Normal view
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Journal of Medical Internet Research
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Authors’ Reply: Clarifying the Comparative Interpretation and Clinical Implications of Radiomics-Based AI for Pathological Response Prediction
This author reply responds to a Letter to the Editor commenting on our systematic review and meta‑analysis evaluating radiomics‑based artificial intelligence for predicting pathological response following neoadjuvant immunochemotherapy in non‑small‑cell lung cancer. We clarify several methodological points raised in the comment, including patient versus assessment counts in a cited study, cross‑study versus within‑patient comparisons of diagnostic metrics, and the sensitivity‑specificity trade‑o
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Omics in Hepatocellular
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Spatial, single-nucleus and pathological profiling of the invasive front in early hepatocellular carcinoma for characterizing specific leading-edge cell niche and improving recurrence modeling
Int J Biol Sci. 2026 Sep 10;22(14):8090-8118. doi: 10.7150/ijbs.137262. eCollection 2026.ABSTRACTThe tumor leading edge (TLE) is a critical region where tumor cells interact with the microenvironment to drive invasion and metastasis; however, its cellular architecture in early hepatocellular carcinoma (HCC) remains poorly understood. Here, we integrated single-nucleus RNA-seq (snRNA-seq), spatial transcriptomics, and computational pathology to investigate TLE in early HCC. We annotated 35 cell s
Spatial, single-nucleus and pathological profiling of the invasive front in early hepatocellular carcinoma for characterizing specific leading-edge cell niche and improving recurrence modeling
Int J Biol Sci. 2026 Sep 10;22(14):8090-8118. doi: 10.7150/ijbs.137262. eCollection 2026.
ABSTRACT
The tumor leading edge (TLE) is a critical region where tumor cells interact with the microenvironment to drive invasion and metastasis; however, its cellular architecture in early hepatocellular carcinoma (HCC) remains poorly understood. Here, we integrated single-nucleus RNA-seq (snRNA-seq), spatial transcriptomics, and computational pathology to investigate TLE in early HCC. We annotated 35 cell subpopulations and identified STMN1-high tumor cells as a key malignant subset enriched at the invasive front, interacting with Treg, plasma B, LAMP3⁺ dendritic cells and SPP1⁺ macrophages. Spatial analysis revealed three co-localized cell pairs-(SPP1⁺ macrophages co-localized with Tip-like and inflammatory endothelial cells), (LAMP3⁺ DCs co-localized with naive T cells), and (plasma B cells co-localized with cancer-associated fibroblasts)-forming a leading-edge tumor microenvironment (L-TME) niche associated with early relapse. We developed an L-TME-related machine-learning benchmark framework incorporating 71 imaging features (65 deep-learning + 6 pathological) based on the snRNA-seq, spatial transcriptomics and pathomics. The pathology model achieved robust performance (mean C-index=0.77) and successfully predicted the recurrence of early HCC (log-rank p < 0.05) in TCGA (n=147) and an independent in-house cohort (n=123). This study delineates the TLE cellular ecosystem of early HCC, defines a spatially coordinated immunosuppressive L-TME niche, and provides a clinically applicable predictive tool for postoperative recurrence. Integrating multi-omics with computational pathology deepens our understanding of early HCC metastasis and offers insights into improved prognostication and therapeutic strategies.
PMID:42807944 | PMC:PMC13618224 | DOI:10.7150/ijbs.137262
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Omics in Hepatocellular
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Transketolase-like 1 potentiates PD-1 blockade in hepatocellular carcinoma by glycolysis to prime dendritic cell lactylation
Signal Transduct Target Ther. 2026 Sep 28;11(1):418. doi: 10.1038/s41392-026-02875-2.ABSTRACTHepatocellular carcinoma (HCC) exhibits a suboptimal response to immune checkpoint blockade (ICB) therapy; to overcome this resistance, we aimed to delineate key immune resistance factors via multi-omics analysis, develop strategies to block their immunosuppressive axes, and engineer a targeted nanosystem to enhance immunotherapy efficacy against PD-1 resistance in HCC. Using transcriptomic and proteomic
Transketolase-like 1 potentiates PD-1 blockade in hepatocellular carcinoma by glycolysis to prime dendritic cell lactylation
Signal Transduct Target Ther. 2026 Sep 28;11(1):418. doi: 10.1038/s41392-026-02875-2.
