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Background: As survival rates for individuals with sickle cell disease (SCD) increase, calls have been made to improve their reproductive healthcare and outcomes. The research team created a web-based program entitled Fertility edUcaTion to Understand ReproductivE health in Sickle cell disease (FUTURES). The study aim was to use the Consolidated Framework for Implementation Research (CFIR) during pre-implementation to identify challenges and opportunities from the individual to systems level of implementation to ultimately optimize the integration of FUTURES into clinical practice., Methods: Semi-structured interviews were conducted with clinicians, research team members, and adolescent and young adult (AYA) males with SCD and their caregivers who participated in pilot testing. Interviews (N = 31) were coded inductively and then mapped onto CFIR domains (i.e., outer setting, inner setting, characteristics of individuals, and intervention characteristics)., Results: Research team interviews indicated the lack of universal guidelines for reproductive care in this population and gaps in reproductive health knowledge as key reasons for developing FUTURES, also highlighting the importance of collaboration with community members during development. Clinicians reported intraorganizational communication as essential to implementing FUTURES and discussed challenges in addressing reproductive health due to competing priorities. Clinicians, AYAs, and caregivers reported positive views of FUTURES regarding length, engagement, accessibility, and content. Suggestions for the best setting and timing for implementation varied., Conclusions: Using CFIR during the pre-implementation phase highlighted challenges and opportunities regarding integrating this program into SCD care. These findings will inform adaptation and further testing of FUTURES to ensure effective implementation of this novel education program., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Numerous studies have been conducted to investigate the impact of microplastics on soil eco-system, yet little attention has been given to the specific effects of mulch microplastics and the leaching of plastic additives from mulch films. This review inspects the propensity of commonly used plastic additives in mulch films, such as Di(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), and benzophenones (BPs), to migrate into soils and pose potential risks to soil biota. Further, we highlight the degradation of non-biodegradable plastic mulch films over time, which leads to an increase in the release of plastic additives and microplastics into agricultural soils. DEHP has been detected in high concentrations for example 25.2 mg/kg in agricultural soils, indicating a potential risk of uptake, translocation and accumulation in plants, ultimately altering soil physicochemical properties and affecting soil microflora and invertebrates. The review also explores how exposure to ultraviolet (UV) radiation and microbial activities accelerates the weathering of mulch films. Moreover, the resultant plastic additives and mulch microplastics can lead to genotoxicity and growth inhibition in earthworms (Eisenia fetida) and negatively impact the soil microbiome. Despite the significant implications, there has been a lack of comprehensive reviews comparing the effects of non-biodegradable mulch film additives on agricultural soil flora and fauna. Therefore, this review addresses the knowledge gaps providing a bibliometric analysis and eco-toxicological evaluation, discussing the challenges and future perspectives regarding mulch plastic additives and microplastics, thus offering a comprehensive understanding of their impact., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to understand the meaning physically impaired 1 wheelchair sport athletes attributed to wheelchair basketball participation as well as potential physical, psychological, and social health-related quality of life (HRQOL) benefits. Specifically, the experiences of wheelchair sport athletes from low- and middle-income countries (LMIC) affected by ongoing or recent conflict were examined. Focus group participants for this study included 108 wheelchair basketball athletes (77 men and 31 women) from seven men's and three women's national teams at an international wheelchair basketball tournament held in India. All teams were from LMICs in Africa and Asia that were served by the International Committee of the Red Cross due to recent or ongoing armed conflict. Data analysis produced three interrelated themes related to HRQOL: (1) improvements to physical health, (2) psychological impact of sport participation, and (3) social well-being. Physical benefits included improvements to physical functional capacity and decreases in medical complications. Psychological benefits included freedom and respite from inaccessibility and improved self-beliefs and feelings of capability on and off the court. Social well-being benefits included camaraderie in the team setting and positive interpersonal interactions with members of the broader community. Overall, the findings indicated that wheelchair sport is indicated as positively impacting numerous HRQOL indicators for disabled participants in LMIC and is a valuable rehabilitative option and meaningful endeavor for disabled persons.

At the end of 2022 into early 2023, the UK Health Security Agency reported unusually high levels of scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA or group A Streptococcus ). During this time, we collected and genome-sequenced 341 non-invasive throat and skin S. pyogenes isolates identified during routine clinical diagnostic testing in Sheffield, a large UK city. We compared the data with that obtained from a similar collection of 165 isolates from 2016 to 2017. Numbers of throat-associated isolates collected peaked in early December 2022, reflecting the national scarlet fever upsurge, while skin infections peaked later in December. The most common emm -types in 2022-2023 were emm 1 (28.7 %), emm 12 (24.9 %) and emm 22 (7.7 %) in throat and emm 1 (22 %), emm 12 (10 %), emm 76 (18 %) and emm 49 (7 %) in skin. While all emm 1 isolates were the M1 UK lineage, the comparison with 2016-2017 revealed diverse lineages in other emm -types, including emm 12, and emergent lineages within other types including a new acapsular emm 75 lineage, demonstrating that the upsurge was not completely driven by a single genotype. The analysis of the capsule locus predicted that only 51 % of throat isolates would produce capsule compared with 78% of skin isolates. Ninety per cent of throat isolates were also predicted to have high NADase and streptolysin O (SLO) expression, based on the promoter sequence, compared with only 56% of skin isolates. Our study has highlighted the value in analysis of non-invasive isolates to characterize tissue tropisms, as well as changing strain diversity and emerging genomic features which may have implications for spillover into invasive disease and future S. pyogenes upsurges.

Here, the novel technique of extended-range high-energy-resolution fluorescence detection (XR-HERFD) has successfully observed the n = 2 satellite in manganese to a high accuracy. The significance of the satellite signature presented is many hundreds of standard errors and well beyond typical discovery levels of three to six standard errors. This satellite is a sensitive indicator for all manganese-containing materials in condensed matter. The uncertainty in the measurements has been defined, which clearly observes multiple peaks and structure indicative of complex physical quantum-mechanical processes. Theoretical calculations of energy eigenvalues, shake-off probability and Auger rates are also presented, which explain the origin of the satellite from physical n = 2 shake-off processes. The evolution in the intensity of this satellite is measured relative to the full Kα spectrum of manganese to investigate satellite structure, and therefore many-body processes, as a function of incident energy. Results demonstrate that the many-body reduction factor S 0 2 should not be modelled with a constant value as is currently done. This work makes a significant contribution to the challenge of understanding many-body processes and interpreting HERFD or resonant inelastic X-ray scattering spectra in a quantitative manner., (open access.)

This study sought to understand the lived experiences of wheelchair basketball athletes from low- and middle-income countries of recent or current armed conflict and the meaning that they ascribed to their participation. Wheelchair basketball athletes (N = 108) from eight national teams participated in semistructured focus-group interviews. Study data were analyzed thematically using an interpretive descriptive approach. Three themes were developed: "I can do anything I want; not only basketball," self-concept changes through sport participation; "Now they see me as a respectable person," societal belonging through sport; and "I have motivated other disabled people," influence on nonparticipating disabled persons. The findings indicated that participation in wheelchair sports may help disabled persons see themselves as capable individuals on the court and in aspects of daily living, perhaps even peer role models for other disabled persons in their communities and countries.

The antibacterial effects of a selection of volatile fatty acids (acetic, propionic, butyric, valeric, and caproic acids) relevant to anaerobic digestion were investigated at 1, 2 and 4 g/L. The antibacterial effects were characterised by the dynamics of Enterococcus faecalis NCTC 00775, Escherichia coli JCM 1649 and Klebsiella pneumoniae A17. Mesophilic anaerobic incubation to determine the minimum bactericidal concentration (MBC) and median lethal concentration of the VFAs was carried out in Luria Bertani broth at 37 °C for 48 h. Samples collected at times 0, 3, 6, 24 and 48 h were used to monitor bacterial kinetics and pH. VFAs at 4 g/L demonstrated the highest bactericidal effect ( p < 0.05), while 1 g/L supported bacterial growth. The VFA cocktail was the most effective, while propionic acid was the least effective. Enterococcus faecalis NCTC 00775 was the most resistant strain with the VFAs MBC of 4 g/L, while Klebsiella pneumoniae A17 was the least resistant with the VFAs MBC of 2 g/L. Allowing a 48 h incubation period led to more log decline in the bacterial numbers compared to earlier times. The VFA cocktail, valeric, and caproic acids at 4 g/L achieved elimination of the three bacteria strains, with over 7 log 10 decrease within 48 h.

