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Alzheimers Disease Neuroimaging Initiative (1U01AG024904-01)
101 Research products (1 rule applied)

  • 2014-2023
  • English

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    Authors: Lee, Brian N.; Wang, Junwen; Nho, Kwangsik; Saykin, Andrew J.; +1 Authors

    Alzheimer's Disease (AD) is a highly heritable neurodegenerative disorder characterized by memory impairments. Understanding how genetic factors contribute to AD pathology may inform interventions to slow or prevent the progression of AD. We performed stratified genetic analyses of 1,574 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants to examine associations between levels of quantitative traits (QT's) and future diagnosis. The Chow test was employed to determine if an individual's genetic profile affects identified predictive relationships between QT's and future diagnosis. Our chow test analysis discovered that cognitive and PET-based biomarkers differentially predicted future diagnosis when stratifying on allelic dosage of AD loci. Post-hoc bootstrapped and association analyses of biomarkers confirmed differential effects, emphasizing the necessity of stratified models to realize individualized AD diagnosis prediction. This novel application of the Chow test allows for the quantification and direct comparison of genetic-based differences. Our findings, as well as the identified QT-future diagnosis relationships, warrant future investigation from a biological context.

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    Europe PubMed Central
    Other literature type . 2023
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    Authors: Giorgio, Joseph; Tanna, Ankeet; Malpetti, Maura; White, Simon R; +12 Authors

    INTRODUCTION: Although many cognitive measures have been developed to assess cognitive decline due to Alzheimer's disease (AD), there is little consensus on optimal measures, leading to varied assessments across research cohorts and clinical trials making it difficult to pool cognitive measures across studies. METHODS: We used a two-stage approach to harmonize cognitive data across cohorts and derive a cross-cohort score of cognitive impairment due to AD. First, we pool and harmonize cognitive data from international cohorts of varying size and ethnic diversity. Next, we derived cognitive composites that leverage maximal data from the harmonized dataset. RESULTS: We show that our cognitive composites are robust across cohorts and achieve greater or comparable sensitivity to AD-related cognitive decline compared to the Mini-Mental State Examination and Preclinical Alzheimer Cognitive Composite. Finally, we used an independent cohort validating both our harmonization approach and composite measures. DISCUSSION: Our easy to implement and readily available pipeline offers an approach for researchers to harmonize their cognitive data with large publicly available cohorts, providing a simple way to pool data for the development or validation of findings related to cognitive decline due to AD.

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    Apollo
    Article . 2023
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    Authors: Steyer, Lisa; Stöcker, Almond; Greven, Sonja;

    We propose regression models for curve-valued responses in two or more dimensions, where only the image but not the parametrization of the curves is of interest. Examples of such data are handwritten letters, movement paths or outlines of objects. In the square-root-velocity framework, a parametrization invariant distance for curves is obtained as the quotient space metric with respect to the action of re-parametrization, which is by isometries. With this special case in mind, we discuss the generalization of 'linear' regression to quotient metric spaces more generally, before illustrating the usefulness of our approach for curves modulo re-parametrization. We address the issue of sparsely or irregularly sampled curves by using splines for modeling smooth conditional mean curves. We test this model in simulations and apply it to human hippocampal outlines, obtained from Magnetic Resonance Imaging scans. Here we model how the shape of the irregularly sampled hippocampus is related to age, Alzheimer's disease and sex.

