Toxicological testing seeks to enable robust regulatory decisions while reducing uncertainty. Advances in modern biomedical technologies now allow the generation of data at an unprecedented scale and granularity. However, the proliferation of assays and datasets does not in itself translate into decision-relevant knowledge. This Comment article examines when testing turns into a case of frustra laborare — i.e. expending effort without proportional epistemic gain. We argue that exposure realism and toxicokinetic plausibility function as gatekeepers of relevance: mechanistic effects observed only at implausible internal concentrations rarely alter risk characterisation. Likewise, the act of expanding batteries of new approach methodologies (NAMs) without establishing predefined integration rules, inflates false-positive accumulation and amplifies uncertainty. Reproducibility limits and borderline outcomes are structural features of both animal and non-animal methods, and these factors must be quantified rather than obscured. A value-of-information (VoI) view brings much-needed discipline: the value of a test lies in its ability to shift decisions; those that cannot do so, do not meaningfully contribute. Across all domains discussed, reproducibility stands out as the essential constraint — exposure anchoring, probabilistic integration and uncertainty quantification all depend on assays that perform consistently across laboratories. In order for toxicologists to avoid frustra laborare , testing should be aligned with internal exposure, reproducible, and embedded within decision frameworks that yield actionable outcomes.

As of 2018, more than 65,000 Chinese students had pursued overseas studies with funding from the Chinese Scholarship Council (CSC). While CSC funding expands access to international education, it also entails contractual obligations that may create tensions between state expectations and individual agency. This study examines whether differences between CSC-funded and non-CSC students align with documented features of the CSC programme, which forms part of China's broader talent and state-building strategy. Drawing on a 2023 survey of 474 Chinese students in Germany, the analysis compares study motivations, future plans, media orientations, and political attitudes across the two groups. The findings show that CSC students report more pronounced nationally oriented attitudes than their non-CSC peers, consistent with programme characteristics. Yet, the results also point to the limits of state influence, shaped by student agency and opportunity structures. Owing to its cross-sectional design, the study cannot distinguish between selection and socialisation mechanisms.

The influence of Zn II , Fe II , and Co III metal centers on the photoisomerization of a pentadentate azopyridine ligand, a potential scaffold for ligand-driven light-induced spin change (LD-LISC) systems, is investigated. Steady-state UV–vis and NMR spectroscopy reveal a systematic increase in the cis -isomer fraction in the photostationary state from the Fe II to the Co III to the Zn II complex. Time-resolved electronic absorption spectroscopy links these trends to distinct competing ultrafast relaxation pathways. While the Zn II complex exhibits predominantly ligand-centered (LC) excited-state dynamics, the Fe II analogue shows rapid population of low-lying metal-centered (MC) quintet states, as we reported previously. The isoelectronic Co III complex exhibits an alternative relaxation pathway that partially restores the desired photoswitching behavior; however, weak signatures of a long-lived excited-state species remain detectable. Spectroelectrochemical measurements combined with quantum chemical calculations identify a 3 MC state as the most likely origin of this residual signal. These findings further highlight the critical role of charge-transfer states in controlling photoswitching efficiency and underscore fundamental limitations in the design of LD-LISC systems.

Hintergrund

Eltern mit psychischen Erkrankungen stehen in ihrer Elternrolle vor spezifischen Herausforderungen, die in der psychotherapeutischen Versorgung häufig unzureichend berücksichtigt werden. Digitale, zielgruppenspezifische Angebote können eine niedrigschwellige Ergänzung sein, um elterliche Kompetenzen zu stärken und Belastungen zu reduzieren.

Ziel der Arbeit

Ziele waren die partizipative Entwicklung eines transdiagnostischen digitalen Elterntrainings (TEPSY) für psychisch belastete Eltern sowie die erste Untersuchung der Nutzungserfahrungen.

Material und Methoden

Gemeinsam mit psychisch belasteten Eltern wurde eine App mit 10 Modulen zu elternschaftsrelevanten Themen wie Stress, Emotionsregulation und Kommunikation entwickelt. In einer qualitativen Machbarkeitsstudie wurden die Rückmeldungen der Teilnehmenden zu den Inhalten in Bezug auf Akzeptanz, Verständlichkeit und Nutzen untersucht.

