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The Alignment Paradox of Medical Large Language Models in Infertility Care: Decoupling Algorithmic Improvement from Clinical Decision-making Quality

arXiv:2511.18084v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly adopted in clinical decision support, yet aligning them with the multifaceted reasoning pathways of real-world medicine remains a major challenge. Using more than 8,000 infertility treatment records, we systematically evaluate four alignment strategies: Supervised Fine-Tuning (SFT), Direct Preference Optimization (DPO), Group Relative Policy Optimization (GRPO), and In-Context Learning (ICL) through a dual-layer framework combining automatic benchmarks with blinded doctor-in-the-loop assessments. GRPO achieves the highest algorithmic accuracy across multiple decision layers, confirming the value of reinforcement-based optimization for structured prediction tasks. However, clinicians consistently prefer the SFT model, citing clearer reasoning processes (p = 0.035) and higher therapeutic feasibility (p = 0.019). In blinded pairwise comparisons, SFT attains the highest winning rate (51.2%), outperforming both GRPO (26.2%) and even physicians' original decisions (22.7%). These results reveal an alignment paradox: algorithmic improvements do not necessarily translate into higher clinical trust, and may diverge from human-centered preferences. Our findings highlight the need for alignment strategies that prioritize clinically interpretable and practically feasible reasoning, rather than solely optimizing decision-level accuracy.

New advances in oral microbiology and tumor research

World J Clin Oncol. 2025 Jul 24;16(7):106981. doi: 10.5306/wjco.v16.i7.106981.

ABSTRACT

Cancer remains a major global health concern, with escalating incidence and mortality rates underscoring the urgent need for novel diagnostic and therapeutic strategies. Increasing evidence has identified the oral microbiota as a critical contributor to tumorigenesis, thereby expanding the understanding of cancer pathogenesis beyond conventional risk factors such as tobacco use and genetic predisposition. This review summarizes recent progress in elucidating the complex relationship between the oral microbiota and various malignancies, particularly oral squamous cell carcinoma, esophageal adenocarcinoma, and pancreatic ductal adenocarcinoma. Pathogenic bacteria, including Porphyromonas gingivalis and Fusobacterium nucleatum, have been implicated in promoting tumor progression through mechanisms involving chronic inflammation, the production of metabolic toxins, and immune evasion. The dysbiosis of the oral microbiota, often driven by lifestyle factors such as poor diet, tobacco use, and alcohol consumption, further exacerbates these carcinogenic processes. Emerging therapeutic approaches including probiotics, oral microbiota transplantation, and CRISPR-based bacterial editing are under investigation for their potential to restore microbial homeostasis and suppress pathogenic species. Additionally, saliva-based microbial biomarkers have shown promise for non-invasive cancer screening. The integration of multi-omics technologies and artificial intelligence-driven platforms is further advancing the development of precision oncology. This review aims to consolidate fragmented findings concerning the oral microbiota-cancer axis and address existing gaps in mechanistic understanding. The review's significance lies in the translational potential of microbial research to clinical applications, offering opportunities to reduce the global cancer burden through early detection and microbiota-targeted therapies.

PMID:40741186 | PMC:PMC12304933 | DOI:10.5306/wjco.v16.i7.106981

Liquid Biopsy: Current advancements in clinical practice for bladder cancer

J Liq Biopsy. 2025 Jul 8;9:100310. doi: 10.1016/j.jlb.2025.100310. eCollection 2025 Sep.

ABSTRACT

Bladder cancer is the ninth most common malignancy worldwide, with two clinically distinct forms: non-muscle-invasive disease, characterized by high recurrence and excellent long-term survival, and muscle-invasive disease, associated with poorer outcomes. Current surveillance-cystoscopy and urine cytology-offers high specificity but is invasive, costly, and insensitive to low-grade tumors, underscoring the need for reliable, non-invasive biomarkers. Liquid biopsy approaches in urine and blood have demonstrated promise for real-time assessment of tumor burden, molecular heterogeneity, and early recurrence. Circulating tumor DNA (ctDNA) assays detect tumor-derived genetic and epigenetic alterations, enabling dynamic monitoring of minimal residual disease and treatment response. Methylation-based tests and CpG-targeted sequencing in urine achieve high diagnostic accuracy, potentially reducing dependence on cystoscopy. Molecular classification of bladder tumors into luminal and basal subtypes has refined therapeutic strategies: FGFR inhibitors for luminal-papillary tumors, EGFR-targeted and chemotherapy approaches for basal/squamous cases, and immune-checkpoint inhibitors guided by immune-infiltration profiles. Integration of artificial intelligence with multi-omic liquid biopsy data further enhances predictive modeling for recurrence, treatment response, and minimal residual disease detection. Despite these advances, clinical implementation faces challenges including pre-analytical variability, lack of standardized assays, limited prospective validation, and unclear cost-effectiveness. Harmonized protocols, large multicenter trials, and health-economic evaluations are essential to translate liquid biopsy technologies into routine practice. Future integration with advanced imaging, tissue biopsy, and digital pathology-supported by multidisciplinary collaboration and formal guideline endorsement-holds the potential to personalize bladder cancer management, reduce invasive procedures, and improve patient outcomes.

PMID:40698358 | PMC:PMC12281373 | DOI:10.1016/j.jlb.2025.100310

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