bluuebunny/crossref_metadata_2025_split huggingface dataset:
34 Placental-Fetal Distribution of Carbon Particles in a Pregnant Rabbit Model After Repeated Exposure to Diluted Diesel Engine Exhaust
Authors: Bongaerts Eva , Nawrot Tim , Wang Congrong , Chavatte-Palmer Pascale , Ameloot Marcel , Bové Hannelore , Roeffaers Maarten , Couturier-Tarrade Anne , Cassee Flemming 
Published: May 2023

Abstract
Airborne pollution particles have been shown to translocate from the mother’s lung to the fetal circulation but their placental-fetal distribution and internal tissue load remain poorly explored. Here, we investigated the placental-fetal distribution of diesel engine exhaust particles during gestation under controlled exposure conditions using a pregnant rabbit model. Pregnant dams were exposed by nose-only inhalation to either clean air (controls) or diluted and filtered diesel engine exhaust (1 mg/m3) for 2h/day, 5 days/week, from gestational day (GD) 3 to GD27. At GD28, placental and fetal tissues (i.e., heart, kidney, liver, lung and gonads) were collected for biometry and to study the accumulation of carbon particles (CPs) using white light generation by carbon particles under femtosecond pulsed laser illumination. CPs were detected in the placenta, fetal heart, kidney, liver, lung and gonads in significantly higher amounts compared with controls. By using multiple factor analysis, we were able to discriminate the diesel engine-exposed pregnant rabbits from the control group taking all variables related to fetoplacental biometry and CP load into consideration. Although our findings did not reveal a sex effect, a potential interaction effect might be present between exposure and fetal sex. The results confirm the translocation of maternally inhaled CPs from diesel engine exhaust to the placenta and the ability to reach fetal organs during late-stage pregnancy. The differential particle load in the fetal organs may contribute to the disruption of blood flow in the placenta with possible effects on fetoplacental biometry and placental function.
86 Persistent Macrophage Depletion and Arrested Replenishment is Dependent on Carbon Nanotube type as Shown by Single Cell Transcriptomics
Authors: Voss Carola , Han Lianyong , Ansari Meshal , Liu Qiongliang , Ballester-Lopez Carol , Conlon Thomas M , Haefner Verena , Strunz Maximilian , Angelidis Ilias , Mayr Christoph , Rehberg Markus , Yildirim Ali Önder , Schiller Herbert B , Stoeger Tobias 
Published: May 2023

Abstract
Inhalation of carbon nanomaterials (NMs) can cause severe health effects, including chronic inflammation and fibrosis. We aim for a better understanding of NM specific cellular perturbation patterns. Therefore, we exposed mice intratracheally to soot like carbon black, tangled double-walled (DWCNT) and rigid, multi-walled carbon nanotubes (MWCNT). All lungs underwent single cell RNA sequencing and BAL analysis at 12h, 6d and 28d. At the chosen doses, all NMs caused comparable airspace neutrophilia at 12h, which increased until d6 for CNTs and remained elevated until d28 for MWCNT. We observed a significant increase in total BAL macrophages, however, exclusively after 6d CNT instillation. This d6 peak coincided with the loss of F4/80+/CD11c+/CD11b- alveolar macrophages (AMs) for MWCNTs, and to a lesser extent DWCNTs, in lung FACS. In parallel, we noticed the pulmonary accumulation of a transitional macrophage population at d6 uniquely after MWCNT instillation, and not DWCNTs. According to RNA velocity analysis, blood monocytes differentiate into Lyve1-/CD163- interstitial macrophages and subsequently give rise to this transitional population which fails to replenish the CD11c+/SiglecFhigh AM pool. These cells show high similarity with the initiating monocyte-derived macrophage population necessary for bleomycin- and asbestos-induced lung fibrosis (Misharin et al.,JEM,2017.214(8)). The pro-fibrotic role of this population also has been demonstrated in context of SARsCoV2 infection-associated acute respiratory distress (Wendisch et al.,Cell,2021.184(26)).
We summarize, that this transitional cell population are monocyte-derived AM precursors, which lack the ability to differentiate into mature AMs being the decisive mechanism for MWCNT induced, not resolving lung fibrosis.
146 Meteorological Influence on Measurement Strategy and Estimated Respirable Dust and Respirable Crystalline Silica Exposure Levels Within the European Minerals Industry
Authors: Blagrove-Hall Nicola , Houba Remko , Kromhout Hans 
Published: May 2023