ABSTRACT
Hepatocellular carcinoma (HCC) exhibits a suboptimal response to immune checkpoint blockade (ICB) therapy; to overcome this resistance, we aimed to delineate key immune resistance factors via multi-omics analysis, develop strategies to block their immunosuppressive axes, and engineer a targeted nanosystem to enhance immunotherapy efficacy against PD-1 resistance in HCC. Using transcriptomic and proteomic data from anti-PD-1-treated HCC patients, along with functional validation in murine models and mechanistic molecular and cell biology studies, we identified transketolase-like 1 (TKTL1) as a dual-nature biomarker where overexpression predicted poor baseline prognosis yet enhanced response to ICB. Mechanistically, TKTL1 diverts glucose flux into glycolysis rather than pentose phosphate pathway (PPP), recruiting USP9X to deubiquitinate and stabilize HIF-1α, which upregulates HK2 to amplify glycolytic output and lactate accumulation. This metabolic rewiring orchestrates dual immunosuppressive circuits through HIF-1α-driven CCL4 secretion recruiting PD-L1high dendritic cells (DCs), coupled with lactate-induced TRIM28K408 lactylation that stabilizes PD-L1 by blocking ubiquitin-mediated degradation. We engineered a hepatoma-membrane-coated MnO₂ nanosystem (CQLH) co-delivering a TKTL1 inhibitor and lactate oxidase, which disrupted the TKTL1-HIF-1α-HK2 axis, depleted lactate, and reprogrammed the tumor microenvironment, thereby enhanced anti-PD-1 therapy to suppress tumor growth, especially in TKTL1high tumors. These findings define a critical "TKTL1-glycolysis-lactate-DC" axis driving anti-PD-1 sensitivity in HCC, position TKTL1 as both a potential biomarker for ICB response and a tractable therapeutic target, and demonstrate that the targeted CQLH nanosystem overcomes resistance and enhances anti-PD-1 efficacy, offering a precision immunotherapeutic strategy for TKTL1high HCC.
PMID:42802226 | PMC:PMC13616917 | DOI:10.1038/s41392-026-02875-2
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cs.AI, q-bio.NC updates on arXiv.org
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Occamy-1.0: Open Pareto-frontier 35B Intelligence for Co-work
arXiv:2609.11977v1 Announce Type: new Abstract: Co-work agents execute complex workflows that combine information gathering, tool use, coding, and file manipulation across many model invocations. Because cost and latency accumulate over the full episode, their practical value depends not only on peak capability but also on how efficiently that capability is delivered. Yet many steps in everyday work emphasize state tracking, coordination, recovery, and follow-through rather than frontier-scale
Occamy-1.0: Open Pareto-frontier 35B Intelligence for Co-work
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cs.AI, q-bio.NC updates on arXiv.org
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AsyncFlow: An Asynchronous Streaming RL Framework for Efficient LLM Post-Training
arXiv:2507.01663v2 Announce Type: replace-cross Abstract: Reinforcement learning (RL) has become a pivotal technology in the post-training phase of large language models (LLMs). Traditional task-collocated RL frameworks suffer from significant scalability bottlenecks, while task-separated RL frameworks face challenges in managing complex dataflows and resolving resource idling. Furthermore, most existing frameworks are tightly coupled with LLM training or inference engines, making them difficul
AsyncFlow: An Asynchronous Streaming RL Framework for Efficient LLM Post-Training
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cs.AI, q-bio.NC updates on arXiv.org
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Dynamic Expert Quantization for Scalable Mixture-of-Experts Inference
arXiv:2511.15015v4 Announce Type: replace-cross Abstract: Mixture-of-Experts (MoE) has become a practical architecture for scaling LLM capacity while keeping per-token compute modest, but deploying MoE models on a single, memory-limited GPU remains difficult because expert weights dominate the HBM footprint. Existing expert offloading and prefetching systems reduce the resident set, yet they often pay expert-loading costs on the critical path when activation becomes dense. Post-training quantiz
Dynamic Expert Quantization for Scalable Mixture-of-Experts Inference
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Nature Biotechnology - Issue - nature.com science feeds
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An engineered nanopore identifies saccharides, amino acids, peptides and ribonucleotides
Nature Biotechnology, Published online: 14 September 2026; doi:10.1038/s41587-026-03308-9Modified nanopore simultaneously identifies diverse biomolecules and their modifications.