Ergebnisse

Die Rückmeldungen zeigten eine hohe Akzeptanz und Verständlichkeit der Inhalte. Ansprache und Inhalte der App wurden als entlastend wahrgenommen. Gleichzeitig wurden Hinweise auf Weiterentwicklungsbedarf identifiziert, insbesondere hinsichtlich einer stärkeren Berücksichtigung unterschiedlicher Altersgruppen von Kindern und einer inhaltlichen Vertiefung einzelner Module.

Diskussion

Die Ergebnisse unterstreichen das Potenzial partizipativ entwickelter digitaler Interventionen zur Unterstützung psychisch belasteter Eltern. Sie können die psychotherapeutische Versorgung ergänzen, zur Selbsthilfe genutzt werden und einen wertvollen Beitrag zur Unterstützung belasteter Eltern leisten. Durch weitere Anpassungen könnte die Zufriedenheit der Nutzenden gesteigert werden.

This paper contributes to the discussion on the relationship between communication studies and society by examining the norms and values that guide graduates from communication science and journalism programs in their professional practice. It introduces a novel perspective by positioning these graduates as key intermediaries between academia and society. Each year, thousands of professional communicators—working in journalism, public relations, corporate communication, and consulting—enter the field after completing these programs. Their work becomes part of the very public communication phenomena that the discipline seeks to analyze and assess through normative frameworks. Yet, surprisingly little is known about the values and normative assumptions they carry into their professional roles.

To explore this, 25 semi-structured interviews were conducted with graduates from 15 different universities, aged in their early 20s to early 50s, currently working in journalism, strategic communication, consulting, academia, and management. Analysis revealed three graduate types: (1) those who find theoretical knowledge from their studies irrelevant, emphasizing personal moral compasses and individual values like creativity and interpersonal relationships; (2) those who developed useful analytical skills and prioritize professional values such as independence and transparency; and (3) those who actively apply theoretical knowledge to understand their professional environments, emphasizing democracy and truth in public discourse.

By expanding our understanding of what graduates take from their studies and apply to their careers, this research bridges theory and practice, offering insights into how communication education prepares individuals for societal challenges.

The authors causally identify the effects of intense survey participation on key labor market outcomes by randomly excluding individuals willing to sign up for a high-intensity survey with a focus on job search and well-being. Using administrative data, they find that, on average, survey participation had no effect on labor market outcomes during the year after signing up. They also demonstrate that an alternative selection-on-observables approach would yield misleading results. These findings underscore the value of experiments in examining effects of survey participation.

Faith-based organizations (FBOs) occupy an ambivalent position in civic life, often bridging divides while also reproducing boundaries. This study examines how Saylani Welfare Trust, a major Islamic welfare organization in Pakistan, organizes civility through the Sufi-inspired ethics of Adab. Drawing on practice theory, participant observation and interviews, we analyze how Saylani translates virtues of patience, humility and sincerity into routine practices of food provision and fundraising. These practices act as cultural anchors and boundary objects that foster reciprocity and inclusion across class and sectarian lines, while remaining shaped by gendered exclusions. In this way, Adab functions not as abstract doctrine but as a repertoire of ethical behaviors embedded in organizational routines. The case contributes to debates on civil repair by showing how universalizing norms are enacted through socio-material practices that manage, rather than erase, difference, thereby expanding our understanding of how civility is organized in diverse contexts.

Background

The PTSD Checklist for DSM-5 (PCL-5) is widely used to assess posttraumatic stress disorder (PTSD), yet validation in Arabic-speaking populations remains limited, and no guideline-based cutoff scores have been established. This study evaluated the structural validity, reliability, and diagnostic performance of the Arabic PCL-5 in a large treatment-seeking sample.

Methods

As part of a broader treatment study, a total of 1140 participants from across the Southwest Asia and North Africa (SWANA) region completed the Arabic PCL-5 among other measures. PTSD diagnoses were established via the SCID-5-CV interview. Exploratory and confirmatory factor analyses assessed dimensionality. Reliability, convergent validity, and diagnostic utility were evaluated along STARD guidelines, with emphasis on ROC analyses and cutoff performance.

