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Wlad, M., Struckmann, W., Persson, J., Rosen, J., Fällmar, D., Bodén, R. & Gingnell, M. (2025). Emotion anticipation and processing in depression: Behavioral, neural, and physiological reactivity. European psychiatry, 68(1), Article ID e68.
Open this publication in new window or tab >>Emotion anticipation and processing in depression: Behavioral, neural, and physiological reactivity
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2025 (English)In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 68, no 1, article id e68Article in journal (Refereed) Published
Abstract [en]

Background: Depression is characterized by disturbed emotion processing, with aberrant neural and physiological responses to emotional stimuli. Here, we applied an emotion anticipation and processing paradigm to investigate brain neural and electrodermal reactivities in patients with depression compared with healthy controls.

Methods: The study included 42 patients (27 females) and 44 healthy controls (21 females). Subjects underwent functional magnetic resonance imaging with simultaneous measurement of electrodermal activity. During scanning, red or green color cues were presented, followed by pictures of negative or positive valence, respectively. Behavioral valence and arousal ratings of the picture stimuli were conducted after scanning. Anhedonia was assessed through a semi-structured interview in both subject groups.

Results: Patients perceived positive pictures as less positive than controls did. Positive anticipation (i.e., green color cues) elicited stronger activations in the anterior cingulate cortex and the right insula in patients than in healthy controls, indicating salience network disturbances. An exploratory analysis of all regions in the Automated Anatomical Labeling Atlas 2 found significant differences in activity to positive anticipation between groups in several brain regions involved in cognition and emotion processing. Positive and negative anticipation elicited stronger electrodermal responses in healthy controls. However, electrodermal reactivity to negative pictures was higher in patients than in controls.

Conclusions: Ongoing depression affects emotion anticipation and processing at the behavioral, neural, and physiological levels. These findings contribute to increased understanding of the disorder.

Place, publisher, year, edition, pages
Cambridges Institutes Press, 2025
Keywords
anterior cingulate cortex, depression, electrodermal activity, functional magnetic resonance imaging, insula, salience network
National Category
Neurosciences Psychiatry
Identifiers
urn:nbn:se:uu:diva-561334 (URN)10.1192/j.eurpsy.2025.10043 (DOI)001505482700001 ()40495283 (PubMedID)
Funder
Swedish Research Council, 2016-02362Swedish Society of MedicineMärta och Nicke Nasvells stiftelseThe Swedish Brain Foundation, PS2021-0026Swedish Society for Medical Research (SSMF)
Available from: 2025-06-26 Created: 2025-06-26 Last updated: 2025-06-26Bibliographically approved
Widegren, E., Vegelius, J., Frick, M. A., Roy, A. A., Möller, S., Kleberg, J. L., . . . Frick, A. (2025). Fear extinction retention in children, adolescents, and adults. Developmental Cognitive Neuroscience, 71, Article ID 101509.
Open this publication in new window or tab >>Fear extinction retention in children, adolescents, and adults
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2025 (English)In: Developmental Cognitive Neuroscience, ISSN 1878-9293, E-ISSN 1878-9307, Vol. 71, article id 101509Article in journal (Refereed) Published
Abstract [en]

Past results suggest that fear extinction and the return of extinguished fear are compromised in adolescents. However, findings have been inconclusive as there is a lack of fear extinction and extinction retention studies including children, adolescents and adults. In the present study, 36 children (6-9 years), 40 adolescents (13-17 years) and 44 adults (30-40 years), underwent a two-day fear conditioning task. Habituation, acquisition, and extinction were performed on the first day and an extinction retention test > 24 h later. Skin conductance responses were recorded during all phases of fear conditioning and functional magnetic resonance imaging (fMRI) was conducted during the fear retention test. All groups acquired and extinguished fear as measured with SCR, with no group differences in SCR during extinction retention. The groups had largely similar neural fear responses during the retention test, apart from adolescents displaying stronger amygdala fear response than children, with no differences between adolescents and adults. The findings do not support an adolescent extinction dip, and there was only marginal evidence of progressive changes in fear conditioning across development. In contrast to findings in rodents, fear conditioning in humans may elicit similar physiological responses and recruit similar neural networks from childhood to adulthood.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
Development, FMRI, Fear conditioning, Fear extinction, Fear retention, Threat conditioning
National Category
Neurosciences Psychology
Identifiers
urn:nbn:se:uu:diva-548186 (URN)10.1016/j.dcn.2025.101509 (DOI)001398990500001 ()39799854 (PubMedID)2-s2.0-85214494012 (Scopus ID)
Funder
Riksbankens Jubileumsfond, P17–0256:1Swedish Society for Medical Research (SSMF), PD21–0136The Swedish Brain Foundation, PS2021-0026Swedish Research Council, 2022-06725
Note

The two last authors contributed equally.