An engineered nanopore identifies saccharides, amino acids, peptides and ribonucleotides
Nature Biotechnology, Published online: 14 September 2026; doi:10.1038/s41587-026-03308-9
Modified nanopore simultaneously identifies diverse biomolecules and their modifications.-
Omics In Lung
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Advanced and underlying therapeutic strategies in transformed small cell lung cancer
Front Med (Lausanne). 2026 Aug 27;13:1865050. doi: 10.3389/fmed.2026.1865050. eCollection 2026.ABSTRACTTransformed small-cell lung cancer (T-SCLC) is a clinically important form of histologic transformation and a mechanism of acquired resistance in non-small-cell lung cancer (NSCLC). It is associated with poor prognosis, with a median overall survival of only about 9-13 months. This review summarizes recent advances in the mechanisms, diagnosis, monitoring, and treatment of T-SCLC. Repeat biopsy
Advanced and underlying therapeutic strategies in transformed small cell lung cancer
Front Med (Lausanne). 2026 Aug 27;13:1865050. doi: 10.3389/fmed.2026.1865050. eCollection 2026.
ABSTRACT
Transformed small-cell lung cancer (T-SCLC) is a clinically important form of histologic transformation and a mechanism of acquired resistance in non-small-cell lung cancer (NSCLC). It is associated with poor prognosis, with a median overall survival of only about 9-13 months. This review summarizes recent advances in the mechanisms, diagnosis, monitoring, and treatment of T-SCLC. Repeat biopsy remains the gold standard for confirming histologic transformation, whereas molecular profiling and liquid biopsy may facilitate early detection and longitudinal disease monitoring. Platinum-etoposide remains the most commonly used clinical standard after transformation, but its benefit is typically transient and durable disease control remains uncommon. Continuation of EGFR tyrosine kinase inhibitors combined with chemotherapy may prolong progression-free survival in selected patients but has not consistently improved overall survival. Anti-angiogenic therapy, particularly anlotinib, and chemo-immunotherapy have shown encouraging activity in selected patients, while emerging strategies targeting DLL3, MYC, SOX2, and epigenetic regulators may broaden the therapeutic landscape. Prospective studies integrating repeat tissue sampling, comprehensive genomic profiling, biomarker-guided patient stratification, pharmacogenomics, functional drug-sensitivity testing where feasible, and integrated multi-omics approaches are needed to advance molecularly guided and individualized treatment for T-SCLC.
PMID:42724635 | PMC:PMC13560167 | DOI:10.3389/fmed.2026.1865050
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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Advanced and underlying therapeutic strategies in transformed small cell lung cancer
Front Med (Lausanne). 2026 Aug 27;13:1865050. doi: 10.3389/fmed.2026.1865050. eCollection 2026.ABSTRACTTransformed small-cell lung cancer (T-SCLC) is a clinically important form of histologic transformation and a mechanism of acquired resistance in non-small-cell lung cancer (NSCLC). It is associated with poor prognosis, with a median overall survival of only about 9-13 months. This review summarizes recent advances in the mechanisms, diagnosis, monitoring, and treatment of T-SCLC. Repeat biopsy
Advanced and underlying therapeutic strategies in transformed small cell lung cancer
Front Med (Lausanne). 2026 Aug 27;13:1865050. doi: 10.3389/fmed.2026.1865050. eCollection 2026.
ABSTRACT
Transformed small-cell lung cancer (T-SCLC) is a clinically important form of histologic transformation and a mechanism of acquired resistance in non-small-cell lung cancer (NSCLC). It is associated with poor prognosis, with a median overall survival of only about 9-13 months. This review summarizes recent advances in the mechanisms, diagnosis, monitoring, and treatment of T-SCLC. Repeat biopsy remains the gold standard for confirming histologic transformation, whereas molecular profiling and liquid biopsy may facilitate early detection and longitudinal disease monitoring. Platinum-etoposide remains the most commonly used clinical standard after transformation, but its benefit is typically transient and durable disease control remains uncommon. Continuation of EGFR tyrosine kinase inhibitors combined with chemotherapy may prolong progression-free survival in selected patients but has not consistently improved overall survival. Anti-angiogenic therapy, particularly anlotinib, and chemo-immunotherapy have shown encouraging activity in selected patients, while emerging strategies targeting DLL3, MYC, SOX2, and epigenetic regulators may broaden the therapeutic landscape. Prospective studies integrating repeat tissue sampling, comprehensive genomic profiling, biomarker-guided patient stratification, pharmacogenomics, functional drug-sensitivity testing where feasible, and integrated multi-omics approaches are needed to advance molecularly guided and individualized treatment for T-SCLC.