Results

The Anhedonia model fit the data acceptably, with good to excellent internal consistencies. ROC analyses indicated moderate diagnostic utility (AUC = 0.658), with no cutoff achieving both high sensitivity and specificity. Lower cutoffs (31–33) maximized sensitivity (0.87–0.89) and positive predictive values (0.78–0.81), while a cutoff of 38 offered a more balanced compromise (sensitivity: 0.799, specificity: 0.419). The PCL-5 algorithm performed worse than optimized cutoffs.

Discussion

The Arabic PCL-5 shows strong structural validity and reliability and is suitable for screening within a stepped-care approach. Its limited diagnostic accuracy likely reflects effects of the spectrum bias, sample heterogeneity and methodological differences between self-report and interviews. Based on this study, the PCL-5 is recommended for symptom monitoring and screening with clinical follow-up rather than as a stand-alone diagnostic tool in Arabic-speaking treatment-seeking individuals.

Introduction

CD150-positive (CD150 + ) lymphocytes are the primary targets of measles virus (MV) infection during the acute phase. The depletion of infected CD150 + memory cells leads to a profound suppression of immune memory, resulting in increased susceptibility to secondary infections and severe complications in infected individuals. While lipids are known to be critical for viral life cycles, the specific lipid metabolic conditions facilitating MV replication in immune cells remain poorly understood.

Methods and Results

In this study, a comprehensive lipidomic analysis of MV-infected primary CD4 + T cells revealed significant alterations in three major lipid classes: sphingolipids, triacylglycerols, and glycerophospholipids. Specifically, MV infection increased the abundance of ceramides, dihydroceramides and triacylglycerols, while significantly reducing the levels of glucosylceramides and glycerophospholipids. Pharmacological intervention in the pathways of de novo sphingolipid synthesis, triacylglycerol synthesis and lipolysis significantly impaired measles virus replication in activated CD4 + CD150 + T cells.

Discussion

Mechanistically, we demonstrate that MV glycoprotein-mediated membrane fusion, essential for viral entry and cell-to-cell spread, requires glucosylceramide synthase (GCS) activity and is further promoted by plasma membrane triacylglycerol content. Collectively, these findings highlight the essential role of MV-modulated triacylglycerol and sphingolipid metabolism in viral entry, dissemination, and intracellular replication within CD4 + T cells.

Neural circuits must remain functionally stable while adapting to changing demands and levels of stress. While this balance is thought to rely on plasticity programs integrating molecular and activity-dependent signals, mechanistic models of how such adaptations are orchestrated remain limited. Here, we show that impairment of autophagy in the Drosophila mushroom body (MB) induces brain-wide, post-transcriptional remodeling of presynaptic active zones, characterized by increased expression levels of active zone scaffold proteins, reduced abundance of calcium channel subunits, and elevated levels of Shaker-type potassium channels. This remodeling promotes organismal resilience, as reflected by increased sleep and extended lifespan. Mechanistically, early-life activation of this program is sufficient to extend lifespan, identifying synaptic remodeling as a causal driver of adaptive responses. MB-specific autophagy disruption further leads to non-cell autonomous accumulation of autophagic substrates across the brain, consistent with a system-level proteostatic imbalance in which degradative pathways remain active, but appear insufficient to match cargo load. Our findings identify autophagy in the mushroom body as a key regulator of brain-wide synaptic architecture and resilience, and establish a genetically tractable model for how local proteostatic impairment can trigger adaptive, system-level circuit remodeling.

Background

Tungiasis is a neglected tropical zoonotic skin disease which is endemic to Sub-Saharan Africa and Latin America, caused by sand fleas of the genus Tunga , which burrow into the skin of affected humans and animals, most commonly when the feet come in contact with infested soil. Sand flea infection leads to inflammation, severe itching, and pain, with the potential for secondary bacterial or viral infections, gangrene, and disfigurement. Tungiasis disproportionately affects poor rural communities, and individuals living in unhygienic settlements. To date, the existing burden of tungiasis has never been estimated, despite being included in the World Health Organisation Neglected Tropical Diseases roadmap since 2021.

