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Introduction Double‐negative prostate cancer, an androgen receptor–independent prostate cancer without features of neuroendocrine tumors, is refractory to treatment but could be an ideal candidate for individualized treatment. Case presentation An 85‐year‐old patient with metastatic castration‐resistant prostate cancer without prostate‐specific antigen progression presented with local recurrence and liver and lung metastases 6 months after orchiectomy and apalutamide. A liver tumor biopsy led to a diagnosis of double‐negative prostate cancer. FoundationOne® CDx showed BRCA2 mutation and high tumor mutation burden. Olaparib and pembrolizumab were administered sequentially, and the patient responded to each treatment for 5 months until radiographic progression. Conclusion Sequential use of olaparib and pembrolizumab may be effective for double‐negative prostate cancer with BRCA2 mutations and high tumor mutation burden.

Abstract Ice nucleation is a crucial process in nature and industries; however, the role of the free surface of water in this process remains unclear. To address this, we investigate the microscopic freezing process using brute-force molecular dynamics simulations. We discover that the free surface assists ice nucleation through an unexpected mechanism. The surface-induced negative pressure enhances the formation of local structures with a ring topology characteristic of Ice 0-like symmetry, promoting ice nucleation despite the symmetry differing from ordinary ice crystals. Unlike substrate-induced nucleation via water-solid interactions that occurs directly on the surface, this negative-pressure-induced mechanism promotes ice nucleation slightly inward the surface. Our findings provide a molecular-level understanding of the mechanism and pathway behind free-surface-induced ice formation, resolving the longstanding debate. The implications of our discoveries are of substantial importance in areas such as cloud formation, food technology, and other fields where ice nucleation plays a pivotal role.

Introduction While immune checkpoint inhibitors represent the mainstream treatment for metastatic renal cell carcinoma, a standardized approach following immune checkpoint inhibitors remains unclear. We report a case of metastatic renal cell carcinoma treated with nivolumab rechallenge. Case presentation A 60‐year‐old male with metastatic melanoma was referred to the urology division due to right renal cancer. He was undergoing nivolumab treatment for metastatic melanoma. Radical nephrectomy revealed clear cell renal cell carcinoma, pT3a. Two months post‐surgery, multiple metastases were identified. Despite subsequent administration of interferon‐α, axitinib, and temsirolimus, the metastases progressed. Consequently, nivolumab rechallenge and palliative radiotherapy were initiated, resulting in a durable response for 20 months. However, disease progression occurred, and he died of cancer 4 years after nephrectomy. Conclusion This is the first report of nivolumab rechallenge in metastatic renal cell carcinoma. Although the utility remains unclear, this case suggests that some patients may benefit from nivolumab rechallenge.

Abstract Some low-coordination materials, including water, silica, and silicon, exhibit polyamorphism, having multiple amorphous forms. However, the microscopic mechanism and kinetic pathway of amorphous-amorphous transition (AAT) remain largely unknown. Here, we use a state-of-the-art machine-learning potential and local structural analysis to investigate the microscopic kinetics of AAT in silicon after a rapid pressure change. We find that the transition from low-density-amorphous (LDA) to high-density-amorphous (HDA) occurs through nucleation and growth, resulting in non-spherical interfaces that underscore the mechanical nature of AAT. In contrast, the reverse transition occurs through spinodal decomposition. Further pressurisation transforms LDA into very-high-density amorphous (VHDA), with HDA serving as an intermediate state. Notably, the final amorphous states are inherently unstable, transitioning into crystals. Our findings demonstrate that AAT and crystallisation are driven by joint thermodynamic and mechanical instabilities, assisted by preordering, occurring without diffusion. This unique mechanical and diffusion-less nature distinguishes AAT from liquid-liquid transitions.

