This narrative review summarizes the most relevant ectopic models, among which subcutaneous, intramuscular, and kidney capsule transplantation and elaborates on implanted cells and biomaterial scaffolds and on their use to recapitulate morphological and functional features of articular cartilage. Although the absence of a physiological joint environment and biomechanical stimuli is the major limiting factor, ectopic models are an established component for articular cartilage research aiming to generate a bridge between in vitro data and the clinically more relevant translational orthotopic in vivo models when their limitations are considered.Parageobacillus thermoglucosidasius represents a thermophilic, facultative anaerobic bacterial chassis, with several desirable traits for metabolic engineering and industrial production. To further optimize strain productivity, a systems level understanding of its metabolism is needed, which can be facilitated by a genome-scale metabolic model. Here, we present p-thermo, the most complete, curated and validated genome-scale model (to date) of Parageobacillus thermoglucosidasius NCIMB 11955. It spans a total of 890 metabolites, 1175 reactions and 917 metabolic genes, forming an extensive knowledge base for P. https://www.selleckchem.com/products/trolox.html thermoglucosidasius NCIMB 11955 metabolism. The model accurately predicts aerobic utilization of 22 carbon sources, and the predictive quality of internal fluxes was validated with previously published 13C-fluxomics data. In an application case, p-thermo was used to facilitate more in-depth analysis of reported metabolic engineering efforts, giving additional insight into fermentative metabolism. Finally, p-thermo was used to resolve a previously uncharacterised bottleneck in anaerobic metabolism, by identifying the minimal required supplemented nutrients (thiamin, biotin and iron(III)) needed to sustain anaerobic growth. This highlights the usefulness of p-thermo for guiding the generation of experimental hypotheses and for facilitating data-driven metabolic engineering, expanding the use of P. thermoglucosidasius as a high yield production platform.
We compared the process of developing searches with and without using text-mining tools (TMTs) for evidence synthesis products.

This descriptive comparative analysis included seven systematic reviews, classified as simple or complex. Two librarians created MEDLINE strategies for each review, using either usual practice (UP) or TMTs. For each search we calculated sensitivity, number-needed-to-read (NNR) and time spent developing the search strategy.

We found UP searches were more sensitive (UP 92% (95% CI, 85-99); TMT 84.9% (95% CI, 74.4-95.4)), with lower NNR (UP 83 (SD 34); TMT 90 (SD 68)). UP librarians spent an average of 12 h (SD 8) developing search strategies, compared to TMT librarians' 5 hours (SD 2).

Across all reviews, TMT searches were less sensitive than UP searches, but confidence intervals overlapped. For simple SR topics, TMT searches were faster and slightly less sensitive than UP. For complex SR topics, TMT searches were faster and less sensitive than UP searches but identified unique eligible citations not found by the UP searches.
Across all reviews, TMT searches were less sensitive than UP searches, but confidence intervals overlapped. For simple SR topics, TMT searches were faster and slightly less sensitive than UP. For complex SR topics, TMT searches were faster and less sensitive than UP searches but identified unique eligible citations not found by the UP searches.
To identify and suggest strategies to make insufficient evidence ratings in systematic reviews more actionable.

A workgroup comprising members from the Evidence-Based Practice (EPC) Program of the Agency for Healthcare Research and Quality convened throughout 2020. We conducted iterative discussions considering information from three data sources a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs.

We identified five strategies for supplementing systematic review findings when evidence on benefits or harms is expected to be, or found to be, insufficient 1) reconsider eligible study designs, 2) summarize indirect evidence, 3) summarize contextual and implementation evidence, 4) consider modelling, and 5) incorporate unpublished health system data in the evidence synthesis. While these strategies may not increase the strength of evidence, they may improve the utility of reports for decision makers. Adopting these strategies depends on feasibility, timeline, funding, and expertise of the systematic reviewers.

Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users.
Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users.
The aim was to investigate the relative validity of the preference-based measure EORTC QLU-C10D in comparison with the EQ-5D-3L in myelodysplastic syndromes (MDS) patients.

We used data from an international multicentre, observational cohort study of MDS patients. Baseline EORTC QLU-C10D and EQ-5D-3L scores were used and index scores calculated for Italy, Australia, and the UK. Criterion validity was established by Spearman and intraclass correlations (ICC) and Bland-Altman plots. Construct validity was established by the instruments' ability to discriminate known groups, i.e. groups whose health status is expected to differ.

