Improving the composition of donor milk using machine learning and optimisation techniques

by Jacqueline Muts, Danée Knevel, Dick den Hertog, Rachel K. Wong, Timothy C.Y. Chan, Britt J. van Keulen, Johannes B. van Goudoever, Chris H.P. van den Akker

Background and aims

The macronutrient composition of donor human milk (DHM) can vary substantially due to several factors such as maternal age, diet, and lactation duration. However, consistent macronutrient levels in DHM facilitate the administration of the required amounts to preterm infants. The current pooling strategy at most human milk banks combines milk from different batches from a single donor. This study aims to stabilize the macronutrient quality of DHM by pooling milk from different donors by utilizing machine learning prediction and optimisation techniques.

Methods

The current pooling strategy is compared with a new theoretical approach that pools milk batches from up to 5 donors. To predict the crude protein and energy content, we used the following variables: body mass index, the donor’s diet (vegetarian or non-vegetarian), maternal age, full-term or preterm delivery, lactation stage, and volume pumped. These predictions are then used within an optimisation model to create milk pools that minimize the deviations from the target macronutrient levels (1.0 g protein/100 mL and 70 kcal/100 mL).

Results

The prediction model is based on 2236 created single-donor pools from 480 donors. Random forest regression models provided the most accurate predictions of macronutrient content. The new pooling strategy using multiple donors shows reduced deviations from target values compared to the current single-donor approach (average total absolute deviation 0.402 versus 0.664).

Conclusion

This study proves the potential of data-driven methods to improve operational efficiency in human milk banks, and improving the consistency of donor human milk.

Habitual coffee consumption poorly correlates with sleep quality and daytime sleepiness: A cross-sectional study

by Simon Söderholm, Martin Ulander, Vanessa William Toma, Sara Kaufmann, Xiangyu Qiao, Daniel Berglind, Susanna Calling, Bledar Daka, Ludger Grote, Mats Martinell, Frida Bergman, Pontus Henriksson, Carl-Johan Östgren, Wen Zhong, Claudio Cantù, Fredrik Iredahl

Coffee is the most common drink in the world, second only to water. This makes caffeine, the ingredient of coffee known for its wakefulness-promoting effects, one of the most used psychoactive substances. The psychoactive property of caffeine is well-characterized, and entails its interaction with the adenosine receptors, involved in sleep regulation. While studies have shown a deleterious immediate effect of caffeine on sleep, less is known about the effects of chronic caffeine exposure. In the present cross-sectional study, we investigated this relationship across a large cohort of 30,154 individuals participating in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), which allowed us to compare habitual coffee intake with sleep habits, subjective estimate of daytime sleepiness, and underlying genetic variants. According to our analyses, different degrees of coffee consumption, confirmed by statistical association with previously reported genetic variants, showed very low association with estimated patterns of sleep habits or perceived daytime sleepiness. These results indicate that coffee may be less impactful on sleep habits than previously thought, or that other mechanisms, such as the adaptive capabilities of the adenosine system in adult coffee users, may dampen its psychoactive potency.

Integrating sequence-based GWAS and comparative genomic analysis reveals conservation and species-specificity of putative functional variants influencing tail length and tail abnormalities in pigs and sheep

by Xuying Zhang, Johanna Mainzer, Isabella Giambra, Tong Yin, Petra Engel, Hannah Hümmelchen, Henrik Wagner, Axel Wehrend, Christiane Egerer, Katharina Gerhards, Gerald Reiner, Sven König

