| 1. |
- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 2. |
- Acerbo, E, et al.
(författare)
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Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers
- 2022
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Ingår i: Frontiers in neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16, s. 945221-
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Tidskriftsartikel (refereegranskat)abstract
- Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 and 165 Hz, to various deep-seated targets, such as the Mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely an increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs).Materials and methodsIn the current study, we use Temporal Interference (TI) stimulation to provide a non-invasive DBS (130 Hz) of the MTL, specifically the hippocampus, in both mouse models of epilepsy, and scale the method using human cadavers to demonstrate the potential efficacy in human patients. Simulations for both mice and human heads were performed to calculate the best coordinates to reach the hippocampus.ResultsThis non-invasive DBS increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. We therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs. TCS in human cadavers. Results show a better penetration of TI fields into the human hippocampus as compared with TCS.SignificanceThese results constitute the first proof of the feasibility and efficiency of TI to stimulate at depth an area without impacting the surrounding tissue. The data tend to show the sufficiently focal character of the induced effects and suggest promising therapeutic applications in epilepsy.
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| 3. |
- Bauer, Ann Z., et al.
(författare)
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Paracetamol use during pregnancy - a call for precautionary action
- 2021
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Ingår i: Nature Reviews Endocrinology. - : Springer Nature. - 1759-5029 .- 1759-5037. ; 17, s. 757-766
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Tidskriftsartikel (refereegranskat)abstract
- Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe. A growing body of research suggests that prenatal exposure to paracetamol (APAP) might alter development and increase the risk of some reproductive, urogenital and neurodevelopmental disorders. This Consensus Statement calls for precautionary action, including a focused research effort, increasing awareness among health professionals and pregnant women and, whenever possible, minimizing use.
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| 4. |
- Bauer, Ann Z., et al.
(författare)
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Paracetamol Use During Pregnancy-A Call for Precautionary Action
- 2022
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Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 77:3, s. 133-134
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Tidskriftsartikel (refereegranskat)abstract
- Paracetamol, otherwise known as acetaminophen, is the active ingredient in over 600 prescription and nonprescription analgesic and antipyretic medications. Worldwide and in the United States, more than 50% and 65% of pregnant women use acetaminophen, respectively. Currently, acetaminophen is considered to be of minimal risk and appropriate for use during pregnancy by the US Food and Drug Administration and European Medicines Agency. Despite this, there exists concern that environmental exposure to pharmaceuticals including acetaminophen during fetal life may contribute to the increased rates of neurological, urogenital, and reproductive disorders.This consensus statement aimed to provide an evidence-based summary of the literature relating to neurological, urogenital, and reproductive outcomes that have been associated with maternal and perinatal use of acetaminophen. This consensus statement was created by an international multidisciplinary group consisting of experts in neurology, obstetrics/gynecologists, pediatrics, epidemiology, toxicology, endocrinology, reproductive medicine, and neurodevelopment. A literature review was conducted for studies published between 1995 and 2020, including only those with acetaminophen as an independent exposure. There is a limitation in the existing epidemiological literature addressing these questions, and future efforts are required.This consensus statement and systematic review finds evidence of significant neurodevelopmental and reproductive adverse effects of acetaminophen prenatal exposure, particularly with long-term use. It is recommended by this document that acetaminophen be used by pregnant women cautiously at the lowest effective dose for the shortest possible time and longer or higher-dose use be discussed with a health professional. It is also advised that packaging display warning labels related to the evidence discussed here.
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| 5. |
- Chen, Ping, et al.
(författare)
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A 12.4-day periodicity in a close binary system after a supernova
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 253-258
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Tidskriftsartikel (refereegranskat)abstract
- Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.
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| 8. |
- Jégou, F., et al.
