Browse Articles

A Water‐Soluble PVA Macrothiol Enables Two‐Photon Microfabrication of Cell‐Interactive Hydrogel Structures at 400 mm s ⁻¹ (Adv. Mater. 18/2026)

Clinical characteristics and survival outcomes of primary sarcoma of the kidney (PSK).

566 Background: Primary sarcoma of the kidney (PSK) is a rare malignancy. Clinical characteristics and survival outcomes of PSK have not been well studied. Methods: Patients with PSK were identified in the Surveillance, Epidemiology, End Results (SEER) database from year 2000 to 2020 by using the primary cancer site codes for kidney as well as histological codes (ICD-O-3) that matches the list of sarcoma histology found in the NCCN soft tissue sarcoma and bone cancer guidelines. Data for demographics, disease extent, median overall survival (OS), and treatment modality were obtained. Sarcomas mixed with non-sarcoma histology, such as carcinosarcoma and clear cell sarcoma, were included in the analysis. OS data of patients with renal cell carcinoma (RCC) were obtained for comparison. Results: A total of 260,569 patients with primary kidney neoplasms were identified in the SEER database; 864 (0.003%) had PSK and . The majority were Caucasian (62.1%) followed by Hispanics (19.6%) and African Americans (8.9%). The most common histology was leiomyosarcoma (23.1%), followed by clear cell sarcoma (15.1%), and liposarcoma (15%). Other histology types were synovial sarcoma (4.4%), Ewing sarcoma (4.2%), and carcinosarcoma (2.8%). Pure sarcomas (n=709, 82.1%) were more frequent than mixed sarcomas (n=155, 17.9%). Majority of patients with pure sarcoma (68.1%) were ≥ 50 years of age and the majority with mixed sarcoma (62.0%) were ≤ 10 years of age. Among the 823 patients with known extent of disease at diagnosis, 36.2%, 33.0%, and 30.8% had localized, locoregional, and distant metastatic disease, respectively. Lung (18.2%) was the most common site of metastasis followed by liver (10.4%) and bone (8.8%). OS of PSK was 42 months compared to 122 months seen with RCC (p< 0.001). OS for patients with localized, regional, and distant diseases were 145, 46, and 9 months, respectively (P<0.001 with all comparisons). Among the 855 patients with treatment data available, 65 (7.6%) received chemotherapy only, 436 (51.0%) received surgical resection only, 252 (29.5%) received both, and 102 (11.9%) received neither. Both chemotherapy and surgery were associated with longer OS. Those who received chemotherapy showed OS of 47 months compared to 42 months seen in the no chemotherapy group (P=0.003). As for surgical resection, OS of those who underwent surgery was 63 months compared to 6 months in those who did not (P<0.001). Conclusions: PSK is rare and associated with worse outcomes compared to RCC. While pure sarcomas of kidneys were more common in older populations, mixed sarcomas had a bimodal age distribution and the majority were young. Disease stages at the time of diagnosis were comparable among local, locoregional, and distant metastatic diseases, but patients with distant metastases had worse survival. Chemotherapy and surgical resection were associated with better survival.

Genetic ancestry and stage-specific differences in prostate cancer genomic alterations.

262 Background: Men of African ancestry have higher prostate cancer-specific mortality than men of European ancestry. Socioeconomic and access-to-care factors contribute, but mounting evidence suggests differences in tumor genomics may also play a role. Most prior studies have relied on self-reported race and have evaluated localized and metastatic tumors either in aggregate or in isolation. Whether ancestry-associated genomic differences vary disease stage remains unknown. Methods: We analyzed 3,574 prostate cancer patients with genetically inferred ancestry who underwent matched tumor-normal targeted sequencing via MSK-IMPACT (468 genes). Genetic ancestry was estimated using ADMIXTURE with the 1000 Genomes reference panel; patients were classified as predominantly African (AFR, ≥80% African ancestry; n=291) or European (EUR, ≥80% European ancestry; n=3,283). Somatic mutations, copy-number alterations, gene fusions, and pathogenic germline variants were assessed. Multivariable logistic regression, adjusted for age, Gleason score, and sequencing year, tested for differences by ancestry, stage (localized [stage 1-3] vs metastatic [stage 4]), and ancestry-stage interaction. Results: SPOP mutations demonstrated a significant ancestry-stage interaction (p<0.05), with opposing trends across ancestry groups. In metastatic disease, SPOP alterations were enriched in AFR tumors (OR 1.9; 95% CI, 1.1-3.1) but depleted in EUR tumors (OR 0.7; 95% CI, 0.5-0.9), despite comparable prevalence in localized tumors (AFR 11% vs EUR 10%). ERG fusions were substantially less frequent in AFR tumors overall (localized: 14% vs EUR 50%; metastatic: 24% vs EUR 41%; both p < 0.001). MYC amplification was more common in AFR metastatic tumors (23% vs 15% in EUR; p = 0.01), whereas frequencies in localized disease were similar (13% vs 11%). BRAF mutations were enriched in localized AFR tumors (4% vs 1% in EUR; p = 0.03) but not in metastatic cases. BRCA2 and other DNA repair gene alterations showed no significant differences by ancestry in either stage category. Conclusions: Prostate cancer genomic profiles differ by genetic ancestry, with some differences modulated by disease stage. The novel SPOP ancestry-stage interaction suggests distinct molecular progression pathways in AFR vs EUR men. Many actionable alterations occur at similar rates across ancestries, supporting equitable genomic testing and precision therapy access.

