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SummaryWith the recent rapid advancements in sequencing technology, the analysis of omics data has become increasingly important for biomedical research. However, many laboratories lack the time or expertise to thoroughly analyze such data. Among omics assays, ATAC-Seq (Assay for transposase-accessiblechromatin usingsequencing) and mRNA-Seq (messengerRNA sequencing) are easy and cost-effective methods that are commonly used to define chromatin accessibility and gene expression levels, respectively. Here we introduce Cactus (Chromatinaccessibility and transcriptomicsunifyingsoftware), a pipeline that streamlines the individual or integrated analysis of ATAC-Seq and mRNA-Seq data. The pipeline is written in Nextflow for efficient scaling, caching, and parallelization, and all tools are packaged in Singularity/Docker containers or conda/Mamba virtual environments for simple installation and high reproducibility. Cactus conducts preprocessing on raw sequencing reads, followed by differential analysis between conditions. Results are split into Differential Analysis Subsets (DASs) based on significance threshold, direction of change, annotated genomic regions, and experiment type. Then, Cactus computes enrichments of entries from internal (i.e., DASs) and external (i.e., ontologies, pathways, DNA binding motifs, ChIP-Seq (Chromatin immunoprecipitationsequencing) binding sites, and chromatin states) databases in DASs and presents results in barplots and customizable heatmaps. The visualization of the results is simplified by the generation of merged PDFs, merged tables, and formatted Excel tables. In conclusion, Cactus can assist researchers in gaining comprehensive insights from chromatin accessibility and gene expression data in a quick, easy, and reproducible manner.Availability and implementationCactus can be installed via Nextflow pull jsalignon/cactus. Source code and documentation are available online (https://github.com/jsalignon/cactus).Contactjerome.salignon@ki.seorchristian.riedel@ki.se

Acoustic allometry occurs when features of animal vocalisations can be predicted from body size measurements. Despite this being considered the norm, allometry sometimes breaks, resulting in species sounding smaller or larger than expected for their size. A recent hypothesis suggests that allometry-breaking mammals cluster into two groups: those with anatomical adaptations to their vocal tracts and those capable of learning new sounds (vocal learners). Here, we tested which mechanism is used to escape from acoustic allometry by probing vocal tract allometry in a proven mammalian vocal learner, the harbour seal (Phoca vitulina). We tested whether vocal tract structures and body size scale allometrically in 68 young individuals. We found that both body length and body mass accurately predict vocal tract length and one tracheal dimension. Independently, body length predicts vocal fold length while body mass predicts a second tracheal dimension. All vocal tract measures are larger in weaners than in pups and some structures are sexually dimorphic within age classes. We conclude that harbour seals do comply with anatomical allometric constraints. However, allometry between body size and vocal fold length seems to emerge after puppyhood, suggesting that ontogeny may modulate the anatomy–learning distinction previously hypothesised as clear cut. We suggest that seals, and perhaps other species producing signals that deviate from those expected from their vocal tract dimensions, may break allometry without morphological adaptations. In seals, and potentially other vocal learning mammals, advanced neural control over vocal organs may be the main mechanism for breaking acoustic allometry.

Vocal production learning (VPL) is the experience-driven ability to produce novel vocal signals through imitation or modification of existing vocalizations. A parallel strand of research investigates acoustic allometry, namely how information about body size is conveyed by acoustic signals. Recently, we proposed that deviation from acoustic allometry principles as a result of sexual selection may have been an intermediate step towards the evolution of vocal learning abilities in mammals. Adopting a more hypothesis-neutral stance, here we perform phylogenetic regressions and other analyses further testing a potential link between VPL and being an allometric outlier. We find that multiple species belonging to VPL clades deviate from allometric scaling but in the opposite direction to that expected from size exaggeration mechanisms. In other words, our correlational approach finds an association between VPL and being an allometric outlier. However, the direction of this association, contra our original hypothesis, may indicate that VPL did not necessarily emerge via sexual selection for size exaggeration: VPL clades show higher vocalization frequencies than expected. In addition, our approach allows us to identify species with potential for VPL abilities: we hypothesize that those outliers from acoustic allometry lying above the regression line may be VPL species. Our results may help better understand the cross-species diversity, variability and aetiology of VPL, which among other things is a key underpinning of speech in our species. This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part II)’.

Vocal production learning (VPL) is the experience-driven ability to produce novel vocal signals through imitation or modification of existing vocalizations. A parallel strand of research investigates acoustic allometry, namely how information about body size is conveyed by acoustic signals. Recently, we proposed that deviation from acoustic allometry principles as a result of sexual selection may have been an intermediate step towards the evolution of vocal learning abilities in mammals. Adopting a more hypothesis-neutral stance, here we perform phylogenetic regressions and other analyses further testing a potential link between VPL and being an allometric outlier. We find that multiple species belonging to VPL clades deviate from allometric scaling but in the opposite direction to that expected from size exaggeration mechanisms. In other words, our correlational approach finds an association between VPL and being an allometric outlier. However, the direction of this association, contra our original hypothesis, may indicate that VPL did not necessarily emerge via sexual selection for size exaggeration: VPL clades show higher vocalization frequencies than expected. In addition, our approach allows us to identify species with potential for VPL abilities: we hypothesize that those outliers from acoustic allometry lying above the regression line may be VPL species. Our results may help better understand the cross-species diversity, variability and aetiology of VPL, which among other things is a key underpinning of speech in our species. This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part II)’.

