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Article ; Online: Cortical alterations after very preterm birth and the association with socio-emotional abilities from childhood to early adolescence.

Siffredi, Vanessa / Liverani, Maria Chiara / Borradori-Tolsa, Cristina / Leuchter, Russia Hà-Vinh / Thiran, Jean-Philippe / Hüppi, Petra S / Fischi-Gómez, Elda

Cerebral cortex (New York, N.Y. : 1991)

2023 Volume 33, Issue 14, Page(s) 9117–9129

Abstract: Very preterm birth (VPT; <32 weeks' gestation) leads to a situation where crucial steps of brain development occur in an abnormal ex utero environment, translating to vulnerable cortical and subcortical development. Associated with this atypical brain ... ...

Abstract	Very preterm birth (VPT; <32 weeks' gestation) leads to a situation where crucial steps of brain development occur in an abnormal ex utero environment, translating to vulnerable cortical and subcortical development. Associated with this atypical brain development, children and adolescents born VPT are at a high risk of socio-emotional difficulties. In the current study, we unravel developmental changes in cortical gray matter (GM) concentration in VPT and term-born controls aged 6-14 years, together with their associations with socio-emotional abilities. T1-weighted images were used to estimate signal intensities of brain tissue types in a single voxel (GM, white matter, and cortico-spinal fluid) and extract GM concentration disentangled from the presence of partial volume effects (PVEs). General linear model analysis was used to compare groups. Socio-emotional abilities were assessed and associations with GM concentration were explored using univariate and multivariate analyses. The effects of prematurity were far-reaching, with intricated patterns of increases and decreases of GM concentration mainly in frontal, temporal, parietal, and cingular regions. Better socio-emotional abilities were associated with increased GM concentration in regions known to be involved in such process for both groups. Our findings suggest that the trajectory of brain development following VPT birth may be fundamentally distinctive and impact socio-emotional abilities.
MeSH term(s)	Female ; Humans ; Child ; Infant, Newborn ; Adolescent ; Premature Birth ; Brain ; Infant, Premature/psychology ; Emotions ; White Matter ; Magnetic Resonance Imaging/methods
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhad187
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Article ; Online: Impact of a mindfulness-based intervention on neurobehavioral functioning and its association with large-scale brain networks in preterm young adolescents.

Siffredi, Vanessa / Liverani, Maria Chiara / Fernandez, Natalia / Freitas, Lorena G A / Borradori Tolsa, Cristina / Van De Ville, Dimitri / Hüppi, Petra Susan / Ha-Vinh Leuchter, Russia

Psychiatry and clinical neurosciences

2024

Abstract: Aim: Adolescents born very preterm (VPT; <32 weeks of gestation) face an elevated risk of executive, behavioral, and socioemotional difficulties. Evidence suggests beneficial effects of mindfulness-based intervention (MBI) on these abilities. This study ...

Abstract	Aim: Adolescents born very preterm (VPT; <32 weeks of gestation) face an elevated risk of executive, behavioral, and socioemotional difficulties. Evidence suggests beneficial effects of mindfulness-based intervention (MBI) on these abilities. This study seeks to investigate the association between the effects of MBI on executive, behavioral, and socioemotional functioning and reliable changes in large-scale brain networks dynamics during rest in VPT young adolescents who completed an 8-week MBI program. Methods: Neurobehavioral assessments and resting-state functional magnetic resonance imaging were performed before and after MBI in 32 VPT young adolescents. Neurobehavioral abilities in VPT participants were compared with full-term controls. In the VPT group, dynamic functional connectivity was extracted by using the innovation-driven coactivation patterns framework. The reliable change index was used to quantify change after MBI. A multivariate data-driven approach was used to explore associations between MBI-related changes on neurobehavioral measures and temporal brain dynamics. Results: Compared with term-born controls, VPT adolescents showed reduced executive and socioemotional functioning before MBI. After MBI, a significant improvement was observed for all measures that were previously reduced in the VPT group. The increase in executive functioning, only, was associated with reliable changes in the duration of activation of large-scale brain networks, including frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks. Conclusion: The improvement in executive functioning after an MBI was associated with reliable changes in large-scale brain network dynamics during rest. These changes encompassed frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks that are related to different executive processes including self-regulation, attentional control, and attentional awareness of relevant sensory stimuli.
Language	English
Publishing date	2024-05-17
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1292906-2
ISSN	1440-1819 ; 1323-1316
ISSN (online)	1440-1819
ISSN	1323-1316
DOI	10.1111/pcn.13675
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Article ; Online: Amygdala volumes and associations with socio-emotional competencies in preterm youth: cross-sectional and longitudinal data.

