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A new strategy for clinical decision making: censors and neuroendocrinological diseases.

A patient rarely has a single, isolated disease. The situation is usually much more complex since the different parts of the human organism and its metabolism interact with each other on multiple levels and follow several feedback patterns. These interactions and feedback patterns become even more complex when the effects of the external environment are considered. When several diseases are present, the first steps in medical diagnosis are to determine whether one of the diseases interacts with ("Censors") or changes the significant symptoms, signs, or results of the laboratory tests of the other diseases. We will try, within this paper, to go beyond the scope of the first generation of Artificial Intelligence systems in medicine to determine the effects of two diseases on each other. One important part of the effect of two diseases on each other is the effect of Censors. In addition, causal reasoning, reasoning by analogy, and learning from precedents are important and necessary for a human-like expert in medicine. Their application to thyroid diseases, with an implemented system, are considered in this paper.

Artificial Intelligence↗

AI Health message intervention: The role of message customization and message source in breast cancer screening among women of color.

OBJECTIVES: To examine the effectiveness of breast cancer screening messages with varying levels of customization (generic, targeted, and tailored) and to compare AI-generated versus human-generated messages. METHODS: A between-subjects experimental design with a control condition was employed. Message content followed a standardized structure and varied by level of customization: generic, targeted (demographic-based), and tailored (perceived susceptibility- and barrier-based). Messages were developed by either the authors or GenAI (ChatGPT-4o). A total of 391 participants recruited via Prolific were randomly assigned to five groups (generic, targeted-human, targeted-AI, tailored-human, and tailored-AI). Self-efficacy, behavioral intentions, attitudes, and message believability were measured using different scales. RESULTS: Customized (tailoring and targeting) health messages performed comparably to generic messages in shaping positive health outcomes. GenAI-generated messages also produced outcomes comparable to those of human-generated messages under standardized conditions. Significant negative indirect effects through message believability for the human-tailored condition was found relative to the generic condition. CONCLUSIONS: GenAI may be a useful tool for developing and customizing scalable health messages. Its effectiveness depends not only on customization but also on maintaining message quality, including readability, clarity, coherence, naturalness, and credibility. PRACTICAL IMPLICATIONS: GenAI may support health practitioners in developing customized and scalable breast cancer messages. However, professional review remains necessary to ensure that the message is culturally appropriate, responsive to patient concerns, and suitable for use alongside patient-provider communication.

Humans↗

Classification of observational data with artificial neural networks versus discriminant analysis in pharmacoepidemiological studies--can outcome of fluoxetine treatment be predicted?

For several years, there has been an ongoing discussion about appropriate methodological tools to be applied to observational data in pharmacoepidemiological studies. It is now suggested by our research group that artificial neural networks (ANN) might be advantageous in some cases for classification purposes when compared with discriminant analysis. This is due to their inherent capability to detect complex linear and nonlinear functions in multivariate data sets, the possibility of including data on different scales in the same model, as well as their relative resistance to "noisy" input. In this paper, a short introduction is given to the basics of neural networks and possible applications. For demonstration, a comparison between artificial neural networks and discriminant analysis was performed on a multivariate data set, consisting of observational data of 19738 patients treated with fluoxetine. It was tested, which of the two statistical tools outperforms the two other in regard to the therapeutic response prediction from the clinical input data. Essentially, it was found that neither discriminant analysis nor ANN are able to predict the clinical outcome on the basis of the employed clinical variables. Applying ANN, we were able to rule out the possibility of undetected suppressor effects to a greater extent than would have been possible by the exclusive application of discriminant analysis.

Antidepressive Agents, Second-Generation↗

PRISM-G: an interpretable privacy scoring framework for assessing risk in synthetic human genome data.

MOTIVATION: Synthetic genomic data promises broader data access, but unresolved privacy risks remain a major concern. Existing evaluations often rely on similarity-based metrics that measure proximity between real and synthetic genomes, overlooking additional mechanisms through which genomic information may leak. RESULTS: We introduce PRISM-G, a model-agnostic framework that quantifies privacy exposure in synthetic genomic data across three complementary components: proximity to real genomes in genetic-coordinate space, replay of familial or population-structure patterns, and trait-linked exposure through rare variants and membership-inference signals. These components are normalized and combined through a risk-averse aggregation into a single 0-100 PRISM-G score. By pairing PRISM-G with downstream utility metrics, the framework also enables analysis of privacy-utility trade-offs across generative models. We evaluated PRISM-G on synthetic cohorts generated by a generative adversarial network (GAN), a restricted Boltzmann machine (RBM), and a logic-based SAT solver (Genomator). Our results show that privacy vulnerabilities arise along different axes across models and marker densities, demonstrating that a single similarity-based metric is insufficient to characterize genomic privacy risk. AVAILABILITY AND IMPLEMENTATION: The source code of PRISM-G is available at https://github.com/alejocrojo09/prismg.

