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Sökning: WFRF:(Schneider Nadine) > (2020-2024)

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1.
  • Bender, Andreas, et al. (författare)
  • Evaluation guidelines for machine learning tools in the chemical sciences
  • 2022
  • Ingår i: Nature Reviews Chemistry. - : Springer Science and Business Media LLC. - 2397-3358. ; 6:6, s. 428-442
  • Tidskriftsartikel (refereegranskat)abstract
    • Machine learning (ML) promises to tackle the grand challenges in chemistry and speed up the generation, improvement and/or ordering of research hypotheses. Despite the overarching applicability of ML workflows, one usually finds diverse evaluation study designs. The current heterogeneity in evaluation techniques and metrics leads to difficulty in (or the impossibility of) comparing and assessing the relevance of new algorithms. Ultimately, this may delay the digitalization of chemistry at scale and confuse method developers, experimentalists, reviewers and journal editors. In this Perspective, we critically discuss a set of method development and evaluation guidelines for different types of ML-based publications, emphasizing supervised learning. We provide a diverse collection of examples from various authors and disciplines in chemistry. While taking into account varying accessibility across research groups, our recommendations focus on reporting completeness and standardizing comparisons between tools. We aim to further contribute to improved ML transparency and credibility by suggesting a checklist of retro-/prospective tests and dissecting their importance. We envisage that the wide adoption and continuous update of best practices will encourage an informed use of ML on real-world problems related to the chemical sciences. [Figure not available: see fulltext.]
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2.
  • Berron, David, et al. (författare)
  • A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices
  • 2024
  • Ingår i: npj Digital Medicine. - 2398-6352. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer’s disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls (n = 97), individuals with subjective cognitive decline (n = 59), or patients with mild cognitive impairment (n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.
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3.
  • Gauss, Patrick, et al. (författare)
  • Regulating the sharing economy : The effects of day caps on short- and long-term rental markets and stakeholder outcomes
  • 2024
  • Ingår i: Journal of the Academy of Marketing Science. - : Springer. - 0092-0703 .- 1552-7824.
  • Tidskriftsartikel (refereegranskat)abstract
    • Home sharing platforms have experienced a rapid growth over the last decade. Following negative publicity, many cities have started regulating the short-term rental market. Regulations often involve a cap on the number of days a property can be rented out on a short-term basis. We draw on rich data for short-term rentals on Airbnb and for the long-term rental market to examine the impact of short-term rental regulations with a day cap on various stakeholders: hosts, guests, the platform provider, and residents. Based on a difference-in-differences design, we document a sizable drop in Airbnb activity. Interestingly, not only targeted hosts (i.e., hosts with reservation days larger than the day cap), but also non-targeted hosts reduce their Airbnb activity. The reservation days of non-targeted hosts decrease between 26.27% and 51.89% depending on the treatment. Targeted hosts experience a similar decline. There is, nevertheless, significant non-compliance: more than one third of hosts do not comply with enacted short-term rental regulations. Additional analyses show that few properties are redirected from short-term rental to long-term rental use and that there is no significant drop in long-term rents. Drawing on a theoretical model, we tie the estimated effects to changes in stakeholders' welfare: Regulations significantly reduce the welfare of hosts, and the loss ranges between 46.30% and 9.02%. The welfare loss of the platform provider is proportional to the loss of the hosts. Welfare of guests decreases moderately ranging between 4.5% to 4.1%. The welfare of residents increases minimal. These results question the effectiveness and desirability of the studied short-term rental regulations.
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4.
