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Novel Systemic Anticancer Treatments and Health Services Use at the End of Life Among Adults With Cancer
No full textPURPOSE Use of chemotherapy at the end of life (EOL) is discouraged, but evidence to guide decisions on the use of novel systemic anticancer treatment (SACT) agents is lacking. We examined trends of use among SACT types and association with health services use at the EOL.MATERIALS AND METHODS We analyzed Canadian Ontario Cancer Registry data for adults diagnosed with solid tumors or hematologic malignancies within 5 years of death who received SACT between March 2015 and March 2021. Receipt of SACT in the last 30 days of life was categorized as chemotherapy alone, chemotherapy and immunotherapy, immunotherapy alone, and targeted therapy alone. Outcomes included high health services use, including multiple (≥2) emergency department (ED) visits, multiple (≥2) hospitalizations, or any (≥1) intensive care unit admission, and hospital deaths. Segmented linear regression estimated monthly trends; multivariable logistic regression estimated adjusted odds ratios (aORs) of outcomes for various SACT types.RESULTSAmong 68,963 patients, 18,337 (26.6%) received SACT at the EOL. From March 2015 to March 2020, use of SACT at the EOL increased (0.072% per month; P <.001), mainly driven by increased use of immunotherapy alone (0.064% per month; P <.001). Adjusted odds of high health services use and hospital death were more than two-fold greater among patients receiving SACT at the EOL (vs. none); individual aORs of high health services use and hospital death were 2.20 and 2.72 for chemotherapy alone, 2.36 and 3.10 for chemotherapy and immunotherapy, 1.92 and 2.27 for immunotherapy alone, and 1.75 and 2.37 for targeted therapy alone, respectively.CONCLUSION Use of SACT at the EOL increased significantly over time, driven by increased use of immunotherapy. SACT use at the EOL, regardless of its type, was associated with high health services use and hospital death. Guidelines on the use of SACT at the EOL should include novel cancer treatments.</p
荀子對法家的批判
No full text《荀子》有句著名主張：「有治人，無治法」（《荀子‧君道》）。本章將
這一主張置於先秦晚期的「法家」思想脈絡中，將它解讀為對法家的一種批
判之基礎，並闡明它對「法」惑「標準」（standards）、規範、法律及制度之
運作所抱持的深刻見解。法家思想試圖透過建立一套明確的、精準的行為標
準之體系，來達成治理的無偏私性（impartiality）與一致性（consistency），
並透過獎勵合作與懲罰失敗，來消除人類判斷及動機之不可靠所帶來的風
險。《荀子》提出強而有力的論證，駁斥企圖建立上述體系的想法，並強
調倫理專技（ethical expertise）、權衡（discretion）以及品格，在包括法治
（rule of law）在內的任何制度之運作中的核心地位。荀子認為，唯有透過讓
具備資格的各方人士，針對法制或其他標準的含義及其應用進行公開的、批
判性的討論，才能達成治理的無偏私性與一致性。本章的結論是：《荀子》
用以反對法家的論點，至今依然適用，並且它們有助於解釋當代體制的敗筆
所在。儒家傳統對於道德教育在公民制度之存續上所起的作用的強調，即使
其具體內容可能不合於今日，從形式來看仍然具有現實意義
Study of the effectiveness of different pelvic floor muscle training methods for improving urinary incontinence in patients with prostate cancer after radical prostatectomy
Get PDFIntroduction: To compare the effects of different pelvic floor muscle training (PFMT) modes on improving iatrogenic stress urinary incontinence (SUI) recovery in prostate cancer (PCa) patients after radical prostatectomy (RP). Methods: PCa patients who underwent RP were prospectively enrolled and randomized into standard PFMT (S-PFMT) group, somatosensory interactive PFMT (SI-PFMT, an enhanced PFMT) group, and standard PFMT combined with magnetic stimulation (S-PFMT+MS) group. SUI status was evaluated through the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores and 1-hour pad test. Results: 101 subjects were enrolled, including 48 in S-PFMT group, 39 in SI-PFMT group, and 14 in S-PFMT+MS group. All groups showed significant ICIQ-UI SF score improvement at 3 and 6 months post-RP compared with baseline (all p p = 0.012). Compared with those in the other two groups, patients in the S-PFMT+MS group exhibited significantly better SUI improvement (p = 0.033 vs. S-PFMT; p = 0.011 vs. SI-PFMT) at 6 months. Bayesian survival analysis revealed the superior efficacy of the S-PFMT+MS intervention over an extended period. Conclusions: PCa patients may benefit from magnetic stimulation in addition to standard PFMT for post-RP SUI recovery. published_or_final_versio
CEST MRI data analysis using Kolmogorov-Arnold network (KAN) and Lorentzian-KAN (LKAN) models
