| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 8. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 9. |
- de Erausquin, Gabriel A, et al.
(författare)
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Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.
- 2022
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Ingår i: Alzheimer's & dementia (New York, N. Y.). - : Wiley. - 2352-8737. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term.This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions.Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe.The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection.The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.
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| 12. |
- Claret, Guillaume, et al.
(författare)
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Bayesian Inference Using Data Flow Analysis
- 2013
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Ingår i: ESEC/FSE '13. - New York, NY, USA : ACM Press. - 9781450322379 ; , s. 92-102
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Konferensbidrag (refereegranskat)abstract
- We present a new algorithm for Bayesian inference over probabilistic programs, based on data flow analysis techniques from the program analysis community. Unlike existing techniques for Bayesian inference on probabilistic programs, our data flow analysis algorithm is able to perform inference directly on probabilistic programs with loops. Even for loop-free programs, we show that data flow analysis offers better precision and better performance benefits over existing techniques. We also describe heuristics that are crucial for our inference to scale, and present an empirical evaluation of our algorithm over a range of benchmarks.
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| 13. |
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| 14. |
- Ferro, Marc D., et al.
(författare)
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NeuroRoots, a bio-inspired, seamless brain machine interface for long-term recording in delicate brain regions
- 2024
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Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Scalable electronic brain implants with long-term stability and low biological perturbation are crucial technologies for high-quality brain-machine interfaces that can seamlessly access delicate and hard-to-reach regions of the brain. Here, we created "NeuroRoots," a biomimetic multi-channel implant with similar dimensions (7 mu m wide and 1.5 mu m thick), mechanical compliance, and spatial distribution as axons in the brain. Unlike planar shank implants, these devices consist of a number of individual electrode "roots," each tendril independent from the other. A simple microscale delivery approach based on commercially available apparatus minimally perturbs existing neural architectures during surgery. NeuroRoots enables high density single unit recording from the cerebellum in vitro and in vivo. NeuroRoots also reliably recorded action potentials in various brain regions for at least 7 weeks during behavioral experiments in freely-moving rats, without adjustment of electrode position. This minimally invasive axon-like implant design is an important step toward improving the integration and stability of brain-machine interfacing.
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| 15. |
- Frykholm, Karolin, 1977, et al.
(författare)
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DNA in Nanochannels - Theory and Applications
- 2022
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Ingår i: Quarterly Reviews of Biophysics. - 0033-5835 .- 1469-8994. ; 55
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Forskningsöversikt (refereegranskat)abstract
- Nanofluidic structures have over the last two decades emerged as a powerful platform for detailed analysis of DNA on the kilobase pair length scale. When DNA is confined to a nanochannel, the combination of excluded volume and DNA stiffness leads to the DNA being stretched to near its full contour length. Importantly, this stretching takes place at equilibrium, without any chemical modifications to the DNA. As a result, any DNA can be analyzed, such as DNA extracted from cells or circular DNA, and it is relatively easy to study reactions on the ends of linear DNA. In this comprehensive review, we first give a thorough description of the current understanding of the polymer physics of DNA and how that leads to stretching in nanochannels. We then describe how the versatility of nanofabrication can be used to design devices specifically tailored for the problem at hand, either by controlling the degree of confinement or enabling facile exchange of reagents to measure DNA-protein reaction kinetics. The remainder of the review focuses on two important applications of confining DNA in nanochannels. The first is optical DNA mapping, which provides kilobase pair resolution of the genomic sequence of intact DNA molecules in excess of 100 kilobase pairs in size through labeling strategies that are suitable for fluorescence microscopy. In this section, we highlight solutions to the technical aspects of genomic mapping, rather than recent applications in human genetics, including the use of enzyme-based labeling and affinity-based labeling to produce the genomic maps. The second is DNA-protein interactions, and several recent examples of such studies on DNA compaction, filamentous protein complexes, and reactions with the chain ends are presented. Taken together, these two applications demonstrate the power of DNA confinement and nanofluidics in genomics, molecular biology and biophysics.
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| 16. |
- Gordon, Andrew D., et al.
(författare)
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A Model-Learner Pattern for Bayesian Reasoning
- 2013
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Ingår i: Proceedings of the 40th annual ACM SIGPLAN-SIGACT symposium on Principles of programming languages. - New York, NY : Association for Computing Machinery (ACM). - 9781450318327 ; , s. 403-416
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Konferensbidrag (refereegranskat)abstract
- A Bayesian model is based on a pair of probability distributions, known as the prior and sampling distributions. A wide range of fundamental machine learning tasks, including regression, classification, clustering, and many others, can all be seen as Bayesian models. We propose a new probabilistic programming abstraction, a typed Bayesian model, which is based on a pair of probabilistic expressions for the prior and sampling distributions. A sampler for a model is an algorithm to compute synthetic data from its sampling distribution, while a learner for a model is an algorithm for probabilistic inference on the model. Models, samplers, and learners form a generic programming pattern for model-based inference. They support the uniform expression of common tasks including model testing, and generic compositions such as mixture models, evidence-based model averaging, and mixtures of experts. A formal semantics supports reasoning about model equivalence and implementation correctness. By developing a series of examples and three learner implementations based on exact inference, factor graphs, and Markov chain Monte Carlo, we demonstrate the broad applicability of this new programming pattern.
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| 17. |
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| 18. |
- Jiang, Kai, 1988, et al.