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    Authors: Zong, Yongshuo; Yang, Yongxin; Hospedales, Timothy M;

    A multitude of work has shown that machine learning-based medical diagnosis systems can be biased against certain subgroups of people. This has motivated a growing number of bias mitigation algorithms that aim to address fairness issues in machine learning. However, it is difficult to compare their effectiveness in medical imaging for two reasons. First, there is little consensus on the criteria to assess fairness. Second, existing bias mitigation algorithms are developed under different settings, e.g., datasets, model selection strategies, backbones, and fairness metrics, making a direct comparison and evaluation based on existing results impossible. In this work, we introduce MEDFAIR, a framework to benchmark the fairness of machine learning models for medical imaging. MEDFAIR covers eleven algorithms from various categories, ten datasets from different imaging modalities, and three model selection criteria. Through extensive experiments, we find that the under-studied issue of model selection criterion can have a significant impact on fairness outcomes; while in contrast, state-of-the-art bias mitigation algorithms do not significantly improve fairness outcomes over empirical risk minimization (ERM) in both in-distribution and out-of-distribution settings. We evaluate fairness from various perspectives and make recommendations for different medical application scenarios that require different ethical principles. Our framework provides a reproducible and easy-to-use entry point for the development and evaluation of future bias mitigation algorithms in deep learning. Code is available at https://github.com/ys-zong/MEDFAIR.

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    Contribution for newspaper or weekly magazine . 2023
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    Authors: Eitel, Fabian;

    Deep learning and especially convolutional neural networks (CNNs) have a high potential of being implemented into clinical decision support software for tasks such as diagnosis and prediction of disease courses. This thesis has studied the application of CNNs on structural MRI data for diagnosing neurological diseases. Specifically, multiple sclerosis and Alzheimer’s disease were used as classification targets due to their high prevalence, data availability and apparent biomarkers in structural MRI data. The classification task is challenging since pathology can be highly individual and difficult for human experts to detect and due to small sample sizes, which are caused by the high acquisition cost and sensitivity of medical imaging data. A roadblock in adopting CNNs to clinical practice is their lack of interpretability. Therefore, after optimizing the machine learning models for predictive performance (e.g. balanced accuracy), we have employed explainability methods to study the reliability and validity of the trained models. The deep learning models achieved good predictive performance of over 87% balanced accuracy on all tasks and the explainability heatmaps showed coherence with known clinical biomarkers for both disorders. Explainability methods were compared quantitatively using brain atlases and shortcomings regarding their robustness were revealed. Further investigations showed clear benefits of transfer-learning and image registration on the model performance. Lastly, a new CNN layer type was introduced, which incorporates a prior on the spatial homogeneity of neuro-MRI data. CNNs excel when used on natural images which possess spatial heterogeneity, and even though MRI data and natural images share computational similarities, the composition and orientation of neuro-MRI is very distinct. The introduced patch-individual filter (PIF) layer breaks the assumption of spatial invariance of CNNs and reduces convergence time on different data sets without reducing predictive performance. The presented work highlights many challenges that CNNs for disease diagnosis face on MRI data and defines as well as tests strategies to overcome those. In dieser Doktorarbeit wird die Frage untersucht, wie erfolgreich deep learning bei der Diagnostik von neurodegenerativen Erkrankungen unterstützen kann. In 5 experimentellen Studien wird die Anwendung von Convolutional Neural Networks (CNNs) auf Daten der Magnetresonanztomographie (MRT) untersucht. Ein Schwerpunkt wird dabei auf die Erklärbarkeit der eigentlich intransparenten Modelle gelegt. Mit Hilfe von Methoden der erklärbaren künstlichen Intelligenz (KI) werden Heatmaps erstellt, die die Relevanz einzelner Bildbereiche für das Modell darstellen. Die 5 Studien dieser Dissertation zeigen das Potenzial von CNNs zur Krankheitserkennung auf neurologischen MRT, insbesondere bei der Kombination mit Methoden der erklärbaren KI. Mehrere Herausforderungen wurden in den Studien aufgezeigt und Lösungsansätze in den Experimenten evaluiert. Über alle Studien hinweg haben CNNs gute Klassifikationsgenauigkeiten erzielt und konnten durch den Vergleich von Heatmaps zur klinischen Literatur validiert werden. Weiterhin wurde eine neue CNN Architektur entwickelt, spezialisiert auf die räumlichen Eigenschaften von Gehirn MRT Bildern.

