Clinical and translational discovery最新文献

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148079855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148081999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148082000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148082001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translation products of circular RNAs and their functions and application prospects in colorectal cancer","authors":"Fengsen Wang,&nbsp;Xuezhou Gu,&nbsp;Xinxiang Li,&nbsp;Maoguang Ma","doi":"10.1002/ctd2.70144","DOIUrl":"10.1002/ctd2.70144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The discovery of translatable circular RNAs has fundamentally expanded the functional landscape of non-coding transcripts in colorectal cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to synthesize current evidence on circRNA-encoded proteins and micropeptides in colorectal cancer, assess their functional dichotomy as oncogenic drivers or tumor suppressors, and evaluate the therapeutic opportunities and translational barriers in targeting these molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Findings</h3>\u0000 \u0000 <p>A growing number of circRNA-encoded proteins and micropeptides exert distinct biological activities independent of their linear host genes. Specific subsets function as either oncogenic drivers or tumor suppressors, converging on key pathways such as Hippo-YES-associated protein (Hippo-YAP), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Mitogen-activated protein kinase (MAPK) signaling, while also contributing to metabolic reprogramming and therapy resistance. This functional dichotomy establishes a dual therapeutic framework: inhibiting oncogenic circRNA translation products while restoring tumor-suppressive ones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Significant translational barriers remain, particularly in achieving efficient and tumor-selective in vivo delivery and systematically defining the full circRNA-encoded proteome. Addressing these challenges will require innovations in delivery platforms, functional screening technologies, and mechanistic characterization. circRNA-derived proteins are emerging as uniquely specific therapeutic targets owing to their cancer-restricted expression patterns and non-canonical regulation, positioning them to meaningfully contribute to precision oncology in colorectal cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translation products of circular RNAs and their functions and application prospects in colorectal cancer","authors":"Fengsen Wang,&nbsp;Xuezhou Gu,&nbsp;Xinxiang Li,&nbsp;Maoguang Ma","doi":"10.1002/ctd2.70144","DOIUrl":"https://doi.org/10.1002/ctd2.70144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The discovery of translatable circular RNAs has fundamentally expanded the functional landscape of non-coding transcripts in colorectal cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to synthesize current evidence on circRNA-encoded proteins and micropeptides in colorectal cancer, assess their functional dichotomy as oncogenic drivers or tumor suppressors, and evaluate the therapeutic opportunities and translational barriers in targeting these molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Findings</h3>\u0000 \u0000 <p>A growing number of circRNA-encoded proteins and micropeptides exert distinct biological activities independent of their linear host genes. Specific subsets function as either oncogenic drivers or tumor suppressors, converging on key pathways such as Hippo-YES-associated protein (Hippo-YAP), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Mitogen-activated protein kinase (MAPK) signaling, while also contributing to metabolic reprogramming and therapy resistance. This functional dichotomy establishes a dual therapeutic framework: inhibiting oncogenic circRNA translation products while restoring tumor-suppressive ones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Significant translational barriers remain, particularly in achieving efficient and tumor-selective in vivo delivery and systematically defining the full circRNA-encoded proteome. Addressing these challenges will require innovations in delivery platforms, functional screening technologies, and mechanistic characterization. circRNA-derived proteins are emerging as uniquely specific therapeutic targets owing to their cancer-restricted expression patterns and non-canonical regulation, positioning them to meaningfully contribute to precision oncology in colorectal cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in structural cell-mediated immune regulation: Implications for precision respiratory medicine","authors":"Quocdai Vu,&nbsp;Wei Gao,&nbsp;Wujian Xu,&nbsp;Ximing Liao,&nbsp;Qiang Li","doi":"10.1002/ctd2.70142","DOIUrl":"https://doi.org/10.1002/ctd2.70142","url":null,"abstract":"&lt;p&gt;For a long time, sex dimorphism has been recognised as an important factor modulating immune function in health and disease across the lifespan, contributing to disparities in epidemiology, pathophysiology, clinical manifestations, progression and therapeutic outcomes across multiple diseases. Respiratory diseases such as pulmonary arterial hypertension (PAH), pneumonia, and asthma exhibit notable sex differences in incidence and prognosis, yet the underlying mechanisms remain incompletely understood. In the respiratory system, investigating how structural cells respond to sex hormone signals and elucidating their sex dimorphism in gene expression and secretion of immune mediators may help elucidate the complexities of sex-dimorphic immune homeostasis in both physiological and pathological circumstances (Figure 1). Such insights are essential for establishing a foundation for precision medicine strategies tailored to sex-based considerations in clinical practice.