Browsing by Subject "PATHWAYS"

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  • Holster, Savanne; Hooiveld, Guido J.; Repsilber, Dirk; de Vos, Willem M.; Brummer, Robert J.; König, Julia (2019)
    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.
  • Haider, Zahra; Larsson, Pär; Landfors, Mattias; Köhn, Linda; Schmiegelow, Kjeld; Flægstad, Trond; Kanerva, Jukka; Heyman, Mats; Hultdin, Magnus; Degerman, Sofie (2019)
    Classification of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T-ALL patients were characterized by genome-wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P <0.001) and mitotic age (P <0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2-1, and novel genes in T-ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP- subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL-TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP-), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T-ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.
  • Kortesoja, Laura; Vainikainen, Mari-Pauliina; Hotulainen, Risto; Rimpelä, Arja; Dobewall, Henrik; Lindfors, Pirjo; Karvonen, Sakari; Merikanto, Ilona (2020)
    The long-term effects of sleep on adolescent psychosocial well-being are mostly unknown, although insufficient sleep has been associated with emotional and behavioral difficulties in cross-sectional studies. With a five-year follow-up of Finnish adolescents (Time 1: n = 8834; Mean age = 13 years, 51.1% female, Time 2: n = 5315, Mean age = 15 years, 51.6% female, Time 3: n = 3712; Mean age = 17 years; 50.2% female), the purpose of this longitudinal study was to investigate the relations between self-reported sleep duration, sleep problems, and emotional and behavioral difficulties during adolescence. Emotional and behavioral difficulties were assessed using The Strengths and Difficulties Questionnaire (SDQ) measuring emotional symptoms, conduct problems, hyperactivity, peer problems and total difficulties. Sleep duration was calculated by counting the hours between self-reported bedtime and wake-up time. Sleep problems were assessed with a single question about the general sleep problems. According to the cross-lagged models for sleep and emotional and behavioral difficulties, the findings of this study indicate a developmental process during adolescence where, firstly, short sleep duration is a stronger predictor for current and prospective emotional and behavioral difficulties than vice versa. Secondly, increased emotional and behavioral difficulties expose adolescents to current and later sleep problems more strongly than reverse. Thus, the results show that short sleep duration predisposed to emotional and behavioral difficulties across adolescence, which then led to more prospective sleep problems. These findings suggest a developmental process where sleep and emotional and behavioral difficulties are intertwined in shaping adolescents' health.
  • Manninen, Atte A.; Gardberg, Maria; Juteau, Susanna; Ilmonen, Suvi; Jukonen, Joonas; Andersson, Noora; Carpen, Olli (2019)
    Background Sentinel node biopsy (SNB) is an important step in melanoma staging and prognostication. It is commonly performed for patients with intermediate thickness melanomas, based on clinicopathological features. However, only 20-25% of patients eventually demonstrate nodal involvement. The aim of this study was to evaluate whether tissue biomarkers with links to melanoma biology, together with clinicopathological parameters, could aid in the prediction of sentinel node involvement and improve selection of patients for SNB. In addition, we examined the role of these clinical or biological markers in disease outcome. Methods We collected a case-control cohort of 140 intermediate thickness (Breslow 0,9-4,0mm) melanoma patients with or without SNB involvement matched for age, gender, Breslow thickness and location. From this cohort, we tested the predictive value of common clinicopathological parameters (ulceration, mitotic count and tumor regression) and FMNL-2, ezrin and BRAF V600E immunoreactivity, for sentinel node involvement and survival. We further analyzed the correlations in the superficial spreading melanoma subtype. Results Based on our case control analysis, of the markers, BRAF V600E status (p = 0.010) and mitotic count (p = 0.036) correlated with SNB involvement. SNB status was a strong independent prognosticator for recurrence free survival (RFS p Conclusions These results demonstrate that BRAF immunohistochemistry could serve as a useful addition to a marker panel for selecting intermediate thickness melanoma patients for SNB.
