Christopher D. Rosin

Jianyou Wang, Youze Zheng, Longtian Bao et al.

Scientists have long sought to accurately predict outcomes of real-world events before they happen. Can AI systems do so more reliably? We study this question through clinical trial outcome prediction, a high-stakes open challenge even for domain experts. We introduce CT Open, an open-access, live platform that will run four challenge every year. Anyone can submit predictions for each challenge. CT Open evaluates those submissions on trials whose outcomes were not yet public at the time of submission but were made public afterwards. Determining if a trial's outcome is public on the internet before a certain date is surprisingly difficult. Outcomes posted on official registries may lag behind by years, while the first mention may appear in obscure articles. To address this, we propose a novel, fully automated decontamination pipeline that uses iterative LLM-powered web search to identify the earliest mention of trial outcomes. We validate the pipeline's quality and accuracy by human expert's annotations. Since CT Open's pipeline ensures that every evaluated trial had no publicly reported outcome when the prediction was made, it allows participants to use any methodology and any data source. In this paper, we release a training set and two time-stamped test benchmarks, Winter 2025 and Summer 2025. We believe CT Open can serve as a central hub for advancing AI research on forecasting real-world outcomes before they occur, while also informing biomedical research and improving clinical trial design. CT Open Platform is hosted at $\href{https://ct-open.net/}{https://ct-open.net/}$

Jianyou Wang, Weili Cao, Kaicheng Wang et al.

We study the task of automatically finding evidence relevant to hypotheses in biomedical papers. Finding relevant evidence is an important step when researchers investigate scientific hypotheses. We introduce EvidenceBench to measure models performance on this task, which is created by a novel pipeline that consists of hypothesis generation and sentence-by-sentence annotation of biomedical papers for relevant evidence, completely guided by and faithfully following existing human experts judgment. We demonstrate the pipeline's validity and accuracy with multiple sets of human-expert annotations. We evaluated a diverse set of language models and retrieval systems on the benchmark and found that model performances still fall significantly short of the expert level on this task. To show the scalability of our proposed pipeline, we create a larger EvidenceBench-100k with 107,461 fully annotated papers with hypotheses to facilitate model training and development. Both datasets are available at https://github.com/EvidenceBench/EvidenceBench

Duncan Soiffer, Nathaniel Itty, Christopher D. Rosin et al.

A collection of hyperplanes $\mathcal{H}$ slices all edges of the $n$-dimensional hypercube $Q_n$ with vertex set $\{-1,1\}^n$ if, for every edge $e$ in the hypercube, there exists a hyperplane in $\mathcal{H}$ intersecting $e$ in its interior. Let $S(n)$ be the minimum number of hyperplanes needed to slice $Q_n$. We prove that $S(n) \leq \lceil \frac{4n}{5} \rceil$, except when $n$ is an odd multiple of $5$, in which case $S(n) \leq \frac{4n}{5} +1$. This improves upon the previously known upper bound of $S(n) \leq \lceil\frac{5n}{6} \rceil$ due to Paterson reported in 1971. We also obtain new lower bounds on the maximum number of edges in $Q_n$ that can be sliced using $k<n$ hyperplanes. We prove the improved upper bound on $S(n)$ by constructing $8$ hyperplanes slicing $Q_{10}$ aided by the recently introduced CPro1: an automatic tool that uses reasoning LLMs coupled with automated hyperparameter tuning to create search algorithms for the discovery of mathematical constructions.

Youze Zheng, Jianyou Wang, Yuhan Chen et al.

Predicting the outcomes of prospective clinical trials remains a major challenge for large language models. Prior work has shown that both traditional correlational predictors, such as random forests and logistic regression, and strong commercial LLMs achieve limited performance on this task. In this paper, we propose DeepImagine, a framework for teaching LLMs biomedical reasoning through successive counterfactual imagining. The central idea is to approximate hidden causal mechanisms of clinical trials by training models to infer how observed trial results would change under controlled perturbations of experimental conditions, such as dosage, outcome measures, study arms, geography, and other trial attributes. To support this objective, we construct both natural and approximate counterfactual pairs from real clinical trials with reported outcomes. For settings where strict counterfactual supervision is available, such as paired outcome measures or dose-ranging study arms within the same trial, we train models with supervised fine-tuning. For broader settings where only approximate counterfactual pairs can be retrieved, we optimize models with reinforcement learning using verifiable rewards based on downstream benchmark correctness. We further augment training with synthetic reasoning traces that provide causally plausible explanations for local counterfactual transitions. Using this pipeline, we train language models under 10B parameters, including Qwen3.5-9B, and evaluate them on clinical trial outcome prediction. We aim to show that DeepImagine consistently improves over untuned language models and traditional correlational baselines. Finally, we aim to show that the learned reasoning trajectories provide interpretable signals about how models represent trial-level mechanisms, suggesting a practical path toward more mechanistic and scientifically useful biomedical language models.

