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Zoonotic diseases pose significant threats to global health security, societal stability, and economic well-being by causing widespread illness, overwhelming healthcare systems, disrupting communities, and driving the majority of emerging infectious diseases. This editorial synthesizes key insights on surveillance and response to zoonotic diseases, arguing that current systems must evolve from fragmented, human-centric detection toward integrated, anticipatory platforms. The collected papers underscore that traditional surveillance fails to address the accelerating drivers of zoonotic emergence, such as climate change, agricultural intensification, and antimicrobial resistance. Instead, they advocate for a paradigm shift wherein genomics, artificial intelligence, and digital tools are leveraged to interpret risk signals across human, animal, and environmental domains-enabling early warning and source attribution. Critically, the issue emphasizes that technological advances alone are insufficient; effective response depends on embedding these tools within robust One Health governance, sustained cross-sectoral collaboration, and equity-focused investments. By framing surveillance as an action-oriented continuum, the contributions collectively assert that preventing future zoonotic crises requires transforming One Health from a conceptual ideal into an operational infrastructure capable of translating data into timely, context-specific interventions.

Major depressive disorder (MDD) constitutes a substantial global health burden, profoundly undermining psychosocial functioning and quality of life, and the persistent limitations of treatment efficacy-despite advances in neurobiology and pharmacotherapy-underscore its considerable clinical complexity. Recent research increasingly delineates the heterogeneity of depressive symptomatology, particularly emotional blunting, and emerging evidence further implicates metabolic and inflammatory pathways processes in shaping treatment response. Insulin resistance (IR), immune dysregulation, individual circadian preference, and trait-level vulnerabilities associated with neurodevelopmental or trauma-related characteristics may contribute to reduced responsiveness to standard therapies and limited adherence to antidepressant treatment. Taken together, these converging findings emphasize the need for individualized interventions rather than continued reliance on broad diagnostic categories. The study consists of two phases with distinct hypotheses: phase I) evaluating emotional blunting along other clinical/psychopathological variables as potential predictors of treatment non-response to SSRI/SNRI in MDD, and phase II) assessing relationships between IR and treatment non-response to vortioxetine in MDD. Further exploratory objectives encompass assessment of: links between psychopathological and metabolic predictors of health status; longitudinal association between emotional blunting and both sexual and cognitive functioning. The METOD study is an open, non-randomized two-phase observational study conducted in accordance with clinical standards and with all required ethical approvals. The protocol was prepared in line with STROBE recommendations. In Phase I, MDD patients meeting eligibility criteria and initiating antidepressant treatment with one of the first-line SSRIs or SNRIs are observed, whereas in Phase II, individuals showing an inadequate response are switched to vortioxetine as a second-line option. Validated clinical assessment tools are administered alongside anthropometric and laboratory evaluations. By examining these interrelations within a naturalistic cohort treated in accordance with current clinical standards, this innovative study-with its strong emphasis on patient-reported outcomes-may increase insight into the lived experience of depression, enhance understanding of the pathophysiological mechanisms shaping its diverse symptomatology, and provide a foundation for more precisely targeted therapeutic approaches.

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A growing body of evidence suggests that aging is not simply the accumulation of damage, but a systemic progression of increasing entropy across biological scales. Synthesizing concepts from thermodynamics and information theory, we outline a tentative three-stage entropy model of the lifespan: order-building development, homeostatic adulthood, and disorder-dominant aging. Within this model, we attempt to reframe the established hallmarks of aging as interconnected nodes in an entropy-centered network and detail the multiscale manifestations of disorder from molecules to systems. To quantify this trajectory, we introduce a Multiscale Entropic Aging Index (MEAI) as a proof-of-concept conceptual framework, designed to integrate measurements of disorder across biological levels. This framework seeks to offer a potential unifying, quantitative language for aging research and suggests that entropy reduction could serve as a testable mechanism underlying interventions, laying a principled foundation for the future development of biomarkers and rejuvenative strategies.