Disruption of neutrophil homeostasis is associated with functional alterations in mitochondria of critically ill COVID−19 patients

Abstract Understanding the molecular mechanisms underlying neutrophil dynamics during COVID−19 disease progression is essential for managing severe inflammatory conditions. We investigated whether alterations in neutrophil mitochondrial function and calcium handling are associated with disrupted neutrophil homeostasis in critically ill COVID−19 patients. We analyzed neutrophil counts, phenotypes, and apoptotic profiles in critically ill COVID−19 survivors (ICU-S) and non-survivors (ICU-NS) compared with healthy controls. Flow cytometry, metabolic profiling, immunofluorescence imaging, and small RNA sequencing (miRNA-seq) were used to characterize neutrophil apoptosis-related pathways and mitochondrial function in freshly isolated neutrophils. Critically ill COVID−19 patients showed marked neutrophilia and a higher proportion of immature CD16low neutrophils relative to controls. Both ICU-S and ICU-NS groups exhibited reduced neutrophil apoptosis, as evidenced by fewer annexin V+ cells and lower cleaved caspase−3 signal compared with healthy controls. Although exploratory miRNA-seq in a small subset of ICU patients identified differentially expressed miRNAs with predicted enrichment in apoptosis- and calcium-related pathways, these mortality-associated miRNA signatures were not corroborated by functional apoptosis readouts (cleaved caspase−3 and annexin V) between ICU-S and ICU-NS. Neutrophils from ICU patients also demonstrated altered calcium handling, hyperpolarized mitochondrial membrane potential, increased complex II–linked respiration, and elevated mitochondrial ROS relative to controls. Neutrophils from critically ill COVID−19 patients display coordinated alterations in calcium handling, mitochondrial activity, and apoptosis consistent with impaired neutrophil clearance and disrupted homeostasis. These findings are observational and do not establish causality; the miRNA results should be interpreted as hypothesis-generating rather than validated mortality biomarkers.

Safety data from UPLIFT: Phase I/II study of CDK4/6 inhibition with abemaciclib to upregulate PSMA expression prior to ¹⁷⁷ Lu-PSMA-617 treatment in patients with metastatic castrate resistant prostate cancer (mCRPC).

