bluuebunny/crossref_metadata_2025_split huggingface dataset:
107 Assessment of in Vitro Toxicity of Inhalable Incidental Nanoparticles Originating in the Ceramic Industry
Authors: Martín Verónica Moreno , López Maria , Fraga Sonia , Sanfélix Vicenta , Viana Mar 
Published: May 2023

Abstract
Assessing exposure to nanomaterials in industrial workplaces is a widespread challenge. Nanoparticle release was evaluated, under real-world operating conditions, in one thermal spraying and one tile firing facility. Nanoparticles were characterised in terms of mass and number concentrations (µg/m3; /cm3), particle size distribution, chemical composition and morphology, and in vitro toxicity. The present work targets especially the toxicological characterisation of the aerosols sampled. Particles &lt;2 microns in size were sampled in cell-culture medium using an SKC Biosampler connected to a pump operating at 12 lpm. Samples were conserved frozen at -20ºC until analysis. Submerged-cell cultures using the commercially-available A549 cell line were used for the in-vitro assays, where cell viability and generation of reactive-oxygen species (ROS) were assessed. Preliminary results evidenced a relatively large variability across samples in terms of cell viability, with reductions ranging between &lt;5% and up to 60% after 2-hour exposures. Results suggested that the initial INP concentration in the samples may play a relevant role in the results, as in highly concentrated samples nanoparticles may interfere with the cellular uptake of the Alamar Blue dye used and, subsequently, on fluorescence results. ROS generation was detected increasingly over time during the test period (1-4 hours). Readings obtained after 3-4 hour became mostly stable. Finally, these results provide the baseline for the subsequent assessment of the expected reduction in INP concentrations and toxicity resulting from the implementation of risk mitigation measures, which will focus on a custom-designed air filtration system developed in the framework of this project.
136 Lung Clearance Kinetics and Biotransformation of Iron Oxide Nanoparticles: the Role of Particle Dissolution
Authors: Jeong Jiyoung , Cho Wan-Seob 
Published: May 2023

Abstract
It has been recognized that toxicological data such as kinetics and mechanism of action play a key role to understand toxicity of nanoparticle comprehensively, It has become more and more important to study kinetics and mechanism of action. Although there have been many reports regarding the toxicokinetics or toxic mechanism based on physicochemical properties, further research is still required to elucidate the toxic effect of nanoparticles. Here, we investigated the impact of particle dissolution on clearance kinetics and biotransformation using two types of nanoparticles (Fe2O3NPs, TiO2NPs; a reference material for poorly soluble nanoparticle) in rats upon intratracheal instillation. Quantitative analysis of lung burden by ICP-OES and time-course observation of particle morphological transformation by TEM were performed at 0 h, 1, 7, 14, 30, and 90days post-treatment to evaluate the lung clearance kinetics and biotransformation. As a result, Fe2O3NPs showed relatively rapid clearance from the lung with two phases, while TiO2NPs showed prolonged retention in the lung with one phase. Under TEM observation of Fe2O3NPs and TiO2NPs recovered from the lung tissues, no significant morphological changes were observed for TiO2NPs at any time points during the study. However, morphological changes of Fe2O3NPs occur, in particular at later time points (7, 14, 30 and 90 d), which is assumed particle dissolution affect morphological transformation. These findings would provide additional information on lung clearance kinetics and biotransformation of Fe2O3NPs and TiO2NPs for better understanding the relationship between particle dissolution and particle clearance.
137 Analysis of Debris Generated During the Process of Cutting and Grinding of Carbon Fibers-Reinforced Plastics
Authors: Kumoi Jun , Ikegami Akihiko , Fujitani Yuji , Ichihara Gaku , Yano Takeo , Ichihara Sahoko 
Published: May 2023