The effects of the inoculum (anaerobic digestion effluent) to substrate (simulated food waste) ratio (ISR) 4.00 to 0.25 on putative pathogens and microbial kinetics during batch mesophilic anaerobic digestion were investigated. Red fluorescent protein labelled (RFPAKN132) Escherichia coli JM105 was introduced as a marker species, and together with the indigenous Clostridium sp., Enterococcus sp., Escherichia coli , and total coliforms were used to monitor pathogen death kinetics. Quantitative polymerase chain reaction was also used to estimate the bacterial, fungal, and methanogenic gene copies. All the ISRs eliminated E. coli and other coliforms (4 log 10 CFU/mL), but ISR 0.25 achieved this within the shortest time (≤2 days), while ISR 1.00 initially supported pathogen proliferation. Up to 1.5 log 10 CFU/mL of Clostridium was reduced by acidogenic conditions (ISR 0.25 and 0.50), while Enterococcus species were resistant to the digestion conditions. Fungal DNA was reduced (≥5 log 10 copies/mL) and was undetectable in ISRs 4.00, 2.00, and 0.50 at the end of the incubation period. This study has demonstrated that ISR influenced the pH of the digesters during batch mesophilic anaerobic digestion, and that acidic and alkaline conditions achieved by the lower (0.50 and 0.25) and higher (4.00 and 2.00) ISRs, respectively, were critical to the sanitisation of waste.

Context: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, with disease loci identified from genome-wide association studies (GWAS) having largely unknown relationships to disease pathogenesis., Objective: This work aimed to group PCOS GWAS loci into genetic clusters associated with disease pathophysiology., Methods: Cluster analysis was performed for 60 PCOS-associated genetic variants and 49 traits using GWAS summary statistics. Cluster-specific PCOS partitioned polygenic scores (pPS) were generated and tested for association with clinical phenotypes in the Mass General Brigham Biobank (MGBB, N = 62 252). Associations with clinical outcomes (type 2 diabetes [T2D], coronary artery disease [CAD], and female reproductive traits) were assessed using both GWAS-based pPS (DIAMANTE, N = 898,130, CARDIOGRAM/UKBB, N = 547 261) and individual-level pPS in MGBB., Results: Four PCOS genetic clusters were identified with top loci indicated as following: (i) cluster 1/obesity/insulin resistance (FTO); (ii) cluster 2/hormonal/menstrual cycle changes (FSHB); (iii) cluster 3/blood markers/inflammation (ATXN2/SH2B3); (iv) cluster 4/metabolic changes (MAF, SLC38A11). Cluster pPS were associated with distinct clinical traits: Cluster 1 with increased body mass index (P = 6.6 × 10-29); cluster 2 with increased age of menarche (P = 1.5 × 10-4); cluster 3 with multiple decreased blood markers, including mean platelet volume (P = 3.1 ×10-5); and cluster 4 with increased alkaline phosphatase (P = .007). PCOS genetic clusters GWAS-pPSs were also associated with disease outcomes: cluster 1 pPS with increased T2D (odds ratio [OR] 1.07; P = 7.3 × 10-50), with replication in MGBB all participants (OR 1.09, P = 2.7 × 10-7) and females only (OR 1.11, 4.8 × 10-5)., Conclusion: Distinct genetic backgrounds in individuals with PCOS may underlie clinical heterogeneity and disease outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Food and formulation characteristics are crucial factors affecting the gastrointestinal release and absorption kinetics of oral solid preparations. In the present study, the dynamic continuous release and bioaccessibility of metformin hydrochloride immediate-release (IR) and sustained-release (SR) tablets were investigated in the dynamic human stomach-intestine (DHSI-IV) system simulating fasted and fed states in healthy adults. Both tablet formulations (particularly IR tablet) exhibited a postponed release in the fed state compared to the fasted state. Correspondingly, the bioaccessible fraction of metformin from IR tablets in the presence of high-fat meal was significantly reduced to 76.2 % of the fasted state. However, the in vitro bioaccessibility was less impaired by food for SR tablets with a fed/fasted ratio of 95.5 %. A convolution-based approach was used to convert in vitro bioaccessibility results to plasma concentration data. The predicted plasma concentration curve showed good agreement with human data in terms of pharmacokinetic (PK) parameters. In the fasted state, the predicted C max , T max and AUC 0-24h of IR tablets were 943.9 ± 25.7 ng/mL, 2.0 ± 0.4 h and 7090.7 ± 112.0 ng.h/mL, respectively, mirroring values observed in healthy subjects. Overall, the DHSI-IV system has demonstrated potential to assess and predict the impact of meal intake on the in vivo release and absorption behaviors of oral solid preparations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The usage of multi-walled carbon nanotubes (MWCNT) has increased exponentially in the past years, but, potential toxicity mechanisms are not clear. We studied the transcriptomic alterations induced by one multi-walled carbon nanotube (MWCNT) and its -OH and -COOH functionalized derivatives in human HepG2 cells. We showed that all three MWCNT treatments induced alterations in stress-related signaling pathways, inflammation-related signaling pathways, cholesterol synthesis pathways, proliferation-related pathways, senescence-related pathways and cancer-related pathways. In stress-related pathways, the acute phase response was induced in all three MWCNTs and all doses treated and ranked high. Other stress-related pathways were also related to the oxidative-induced signaling pathways, such as NRF-2 mediated oxidative stress response, hepatic fibrosis/Stella cell activation, iNOS signaling, and Hif1α signaling. Many inflammation-related pathways were altered, such as IL-8, IL-6, TNFR1, TNFR2, and NF-κB signaling pathways. These results were consistent with our previous results with exposures to the same three multi-walled carbon nanotubes in human lung BEAS-2B and also with results in mice and rats. From the microRNA target filter analysis, TXNIP & miR-128-3p interaction was present in all three MWCNT treatments, and maybe important for the induction of oxidative stress. CXCL-8 & miR-146-5p and Wee1 & miR-128-3p were only present in the cells treated with the parent and the OH-functionalized MWCNTs. These mRNA-miRNA interactions were involved in oxidative stress, inflammation, cell cycle, cholesterol biosynthesis and cancer related pathways. Target filter analysis also showed altered liver hyperplasia/hyperproliferation and hepatic cancer pathways. In short, target filter analysis complemented the transcriptomic analysis and pointed to specific gene/microRNA interactions that can help inform mechanism of action. Moreover, our study showed that the signaling pathways altered in HepG2 cells correlated well with the toxicity and carcinogenicity observed in vivo, indicating that HepG2 may be a good in vitro predictive model for MWCNT toxicity studies., Competing Interests: Declaration of interest: The authors declare that they have no potential conflicts of interest.

Multi-walled Carbon nanotubes (MWCNTs) lack sufficient quality cytotoxicity, toxicity, genotoxicity and genomic data on which to make environmental and regulatory decisions. Therefore, we did a multidisciplinary in vitro study of 3 MWCNTs in human lung cells (BEAS-2B) with the following endpoints: cytotoxicity, DNA damage, reactive oxygen and nitrogen species, lipid peroxidation and mRNA and microRNA expression analyses. The MWCNTs were either unfunctionalized or functionalized with either -OH or -COOH. Doses studied ranged from 0.3 to 100 ug/ml and were exposed to a human lung cell line in vitro for 72 h., with genomic studies being done from 30 ug/ml downward. Some of the genomic pathways that were altered by MWCNT exposure were NRF2 mediated oxidative stress response, DNA damage repair, nuclear excision repair, base excision repair, mitochondrial dysfunction, oxidative phosphorylation, HIF1α signaling, unfolded protein response, protein ubiquitination, ferroptosis and sirtuin signaling pathways. The data suggested that OH functionalized MWCNT caused more and larger gene/microRNA changes, followed by COOH functionalized MWCNT and unfunctionalized MWCNT being the least biologically active. From microRNA target filter analysis, there were altered signaling hubs. MYC is the only hub that altered by all 3 MWCNTs. Signaling hubs that are common to OH and COOH functionalized MWCNTs are GRB2, AR, TP63 and AGO2. The signaling hubs that were only present in OH functionalized MWCNTs are TP53, STAT3 and BRCA1. These signaling pathways and hubs we found in vitro correlated well with the published in vivo pathological effects like oxidative stress DNA damage, inflammation and cancer in MWCNTs treated mice., Competing Interests: Conflicts of interest There are no conflicts to declare.