Humans↗

PepGen: conditional generation of peptides for MHC binding.

MOTIVATION: Peptide-MHC II binding drives adaptive immunity, yet discovery of novel binder peptides remains challenging due to open binding grooves of MHC-II that accommodate variable-length peptides. While discriminative models perform well, they are unfeasible for generation via enumeration due to vast peptide space (2013≈8×1016 for peptides of length 13 amino acids). Generative AI approaches could accelerate binder design to enable vaccines targeted to particular MHC-II alleles or optimize other peptide chemical properties. RESULTS: We introduce PepGen, the first protein language model for MHC II peptide generation building on Generalized Language Modeling. PepGen conditions on alleles, arbitrary partial peptides including putative TCR-interacting motifs, and continuous binding affinity. Across multiple benchmarks including infilling and de novo generation, PepGen outperformed frequency sampling, Gibbs clustering, and autoregressive baselines. Adjusted log-probabilities enable good classification performance. Experimental validation confirmed that the SARS-CoV-2 peptide TEGALNTPKDHIGTR binding the HLA-DQA101:03-DQB106:03 allele can be redesigned to bind the HLA-DQA101:02-DQB105:02 allele. PepGen generated three putative TCR-motif-preserving binders gaining up to 70% of original MFI. Overall, PepGen provides scalable, motif-constrained MHC II peptide redesign and de novo generation, validated through thorough benchmarks and functional assays. AVAILABILITY AND IMPLEMENTATION: Code and Data are available at https://github.com/DaniTheOrange/PepGen.

Peptides↗

Discrimination between chronic pancreatitis and pancreatic adenocarcinoma using artificial intelligence-related algorithms based on image cytometry-generated variables.

The incidence of pancreatic adenocarcinomas (PA) is increased in the setting of chronic pancreatitis. Distinguishing chronic pancreatitis from pancreatic adenocarcinomas is often difficult, and is based on routine brush cytological specimens provided during endoscopic retrograde cholangiopancreatography (ERCP). Reactive epithelial changes in chronic pancreatitis may appear similar to those of a well-differentiated cancer. Brush cytology specimens were obtained during ERCP from 49 patients with diseases for which the differential diagnosis included chronic pancreatitis and/or pancreatic adenocarcinoma Image cytometry was performed involving the assessment of between 200-400 Feulgen-stained nuclei per case; for each case, 40 quantitative cytometric variables were generated. Data analysis was performed using artificial intelligence methods of data classification that produced decision trees and production rule systems. Different classification models were produced for a subset of 34 patients. The best models were identified by the use of a sampling technique (leave-one-out), and were tested on the remaining 15 patients. These models were based on 5 of the 40 variables associated with a significant discriminatory function. Pancreatic adenocarcinoma was diagnosed in the training data set of 34 patients during a leave-one-out process with an estimated sensitivity of 91% and specificity of 87%. Both sensitivity and specificity were 80% in the independent test set of 15 patients. We conclude that inflammatory and malignant pancreatic epithelia exhibit distinct morphological features that can be distinguished by decision tree-based classifiers employing image-cytometric numerical data.

Adenocarcinoma↗

Tissue engineering scheming by artificial intelligence.

Tissue engineers are often confused when seeking the most effective, economical and secure scheme for tissue engineering. The aim of this study is to generate tissue engineering schemes with artificial intelligence instead of human intelligence. The experimental data of tissue engineered cartilage were integrated and standardized with a centralized database, and a scheme engine was developed using artificial intelligent methods (artificial neural networks and decision trees). The scheme engine was trained with existing cases in the database, and then was used to generate tissue engineering schemes for new experimental animals. Following the schemes generated by the artificial intelligent system, we cured 18 of the 20 experimental animals. In conclusion, artificial intelligence is a powerful method for decision making in the tissue engineering realm.

