We solve a Bayesian inverse Reynolds-averaged Navier-Stokes (RANS) problem that assimilates mean flow data by jointly reconstructing the mean flow field and learning its unknown RANS parameters. We devise an algorithm that learns the most likely parameters of an algebraic effective viscosity model, and estimates their uncertainties, from mean flow data of a turbulent flow. We conduct a flow MRI experiment to obtain mean flow data of a confined turbulent jet in an idealized medical device known as the FDA (Food and Drug Administration) nozzle. The algorithm successfully reconstructs the mean flow field and learns the most likely turbulence model parameters without overfitting. The methodology accepts any turbulence model, be it algebraic (explicit) or multi-equation (implicit), as long as the model is differentiable, and naturally extends to unsteady turbulent flows.

The drug development process is a critical challenge in the pharmaceutical industry due to its time-consuming nature and the need to discover new drug potentials to address various ailments. The initial step in drug development, drug target identification, often consumes considerable time. While valid, traditional methods such as in vivo and in vitro approaches are limited in their ability to analyze vast amounts of data efficiently, leading to wasteful outcomes. To expedite and streamline drug development, an increasing reliance on computer-aided drug design (CADD) approaches has merged. These sophisticated in silico methods offer a promising avenue for efficiently identifying viable drug candidates, thus providing pharmaceutical firms with significant opportunities to uncover new prospective drug targets. The main goal of this work is to review in silico methods used in the drug development process with a focus on identifying therapeutic targets linked to specific diseases at the genetic or protein level. This article thoroughly discusses A-to-Z in silico techniques, which are essential for identifying the targets of bioactive compounds and their potential therapeutic effects. This review intends to improve drug discovery processes by illuminating the state of these cutting-edge approaches, thereby maximizing the effectiveness and duration of clinical trials for novel drug target investigation.

A kind of pancreatic cancer called Pancreatic Ductal Adenocarcinoma (PDAC) is anticipated to be one of the main causes of mortality during past years. Evidence from several researches supported the concept that the oncogenic KRAS (Ki-ras2 Kirsten rat sarcoma viral oncogene) mutation is the major cause of pancreatic cancer. KRAS acts as an on-off switch that promotes cell growth. But when the KRAS gene is mutated, it will be in one position, allowing the cell growth uncontrollably. This uncontrollable multiplication of cells causes cancer growth. Therefore, KRAS was selected as the target protein in the study. Fifty plant-derived compounds are selected for the study. To determine whether the examined drugs could bind to the KRAS complex's binding pocket, molecular docking was performed. Computational analyses were used to assess the possible ability of tested substances to pass the Blood Brain Barrier (BBB). To predict the bioactivity of ligands a machine learning model was created. Five machine learning models were created and have chosen the best one among them for analyzing the bioactivity of each ligand. From the fifty plant-derived compounds the compounds with the least binding energies are selected. Then bioactivity of these six compounds is analyzed using Random Forest Regression model. Adsorption, Distribution, Metabolism, Excretion (ADME) properties of compounds are analyzed. The results showed that borneol has powerful effects and acts as a promising agent for the treatment of pancreatic cancer. This suggests that borneol found in plants like mint, ginger, rosemary, etc., is a successful compound for the treatment of pancreatic cancer.

Although Large Language Models (LLMs) have shown promising performance in healthcare-related applications, their deployment in the medical domain poses unique challenges of ethical, regulatory, and technical nature. In this study, we employ a systematic participatory approach to investigate the needs and expectations regarding clinical applications of LLMs at Lausanne University Hospital, an academic medical center in Switzerland. Having identified potential LLM use-cases in collaboration with thirty stakeholders, including clinical staff across 11 departments as well nursing and patient representatives, we assess the current feasibility of these use-cases taking into account the regulatory frameworks, data protection regulation, bias, hallucinations, and deployment constraints. This study provides a framework for a participatory approach to identifying institutional needs with respect to introducing advanced technologies into healthcare practice, and a realistic analysis of the technology readiness level of LLMs for medical applications, highlighting the issues that would need to be overcome LLMs in healthcare to be ethical, and regulatory compliant.