&lt;/p&gt;&lt;p&gt;Epithelial cells constitute the primary protective barrier at key host-environment interfaces, including the respiratory and gastrointestinal tracts, skin, and glands. Beyond serving as a physical barrier, they actively orchestrate local immune responses against pathogens and harmful substances, and directly coordinate tissue repair and regeneration through cellular proliferation and extracellular matrix remodelling.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; During lung development, sex hormones are key regulators of alveolar epithelial maturation, significantly influencing the production of pulmonary surfactant, which is critical for gas exchange and structural integrity. In adult mice, ovariectomy-induced oestrogen deficiency results in a marked reduction in alveolar number and surface area, a detrimental effect reversible with exogenous oestrogen supplementation, underscoring the hormone's role in maintaining lung parenchymal structure.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; Oestrogen also upregulates the expression and surface abundance of epithelial sodium channel following lipopolysaccharide challenge via activation of the phosphatidylinositol 3-kinase/protein kinase B/serum glucocorticoid regulated kinase 1 pathway, thereby mitigating pulmonary inflammation and lung oedema.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; In contrast, androgens generally suppress alveolar epithelial function, with effects that exhibit clear sexual dimorphism. For instance, dihydrotestosterone was found to inhibit sodium transport exclusively through non-classical, receptor-independent pathways in foetal distal lung epithelial cells from male rats, an effect not reversed by the androgen receptor antagonist flutamide (Table 1).&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;Airway epithelial cells release interleukin (IL)-33 upon allergen exposure, initiating type 2 immunity, activating group 2 innate lymphoid cells (ILC2s), and inducing IL-13 secretion to drive air","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in structural cell-mediated immune regulation: Implications for precision respiratory medicine","authors":"Quocdai Vu,&nbsp;Wei Gao,&nbsp;Wujian Xu,&nbsp;Ximing Liao,&nbsp;Qiang Li","doi":"10.1002/ctd2.70142","DOIUrl":"10.1002/ctd2.70142","url":null,"abstract":"&lt;p&gt;For a long time, sex dimorphism has been recognised as an important factor modulating immune function in health and disease across the lifespan, contributing to disparities in epidemiology, pathophysiology, clinical manifestations, progression and therapeutic outcomes across multiple diseases. Respiratory diseases such as pulmonary arterial hypertension (PAH), pneumonia, and asthma exhibit notable sex differences in incidence and prognosis, yet the underlying mechanisms remain incompletely understood. In the respiratory system, investigating how structural cells respond to sex hormone signals and elucidating their sex dimorphism in gene expression and secretion of immune mediators may help elucidate the complexities of sex-dimorphic immune homeostasis in both physiological and pathological circumstances (Figure 1). Such insights are essential for establishing a foundation for precision medicine strategies tailored to sex-based considerations in clinical practice.&lt;/p&gt;&lt;p&gt;Epithelial cells constitute the primary protective barrier at key host-environment interfaces, including the respiratory and gastrointestinal tracts, skin, and glands. Beyond serving as a physical barrier, they actively orchestrate local immune responses against pathogens and harmful substances, and directly coordinate tissue repair and regeneration through cellular proliferation and extracellular matrix remodelling.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; During lung development, sex hormones are key regulators of alveolar epithelial maturation, significantly influencing the production of pulmonary surfactant, which is critical for gas exchange and structural integrity. In adult mice, ovariectomy-induced oestrogen deficiency results in a marked reduction in alveolar number and surface area, a detrimental effect reversible with exogenous oestrogen supplementation, underscoring the hormone's role in maintaining lung parenchymal structure.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; Oestrogen also upregulates the expression and surface abundance of epithelial sodium channel following lipopolysaccharide challenge via activation of the phosphatidylinositol 3-kinase/protein kinase B/serum glucocorticoid regulated kinase 1 pathway, thereby mitigating pulmonary inflammation and lung oedema.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; In contrast, androgens generally suppress alveolar epithelial function, with effects that exhibit clear sexual dimorphism. For instance, dihydrotestosterone was found to inhibit sodium transport exclusively through non-classical, receptor-independent pathways in foetal distal lung epithelial cells from male rats, an effect not reversed by the androgen receptor antagonist flutamide (Table 1).