A bidirectional relationship between obesity and anxiety disorders has been increasingly associated with neuroinflammation and dysregulation of the gut-brain axis. Here, we investigated the pharmacological effects of the N-palmitoylethanolamine oxazoline derivative 2-pentadecyl-2-oxazoline (C15OXA) in a mouse model of high-fat diet (HFD)-induced obesity, with particular attention to its central and peripheral mechanisms of action. Male C57Bl/6J mice were fed an HFD for 12 weeks and subsequently treated with C15OXA (30 mg·kg-1, p. o.) for 7 weeks. Behavioural, molecular, and microbiota analyses were performed to evaluate the effects of the compound. C15OXA significantly reduced anxiety-like behaviour in obese mice without affecting body weight, fat mass, or glucose tolerance. At the central level, C15OXA attenuated hippocampal neuroinflammation, as shown by reduced expression of COX-2, TLR4, NLRP3 and IL-1β. In parallel, C15OXA restored tight junction gene expression associated with blood-brain barrier integrity, and modulated unfolded protein response signalling. In addition, C15OXA enhanced markers of neurogenesis and synaptic plasticity. At the peripheral level, C15OXA treatment reduced colonic inflammation and improved gut barrier integrity. These effects were associated with a targeted reshaping of gut microbiota composition. In particular, C15OXA promoted the enrichment of butyrate- and menaquinone-producing bacteria, as taxa linked to beneficial metabolic functions. Overall, these findings suggest that C15OXA exerts anxiolytic-like effects associated with coordinated central and peripheral pathways involving the modulation of neuroinflammatory pathways, barrier integrity, and gut-brain axis signalling. This study provides novel pharmacological insight into the therapeutic potential of C15OXA for the treatment of obesity-associated neuropsychiatric disorders.

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Behavioral interventions for Tourette syndrome (TS) involve tic suppression and attention to premonitory urges. However, some patients believe that focusing on tic symptoms or urges may worsen symptoms, and that suppressing tics may exacerbate urges. Using a single experimental dataset with real-time urge monitoring, this study addressed two analytical aims. Aim 1 examined whether tic suppression worsens the intensity, frequency, and persistence of premonitory urges. Aim 2 examined whether sustained attention to urges increases tic frequency or worsens subjective urges. Ten adult men with TS and frequent tic symptoms (mean age=28.3 years, standard deviation=9.1 years) completed four 5-min conditions twice: rest, suppression, urge-reporting, and suppression+urge-reporting. In the urge-reporting conditions, participants used a handheld monitor to continuously report urges. The sessions were video-recorded, and tic frequency was coded. For Aim 1, the mean urge intensity, frequency of threshold-crossing urge episodes, and post-threshold persistence patterns were compared between the urge-reporting and suppression+urge-reporting conditions. For Aim 2, tic frequency and subjective states were compared between the conditions with and without urge-reporting. At the group level, tic suppression was not associated with consistent worsening of mean urge intensity, frequency of threshold-crossing urge episodes, or post-threshold persistence patterns. This overall pattern did not clearly differ by obsessive-compulsive symptoms, although participants with these symptoms showed larger and more persistent urge responses in the descriptive plots. Sustained urge-reporting was not associated with a consistent group-level increase in tic frequency; instead, marked individual variability was observed. Subjective urge intensity and fatigue were higher after suppression+urge-reporting condition than after suppression condition. Under short-term laboratory conditions, tic suppression was not associated with a consistent group-level worsening pattern in premonitory urge indices, and real-time urge reporting was not associated with a consistent group-level increase in tic frequency. However, individual variability was substantial; this variability may be partly related to obsessive-compulsive symptoms.