Christopher D. Rosin

Large Language Models (LLMs) with reasoning are trained to iteratively generate and refine their answers before finalizing them, which can help with applications to mathematics and code generation. We apply code generation with reasoning LLMs to a specific task in the mathematical field of combinatorial design. This field studies diverse types of combinatorial designs, many of which have lists of open instances for which existence has not yet been determined. The Constructive Protocol CPro1 uses LLMs to generate search heuristics that have the potential to construct solutions to small open instances. Starting with a textual definition and a validity verifier for a particular type of design, CPro1 guides LLMs to select and implement strategies, while providing automated hyperparameter tuning and execution feedback. CPro1 with reasoning LLMs successfully solves long-standing open instances for 7 of 16 combinatorial design problems selected from the 2006 Handbook of Combinatorial Designs, including new solved instances for 3 of these (Bhaskar Rao Designs, Symmetric Weighing Matrices, Balanced Ternary Designs) that were unsolved by CPro1 with non-reasoning LLMs. It also solves open instances for several problems from recent (2025) literature, generating new Covering Sequences, Johnson Clique Covers, Deletion Codes, and a Uniform Nested Steiner Quadruple System.

Christopher D. Rosin

The Handbook of Combinatorial Designs catalogs many types of combinatorial designs, together with lists of open instances for which existence has not yet been determined. We develop a constructive protocol CPro1, which uses Large Language Models (LLMs) to generate code that constructs combinatorial designs and resolves some of these open instances. The protocol starts from a definition of a particular type of design, and a verifier that reliably confirms whether a proposed design is valid. The LLM selects strategies and implements them in code, and scaffolding provides automated hyperparameter tuning and execution feedback using the verifier. Most generated code fails, but by generating many candidates, the protocol automates exploration of a variety of standard methods (e.g. simulated annealing, genetic algorithms) and experimentation with variations (e.g. cost functions) to find successful approaches. Testing on 16 different types of designs, CPro1 constructs solutions to open instances for 6 of them: Symmetric and Skew Weighing Matrices, Equidistant Permutation Arrays, Packing Arrays, Balanced Ternary Designs, and Florentine Rectangles.

Christopher D. Rosin

A constant weight binary code consists of $n$-bit binary codewords, each with exactly $w$ bits equal to 1, such that any two codewords are at least Hamming distance $d$ apart. $A(n,d,w)$ is the maximum size of a constant weight binary code with parameters $n,d,w$. We establish improved lower bounds on $A(n,d,w)$ by constructing new larger codes, for 24 values of $(n,d,w)$ with $6 \leq d \leq 18$ and $18 \leq n \leq 35$. The improved lower bounds come from two strategies. The first is a tabu search that operates at the level of bit swaps. The second is a novel greedy heuristic that repeatedly chooses the candidate codeword that maximizes a randomly-scored histogram of distances to previously-added codewords. These strategies were proposed by CPro1, an automated protocol that generates, implements, and tests diverse strategies for combinatorial constructions.

Christopher D. Rosin

Inductive program synthesis, from input/output examples, can provide an opportunity to automatically create programs from scratch without presupposing the algorithmic form of the solution. For induction of general programs with loops (as opposed to loop-free programs, or synthesis for domain-specific languages), the state of the art is at the level of introductory programming assignments. Most problems that require algorithmic subtlety, such as fast sorting, have remained out of reach without the benefit of significant problem-specific background knowledge. A key challenge is to identify cues that are available to guide search towards correct looping programs. We present MAKESPEARE, a simple delayed-acceptance hillclimbing method that synthesizes low-level looping programs from input/output examples. During search, delayed acceptance bypasses small gains to identify significantly-improved stepping stone programs that tend to generalize and enable further progress. The method performs well on a set of established benchmarks, and succeeds on the previously unsolved "Collatz Numbers" program synthesis problem. Additional benchmarks include the problem of rapidly sorting integer arrays, in which we observe the emergence of comb sort (a Shell sort variant that is empirically fast). MAKESPEARE has also synthesized a record-setting program on one of the puzzles from the TIS-100 assembly language programming game.

Christopher D. Rosin

We present ULSA, a novel stochastic local search algorithm for random binary constraint satisfaction problems (CSP). ULSA is many times faster than the prior state of the art on a widely-studied suite of random CSP benchmarks. Unlike the best previous methods for these benchmarks, ULSA is a simple unweighted method that does not require dynamic adaptation of weights or penalties. ULSA obtains new record best solutions satisfying 99 of 100 variables in the challenging frb100-40 benchmark instance.