| 1. |
- Adewoye, AB, et al.
(författare)
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Human CCL3L1 copy number variation, gene expression, and the role of the CCL3L1-CCR5 axis in lung function
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3, s. 13-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The CCL3L1-CCR5 signaling axis is important in a number of inflammatory responses, including macrophage function, and T-cell-dependent immune responses. Small molecule CCR5 antagonists exist, including the approved antiretroviral drug maraviroc, and therapeutic monoclonal antibodies are in development. Repositioning of drugs and targets into new disease areas can accelerate the availability of new therapies and substantially reduce costs. As it has been shown that drug targets with genetic evidence supporting their involvement in the disease are more likely to be successful in clinical development, using genetic association studies to identify new target repurposing opportunities could be fruitful. Here we investigate the potential of perturbation of the CCL3L1-CCR5 axis as treatment for respiratory disease. Europeans typically carry between 0 and 5 copies of CCL3L1 and this multi-allelic variation is not detected by widely used genome-wide single nucleotide polymorphism studies. Methods: We directly measured the complex structural variation of CCL3L1 using the Paralogue Ratio Test and imputed (with validation) CCR5d32 genotypes in 5,000 individuals from UK Biobank, selected from the extremes of the lung function distribution, and analysed DNA and RNAseq data for CCL3L1 from the 1000 Genomes Project. Results: We confirmed the gene dosage effect of CCL3L1 copy number on CCL3L1 mRNA expression levels. We found no evidence for association of CCL3L1 copy number or CCR5d32 genotype with lung function. Conclusions: These results suggest that repositioning CCR5 antagonists is unlikely to be successful for the treatment of airflow obstruction.
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| 2. |
- Ahmad, MS, et al.
(författare)
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A patient satisfaction survey and educational package to improve the care of people hospitalised with COVID-19: a quality improvement project, Liverpool, UK
- 2021
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 6, s. 222-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The perspectives and experiences of people hospitalised with COVID-19 have been under-reported during the coronavirus pandemic. We developed and conducted a COVID-19 patient satisfaction survey in a large university-affiliated secondary healthcare centre in Liverpool, UK, during Europe’s first coronavirus wave (April-June 2020). The survey found that care was rated highly, including among people of Black Asian and Minority Ethnic (BAME) backgrounds. However, sleep-quality and communication about medications and discharge-planning were identified as areas for improvement. Methods: To improve care for people with COVID-19 admitted to our centre, we designed an educational package for healthcare professionals working on COVID-19 wards. The package, implemented in August 2020, included healthcare worker training sessions on providing holistic care and placement of “Practice Pointers” posters. Patient satisfaction was re-evaluated during the second/third COVID-19 waves in Liverpool (September 2020 - February 2021). Results: Across waves, most (95%) respondents reported that they would recommend our hospital to friends and/or family and rated overall care highly. Comparison of the responses of second/third-wave respondents (n=101) with first-wave respondents (n=94) suggested improved patient satisfaction across most care domains but especially those related to having worries and fears addressed and being consulted about medications and their side-effects. Conclusions: People admitted with COVID-19 to our centre in Liverpool, including those from BAME backgrounds, rated the care they received highly. A simple education package improved the feedback on care received by respondents between the first and second/third waves. These UK-first findings are informing regional strategies to improve person-centred care of hospitalised people with COVID-19.
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| 3. |
- Austin, CC, et al.
(författare)
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Fostering global data sharing: highlighting the recommendations of the Research Data Alliance COVID-19 working group
- 2020
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 5, s. 267-
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Tidskriftsartikel (refereegranskat)abstract
- The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research. These guidelines include recommendations for clinicians, researchers, policy- and decision-makers, funders, publishers, public health experts, disaster preparedness and response experts, infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations), and other potential users. These guidelines include recommendations for researchers, policymakers, funders, publishers and infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations). Several overarching themes have emerged from this document such as the need to balance the creation of data adherent to FAIR principles (findable, accessible, interoperable and reusable), with the need for quick data release; the use of trustworthy research data repositories; the use of well-annotated data with meaningful metadata; and practices of documenting methods and software. The resulting document marks an unprecedented cross-disciplinary, cross-sectoral, and cross-jurisdictional effort authored by over 160 experts from around the globe. This letter summarises key points of the Recommendations and Guidelines, highlights the relevant findings, shines a spotlight on the process, and suggests how these developments can be leveraged by the wider scientific community.
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| 4. |
- Birgersson, Sofia, 1976, et al.
(författare)
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Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: An open label trial [version 2; peer review: 2 approved]
- 2020
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach. Methods: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated P. falciparum malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling. Results: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete in vivo conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver enzyme levels (alanine aminotransferase) were found to affect the relative bioavailability of artesunate. Conclusions: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development especially in low transmission settings where relative immunity is lower. Trial registration: ClinicalTrials.gov NCT00701961 (19/06/2008). © 2020 Birgersson S et al.
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| 5. |
- Carlsson, Camilla, 1993, et al.