Methods

We applied a prevalence-based Disability Adjusted Life Year (DALY) approach focusing on Years Lived with Disability (YLD) to model the burden of human tungiasis in endemic countries. Prevalence range estimates were derived using a Bayesian hierarchical Beta-Binomial model, with probability distributions applied to represent uncertainty in estimates based on highly heterogeneous local reports, capture local and regional variation, and reflect fluctuations in symptom severity among affected individuals. A discrete time point model was implemented over a 52-week period to estimate annual DALYs lost per country included in the analysis. Monte Carlo simulation with 1000 iterations was used to generate mean DALY estimates.

Results

Globally, we estimate that up to 379,645 (95% UI 361,792–398,309) DALYs are lost annually, with the bulk of the burden in Sub-Saharan Africa. When comorbidities are included, this increases to 575,298 (95% UI 548,948–602,597). When adjusted for population size, we estimate that 24.2 DALYs (36.4 with comorbidities included) are lost annually per 100,000 people. In terms of DALYs lost, the disease burden is disproportionately concentrated in Sub-Saharan Africa, and Brazil.

Conclusions

Our estimates suggest tungiasis exerts a substantial burden of disease in endemic countries, comparable in absolute terms to that of soil-transmitted helminths and echinococcosis, and greater than that of toxocariasis, fascioliasis. Furthermore, we observe marked regional concentration of disease burden within Sub-Saharan Africa, with the disease burden in this region driven by large at-risk rural, and urban slum-dwelling, populations living within the ecological zone of transmission.

The ventral visual stream contains category-selective regions with distinct feature tuning, most prominently the fusiform face area (FFA) and parahippocampal place area (PPA). Why do these brain regions exhibit distinct tuning properties? Recent work suggests that brain-like category-selective features emerge from a general visual learning mechanism without domain-specific biases. Here, we test this proposal by applying a functional localizer approach to both humans and self-supervised neural networks, identifying face- and scene-selective units in the brain and in models. We then compared fMRI and model responses across a broad stimulus set probing classic representational signatures of the FFA and PPA, including preferences relating to curvature, animacy, real-world size, mid-level features, face shapes, and spatial layout information. Category-selective model units largely recapitulate the distinct representational signatures of category-selective brain regions, capturing most of the effects in our test battery. Our findings demonstrate that domain-general learning objectives are sufficient to create humanlike category-selectivity, suggesting that the distinct representational signatures of category-selective cortex may emerge from a unified computational goal akin to self-supervised learning.

Educational Robotics is increasingly being integrated into regular classroom teaching and offered as part of extended education to foster 21st-century skills. Among various Educational Robotics tools, LEGO® Education WeDo and WeDo 2.0 are frequently used in school-based settings, including regular instruction and extended education programs. This systematic review examines empirical intervention studies utilizing LEGO® Education WeDo or WeDo 2.0 to identify outcome variables, categorize them into broader domains (cognitive, socio-emotional/motivational, and creativity-related), and analyse the effects of these interventions. Following PRISMA guidelines, peer-reviewed studies from the last 10 years were identified via academic databases and a search engine. Inclusion criteria focused on participants aged 5–11 (ISCED levels 0 and 1), interventions using LEGO® Education WeDo or WeDo 2.0, and quantitative research designs with pre- and post-tests or at least two comparison groups. From an initial pool of N = 193 publications, n = 20 met the inclusion criteria. Findings indicate that WeDo and WeDo 2.0 interventions positively impact cognitive (e.g., computational thinking, problem-solving), socio-emotional and motivational (e.g., intrinsic motivation, STEM attitudes, self-efficacy), and creativity-related outcomes (e.g., divergent thinking), with reported effect sizes ranging from medium to large. However, methodological limitations remain, including small sample sizes and insufficient intervention descriptions. The review highlights the value of LEGO® Education WeDo and WeDo 2.0 for fostering diverse competencies in young learners and underlines the need for more rigorous research designs characterized by greater methodological transparency and robustness.

Background and aims

Drained peatlands are being rewetted to restore a variety of important ecosystem services and functions. Yet, the effect of realized groundwater level on fine-root traits and plant functioning is inconclusive so far. The aim of this study was to investigate fine-root traits and plant functioning at surface near groundwater levels on peat soil aiming at detecting drivers of intraspecific trait variation and coordination using plant economics concepts.

