Deterministic Integrity Gates for LLM-Assisted Clinical Manuscript Preparation: An Auditable Biomedical Informatics Architecture

While recent advances in large language models have enabled end-to-end automated manuscript generation, existing systems suffer from three critical deficiencies: (i) generated claims are not deterministically grounded in verifiable literature, (ii) experimental results are frequently fabricated rather than executed, and (iii) there exists no standardized, multi-dimensional framework to assess whether AI-generated manuscripts meet the quality and rigor required for real-world publication. We present Prompt-to-Paper, a multi-agent framework that directly addresses this evaluation gap through three integrated innovations. First, a deterministic retrieval-augmented generation pipeline with section-aware relevance scoring and snowball citation expansion grounds every claim in a verifiable corpus of 60--100 papers. Second, an autonomous coding agent executes real computational biology experiments replacing synthetic outputs with genuine numerical results. Third, an eight-dimensional automated quality scorer, benchmarked with approximate reference statistics from published papers and augmented with explicit hallucination penalties, provides standardized, reproducible quality assessments. The quality-driven improvement loop uses a context-rich reviser that routes each iteration to one of three researcher actions and fires a deep research cycle every ten iterations to re-run experiments and re-manuscript from stronger outputs. We validate the system on five bioinformatics case studies; all five cases compiled submission-formatted PDFs with zero out-of-range citations. The improvement loop raises manuscript quality by an average of +17.96 points on a 0--100 scale (maximum +26.04. As partial external checks, a human reviewer scored the five manuscripts at an average of 7.0 out of 10. Complete manuscripts are produced at approximately 0.31 USD per paper.

Recent advances in large language models (LLMs) have enabled AI systems to assist scientific research and peer review. However, an essential capability for reliable AI-assisted scientific workflows remains underexplored: verifying whether reviewer feedback leads to meaningful and evidence-supported manuscript improvements. We introduce AutoSupervision, which evaluates whether scientific manuscript revisions genuinely address reviewer concerns through grounded evidence. AutoSupervision leverages transparent peer-review records as a natural source of supervision, where reviewer comments specify scientific concerns, author responses describe claimed resolutions, and revised manuscripts provide evidence of changes. Given reviewer comments, author responses, and revised manuscripts, models must characterize reviewer concerns, determine whether concerns have been addressed, and identify supporting manuscript evidence. We construct AutoSupervision from 56,000 Nature Communications articles and corresponding review records. Then we conducted experiments on LLMs, the ablation study, and the case study. Our results show that while LLMs perform well in characterizing reviewer concerns, with GPT-5.5 achieving a score of 0.754, evidence-based verification remains the primary bottleneck, with the best-performing model reaching only 0.501.

Large language models (LLMs) now routinely draft literature reviews and assist with academic writing, which means a higher risk of fabricated references: GPTZero found 53 papers with hallucinated citations among NeurIPS 2025's accepted set. Rule- and LLM-based verifiers are emerging, but no shared benchmark compares them and gives detailed failure diagnostics. We close that gap with HALLMARK (Hallucination benchmark): 2,526 BibTeX entries spanning 14 hallucination types, three difficulty tiers, six diagnostic sub-tests per entry, and a contamination-resistant held-out split. On it we evaluate a DOI-lookup baseline, frontier LLMs zero-shot, tool-augmented agents, and our own rule-based, co-designed verifier bibtex-updater. Across the benchmark one result is consistent: the false-positive rate, not recall, decides whether a verifier is deployable. HALLMARK makes it concrete through three failure modes: agentic lookups buy recall but inflate false positives; at a venue-realistic base rate, the order-of-magnitude spread in false-positive rates (FPRs) -- not recall -- governs whether a verifier's flags are mostly true catches or mostly noise; and most LLMs over-flag papers published past their training cutoff, where only the two latest-cutoff models hold their false-positive rate near in-distribution levels (a signal we report as descriptive, since it is confounded with possible recall of those entries). Thus FPR is the deployment bottleneck, but an undetected fabrication remains the costlier error for the scientific record.