Abstract
Carbon fiber reinforced plastics (CFRP) is a leading functional material with superior strength and low mass density compared to metal. Recently, due to its excellent property, it has spread to a wide range of fields from sporting goods, such as golf clubs and fishing rods, to aerospace products. However, there is concern that debris (microparticles) is easily released in the processing process of CFRP. The present study investigated the ambient level, size, and shape of particles generated from CFRP during various machining processes in an occupational setting. The size and shape of particles were observed using scanning electron microscopy (SEM) and their chemical compositions were also analyzed using energy dispersive spectroscopy (EDS). The majority of debris from CFRP was cylindrical with a diameter comparable to the diameter of the original carbon fiber, suggesting transversally split carbon fiber. However, some of the debris was fibrous, length &gt;5 μm, width 3, suggesting longitudinally split carbon fiber. These fibrous fragments were morphologically compatible with the WHO definition of respirable fibers. The particles in the working environment were also monitored with a real-time monitoring device, NanoScan SMPS Model 3910. Measurement by real-time monitoring device showed that not only microparticles but also smaller particles were released in the processing process of CFRP. These particles are probably breakdown elements of the epoxy thermoset polymer (resin) in CFRP. The potential hazard of debris from CFRP in the processing process in an occupational setting and risk assessment is needed for the safe handling of CFRP.
145 Cumulative Occupational Exposure to Nanoparticles, Inflammatory Biomarkers and Respiratory Health in the Nanoexplore Cohort
Authors: Squillacioti Giulia , Garzaro Giacomo , Charreau Thomas , Wild Pascal , Bellisario Valeria , Panizzolo Marco , Antonello Giulia , Bono Roberto , Bergamaschi Enrico , Guseva-Canu Irina 
Published: May 2023

Abstract
Exposure to nanomaterials (NMs) may harm biological systems by altering the redox status and triggering inflammatory processes, which in turn may affect respiratory health. In the NanoExplore cohort of 141 workers, we observed a positive dose-response relationship between the short-term exposure to NMs and biomarkers of inflammation, measured in Exhaled Breath Condensate (EBC), but no relationship with lung function parameters (LFP). This study focuses on the association between cumulative exposure to NMs over the last 10 years and changes in LFP and the potential mediating role of airways inflammation. Individual cumulative exposure was estimated by multiplying the nanoparticle concentration, measured at workers’ workstations by DiSCmini, by the duration of worker’s employment at the corresponding workstation up to last 10 years. In EBC, we measured High-Sensitivity CRP (Hs-CRP), IL-1β, TNF-α, and IL-10 as biomarkers of inflammation. LFP were assessed according to ATS/ERS standards. Their association with cumulative exposure was examined using logistic regression models adjusted for tobacco consumption (in pack-years), among 136 workers with complete data (19-62 yrs., 70% males). We found that per unit increase in 10-year exposure, the risk of observing FEV1 values below the normal limit increases by 0.3% (95%CI: 1.000-1.005, p=0.049) and by 0.8% (95%CI: 1.000-1.015, p=0.039) with the exposure expressed as number of particles and lung deposited surface area, respectively. The ongoing mediation analysis will investigate the potential mediating role of inflammation in the association between cumulative exposure to NMs and lung function
152 Top-down Preparation and Characterization of Crystalline Nanosilica for Toxicological Investigations
Authors: Bellomo Chiara , Pavan Cristina , Fiore Gianluca , Escolano-Casado Guillermo , Mino Lorenzo , Turci Francesco 
Published: May 2023

Abstract
Crystalline silica (CS) is a well-known human carcinogen and freshly fractured CS is strongly held to be more toxic than aged dust. Mechanical fracturing indeed generates on CS surface a specific family of Nearly-Free Silanols (NFS), a moiety that was proved to destabilize cell membranes and initiate inflammation in vivo. During milling, silica nanoparticles are also generated, however their contribution to the overall toxicity of quartz is still largely unexplored. Nanoquartz can be synthetized via bottom-up methods, but the surface chemistry of those crystals strongly differs from nanoparticles resulting from fracturing. We report here a top-down milling procedure to obtain a nanometric quartz that shares with fractured quartz the key surface properties relevant to toxicity. Fracturing procedure was optimized by coupling dry and wet milling steps, using water as a dispersing agent, and varying milling times and rotational speeds. We obtained a set of samples that would be classified as nanomaterials under EU CLP regulation (&gt;50% of particles in number are &lt; 100 nm) and exhibited a strong tendency to form submicrometric agglomerates. Deagglomeration with surfactants or simulated body fluids was negligible. Partial lattice amorphization and bimodal crystallite domain size were observed, as confirmed by the presence of two distinct domains of scattering with nanometric (&lt; 50 nm) and submicrometric (0.8-1 µm) crystallite size. A moderate membranolytic activity, which nicely correlated with the amount of surface NFS, signalled that our nanoquartz may induce inflammation in vivo. Overall, a membranolytic nanoquartz for investigating the toxic activity of nanometric silica was obtained.
A rapidly evolving cricket produces percussive vibrations: how, who, when, and why
Authors: Wikle Aaron W , Broder E Dale , Gallagher James H , Tinghitella Robin M 
Published: May 2023

