bluuebunny/crossref_metadata_2025_split huggingface dataset:
54 Impact of Carbon Nanoparticle–Triggered Gammaherpesvirus Reactivation on Lung Immunity and Diseases
Authors: Guenther Eva M , Haefner Verena , Han Lianyong , Voss Carola , Yildirim Ali Oender , Adler Heiko , Stoeger Tobias 
Published: May 2023

Abstract
Inhalation of environmental particles and herpesvirus infection are ubiquitous in our society. Herpesviruses persist lifelong in the host in a latent state, which can be exited by stress-induced reactivation with production of lytic virus. Our previous investigations show that pulmonary exposure to carbon nanoparticles (CNP) triggers reactivation of latent murine gammaherpesvirus 68 (MHV-68) in mouse lungs, mainly localizing to CD11b+ infiltrating macrophages and dependent on p38 MAPK signaling. Furthermore, we observed that a two-time repeated CNP administration to latently infected mice resulted in alveolar damage leading to progressive emphysema. However, the underlying adverse mechanisms causing alveolar damage and the corresponding cell communication upon CNP exposure in latently infected lungs is still unclear. To investigate this, we developed a 3D lung organoid culture from primary murine epithelial cells in combination with persistently MHV-68 infected macrophages. This model enables us to detect reactivation and cytokine release upon CNP exposure, and to gain insights into the cellular communication of epithelial cells and macrophages, to understand the mechanisms underlying reactivation-triggered damage. In parallel, adverse effects of this second hit scenario on the alveolar epithelium and subsequent disease development get investigated in vivo. Latently infected mice are exposed to CNP up to 5 times, and virus reactivation and further epithelial damage is analyzed. By uncovering molecular mechanisms underlying the adverse effects and elucidating the communication occurring in vitro and in vivo we want to identify potential targets to prevent exacerbation of lung diseases caused by these two omnipresent factors, herpesvirus infection and ambient particle exposure.
94 Metalsafety – In Vitro, ex Vivo and in Vivo Investigations on Particulate and Nanofibrous Metal Compounds
Authors: Schulz Florian , Sewald Katherina , Hansen Tanja , Honarvar Naveed , Hartwig Andrea , Bitsch Annette 
Published: May 2023

Abstract
Metals and metal compounds are essential in daily life. Besides particulate materials nanofibrous material (nanowires) gain importance in innovative processes like optoelectronics. Toxicological data to assess the hazard is often available only for granular metals while data on nanowires is sparse. The project MetalSafety funded by the German BMBF aims at the development of an in vitro model to allow the grouping of different metal compounds with different bioavailability according to their toxicological hazard. Ex vivo and in vivo investigations are used to analyse the predictivity of the in vitro results and the underlying mode-of-action and dose-response relationship. Within this contribution the study concept is introduced. Silver and copper, both in particulate and nanofibrous form, are used across all examinations in vitro, ex vivo and in vivo. To allow an interspecies comparison cell lines derived from human and rat lung are used. Exposure to the materials can be investigated either submerse or with air-liquid-interface (ALI) conditions. The correlation between both species can also be examined ex vivo using precision-cut lung slices (PCLS) derived from human and rat lung tissue. Application in vivo by intratracheal instillation in rats is conducted to enable a validation of the in vitro and ex vivo screening models in a best case scenario under physiological conditions. Comparable endpoints in vitro, ex vivo as well as in vivo are measured during the study. This includes cytotoxicity endpoints and cytokine measurements as well as gene expression analyses. The lung tissue is also subjected to a histopathological examination.
113 Development of a Direct Reading Instrument for Oxidative Potential Measurement in Air
Authors: Sauvain Jean-Jacques , Toto Antonio , Montet Estelle , Niquille Adeline , Suarez Guillaume 
Published: May 2023

