cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4270112.v1
title: New draft item

description: <b><i>Background:</i></b> Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). <b><i>Methods:</i></b> First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. <b><i>Results:</i></b> In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. <b><i>Conclusion:</i></b> This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.
DOI: 10.6084/m9.figshare.4270097
title: Supplementary Material for: Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis

description: <b><i>Background:</i></b> There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. <b><i>Methods:</i></b> The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. <b><i>Results:</i></b> There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for <i>RORC1</i> and <i>RORC2</i> in SSc, particularly in patients with high inflammatory activity. <b><i>Conclusions:</i></b> Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.
DOI: 10.6084/m9.figshare.4270097.v1
title: Supplementary Material for: Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis

description: <b><i>Background:</i></b> There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. <b><i>Methods:</i></b> The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. <b><i>Results:</i></b> There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for <i>RORC1</i> and <i>RORC2</i> in SSc, particularly in patients with high inflammatory activity. <b><i>Conclusions:</i></b> Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.
DOI: 10.6084/m9.figshare.4270082
title: Supplementary Material for: Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease

description: <b><i>Background:</i></b> Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during <i>Trypanosoma cruzi </i>(<i>Tc</i>) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. <b><i>Methods:</i></b> MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with <i>Tc </i>(control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs. normal/healthy [NH] controls), and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of mφ activation by flow cytometry, cytokine profile by means of an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by means of colorimetric and fluorometric assays. <b><i>Results:</i></b><i>Tc</i>- and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile, and nitric oxide (<b>∙</b>NO) release in human THP-1 mφs. LPS-MPs were more immunostimulatory than <i>Tc</i>-MPs. Endothelial cells, T lymphocytes, and mφs were the major source of MPs shed in the plasma of chagasic humans and experimentally infected mice. The CS and CA (vs. NH) MPs elicited &gt;2-fold increase in NO and mitochondrial oxidative stress in THP-1 mφs; however, CS (vs. CA) MPs elicited a more pronounced and disease-state-specific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2, and CCL3), cytokine release (IL-2 + IFN-γ &gt; GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of nonvaccinated/infected mice induced 7.5-fold and 40% increases in <b>∙</b>NO and IFN-γ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. <b><i>Conclusion:</i></b> Circulating MPs reflect in vivo levels of an oxidative, nitrosative, and inflammatory state, and have potential utility in evaluating disease severity and the efficacy of vaccines and drug therapies against CCM.
DOI: 10.6084/m9.figshare.4270085
title: rear_soiling_mechanism.emf

description: Schematic of rear surface self-soiling for an SUV in an XZ plane behind a rear tyre.
DOI: 10.6084/m9.figshare.4270079
title: AGPathFinder_data

description: The data and program for AGPathFinder
DOI: 10.6084/m9.figshare.4270037
title: Seasonal fish abundance and seagrass cover data, Zanzibar, Tanzania 2014-2015

description: We conducted a field survey in four sites around Unguja Island (Zanzibar, Tanzania): two no-take MPAs (Chumbe and Mnemba Islands) and two unprotected, fished sites (Changuu island and Mnemba reef).The study was conducted during three seasons in 2014-2015: November-December 2014, April-May 2015 and July-August 2015. Sampling was carried out in sub-tidal seagrass beds dominated by <i>Thalassodendron ciliatum.</i>At each site, fish and seagrass sampling was conducted in 10 replicate transects (except in one of the MPAs, where only 7 transects could be sampled due to the limited size of the protected seagrass bed), which were randomly placed &gt; 5 m apart and parallel to the shore. The surveys were carried out during high neap tide (± 3 h) through underwater visual census by snorkelling along 25×4 m belt transects. A snorkeler swam the transects twice during approx. 10 min. All fish observed within or crossing the transect were counted, identified to the lowest taxonomic level possible (usually species), and their body length was visually estimated to the nearest 5 cm. Based on the estimated sizes, all individual fish were then grouped into three age classes (juveniles, subadults and adults). The bottom per cent cover of seagrass was visually estimated within 0.25 m² quadrates placed at 5 m intervals along each transect (resulting in six subsamples per transect).
DOI: 10.6084/m9.figshare.4270079.v1
title: AGPathFinder_data

description: The data and program for AGPathFinder
DOI: 10.6084/m9.figshare.4270013
title: Medicinal plant databse of Baitadi and Darchula districts, Far West Nepal

description: Database of medicinal plants of Darchula, Baitadi districts<br>
DOI: 10.6084/m9.figshare.4270013.v2
title: Medicinal plant databse of Baitadi and Darchula districts, Far West Nepal

description: Database of medicinal plants of Darchula, Baitadi districts<br>
DOI: 10.6084/m9.figshare.4270013.v1
title: Supplementary.Table.docx

description: Database of medicinal plants of Darchula, Baitadi districts<br>
DOI: 10.6084/m9.figshare.4269962
title: simtegr8

