Laura Montagnani, Anthony CC Coolen, Marianne A Jonkerstat.ME math.ST stat.CO stat.ML
Joint analyses across multiple institutions are increasingly important in biomedical and epidemiological research, particularly for rare diseases where datasets are typical small. However, privacy regulations and institutional policies often prevent the sharing of individual-level patient data. In this paper we present an accurate and single-communication federated inference algorithm. Single-communication federated inference enables statistical analyses through a single exchange of summary statistics between participating centers and a coordinating server, preserving privacy while reducing communication and computational costs compared with iterative federated learning. We extend a recently proposed single-communication federated inference strategy that is based on second-order Taylor expansions by using third-order expansions to better approximate local log-likelihood functions. The proposed method is evaluated through simulation studies based on real data and compared with existing federated inference strategies. The simulation studies assess the performance of the proposed method, with a particular focus on scenarios involving small local sample sizes, where quadratic approximations may fail to capture skewness and other higher-order characteristics of the log-likelihood function. They demonstrate that incorporating higher-order information of the log-likelihood function improves the accuracy while preserving the privacy, communication efficiency, and scalability required for collaborative biomedical and epidemiological research.
A working citation looks like proof -- but the fact that a link resolves does not mean the cited paper supports the claim. I find that current agentic models rarely fabricate citations (over $99\%$ resolve), yet roughly $15.9\%$ link to the wrong paper. Existing benchmarks miss this failure mode: when a question has a fixed answer key, a model can reproduce the expected source from that key rather than independently verifying that the source supports the claim. I introduce \textbf{\openbiorq{}}, a retrieval-grounded agentic benchmark of $12{,}553$ unsolved biomedical research questions across $12$ domains that treats open questions as a faithfulness-and-abstention probe. To my knowledge, this is the first biomedical benchmark to combine an agentic setting -- where the model must issue multiple tool calls -- with unsolved questions that have no answer key. Openness is verified against real follow-up evidence rather than a model's parametric knowledge. Difficulty is empirical: I anchor it on questions that three open-weight reference models fail to answer, rather than on subjective hardness labels. On this hardest subset, held-out models from the same lineage as the difficulty anchors solve only ~17%, while three independent frontier agents (Gemini-3-Pro, Opus-4.7, GPT-5.5) span a wide 29-60% range. The benchmark is thus hard, non-saturating (the best agent still leaves ~33-40\% unsolved), and discriminating across capability tiers. Beyond difficulty, I observe agentic collapse on the hardest questions, where agents stop using their tools. For the most collapse-prone model, blocking tool access entirely barely changes its score -- so tools stop paying off exactly where they are needed most. A frozen per-question checklist raises inter-judge agreement from Spearman 0.35 to 0.82.
Background. Large language models and AI agents are increasingly used to support biomedical research, but native model outputs may omit key analytical steps, misuse methods, or overstate conclusions. We evaluated whether autonomous access to a medical research skill package was associated with higher-quality AI-generated transcriptomic research-analysis outputs compared with native AI without skills. Methods. We conducted an exploratory multi-model human evaluation using a non-small cell lung cancer immunotherapy biomarker task. Six model backbones were tested. The evaluation included 21 anonymized outputs: 9 native-AI outputs and 12 skill-augmented outputs generated through an AI agent implementation represented by OpenClaw. Four non-expert biomedical reviewers and two blinded experts evaluated each output, with two ratings from each reviewer type. The primary outcome was expert-rated overall quality. Results. Skill-augmented outputs showed directionally higher expert overall quality than native-AI outputs (mean 5.50 vs 5.11; difference=0.39; bootstrap 95\% CI, -0.04 to 0.90; Welch p=0.156). Non-expert reviewer quality showed the same direction (mean 4.72 vs 4.47; difference=0.26; bootstrap 95\% CI, -0.25 to 0.80; Welch p=0.373). Expert agreement was limited (single-rating ICC=-0.15), and model-specific effects were descriptive and heterogeneous. Conclusions. Autonomous skill access showed a directional quality signal in this exploratory sample, but the signal was smaller than expert-rating noise and should not be interpreted as confirmatory evidence. The findings primarily motivate larger evaluations of skill-augmented AI agents with stronger reliability controls, platform replication, and biological-validity assessment.