Introduction: Engaging patients, caregivers, and other stakeholders to help guide the research process is a cornerstone of patient-centered research. Lived expertise may help ensure the relevance of research questions, promote practices that are satisfactory to research participants, improve transparency, and assist with disseminating findings., Methods: Traditionally engagement has been conducted face-to-face in the local communities in which research operates. Decentralized platform trials pose new challenges for the practice of engagement. We used a remote model for stakeholder engagement, relying on Zoom meetings and blog communications., Results: Here we describe the approach used for research partnership with patients, caregivers, and clinicians in the planning and oversight of the ACTIV-6 trial and the impact of this work. We also present suggestions for future remote engagement., Conclusions: The ACTIV-6 experience may inform proposed strategies for future engagement in decentralized trials., Competing Interests: No authors have any conflicts of interest to disclose., (© The Author(s) 2023.)

The objectives of this study were to assess the role of soil organic matter on retaining plastic additives, Di(2-ethylhexyl) phthalate (DEHP), Bisphenol A (BPA) and Benzophenone (BP), to postulate the retention mechanisms and mobility in soil. Batch experiments were conducted for red yellow podzolic soil (OM) and soil subjected to high temperature oxidation at 600 °C for 2 h to remove total organic matter (OMR). Pristine soil, which contains organic matter abbreviated as OM (soil with organic matter) whereas total organic matter removed soil is abbreviated as OMR (organic matter removed soil). The pH edge and kinetic experiments were conducted with 20 g/L soil suspension spiked with 10 mg/L of each additive, whereas 1-20 mg/L concentration range was used in isotherm experiments and analyzed using high performance liquid chromatography. DEHP demonstrated the highest retention, 331 and 615.16 mg/kg in OM and OMR soils respectively, at pH 6.6. However, BPA and BP showed highest retentions of 132 and 128 mg/kg, respectively around pH 4.3 in pristine soil. DEHP interaction with soil OM indicated weak physical bonding whereas chemisorption to OMR soil. In the case of BPA, physisorption governed its interaction with both soil organic matter and mineral fraction. Nevertheless, BP demonstrated chemical interactions with OM and minerals. Desorption of DEHP was close to 100% however, BPA and BP were <15%. Overall, DEHP and BPA could be easily released into soil water and possibly be available for plant uptake while, BP is immobilized in soil., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sammani Ramanayaka reports financial support was provided by Lancaster University, United Kingdom., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In dose-response and structure-activity studies, human hepatic HepG2 cells were exposed for 3 days to nano Cu, nano CuO or CuCl 2 (ions) at doses between 0.1 and 30 ug/ml (approximately the no observable adverse effect level to a high degree of cytotoxicity). Various biochemical parameters were then evaluated to study cytotoxicity, cell growth, hepatic function, and oxidative stress. With nano Cu and nano CuO, few indications of cytotoxicity were observed between 0.1 and 3 ug/ml. In respect to dose, lactate dehydrogenase and aspartate transaminase were the most sensitive cytotoxicity parameters. The next most responsive parameters were alanine aminotransferase, glutathione reductase, glucose 6-phosphate dehydrogenase, and protein concentration. The medium responsive parameters were superoxide dismutase, gamma glutamyltranspeptidase, total bilirubin, and microalbumin. The parameters glutathione peroxidase, glutathione reductase, and protein were all altered by nano Cu and nano CuO but not by CuCl 2 exposures. Our chief observations were (1) significant decreases in glucose 6-phosphate dehydrogenase and glutathione reductase was observed at doses below the doses that show high cytotoxicity, (2) even high cytotoxicity did not induce large changes in some study parameters (e.g., alkaline phosphatase, catalase, microalbumin, total bilirubin, thioredoxin reductase, and triglycerides), (3) even though many significant biochemical effects happen only at doses showing varying degrees of cytotoxicity, it was not clear that cytotoxicity alone caused all of the observed significant biochemical effects, and (4) the decreased glucose 6-phosphate dehydrogenase and glutathione reductase support the view that oxidative stress is a main toxicity pathway of CuCl 2 and Cu-containing nanomaterials., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The objective of this research was to perform a genomics study of five cerium oxide particles, 4 nano and one micrometer-sized particles which have been studied previously by our group with respect to cytotoxicity, biochemistry and metabolomics. Human liver carcinoma HepG2 cells were exposed to between 0.3 to 300 ug/ml of CeO 2 particles for 72 hours and then total RNA was harvested. Fatty acid accumulation was observed with W4, X5, Z7 and less with Q but not Y6. The gene expression changes in the fatty acid metabolism genes correlated the fatty acid accumulation we detected in the prior metabolomics study for the CeO 2 particles named W4, Y6, Z7 and Q, but not for X5. In particular, the observed genomics effects on fatty acid uptake and fatty acid oxidation offer a possible explanation of why many CeO 2 particles increase cellular free fatty acid concentrations in HepG2 cells. The major genomic changes observed in this study were sirtuin, ubiquitination signaling pathways, NRF2-mediated stress response and mitochondrial dysfunction. The sirtuin pathway was affected by many CeO 2 particle treatments. Sirtuin signaling itself is sensitive to oxidative stress state of the cells and may be an important contributor in CeO 2 particle induced fatty acid accumulation. Ubiquitination pathway regulates many protein functions in the cells, including sirtuin signaling, NRF2 mediated stress, and mitochondrial dysfunction pathways. NRF2-mediated stress response and mitochondrial were reported to be altered in many nanoparticles treated cells. All these pathways may contribute to the fatty acid accumulation in the CeO 2 particle treated cells.

Research investigating the desorptive behaviour of PAHs from contaminated soils often overlooked the effects of source materials, especially coal tar and coal tar pitch and materials alike. In this study, a refined experimental approach was adopted to establish a simple-to-complex continuum of systems that allow the investigation of desorption kinetics of benzo(a)pyrene (BaP) and 3 other carcinogenic PAHs (cPAHs) over an incubation period of 48 d. By comparing the modelled desorption parameters, elucidation of the effects of PAH source materials on their desorptive behaviour was achieved. Desorption of cPAHs from coal tar and pitch was enhanced when they were added to soils, with rapidly desorbing fraction (F rap ) of BaP increased from 0.68% for pitch to 1.10% and 2.66% for pitch treated soils, and from 2.57% for coal tar to 6.24% for coal tar treated soil G and 8.76% for coal tar treated sand (1 d). At 1 d, desorption of target cPAHs from solvent and source material spiked soils generally followed the order of solvent > coal tar > pitch. Increases in F rap of cPAHs were observed in coal tar-treated soils after 48 d soil incubation (0.33%-1.16% for soil M, p ≥ 0.05, 6.24%-9.21% for soil G, p < 0.05) and was attributed to the continuous migration of coal tar as a non-aqueous phase liquid (NAPL) into soil pore structures. Slow desorption was dominated by source materials, whereas the extents and rates of rapid desorption (F rap and k rap ) were more controlled by the quantity of soil organic matter (SOM), rather than quality of SOM (as in solvent-spiked soils). The results of this study challenged the role of PAH source materials as 'sinks' and led to the proposed roles of coal tar and pitch and source materials alike as 'reservoirs' with a risk-driven perspective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Citrullination and homocitrullination are stress induced post-translational modifications (siPTMs) which can be recognized by T cells. Peripheral blood mononuclear cells isolated from healthy donors and rheumatoid arthritis (RA) patients were stimulated with nine siPTM-peptides. CD45RA/CD45RO depletion was employed to determine if peptide-specific responses are naïve or memory. Human leucocyte antigen (HLA)-DP4 and HLA-DR4 transgenic mice were immunized with siPTM-peptides and immune responses were determined with ex vivo ELISpot assays. The majority (24 out of 25) of healthy donors showed CD4 T cell-specific proliferation to at least 1 siPTM-peptide, 19 to 2 siPTM-peptides, 14 to 3 siPTM-peptides, 9 to 4 siPTM-peptides, 6 to 5 siPTM-peptides and 4 to 6 siPTM-peptides. More donors responded to Vim28-49cit (68%) and Bip189-208cit (75%) compared with Vim415-433cit (33%). In RA patients, the presentation of citrullinated epitopes is associated with HLA-SE alleles; however, we witnessed responses in healthy donors who did not express the SE allele. The majority of responding T cells were effector memory cells with a Th1/cytotoxic phenotype. Responses to Vim28-49cit and Eno241-260cit originated in the memory pool, while the response to Vim415-433cit was naïve. In the HLA-DP4 and HLA-DR4 transgenic models, Vim28cit generated a memory response. Peptide-specific T cells were capable of Epstein-Barr virus transformed lymphoblastoid cell line recognition suggesting a link with stress due to infection. These results suggest siPTM-peptides are presented under conditions of cellular stress and inflammation and drive cytotoxic CD4 T cell responses that aid in the removal of stressed cells. The presentation of such siPTM-peptides is not restricted to HLA-SE in both humans and animal models., (© 2023 Scancell and The Authors. Immunology published by John Wiley & Sons Ltd.)

