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Research is the vital expression of humankind’s most important qualities: curiosity and imagination.

Explorers, inventors, pioneers—dedicated researchers on the frontiers of science and the humanities.

Insight, when it comes, changes everything.

Publications

The NOMIS community of researchers and partners is instrumental in driving interdisciplinary collaboration, generating insights and ultimately advancing our understanding of the world. A key component of these efforts is knowledge sharing. Comprising a unique offering of engaging scientific lectures, insightful films about our awardees’ research, and a comprehensive publication database, NOMIS Insights are designed to facilitate the sharing of knowledge. They showcase the groundbreaking findings and innovative perspectives born from NOMIS-supported research endeavors, embodying our dedication to enabling scientific progress.

Our NOMIS Insight database provides a comprehensive source of all publications resulting from NOMIS-supported research projects.

A male-essential miRNA is key for avian sex chromosome dosage compensation

NOMIS Researcher(s)

Published in

July 16, 2025

Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ)1. The differentiation of avian sex chromosomes from ancestral autosomes entails the loss of most genes from the W chromosome during evolution1,2. However, the extent to which mechanisms evolved that counterbalance this substantial reduction in female gene dosage remains unclear. Here we report functional in vivo and evolutionary analyses of a Z-linked microRNA (miR-2954) with strong male-biased expression, previously proposed to mediate avian sex chromosome dosage compensation3. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality in homozygous knockout males, probably driven by specific upregulation of dosage-sensitive Z-linked target genes. Evolutionary gene expression analyses further revealed that these dosage-sensitive target genes underwent both transcriptional and translational upregulation on the single Z in female birds. Altogether, this work unveils a scenario in which evolutionary pressures following W gene loss drove transcriptional and translational upregulation of dosage-sensitive Z-linked genes in females but also their transcriptional upregulation in males. The resulting excess of transcripts in males, resulting from the combined activity of two upregulated dosage-sensitive Z gene copies, was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. This study uncovered a unique sex chromosome dosage compensation system in birds, in which a microRNA has become essential for male survival.

Research field(s)
Bioinformatics, Biochemistry & Molecular Biology, Developmental Biology, Genetics & Heredity, Evolutionary Biology

DOI
10.1038/s41586-025-09256-9

Atlas of amnion development during the first trimester of human pregnancy

NOMIS Researcher(s)

Published in

July 14, 2025

The amnion is a critical extra-embryonic structure that supports foetal development, yet its ontogeny remains poorly defined. Here, using single-cell transcriptomics, we identified major cell types and subtypes in the human amnion across the first trimester of pregnancy, broadly categorized into epithelial, mesenchymal and macrophage lineages. We uncovered epithelial–mesenchymal and epithelial–immune transitions, highlighting dynamic remodelling during early pregnancy. Our results further revealed key intercellular communication pathways, including BMP4 signalling from mesenchymal to epithelial cells and TGF-β signalling from macrophages to mesenchymal cells, suggesting coordinated interactions that drive amnion morphogenesis. In addition, integrative comparisons across humans, non-human primates and in vitro stem cell-based models reveal that stem cell-based models recapitulate various stages of amnion development, emphasizing the need for careful selection of model systems to accurately recapitulate in vivo amnion formation. Collectively, our findings provide a detailed view of amnion cellular composition and interactions, advancing our understanding of its developmental role and regenerative potential.

Research field(s)
Molecular Biology, Developmental Biology, Microbiology

DOI
10.1038/s41556-025-01696-9

A foundation model to predict and capture human cognition

NOMIS Researcher(s)

Published in

July 2, 2025

Establishing a unified theory of cognition has been an important goal in psychology1,2. A first step towards such a theory is to create a computational model that can predict human behaviour in a wide range of settings. Here we introduce Centaur, a computational model that can predict and simulate human behaviour in any experiment expressible in natural language. We derived Centaur by fine-tuning a state-of-the-art language model on a large-scale dataset called Psych-101. Psych-101 has an unprecedented scale, covering trial-by-trial data from more than 60,000 participants performing in excess of 10,000,000 choices in 160 experiments. Centaur not only captures the behaviour of held-out participants better than existing cognitive models, but it also generalizes to previously unseen cover stories, structural task modifications and entirely new domains. Furthermore, the model’s internal representations become more aligned with human neural activity after fine-tuning. Taken together, our results demonstrate that it is possible to discover computational models that capture human behaviour across a wide range of domains. We believe that such models provide tremendous potential for guiding the development of cognitive theories, and we present a case study to demonstrate this.

