A Frankenstein's lab for growing'spare' human bodies sounds like something ripped straight from an episode of Black Mirror. But scientists really want to make this gruesome concept a reality. In an article published in the MIT Technology Review, three Stanford University scientists argue that so-called'bodyoids' could'revolutionise' medicine. Bodyoids would be physiologically identical to a normal human but engineered not to have consciousness or experience pain, they write. The researchers argue that modern medical science is being held back by a severe shortage of'ethically sourced human bodies'.

Left: PHATE visualization of scRNA-seq data color coded by time intervals. Right: PHATE plot colored by diffusion curvature values. We applied diffusion curvature to a single-cell RNA-sequencing dataset of human embryonic stem cells [1]. These cells were grown as embryoid bodies over a period of 27 days, during which they start as human embryonic stem cells and differentiate into diverse cellular lineages including neural progenitors, cardiac progenitors, muscle progenitors, etc. This developmental process is visualized using PHATE in Figure A1 (left), where embryonic cells (at days 0-3, annotated in blue) progressively branch into the two large splits of endoderm (upper split) and ectoderm (lower split around day 6.

Medication adherence is critical for the recovery of adolescents and young adults (AYAs) who have undergone hematopoietic cell transplantation (HCT). However, maintaining adherence is challenging for AYAs after hospital discharge, who experience both individual (e.g. physical and emotional symptoms) and interpersonal barriers (e.g., relational difficulties with their care partner, who is often involved in medication management). To optimize the effectiveness of a three-component digital intervention targeting both members of the dyad as well as their relationship, we propose a novel Multi-Agent Reinforcement Learning (MARL) approach to personalize the delivery of interventions. By incorporating the domain knowledge, the MARL framework, where each agent is responsible for the delivery of one intervention component, allows for faster learning compared with a flattened agent. Evaluation using a dyadic simulator environment, based on real clinical data, shows a significant improvement in medication adherence (approximately 3%) compared to purely random intervention delivery. The effectiveness of this approach will be further evaluated in an upcoming trial.

For the last couple of years we've had a go at predicting what's coming next in AI. A fool's game given how fast this industry moves. How did we score last time round? Our four hot trends to watch out for in 2024 pretty much nailed it by including what we called customized chatbots (we didn't know it yet, but we were talking about what everyone now calls agents, the hottest thing in AI right now), generative video, and more general-purpose robots that can do a wider range of tasks. Here are five picks from our AI team.

We present a new annotated microscopic cellular image dataset to improve the effectiveness of machine learning methods for cellular image analysis. Cell counting is an important step in cell analysis. Typically, domain experts manually count cells in a microscopic image. Automated cell counting can potentially eliminate this tedious, time-consuming process. However, a good, labeled dataset is required for training an accurate machine learning model. Our dataset includes microscopic images of cells, and for each image, the cell count and the location of individual cells. The data were collected as part of an ongoing study investigating the potential of electrical stimulation to modulate stem cell differentiation and possible applications for neural repair. Compared to existing publicly available datasets, our dataset has more images of cells stained with more variety of antibodies (protein components of immune responses against invaders) typically used for cell analysis. The experimental results on this dataset indicate that none of the five existing models under this study are able to achieve sufficiently accurate count to replace the manual methods. The dataset is available at https://figshare.com/articles/dataset/Dataset/21970604.

Matching patients to clinical trials demands a systematic and reasoned interpretation of documents which require significant expert-level background knowledge, over a complex set of well-defined eligibility criteria. Moreover, this interpretation process needs to operate at scale, over vast knowledge bases of trials. In this paper, we propose a scalable method that extends the capabilities of LLMs in the direction of systematizing the reasoning over sets of medical eligibility criteria, evaluating it in the context of real-world cases. The proposed method overlays a Set-guided reasoning method for LLMs. The proposed framework is evaluated on TREC 2022 Clinical Trials, achieving results superior to the state-of-the-art: NDCG@10 of 0.693 and Precision@10 of 0.73.

Chinese scientists have created a Frankenstein-like robot that is powered by a tiny human brain in a first-of-its-kind feat. The robot works by using a lab-grown brain organoid, a mass of cells, and a computer chip that interacts with the brain's nervous system. It has been described as a'brain on a chip' that functions like a human brain using sensors and an AI-powered algorithm which prompts the robot to move, grab objects and avoid obstacles. The team claimed that the brain shows signs of intelligence, similar to a human brain, by autonomously moving its extremities, and could lead to methods for repairing damage to a human's cerebral cortex and create other techniques to heal neurological disorders. A team of Chinese scientists used stem cells to build the brain and paired it with a computer chip that passes instructions to the robot's body that helps move its limbs, avoid obstacles and track targets A team of Chinese scientists used stem cells – a type of cell that forms brain tissue in the body - to build the brain.