PMID:42724635 | PMC:PMC13560167 | DOI:10.3389/fmed.2026.1865050
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(Multiomics OR Omics) AND (Pancreatic)
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Baseline cellular state shapes the molecular impact of mutant KRAS alleles in reconstituted pancreatic cancer cells
Mol Omics. 2026 Sep 10:aaiag022. doi: 10.1093/molecular-omics/aaiag022. Online ahead of print.ABSTRACTKRAS is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC), where hotspot alterations in codons 12, 13, and 61 drive tumor initiation and progression. Although distinct biochemical properties have been described for individual KRAS mutants, whether they generate unique allele-specific signaling programs in PDAC cells remains unresolved. Here, we systematically interrogated the molec
Baseline cellular state shapes the molecular impact of mutant KRAS alleles in reconstituted pancreatic cancer cells
Mol Omics. 2026 Sep 10:aaiag022. doi: 10.1093/molecular-omics/aaiag022. Online ahead of print.
ABSTRACT
KRAS is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC), where hotspot alterations in codons 12, 13, and 61 drive tumor initiation and progression. Although distinct biochemical properties have been described for individual KRAS mutants, whether they generate unique allele-specific signaling programs in PDAC cells remains unresolved. Here, we systematically interrogated the molecular consequences of seven common KRAS mutant variants in reconstituted isogenic, KRAS-deficient PDAC cell lines by integrated transcriptomic, proteomic, and phosphoproteomic profiling. We found that baseline cellular state, rather than allele identity, was the predominant driver of molecular variation. Comparisons with established KRAS reference signatures revealed significant but moderate overlap at the mRNA level and less so at the proteome level. Pathway analyses highlighted interferon response and mitochondrial translation-related proteins as recurrently altered across mutant alleles, while phosphoproteomic data confirmed robust ERK1/2 activity and suppression of DYRK kinase substrates by mutant KRAS expression. Importantly, no robust mutant allele-specific molecular programs were identified in our KRAS-reconstituted cell lines. Together, our study establishes a comprehensive multi-omics resource for KRAS signaling in PDAC and demonstrates that cellular context exerts a stronger influence than allele identity in shaping molecular profiles, with implications for interpreting putative allele-specific signaling dependencies.
PMID:42720273 | DOI:10.1093/molecular-omics/aaiag022
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npj Digital Medicine
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Impact of LLM-supported patient education on patient perspectives and patient-reported outcomes: a mixed-methods systematic review
npj Digital Medicine, Published online: 10 September 2026; doi:10.1038/s41746-026-03228-7Impact of LLM-supported patient education on patient perspectives and patient-reported outcomes: a mixed-methods systematic review
Impact of LLM-supported patient education on patient perspectives and patient-reported outcomes: a mixed-methods systematic review
npj Digital Medicine, Published online: 10 September 2026; doi:10.1038/s41746-026-03228-7
Impact of LLM-supported patient education on patient perspectives and patient-reported outcomes: a mixed-methods systematic review-
Molecular Therapy
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Targeting the MNK1-MYH9 axis blocks YAP1 recruitment to prevent thrombosis and platelet activation-induced NETosis
MNK1 acts as a structural shield on MYH9, preventing YAP1-mediated platelet activation. Developing MD2 to lock this MNK1-MYH9 complex introduces a safe antithrombotic strategy, shifting the therapeutic paradigm from kinase inhibition to stabilizing protein-protein interactions against immunothrombosis.
Targeting the MNK1-MYH9 axis blocks YAP1 recruitment to prevent thrombosis and platelet activation-induced NETosis
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Nature Nanotechnology
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Switchable single-atom catalysts for highly selective C–C coupling in direct methane oxidation
Nature Nanotechnology, Published online: 07 September 2026; doi:10.1038/s41565-026-02271-5Single copper atoms on boron nanosheets dynamically and reversibly switch to clusters, enabling the direct conversion of methane to acetic acid with 97% selectivity and high activity without the requirement for carbon monoxide.