163 Background: 177 Lu-PSMA-617, a PSMA-targeting radioligand therapy, has shown robust responses in patients with mCRPC that correlate with PSMA expression. A CRISPR screen identified CDK4/6 as a key regulator of PSMA, and CDK4/6 inhibition induced PSMA upregulation in prostate cancer cell lines. The Phase I/II UPLIFT trial is investigating lead-in treatment with the CDK4/6 inhibitor abemaciclib with the goal of upregulating PSMA expression immediately prior to treatment with 177 Lu-PSMA-617 in patients with mCRPC (NCT05113537). Safety data from the phase I portion of the study investigating dose escalation of abemaciclib is presented here. Methods: Eligible patients (pts) had mCRPC which had progressed on a prior ARSI with or without taxane chemotherapy, with PSMA-avid disease (≥3 lesions with PSMA uptake greater than liver). Pts were enrolled to a 3+3 dose escalation of abemaciclib at 3 dose levels (100 mg BID, 150 mg BID, 200 mg BID). With each 6-week cycle, abemaciclib was given as a 14-day lead-in treatment prior to standard administration of 177 Lu-PSMA-617 (7.4 GBq (±10%) per cycle), for up to 4 cycles. 68 Ga-PSMA-11 PET scans were obtained pre and post abemaciclib treatment during cycle 1 to assess changes in PSMA expression. DLTs were assessed during the first cycle (6 weeks) of combination treatment. Primary endpoints of the phase I portion were safety profile of the combination regimen and determination of the recommended phase II dose (RP2D) of abemaciclib in combination with 177 Lu-PSMA-617. Results: Nine patients were enrolled in phase I (3 at each dose level). Median age was 69 (range 60-84), 78% were Caucasian, median baseline PSA was 40.6 ug/L (range 0-744), and 8 pts (89%) had prior taxane chemotherapy. Treatment related adverse events (TRAEs) were reported by all 9 pts, with G3 TRAEs in 22% (2 pts; syncope, PE). Most common TRAEs were fatigue (n=6, 67%), diarrhea (n=5, 56%) and dry mouth (n=4, 44%) (see Table). No G4-5 TRAEs were reported. One pt passed away while on trial from an event unrelated to treatment (CVA). No dose-limiting toxicities (DLTs) were noted at any of the 3 dose levels. The RP2D of abemaciclib as part of this regimen was established at 200 mg BID. Conclusions: Abemaciclib 14 day lead-in treatment prior to 177 Lu-PSMA-617 was well tolerated and deemed safe in patients with mCRPC, with a RP2D of 200 mg BID abemaciclib. The Phase II portion of the trial is ongoing to assess PSMA upregulation on scans during cycle 1 and the potential efficacy of this combination. Clinical trial information: NCT05113537 . TRAE (Most Common) Grade 1 Grade 2 All Grades Fatigue 5 (56%) 1 (11%) 6 (67%) Diarrhea 3 (33%) 2 (22%) 5 (56%) Dry Mouth 4 (44%) 0 4 (44%) Nausea 1 (11%) 2 (22%) 3 (33%) Anemia 1 (11%) 2 (22%) 3 (33%) Constipation 3 (33%) 0 3 (33%) Decreased appetite 2 (22%) 1 (11%) 3 (33%) Leukopenia 0 2 (22%) 2 (22%) Lightheadedness 2 (22%) 0 2 (22%)

Intrinsically Disordered Protein‐Inspired Nanovector‐Based Coacervates for the Direct Cytosolic Transport of Biomacromolecules (Adv. Mater. 17/2026)

Functional Polymers for Ionic Thermoelectrics: Multiscale Design Strategies for Ion Dynamics, Mechanics, and Energy Harvesting

ABSTRACT The efficient conversion of dissipated heat into useful electrical energy has emerged as a promising approach for sustainable energy technologies. Ionic thermoelectrics (iTEs) are particularly attractive because they generate substantial thermo‐voltages, effectively harvest low‐grade heat, and offer advantages such as cost‐effectiveness, easy scalability, and remarkable performance. Unlike liquid‐state platforms, quasi‐solid‐state iTEs exhibit properties that are critically governed by the polymer matrix and polymer‐ion interactions, which are closely related to the overall device performance. Consequently, the use of functional polymers effectively improves the characteristics and performance of quasi‐solid‐state iTEs. Therefore, this paper highlights the impact of the polymer matrix on performance and mechanical properties in iTEs from molecular‐, micro‐, to macro‐scale engineering. Particular emphasis is placed on clarifying the role of polymers at various scales to provide an in‐depth understanding of performance enhancement. Furthermore, the current challenges and prospective research directions are discussed, offering guidance toward the development of next‐generation iTE‐based energy harvesting platforms.

Clinical outcomes of neoadjuvant chemotherapy–guided bladder preservation in muscle-invasive bladder cancer: Long-term results of a phase II trial.

