bluuebunny/crossref_metadata_2025_split huggingface dataset:
88 Microplastic References for Inhalation Studies
Authors: Santizo Katherine , Mangold Hannah , Wohlleben Wendel , Illies Sarah , Sarau George , Kraus Annelena , Christiansen Silke , Hansen Tanja 
Published: May 2023

Abstract
Microplastic research has been increasing due to the uncertainty of potential effects on the environment and human health. However, microplastic references are currently missing. Not only is there a lack of references there is also a lack of diversity in polymer type for references, especially in toxicological studies. In specific, inhalation studies must rely on microplastics that are respirable and/or inhalable (&lt; 10 µm) to result in toxicological outcomes. Therefore, in this project, we focus on using solvent precipitation to produce microplastic references from TPU, PA-6, PET, and LDPE for microplastic inhalation toxicity studies. Particle size distribution of the dispersion is used to verify that the desired size range is achieved. To demonstrate that the produced microplastic references are representative from its original material, molecular and particle descriptors are characterized. Chemical composition, molecular weight, crystallinity, solidity, density, are among the descriptors tested for both the produced microplastic references and its corresponding commercial counterpart. Preliminary results have shown that quantities needed for in-vitro testing and particle size range desired is achieved with successful production of sub-100 nm constituent particle counts and all-respirable mass-based diameters. SEM images confirm the size distribution and show distribution of particle shapes. Chemical composition via spontaneous Raman Scattering illustrates clear polymer spectra signals from the microplastic dispersions. These microplastic reference materials are complemented by toxicology controls. In addition, the in-vitro screening uses both submersed and air-liquid interface cultures to expose cells. This study will thus provide information on microplastic material descriptors relevant for inhalation toxicity.
99 The Relative Toxicity and Bioreactivity of Ambient Microplastic Pollution to Human Alveolar Lung Epithelial Cells with and Without Urban PM2.5
Authors: Laskowska Julia , Alzahabi Khaled , Auyang Eric , Mudway Ian , Wright Stephanie , Tetley Teresa 
Published: May 2023

Abstract
Plastic has unique properties with multiple applications. Microsized plastic fragments (0.1−1000µm; secondary microplastics) are generated throughout the lifespan of plastic materials; primary microplastics are manufactured. Microplastics are present in PM2.5. With increased use of electric cars and reduction in tail pipe emissions, the amount and proportion of microplastics in airborne PM2.5 could increase. We know little about the effects of microplastic inhalation on human health. Hypothesis: Inhaled plastic microparticles will have adverse effects on the respiratory epithelium, both independently and in combination with PM2.5. Two atmospheric plastics, polypropylene (PP) and polyamide (PA), were generated and characterized prior to study. They had a similar size distribution (1-3µm), polydispersity (PA: 0.9002; PP: 0.9037) and charge (PA: -9.66; PP: -5.79) in culture medium. Human alveolar epithelial type 1-like cells (TT1) were exposed for 24h to 1.25-80µg/ml of PP, PA, and PM2.5; viability fell after PA exposure to 10µg/ml (~10%), reaching ~30% at 80µg/ml (p&lt;0.0001); only 40 and 80µg/ml of PP caused a 15 and 20% drop in viability, respectively (p&lt;0.01). PM2.5 had no effect on viability. Although plastics had no effect on IL-6 or IL-8 release, PM2.5 stimulated release at 20-80µg/ml, reaching 10-fold (p&lt;0.001) and 2.5-fold (p&lt;0.05) for IL6 and IL8 respectively. Exposure to plastic/PM2.5 ratios from 0.0001:1 to 1:1 had no consistent effect. TEM suggests internalization of PA, PP and PM2.5 by TT1 cells. Thus, microplastics exhibit different responses (increased cell death) to PM2.5 (increased mediator production). The inconsistent response to particle mixtures is likely dependent upon the proportion of microplastics.
135 Downregulation of ABCG1 and ABCG4 Transporters by rare Earth Oxide Nanoparticles Induces the Pulmonary Alveolar Proteinosis
Authors: Jeon Soyeon , Cho Wan-Seob 
Published: May 2023

