| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)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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| 2. |
- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Journal article (peer-reviewed)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. |
- Nobre, Liana, et al.
(author)
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Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition
- 2020
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In: JCO Precision Oncology. - 2473-4284. ; 3, s. 561-571
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Journal article (peer-reviewed)abstract
- © 2020 by American Society of Clinical Oncology PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy (P, .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively (P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.
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| 4. |
- Schmit, Stephanie L, et al.
(author)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Journal article (peer-reviewed)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 5. |
- Byndloss, Mariana, et al.
(author)
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The gut microbiota and diabetes: research, translation, and clinical applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum
- 2024
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In: DIABETOLOGIA. - 0012-186X .- 1432-0428.
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Research review (peer-reviewed)abstract
- This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.
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| 6. |
- Colonna, Anna, et al.
(author)
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Ecological Momentary Assessment of Awake Bruxism Behaviors : A Scoping Review of Findings from Smartphone-Based Studies in Healthy Young Adults
- 2023
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:5
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Research review (peer-reviewed)abstract
- Background: The recent introduction of ecological momentary assessment (EMA) smartphone-based strategies has allowed achieving some interesting data on the frequency of different awake bruxism (AB) behaviors reported by an individual in the natural environment. Objective: The present paper aims to review the literature on the reported frequency of AB based on data gathered via smartphone EMA technology. Methods: On September 2022, a systematic search in the Pubmed, Scopus and Google Scholar databases was performed to identify all peer-reviewed English-language studies assessing awake bruxism behaviors using a smartphone-based Ecological Momentary Assessment. The selected articles were assessed independently by two authors according to a structured reading of the articles’ format (PICO). Results: A literature search, for which the search terms “Awake Bruxism” and “Ecological Momentary Assessment” were used, identified 15 articles. Of them, eight fulfilled the inclusion criteria. The results of seven studies using the same smartphone-based app reported a frequency of AB behaviors in the range between 28.3 and 40% over one week, while another investigation adopted a different smartphone-based EMA approach via WhatsApp using a web-based survey program and reported an AB frequency of 58.6%. Most included studies were based on convenience samples with limited age range, highlighting the need for more studies on other population samples. Conclusions: Despite the methodological limits, the results of the reviewed studies provide a standpoint for comparison for future studies on the epidemiology of awake bruxism behaviors.
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| 7. |
- Conti, David, V, et al.
(author)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 8. |
- Edwards, Robert A., et al.
(author)
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Global phylogeography and ancient evolution of the widespread human gut virus crAssphage
- 2019
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In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:10, s. 1727-1736
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Journal article (peer-reviewed)abstract
- Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
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| 9. |
- Frank, Mariana, et al.
(author)
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A novel search strategy for right-handed charged gauge bosons at the Large Hadron Collider
- 2024
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In: Journal of High Energy Physics (JHEP). - : Springer. - 1126-6708 .- 1029-8479.
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Journal article (peer-reviewed)abstract
- We explore the potential of the Large Hadron Collider (LHC) in detecting a signal originating from the production of a heavy SU(2)R charged gauge boson that then decays into a top-bottom quark pair via the mediation of a right-handed neutrino, pp → WR → NRℓ → (ℓ' tb)ℓ. Such a channel, that we study in the context of the minimal Left-Right Symmetric Model, contrasts with conventional smoking-gun signatures targeted experimentally and phenomenologically in which only light quarks are involved. We propose a selection strategy aimed at extracting such a top-bottom signal and we estimate the resulting sensitivity of the LHC to the model. Our results demonstrate the potential impact of such a search and we therefore urge the experimental collaborations to carry out a similar analysis in the light of present and future data.
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| 10. |
- Gomes, Daniel A, et al.
(author)
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Impact of common rhythm disturbances on echocardiographic measurements and interpretation
- 2022
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In: Clinical Research in Cardiology. - : Springer Nature. - 1861-0684 .- 1861-0692. ; 111:12, s. 1301-1312
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Journal article (peer-reviewed)abstract
- Transthoracic echocardiography (TTE) remains the workhorse of noninvasive cardiac imaging, allowing to easily obtain precise information on cardiac structure and function. Over time, Doppler interrogation of blood flow velocities, direction, and timing in several locations within the heart became the primary method for haemodynamic assessment, replacing cardiac catheterization in most clinical settings and providing valuable diagnostic and prognostic information on a wide spectrum of cardiac pathological processes. Abnormalities in heart rate, rhythm, and intracardiac electrical conduction are commonly encountered during the performance of echocardiographic studies. Up to now, only a modest attention has been given to the impact of these abnormalities on the reading and interpretation of echocardiographic examination and this assessment has not yet been carried out in a global and systematic way. Tachyarrhythmias, bradyarrhythmias and atrioventricular conduction disturbances influence cardiac structure and mechanics as well as Doppler flow patterns. For this reason, and to be able to avoid misinterpretation, echocardiographers must be aware of the consequences of these common rhythm disturbances on echocardiographic findings. This narrative review aims to describe the current knowledge on this topic, focusing on the expected mechanical effects and Doppler patterns observed on transthoracic echocardiography in patients with common rhythm (tachycardia and bradycardia, atrial flutter and fibrillation and ectopic beats) and conduction disturbances (namely, atrioventricular block).
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