Artificial intelligence-powered early identification of refractory constipation in children
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ABSTRACT:
SUBMITTER: Huang Y
PROVIDER: S-EPMC10915451 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Project description:Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with B7 proteins CD80 and CD86. CTLA-4 is the first immune checkpoint targeted with a monoclonal antibody inhibitor. Checkpoint inhibitors have generated durable responses in many cancer patients, representing a revolutionary milestone in cancer immunotherapy. However, therapeutic efficacy is limited to a small portion of patients, and immune-related adverse events are noteworthy, especially for monoclonal antibodies directed against CTLA-4. Previously, small molecules have been developed to impair the CTLA-4: CD80 interaction; however, they directly targeted CD80 and not CTLA-4. In this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to target CTLA-4. We validated primary hits with biochemical, biophysical, immunological, and experimental animal assays. We then optimized lead compounds and obtained inhibitors with an inhibitory concentration of 1 micromole in disrupting the interaction between CTLA-4 and CD80. Unlike ipilimumab, these small molecules did not degrade CTLA-4. Several compounds inhibited tumor development prophylactically and therapeutically in syngeneic and CTLA-4-humanized mice. This project supports an AI-based framework in designing small molecules targeting immune checkpoints for cancer therapy.
2024-02-15 | GSE228560 | GEO
Project description:BackgroundThe management of acne requires the consideration of its severity; however, a universally adopted evaluation system for clinical practice is lacking. Artificial intelligence (AI) evaluation systems hold the promise of enhancing the efficiency and reproducibility of assessments. Artificial intelligence (AI) evaluation systems offer the potential to enhance the efficiency and reproducibility of assessments in this domain. While the identification of skin lesions represents a crucial component of acne evaluation, existing AI systems often overlook lesion identification or fail to integrate it with severity assessment. This study aimed to develop an AI-powered acne grading system and compare its performance with physician image-based scoring.MethodsA total of 1,501 acne patients were included in the study, and standardized pictures were obtained using the VISIA system. The initial evaluation involved 40 stratified sampled frontal photos assessed by seven dermatologists. Subsequently, the three doctors with the highest inter-rater agreement annotated the remaining 1,461 images, which served as the dataset for the development of the AI system. The dataset was randomly divided into two groups: 276 images were allocated for training the acne lesion identification platform, and 1,185 images were used to assess the severity of acne.ResultsThe average precision of our model for skin lesion identification was 0.507 and the average recall was 0.775. The AI severity grading system achieved good agreement with the true label (linear weighted kappa = 0.652). After integrating the lesion identification results into the severity assessment with fixed weights and learnable weights, the kappa rose to 0.737 and 0.696, respectively, and the entire evaluation on a Linux workstation with a Tesla K40m GPU took less than 0.1s per picture.ConclusionThis study developed a system that detects various types of acne lesions and correlates them well with acne severity grading, and the good accuracy and efficiency make this approach potentially an effective clinical decision support tool.
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Project description:Artificial Intelligence-powered Drug Discovery against CTLA-4 in Cancer
| PRJNA950363 | ENA
Project description:Computational docking is an instrumental method of the structural biology toolbox. Specifically, integrative modeling software, such as LightDock, arise as complementary and synergetic methods to experimental structural biology techniques. Ubiquitousness and accessibility are fundamental features to promote ease of use and to improve user experience. With this goal in mind, we have developed the LightDock Server, a web server for the integrative modeling of macromolecular interactions, along with several dedicated usage modes. The server builds upon the LightDock macromolecular docking framework, which has proved useful for modeling medium-to-high flexible complexes, antibody-antigen interactions, or membrane-associated protein assemblies. We believe that this free-to-use resource will be a valuable addition to the structural biology community and can be accessed online at: https://server.lightdock.org/.
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| S-EPMC8280054 | biostudies-literature
Project description:Background/objectivesCheckpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4.Subjects/methodsIn this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to identify those targeting CTLA-4. We validated the hits molecules with biochemical, biophysical, immunological, and experimental animal assays.ResultsThe primary hits obtained from the virtual screening were successfully validated in vitro and in vivo. We then optimized lead compounds and obtained inhibitors (inhibitory concentration, 1 micromole) that disrupted the CTLA-4/CD80 interaction without degrading CTLA-4.ConclusionsSeveral compounds inhibited tumor development prophylactically and therapeutically in syngeneic and CTLA-4-humanized mice. Our findings support using AI-based frameworks to design small molecules targeting immune checkpoints for cancer therapy.
| S-EPMC10838660 | biostudies-literature
Project description:The integration of phenotypes and genotypes is at an unprecedented level and offers new opportunities to establish deep phenotypes. There are a number of challenges to overcome, specifically, accelerated growth of data, data silos, incompleteness, inaccuracies, and heterogeneity within and across data sources. This perspective report discusses artificial intelligence (AI) approaches that hold promise in addressing these challenges by automating computable phenotypes and integrating them with genotypes. Collaborations between biomedical and AI researchers will be highlighted in order to describe initial successes with an eye toward the future.