742 Background: Radical cystectomy (RC) remains the standard of care for muscle-invasive bladder cancer (MIBC), yet it profoundly impacts quality of life. For carefully selected patients achieving a major response to neoadjuvant chemotherapy (NAC), bladder-sparing strategies may offer durable control. Our previous study revealed that selected patients with favourable NAC responses showed satisfactory bladder-sparing rate, prognosis, and bladder function. However, long-term outcomes of NAC-guided bladder-sparing therapy remain underexplored. Methods: This single-center, prospective phase II clinical trial (NCT02861196) enrolled patients with cT2–T4aN0M0 muscle-invasive bladder cancer (MIBC) between August 31, 2015, and August 31, 2018. All patients received neoadjuvant chemotherapy consisting of gemcitabine (1,000 mg/m² on days 1 and 8) plus cisplatin (75 mg/m² on day 2) every 21 days. Definite responders (≤T1) underwent transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy, whereas incomplete responders proceeded to radical or partial cystectomy. Post-treatment follow-up was conducted every 3–6 months for the first 2 years, every 6–12 months for years 3–5, and annually thereafter. Results: Fifty-nine patients were enrolled (median age 63 years, range 39–73); 75% had cT3–T4a disease. Median follow-up was 102.2 months (IQR 99.4–107.7). Overall, 52.5% achieved a definite response, and 59.3% received bladder-sparing therapy. Bladder preservation was achieved in 86.7% (13/15) of cT2 and 50.0% (22/44) of cT3–4 patients. The bladder-sparing cohort showed superior survival by (both p < 0.05), with 5-year OS of 80.0% (95% CI, 67.8–94.4) and RFS of 59.1% (95% CI, 44.7–78.1), compared with 33.3% (95% CI, 18.9–58.7) and 28.6% (95% CI, 15.0–54.3) in the non-bladder-sparing group. In cT2 patients, 5-year OS and RFS were 86.7% (95% CI, 71.1–100.0) and 73.3% (95% CI, 54.0–99.5), respectively. In cT3–4 patients treated with bladder-sparing therapy, 5-year OS and RFS were 72.7% (95% CI, 56.3–93.9) and 48.3% (95% CI, 31.0–75.1), compared with 31.8% (95% CI, 17.3–58.7) and 26.5% (95% CI, 13.1–53.9) after RC, respectively. Among definite responders, OS and RFS did not differ significantly between those downstaged to T0/Ta and T1 (p = 0.46 and 0.67, respectively). Conclusions: NAC-guided bladder-sparing therapy in MIBC achieved durable long-term survival, outperforming RC in selected patients. Patients achieving ≤T1 after NAC derived comparable survival whether downstaged to T0/Ta or T1, supporting a selective bladder-sparing approach for well-responding MIBC. Clinical trial information: NCT02861196 .

A phase II study of lutetium-177 DOTATATE in metastatic prostate cancer with neuroendocrine differentiation.

TPS292 Background: Neuroendocrine differentiated prostate cancer (NED PCa) is an aggressive form of prostate cancer with few treatment options and a poor prognosis. There is evidence that NED PCa and advanced castration resistant prostate cancers (CRPC) overexpress the somatostatin receptor (SSTR), which can be targeted with Lu-177 DOTATATE, a radiopharmaceutical therapy that improves survival in neuroendocrine tumors of the midgut. We are conducting a phase II trials investigating Lu-177 DOTATATE in NED PCa. Methods: This is a phase II trial run through the National Cancer Institute’s (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN). Key inclusion criteria include evidence of neuroendocrine differentiation by histology (i.e. small cell carcinoma or positivity for synaptophysin or chromogranin A), molecular features (TP53, PTEN, and/ or RB1 loss), serum markers (chromogranin A or neuron-specific enolase), or clinical factors (progression of visceral metastases in the absence of PSA progression). Patients must have a positive Ga-68 DOTATATE PET/CT to proceed with Lu-177 DOTATATE therapy, defined as at least 1 lesion with a maximum standardized uptake value (SUV max ) greater than the mean SUV of normal liver. The primary objective for the trial is objective response rate (ORR), defined by Prostate Cancer Working Group 3 (PCWG3) criteria. Secondary objectives include 6-month radiographic progression-free survival as well as the correlation between ORR and change in fluorodeoxyglucose PET/CT signal pre- to mid-treatment. Exploratory objectives include SPECT/CT-based dosimetry of Lu-177 DOTATATE and gene expression analysis of circulating tumor cells collected prior to treatment, during treatment, and at time of progression. A pre-specified activity goal for the first 15 enrolled patients was met, and accrual of an additional 10 patients is currently in progress. Clinical trial information: NCT05691465 .