Research field(s)
Information & Communication Technologies, Psychology & Cognitive Sciences, Psychology & Cognitive Sciences, Behavioral Science & Comparative Psychology

DOI
10.1038/s41586-025-09215-4

Capturing the complexity of human strategic decision-making with machine learning

NOMIS Researcher(s)

Published in

June 25, 2025

Strategic decision-making is a crucial component of human interaction. Here we conduct a large-scale study of strategic decision-making in the context of initial play in two-player matrix games, analysing over 90,000 human decisions across more than 2,400 procedurally generated games that span a much wider space than previous datasets. We show that a deep neural network trained on this dataset predicts human choices with greater accuracy than leading theories of strategic behaviour, revealing systematic variation unexplained by existing models. By modifying this network, we develop an interpretable behavioural model that uncovers key insights: individuals’ abilities to respond optimally and reason about others’ actions are highly context dependent, influenced by the complexity of the game matrices. Our findings illustrate the potential of machine learning as a tool for generating new theoretical insights into complex human behaviours.

Research field(s)
Information & Communication Technologies, Psychology & Cognitive Sciences

DOI
10.1038/s41562-025-02230-5

SARS-CoV-2 nucleocapsid protein directly prevents cGAS–DNA recognition through competitive binding

NOMIS Researcher(s)

Published in

June 23, 2025
A hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the delayed interferon response. Interferons are typically produced upon host recognition of pathogen- or damage-associated molecular patterns, such as nucleic acids. While the mechanisms by which SARS-CoV-2 evades host recognition of its RNA are well studied, how it evades immune responses to cytosolic DNA—leaked from mitochondria or nuclei during infection—remains poorly understood. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein directly suppresses DNA sensing by cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS). Although primarily known for packaging the viral RNA genome, we uncover that the SARS-CoV-2 nucleocapsid protein also binds DNA with high affinity and competitively blocks cGAS activation. Using cell-free biochemical and biophysical approaches, including single-molecule optical tweezers, we show that the nucleocapsid protein binds to DNA at nanomolar concentrations and cocondenses with DNA at micromolar concentrations, thereby impeding stable cGAS-DNA interactions required for signal propagation. Hyperphosphorylation of the nucleocapsid protein diminishes its competitive binding capacity. Our findings reveal an unexpected role of the SARS-CoV-2 nucleocapsid protein in directly suppressing the cGAS-STING pathway, strongly suggesting that this contributes to the delayed interferon response during infection. This study raises the possibility that nucleocapsid proteins of other RNA viruses may also exhibit moonlighting functions by antagonizing host nucleic acid–sensing pathways.

Research field(s)
Biological Physics, Biochemistry & Molecular Biology, Virology, Immunology

DOI
10.1073/pnas.2426204122

Succinate undermines FOXP3 stability and disrupts Treg cell function

NOMIS Researcher(s)

Published in

June 2, 2025

Increased levels of succinate in individuals with inflammatory bowel disease suppress succinylation of the transcription factor FOXP3, leading to its increased ubiquitination and degradation in intestinal regulatory T cells. This process exacerbates colon inflammation and contributes to disease progression.

DOI
10.1038/s41590-025-02167-x

Mesoscale properties of protein clusters determine the size and nature of liquid-liquid phase separation (LLPS)

NOMIS Researcher(s)

Published in

June 2, 2025

The observation of Liquid-Liquid Phase Separation (LLPS) in biological cells has dramatically shifted the paradigm that soluble proteins are uniformly dispersed in the cytoplasm or nucleoplasm. The LLPS region is preceded by a one-phase solution, where recent experiments have identified clusters in an aqueous solution with 102-103 proteins. Here, we theoretically consider a core-shell model with mesoscale core, surface, and bending properties of the clusters’ shell and contrast two experimental paradigms for the measured cluster size distributions of the Cytoplasmic Polyadenylation Element Binding-4 (CPEB4) and Fused in Sarcoma (FUS) proteins. The fits to the theoretical model and earlier electron paramagnetic resonance (EPR) experiments suggest that the same protein may exhibit hydrophilic, hydrophobic, and amphiphilic conformations, which act to stabilize the clusters. We find that CPEB4 clusters are much more stable compared to FUS clusters, which are less energetically favorable. This suggests that in CPEB4, LLPS consists of large-scale aggregates of clusters, while for FUS, clusters coalesce to form micron-scale LLPS domains.