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    https://doi.org/10.18452/25413...
    Doctoral thesis . 2022
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      https://doi.org/10.18452/25413...
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  • Authors: Bouayed, Aymene Mohammed; Deslauriers-Gauthier, Samuel; Zucchelli, Mauro; Deriche, Rachid;

    International audience; Recently, a general analytical formula to extract all the Rotation Invariant Features (RIFs) of the diffusion Magnetic Resonance Imaging (dMRI) signal was proposed. The features extracted using this formula represent a generalisation of the usual second degree RIFs such as the mean diffusivity. In this work, we study the usefulness of all the 12 algebraically independent RIFs extracted from 4th degree spherical harmonics that model the dMRI signal per voxel in the context of Alzheimer Disease (AD) identification. To do so, and since we are working with imbalanced data sets, we first introduce a non-linear metric to evaluate the performance of the models, the (B-score). This proposed metric allows high score only when both classes are distinguished correctly. We use the proposed metric in conjunction with a deep Convolutional Neural Network that operates on subject slices to identify if a subject has AD or not. We find that micro-structure information communicated by RIFs is indeed useful to AD identification and that not all RIFs are equivalently useful. We also identify the two best RIF combinations for the ADNI-SIEMENS and the ADNI-GE medical data sets respectively. The combination of these RIFs achieves a classification B-score of 73.62% and 72.31% on the previous data sets respectively. We note the importance of combining high degree RIFs with low degree ones to improve the classification performance.

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    Authors: Timsina, Jigyasha; Gomez-Fonseca, Duber; Xiong, Chengjie; Schindler, Suzanne E; +22 Authors

    BACKGROUND: The SOMAscan assay has an advantage over immunoassay-based methods because it measures a large number of proteins in a cost-effective manner. However, the performance of this technology compared to the routinely used immunoassay techniques needs to be evaluated. OBJECTIVE: We performed comparative analyses of SOMAscan and immunoassay-based protein measurements for five cerebrospinal fluid (CSF) proteins associated with Alzheimer’s disease (AD) and neurodegeration: NfL, Neurogranin, sTREM2, VILIP-1 and SNAP-25. METHODS: We compared biomarkers measured in ADNI (N=689), Knight-ADRC (N=870), DIAN (N=115), and Barcelona-1 (N=92) cohorts. Raw protein values were transformed using z-score in order to combine measures from the different studies. sTREM2 and VILIP-1 had more than one analyte in SOMAscan; all available analytes were evaluated. Pearson’s correlation coefficients between SOMAscan and immunoassays were calculated. Receiver operating characteristic curve and area under the curve were used to compare prediction accuracy of these biomarkers between the two platforms. RESULTS: Neurogranin, VILIP-1 and NfL showed high correlation between SOMAscan and immunoassay measures (r > 0.9). sTREM2 had a fair correlation (r > 0.6), whereas SNAP-25 showed weak correlation (r = 0.06). Measures in both platforms provided similar predicted performance for all biomarkers except SNAP-25 and one of the sTREM2 analytes. sTREM2 showed higher AUC for SOMAscan based measures. CONCLUSION: Our data indicate that SOMAscan performs as well as immunoassay approaches for NfL, Neurogranin, VILIP-1 and sTREM2. Our study shows promise for using SOMAscan as an alternative to traditional immunoassay-based measures. Follow-up investigation will be required for SNAP-25 and additional established biomarkers.