| S-EPMC6356893 | biostudies-literature
Project description:ImportanceThe Gleason grading system has been the most reliable tool for the prognosis of prostate cancer since its development. However, its clinical application remains limited by interobserver variability in grading and quantification, which has negative consequences for risk assessment and clinical management of prostate cancer.ObjectiveTo examine the impact of an artificial intelligence (AI)-assisted approach to prostate cancer grading and quantification.Design, setting, and participantsThis diagnostic study was conducted at the University of Wisconsin-Madison from August 2, 2017, to December 30, 2019. The study chronologically selected 589 men with biopsy-confirmed prostate cancer who received care in the University of Wisconsin Health System between January 1, 2005, and February 28, 2017. A total of 1000 biopsy slides (1 or 2 slides per patient) were selected and scanned to create digital whole-slide images, which were used to develop and validate a deep convolutional neural network-based AI-powered platform. The whole-slide images were divided into a training set (n = 838) and validation set (n = 162). Three experienced academic urological pathologists (W.H., K.A.I., and R.H., hereinafter referred to as pathologists 1, 2, and 3, respectively) were involved in the validation. Data were collected between December 29, 2018, and December 20, 2019, and analyzed from January 4, 2020, to March 1, 2021.Main outcomes and measuresAccuracy of prostate cancer detection by the AI-powered platform and comparison of prostate cancer grading and quantification performed by the 3 pathologists using manual vs AI-assisted methods.ResultsAmong 589 men with biopsy slides, the mean (SD) age was 63.8 (8.2) years, the mean (SD) prebiopsy prostate-specific antigen level was 10.2 (16.2) ng/mL, and the mean (SD) total cancer volume was 15.4% (20.1%). The AI system was able to distinguish prostate cancer from benign prostatic epithelium and stroma with high accuracy at the patch-pixel level, with an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.88-0.95). The AI system achieved almost perfect agreement with the training pathologist (pathologist 1) in detecting prostate cancer at the patch-pixel level (weighted κ = 0.97; asymptotic 95% CI, 0.96-0.98) and in grading prostate cancer at the slide level (weighted κ = 0.98; asymptotic 95% CI, 0.96-1.00). Use of the AI-assisted method was associated with significant improvements in the concordance of prostate cancer grading and quantification between the 3 pathologists (eg, pathologists 1 and 2: 90.1% agreement using AI-assisted method vs 84.0% agreement using manual method; P < .001) and significantly higher weighted κ values for all pathologists (eg, pathologists 2 and 3: weighted κ = 0.92 [asymptotic 95% CI, 0.90-0.94] for AI-assisted method vs 0.76 [asymptotic 95% CI, 0.71-0.80] for manual method; P < .001) compared with the manual method.Conclusions and relevanceIn this diagnostic study, an AI-powered platform was able to detect, grade, and quantify prostate cancer with high accuracy and efficiency and was associated with significant reductions in interobserver variability. These results suggest that an AI-powered platform could potentially transform histopathological evaluation and improve risk stratification and clinical management of prostate cancer.
| S-EPMC8567112 | biostudies-literature
Project description:AimsA majority of acute coronary syndromes (ACS) present without typical ST elevation. One-third of non-ST-elevation myocardial infarction (NSTEMI) patients have an acutely occluded culprit coronary artery [occlusion myocardial infarction (OMI)], leading to poor outcomes due to delayed identification and invasive management. In this study, we sought to develop a versatile artificial intelligence (AI) model detecting acute OMI on single-standard 12-lead electrocardiograms (ECGs) and compare its performance with existing state-of-the-art diagnostic criteria.Methods and resultsAn AI model was developed using 18 616 ECGs from 10 543 patients with suspected ACS from an international database with clinically validated outcomes. The model was evaluated in an international cohort and compared with STEMI criteria and ECG experts in detecting OMI. The primary outcome of OMI was an acutely occluded or flow-limiting culprit artery requiring emergent revascularization. In the overall test set of 3254 ECGs from 2222 patients (age 62 ± 14 years, 67% males, 21.6% OMI), the AI model achieved an area under the curve of 0.938 [95% confidence interval (CI): 0.924-0.951] in identifying the primary OMI outcome, with superior performance [accuracy 90.9% (95% CI: 89.7-92.0), sensitivity 80.6% (95% CI: 76.8-84.0), and specificity 93.7 (95% CI: 92.6-94.8)] compared with STEMI criteria [accuracy 83.6% (95% CI: 82.1-85.1), sensitivity 32.5% (95% CI: 28.4-36.6), and specificity 97.7% (95% CI: 97.0-98.3)] and with similar performance compared with ECG experts [accuracy 90.8% (95% CI: 89.5-91.9), sensitivity 73.0% (95% CI: 68.7-77.0), and specificity 95.7% (95% CI: 94.7-96.6)].ConclusionThe present novel ECG AI model demonstrates superior accuracy to detect acute OMI when compared with STEMI criteria. This suggests its potential to improve ACS triage, ensuring appropriate and timely referral for immediate revascularization.
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