Individuals with sickle cell disease are increasingly surviving into adulthood, many of whom have interest in future biological parenthood. Reproductive health knowledge is low among adolescent and young adult males and their caregivers. Their understanding of these topics is needed to optimize their reproductive health outcomes. As such, through collaboration with a community advisory board (adolescents and young adults with sickle cell disease and mothers of adolescent and young adult males with sickle cell disease) and digital design team, we developed a web-based sickle cell disease-focused reproductive health program entitled FUTURES to address these knowledge gaps. For phase I of this two phase feasibility and acceptability study, adolescent and young adult males and their caregivers will complete a pre- and post-program reproductive health knowledge and attitudes questionnaire to assess change in knowledge. In phase II, after learning about fertility testing as part of the FUTURES curriculum, adolescent and young adult male participants are given the option to pursue testing. The two-phase study aims to: 1) develop and test the feasibility, acceptability, and efficacy of a reproductive health web-based educational program at increasing reproductive health knowledge in male adolescent and young adult males with sickle cell disease and their caregivers, and 2) assess feasibility of fertility testing. The long-term goal is to improve reproductive and psychosocial outcomes among adolescent and young adult males with sickle cell disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Colton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The discovery of a new physical process in manganese metal is reported. This process will also be present for all manganese-containing materials in condensed matter. The process was discovered by applying our new technique of XR-HERFD (extended-range high-energy-resolution fluorescence detection), which was developed from the popular high-resolution RIXS (resonant inelastic X-ray scattering) and HERFD approaches. The acquired data are accurate to many hundreds of standard deviations beyond what is regarded as the criterion for `discovery'. Identification and characterization of many-body processes can shed light on the X-ray absorption fine-structure spectra and inform the scientist on how to interpret them, hence leading to the ability to measure the dynamical nanostructures which are observable using the XR-HERFD method. Although the many-body reduction factor has been used universally in X-ray absorption spectroscopy in analysis over the past 30 years (thousands of papers per year), this experimental result proves that many-body effects are not representable by any constant reduction factor parameter. This paradigm change will provide the foundation for many future studies and X-ray spectroscopy., (open access.)

In this study, the biodegradation of phenanthrene was investigated in newly isolated endophytic fungal strains, Fusarium sp. (KTS01), Trichoderma harzianum (LAN03), Fusarium oxysporum (KTS02), Fusarium oxysporum (LAN04), and Clonostachys rosea (KTS05). This was performed under different carbon:nitrogen ratios (10:1, 20:1, and 30:1) using different nitrogen sources (urea and malt extract and ammonium nitrate) over a 30 d incubation period in both static and agitated liquid media. The kinetics of polycyclic aromatic hydrocarbons (PAH) mineralisation to CO 2 (lag phases, fastest rates, and overall extents) were measured for all of the fungal strains and nutrient conditions using 14 C-phenanthrene. All fungal strains were able to biodegrade 14 C-phenanthrene to 14 CO 2 under the different nutrient amendments. However, 14 C-phenanthrene mineralisation varied for most of the fungal strains in static and agitated culture conditions. Greater extents of mineralisation were found in fungal cultures (strains KTS05 and KTS01) with C:N ratio of 10:1 in both static and agitated conditions, while the fungal strains (KTS05 and LAN03) showed the greatest phenanthrene mineralisation after N source amendments, particularly with malt extract. In addition, the phenanthrene mineralisation increased with higher C:N ratios for Clonostachys rosea (KTS05) only. Consequently, the results reported here provide a promising potential for the endophytic fungal strains and the importance of nutrients amendments for the enhanced degradation of PAHs contaminated environments., Competing Interests: Declaration of Competing Interest The authors hereby declare no conflict of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

To increase Soldiers' access to HPV vaccination, we evaluated the feasibility and sustainability of a nurse-led intervention to integrate HPV vaccination into medical processing procedures for Soldiers. We partnered with nursing staff to introduce HPV vaccine into existing vaccination services at a nurse-led clinic that serves Soldiers at Fort Bragg, North Carolina. In addition to stocking the vaccine, the intervention included training nursing staff ( n  = 11) strategies for recommending HPV vaccination for Soldiers ages 18-26. We conducted surveys of nursing staff to assess their perspectives on feasibility. Nursing staff tracked HPV vaccine uptake among Soldiers for 4 weeks post-training to assess adoption and again for 2 weeks at 4-month follow-up to assess sustainability. We assessed delivery cost as the cost of personnel time, vaccine doses, and other materials during the initial 4-week intervention period. Nursing staff agreed that recommending HPV vaccination fit in with medical processing procedures (mean = 4.6 of 5.0). Of the 516 Soldiers offered HPV vaccine in the 4 weeks following the training, 198 (38%) accepted and received the vaccine. Soldier ages 18-20 more often accepted HPV vaccination than older Soldier ages 21-26 (46% versus 32%, p  < .01). Vaccine uptake was similar at follow-up, with 98 of 230 eligible Soldiers (43%) receiving HPV vaccine. The total delivery cost was $12,737, with an average cost per vaccine dose delivered of $64. Our findings suggest that training nursing staff to recommend and administer HPV vaccinations to Soldiers is feasible and warrants wider-scale testing as a strategy to protect soldiers from HPV-attributable cancers.

While implementation and dissemination of research is a rapidly growing area, critical questions remain about how, why, and under what conditions everyday people integrate and utilize research evidence. This mixed-methods study investigates how participants of Promoting Community Conversations About Research to End Suicide (PC CARES) make sense of and use research evidence about suicide prevention in their own lives. PC CARES is a health intervention addressing the need for culturally responsive suicide prevention practices in rural Alaska through a series of community Learning Circles. We analyzed PC CARES transcripts and surveys for 376 participants aged 15+ across 10 Northwest Alaska Native villages. Quantitative analysis showed significant correlations between five utilization of research evidence (URE) factors and participants' intent to use research evidence from PC CARES Learning Circles. Key qualitative themes from Learning Circle transcripts expanded upon these URE constructs and included navigating discordant information, centering relationships, and Indigenous worldviews as key to interpreting research evidence. We integrate and organize our findings to inform two domains from the Consolidated Framework for Research Implementation: (1) intervention characteristics and (2) characteristics of individuals, with emphasis on findings most relevant for community settings where self-determined, evidence-informed action is especially important for addressing health inequities., (© 2022 The Authors. American Journal of Community Psychology published by Wiley Periodicals LLC on behalf of Society for Community Research and Action.)