Pereira Camejo, Maricé / Escobar Saade, Luciana / Liverani, Maria Chiara / Fischi-Gomez, Elda / Gui, Laura / Borradori Tolsa, Cristina / Ha-Vinh Leuchter, Russia / Hüppi, Petra Susan / Siffredi, Vanessa

Pediatric research

2024

Abstract: Background: Socio-emotional difficulties often result from very preterm (VPT) birth. The amygdala's developmental trajectory, including its nuclei, has been recognized as a significant factor in observed difficulties. This study aims to assess the ... ...

Abstract	Background: Socio-emotional difficulties often result from very preterm (VPT) birth. The amygdala's developmental trajectory, including its nuclei, has been recognized as a significant factor in observed difficulties. This study aims to assess the relationship between amygdala volume and socio-emotional competencies in VPT children and adolescents. Methods: Socio-emotional competencies were assessed, and amygdala volumes, including subnuclei, were extracted automatically from structural scans in a cross-sectional cohort of VPT (n = 75) and full-term (FT, n = 41) aged 6-14 years. Group differences in amygdala volumes were assessed using ANCOVA, and associations with socio-emotional competencies were studied using partial least squares correlation (PLSC). In a VPT subgroup, additional longitudinal data with amygdala volumes at term-equivalent age (TEA) were manually extracted, growth rates calculated, and associations with school-age socio-emotional competencies investigated using PLSC. Results: Using cross-sectional data at school-age, amygdala volumes displayed comparable developmental patterns between the VPT and the FT groups. Greater volumes were associated with more emotional regulation difficulties in VPT and lower affect recognition competencies in FT. In the longitudinal VPT subgroup, no significant associations were found between amygdala volume trajectory and socio-emotional competencies. Conclusion: Although our findings suggest typical amygdala development after VPT birth, further research is necessary to elucidate the developmental trajectory of amygdala and the role of resilience factors. Impact: In our cohort, amygdala volumes, including subnuclei, displayed comparable developmental trajectories between the very preterm and the full-term groups. Higher amygdala volumes at school-age were associated with higher emotional regulation difficulties in the very-preterm born group, and with lower affect recognition abilities in full-term born children and adolescents. In a subgroup of very-preterm children and adolescents followed from birth to school-age, no significant associations were found between amygdala volumes at term-equivalent age and socio-emotional competencies at school-age.
Language	English
Publishing date	2024-05-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-024-03227-y
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Article ; Online: The effect of mindfulness-based intervention on neurobehavioural functioning and its association with white-matter microstructural changes in preterm young adolescents.

Siffredi, Vanessa / Liverani, Maria Chiara / Van De Ville, Dimitri / Freitas, Lorena G A / Borradori Tolsa, Cristina / Hüppi, Petra Susan / Ha-Vinh Leuchter, Russia

Scientific reports

2023 Volume 13, Issue 1, Page(s) 2010

Abstract: Very preterm (VPT) young adolescents are at high risk of executive, behavioural and socio-emotional difficulties. Previous research has shown significant evidence of the benefits of mindfulness-based intervention (MBI) on these abilities. This study aims ...

Abstract	Very preterm (VPT) young adolescents are at high risk of executive, behavioural and socio-emotional difficulties. Previous research has shown significant evidence of the benefits of mindfulness-based intervention (MBI) on these abilities. This study aims to assess the association between the effects of MBI on neurobehavioral functioning and changes in white-matter microstructure in VPT young adolescents who completed an 8-week MBI program. Neurobehavioural assessments (i.e., neuropsychological testing, parents- and self-reported questionnaires) and multi-shell diffusion MRI were performed before and after MBI in 32 VPT young adolescents. Combined diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) measures were extracted on well-defined white matter tracts (TractSeg). A multivariate data-driven approach (partial least squares correlation) was used to explore associations between MBI-related changes on neurobehavioural measures and microstructural changes. The results showed an enhancement of global executive functioning using parent-reported questionnaire after MBI that was associated with a general pattern of increase in fractional anisotropy (FA) and decrease in axonal dispersion (ODI) in white-matter tracts involved in executive processes. Young VPT adolescents with lower gestational age at birth showed the greatest gain in white-matter microstructural changes after MBI.
MeSH term(s)	Infant, Newborn ; Female ; Humans ; Adolescent ; Diffusion Tensor Imaging/methods ; Brain ; Mindfulness ; White Matter/diagnostic imaging ; Diffusion Magnetic Resonance Imaging/methods ; Neurites
Language	English
Publishing date	2023-02-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-29205-8
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Article ; Online: Corpus callosum structural characteristics in very preterm children and adolescents: Developmental trajectory and relationship to cognitive functioning.

