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38,743 results for “efficacy”
Dataset / Code: Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy
<p><strong>Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy</strong></p> <p><strong> </strong></p> <p>Harim I. Won<sup>1,#</sup>, Samuel Zinga<sup>1,#</sup>, Olga Kandror<sup>1</sup>, Tatos Akopian<sup>1</sup>, Ian D. Wolf<sup>1</sup>, Jessica T.P. Schweber<sup>1</sup>, Ernst W. Schmid<sup>2</sup>, Michael C. Chao<sup>1</sup>, Maya Waldor<sup>1</sup>, Eric J. Rubin<sup>1,*</sup>, Junhao Zhu<sup>1,3,*</sup></p> <p><strong> </strong></p> <p><sup>1</sup>Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.</p> <p><sup>2</sup>Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts 02115, USA.</p> <p><sup>3</sup>CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.</p> <p><sup>#</sup>These authors contributed equally to this work.</p> <p>*Corresponding authors: <a href="mailto:zhujh@im.ac.cn">zhujh@im.ac.cn</a> (J.Z.), <a href="mailto:erubin@hsph.harvard.edu">erubin@hsph.harvard.edu</a> (E. J. R.)</p> <p><strong> </strong></p> <p><strong>Abstract</strong></p> <p>Proteolysis-targeting chimeras (PROTACs) represent a new therapeutic modality involving selectively directing disease-causing proteins for degradation through proteolytic systems. Our ability to exploit targeted protein degradation (TPD) for antibiotic development remains nascent due to our limited understanding of which bacterial proteins are amenable to a TPD strategy. Here, we use a genetic system to model chemically-induced proximity and degradation to screen essential proteins in <em>Mycobacterium smegmatis </em>(<em>Msm</em>)<em>, </em>a model for the human pathogen <em>M. tuberculosis </em>(<em>Mtb</em>). By integrating experimental screening of 72 protein candidates and machine learning, we find that drug-induced proximity to the bacterial ClpC1P1P2 proteolytic complex leads to the degradation of many endogenous proteins, especially those with disordered termini. Additionally, TPD of essential <em>Msm </em>proteins inhibits bacterial growth and potentiates the effects of existing antimicrobial compounds. Together, our results provide biological principles to select and evaluate attractive targets for future <em>Mtb</em> PROTAC development, as both standalone antibiotics and potentiators of existing antibiotic efficacy.</p> <p> </p>
FULFILL dataset - diet policy acceptability - efficacy and acceptability framing Denmark
<p>This dataset represents survey data on sufficiency-oriented policy acceptability in regard to dietary consumption. The study was part of the second round surveys in Denmark in 2023 within the FULFILL project - Fundamental Decarbonisation Through Sufficiency By Lifestyle Changes.</p> <p>As part of Work Package 3 (WP3) in the FULFILL project, we collected quantitative data from two countries: Denmark and Germany, with representative sampling (age, income, gender, current region). In this survey on the acceptability of sufficiency-oriented diet policies we recruited a representative sample with approximately 800 participants from Denmark and Germany, taking into account primarily the individual perspective, added by some questions on the household level.</p> <p>The central part of the survey includes a framing experiment including three groups with participants being randomly assigned to. We were interested in peoples' acceptability on three majorly discussed and sufficiency-relevant policies, i.e. meat tax, carbon label or meat-free day at public canteens. We investigated if an information on either the efficacy of the measures or a combination of information with acceptance information or none of these information could influence people's acceptability (overall, self vs. others perspective). We measured several control variables (socio-economics such as age, gender, income, education, household size, life stage, ideological measures such as political orientation or attitudinal measures such as sufficiency orientation and climate change denial). A quantitative assessment of the carbon footprint in the food consumption domain was also included.</p>
FULFILL dataset - diet policy acceptability - efficacy and acceptability framing Germany