Research field(s)
Biological Physics, Chemical Physics

DOI
10.1038/s42005-025-02134-w

Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates

NOMIS Researcher(s)

Published in

May 23, 2025

Cytosolic aggregation of the nuclear protein TAR DNA-binding protein 43 (TDP-43) is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress. These two events collectively induce intra-condensate demixing, giving rise to a dynamic TDP-43-enriched phase within stress granules, which subsequently transition into pathological aggregates. Intra-condensate demixing of TDP-43 is observed in iPS-motor neurons, a disease mouse model, and patient samples. Mechanistically, intra-condensate demixing is triggered by local unfolding of the RRM1 domain for intermolecular disulfide bond formation and by increased hydrophobic patch interactions in the C-terminal domain. By engineering TDP-43 variants resistant to intra-condensate demixing, we successfully eliminate pathological TDP-43 aggregates in cells. We suggest that up-concentration inside condensates followed by intra-condensate demixing could be a general pathway for protein aggregation.

Research field(s)
Neuroscience, Biochemistry & Molecular Biology, Biophysics

DOI
10.1016/j.cell.2025.04.039

Robust prediction of synthetic gRNA activity and cryptic DNA repair by disentangling cellular CRISPR cleavage outcomes

NOMIS Researcher(s)

Published in

May 21, 2025

The ability to robustly predict guide RNA (gRNA) activity is a long-standing goal for CRISPR applications, as it would reduce the need to pre-screen gRNAs. Quantification of formation of short insertions and deletions (indels) after DNA cleavage by transcribed gRNAs has been typically used to measure and predict gRNA activity. We evaluate the effect of chemically synthesized Cas9 gRNAs on different cellular DNA cleavage outcomes and find that the activity of different gRNAs is largely similar and often underestimated when only indels are scored. We provide a simple linear model that reliably predicts synthetic gRNA activity across cell lines, robustly identifies inefficient gRNAs across different published datasets, and is easily accessible via online genome browser tracks. In addition, we develop a homology-directed repair efficiency prediction tool and show that unintended large-scale repair events are common for Cas9 but not for Cas12a, which may be relevant for safety in gene therapy applications.

Research field(s)
Genetics & Heredity

DOI
10.1038/s41467-025-59947-0

Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS

NOMIS Researcher(s)

Published in

May 19, 2025

Mutations in FUS and TARDBP cause amyotrophic lateral sclerosis (ALS), but the precise mechanisms of selective motor neuron degeneration remain unresolved. To address if pathomechanisms are shared across mutations and related to either gain- or loss-of-function, we performed single-cell RNA sequencing across isogenic induced pluripotent stem cell-derived neuron types, harbouring FUS P525L, FUS R495X, TARDBP M337V mutations or FUS knockout. Transcriptional changes were far more pronounced in motor neurons than interneurons. About 20% of uniquely dysregulated motor neuron transcripts were shared across FUS mutations, half from gain-of-function. Most indicated mitochondrial impairments, with attenuated pathways shared with mutant TARDBP M337V as well as C9orf72-ALS patient motor neurons. Mitochondrial motility was impaired in ALS motor axons, even with nuclear localized FUS mutants, demonstrating shared toxic gain-of-function mechanisms across FUS- and TARDBP-ALS, uncoupled from protein mislocalization. These early mitochondrial dysfunctions unique to motor neurons may affect survival and represent therapeutic targets in ALS.

