in Laos. We conducted a case–control study at Mahosot Hospital, Laos, enrolling children under five years of age hospitalised with ARI, and community controls matched on age, sex and time of recruitment. Demographics and clinical characteristics were collected, and throat swabs taken. Swabs were analysed using probe-based real-time polymerase chain reaction (PCR) to detect bacterial and viral microorganisms. Risk factors for ARI were determined through regression analysis, and microorganism-specific attributable fractions (AF) were calculated to estimate each microorganism’s contribution to hospitalised ARI. We enrolled 307 cases and 564 controls over 12 months in 2016/17. Microorganisms were detected in 93.8% of cases and 58.9% of controls. Respiratory syncytial virus (RSV) was the leading viral cause of hospitalised ARI, attributed to 29.6% of cases, followed by influenza viruses (11.6%). H. influenzae was attributed to 40.8% of cases. RSV exhibited clear seasonality, peaking during the wet season. Exclusive breastfeeding for 3 months (OR: 0.62; 95% CI 0.45–0.86), and being up to date with pneumococcal conjugate vaccination (odds ratio: 0.6; 95% CI 0.41–0.80), were associated with a lower risk of hospitalised ARI; while low birth weight (OR: 2.91; 95% CI 1.63–5.28), and household smoking (OR: 3.07; 95% CI 2.25–4.18), were associated with increased risk. RSV and H. influenzae remain major causes of ARI in Laos. The findings highlight the potential benefit of tailoring interventions to the local context, including vaccination and risk mitigation strategies, to reduce the burden of ARI in Laos and other low and middle-income countries.

Clinical validity of FoundationOne CDx assay to identify <i>HRR</i> -positive or <i>BRCA</i> -positive mCSPC patients in the phase 3 AMPLITUDE study.

166 Background: AMPLITUDE, a Phase 3, randomized, double-blind, placebo-controlled trial, evaluated the safety and efficacy of niraparib plus abiraterone acetate with prednisone (NIRA+AAP) in patients (pts) with homologous recombination repair-positive ( HRR +) mCSPC. Nira+AAP is indicated for BRCA + metastatic castration-resistant prostate cancer (mCRPC) pts, as identified by an approved companion diagnostic tissue (FoundationOne CDx (F1CDx). We evaluated the clinical utility of the tissue F1CDx test to identify HRR + or BRCA+ mCSPC pts in the AMPLITUDE study. Methods: HRR status was prospectively evaluated in AMPLITUDE pts utilizing central (tissue- F1CDx) and/or local tests as clinical trial assays (CTAs), and the efficacy of Nira+AAP was evaluated by the primary endpoint of radiographic progression-free survival (rPFS). Clinical utility of F1CDx was explored by comparing rPFS between treatment arms in HRR + and BRCA + pts identified by F1CDx and overall enrolled by CTAs in AMPLITUDE. Results: Out of 696 enrolled HRR+ pts, 549 (78.9%) were evaluated by F1CDx assay. Out of 549 pts, 468 (85.2%) were HRR + (including 273 [49.7%] BRCA + pts), 81 (14.7%) were neg. The Hazard Ratio (HR) of rPFS in HRR + pts identified by F1CDx was 0.56 (95% 2-sided Confidence Interval (CI): 0.42,0.76) vs overall HRR+ pts in the study 0.62 (95% CI: 0.49, 0.79). In BRCA + pts identified by F1CDx, the HR was 0.46 (95% 2-sided CI: 0.30, 0.69) vs overall BRCA + 0.515 (95% CI: 0.37, 0.717). Conclusions: Clinical efficacy of NIRA+AAP was consistent in F1CDx-identified HRR + or BRCA + pts compared with the overall patient population in AMPLITUDE, demonstrating the clinical utility of the F1CDx assay to identify HRR + or BRCA + mCSPC patients to help guide treatment decision regarding NIRA+AAP. Clinical trial information: NCT04497844 .

Matrix Stiffness Governs Fibroblasts’ Regulation of Gingival Immune Homeostasis

ABSTRACT Periodontal disease is characterized by inflamed gingival tissues and degradation of the gingival extracellular matrix (ECM), yet the role of mechanical cues remains poorly understood. Gingival ECM in periodontal disease showed reduced fibrillar collagen compared to healthy samples. We hypothesized that ECM softening in periodontal disease contributes to inflammation by dysregulating gingival fibroblasts (GFs). A mechanically tunable hydrogel model of the gingival ECM was developed to investigate the mechano‐immune crosstalk. Stiff and soft collagen‐alginate hydrogels matched the rheological properties of healthy and diseased gingival biopsies respectively. Human donor GFs encapsulated in these stiff hydrogels showed significantly suppressed toll‐like receptor‐mediated inflammatory responses compared to those in soft hydrogels. The non‐canonical NFκB pathway and epigenetic nuclear organization directed stiffness‐dependent inflammatory responses of GFs. The direct impact of mechanical cues on immune responses was investigated ex vivo by co‐culture of donor‐derived human GFs with myeloid cells and in human gingival explants. Myeloid progenitors co‐cultured with GFs in stiff hydrogels differentiated into immunomodulatory dendritic cells. Ex vivo crosslinking of human gingival tissue increased stiffness and reduced the production of inflammatory cytokines. Gingival mechano‐immune regulation offers a novel approach to biomaterial‐based treatments for periodontitis.

Light‐Responsive Block Copolymer Particles with Persistent Shape Memory and Programmable Reconfiguration

ABSTRACT Light‐responsive polymeric particles provide a versatile platform that can undergo precisely programmed shape and color transformations, offering opportunities for advanced multi‐level memory systems. We report a block copolymer (BCP) particle system that functions as a structural memory element by reversibly switching among distinct morphologies and retaining each state with long‐term stability. The incorporation of hydrazone‐based photoswitches into polystyrene‐ block ‐poly(2‐vinylpyridine) (PS‐ b ‐P2VP) particles enables reversible and light‐programmed transformations, governed by ( E )/( Z ) isomerization under dual‐wavelength irradiation at 410 and 365 nm. The photoisomerization modulates the charge‐transfer character of the N─Br interaction within P2VP domains, yielding three well‐defined and distinct morphologies: lamellar ellipsoids (dark), networked lamellae (410 nm), and surface‐wrapped discs (365 nm). These photoinduced morphologies can be reversibly switched over multiple cycles without detectable fatigue. Importantly, each programmed state persists as a metastable configuration over 30 days in the dark, retaining &gt; 97% of its original morphology. Furthermore, the incorporation of domain‐selective fluorescent dyes enables the system to provide real‐time, color‐coded visual readout of its encoded states via Förster resonance energy transfer modulation, opening new avenues for multi‐level data storage with direct optical access.

Conformation-specific monoclonal antibodies reveal early Tau structural intermediates in Alzheimer’s disease