Abstract
The evidence of meteorological conditions on occupational exposure measurements is limited, despite is expected to be important determinants of long-term exposures. We describe meteorological conditions for measurement and non-measurement days and evaluate associations between temperature and total precipitation and respirable dust and respirable crystalline silica (RCS) concentrations of the European Industrial Minerals Association-Dust Monitoring Programme. Geo-matched RCS and dust measurements were evaluated against meteorological data (archived satellite observations and weather station measurements). Temperature(0C) and total precipitation (mm) for RCS measurement and non-measurement days were described. A linear regression model was used to investigate the association between dust and RCS concentration and meteorological conditions. Overall, 2,840 dust measurements (GM=0.20mg/m3; GSD=3.43mg/m3) and 2,658 quartz measurements (GM=0.01mg/m3; GSD=5.23mg/m3) were collected across 96 an 94 industrial mineral sites over 262 and 259 days in 2011. Mean temperature and precipitation for dust and RCS measurements were similar for measurement and non-measurement days (dust: 10.490C and 10.830C, 2.23mm and 2.12mm; RCS: 11.050C and 10.820C, 2.08mm and 2.12mm). For respirable dust concentrations a 6.4% decrease per 1°C was estimated for temperatures&lt;200C (p&lt;0.001) and an 8.2% increase for temperatures≥200C (p=0.002). For RCS a 2% decrease in was estimated for every 1mm increase in total precipitation (p=0.02). No difference in meteorological conditions were seen between measurements days and non-measurement days. Associations of these conditions with exposure concentrations with showed differences between agents despite being collected and measured on the same filter. Long-term changes in meteorological conditions might be an important factor when estimating long term exposures.
153 Nearly free Surface Silanols: from Silica Towards a new Paradigm for Particle Toxicity
Authors: Pavan Cristina , Bellomo Chiara , Cananà Stefania , Tomatis Maura , Escolano-Casado Guillermo , Mino Lorenzo , Lison Dominique , Turci Francesco 
Published: May 2023

Abstract
Respirable crystalline silica (RCS) is the leading cause of occupational respiratory diseases worldwide. RCS is associated with inflammatory lung reactions, which can lead to silicosis, cancer, and autoimmune diseases. The extreme variability of silica specimens, including its amorphous forms, the surface heterogeneity, and variable toxicity effects, generated one of the most intriguing enigmas in particle toxicology, i.e., deciphering which physico-chemical features explain and predict the variable hazard of silica. Using a set of ad hoc prepared synthetic and natural quartz particles, we have identified a unique subfamily of surface silanols as a key initiator of the toxicity of silica particles. These moieties, namely the "nearly-free silanols" (NFS), appear on the surface of quartz when crystals are fractured, and their amount can be modulated by physico-chemical processes. The peculiar spatial arrangement of NFS was demonstrated as the most energetically favorable and selective for interacting zwitterionic phospholipids that make up cell membranes. The toxic activity of NFS was also confirmed with amorphous nanosilica synthesized at high temperatures, and our recent findings suggest that NFS could impart toxic properties to other silica polymorphs and hydroxylated surfaces, including aluminosilicates and engineered stones. Overall, NFS occurrence accounts for the origin and variability of the toxicity of silica, opening perspectives for controlling RCS hazard, and may contribute to understand other important interfacial phenomena of hydroxylated materials.
19 Does Developmental Status and age of the Lung Influence the Hazard Elicited by Exposure to Both Indoor and Outdoor Pollutants?
Authors: Meldrum Kirsty , Doak Shareen H , Clift Martin J D 
Published: May 2023