Abstract
Sexual signals are often transmitted through multiple modalities (e.g., visual and chemical) and under selection from both intended and unintended receivers. Each component of a multimodal signal may be more or less conspicuous to receivers, and signals may evolve to take advantage of available private channels. We recently documented percussive substrate-borne vibrations in the Pacific field cricket (Teleogryllus oceanicus), a species that uses airborne acoustic and chemical signals to attract and secure mates. The airborne signals of Hawaiian T. oceanicus are currently undergoing rapid evolution; at least five novel male morphs have arisen in the past 20 years. Nothing is yet known about the newly discovered percussive substrate-borne vibrations, so we ask “how” they are produced, “who” produces them (e.g., population, morph), “when” they produce them (e.g., whether they are plastic), and “why” (e.g., do they play a role in mating). We show that the vibrations are produced exclusively by males during courtship via foreleg drumming. One novel morph, purring, produces quieter airborne songs and is more likely to drum than the ancestral morph. However, drumming behavior is also contextually plastic for some males; when we removed the ability of males to produce airborne song, ancestral males became more likely to drum, whereas two novel morphs were equally likely to drum regardless of their ability to produce song. Opposite our prediction, females were less likely to mate with males who drummed. We discuss why that might be and describe what we can learn about complex signal evolution from this newly discovered behavior.
High-quality, customizable heuristics for RNA 3D structure alignment
Authors: Zurkowski Michal , Antczak Maciej , Szachniuk Marta 
Published: May 2023

Abstract

Motivation
Tertiary structure alignment is one of the main challenges in the computer-aided comparative study of molecular structures. Its aim is to optimally overlay the 3D shapes of two or more molecules in space to find the correspondence between their nucleotides. Alignment is the starting point for most algorithms that assess structural similarity or find common substructures. Thus, it has applications in solving a variety of bioinformatics problems, e.g. in the search for structural patterns, structure clustering, identifying structural redundancy, and evaluating the prediction accuracy of 3D models. To date, several tools have been developed to align 3D structures of RNA. However, most of them are not applicable to arbitrarily large structures and do not allow users to parameterize the optimization algorithm.

Results
We present two customizable heuristics for flexible alignment of 3D RNA structures, geometric search (GEOS), and genetic algorithm (GENS). They work in sequence-dependent/independent mode and find the suboptimal alignment of expected quality (below a predefined RMSD threshold). We compare their performance with those of state-of-the-art methods for aligning RNA structures. We show the results of quantitative and qualitative tests run for all of these algorithms on benchmark sets of RNA structures.

Availability and implementation
Source codes for both heuristics are hosted at https://github.com/RNApolis/rnahugs.
O004 Impact of normothermic regional perfusion on recipient outcomes after simultaneous pancreas and kidney transplantation – a UK analysis from the NHSBT Pancreas Advisory Group
Authors: Owen R , Counter C , Tingle S , Simmonds L , Callaghan C , Casey J , Currie I , Drage M , Elker D , Manas D , Muthusamy A , Oniscu G , Pettigrew G , Sinha S , Sutherland A , Van Dellen D , Watson C , Wilson C , White S 
Published: May 2023

Abstract

Introduction
A quarter of UK SPK transplants are from Deceased Cardiac Donors(DCD), with an increasing number recovered following in-situ normothermic regional perfusion(NRP). The aim of this study was to review the UK experience of SPK transplantation following NRP in DCD.

Methods
Data were collected on all first DCD SPKTs(n=360) performed during 2013–2021 from the UK Transplant Registry. Non-NRP DCD SPK were compared to NRP DCD SPKs. Kaplan Meier plots and cox regression analyses were performed.

Results
Some 198 pancreas were offered from NRP donors with 83 being retrieved. The majority of SPK grafts were from nonNRP donors n=324(90.0%) with n=36(10.0%) from NRP donors. The median cold ischaemic time (CIT) from NRP donors (9.7 hours) was significantly less than nonNRP donors (10.2 hours) (p=0.013). For all other parameters, donors were well matched. Recipients who received a graft from an NRP donor were also well matched with the recipients who received a graft from a nonNRP donor. Univariate analysis showed no statistically significant difference in one-year pancreas graft (NRP 97.2%, non-NRP 89.2%, p=0.145), kidney graft (NRP 100%, nonNRP 95.9%, p=0.221) or patient survival (NRP 100%, nonNRP 98.3%, p=0.442) despite an increasing trend in favour of NRP SPK.

