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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
- de Jager, Vincent D., et al.
(författare)
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Developments in predictive biomarker testing and targeted therapy in advanced stage non-small cell lung cancer and their application across European countries
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 38
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Forskningsöversikt (refereegranskat)abstract
- In the past two decades, the treatment of metastatic non-small cell lung cancer (NSCLC), has undergone significant changes due to the introduction of targeted therapies and immunotherapy. These advancements have led to the need for predictive molecular tests to identify patients eligible for targeted therapy. This review provides an overview of the development and current application of targeted therapies and predictive biomarker testing in European patients with advanced stage NSCLC. Using data from eleven European countries, we conclude that recommendations for predictive testing are incorporated in national guidelines across Europe, although there are differences in their comprehensiveness. Moreover, the availability of recently EMA-approved targeted therapies varies between European countries. Unfortunately, routine assessment of national/regional molecular testing rates is limited. As a result, it remains uncertain which proportion of patients with metastatic NSCLC in Europe receive adequate predictive biomarker testing. Lastly, Molecular Tumor Boards (MTBs) for discussion of molecular test results are widely implemented, but national guidelines for their composition and functioning are lacking. The establishment of MTB guidelines can provide a framework for interpreting rare or complex mutations, facilitating appropriate treatment decision-making, and ensuring quality control.
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| 4. |
- Elimian, K, et al.
(författare)
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COVID-19 mortality rate and its associated factors during the first and second waves in Nigeria
- 2022
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Ingår i: PLOS global public health. - : Public Library of Science (PLoS). - 2767-3375. ; 2:6, s. e0000169-
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 mortality rate has not been formally assessed in Nigeria. Thus, we aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria. This was a retrospective analysis of national surveillance data from all 37 States in Nigeria between February 27, 2020, and April 3, 2021. The outcome variable was mortality amongst persons who tested positive for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction. Incidence rates of COVID-19 mortality was calculated by dividing the number of deaths by total person-time (in days) contributed by the entire study population and presented per 100,000 person-days with 95% Confidence Intervals (95% CI). Adjusted negative binomial regression was used to identify factors associated with COVID-19 mortality. Findings are presented as adjusted Incidence Rate Ratios (aIRR) with 95% CI. The first wave included 65,790 COVID-19 patients, of whom 994 (1∙51%) died; the second wave included 91,089 patients, of whom 513 (0∙56%) died. The incidence rate of COVID-19 mortality was higher in the first wave [54∙25 (95% CI: 50∙98–57∙73)] than in the second wave [19∙19 (17∙60–20∙93)]. Factors independently associated with increased risk of COVID-19 mortality in both waves were: age ≥45 years, male gender [first wave aIRR 1∙65 (1∙35–2∙02) and second wave 1∙52 (1∙11–2∙06)], being symptomatic [aIRR 3∙17 (2∙59–3∙89) and 3∙04 (2∙20–4∙21)], and being hospitalised [aIRR 4∙19 (3∙26–5∙39) and 7∙84 (4∙90–12∙54)]. Relative to South-West, residency in the South-South and North-West was associated with an increased risk of COVID-19 mortality in both waves. In conclusion, the rate of COVID-19 mortality in Nigeria was higher in the first wave than in the second wave, suggesting an improvement in public health response and clinical care in the second wave. However, this needs to be interpreted with caution given the inherent limitations of the country’s surveillance system during the study.
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| 5. |
- Lehmann, Laura C., et al.
(författare)
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Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 33:12
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Tidskriftsartikel (refereegranskat)abstract
- Upon DNA damage, the ALC1/CHD1L nucleosome remodeling enzyme (remodeler) is activated by binding to poly(ADP-ribose). How activated ALC1 recognizes the nucleosome, as well as how this recognition is coupled to remodeling, is unknown. Here, we show that remodeling by ALC1 requires a wild-type acidic patch on the entry side of the nucleosome. The cryo-electron microscopy structure of a nucleosome-ALC1 linker complex reveals a regulatory linker segment that binds to the acidic patch. Mutations within this interface alter the dynamics of ALC1 recruitment to DNA damage and impede the ATPase and remodeling activities of ALC1. Full activation requires acidic patch-linker segment interactions that tether the remodeler to the nucleosome and couple ATP hydrolysis to nucleosome mobilization. Upon DNA damage, such a requirement may be used to modulate ALC1 activity via changes in the nucleosome acidic patches.
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| 6. |
- Akande, OW, et al.
