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It is estimated that only 0.02% of disseminated tumour cells are able to seed overt metastases 1 . While this suggests the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unclear. Here, combining transposon technology 2 and fluorescence niche labelling 3 , we developed an in vivo CRISPR activation screen to systematically investigate the interactions between hepatocytes and metastatic cells. We identify plexin B2 as a critical host-derived regulator of liver colonization in colorectal and pancreatic cancer and melanoma syngeneic mouse models. We dissect a mechanism through which plexin B2 interacts with class IV semaphorins on tumour cells, leading to KLF4 upregulation and thereby promoting the acquisition of epithelial traits. Our results highlight the essential role of signals from the liver parenchyma for the seeding of disseminated tumour cells before the establishment of a growth-promoting niche. Our findings further suggest that epithelialization is required for the adaptation of CRC metastases to their new tissue environment. Blocking the plexin-B2-semaphorin axis abolishes metastatic colonization of the liver and therefore represents a therapeutic strategy for the prevention of hepatic metastases. Finally, our screening approach, which evaluates host-derived extrinsic signals rather than tumour-intrinsic factors for their ability to promote metastatic seeding, is broadly applicable and lays a framework for the screening of environmental constraints to metastasis in other organs and cancer types., (© 2024. The Author(s).)

Objective: To examine the presence of women in the organs of the Interterritorial Council of the Spanish National Health System (CISNS)., Method: Annual reports of the CISNS from 2005 to 2022 were analyzed. Artificial intelligence was used to assign gender, and percentages of women's participation were calculated. Temporal evolution, vertical segregation, and horizontal segregation were analyzed., Results: Between 2005 and 2022, there were 14,308 participations in 85 organs, with 52% women, rising from 42% in 2005 to 61% in 2022. There was a higher participation of women in propositional organs (54%), followed by executive ones (50%), and plenary sessions (40%). The General State Administration had 61% women compared to 48% in autonomous communities. Women's participation varied by topic, being higher (82%) in gender violence and lower (35%) in inspection., Conclusions: Although there is a slight reduction in the participation gap between women and men, inequalities persist. Women have less presence in higher hierarchical levels (plenary sessions), maintaining vertical segregation. Additionally, women's representation in certain topics remains low, maintaining horizontal segregation. Concrete actions must be taken to continue advancing equality and improving health outcomes in society as a whole., (Copyright © 2024 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Microelectrode recordings from human peripheral and cranial nerves provide a means to study both afferent and efferent axonal signals at different levels of detail, from multi- to single-unit activity. Their analysis can lead to advancements both in diagnostic and in the understanding of the genesis of neural disorders. However, most of the existing computational toolboxes for the analysis of microneurographic recordings are limited in scope or not open-source. Additionally, conventional burst-based metrics are not suited to analyze pathological conditions and are highly sensitive to distance of the microelectrode tip from the active axons. To address these challenges, we developed an open-source toolbox that offers advanced analysis capabilities for studying neuronal reflexes and physiological responses to peripheral nerve activity. Our toolbox leverages the observation of temporal sequences of action potentials within inherently cyclic signals, introducing innovative methods and indices to enhance analysis accuracy. Importantly, we have designed our computational toolbox to be accessible to novices in biomedical signal processing. This may include researchers and professionals in healthcare domains, such as clinical medicine, life sciences, and related fields. By prioritizing user-friendliness, our software application serves as a valuable resource for the scientific community, allowing to extract advanced metrics of neural activity in short time and evaluate their impact on other physiological variables in a consistent and standardized manner, with the final aim to widen the use of microneurography among researchers and clinicians., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Eosinophils are a class of granulocytes with pleiotropic functions in homeostasis and various human diseases. Nevertheless, they are absent from conventional single-cell RNA sequencing atlases owing to technical difficulties preventing their transcriptomic interrogation. Consequently, eosinophil heterogeneity and the gene regulatory networks underpinning their diverse functions remain poorly understood. We have developed a stress-free protocol for single-cell RNA capture from murine tissue-resident eosinophils, which revealed distinct intestinal subsets and their roles in colitis. Here we describe in detail how to enrich eosinophils from multiple tissues of residence and how to capture high-quality single-cell transcriptomes by preventing transcript degradation. By combining magnetic eosinophil enrichment with microwell-based single-cell RNA capture (BD Rhapsody), our approach minimizes shear stress and processing time. Moreover, we report how to perform genome-wide CRISPR pooled genetic screening in ex vivo-conditioned bone marrow-derived eosinophils to functionally probe pathways required for their differentiation and intestinal maturation. These protocols can be performed by any researcher with basic skills in molecular biology and flow cytometry, and can be adapted to investigate other granulocytes, such as neutrophils and mast cells, thereby offering potential insights into their roles in both homeostasis and disease pathogenesis. Single-cell transcriptomics of eosinophils can be performed in 2-3 d, while functional genomics assays may require up to 1 month., (© 2024. Springer Nature Limited.)

