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  1. Article ; Online: The exposome as the science of social-to-biological transitions

    Paolo Vineis / Robert Barouki

    Environment International, Vol 165, Iss , Pp 107312- (2022)

    2022  

    Abstract: The understanding of disease etiology and pathogenesis has radically changed as a consequence of the new challenges posed by climate change, environmental degradation and emerging infectious diseases. The awareness of the influence of distal causes (e.g. ...

    Abstract The understanding of disease etiology and pathogenesis has radically changed as a consequence of the new challenges posed by climate change, environmental degradation and emerging infectious diseases. The awareness of the influence of distal causes (e.g. planetary changes at the roots of new pandemics), of the social environment and of early life exposures calls for innovative models of disease onset. Here we propose a scheme for the practice of epidemiology and toxicology that incorporates new recent advancements in both disciplines, under the general umbrella of the “exposome”. The exposome approach to disease encompasses a lifecourse perspective from conception onwards, and the investigation of the role played by all exposures individuals undergo in their lives. These include social inequalities and psychosocial influences, in addition to chemical, biological and physical exposures. We stress the role played by social differences and inequalities in the course of life as an overarching factor that influences downstream layers (including behaviours). We show that the idea of “lifecourse exposome” is compatible with the current interpretation of Adverse Outcome Pathways in toxicology, and in fact we propose an extension of the concept towards “lifecourse Adverse Outcome Pathways”. We propose to merge different research perspectives and promote an encounter between the sociological perspective of “biography” (using Pierre Bourdieu’s conceptual framework) and biology, according to the idea of accumulated biological capital of individuals. We also propose to treat social capital (including inequalities) no longer as a confounding factor but as an overarching determinant, perhaps the most important of all because it is the one that influences all other exposures downstream. The importance of early exposures in a lifecourse perspective leads to policy implications, i.e. investing more in the various forms of capital (social, economic, cultural) in early life.
    Keywords Exposome ; Social to biological transitions ; Embodiment ; AOP ; Toxicology ; Epidemiology ; Environmental sciences ; GE1-350
    Subject code 300
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Endocrine disrupting chemicals and COVID-19 relationships

    Qier Wu / Xavier Coumoul / Philippe Grandjean / Robert Barouki / Karine Audouze

    Environment International, Vol 157, Iss , Pp 106232- (2021)

    A computational systems biology approach

    2021  

    Abstract: Background: Patients at high risk of severe forms of COVID-19 frequently suffer from chronic diseases, but other risk factors may also play a role. Environmental stressors, such as endocrine disrupting chemicals (EDCs), can contribute to certain chronic ... ...

    Abstract Background: Patients at high risk of severe forms of COVID-19 frequently suffer from chronic diseases, but other risk factors may also play a role. Environmental stressors, such as endocrine disrupting chemicals (EDCs), can contribute to certain chronic diseases and might aggravate the course of COVID-19. Objectives: To explore putative links between EDCs and COVID-19 severity, an integrative systems biology approach was constructed and applied. Methods: As a first step, relevant data sets were compiled from major data sources. Biological associations of major EDCs to proteins were extracted from the CompTox database. Associations between proteins and diseases known as important COVID-19 comorbidities were obtained from the GeneCards and DisGeNET databases. Based on these data, we developed a tripartite network (EDCs-proteins-diseases) and used it to identify proteins overlapping between the EDCs and the diseases. Signaling pathways for common proteins were then investigated by over-representation analysis. Results: We found several statistically significant pathways that may be dysregulated by EDCs and that may also be involved in COVID-19 severity. The Th17 and the AGE/RAGE signaling pathways were particularly promising. Conclusions: Pathways were identified as possible targets of EDCs and as contributors to COVID-19 severity, thereby highlighting possible links between exposure to environmental chemicals and disease development. This study also documents the application of computational systems biology methods as a relevant approach to increase the understanding of molecular mechanisms linking EDCs and human diseases, thereby contributing to toxicology prediction.
    Keywords Endocrine disruptor ; Systems toxicology ; Integrative computational approach ; Network science ; OBERON ; Environmental sciences ; GE1-350
    Subject code 610
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Impact of mixtures of persistent organic pollutants on breast cancer aggressiveness

    Louise Benoit / Meriem Koual / Céline Tomkiewicz / Anne-Sophie Bats / Jean-Philippe Antignac / Xavier Coumoul / Robert Barouki / German Cano-Sancho

    Environment International, Vol 170, Iss , Pp 107615- (2022)

    2022  

    Abstract: Introduction: Breast cancer (BC) is frequent with a poor prognosis in case of metastasis. The role of the environment has been poorly evaluated in its progression. We searched to assess whether a mixture of pollutants could be responsible of BC ... ...