(författare)
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A protocol for a systematic review and meta-analysis of tuberculosis care around the time of pregnancy
- 2024
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Ingår i: Wellcome Open Research. - 2398-502X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tuberculosis is estimated to cause 1.5 million deaths annually and is most common during the reproductive years. Despite that fact, we found that tuberculosis screening, prevention or care recommendations for people around the time of pregnancy were absent from some national policy recommendations and varied in others. Objectives: To address the apparent gaps and inconsistencies in policy, we aim to design a systematic review and meta-analysis of the original research evidence informing tuberculosis care around the time of pregnancy. Methods: With assistance from librarians at the Biomedical library of the University of Gothenburg, Pubmed, CINAHL and Scopus databases will be searched. Search terms will aim to identify studies generating original research evidence informing care for tuberculosis around the time of pregnancy. Evidence may include: the outcome of TB and/or of pregnancy; the cost-effectiveness or acceptability of any intervention; the sensitivity and specificity of any assessment, selection, diagnostic or test criterion. The output from these literature searches will be screened by two independent reviewers to select the eligible studies for inclusion. Discrepancies will be resolved with a third reviewer. Firstly, publications that provide contextual data will be tabulated, summarising their main contributions. Secondly, studies that provide evidence directly guiding patient care will be our focus and will be considered to be key. The key studies will be subject to quality assessment, data extraction and when possible, meta-analysis. Conclusions: This systematic review and meta-analysis aims to guide policy, practice and future research priorities concerning tuberculosis care around the time of pregnancy.
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| 6. |
- Dixit, K, et al.
(författare)
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Research protocol for a mixed-methods study to characterise and address the socioeconomic impact of accessing TB diagnosis and care in Nepal
- 2020
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 5, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- Background: WHO’s 2015 End TB Strategy advocates social and economic (socioeconomic) support for TB-affected households to improve TB control. However, evidence concerning socioeconomic support for TB-affected households remains limited, especially in low-income countries. Protocol: This mixed-methods study in Nepal will: evaluate the socioeconomic impact of accessing TB diagnosis and care (Project 1); and create a shortlist of feasible, locally-appropriate interventions to mitigate this impact (Project 2). The study will be conducted in the Chitwan, Mahottari, Makawanpur, and Dhanusha districts of Nepal, which have frequent TB and poverty. The study population will include: approximately 200 people with TB (Cases) starting TB treatment with Nepal’s National TB Program and 100 randomly-selected people without TB (Controls) in the same sites (Project 1); and approximately 40 key in-country stakeholders from Nepal including people with TB, community leaders, and TB healthcare professionals (Project 2). During Project 1, visits will be made to people with TB’s households during months 3 and 6 of TB treatment, and a single visit made to Control households. During visits, participants will be asked about: TB-related costs (if receiving treatment), food insecurity, stigma; TB-related knowledge; household poverty level; social capital; and quality of life. During Project 2, stakeholders will be invited to participate in: a survey and focus group discussion (FGD) to characterise socioeconomic impact, barriers and facilitators to accessing and engaging with TB care in Nepal; and a one-day workshop to review FGD findings and suggest interventions to mitigate the barriers identified. Ethics and dissemination: The study has received ethical approval. Results will be disseminated through scientific meetings, open access publications, and a national workshop in Nepal. Conclusions: This research will strengthen understanding of the socioeconomic impact of TB in Nepal and generate a shortlist of feasible and locally-appropriate socioeconomic interventions for TB-affected households for trial evaluation.
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| 7. |
- Dodhia, Serena A., et al.
(författare)
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Examining the causal association between 25-hydroxyvitamin D and caries in children and adults : A two-sample Mendelian randomization approach
- 2021
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a two-sample MR approach which estimates the causal effect of an exposure on an outcome.Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years).Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68)Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence for a causal relationship between 25(OH)D and dental caries.
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| 8. |
- Fuady, A, et al.
(författare)
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Characterising and Addressing the Psychosocial Impact of Tuberculosis in Indonesia (CAPITA): A study protocol
- 2022
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 7, s. 42-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tuberculosis (TB)-related stigma remains a key barrier for people with TB to access and engage with TB services and can contribute to the development of mental illnesses. This study aims to characterise stigmatisation towards people with TB and its psychosocial impact in Indonesia. Methods: This study will apply a sequential mixed method in two main settings: TB services-based population (setting 1) and workplace-based population (setting 2). In setting 1, we will interview 770 adults with TB who undergo sensitive-drug TB treatment in seven provinces of Indonesia. The interview will use the validated TB Stigma Scale questionnaire, Patient Health Questionnaire-9, and EQ-5D-5L to assess stigma, mental illness, and quality of life. In Setting 2, we will deploy an online questionnaire to 640 adult employees in 12 public and private companies. The quantitative data will be followed by in-depth interview to TB-related stakeholders. Results: CAPITA will not only characterise the enacted stigma which are directly experienced by people with TB, but also self-stigma felt by people with TB, secondary stigma faced by their family members, and structural stigma related to the law and policy. The qualitative analyses will strengthen the quantitative findings to formulate the potential policy direction for zero TB stigma in health service facilities and workplaces. Involving all stakeholders, i.e., people with TB, healthcare workers, National Tuberculosis Program officers, The Ministry of Health Workforce, company managers, and employees, will enhance the policy formulation. The validated tool to measure TB-related stigma will also be promoted for scaling up to be implemented at the national level. Conclusions: To improve patient-centered TB control strategy policy, it is essential to characterise and address TB-related stigma and mental illness and explore the needs for psychosocial support for an effective intervention to mitigate the psychosocial impact of TB.
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| 9. |
- Hayward, Alex, et al.
(författare)
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The genome sequence of the Brown Argus, Aricia agestis (Denis & Schiffermüller, 1775)
- 2023
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Ingår i: Wellcome Open Research. - 2398-502X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- We present genome assemblies from two male Aricia agestis specimens (the Brown Argus; Arthropoda; Insecta; Lepidoptera; Lycaenidae). The genome sequences are 435.3 and 437.4 megabases in span. Each assembly is scaffolded into 23 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genomes were assembled and are 15.47 and 15.45 kilobases in length. Gene annotation of these assemblies on Ensembl identified 12,688 and 12,654 protein coding genes.
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| 10. |
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