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In Forster and Neugebauer (2024), we examine to what extent a factorial survey (FS) on invitations of fictitious applicants can replicate the findings of a nearly identical field experiment conducted with the same employers. In addition to exploring the conditions under which FSs provide valid behavioral predictions, we varied the topic sensitivity and tested whether behavioral predictions were more accurate after filtering out respondents who provided socially desirable answers or did not exert sufficient effort in responding to FS vignettes. Across these conditions, the FS results did not align well with the real-world benchmark. We conclude that researchers must exercise caution when using FSs to study (hiring) behavior. In this rejoinder, we respond to the critique of our study by Pickett (2025).

Abstract Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication. Analysis of single-cell sequencing data sets from patients shows that viral DUX4 activation is of relevance in vivo. Herpes-simplex virus 1 (HSV-1) immediate early proteins directly induce expression of DUX4 and its target genes, which mimics zygotic genome activation. Upon HSV-1 infection, DUX4 directly binds to the viral genome and promotes viral transcription. DUX4 is functionally required for infection, since genetic depletion by CRISPR/Cas9 as well as degradation of DUX4 by nanobody constructs abrogates HSV-1 replication. Our results show that DNA viruses including herpesviruses mimic an embryonic-like transcriptional program that prevents epigenetic silencing of the viral genome and facilitates herpesviral gene expression.

Abstract Bone tissue, with its complex structure, often necessitates decalcification of the hard tissue for ex vivo morphological studies. The choice of a suitable decalcification method plays a crucial role in preserving desired features and ensuring compatibility with diverse imaging techniques. The search for a universal decalcification method that is suitable for a range of biophotonic analyses remains an ongoing challenge. In this study, we systematically assessed five standard bone decalcification protocols, encompassing strong mineralic acids (3% and 5% nitric acid), a commercially available formulation of hydrochloric and formic acid), as well as weak organic acids (5% trichloroacetic acid and 8% formic acid), and a chelating agent (25% ethylenediamine-tetraacetic acid) with varying decalcification durations, using mouse long bones as our experimental model. Our imaging analysis panel included classical histological staining (Hematoxylin and Eosin, H&E), immunofluorescence staining, and label-free Raman microspectroscopic imaging. We used cryosections instead of paraffin sections since paraffin interferes with tissue Raman signals. This approach is not as commonly used as it is more prone to handling artifacts, but is the preferred method for subsequent Raman analysis. Decalcification efficacy was evaluated based on various qualitative and some quantitative imaging parameters by 2–3 independent observers. Our systematic approach revealed that the chelating agent, when used for 24 h, optimally preserved bone features and, thus, would be the ideal decalcifying agent for comprehensive subsequent analysis. However, the choice of decalcifier and the ideal decalcification duration may vary depending on the type and thickness of bone, necessitating tailored adjustments to meet specific experimental requirements.

Post-transcriptional regulation by RNA binding proteins can determine gene expression levels and drive changes in cancer cell proteomes. Identifying mechanisms of protein-RNA binding, including preferred sequence motifs bound in vivo, provides insights into protein-RNA networks and how they impact mRNA structure, function, and stability. In this review, we will focus on proteins that bind to AU-rich elements (AREs) in nascent or mature mRNA where they play roles in response to stresses encountered by cancer cells. ARE-binding proteins (ARE-BPs) specifically impact alternative splicing, stability, decay and translation, and formation of RNA-rich biomolecular condensates like cytoplasmic stress granules (SGs). For example, recent findings highlight the role of ARE-BPs – like TIAR and HUR – in chemotherapy resistance and in translational regulation of mRNAs encoding pro-inflammatory cytokines. We will discuss emerging evidence that different modes of ARE-BP activity impact leukaemia and lymphoma development, progression, adaptation to microenvironment and chemotherapy resistance.

This study examines the influence of economic factors on crime in the regions of the Czech Republic from 2005 to 2023. The analysis utilizes panel data encompassing economic indicators such as Gross Domestic Product (GDP), the number of business entities exiting the market, and the number of unemployed individuals, alongside crime data across various types. Fixed effects models estimate the relationship between economic activity and crime, with robust standard errors corrected for heteroskedasticity and autocorrelation. Results indicate that GDP and the number of entities exiting the market significantly influence crime rates, while unemployment plays a minor role. An increase in entities exiting the market correlates with a rise in overall and general crime, whereas higher GDP reduces rates of economic crimes, robberies, and burglaries. These findings suggest that economic stability has the potential to mitigate certain types of crime, while economic instability may heighten general criminal activity. The results align with international studies and contribute to a deeper understanding of regional variations in crime dynamics in the Czech Republic, highlighting the need for targeted social policy measures and policies at the organizational level.