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    Authors: Khorramyar, Pooriya;

    A Neurodegenerative Disease (ND) is progressive damage to brain neurons, which the human body cannot repair or replace. The well-known examples of such conditions are Dementia and Alzheimer’s Disease (AD), which affect millions of lives each year. Although conducting numerous researches, there are no effective treatments for the mentioned diseases today. However, early diagnosis is crucial in disease management. Diagnosing NDs is challenging for neurologists and requires years of training and experience. So, there has been a trend to harness the power of deep learning, including state-of-the-art Convolutional Neural Network (CNN), to assist doctors in diagnosing such conditions using brain scans. The CNN models lead to promising results comparable to experienced neurologists in their diagnosis. But, the advent of transformers in the Natural Language Processing (NLP) domain and their outstanding performance persuaded Computer Vision (CV) researchers to adapt them to solve various CV tasks in multiple areas, including the medical field. This research aims to develop Vision Transformer (ViT) models using Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset to classify NDs. More specifically, the models can classify three categories (Cognitively Normal (CN), Mild Cognitive Impairment (MCI), Alzheimer’s Disease (AD)) using brain Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) scans. Also, we take advantage of Automated Anatomical Labeling (AAL) brain atlas and attention maps to develop explainable models. We propose three ViTs, the best of which obtains an accuracy of 82% on the test dataset with the help of transfer learning. Also, we encode the AAL brain atlas information into the best performing ViT, so the model outputs the predicted label, the most critical region in its prediction, and overlaid attention map on the input scan with the crucial areas highlighted. Furthermore, we develop two CNN models with 2D and 3D convolutional kernels as baselines to classify NDs, which achieve accuracy of 77% and 73%, respectively, on the test dataset. We also conduct a study to find out the importance of brain regions and their combinations in classifying NDs using ViTs and the AAL brain atlas. This thesis was awarded a prize of 50,000 SEK by Getinge Sterilization for projects within Health Innovation.

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    Authors: Ge, Xinting; Qiao, Yuchuan; Choi, Jiyoon; Raman, Rema; +2 Authors

    BACKGROUND: Mild cognitive impairment (MCI) individuals with neuropsychiatric symptoms (NPS) are more likely to develop dementia. OBJECTIVE: We sought to understand the relationship between neuroimaging markers such as tau pathology and cognitive symptoms both with and without the presence of NPS during the prodromal period of Alzheimer’s disease (AD). METHODS: A total of 151 MCI subjects with tau positron emission tomographic (PET) scanning with (18)F AV-1451, β-amyloid (Aβ) PET scanning with florbetapir or florbetaben, magnetic resonance imaging (MRI), and cognitive and behavioral evaluations were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A 4-group division approach was proposed using amyloid (A−/A+) and behavior (B−/B+) status: A−B−, A−B+, A+B−, and A+B+. Pearson’s correlation test was conducted for each group to examine the association between tau deposition and cognitive performance. RESULTS: No statistically significant association between tau deposition and cognitive impairment was found for subjects without behavior symptoms in either the A−B− or A+B− groups after correction for false discovery rate (FDR). In contrast, tau deposition was found to be significantly associated with cognitive impairment in entorhinal cortex and temporal pole for the A−B+ group and nearly the whole cerebrum for the A+B+ group. CONCLUSIONS: Enhanced associations between tauopathy and cognitive impairment are present in MCI subjects with behavior symptoms, which is more prominent in the presence of elevated amyloid pathology. MCI individuals with NPS may thus be at greater risk for further cognitive decline with the increase of tau deposition in comparison to those without NPS.

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    Authors: LoBue, Christian; Kelley, Brendan J.; Hart, John; Helphrey, Jessica; +4 Authors

    Few studies have examined an association between mild traumatic brain injury (mTBI) and Alzheimer's disease (AD). For this reason, we compared an AD dementia group with an mTBI history (n = 10) to a matched AD control group (n = 20) on measures of cognitive function, cerebral glucose metabolism, and markers of amyloid and tau deposition. Only a trend and medium-to-large effect size for higher phosphorylated and total tau was identified for the mTBI group. A history of mTBI may be associated with greater tau in AD, indicating a potential pathway for increasing risk for AD, though further evaluation with larger samples is needed.