    Abstract Introduction: Breast cancer (BC) is frequent with a poor prognosis in case of metastasis. The role of the environment has been poorly evaluated in its progression. We searched to assess whether a mixture of pollutants could be responsible of BC aggressiveness. Methods: Patients undergoing surgery for their BC were prospectively included in the METAPOP cohort. Forty-two POPs were extracted, among them 17 dioxins (PCDD/F), 16 polychlorobiphenyls (PCB), 8 polybromodiphenylethers (PBDE) and 2,2′,4,4′,5,5′-hexabromobiphenyl (PBB153) were measured in the adipose tissue surrounding the tumor. BC aggressiveness was defined using tumor size and metastasis (distant or lymph nodes). Two complementary models were used to evaluate the impact of the mixture of pollutants: the BKMR (Bayesian Kernel machine regression) and WQS (weighted quantile sum regression) models. The WQS estimates the weight (positive or negative) of a certain chemical based on its quantile and the BKMR model applies a kernel-based approach to estimate posterior inclusion probabilities. The sub-group of patients with a body mass index (BMI) > 22 kg/ m2 was also analyzed. Results: Ninety-one patients were included. Of these, 38 patients presented a metastasis, and the mean tumor size was 25.4 mm. The mean BMI was 24.5 kg/m2 (+/- 4.1). No statistical association was found in the general population. However, in patients with a BMI > 22 kg/ m2, our mixture was positively associated with tumor size (OR: 9.73 95 %CI: 1.30–18.15) and metastasis (OR = 3.98 95 %CI = 1.09–17.53) using the WQS model. Moreover, using the BKMR model on chemical families, dioxin like chemicals and PCDD were associated with a higher risk of metastasis. Discussion: These novel findings identified a mixture associated with breast cancer aggressiveness in patients with a BMI > 22 kg/ m2.
    Keywords Adipose tissue ; Mammary cancer ; Endocrine disrupting chemicals ; Environmental exposure ; Metastasis ; Environmental sciences ; GE1-350
    Subject code 610
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Adverse outcome pathway from activation of the AhR to breast cancer-related death

    Louise Benoit / Florence Jornod / Elias Zgheib / Celine Tomkiewicz / Meriem Koual / Thibaut Coustillet / Robert Barouki / Karine Audouze / Mathieu Vinken / Xavier Coumoul

    Environment International, Vol 165, Iss , Pp 107323- (2022)

    2022  

    Abstract: Adverse outcome pathways (AOPs) are formalized and structured linear concepts that connect one molecular initiating event (MIE) to an adverse outcome (AO) via different key events (KE) through key event relationships (KER). They are mainly used in eco- ... ...

    Abstract Adverse outcome pathways (AOPs) are formalized and structured linear concepts that connect one molecular initiating event (MIE) to an adverse outcome (AO) via different key events (KE) through key event relationships (KER). They are mainly used in eco-toxicology toxicology, and regulatory health issues. AOPs must respond to specific guidelines from the Organization for Economic Co-operation and Development (OECD) to weight the evidence between each KE.Breast cancer is the deadliest cancer in women with a poor prognosis in case of metastatic breast cancer. The role of the environments in the formation of metastasis has been suggested. We hypothesized that activation of the AhR (MIE), a xenobiotic receptor, could lead to breast cancer related death (AO), through different KEs, constituting a new AOP.An artificial intelligence tool (AOP-helpfinder), which screens the available literature, was used to collect all existing scientific abstracts to build a novel AOP, using a list of key words. Four hundred and seven abstracts were found containing at least a word from our MIE list and either one word from our AO or KE list. A manual curation retained 113 pertinent articles, which were also screened using PubTator. From these analyses, an AOP was created linking the activation of the AhR to breast cancer related death through decreased apoptosis, inflammation, endothelial cell migration, angiogenesis, and invasion. These KEs promote an increased tumor growth, angiogenesis and migration which leads to breast cancer metastasis and breast cancer related death.The evidence of the proposed AOP was weighted using the tailored Bradford Hill criteria and the OECD guidelines. The confidence in our AOP was considered strong. An in vitro validation must be carried out, but our review proposes a strong relationship between AhR activation and breast cancer-related death with an innovative use of an artificial intelligence literature search.
    Keywords Mammary metastasis ; Aryl hydrocarbon receptor ; Chemical toxicity ; Adverse outcome pathway ; Cancer development ; Environmental sciences ; GE1-350
    Subject code 610
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Setting the European environment and health research agenda –under-researched areas and solution-oriented research

