Due to evolutionary conservation of biology, experimental knowledge captured from genetic studies in eukaryotic model organisms provides insight into human cellular pathways and ultimately physiology. Yeast chemogenomic profiling is a powerful approach for annotating cellular responses to small molecules. Using an optimized platform, we provide the relative sensitivities of the heterozygous and homozygous deletion collections for nearly 1800 biologically active compounds. The data quality enables unique insights into pathways that are sensitive and resistant to...

Supplemental material, sj-docx-1-mso-10.1177_20552173231153557 for Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers by Lars Forsberg, Tim Spelman, Pernilla Klyve, Ali Manouchehrinia, Ryan Ramanujam, Elena Mouresan, Jiri Drahota, Dana Horakova, Hanna Joensen, Luigi Pontieri, Melinda Magyari, David Ellenberger, Alexander Stahmann, Jeff Rodgers, James Witts, Rod Middleton, Richard Nicholas, Vladimir Bezlyak, Nicholas Adlard, Thomas Hach, Carol Lines, Sandra Vukusic, Merja Soilu-Hänninen, Anneke van der Walt, Helmut Butzkueven, Pietro Iaffaldano, Maria...

Cette année 2020 aura été marquée par un évènement sans précédent dans notre monde contemporain : la pandémie de COVID-19 (COronaVirus Disease), appelée aussi 2019-nCoV (2019 new Coronavirus) ou encore SARS-CoV2 (Severe Acute Respiratory Syndrome – CoronaVirus 2). Nous ne pouvions pas publier notre revue 2020 sans parler de ce sujet qui aura modifié nos comportements et marqué nos modes de vie comme jamais auparavant. Nous l’abordons ici à travers un prisme historique et histologique.

Objectives To evaluate the impact of early (at first-line) vs delayed (3-year delay) ofatumumab initiation and long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis (RMS) patients from a Spanish societal perspective. Methods A cost-consequence analysis was conducted using an Expanded Disability Status Scale (EDSS)-based Markov model. Inputs were sourced from ASCLEPIOS I and II trials and published literature. Results At the end of 10 years, compared with first-line teriflunomide...

BackgroundTo assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing–remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported.Materials and methodsData were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the...

High-throughput phenotypic screening against yeast Saccharomyces cerevisiae revealed a series of triazolo-pyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. To elucidate the target of this series we have applied a chemogenomic profiling approach using the S. cerevisiae deletion collection. All compounds of the series yielded highly similar profiles that suggested acetolactate synthase (Ilv2p, catalyzes the first common step in branched chain amino acid biosynthesis) as a possible target. High correlation...

Millions of putative transcriptional regulatory elements (TREs) have been cataloged in the human genome, yet their functional relevance in specific pathophysiological settings remains to be determined. This is critical to understand how oncogenic transcription factors (TFs) engage specific TREs to impose transcriptional programs underlying malignant phenotypes. Here, we combine cutting edge CRISPR screens and epigenomic profiling to functionally survey ≈15,000 TREs engaged by estrogen receptor (ER). We show that ER exerts its oncogenic role in...

En 2015, la 2ème journée à thème de l’AFH a réuni six participants venus échanger leurs expériences sur le thème retenu de l’immunofluorescence en coupe paraffine. En effet si le plus souvent la détection d’antigènes par des techniques d’immunofluorescence est pratiquée sur des coupes de tissus congelés, son usage sur des coupes en paraffine est beaucoup plus rare et tient essentiellement au fait de la réputation qu’elle soit limitée par des problèmes d’autofluorescence par exemple....

Supplemental material, sj-pdf-2-mso-10.1177_20552173231153557 for Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers by Lars Forsberg, Tim Spelman, Pernilla Klyve, Ali Manouchehrinia, Ryan Ramanujam, Elena Mouresan, Jiri Drahota, Dana Horakova, Hanna Joensen, Luigi Pontieri, Melinda Magyari, David Ellenberger, Alexander Stahmann, Jeff Rodgers, James Witts, Rod Middleton, Richard Nicholas, Vladimir Bezlyak, Nicholas Adlard, Thomas Hach, Carol Lines, Sandra Vukusic, Merja Soilu-Hänninen, Anneke van der Walt, Helmut Butzkueven, Pietro Iaffaldano, Maria...

BackgroundTo assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing–remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported.Materials and methodsData were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the...