<div> <p>This dataset represents survey data on sufficiency-oriented policy acceptability in regard to dietary consumption. The study was part of the second round surveys in Germany in 2023 within the FULFILL project - Fundamental Decarbonisation Through Sufficiency By Lifestyle Changes.</p> <p>As part of Work Package 3 (WP3) in the FULFILL project, we collected quantitative data from two countries: Denmark and Germany, with representative sampling (age, income, gender, current region). In this survey on the acceptability of sufficiency-oriented diet policies we recruited a representative sample with approximately 800 participants from Denmark and Germany, taking into account primarily the individual perspective, added by some questions on the household level.</p> <p>The central part of the survey includes a framing experiment including three groups with participants being randomly assigned to. We were interested in peoples' acceptability on three majorly discussed and sufficiency-relevant policies, i.e. meat tax, carbon label or meat-free day at public canteens. We investigated if an information on either the efficacy of the measures or a combination of information with acceptance information or none of these information could influence people's acceptability (overall, self vs. others perspective). We measured several control variables (socio-economics such as age, gender, income, education, household size, life stage, ideological measures such as political orientation or attitudinal measures such as sufficiency orientation and climate change denial). A quantitative assessment of the carbon footprint in the food consumption domain was also included.</p> </div>
Efficacy and fate of fluridone applications for control of invasive submersed aquatic vegetation in the estuarine environment of the Sacramento-San Joaquin Delta
We conducted a study in the Sacramento-San Joaquin Delta to determine efficacy of the widely used herbicide fluridone in an estuarine ecosystem. The primary goal of SAV removal was restoration of open water habitat for endangered Hypomesus transpacificus (Delta Smelt). Over 18 months and multiple sets of multi-week fluridone applications, we monitored concentrations of fluridone and responses by SAV across pairs of treated and reference sites. Fluridone concentrations in the water were generally below the 2-5 parts per billion required for SAV control. Monitoring demonstrated these low water concentrations were likely due to dissipation by tides, despite use of pelleted fluridone formulations marketed for flowing water environments. Fluridone did, however, accumulate in sediment at concentrations hundreds of times higher than those measured in the water. Nonetheless, we did not observe lasting reductions in SAV abundance or changes in SAV community composition. By demonstrating lack of efficacy of one of the few herbicides permitted for use in this estuary, this study highlights the need for development of SAV management tools tailored to the challenges of hydrologically complex environments like estuaries.
Efficacy and safety of subcutaneous vs. sublingual immunotherapy in allergic rhinitis: a systematic review and meta-analysis
<p>Allergic rhinitis significantly impacts patients' quality of life, and allergen immunotherapy (AIT) offers an alternative to conventional treatments. This study compares the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis. A comprehensive search of PubMed, Embase, and ClinicalTrials.gov identified nine randomized controlled trials involving 780 patients (427 SCIT, 353 SLIT). The primary outcome was symptom score; secondary outcomes included medication score, symptom medication score, and local and systemic reactions. Results showed SCIT significantly reduced symptom scores compared to SLIT (Pooled SMD: -0.52, 95% CI: -0.60, -0.03, I2 =83%, P<0.05). However, SCIT patients experienced more severe systemic reactions (grade 3&4) than SLIT patients (Pooled SMD: 6.27, 95% CI: 1.47, 26.73, I2 =0%, P=0.01). Other outcomes were comparable between both groups. In conclusion, SCIT is slightly more effective than SLIT but is associated with a higher frequency of severe systemic reactions, guiding clinicians to tailor treatments to individual patient needs.</p>
Multi-omics analysis reveals the link between Treg distribution and therapy efficacy in Hepatocellular Carcinoma patients treated with tremelimumab plus durvalumab