Background: Public health programs are tasked with educating the community on health topics, but it is unclear whether these programs are acceptable to learners. Currently, these programs are delivered via a variety of platforms including in-person, virtually, and over the telephone. Sickle cell trait (SCT) education for parents of children with this trait is one of many education programs provided by the Ohio Department of Health. The novel SCTaware videoconference education program was developed by a research team after central Ohio's standard program transitioned from in-person to telephone-only education during the COVID-19 pandemic., Objective: Our objectives were to investigate the acceptability of the format and engagement with the SCTaware education and assess parental worry about having a child with SCT before and after receiving SCTaware., Methods: This was a single-center, prospective study of English-speaking parents of children <3 years of age identified to have hemoglobin S trait by newborn screening. Parents who previously received SCT education by telephone, were able to be contacted, and had access to an electronic device capable of videoconferencing were eligible to complete surveys after receiving the virtual SCTaware education program. The SCTaware educator also completed a survey to assess participant engagement. Data were summarized descriptively and a McNemar test was used to compare parental worry before and after receiving SCTaware., Results: In total, 55 participants completed follow-up surveys after receiving standard SCT telephone education and then completing SCTaware. Most (n=51) participants reported that the SCTaware content and visuals were very easy to understand (n=47) and facilitated conversation with the educator (n=42). All of them said the visuals were respectful and trustworthy, helped them understand content better, and that their questions were addressed. Nearly two-thirds (62%, n=34) reported that the pictures appeared very personal and applied to them. The educator noted most participants (n=45) were engaged and asked questions despite having to manage distractions during their education sessions. Many participants (n=33) reported some level of worry following telephone-only education; this was significantly reduced after receiving SCTaware (P<.001)., Conclusions: Our results suggest that SCTaware is acceptable and engaging to parents. While telephone education may make SCT education more accessible, these findings suggest that many parents experience significant worry about their child with SCT after these sessions. A study to evaluate SCTaware's effectiveness at closing parents' SCT knowledge gaps is ongoing., (©Chase M Beeman, Mary Ann Abrams, Kristin N Zajo, Joseph Stanek, Sarah H O'Brien, Peter Chan, Yvette Shen, Ben McCorkle, Latrice Johnson, Deena Chisolm, Toyetta Barnard-Kirk, John D Mahan, Alexandra Martinez-Mendez, Whitney L Phillips, Susan E Creary. Originally published in JMIR Formative Research (https://formative.jmir.org), 17.11.2022.)

Background: Using the theory of planned behavior (TPB), Haegele et al. 1 created the beliefs of individuals with visual impairments about physical activity scale (BIVIPA-1) to examine individuals with visual impairments' (VI) motivation toward physical activity (PA). The overall factorial tenability of the BIVIPA-1 remains unclear due to its item configuration., Objective/hypothesis: The purposes of this cross-sectional study were to: (a) use confirmatory factor analysis to explore the structure of the expanded BIVIPA-2 and (b) test the predictive utility of TPB constructs on PA among adults with VI., Methods: Adults with VI (n = 236) completed the BIVIPA-2 and a multi-item PA recall instrument. A CFA was performed on the BIVIPA-2, and structural equation modeling was used to explore the relationship between theory constructs and PA., Results: The CFA results showed that the underlying structure of BIVIPA-2 was tenable for adults with VI based on TPB. Structural equation modeling showed limited support for the theorized predictive roles of theory variables on PA, as attitude predicted physical activity intention. Interestingly, subjective norm was a direct predictor for PA among adults with VI (β = 0.145)., Conclusions: TPB had limited predictive utility for physical activity among individuals with VI. The predictive relationship of subjective norms on PA may be somewhat unique to this population. Researchers may consider expanding the model to examine social support and subjective norms constructs and PA among individuals with VI., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare. This study received no external funding., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Arterial spin labeling (ASL) is a non-invasive MRI technique that allows for quantitative measurement of cerebral perfusion. Incomplete or inaccurate reporting of acquisition parameters complicates quantification, analysis, and sharing of ASL data, particularly for studies across multiple sites, platforms, and ASL methods. There is a strong need for standardization of ASL data storage, including acquisition metadata. Recently, ASL-BIDS, the BIDS extension for ASL, was developed and released in BIDS 1.5.0. This manuscript provides an overview of the development and design choices of this first ASL-BIDS extension, which is mainly aimed at clinical ASL applications. Discussed are the structure of the ASL data, focussing on storage order of the ASL time series and implementation of calibration approaches, unit scaling, ASL-related BIDS fields, and storage of the labeling plane information. Additionally, an overview of ASL-BIDS compatible conversion and ASL analysis software and ASL example datasets in BIDS format is provided. We anticipate that large-scale adoption of ASL-BIDS will improve the reproducibility of ASL research., (© 2022. The Author(s).)

Numerous harmful chemicals are introduced every year in the environment through anthropogenic and geological activities raising global concerns of their ecotoxicological effects and decontamination strategies. Biochar technology has been recognized as an important pillar for recycling of biomass, contributing to the carbon capture and bioenergy industries, and remediation of contaminated soil, sediments and water. This paper aims to critically review the application potential of biochar with a special focus on the synergistic and antagonistic effects on contaminant-degrading microorganisms in single and mixed-contaminated systems. Owing to the high specific surface area, porous structure, and compatible surface chemistry, biochar can support the proliferation and activity of contaminant-degrading microorganisms. A combination of biochar and microorganisms to remove a variety of contaminants has gained popularity in recent years alongside traditional chemical and physical remediation technologies. The microbial compatibility of biochar can be improved by optimizing the surface parameters so that toxic pollutant release is minimized, biofilm formation is encouraged, and microbial populations are enhanced. Biocompatible biochar thus shows potential in the bioremediation of organic contaminants by harboring microbial populations, releasing contaminant-degrading enzymes, and protecting beneficial microorganisms from immediate toxicity of surrounding contaminants. This review recommends that biochar-microorganism co-deployment holds a great potential for the removal of contaminants thereby reducing the risk of organic contaminants to human and environmental health., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aquatic toxicity posed by the complex mixture of biodegradation metabolites and related oxygen-containing organic compounds (OCOCs) in groundwater at typical petroleum release sites is of concern to regulatory agencies; several are using results from laboratory studies in older literature that are not appropriate analogs for risk management. Recent field studies from typical sites and natural groundwater should be utilized. In this study, OCOCs downgradient of the biodegrading crude oil release at the USGS Bemidji site were tested for freshwater aquatic toxicity using unaltered whole groundwater samples. This type of testing is optimal because the entire mixture of OCOCs present is tested directly and assessment is not affected by analytical limitations. Ceriodaphnia dubia and Pimephales promelas were tested for toxicity using USEPA Methods 1002 and 1000, which estimate chronic toxicity. OCOCs in representative samples up to the maximum concentration tested of 1710 ug/L Total Petroleum Hydrocarbons (TPH) (nC10 to nC40; without silica gel cleanup) did not result in effects relative to the lab control for C. dubia survival, or for P. promelas survival or growth; and did not result in effects above background for C. dubia reproduction. This is consistent with findings using the same testing methods and species on samples from 14 biodegrading fuel release sites: OCOCs did not cause increased toxicity relative to background at a maximum tested concentration of 1800 ug/L TPH (nC10 to nC28). Based on their toxicity testing using the same species and USEPA methods on groundwater from a biodegrading diesel release site, Washington Department of Ecology recently set a freshwater screening level for OCOCs at 3000 ug/L TPH ("Weathered DRO"). These studies indicate that, in the absence of dissolved hydrocarbons, OCOCs in groundwater from typical biodegrading fuel or crude oil releases are not toxic to C. dubia or P. promelas at typical concentrations., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Wood bottom and fly ashes were added to the anaerobic digestate using sulfuric, hydrochloric, nitric, and lactic acids, as pH conditioners and sorption activating agents. Minimum (pH of zero-point charge), mild, and severe acidification of the samples were tested. The solid-liquid separation achieved was accounted visually and with the measurement of the masses of water-soluble extract and water-insoluble material isolated. The average mass of the blend was 36.61 ± 0.68 g, including the extractant agent that was prepared with the commercial acids and ultrapure milli-Q Ⓡ water. During the 144-h incubation of the mixtures at 20 °C and 0.17 x g, the shares of the solid and liquid were determined by centrifugation of the destructive samples at 3,130.40 x g for 5 minutes and 3-µm filtration of the supernatant. Before weighing the water-insoluble material, both the pellet that remained in the tube and the filter cake were dried at 70 °C until reaching constant weight. There was a significant increase in the amount of water-insoluble phase of the wood bottom ash due to the activation with lactic and sulfuric acids. The treatment of the wood fly ash and the agrowaste digestate with the hydrochloric acid showed an increase in the formation of water-soluble extract, in direct relation with the acidic pH of the blend. The characterization of the pH of the WS extract was performed with a Mettler Toledo Ⓡ Seven Compact TM S220 pH/Ion meter. The conditions of this process can be further optimized and each of the fractions can be characterized, in terms of nutrient content, to confirm the efficiency of the separation. More complex and ambitious processes can be designed for combining the wood ash and the anaerobic digestate. The performance of this treatment involving wood ashes and commercial acids can be extrapolated to other type of organic manures with a moisture content of approximately 95%, to improve their management in terms of reducing the cost of storage and transportation for land application below £5 per tonne., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Rapid urbanisation in China has resulted in an increased demand for land in towns and cities. To upgrade and modernise, China has also moved many major industries from urban centres to less populated areas. With the high economic value of urban land, the transformation and utilisation of brownfield areas have become important economically and socially. The Chinese government has recognised the need for strong frameworks to safeguard soil and groundwater quality, with brownfield sites a key category for management. Strong scientific, regulatory and decision-making frameworks are needed and being adopted to ensure practical, careful and wise use of central and localised government resources, to manage the reuse and regeneration of these brownfield sites. This paper reviews the context, policies and management procedures of developing brownfield sites in countries with a history of brownfield management and discusses China's current situation and priorities for brownfield governance and redevelopment. These include (1) clarification of brownfield site soil contamination risk control standards and risk assessment procedures, (2) the responsibilities of different national and local agencies, (3) the establishment of a national expert committee to advise on best practices, policy and process, (4) the use of registered brownfield databases at national, provincial, municipal and county levels, and (5) the set up of soil pollution prevention fund at the provincial level., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Author(s).)