To support interpretable predictions and optimal control of biomanfuacturing processes, in this paper, we develop a digital twin calibration approach for multi-scale bioprocess mechanistic model or Biological System-of-Systems (Bio-SoS) [Zheng et al., 2024] characterizing causal interdependence from molecular-to cellular-to macro-kinetics. Even though this study is motivated by cell culture process, it can be extended to calibrate general Bio-SoS with modular design. Basically, cell culture process dynamics and variations depend on the modules: (1) a single cell mechanistic model characterizing each living cell behaviors and their interactions with environment; (2) a metabolic shift model characterizing the change of cell metabolic phase and behaviors as a response to culture conditions and cell age; and (3) macro-kinetic model of a bioreactor system composed of many living cells under different metabolic phases. The benefits of considering the Bio-SoS mechanistic model with modular design include: a) support flexible manufacturing through assembling a system of modules to account for biomanufacturing processes under different conditions and inputs; and b) facilitate the integration of heterogeneous data from different production processes, such as 2D culture and 3D aggregate culture for Induced Pluripotent Stem Cells (iPSCs) [Wang et al., 2024, Zheng et al., 2024]. By incorporating the structure property of the Bio-SoS mechanistic model into the calibration method, we can quantify how the model uncertainties or approximation errors of different modules interact with each other and propagate through the reaction pathways to the prediction of outputs (e.g., yield and product quality attributes), which can guide interpretable and most informative Design of Experiments (DoEs) to efficiently improve model fidelity with less experiments. The model uncertainty quantification approaches for digital twin calibration can be divided into two main categories: Bayesian and frequentist approaches [Corlu et al., 2020]. Bayesian approaches treat unknown model parameters as random variables and quantify our belief by posterior distributions. It involves specifying prior distributions for model parameters and updating these distributions based on the information from observed data by applying Bayes' theorem.

Recent advances have enabled the study of human brain development using brain organoids derived from stem cells. Quantifying cellular processes like mitosis in these organoids offers insights into neurodevelopmental disorders, but the manual analysis is time-consuming, and existing datasets lack specific details for brain organoid studies. We introduce BOrg, a dataset designed to study mitotic events in the embryonic development of the brain using confocal microscopy images of brain organoids. BOrg utilizes an efficient annotation pipeline with sparse point annotations and techniques that minimize expert effort, overcoming limitations of standard deep learning approaches on sparse data. We adapt and benchmark state-of-the-art object detection and cell counting models on BOrg for detecting and analyzing mitotic cells across prophase, metaphase, anaphase, and telophase stages. Our results demonstrate these adapted models significantly improve mitosis analysis efficiency and accuracy for brain organoid research compared to existing methods. BOrg facilitates the development of automated tools to quantify statistics like mitosis rates, aiding mechanistic studies of neurodevelopmental processes and disorders. Data and code are available at https://github.com/awaisrauf/borg.

Automatic medical discovery by AI is a dream of many. One step toward that goal is to create an AI model to understand clinical studies and synthesize clinical evidence from the literature. Clinical evidence synthesis currently relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating evidence. We introduce TrialMind, a generative AI-based pipeline for conducting medical systematic reviews, encompassing study search, screening, and data extraction phases. We utilize large language models (LLMs) to drive each pipeline component while incorporating human expert oversight to minimize errors. To facilitate evaluation, we also create a benchmark dataset TrialReviewBench, a custom dataset with 870 annotated clinical studies from 25 meta-analysis papers across various medical treatments. Our results demonstrate that TrialMind significantly improves the literature review process, achieving high recall rates (0.897-1.000) in study searching from over 20 million PubMed studies and outperforming traditional language model embeddings-based methods in screening (Recall@20 of 0.227-0.246 vs. 0.000-0.102). Furthermore, our approach surpasses direct GPT-4 performance in result extraction, with accuracy ranging from 0.65 to 0.84. We also support clinical evidence synthesis in forest plots, as validated by eight human annotators who preferred TrialMind over the GPT-4 baseline with a winning rate of 62.5%-100% across the involved reviews. Our findings suggest that an LLM-based clinical evidence synthesis approach, such as TrialMind, can enable reliable and high-quality clinical evidence synthesis to improve clinical research efficiency.