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See detailGeneralising from conventional pipelines using deep learning in high‑throughput screening workfows
Garcia Santa Cruz, Beatriz UL; Sölter, Jan; Gomez Giro, Gemma UL et al

in Scientific Reports (2022)

The study of complex diseases relies on large amounts of data to build models toward precision medicine. Such data acquisition is feasible in the context of high-throughput screening, in which the quality ... [more ▼]

The study of complex diseases relies on large amounts of data to build models toward precision medicine. Such data acquisition is feasible in the context of high-throughput screening, in which the quality of the results relies on the accuracy of the image analysis. Although state-of-the-art solutions for image segmentation employ deep learning approaches, the high cost of manually generating ground truth labels for model training hampers the day-to-day application in experimental laboratories. Alternatively, traditional computer vision-based solutions do not need expensive labels for their implementation. Our work combines both approaches by training a deep learning network using weak training labels automatically generated with conventional computer vision methods. Our network surpasses the conventional segmentation quality by generalising beyond noisy labels, providing a 25% increase of mean intersection over union, and simultaneously reducing the development and inference times. Our solution was embedded into an easy-to-use graphical user interface that allows researchers to assess the predictions and correct potential inaccuracies with minimal human input. To demonstrate the feasibility of training a deep learning solution on a large dataset of noisy labels automatically generated by a conventional pipeline, we compared our solution against the common approach of training a model from a small manually curated dataset by several experts. Our work suggests that humans perform better in context interpretation, such as error assessment, while computers outperform in pixel-by-pixel fne segmentation. Such pipelines are illustrated with a case study on image segmentation for autophagy events. This work aims for better translation of new technologies to real-world settings in microscopy-image analysis. [less ▲]

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See detailMagnetic order and disorder environments in superantiferromagnetic NdCu2 nanoparticles
Jefremovas, E.M.; Svedlindh, P.; Damay, F. et al

in Scientific Reports (2022), 12

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See detailCharacteristics associated with COVID‑19 vaccine hesitancy
Borga, Liyousew UL; Clark, Andrew; d'Ambrosio, Conchita UL et al

in Scientific Reports (2022)

Understanding what lies behind actual COVID-19 vaccine hesitancy is fundamental to help policy makers increase vaccination rates and reach herd immunity. We use June 2021 data from the COME-HERE survey to ... [more ▼]

Understanding what lies behind actual COVID-19 vaccine hesitancy is fundamental to help policy makers increase vaccination rates and reach herd immunity. We use June 2021 data from the COME-HERE survey to explore the predictors of actual vaccine hesitancy in France, Germany, Italy, Luxembourg, Spain and Sweden. We estimate a linear-probability model with a rich set of covariates and address issues of common-method variance. 13% of our sample say they do not plan to be vaccinated. Post-Secondary education, home-ownership, having an underlying health condition, and one standard-deviation higher age or income are all associated with lower vaccine hesitancy of 2–4.5% points. Conservative-leaning political attitudes and a one standard-deviation lower degree of confidence in the government increase this probability by 3 and 6% points respectively. Vaccine hesitancy in Spain and Sweden is significantly lower than in the other countries. [less ▲]

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See detailRadial analysis and scaling of urban land use
Lemoy, Rémi UL; Caruso, Geoffrey UL

in Scientific Reports (2021), (22044),

We determine the functional form and scaling law of radial artificial land use profiles in 300 European functional urban areas (FUAs). These profiles, starting from a fully artificial surface in the city ... [more ▼]

We determine the functional form and scaling law of radial artificial land use profiles in 300 European functional urban areas (FUAs). These profiles, starting from a fully artificial surface in the city center, decrease exponentially, the faster the smaller the city. More precisely, the characteristic decrease distance scales like the square root of total population, meaning that the artificial surface of cities is proportional to their population. This also means that the amount of artificial land per capita is independent of city size, and that larger cities are not more or less parsimonious in terms of land use than smaller ones. [less ▲]

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See detailGene-corrected p.A30P SNCA patient-derived isogenic neurons rescue neuronal branching and function
Barbuti, Peter A; Ohnmacht, Jochen UL; Santos, Bruno FR et al

in Scientific Reports (2021), 11

Parkinson’s disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the ... [more ▼]