Available from: 2025-01-22 Created: 2025-01-22 Last updated: 2025-02-03Bibliographically approved
Silfwerbrand, L., Ekselius, L., Koike, Y. & Gingnell, M. (2024). A Japanese translation of the Swedish Universities Scales of Personality. Upsala Journal of Medical Sciences, 129
Open this publication in new window or tab >>A Japanese translation of the Swedish Universities Scales of Personality
2024 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 129Article in journal (Refereed) Published
Abstract [en]

Background: The Swedish Universities Scales of Personality (SSP) is a personality measurement tool with a short test battery of high psychometric quality, previously not availiable in Japanese.

Methods: We translated the SSP into Japanese and administered it to 103 Japanese nationals. For 11 of the 13 SSP scales in the Japanese version of the SSP (SSP-J11), the Cronbach’s alpha ranged from 0.50 to 0.82 with good internal scale reliability.

Results: A principal factor analysis replicated the previous work by identifying the same three principal dimensions of Neuroticism, Aggression, and Extraversion factors.

Conclusion: The resulting three-factor SSP-J11 shows acceptable reliability and should provide informative insights about personality traits in research and clinical practice in a Japanese context.

Place, publisher, year, edition, pages
Upsala Medical Society, 2024
Keywords
Swedish Universities Scales of Personality, SSP, Cross-cultural translation, Reliability, Swedish to Japanese, Personality inventory
National Category
Sociology (Excluding Social Work, Social Anthropology, Demography and Criminology)
Identifiers
urn:nbn:se:uu:diva-500849 (URN)10.48101/ujms.v129.10349 (DOI)001251484900001 ()38571888 (PubMedID)
Available from: 2023-04-26 Created: 2023-04-26 Last updated: 2025-02-17Bibliographically approved
Thörnblom, E., Cunningham, J. L., Gingnell, M., Landén, M., Bergquist, J. & Bodén, R. (2024). Allopregnanolone and progesterone in relation to a single electroconvulsive therapy seizure and subsequent clinical outcome: an observational cohort study. BMC Psychiatry, 24(1), Article ID 687.
Open this publication in new window or tab >>Allopregnanolone and progesterone in relation to a single electroconvulsive therapy seizure and subsequent clinical outcome: an observational cohort study
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2024 (English)In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 24, no 1, article id 687Article in journal (Refereed) Published
Abstract [en]

Background

Electroconvulsive therapy (ECT) is an important treatment for several severe psychiatric conditions, yet its precise mechanism of action remains unknown. Increased inhibition in the brain after ECT seizures, mediated by γ-aminobutyric acid (GABA), has been linked to clinical effectiveness. Case series on epileptic patients report a postictal serum concentration increase of the GABAA receptor agonist allopregnanolone. Serum allopregnanolone remains unchanged after a full ECT series, but possible transient effects directly after a single ECT seizure remain unexplored. The primary aim was to measure serum concentrations of allopregnanolone and its substrate progesterone after one ECT seizure. Secondary aims were to examine whether concentrations at baseline, or postictal changes, either correlate with seizure generalization or predict clinical outcome ratings after ECT.

Methods

A total of 130 participants (18–85 years) were included. Generalization parameters comprised peak ictal heart rate, electroencephalographic (EEG) seizure duration, and prolactin increase. Outcome measures were ratings of clinical global improvement, perceived health status and subjective memory impairment. Non-parametric tests were used for group comparisons and correlations. The prediction analyses were conducted with binary logistic and simple linear regression analyses.