Methods

The study was conducted on nine fen soil lysimeters covered with populations of Phalaris arundinacea . We investigated fine-root traits and aboveground productivity in response to an applied groundwater gradient and seasonality over two years. Trait coordination was examined using redundancy analysis.

Results

Fine-root average diameter and mycorrhizal colonization decreased with increasing groundwater level while root tissue density increased, and specific root length decreased at the end of the growing season. Productivity increased linearly with the groundwater level in the first year and reached an optimum at 9.5 cm below surface in the second. Overall trait coordination was affected by groundwater level as well as seasonality.

Conclusion

Our findings suggest that distinct fine-root traits and corresponding economic functions of Phalaris arundinacea vary with either groundwater level or seasonal shifts in rewetted peatlands with consequences for overall trait coordination.

Small-animal practice faces recruitment and retention challenges. This cross-sectional online survey conducted in 2023 examined workplace-related factors associated with the intention to change jobs among employed small-animal veterinarians in Germany. Data from 386 participants were analysed using exploratory factor analysis and structural equation modelling. Five latent constructs were identified: work atmosphere, occupational strain, work-privacy balance, onboarding, and team climate. The model explained 61% of the variance in intention to change jobs. Occupational strain showed the strongest positive association with intention to change jobs, whereas a favourable work atmosphere was associated with lower intention to change jobs. Work-privacy balance also appeared relevant, although the direct effect estimated in the multivariable model should be interpreted cautiously because its direction differed from the bivariate association. Onboarding was positively associated with work atmosphere, and team climate correlated positively with work atmosphere and negatively with occupational strain. Overall, the findings suggest that reducing occupational strain and strengthening the work atmosphere are central starting points for lowering the intention to change jobs in small-animal practice. The findings point to professional leadership, reliable communication structures, predictable scheduling, fair overtime regulation, structured onboarding, and team culture as relevant areas for retention-oriented workplace development.

Scientific workflows automate complex data analysis processes and are increasingly employed to handle large-scale datasets. Scientific communities leverage heterogeneous computing clusters, consisting of interconnected resources with diverse computational capabilities, to execute their large-scale data analysis workflows due to privacy and economic factors. Consequently, they often impose high computational demands and lead to significant energy consumption. Designing an effective energy-aware scheduling approach is therefore crucial for heterogeneous computing systems, as it enables high processing efficiency while minimizing overall energy usage. However, achieving both generality in workflow structures and solvability of the corresponding optimization models remains a major challenge in workflow scheduling. In this paper, we introduce a novel mathematical approach that models the non-overlapping execution of tasks successfully by representing disjoint time intervals as linear constraints. By applying this technique, we formulate a mixed-integer linear programming model that can be solved within a reasonable time, providing exact optimal solutions for arbitrary DAG workflow structures whenever computationally tractable. We analyze the trade-off between energy consumption and makespan. In addition, post-optimality analyses, including sensitivity analysis and relaxation of optimal energy consumption for makespan improvement, are investigated. Experimental results demonstrate that the proposed MILP approach consistently outperforms competing methods, achieving up to approximately 6%–7% reduction in energy consumption compared with the best competing approach and up to about 10%–11% compared with the worst-performing method.

Background

T cell-based immunotherapies have improved cancer treatment, however their efficacy is frequently limited by tumor-intrinsic resistance mechanisms and by the immune suppressive tumor microenvironment, counteracting tumor specific immune responses through impaired antigen presentation and the accumulation of M2-like tumor-associated macrophages. MicroRNAs have emerged as regulators of tumor cell – immune cell interactions, yet the miRNAs’ capacity to coordinate anti-tumor effects across different cell types is poorly understood. This study aimed to investigate whether miR-155-5p and miR-3535 represent regulators capable of driving coordinated functional reprogramming of both, tumor cells and macrophages.

Methods

Human tumor cell lines of various cancer entities were transfected with miR-155-5p or miR-3535 and the resulting effects on immune checkpoint molecule expression and tumor cell proliferation were assessed on transcriptional and functional level. Similarly, human PBMC-derived M2 polarized macrophages were transfected with the same microRNAs, followed by analysis of the cytokine secretion patterns and by transcriptomic profiling to evaluate the macrophage polarization states and the immune-regulatory pathways involved. Transcription factor activity and pathway enrichment analyses were performed to identify the regulatory mechanisms affected.