Algorithms↗

Humans can consciously generate random number sequences: a possible test for artificial intelligence.

Computer algorithms can only produce seemingly random or pseudorandom numbers whereas certain natural phenomena, such as the decay of radioactive particles, can be utilized to produce truly random numbers. In this study, the ability of humans to generate random numbers was tested in healthy adults. Subjects were simply asked to generate and dictate random numbers. Generated numbers were tested for uniformity, independence and information density. The results suggest that humans can generate random numbers that are uniformly distributed, independent of one another and unpredictable. If humans can generate sequences of random numbers then neural networks or forms of artificial intelligence, which are purported to function in ways essentially the same as the human brain, should also be able to generate sequences of random numbers. Elucidating the precise mechanism by which humans generate random number sequences and the underlying neural substrates may have implications in the cognitive science of decision-making. It is possible that humans use their random-generating neural machinery to make difficult decisions in which all expected outcomes are similar. It is also possible that certain people, perhaps those with neurological or psychiatric impairments, are less able or unable to generate random numbers. If the random-generating neural machinery is employed in decision making its impairment would have profound implications in matters of agency and free will.

Adult↗

Decision support for tendon tissue engineering.

The aim of this study is to provide decision support with artificial intelligence for tendon tissue engineering strategies. The experimental data of tissue-engineered tendons were integrated and standardized with a centralized database, and a decision support system was developed using both artificial neural networks and decision trees. The decision support system was trained with existing cases in the database, and then was used to generate tissue engineering schemes for new experimental animals. Following the schemes generated by the artificial intelligent system, we cured 28 of the 30 experimental animals. In conclusion, artificial intelligence is a powerful method for decision support in the tendon tissue engineering realm.

Animals↗

An intelligent system for comparing protein structures.

An approach to protein structure comparison is presented which uses techniques of artificial intelligence (AI) to generate a mapping between two protein structures. The approach proceeds by first identifying the seed of a possible mapping, and then searching for ways to extend the seed by incorporating corresponding elements from the two proteins. Correspondence is judged using heuristic functions which assess the similarity of the structural environments of the elements. The search can be guided by separately encoded knowledge. A prototype has been implemented which is able to rapidly create mappings with a high degree of accuracy in test cases.

Animals↗

The dynamic lift of developmental process.

What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building human-like intelligence: the heterogeneity of the component processes, the embedding of development in a social world, and developmental processes that change the cognitive system as a function of the history of soft-assemblies of these heterogeneous processes in specific tasks. The paper uses examples from human development and from developmental robotics to show how these processes also may underlie biological intelligence and enable us to generate more advanced forms of artificial intelligence.

Brain↗

Creating bottom-up RNA transfer vehicles from synthetic protein assemblies.

Evolution guides biological systems to populate ecological niches, with viruses among the most successful examples of this principle. Viruses evolved over billions of years to efficiently transfer genetic information. Although viruses are highly diverse, most have converged towards remarkable similarity in the size and shape of their capsids1,2. By contrast, generative models for protein design enable the creation of protein architectures that are absent from nature3-5. Here we investigate whether protein assemblies designed by artificial intelligence can be functionalized to construct nucleic acid transport vehicles that are independent of evolutionary trajectories. By combining natural protein domains with synthetic protein assemblies, we create more than 100 bottom-up RNA transfer vehicles with unique sizes and shapes. These vehicles surpass the RNA transfer efficiency of widely used delivery vehicles by several orders of magnitude. In addition, we demonstrate that their tropism can be programmed by incorporation of computationally designed peptide binders and use them to deliver therapeutically relevant cargo RNAs into a wide range of cellular models. We show the in vivo biodistribution of one of these vehicles in a mouse at near-single-cell resolution, confirm its safety, and use it to perform a gene-editing treatment strategy for Duchenne muscular dystrophy in patient-derived cells and a pig. Our work demonstrates how proteins created by generative artificial intelligence can be harnessed for the rational engineering of RNA transport systems with the desired properties by overcoming the limitations of natural protein diversity.

Journal Article↗

Beyond antibiotics: artificial intelligence-enabled anti-infective ecosystems for next-generation precision therapeutics against antimicrobial resistance.