Research field(s)
Molecular Biology, Neuroscience, Biochemistry & Molecular Biology

DOI
10.1038/s41467-025-59679-1

Small-molecule dissolution of stress granules by redox modulation benefits ALS models

NOMIS Researcher(s)

Published in

May 14, 2025

Neurodegenerative diseases, such as amyotrophic lateral sclerosis, are often associated with mutations in stress granule proteins. Aberrant stress granule condensate formation is associated with disease, making it a potential target for pharmacological intervention. Here, we identified lipoamide, a small molecule that specifically prevents cytoplasmic condensation of stress granule proteins. Thermal proteome profiling showed that lipoamide stabilizes intrinsically disordered domain-containing proteins, including SRSF1 and SFPQ, which are stress granule proteins necessary for lipoamide activity. SFPQ has redox-state-specific condensate dissolving behavior, which is modulated by the redox-active lipoamide dithiolane ring. In animals, lipoamide ameliorates aging-associated aggregation of a stress granule reporter protein, improves neuronal morphology and recovers motor defects caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants. Thus, lipoamide is a well-tolerated small-molecule modulator of stress granule condensation, and dissection of its molecular mechanism identified a cellular pathway for redox regulation of stress granule formation.

Research field(s)
Neuroscience, Biochemistry & Molecular Biology

DOI
10.1038/s41589-025-01893-5

Exchange anisotropies in microwave-driven singlet-triplet qubits

NOMIS Researcher(s)

Published in

April 24, 2025

Hole spin qubits are emerging as the workhorse of semiconducting quantum processors because of their large spin-orbit interaction, enabling fast, low-power, all-electric operations. However, this interaction also causes non-uniformities, resulting in site-dependent qubit energies and anisotropies. Although these anisotropies enable single-spin control, if not properly harnessed, they can hinder scalability. Here, we report on microwave-driven singlet-triplet qubits in planar germanium and use them to investigate spin anisotropies. For in-plane magnetic fields, the spins are largely anisotropic and electrically tunable, allowing access to all transitions and coherence times exceeding 3 μs are extracted. For out-of-plane fields they have an isotropic response. Even in this field direction, where the qubit lifetime is strongly affected by nuclear spins, we find 400 ns coherence times. Our work adds a valuable tool to investigate and harness the spin anisotropies, applicable to two-dimensional devices, facilitating the path towards scalable quantum processors.

Research field(s)
Quantum, Microwave, Qubits

DOI
10.1038/s41467-025-58969-y

Binary climate data visuals amplify perceived impact of climate change

NOMIS Researcher(s)

Published in

April 17, 2025

For much of the global population, climate change appears as a slow, gradual shift in daily weather. This leads many to perceive its impacts as minor and results in apathy (the ‘boiling frog’ effect). How can we convey the urgency of the crisis when its impacts appear so subtle? Here, through a series of large-scale cognitive experiments (N = 799), we find that presenting people with binary climate data (for example, lake freeze history) significantly increases the perceived impact of climate change (Cohen’s d = 0.40, 95% confidence interval 0.26–0.54) compared with continuous data (for example, mean temperature). Computational modelling and follow-up experiments (N = 398) suggest that binary data enhance perceived impact by creating an ‘illusion’ of sudden shifts. Crucially, our approach does not involve selective data presentation but rather compares different datasets that reflect equivalent trends in climate change over time. These findings, robustly replicated across multiple experiments, provide a cognitive basis for the ‘boiling frog’ effect and offer a psychologically grounded approach for policymakers and educators to improve climate change communication while maintaining scientific accuracy.

Research field(s)
Information & Communication Technologies, Psychology & Cognitive Sciences, Behavioral Science & Comparative Psychology

DOI
10.1038/s41562-025-02183-9

DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation

NOMIS Researcher(s)

Published in

April 15, 2025
Polyglutamine (polyQ) expansion is associated with pathogenic protein aggregation in neurodegenerative disorders. However, long polyQ tracts are also found in many transcription factors (TFs), such as FOXP2, a TF implicated in human speech. Here, we explore how FOXP2 and other glutamine-rich TFs avoid unscheduled assembly. Throughout interphase, DNA binding, irrespective of sequence specificity, has a solubilizing effect. During mitosis, multiple phosphorylation events promote FOXP2’s eviction from chromatin and supplant the solubilizing function of DNA. Further, human-specific amino acid substitutions linked to the evolution of speech map to a mitotic phospho-patch, the “EVO patch,” and reduce the propensity of the human FOXP2 to assemble. Fusing the pathogenic form of Huntingtin to either a DNA-binding domain, a phosphomimetic variant of this EVO patch, or a negatively charged peptide is sufficient to diminish assembly formation, suggesting that hijacking mechanisms governing solubility of glutamine-rich TFs may offer new strategies for treatment of polyQ expansion diseases.