Conclusions
This is the largest reported analysis of NRP for SPK transplants to date. NRP has previously been shown to be beneficial for liver transplants. Despite some concerns that NRP may preferentially benefit the liver at the expense of other organs our study has shown no adverse effects. Larger studies are needed to evaluate whether NRP improves graft utilisation rates for SPK.
O005 Perturbations in gut microbial metabolites promotes a pro-inflammatory state increasing risk of acute rejection post renal transplantation
Authors: Chang F , Vaitkute A , Attrill M , Chong S , Mahdi H , Blair P , Salama A , Mauri C , Eaton S , Bajaj-Elliott M , Pesenacker A , Motallebzadeh R 
Published: May 2023

Abstract

Introduction
Emerging evidence suggests that the gastrointestinal microbiota-immune axis impacts on extra-intestinal health. We aim to identify the influence of microbial metabolites on recipient's immunity; testing the hypothesis that reduced availability of bacterial-derived metabolites associated with immunoregulation e.g., short chain fatty acids (SCFAs) and tryptophan-derivatives promote a pro-inflammatory state increasing risk of acute rejection (AR).

Methods
Ninety recipients and 21 live-donors were recruited with urine, stool and blood samples collected at baseline and up to 12-months after surgery. Flow cytometry was used to assess for circulating subpopulations of CD19+ B-cells and CD4+ T cells (cTFH - CD3+CD4+CD45RA-CXCR5+ and cTFR -CD3+CD4+CXCR5+FoxP3+). Faecal SCFAs and indole derivatives were identified by mass spectroscopy and high-performance liquid chromatography.

Results
Patients with AR had an almost 10-fold reduction of FoxP3+ cTFR cells after transplantation compared to baseline (p=0.03). There were lower frequencies of cTFR cells at 3-months when compared to matched recipients without AR (0.009%±0.014% vs 0.10%±0.12%; p=0.01). In AR, there was a trend for higher frequencies of plasmablasts, resting memory B-cells and TFH cells at baseline, with fewer transitional B-cells at 3-months. Despite tryptophan availability increasing after transplantation, patients with AR displayed reduced levels of SCFAs at 1-month.

Conclusion
Complex changes in microbial metabolites exist after transplantation that may influence the balance of cTFH vs cTFR cells. Despite increase in dietary tryptophan, recipients with AR may harbour gut microbes that are unable to metabolise tryptophan into immune-regulatory metabolites, which predisposes a pro-inflammatory immune state.
O007 Glycaemic variability is a predictor of graft failure following infra-inguinal bypass for peripheral arterial disease (PAD). A retrospective cohort study
Authors: Farndon D , Bennett P , Nunney I , Dhatariya K 
Published: May 2023

Abstract

Introduction
Many factors influence graft patency following infra-inguinal bypass (IIB). Glycaemic variability (GV) is associated with increased risk of multiple adverse outcomes. However, the impact of GV on outcomes following IIB is unknown.

Methods
A 3-year single centre retrospective case notes analysis of all people undergoing IIB between 2017–2019. Rutherford stage, graft conduit, bypass level, procedure details, baseline demographics, co-morbidities, mean HbA1c and GV (HbA1c SD) were assessed. Time to re-intervention, ipsilateral amputation or death were recorded to determine primary (PP).

Results
Were reported as hazard ratios (HR) following multivariate adjustment.193 IIB outcomes were analysed: mean (±SD) age 68.9(9.2) years; 135(69.9%) male. 156 (80.8%) had pre-operative HbA1c for analysis and 88(45.6%) had DM; 87(45.1%) were current smokers; 107(55.4%) underwent emergency procedures. Those without diabetes were more likely to smoke (P=0.011), but those with DM were more likely to have IHD (0.007), had higher Rutherford stage (p=0.0006), underwent more distal bypasses (p=0.004) and more emergency procedures (p=0.04). GV&gt;9.1% was associated with significantly lower PP than GV&lt;9.1%, 198 [105–377] vs. 713 [313-1287] days (p=0.02). Univariate predictors of PP included Rutherford stage 4 vs 3 (p=0.01), level of bypass, (p=0.0003), DM (p=0.04) and GV&gt;9.1% (p=0.02). On multivariate adjustment, GV &gt;9.1% and level of bypass remained independent predictors of primary patency, HR 1.96 (95% CI:1.12-3.42, p=0.018) and HR 2.54 (95%CI:1.24-5.22, p=0.038) respectively.