Novel gene-editing (GE) technologies provide promising opportunities to increase livestock productivity and to tackle several global livestock production sustainability and food security challenges. However, these technologies, as with previous genetic modification technologies in food production, are very likely to generate social controversy and opposition toward their use in the meat industry. Here, we explored public attitudes and consumption predisposition toward gene-edited meat products and their potential added benefits to livestock farming. Our results show that societal perception currently comes as a package, where the use of gene-editing technology acts as an extrinsic cue of meat products quality, and is used to make a range of inferences about all quality facets at once. Although consumers with anti-GE attitudinal positions generally were not sensitive to price discounts or added benefits, added benefits increased the consumption predisposition of most moderate and pro-GE consumers, where benefits related to animal welfare had larger effects than those relating to the environment or human health issues., Competing Interests: TB, JC, and TK were employed by AbacusBio International Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martin-Collado, Byrne, Crowley, Kirk, Ripoll and Whitelaw.)

In this study, an investigation was carried out to explore the the impact of white-rot fungi (WRF) on enhancing the development of phenanthrene catabolism in soil over time (1, 25, 50, 75 and 100 d). The WRF were immobilised on spent brewery grains (SBG) prior to inoculation to the soil. The results showed that SBG-immobilised WRF-amended soils reduced the lag phases and increased the extents of 14 C-phenanthrene mineralisation. Greater reductions in the lag phases and increases in the rates of mineralisation were observed in immobilised Trametes versicolor-amended soil compared to the other WRF-amendments. However, the presence of Pleurotus ostreatus and Phanerochaete chrysosporium influenced biodegradation more strongly than the other fungal species. In addition, fungal enzyme activities increased in the amended soils and positively correlated with the extents of 14 C-phenanthrene mineralisation in all soil amendments. Maximum ligninolytic enzyme activities were observed in P. ostreatus-amended soil. Microbial populations increased in all amended soils while PAH-degrading fungal numbers increased with increased soil-PAH contact time and strongly positively correlated with fastest rates of mineralisation. The findings presented in this study demonstrate that inoculating the soil with these immobilised WRFs generally enhanced the mineralisation of the 14 C-phenanthrene in soil. This has the potential to be used to stimulate or enhance PAH catabolism in field-contaminated soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS)., Methods: The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator's ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator's functionality, and ability to support spontaneous breathing., Findings: Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates >825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH 2 O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support., Interpretation: The mechanical ventilator presented meets the MHRA therapy standards for RMVS and, being based on largely available components, can be manufactured at scale., Funding: Work supported by Wellcome/EPSRC Centre for Medical Engineering,King's Together Fund and Oxford University., Competing Interests: Declaration of interests FFo reports grants from the National Institute for Health Research (UK), the National Institute of Academic Anaesthesia, and the Wellcome/EPSRC Centre for Medical Engineering. AF, FFo, SO and MT are volunteering directors of OxVent, a joint-venture social enterprise for mechanical ventilation between Oxford University and King's College London. TD is on the advisory board of OxVent. AAC-P, AF, FFo, MT, PG, SO and TD have shares in OxVent Ltd. AH and CVF are part-time employees of OxVent Ltd., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

There is a strong need for certified reference materials in the quality assurance of nonionic soil contaminant bioavailability estimations through physicochemical methods. We applied desorption extraction, a method recently standardized as ISO16751, to determine the bioavailable concentration of the most commonly regulated polycyclic aromatic hydrocarbon (PAH), benzo(a)pyrene (BaP), in the reference industrial soil BCR-524 with a certified BaP total concentration of 8.60 mg kg -1 . This concentration represented BaP levels found in many PAH-polluted soils. The method, based on single-point extraction of the analyte desorbed into the aqueous phase by a receiving phase (Tenax or cyclodextrin), was applied ten times. The data fulfilled highly demanding quality criteria based on recovery and repeatability. The bioavailable BaP concentration detected through Tenax extraction, 1.82 mg kg -1 , was comparable to bioavailable concentrations determined in field-contaminated soils and to environmental quality standards based on previously observed total BaP concentrations. There was good agreement (Student's t-test, P ≤ 0.05) with the bioavailable BaP concentration determined by cyclodextrin extraction (1.53 mg kg -1 ). The methods were extended to four other certified 4- and 5-ringed PAHs for comparative purposes. We suggest ways of improving of the ISO16751 standard related to further systematic assessment of the Tenax-to-soil ratio and incorporation of mass balances. Furthermore, BCR-524 is suitable for quality-assurance protocols with these methods when used in site-specific risk assessments of PAH-polluted environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Approximately 8% of African Americans born annually have sickle cell trait (SCT), a public health concern that may contribute to health disparities if individuals with SCT do not know it and lack access to understandable information about reproductive implications. Pre-pandemic, Ohio offered in-person SCT education for parents of SCT-affected children but many did not attend. Those with limited health literacy (HL) were less likely to achieve high knowledge. We used a HL-focused evaluation of this education to develop a virtual program (SCTaware) to communicate clear, actionable information and promote knowledge retention., Methods: Seven English-speaking parents, three with limited HL, were recruited in 2019 for in-person session videotaping and SCT knowledge assessments. Clinicians, HL experts, educators, genetic counselors, and parent stakeholders (evaluators) reviewed sessions, assessments, and accompanying visuals., Results: Evaluators: observed parents asked few questions; noted undefined technical terms, closed questions, key concept omission, and limited explanation of visuals scoring low for understandability, actionability, and clarity; and developed SCTaware for individual videoconference delivery (knowledge objectives; plain language guide; HL-informed communication strategies; new visuals scoring highly for understandability, actionability, and clarity; narrated post-education version; standardized educator training)., Conclusions: Using a HL-focused evaluation, our diverse team created a promising virtual SCT education program addressing a common issue affecting populations at risk for disparities. Given virtual education will likely continue post-pandemic and limited HL is common, this approach may be essential and replicable for other public health education programs, especially those transitioning to virtual formats, to convey clear, actionable information and promote health equity.