Abstract
Many in vitro studies that focus upon lung toxicology use models that assume, or are specifically based upon adult lung structure, function, and physiology. Yet, the most vulnerable groups of the human population (i.e., young, elderly, and diseased) have an altered lung structure and function. Notably, the developing lung (in utero) and infant lungs exhibit notable differences in term of cell type, number, ratio, organ size and surface area. Recent work has identified the detrimental implications of being exposed to AP while the lung is developing. To elucidate the mechanisms associated with AP exposure to the developing lung, the aim of this study will create and characterise an in vitro model of the foetal human bronchial region composed of cells physiologically appropriate to various stages of development, as well as an older child’s airway, notably the developing alveoli. This will allow us to determine the developmental effects of air pollution particles at an air-liquid interface (ALI) utilising a physiologically relevant aerosol exposure and standardised particulate aiming to mimic indoor and outdoor air pollution. For this work, a global approach will be utilised to determine up and down regulation of various pathways associated with both development and exposure to AP. A further aim will include comparison with an “adult” lung to analysis the potential developmental implications exposure to AP may illicit.
This project is funded by the recently initiated RESPIRE project (NE/W002264/1), as part of the SPF Clean Air Programme.
26 An Advanced Triple Cell co-Culture of the Alveolar Epithelial Barrier for Inhalation Hazard Assessment in Vitro
Authors: Bateman Joshua , Doak Shareen H , Clift Martin J D 
Published: May 2023

Abstract
In vitro lung models are a valuable tool to assess the inhalation hazard of air pollutants, bioaerosols, chemicals and nanomaterials. Though it is essential that these models are characterised and anatomically relevant to the area of the human lung they seek to represent. Previously within inhalation toxicology, focus has been placed on the use of monocultures of alveolar epithelial cells, however use of alveolar co-culture models have been presented as more realistic and sensitive models. Here, we present the development of a novel triple cell co-culture system, cultured at the air-liquid interface that is sensitive to LPS and particulate matter. This co-culture contains alveolar type 1 cells (hAELVi), alveolar type 2 cells (NCI-H441) and alveolar macrophages (differentiated THP-1 (dTHP-1) using PMA (20 nM)). Using CellTrackers™ with confocal microscopy, the ratio of hAELVi cells to NCI-H441 cells was confirmed to be a histologically relevant 16:1 ratio forming a tight monolayer shown through blue dextran membrane permeability assay. Macrophages were seeded on top of the epithelial co-culture at an anatomically relevant density of 1 macrophage per 18x103 μm2 (confirmed via confocal microscopy) to form the triple cell co-culture. The model, when challenged, released more interleukin-8 and TNF-α than the epithelial mono- and bi-culture systems when exposed to LPS (1 μg/mL for 24 hrs) (p&lt;0.05), suggesting that the macrophages do mount the theoretical (pro-)inflammatory response. This anatomically relevant in vitro model forms the basis to investigate inhaled exogenous substances, such as the differential toxicology impacts of particulate matter and nitrogen dioxide.
41 The Mechanisms of Allergy to Fungal Bioaerosols in the Lung
Authors: Goode Emma-Jane , Marczylo Emma 
Published: May 2023

Abstract
Allergic airways disease (AAD) is a collective term for respiratory disorders that can be exacerbated upon exposure to airborne allergens. The contribution of fungal allergens to the pathogenesis of AAD has become well established over recent years and can be present in the air we breathe as bioaerosols. Understanding the mechanisms allergy to fungal bioaerosols can help to better manage symptoms and conditions, reducing the burden of disease. We conducted a comprehensive review to collate the current understanding of mechanisms involved in the allergic response to fungal bioaerosols in airway epithelia. To be included in the final analysis, studies were compared to defined inclusion/exclusion criteria, relevant data was extracted, and each paper was assessed using a quality scoring tool. The search string provided 440 initial results with 60 studies selected for final analysis. 120 potential target mechanisms were identified within the selected studies and 17 were identified in more than 5 studies. The major pathways identified in allergic response include 1) a role for proteases and the activation of the PAR2 receptor, 2) release of IL33, 3) EGFR pathway and mucin expression, and 4) a skewing towards a Th2 profile promoting eosinophil recruitment. However, there was conflicting evidence when comparing results from individual studies. Thus, further research is required to better understand which fungi/fungal components drive the allergic response.
Funding: This work has been funded under the NIHR Health Protection Research Unit for Environmental Exposures and Health with Imperial College London
67 Development of a Physiologically-Relevant in Vitro Model of the Lung, Incorporating Novel Peptide Hydrogels as Biomimetic Extracellular Matrix Scaffolds
Authors: Murphy Fiona 
Published: May 2023