<p><strong><span><span>Introduction</span></span></strong></p> <p><span>Hepatocellular carcinoma (HCC) remains a significant contributor to cancer-related deaths. Immunotherapy, either alone or in combination, has emerged as the standard treatment for advanced HCC. Notably, the combination of durvalumab (dur) and tremelimumab (trem) has received FDA approval based on findings from the HIMALAYA trial. However, comprehensive studies elucidating immune responses are lacking. We conducted a thorough analysis utilizing clinical samples from tumor biopsies to understand the mechanism of response.</span></p> <p><strong><span><span>Methods</span></span></strong></p> <p><span>Multiplexed immunofluorescence microscopy was used to analyze immune cell infiltration in primary human liver cancer samples. We developed and validated a comprehensive 37-plex antibody panel for immunofluorescence imaging of human FFPE samples. We applied highly multiplexed co-detection by indexing (CODEX) technology to simultaneously profile in situ expression of 37 proteins at sub-cellular resolution in 20 HCC patient samples using whole slide scanning. We established an image analysis pipeline to quantify all major cell populations in the human liver using supervised manual gating and unsupervised clustering algorithms using the exported matrix of the marker expression and spatial information. Clinical metadata including sex, gender, ethnicity, pretreatment, and histopathological reports are available for all patient samples.</span></p> <p><strong><span><span>Results</span></span></strong></p> <p><span><span>Using high-dimensional spatially resolved quantitative analysis of multiplexed immunofluorescence microscopy images, we generated a unique dataset and profiled the single-cell pathology landscape for human HCC treated with immunotherapy. In situ phenotyping of 400,000 single cells (including 130,000 CD45+ immune cells) allowed for the quantification of cell phenotype clusters, differential analysis of activation markers, and spatial features of each individual cell. This analysis revealed the comprehensive profile of the cell composition and spatial interactions of different cells in the TiME of patients treated with immunotherapy. Further details on the study can be obtained in our paper once it’s published.</span></span></p> <p><strong><span><span>Conclusion</span></span></strong></p> <p><span><span>We developed the CODEX panel for FFPE biopsy samples of HCC patients.</span></span></p>
Self-efficacy questionnaire for children - Results
<p>The dataset (csv) contains data from a self-efficacy questionnaire for children between the age of 6 and 16. This questionnaire (also attached) was specifially developed for the purposes of the DOIT project, which aimed at bringing entrepreneurial education, maker skills and social innovation together and at developing an educational programme lasting for at least 15 hours.</p> <p>Children participating in the DOIT progamme filled in the survey two times (pre and post survey). The dataset contains the questionnaire results from 633 children from 10 different European countries, some basic demographic (age, gender, country, disability) and some variables regarding the DOIT programme (attended hours, Age of facilitators, gender ratio of facilitator, etc.). For context information also a related DOIT report has been attached.</p>
Analysis of human humoral responses in a typhoid vaccine efficacy trial used for SIMON analysis
<p>The VAST dataset contains data from 72 individuals enrolled in the clinical study to evaluate humoral responses in a typhoid vaccine efficacy trial in a controlled human <em>Salmonella </em>Typhi infection model (see original publication: <a href="https://doi.org/10.3389/fimmu.2019.02582">https://doi.org/10.3389/fimmu.2019.02582</a>). Only day 0 (day of the challenge) log-transformed data were used in the SIMON analysis, as described in the publication (<a href="https://doi.org/10.1101/2020.08.16.252767">https://doi.org/10.1101/2020.08.16.252767</a>). Individuals were vaccinated with either a purified Vi polysaccharide (Vi-PS) vaccine (35 individuals) or the Vi tetanus toxoid conjugate (Vi-TT) vaccine (37 individuals) one month prior to oral challenge with live <em>Salmonella </em>Typhi. Out of 72 individuals, 26 developed an acute typhoid infection following the challenge.</p>
The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy.
