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Publications in Health Sciences by NOMIS researchers

Perceptions of science, science communication, and climate change attitudes in 68 countries – the TISP dataset

NOMIS Researcher(s)

Published in

January 20, 2025

Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries. The data were collected between November 2022 and August 2023 as part of the global Many Labs study “Trust in Science and Science-Related Populism” (TISP). The questionnaire contained comprehensive measures for individuals’ trust in scientists, science-related populist attitudes, perceptions of the role of science in society, science media use and communication behaviour, attitudes to climate change and support for environmental policies, personality traits, political and religious views and demographic characteristics. Here, we describe the dataset, survey materials and psychometric properties of key variables. We encourage researchers to use this unique dataset for global comparative analyses on public perceptions of science and its role in society and policy-making.

Research field(s)
Social Sciences, Psychology & Cognitive Sciences, Social Psychology, Public Health

DOI
10.1038/s41597-024-04100-7

Bile acid synthesis impedes tumor-specific T cell responses during liver cancer

NOMIS Researcher(s)

Published in

January 9, 2025

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid–CoA:amino acid N-acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti–programmed cell death protein 1 (anti–PD-1) immunotherapy. Furthermore, different BAs regulated CD8+ T cells differently; primary BAs induced oxidative stress, whereas the secondary BA lithocholic acid inhibited T cell function through endoplasmic reticulum stress, which was countered by ursodeoxycholic acid. We demonstrate that modifying BA synthesis or dietary intake of ursodeoxycholic acid could improve tumor immunotherapy in liver cancer model systems.

Partnership(s)

Research field(s)
Biomedical Research, Biochemistry & Molecular Biology, Microbiology, Immunology, Oncology & Carcinogenesis

DOI
10.1126/science.adl4100

Stochastic decisions support optimal foraging of volatile environments, and are disrupted by anxiety

NOMIS Researcher(s)

Published in

January 9, 2025

Adolescence is a developmental period of relative volatility, where the individual experiences significant changes to their physical and social environment. The ability to adapt to the volatility of one’s surroundings is an important cognitive ability, particularly while foraging, a near-ubiquitous behaviour across the animal kingdom. As adolescents experience more volatility in their surroundings, we predicted that this age group would be more adept than adults at using exploration to adjust to volatility. We employed a foraging task with a well-validated computational model to characterise the mechanisms of exploration in volatile environments, preregistering the hypothesis that adolescents (aged 16–17; N = 91) would exhibit more optimal adaptation of their learning rate to changes in environmental volatility compared with adults (aged 24+; N = 90). However, surprisingly, both adolescents and adults exhibited suboptimal adjustment of their learning rate to environmental volatility. In contrast to the learning rate, it was instead participants’ stochasticity (i.e., decision variability) that better resembled the adjustment to volatility made by the optimal RL agent. Although heightened stochasticity in the volatile environment led participants to more often trial different responses that facilitated discovery of changes to the environment, we also found that anxiety impaired this adaptive ability. The finding of heightened stochasticity in volatile environments contradicts expectations that the learning rate is responsible for successful adaptation and motivates future work on the deleterious role that anxiety plays when adolescents manage periods of transition.

Research field(s)
Psychology & Cognitive Sciences

DOI
10.3758/s13415-024-01256-y

Astrocytes in aging

NOMIS Researcher(s)

Published in

January 8, 2025

The mammalian nervous system is impacted by aging. Aging alters brain architecture, is associated with molecular damage, and can manifest with cognitive and motor deficits that diminish the quality of life. Astrocytes are glial cells of the CNS that regulate the development, function, and repair of neural circuits during development and adulthood; however, their functions in aging are less understood. Astrocytes change their transcriptome during aging, with astrocytes in areas such as the cerebellum, the hypothalamus, and white matter-rich regions being the most affected. While numerous studies describe astrocyte transcriptional changes in aging, many questions still remain. For example, how is astrocyte function altered by transcriptional changes that occur during aging? What are the mechanisms promoting astrocyte aged states? How do aged astrocytes impact brain function? This review discusses features of aged astrocytes and their potential triggers and proposes ways in which they may impact brain function and health span.