Parkinson’s disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the alpha-synuclein protein causing an autosomal-dominant form of PD. There are limited studies assessing pathogenic SNCA mutations in patient-derived isogenic cell models. Here we provide a functional assessment of dopaminergic neurons derived from a patient harbouring the p.A30P SNCA mutation. Using two clonal gene-corrected isogenic cell lines we identified image-based phenotypes showing impaired neuritic processes. The pathological neurons displayed impaired neuronal activity, reduced mitochondrial respiration, an energy deficit, vulnerability to rotenone, and transcriptional alterations in lipid metabolism. Our data describes for the first time the mutation-only effect of the p.A30P SNCA mutation on neuronal function, supporting the use of isogenic cell lines in identifying image-based pathological phenotypes that can serve as an entry point for future disease-modifying compound screenings and drug discovery strategies. [less ▲]

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See detailAutomatic Integration of Numerical Formats Examined with Frequency-tagged EEG
Marinova, Mila UL; Georges, Carrie UL; Guillaume, Mathieu et al

in Scientific Reports (2021)

How humans integrate and abstract numerical information across different formats is one of the most debated questions in human cognition. We addressed the neuronal signatures of the numerical integration ... [more ▼]

How humans integrate and abstract numerical information across different formats is one of the most debated questions in human cognition. We addressed the neuronal signatures of the numerical integration using an EEG technique tagged at the frequency of visual stimulation. In an oddball design, participants were stimulated with standard sequences of numbers (<5) depicted in single (digits, dots, number words) or mixed notation (dots – digits, number words – dots, digits – number words), presented at 10Hz. Periodically, a deviant stimulus (>5) was inserted at 1.25 Hz. We observed significant oddball amplitudes for all single notations, showing for the first time using this EEG technique, that the magnitude information is spontaneously and unintentionally abstracted, irrespectively of the numerical format. Significant amplitudes were also observed for digits – number words and number words – dots, but not for digits – dots, suggesting an automatic integration across some numerical formats. These results imply that direct and indirect neuro-cognitive links exist across the different numerical formats. [less ▲]

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See detailTowards global flood mapping onboard low cost satellites with machine learning
Mateo‑Garcia, Gonzalo; Veitch‑Michaelis, Joshua; Smith, Lewis et al

in Scientific Reports (2021), 11(7249 (2021)),

Spaceborne Earth observation is a key technology for flood response, offering valuable information to decision makers on the ground. Very large constellations of small, nano satellites— ’CubeSats’ are a ... [more ▼]

Spaceborne Earth observation is a key technology for flood response, offering valuable information to decision makers on the ground. Very large constellations of small, nano satellites— ’CubeSats’ are a promising solution to reduce revisit time in disaster areas from days to hours. However, data transmission to ground receivers is limited by constraints on power and bandwidth of CubeSats. Onboard processing offers a solution to decrease the amount of data to transmit by reducing large sensor images to smaller data products. The ESA’s recent PhiSat-1 mission aims to facilitate the demonstration of this concept, providing the hardware capability to perform onboard processing by including a power-constrained machine learning accelerator and the software to run custom applications. This work demonstrates a flood segmentation algorithm that produces flood masks to be transmitted instead of the raw images, while running efficiently on the accelerator aboard the PhiSat-1. Our models are trained on WorldFloods: a newly compiled dataset of 119 globally verified flooding events from disaster response organizations, which we make available in a common format. We test the system on independent locations, demonstrating that it produces fast and accurate segmentation masks on the hardware accelerator, acting as a proof of concept for this approach. [less ▲]

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See detailEstimating worldwide effects of non‐pharmaceutical interventions on COVID‐19 incidence and population mobility patterns using a multiple‐event study
Askitas, Nikolaos; Tatsiramos, Konstantinos UL; Verheyden, Bertrand

in Scientific Reports (2021), 11(1972 (2021)), 1-13

Various non‐pharmaceutical interventions were adopted by countries worldwide in the fight against the COVID‐19 pandemic with adverse socioeconomic side effects, which raises the question about their ... [more ▼]

Various non‐pharmaceutical interventions were adopted by countries worldwide in the fight against the COVID‐19 pandemic with adverse socioeconomic side effects, which raises the question about their differential effectiveness. We estimate the average dynamic effect of each intervention on the incidence of COVID‐19 and on people’s whereabouts by developing a statistical model that accounts for the contemporaneous adoption of multiple interventions. Using daily data from 175 countries, we show that, even after controlling for other concurrent lockdown policies, cancelling public events, imposing restrictions on private gatherings and closing schools and workplaces had significant effects on reducing COVID‐19 infections. Restrictions on internal movement and public transport had no effects because the aforementioned policies, imposed earlier on average, had already de facto reduced human mobility. International travel restrictions, although imposed early, had a short‐lived effect failing to prevent the epidemic from turning into a pandemic because they were less stringent. We interpret the impact of each intervention on containing the pandemic using a conceptual framework which relies on their effects on human mobility behaviors in a manner consistent with time‐use and epidemiological factors. [less ▲]