Results

Allopregnanolone and progesterone remained unchanged and correlated neither with seizure generalization nor with clinical outcome. In men (n = 50), progesterone increased and allopregnanolone change correlated negatively with EEG seizure duration. In a subgroup analysis (n = 62), higher baseline allopregnanolone and progesterone correlated with postictal EEG suppression.

Conclusions

ECT seizures have different physiologic effects than generalized seizures in epilepsy. Progesterone might have implications for psychiatric illness in men.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
Electroconvulsive therapy, epileptic seizures, Allopregnanolone, Progesterone
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:uu:diva-539836 (URN)10.1186/s12888-024-06167-3 (DOI)001333483000003 ()39407178 (PubMedID)
Funder
Swedish Research Council, 2018-02653Swedish Foundation for Strategic Research, KF10-0039Stiftelsen Professor Bror Gadelius MinnesfondFredrik och Ingrid Thurings Stiftelse, 2015-00148Swedish Research Council, 2016-02362Region UppsalaUppsala University
Available from: 2024-10-05 Created: 2024-10-05 Last updated: 2024-11-06Bibliographically approved
Silfwerbrand, L., Koike, Y., Nyström, P. & Gingnell, M. (2024). Directed causal effect with PCMCI in hyperscanning EEG time series. Frontiers in Neuroscience, 18, Article ID 1305918.
Open this publication in new window or tab >>Directed causal effect with PCMCI in hyperscanning EEG time series
2024 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 18, article id 1305918Article in journal (Refereed) Published
Abstract [en]

Social activities are likely to cause effects or reactivity in the brains of the people involved in collaborative social situations. This study assesses a new method, Tigramite, for time domain analysis of directed causality between the prefrontal cortex (PFC) of persons in such situations. An experimental situation using hyperscanning EEG was applied while individuals led and followed each other in finger-tapping rhythms. This structured task has a long duration and a high likelihood of inter-brain causal reactions in the prefrontal cortices. Tigramite is a graph-based causal discovery method to identify directed causal relationships in observational time series. Tigramite was used to analyze directed causal connections within and between the PFC. Significantly directed causality within and between brains could be detected during the social interactions. This is the first empirical evidence the Tigramite can reveal inter- and intra-brain-directed causal effects in hyperscanning EEG time series. The findings are promising for further studies of causality in neural networks during social activities using Tigramite on EEG in the time domain.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2024
Keywords
dual-EEG, hyperscanning EEG, causal effect, directed causality, PCMCI, Tigramite
National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:uu:diva-527880 (URN)10.3389/fnins.2024.1305918 (DOI)001209384000001 ()38686325 (PubMedID)
Available from: 2024-05-15 Created: 2024-05-15 Last updated: 2024-09-14Bibliographically approved
Widegren, E., Frick, M. A., Motilla Hoppe, J., Weis, J., Möller, S., Fällmar, D., . . . Frick, A. (2024). The influence of anterior cingulate GABA+ and glutamate on emotion regulation and reactivity in adolescents and adults. Developmental Psychobiology, 66(4), Article ID e22492.
Open this publication in new window or tab >>The influence of anterior cingulate GABA+ and glutamate on emotion regulation and reactivity in adolescents and adults
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2024 (English)In: Developmental Psychobiology, ISSN 0012-1630, E-ISSN 1098-2302, Vol. 66, no 4, article id e22492Article in journal (Refereed) Published
Abstract [en]

