The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT 1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use ( n = 1869). Two meta-analyses of overlapping studies examining the 5-HT 1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers ( n = 566), but weak evidence of an effect in those with a family history of depression ( n = 75). Another systematic review ( n = 342) and a sample of ten subsequent studies ( n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study ( n = 115,257) and one collaborative meta-analysis ( n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
This study examines how digital technologies enable sustainable value creation in industrial Product–Service Systems (PSS). Focusing on the Internet of Things (IoT), Business-to-Business (B2B) platforms, and digitalization and servitization, the paper synthesises findings from a semi-systematic review of 123 publications. The analysis identifies key benefits and barriers associated with each technological domain and highlights how they collectively support data-driven coordination, service-based value creation, and resource-efficient operations. At the same time, the review reveals fragmented treatment of sustainability and a lack of methods capable of assessing environmental, economic, and social impacts, especially in the early stages of PSS design. The study integrates insights across previously disconnected research streams and shows that sustainability outcomes cannot be understood through single technologies alone but emerge from their interaction within broader socio-technical systems. On this basis, the paper outlines implications for theory and practice and identifies priorities for future research, including integrated assessment approaches, improved modelling of dynamic system behaviour, and stronger consideration of social impacts.
Background: Agents for computer use (ACUs) are systems that execute complex tasks on digital devices-such as personal computers or mobile phones-given instructions in natural language. These agents automate tasks by controlling software through low-level actions like mouse clicks and touchscreen gestures. However, despite rapid progress, ACUs are not yet mature for everyday use. Objectives: This survey examines the current state-of-the-art, identifies trends, and points out research gaps in the development of practical ACUs. The goal is to provide a comprehensive review and analysis that helps advance general-purpose, robust, and scalable agents for real-world computer use. Methods: We introduce a multifaceted taxonomy of ACUs across three dimensions: (I) the domain perspective, characterizing the contexts in which agents operate; (II) the interaction perspective, describing observation modalities (e.g., screenshots, HTML) and action modalities (e.g., mouse, keyboard, code execution); and (III) the agent perspective, detailing how agents perceive, reason, and learn. We review 87 original research papers about ACUs and 33 relevant datasets, covering both foundation model-based and specialized approaches. Results: Our taxonomy comprehensively structures state-of-the-art approaches and establishes the groundwork for guiding future ACU research. We found that the field is transitioning from specialized agents toward foundation-model-based agents, a shift from text to image-based observation space, and an increasing adoption of behavior cloning methodologies. Furthermore, we identify six key research gaps: insufficient generalization, inefficient learning, limited planning, low task complexity in benchmarks, non-standardized evaluation, and a disconnect between research and practical conditions. Conclusions: To continue rapid improvements in the field, we recommend focusing on: (a) vision-based observations and low-level control to enhance generalization; (b) adaptive learning beyond static prompting; (c) effective planning and reasoning capabilities; (d) realistic, high-complexity benchmarks; (e) standardized evaluation criteria based on task success; and (f) aligning agent design with real-world deployment constraints. Collectively, our findings and proposed directions help develop more general-purpose agents for everyday digital tasks.
Metal halide perovskite solar cells have considerable potential for next-generation solar power production. However, if not controlled, the migration of mobile ions can hamper the stability of perovskite solar cells. Intensive research efforts have devised methods of suppressing ion migration and degradation in perovskite materials, resulting in solar cells that are stable over thousands of hours during accelerated ageing testing. Here, we review the chemical origins of ion migration, its effect on material and device performance and stability, and strategies to mitigate its impact. Ion migration originates in the soft lattice of the halide perovskite framework and its low defect-formation energy, but there are many different strategies to reduce its effects, from compositional engineering of materials and device architecture changes to additives and strain engineering. The field has made great progress in understanding the origin and properties of mobile ions in halide perovskites and has improved operational stability beyond expectations. Nonetheless, there are still ample opportunities to further improve the long-term durability of perovskite solar cells, either by reducing ion migration or its effect on solar cell efficiency. Ion migration plays a crucial role in perovskite solar cells. This Review covers its mechanisms, impact on device performance and degradation, measurement techniques, and emerging strategies towards controlling ion migration.
Ensembles improve prediction performance and allow uncertainty quantification by aggregating predictions from multiple models. In deep ensembling, the individual models are usually black box neural networks, or recently, partially interpretable semi-structured deep transformation models. However, interpretability of the ensemble members is generally lost upon aggregation. This is a crucial drawback of deep ensembles in high-stake decision fields, in which interpretable models are desired. We propose a novel transformation ensemble which aggregates probabilistic predictions with the guarantee to preserve interpretability and yield uniformly better predictions than the ensemble members on average. Transformation ensembles are tailored towards interpretable deep transformation models but are applicable to a wider range of probabilistic neural networks. In experiments on several publicly available data sets, we demonstrate that transformation ensembles perform on par with classical deep ensembles in terms of prediction performance, discrimination, and calibration. In addition, we demonstrate how transformation ensembles quantify both aleatoric and epistemic uncertainty, and produce minimax optimal predictions under certain conditions.
