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Major depressive disorder (MDD) is a complex disorder caused by genetic and environmental factors. Previous evidence implicates a potential depression subtype from interaction between childhood maltreatment (CM) and kynurenine pathway (KP) gene. Here, we investigated the top-down multi-omics KP alterations for this subtype.
Methods
A total of 142 patients with MDD receiving monotherapy were included. Individuals carrying IDO2 rs2340953 TT genotype and reporting CM were classified as IDO2-CM group, whereas the remaining patients were categorized as non-IDO2-CM group. Plasma KP metabolites, DNA methylation, KP-related protein, and inflammatory protein were profiled. Group differences were examined using regression models adjusting for relevant covariates.
Results
Thirty patients met criteria for the IDO2-CM group. Compared with non-IDO2-CM, IDO2-CM individuals exhibited significantly poorer response rate to antidepressant at weeks 4 and 8. Metabolite analyses revealed a significantly elevated quinolinic acid (QA)/kynurenine (KYN) ratio and QA/kynurenic acid (KYNA) ratio in IDO2-CM group (β = 0.086, SE = 0.042, P = 0.023; β = 0.164, SE = 0.045, P = 0.0006). Epigenetic analyses of KP genes demonstrated coordinated methylation shifts favoring QA production (hypomethylation of KMO and AFMID; hypermethylation of ACMSD) and suppression of KYNA related enzymes (hypermethylation of CCBL1, CCBL2, AADAT, and GOT2). Proteomic profiling identified reduced circulating levels of KYNU and VCAM1 in IDO2-CM group.
Conclusions
CM interacting with IDO2 genotype defines a biologically distinct MDD subtype characterized by poor antidepressant response and convergent multi-omics evidence of KP bias toward neurotoxic metabolism. These findings support a stratification strategy and highlight the KP as a potential target for precision treatment in depression.
Self-report checklists are commonly used to collect health information in social and epidemiological studies. Little is known about the reliability of such self-report data. This study examined the 6-month test–retest reliability of 28 clinical diagnoses and health histories as self-reported by a sample of adult female mental health service users.
Methods
A convenience sample of female mental health service users (N = 293) provided self-report data on their health histories – including physical, psychiatric, neurodevelopmental and functional domains – two times, approximately 6 months apart. We calculated the agreement rates and Cohen’s kappa of the results.
Results
The results demonstrated high levels of temporal consistency. Agreement rates were ≥84.5% for all conditions, while Cohen’s kappa values were above 0.50 for 21 out of 28 conditions.
Conclusions
Self-report checklists, as widely used in survey studies, can yield reliable health data. Social and health science researchers can employ such checklists to collect health background information of research participants, especially when clinical validation is not feasible or when hospital records are not accessible.
Virtual reality (VR) is a transformative technology for studying language processing and learning. It offers realistic and naturalistic environments while maintaining experimental control, supporting the exploration of social and sensorimotor cues that have often been overlooked in traditional psycholinguistic research. It can also be integrated with behavioral and neurocognitive measures to examine how learning processes influence learning outcomes. These VR characteristics have brought new opportunities and contributed to the expansion of theoretical frameworks on language processing and learning. Through reviewing recent empirical findings, we establish VR as a novel methodology for investigating how embodied and social experiences shape language processing and learning. We emphasize that realizing this potential fully requires real-time multimodal tracking of learning processes, systematic examination of individual differences and development of richer virtual environments and VR-suitable assessment tasks. This review provides methodological insights for future VR research on the neurocognitive bases of language processing and learning.