(författare)
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Epidemiological comparison of the first and second waves of the COVID-19 pandemic in Nigeria, February 2020-April 2021
- 2021
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- With reports of surges in COVID-19 case numbers across over 50 countries, country-level epidemiological analysis is required to inform context-appropriate response strategies for containment and mitigation of the outbreak. We aimed to compare the epidemiological features of the first and second waves of COVID-19 in Nigeria.MethodsWe conducted a retrospective analysis of the Surveillance Outbreak Response Management and Analysis System data of the first and second epidemiological waves, which were between 27 February and 24 October 2020, and 25 October 2020 to 3 April 2021, respectively. Descriptive statistical measures including frequencies and percentages, test positivity rate (TPR), cumulative incidence (CI) and case fatality rates (CFRs) were compared. A p value of <0.05 was considered statistically significant. All statistical analyses were carried out in STATA V.13.ResultsThere were 802 143 tests recorded during the study period (362 550 and 439 593 in the first and second waves, respectively). Of these, 66 121 (18.2%) and 91 644 (20.8%) tested positive in the first and second waves, respectively. There was a 21.3% increase in the number of tests conducted in the second wave with TPR increasing by 14.3%. CI during the first and second waves were 30.3/100 000 and 42.0/100 000 respectively. During the second wave, confirmed COVID-19 cases increased among females and people 30 years old or younger and decreased among urban residents and individuals with travel history within 14 days of sample collection (p value <0.001). Most confirmed cases were asymptomatic at diagnosis during both waves: 74.9% in the first wave; 79.7% in the second wave. CFR decreased during the second wave (0.7%) compared with the first wave (1.8%).ConclusionNigeria experienced a larger but less severe second wave of COVID-19. Continued implementation of public health and social measures is needed to mitigate the resurgence of another wave.
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| 7. |
- Andreasson, Ulf, 1968, et al.
(författare)
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A Practical Guide to Immunoassay Method Validation.
- 2015
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Biochemical markers have a central position in the diagnosis and management of patients in clinical medicine, and also in clinical research and drug development, also for brain disorders, such as Alzheimer's disease. The enzyme-linked immunosorbent assay (ELISA) is frequently used for measurement of low-abundance biomarkers. However, the quality of ELISA methods varies, which may introduce both systematic and random errors. This urges the need for more rigorous control of assay performance, regardless of its use in a research setting, in clinical routine, or drug development. The aim of a method validation is to present objective evidence that a method fulfills the requirements for its intended use. Although much has been published on which parameters to investigate in a method validation, less is available on a detailed level on how to perform the corresponding experiments. To remedy this, standard operating procedures (SOPs) with step-by-step instructions for a number of different validation parameters is included in the present work together with a validation report template, which allow for a well-ordered presentation of the results. Even though the SOPs were developed with the intended use for immunochemical methods and to be used for multicenter evaluations, most of them are generic and can be used for other technologies as well.
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| 8. |
- Bacic, Luka, et al.
(författare)
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Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro using PARP2 and HPF1. This complex was amenable to cryo-EM structure determination without cross-linking, which enabled visualization of several intermediate states of ALC1 from the recognition of the PARylated nucleosome to the tight binding and activation of the remodeler. Functional biochemical assays with PARylated nucleosomes highlight the importance of nucleosomal epitopes for productive remodeling and suggest that ALC1 preferentially slides nucleosomes away from DNA breaks.
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| 9. |
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| 10. |
- Elimian, K, et al.
(författare)
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Epidemiology, diagnostics and factors associated with mortality during a cholera epidemic in Nigeria, October 2020-October 2021: a retrospective analysis of national surveillance data
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e063703-
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Tidskriftsartikel (refereegranskat)abstract
- Nigeria reported an upsurge in cholera cases in October 2020, which then transitioned into a large, disseminated epidemic for most of 2021. This study aimed to describe the epidemiology, diagnostic performance of rapid diagnostic test (RDT) kits and the factors associated with mortality during the epidemic.DesignA retrospective analysis of national surveillance data.Setting33 of 37 states (including the Federal Capital Territory) in Nigeria.ParticipantsPersons who met cholera case definition (a person of any age with acute watery diarrhoea, with or without vomiting) between October 2020 and October 2021 within the Nigeria Centre for Disease Control surveillance data.Outcome measuresAttack rate (AR; per 100 000 persons), case fatality rate (CFR; %) and accuracy of RDT performance compared with culture using area under the receiver operating characteristic curve (AUROC). Additionally, individual factors associated with cholera deaths and hospitalisation were presented as adjusted OR with 95% CIs.ResultsOverall, 93 598 cholera cases and 3298 deaths (CFR: 3.5%) were reported across 33 of 37 states in Nigeria within the study period. The proportions of cholera cases were higher in men aged 5–14 years and women aged 25–44 years. The overall AR was 46.5 per 100 000 persons. The North-West region recorded the highest AR with 102 per 100 000. Older age, male gender, residency in the North-Central region and severe dehydration significantly increased the odds of cholera deaths. The cholera RDT had excellent diagnostic accuracy (AUROC=0.91; 95% CI 0.87 to 0.96).ConclusionsCholera remains a serious public health threat in Nigeria with a high mortality rate. Thus, we recommend making RDT kits more widely accessible for improved surveillance and prompt case management across the country.
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