Siffredi, Vanessa / Liverani, Maria Chiara / Van De Ville, Dimitri / Freitas, Lorena G A / Borradori Tolsa, Cristina / Hüppi, Petra Susan / Ha-Vinh Leuchter, Russia

Developmental cognitive neuroscience

2023 Volume 60, Page(s) 101211

Abstract: Previous studies suggest that structural alteration of the corpus callosum, i.e., the largest white matter commissural pathway, occurs after a preterm birth in the neonatal period and lasts across development. The present study aims to unravel corpus ... ...

Abstract	Previous studies suggest that structural alteration of the corpus callosum, i.e., the largest white matter commissural pathway, occurs after a preterm birth in the neonatal period and lasts across development. The present study aims to unravel corpus callosum structural characteristics across childhood and adolescence in very preterm (VPT) individuals, and their associations with general intellectual, executive and socio-emotional functioning. Neuropsychological assessments, T1-weighted and multi-shell diffusion MRI were collected in 79 VPT and 46 full term controls aged 6-14 years. Volumetric, diffusion tensor and neurite orientation dispersion and density imaging (NODDI) measures were extracted on 7 callosal portions using TractSeg. A multivariate data-driven approach (partial least squares correlation) and a cohort-based age normative modelling approach were used to explore associations between callosal characteristics and neuropsychological outcomes. The VPT and a full-term control groups showed similar trends of white-matter maturation over time, i.e., increase FA and reduced ODI, in all callosal segments, that was associated with increase in general intellectual functioning. However, using a cohort-based age-related normative modelling, findings show atypical pattern of callosal development in the VPT group, with reduced callosal maturation over time that was associated with poorer general intellectual and working memory functioning, as well as with lower gestational age.
MeSH term(s)	Adolescent ; Child ; Humans ; Infant, Newborn ; Cognition/physiology ; Corpus Callosum/anatomy & histology ; Corpus Callosum/diagnostic imaging ; Corpus Callosum/growth & development ; Gestational Age ; Infant, Extremely Premature/growth & development ; Neuropsychology ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-02-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2572271-2
ISSN	1878-9307 ; 1878-9307
ISSN (online)	1878-9307
ISSN	1878-9307
DOI	10.1016/j.dcn.2023.101211
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Article ; Online: Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children.

Soon, Emilyn / Siffredi, Vanessa / Anderson, Peter J / Anderson, Vicki A / McIlroy, Alissandra / Leventer, Richard J / Wood, Amanda G / Spencer-Smith, Megan M

Journal of the International Neuropsychological Society : JINS

2023 Volume 30, Issue 1, Page(s) 18–26

Abstract: Objectives: The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and ... ...

Abstract	Objectives: The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete Methods: Participants were 27 children with AgCC and 32 TD children 8-16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure. Results: The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC. Conclusions: This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (
MeSH term(s)	Child ; Humans ; Corpus Callosum/diagnostic imaging ; Agenesis of Corpus Callosum/complications ; Agenesis of Corpus Callosum/diagnostic imaging ; Magnetic Resonance Imaging ; Neuroimaging ; White Matter/diagnostic imaging
Language	English
Publishing date	2023-04-14
Publishing country	England
Document type	Journal Article
ZDB-ID	1230632-0
ISSN	1469-7661 ; 1355-6177
ISSN (online)	1469-7661
ISSN	1355-6177
DOI	10.1017/S1355617723000218
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Article ; Online: Large-scale brain network dynamics in very preterm children and relationship with socio-emotional outcomes: an exploratory study.

Siffredi, Vanessa / Liverani, Maria Chiara / Freitas, Lorena G A / Tadros, D / Farouj, Y / Borradori Tolsa, Cristina / Van De Ville, Dimitri / Hüppi, Petra Susan / Ha-Vinh Leuchter, Russia

Pediatric research

2022 Volume 93, Issue 7, Page(s) 2072–2080

Abstract: Background: Children born very preterm (VPT; <32 weeks' gestation) are at high risk of neurodevelopmental and behavioural difficulties associated with atypical brain maturation, including socio-emotional difficulties. The analysis of large-scale brain ... ...

