Acute-on-chronic liver failure (ACLF) is a complex syndrome characterized by acute hepatic decompensation superimposed on pre-existing chronic liver disease or cirrhosis that is associated with acute worsening of portal hypertension, increased risk of infection, organ dysfunction and high short-term mortality. This Review provides a comprehensive update on definitions, pathophysiological mechanisms, clinical presentation and management of ACLF. The severe hepatic injury in ACLF triggers systemic inflammation, which is driven by damage-associated molecular patterns, gut-derived microbial products, and immunometabolic and functional dysregulation. Immune dysfunction can range from hyperinflammation and hypercytokinaemia to immune paresis, which in turn predisposes patients to infection and organ failure. The principles of ACLF management prioritize ameliorating the acute hepatic insult, managing portal hypertension, preventing organ failure and optimizing patients who are eligible for liver transplantation. Emerging options include novel therapies targeting immune modulation and liver regeneration, therapeutic plasma exchange and artificial liver support systems. Well-defined criteria for prompt interventions and selection of patients for transplantation within the first week after diagnosis — the ‘golden window’ — have improved outcomes of liver transplantation in patients with ACLF. The Kyoto ACLF Consensus reflects global efforts on unifying definitions, simplifying treatment end points, refining prediction tools, and filling the void of targeted non-transplantation interventions to improve outcomes in patients with ACLF; however, large knowledge gaps remain and further research is needed. Acute-on-chronic liver failure (ACLF) is a complex syndrome characterized by acute hepatic decompensation superimposed on pre-existing chronic liver disease or cirrhosis. This Review provides an update on definitions, pathophysiological mechanisms, clinical presentation and management of ACLF.
Generative artificial intelligence (AI) is increasingly used in writing assessment, particularly for automated essay scoring (AES) and for generating formative feedback within automated writing evaluation (AWE). While AI-driven AES enhances efficiency and consistency, concerns regarding accuracy, bias, and ethical implications raise critical questions about its role in assessment. This paper examines the impact of generative AI on teacher agency through an ecological perspective, which considers agency as shaped by personal, institutional, and sociocultural factors. The analysis highlights the need for teachers to critically mediate AI-generated scores and feedback to align them with pedagogical goals, ensuring AI functions as an assistive tool rather than a determinant of assessment outcomes. Although AI can streamline assessment, over-reliance risks diminishing teachers’ evaluative expertise and reinforcing biases embedded in AI systems. Ethical concerns, including transparency, data privacy, and fairness, further complicate its adoption. To address these challenges, this paper proposes a framework for responsible AI integration that prioritizes bias mitigation, data security, and teacher-driven decision-making. The discussion concludes with pedagogical implications and directions for future research on AI-assisted writing assessment.
Land ownership disputes often result in final and binding civil judgments that are ineffective in practice, leaving the prevailing party with only a normative victory and no actual restoration of rights. Dwangsom functions as a coercive mechanism to ensure compliance with judgments; however, its application in Indonesia remains jurisprudential and lacks a standardized operational framework. Moreover, studies integrating dwangsom within the frameworks of justice in judgment enforcement, maqāṣid al-sharī‘a, and the Sustainable Development Goals (SDGs) remain limited. This article examines dwangsom as an instrument of judgment enforcement by analyzing Supreme Court Decision No. 1429K/Pdt/2006. It evaluates its relevance from the perspectives of maqāṣid al-sharī‘a and SDG 16. Employing a normative juridical method with statutory, case, and conceptual approaches, the study finds that dwangsom is effective in enforcing non-monetary obligations by altering the incentives of non-compliant parties and accelerating the restoration of rights. It further develops a maqāṣid-based framework for the enforcement of judgments, comprising three indicators: legal certainty, expediency, and proportionality. This framework positions dwangsom as a strategic tool to strengthen the effectiveness of court decisions and enhance access to justice.
In the phase 3 EV-302 study, enfortumab vedotin–pembrolizumab (EV + P) significantly prolonged overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with untreated locally advanced/metastatic urothelial carcinoma (la/mUC). We present a post hoc analysis in a pan-Asian population. Patients from China, Japan, Singapore, South Korea, Taiwan, and Thailand received 3-week cycles of EV (1.25 mg/kg; intravenously; Days 1 and 8) plus P (200 mg; intravenously; Day 1) or chemotherapy (gemcitabine [Days 1 and 8] plus cisplatin/carboplatin [Day 1]). Primary endpoints were PFS and OS. Secondary endpoints included objective response rate (ORR) and safety. Overall, 176 patients were included (EV + P, n = 94; chemotherapy, n = 82). Median follow-up was 28.9 months for EV + P recipients and 26.6 months for chemotherapy recipients. EV + P prolonged PFS and OS versus chemotherapy, reducing the risk of disease progression or death by 63
Dietary patterns rich in plant-based foods, fish, and healthier fats are reportedly beneficial for fertility, but forming generalizable recommendations has been hindered by the lack of studies examining dietary patterns and time-to-conception (TTC) in cohorts with different ethnicities across geographical regions. To study the association of preconception dietary patterns with TTC in the multi-country NiPPeR trial. This study is a secondary analysis of data collected in the NiPPeR randomized controlled trial. Women planning to conceive, without known fertility impairment, were recruited from the community in the UK, Singapore, and New Zealand (NZ). Dietary intake was assessed at preconception prior randomization, and across-site (“pooled”) data-driven dietary patterns were derived (n = 1406). TTC, derived as the number of days between recruitment and the estimated date of achieving a clinical pregnancy, and the chance of achieving a clinical pregnancy within a year, expressed as hazard ratios (HR), were analyzed using Cox proportional hazards models adjusted for preconception body mass index, age and gravidity. Two pooled dietary patterns were identified: “Vegetables, Fruits and Nuts” (VFN), and “Fried potatoes, Processed meat and Sweetened beverages” (FPS). Compared with the lowest quartile of VFN score, those in the highest quartile took a shorter time to conceive [Days till 20