The rapid global expansion of antimicrobial resistance (AMR) threatens to undermine decades of progress in infectious disease management and highlights the limitations of conventional antibiotic-centered therapeutic strategies. Although emerging technologies-including antimicrobial peptides, bacteriophage therapy, CRISPR-based antimicrobials, microbiome therapeutics, anti-virulence approaches, nanotechnology-enabled drug delivery, and artificial intelligence (AI)-have individually demonstrated considerable promise, they are predominantly being developed as independent interventions rather than as coordinated components of an integrated therapeutic strategy. This Perspective proposes the Intelligent Anti-Infective Ecosystem (IAIE) as a conceptual systems-level framework that computationally integrates multimodal diagnostics, pathogen genomics, microbiome profiling, AI-assisted decision support, programmable precision therapeutics, ecological monitoring, and longitudinal clinical feedback within a continuously learning dynamically optimized workflow. Unlike existing paradigms that primarily optimize individual technologies or therapeutic decisions, IAIE emphasizes closed-loop coordination among complementary antimicrobial approaches to support precision-guided infection management while preserving microbiome integrity and mitigating resistance selection pressure. We further outline the core components, operational principles, translational challenges, and technology readiness of the major therapeutic platforms that could contribute to such an ecosystem, while distinguishing clinically established interventions from emerging experimental strategies. Importantly, IAIE should be interpreted as a prospective conceptual architecture rather than an existing clinical platform. Its proposed clinical value remains to be established through sequential computational, preclinical, and prospective clinical investigations using standardized microbiological, ecological, and patient-centered outcome measures. By framing antimicrobial innovation within an responsive systems perspective, IAIE provides a roadmap for future multidisciplinary research aimed at integrating artificial intelligence and systems microbiology to enable sustainable management of antimicrobial resistance.

Humans↗

Design of highly functional genome editors by modelling CRISPR-Cas sequences.

Gene editing has the potential to solve fundamental challenges in agriculture, biotechnology and human health. CRISPR-based gene editors derived from microorganisms, although powerful, often show notable functional tradeoffs when ported into non-native environments, such as human cells1. Artificial-intelligence-enabled design provides a powerful alternative with the potential to bypass evolutionary constraints and generate editors with optimal properties. Here, using large language models2 trained on biological diversity at scale, we demonstrate successful precision editing of the human genome with a programmable gene editor designed with artificial intelligence. To achieve this goal, we curated a dataset of more than 1 million CRISPR operons through systematic mining of 26 terabases of assembled genomes and metagenomes. We demonstrate the capacity of our models by generating 4.8× the number of protein clusters across CRISPR-Cas families found in nature and tailoring single-guide RNA sequences for Cas9-like effector proteins. Several of the generated gene editors show comparable or improved activity and specificity relative to SpCas9, the prototypical gene editing effector, while being 400 mutations away in sequence. Finally, we demonstrate that an artificial-intelligence-generated gene editor, denoted as OpenCRISPR-1, exhibits compatibility with base editing. We release OpenCRISPR-1 to facilitate broad, ethical use across research and commercial applications.

CRISPR-Cas Systems↗

Community-driven advances in computational mass spectrometry: The perspective of EuBIC-MS members.

Advances in data acquisition, artificial intelligence, and integrative bioinformatics are driving the rapid evolution of computational mass spectrometry, and in turn, transforming modern proteomics, metabolomics, and lipidomics. These developments have greatly increased the scale and complexity of mass spectrometry data, underscoring the importance of evolving accurate, transparent, efficient and reproducible data processing workflows. Addressing these challenges requires collaborative innovation that brings together expertise in software engineering, statistics, and biology. The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS), an initiative of the European Proteomics Association (EuPA), fosters a culture of open, community-driven development through its biennial Developers Meetings and Winter Schools. This commentary summarizes the scientific background and outcomes of the EuBIC-MS Developers Meeting 2025, which took place in Novacella, Italy. Three keynote presentations highlighted major frontiers in the field: deep proteome and phosphoproteome profiling, text mining for protein-protein interaction extraction, and scalable proteomics for AI-driven drug discovery. Seven community-selected hackathons addressed emerging challenges such as single-cell proteomics data analysis, FAIR metadata extraction, deep learning frameworks, R-Python interoperability, and DIA validation. Together, these efforts demonstrate the potential for scientific and technical innovation to arise from open collaboration, and highlight how community-driven initiatives can accelerate progress in computational mass spectrometry. SIGNIFICANCE: Modern proteomics increasingly depends on computational advances to translate complex, high-dimensional data into biological knowledge. The EuBIC-MS Developers Meeting 2025 exemplifies how community-driven collaboration can directly accelerate this process by bringing together experts from bioinformatics, statistics, and experimental proteomics to co-develop open, interoperable, and reproducible analytical tools. By fostering shared software frameworks, transparent benchmarking, and collaborative problem solving, the EuBIC-MS community helps ensure that technological innovation translates into reliable biological insights. This collaborative model strengthens the foundation for quantitative, system-level understanding of proteomes and establishes a sustainable path for integrating artificial intelligence and next-generation data acquisition into routine biological discovery. This commentary shows some current highlights in the field of computational mass spectrometry and community-based approaches undertaken during the most recent Developers Meeting to solve these challenges. The approaches discussed and initiated during the meeting - ranging from deep proteome profiling and phosphosite mapping to text mining, single-cell data analysis, and FAIR metadata extraction - address key bottlenecks that currently limit the biological interpretability and comparability of proteomics data.