  • Cadilhac, Dominique A.; Dewey, Helen M.; Denisenko, Sonia; Bladin, Christopher F.; Meretoja, Atte (2019)
    BackgroundHospital costs for stroke are increasing and variability in care quality creates inefficiencies. In 2007, the Victorian Government (Australia) employed clinical facilitators for three years in eight public hospitals to improve stroke care. Literature on the cost implications of such roles is rare. We report changes in the costs of acute stroke care following implementation of this program.MethodsObservational controlled before-and-after cohort design. Standardised hospital costing data were compared pre-program (financial year 2006-07) and post-program (2010-11) for all admitted episodes of stroke or transient ischaemic attack (TIA) using ICD-10 discharge codes. Costs in Australian dollars (AUD) were adjusted to a common year 2010. Generalised linear regression models were used for adjusted comparisons.ResultsA 20% increase in stroke and TIA episodes was observed: 2624 pre-program (age>75years: 53%) and 3142 post-program (age>75years: 51%); largely explained by more TIA admissions (up from 785 to 1072). Average length of stay reduced by 22% (pre-program 7.3days to post-program 5.7days, p
  • Koivisto, Elina; Acosta, Alicia Jurado; Moilanen, Anne-Mari; Tokola, Heikki; Aro, Jani; Pennanen, Harri; Sakkinen, Hanna; Kaikkonen, Leena; Ruskoaho, Heikki; Rysa, Jaana (2014)
  • Landreau, Armand; Juhola, Sirkku; Jurgilevich, Alexandra; Räsänen, Aleksi (2021)
    The assessments of future climate risks are common; however, usually, they focus on climate projections without considering social changes. We project heat risks for Finland to evaluate (1) what kind of differences there are in heat vulnerability projections with different scenarios and scales, and (2) how the use of socio-economic scenarios influences heat risk assessments. We project a vulnerability index with seven indicators downscaled to the postal code area scale for 2050. Three different scenario sets for vulnerability are tested: one with five global Shared Socioeconomic Pathways (SSPs) scenarios; the second with three European SSPs (EUSSPs) with data at the sub-national scale (NUTS2); and the last with the EUSSPs but aggregated data at the national scale. We construct projections of heat risk utilizing climatic heat hazard data for three different Representative Concentration Pathways (RCPs) and vulnerability and exposure data for five global SSPs up to 2100. In the vulnerability projections, each scenario in each dataset shows a decrease in vulnerability compared to current values, and the differences between the three scenario sets are small. There are evident differences both in the spatial patterns and in the temporal trends when comparing the risk projections with constant vulnerability to the projections with dynamic vulnerability. Heat hazard increases notably in RCP4.5 and RCP8.5, but a decrease of vulnerability especially in SSP1 and SSP5 alleviates risks. We show that projections of vulnerability have a considerable impact on future heat-related risk and emphasize that future risk assessments should include the combination of long-term climatic and socio-economic projections.
  • Pitkanen, Esa; Jouhten, Paula; Hou, Jian; Syed, Muhammad Fahad; Blomberg, Peter; Kludas, Jana; Oja, Merja; Holm, Liisa; Penttila, Merja; Rousu, Juho; Arvas, Mikko (2014)
  • Karinen, Sirkku; Heikkinen, Tuomas; Nevanlinna, Heli; Hautaniemi, Sampsa (2011)
  • Kallankari, Hanna; Saunavaara, Virva; Parkkola, Riitta; Haataja, Leena; Hallman, Mikko; Kaukola, Tuula (2021)
    Background Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (P
  • Bousquet, Jean; Anto, Josep M.; Haahtela, Tari; Jousilahti, Pekka; Erhola, Marina; Basagana, Xavier; Czarlewski, Wienczyslawa; Odemyr, Mikaela; Palkonen, Susanna; Sofiev, Mikael; Velasco, Cesar; Bedbrook, Anna; Delgado, Rodrigo; Kouznetsov, Rostislav; Mäkelä, Mika; Palamarchuk, Yuliia; Saarinen, Kimmo; Tommila, Erja; Valovirta, Erkka; Vasankari, Tuula; Zuberbier, Torsten; Annesi-Maesano, Isabella; Benveniste, Samuel; Mathieu-Dupas, Eve; Pepin, Jean-Louis; Picard, Robert; Zeng, Stephane; Ayache, Julia; Calves Venturos, Nuria; Micheli, Yann; Jullian-Desayes, Ingrid; Laune, Daniel (2020)
    In December 2019, a conference entitled "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki. It was co-organized by the Finnish Institute for Health and Welfare, the Finnish Environment Institute and the European Commission, under the auspices of Finland's Presidency of the EU. As a side event, a symposium organized as the final POLLAR (Impact of air POLLution on Asthma and Rhinitis) meeting explored the digital transformation of health and care to sustain planetary health in airway diseases. The Finnish Allergy Programme collaborates with MASK (Mobile Airways Sentinel NetworK) and can be considered as a proof-of-concept to impact Planetary Health. The Good Practice of DG Sante (The Directorate-General for Health and Food Safety) on digitally-enabled, patient-centred care pathways is in line with the objectives of the Finnish Allergy Programme. The ARIACARE-Digital network has been deployed in 25 countries. It represents an example of the digital cross-border exchange of real-world data and experience with the aim to improve patient care. The integration of information technology tools for climate, weather, air pollution and aerobiology in mobile Health applications will enable the development of an alert system. Citizens will thus be informed about personal environmental threats, which may also be linked to indicators of Planetary Health and sustainability. The digital transformation of the public health policy was also proposed, following the experience of the Agency for Health Quality and Assessment of Catalonia (AQuAS).