Partnership(s)
,

Research field(s)
Immunology, Neurology & Neurosurgery

DOI
10.1016/j.neuron.2024.12.010

Building global collaborative research networks in paediatric critical care: a roadmap

NOMIS Researcher(s)

Published in

December 20, 2024

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations.

Research field(s)
Emergency & Critical Care Medicine, Pediatrics

DOI
10.1016/S2352-4642(24)00303-1

Alzheimer’s disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain

NOMIS Researcher(s)

Published in

December 19, 2024

INTRODUCTION: While there may be microbial contributions to Alzheimer’s disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+)microglia subtype associated with increased immunoglobulinG4(IgG4) in the transverse colon (TC).

METHODS: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

RESULTS: CD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV-infected cerebral organoids showed accelerated AD pathophysiological features (Aβ42 and pTau-212) and neuronal death.

DISCUSSION: Findings indicate complex, cross-tissue interactions between HCMV and the adaptive immune response associated with CD83(+)microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+)microglia.

Research field(s)
Genetics & Heredity, Neurology & Neurosurgery, Biology

DOI
10.1002/alz.14401

Biased expectations about future choice options predict sequential economic decisions

NOMIS Researcher(s)

Published in

December 18, 2024

Considerable research has shown that people make biased decisions in “optimal stopping problems”, where options are encountered sequentially, and there is no opportunity to recall rejected options or to know upcoming options in advance (e.g. when flat hunting or choosing a spouse). Here, we used computational modelling to identify the mechanisms that best explain decision bias in the context of an especially realistic version of this problem: the full-information problem. We eliminated a number of factors as potential instigators of bias. Then, we examined sequence length and payoff scheme: two manipulations where an optimality model recommends adjusting the sampling rate. Here, participants were more reluctant to increase their sampling rates when it was optimal to do so, leading to increased undersampling bias. Our comparison of several computational models of bias demonstrates that many participants maintain these relatively low sampling rates because of suboptimally pessimistic expectations about the quality of future options (i.e. a mis-specified prior distribution). These results support a new theory about how humans solve full information problems. Understanding the causes of decision error could enhance how we conduct real world sequential searches for options, for example how online shopping or dating applications present options to users.

Research field(s)
Behavioral Science & Comparative Psychology

DOI
10.1038/s44271-024-00172-8

Spatial transcriptomic clocks reveal cell proximity effects in brain ageing

NOMIS Researcher(s)

Published in

December 18, 2024

Old age is associated with a decline in cognitive function and an increase in neurodegenerative disease risk1. Brain ageing is complex and is accompanied by many cellular changes2. Furthermore, the influence that aged cells have on neighbouring cells and how this contributes to tissue decline is unknown. More generally, the tools to systematically address this question in ageing tissues have not yet been developed. Here we generate a spatially resolved single-cell transcriptomics brain atlas of 4.2 million cells from 20 distinct ages across the adult lifespan and across two rejuvenating interventions—exercise and partial reprogramming. We build spatial ageing clocks, machine learning models trained on this spatial transcriptomics atlas, to identify spatial and cell-type-specific transcriptomic fingerprints of ageing, rejuvenation and disease, including for rare cell types. Using spatial ageing clocks and deep learning, we find that T cells, which increasingly infiltrate the brain with age, have a marked pro-ageing proximity effect on neighbouring cells. Surprisingly, neural stem cells have a strong pro-rejuvenating proximity effect on neighbouring cells. We also identify potential mediators of the pro-ageing effect of T cells and the pro-rejuvenating effect of neural stem cells on their neighbours. These results suggest that rare cell types can have a potent influence on their neighbours and could be targeted to counter tissue ageing. Spatial ageing clocks represent a useful tool for studying cell–cell interactions in spatial contexts and should allow scalable assessment of the efficacy of interventions for ageing and disease.

Research field(s)
Bioinformatics, Biochemistry & Molecular Biology, Immunology, Neurology & Neurosurgery

DOI
10.1038/s41586-024-08334-8

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19

NOMIS Researcher(s)

Published in

December 11, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.