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Social workers regularly encounter clients affected by substance use disorders (SUD), yet training in evidence-based assessment and interventions remains limited. In Sweden, municipal social workers have statutory responsibility for SUD assessment, intervention planning and client follow-up which underscores the need for targeted professional education. This study aimed to: (i) describe social workers' baseline self-assessed competence in evidence-based practices for SUD and its associations with demographic and professional characteristics, and; (ii) examine knowledge gains associated with completion of an evidence-based educational intervention. A non-randomized pre-post design included 173 municipal social workers recruited from 64 municipalities across five cohorts (2021-2023). Baseline self-assessed competence was analyzed using ordinal logistic regression, and knowledge gains were assessed using module-specific pre-post items with paired t-tests with Cohen's d. Baseline competence was rated as low to moderate, with professional experience predicting higher perceived competence. Substantial baseline knowledge gaps were observed, particularly in evidence-based psychosocial interventions and use of digital technology in assessment and planning of treatment. Knowledge increased significantly across all modules after training completion (d = 0.26-1.41). The largest knowledge gains were for modules on use of technology in the assessment and treatment-planning, biopsychosocial interventions, research-informed use of the assessment tool Addiction Severity Index (ASI), and the professional role in assessment and care planning. Score variability decreased across several modules. Completion of an immersive, online, evidence-based training was associated with meaningful improvements in social workers' knowledge related to substance use assessment, intervention planning, and use of technology. Although causal inference is limited by the non-randomized single-group pre-post design, the findings support the potential of scalable educational interventions to address competence gaps in substance use services even in organizations with high caseloads, workforce turnover, and limited training opportunities.

Autologous minced cartilage offers a single-stage, low-cost alternative to cell therapies for treatment of chondral defects. It is often derived from debrided defects or loose bodies, then minced for reimplantation. However, there is a paucity of knowledge on how mincing cartilage impacts viability and extracellular matrix deposition compared to quality-controlled cell therapies. The purpose is therefore to better characterize minced cartilage by comparing different mincing techniques to isolated cells. Cartilage samples were obtained from fresh human osteochondral allografts (JRF Ortho) and divided into: chondral allograft biopsy (control), manually minced cartilage, arthroscopically minced cartilage, isolated chondrons, and isolated chondrocytes. Samples were embedded in fibrin gels and cultured for 28 days. Staining for viability and histology for collagen and proteoglycan components were performed. Cartilage samples derived from debrided defects or loose bodies were evaluated for sulphated glycosaminoglycans (sGAGs), DNA, and wet weight. At 28 days, viability of chondrons (93.7 ± 2.9%), chondrocytes (94 ± 22%) and manually minced cartilage (79.8 ± 16.2%) were significantly higher than arthroscopically minced cartilage (56.6 ± 15.4%). Over time, isolated cells showed proteoglycan and type II collagen deposition, while minced cartilage groups showed reduced proteoglycan content on histology. Clinical cartilage samples varied >10-fold in wet weight, total DNA, sGAGs/weight, and DNA/weight. This study showed isolated cells have consistently high viability and deposit more proteoglycans over time compared to both minced cartilage groups. Samples typically used for clinical application of minced cartilage can vary over 10-fold in cellularity and proteoglycan content. As consequences for treatment effect are unknown, implementation in clinical practice without quality regulation is not recommended.

Anticipatory action (AA) has transformed how humanitarian actors respond to forecasted crises, yet most systems remain built around single hazards. This perspective argues that to stay effective in a world where climate, conflict, and economic shocks increasingly intersect, AA must evolve toward a multi-risk approach. Drawing on a review of 105 active frameworks in 2023 and 154 in 2024 from the Anticipation Hub's 2024 and 2025 global overview reports, expert consultations, and 17 interviews, we examine how practitioners and scientists are beginning to bridge this gap. Emerging innovations-such as multi-risk analysis informing AA design, scenario-based triggers, conflict-sensitive planning, and adaptive financing-offer promising pathways, but current systems still struggle to capture dynamic vulnerabilities and interactions between risks. Advancing AA will require embracing uncertainty and redesigning systems to learn, adapt, and act across interconnected risks-moving from anticipating single hazards to anticipating intersected crises.