Novel SLC16A2 mutations impair thyroid hormone transport and drive neurodevelopmental deficits in Chinese patients with allan-herndon-dudley syndrome

Abstract This study elucidates the molecular pathogenesis of neurodevelopmental deficits in Chinese Allan-Herndon-Dudley syndrome (AHDS) patients caused by pathogenic SLC16A2 mutations. Genetic analysis of three Han Chinese patients with severe intellectual disability and global developmental delay identified two novel truncating mutations (c.1093del [p.A365Lfs35] and c.270_271del [p.G91Lfs28]) and a hemizygous de novo splice-site mutation (c.1026 + 1G > A). Structural modeling predicted that the c.1093del variant causes C-terminal truncation of transmembrane helix 12, which is likely to disrupt the T3-binding pocket by impairing the critical Arg445–His415 hydrogen bond. Functional studies confirmed significantly reduced SLC16A2 expression ( P  < 0.05) accompanied by dysregulated thyroid metabolism (increased DIO2 and HR ; P  < 0.01) and downregulated neurodevelopmental genes ( Nrgn and KIF9 ; P  < 0.001). Mechanistically, MCT8 deficiency impaired cerebral thyroid hormone uptake, driving synaptic and axonal defects through dysregulation of both transcriptional and cytoskeletal programs: T3-dependent transcriptional suppression via inactivation of the Nrgn promoter thyroid response element, and disruption of the KIF9 signaling axis. These findings establish novel genotype-phenotype correlations in Chinese AHDS patients and provide a mechanistic framework for understanding the neurodevelopmental consequences of impaired thyroid hormone transport, with patient-derived iPSCs serving as a valuable resource for future therapeutic development.

Overall survival from the phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in first-line metastatic castration-resistant prostate cancer (mCRPC) with DNA repair defects (BRCAAway).

16 Background: The BRCAAway trial evaluated the efficacy of abiraterone (Abi) versus olaparib (Ola) versus their combination as first-line therapy in patients (pts) with mCRPC harboring germline or somatic homologous recombination repair mutations (HRRm). It showed that first-line treatment with the Abi/Ola combination significantly improved progression-free survival (PFS) compared with either agent alone or sequentially in pts with BRCA1/2 or ATM alterations. Here, we report the overall survival (OS) outcomes per arm. Methods: BRCAAway was a multi-center, open-label, randomized, phase 2 trial. Eligible pts had progressive mCRPC with HRRm and no prior exposure to PARPi or Abi. Pts with HRRm in BRCA1/2 and/or ATM alterations were randomized 1:1:1 to Arm 1: abiraterone 1000 mg QD + prednisone 5 mg BID (Abi/pred), Arm 2: olaparib 300 mg BID (Ola), or Arm 3: abiraterone/prednisone + olaparib (Abi/pred + Ola). Pts with noncanonical HRRm received olaparib alone (nonrandomized Arm 4: exploratory). Crossover was permitted in Arms 1 and 2. OS was assessed as a key secondary endpoint. OS was measured from randomization until death, and pts were censored at their last clinical encounter. Median OS and landmark OS rates at 24, 36, and 60 months for each arm were estimated using the Kaplan-Meier method. Hazard ratios (HRs) between the randomized arms were obtained using Cox proportional hazards regression, separately comparing Arm 3 vs 1 and Arm 3 vs 2. Results: As of September 30, 2025 (data cutoff), there were 34/61 deaths in the randomized pts (11/19 Arm 1 pts, 13/21 Arm 2 pts, and 10/21 Arm 3 pts) and 12/17 deaths in exploratory Arm 4 pts. Median follow-up time was 46.2 months (m). Arm 3 had the longest median OS of 68 m (95% CI: 38–not reached [NR]), compared to Arm 1 median of 28 m (95% CI: 13–NR) and HR = 0.39 (95% CI: 0.16–0.93), and compared to Arm 2 median of 37 m (95% CI: 26–NR) and HR = 0.51 (95% CI: 0.22–1.18) (Table 1). Arm 3 also had the highest 24-, 36-, and 60-month landmark OS rates compared to Arms 1 and 2. Median OS for the exploratory Arm 4 was 39 m (95% CI: 21–49). Conclusions: In pts with mCRPC harboring BRCA1/2 or ATM alterations, abiraterone/prednisone + olaparib was well tolerated and resulted in significantly improved OS (median of >5 years) compared to either agent used alone or sequentially. Clinical trial information: NCT03012321 . Treatment Median OS (95% CI) in Months 24-Month OS Rate (95% CI) 36-Month OS Rate (95% CI) 60-Month OS Rate (95% CI) HR (95% CI) for Arm 3 vs Arm 1 and Arm 2 Arm 1: Abi/pred (n=19) 28 (13, NR) 55% (29%, 75%) 41% (18%, 63%) 31% (9.5%, 55%) 0.39 (0.16, 0.93) Arm 2: Ola (n=21) 37 (26, NR) 85% (60%, 95%) 53% (29%, 72%) 42% (21%, 63%) 0.51 (0.22, 1.18) Arm 3: Abi/pred + Ola (n=21) 68 (38, NR) 90% (67%, 98%) 86% (62%, 95%) 55% (30%, 74%) 1 [reference] Arm 4: Exploratory (n=17) 39 (21, 49) 66% (36%, 84%) 51% (24%, 73%) 15% (2.4%, 37%) -