Abstract	Background: Children born very preterm (VPT; <32 weeks' gestation) are at high risk of neurodevelopmental and behavioural difficulties associated with atypical brain maturation, including socio-emotional difficulties. The analysis of large-scale brain network dynamics during rest allows us to investigate brain functional connectivity and its association with behavioural outcomes. Methods: Dynamic functional connectivity was extracted by using the innovation-driven co-activation patterns framework in VPT and full-term children aged 6-9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity (VPT, n = 28; full-term, n = 12). Multivariate analysis was used to explore potential biomarkers for socio-emotional difficulties in VPT children. Results: The spatial organisation of the 13 retrieved functional networks was comparable across groups. Dynamic features and lateralisation of network brain activity were also comparable for all brain networks. Multivariate analysis unveiled group differences in associations between dynamical functional connectivity parameters with socio-emotional abilities. Conclusion: In this exploratory study, the group differences observed might reflect reduced degrees of maturation of functional architecture in the VPT group in regard to socio-emotional abilities. Dynamic features of functional connectivity could represent relevant neuroimaging markers and inform on potential mechanisms through which preterm birth leads to neurodevelopmental and behavioural disorders. Impact: Spatial organisation of the retrieved resting-state networks was comparable between school-aged very preterm and full-term children. Dynamic features and lateralisation of network brain activity were also comparable across groups. Multivariate pattern analysis revealed different patterns of association between dynamical functional connectivity parameters and socio-emotional abilities in the very preterm and full-term groups. Findings suggest a reduced degree of maturation of the functional architecture in the very preterm group in association with socio-emotional abilities.
MeSH term(s)	Female ; Humans ; Infant, Newborn ; Child ; Infant, Extremely Premature ; Premature Birth ; Brain/diagnostic imaging ; Brain/physiology ; Emotions ; Gestational Age ; Magnetic Resonance Imaging
Language	English
Publishing date	2022-11-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-022-02342-y
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Article: Interventions basées sur la pleine conscience pour les enfants et les adolescents.

Hà-Vinh Leuchter, Russia / Siffredi, Vanessa / Magnus Smith, Mariana / Liverani, Maria Chiara / Merglen, Arnaud / Borradori Tolsa, Cristina

Revue medicale suisse

2020 Volume 16, Issue 716, Page(s) 2297–2300

Abstract: Mindfulness based interventions (MBI) are widely available to adults. Programs are also offered to children and adolescents. Interventions in school and clinical settings are increasingly being published in scientific literature. In the school context, ... ...

Title translation	Mindfulness based interventions for children and adolescents.
Abstract	Mindfulness based interventions (MBI) are widely available to adults. Programs are also offered to children and adolescents. Interventions in school and clinical settings are increasingly being published in scientific literature. In the school context, the effects are promising on psychological health, such as stress, anxiety, depression or externalized behaviours, and on executive functions, attention, and socio-emotional skills. In the clinical context, MBI has a particular effect on stress/anxiety and depression as well as on the key symptoms of Attention Deficit Hyperactivity Disorder. These results are very encouraging, but all meta-analyses and literature reviews nevertheless emphasize the need for studies with robust methodology before proposing MBI on a large scale for this population.
MeSH term(s)	Adolescent ; Anxiety/therapy ; Attention Deficit Disorder with Hyperactivity/therapy ; Child ; Depression/therapy ; Emotions ; Humans ; Mental Health ; Mindfulness
Language	French
Publishing date	2020-08-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2177010-4
ISSN	1660-9379
ISSN	1660-9379
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Article: Large-scale brain network dynamics in very preterm children and relationship with socio-emotional outcomes

Siffredi, Vanessa / Liverani, Maria Chiara / Freitas, Lorena G. A. / Tadros, D. / Farouj, Y. / Borradori Tolsa, Cristina / Van de Ville, Dimitri / Hüppi, Petra Susan / Ha-Vinh Leuchter, Russia