Abstract
To protect the general population as well as workers, authorities have to identify the most toxic compounds in the particulate aerosol and effectively reduce their concentrations. As the oxidative potential (OP) is suggested to be linked with health effects, it may be more effective to control specific sources of oxidizing particles rather than overall particulate mass. In that case, the use of direct-reading instruments for OP measurement could help to the effective control of noxious air pollutant sources. We present here the development and characterization of a direct-reading instrument based on the acellular ferrous-orange xylenol (FOX) assay, allowing a continuous sensing of ambient oxidizing compounds. The detection principle relies on multiscattering-enhanced absorbance strategy enabling sensitive detection of airborne oxidants (e.g. hydrogen peroxide, hydroxyl radical) with a time resolution of 5 min. Two parallel tasks to improve the reading instrument are underway: 1. A better understanding of the FOX response to the potentially interfering ozone and NOx gases and it relationship with emission sources; 2. Improving the interface for transferring the aerosol in the FOX solution and characterizing the instrument regarding it sensibility, linearity, repeatability and response time. Continuous determination of OP will enable robust epidemiological studies to evidence potential associations with oxidative stress-related and inflammatory disorders. In the future, mapping the average annual OP – together with current PM10, NOx and O3 – will be an essential chemical dimension of the pollution profile.
134 Hybrid Nanostructures Using Polymers to Reduce the Toxicity of Inorganic Luminescent Nanomaterials and Organic Dyes
Authors: Umezawa Masakazu , Soga Kohei 
Published: May 2023

Abstract
There is a growing research effort to use polymers to encapsulate functional molecules and nanomaterials to control their beneficial effects and toxicity, by minimizing their interactions with biomolecules and organs outside of the target sites. This concept is well known as drug delivery systems using nanoparticles. A good example is the RNA vaccines that encapsulates highly degradable RNA in lipid nanoparticles and delivers RNAs stably to immune cells. Such strategies are expected to be effective in designing nanoscale materials with low toxicity. Here, we investigated a potential of inorganic and organic hybrid nanomaterials (HNMs) for photodynamic therapy (PDT) for lesions in deep tissues, by combining (1) dyes for PDT and (2) upconversion luminescent nanoparticles (UCL-NPs) that activate the dyes under irradiation with the light of near-infrared (NIR), which is in the biological window with high transparency in biological tissues. In this context, we designed an HNM in which a PDT dye, rose Bengal (RB), and UCL-NPs are encapsulated using biodegradable polymer nanoparticles. HNMs significantly reduced the toxicity of RB and protected NPs’ luminescence. By using ultrasmall UCL-NPs (&lt;10 nm) for RB activation, the HNP was designed for UCL-NPs to be excreted via the kidneys. UCL-NPs also emit near-infrared (1550 nm) fluorescence, which enables imaging of deep tissues. Therefore, the PDT-HNM works as a “theranostic” probe to be used for PDT therapy while real-time monitoring the target location. The design of such nanostructures is expected to lead to further biomedical applications of molecular drugs as well as highly functional inorganic nanomaterials.
Best Practices for FACE-Q Aesthetics Research: A Systematic Review of Study Methodology
Authors: Gallo Lucas , Kim Patrick , Yuan Morgan , Gallo Matteo , Thoma Achilles , Voineskos Sophocles H , Cano Stefan J , Pusic Andrea L , Klassen Anne F 
Published: May 2023

Abstract

Background
The FACE-Q Aesthetics module is a validated patient-reported outcome measure (PROM) that evaluates perspectives on facial aesthetic treatments. Improper administration and poor study methodology can compromise the validity and interpretation of this PROM.

Objectives
This systematic review sought to evaluate the administration and scoring of the FACE-Q Aesthetics scales within the literature.

Methods
A search of Ovid Medline, Embase, Cochrane, and Web of Science was performed on December 20, 2022, with the assistance of a health-research librarian (CRD42022383676). Studies that examined facial aesthetic interventions using the FACE-Q Aesthetics module as a primary or secondary outcome measure were included for analysis.

Results
There were 114 studies included. The Face Overall (n = 52, 45.6%), Psychological (n = 45, 39.4%), and Social (n = 43, 37.7%) scales were most frequently reported. Errors in FACE-Q administration were identified in 30 (26.3%) studies. The most common error was the presentation of raw ordinal scores rather than the converted Q score (n = 23). Most studies reported a time horizon for their primary analysis (n = 76, 66.7%); however, only 4 studies provided a rationale for this selection. Sample size calculations for the primary outcome were rarely performed (n = 9, 7.9%).

