Biology subjects

Sonbol, M. B.

Publications and source records attributed to Sonbol, M. B..

4 recordsLinked to original sources

bioRxiv2026

Version-aware question answering over living oncology guidelines

Living clinical guidelines revise recommendations as evidence emerges, so an AI answer can be faithful to a real guideline and still be out of date. Here we examine this failure using ASCOBench, 288 unique questions in 96 three-turn conversations grounded in versioned American Society of Clinical Oncology (ASCO) breast and prostate cancer guidelines, with oncologist-reviewed reference answers. Oncologists corrected one in four version-sensitive answers drafted by a frontier model, against fewer than one in ten factual ones. Across the guideline corpus, 19 recommendations changed between versions, seven of them reversals, yet only 1 of 14 superseded documents states that it has been replaced. With a strong model, retrieval over several guideline versions made stale answers four times more frequent than answering without retrieval. SentryLine, a verification-first system, lowered incorrect answers to 4.2-5.2% from 9.7-22.9% for baselines across three models. Recognizing change before a guideline declares it remains an open problem.

bioinformatics↗

bioRxiv2026

Reliable extraction of clinical-trial evidence with provenance, verification, and targeted review

Reliable extraction of trial characteristics and outcomes is essential for systematic reviews, yet incorrect values can alter evidence synthesis and are difficult to detect without clear source evidence. We evaluate EviSearch, a clinical evidence-curation system that links extracted values to source passages, independently verifies cited evidence, and prioritizes higher-risk cells for review. Using ten trial publications, a 133-column schema, reference annotations, and consistent scoring across model families, we assess answer quality, inter-reading agreement, evidence reproduction, targeted review, and evidence modality. In the Qwen evaluation, EviSearch achieved 91.70% accuracy, cited 100.0% of admitted values, and reproduced 98.9% independently. Reviewing 15.6% of cells increased accuracy to 95.22%.

bioinformatics↗

bioRxiv2026

Answering clinicians' questions over trial evidence tables with verifiable, feedback-driven language models

Systematic reviews condense clinical trials into evidence tables, yet clinicians can interrogate these tables only through database queries, and many questions concern attributes that the table does not record, such as a drug's target class or a harmonised endpoint. Here we introduce FD-SCoPE, a language-model framework that answers both kinds of question, exposes the query, the selected trials and the derivation rule behind every answer, and learns from expert corrections. On an oncology evidence table of 159 immune checkpoint inhibitor trial records, FD-SCoPE completed all 140 clinician-style tasks (alternatives, 90.7--97.9%). For questions needing derived attributes it retrieved 99.3% of relevant trial records at a positive predictive value of 89.8% and outperformed four alternative approaches (derived-value F1 77.7% versus 64.8--73.4%). Corrections on 299 questions, simulated from reference answers, raised F1 on 1,201 unseen questions from 77.9% to 84.9%. Language models coupled with executable queries, verified programs and expert feedback can give clinicians auditable access to trial evidence.

bioengineering↗

bioRxiv2020

Synergistic Combination of Cytotoxic Chemotherapy and Cyclin Dependent Kinase 4/6 Inhibitors in Biliary Tract Cancers

Biliary tract cancers (BTCs) are uncommon but highly lethal gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care (SOC) systemic therapy, but has a modest impact on survival and harbor toxicities including myelosuppression, nephropathy, neuropathy and ototoxicity. While BTCs are characterized by aberrations activating the cyclinD1-CDK4/6-CDKN2A-RB pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident pre-clinical efficacy and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the anti-tumor efficacy of CDK4/6 inhibitors by combination with chemotherapy-regimens but their mechanism of action remains elusive. Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy due to autophagy induced resistance. Notably, triplettherapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated RRM1 reduction, resulting in sensitization to gemcitabine. Conclusions: As such, these data provide robust pre-clinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors, and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.

cancer biology↗