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Ruxolitinib (RUX) is approved for the treatment of steroid-refractory acute and chronic graft versus host disease (GvHD). It is predominantly metabolized via cytochrome P450 (CYP) 3A4. As patients with GvHD have an increased risk of invasive fungal infections, RUX is frequently combined with posaconazole (POS), a strong CYP3A4 inhibitor. Knowledge of RUX exposure under concomitant POS treatment is scarce and recommendations on dose modifications are inconsistent. A physiologically based pharmacokinetic (PBPK) model was developed to investigate the drug–drug interaction (DDI) between POS and RUX. The predicted RUX exposure was compared to observed concentrations in patients with GvHD in the clinical routine. PBPK models for RUX and POS were independently set up using PK-Sim® Version 11. Plasma concentration-time profiles were described successfully and all predicted area under the curve (AUC) values were within 2-fold of the observed values. The increase in RUX exposure was predicted with a DDI ratio of 1.21 (Cmax) and 1.59 (AUC). Standard dosing in patients with GvHD led to higher RUX exposure than expected, suggesting further dose reduction if combined with POS. The developed model can serve as a starting point for further simulations of the implemented DDI and can be extended to further perpetrators of CYP-mediated PK-DDIs or disease-specific physiological changes.

Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without Aspergillus infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested LGALS2, MMP1, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during Aspergillus infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools.

The moisture content of the human skin, but also the loss of water through the skin, the transepidermal water loss (TEWL), plays a significant role in the skin’s health. Various medical indications require the use of a wound dressing. However, how the skin environment changes under a wound dressing has not yet been sufficiently investigated. Skin moisture and TEWL values were measured in 20 healthy volunteers before and after the application of a total of 23 different wound dressings distributed over the back. Significant changes in the parameters from day 1 to day 2 were tested. Wound dressings change the underlying skin environment. Occlusive dressings significantly increase skin hydration and TEWL. The findings could contribute to quantitative analysis and monitoring of topical-wound therapy in the future.

The attachment representation (AR) of individuals affects emotional and cognitive information processes and is considered an important modulating factor of neuroendocrine stress responses. The neuropeptide oxytocin is studied as one biomolecular component underpinning this modulation. A validated procedure used in attachment-related research is the Adult Attachment Projective Picture System (AAP). To date, only a limited number of studies investigated oxytocin and neuroendocrine reactivity in the context of an attachment-related stimulus similar to the APP. In this pilot study, N = 26 men of recent fatherhood were exposed to the AAP to classify AR and to investigate salivary changes in oxytocin, cortisol and dehydroepiandrosterone (DHEA) after AAP stimulation. We observed increased oxytocin levels in response to AAP exposure, and this increase was more pronounced in fathers with unresolved/disorganized AR. No significant changes in cortisol and DHEA concentrations were observed in response to AAP administration. Interestingly, differences in basal cortisol levels (before the AAP) also depended on AR classification. Here, the group of men with unresolved/disorganized AR showed higher levels of cortisol compared to fathers with organized AR. To conclude, the finding of increased salivary oxytocin levels in response to the AAP further indicates its validity as an instrument to stimulate the attachment system.

The availability of nesting resources influences the persistence and survival of bee communities. Although a positive effect of artificial nesting structures has frequently been shown for aboveground cavity-nesting wild bees, studies on below ground-nesting bees are rare. Artificial nesting hills designed to provide nesting habitats for ground-nesting bees were therefore established within the BienABest project in 20 regions across Germany. Wild bee communities were monitored for two consecutive years, accompanied by recordings of landscape and abiotic nest site variables. Bee activity and species richness increased from the first to the second year after establishment; this was particularly pronounced in landscapes with a low cover of semi-natural habitat. The nesting hills were successively colonized, indicating that they should exist for many years, thereby promoting a species-rich bee community. We recommend the construction of nesting hills on sun-exposed sites with a high thermal gain of the substrate because the bees prefer south-facing sites with high soil temperatures. Although the soil composition of the nesting hills plays a minor role, we suggest using local soil to match the needs of the local bee community. We conclude that artificial nesting structures for ground-nesting bees act as a valuable nesting resource for various bee species, particularly in highly degraded landscapes. We offer a construction and maintenance guide for the successful establishment of nesting hills for bee conservation.

In recent years, breast cancer treatment has become increasingly individualized. Circulating tumor cells (CTCs) have the potential to move personalized medicine another step forward. The prognostic relevance of CTCs has already been proven both in early and metastatic breast cancer. In addition, there is evidence that changes in CTC numbers during the course of therapy can predict treatment response. Thus, CTCs are a suitable tool for repeated treatment monitoring through noninvasive liquid biopsy. The next step is to evaluate how this information can be used for clinical decision making with regard to the extension, modification, or abandonment of a treatment regimen. This review will summarize the completed and ongoing clinical trials using CTC number or phenotype for treatment decisions. Based on current knowledge, CTCs can be regarded as a useful prognostic and predictive marker that is well suited for both risk stratification and treatment monitoring in breast cancer patients. However, there is still the need to provide sufficient and unequivocal evidence for whether CTCs may indeed be used to guide treatment decisions in everyday clinical practice. The results of the ongoing trials described in this review are eagerly awaited to answer these important questions.