Objectives: To estimate the incidence and prevalence of SLE in Italy, and to describe the demographic and clinical characteristics of patients with newly diagnosed SLE., Methods: A retrospective cohort study was conducted using The Health Improvement Network general practice database in Italy, encompassing data from 634 753 people. SLE cases were identified over the period 2017-2022, employing three alternative definitions to provide a more detailed understanding of SLE characteristics. Incidence rates were expressed as cases per 100 000 person-years and prevalence as cases per 100 000 people. Demographic and clinical characteristics of incident SLE cases were also studied., Results: From 2017 to 2022, a total of 191 incident and 1385 prevalent cases were identified under our first definition. In 2022, the incidence rate was 6.51 cases (95% CI 6.29 to 6.74) per 100 000 person-years, and the prevalence 60.57 (95% CI 59.89 to 61.25) per 100 000 people, being the prevalence five times higher in women compared with men. Both estimates have trended upwards since 2017. A geographical variation across the country was also seen. The demographic and clinical characteristics of incident SLE cases were described, while the potential associations of SLE incidence with some pre-existing conditions were observed, such as chronic kidney disease, chronic hepatic disease, rheumatoid arthritis and Sjogren's syndrome., Conclusions: The results of this nationwide study, the first conducted in Italy, showed that the incidence of SLE has increased in Italy in recent years. Age, sex, and area of residence strongly correlate with the epidemiology of this condition., Competing Interests: Competing interests: PF, ICA, MZ, CF, AB, IM and GE declare no conflicts of interest. EZF and PP are employees of Cegedim Srl, which is a private company that performs financially supported studies for several pharmaceutical companies.CB are SB are employees of AstraZeneca Italy. LGM reports receiving grants from Bayer, Daiiki-Sankyo, and Boehringer Ingelheim and speaker fees from Pfizer and Bayer, outside this work. GM reports receiving grants from CSL Behring for consultancy outside this work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and skeletal muscles; diagnostic criteria of JDM include an unforeseeable mixture of clinical features, while treatment modalities commonly require corticosteroids or immunosuppressant agents. Although the pathogenesis of JDM is not completely understood, several infectious triggers have been linked to its priming via anecdotal reports related to children. Pediatric cases of recent-onset JDM have been temporally associated to an infectious disease by the power of increased titers of circulating antibodies to a putative infectious agent, including parasites, and/or detectable viral RNA or bacterial DNA. With this narrative review we offer an update about JDM association with a host of infections, namely parvovirus B19, Epstein-Barr virus, Coxsackie virus, human immune deficiency virus, severe acute respiratory syndrome coronavirus 2, Mycoplasma pneumoniae and Toxoplasma gondii , as resulting from the medical literature. Few are the evidence-proved results addressing JDM as an unambiguous post-infectious disorder and available data specifically related to children are poor, highlighting the need of further research into the exploration between environmental cut-out factors and JDM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sassetti, Borrelli, Mazuy, Turrini, Rigante and Esposito.)

In recent decades, nature-based solutions (NBSs) have spread in scientific research, and they are increasingly deployed in cities' strategic planning. While the number of nonhuman animals in cities is growing, a specific reflection on the advantages of human-animal interactions as potential NBSs is still lacking. This article aims to provide an overview of the current situation of animals in cities and to explore the roles of animals and their interactions with humans in such a context. These topics are crucial to the European project IN-HABIT in Lucca (Italy), which aims to codify an integrated policy on the relationship between people and animals; its outputs will then be transferred and replicated in other cities. This article concludes by highlighting the need for the involvement of different stakeholders in public-private-people partnerships to implement actions that aim to valorize human-animal relationships and their positive effects. This study presents a perspective on the relevance of animal NBSs to increase the quality of life in cities, both for citizens and for animals living in cities, and to also introduce the opportunity to develop an integrated animal urban policy able to valorize human-animal interactions in cities., Competing Interests: The authors declare no conflicts of interest.

Sequencing-based spatial transcriptomics (ST) methods allow unbiased capturing of RNA molecules at barcoded spots, charting the distribution and localization of cell types and transcripts across a tissue. While the coarse resolution of these techniques is considered a disadvantage, we argue that the inherent proximity of transcriptomes captured on spots can be leveraged to reconstruct cellular networks. To this end, we developed ISCHIA (Identifying Spatial Co-occurrence in Healthy and InflAmed tissues), a computational framework to analyze the spatial co-occurrence of cell types and transcript species within spots. Co-occurrence analysis is complementary to differential gene expression, as it does not depend on the abundance of a given cell type or on the transcript expression levels, but rather on their spatial association in the tissue. We applied ISCHIA to analyze co-occurrence of cell types, ligands and receptors in a Visium dataset of human ulcerative colitis patients, and validated our findings at single-cell resolution on matched hybridization-based data. We uncover inflammation-induced cellular networks involving M cell and fibroblasts, as well as ligand-receptor interactions enriched in the inflamed human colon, and their associated gene signatures. Our results highlight the hypothesis-generating power and broad applicability of co-occurrence analysis on spatial transcriptomics data., (© 2024. The Author(s).)