<p>Data used for the publication of a paper entitled: <strong>The within-host population dynamics of <em>Mycobacterium tuberculosis</em> vary with treatment efficacy.</strong></p> <p>The data were derived from:</p> <p>1. the deep sequencing of serial sputum samples from 12 TB patients,</p> <p>2. the deep sequencing of liquid cultures derived from the expansion of individual colonies <em>in vitro</em>,</p> <p>3. <em>In </em><em>silico</em> simulations of DNA sequencing, populations and mutagenesis.</p> <p>The analytical scripts associated with the generation of the data can be found at:</p> <p>https://github.com/swisstph/TBRU_serialTB/</p> <p><strong>Paper Abstract:</strong></p> <p><strong>Background:</strong></p> <p>Combination therapy is one of the most effective tools for limiting the emergence of drug resistance. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We addressed this question by studying the population dynamics of <em>Mycobacterium tuberculosis</em> within tuberculosis patients undergoing treatment with different combinations of antibiotics.</p> <p><strong>Results:</strong></p> <p>By combining very deep whole genome sequencing (~1,000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy had a clear impact on the population dynamics: sufficient drug pressure bore a clear signature of purifying selection leading to apparent genetic stability. In contrast, <em>M. tuberculosis</em> populations subject to less drug pressure showed markedly different dynamics, including cases of acquisition of additional drug resistance.</p> <p><strong>Conclusions:</strong></p> <p>Our findings show that for a pathogen like <em>M. tuberculosis</em>, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.</p>
Neither alpha-synuclein-preformed fibrils derived from patients with GBA1 mutations nor the host murine genotype significantly influence seeding efficacy in the mouse olfactory bulb
<p>Data sets for;</p> <p>Neither alpha-synuclein-preformed fibrils derived from patients with <em>GBA1</em> mutations nor the host murine genotype significantly influence seeding efficacy in the mouse olfactory bulb</p>
Data associated with the article 'Intervention factors associated with efficacy, when targeting oral language comprehension of children with or at risk for (Developmental) Language Disorder: A meta-analysis'
<p>The efficacy of oral language comprehension interventions varies, but the reasons for this variation have received little attention. A meta-analysis was conducted to examine intervention factors associated with the efficacy (as expressed with effect sizes) of oral language comprehension interventions in children under the age of 18 with or at risk for (Developmental) Language Disorder, (D)LD.</p> <p>The meta-analysis article together with this additional material comprise the content needed for a thorough understanding and replication of the results.</p> <p>This dataset is based on two systematic scoping reviews on oral language comprehension interventions (Tarvainen et al., 2020, 2021). Further information from the sourced articles was extracted for this study titled ‘Intervention factors associated with efficacy, when targeting oral language comprehension of children with or at risk for (Developmental) Language Disorder: A meta-analysis’. </p> <p>In the future, we hope that this data is used with a growing body of oral language comprehension interventions to conduct further and more detailed examinations of intervention factors associated with efficacy.</p> <p>References:</p> <p>Tarvainen, S., Launonen, K., & Stolt, S. (2021). Oral language comprehension interventions in school-age children and adolescents with developmental language disorder: A systematic scoping review. <em>Autism & Developmental Language Impairments</em>, <em>6</em>, 1–24. https://doi.org/10.1177/23969415211010423</p> <p>Tarvainen, S., Stolt, S., & Launonen, K. (2020). Oral language comprehension interventions in 1–8-year-old children with language disorders or difficulties: A systematic scoping review. <em>Autism & Developmental Language Impairments</em>, <em>5</em>, 1–24. https://doi.org/10.1177/2396941520946</p> <p> </p>
Data from: Efficacy of labile carbon addition to reduce fast-growing, invasive non-native plants: A review and meta-analysis
<p>Data and analysis in R for the publication "Efficacy of labile carbon addition to reduce fast-growing, invasive non-native plants: A review and meta-analysis" by Ossanna & Gornish (2023), <em>Journal of Applied Ecology</em>, <em>60</em>(2), 218-228. <a href="http://doi.org/10.1111/1365-2664.14324">https://doi.org/10.1111/1365-2664.14324</a>.</p>
EU Lighting Efficacy Policy History Tool
<p>As of 2020, the EU has published <a href="https://ec.europa.eu/energy/en/topics/energy-efficiency/energy-efficient-products/list-regulations-product-groups-energy-efficient-products">three regulations on lighting efficiency</a>. This Excel tool can be used to calculate the corresponding luminous efficacy [lm/W] for each regulation.</p> <p>Compiled as part of the research project <a href="https://web.archive.org/web/20220920225758/https://www.ceenrg.landecon.cam.ac.uk/research/climate-change-and-energy-policy/what-factors-drive-innovation-in-energy-technologies-the-role-of-technology-spillovers-and-government-investment">"What factors drive innovation in energy technologies? The role of technology spillovers and government investment"</a>, funded by the Alfred P. Sloan Foundation.</p>
Figure 5 in Does your preservative preserve? A comparison of the efficacy of some pitfall trap solutions in preserving the internal reproductive organs of dung beetles
Figure 5. Pitfall trap with protective caging and cover placed on-top of a manually constructed soil mound so as to prevent interference from mammals and dilution and/or overspilling from precipitation and surface runoff.