Bees, as vital pollinators, are currently confronting numerous survival threats. Balanced amino acid nutrient have a positive impact on helping bees to resist pathogens and pesticides. This study aims to explore the interaction between leucine (Leu) and isoleucine (Ile) on key physiological parameters of Apis mellifera ligustica (Apidae: Hymenoptera) colony. The experiment was designed into four distinct dietary groups, including control diet (CK): 6.8 g/kg Leu + 3.9 g/kg Ile; high Ile diet: 6.8 g/kg Leu + 21.9 g/kg Ile; high Leu diet: 43.8 g/kg Leu + 3.9 g/kg Ile; diet with both high L-I: 43.8 g/kg Leu + 21.9 g/kg Ile. The results showed that Leu and Ile, to a considerable extent, promote the growth and vitality of the bee colony, with Ile mitigating Leu-induced absorption inhibition. Leu and Ile synergistically reduced haemolymph triglyceride via upregulated activities of fatty acid synthase and acetyl-CoA carboxylase, and expression of Lipase 1 and adipokinetic hormone receptor compared with CK. Furthermore, L-I treatment increased key activities of immune enzymes like phenol oxidase, lysozyme, glucose oxidase, and altered expression of antimicrobial peptides (abaecin, apidaecin, and defensin 1), indicating coordinated immunomodulation. In conclusion, within the context of this study, 43.8 g/kg Leu and 21.9 g/kg Ile in the artificial pollen substitute feed prove to be beneficial for the nutrient deposition and immunity of individual bees. This work provides a framework for optimising artificial pollen diets, offering experimental guidance towards more effective strategies in sustainable beekeeping.
Although home is frequently the preferred place of death, little is known regarding how home healthcare (HHC) influences this outcome for people with dementia (PWD), particularly within Asian contexts. This study investigates the impact of HHC and its 2016 “Integrated Home-Based Medical Care” reform on home death in Taiwan, explicitly accounting for the cultural phenomenon of “impending death discharge.”
Methods
This nationwide retrospective cohort study utilized Taiwan’s National Health Insurance Research Database. We identified PWD decedents from 2011 to 2022 and conducted a nested case–control analysis. Cases (home deaths) and controls (hospital deaths) were matched 1:1 using propensity scores to balance demographics and health status. HHC models included pre-2016 primary HHC, post-2016 primary HHC, and the reformed “HBPC Plus” (Home-Based Primary Care Plus). The outcome was adjusted to include patients discharged terminally to die at home, reflecting distinctive cultural practices.
Results
Among 209,468 decedents, 95,594 were selected after matching. Overall, HHC use was associated with higher odds of home death (adjusted odds ratio [aOR]: 1.17; 95% CI: 1.13–1.21). The reformed HBPC Plus program showed the strongest association compared to pre-2016 primary HHC (aOR: 1.63; 95% CI: 1.34–1.98). Crucially, this association strengthened further when accounting for impending death discharge (aOR: 1.82; 95% CI: 1.40–2.35). Higher visit frequency and services from hospital-based teams were also significantly linked to home death.
Conclusions
HHC significantly increases the likelihood of home death among PWD in culturally influenced contexts. The 2016 reform, particularly the HBPC Plus program, proved highly effective. Policy components like flexible visit frequencies and enhanced hospital–physician coordination appear vital for supporting end-of-life care at home, offering key insights for policy planning in aging societies.
Conventional active ankle exoskeletons are often bulky and heavily reliant on external power sources. This study presents a lightweight and flexible passive ankle exoskeleton (LFPA-EXO) aimed at reducing metabolic cost of walking. The LFPA-EXO features a gait-adaptive clutch (GA-clutch) and a super-elastic composite booster (SC-booster). By matching the walking gait, it stores gravitational potential energy and converts it into elastic energy through the booster, thereby reducing the metabolic cost of human locomotion. Mechanical and biomechanical evaluations demonstrate that the GA-clutch achieves less than 5% interference and over 85% assistance, indicating that the LFPA-EXO operates within the natural ankle joint range of motion without disrupting normal gait patterns. It delivers a peak assisting moment of 24.56 Nm during normal walking. Notably, it decreases the activation of the soleus muscle while moderately reducing the activation of the gastrocnemius muscle, with minimal impact on the tibialis anterior muscle. The LFPA-EXO achieves a 12.22% reduction in metabolic cost and an 11.17% decrease in average heart rate, underscoring its effectiveness in reducing metabolic cost during walking.