    Anke Huss / Annette Peters / Tianyu Zhao / Robert Barouki / Manolis Kogevinas / Roel Vermeulen / Franziska Matthies-Wiesler

    Environment International, Vol 163, Iss , Pp 107202- (2022)

    2022  

    Abstract: Background: The aim of the EU-funded HERA (health and environment research agenda) project is to set priorities for the future European research agenda in the environment, climate and health nexus. We report results from a European researcher’s ... ...

    Abstract Background: The aim of the EU-funded HERA (health and environment research agenda) project is to set priorities for the future European research agenda in the environment, climate and health nexus. We report results from a European researcher’s perspective and identify research areas that have been inadequately investigated to date. Methods: An online survey was completed by European researchers to assess, evaluate and visualise research gaps. These research gaps were identified for 21 predefined areas within 3 main categories: i) classical environment and health paradigm; ii) problem or sector-based research areas and approaches and iii) holistic research areas and concepts. All research gaps were then evaluated by expert groups with the pre-defined criteria and systematically summarized. For areas identified within the survey as under-reported, additional input was sought from a range of key selected experts. The EU project database Cordis was utilized to verify that these areas were under-researched. Results: Between May and July 2019, 318 respondents from 38 countries reported 624 research gaps. The main areas for attention identified were: urban environments; chemicals; and climate change, (combined n = 313 gaps). Biodiversity loss and health; transport, mobility, sustainable solutions and health; energy transition and health; waste and the circular economy and health; ethics and philosophy and health were areas that were acknowledged as under-researched (combined n = 27 gaps). These under-researched areas were identified as having certain commonalities, they: i) mostly fell in the category “problem or sector based approaches“; ii) they are essential for developing and implementing solutions; and iii) require trans-disciplinary and cross-sectoral collaboration. Conclusions: Currently attention is given to topical and highly researched areas in environmental health. In contrast, this paper identifies key topics and approaches that are under-researched, yet, are critical for the implementation of the EU Green ...
    Keywords Research agenda ; Environment health under-researched green deal ; Environmental sciences ; GE1-350
    Subject code 300
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: High-resolution mass spectrometry identifies delayed biomarkers for improved precision in acetaminophen/paracetamol human biomonitoring

    Eva Gorrochategui / Marc Le Vee / Habiba Selmi / Anne Gérard / Jade Chaker / Annette M. Krais / Christian Lindh / Olivier Fardel / Cécile Chevrier / Pierre Le Cann / Gary W. Miller / Robert Barouki / Bernard Jégou / Thomas Gicquel / David M. Kristensen / Arthur David

    Environment International, Vol 181, Iss , Pp 108299- (2023)

    2023  

    Abstract: Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP ... ...

    Abstract Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g., developmental disorders, drug-induced liver injury), there is a need to improve current APAP biomonitoring methods that are limited by APAP short half-life. Here, we demonstrate using high-resolution mass spectrometry (HRMS) in several human studies that APAP thiomethyl metabolite conjugates (S-methyl-3-thioacetaminophen sulfate and S-methyl-3-thioacetaminophen sulphoxide sulfate) are stable biomarkers with delayed excretion rates compared to conventional APAP metabolites, that could provide a more reliable history of APAP ingestion in epidemiological studies. We also show that these biomarkers could serve as relevant clinical markers to diagnose APAP acute intoxication in overdosed patients, when free APAP have nearly disappeared from blood. Using in vitro liver models (HepaRG cells and primary human hepatocytes), we then confirm that these thiomethyl metabolites are directly linked to the toxic N-acetyl-p-benzoquinone imine (NAPQI) elimination, and produced via an overlooked pathway called the thiomethyl shunt pathway. Further studies will be needed to determine whether the production of the reactive hepatotoxic NAPQI metabolites is currently underestimated in human. Nevertheless, these biomarkers could already serve to improve APAP human biomonitoring, and investigate, for instance, inter-individual variability in NAPQI production to study underlying causes involved in APAP-induced hepatotoxicity. Overall, our findings demonstrate the potential of exposomics-based HRMS approach to advance towards a better precision for human biomonitoring.
    Keywords Human biomonitoring ; High-resolution mass spectrometry ; Acetaminophen/paracetamol ; Exposomics ; Thiomethyl metabolites ; Chemical exposome ; Environmental sciences ; GE1-350
    Subject code 500
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Priorities for research on environment, climate and health, a European perspective