Conclusions
There continues to be limitations in PROM administration and the quality of articles that report FACE-Q Aesthetic scale data. The authors suggest that future investigators using the FACE-Q refer to the User's Guide regarding administration and scoring of this scale, report a rationale for the study time horizon, and provide an a priori sample size calculation for the primary outcome of interest.
Species divergence despite minimal morphological differentiation and habitat overlap in the Patelloida saccharina (Patellogastropoda: Lottiidae) species complex
Authors: Paran Faith Jessica , Ikeo Kazuho , Asakura Akira , Nakano Tomoyuki 
Published: May 2023

Abstract
We describe the current state of speciation in the species complex of the marine gastropod Patelloida saccharina, using mitochondrial COI, 16S RNA, nuclear histone 3 gene and single-nucleotide polymorphism (SNP) markers from 165 specimens collected from 37 localities across the Japanese archipelago. In total, 28 unique COI haplotypes, 16 16S haplotypes, 11 histone 3 haplotypes and 148 734 SNPs were obtained. Genetic assignments and phylogenetic trees recovered three genetically distinct lineages: P. saccharina saccharina, P. saccharina lanx and an unknown P. sp. from Shionomisaki, Wakayama Prefecture. The divergence between P. saccharina saccharina and P. saccharina lanx was estimated to have occurred around 44 000 years ago—too recent to have accumulated the morphological differences that have confounded taxonomic identification. Continuous gene exchange after an initial split is suggested based on demographic history analyses, which allowed for introgression of the P. saccharina lanx genome and the proliferation of intermediate individuals. Speciation, despite the existence of a contact zone in the Ryukyu Islands, possibly occurred due to the eventual reproductive isolation that followed the initial split with gene flow. Patelloida saccharina saccharina and P. saccharina lanx were strongly supported by our results as two separate species, and a revision of the current taxonomic descriptions based on their phylogeny, demographic history and species distribution is proposed.
O006 Hepatitis A virus cellular receptor 1 (HAVCR1) influences the integrity of blood brain barrier (BBB) of cerebral endothelial cells
Authors: Cao X S , Cong B B , Jiang W G , Martin T A 
Published: May 2023

Abstract

Introduction
Hepatitis A virus cellular receptor 1 (HAVcR1) has been established to play an important role in tight junction (TJ) in cancer cells and in peripheral endothelial cells. Its role in blood brain barrier (BBB) of cerebral endothelium remains unknown. This study aimed to investigate the association and functionality of HAVcR1 in BBB.

Methods
HAVcR1 was knocked down by siRNA in human cerebral microvessel endothelial cell/D3 (hCMEC/D3) cell lines. Changes in tight junction (TJ) behaviour were assessed using electric cell impedance sensing (ECIS), transendothelial resistance (TER), and paracellular permeability (PCP). The expression of HAVcR1 and the binding partners of HAVcR1 protein was assessed using quantitative polymerase chain reaction (qPCR).

Results
The HAVcR1 gene transcript, highly expressed in hCMEC/D3 cells, was successfully knocked down from the cell by anti-HAVcR1 siRNA. HAVcR1 knockdown resulted in an increase in four TJ molecules and a decrease in eight TJ molecules as demonstrated by transcript analysis. HAVcR1 knockdown cells displayed lower electric resistance compared with wild type cells during initial attachment and spreading in hCMEC/D3 cells shown by ECIS. Similarly, TER in HAVcR1 knockdown cells were also reduced. Higher PCP fluorescence signals were detected in HAVcR1 knockdown cell lines compared with wild type.

Conclusion
HAVcR1 regulates paracellular leakage of cerebral endothelial cells and loss of HAVcR1 renders the cells with weaker tight junction by influencing TJ protein expression. HAVcR1 have a function as part of the regulatory apparatus for TJ in BBB.
O011 Investigating the effect of supraphysiological levels of calcium on irreversible electroporation (IRE) of pancreatic cancer cell lines
Authors: Rai Z , Correa R , Khawaja I A , Acedo P , Davidson B R 
Published: May 2023

Abstract

Introduction
Pancreatic cancer remains difficult to treat with a 5-year survival of 2%. Loco-regional therapies are being introduced such as Irreversible Electroporation (IRE); a non-thermal ablative therapy thought to cause cell death by increasing the cell membrane potential resulting in the formation of aqueous pores, leading to cell death. Mitochondrial changes have previously been reported to be a key driver of apoptosis and calcium has been implicated in this process. We aimed to study the influence of calcium in combination with IRE in pancreatic cancer.