Radio recombination line (RRL) maser is a useful tool to study massive star formation regions with ionised gas close to new born massive stars. Masers often show sharp line profiles and/or extreme narrow widths, and high brightness temperatures. However, RRL masers were rarely detected only in several sources. Here we report the detection of sharp line profiles of the RRL H29$\alpha$, which can be interpreted as maser candidates, in two sources within W49A, a mini-starburst region in our Galaxy. These observations, conducted with high resolution ($\sim0.03''$) using the Atacama Large Millimeter/sub-millimeter Array (ALMA), reveal high brightness temperatures up to $\sim$9 000 K for H29$\alpha$ emission in another two sources, which might also be regarded as maser candidates. Additionally, suggestions for efficiently identifying RRL maser candidates are also provided.
Unmet healthcare needs remain a major barrier to achieving universal health coverage (UHC) globally. The intersection of aging and disability intensifies individual vulnerability and deepens structural health inequalities. Using Andersen’s Behavioural Model of healthcare utilisation as the theoretical framework, this study examines the determinants of healthcare utilisation at the individual and contextual levels among older adults with disabilities living in China. We use a dataset in China from 319 prefectures, with a total sample size of 634,445 individuals. Our findings reveal the presence of higher-income and urban-residence advantages in healthcare utilisation for older adults with disabilities in China. Regional economic development positively affects healthcare utilisation and reduces urban-rural inequality in healthcare utilisation, but its impact on income-based inequality is limited. These results highlight the need for targeted social assistance programmes for low-income groups to promote universal healthcare coverage and social equity.
The emergence of large language models, exemplified by ChatGPT, has garnered growing attention for their potential to generate feedback in second language writing, particularly automated written corrective feedback (AWCF). In this study, we examined how prompt design – a generic prompt and two domain-specific prompts (zero-shot and one-shot) enriched with comprehensive domain knowledge about written corrective feedback (WCF) – influences ChatGPT’s ability to provide AWCF. The accuracy and coverage of ChatGPT’s feedback across these three prompts were benchmarked against Grammarly, a widely used traditional automated writing evaluation (AWE) tool. We find that ChatGPT’s ability in flagging language errors grew considerably with prompt sophistication driven by the integration of domain-specific knowledge and examples. While the generic prompt resulted in substantially lower performance than Grammarly, the zero-shot prompt achieved comparable results to it and the one-shot prompt surpassed it considerably in error detection. Notably, the most pronounced improvement in ChatGPT’s performance was observed in its detection of frequent error categories, including those of word choice or expression, direct translation, sentence structure and pronoun. Nonetheless, even with the most sophisticated prompt, ChatGPT still displayed certain limitations when compared to Grammarly. Our study has both theoretical and practical implications. Theoretically, it lends empirical evidence to Knoth et al.’s (2024) proposition to separate domain-specific AI literacy from generic AI literacy. Practically, it sheds light on the pedagogical application and technical development of AWE systems.
Persistent pulmonary hypertension of the newborn is a serious disease with significant morbidity and mortality. Magnesium sulphate has been proposed as a potential treatment for persistent pulmonary hypertension of the newborn, but its efficacy remains unclear. The article aims to evaluate the effects of magnesium sulphate on persistent pulmonary hypertension of the newborn.
Methods:
A comprehensive search of PubMed, Web of Science, Embase, and Cochrane Library was conducted to identify relevant studies. The primary outcomes were pulmonary artery pressure and oxygenation index, while secondary outcomes included mean blood pressure, alveolar-arterial oxygen difference, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and arterial oxygen saturation. Statistical analysis was performed by Cochrane Review Manager 5.3.