Research field(s)
Molecular Biology, Virology, Immunology

DOI
10.1016/j.chom.2024.11.007

Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes

NOMIS Researcher(s)

Published in

December 4, 2024

Arrayed CRISPR libraries extend the scope of gene-perturbation screens to non-selectable cell phenotypes. However, library generation requires assembling thousands of vectors expressing single-guide RNAs (sgRNAs). Here, by leveraging massively parallel plasmid-cloning methodology, we show that arrayed libraries can be constructed for the genome-wide ablation (19,936 plasmids) of human protein-coding genes and for their activation and epigenetic silencing (22,442 plasmids), with each plasmid encoding an array of four non-overlapping sgRNAs designed to tolerate most human DNA polymorphisms. The quadruple-sgRNA libraries yielded high perturbation efficacies in deletion (75–99%) and silencing (76–92%) experiments and substantial fold changes in activation experiments. Moreover, an arrayed activation screen of 1,634 human transcription factors uncovered 11 novel regulators of the cellular prion protein PrPC, screening with a pooled version of the ablation library led to the identification of 5 novel modifiers of autophagy that otherwise went undetected, and ‘post-pooling’ individually produced lentiviruses eliminated template-switching artefacts and enhanced the performance of pooled screens for epigenetic silencing. Quadruple-sgRNA arrayed libraries are a powerful and versatile resource for targeted genome-wide perturbations.

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

DOI
10.1038/s41551-024-01278-4

Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations

NOMIS Researcher(s)

Published in

November 27, 2024

The DNA-PKcs inhibitor AZD7648 enhances CRISPR–Cas9-directed homology-directed repair efficiencies, with potential for clinical utility, but its possible on-target consequences are unknown. We found that genome editing with AZD7648 causes frequent kilobase-scale and megabase-scale deletions, chromosome arm loss and translocations. These large-scale chromosomal alterations evade detection through typical genome editing assays, prompting caution in deploying AZD7648 and reinforcing the need to investigate multiple types of potential editing outcomes.

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

DOI
10.1038/s41587-024-02488-6

Archaeal type six secretion system mediates contact-dependent antagonism

NOMIS Researcher(s)

Published in

November 15, 2024

Microbial communities are shaped by cell-cell interactions. Although archaea are often found in associations with other microorganisms, the mechanisms structuring these communities are poorly understood. Here, we report on the structure and function of haloarchaeal contractile injection systems (CISs). Using a combination of functional assays and time-lapse imaging, we show that Halogeometricum borinquense exhibits antagonism toward Haloferax volcanii by inducing cell lysis and inhibiting proliferation. This antagonism is contact-dependent and requires a functional CIS, which is encoded by a gene cluster that is associated with toxin-immunity pairs. Cryo–focused ion beam milling and imaging by cryo–electron tomography revealed that these CISs are bound to the cytoplasmic membrane, resembling the bacterial type six secretion systems (T6SSs). We show that related T6SS gene clusters are conserved and expressed in other haloarchaeal strains, which exhibit antagonistic behavior. Our data provide a mechanistic framework for understanding how archaea may shape microbial communities and affect the food webs they inhabit.

Research field(s)
Microbiology

DOI
10.1126/sciadv.adp7088

A leader I can(not) trust: understanding the path from epistemic trust to political leader choices via dogmatism

NOMIS Researcher(s)

Published in

October 31, 2024

There is growing concern about the impact of declining political trust on democracies. Psychological research has introduced the concept of epistemic (mis)trust as a stable disposition acquired through development, which may influence our sociopolitical engagement. Given trust’s prominence in current politics, we examined the relationship between epistemic trust and people’s choices of (un)trustworthy political leaders. In two representative samples in the UK and US (N = 1096), we tested whether epistemic trust predicts political leader choices through three political dimensions: dogmatism, political trust, and ideology. Although epistemic trust did not directly predict choices of political leaders, it predicted dogmatism and political ideology, which in turn predicted choices of political leaders. A network analysis revealed that epistemic trust and political dimensions only interact through their common connection with dogmatism. These findings suggest that cognitive and affective development may underlie an individual’s political ideology and associated beliefs.