Research field(s)
Neuroscience, Biochemistry & Molecular Biology, Genetics & Heredity, Evolutionary Biology

DOI
10.1016/j.cell.2025.03.031

Comprehensive interrogation of synthetic lethality in the DNA damage response

NOMIS Researcher(s)

Published in

April 9, 2025

The DNA damage response (DDR) is a multifaceted network of pathways that preserves genome stability1,2. Unravelling the complementary interplay between these pathways remains a challenge3,4. Here we used CRISPR interference (CRISPRi) screening to comprehensively map the genetic interactions required for survival during normal human cell homeostasis across all core DDR genes. We captured known interactions and discovered myriad new connections that are available online. We defined the molecular mechanism of two of the strongest interactions. First, we found that WDR48 works with USP1 to restrain PCNA degradation in FEN1/LIG1-deficient cells. Second, we found that SMARCAL1 and FANCM directly unwind TA-rich DNA cruciforms, preventing catastrophic chromosome breakage by the ERCC1–ERCC4 complex. Our data yield fundamental insights into genome maintenance, provide a springboard for mechanistic investigations into new connections between DDR factors and pinpoint synthetic vulnerabilities that could be exploited in cancer therapy.

Partnership(s)
,

Research field(s)
Bioinformatics, Biochemistry & Molecular Biology, Genetics & Heredity, Oncology & Carcinogenesis

DOI
10.1038/s41586-025-08815-4

Glacier-fed stream diatoms (Bacillariophyta) from the Rwenzori Mountains, Uganda, with the description of one new species from the genus Neidium

NOMIS Researcher(s)

Published in

April 8, 2025

Glacier-fed streams (GFSs) are harsh environments hosting unique, highly specialized communities. Interestingly, glaciers and their GFSs are also present in Earth’s tropical regions, where environmental characteristics contrast with GFS conditions elsewhere. Yet, despite the unique and isolated nature of tropical GFSs, little is known about their inhabitants, even though they may disappear later this century with ongoing climate change. Here, we examined diatom communities from one of the last tropical African GFSs in the Rwenzori Mountains, Uganda, to characterize the composition and diversity of this unique system. Six sediment-associated biofilm samples were collected from two reaches of a stream draining the Mt. Stanley Glacier, and the resident diatom communities were studied morphologically using light and scanning electron microscopy, as well as through the sequencing of amplicons from extracted DNA (18S and rbcL). In general, morphological results agree well with barcoding results, but each individually provides irreplaceable insights. In total, we identify 24 morphotypes utilizing light microscopy, 101 diatom Amplicon Sequence Variants (ASVs) using 18S sequences, and 65 ASVs with rbcL. Across approaches, common genera include Achnanthidium, Psammothidium, Neidium, Cymbopleura, Eunotia, and Pinnularia. However, only about half of the diversity could be assigned to the species level across methodologies, including several of the most common taxa, indicating a high level of uniqueness. Accordingly, one of the most common taxa encountered is described here as a new species, Neidium rwenzoriense sp. nov. Our results emphasize the Rwenzori Mountains as a global hotspot for endemism, and the novelty of disappearing tropical GFSs as diatom habitats.

Research field(s)
Conservation Biology, Ecology, Environmental Sciences

DOI
10.1080/0269249X.2025.2474765

Belief in belief: Even atheists in secular countries show intuitive preferences favoring religious belief

NOMIS Researcher(s)

Published in

March 27, 2025

We find evidence of belief in belief—intuitive preferences for religious belief over atheism, even among atheist participants—across eight comparatively secular countries. Religion is a cross-cultural human universal, yet explicit markers of religiosity have rapidly waned in large parts of the world in recent decades. We explored whether intuitive religious influence lingers, even among nonbelievers in largely secular societies. We adapted a classic experimental philosophy task to test for this intuitive belief in belief among people in eight comparatively nonreligious countries: Canada, China, Czechia, Japan, the Netherlands, Sweden, the United Kingdom, and Vietnam (total N = 3,804). Our analyses revealed strong evidence that 1) people intuitively favor religious belief over atheism and that 2) this pattern was not moderated by participants’ own self-reported atheism. Indeed, 3) even atheists in relatively secular societies intuitively prefer belief to atheism. These inferences were robust across different analytic strategies and across other measures of individual differences in religiosity and religious instruction. Although explicit religious belief has rapidly declined in these countries, it is possible that belief in belief may still persist. These results speak to the complex psychological and cultural dynamics of secularization.