The application of deep learning methods, particularly foundation models, in biological research has surged in recent years. These models can be text-based or trained on underlying biological data, especially omics data of various types. However, comparing the performance of these models consistently has proven to be a challenge due to differences in training data and downstream tasks. To tackle this problem, we developed an architecture-agnostic benchmarking approach that, instead of evaluating the models directly, leverages entity representation vectors from each model and trains simple predictive models for each benchmarking task. This ensures that all types of models are evaluated using the same input and output types. Here we focus on gene properties collected from professionally curated bioinformatics databases. These gene properties are categorized into five major groups: genomic properties, regulatory functions, localization, biological processes, and protein properties. Overall, we define hundreds of tasks based on these databases, which include binary, multi-label, and multi-class classification tasks. We apply these benchmark tasks to evaluate expression-based models, large language models, protein language models, DNA-based models, and traditional baselines. Our findings suggest that text-based models and protein language models generally outperform expression-based models in genomic properties and regulatory functions tasks, whereas expression-based models demonstrate superior performance in localization tasks. These results should aid in the development of more informed artificial intelligence strategies for biological understanding and therapeutic discovery. To ensure the reproducibility and transparency of our findings, we have made the source code and benchmark data publicly accessible for further investigation and expansion at github.com/BiomedSciAI/gene-benchmark.

The use of artificial intelligence (AI) in automated disease classification significantly reduces healthcare costs and improves the accessibility of services. However, this transformation has given rise to concerns about the fairness of AI, which disproportionately affects certain groups, particularly patients from underprivileged populations. Recently, a number of methods and large-scale datasets have been proposed to address group performance disparities. Although these methods have shown effectiveness in disease classification tasks, they may fall short in ensuring fair prediction of disease progression, mainly because of limited longitudinal data with diverse demographics available for training a robust and equitable prediction model. In this paper, we introduce TransFair to enhance demographic fairness in progression prediction for ocular diseases. TransFair aims to transfer a fairness-enhanced disease classification model to the task of progression prediction with fairness preserved. Specifically, we train a fair EfficientNet, termed FairEN, equipped with a fairness-aware attention mechanism using extensive data for ocular disease classification. Subsequently, this fair classification model is adapted to a fair progression prediction model through knowledge distillation, which aims to minimize the latent feature distances between the classification and progression prediction models. We evaluate FairEN and TransFair for fairness-enhanced ocular disease classification and progression prediction using both two-dimensional (2D) and 3D retinal images. Extensive experiments and comparisons with models with and without considering fairness learning show that TransFair effectively enhances demographic equity in predicting ocular disease progression.

The abundance of complex and interconnected healthcare data offers numerous opportunities to improve prediction, diagnosis, and treatment. Graph-structured data, which includes entities and their relationships, is well-suited for capturing complex connections. Effectively utilizing this data often requires strong and efficient learning algorithms, especially when dealing with limited labeled data. It is increasingly important for downstream tasks in various domains to utilize self-supervised learning (SSL) as a paradigm for learning and optimizing effective representations from unlabeled data. In this paper, we thoroughly review SSL approaches specifically designed for graph-structured data in healthcare applications. We explore the challenges and opportunities associated with healthcare data and assess the effectiveness of SSL techniques in real-world healthcare applications. Our discussion encompasses various healthcare settings, such as disease prediction, medical image analysis, and drug discovery. We critically evaluate the performance of different SSL methods across these tasks, highlighting their strengths, limitations, and potential future research directions. Ultimately, this review aims to be a valuable resource for both researchers and practitioners looking to utilize SSL for graph-structured data in healthcare, paving the way for improved outcomes and insights in this critical field. To the best of our knowledge, this work represents the first comprehensive review of the literature on SSL applied to graph data in healthcare.

