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.
Hospital-at-home (HaH) is increasingly adopted to expand hospital capacity, however, data from Asian healthcare remain limited. The study compares cost, utilisation, and clinical outcomes of HaH program compared to traditional hospital care in Singapore. This prospective quasi-experimental study compared patients enrolled in the HaH programme with a comparator group of clinically eligible patients who received ward-based care because they lived outside the programme’s catchment area or when HaH capacity was full. Adults admitted to two hospitals within an academic health system between January 2021 and May 2023 screened for eligibility based on clinical, social and functional criteria. The primary outcome was cost per bed day, with secondary outcomes including total episode cost, clinical outcomes, and patient-reported measures. Inverse probability treatment weighting was applied to balance baseline confounders, and regression analyses were used to evaluate outcomes. Among 302 patients (151 HaH, 151 ward), HaH patients were older (mean [SD] age, 58 [21] vs 51 [21] years) with higher Charlson Comorbidity Index (3 [3] vs 2 [3]). The top three diagnoses were cellulitis (43.0
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.
Alternaria alternata is a common airborne fungus that can be found in both indoor and outdoor environments. It is a major allergen linked to respiratory diseases such as allergic rhinitis and asthma. It may also infect the skin, nails, or eyes. In addition, uncharacterized or hypothetical proteins are present but have not yet been identified or associated with specific protein sequences. Domains of undetermined activity refer to molecules with known, experimentally determined activity. Yet, the exact role or structural features of these proteins have not been identified. Many proteins encoded in A. alternata genome remain uncharacterized, including the hypothetical protein XP_018378625.1 containing the SRC1lrK2f domain, whose function is unknown. This research employed a comprehensive in-silico approach to predict its physicochemical features, structural properties, subcellular localization, and protein–protein interactions and 3D structure. The protein was found to be hydrophilic, with an instability index of 46.62 and isoelectric point value of 6.41 which indicates acidic nature. The in-silico analysis indicated that the protein is soluble, with its secondary structure mainly composed of a random coil suggesting structural flexibility. The analysis showed that the protein contains a cytoplasmic domain. Moreover, the protein-protein interactions were examined using STRING software, which showed that the SRC1lrK2f protein has a strong interaction with exodeoxyribonuclease 1, implying a possible role in DNA repair or genome maintenance. These findings provide the first functional insights into the SRC1lrK2f domain in A. alternata and may support the future development of pharmaceutical strategies for managing Alternaria-induced allergic and infectious diseases by advancing our understanding of the biological role of the SRC1lrK2f domain.
