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  • Lewin, Harris A., et al. (författare)
  • The Earth BioGenome Project 2020 : Starting the clock
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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4.
  • Danko, David, et al. (författare)
  • A global metagenomic map of urban microbiomes and antimicrobial resistance
  • 2021
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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5.
  • Wilkinson, John L., et al. (författare)
  • Pharmaceutical pollution of the world's rivers
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
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6.
  • Godtman, Rebecka Arnsrud, 1981, et al. (författare)
  • Intervention-related Deaths in the European Randomized Study of Screening for Prostate Cancer
  • 2021
  • Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 34, s. 27-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. Objective: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). Design, setting, and participants: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55-69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. Outcome measurements and statistical analysis: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. Results and limitations: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99-1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. Conclusions: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. Patient summary: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified. (c) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative- commons.org/licenses/by-nc-nd/4.0/).
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  • Remmers, S., et al. (författare)
  • Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer
  • 2023
  • Ingår i: European Urology. - 0302-2838. ; 84:5, s. 503-509
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age.Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2-4 yr). Design, setting, and participants: We evaluated 25 589 men aged 55-59 yr, 16 898 men aged 60-64 yr, and 12 936 men aged 65-69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2-4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU).Outcome measurements and statistical analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason >7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA andPCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60-61 yr.Results and limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial proba-bility of csPCa at 16 yr ranged from 1.2-1.5% for men with PSA <1.0 ng/ml to 13.3-13.8% for men with PSA >3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60-61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ ml). In addition, for men initially screened at age 60-61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68-70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76-78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. Conclusions: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55-69 yr is a strong indicator to delay or stop further screening. Patient summary: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.
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  • Bertola, Laura D., et al. (författare)
  • A pragmatic approach for integrating molecular tools into biodiversity conservation
  • 2024
  • Ingår i: Conservation science and practice. - 2578-4854. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular tools are increasingly applied for assessing and monitoring biodiversity and informing conservation action. While recent developments in genetic and genomic methods provide greater sensitivity in analysis and the capacity to address new questions, they are not equally available to all practitioners: There is considerable bias across institutions and countries in access to technologies, funding, and training. Consequently, in many cases, more accessible traditional genetic data (e.g., microsatellites) are still utilized for making conservation decisions. Conservation approaches need to be pragmatic by tackling clearly defined management questions and using the most appropriate methods available, while maximizing the use of limited resources. Here we present some key questions to consider when applying the molecular toolbox for accessible and actionable conservation management. Finally, we highlight a number of important steps to be addressed in a collaborative way, which can facilitate the broad integration of molecular data into conservation. Molecular tools are increasingly applied in conservation management; however, they are not equally available to all practitioners. We here provide key questions when establishing a conservation genetic study and highlight important steps which need to be addressed when these tools are globally applied.image
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  • Bieder, A, et al. (författare)
  • Dyslexia Candidate Gene and Ciliary Gene Expression Dynamics During Human Neuronal Differentiation
  • 2020
  • Ingår i: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 57:7, s. 2944-2958
  • Tidskriftsartikel (refereegranskat)abstract
    • Developmental dyslexia (DD) is a neurodevelopmental condition with complex genetic mechanisms. A number of candidate genes have been identified, some of which are linked to neuronal development and migration and to ciliary functions. However, expression and regulation of these genes in human brain development and neuronal differentiation remain uncharted. Here, we used human long-term self-renewing neuroepithelial stem (lt-NES, here termed NES) cells derived from human induced pluripotent stem cells to study neuronal differentiation in vitro. We characterized gene expression changes during differentiation by using RNA sequencing and validated dynamics for selected genes by qRT-PCR. Interestingly, we found that genes related to cilia were significantly enriched among upregulated genes during differentiation, including genes linked to ciliopathies with neurodevelopmental phenotypes. We confirmed the presence of primary cilia throughout neuronal differentiation. Focusing on dyslexia candidate genes, 33 out of 50 DD candidate genes were detected in NES cells by RNA sequencing, and seven candidate genes were upregulated during differentiation to neurons, including DYX1C1 (DNAAF4), a highly replicated DD candidate gene. Our results suggest a role of ciliary genes in differentiating neuronal cells and show that NES cells provide a relevant human neuronal model to study ciliary and DD candidate genes.
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  • Chng, Kern Rei, et al. (författare)
  • Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
  • 2020
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
  • Tidskriftsartikel (refereegranskat)abstract
    • Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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  • Formenti, Giulio, et al. (författare)
  • The era of reference genomes in conservation genomics
  • 2022
  • Ingår i: Trends in Ecology & Evolution. - : Elsevier. - 0169-5347 .- 1872-8383. ; 37:3, s. 197-202
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Progress in genome sequencing now enables the large-scale generation of reference genomes. Various international initiatives aim to generate reference genomes representing global biodiversity. These genomes provide unique insights into genomic diversity and architecture, thereby enabling comprehensive analyses of population and functional genomics, and are expected to revolutionize conservation genomics.