When ctDNA says ‘maybe’: improving the dynamics of MRD trials

Submicron Structure Confined Polymers for High‐Performance Intrinsically Stretchable Light‐Emitting Diodes (Adv. Mater. 16/2026)

The clinical impact of germline variants in DNA repair genes in patients who underwent curative surgery for localized prostate cancer.

321 Background: Family history represents a significant risk factor for prostate cancer (PCa), emphasizing its genetic basis. Early identification of germline pathogenic variants (PVs) in DNA repair genes (DRGs) is crucial for timely PCa diagnosis, prognosis, and for informing at-risk relatives. Conversely, the presence of variants of uncertain significance (VUS) has been associated with worse clinical outcomes. This study aimed to assess how the presence of germline PVs and VUS affect clinical and pathological outcomes in a monocentric cohort of patients who underwent robot-assisted laparoscopic prostatectomy (RALP) for PCa. Methods: This prospective study, supported by AIRC - Fondazione AIRC per la Ricerca sul Cancro (registered and emended with the number ID-IG-25027-V1.3), was conducted at a tertiary referral center in collaboration with the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics. A total of 179 men aged 58–70 years who underwent RALP for localized PCa were screened for germline PVs and VUS in DRGs prior to surgery. Patients were enrolled if they had an ISUP grade ≥3 at biopsy and/or a confirmed PCa diagnosis at ≤50 years of age. Individuals harboring a VUS or PVs were compared to those with negative genetic results. Results: Of the 179 patients screened between 2021 and 2024, 163 shared the results of genetic testing. Median age at surgery did not differ between groups (65 years, IQR 59–70). Among them, 114 (69.9%) tested negative, while 39 (29.4%) and 9 (5%) carried a VUS or PVs in DRGs, respectively. The most frequent VUS involved ATM (22.2%), CHEK2 (15.6%), BRCA2 (13.3%), ATR (6.7%), NBN (6.7%), RAD51D (6.7%), and MSH6 (4.4%). The nine PVs identified were: BRCA2, PALB2 + NBN, PALB2 + BRCA2, BRCA1 PALB2, CHEK2 + PMS2, CHEK2, and ATM . A family history of cancer was reported in 50% of VUS/PV carriers compared to 34.6% of non-carriers. High-grade PCa (ISUP >3) was found in 46.3% of carriers versus 38.0% of non-carriers. A pathological stage ≥pT3a occurred in 53.6% of carriers versus 45.1% of non-carriers, while nodal involvement (pN1) was more frequent among carriers (21.4% vs 12.6%). Biochemical recurrence (BCR) occurred in 36.8% of carriers versus 30.4% of non-carriers. Conclusions: This study provides valuable insight into the role of germline VUS, by the first, and PVs in DRGs among PCa patients, suggesting that such variants may confer a less favorable disease course. Although differences did not reach statistical significance, carriers tended to present with higher-grade and more advanced disease at final pathology. Genetic screening for PCa may therefore aid not only in early detection among high-risk individuals but also in guiding clinical management and follow-up strategies.

Using large language models for grading CTCAE toxicity after radiation therapy for prostate cancer.