During adolescence, emotion regulation and reactivity are still developing and are in many ways qualitatively different from adulthood. However, the neurobiological processes underpinning these differences remain poorly understood, including the role of maturing neurotransmitter systems. We combined magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (dACC) and self-reported emotion regulation and reactivity in a sample of typically developed adolescents (n = 37; 13-16 years) and adults (n = 39; 30-40 years), and found that adolescents had higher levels of glutamate to total creatine (tCr) ratio in the dACC than adults. A glutamate i age group interaction indicated a differential relation between dACC glutamate levels and emotion regulation in adolescents and adults, and within-group follow-up analyses showed that higher levels of glutamate/tCr were related to worse emotion regulation skills in adolescents. We found no age-group differences in gamma-aminobutyric acid+macromolecules (GABA+) levels; however, emotion reactivity was positively related to GABA+/tCr in the adult group, but not in the adolescent group. The results demonstrate that there are developmental changes in the concentration of glutamate, but not GABA+, within the dACC from adolescence to adulthood, in accordance with previous findings indicating earlier maturation of the GABA-ergic than the glutamatergic system. Functionally, glutamate and GABA+ are positively related to emotion regulation and reactivity, respectively, in the mature brain. In the adolescent brain, however, glutamate is negatively related to emotion regulation, and GABA+ is not related to emotion reactivity. The findings are consistent with synaptic pruning of glutamatergic synapses from adolescence to adulthood and highlight the importance of brain maturational processes underlying age-related differences in emotion processing.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
brain maturation, emotion regulation, emotional reactivity, GABA plus, glutamate, magnetic resonance spectroscopy
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-527463 (URN)10.1002/dev.22492 (DOI)001205384700001 ()38643360 (PubMedID)
Funder
Riksbankens JubileumsfondSwedish Research CouncilThe Swedish Brain FoundationSwedish Society for Medical Research (SSMF)Kjell and Marta Beijer Foundation
Available from: 2024-05-13 Created: 2024-05-13 Last updated: 2024-11-21Bibliographically approved
Bengtsson, J., Frick, A. & Gingnell, M. (2023). Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression. International Journal of Clinical and Health Psychology, 23(4), Article ID 100390.
Open this publication in new window or tab >>Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression
2023 (English)In: International Journal of Clinical and Health Psychology, ISSN 1697-2600, E-ISSN 2174-0852, Vol. 23, no 4, article id 100390Article in journal (Refereed) Published
Abstract [en]

Background: The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) is partly placebo, making blinding integrity important. Blinding of high-frequency rTMS and intermittent theta burst stimulation (iTBS) has been reported as successful at study end. However, blinding integrity at study start is rarely reported. The aim of this study was to investigate blinding integrity during a treatment course of iTBS over the dorsomedial prefrontal cortex (DMPFC) in depression.

Methods: Forty-nine patients with depression from a double-blind-designed randomized controlled trial (NCT02905604) were included. Patients received either active or sham iTBS over the DMPFC with a placebo coil. The sham group received iTBS-synchronized transcutaneous electrical nerve stimulation.

Results: After one session, 74% of participants were able to correctly guess their treatment allocation. This was above chance level (p = 0.001). The percentage dropped to 64% and 56% after the fifth and last sessions. Belong-ing to the active group influenced the choice to guess "active" (odds ratio: 11.7, 95% CI 2.5-53.7). A higher treat-ment intensity of the sham treatment increased the probability to guess "active", but pain did not influence the choice.

Conclusions: Blinding integrity in iTBS trials must be investigated at study start to avoid uncontrolled confounding. Better sham methods are needed.

Place, publisher, year, edition, pages
ElsevierElsevier BV, 2023
Keywords
RTMS, Blinding, Placebo, Sham
National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:uu:diva-506400 (URN)10.1016/j.ijchp.2023.100390 (DOI)001002167400001 ()37223390 (PubMedID)
Funder
Swedish Research Council
Available from: 2023-06-28 Created: 2023-06-28 Last updated: 2024-12-03Bibliographically approved
Wlad, M., Frick, A., Engman, J., Hjorth, O., Motilla Hoppe, J., Faria, V., . . . Gingnell, M. (2023). Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder. Behavioural Brain Research, 442, Article ID 114304.
Open this publication in new window or tab >>Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder
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2023 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 442, article id 114304Article in journal (Refereed) Published
Abstract [en]

Background: Social anxiety disorder (SAD) is associated with aberrant emotional information processing while little is known about non-emotional cognitive processing biases. The dorsal anterior cingulate cortex (dACC) has been implicated in SAD neuropathology and is activated both by emotional and non-affective cognitive challenges like the Multisource Interference Task (MSIT).

Methods: Here, we used fMRI to compare dACC activity and test performance during MSIT in 69 SAD patients and 38 healthy controls. In addition to patient-control comparisons, we examined whether neural activity in the dACC correlated with social anxiety, trait anxiety or depression levels.

Results: The MSIT activated the dACC as expected but with no differences in task performance or neural reactivity between SAD patients and controls. There were no significant correlations between dACC activity and social or trait anxiety symptom severity. In patients, there was a significant negative correlation between dACC activity and depressive symptoms.