description: The purposes of the SIMTEGR8 project are to evaluate how emergency admissions to hospitals can be reduced andhelp improve the patient journey through new integrated interventions. The objectives of this study are to: 1. Evaluate the current interventions to identify the critical points (touchpoints, handoffs and failure demand) for the patient journey.2. Provide Innovation and testing of some new models of thinking and metrics that could be implemented to align transformation of health and social care related to patient journey experience.3. Influence policy nationally by building an evidence base and online application to inform the design of future service delivery. The 1-year project will form an important piece of work that will contribute to the ongoing evaluation of the impact of the Better Care Fund programme. A robust evaluation of the impact of new integrated care interventions on admissions to hospital will provide important evidence to inform the future health and care commissioning plans.
DOI: 10.6084/m9.figshare.4269962.v1
title: simtegr8 website

description: The purposes of the SIMTEGR8 project are to evaluate how emergency admissions to hospitals can be reduced andhelp improve the patient journey through new integrated interventions. The objectives of this study are to: 1. Evaluate the current interventions to identify the critical points (touchpoints, handoffs and failure demand) for the patient journey.2. Provide Innovation and testing of some new models of thinking and metrics that could be implemented to align transformation of health and social care related to patient journey experience.3. Influence policy nationally by building an evidence base and online application to inform the design of future service delivery. The 1-year project will form an important piece of work that will contribute to the ongoing evaluation of the impact of the Better Care Fund programme. A robust evaluation of the impact of new integrated care interventions on admissions to hospital will provide important evidence to inform the future health and care commissioning plans.
DOI: 10.6084/m9.figshare.4269962.v2
title: simtegr8

description: The purposes of the SIMTEGR8 project are to evaluate how emergency admissions to hospitals can be reduced andhelp improve the patient journey through new integrated interventions. The objectives of this study are to: 1. Evaluate the current interventions to identify the critical points (touchpoints, handoffs and failure demand) for the patient journey.2. Provide Innovation and testing of some new models of thinking and metrics that could be implemented to align transformation of health and social care related to patient journey experience.3. Influence policy nationally by building an evidence base and online application to inform the design of future service delivery. The 1-year project will form an important piece of work that will contribute to the ongoing evaluation of the impact of the Better Care Fund programme. A robust evaluation of the impact of new integrated care interventions on admissions to hospital will provide important evidence to inform the future health and care commissioning plans.
DOI: 10.6084/m9.figshare.4269926
title: Sparrowhawk wing CT images

description: CT images of a wing (left) of an adult female sparrowhawk (Accipiter nisus) scanned with a Nikon XTEK XTH 225 kV µCT system (80 kV, 100 µA, 0.25 mm aluminium filter, 25 µm/voxel of resolution ) at the Henry Moseley X-ray Imaging Facility, University of Manchester. Before the scan, the wing was treated with an ~3% iodine-based formalin buffered solution for enhancing the contrast of soft tissue (Li et al., 2015).
DOI: 10.6084/m9.figshare.4269887
title: Adherence to antiretroviral therapy (biomarker and self reported data) in East Zimbabwe.

description: This data is an accompaniment to the journal article 'Might ART Adherence Estimates Be Improved by Combining Biomarker and Self-Report Data?' (Rhead et al. 2016) Abstract: As we endeavour to examine rates of viral suppression in PLHIV, reliable data on ART adherence are needed to distinguish between the respective contributions of poor adherence and treatment failure on high viral load. Self-reported data are susceptible to response bias and although biomarker data on drug presence and concentration can provide a superior, alternative method of measurement, complications due to drug-drug interactions and genetic variations can cause some inaccuracies. We investigate the feasibility of combining both biomarker and self-report data to produce a potentially more accurate measure of ART adherence. Data were taken from a large general-population survey in the Manicaland province, Zimbabwe, conducted in 2009-2011. HIV-infected adults who had initiated ART (N=560) provided self-report data on adherence and dried blood spot samples that were analysed for traces of ART medication. Using this data, new three-category measure of ART adherence was constructed, based on biomarker data but using self-report data to adjust for cases with abnormally low and high drug concentrations due to possible drug-drug interactions and genetic factors, and was assessed for plausibility using survey data on socio-demographic correlates.<br>The Manicaland Centre is a major collaborative scientific HIV/STD Prevention research initiative that has been underway in rural areas of eastern Zimbabwe since the early 1990s. The principal collaborating institutions in the project are the Biomedical Research and Training Institute in Harare and Imperial College London. We also have joint research projects with people from the London School of Hygiene and Tropical Medicine and the University of Copenhagen. The Manicaland Project has one of the largest prospective population-based surveys in Africa. This has allowed us to uniquely track trends in the spread, impact and control of the epidemic in Zimbabwe. Using quantitative, qualitative and mathematical modelling methods to describe and interpret trends in the HIV epidemic in eastern Zimbabwe, the Project has contributed significantly to our understanding of the HIV epidemic in Africa.<br><br>
DOI: 10.6084/m9.figshare.4269833
title: Echocardiographic longitudinal function in English springer spaniels dataset

description: Dataset of echocardiographic longitudinal assessments in English springer spaniels<br>
DOI: 10.6084/m9.figshare.4269887.v1
title: Adherence to antiretroviral therapy (biomarker and self reported data) in East Zimbabwe.

