Bruyn, G A W* Dotaz Zobrazit nápovědu
svazky : ilustrace ; 27 cm
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
Handbook of clinical neurology ; 9
xi, 706 p. : ill. ; 27 cm.
- MeSH
- autoimunitní nemoci nervového systému MeSH
- demyelinizační nemoci MeSH
- roztroušená skleróza MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
Handbook of clinical neurology ; rev. ser., 20 = vol. 64
xii, 506 s. : il., tab., grafy ; 27 cm
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
- toxikologie
BACKGROUND: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. METHODS: RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test and Cochrane-Q test respectively, including the comparison of palmar vs. dorsal regions (chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response means (SRM)/linear regression. Analyses were also performed separately for early and established RA. RESULTS: A total of 435 patients (N = 138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p ≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p < 0.001) and the palmar side of the finger joints by PD (p < 0.001) were more frequently pathologic. The reduced US7 score (GS/PD: palmar MCP2, dorsal wrist, EDC and ECU, only PD: dorsal MCP2) showed therapy response (SRM 0.433) after 6 months and retained 76% of the full US7 score's information. No major differences between the groups of early and established RA could be detected. CONCLUSIONS: The wrist, MCP2, EDC, and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.
- MeSH
- lidé MeSH
- mladiství MeSH
- revmatoidní artritida * diagnostické zobrazování farmakoterapie patologie MeSH
- šlachy diagnostické zobrazování MeSH
- stupeň závažnosti nemoci MeSH
- synovitida * patologie MeSH
- ultrasonografie MeSH
- zápěstí MeSH
- zápěstní kloub diagnostické zobrazování patologie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
SUMMARY: The New E-Resource for Drug Discovery (NERDD) is a quickly expanding web portal focused on the provision of peer-reviewed in silico tools for drug discovery. NERDD currently hosts tools for predicting the sites of metabolism (FAME) and metabolites (GLORY) of small organic molecules, for flagging compounds that are likely to interfere with biological assays (Hit Dexter), and for identifying natural products and natural product derivatives in large compound collections (NP-Scout). Several additional models and components are currently in development. AVAILABILITY AND IMPLEMENTATION: The NERDD web server is available at https://nerdd.zbh.uni-hamburg.de. Most tools are also available as software packages for local installation.
Handbook of clinical neurology ; vol. 66 = rev. ser. 22
xviii, 772 s. : il., tab. ; 27 cm
- MeSH
- lipidózy MeSH
- Schilderova difuzní cerebroskleróza MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
OBJECTIVE: To identify and synthesize the best available evidence on the application of musculoskeletal (MSK) ultrasound (US) in patients with systemic lupus erythematosus (SLE) and to present the measurement properties of US in different elementary lesions and pathologies. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library was performed. Original articles were included that were published in English between August 1, 2014, and December 31, 2018, reporting US, Doppler, synovitis, joint effusion, bone erosion, tenosynovitis, and enthesitis in patients with SLE. Data extraction focused on the definition and quantification of US-detected synovitis, joint effusion, bone erosion, tenosynovitis, enthesitis, and the measurement properties of US according to the OMERACT Filter 2.1 instruments selection. RESULTS: Of the 143 identified articles, 15 were included. Most articles were cross-sectional studies (14/15, 93%). The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Regarding the measurement properties of US in different elementary lesions and pathologies, all studies dealt with face validity, content validity, and feasibility. Most studies achieved construct validity. Concerning the reliability of image reading, 1 study (1/15, 7%) assessed both intraobserver and interobserver reliability. For image acquisition, 4 studies (4/15, 27%) evaluated interobserver reliability and none had evaluated intraobserver reliability. Criterion validity was assessed in 1 study (1/15, 7%). Responsiveness was not considered in any of the studies. CONCLUSION: This literature review demonstrates the need for further research and validation work to define the involvement of US as an outcome measurement instrument for the MSK manifestations in patients with SLE.
- MeSH
- dospělí MeSH
- entezopatie diagnostické zobrazování MeSH
- hodnocení výsledků zdravotní péče metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- muskuloskeletální systém diagnostické zobrazování MeSH
- průřezové studie MeSH
- psoriatická artritida diagnostické zobrazování MeSH
- reprodukovatelnost výsledků MeSH
- revmatoidní artritida diagnostické zobrazování MeSH
- studie proveditelnosti MeSH
- stupeň závažnosti nemoci MeSH
- synovitida diagnostické zobrazování MeSH
- systémový lupus erythematodes diagnostické zobrazování MeSH
- tenosynovitida diagnostické zobrazování MeSH
- ultrasonografie dopplerovská metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Handbook of clinical neurology ; vol. 67-69 = rev. ser. 23-25
3 sv. : il., tab. ; 27 cm
- MeSH
- nádory nervového systému MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
- onkologie
In this work we present the third generation of FAst MEtabolizer (FAME 3), a collection of extra trees classifiers for the prediction of sites of metabolism (SoMs) in small molecules such as drugs, druglike compounds, natural products, agrochemicals, and cosmetics. FAME 3 was derived from the MetaQSAR database ( Pedretti et al. J. Med. Chem. 2018 , 61 , 1019 ), a recently published data resource on xenobiotic metabolism that contains more than 2100 substrates annotated with more than 6300 experimentally confirmed SoMs related to redox reactions, hydrolysis and other nonredox reactions, and conjugation reactions. In tests with holdout data, FAME 3 models reached competitive performance, with Matthews correlation coefficients (MCCs) ranging from 0.50 for a global model covering phase 1 and phase 2 metabolism, to 0.75 for a focused model for phase 2 metabolism. A model focused on cytochrome P450 metabolism yielded an MCC of 0.57. Results from case studies with several synthetic compounds, natural products, and natural product derivatives demonstrate the agreement between model predictions and literature data even for molecules with structural patterns clearly distinct from those present in the training data. The applicability domains of the individual models were estimated by a new, atom-based distance measure (FAMEscore) that is based on a nearest-neighbor search in the space of atom environments. FAME 3 is available via a public web service at https://nerdd.zbh.uni-hamburg.de/ and as a self-contained Java software package, free for academic and noncommercial research.
In search of a potent small molecular PD-L1 inhibitor, we designed and synthesized a compound based on a 2-hydroxy-4-phenylthiophene-3-carbonitrile moiety. Ligand's performance was tested in vitro and compared side-by-side with a known PD-L1 antagonist with a proven bioactivity BMS1166. Subsequently, we modified both compounds to allow 18F labeling that could be used for PET imaging. Radiolabeling, which is used in drug development and diagnosis, was applied to investigate the properties of those ligands and test them against tissue sections with diverse expression levels of PD-L1. We confirmed biological activity toward hPD-L1 for this inhibitor, comparable with BMS1166, while holding enhanced pharmacological properties.
- MeSH
- antigeny CD274 * MeSH
- inhibitory kontrolních bodů * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