Colloidal gels, sparse particle networks with large voids, are fundamental model systems of disordered porous materials. Unlike dense amorphous solids, they exhibit significant volumetric deformation while expelling solvents when subjected to external compression. Despite their importance in both natural and industrial settings, the relationship between their network microstructure and compressive yielding behavior has remained elusive. To address this problem, we employ confocal microscopy and a specially designed sample cell to observe the gravity-induced collapsing of colloidal gels at a single-particle level. The experimental insight gained is complemented by simulation results for gravitational collapse and homogeneous uniaxial compression. We find that, during compression, the microstructure of gels is uniquely determined solely by the local volume fraction. This relationship remains independent of the deformation strain history but is subtly influenced by the preparation history of the initial state. In contrast, compressive stress evolves as a unique function of local volume fraction, unaffected by both preparation and strain history, as long as the interparticle interaction remains identical. Moreover, we unveil that local yielding occurs in highly strained, narrow network domains, while highly stressed particles form chainlike structures to support the external stress. These findings suggest that colloidal gels undergoing compressive plastic deformation mechanically self-organize into a unique history-independent state to satisfy mechanical balance in a quasistatic condition, providing crucial microscopic insights into the compressive yielding behavior of particle network materials.

Free electron mobility ( μ _free ) in 4H-SiC(0001) MOSFETs with gate oxides annealed in NO or POCl _3 was calculated in a wide range of effective normal field ( E _eff ) from 0.02 to 2 MV cm ^−1 , taking account of scattering by fixed charges and trapped electrons. The present calculation indicates that the Hall mobility in the high- E _eff region experimentally obtained for NO-annealed MOSFETs (14 cm ^2 V ^−1 s ^−1 at 1.1 MV cm ^−1 ) is much lower than that for POCl _3 -annealed MOSFETs (41 cm ^2 V ^−1 s ^−1 ) due to severe Coulomb scattering by electrons trapped at a very high density of interface states.

Importance sampling techniques significantly reduce variance in physically based rendering. In this article, we propose a novel online framework to learn the spatial-varying distribution of the full product of the rendering equation, with a single small neural network using stochastic ray samples. The learned distributions can be used to efficiently sample the full product of incident light. To accomplish this, we introduce a novel closed-form density model, called the Normalized Anisotropic Spherical Gaussian mixture, that can model a complex light field with a small number of parameters and that can be directly sampled. Our framework progressively renders and learns the distribution, without requiring any warm-up phases. With the compact and expressive representation of our density model, our framework can be implemented entirely on the GPU, allowing it to produce high-quality images with limited computational resources. The results show that our framework outperforms existing neural path guiding approaches and achieves comparable or even better performance than state-of-the-art online statistical path guiding techniques. [ABSTRACT FROM AUTHOR]

This study investigated the efficacy and safety profiles of neoadjuvant chemoradiotherapy (NCRT) followed by radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). Of the 119 patients, 111 underwent RC; ypT0 and downstaging to ≤ypT1 were observed in 42 and 76 patients, respectively. This is the largest series of patients with MIBC undergoing NCRT followed by RC. Introduction: Cisplatin-based systemic chemotherapy is recommended as neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) before radical cystectomy (RC). However, clinical challenges include the possibility of primary chemoresistance and limited feasibility in patients with renal impairment. This study investigated the efficacy and safety profiles of neoadjuvant chemoradiotherapy (NCRT) followed by RC. Materials and Methods: We retrospectively analyzed 119 patients with nonmetastatic MIBC, who were pathologically diagnosed with urothelial carcinoma and underwent NCRT before RC. The pathological response to NCRT was evaluated using RC specimens. Recurrencefree survival (RFS) and cancer-specific survival (CSS) were compared according to pathological responses to NCRT. Results: Of the 119 patients, 111 (93%) underwent RC; ypT0 and downstaging to ≤ypT1 were observed in 42 (38%) and 76 (68%) patients, respectively. In the multivariable analysis, smaller tumor size was independently associated with ypT0. During a median follow-up of 5.2 years, 28 (25%) patients developed recurrence and 22 (20%) died of bladder cancer after RC. The 5-year RFS and CSS rates were 75% and 80%, respectively. The 5-year RFS rates in patients with ypT0, ypTa/is/1, and ≥ypT2 were 87%, 87%, and 46%, respectively. Similarly, patients with ypT0 and ypTa/is/1 had more favorable CSS (90% and 87% at 5 years, respectively) than those with ≥ypT2 (60%, P = .001). None of the patients experienced ≥grade 4 adverse events related to NCRT or ≥grade 4 complications of RC. Conclusions: This study demonstrated sufficient efficacy and safety profile of NCRT followed by RC. Chemoradiotherapy may be a helpful alternative for neoadjuvant treatment before RC. [ABSTRACT FROM AUTHOR]