description: This data is an accompaniment to the journal article 'Might ART Adherence Estimates Be Improved by Combining Biomarker and Self-Report Data?' (Rhead et al. 2016) Abstract: As we endeavour to examine rates of viral suppression in PLHIV, reliable data on ART adherence are needed to distinguish between the respective contributions of poor adherence and treatment failure on high viral load. Self-reported data are susceptible to response bias and although biomarker data on drug presence and concentration can provide a superior, alternative method of measurement, complications due to drug-drug interactions and genetic variations can cause some inaccuracies. We investigate the feasibility of combining both biomarker and self-report data to produce a potentially more accurate measure of ART adherence. Data were taken from a large general-population survey in the Manicaland province, Zimbabwe, conducted in 2009-2011. HIV-infected adults who had initiated ART (N=560) provided self-report data on adherence and dried blood spot samples that were analysed for traces of ART medication. Using this data, new three-category measure of ART adherence was constructed, based on biomarker data but using self-report data to adjust for cases with abnormally low and high drug concentrations due to possible drug-drug interactions and genetic factors, and was assessed for plausibility using survey data on socio-demographic correlates.<br>The Manicaland Centre is a major collaborative scientific HIV/STD Prevention research initiative that has been underway in rural areas of eastern Zimbabwe since the early 1990s. The principal collaborating institutions in the project are the Biomedical Research and Training Institute in Harare and Imperial College London. We also have joint research projects with people from the London School of Hygiene and Tropical Medicine and the University of Copenhagen. The Manicaland Project has one of the largest prospective population-based surveys in Africa. This has allowed us to uniquely track trends in the spread, impact and control of the epidemic in Zimbabwe. Using quantitative, qualitative and mathematical modelling methods to describe and interpret trends in the HIV epidemic in eastern Zimbabwe, the Project has contributed significantly to our understanding of the HIV epidemic in Africa.<br><br>
DOI: 10.6084/m9.figshare.4269827
title: The data for Metabolic pathway alignment tool MPBR.

description: The data for Metabolic pathway alignment tool MPBR.
DOI: 10.6084/m9.figshare.4269833.v1
title: ESS Longitudinal function dataset

description: Dataset of echocardiographic longitudinal assessments in English springer spaniels<br>
DOI: 10.6084/m9.figshare.4269827.v2
title: The data for Metabolic pathway alignment tool MPBR.

description: The data for Metabolic pathway alignment tool MPBR.
DOI: 10.6084/m9.figshare.4269827.v1
title: MPBR_data.zip

description: The data for Metabolic pathway alignment tool MPBR
DOI: 10.6084/m9.figshare.4269806
title: Characterization of genetic loss-of-function of Fus in zebrafish

description: The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted <i>fus</i> in zebrafish (<i>Danio rerio</i>) using the CRISPR-Cas9 system. The <i>fus</i> knockout animals are fertile and did not show any distinctive phenotype. Mutation of <i>fus</i> induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3′UTR usage, which could mask the effects of loss of Fus. Unlike published <i>fus</i> morphants, maternal zygotic <i>fus</i> mutants do not show motoneuronal degeneration and exhibit normal locomotor activity.
DOI: 10.6084/m9.figshare.4269806.v1
title: Characterization of genetic loss-of-function of Fus in zebrafish

description: The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted <i>fus</i> in zebrafish (<i>Danio rerio</i>) using the CRISPR-Cas9 system. The <i>fus</i> knockout animals are fertile and did not show any distinctive phenotype. Mutation of <i>fus</i> induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3′UTR usage, which could mask the effects of loss of Fus. Unlike published <i>fus</i> morphants, maternal zygotic <i>fus</i> mutants do not show motoneuronal degeneration and exhibit normal locomotor activity.
DOI: 10.6084/m9.figshare.4269782
title: Pregestational type 2 diabetes and gestational diabetes exhibit different sexual steroid profiles during pregnancy

description: Higher androgen levels are observed in non-pregnant women with diabetes. Whether this hormonal profile is found during pregnancy is unknown. The aim of this study was to determine the sexual steroids levels in pregnant women with pregestational type 2 (T2D) and gestational diabetes (GD) compared to healthy control (C) pregnant women during the second half of pregnancy. A prospective study of 69 pregnant women with T2D (<i>n</i> = 21), GD (<i>n =</i> 24) and control (C, <i>n</i> = 24) was followed up during the second half of gestation. Clinical assessments and blood samples were collected at 26.7 (25–27.8); 34 (32–34.9) and 37.5 (37–40) weeks of gestation. Androgens, sex hormone-binding globulin (SHBG), estrogens, estradiol/testosterone (E/T) ratio, insulin, glucose, HOMA-IR, were measured. Testosterone, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels were higher in T2D compared with C at each sampling point during pregnancy, even after adjusting for BMI and age. Estrogens levels and estradiol/testosterone ratio were lower in T2D and GD compared with C. Hyperandrogenemia, and higher insulin resistance is observed in T2D, but not in GD during pregnancy. Decreased estrogen and E/T ratio found in T2D and GD suggests a diminished aromatase activity during gestation. T2D and GD are associated with specific changes in sexual steroids and insulin resistance levels during pregnancy.