  • Jämsen, Eemeli; Pajarinen, Jukka; Lin, Tzu-hua; Lo, Chi-Wen; Nabeshima, Akira; Lu, Laura; Nathan, Karthik; Eklund, Kari K.; Yao, Zhenyu; Goodman, Stuart B. (2020)
    Macrophage-mediated inflammatory reaction to implant wear particles drives bone loss around total joint replacements (TJR). Although most TJR recipients are elderly, studies linking wear particle-activated macrophages and peri-implant osteolysis have not taken into account the multiple effects that aging has on the innate immune system and, in particular, on macrophages. To address this, we compared the wear particle responses of bone marrow macrophages obtained from young (2-month) and aged (18-month) mice. Macrophages were polarized to M0, M1, or M2 phenotypes in vitro, challenged with titanium particles, and their inflammatory response was characterized at multiple time points by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, age-dependent changes in activation of transcription factor nuclear factor-kappa B were analyzed by a lentiviral vector-based luciferase reporter system. The particle stimulation experiment was further repeated using human primary macrophages isolated from blood donors of different ages. We found that the pro-inflammatory responses were generally higher in macrophages obtained from young mice, but differences between the age groups remained small and of uncertain biological significance. Noteworthily, M2 polarization effectively suppressed the particle-induced inflammation in both young and aged macrophages. These results suggest that aging of the innate immune system per se plays no significant role in the response of macrophages to titanium particles, whereas induction of M2 polarization appears a promising strategy to limit macrophage-mediated inflammation regardless of age.
  • Anwar, Tahira; Liu, Xiaonan; Suntio, Taina; Marjamäki, Annika; Biazik, Joanna; Chan, Edmond Y. W.; Varjosalo, Markku; Eskelinen, Eeva-Liisa (2019)
    Autophagy transports cytoplasmic material and organelles to lysosomes for degradation and recycling. Beclin 1 forms a complex with several other autophagy proteins and functions in the initiation phase of autophagy, but the exact role of Beclin 1 subcellular localization in autophagy initiation is still unclear. In order to elucidate the role of Beclin 1 localization in autophagosome biogenesis, we generated constructs that target Beclin 1 to the endoplasmic reticulum (ER) or mitochondria. Our results confirmed the proper organelle-specific targeting of the engineered Beclin 1 constructs, and the proper formation of autophagy-regulatory Beclin 1 complexes. The ULK kinases are required for autophagy initiation upstream of Beclin 1, and autophagosome biogenesis is severely impaired in ULK1/ULK2 double knockout cells. We tested whether Beclin 1 targeting facilitated its ability to rescue autophagosome formation in ULK1/ULK2 double knockout cells. ER-targeted Beclin 1 was most effective in the rescue experiments, while mitochondria-targeted and non-targeted Beclin 1 also showed an ability to rescue, but with lower activity. However, none of the constructs was able to increase autophagic flux in the knockout cells. We also showed that wild type Beclin 1 was enriched on the ER during autophagy induction, and that ULK1/ULK2 facilitated the ER-enrichment of Beclin 1 under basal conditions. The results suggest that one of the functions of ULK kinases may be to enhance Beclin 1 recruitment to the ER to drive autophagosome formation.