Additional file 1: Supplementary Table 1. Definitions used in the study. Supplementary Table 2. Details of eligibility criteria. Supplementary Table 3. Patient reported outcome tool: mMIDAS. Supplementary Table 4. Change from baseline in MMD by visit, observed,mixed model repeated measures (full analysis set). Supplementary Table 5. Patientincidence rates of treatment-emergent SAEs in the study by primary SOC (Safety analysis set).

Abstact Background DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. Methods DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18–65 years) were randomised (1:1)...

Background and objectives: Beneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures simultaneously may allow for a greater number of adaptive mutations, increasing the opportunities for competition between selectively advantageous alterations, and thereby reducing the rate of adaptation. Methodology: We evolved a strain of Saccharomyces cerevisiae that could...

Additional file 1: Supplementary Table 1. Definitions used in the study. Supplementary Table 2. Details of eligibility criteria. Supplementary Table 3. Patient reported outcome tool: mMIDAS. Supplementary Table 4. Change from baseline in MMD by visit, observed,mixed model repeated measures (full analysis set). Supplementary Table 5. Patientincidence rates of treatment-emergent SAEs in the study by primary SOC (Safety analysis set).

Abstact Background DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. Methods DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18–65 years) were randomised (1:1)...

Supplemental material, sj-pdf-2-mso-10.1177_20552173231153557 for Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers by Lars Forsberg, Tim Spelman, Pernilla Klyve, Ali Manouchehrinia, Ryan Ramanujam, Elena Mouresan, Jiri Drahota, Dana Horakova, Hanna Joensen, Luigi Pontieri, Melinda Magyari, David Ellenberger, Alexander Stahmann, Jeff Rodgers, James Witts, Rod Middleton, Richard Nicholas, Vladimir Bezlyak, Nicholas Adlard, Thomas Hach, Carol Lines, Sandra Vukusic, Merja Soilu-Hänninen, Anneke van der Walt, Helmut Butzkueven, Pietro Iaffaldano, Maria...

To evaluate the impact of early (at first-line) vs delayed (3-year delay) ofatumumab initiation and long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis (RMS) patients from a Spanish societal perspective. A cost-consequence analysis was conducted using an Expanded Disability Status Scale (EDSS)-based Markov model. Inputs were sourced from ASCLEPIOS I and II trials and published literature. At the end of 10 years, compared with first-line teriflunomide treatment, early first-line...

ObjectivesTo examine healthcare utilisation patterns in a sample of young people with self-reported experiences of self-harm and/or suicidal behaviours.MethodsA national survey examining mental health in a nationally representative sample of young Australians aged 12–17 years, linked to routinely collected healthcare and dispensing data. For respondents that self-reported experience of self-harm, suicidal ideation, suicidal plan and/or suicide attempt, we assessed attendance at a Medicare Benefits Scheme (MBS) subsidised MH service or non-MH general practitioner (GP) attendance...

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ~380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a...

Supplemental material, sj-docx-1-mso-10.1177_20552173231153557 for Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers by Lars Forsberg, Tim Spelman, Pernilla Klyve, Ali Manouchehrinia, Ryan Ramanujam, Elena Mouresan, Jiri Drahota, Dana Horakova, Hanna Joensen, Luigi Pontieri, Melinda Magyari, David Ellenberger, Alexander Stahmann, Jeff Rodgers, James Witts, Rod Middleton, Richard Nicholas, Vladimir Bezlyak, Nicholas Adlard, Thomas Hach, Carol Lines, Sandra Vukusic, Merja Soilu-Hänninen, Anneke van der Walt, Helmut Butzkueven, Pietro Iaffaldano, Maria...

To evaluate the impact of early (at first-line) vs delayed (3-year delay) ofatumumab initiation and long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis (RMS) patients from a Spanish societal perspective. A cost-consequence analysis was conducted using an Expanded Disability Status Scale (EDSS)-based Markov model. Inputs were sourced from ASCLEPIOS I and II trials and published literature. At the end of 10 years, compared with first-line teriflunomide treatment, early first-line...

Supplemental Material for Use of Medicare Benefit Scheme mental health services in young people who experienced self-harm and/or suicidal behaviours: Data from the Young Minds Matter survey by Kate M Chitty, Michael Sawyer, Gregory Carter, and David Lawrence in Australasian Psychiatry