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  • Sahlén, Pelin, et al. (författare)
  • Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes
  • 2020
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Mosby Inc.. - 0091-6749 .- 1097-6825.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hundreds of variants associated with atopic dermatitis (AD) and psoriasis, 2 common inflammatory skin disorders, have previously been discovered through genome-wide association studies (GWASs). The majority of these variants are in noncoding regions, and their target genes remain largely unclear. Objective: We sought to understand the effects of these noncoding variants on the development of AD and psoriasis by linking them to the genes that they regulate. Methods: We constructed genomic 3-dimensional maps of human keratinocytes during differentiation by using targeted chromosome conformation capture (Capture Hi-C) targeting more than 20,000 promoters and 214 GWAS variants and combined these data with transcriptome and epigenomic data sets. We validated our results with reporter assays, clustered regularly interspaced short palindromic repeats activation, and examination of patient gene expression from previous studies. Results: We identified 118 target genes of 82 AD and psoriasis GWAS variants. Differential expression of 58 of the 118 target genes (49%) occurred in either AD or psoriatic lesions, many of which were not previously linked to any skin disease. We highlighted the genes AFG1L, CLINT1, ADO, LINC00302, and RP1-140J1.1 and provided further evidence for their potential roles in AD and psoriasis. Conclusions: Our work focused on skin barrier pathology through investigation of the interaction profile of GWAS variants during keratinocyte differentiation. We have provided a catalogue of candidate genes that could modulate the risk of AD and psoriasis. Given that only 35% of the target genes are the gene nearest to the known GWAS variants, we expect that our work will contribute to the discovery of novel pathways involved in AD and psoriasis.
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  • Theissinger, Kathrin, et al. (författare)
  • How genomics can help biodiversity conservation
  • 2023
  • Ingår i: Trends in Genetics. - : Elsevier. - 0168-9525 .- 1362-4555. ; 39:7, s. 545-559
  • Forskningsöversikt (refereegranskat)abstract
    • The availability of public genomic resources can greatly assist biodiversity assessment, conservation, and restoration efforts by providing evidence for scientifically informed management decisions. Here we survey the main approaches and applications in biodiversity and conservation genomics, considering practical factors, such as cost, time, prerequisite skills, and current shortcomings of applications. Most approaches perform best in combination with reference genomes from the target species or closely related species. We review case studies to illustrate how reference genomes can facilitate biodiversity research and conservation across the tree of life. We conclude that the time is ripe to view reference genomes as fundamental resources and to integrate their use as a best practice in conservation genomics.
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  • van Huizen, Astrid M., et al. (författare)
  • International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis
  • 2022
  • Ingår i: JAMA dermatology. - : American Medical Association (AMA). - 2168-6068 .- 2168-6084. ; 158:5, s. 561-561
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance  A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.Objective  To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.Design, Setting, and Participants  Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience).Main Outcomes and Measures  In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree.Results  Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients.Conclusions and Relevance  In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.
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  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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  • Carvalho, M. R., et al. (författare)
  • Extinction at the end-Cretaceous and the origin of modern Neotropical rainforests
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6537
  • Tidskriftsartikel (refereegranskat)abstract
    • The end-Cretaceous event was catastrophic for terrestrial communities worldwide, yet its long-lasting effect on tropical forests remains largely unknown. We quantified plant extinction and ecological change in tropical forests resulting from the end-Cretaceous event using fossil pollen (>50,000 occurrences) and leaves (>6000 specimens) from localities in Colombia. Late Cretaceous (Maastrichtian) rainforests were characterized by an open canopy and diverse plant-insect interactions. Plant diversity declined by 45% at the Cretaceous-Paleogene boundary and did not recover for similar to 6 million years. Paleocene forests resembled modern Neotropical rainforests, with a closed canopy and multistratal structure dominated by angiosperms. The end-Cretaceous event triggered a long interval of low plant diversity in the Neotropics and the evolutionary assembly of today's most diverse terrestrial ecosystem.
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19.
  • Kuhrmann, Marco, et al. (författare)
  • What Makes Agile Software Development Agile
  • 2022
  • Ingår i: IEEE Transactions on Software Engineering. - 0098-5589 .- 1939-3520. ; 48:9, s. 3523-3539
  • Tidskriftsartikel (refereegranskat)abstract
    • Together with many success stories, promises such as the increase in production speed and the improvement in stakeholders' collaboration have contributed to making agile a transformation in the software industry in which many companies want to take part. However, driven either by a natural and expected evolution or by contextual factors that challenge the adoption of agile methods as prescribed by their creator(s), software processes in practice mutate into hybrids over time. Are these still agile In this article, we investigate the question: what makes a software development method agile We present an empirical study grounded in a large-scale international survey that aims to identify software development methods and practices that improve or tame agility. Based on 556 data points, we analyze the perceived degree of agility in the implementation of standard project disciplines and its relation to used development methods and practices. Our findings suggest that only a small number of participants operate their projects in a purely traditional or agile manner (under 15%). That said, most project disciplines and most practices show a clear trend towards increasing degrees of agility. Compared to the methods used to develop software, the selection of practices has a stronger effect on the degree of agility of a given discipline. Finally, there are no methods or practices that explicitly guarantee or prevent agility. We conclude that agility cannot be defined solely at the process level. Additional factors need to be taken into account when trying to implement or improve agility in a software company. Finally, we discuss the field of software process-related research in the light of our findings and present a roadmap for future research.
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  • Lu, Dasheng, et al. (författare)
  • Exploring Single-Nanoparticle Dynamics at High Temperature by Optical Tweezers
  • 2020
  • Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 20:11, s. 8024-8031
  • Tidskriftsartikel (refereegranskat)abstract
    • The experimental determination of the velocity of a colloidal nanoparticle (v(Np)) has recently became a hot topic. The thermal dependence of v(Np) is still left to be explored although it is a valuable source of information allowing, for instance, the discernment between ballistic and diffusive regimes. Optical tweezers (OTs) constitute a tool especially useful for the experimental determination of v m , although they have only been capable of determining it at room temperature. In this work, we demonstrate that it is possible to determine the temperature dependence of the diffusive velocity of a single colloidal nanoparticle by analyzing the temperature dependence of optical forces. The comparison between experimental results and theoretical predictions allowed us to discover the impact that the anomalous temperature dependence of water properties has on the dynamics of colloidal nanoparticles in this temperature range.
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