Factorial surveys (FSs) are increasingly used to predict real-world decisions. However, there is a paucity of research assessing whether these predictions are valid and, if so, under what conditions. In this preregistered study, we sent out N = 3, 002 applications to job vacancies in Germany and measured real-world responses. Eight weeks later, we presented nearly identical applicant profiles to the same employers as a part of an FS. To explore the conditions under which FSs provide valid behavioral predictions, we varied the topic sensitivity and tested whether behavioral predictions were more successful after filtering out respondents who gave socially desirable answers or did not exert sufficient effort when answering FS vignettes. Across conditions, the FS results did not correspond well with the real-world benchmark. We conclude that researchers must exercise caution when using FSs to study (hiring) behavior.

The educational disadvantages of migrant students are a persistent problem in many Western countries. Against this background, policymakers often call for more diversity in the teacher workforce, arguing that migrant students might benefit from being taught by migrant teachers. Despite the popularity of this claim, there is almost no research-based rationale for increasing the diversity of teachers in Europe. This paper is a step toward filling this research gap for Germany, aiming to assess whether migrant teachers reduce ethnic educational disadvantages. Our analyses are based on a nationally representative large-scale assessment of ninth graders that provides information on the migration status of both students and teachers, with achievement tests and teacher-assigned grades in German as dependent variables. The results run contrary to widely held expectations, indicating little evidence that migrant students benefit from being taught by migrant teachers.

Teachers have faced a variety of challenges since the onset of COVID-19 in the spring of 2020, including increased workloads, a range of modalities, and COVID-19 protocols. The challenges associated with teaching during the COVID-19 pandemic have led to increased burnout and stress, as well as diminished well-being and mental health in teachers. This study seeks to explore teacher burnout and subjective mental health from the start of the pandemic to the end of the 2020-21 school year. To better understand teachers' experiences during this time, we conducted a nationwide survey (n = 302) with teachers between May and June 2021, as well as four focus groups and four one-on-one interviews in the fall of 2021. Results suggest that teachers' subjective mental health, morale, and work-life balance have significantly declined since the beginning of the pandemic. Teachers reported feeling anxious and burned out from teaching due to greater workloads and decreased support from administrators and parents. We conclude by discussing the implications of teacher subjective mental health and burnout and offer suggestions for better supporting teachers, practitioners, and their mental well-being.

Sepsis is a life-threatening organ failure resulting from a poorly regulated infection response. Organ dysfunction includes hepatic involvement, weakening the immune system due to excretory liver failure, and metabolic dysfunction, increasing the death risk. Although experimental studies correlated excretory liver functionality with immune performance and survival rates in sepsis, the proteins and pathways involved remain unclear. This study identified protein kinase C-α (PKCα) as a novel target for managing excretory liver function during sepsis. Using a preclinical murine sepsis model, we found that both PKCα knockout and the use of a PKCα-inhibitor midostaurin successfully restored liver function without hindering the host’s response or ability to clear the pathogen, highlighting PKCα’s vital role in excretory liver failure. In septic animals, both approaches significantly boosted survival rates. Midostaurin is the clinically approved active pharmaceutical ingredient in Rydapt, approved for the adjuvant treatment of FTL3-mutated AML. Here, it reduced plasma bile acids and related inflammation in those patients, opening a translational avenue for therapeutics in sepsis. Conclusively, our research underscores the significance of PKCα in controlling excretory liver function during inflammation. This suggests that targeting this protein could restore liver function without compromising the immune system, thereby decreasing sepsis mortality and supporting the recent paradigm that the liver is a hub for the host response to infection that might, in the future, result in novel host-directed therapies supporting the current state-of-the-art intensive care medicine in patients with sepsis-associated liver failure.

RationaleMusic therapy has been in practice for years. However, the mechanism of action of music or music therapy is not well understood. It is only recently that the neuroendocrinological basis of therapeutic relationships has become the subject of growing research interest. The aim of this pilot study (Clinical Trial No: DRKS00035174) is to investigate whether oxytocin is usable and feasible as a biomarker of attachment to demonstrate the development of therapeutic alliance between therapist and patient in a dyadic music therapy setting.MethodsIn a single-measure crossover design, children aged 6–12 years from a special school for social and emotional disorders, were randomly with either music therapy followed by a waiting list control group that performed silent work, or vice versa. The respective interventions were conducted on the school premises on different days over a period of 1 month. The primary outcome was salivary oxytocin, with tests performed immediately before and after each 30-min intervention.ResultsThirty-two children were included in the study, resulting in n = 16 children per allocation sequence. During the implementation of the study, difficulties were encountered with protocol adherence both in terms of the duration of the music therapy and the implementation of the silent work in the control group. There were no dropouts, however, only 28 children were included in the final data analysis as two participants in each group were excluded due to large fluctuations in oxytocin levels. Between-group comparison and within-group comparisons showed no significant changes in oxytocin levels. However, the music therapist showed a significant increase in oxytocin levels in the before after measurement. No side effects or adverse events were reported during the trial.ConclusionThe findings indicated a responsiveness of oxytocin to musical stimulation. Although feasibility of oxytocin measurement was clearly demonstrated, evaluation of the results is difficult against the background of many remaining questions regarding individual and contextual factors influencing the oxytocinergic system. Moreover, the clinical significance of changes in oxytocin levels remains a topic for further research to better understand the role of oxytocin in the attachment formation between therapist and patient in music therapy.