Conclusions: In absence of affective challenge, we found no disorder-related cognitive profile in SAD patients since neither MSIT task performance nor dACC neural activity deviated in patients relative to controls.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Social Anxiety Disorder, Functional magnetic resonance imaging, Anterior Cingulate Cortex
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-494834 (URN)10.1016/j.bbr.2023.114304 (DOI)000923264600001 ()36681164 (PubMedID)
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2023-01-20 Created: 2023-01-20 Last updated: 2023-03-07Bibliographically approved
Thörnblom, E., Gingnell, M., Cunningham, J. L., Landen, M. & Bodén, R. (2023). Intercorrelation of physiological seizure parameters and hormonal changes in electroconvulsive therapy. Nordic Journal of Psychiatry, 77(3), 312-318
Open this publication in new window or tab >>Intercorrelation of physiological seizure parameters and hormonal changes in electroconvulsive therapy
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2023 (English)In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 77, no 3, p. 312-318Article in journal (Refereed) Published
Abstract [en]

Objective Physiological parameters that predict electroconvulsive therapy (ECT) effectiveness may reflect propagation of the induced epileptic seizure. As an indication of seizure propagation to the diencephalon, we here examined the correlation between prolactin increase after ECT and clinical seizure evaluation parameters, focusing on peak heart rate. As a proxy for peripheral endocrine stress response, we examined the correlation to postictal cortisol increase. Methods Participants were consecutively recruited from clinical ECT patients (n = 131, age 18-85 years). The first ECT session in a series was examined. For each participant, blood serum concentrations of prolactin and cortisol were measured immediately before and within 30 min after the seizure. Physiological parameters were extracted from clinical records: peak heart rate (HR) during seizure, electroencephalography (EEG) seizure duration, and motor seizure duration. Correlations were calculated using non-parametric tests. Results Serum prolactin increased after ECT and correlated with peak HR, EEG seizure duration, and motor seizure duration. Peak HR during seizure also correlated positively with both EEG seizure duration and motor seizure duration. Correlations were unaffected by age, sex, baseline prolactin levels, antipsychotics, or beta-blocking agents. Serum cortisol increased after ECT but did not correlate with the seizure evaluation parameters, nor with prolactin concentrations. Conclusions Our findings of a positive correlation between peak HR and prolactin that was independent from the peripheral endocrine stress response might be in line with the idea that tachycardia during ECT seizures reflects seizure propagation to the diencephalon. This supports the practice of monitoring cardiovascular response for ECT seizure evaluation.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2023
Keywords
Electroconvulsive therapy, epileptic seizure, heart rate, prolactin, cortisol
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-501607 (URN)10.1080/08039488.2022.2107237 (DOI)000840569000001 ()35968653 (PubMedID)
Funder
Swedish Research Council, 2016-02362Swedish Research Council, 2018-02653Swedish Foundation for Strategic Research, KF10-0039Fredrik och Ingrid Thurings Stiftelse, 2015-00148
Available from: 2023-05-11 Created: 2023-05-11 Last updated: 2024-10-07Bibliographically approved
Guath, M., Kleberg, J. L., Weis, J., Widegren, E., Frick, M., Möller, S., . . . Frick, A. (2023). Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents. Behavioural Brain Research, 436, Article ID 114060.
Open this publication in new window or tab >>Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents
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2023 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 436, article id 114060Article in journal (Refereed) Published
Abstract [en]

Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Magnetic resonance spectroscopy, Mood disorders, Reward learning, Operant conditioning
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-482772 (URN)10.1016/j.bbr.2022.114060 (DOI)000874756400003 ()
Funder
Riksbankens Jubileumsfond, P17–0256:1Kjell and Marta Beijer FoundationÅke Wiberg Foundation, M20-0152Magnus Bergvall FoundationSwedish Psychiatric Foundation
Available from: 2022-08-26 Created: 2022-08-26 Last updated: 2022-12-05Bibliographically approved
Projects
Better than expected: a simultaneous PET/fMRI study of how prediction errors shape long-term fear reduction [2021-03106_VR]; Uppsala UniversityPlacebo and dopamine - true or false? [2022-01928_VR]; Uppsala UniversityWomen’s mental health – what are the issues? [2023-01182_Forte]; Uppsala University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5310-6843

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