This paper presents how a community mobilization program to prevent suicide was adapted to an online format to accommodate the impossibility of in-person delivery in Alaska Native communities during the COVID-19 pandemic. The intervention, Promoting Community Conversations About Research to End Suicide (PC CARES), was created collaboratively by researchers and Alaska Native communities with the goal of bringing community members together to create research-informed and community-led suicide prevention activities in their communities. To continue our work during the COVID-19 pandemic and restrictions, we adapted the PC CARES model to a synchronous remote delivery format. This shift included moving from predominantly Alaska Native participants to one of a mainly non-Native school staff audience. This required a pivot from Alaska Native self-determination toward cultural humility and community collaboration for school-based staff, with multilevel youth suicide prevention remaining the primary aim. This reorientation can offer important insight into how to build more responsive programs for those who are not from the communities they serve. Here, we provide a narrative overview of our collaborative adaptation process, illustrated by data collected during synchronous remote facilitation of the program, and reflect on how the shift in format and audience impacted program delivery and content. The adaptation process strove to maintain the core animating features of self-determination for Alaska Native communities and people as well as the translation of scientific knowledge to practice for greater impact.

Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing, and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin. Lineage tracing and in vivo live imaging revealed that repair following acute UVR is predominantly mediated by papillary fibroblast proliferation and fibroblast reorganisation occurs with minimal migration. In contrast, chronic UVR exposure led to a permanent loss of papillary fibroblasts, with expansion of fibroblast membrane protrusions partially compensating for the reduction in cell number. Although UVR strongly activated Wnt signalling in skin, stimulation of fibroblast proliferation by epidermal β-catenin stabilisation did not enhance papillary dermis repair. Acute UVR triggered an infiltrate of neutrophils and T cell subpopulations and increased pro-inflammatory prostaglandin signalling in skin. Depletion of CD4- and CD8-positive cells resulted in increased papillary fibroblast depletion, which correlated with an increase in DNA damage, pro-inflammatory prostaglandins, and reduction in fibroblast proliferation. Conversely, topical COX-2 inhibition prevented fibroblast depletion and neutrophil infiltration after UVR. We conclude that loss of papillary fibroblasts is primarily induced by a deregulated inflammatory response, with infiltrating T cells supporting fibroblast survival upon UVR-induced environmental stress., Competing Interests: ER, GG, TH, KS, TK, KK, PL, VT, NH, SP, IC, NA, LR No competing interests declared, FW FW is on secondment as Executive Chair of the Medical Research Council. The author has no other competing interests to declare, (© 2021, Rognoni et al.)

Discussions on African responses to Covid-19 have focused on the state and its international backers. Far less is known about a wider range of public authorities, including chiefs, humanitarians, criminal gangs, and armed groups. This paper investigates how the pandemic provided opportunities for claims to and contests over power in Uganda, the Democratic Republic of the Congo, and South Sudan. Ethnographic research is used to contend that local forms of public authority can be akin to miniature sovereigns, able to interpret dictates, policies, and advice as required. Alongside coping with existing complex protracted emergencies, many try to advance their own agendas and secure benefits. Those they seek to govern, though, do not passively accept the new normal, instead often challenging those in positions of influence. This paper assesses which of these actions and reactions will have lasting effects on local notions of statehood and argues for a public authorities lens in times of crisis., (© 2021 The Authors Disasters © 2021 Overseas Development Institute.)

Purpose: In this study, we determined ketone oxidation rates in athletes under metabolic conditions of high and low carbohydrate (CHO) and fat availability. Methods: Six healthy male athletes completed 1 h of bicycle ergometer exercise at 75% maximal power (WMax) on three occasions. Prior to exercise, participants consumed 573 mg·kg bw -1 of a ketone ester (KE) containing a 13 C label. To manipulate CHO availability, athletes undertook glycogen depleting exercise followed by isocaloric high-CHO or very-low-CHO diets. To manipulate fat availability, participants were given a continuous infusion of lipid during two visits. Using stable isotope methodology, β-hydroxybutyrate (βHB) oxidation rates were therefore investigated under the following metabolic conditions: (i) high CHO + normal fat (KE+CHO); (ii) high CHO + high fat KE+CHO+FAT); and (iii) low CHO + high fat (KE+FAT). Results: Pre-exercise intramuscular glycogen (IMGLY) was approximately halved in the KE+FAT vs. KE+CHO and KE+CHO+FAT conditions (both p < 0.05). Blood free fatty acids (FFA) and intramuscular long-chain acylcarnitines were significantly greater in the KE+FAT vs. other conditions and in the KE+CHO+FAT vs. KE+CHO conditions before exercise. Following ingestion of the 13 C labeled KE, blood βHB levels increased to ≈4.5 mM before exercise in all conditions. βHB oxidation was modestly greater in the KE+CHO vs. KE+FAT conditions (mean diff. = 0.09 g·min -1 , p = 0.03; d = 0.3), tended to be greater in the KE+CHO+FAT vs. KE+FAT conditions (mean diff. = 0.07 g·min -1 ; p = 0.1; d = 0.3) and were the same in the KE+CHO vs. KE+CHO+FAT conditions ( p < 0.05; d < 0.1). A moderate positive correlation between pre-exercise IMGLY and βHB oxidation rates during exercise was present ( p = 0.04; r = 0.5). Post-exercise intramuscular βHB abundance was markedly elevated in the KE+FAT vs. KE+CHO and KE+CHO+FAT conditions (both, p < 0.001; d = 2.3). Conclusion: βHB oxidation rates during exercise are modestly impaired by low CHO availability, independent of circulating βHB levels., Competing Interests: KC is the director of TΔS Ltd., a spin-out company of the University of Oxford, established to develop and commercialise products based on the BHB monoester used in this study. DD is a current employee of TΔS Ltd and TK and BS are former employees. AB was employed by the company Sterling Pharma Solutions Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dearlove, Holdsworth, Kirk, Hodson, Charidemou, Kvalheim, Stubbs, Beevers, Griffin, Evans, Robertson, Clarke and Cox.)

Anthropogenic chemical pollution has the potential to pose one of the largest environmental threats to humanity, but global understanding of the issue remains fragmented. This article presents a comprehensive perspective of the threat of chemical pollution to humanity, emphasising male fertility, cognitive health and food security. There are serious gaps in our understanding of the scale of the threat and the risks posed by the dispersal, mixture and recombination of chemicals in the wider environment. Although some pollution control measures exist they are often not being adopted at the rate needed to avoid chronic and acute effects on human health now and in coming decades. There is an urgent need for enhanced global awareness and scientific scrutiny of the overall scale of risk posed by chemical usage, dispersal and disposal., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In order to understand toxicity of nano silver, human hepatocellular carcinoma (HepG2) cells were treated either with silver nitrate (AgNO₃) or with nano silver capped with glutathione (Ag-S) at various concentration. Differentially expressed genelists for mRNA and microRNA were obtained through Illumina RNA sequencing and DEseq data analyses. Both treatments showed non-linear dose response relationships for mRNA and microRNA. Gene expression analysis showed signaling pathways common to both nano Ag-S and AgNO₃, such as cell cycle regulation, DNA damage response and cancer related pathways. But, nano Ag-S caused signaling pathway changes that were not altered by AgNO₃ such as NRF2-mediated oxidative stress response inflammation, cell membrane signaling, and cell proliferation. Nano Ag-S also affected p53 signaling, survival, apoptosis, tissue repair, lipid synthesis, angiogenesis, liver fibrosis and tumor development. Several of the pathways affected by nano Ag-S are hypothesized as major contributors to nanotoxicity. MicroRNA target filter analysis revealed additional affected pathways that were not reflected in the mRNA expression response alone, including DNA damage signaling, genomic stability, ROS, cell cycle, ubiquitination, DNA methylation, cell proliferation and fibrosis for AgNO₃; and cell cycle regulation, P53 signaling, cell proliferation, survival, apoptosis, tissue repair and so on for nano Ag-S. These pathways may be mediated by microRNA repression of protein translation.Our study clearly showed that the addition of microRNA profiling increased the numbers of signaling pathways discovered that affected by the treatments on HepG2 cells and gave US a better picture of the effects of these reagents in the cells.