  • Ge, Changrong, et al. (författare)
  • Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor
  • 2022
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 81:4, s. 480-489
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Rheumatoid arthritis (RA) is an autoimmune disease strongly associated with the major histocompatibility complex (MHC) class II allele DRB1*04:01, which encodes a protein that binds self-peptides for presentation to T cells. This study characterises the autoantigen-presenting function of DRB1*04:01 (HLA-DRA*01:01/HLA-DRB1*04:01) at a molecular level for prototypic T-cell determinants, focusing on a post-translationally modified collagen type II (Col2)-derived peptide.Methods The crystal structures of DRB1*04:01 molecules in complex with the peptides HSP70(289-306), citrullinated CILP982-996 and galactosylated Col2(259-273) were determined on cocrystallisation. T cells specific for Col2(259-273) were investigated in peripheral blood mononuclear cells from patients with DRB1*04:01-positive RA by cytofluorometric detection of the activation marker CD154 on peptide stimulation and binding of fluorescent DRB1*0401/Col2(259-273) tetramer complexes. The cDNAs encoding the T-cell receptor (TCR) alpha-chains and beta-chains were cloned from single-cell sorted tetramer-positive T cells and transferred via a lentiviral vector into TCR-deficient Jurkat 76 cells.Results The crystal structures identified peptide binding to DRB1*04:01 and potential side chain exposure to T cells. The main TCR recognition sites in Col2(259-273) were lysine residues that can be galactosylated. RA T-cell responses to DRB1*04:01-presented Col2(259-273) were dependent on peptide galactosylation at lysine 264. Dynamic molecular modelling of a functionally characterised Col2(259-273)-specific TCR complexed with DRB1*04:01/Col2(259-273) provided evidence for differential allosteric T-cell recognition of glycosylated lysine 264.Conclusions The MHC-peptide-TCR interactions elucidated in our study provide new molecular insights into recognition of a post-translationally modified RA T-cell determinant with a known dominant role in arthritogenic and tolerogenic responses in murine Col2-induced arthritis.
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5.
  • Rieke, Johanna Magdalena, et al. (författare)
  • SLC20A1Is Involved in Urinary Tract and Urorectal Development
  • 2020
  • Ingår i: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
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6.
  • Schneider, Edith, et al. (författare)
  • MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.
  • 2020
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 34, s. 1253-1265
  • Tidskriftsartikel (refereegranskat)abstract
    • MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved. We identified miR-708 to be upregulated in Hoxa9/Meis1 AML inducing cell lines as well as in AML patients. We further showed Meis1 directly targeting miR-708 and modulating its expression through epigenetic transcriptional regulation. CRISPR/Cas9 mediated knockout of miR-708 in Hoxa9/Meis1 cells delayed disease onset in vivo, demonstrating for the first time a pro-leukemic contribution of miR-708 in this context. Overexpression of miR-708 however strongly impeded Hoxa9 mediated transformation and homing capacity in vivo through modulation of adhesion factors and induction of myeloid differentiation. Taken together, we reveal miR-708, a putative tumor suppressor miRNA and direct target of Meis1, as a potent antagonist of the Hoxa9 phenotype but an effector of transformation in Hoxa9/Meis1. This unexpected finding highlights the yet unexplored role of miRNAs as indirect regulators of the Hox program during normal and aberrant hematopoiesis.
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7.
  • Thurner, Lorenz, et al. (författare)
  • Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma
  • 2020
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD(+) LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/kappa -type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD(+) B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-kappa B pathway and the proliferation of IgD(+) DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD(+) BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies. Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.
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8.
  • Urbonaviciute, Vilma, et al. (författare)
  • Therapy targeting antigen-specific T cells by a peptide-based tolerizing vaccine against autoimmune arthritis
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Stockholm : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:25
  • Tidskriftsartikel (refereegranskat)abstract
    • A longstanding goal has been to find an antigen-specific preventive therapy, i.e., a vaccine, for autoimmune diseases. It has been difficult to find safe ways to steer the targeting of natural regulatory antigen. Here, we show that the administration of exog-enous mouse major histocompatibility complex class II protein bounding a unique galactosylated collagen type II (COL2) peptide (Aq-galCOL2) directly interacts with the antigen-specific TCR through a positively charged tag. This leads to expanding a VISTA-positive nonconventional regulatory T cells, resulting in a potent dominant suppressive effect and protection against arthritis in mice. The therapeutic effect is dom-inant and tissue specific as the suppression can be transferred with regulatory T cells, which downregulate various autoimmune arthritis models including antibody-induced arthritis. Thus, the tolerogenic approach described here may be a promising dominant antigen-specific therapy for rheumatoid arthritis, and in principle, for autoimmune diseases in general.
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