Long tails trigger tail biting in pigs and increase the risk of flystrike infections in sheep. Tail docking has been a common management practice in both species for decades, but increasingly conflicts with legal animal welfare guidelines. Sustainable solutions require breeding strategies targeting shorter tails. In consequence, the aims were to conduct whole-genome sequencing (WGS)-based genome-wide association studies (GWAS) and comparative genomic analyses (CGA) to explore functional elements influencing tail traits. Phenotypically divergent experimental populations of pigs and sheep were established through unified selection and mating experiments. Tail traits included tail length (TL) measured at birth, and tail abnormalities (TA) assessed radiographically at 14 weeks of age. WGS-based GWAS identified a significant locus on SSC18 in pigs and suggestive loci for TL in both species, which, together with previously reported loci for TA, were further analyzed by CGA. The genomic windows of the significant locus on SSC18 in pigs and the TL GWAS locus on OAR4 in sheep were found to be conserved, harboring six common genes with predicted functional variants. These variants were jointly associated with TL (P_lm ) in both species in linear regression models adjusted for sex, age of the dam, body length, and body weight. In other GWAS locus windows (±1 Mb), species-specific TL candidate genes were identified in sheep (HOXB13, MUC5B, EPB41L3, MTCL1, PIEZO2, MPPE1, and LOXHD1) and in pigs (KNL1, DISP2, SPRED1, TGFB2, and HAND1), each harboring associated putative functional variants. For TA, sheep-specific candidates (PGM2, LRRC66, CRACD, LOC105601916, and SH2D4B) and pig-specific candidates (MYOT, TMCO6, and PCDHAC2) were revealed using logistic regression models (P_glm ). GO analyses of candidate genes predicted shared biological processes between sheep and pigs, whereas pathway analyses indicated that common carbohydrate metabolism pathways, along with species-specific immune and inflammatory signaling, and pig-specific TGF-β signaling and endochondral ossification, may contribute to tail length variation and abnormalities. These findings provided deeper insights into the genetic basis of differential embryonic tail morphogenesis and perinatal tail development across species.

“You could get the best of both breeds or the worst of both”: UK public attitudes towards crossbreeding in dogs - with a specific focus on brachycephalic dogs

by Elizabeth Youens, Dan G. O’Neill, Zoe Belshaw, Johanna Neufuss, Mickey S. Tivers, Rowena M. A. Packer

Extreme conformation and reduced genetic diversity are recognised to lead to severely reduced health, welfare and longevity in certain dog breeds. There is growing interest in applying strategic crossbreeding to promote more moderate conformations and greater genetic diversity within currently problematic breeds. Crossbreeding could therefore lead to more rapid and effective improvements in welfare compared to current practices of within-breed selection. Deliberate crossbreeding between distinct different dog breeds is not a new concept; it was historically commonly used to create the current pure breeds, to increase genetic diversity and to bring new physical and/or temperament traits into existing breeds. However, a recent surge in the popularity of ‘designer crossbreeds’ (intentional crosses between established purebreds) has elicited fresh interest around the potential positives and negatives of crossbreeding practices. Further research on crossbred brachycephalic dogs is urgently required for a greater understanding of the motivators and barriers to their acquisition. An online survey explored factors that motivate dog breed choice and acquisition of both crossbreed and purebred dogs. In addition, the survey used both closed and open questioning to explore the UK public’s perceptions of crossbreeding, specifically (i) between a brachycephalic breed and a non-brachycephalic breed, and (ii) between two non-brachycephalic breeds. Free-text results were analysed using content analysis and subsequently quantified. Results from 4,899 participants identified that key motivators to acquire a brachycephalic crossbreed vs a brachycephalic purebred included perceptions of improved health, including the reduction in risk of breed and conformation-related disorders, and increased genetic diversity. However, the desire to acquire a purebred dog, or even a specific breed, remained a significant barrier to crossbreed acquisition, alongside concerns surrounding the ethics of crossbreeding. Other barriers included perceived negative changes to appearance and temperament of the offspring from crossbreeding. The current study identified a common set of acquisition decision-making factors across all ownership groups, including desiring a dog who the owner perceives to enjoy being loved and to enjoy physical affection, but further demonstrated that good health is of motivational low priority to some dog owners, particularly to owners of purebred brachycephalic dogs. The mix of positive and negative public perceptions and beliefs around crossbreeding and crossbreed dogs demonstrate the need for further research into the health, temperament and appearance of brachycephalic crossbreed dogs. The suitability of crossbreed dogs as an alternative to certain current purebred breeds with high risk of genetic or conformational disorders depends on both public desire and on evidence-based selection of suitable breeds to encourage crosses which maximise canine welfare.