  • Hoornstra, Douwe; Vesterlin, Jenni; Parnanen, Pirjo; Al-Samadi, Ahmed; Zlotogorski-Hurvitz, Ayelet; Vered, Marilena; Salo, Tuula (2018)
    Background: Oral tongue squamous cell carcinoma (OTSCC) cells are highly proliferative and invasive. Lingonberry contains several polyphenolic compounds similar to curcumin. We hypothesize that fermented lingonberry juice (FLJ) has an anti-invasive and anti-proliferative effect on OTSCC cells similarly to curcumin, which is known to be anti-carcinogenic. Materials and Methods: FLJ, curcumin dissolved in ethanol, or curcumin loaded in Candida extracellular vesicles (EVs) were added to more (HSC-3) and less aggressive (SCC-25) OTSCC cells. Cell proliferation was measured with a 5-bromo-2'-deoxyuridine kit and invasion in the three-dimensional Myogel spheroid assay. Statistical analyses were completed with one-way ANOVA and Bonferroni post-hoc testing. Results: Both FLJ and curcumin significantly reduced the proliferation and invasion of HSC-3 and SCC-25 cells. The effects of curcumin were not improved when cells were treated with curcumin loaded within EVs. Conclusion: Our results suggest that FLJ, like curcumin, has an anti-carcinogenic effect on aggressive OTSCC cells in vitro.
  • Haapa-Paananen, Saija; Chen, Ping; Hellström, Kirsi; Kohonen, Pekka; Hautaniemi, Sampsa; Kallioniemi, Olli; Perala, Merja (2013)
  • Evsyukov, Valentin; Domanskyi, Andrii; Bierhoff, Holger; Gispert, Suzana; Mustafa, Rasem; Schlaudraff, Falk; Liss, Birgit; Parlato, Rosanna (2017)
    Genetic mutations underlying neurodegenerative disorders impair ribosomal DNA (rDNA) transcription suggesting that nucleolar dysfunction could be a novel pathomechanism in polyglutamine diseases and in certain forms of amyotrophic lateral sclerosis/frontotemporal dementia. Here, we investigated nucleolar activity in pre-symptomatic digenic models of Parkinson's disease (PD) that model the multifactorial aetiology of this disease. To this end, we analysed a novel mouse model mildly overexpressing mutant human alpha-synuclein (hA53T-SNCA) in a PTEN-induced kinase 1 (PINK1/ PARK6) knockout background and mutant mice lacking both DJ-1 (also known as PARK7) and PINK1. We showed that overexpressed hA53T-SNCA localizes to the nucleolus. Moreover, these mutants show a progressive reduction of rDNA transcription linked to a reduced mouse lifespan. By contrast, rDNA transcription is preserved in DJ-1/PINK1 double knockout (DKO) mice. mRNA levels of the nucleolar transcription initiation factor 1A (TIF-IA, also known as RRN3) decrease in the substantia nigra of individuals with PD. Because loss of TIF-IA, as a tool to mimic nucleolar stress, increases oxidative stress and because DJ-1 and PINK1 mutations result in higher vulnerability to oxidative stress, we further explored the synergism between these PD-associated genes and impaired nucleolar function. By the conditional ablation of TIF-IA, we blocked ribosomal RNA (rRNA) synthesis in adult dopaminergic neurons in a DJ-1/PINK1 DKO background. However, the early phenotype of these triple knockout mice was similar to those mice exclusively lacking TIF-IA. These data sustain a model in which loss of DJ-1 and PINK1 does not impair nucleolar activity in a pre-symptomatic stage. This is the first study to analyse nucleolar function in digenic PD models. We can conclude that, at least in these models, the nucleolus is not as severely disrupted as previously shown in DA neurons from PD patients and neurotoxin-based PD mouse models. The results also show that the early increase in rDNA transcription and nucleolar integrity may represent specific homeostatic responses in these digenic pre-symptomatic PD models.
  • SUMMIT Steering Comm; CARDIOGRAMplusC4D Steering Comm; van Zuydam, Natalie R.; Ladenvall, Claes; Vlachopoulou, Efthymia; Perola, Markus; Sinisalo, Juha; Salomaa, Veikko; Groop, Leif; Ripatti, Samuli (2020)
    BACKGROUND: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). METHODS: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). RESULTS: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.
  • Honkela, Antti; Peltonen, Jaakko; Topa, Hande; Charapitsa, Iryna; Matarese, Filomena; Grote, Korbinian; Stunnenberg, Hendrik G.; Reid, George; Lawrence, Neil D.; Rattray, Magnus (2015)
    Genes with similar transcriptional activation kinetics can display very different temporal mRNA profiles because of differences in transcription time, degradation rate, and RNA-processing kinetics. Recent studies have shown that a splicing-associated RNA production delay can be significant. To investigate this issue more generally, it is useful to develop methods applicable to genome-wide datasets. We introduce a joint model of transcriptional activation and mRNA accumulation that can be used for inference of transcription rate, RNA production delay, and degradation rate given data from high-throughput sequencing time course experiments. We combine a mechanistic differential equation model with a nonparametric statistical modeling approach allowing us to capture a broad range of activation kinetics, and we use Bayesian parameter estimation to quantify the uncertainty in estimates of the kinetic parameters. We apply the model to data from estrogen receptor alpha activation in the MCF-7 breast cancer cell line. We use RNA polymerase II ChIP-Seq time course data to characterize transcriptional activation and mRNA-Seq time course data to quantify mature transcripts. We find that 11% of genes with a good signal in the data display a delay of more than 20 min between completing transcription and mature mRNA production. The genes displaying these long delays are significantly more likely to be short. We also find a statistical association between high delay and late intron retention in pre-mRNA data, indicating significant splicing-associated production delays in many genes.