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See detailPINK1 deficiency impairs adult neurogenesis of dopaminergic neurons
Brown, Sarah J; Boussaad, Ibrahim UL; Jarazo, Javier UL et al

in Scientific Reports (2021)

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See detailIntraoperative discrimination of native meningioma and dura mater by Raman spectroscopy
Jelke, Finn; Mirizzi, Giulia; Borgmann, Felix Kleine et al

in Scientific Reports (2021)

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See detailGene expression profile of CD14+ blood monocytes following lifestyle-induced weight loss in individuals with metabolic syndrome.
Noor, Fozia UL; Biemann, Ronald; Roomp, Kirsten UL et al

in Scientific Reports (2020), 10(1), 17855

Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle ... [more ▼]

Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14+ cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (- 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (- 45.84%) and circulating CD14+ cells (- 21.0%). Four genes were differentially expressed (DEG's) in CD14+ cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14+ monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14+ monocytes, which may affect ubiquitination, histone methylation and autophagy [less ▲]

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See detailHaploinsufficiency due to a novel ACO2 deletion causes mitochondrial dysfunction in fibroblasts from a patient with dominant optic nerve atrophy
Neumann, Marie Anne-Catherine UL; Grossmann, Dajana UL; Schimpf-Linzenbold, Simone et al

in Scientific Reports (2020)

ACO2 is a mitochondrial protein, which is critically involved in the function of the tricarboxylic acid cycle (TCA), the maintenance of iron homeostasis, oxidative stress defense and the integrity of ... [more ▼]

ACO2 is a mitochondrial protein, which is critically involved in the function of the tricarboxylic acid cycle (TCA), the maintenance of iron homeostasis, oxidative stress defense and the integrity of mitochondrial DNA (mtDNA). Mutations in the ACO2 gene were identified in patients suffering from a broad range of symptoms, including optic nerve atrophy, cortical atrophy, cerebellar atrophy, hypotonia, seizures and intellectual disabilities. In the present study, we identified a heterozygous 51 bp deletion (c.1699_1749del51) in ACO2 in a family with autosomal dominant inherited isolated optic atrophy. A complementation assay using aco1-deficient yeast revealed a growth defect for the mutant ACO2 variant substantiating a pathogenic effect of the deletion. We used patient-derived fibroblasts to characterize cellular phenotypes and found a decrease of ACO2 protein levels, while ACO2 enzyme activity was not affected compared to two age- and gender-matched control lines. Several parameters of mitochondrial function, including mitochondrial morphology, mitochondrial membrane potential or mitochondrial superoxide production, were not changed under baseline conditions. However, basal respiration, maximal respiration, and spare respiratory capacity were reduced in mutant cells. Furthermore, we observed a reduction of mtDNA copy number and reduced mtDNA transcription levels in ACO2-mutant fibroblasts. Inducing oxidative stress led to an increased susceptibility for cell death in ACO2-mutant fibroblasts compared to controls. Our study reveals that a monoallelic mutation in ACO2 is sufficient to promote mitochondrial dysfunction and increased vulnerability to oxidative stress as main drivers of cell death related to optic nerve atrophy. [less ▲]

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See detailGreat apes selectively retrieve relevant memories to guide action
Bobrowicz, Katarzyna UL; Johansson, Mikael; Osvath, Mathias

in Scientific Reports (2020)

Memory allows us to draw on past experiences to inform behaviour in the present. However, memories rarely match the situation at hand exactly, and new situations regularly trigger multiple related ... [more ▼]

Memory allows us to draw on past experiences to inform behaviour in the present. However, memories rarely match the situation at hand exactly, and new situations regularly trigger multiple related memories where only some are relevant to act upon. The flexibility of human memory systems is largely attributed to the ability to disregard irrelevant, but salient, memories in favour of relevant ones. This is considered an expression of an executive function responsible for suppressing irrelevant memories, associated with the prefrontal cortex. It is unclear to what extent animals have access to this ability. Here, we demonstrate, in a series of tool-use tasks designed to evoke conflicting memories, that chimpanzees and an orangutan suffer from this conflict but overcome it in favour of a more relevant memory. Such mnemonic flexibility is among the most advanced expressions of executive function shown in animals to date and might explain several behaviours related to tool-use, innovation, planning and more. [less ▲]

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See detailFibroblast mitochondria in idiopathic Parkinson’s disease display morphological changes and enhanced resistance to depolarization
Krüger, Rejko UL; Balling, Rudolf UL; Antony, Paul UL et al

in Scientific Reports (2020)