Abstract
The vast number of different nanomaterials (NMs) in production and under development precludes the complete hazard assessment of each individual substance according to current regulatory standards which require long term in vivo studies. To reduce the burden of in vivo toxicity testing more physiologically relevant in vitro pulmonary models are required to predict the inhalation hazard posed by aerosolized particles, including NMs. Recently significant progress has been made in the development of multi-cell 3D models which mimic the cellular constituents of tissues and organs, few models under development concomitantly take into account the functional role of the extracellular matrix (ECM) in determining the tissue microenvironment and behaviour of cells. This project specifically aims to develop an in vitro model composed of multiple cells-types grown directly in contact with hydrogel scaffolds which mimic the ECM to better replicate the in vivo microenvironment. We hypothesize the novel addition of an ECM mimetic will influence cell phenotype and activation after exposure to NMs. Preliminary data summarising the process of model building and characterisation including selection of appropriate cell lines and gel formulations, optimisation of culture conditions and evaluation of the integrity of the hydrogel scaffolds is presented. This application of this model will then be evaluated for use in toxicology testing of NMs and predictivity of hazard compared to existing data from both simple 2D in vitro systems and in vivo toxicology studies. In future the potential advantages and limitations of the approach will be evaluated and relevant adaptions to be further explored.
81 Traac Framework and tool for Regulatory Acceptance and Wider Usability of Tools/Methods for safe Innovation and Sustainability of Nanomaterials
Authors: Shandilya Neeraj , Barreau Marie-Sophie , Suarez-Merino Blanca , Porcari Andrea , Pimponi Daniela , Jensen Keld , Dekkers Susan , Fransman Wouter , Kalkman Gino , Otto Marlies , van Someren Eugene , Franken Remy 
Published: May 2023

Abstract
There has been an increasing use of manufactured nanomaterials in industrial applications and consumer products. It has instigated concerns about the sustainability, risks and uncertainties regarding the interactions of the nanomaterials with humans and the environment. Consequently, significant resources in Europe have been invested into tool and method development to support risk mitigation and management, facilitating the research and innovation process of manufactured nanomaterials. Extended risk analysis, including socio-economic impact and sustainability assessment is moving the conventional risk-based approach towards a wider safety-and-sustainability-by-design perspective. Despite growing tool and method developments, the level of awareness and use by stakeholders is still limited. Regulatory compliance and acceptance, reliability and trust, user-friendliness and compatibility with the users’ needs are important factors traditionally known to hinder their widespread use. Therefore, a framework is presented to quantify the readiness of different tools and methods towards their wider regulatory acceptance and downstream use by different stakeholders. The framework, developed within Gov4Nano, diagnoses barriers which hinder regulatory acceptance and wider usability of a tool/method based on their Transparency, Reliability, Accessibility, Applicability and Completeness (TRAAC framework). An online TRAAC tool is being developed within HARMLESS that will be freely available on https://diamonds.tno.nl/#traac. Fourteen tools and methods were assessed using the TRAAC framework as proof-of-concept. The results provide insights into any gaps, opportunities, and challenges in the context of each of the 5 pillars of the TRAAC framework.
120 An Evaluation of Uncertainty Within Control Banding Tools used for Occupational Exposure Assessment of Nanoforms and Nano-Enabled Products
Authors: Nebbia Rebecca , Hanlon James , Boyles Matthew , Genta Gianfranco , Galetto Maurizio , Bergamaschi Enrico , Tran Lang 
Published: May 2023