Conclusion
We have demonstrated GV and level of bypass as independent predictors of graft failure on multivariate analysis. Therefore, optimising GV should be a therapeutic target to improve outcomes.
O009 Completion of supervised exercise therapy improves outcomes for patients with intermittent claudication: propensity score-matched analysis of 7-year outcomes
Authors: Ravindhran B , Lim A , Walshaw J , Kurian T , Sidapra M , Lathan R , Hitchman L , Mohamed A , Carradice D , Smith G , Chetter I , Pymer S 
Published: May 2023

Abstract

Introduction
The goal of this study was to compare the long-term outcomes of patients with intermittent claudication (IC) who completed supervised exercise therapy (SET) versus patients who either declined or prematurely discontinued SET.

Methods
A retrospective, observational, single-centre cohort study of patients with IC referred to SET. Outcomes included progression to chronic limb-threatening ischemia (CLTI), revascularization requirement, and cardiovascular death.1:1 propensity score matching (PSM) using nearest-neighbour (caliper=0.2) was performed. Multivariate analysis (MVA) and logistic-regression (LR) were used to identify significant effect modifiers to guide PSM. Time-to-event data were analysed using Kaplan-Meier survival analysis.

Results
241 patients were referred to SET between July 2015 and July 2016. Forty-nine patients completed SET and 192 patients did not. There was no significant difference in age, diabetes, smoking-cessation, and medication compliance between groups. After PSM, 49 patients who declined SET and 41 patients who completed SET were analysed. Progression to CLTI was significantly lower (10.2% vs 65.9%; p&lt;0.001) in patients who completed SET. There was also a significant difference (p&lt;0.001) in the median time to develop CLTI (1952 days [IQR 151;95% CI:1655 to 2249] vs 858 days [IQR 282; 95% CI:305 to 1411]). Revascularisation requirement: SET completion was associated with a significantly lower incidence of revascularisation (42.5% vs 57.5%; p=0.04) and a lower number of revascularization procedures SET(p&lt;0.001). SET completion significantly delayed revascularization (1158 days [IQR 131;95% CI:931 to 1443] vs 326 days [IQR 38;95% CI:252 to 400]; p=0.03). There was no significant difference in the incidence (26% vs 35%; p=0.4) or time to cardiovascular death.

Conclusion
SET for claudication reduces requirement for future revascularisation by slowing disease progression.
O010 A novel microfluidic immunoassay for in-solution quantification of alloantibody affinity and concentration in transplantation and beyond
Authors: Priddey A , Karahan G , Schneider M , Meisl G , Scheidt T , Xu C , Peacock S , Buchli R , Mulder A , Heidt S , Class F , Knowles T , Kosmolipaptsis V 
Published: May 2023

Abstract

Introduction
Antibody characterisation is fundamental in transplantation and infectious diseases, but current immunoassays cannot determine two fundamental antibody properties, affinity (KD) and concentration ([Ab]). We aimed to overcome these limitations to allow in-depth profiling of antibodies directly in sera and provide insights into clinical translation.

Methods
Using a microfluidic diffusional sizing-based strategy, we developed microfluidic antibody affinity profiling (MAAP), a novel in-solution immunoassay that simultaneously determines KD and [Ab] directly in serum. MAAP was developed and validated using the HLA-alloantibody system and applied in HLA Ab-incompatible (HLAi) transplantation and in anti-SARS-CoV-2 immunity.

Results
MAAP enabled quantification (KD and [Ab]) of alloantibody-HLA interactions in both purified and alloantibody-spiked sera. We demonstrated that transplant single-HLA-bead (SAB) immunoassays were avidity and [Ab]-dependent, cellular immunoassays (flow-cytometry and complement-dependent-cytotoxicity) were KD and [Ab]-dependent, antibody-mediated cytotoxicity was proportional to antibody-HLA KD, and micromolar antibody-HLA interactions were functionally insignificant despite high SAB signal. In HLAi transplants, MAAP differentiated clinically significant donor-specific-alloantibodies (leading to rejection) from those tolerated despite similar SAB assay output and provided insights into memory re-activation and immune-monitoring post-transplantation. In SARS-CoV-2, MAAP showed wide variation in anti-RBD antibody KD in convalescent sera (n=34), good correlation with serum neutralisation capacity (p&lt;0.001), and evidence of affinity maturation 3-months post-infection (despite [Ab] reduction). In vaccinated sera (n=17), anti-RBD antibody KD was significantly weaker against Omicron than wild-type (p&lt;0.001), providing insights into variant immune-escape strategies.

Conclusion
This work outlines a path towards in-depth antibody profiling and demonstrates the importance of antibody abundance and affinity in clinically relevant humoral immunity.