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Alzheimers Disease Neuroimaging Initiative (1U01AG024904-01)
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    Authors: Lee, Brian N.; Wang, Junwen; Nho, Kwangsik; Saykin, Andrew J.; +1 Authors

    Alzheimer's Disease (AD) is a highly heritable neurodegenerative disorder characterized by memory impairments. Understanding how genetic factors contribute to AD pathology may inform interventions to slow or prevent the progression of AD. We performed stratified genetic analyses of 1,574 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants to examine associations between levels of quantitative traits (QT's) and future diagnosis. The Chow test was employed to determine if an individual's genetic profile affects identified predictive relationships between QT's and future diagnosis. Our chow test analysis discovered that cognitive and PET-based biomarkers differentially predicted future diagnosis when stratifying on allelic dosage of AD loci. Post-hoc bootstrapped and association analyses of biomarkers confirmed differential effects, emphasizing the necessity of stratified models to realize individualized AD diagnosis prediction. This novel application of the Chow test allows for the quantification and direct comparison of genetic-based differences. Our findings, as well as the identified QT-future diagnosis relationships, warrant future investigation from a biological context.

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    Authors: Giorgio, Joseph; Tanna, Ankeet; Malpetti, Maura; White, Simon R; +12 Authors

    INTRODUCTION: Although many cognitive measures have been developed to assess cognitive decline due to Alzheimer's disease (AD), there is little consensus on optimal measures, leading to varied assessments across research cohorts and clinical trials making it difficult to pool cognitive measures across studies. METHODS: We used a two-stage approach to harmonize cognitive data across cohorts and derive a cross-cohort score of cognitive impairment due to AD. First, we pool and harmonize cognitive data from international cohorts of varying size and ethnic diversity. Next, we derived cognitive composites that leverage maximal data from the harmonized dataset. RESULTS: We show that our cognitive composites are robust across cohorts and achieve greater or comparable sensitivity to AD-related cognitive decline compared to the Mini-Mental State Examination and Preclinical Alzheimer Cognitive Composite. Finally, we used an independent cohort validating both our harmonization approach and composite measures. DISCUSSION: Our easy to implement and readily available pipeline offers an approach for researchers to harmonize their cognitive data with large publicly available cohorts, providing a simple way to pool data for the development or validation of findings related to cognitive decline due to AD.

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    Authors: Steyer, Lisa; Stöcker, Almond; Greven, Sonja;

    We propose regression models for curve-valued responses in two or more dimensions, where only the image but not the parametrization of the curves is of interest. Examples of such data are handwritten letters, movement paths or outlines of objects. In the square-root-velocity framework, a parametrization invariant distance for curves is obtained as the quotient space metric with respect to the action of re-parametrization, which is by isometries. With this special case in mind, we discuss the generalization of 'linear' regression to quotient metric spaces more generally, before illustrating the usefulness of our approach for curves modulo re-parametrization. We address the issue of sparsely or irregularly sampled curves by using splines for modeling smooth conditional mean curves. We test this model in simulations and apply it to human hippocampal outlines, obtained from Magnetic Resonance Imaging scans. Here we model how the shape of the irregularly sampled hippocampus is related to age, Alzheimer's disease and sex.

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    Authors: Zong, Yongshuo; Yang, Yongxin; Hospedales, Timothy M;

    A multitude of work has shown that machine learning-based medical diagnosis systems can be biased against certain subgroups of people. This has motivated a growing number of bias mitigation algorithms that aim to address fairness issues in machine learning. However, it is difficult to compare their effectiveness in medical imaging for two reasons. First, there is little consensus on the criteria to assess fairness. Second, existing bias mitigation algorithms are developed under different settings, e.g., datasets, model selection strategies, backbones, and fairness metrics, making a direct comparison and evaluation based on existing results impossible. In this work, we introduce MEDFAIR, a framework to benchmark the fairness of machine learning models for medical imaging. MEDFAIR covers eleven algorithms from various categories, ten datasets from different imaging modalities, and three model selection criteria. Through extensive experiments, we find that the under-studied issue of model selection criterion can have a significant impact on fairness outcomes; while in contrast, state-of-the-art bias mitigation algorithms do not significantly improve fairness outcomes over empirical risk minimization (ERM) in both in-distribution and out-of-distribution settings. We evaluate fairness from various perspectives and make recommendations for different medical application scenarios that require different ethical principles. Our framework provides a reproducible and easy-to-use entry point for the development and evaluation of future bias mitigation algorithms in deep learning. Code is available at https://github.com/ys-zong/MEDFAIR.