Get PDFPurposeTo investigate the potential of using Kolmogorov-Arnold Network (KAN) and propose Lorentzian-KAN (LKAN) for CEST MRI data analysis (CEST-KAN/CEST-LKAN).MethodsCEST MRI data acquired from 27 healthy volunteers at 3 T were used in this study. Data from 25 subjects were used for training and validation (548 865 Z-spectra), whereas the remaining two were reserved for testing (51 977 Z-spectra). The performance of multi-layer perceptron (MLP), KAN, and LKAN models was evaluated and compared to conventional multi-pool Lorentzian fitting (MPLF) method in generating ΔB0, water, and multiple CEST contrasts, including amide, relayed nuclear Overhauser effect (rNOE), and magnetization transfer (MT).ResultsThe KAN and LKAN showed higher accuracy in predicting CEST parameters compared to MLP, with average reductions in test loss of 28.37% and 32.17%, respectively. Voxel-wise correlation analysis also revealed that ΔB0 and four other CEST parameters from the KAN and LKAN had higher average Pearson coefficients than MLP by 1.57% and 2.84%, indicating superior performance. LKAN exhibited a shorter average training time by 37.26% and a smaller average test loss by 5.29% compared to the KAN. Furthermore, our results demonstrated that even smaller KAN and LKAN could achieve better accuracy than MLPs, with both KAN and LKAN showing greater robustness to noisy data compared to MLP.ConclusionThis study demonstrates the feasibility of KAN and LKAN for CEST MRI data analysis, highlighting their superiority over MLP. The findings suggest that CEST-KAN and CEST-LKAN have the potential to be robust and reliable post-analysis tools for CEST MRI in clinical settings.published_or_final_versio
Exploring ribosomally synthesized and post-translationally modified peptides through SPECO-based genome mining
No full textGenome mining is a computational method that automatically identifies and annotates biosynthetic gene clusters (BGCs) from genomic data, making it a valuable resource for discovering natural products (NPs) due to the wealth of sequencing data available. While different genome mining tools exhibit some similarities, each possesses unique strengths and operates in distinct manners. However, finding new ribosomally synthesized and post-translationally modified peptides (RiPPs), one of the largest yet primarily underexplored NP families in bacteria, remains challenging, primarily because many available mining tools are based on logic with inherent biases towards known RiPP families. To help address this limitation, we have developed a large-scale small peptide and enzyme co-occurrence (SPECO) analysis workflow founded on the universal biosynthetic logic of bacterial RiPPs. This logic implies that precursor and modifying enzymes are clustered together in genetic content and co-conserved, similar precursors undergo modification by homologous tailoring enzymes. In this chapter, we provide detailed instructions for utilizing SPECO to uncover new RiPP chemistry. Additionally, we present a holistic genome mining workflow that merges the capabilities of SPECO with existing bioinformatics tools, such as AlphaFold-Multimer. We use the radical S-adenosylmethionine (rSAM) enzyme as an example to provide a step-by-step guide, revealing the largely unexplored enzymology of rSAM enzymes in peptide macrocyclization. Given the rapidly increasing number of available bacterial genome sequences, we envisage that our approach will be highly applicable for discovering new enzymes for RiPPs biosynthesis.</p
Contested rent-based urban governance: Land rent dissipation and redistribution under scalar politics in China