357 Background: Prostate cancer (PCa) is the most incident cancer in adult males in the United States, and the second highest in the world. CTCAE is the standardized method to grade the severity of treatment-related adverse events (AEs), but are tedious to collect and subject to inter-observer variability. This study aimed to evaluate the performance of LLMs in automatically extracting and grading CTCAE toxicities from clinical notes and patient-reported outcomes of PCa patients from a clinical trial. Methods: A total of 55 patients from NCT02874014 trial, undergoing proton therapy (PT) for localized PCa, were included. The ground truth of CTCAE graded toxicities was obtained from the trial’s results. Clinical notes within 3 days, and the most recent patient questionnaires within 90 days of toxicity assessment were retrieved from the electronic health record. A comprehensive prompt was developed to extract and CTCAE grade toxicities from the retrieved records. LLMs used for this analysis were OpenAI GPT-4o and Gemini 2.0 Flash. Phase 1 evaluated both LLMs' performance against the ground truth. To ensure the metrics reflected the models’ performance based only on the information available in the text provided, cases where both LLMs contradicted the ground truth were manually reviewed. Phase 2 recalculated LLMs' performance metrics using this adapted ground truth. A conservative stepwise ensemble model was developed to leverage the complementary strengths of both LLMs. Results: In the conservative stepwise ensemble model, Gemini 2.0 Flash served as the initial screening platform to identify AEs in step 1. All cases with identified toxicity events were then reviewed and confirmed using OpenAI GPT-4o in step 2. This effectively reduced false positive rates while preserving high sensitivity. The ensemble model achieved strong performance metrics: binary accuracy (0.954), sensitivity (0.961), specificity (0.953), F1 score (0.836), and grade accuracy (0.932). Conclusions: This study demonstrates the feasibility of the use of LLMs for extraction and CTCAE toxicity grading in PCa patients treated with RT. The ensemble model achieved strong performance metrics. Further validation is needed for other cancer diagnosis and treatment modalities. Phase Model Binary Accuracy Precision Sensitivity Specificity F1 Score Grade Accuracy 1 Gemini 0.946 0.672 1.000 0.939 0.804 0.919 1 OpenAI 0.940 0.785 0.637 0.978 0.703 0.895 2 Gemini 0.956 0.735 1.000 0.950 0.848 0.927 2 OpenAI 0.954 0.917 0.679 0.991 0.780 0.903

Hydrostructural and dynamic characteristics of compacted Nanning red clay considering wetting-drying impacts

EMPOWER01: A phase II study of zanidatamab combined with bacillus Calmette-Guerin (BCG) in HER2-positive high-risk non-muscle-invasive bladder cancer (HR NMIBC).

TPS899 Background: Zanidatamab was a humanised, bispecific monoclonal antibody directed against two non-overlapping domains of HER2. Zanidatamab binded adjacent HER2 molecules in trans and initiates distinct HER2 reorganization, induced HER2 capping and the formation of large HER2 clusters on the cell surface. Thus, zanidatamab promoted potent CDC and also mediated HER2 internalization and downregulation, inhibition of cell signaling and tumor growth, as well as ADCC, and ADCP. HER2-targeted therapies may improved outcomes for patients (pts) with HER2-positive cancers. BCG induction and maintenance after transurethral resection of bladder tumor (TURBT) was standard of care in HR NMIBC. Our study was established to evaluate the efficacy and safety of zanidatamab combined with BCG as a novel bladder-preserving treatment for HER2-positive HR NMIBC pts. Methods: This open-label phase II study enrolled BCG-naïve HR NMIBC pts with multiple papillary tumors (high-grade Ta or T1 tumors), and all pts were HER2-positive (IHC 3+ or 2+ with FISH+). Firstly, the papillary tumors should be removed all visible lesions by TURBT. Secondly, pts were administered zanidatamab (30 mg/kg, ivgtt), every 3 weeks for 1 cycle. Then, pts received second TURBT, and pts were administered 4 cycles of zanidatamab (30 mg/kg, Q3W, ivgtt) and 18 instillations of BCG. Specifically, pts were started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks. The primary end point was recurrence-free survival (RFS) rate at 12 months. Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a RFS rate at 12 months was no less than 75.5% and the study would enroll 20 pts. Clinical trial information: ChiCTR2200067158.

Pressure‐Induced Forward‐Shift of Proton‐Coupled Electron Transfer Step Boosts CO‐to‐Acetate Throughput

ABSTRACT Regulating the rate‐determining step (RDS) constitutes the central challenge in catalysis science, as it governs both reaction efficiency and pathway selectivity. In CO/CO 2 electroreduction, the voltage‐insensitive * CO‐ * CO dimerization — a non‐proton‐coupled electron transfer (PCET) step — critically limits multi‐carbon production rates by restricting accessible current densities below industrial demands. Traditional catalyst modification strategies often induce undesired perturbations to downstream pathways while addressing this bottleneck. Here, we demonstrate a physical microenvironment engineering strategy that reconfigures reaction sequences through pressure modulation. Elevated CO pressure enriches surface * CO coverage, redirecting proton reaction pathways to preferentially hydrogenate * CO intermediates rather than coupling for hydrogen evolution, evidenced by a reduced Tafel slope for acetate and hydrogenated intermediates resolved from high‐pressure operando Raman spectroscopy. When integrated with a synthetic Cu–Pd single‐atom alloy (SAA) catalyst, the CO‐to‐acetate conversion system is selective with a Faradaic efficiency of 85%, energy‐efficient with an energy efficiency of 33%, and selective with an operation duration of 700 h. Interestingly, our system can maintain a high acetate selectivity (>75%) across an exceptionally broad current density range from 3 to 1500 mA cm − 2 , potentially compatible with intermittent renewable power sources.

