We developed a new probabilistic model to assess the impact of recommendations rectifying the reproducibility crisis (by publishing both positive and ‘negative‘ results and increasing statistical power) on competing objectives, such as discovering causal relationships, avoiding publishing false positive results, and reducing resource consumption. In contrast to recent publications our model quantifies the impact of each single suggestion not only for an individual study but especially their relation and consequences for the overall scientific process. We can prove that higher-powered experiments can save resources in the overall research process without generating excess false positives. The better the quality of the pre-study information and its exploitation, the more likely this beneficial effect is to occur. Additionally, we quantify the adverse effects of both neglecting good practices in the design and conduct of hypotheses-based research, and the omission of the publication of ‘negative‘ findings. Our contribution is a plea for adherence to or reinforcement of the good scientific practice and publication of ‘negative‘ findings.

Assessing the impact of recommendations rectifying the reproducibility crisis (publishing both positive and “negative” results and increasing statistical power) on competing objectives, such as discovering causal relationships, avoiding publishing false positive results, and reducing resource consumption, we developed a new probabilistic model. Our model quantifies the impact of each single suggestion for an individual study and their relation and consequences for the entire research process. We can prove that higher-powered experiments can save resources in the overall research process without generating excess false positives. The better the quality of the pre-study information and its exploitation, the more likely this beneficial effect is to occur. Additionally, we quantify the adverse effects of neglecting good practices in the design and conduct of hypotheses-based research, and the responsibility to publish “negative” findings. Our contribution is a plea for adherence to or reinforcement of the good scientific practice and publication of “negative” findings.

Blood sampling by venepuncture is a routine procedure in animal experiments and veterinary diagnostics. It can cause stress due to restraint and pain associated with a penetration of the skin by a needle. When stressful procedures are repeated, stress can increase through anticipation after negative experiences or decrease due to habituation and/or positive reinforcement. The aim of this study was to describe the reaction to repeated blood sampling on the affective state of the animals. We wanted to observe how repeated blood sampling would effect stress parameters in goats in a experiment with repeated blood sampling that underwent an intensive cooperative vet care training and were handled with focus on gentle handling. Eight dairy goats underwent weekly blood sampling over a four-month period as part of a transfer study. Stress parameters were assessed by serum cortisol concentration, temperature changes in the inner corner of the eye measured by infrared thermography, and an ethogram of voluntary and aversive behavior. Neither the serum cortisol concentration nor the eye temperature changed significantly over time during blood sampling. However, the ethogram showed that the goats approached the blood sampling position significantly faster and more voluntarily. In this study we observed that repetition of blood sampling not necessary lead to increased stress. However, the voluntary behavior of the trained goats increased over time as a result of positive reinforcement training and habituation.

Blood sampling by venipuncture is a routine procedure used in animal experiments and veterinary diagnostics. It can cause stress due to restraint and pain associated with penetration of the skin by a needle. When stressful procedures are repeated, stress can increase through anticipation after negative experiences or decrease due to habituation and/or positive reinforcement. The aim of this study was to describe the reaction to repeated blood sampling on the affective state of the animals. We wanted to observe how repeated blood sampling would affect stress parameters in goats that underwent an intensive cooperative vet care training protocol and were managed with a focus on gentle handling. Eight dairy goats underwent weekly blood sampling over a four-month period as part of a transfer study. Stress parameters were assessed using serum cortisol concentration, temperature changes in the inner corner of the eye measured by infrared thermography, and an ethogram showing voluntary and aversive behavior. Neither the serum cortisol concentration nor the eye temperature changed significantly over time during blood sampling. However, the ethogram showed that the goats approached the blood sampling position significantly faster and more voluntarily. In this study, we did not observe changes within the measured physiological stress parameters due to repeated blood sampling over three months. However, the voluntary behavior of the trained goats increased over time as a result of positive reinforcement training and habituation.

Osteocytes form an extensive dendritic network within bone tissue that senses mechanical and biochemical stimuli, critical for bone homeostasis. However, the complex interplay between mechanotransduction, oxygen tension, and osteocyte differentiation remains difficult to study due to the lack of physiologically relevant human in vitro models. Previously, we developed a microphysiological system (MPS) that integrates perfusion, mechanical loading, and oxygen control within a culture platform that enables the culture of bone-like three-dimensional (3D) constructs [1]. Here, we demonstrate the application of this MPS as Bonoid-on-a-chip (BoC)-platform to investigate osteoblast-to-early osteocyte transition and mechanosensitive signalling in a human-relevant 3D context, under different physical and chemical conditions. We generated bonoids by bioprinting primary human osteoblasts into a gelatine-hydrogel and cultured them under either static conditions or as dynamic BoC. Different BoC environments consisting in controlled perfusion (0.5 ml min⁻¹), mechanical loading (0% or 10% compression, 1 Hz frequency), and physiological oxygen tension (21% or 12%) over a seven-day period were compared. These different models were additionally treated with dexamethasone (DEXA), to evaluate early osteocyte-targeted effects of drug exposure under these different conditions. We observed high cell viability across all conditions, but clear differences in metabolic activity, morphological changes, and mechanotransduction markers between static and dynamic cultures. Notably, cells within the BoC-platform exhibited extended dendritic processes and significantly increased secretion of prostaglandin E2 and nitrite in response to mechanical stimulation - hallmarks of osteocytic signalling in mechanotransduction. When testing the new BoC as platform for early osteocyte-targeted investigations, we found DEXA exposure disrupting this mechanoresponsive phenotype, highlighting the model’s applicability for pharmacological screening. These findings demonstrate the value of our BoC-platform as a human-relevant model for studying bone mechanobiology and drug responses in vitro. This approach offers a promising alternative to animal models in bone research and opens new avenues for investigating osteocyte function under physiologically dynamic conditions.