Fibroblasts are the major cell population in the connective tissue of most organs, where they are essential for their structural integrity. They are best known for their role in remodelling the extracellular matrix, however more recently they have been recognised as a functionally highly diverse cell population that constantly responds and adapts to their environment. Biological memory is the process of a sustained altered cellular state and functions in response to a transient or persistent environmental stimulus. While it is well established that fibroblasts retain a memory of their anatomical location, how other environmental stimuli influence fibroblast behaviour and function is less clear. The ability of fibroblasts to respond and memorise different environmental stimuli is essential for tissue development and homeostasis and may become dysregulated in chronic disease conditions such as fibrosis and cancer. Here we summarise the four emerging key areas of fibroblast adaptation: positional, mechanical, inflammatory, and metabolic memory and highlight the underlying mechanisms and their implications in tissue homeostasis and disease.

The concentrations of oxygen-containing organic compounds (OCOC), measured as dissolved organic carbon (DOC), in groundwater exceeds those of dissolved hydrocarbons, measured as total petroleum hydrocarbons (TPH), at a crude oil release site. Orbitrap mass spectrometry was used to characterize OCOC in samples of the oil, water from upgradient of the release, source area, and downgradient wells, and a local lake. Chemical characterization factors included carbon number, oxygen number, formulae similarity, double bond equivalents (DBE) and radiocarbon dating. Oil samples were dominated by formulae with less than 30 carbons, four or fewer oxygens, and a DBE of less than four. In water samples, formulae were identified with more than 30 carbons, more than 10 oxygens, and a DBE exceeding 30. These characteristics are consistent with DOC found in unimpacted water. Between 65% and 92% of the formulae found in samples collected within the elevated OCOC plume were also found in the upgradient or surface water samples. Evidence suggests that many of the OCOC are not petroleum degradation intermediates, but microbial products generated as a result of de novo synthesis by organisms growing on carbon supplied by the oil. Implications of these results for understanding the fate and managing the risk of hydrocarbons in the subsurface are discussed., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

With the advancement of nanotechnology, nanoparticles are widely used in many different industrial processes and consumer products. Copper nanoparticles (Cu NPs) are among the most toxic nanomaterials. We investigated Cu NPs toxicity in Human Hepatocellular carcinoma (HepG2) cells by examining signaling pathways, and microRNA/mRNA interactions. We compared the effects of exposures to Cu NPs at various concentrations and CuCl₂ was used as a control. The number of differentially expressed mRNA did not follow a linear dose-response relationship for either Cu NPs or CuCl₂ treatments. The most significantly altered genes and pathways by Cu NPs exposure were NRF2 (nuclear factor erythroid 2 related factor 2)-mediated oxidative stress response, protein ubiquitination, Tumor protein p53 (p53), phase I and II metabolizing enzymes, antioxidant proteins and phase III detoxifying gene pathways.Messenger RNA-microRNA interaction from MicroRNA Target Filter Analyses revealed more signaling pathways altered in Cu NPs treated samples than transcriptomics alone, including cell proliferation, DNA methylation, endoplasmic reticulum (ER) stress, apoptosis, autophagy, reactive oxygen species, inflammation, tumorigenesis, extracellular matrix/angiogenesis and protein synthesis. In contrast, in the control (CuCl₂) treated samples showed mostly changes in inflammation mainly through regulation of the Nuclear Factor Kappa-light-chain-enhancer of Activated B-cells (NF κ B). Further, some RNA based parameters that showed promise as biomarkers of Cu NPs exposure including both well and lesser known genes: heme oxygenase 1 (HMOX1), heat shock protein, c-Fos proto-oncogene, DNA methyltransferases, and glutamate-cysteine ligase modifier subunit (GCLM, part of the glutathione synthesis pathway). The differences in signaling pathways altered by the Cu NPs and CuCl₂ treatments suggest that the effects of the Cu NPs were not the results of nanomaterial dissolution to soluble copper ions.

Unequivocal functional assessment of candidate genomic regulatory regions, such as transcriptional response elements, requires genetic alteration at their native chromosomal loci. Targeted DNA cleavage by Cas9 or other programmable nucleases enables analysis at virtually any genomic region, and diverse alleles generated by editing can be defined by deep sequencing for functional analysis. Interpretation of disrupted response elements, however, presents a special challenge, as these regions typically comprise clustered DNA binding motifs for multiple transcriptional regulatory factors (TFs); DNA sequence differences, natural or engineered, that affect binding by one TF can confer loss or gain of binding sites for other TFs. To address these and other analytical complexities, we created three computational tools that together integrate, in a single experiment, allele definition and TF binding motif evaluation for up to 9216 clones isolated, sequenced and propagated from Cas9-treated cell populations. We demonstrate 1) the capacity to functionally assess edited TF binding sites to query response element function, and 2) the efficacy and utility of these tools, by analyzing cell populations targeted by Cas9 for disruption of example glucocorticoid receptor (GR) binding motifs near FKBP5, a GR-regulated gene in the human adenocarcinoma cell line A549., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: The primary purpose of this study was to examine physical activity, nutritional intake, and psychological well-being differences between youth with visual impairments and their siblings residing in the same household. A secondary purpose was to examine the relationship between physical activity behavior and psychological well-being among youth with visual impairments., Materials and Methods: A sample of 22 dyads of youth with visual impairments and siblings completed this study. Data were collected through parent-reported demographic and psychological well-being questionnaires, nutritional intake questionnaires, and accelerometry. Data were analyzed descriptively and inferentially, examining proportion difference using McNemar's z -test, and mean differences using multivariate analyses of variance., Results: Siblings without visual impairments had higher but not significantly higher daily average moderate-to-vigorous physical activity ( d  = 0.46), significantly higher prosocial score ( d  = 0.63), and lower but not significantly lower difficulty scores ( d  = 0.39), than youth with visual impairments. Small, not statistically significant, nutritional intake differences between siblings were found., Conclusions: Differences in physical activity and nutritional habits between those with visual impairments and their siblings were not significant, supporting the environmentally driven nature of these variables. Associations between physical activity and well-being were not apparent in this study but may be partially explained by low participant physical activity.Implications for RehabilitationYouth with visual impairments and the siblings may be influenced by the same familial factors and molded in a similar fashion by parenting behaviors regarding health-related behaviors.In this study, youth with visual impairments engaged in similar physical activity and nutritional behaviors to their siblings without visual impairments.Efforts to improve health-related behaviors among those with visual impairments may be most effective at the family level.Small subsets of youth with visual impairments gain mental health benefits from physical activity engagement.

Trace-level plutonium in the environment often comprises local and global contributions, and is usually anthropogenic in origin. Here, we report estimates of local and global contributions to trace-level plutonium in soil from a former, fast-breeder reactor site. The measured 240 Pu/ 239 Pu ratio is anomalously low, as per the reduced 240 Pu yield expected in plutonium bred with fast neutrons. Anomalies in plutonium concentration and isotopic ratio suggest forensic insight into specific activities on site, such as clean-up or structural change. Local and global 239 Pu contributions on-site are estimated at (34 ± 1)% and (66 ± 3)%, respectively, with mass concentrations of (183 ± 6) fg g -1 and (362 ± 13) fg g -1 . The latter is consistent with levels at undisturbed and distant sites, (384 ± 44) fg g -1 , where no local contribution is expected. The 240 Pu/ 239 Pu ratio for site-derived material is estimated at 0.05 ± 0.04. Our study demonstrates the multi-faceted potential of trace plutonium assay to inform clean-up strategies of fast breeder legacies.