Switchable single-atom catalysts for highly selective C–C coupling in direct methane oxidation
Nature Nanotechnology, Published online: 07 September 2026; doi:10.1038/s41565-026-02271-5
Single copper atoms on boron nanosheets dynamically and reversibly switch to clusters, enabling the direct conversion of methane to acetic acid with 97% selectivity and high activity without the requirement for carbon monoxide.-
cs.AI, q-bio.NC updates on arXiv.org
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PACE: Perceived-Latency-Aware Cascading Service Routing and Filler Control for QoE-Efficient Retrieval-Augmented Dialogue Serving
arXiv:2609.10372v1 Announce Type: cross Abstract: We present the PACE, a framework for retrieval-augmented dialogue serving that formalizes Perceived Time-to-First-Response (PTFR) as a QoE objective and minimizes it under quality/cost constraints. Unlike prior work on cascaded routing, semantic caching, or adaptive retrieval, PACE jointly controls which answer source composes the response and what fills the waiting window. Deployed on a humanoid-robot sales service, it combines three mechanisms
PACE: Perceived-Latency-Aware Cascading Service Routing and Filler Control for QoE-Efficient Retrieval-Augmented Dialogue Serving
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cs.AI, q-bio.NC updates on arXiv.org
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EvolveScaler: Synthesizing Information-Evolution Contexts via Executable State Machines and Natural-Language Rendering
arXiv:2609.08435v2 Announce Type: replace Abstract: In persistent interactions, long contexts may encode an evolving process rather than a fixed record: later events can revise or revoke earlier information, changing what remains valid and what conclusions follow. We call this setting information evolution (IE). Solving IE requires identifying valid records, applying updates in order, and reconstructing the query-relevant state from the event history. Existing text-first synthesis pipelines mak
EvolveScaler: Synthesizing Information-Evolution Contexts via Executable State Machines and Natural-Language Rendering
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Oncogene - Issue - nature.com science feeds
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The RNA-binding protein La/SSB is associated with HNSCC progression and TFAP2C/FSCN1-linked transcriptional regulation
Oncogene, Published online: 03 September 2026; doi:10.1038/s41388-026-03959-7The RNA-binding protein La/SSB is associated with HNSCC progression and TFAP2C/FSCN1-linked transcriptional regulation
The RNA-binding protein La/SSB is associated with HNSCC progression and TFAP2C/FSCN1-linked transcriptional regulation
Oncogene, Published online: 03 September 2026; doi:10.1038/s41388-026-03959-7
The RNA-binding protein La/SSB is associated with HNSCC progression and TFAP2C/FSCN1-linked transcriptional regulation-
cs.AI, q-bio.NC updates on arXiv.org
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Accelerating Long-Tail Generation in Synchronous RLHF Training via Adaptive Tensor Parallelism
arXiv:2605.23945v1 Announce Type: new Abstract: Reinforcement Learning from Human Feedback (RLHF) has become a key post-training paradigm for improving model quality. However, the synchronous three-stage RLHF pipeline is often bottlenecked by the generation stage, where response-length skew causes the effective batch size to shrink rapidly during decoding, leaving GPUs underutilized while a few long responses remain unfinished. Mainstream frameworks employ a static tensor parallelism (TP) confi
Accelerating Long-Tail Generation in Synchronous RLHF Training via Adaptive Tensor Parallelism
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cs.AI, q-bio.NC updates on arXiv.org
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SAM: State-Adaptive Memory for Long-Horizon Reasoning Agent
arXiv:2605.24468v1 Announce Type: new Abstract: Long-horizon agentic reasoning requires large language models to act over long interaction histories containing thoughts, tool calls, observations, and partial conclusions. The challenge is not merely that these histories grow long, but that information needed for the current decision may be scattered across distant steps and only become relevant later. Existing approaches address this difficulty by truncating the interaction history, compressing
SAM: State-Adaptive Memory for Long-Horizon Reasoning Agent
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cs.AI, q-bio.NC updates on arXiv.org
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AgentFugue: Agent Scaling for Long-Horizon Tasks through Collective Reasoning
arXiv:2605.24486v1 Announce Type: new Abstract: Recent progress on long-horizon agentic tasks has been driven largely by scaling up individual agents through stronger models, better tools, and more effective scaffolding. In contrast, much less is understood about scaling out: whether multiple peer agents, all targeting the same task, can become an additional source of capability without relying on explicit role specialization or workflow orchestration. We study this question and propose AgentFu
AgentFugue: Agent Scaling for Long-Horizon Tasks through Collective Reasoning
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cs.AI, q-bio.NC updates on arXiv.org
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Hera: Learning Long-Horizon Coordination for Device-Cloud Collaborative LLM Agents
arXiv:2605.24598v1 Announce Type: new Abstract: Large language model (LLM) agents excel at solving complex long-horizon tasks through autonomous interaction with environments. However, their real-world deployment faces a fundamental device--cloud dilemma: on-device models are efficient but often brittle, while cloud models are stronger but costly in computation. State-of-the-art LLM device--cloud routers usually make coarse task-level decisions, which cannot adapt to the changing difficulty of