Abstract
Pulmonary alveolar proteinosis (PAP) is rare disease that accumulates alveolar surfactant. PAP can be induced by nanoparticles (NPs), but there is little information about PAP-producing NPs and their mechanism. Here, we evaluated PAP-producing NPs including 6 of rare earth oxide (REO) NPs and NiO NPs and investigated the magnitude and related gene expression (ATP-binding cassette, ATP) of PAP at 1 and 6 months after single intratracheal instillation to Wistar rats. Furthermore, we evaluated morphological change of REO NPs because biotransformation is critical to understand the toxicity. The 6 REO NPs (Dy2O3, Eu2O3, In2O3, Pr6O11, Sm2O3, and Tb4O7) and NiO NPs caused PAP at 1 month, while only In2O3 NPs showed a persistent PAP at 6 months. All the REO NPs transformed sea urchin-shaped within the alveolar macrophage up to 6 months. The levels of phospholipids, indicators of PAP, showed good correlation with gene expression of five ABC transporters (ABCA1, ABCB4, ABCB8, ABCG1, and ABCG4), which effluxing phospholipids in PAP. Among them, ABCG1 and ABCG4 might be key transporters involved in PAP development because both showed negative correlation with the magnitude of PAP, while others might be compensatory transporters for PAP recovery, as they showed a positive correlation. In conclusion, the identification of seven PAP-producing NPs implies that PAP may be an emerging occupational disease and that ABCG1 and ABCG4 may be therapeutic targets for PAP. In this regard, we are studying therapeutic agent for PAP induced by NPs using medicine related PPAR-gamma, which is upstream mechanism of ABCG1 and ABCG4.
18 Can the Indoor Environment Influence the Toxicity of Indoor and Outdoor Air Pollution Particulates?
Authors: Meldrum Kirsty , Bateman Joshua W P , Doak Shareen H , Clift Martin J D 
Published: May 2023

Abstract
When considering air pollution particles (AP), they are often assessed in isolation, when this is not how the population is exposed to them. Within the indoor environment, there are bioaerosols present, which contain various allergens including house dust mite (HDM) and lipopolysaccharides (LPS). This RESPIRE study aims to apply a well-characterised in vitro model of the alveolar barrier (type I and II epithelial cells (NCI-H441 and hAELVi at relevant in vivo ratios) and macrophage-like cells) to determine the effects of these bioaerosols on the toxicological and immunological responses to AP. To achieve this, we will investigate cytotoxicity, inflammatory responses, morphology, oxidative stress, membrane integrity and genetic toxicology of these models with specific focus on responses from human allergic responses and airway diseases (i.e., bronchiolitis-interstitial lung disease and sarcoidosis) to determine the additional health considerations the addition of bioaerosols to AP has on our models. We will utilise a physiologically relevant aerosolization exposure method) and a standardised indoor (NIST2583) particulate at an environmentally relevant concentration to mimic air pollution along with HDM and LPS to determine if the addition of these environmentally appropriate bioaerosols influence the responses to IAP.
This project is funded by the recently initiated RESPIRE project (NE/W002264/1), as part of the SPF Clean Air Programme.
69 Activation of the Aryl Hydrocarbon Receptor - a Major mode of Combustion Particle Toxicity?
Authors: Øvrevik Johan , Grytting Vegard S , Brinchmann Bendik C , Skuland Tonje S , Chand Prem , Refsnes Magne , Låg Marit , Holme Jørn A 
Published: May 2023

Abstract
Combustion-derived particles constitute an important part of the fine fraction of particulate matter with aerodynamic diameter less than 2.5 microns (PM2.5) and are considered central for the adverse effects of air pollution. Understanding the mechanisms of combustion particle toxicity may shed light on the components and characteristics of outdoor air PM driving adverse health effects. This may also enable more targeted and efficient policies to improve air quality and promote health and wellbeing. The aryl hydrocarbon receptor (AhR) is a ligand dependent transcription factor, originally discovered for its ability to bind polycyclic aromatic hydrocarbons (PAHs) and dioxin-like compounds and regulate PAH metabolism. It is now clear that AhR regulates a variety of biological and toxicological responses, overlapping to a considerable degree with the effects of combustion PM and ambient PM2.5. Studies from our lab and others also suggest that AhR activation is among the most sensitive responses to combustion PM exposure, induced at orders of magnitude lower concentrations than many other endpoints. This talk will discuss the potential role of the AhR and PAHs in combustion PM toxicity based on previous and ongoing work, with a main focus on intracellular signalling and regulation of inflammatory reactions in lung epithelial cells and vascular endothelial cells.
100 Co-Culture of Human type I and type II Pneumocyte Cell Lines as a Model of Alveolar Epithelium for Toxicity Testing
Authors: Boland Sonja , Brookes Oliver , Miremont Dorian , Kuen René Lai , Eon-Bertho Alice , Baeza-Squiban Armelle 
Published: May 2023