  • Lorey, Martina B.; Rossi, Katriina; Eklund, Kari; Nyman, Tuula A.; Matikainen, Sampsa (2017)
    Gram-negative bacteria are associated with a wide spectrum of infectious diseases in humans. Inflammasomes are cytosolic protein complexes that are assembled when the cell encounters pathogens or other harmful agents. The non-canonical caspase-4/5 inflammasome is activated by Gram-negative bacteria-derived lipopolysaccharide (LPS) and by endogenous oxidized phospholipids. Protein secretion is a critical component of the innate immune response. Here, we have used label-free quantitative proteomics to characterize global protein secretion in response to non-canonical inflammasome activation upon intracellular LPS recognition in human primary macrophages. Before proteomics, the total secretome was separated into two fractions, enriched extracellular vesicle (EV) fraction and rest-secretome (RS) fraction using size-exclusion centrifugation. We identified 1048 proteins from the EV fraction and 1223 proteins from the RS fraction. From these, 640 were identified from both fractions suggesting that the non-canonical inflammasome activates multiple, partly overlapping protein secretion pathways. We identified several secreted proteins that have a critical role in host response against severe Gram-negative bacterial infection. The soluble secretome (RS fraction) was highly enriched with inflammation-associated proteins upon intracellular LPS recognition. Several ribosomal proteins were highly abundant in the EV fraction upon infection, and our data strongly suggest that secretion of translational machinery and concomitant inhibition of translation are important parts of host response against Gram-negative bacteria sensing caspase-4/5 inflammasome. Intracellular recognition of LPS resulted in the secretion of two metalloproteinases, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and MMP14, in the enriched EV fraction. ADAM10 release was associated with the secretion of TNF, a key inflammatory cytokine, and M-CSF, an important growth factor for myeloid cells probably through ADAM10-dependent membrane shedding of these cytokines. Caspase-4/5 inflammasome activation also resulted in secretion of danger-associated molecules S100A8 and prothymosin- in the enriched EV fraction. Both S100A8 and prothymosin- are ligands for toll-like receptor 4 recognizing extracellular LPS, and they may contribute to endotoxic shock during non-canonical inflammasome activation.
  • Hakkarainen, Viola T; Anderson, Christopher B.; Eriksson, Max; van Riper, Carena J.; Horcea-Milcu, Andra-Ioana; Raymond, C.M (2020)
    This study identifies and analyses the underlying assumptions of experts involved in the first author meeting (FAM) of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES)’s Values Assessment, and how they shape understandings of the multiple values of nature. We draw from survey data collected from 94 experts attending the FAM. Respondents self-report the tendencies and aims they bring to the assessment (i.e. motivation), the type and amount of evidence they require for knowledge to be valid (i.e. confirmation) and their epistemic worldviews (i.e. objectivity). Four clusters emerged that correspond to Pragmatist, Post-Positivist, Constructivist and Transformative epistemic worldviews. This result clarifies how different knowledge claims are represented in science-policy processes. Despite the proportionately higher number of social scientists in the Values Assessment, compared with previous IPBES assessments, we still found that fewer experts have Constructivist or Transformative worldviews than Pragmatist or Post-Positivist outlooks, an imbalance that may influence the types of values and valuation perspectives emphasised in the assessment. We also detected a tension regarding what constitutes valid knowledge between Post-Positivists, who emphasised high levels of agreement, and Pragmatists and Constructivists, who did not necessarily consider agreement crucial. Conversely, Post-Positivists did not align with relational values and were more diverse in their views regarding definitions of multiple values of nature compared to other clusters. Pragmatists emphasized relational values, while Constructivists tended to consider all value types (including relational values) as important. We discuss the implications of our findings for future design and delivery of IPBES processes and interdisciplinary research.