We analyzed data from 619 MDS patients (61.1% male; median age 73.8 years). Correlations between theoretically corresponding domains were largely higher than between unrelated domains. ICCs and Bland-Altman plots indicated moderate to good criterion validity. Ceiling effects were lower for the QLU-C10D (4.7%) than for the EQ-5D-3L (22.6%). The EQ-5D-3L failed to discriminate known-groups in two and the QLU-C10D in one of the comparisons; the QLU-C10D's efficiency in doing so was higher in clinical known-groups.
This narrative review summarizes the most relevant ectopic models, among which subcutaneous, intramuscular, and kidney capsule transplantation and elaborates on implanted cells and biomaterial scaffolds and on their use to recapitulate morphological and functional features of articular cartilage. Although the absence of a physiological joint environment and biomechanical stimuli is the major limiting factor, ectopic models are an established component for articular cartilage research aiming to generate a bridge between in vitro data and the clinically more relevant translational orthotopic in vivo models when their limitations are considered.Parageobacillus thermoglucosidasius represents a thermophilic, facultative anaerobic bacterial chassis, with several desirable traits for metabolic engineering and industrial production. To further optimize strain productivity, a systems level understanding of its metabolism is needed, which can be facilitated by a genome-scale metabolic model. Here, we present p-thermo, the most complete, curated and validated genome-scale model (to date) of Parageobacillus thermoglucosidasius NCIMB 11955. It spans a total of 890 metabolites, 1175 reactions and 917 metabolic genes, forming an extensive knowledge base for P. https://www.selleckchem.com/products/trolox.html thermoglucosidasius NCIMB 11955 metabolism. The model accurately predicts aerobic utilization of 22 carbon sources, and the predictive quality of internal fluxes was validated with previously published 13C-fluxomics data. In an application case, p-thermo was used to facilitate more in-depth analysis of reported metabolic engineering efforts, giving additional insight into fermentative metabolism. Finally, p-thermo was used to resolve a previously uncharacterised bottleneck in anaerobic metabolism, by identifying the minimal required supplemented nutrients (thiamin, biotin and iron(III)) needed to sustain anaerobic growth. This highlights the usefulness of p-thermo for guiding the generation of experimental hypotheses and for facilitating data-driven metabolic engineering, expanding the use of P. thermoglucosidasius as a high yield production platform. We compared the process of developing searches with and without using text-mining tools (TMTs) for evidence synthesis products. This descriptive comparative analysis included seven systematic reviews, classified as simple or complex. Two librarians created MEDLINE strategies for each review, using either usual practice (UP) or TMTs. For each search we calculated sensitivity, number-needed-to-read (NNR) and time spent developing the search strategy. We found UP searches were more sensitive (UP 92% (95% CI, 85-99); TMT 84.9% (95% CI, 74.4-95.4)), with lower NNR (UP 83 (SD 34); TMT 90 (SD 68)). UP librarians spent an average of 12 h (SD 8) developing search strategies, compared to TMT librarians' 5 hours (SD 2). Across all reviews, TMT searches were less sensitive than UP searches, but confidence intervals overlapped. For simple SR topics, TMT searches were faster and slightly less sensitive than UP. For complex SR topics, TMT searches were faster and less sensitive than UP searches but identified unique eligible citations not found by the UP searches. Across all reviews, TMT searches were less sensitive than UP searches, but confidence intervals overlapped. For simple SR topics, TMT searches were faster and slightly less sensitive than UP. For complex SR topics, TMT searches were faster and less sensitive than UP searches but identified unique eligible citations not found by the UP searches. To identify and suggest strategies to make insufficient evidence ratings in systematic reviews more actionable. A workgroup comprising members from the Evidence-Based Practice (EPC) Program of the Agency for Healthcare Research and Quality convened throughout 2020. We conducted iterative discussions considering information from three data sources a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs. We identified five strategies for supplementing systematic review findings when evidence on benefits or harms is expected to be, or found to be, insufficient 1) reconsider eligible study designs, 2) summarize indirect evidence, 3) summarize contextual and implementation evidence, 4) consider modelling, and 5) incorporate unpublished health system data in the evidence synthesis. While these strategies may not increase the strength of evidence, they may improve the utility of reports for decision makers. Adopting these strategies depends on feasibility, timeline, funding, and expertise of the systematic reviewers. Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users. Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users. The aim was to investigate the relative validity of the preference-based measure EORTC QLU-C10D in comparison with the EQ-5D-3L in myelodysplastic syndromes (MDS) patients. We used data from an international multicentre, observational cohort study of MDS patients. Baseline EORTC QLU-C10D and EQ-5D-3L scores were used and index scores calculated for Italy, Australia, and the UK. Criterion validity was established by Spearman and intraclass correlations (ICC) and Bland-Altman plots. Construct validity was established by the instruments' ability to discriminate known groups, i.e. groups whose health status is expected to differ. We analyzed data from 619 MDS patients (61.1% male; median age 73.8 years). Correlations between theoretically corresponding domains were largely higher than between unrelated domains. ICCs and Bland-Altman plots indicated moderate to good criterion validity. Ceiling effects were lower for the QLU-C10D (4.7%) than for the EQ-5D-3L (22.6%). The EQ-5D-3L failed to discriminate known-groups in two and the QLU-C10D in one of the comparisons; the QLU-C10D's efficiency in doing so was higher in clinical known-groups.
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