Non‐Hermitian Edge Burst of Sound

ABSTRACT Non‐Hermitian band topology can give rise to phenomena with no counterparts in Hermitian systems. A well‐known example is the non‐Hermitian skin effect (NHSE), where Bloch eigenstates localize at a boundary, induced by a nontrivial spectrum winding number. In contrast, recent studies on lossy non‐Hermitian lattices have uncovered an unexpected boundary‐localized loss probability—a phenomenon that requires not only non‐Hermitian band topology but also the closure of the imaginary (dissipative) gap. Here, we demonstrate the non‐Hermitian edge burst in a classical‐wave metamaterial: a lossy nonreciprocal acoustic crystal. We show that, when the imaginary gap remains closed, edge bursts can occur at the right boundary, left boundary, or both boundaries simultaneously, all under the same non‐Hermitian band topology; the latter scenario is known as a bipolar edge burst. The occurrence of each scenario depends on the number and location of the imaginary gap closure points in the eigenenergy spectra. These findings generalize the concept of edge burst from quantum to classical wave systems, establish it as an intrinsic material property, and enrich the physics of the complex interplay between non‐Hermitian band topology and other physical properties in non‐Hermitian systems.

Ultra-hypofractionated radiotherapy and concomitant oral relugolix for treatment of intermediate risk prostate cancer (ULTRA-HERO).

TPS411 Background: Radiotherapy (RT) and concomitant short course androgen deprivation therapy (ADT) is one of the standard approaches for patients affected by localized intermediate risk prostate cancer. However, effects of testosterone depletion may have a significant impact on bone mineral density, metabolic changes, increased insulin resistance, sexual dysfunction, hot flashes. Moreover, many men undergoing ADT may fail to recover their mean baseline eugonadal testosterone level even after long term from ADT cessation. Relugolix is an oral, highly selective, GnRH antagonist recently tested in a randomized phase III trial showing reduced risk in terms of cardiovascular events and rapid testosterone recovery if compared to Leuprolide. Given its rapid testosterone recovery, relugolix may significantly reduce the long term negative impact of ADT in the specific setting of a short term duration treatment. However, prospective evidence is needed in order to assess if concomitant treatment with short course ADT with relugolix and RT may obtain the same disease control benefit if compared to historical data related to standard ADT with LH- RH analogues. With this purpose, we designed an interventional trial aimed to evaluate rate of complete biochemical response in an homogeneous cohort of patients affected by intermediate risk localized prostate cancer undergoing prostate radiotherapy+short course oral relugolix. Methods: ULTRA-HERO is a Prospective, no-profit, single arm phase II, interventional multicentric trial aimed to evaluate the effectiveness of concomitant prostate RT and short course oral relugolix. In brief, patients affected by unfavouralbe intermediate risk prostate carcinoma (Gleason 4+3 and or>50% of biopsy cores positive and or >2 intermediate risk factors), who are deemed suitable for ultrahypofractionated treatment on prostate (IPSS < 15, prostate volume <90 cc) will undergo definitive treatment consisting in ultrahypofractionated prostate radiotherapy for a total dose of 36.25 Gy in 5 fractions, 7.25 Gy each, every other day and concomitant treatment with oral relugolix administered with an attack dose of 360 mg (3 tablets) the first day, followed by a daily dose of 120 mg for a total duration of 6 months. All patients with neuroendocrine differentiation, metastatic disease at diagnosis or any high risk features are excluded from the trial. Primary endpoint of the study will be rate of patients with complete biochemical response (nadir < 0.5 ng/ml) at 6 months after end of radiotherapy. Enrollment started in May 2025 and 20 patients have been enrolled up to date. A final sample size of sample size of 73 patients will be needed to estimate the expected proportion of patients with complete biochemical response with a 5% precision margin and a 95% confidence interval. Clinical trial information: CTIS ID: 36502 .