Mitochondrial dysfunction is a hallmark in idiopathic Parkinson’s disease (IPD). Here, we established screenable phenotypes of mitochondrial morphology and function in primary fibroblasts derived from ... [more ▼]

Mitochondrial dysfunction is a hallmark in idiopathic Parkinson’s disease (IPD). Here, we established screenable phenotypes of mitochondrial morphology and function in primary fibroblasts derived from patients with IPD. Upper arm punch skin biopsy was performed in 41 patients with mid-stage IPD and 21 age-matched healthy controls. At the single-cell level, the basal mitochondrial membrane potential (Ψm) was higher in patients with IPD than in controls. Similarly, under carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) stress, the remaining Ψm was increased in patients with IPD. Analysis of mitochondrial morphometric parameters revealed significantly decreased mitochondrial connectivity in patients with IPD, with 9 of 14 morphometric mitochondrial parameters differing from those in controls. Significant morphometric mitochondrial changes included the node degree, mean volume, skeleton size, perimeter, form factor, node count, erosion body count, endpoints, and mitochondria count (all P-values < 0.05). These functional data reveal that resistance to depolarization was increased by treatment with the protonophore FCCP in patients with IPD, whereas morphometric data revealed decreased mitochondrial connectivity and increased mitochondrial fragmentation. [less ▲]

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See detailAn efficient machine learning-based approach for screening individuals at risk of hereditary haemochromatosis.
Martins Conde, Patricia UL; Sauter, Thomas UL; Nguyen, Thanh-Phuong UL

in Scientific reports (2020), 10(1), 20613

Hereditary haemochromatosis (HH) is an autosomal recessive disease, where HFE C282Y homozygosity accounts for 80-85% of clinical cases among the Caucasian population. HH is characterised by the ... [more ▼]

Hereditary haemochromatosis (HH) is an autosomal recessive disease, where HFE C282Y homozygosity accounts for 80-85% of clinical cases among the Caucasian population. HH is characterised by the accumulation of iron, which, if untreated, can lead to the development of liver cirrhosis and liver cancer. Since iron overload is preventable and treatable if diagnosed early, high-risk individuals can be identified through effective screening employing artificial intelligence-based approaches. However, such tools expose novel challenges associated with the handling and integration of large heterogeneous datasets. We have developed an efficient computational model to screen individuals for HH using the family study data of the Hemochromatosis and Iron Overload Screening (HEIRS) cohort. This dataset, consisting of 254 cases and 701 controls, contains variables extracted from questionnaires and laboratory blood tests. The final model was trained on an extreme gradient boosting classifier using the most relevant risk factors: HFE C282Y homozygosity, age, mean corpuscular volume, iron level, serum ferritin level, transferrin saturation, and unsaturated iron-binding capacity. Hyperparameter optimisation was carried out with multiple runs, resulting in 0.94 ± 0.02 area under the receiving operating characteristic curve (AUCROC) for tenfold stratified cross-validation, demonstrating its outperformance when compared to the iron overload screening (IRON) tool. [less ▲]

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See detailMeasuring spontaneous and automatic processing of magnitude and parity information of Arabic digits by frequency-tagging EEG.
Guillaume, Mathieu; Poncin, Alexandre; Schiltz, Christine UL et al

in Scientific reports (2020), 10(1), 22254

Arabic digits (1-9) are everywhere in our daily lives. These symbols convey various semantic information, and numerate adults can easily extract from them several numerical features such as magnitude and ... [more ▼]

Arabic digits (1-9) are everywhere in our daily lives. These symbols convey various semantic information, and numerate adults can easily extract from them several numerical features such as magnitude and parity. Nonetheless, since most studies used active processing tasks to assess these properties, it remains unclear whether and to what degree the access to magnitude and especially to parity is automatic. Here we investigated with EEG whether spontaneous processing of magnitude or parity can be recorded in a frequency-tagging approach, in which participants are passively stimulated by fast visual sequences of Arabic digits. We assessed automatic magnitude processing by presenting a stream of frequent small digit numbers mixed with deviant large digits (and the reverse) with a sinusoidal contrast modulation at the frequency of 10 Hz. We used the same paradigm to investigate numerical parity processing, contrasting odd digits to even digits. We found significant brain responses at the frequency of the fluctuating change and its harmonics, recorded on electrodes encompassing right occipitoparietal regions, in both conditions. Our findings indicate that both magnitude and parity are spontaneously and unintentionally extracted from Arabic digits, which supports that they are salient semantic features deeply associated to digit symbols in long-term memory. [less ▲]

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See detailA robust electrophysiological marker of spontaneous numerical discrimination
Georges, Carrie UL; Guillaume, Mathieu; Schiltz, Christine UL

in Scientific Reports (2020)

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