Abstract
The epithelial tissues of the distal lung are continuously exposed to inhaled air, and are thus of research interest in studying respiratory exposure to therapeutic and hazardous materials such as plastic particles which represent a new threat for human health. There is a need therefore to develop sophisticated models of the human alveolar epithelium, which better represent the different cell types present in the native lung. Our aim was to develop an air-liquid interface model of the alveolar epithelium by incorporating human cell-lines which bear features of type I (hAELVi) and type II (NCI-H441) epithelial cells. Working both in monotypic cultures and cocultures, we compared the morphology of single cells and the structure of cell layers of the two cell-lines using light and electron microscopy. We measured barrier function by trans-epithelial electrical resistance (TEER). We assessed expression of a panel of relevant genes that play important roles in barrier function and differentiation. We demonstrated that barrier properties can be maintained for 30 days. The coculture model was observed to form a stable barrier akin to that seen in hAELVi, while expressing surfactant protein C, and having a profile of expression of claudins and aquaporins appropriate for the distal lung (Brookes (2021) PLoSONE 16(9):e0248798). In summary, our results support the coculture of these two cell-lines to produce a model which better represents the breadth of functions seen in native alveolar epithelium.
Funding: From the European Union’s Horizon 2020 research and innovation programme under grant agreement No965367 (PlasticsFate)
3 An Introduction to the SbD4Nano Project
Authors: Hunt Neil 
Published: May 2023

Abstract
A major challenge for the global nanotechnology sector is the development of safe and functional engineered nanomaterials (ENMs) and nano-enabled products (NEPs). In order to minimise the risks to human and environmental health during the engineering of NEPs the goal of the Safe-by-Design for Nano (SbD4Nano) project is to create a novel e-infrastructure for the definition, performance testing and implementation of Safe-by-Design (SbD) approaches in the nanotechnology supply chains. The project aims to demonstrate how selecting appropriate surface modification of nanomaterials can reduce the hazard and risk to workers, consumers and the environment whilst maintaining its functionality. The presentation will give an introduction to the project and outline the results generated thus far.
This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 862195
36 An Investigation into Mechanisms Responsible for (geno)Toxicity Induced by Exposure to Industrially-Relevant Multi-Component Nanomaterials and high Aspect Ratio Nanomaterials
Authors: Brooks Sian , Saccardo Angela , Vogel Ulla , Wohlleben Wendel , Doak Shareen , Clift Martin 
Published: May 2023

Abstract
Production and application of multi-component nanomaterials (MCNMs) and high aspect ratio nanomaterials (HARN) has raised questions as to their inhalation risk. A PRISMA-orientated systematic literature review indicated a key knowledge gap related to the (geno)toxicity of metal oxide MCNMs and HARN. The aim of this study was to conduct a mechanistic-based toxicology assessment of a number of industrially-relevant MCNMs and HARN materials, in order to fill this knowledge gap and provide vital hazard assessment towards these materials’ safe and sustainable design. A549 monocultures (2.5x105), and A549/dTHP-1 co-cultures (1:10) were seeded in 12-well transwell-membranes at the air-liquid interface. Cell cultures were exposed, via aerosol, to Printex90, LaCo0.5Ni0.05O3, LaCo0.475Ni0.475Pt0.05O3, LaCo0.475Ni0.475Pd0.05O3, LaCo0.25Ni0.75O3, LaNiO3, NiZnFe4O8, ZnFe2O4, and NiFe2O4 to human exposure-relevant concentrations of 390, 780, 3100 ng/cm2 (24hrs). Aerosolised MCNM and HARN were characterised following acellular deposition via electron microscopy. Cellular cytotoxicity, barrier integrity, (pro)inflammatory/fibrotic response, oxidative stress and mutagenicity/DNA damage was assessed. Results indicate barrier integrity and IL-8 production were unaffected by Printex90, LaCo0.5Ni0.05O3, and ZnFe2O4 exposure. A dose-dependent increase in micronucleus frequency was observed for these four materials. Investigations are continuing to determine the mechanisms associated with this noted genotoxic effect, as well as upon further MCNMs/HARN (i.e. Fe2CoO4(Fe1/Co3), Silica-Ref-Std). Emphasis is being placed upon elucidating specific structure-activity relationships for each MCNM/HARN by testing specific key events of inhalation-based adverse outcome pathways relevant to the in vitro models used. This project was funded by EU H2020 research and innovation programme, grant agreement No. 953183 (HARMLESS).
74 Impact of Air Pollution on Lung Immune Responses in a Mouse Model of Influenza Infection
Authors: Martín-Faivre Lydie , Prince Lisa , Chivé Chloé , Sallenave Jean-Michel , Baeza-Squiban Armelle , Garcia-Verdugo Ignacio 
Published: May 2023