&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;Airway epithelial cells release interleukin (IL)-33 upon allergen exposure, initiating type 2 immunity, activating group 2 innate lymphoid cells (ILC2s), and inducing IL-13 secretion to drive air","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ChatCM-RAG: A deep learning-based natural language processing pipeline for analysing ChatGPT applications in medicine using BERTopic and transformer-based retrieval-augmented generation","authors":"Cheng Zhang,&nbsp;Ning Wang,&nbsp;Guoming Chen,&nbsp;Yibin Feng","doi":"10.1002/ctd2.70136","DOIUrl":"https://doi.org/10.1002/ctd2.70136","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The rapid adoption of ChatGPT in healthcare has generated extensive literature. However, systematic analysis of this emerging field using artificial intelligence (AI)-powered tools remains challenging due to the volume and diversity of publications and the risk of AI-generated hallucinations that compromise factual accuracy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We developed ChatCM-RAG, a deep learning pipeline integrating BERTopic with transformer-based retrieval-augmented generation to analyse ChatGPT applications in the Medicine literature.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We processed 904 peer-reviewed articles (2022–2025) using a multi-stage pipeline: BERTopic for topic modelling with UMAP dimensionality reduction and HDBSCAN clustering, Facebook AI Similarity Search for semantic retrieval, and transformer models (T5/GPT) for answer generation. The system was evaluated using representative medical queries across retrieval accuracy, generation quality, and system efficiency metrics.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ChatCM-RAG identified four distinct topic clusters: general medical AI applications (46.2%), performance evaluation (13.9%), clinical applications and patient care (12.6%), and chatbot implementations (6.0%), with 21.2% unclustered documents. To reduce hallucination and ensure citation authenticity, the generation module is constrained to a curated corpus of 904 PubMed-indexed documents and only permits PMID citations that exist in the retrieval set. In our pilot evaluation on eight representative medical queries, we observed 0 fabricated PMIDs and 0 non-existent citations in generated answers. The system achieved an average response time of 1.73 s, an answer quality score of 0.81, and demonstrated topic-aware retrieval with a 0.90 relevance score, where 73% of retrieved documents originated from topically appropriate clusters. The ChatCM-RAG model has been open-sourced at https://huggingface.co/fc28/ChatCM-RAG. Additional reproducible analyses were performed using the released dataset (&lt;i&gt;n&lt;/i&gt; = 904) and code to quantify topic interpretability and retrieval robustness without requiring external LLM calls. Using an 80/20 held-out title-query evaluation, topic-filtered lexical retrieval (TF‑IDF within predicted cluster) improved Cluster-agreement@5 from 0.599 ± 0.309 (global TF‑IDF) to 0.862 ± 0.345. Top TF-IDF terms were identified for each cluster, and retrieval performance was assessed using a held-out evaluation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ChatCM-RAG: A deep learning-based natural language processing pipeline for analysing ChatGPT applications in medicine using BERTopic and transformer-based retrieval-augmented generation","authors":"Cheng Zhang,&nbsp;Ning Wang,&nbsp;Guoming Chen,&nbsp;Yibin Feng","doi":"10.1002/ctd2.70136","DOIUrl":"10.1002/ctd2.70136","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The rapid adoption of ChatGPT in healthcare has generated extensive literature. However, systematic analysis of this emerging field using artificial intelligence (AI)-powered tools remains challenging due to the volume and diversity of publications and the risk of AI-generated hallucinations that compromise factual accuracy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We developed ChatCM-RAG, a deep learning pipeline integrating BERTopic with transformer-based retrieval-augmented generation to analyse ChatGPT applications in the Medicine literature.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We processed 904 peer-reviewed articles (2022–2025) using a multi-stage pipeline: BERTopic for topic modelling with UMAP dimensionality reduction and HDBSCAN clustering, Facebook AI Similarity Search for semantic retrieval, and transformer models (T5/GPT) for answer generation. The system was evaluated using representative medical queries across retrieval accuracy, generation quality, and system efficiency metrics.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ChatCM-RAG identified four distinct topic clusters: general medical AI applications (46.2%), performance evaluation (13.9%), clinical applications and patient care (12.6%), and chatbot implementations (6.0%), with 21.2% unclustered documents. To reduce hallucination and ensure citation authenticity, the generation module is constrained to a curated corpus of 904 PubMed-indexed documents and only permits PMID citations that exist in the retrieval set. In our pilot evaluation on eight representative medical queries, we observed 0 fabricated PMIDs and 0 non-existent citations in generated answers. The system achieved an average response time of 1.73 s, an answer quality score of 0.81, and demonstrated topic-aware retrieval with a 0.90 relevance score, where 73% of retrieved documents originated from topically appropriate clusters. The ChatCM-RAG model has been open-sourced at https://huggingface.co/fc28/ChatCM-RAG. Additional reproducible analyses were performed using the released dataset (&lt;i&gt;n&lt;/i&gt; = 904) and code to quantify topic interpretability and retrieval robustness without requiring external LLM calls. Using an 80/20 held-out title-query evaluation, topic-filtered lexical retrieval (TF‑IDF within predicted cluster) improved Cluster-agreement@5 from 0.599 ± 0.309 (global TF‑IDF) to 0.862 ± 0.345. Top TF-IDF terms were identified for each cluster, and retrieval performance was assessed using a held-out evaluation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}