Mass Spectrometry↗

AI echo INSIGHT study: A prospective blinded randomized trial of artificial intelligence echocardiogram interpretation.

BACKGROUND: Transthoracic echocardiography (TTE) is the most commonly performed cardiac imaging modality with over 30 million studies annually. Demand for timely expert interpretation continues to outpace capacity, creating diagnostic delays and inter-observer variability that impact patient care. Recent research has suggested computer vision artificial intelligence (AI) models can generate accurate preliminary comprehensive TTE reports, however, prospective evaluation is needed to determine whether AI-assisted TTE interpretation can improve clinician efficiency while preserving diagnostic accuracy. METHODS: AI ECHO INSIGHT is a prospective randomized blinded clinical trial conducted at Kaiser Permanente Northern California that will evaluate 1200 historical TTE studies (1000 consecutive unselected studies plus 200 with moderate or greater valvular disease) interpreted using three workflows: (1) AI-generated preliminary report finalized by a blinded cardiologist (AI-assisted); (2) cardiologist-generated preliminary report finalized by a blinded cardiologist (cardiologist-assisted); and (3) sonographer-generated preliminary report finalized by a blinded cardiologist (sonographer-assisted). The primary outcome is the rate of substantial change between preliminary and final reports, comparing the AI-assisted workflow to the pooled cardiologist-assisted and sonographer-assisted workflows. Secondary outcomes include cardiologist interpretation time for report finalization, superiority testing for diagnostic accuracy, and reporting consistency. CONCLUSION: AI ECHO INSIGHT is a prospective randomized blinded clinical trial evaluating the clinical impact of AI-assisted TTE interpretation on diagnostic accuracy, cardiologist efficiency, and reporting consistency in real-world echocardiography workflows. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT07229300.

Humans↗

Relationship between carcinogenicity in rodents and the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells.

Two independent analyses were carried out to compare the induction of sister chromatid exchanges and of chromosomal aberrations as predictors of carcinogenicity. Using both a classical and a Bayesian approach, as well as by analysis of the structural fragments generated by CASE, an artificial intelligence system, it is included that individually neither of these tests is a satisfactory predictor of carcinogenicity. However, because the analysis revealed that each of the cytogenetic assays responds to a different set of structural features associated with carcinogenicity, it can be concluded that the assays can be included in a battery of tests to improve predictivity.

Animals↗

Carotenoid content of fruits and vegetables: an evaluation of analytic data.

The test of the association between dietary intake of specific carotenoids and disease incidence requires the availability of accurate and current food composition data for individual carotenoids. To generate a carotenoid database, an artificial intelligence system was developed to evaluate data for carotenoid content of food in five general categories, namely, number of samples, analytic method, sample handling, sampling plan, and analytic quality control. Within these categories, criteria have been created to rate analytic data for beta-carotene, alpha-carotene, lutein, lycopene, and beta-cryptoxanthin in fruits and vegetables. These carotenoids are also found in human blood. Following the evaluation of data, acceptable values for each carotenoid in the foods were combined to generate a database of 120 foods. The database includes the food description; median, minimum, and maximum values for the specific carotenoids in each food; the number of acceptable values and their references; and a confidence code, which is an indicator of the reliability of a specific carotenoid value for a food. The carotenoid database can be used to estimate the intake of specific carotenoids in order to examine the association between dietary carotenoids and disease incidence.

Carotenoids↗