ABSTRACT Effective population size (Ne) is one of the most important parameters in evolutionary biology, as it is linked to the long‐term survival capability of species. Therefore, Ne greatly interests conservation geneticists, but it is also very relevant to policymakers, managers, and conservation practitioners. Molecular methods to estimate Ne rely on various assumptions, including no immigration, panmixia, random sampling, absence of spatial genetic structure, and/or mutation‐drift equilibrium. Species are, however, often characterized by fragmented populations under changing environmental conditions and anthropogenic pressure. Therefore, the estimation methods' assumptions are seldom addressed and rarely met, possibly leading to biased and inaccurate Ne estimates. To address the challenges associated with estimating Ne for conservation purposes, the COST Action 18134, Genomic Biodiversity Knowledge for Resilient Ecosystems (G‐BiKE), organized an international workshop that met in August 2022 in Brașov, Romania. The overarching goal was to operationalize the current knowledge of Ne estimation methods for conservation practitioners and decision‐makers. We set out to identify datasets to evaluate the sensitivity of Ne estimation methods to violations of underlying assumptions and to develop data analysis strategies that addressed pressing issues in biodiversity monitoring and conservation. Referring to a comprehensive body of scientific work on Ne, this meeting report is not intended to be exhaustive but rather to present approaches, workshop findings, and a collection of papers that serve as fruits of those efforts. We aimed to provide insights and opportunities to help bridge the gap between scientific research and conservation practice.

During indoor-outdoor transitions humans encounter luminance changes beyond the functional range of the photoreceptors, leaving the individual at risk of overlooking harmful low-contrast objects until adaptation processes re-enable optimal vision. To study human visual performance during intense luminance changes, we propose a virtual reality based simulation platform. After linearization of the headset's luminance output, detection times were recorded for ten participants. The small (FWHM = 0.6°) low-contrast stimuli appeared randomly in one of four corners (±10°) after luminance changes of three magnitudes within 1 or 3 s. Significantly decreased detection times were observed for the conditions with simulated self-tinting lenses compared to lenses with fixed transmission rates after luminance decreases. In cases of luminance increases all detection times were similar. In conclusion, the proposed virtual reality simulation platform allows for studying vision during or after steep luminance changes and helps to design technical aids like self-tinting lenses.

Introduction: Target volume delineation is routinely performed in postoperative radiotherapy (RT) for breast cancer patients, but it is a time-consuming process. The aim of the present study was to validate the quality, clinical usability and institutional-specific implementation of different auto-segmentation tools into clinical routine. Methods: Three different commercially available, artificial intelligence-, ESTRO-guideline-based segmentation models (M1-3) were applied to fifty consecutive reference patients who received postoperative local RT including regional nodal irradiation for breast cancer for the delineation of clinical target volumes: the residual breast, implant or chestwall, axilla levels 1 and 2, the infra- and supraclavicular regions, the interpectoral and internal mammary nodes. Objective evaluation metrics of the created structures were conducted with the Dice similarity index (DICE) and the Hausdorff distance, and a manual evaluation of usability. Results: The resulting geometries of the segmentation models were compared to the reference volumes for each patient and required no or only minor corrections in 72 % (M1), 64 % (M2) and 78 % (M3) of the cases. The median DICE and Hausdorff values for the resulting planning target volumes were 0.87–0.88 and 2.96–3.55, respectively. Clinical usability was significantly correlated with the DICE index, with calculated cut-off values used to define no or minor adjustments of 0.82–0.86. Right or left sided target and breathing method (deep inspiration breath hold vs. free breathing) did not impact the quality of the resulting structures. Conclusion: Artificial intelligence-based auto-segmentation programs showed high-quality accuracy and provided standardization and efficient support for guideline-based target volume contouring as a precondition for fully automated workflows in radiotherapy treatment planning.