Abstract
During air pollution peaks, influenza infections are more severe, and the number of hospitalizations associated to flu increases. This project aims to study if air pollution contributes to the severity of influenza infection. To this end, mice were intratracheally exposed once to well-characterized particulate matter collected from Paris atmosphere (PM2.5) and inflammation was determined in the broncho-alveolar lavages (BALs) of mice at different time points post-exposure. We observed that 2 mg/kg PM2.5 induced the recruitment of neutrophils in the BALs at 1-day post-exposure. Neutrophils recruitment decreased since the 3rd day post-exposure while the recruitment of eosinophils, monocytes, and lymphocytes appeared. CD4+ T lymphocyte recruitment was sustained at least until 5-7 days post-exposure. Concomitantly, the levels of proinflammatory cytokines and chemokines were evaluated in the BALs of PM-treated mice. Ongoing experiments of co-infection at different time points after PM2.5 exposure will elucidate if severity of influenza infection is exacerbated after PM exposure.
This work is support by the la Fondation pour la Recherche Médicale (Foundation for Medical Research).
93 Linking the Molecular Mechanisms of Alveolar Macrophage Cell Death Induced by Inhaled Nanoparticles with the Subsequent Pathological Outcome
Authors: Ren Hongyu , Han Lianyong , Stoeger Tobias , Rehberg Markus 
Published: May 2023

Abstract

Background
Carbon Nanomaterials (CNM) get released into the environment as combustion by-products and engineered materials. Our previous work has shown that inhalation of CNMs differing in shape, such as spherical carbon nanoparticles (CNPs) or fiber-shaped nanotubes (CNTs) triggers different response pattern ranging from acute and resolving to persistent and chronic lung inflammation. Furthermore, our cell and mouse data showed that, particularly rigid, multi-walled nanotubes (MWCNTs) can cell-specifically and persistently kill alveolar macrophages (AM). Here we hypothesize that the AM death pathway determines the fate of lung inflammation, as acute or chronic.

Results
Exposure of the murine AM cell line MH-S to MWCNT led to significant decrease of cell viability in a dose-dependent manner (IC50: 10±5 μg/ml). In comparison, CNPs showed relatively low toxicity (IC50: &gt;200 ug/ml) to MH-S cells. Also in contrast to hardly detectable apoptosis (cleaved-Caspase3), immunoblot and -fluorescence analysis demonstrated significant induction of LC3II, a central protein in the autophagy pathway, 12h after MWCNT treatment. The MWCNT triggered cell death response from BMDM-derived AM-like cells however, did not differ between LC3B-/- and wt mice, indicating the autophagy pathway as dispensable. In contrast, inhibition of lysosomal Cathepsins via K777, rescued MWCNT induced cell death of either MH-S or AM-like cells suggesting lysosomal Cathepsins as key player in AM cell death.

Conclusion
Lysosomal damage with subsequent Cathepsin activity seem a central key event in MWCNT triggered AM cell death. Current studies investigate the relevance of Cathepsins for the inflammatory consequences of CNT triggered AM cell death.
Development of a quantitative North and Central European job exposure matrix for wood dust
Authors: Basinas Ioannis , Liukkonen Tuula , Sigsgaard Torben , Andersen Nils T , Vestergaard Jesper M , Galea Karen S , van Tongeren Martie , Wiggans Ruth , Savary Barbara , Eduard Wijnand , Kolstad Henrik A , Vested Anne , Kromhout Hans , Schlünssen Vivi 
Published: May 2023