Research field(s)
Political Science & Public Administration, Psychology & Cognitive Sciences

DOI
10.1017/pls.2024.11

Mechanism of bacterial predation via ixotrophy

NOMIS Researcher(s)

Published in

October 18, 2024

Ixotrophy is a contact-dependent predatory strategy of filamentous bacteria in aquatic environments for which the molecular mechanism remains unknown. We show that predator-prey contact can be established by gliding motility or extracellular assemblages we call “grappling hooks.” Cryo–electron microscopy identified the grappling hooks as heptamers of a type IX secretion system substrate. After close predator-prey contact is established, cryo–electron tomography and functional assays showed that puncturing by a type VI secretion system mediated killing. Single-cell analyses with stable isotope–labeled prey revealed that prey components are taken up by the attacker. Depending on nutrient availability, insertion sequence elements toggle the activity of ixotrophy. A marine metagenomic time series shows coupled dynamics of ixotrophic bacteria and prey. We found that the mechanism of ixotrophy involves multiple cellular machineries, is conserved, and may shape microbial populations in the environment.

Research field(s)
Microbiology

DOI
10.1126/science.adp0614

The Food Socioscope: A new instrument to better understand transitions towards greater sustainability

NOMIS Researcher(s)

Published in

October 15, 2024

The Food Socioscope project aims to understand the systemic transition towards greater sustainability in the food sector. It has two main components: a participatory data collection with a community directory, and a comprehensive research effort. The first component builds a community of practitioners from various sectors (e.g., companies, NGOs, public authorities) who manage initiatives promoting food sustainability. This community, facilitated by the Food Socioscope Netboard, fosters knowledge exchange by publishing key characteristics of these initiatives online. The second component collects qualitative data through in-depth field interviews, site visits and videos with practitioners, following a rigorously tested protocol. This in-depth data, capturing activities from micro to macro levels, feeds into the research project to improve understanding of systemic change in food sustainability. The research spans the entire food supply chain and examines the supporting infrastructure and organizational setups. By analysing 600 initiatives, worldwide, within their broader contexts, the project aims to identify mechanisms of transition, including barriers and success factors. To collect, process and analyse its vast amount of qualitative data, in multiple languages, the project uses novel protocols, AI models, network analysis, and other quantitative methods. This paper presents the project and preliminary findings regarding regulation, the asymmetry of social contracts and the practitioners’ motivations.

Research field(s)
Sociology, Social Psychology

DOI
10.5281/zenodo.13935390

Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition

NOMIS Researcher(s)

Published in

October 14, 2024

Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic gene SRGAP2A, in human cortical pyramidal neurons (CPNs) xenotransplanted in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs led to strongly accelerated synaptic development, indicating their requirement for the neoteny that distinguishes human synaptogenesis. SRGAP2B/C genes promoted neoteny by reducing the synaptic levels of SRGAP2A,thereby increasing the postsynaptic accumulation of the SYNGAP1 protein, encoded by a major intellectual disability/autism spectrum disorder (ID/ASD) gene. Combinatorial loss-of-function experiments in vivo revealed that the tempo of synaptogenesis is set by the reciprocal antagonism between SRGAP2A and SYNGAP1, which in human CPNs is tipped toward neoteny by SRGAP2B/C. Thus, HS genes can modify the phenotypic expression of genetic mutations leading to ID/ASD through the regulation of human synaptic neoteny.

Research field(s)
Genetics & Heredity

DOI
10.1016/j.neuron.2024.08.021

If you please, draw me a neuron — linking evolutionary tinkering with human neuron evolution

NOMIS Researcher(s)

Published in

October 1, 2024

Animal speciation often involves novel behavioral features that rely on nervous system evolution. Human-specific brain features have been proposed to underlie specialized cognitive functions and to be linked, at least in part, to the evolution of synapses, neurons, and circuits of the cerebral cortex. Here, we review recent results showing that, while the human cortex is composed of a repertoire of cells that appears to be largely similar to the one found in other mammals, human cortical neurons do display specialized features at many levels, from gene expression to intrinsic physiological properties. The molecular mechanisms underlying human species-specific neuronal features remain largely unknown but implicate hominid-specific gene duplicates that encode novel molecular modifiers of neuronal function. The identification of human-specific genetic modifiers of neuronal function brings novel insights on brain evolution and function and, could also provide new insights on human species-specific vulnerabilities to brain disorders.