Abstract
The use of control banding tools to aid in diminishing risks to nanomaterial exposure play an important part in early-stage risk assessment. With the inclusive nature of these tools, comes a certain amount of uncertainty with their findings, and uncertainty evaluation is an aspect which has scope for improvement in the current tools. The European Chemicals Agency provide three types of uncertainty to be assessed for chemical safety: Model uncertainty which relates to simplifications the model makes, Parameter uncertainty which relates to individual model parameters and Scenario uncertainty which is user dependent. To define possible improvements, the SAbyNA project has made investigations into Parameter uncertainty, and have used the Theory of Scales of Measurement, developed by Stevens. The identification of the measurement scale leads to the understanding of the permissible statistics (e.g., standard deviation) that can be performed with the data. To facilitate the assessment of the scale and the statistics, a check list was produced. Several control banding tools were analysed, and these tools employ ordinal scoring scales, which means that calculating average values and confidence intervals is not permissible. As evaluating the uncertainty in results greatly helps the exposure assessment, because it would describe the “quality” of the data and allow definitive comparisons among each other, it is recommended to improve the quantitative exposure estimation through sampling methods to get more measurements, which are beneficial for the uncertainty evaluation and for which the uncertainty can be evaluated according to the Guide to the expression of uncertainty in measurement.
144 Occupational Exposure to Particles Measured by Nanoparticles Tracking Analysis (NTA) in Exhaled Breath Condensate (EBC).
Authors: Panizzolo Marco , Barbero Francesco , Squillacioti Giulia , Ghelli Federica , Bono Roberto , Bellisario Valeria , Guseva-Canu Irina , Fenoglio Ivana , Bergamaschi Enrico 
Published: May 2023

Abstract
The production of paints, coatings and construction materials may generate nanoparticles (NP) with potential adverse health effects. We carried out a study aimed at investigating exposure biomarkers reflecting the internal dose of inhaled particles and NP. NTA was used to quantify particle number concentration and size in EBC collected at the end of shift in 81 workers employed in companies producing technological materials. External exposure was characterized in terms of particle number concentration, size and lung deposited surface area (LDSA) in the near operational field by using a set of DiSCmini. Three subgroups were identified: Low-Exposure (LE, n=30), High-Exposure (HE n=35), and non-occupationally exposed (UC, n=16). Comparisons between groups were made using non-parametric analyses. LE and HE workers showed significantly higher number of NP in EBC (p=0.024, p=0.041, respectively) as compared to UC. The HE groups showed higher levels of inflammatory biomarkers, such as IL-1β and IL-10 as compared to LE and UC (p=0.02, p&lt;0.01, respectively). Positive correlations were observed between particle number concentration recorded by DiscMini and NTA data (Rho=0,225, p=0.04) and between the NTA and IL-10 and IL-1β (Rho=0.246, p=0.012; Rho=0.223, p=0.022, respectively). In contrast, LDSA did not correlate with NTA data. These findings provide evidence of the relationship between increasing exposure to NP and the burden of particles in the airways which, in turn, results in sustained inflammation. Given the lack of exposure biomarkers for dusts, these results are promising to investigate the relationship between internal dose of particles and changes in lung pathobiology.
O003 Comprehensive assessment of the management of acute cholecystitis in Scotland: a population wide cohort study of 47,558 patients
Authors: Rajan S , Bekheit M , Wohlgemut J M , Watson A J M , Ramsay G 
Published: May 2023

Abstract

Introduction
Acute cholecystitis (AC) is one of the most common diagnoses within Emergency General Surgery, managed either operatively (cholecystectomy) or conservatively. Surgery in the acute phase has been shown to be safe and superior, however, operative rates vary widely. Furthermore, medium-long term survival rates with each approach are still not definitively established. This real-world population analysis aims to describe the current management and outcomes of patients with AC across Scotland.

Methods
This was a national cohort study using data obtained from Information Services Division, Scotland. All adult patients with the admission diagnostic code for AC were included. Patient level data were used to identify all patients admitted to Scottish hospitals between 1997–2019 and outcomes tracked for inpatients or after discharge through the unique patient identifier. This was mapped to mortality data to establish date and cause of death.

Results
47558 patients diagnosed with AC, admitted in one of 46 hospitals were included. These patients accounted for 58824 episodes (27.2% of patients encountered &gt;1 episode). The study population had a median age of 58 years (IQR=43-71), 64.4% were female, and most had no comorbidities. 28741(60.4%) patients had an operative intervention during the index admission. Patients who had an operation during their index admission had a lower risk of 90-day mortality compared to non-operative management (OR=0.62, 95%CI=0.55-0.70).

Conclusion
In this comprehensive analysis of AC in Scotland, 60% of patients had an index cholecystectomy. Patients undergoing surgery had a superior survival to those managed conservatively, further advocating for an operative approach in this cohort.