Introduction: Immune checkpoint inhibitors (ICIs) are a major breakthrough in cancer treatment. Their increasingly frequent use leads to an uprising incidence of immune-related adverse events (irAEs). Among those, myocarditis is the most reported fatal cardiovascular irAE, frequently associated with ICI-related myositis. Case series: Here, we report three cases of ICI-induced myocarditis/myositis with an extremely severe myasthenia gravis-like (MG-like) presentation, highlighting the main challenges in irAEs management. These patients were over 60 years old and presented an ongoing melanoma, either locally advanced or metastatic, treated with ICI combinations. Shortly after the first or second ICI infusion, they were admitted in an intensive care unit (ICU) for grade 3 ICI-induced MG-like symptoms leading to acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV). The initial misdiagnosis was later corrected to severe ICI-induced seronegative myocarditis/myositis upon biological results and histopathology from muscular/endomyocardial biopsies. All of them received urgent high-dose corticosteroids pulses. The oldest patient died prematurely, but the two others received targeted therapies leading to complete recovery for one of them. Discussion: These cases highlight the four main challenges of irAEs, encompassing the lack of knowledge among physicians, the risk of misdiagnosis due to numerous and non-specific symptoms, the frequent overlapping forms of irAEs, and the extremely rare MG-like misleading presentation of myocarditis/myositis. The exact pathophysiology of irAEs remains unclear, although a major involvement of the lymphoid compartment (specifically T lymphocytes) was evidenced. Therapeutic management is based on urgent high-dose corticosteroids. For the severest forms of irAEs, case-by-case targeted immunosuppressive therapies should be urgently administered upon multidisciplinary meetings. Conclusion: These cases highlight the lack of knowledge of irAEs among physicians, aggravated by misleading overlapping forms, requiring specific management in trained units and multidisciplinary care. Severe MG-like presentation of irAEs constitutes an absolute therapeutic emergency with high-dose corticosteroids and targeted immunosuppressive therapy.

Introduction L’incidence de la syphilis augmente depuis plusieurs annees. Devant un tableau clinique evocateur de forme secondaire, le diagnostic repose habituellement sur la positivite de la serologie. Nous rapportons une observation de syphilis secondaire restant seronegative chez un patient traite par rituximab ou le diagnostic a ete porte par les donnees histologiques et un test PCR sur les lesions cutanees. Materiel et Methodes Un patient de 25 ans traite par rituximab depuis 6 ans pour un pemphigus vulgaire etait adresse pour une recidive atypique de son pemphigus. A l’examen, il avait une eruption maculopapuleuse diffuse non prurigineuse avec localisation palmaire, des lesions acneiformes du menton, et des erosions du gland. Le patient rapportait un rapport homosexuel non protege 3 mois avant le debut de l’eruption. Le tableau etait tres evocateur de syphilis secondaire mais la serologie syphillitique (test treponemique et test non treponemique) ainsi que la PCR treponeme dans les urines etaient negatives. Il y avait un effondrement total de la population lymphocytaire B (zero lymphocyte B) sur l’immunophenotypage sanguin, les autres elements biologiques etant normaux. Le diagnostic de syphilis secondaire [MR2] etait redresse grâce a la positivite des tests PCR treponeme preleves a partir des lesions cutaneomuqueuses. La biopsie cutanee d’une lesion papuleuse mettait egalement en evidence de multiples treponemes en immunohistochimie. Resultats La syphilis seronegative chez les sujets avec un deficit immunitaire humoral est un piege diagnostique. Devant un tableau clinique evocateur, le diagnostic peut etre redresse grâce aux tests PCR et a l’examen histologique. Discussion Le rituximab est un anticorps monoclonal chimerique dirige contre la molecule de surface CD20 present sur les lymphocytes B, entrainant ainsi leur depletion. Les lymphocytes B etant a l’origine de la production des anticorps, leur absence met en defaut une bonne interpretation serologique. Cette observation confirme l’interet des tests PCR sur les lesions cutanees et des examens histologiques en cas de suspicion clinique de syphillis non attestee sur le plan serologique. Il s’agit a notre connaissance du deuxieme cas rapporte dans un contexte de traitement par rituximab. Le premier concernait un patient traite pour une sclerose en plaque, et comme dans notre observation, le diagnostic etait redresse grâce aux PCR treponeme.