Research field(s)
Philosophy & Theology, Psychology & Cognitive Sciences

DOI
10.1073/pnas.2404720122

Glaciers are not just blocks of ice — plans to save them mustn’t overlook their hidden life

NOMIS Researcher(s)

Published in

March 24, 2025

As glaciers begin to disappear, technological fixes to slow or halt ice melt are emerging. But regulations are urgently required before these fixes are used widely.

Research field(s)
Conservation Biology, Environmental Sciences

DOI
10.1038/d41586-025-00897-4

Microtubules in Asgard archaea

NOMIS Researcher(s)

Published in

March 21, 2025
Microtubules are a hallmark of eukaryotes. Archaeal and bacterial homologs of tubulins typically form homopolymers and non-tubular superstructures. The origin of heterodimeric tubulins assembling into microtubules remains unclear.
Here, we report the discovery of microtubule-forming tubulins in Asgard archaea, the closest known relatives of eukaryotes. These Asgard tubulins (AtubA/B) are closely related to eukaryotic α/β-tubulins and the enigmatic bacterial tubulins BtubA/B. Proteomics of Candidatus Lokiarchaeum ossiferum showed that AtubA/B were highly expressed. Cryoelectron microscopy structures demonstrate that AtubA/B form eukaryote-like heterodimers, which assembled into 5-protofilament bona fide microtubules in vitro. The additional paralog AtubB2 lacks a nucleotide-binding site and competitively displaced AtubB. These AtubA/B2 heterodimers polymerized into 7-protofilament non-canonical microtubules. In a sub-population of Ca. Lokiarchaeum ossiferum cells, cryo-tomography revealed tubular structures, while expansion microscopy identified AtubA/B cytoskeletal assemblies.
Our findings suggest a pre-eukaryotic origin of microtubules and provide a framework for understanding the fundamental principles of microtubule assembly.

Partnership(s)

Research field(s)
Molecular Biology, Evolutionary Biology, Microbiology

DOI
10.1016/j.cell.2025.02.027

Adrenaline for the early resuscitation of children with sepsis – a randomized controlled pilot study (ANDES CHILD): study protocol and analysis plan

NOMIS Researcher(s)

Published in

March 12, 2025

Purpose

Sepsis is a leading cause of pediatric morbidity and mortality worldwide. Current guidelines recommend fluid bolus administration of 40–60 mL/kg as part of initial resuscitation, despite limited evidence and concerns about potential harm from high fluid volumes. The ANDES-CHILD pilot study hypothesizes that early initiation of inotropes is feasible and reduces fluid use compared to standard resuscitation.

Methods

Multicenter open label randomized controlled pilot trial conducted in three Pediatric Emergency Departments in Latin America. Children aged 28 days to 18 years with presumed septic shock will be randomized in a 1:1 ratio to receive either early adrenaline infusion after 20 mL/kg fluid bolus versus standard resuscitation with 40–60 mL/kg fluid bolus prior to initiating inotropes. The primary outcome is feasibility, with survival free of organ support censored at 28 days as the exploratory primary clinical outcome. The study will enroll 40 patients, representing approximately 10% of a full trial, with follow-up at 28 days. Baseline characteristics, adverse events and protocol violations will be summarized descriptively. Outcomes will be analyzed using difference estimates with 95% confidence intervals. An intention-to-treat approach will be used for statistical analysis.

Discussion

This pragmatic pilot study will generate essential data to evaluate the feasibility and guide the design of a full trial aimed to assessing the benefits of early inotrope use in pediatric septic shock. The study was registered on ClinicalTrials.gov prior to the start of recruitment (NCT06478797). Recruitment started on July 18, 2024.

Research field(s)
Pediatrics

DOI
10.1007/s44253-025-00066-5

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