No full textDespite the recent resurgence of land rent theory in political economy, its application to China's urban governance, characterised by a land-based development model, remains underexplored. This study introduces the concept of land rent capture, which highlights the rentier nature of the local state, to examine territorial contestation among China's multi-level local governments and its broader implications. The theoretical framework we propose links rent-based urban governance – the strategic use of land rent to finance urban development – with scalar politics, positing that competition over land rent has become a crucial dimension of intergovernmental struggles at the local level. Using a mixed-methods approach that includes in-depth interviews, archival research, and statistical analysis, our case study of Zhongshan investigates the operation and distribution of land rent and its historical interplay with inner-city power dynamics during the post-reform era. The findings reveal that implicit land rent distribution prompted rent-seeking by discretionary lower-level governments, resulting in a developmental crisis and rent dissipation. In response, a scalar restructuring process was initiated to redistribute land rent among government tiers for more efficient rent operation, although these efforts are impaired by entrenched rent dissipation and the real estate downturn. Theoretically, this study contributes to understanding the role of land rent in shaping scalar relationships within China's cities. Practically, it highlights scalar restructuring as an interim strategy for cities with low-rent land markets but critiques the long-term viability of rent-based governance due to the inevitable dissipation of land rents
Virtualized 3D Gaussians: Flexible Cluster-based Level-of-Detail System for Real-Time Rendering of Composed Scenes
No full text3D Gaussian Splatting (3DGS) enables the reconstruction of intricate digital 3D assets from multi-view images by leveraging a set of 3D Gaussian primitives for rendering. Its explicit and discrete representation facilitates the seamless composition of complex digital worlds, offering significant advantages over previous neural implicit methods. However, when applied to large-scale compositions, such as crowd-level scenes, it can encompass numerous 3D Gaussians, posing substantial challenges for real-time rendering. To address this, inspired by Unreal Engine 5’s Nanite system, we propose Virtualized 3D Gaussians (V3DG), a cluster-based LOD solution that constructs hierarchical 3D Gaussian clusters and dynamically selects only the necessary ones to accelerate rendering speed. Our approach consists of two stages: (1) Offline Build, where hierarchical clusters are generated using a local splatting method to minimize visual differences across granularities, and (2) Online Selection, where footprint evaluation determines perceptible clusters for efficient rasterization during rendering. We curate a dataset of synthetic and real-world scenes, including objects, trees, people, and buildings, each requiring 0.1 billion 3D Gaussians to capture fine details. Experiments show that our solution balances rendering efficiency and visual quality across user-defined tolerances, facilitating downstream interactive applications that compose extensive 3DGS assets for consistent rendering performance.</p
Medical Tourism for Gender Identity Affirmation: Transgender Perspectives
Get PDFMedical tourism offers specialized healthcare services and leisure opportunities, serving as a critical journey for transgender individuals seeking gender affirmation. Drawing upon social identity framework, gender affirmation contributes to membership and belongingness within a gender group, enhancing social acceptance. Medical tourism is often the only option for some transgender individuals due to local social stigma and discrimination, exposing them to greater vulnerability. However, there is limited research that explores transgender perspectives. This study deploys planned behavior and protection motivation theories to identify influential factors in transgender medical travel intentions. Employing a structured survey, rigorously designed and distributed among 435 Thai and Filipino transgender participants, the research quantitatively assessed how attitudes, norms, efficacy, and identity factors significantly influence their decisions, overshadowing health threat perceptions. Findings suggest responsible strategies that promote holistic transgender well-being and highlight the need for a nuanced approach when navigating sociocultural and legal dynamics in transgender medical tourism. published_or_final_versio