Placebo and nocebo in clinical practice: An online cross-sectional survey of healthcare professionals from European countries on views, practices and training needs

by Mary O’Keeffe, Nathan Skidmore, Arianna Bagnis, Przemysław Bąbel, Elżbieta A. Bajcar, Alessandra De Palma, Andrea W.M. Evers, Eveliina Glogan, Julia W. Haas, Stefanie H. Meeuwis, Marek Oleszczyk, Antonio Portolés, Johan W.S. Vlaeyen, Katia Mattarozzi, on behalf of PANACEA Consortium

Background

Placebo and nocebo effects significantly influence health outcomes, yet healthcare professionals receive limited training and guidance on their mechanisms and clinical application, creating a gap in education and practical understanding. Conducted within the European PANACEA Consortium, this study evaluated healthcare professionals’ knowledge, attitudes, and practices regarding placebo and nocebo effects, and assessed their needs in further education.

Methods

An online cross-sectional survey among a European multi-country convenience sample of healthcare professionals collected data assessing participants’ knowledge, perceptions, and experiences regarding placebo and nocebo effects; their application and ethical considerations in clinical practice; and investigated educational needs and interest in further training. Quantitative data were analyzed using descriptive statistics, and thematic analysis was applied to the free-text responses.

Results

Amongst 807 participants, 71.7% reported taking advantage of placebo effects in their practice, and over half of participants (55.8%) observing nocebo effects. Participants reported feeling somewhat confident (53.3%) in harnessing placebo effects with 47.5% feeling confident in preventing nocebo effects. The majority of respondents had not received formal training on placebo and nocebo effects, with most expressing an interest in further training in areas such as healthcare education, emphasizing communication skills to enhance placebo effects, and knowledge to recognize and reduce nocebo effects.

Conclusions

There is a significant need for more comprehensive training on placebo and nocebo effects, particularly in early health professional education. These findings informed the development of educational resources and best practice recommendations developed as part of the outcomes from the PANACEA Consortium, improving the understanding and application of these effects among healthcare professionals across Europe.

Study protocol: MRI-based assessment of cerebral blood flow under pharmacologically elevated blood pressure in patients under general anesthesia, and in sedated ICU patients with aneurysmal subarachnoid hemorrhage

by Jonas Österlind, Johan Birnefeld, Elin Birnefeld, Magnus Hultin, Sara Qvarlander, Anders Wåhlin, Petter Holmlund, Laleh Zarrinkoob

Background

Maintaining cerebral perfusion during anesthesia and intensive care is critical, yet the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF) remains poorly defined. In patients with aneurysmal subarachnoid hemorrhage (aSAH), pharmacologically induced hypertension is commonly applied to support cerebral perfusion, but its effects are uncertain.

Methods

This protocol describes two parallel clinical studies using identical methodology. The first study population includes adults undergoing elective general anesthesia (MAP-ANE), and the second comprises sedated intensive care patients with aSAH (MAP-SAH). In both study populations, MAP will be increased stepwise with norepinephrine (NE) infusion under continuous invasive blood pressure monitoring, and CBF measured with phase-contrast MRI (PCMRI) and arterial spin labeling (ASL), while near-infrared spectroscopy (NIRS) will be performed in parallel to evaluate its validity as a surrogate marker. The primary outcome is the change in total CBF between baseline and elevated MAP, directly testing whether induced hypertension increases CBF. Secondary outcomes include ASL perfusion changes, the slope of the MAP–CBF relationship, systemic–cerebral hemodynamic correlations, and NIRS responses.

Expected impact

These studies test the hypothesis that pharmacological MAP augmentation does not predictably increase CBF. By combining quantitative MRI with invasive monitoring, it aims to clarify MAP–CBF interactions, define the physiological basis of induced hypertension, and assess whether NIRS can serve as a clinically useful proxy. Findings are expected to inform safer and more individualized blood pressure management in perioperative and neurocritical care. The studies are registered at ClinicalTrials.gov (MAP-ANE: NCT06855407; MAP-SAH: NCT06033378).

Trial registration

ClinicalTrials.gov, MAP-ANE NCT06855407, MAP-SAH NCT06033378