Pediatric Research

An exploratory study

2023 Volume 93, Page(s) 2072–2080

Title translation	Die Dynamik großräumiger Hirnnetzwerke bei sehr frühgeborenen Kindern und ihre Beziehung zu sozio-emotionalen Leistungen: Eine explorative Studie
Abstract	Background: Children born very preterm (VPT; <32 weeks' gestation) are at high risk of neurodevelopmental and behavioural difficulties associated with atypical brain maturation, including socio-emotional difficulties. The analysis of large-scale brain network dynamics during rest allows us to investigate brain functional connectivity and its association with behavioural outcomes. Methods: Dynamic functional connectivity was extracted by using the innovation-driven co-activation patterns framework in VPT and full-term children aged 6-9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity (VPT, n = 28; full-term, n = 12). Multivariate analysis was used to explore potential biomarkers for socio-emotional difficulties in VPT children. Results: The spatial organisation of the 13 retrieved functional networks was comparable across groups. Dynamic features and lateralisation of network brain activity were also comparable for all brain networks. Multivariate analysis unveiled group differences in associations between dynamical functional connectivity parameters with socio-emotional abilities. Conclusion: In this exploratory study, the group differences observed might reflect reduced degrees of maturation of functional architecture in the VPT group in regard to socio-emotional abilities. Dynamic features of functional connectivity could represent relevant neuroimaging markers and inform on potential mechanisms through which preterm birth leads to neurodevelopmental and behavioural disorders. Impact Spatial organisation of the retrieved resting-state networks was comparable between school-aged very preterm and full-term children. Dynamic features and lateralisation of network brain activity were also comparable across groups. Multivariate pattern analysis revealed different patterns of association between dynamical functional connectivity parameters and socio-emotional abilities in the very preterm and full-term groups. Findings suggest a reduced degree of maturation of the functional architecture in the very preterm group in association with socio-emotional abilities.
Keywords	Behavior Problems ; Biological Neural Networks ; Biologische Neuronale Netze ; Brain Connectivity ; Emotional Development ; Emotionale Entwicklung ; Frühgeburt ; Konnektivität (Gehirn) ; Neuroanatomie ; Neuroanatomy ; Premature Birth ; Psychosocial Development ; Psychosoziale Entwicklung ; Räumliche Organisation (Wahrnehmung) ; Spatial Organization ; Verhaltensprobleme
Language	English
Document type	Article
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-022-02342-y
Database	PSYNDEX

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Article ; Online: The effect of a mindfulness-based intervention on executive, behavioural and socio-emotional competencies in very preterm young adolescents.

Siffredi, Vanessa / Liverani, Maria Chiara / Hüppi, Petra Susan / Freitas, Lorena G A / De Albuquerque, Jiske / Gimbert, Fanny / Merglen, Arnaud / Meskaldji, Djalel Eddine / Borradori Tolsa, Cristina / Hà-Vinh Leuchter, Russia

Scientific reports

2021 Volume 11, Issue 1, Page(s) 19876

Abstract: Very preterm (VPT) children and adolescents show executive, behavioural and socio-emotional difficulties that persists into adulthood. This study aims to assess the effectiveness of a mindfulness-based intervention (MBI) in improving these competencies ... ...

Abstract	Very preterm (VPT) children and adolescents show executive, behavioural and socio-emotional difficulties that persists into adulthood. This study aims to assess the effectiveness of a mindfulness-based intervention (MBI) in improving these competencies in VPT young adolescents using a randomised controlled trial design. 56 young adolescents aged 10-14 years, born before 32 gestational weeks, were randomly assigned to an "intervention" or a "waiting" group and completed an 8-week MBI in a cross-over design. Executive, behavioural and socio-emotional competencies were assessed at three different time points via parent and self-reported questionnaires, neuropsychological testing and computerised tasks. The data were analysed using an intention-to-treat approach with linear regression modelling. Our findings show a beneficial effect of MBI on executive, behavioural and socio-emotional competencies in VPT young adolescents measured by parent questionnaires. Increased executive competencies were also observed on computerised task with enhanced speed of processing after MBI. Two subgroups of participants were created based on measures of prematurity, which revealed increased long-term benefits in the moderate-risk that were not observed in the high-risk subgroups of VPT young adolescents. MBI seems a valuable tool for reducing detrimental consequences of prematurity in young adolescents, especially regarding executive, behavioural and socio-emotional difficulties.Clinical Trial Registration ClinicalTrials, NCT04638101. Registered 20 November 2020-Retrospectively registered, https://clinicaltrials.gov/show/NCT04638101 .
MeSH term(s)	Adolescent ; Adolescent Behavior/psychology ; Adolescent Development ; Child ; Child Behavior/psychology ; Child Development ; Child, Preschool ; Emotions ; Executive Function ; Female ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Mindfulness/methods ; Premature Birth/epidemiology ; Premature Birth/psychology ; Social Behavior
Language	English
Publishing date	2021-10-06
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-98608-2
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