scDrugPrio: A framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseasesIneffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs. In our recent work, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs.scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn’s disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn’s disease patients. The analysis showed great variations in drug predictions between patients, for example,assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment. Application to individual patients indicates scDrugPrio’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package (https://github.com/SDTC-CPMed/scDrugPrio).PsA patients were recruited from different rheumatology departments from university hospitals belonging to the IMIDC. All PsA patients were diagnosed according to the CASPAR diagnostic criteria for PsA (34) with > 1 year of disease evolution and > 18 years old at the time of recruitment. Exclusion criteria for PsA included the presence of any other form of inflammatory arthritis, rheumatoid factor levels greater than twice the normality threshold or confirmed presence of an inflammatory bowel disease. PBMCs were sampled prior to treatment with anti-TNF and cryopreserved. Treatment response was classified at week 12 according to the EULAR response. For the anti-TNF study, 6 males and 10 females were included. Simultaneously, healthy age- and sex-matched control subjects were recruited from healthy volunteers recruited through the Vall d’Hebron University Hospital in Barcelona (Spain). All the controls were screened for the presence of any autoimmune disorder, as well as for first-degree family occurrence of autoimmune diseases. None were found to be positive. All in all, four males and four females were included as controls.Patients in the study of PBMC from patients with psoriatic arthritis consented to participate in this study as approved by Hospital Universitari Vall d'Hebron Clinical Research Ethics Committee with reference number 20/0022. Protocols were reviewed and approved by the local institutional review board of each participating centre. This research conformed to the principles of the Helsinki Declaration.In summary, this data set includes raw scRNA-seq data and metadata of pre-treatment PBMC of psoriatic arthritis patients that did or did not respond to anti-TNF treatment as well as untreated healthy controls. The RDS file also includes the deep count auto encoder (DCA) denoised scRNA-seq matrix as well as clustering outcomes.
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An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures. Related Article: Marlon Winter, Natallia Peshkur, Mathias A. Ellwanger, Alberto Pérez-Bitrián, Patrick Voßnacker, Simon Steinhauer, Sebastian Riedel|2023|Chem.-Eur.J.|29|e202203634|doi:10.1002/chem.202203634
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FNAL-TEV. This Letter reports a measurement of the cross section for producing pairs of central prompt isolated photons in proton-antiproton collisions at a total energy of 1.96 TeV using data corresponding to 9.5/fb integrated luminosity collected with the CDF II detector at the Fermilab Tevatron. The measured differential cross section is compared to three calculations derived from the theory of strong interactions. These include a prediction based on a leading order matrix element calculation merged with parton shower, a next-to-leading order, and a next-to-next-to-leading order calculation. The first and last calculations reproduce most aspects of the data, thus showing the importance of higher-order contributions for understanding the theory of strong interaction and improving measurements of the Higgs boson and searches for new phenomena in diphoton final states. The measured differential cross sections for $y(\gamma\gamma)$, the rapidity of the diphoton system, when $P_T(\gamma\gamma) > M(\gamma\gamma)$ , together with the predictions from the Sherpa and NNLO Monte Carlos.
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doi: 10.18167/dvn1/gitsrp
Antimicrobial resistance is one of the major public health issues and solutions to reduce its usage are urgently needed. This study aims to understand the transition process of Vietnamese chicken farmers toward lower antimicrobial usage (AMU). Semi-structured interviews were conducted with 18 farmers and analysed through thematic analysis in 2021-2022. Motivations and barriers to reduce AMU were identified as well as local solutions.
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Specific neuropeptides regulate in arthropods the shedding of the old cuticle (ecdysis) followed by maturation of the new cuticle. In Drosophila melanogaster, the last ecdysis occurs at eclosion from the pupal case, with a post-eclosion behavioural sequence that leads to wing extension, cuticle stretching and tanning. These events are highly stereotyped and are controlled by a subset of crustacean cardioactive peptide (CCAP) neurons through the expression of the neuropeptide Bursicon (Burs). We have studied the role of the transcription factor Odd-paired (Opa) during the post-eclosion period. We report that opa is expressed in the CCAP neurons of the central nervous system during various steps of the ecdysis process and in peripheral CCAP neurons innerving the larval muscles involved in adult ecdysis. We show that its downregulation alters Burs expression in the CCAP neurons. Ectopic expression of Opa, or the vertebrate homologve Zic2, in the CCAP neurons also affects Burs expression, indicating an evolutionary functional conservation. Finally, our results show that, independently of its role in Burs regulation, Opa prevents death of CCAP neurons during larval development.
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scDrugPrio: A framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseasesIneffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs. In our recent work, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs.scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn’s disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn’s disease patients. The analysis showed great variations in drug predictions between patients, for example,assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment. Application to individual patients indicates scDrugPrio’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package (https://github.com/SDTC-CPMed/scDrugPrio).PsA patients were recruited from different rheumatology departments from university hospitals belonging to the IMIDC. All PsA patients were diagnosed according to the CASPAR diagnostic criteria for PsA (34) with > 1 year of disease evolution and > 18 years old at the time of recruitment. Exclusion criteria for PsA included the presence of any other form of inflammatory arthritis, rheumatoid factor levels greater than twice the normality threshold or confirmed presence of an inflammatory bowel disease. PBMCs were sampled prior to treatment with anti-TNF and cryopreserved. Treatment response was classified at week 12 according to the EULAR response. For the anti-TNF study, 6 males and 10 females were included. Simultaneously, healthy age- and sex-matched control subjects were recruited from healthy volunteers recruited through the Vall d’Hebron University Hospital in Barcelona (Spain). All the controls were screened for the presence of any autoimmune disorder, as well as for first-degree family occurrence of autoimmune diseases. None were found to be positive. All in all, four males and four females were included as controls.Patients in the study of PBMC from patients with psoriatic arthritis consented to participate in this study as approved by Hospital Universitari Vall d'Hebron Clinical Research Ethics Committee with reference number 20/0022. Protocols were reviewed and approved by the local institutional review board of each participating centre. This research conformed to the principles of the Helsinki Declaration.In summary, this data set includes raw scRNA-seq data and metadata of pre-treatment PBMC of psoriatic arthritis patients that did or did not respond to anti-TNF treatment as well as untreated healthy controls. The RDS file also includes the deep count auto encoder (DCA) denoised scRNA-seq matrix as well as clustering outcomes.
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An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures. Related Article: Marlon Winter, Natallia Peshkur, Mathias A. Ellwanger, Alberto Pérez-Bitrián, Patrick Voßnacker, Simon Steinhauer, Sebastian Riedel|2023|Chem.-Eur.J.|29|e202203634|doi:10.1002/chem.202203634
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FNAL-TEV. This Letter reports a measurement of the cross section for producing pairs of central prompt isolated photons in proton-antiproton collisions at a total energy of 1.96 TeV using data corresponding to 9.5/fb integrated luminosity collected with the CDF II detector at the Fermilab Tevatron. The measured differential cross section is compared to three calculations derived from the theory of strong interactions. These include a prediction based on a leading order matrix element calculation merged with parton shower, a next-to-leading order, and a next-to-next-to-leading order calculation. The first and last calculations reproduce most aspects of the data, thus showing the importance of higher-order contributions for understanding the theory of strong interaction and improving measurements of the Higgs boson and searches for new phenomena in diphoton final states. The measured differential cross sections for $y(\gamma\gamma)$, the rapidity of the diphoton system, when $P_T(\gamma\gamma) > M(\gamma\gamma)$ , together with the predictions from the Sherpa and NNLO Monte Carlos.
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