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    Authors: Eitel, Fabian;

    Deep learning and especially convolutional neural networks (CNNs) have a high potential of being implemented into clinical decision support software for tasks such as diagnosis and prediction of disease courses. This thesis has studied the application of CNNs on structural MRI data for diagnosing neurological diseases. Specifically, multiple sclerosis and Alzheimer’s disease were used as classification targets due to their high prevalence, data availability and apparent biomarkers in structural MRI data. The classification task is challenging since pathology can be highly individual and difficult for human experts to detect and due to small sample sizes, which are caused by the high acquisition cost and sensitivity of medical imaging data. A roadblock in adopting CNNs to clinical practice is their lack of interpretability. Therefore, after optimizing the machine learning models for predictive performance (e.g. balanced accuracy), we have employed explainability methods to study the reliability and validity of the trained models. The deep learning models achieved good predictive performance of over 87% balanced accuracy on all tasks and the explainability heatmaps showed coherence with known clinical biomarkers for both disorders. Explainability methods were compared quantitatively using brain atlases and shortcomings regarding their robustness were revealed. Further investigations showed clear benefits of transfer-learning and image registration on the model performance. Lastly, a new CNN layer type was introduced, which incorporates a prior on the spatial homogeneity of neuro-MRI data. CNNs excel when used on natural images which possess spatial heterogeneity, and even though MRI data and natural images share computational similarities, the composition and orientation of neuro-MRI is very distinct. The introduced patch-individual filter (PIF) layer breaks the assumption of spatial invariance of CNNs and reduces convergence time on different data sets without reducing predictive performance. The presented work highlights many challenges that CNNs for disease diagnosis face on MRI data and defines as well as tests strategies to overcome those. In dieser Doktorarbeit wird die Frage untersucht, wie erfolgreich deep learning bei der Diagnostik von neurodegenerativen Erkrankungen unterstützen kann. In 5 experimentellen Studien wird die Anwendung von Convolutional Neural Networks (CNNs) auf Daten der Magnetresonanztomographie (MRT) untersucht. Ein Schwerpunkt wird dabei auf die Erklärbarkeit der eigentlich intransparenten Modelle gelegt. Mit Hilfe von Methoden der erklärbaren künstlichen Intelligenz (KI) werden Heatmaps erstellt, die die Relevanz einzelner Bildbereiche für das Modell darstellen. Die 5 Studien dieser Dissertation zeigen das Potenzial von CNNs zur Krankheitserkennung auf neurologischen MRT, insbesondere bei der Kombination mit Methoden der erklärbaren KI. Mehrere Herausforderungen wurden in den Studien aufgezeigt und Lösungsansätze in den Experimenten evaluiert. Über alle Studien hinweg haben CNNs gute Klassifikationsgenauigkeiten erzielt und konnten durch den Vergleich von Heatmaps zur klinischen Literatur validiert werden. Weiterhin wurde eine neue CNN Architektur entwickelt, spezialisiert auf die räumlichen Eigenschaften von Gehirn MRT Bildern.

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    https://doi.org/10.18452/25413...
    Doctoral thesis . 2022
    Data sources: Datacite
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ edoc-Server. Open-Ac...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      https://doi.org/10.18452/25413...
      Doctoral thesis . 2022
      Data sources: Datacite
      addClaim

      This Research product is the result of merged Research products in OpenAIRE.

      You have already added works in your ORCID record related to the merged Research product.