Abstract
Wood dust is an established carcinogen also linked to several non malignant respiratory disorders. A major limitation in research on wood dust and its health effects is the lack of (historical) quantitative estimates of occupational exposure for use in general population-based case-control or cohort studies. The present study aimed to develop a multinational quantitative Job Exposure Matrix (JEM) for wood dust exposure using exposure data from several Northern and Central European countries. For this, an occupational exposure database containing 12653 personal wood dust measurements collected between 1978 and 2007 in Denmark, Finland, France, The Netherlands, Norway, and the United Kingdom (UK) was established. Measurement data were adjusted for differences in inhalable dust sampling efficiency resulting from the use of different dust samplers and analysed using linear mixed effect regression with job codes (ISCO-88) and country treated as random effects. Fixed effects were the year of measurement, the expert assessment of exposure intensity (no, low, and high exposure) for every ISCO-88 job code from an existing wood dust JEM and sampling duration. The results of the models suggest that wood dust exposure has declined annually by approximately 8%. Substantial differences in exposure levels between countries were observed with the highest levels in the United Kingdom and the lowest in Denmark and Norway, albeit with similar job rankings across countries. The jobs with the highest predicted exposure are floor layers and tile setters, wood-products machine operators, and building construction labourers with geometric mean levels for the year 1997 between 1.7 and 1.9 mg/m3. The predicted exposure estimates by the model are compared with the results of wood dust measurement data reported in the literature. The model predicted estimates for full-shift exposures were used to develop a time-dependent quantitative JEM for exposure to wood dust that can be used to estimate exposure for participants of general population studies in Northern European countries on the health effects from occupational exposure to wood dust.
Juvenile leg autotomy predicts adult male morph in a New Zealand harvestman with weapon polymorphism
Authors: Powell Erin C , Painting Christina J , Machado Glauco , Holwell Gregory I 
Published: May 2023

AbstractIntraspecific weapon polymorphisms that arise via conditional thresholds may be affected by juvenile experience such as predator encounters, yet this idea has rarely been tested. The New Zealand harvestman Forsteropsalis pureora has three male morphs: majors (alphas and betas) are large-bodied with large chelicerae used in male–male contests, while minors (gammas) are small-bodied with small chelicerae and scramble to find mates. Individuals use leg autotomy to escape predators and there is no regeneration of the missing leg. Here, we tested whether juvenile experience affects adult morph using leg autotomy scars as a proxy of predator encounters. Juvenile males that lost at least one leg (with either locomotory or sensory function) had a 45 times higher probability of becoming a minor morph at adulthood than intact juvenile males. Leg loss during development may affect foraging, locomotion, and/or physiology, potentially linking a juvenile’s predator encounters to their final adult morph and future reproductive tactic.
Universal robust regression via maximum mean discrepancy
Authors: Alquier P , Gerber M 
Published: May 2023

Abstract
Many modern datasets are collected automatically and are thus easily contaminated by outliers. This has led to a renewed interest in robust estimation, including new notions of robustness such as robustness to adversarial contamination of the data. However, most robust estimation methods are designed for a specific model. Notably, many methods were proposed recently to obtain robust estimators in linear models, or generalized linear models, and a few were developed for very specific settings, for example beta regression or sample selection models. In this paper we develop a new approach for robust estimation in arbitrary regression models, based on maximum mean discrepancy minimization. We build two estimators that are both proven to be robust to Huber-type contamination. For one of them, we obtain a non-asymptotic error bound and show that it is also robust to adversarial contamination, but this estimator is computationally more expensive to use in practice than the other one. As a by-product of our theoretical analysis of the proposed estimators, we derive new results on kernel conditional mean embedding of distributions that are of independent interest.
Bayesian learning of network structures from interventional experimental data
Authors: Castelletti F , Peluso S 
Published: May 2023

Summary
Directed acyclic graphs provide an effective framework for learning causal relationships among variables given multivariate observations. Under pure observational data, directed acyclic graphs encoding the same conditional independencies cannot be distinguished and are collected into Markov equivalence classes. In many contexts, however, observational measurements are supplemented by interventional data that improve directed acyclic graph identifiability and enhance causal effect estimation. We propose a Bayesian framework for multivariate data partially generated after stochastic interventions. To this end, we introduce an effective prior elicitation procedure leading to a closed-form expression for the directed acyclic graph marginal likelihood and guaranteeing score equivalence among directed acyclic graphs that are Markov equivalent post intervention. Under the Gaussian setting, we show, in terms of posterior ratio consistency, that the true network will be asymptotically recovered, regardless of the specific distribution of the intervened variables and of the relative asymptotic dominance between observational and interventional measurements. We validate our theoretical results via simulation and we implement a Markov chain Monte Carlo sampler for posterior inference on the space of directed acyclic graphs on both synthetic and biological protein expression data.