    Elina Drakvik / Manolis Kogevinas / Åke Bergman / Anais Devouge / Robert Barouki / on behalf of the HERA (Health and Environment Research Agenda) Consortium

    Environmental Health, Vol 21, Iss 1, Pp 1-

    2022  Volume 5

    Abstract: Abstract Climate change, urbanisation, chemical pollution and disruption of ecosystems, including biodiversity loss, affect our health and wellbeing. Research is crucial to be able to respond to the current and future challenges that are often complex ... ...

    Abstract Abstract Climate change, urbanisation, chemical pollution and disruption of ecosystems, including biodiversity loss, affect our health and wellbeing. Research is crucial to be able to respond to the current and future challenges that are often complex and interconnected by nature. The HERA Agenda, summarised in this commentary, identifies six thematic research goals in the environment, climate and health fields. These include research to 1) reduce the effects of climate change and biodiversity loss on health and environment, 2) promote healthy lives in cities and communities, 3) eliminate harmful chemical exposures, 4) improve health impact assessment and implementation research, 5) develop infrastructures, technologies and human resources and 6) promote research on transformational change towards sustainability. Numerous specific recommendations for research topics, i.e., specific research goals, are presented under each major research goal. Several methods were used to define the priorities, including web-based surveys targeting researchers and stakeholder groups as well as a series of online and face-to-face workshops, involving hundreds of researchers and other stakeholders. The results call for an unprecedented effort to support a better understanding of the causes, interlinkages and impacts of environmental stressors on health and the environment. This will require breakdown of silos within policies, research, actors as well as in our institutional arrangements in order to enable more holistic approaches and solutions to emerge. The HERA project has developed a unique and exciting opportunity in Europe to consensuate priorities in research and strengthen research that has direct societal impact.
    Keywords Research agenda ; Climate ; Chemicals ; Cities ; Impact assessment ; Infrastructures ; Industrial medicine. Industrial hygiene ; RC963-969 ; Public aspects of medicine ; RA1-1270
    Subject code 306
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Merging the exposome into an integrated framework for “omics” sciences

    Elliott J. Price / Chiara M. Vitale / Gary W. Miller / Arthur David / Robert Barouki / Karine Audouze / Douglas I. Walker / Jean-Philippe Antignac / Xavier Coumoul / Vincent Bessonneau / Jana Klánová

    iScience, Vol 25, Iss 3, Pp 103976- (2022)

    2022  

    Abstract: Summary: The exposome concept encourages holistic consideration of the non-genetic factors (environmental exposures including lifestyle) that influence an individual’s health over their life course. However, disconnect between the concept and practical ... ...

    Abstract Summary: The exposome concept encourages holistic consideration of the non-genetic factors (environmental exposures including lifestyle) that influence an individual’s health over their life course. However, disconnect between the concept and practical application has promoted divergent interpretations of the exposome across disciplines and reinforced separation of the environmental (emphasizing exposures) and biological (emphasizing responses) research communities. In particular, while knowledge of biological responses can help to distinguish actual (i.e. experienced) from potential exposures, the inclusion of endogenous processes has generated confusion about the position of the exposome in a multi-omics systems biology context. We propose a reattribution of “exposome” to exclusively represent the totality of contact with external factors that a biological entity experiences, and introduce the term “functional exposomics” to denote the systematic study of exposure-phenotype interaction. This reoriented definition of the exposome allows a more readily integrable dataset for multi-omics and systems biology research.
    Keywords Environmental health ; Exposure assessment ; Omics ; Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Towards a comprehensive characterisation of the human internal chemical exposome

    Arthur David / Jade Chaker / Elliott J. Price / Vincent Bessonneau / Andrew J. Chetwynd / Chiara M. Vitale / Jana Klánová / Douglas I. Walker / Jean-Philippe Antignac / Robert Barouki / Gary W. Miller

    Environment International, Vol 156, Iss , Pp 106630- (2021)

    Challenges and perspectives

    2021  

    Abstract: The holistic characterisation of the human internal chemical exposome using high-resolution mass spectrometry (HRMS) would be a step forward to investigate the environmental ætiology of chronic diseases with an unprecedented precision. HRMS-based methods ...