Results:
The study analysed twelve studies involving 380 patients. Results indicated that magnesium sulphate treatment significantly reduced pulmonary artery pressure levels (MD −24.96, 95% CI −28.19 to −21.73, P < 0.0001) and mean blood pressure (MD −3.11, 95% CI −3.91 to −2.32, P < 0.0001) compared to pretreatment. Additionally, it led to a notable decrease in oxygenation index (P < 0.00001) and alveolar-arterial oxygen difference (P < 0.0001), while increasing PaO2 (P < 0.0001) and arterial oxygen saturation (P < 0.001). However, there was no significant effect on PaCO2 levels compared to pretreatment.
Conclusion:
Magnesium sulphate is a valuable therapy for persistent pulmonary hypertension of the newborn. It markedly reduced pulmonary artery pressure, alveolar-arterial oxygen difference, and oxygenation index, while enhancing PaO2, and arterial oxygen saturation, with no impact on PaCO2 levels. Magnesium sulphate may also reduce mean blood pressure following a 2-hour treatment. Additional studies are necessary to further clarify its efficacy and potential side effects.
Registration:
This study was registered with PROSPERO (CRD42024578092).
This chapter examines the critical role of evaluation within the framework of recommender systems, highlighting its significance alongside system construction. We identify three key aspects of evaluation: the impact of metrics on optimization quality, the collaborative nature of evaluation efforts across teams, and the alignment of chosen metrics with organizational goals. Our discussion spans a comprehensive range of evaluation techniques, from offline methods to online experiments. We explore offline evaluation methods and metrics, offline simulation through replay, online A/B testing, and fast online evaluation via interleaving. Ultimately, we propose a multilayer evaluation architecture that integrates these diverse methods to enhance the scientific rigor and efficiency of recommender system assessments.
The introduction of advanced deep learning models such as Microsoft’s Deep Crossing, Google’s Wide&Deep, and others like FNN and PNN in 2016 marked a significant shift in the field of recommender systems and computational advertising, establishing deep learning as the dominant approach. This chapter discusses the evolution of traditional recommendation models and highlights two main advancements in deep learning models: enhanced expressivity for uncovering hidden data patterns and flexible model structures tailored to specific business use cases. Drawing on techniques from computer vision, speech, and natural language processing, deep learning recommendation models have rapidly evolved. The chapter summarizes several influential deep learning models and constructs an evolution map. These models are selected based on their industry impact and their role in advancing deep learning recommender systems. Additionally, the chapter will introduce applications of Large Language Models (LLMs) in recommender systems, exploring how these models further enhance recommendation technologies.
This chapter explores the integration of deep learning in recommender systems, highlighting its significance as a leading application area with substantial business value. We examine notable advancements driven by industry leaders like Meta, Google, Airbnb, and Alibaba. These innovations mark a transformative shift toward deep learning in recommender systems, evidenced by Alibaba’s ongoing innovations in e-commerce and Airbnb’s applications in search and recommendation. For aspiring recommender system engineers, the current era of open-source code and knowledge sharing provides unparalleled access to cutting-edge applications and insights from industry pioneers. This chapter aims to build a foundational understanding of deep learning recommender systems developed by Meta, Airbnb, YouTube, and Alibaba, encouraging readers to focus on technical details and engineering practices for practical application.
This concluding chapter revisits the overarching architecture of recommender systems, encouraging readers to synthesize the technical details discussed throughout the book into a cohesive knowledge framework. Initially introduced in Chapter 1, the technical architecture diagram serves as a foundational reference for understanding the field. With a comprehensive overview of each module now complete, readers are invited to refine their interpretations of the architecture. Establishing a personal knowledge framework is crucial for identifying gaps, appreciating details, and maintaining a holistic view of the subject.
Embedding technology plays a pivotal role in deep learning, particularly in industries such as recommendation, advertising, and search. It is considered a fundamental operation for transforming sparse vectors into dense representations that can be further processed by neural networks. Beyond its basic role, embedding technology has evolved significantly in both academia and industry, with applications ranging from sequence processing to multifeature heterogeneous data. This chapter discusses the basics of embedding, its evolution from Word2Vec to graph embeddings and multifeature fusion, and its applications in recommender systems, with an emphasis on online deployment and inference.