Methods
Immortalised pancreatic cancer cell line, PANC-1, and pancreatic cancer patient-derived xenograft cells (PDX 185) were exposed to calcium (Ca2+) and IRE monotherapy and in combination. Cells were trypsinised and electroporated in 4mm cuvettes with a BTX generator (Harvard Apparatus). Cell proliferation and viability were analysed, and depolarised mitochondria were evaluated by TMRE and analysed using flow cytometry.

Results
IRE combined with calcium was more cytotoxic compared to monotherapy with cell proliferation assays demonstrating a statistically significant reduction in proliferation (p&lt;0.0001) across both cell lines. Interestingly, mitochondrial membrane potential analyses demonstrated a depolarising effect only in cells exposed to both calcium and IRE suggesting a mitochondrial mediated effect in cell death in these groups.

Conclusion
Calcium in combination with IRE may act to potentiate cell death through depolarisation of the mitochondrial membrane. Future work will involve understanding the impact of IRE in combination with calcium in 3D models, allowing the evaluation of molecular cell death mechanisms.
O017 Dupuytren's disease (DD): WNT4 knockdown in normal skin fibroblasts leads to ‘DD-like’ changes in the transcriptome
Authors: O’Brien A , Stevenson A , Barrett L , Hortin N , Deng Z , Allahham A , Quondamatteo F , Wood F , Fear M 
Published: May 2023

Abstract

Introduction
Dupuytren's disease (DD), a fibro-proliferative disorder of unknown aetiology, affects the palm and is characterised by progressive fibrosis, thickening of palmar fascia, and excess collagen deposition. Patients present with nodules, causing flexion deformity in ∼50%, resulting in loss of hand function. Excision is the standard treatment for DD, recurrence remains high. A 2015 Cochrane review concluded there is insufficient evidence to show superiority of any procedure used. Genetic and other studies have implicated WNT signalling in Dupuytren's pathology, including WNT4 dysregulation. It is not clear how WNT signalling/WNT4 plays a role in triggering DD.

Methods
Fibroblasts were isolated from the wrists of control healthy adult males and from a family that had inherited DD. Normal skin fibroblasts were treated with WNT4 siRNA and transcriptome of normal skin untreated, normal skin siRNA treated and DD family fibroblasts compared using RNASeq.

Results
Analysis of the transcriptomes from DD patient and normal fibroblasts showed significant differences including in WNT4 expression. Downregulation of WNT4 in normal fibroblasts using siRNA led to ‘DD-like’ changes in the transcriptome.

Conclusion
In people susceptible to DD WNT4 is downregulated even in non-fibrotic fibroblasts. Knockdown of WNT4 in normal fibroblasts led to changes making cells ‘DD-like’, suggesting downregulation of WNT4 could drive DD. Previous studies have shown that WNT4 is downregulated in DD disease in the cord cells. This study shows that WNT4 is downregulated in ‘non-disease’ cells, that downregulating WNT4 in normal skin fibroblasts leads to widespread ‘DD like’ changes in the transcriptome, suggesting WNT4 downregulation is a driver of DD disease.
O018 Determining the relationships between venous reflux patterns, clinical severity, and health-related quality of life
Authors: Wang R , Tan M , Onida S , Davies A H 
Published: May 2023

Abstract

Introduction
Various classification systems have been created to describe the anatomical distribution of venous reflux, including the VEIN-TERM and Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification. It is still unclear whether different reflux patterns correlate with health-related quality of life (HRQoL) and clinical severity.

Methods
Some 507 chronic venous disease patients and 105 asymptomatic controls underwent duplex ultrasound assessment. Patients were stratified according to VEIN-TERM and the CEAP classification systems. The Aberdeen Varicose Vein Questionnaire (AVVQ) score was used to compare HRQoL and the Venous Clinical Severity Score (VCSS) was used to compare clinical severity between groups.