Figure 2. L in Does your preservative preserve? A comparison of the efficacy of some pitfall trap solutions in preserving the internal reproductive organs of dung beetles
Figure 2. L. militaris (female) after 28 days of submergence in 4% PBF showing the well preserved ovary and oocytes.
Figure 3 in Does your preservative preserve? A comparison of the efficacy of some pitfall trap solutions in preserving the internal reproductive organs of dung beetles
Figure 3. Evaporation rates of the eight preservatives in the riparian vine thicket environment. Water is also shown for comparison. The dotted line represents the critical volume. PG = propylene glycol, w vinegar = white vinegar.
Figure 4 in Does your preservative preserve? A comparison of the efficacy of some pitfall trap solutions in preserving the internal reproductive organs of dung beetles
Figure 4. Evaporation rates of the eight preservatives in the low open woodland environment. Water is also shown for comparison. The dotted line represents the critical volume. PG = propylene glycol, w vinegar = white vinegar.
Self-efficacy and creativity data
<p>The overall difference between the self-efficacy score between the pre and the post-test is significant (t=-4.238, df=470, p=0.000). While the average score in the beginning was 54.56 it increased slightly to an average of 55.51.</p> <p>As the sample paired T-Test shows there is indeed a significant difference between the pre and the post-test (T=-4,706, df=393, p=0,000). While the average raw score in the pre-test was 18,61, the score in the post-test is significantly higher with 20,43. In other words, creativity as measured via the TSD-Z is higher at the end than at the beginning of the DOIT action.</p>
Exaggerated mandibles are correlated with enhanced foraging efficacy in male Auckland tree wētā
<p class="MsoNormal">Sexual selection has driven the evolution of weaponry for males to fight rivals to gain access to females. Although weapons <span>are predicted to increase males' reproductive success, they are also expected to</span> incur costs and may impair functional activities, including foraging. Using feeding assays, we tested whether the enlarged mandibles of Auckland tree wētā (<em>Hemideina thoracica</em>) impact feeding activity (the total volume of biomass consumed, bite rate, and number of foraging visits) and foraging behaviour (time spent moving, feeding, or stationary). We predicted that increased mandible length in male wētā would hinder their feeding rates. However, we found that wētā with longer heads fed at a faster rate and spent less time foraging than wētā with smaller heads, regardless of sex. Contrary to expectations that weapons impede functional activities, our results demonstrate that exaggerated traits can improve feeding performance and may offer benefits other than increased mating success.</p>
Evaluating the efficacy of drone-based thermal images for measuring wildlife abundance and physiology
<p>Monitoring the population dynamics and behaviors of wildlife is crucial for effective conservation. Although drones can provide a promising alternative to traditional monitoring methods, validation studies must be done to quantify the accuracy of drone-based abundance and distribution estimates in various biological systems. Here, we investigate the use of drones equipped with high-resolution Red-Green-Blue (RGB) and thermal cameras, along with machine learning techniques, for assessments of abundance and physiology in northern elephant seals (<em>Mirounga</em> <em>angustirostris</em>). Aerial images of N=3,415 northern elephant seals were collected at Año Nuevo Reserve during N=24 drone flights, along with ambient air temperatures, wind speed, and time-of-day data. The two-dimensional footprints and surface temperatures of seals were measured from the images. Machine learning algorithms were applied to detect seals in the imagery, and model performance was evaluated. Our findings indicate that seal detection was more accurate using RGB images compared to Thermal images, but that Thermal images could be used to determine that time of day and ambient temperature (but not wind speed or body size) strongly influenced seal external skin temperature. In other words, RGB and Thermal cameras have different strengths and weaknesses that should be carefully considered when designing research studies. Our study highlights the promising integration of drones, thermal imaging, and machine learning for wildlife research, contributing to faster, safer, cheaper, less disruptive, and more accurate wildlife monitoring and conservation efforts.</p>
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These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.