(författare)
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Alpha-Synuclein Modulates the Physical Properties of DNA
- 2018
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Ingår i: Chemistry - A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 24:58, s. 15685-15690
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Tidskriftsartikel (refereegranskat)abstract
- Published by Wiley-VCH Verlag GmbH & Co. KGaA. Fundamental research on Parkinson's disease (PD) most often focuses on the ability of α-synuclein (aS) to form oligomers and amyloids, and how such species promote brain cell death. However, there are indications that aS also plays a gene-regulatory role in the cell nucleus. Here, the interaction between monomeric aS and DNA in vitro has been investigated with single-molecule techniques. Using a nanofluidic channel system, it was discovered that aS binds to DNA and by studying the DNA–protein complexes at different confinements we determined that aS binding increases the persistence length of DNA from 70 to 90 nm at high coverage. By atomic force microscopy it was revealed that at low protein-to-DNA ratio, the aS binding occurs as small protein clusters scattered along the DNA; at high protein-to-DNA ratio, the DNA is fully covered by protein. As DNA-aS interactions may play roles in PD, it is of importance to characterize biophysical properties of such complexes in detail.
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| 19. |
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| 20. |
- Martinez, Karina, et al.
(författare)
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Functional implications of glycans and their curation: insights from the workshop held at the 16th Annual International Biocuration Conference in Padua, Italy
- 2024
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Ingår i: DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION. - 1758-0463. ; 2024
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic changes in protein glycosylation impact human health and disease progression. However, current resources that capture disease and phenotype information focus primarily on the macromolecules within the central dogma of molecular biology (DNA, RNA, proteins). To gain a better understanding of organisms, there is a need to capture the functional impact of glycans and glycosylation on biological processes. A workshop titled "Functional impact of glycans and their curation" was held in conjunction with the 16th Annual International Biocuration Conference to discuss ongoing worldwide activities related to glycan function curation. This workshop brought together subject matter experts, tool developers, and biocurators from over 20 projects and bioinformatics resources. Participants discussed four key topics for each of their resources: (i) how they curate glycan function-related data from publications and other sources, (ii) what type of data they would like to acquire, (iii) what data they currently have, and (iv) what standards they use. Their answers contributed input that provided a comprehensive overview of state-of-the-art glycan function curation and annotations. This report summarizes the outcome of discussions, including potential solutions and areas where curators, data wranglers, and text mining experts can collaborate to address current gaps in glycan and glycosylation annotations, leveraging each other's work to improve their respective resources and encourage impactful data sharing among resources.Database URL: https://wiki.glygen.org/Glycan_Function_Workshop_2023
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| 23. |
- Sasanian, Nima, 1993, et al.
(författare)
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Probing physical properties of single amyloid fibrils using nanofluidic channels
- 2023
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Ingår i: Nanoscale. - 2040-3372 .- 2040-3364. ; 15:46, s. 18737-18744
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid fibril formation is central to the pathology of many diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Amyloid fibrils can also have functional and scaffolding roles, for example in bacterial biofilms, and have also been exploited as useful biomaterials. Despite being linear protein homopolymers, amyloid fibrils can exhibit significant structural and morphological polymorphism, making it relevant to study them on the single fibril level. We here introduce the concept of nanofluidic channel analysis to the study of single, fluorescently-labeled amyloid fibrils in solution, monitoring the extension and emission intensity of individual fibrils confined in nanochannels with a depth of 300 nm and a width that gradually increases from 300 to 3000 nm. The change in fibril extension with channel width permitted accurate determination of the persistence length of individual fibrils using Odijk's theory for strongly confined polymers. The technique was applied to amyloid fibrils prepared from the Alzheimer's related peptide amyloid-β(1-42) and the Parkinson's related protein α-synuclein, obtaining mean persistence lengths of 5.9 ± 4.5 μm and 3.0 ± 1.6 μm, respectively. The broad distributions of fibril persistence lengths indicate that amyloid fibril polymorphism can manifest in their physical properties. Interestingly, the α-synuclein fibrils had lower persistence lengths than the amyloid-β(1-42) fibrils, despite being thicker. Furthermore, there was no obvious within-sample correlation between the fluorescence emission intensity per unit length of the labelled fibrils and their persistence lengths, suggesting that stiffness may not be proportional to thickness. We foresee that the nanofluidics methodology established here will be a useful tool to study amyloid fibrils on the single fibril level to gain information on heterogeneity in their physical properties and interactions.
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| 24. |
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| 25. |
- Sharma, Rajhans, 1990, et al.
(författare)
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Real-time compaction of nanoconfined DNA by an intrinsically disordered macromolecular counterion
- 2020
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 533:1, s. 175-180
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate how a recently developed nanofluidic device can be used to study protein-induced compaction of genome-length DNA freely suspended in solution. The protein we use in this study is the hepatitis C virus core protein (HCVcp), which is a positively charged, intrinsically disordered protein. Using nanofluidic devices in combination with fluorescence microscopy, we observe that protein-induced compaction preferentially begins at the ends of linear DNA. This observation would be difficult to make with many other single-molecule techniques, which generally require the DNA ends to be anchored to a substrate. We also demonstrate that this protein-induced compaction is reversible and can be dynamically modulated by exposing the confined DNA molecules to solutions containing either HCVcp (to promote compaction) or Proteinase K (to disassemble the compact nucleo-protein complex). Although the natural binding partner for HCVcp is genomic viral RNA, the general biophysical principles governing protein-induced compaction of DNA are likely relevant for a broad range of nucleic acid-binding proteins and their targets.
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| 26. |
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