Research field(s)
Genetics & Heredity, Evolutionary Biology

DOI
10.1016/j.gde.2024.102260

Digital solutions in paediatric sepsis: current state, challenges, and opportunities to improve care around the world

NOMIS Researcher(s)

Published in

September 1, 2024
The digitisation of health care is offering the promise of transforming the management of paediatric sepsis, which is a major source of morbidity and mortality in children worldwide. Digital technology is already making an impact in paediatric sepsis, but is almost exclusively benefiting patients in high-resource health-care settings. However, digital tools can be highly scalable and cost-effective, and—with the right planning—have the potential to reduce global health disparities. Novel digital solutions, from wearable devices and mobile apps, to electronic health record-embedded decision support tools, have an unprecedented opportunity to transform paediatric sepsis research and care. In this Series paper, we describe the current state of digital solutions in paediatric sepsis around the world, the advances in digital technology that are enabling the development of novel applications, and the potential effect of advances in artificial intelligence in paediatric sepsis research and clinical care.

Research field(s)
Pediatrics

DOI
10.1016/S2589-7500(24)00141-9

Quality improvement programmes in paediatric sepsis from a global perspective

NOMIS Researcher(s)

Published in

September 1, 2024

Sepsis is a major contributor to poor child health outcomes around the world. The high morbidity, mortality, and societal cost associated with paediatric sepsis render it a global health priority, as summarised in Paper 1 of this Series. Sepsis is characterised by a dysregulated host response to infection that manifests as organ failure, and children are uniquely susceptible to sepsis, as discussed in Paper 2. The focus of this third Series paper is quality improvement in paediatric sepsis. The 2017 WHO resolution on sepsis outlined key aims to reduce the burden of sepsis. As of 2024, only a small number of countries have implemented systematic, paediatric-focused quality improvement programmes to raise sepsis awareness, enhance recognition of sepsis, promote timely treatment, and provide long-term support for paediatric sepsis survivors. We examine programme successes and systematic barriers to quality improvement targeting paediatric sepsis. We highlight the need for programme design to consider the entire patient journey, starting with prevention, caregiver awareness, recognition at home, education of the health-care workforce, development of health-care systems, and establishment of long-term family and survivor support extending beyond the intensive care unit. Building on lessons learnt from existing quality improvement programmes, we outline implementation strategies and measures to enable benchmarking. Ultimately, quality improvement on a global scale can only be accelerated through a global learning platform focusing on paediatric sepsis.

This is the third in a Series of four papers on paediatric sepsis (Paper 4 appears in The Lancet Digital Health). All papers in the Series are available at thelancet.com/series/paediatric-sepsis

Research field(s)
Pediatrics

DOI
10.1016/S2352-4642(24)00142-1

Susceptibility to childhood sepsis, contemporary management, and future directions

NOMIS Researcher(s)

Published in

September 1, 2024

Sepsis disproportionally affects children across all health-care settings and is one of the leading causes of morbidity and mortality in neonatal and paediatric age groups. As shown in the first paper in this Series, the age-specific incidence of sepsis is highest during the first years of life, before approaching adult incidence rates during adolescence. In the second paper in this Series, we focus on the unique susceptibility of paediatric patients to sepsis and how the underlying dysregulated host response relates to developmental aspects of children’s immune system, genetic, perinatal, and environmental factors, and comorbidities and socioeconomic determinants of health, which often differ between children and adults. State-of-the-art clinical management of paediatric sepsis is organised around three treatment pillars—diagnosis, early resuscitation, and titration of advanced care—and we examine available treatment guidelines and the limitations of their supporting evidence. Serious evidence gaps remain in key areas of paediatric sepsis care, especially surrounding recognition, common interventions, and survivor support, and to this end we offer a research roadmap for the next decade that could accelerate targeted diagnostics and personalised use of immunomodulation. However, improving outcomes for children with sepsis relies fundamentally on systematic quality improvement in both recognition and treatment, which is the theme of the third paper in this Series. Digital health, as shown in the fourth and final paper of this Series, holds promising potential in breaking down the barriers that hinder progress in paediatric sepsis care and, ultimately, global child health.

This is the second in a Series of four papers on paediatric sepsis (Paper 4 appears in The Lancet Digital Health). All papers in the Series are available at thelancet.com/series/paediatric-sepsis

Research field(s)
Pediatrics

DOI
10.1016/S2352-4642(24)00141-X

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