Results

Both miR-155-5p and miR-3535 reduced expression of the immune checkpoint molecule CD73 (NT5E) in tumor cells, while miR-155-5p additionally suppressed PD-L1 (CD274) expression. At the same time, both microRNAs reprogrammed M2-like macrophages toward a pro-inflammatory M1-like phenotype, characterized by increased TNFα and CXCL10 secretion and the induction of M1-associated gene expression. Transcriptomic analysis revealed activation of STAT1/IRF-driven inflammatory pathways and a reduced activity of ZNF703, representing a transcriptional hub associated with M2 macrophage infiltration and poor prognosis. Both microRNAs increased TAP1 expression, suggesting enhanced antigen-processing capacity. Furthermore, miR-155-5p and miR-3535 exerted anti-proliferative effects across cell lines of various tumor entities.

Conclusions

miR-155-5p and miR-3535 modulate tumor-intrinsic immune checkpoint expression and functional macrophage polarization in a coordinated way, linking tumor cell plasticity to neutralization of the immunosuppressive tumor environment. These findings highlight the potential of coordinated microRNA-mediated regulation via different cell types to overcome immune resistance mechanisms in tumors and support further investigation of microRNA-based strategies in cancer immunotherapy.

Habitat loss and fragmentation, driven by human activities, disrupt habitat connectivity and alter ecological processes through geometric and demographic fragmentation effects. Dispersal plays a fundamental role in shaping the distribution, abundance, and persistence of species in modified landscapes. While previous research looked at the evolution of dispersal strategies at the species level, community-level dynamics remain underexplored. Species exhibit diverse dispersal strategies to persist in modified landscapes, yet predicting how these strategies interact at the community level requires a more integrated approach. This study employed an individual-based simulation model to explore how habitat loss and fragmentation, and other landscape characteristics, influence community-level dispersal strategies. We tested the effects of varying habitat amount and fragmentation, environmental autocorrelation, and disturbance levels on the emerging distribution of dispersal distances within a community in modified and continuous landscapes. We hypothesised that landscape modification, including habitat loss and fragmentation, would significantly shape community composition, favouring particular dispersal strategies under specific environmental conditions. The findings reveal that higher disturbance levels and greater habitat amount increased the community-weighted mean of dispersal distance, while fragmentation had only minor effects. Additionally, low autocorrelation was associated with the highest community-weighted mean of dispersal distance. These results highlight the importance of considering community-level dynamics when predicting ecosystem responses to landscape modification. By clarifying how landscape structure and disturbance shape community-level dispersal strategies, this study advances our understanding of the mechanisms underlying species persistence and community structure in modified landscapes.

Linked photosensitizer-catalyst dyads based on earth-abundant metal complexes are currently potential candidates for sustainable proton reduction systems. Fe(iii) carbene complexes showing low-lying ligand-to-metal charge transfer (LMCT) states with lifetimes in the 0.2–0.3 ns range are promising candidates for the photosensitizer side. The latter must be linked to a proton reduction catalyst, usually of cationic character, like cobaloxime. We explore the feasibility of this approach with a model compound mimicking the inductive effect of the cobaloxime moiety on the electronic state structure of a Fe(iii) photosensitizer. Thus, the homoleptic pyridine-substituted [Fe(ImPPy)2]+ (HImPPy = 1,1′-(5-(pyridin-4-yl)-1,3-phenylene)bis(3-methyl-1H-imidazol-3-ium)) complex was modified by attaching a methyl group at the pyridinyl nitrogen, to model the inductive effect of a positively charged catalytic centre on the Fe(iii) photosensitizer. Reduction of ligand electron density leads to stabilization of metal-to-ligand (2MLCT) excited states, as predicted by TD-DFT calculations. Experimental support is provided by a combination of cyclic voltammetry and ultrafast spectroscopies. [Fe(ImPPyMe)2]3+ shows a characteristic lifetime of 80 ± 10 ps for the stabilized 2MLCT state. This constitutes a promising starting point for later use of [Fe(ImPPy)2]+ as a photosensitizer in bimetallic one-component dyads for photoinduced hydrogen production.