Results
Patients were significantly older than controls (p&lt;0.00001). All VEIN-TERM reflux patterns had significantly greater VCSS than no reflux (p&lt;0.001). Superficial axial and combined axial reflux were associated with significantly greater VCSS than superficial segmental reflux (p&lt;0.001, p=0.042 respectively). All VEIN-TERM reflux types had significantly worse AVVQ scores than no reflux (p&lt;0.03). However, there were no significant differences in AVVQ scores across all VEIN-TERM reflux patterns. Most CEAP reflux patterns had increased VCSS and worse AVVQ scores when compared to no reflux (all p&lt;0.05), except for deep reflux, and deep and perforator reflux only. The deep, superficial and perforator reflux group had significantly higher VCSS (p=0.013) and AVVQ (p&lt;0.001) versus the superficial reflux only group.

Conclusion
When compared to no reflux, both classification systems show associations of any reflux pattern with worse VCSS and AVVQ scores. Combined reflux patterns were associated with the greatest clinical severity and worst HRQoL scores.
O024 Development and validation of a “lab in a box” for remote delivery of core reconstructive surgical skills
Authors: Awad L , Langridge B , Bollen E , Butler P 
Published: May 2023

Abstract

Introduction
Junior doctors and aspiring surgical trainees can have limited surgical exposure and developmental teaching because of rapid rotations, inconsistent rotas, reduced theatre time, and high working pressures. The global pandemic has also initiated a paradigm shift in education, and the methods we use to deliver education. Our aims are to assess the feasibility and validity of a low cost, remote plastic surgical skills course in comparison to the same course delivered face-to-face.

Methods
Our bench-model simulation “Lab in a Box” design was delivered to students remotely and in person. The essential and advanced plastic surgery course included suturing, excision, tendon repair, and local flap design. We undertook a pilot course facilitated by an online platform using a two-device set up. Equipment, including synthetic tendons and skin substitutes, were distributed to each participant. Quantitative evaluation included a global rating assessment and task specific criteria using a 1-5 Likert scale. Results were compared to the face-to-face control group. Qualitative feedback was also collected.

Results
A total of 40 students were recruited. A total cost of less than £30 was achieved. Quantitative feedback demonstrated comparable outcomes in remote training vs face-to-face training. Students reported excellent quality of audio-visual material and equipment, clear feedback, and 100% would recommend this course.

Conclusion
The simulation training course developed provides high-quality, engaging, reproducible and low-cost surgical skills training that can be delivered via distance learning. This model can be used to improve surgical skills training both in the UK and globally in resource poor environments.
O025 Do surgeons’ psychosocial working conditions achieve United Kingdom government standards?
Authors: Houdmont J , Daliya P , Adiamah A , Theophilidou E , Hassard J , Lobo D N 
Published: May 2023

Abstract

Introduction
Burnout is endemic among surgeons in the UK. Identification of contributory work characteristics could inform risk reduction activities. The purpose of this study was to assess the extent to which surgeons’ psychosocial working conditions met aspirational Management Standards delineated by the UK government. A secondary objective was to explore relations between the extent to which the Standards were met and burnout.

Methods
In 2021, trainee surgeons (n = 214) and consultant surgeons (n = 322) completed questionnaire measures of psychosocial working conditions and burnout. Descriptive data were computed for each Standard and hierarchical linear regression was applied to explore relations between the extent to which the Standards were met and burnout.

Results
Trainee surgeons reported significantly poorer psychosocial working conditions than consultant surgeons on the control, peer support, and change Standards. Trainees’ psychosocial working conditions fell below the 10th percentile on four Standards (control, managerial support, role, change) and below the 50th percentile on the remainder (demands, peer support, relationships) when compared to UK workforce norms. Consultant surgeons’ psychosocial working conditions were below the 50th percentile on five of the seven Standards. The Management Standards accounted for 35% of the variance in burnout over and above that accounted for by socio- and occupational-demographic characteristics.

Conclusion
Surgeons’ psychosocial working conditions were poor in comparison to normative data and strongly associated with burnout. These findings suggest that psychosocial risk management activities based on the Management Standards approach would help to reduce stress-related health problems in this population.