(författare)
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Validation of Odin/SMR limb observations of ozone, comparisons with OSIRIS, POAM III, ground-based and balloon-borne intruments
- 2008
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:13, s. 3385-3409
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Tidskriftsartikel (refereegranskat)abstract
- The Odin satellite carries two instruments capable of determining stratospheric ozone profiles by limb sounding: the Sub-Millimetre Radiometer (SMR) and the UV-visible spectrograph of the OSIRIS (Optical Spectrograph and InfraRed Imager System) instrument. A large number of ozone profiles measurements were performed during six years from November 2001 to present. This ozone dataset is here used to make quantitative comparisons with satellite measurements in order to assess the quality of the Odin/SMR ozone measurements. In a first step, we compare Swedish SMR retrievals version 2.1, French SMR ozone retrievals version 222 (both from the 501.8 GHz band), and the OSIRIS retrievals version 3.0, with the operational version 4.0 ozone product from POAM III (Polar Ozone Atmospheric Measurement). In a second step, we refine the Odin/SMR validation by comparisons with ground-based instruments and balloon-borne observations. We use observations carried out within the framework of the Network for Detection of Atmospheric Composition Change (NDACC) and balloon flight missions conducted by the Canadian Space Agency (CSA), the Laboratoire de Physique et de Chimie de l\'{}Environnement (LPCE, Orléans, France), and the Service d'Aéronomie (SA, Paris, France). Coincidence criteria were 5° in latitude×10° in longitude, and 5 h in time in Odin/POAM III comparisons, 12 h in Odin/NDACC comparisons, and 72 h in Odin/balloons comparisons. An agreement is found with the POAM III experiment (10–60 km) within −0.3±0.2 ppmv (bias±standard deviation) for SMR (v222, v2.1) and within −0.5±0.2 ppmv for OSIRIS (v3.0). Odin ozone mixing ratio products are systematically slightly lower than the POAM III data and show an ozone maximum lower by 1–5 km in altitude. The comparisons with the NDACC data (10–34 km for ozonesonde, 10–50 km for lidar, 10–60 for microwave instruments) yield a good agreement within −0.15±0.3 ppmv for the SMR data and −0.3±0.3 ppmv for the OSIRIS data. Finally the comparisons with instruments on large balloons (10–31 km) show a good agreement, within −0.7±1 ppmv. The official SMR v2.1 dataset is consistent in all altitude ranges with POAM III, NDACC and large balloon-borne instruments measurements. In the SMR v2.1 data, no different systematic error has been found in the 0–35km range in comparison with the 35–60 km range. The same feature has been highlighted in both hemispheres in SMR v2.1/POAM III intercomparisons, and no latitudinal dependence has been revealed in SMR v2.1/NDACC intercomparisons.
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| 9. |
- Martin, S., et al.
(författare)
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SARS-CoV-2 integral membrane proteins shape the serological responses of patients with COVID-19
- 2021
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Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 24:10
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has elicited a unique mobilization of the scientific community to develop efficient tools to understand and combat the infection. Like other coronavirae, SARS-CoV-2 hijacks host cell secretory machinery to produce viral proteins that compose the nascent virions; including spike (S), envelope (E), and membrane (M) proteins, the most exposed transmembrane proteins to the host immune system. As antibody response is part of the anti-viral immune arsenal, we investigate the immunogenic potential of S, E, and M using a human cell-based system to mimic membrane insertion and N-glycosylation. Both S and M elicit specific Ig production in patients with SARS-CoV-2. Patients with moderate and severe diseases exhibit elevated Ig responses. Finally, reduced Ig binding was observed with spike G614 compared to D614 variant. Altogether, our assay points toward an unexpected immune response against M and represents a powerful tool to test humoral responses against actively evolving SARS-CoV-2 variants and vaccine effectiveness.
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| 10. |
- Urban, Joachim, 1964, et al.
(författare)
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Odin/SMR limb observations of stratospheric trace gases: Validation of N2O
- 2005
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 110:9, s. D09301-20
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Tidskriftsartikel (refereegranskat)abstract
- The Sub-Millimetre Radiometer (Odin/SMR) on board the Odin satellite, launched on 20 February 2001, performs regular measurements of the global distribution of stratospheric nitrous oxide (N2O) using spectral observations of the J = 20→ 19 rotational transition centered at 502.296 GHz. We present a quality assessment for the retrieved N2O profiles (level 2 product) by comparison with independent balloonborne and aircraftborne validation measurements as well as by cross-comparing with preliminary results from other satellite instruments. An agreement with the airborne validation experiments within 28 ppbv in terms of the root mean square (RMS) deviation is found for all SMR data versions (v222, v223, and v1.2) under investigation. More precisely, the agreement is within 19 ppbv for N2O volume mixing ratios (VMR) lower than 200 ppbv and within 10% for mixing ratios larger than 150 ppbv. Given the uncertainties due to atmospheric variability inherent to such comparisons, these values should be interpreted as upper limits for the systematic error of the Odin/SMR N2O measurements. Odin/SMR N2O mixing ratios are systematically slightly higher than nonvalidated data obtained from the Improved Limb Atmospheric Spectrometer-II (ILAS-II) on board the Advanced Earth Observing Satellite-II (ADEOS-II). Root mean square deviations are generally within 23 ppbv (or 20% for VMR-N2O > 100 ppbv) for versions 222 and 223. The comparison with data obtained from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on the Envisat satellite yields a good agreement within 9-17 ppbv (or 10% for VMR-N2O > 100 ppbv) for the same data versions. Odin/SMR version 1.2 data show somewhat larger RMS deviations and a higher positive bias.
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