    Abstract The holistic characterisation of the human internal chemical exposome using high-resolution mass spectrometry (HRMS) would be a step forward to investigate the environmental ætiology of chronic diseases with an unprecedented precision. HRMS-based methods are currently operational to reproducibly profile thousands of endogenous metabolites as well as externally-derived chemicals and their biotransformation products in a large number of biological samples from human cohorts. These approaches provide a solid ground for the discovery of unrecognised biomarkers of exposure and metabolic effects associated with many chronic diseases. Nevertheless, some limitations remain and have to be overcome so that chemical exposomics can provide unbiased detection of chemical exposures affecting disease susceptibility in epidemiological studies. Some of these limitations include (i) the lack of versatility of analytical techniques to capture the wide diversity of chemicals; (ii) the lack of analytical sensitivity that prevents the detection of exogenous (and endogenous) chemicals occurring at (ultra) trace levels from restricted sample amounts, and (iii) the lack of automation of the annotation/identification process. In this article, we discuss a number of technological and methodological limitations hindering applications of HRMS-based methods and propose initial steps to push towards a more comprehensive characterisation of the internal chemical exposome. We also discuss other challenges including the need for harmonisation and the difficulty inherent in assessing the dynamic nature of the internal chemical exposome, as well as the need for establishing a strong international collaboration, high level networking, and sustainable research infrastructure. A great amount of research, technological development and innovative bio-informatics tools are still needed to profile and characterise the “invisible” (not profiled), “hidden” (not detected) and “dark” (not annotated) components of the internal chemical exposome and concerted ...
    Keywords Exposome ; High-Resolution Mass Spectrometry ; Internal chemical exposome ; Non-targeted analysis ; Suspect screening ; EWAS ; Environmental sciences ; GE1-350
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Identification of non-validated endocrine disrupting chemical characterization methods by screening of the literature using artificial intelligence and by database exploration

    Elias Zgheib / Min Ji Kim / Florence Jornod / Kévin Bernal / Céline Tomkiewicz / Sylvie Bortoli / Xavier Coumoul / Robert Barouki / Kelly De Jesus / Elise Grignard / Philippe Hubert / Efrosini S. Katsanou / Francois Busquet / Karine Audouze

    Environment International, Vol 154, Iss , Pp 106574- (2021)

    2021  

    Abstract: Background: Exposure to endocrine disrupting chemicals (EDCs) represents a critical public health threat. Several adverse health outcomes (e.g., cancers, metabolic and neurocognitive/neurodevelopmental disorders, infertility, immune diseases and ... ...

    Abstract Background: Exposure to endocrine disrupting chemicals (EDCs) represents a critical public health threat. Several adverse health outcomes (e.g., cancers, metabolic and neurocognitive/neurodevelopmental disorders, infertility, immune diseases and allergies) are associated with exposure to EDCs. However, the regulatory tests that are currently employed in the EU to identify EDCs do not assess all of the endocrine pathways. Objective: Our objective was to explore the literature, guidelines and databases to identify relevant and reliable test methods which could be used for prioritization and regulatory pre-validation of EDCs in missing and urgent key areas. Methods: Abstracts of articles referenced in PubMed were automatically screened using an updated version of the AOP-helpFinder text mining approach. Other available sources were manually explored. Exclusion criteria (computational methods, specific tests for estrogen receptors, tests under validation or already validated, methods accepted by regulatory bodies) were applied according to the priorities of the French Public-privatE Platform for the Pre-validation of Endocrine disRuptors (PEPPER) characterisation methods. Results: 226 unique non-validated methods were identified. These experimental methods (in vitro and in vivo) were developed for 30 species using diverse techniques (e.g., reporter gene assays and radioimmunoassays). We retrieved bioassays mainly for the reproductive system, growth/developmental systems, lipogenesis/adipogenicity, thyroid, steroidogenesis, liver metabolism-mediated toxicity, and more specifically for the androgen-, thyroid hormone-, glucocorticoid- and aryl hydrocarbon receptors. Conclusion: We identified methods to characterize EDCs which could be relevant for regulatory pre-validation and, ultimately for the efficient prevention of EDC-related severe health outcomes. This integrative approach highlights a successful and complementary strategy which combines computational and manual curation approaches.
    Keywords Bioassays ; Assay validation ; Endocrine disruptors ; Guidelines ; OECD ; AOP-helpFinder ; Environmental sciences ; GE1-350
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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