Objective: We aimed to develop an advanced multi-task large language model (LLM) framework to extract multiple types of information about dietary supplements (DS) from clinical records. Methods: We used four core DS information extraction tasks--namely, named entity recognition (NER: 2,949 clinical sentences), relation extraction (RE: 4,892 sentences), triple extraction (TE: 2,949 sentences), and usage classification (UC: 2,460 sentences) as our multitasks. We introduced a novel Retrieval-Augmented Multi-task Information Extraction (RAMIE) Framework, including: 1) employed instruction fine-tuning techniques with task-specific prompts, 2) trained LLMs for multiple tasks with improved storage efficiency and lower training costs, and 3) incorporated retrieval augmentation generation (RAG) techniques by retrieving similar examples from the training set. We compared RAMIE's performance to LLMs with instruction fine-tuning alone and conducted an ablation study to assess the contributions of multi-task learning and RAG to improved multitasking performance. Results: With the aid of the RAMIE framework, Llama2-13B achieved an F1 score of 87.39 (3.51% improvement) on the NER task and demonstrated outstanding performance on the RE task with an F1 score of 93.74 (1.15% improvement). For the TE task, Llama2-7B scored 79.45 (14.26% improvement), and MedAlpaca-7B achieved the highest F1 score of 93.45 (0.94% improvement) on the UC task. The ablation study revealed that while MTL increased efficiency with a slight trade-off in performance, RAG significantly boosted overall accuracy. Conclusion: This study presents a novel RAMIE framework that demonstrates substantial improvements in multi-task information extraction for DS-related data from clinical records. Our framework can potentially be applied to other domains.

Transcatheter tricuspid valve replacement (TTVR) is the latest treatment for tricuspid regurgitation and is in the early stages of clinical adoption. Intelligent robotic approaches are expected to overcome the challenges of surgical manipulation and widespread dissemination, but systems and protocols with high clinical utility have not yet been reported. In this study, we propose a complete solution that includes a passive stabilizer, robotic drive, detachable delivery catheter and valve manipulation mechanism. Working towards autonomy, a hybrid augmented intelligence approach based on reinforcement learning, Monte Carlo probabilistic maps and human-robot co-piloted control was introduced. Systematic tests in phantom and first-in-vivo animal experiments were performed to verify that the system design met the clinical requirement. Furthermore, the experimental results confirmed the advantages of co-piloted control over conventional master-slave control in terms of time efficiency, control efficiency, autonomy and stability of operation. In conclusion, this study provides a comprehensive pathway for robotic TTVR and, to our knowledge, completes the first animal study that not only successfully demonstrates the application of hybrid enhanced intelligence in interventional robotics, but also provides a solution with high application value for a cutting-edge procedure.

Molecular optimization, which aims to discover improved molecules from a vast chemical search space, is a critical step in chemical development. Various artificial intelligence technologies have demonstrated high effectiveness and efficiency on molecular optimization tasks. However, few of these technologies focus on balancing property optimization with constraint satisfaction, making it difficult to obtain high-quality molecules that not only possess desirable properties but also meet various constraints. To address this issue, we propose a constrained multi-property molecular optimization framework (CMOMO), which is a flexible and efficient method to simultaneously optimize multiple molecular properties while satisfying several drug-like constraints. CMOMO improves multiple properties of molecules with constraints based on dynamic cooperative optimization, which dynamically handles the constraints across various scenarios. Besides, CMOMO evaluates multiple properties within discrete chemical spaces cooperatively with the evolution of molecules within an implicit molecular space to guide the evolutionary search. Experimental results show the superior performance of the proposed CMOMO over five state-of-the-art molecular optimization methods on two benchmark tasks of simultaneously optimizing multiple non-biological activity properties while satisfying two structural constraints. Furthermore, the practical applicability of CMOMO is verified on two practical tasks, where it identified a collection of candidate ligands of $\beta$2-adrenoceptor GPCR and candidate inhibitors of glycogen synthase kinase-3$\beta$ with high properties and under drug-like constraints.