❌

Normal view

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‑off between artificial‑intelligence models and conventional response criteria (RECIST 1.1, PERCIST). We acknowledge two textual errors in the original discussion and confirm they do not affect primary pooled analyses. We further elaborate on eligibility constraints, heterogeneity across prediction time points, definitions of pathological complete response, and reporting standards such as DECIDE‑AI. Our core conclusion remains unchanged: radiomics‑based artificial intelligence shows promising predictive performance with a potential sensitivity advantage over RECIST 1.1, though definitive evidence requires prospective same‑patient, same‑time‑point validation studies.

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 difficult to support custom-designed engines. To address these challenges, we propose AsyncFlow, an asynchronous streaming RL framework tailored for efficient post-training. Specifically, we introduce a distributed data storage and transfer module that provides panoramic data management and fine-grained scheduling capabilities in a fully streamed manner. This architecture inherently enables automated pipeline overlapping among RL tasks and dynamic load-balancing. Moreover, we propose an asynchronous producer-consumer workflow, which is engineered to minimize computational idleness by strategically deferring the parameter update process within staleness thresholds. Finally, the core capabilities of AsyncFlow are architecturally decoupled from underlying training and inference engines and encapsulated by service-oriented user interfaces, offering a modular and customizable user experience. Extensive experiments demonstrate an average throughput of 1.59x compared to the state-of-the-art baseline. The architecture presented in this work provides actionable insights for designing next-generation RL training systems.

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

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

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.

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: a load-adaptive cascading router, a joint path-filler controller, and volatility-aware cache admission. On 75k CarQA requests, the cascade halves pure-LLM PTFR at P95 (0.29 vs 0.53s at c16). The adaptive controller reaches 0.41s P95, outperforming RAG by 2.4 times at high load with equal quality. The filler controller cuts calls by 94% with zero conflict. Volatility-aware admission reduces stale answers from 86% to 0%. A gating rule ensures the controller never worse than the baseline, with exposure bounded by one hold period. This is the first quantification of filler-answer conflict risk in deployed services.

Visualizing the Invisible: Generative Visual Grounding Empowers Universal EEG Understanding in MLLMs

arXiv:2605.18172v2 Announce Type: replace Abstract: Leveraging the universal representations of pre-trained LLMs and MLLMs offers a promising path toward brain foundation models. However, visually-evoked EEG datasets remain scarce, leading existing methods to align neural signals mainly with abstract text, a lossy translation that may discard fine-grained perceptual information encoded in brain activity. We propose Generative Visual Grounding (GVG), a framework that visualizes the invisible by using an EEG-to-image generative model as a visual translator. Instead of forcing EEG into text alone, GVG hallucinates instance-specific proxy images for non-visual EEG, providing structured visual contexts that allow MLLMs to exploit their visual priors for clinical-state interpretation. We validate this idea on two MLLM backbones, GVG-X-Omni and GVG-Janus. Image-only alignment is already competitive: the lightweight GVG-X-Omni matches 1.7B-parameter text-aligned baselines while tuning only 170M parameters on a frozen 7B backbone. We further extend GVG-Janus with trimodal Image+Text alignment, where text supplies categorical semantic anchors and visual proxies enrich neural representations with perceptual details. Experiments show consistent gains in EEG understanding and visual generation, suggesting visual proxy grounding as an effective complement to textual alignment.

SHP1 expression in tumor-associated dendritic cells drives immunoevasion via impairing CD8<sup>+</sup> memory T cell responses

Oncogenesis, Published online: 15 May 2026; doi:10.1038/s41389-026-00627-z

SHP1 expression in tumor-associated dendritic cells drives immunoevasion via impairing CD8+ memory T cell responses

Baseline cellular state dictates the molecular impact of KRAS mutant variants in pancreatic cancer cells

bioRxiv [Preprint]. 2026 Mar 12:2026.03.10.710185. doi: 10.64898/2026.03.10.710185.

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 as recurrently altered across alleles, while phosphoproteomic data confirmed robust ERK1/2 activity and suppression of DYRK kinase substrates by mutant KRAS expression. Importantly, no robust allele-specific molecular programs were identified. 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 and therapeutic vulnerabilities.

PMID:41959224 | PMC:PMC13060958 | DOI:10.64898/2026.03.10.710185

Unifying Group-Relative and Self-Distillation Policy Optimization via Sample Routing

arXiv:2604.02288v1 Announce Type: cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has become a standard paradigm for post-training large language models. While Group Relative Policy Optimization (GRPO) is widely adopted, its coarse credit assignment uniformly penalizes failed rollouts, lacking the token-level focus needed to efficiently address specific deviations. Self-Distillation Policy Optimization (SDPO) addresses this by providing denser, more targeted logit-level supervision that facilitates rapid early improvement, yet it frequently collapses during prolonged training. We trace this late-stage instability to two intrinsic flaws: self-distillation on already-correct samples introduces optimization ambiguity, and the self-teacher's signal reliability progressively degrades. To resolve these issues, we propose Sample-Routed Policy Optimization (SRPO), a unified on-policy framework that routes correct samples to GRPO's reward-aligned reinforcement and failed samples to SDPO's targeted logit-level correction. SRPO further incorporates an entropy-aware dynamic weighting mechanism to suppress high-entropy, unreliable distillation targets while emphasizing confident ones. Evaluated across five benchmarks and two model scales, SRPO achieves both the rapid early improvement of SDPO and the long-horizon stability of GRPO. It consistently surpasses the peak performance of both baselines, raising the five-benchmark average on Qwen3-8B by 3.4% over GRPO and 6.3% over SDPO, while simultaneously yielding moderate response lengths and lowering per-step compute cost by up to 17.2%.

Correction: Integrative multi-omics and machine learning reveals the spatial niche distribution and role of CYP27A1+TAMs in immunotherapy response in non-small cell lung cancer

Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model

arXiv:2603.29176v1 Announce Type: new Abstract: Parkinson's disease (PD) affects over ten million people worldwide. Although temporal interference (TI) and deep brain stimulation (DBS) are promising therapies, inter-individual variability limits empirical treatment selection, increasing non-negligible surgical risk and cost. Previous explorations either resort to limited statistical biomarkers that are insufficient to characterize variability, or employ AI-driven methods which is prone to overfitting and opacity. We bridge this gap with a pretraining-finetuning framework to predict outcomes directly from resting-state fMRI. Critically, a generative virtual brain foundation model, pretrained on a collective dataset (2707 subjects, 5621 sessions) to capture universal disorder patterns, was finetuned on PD cohorts receiving TI (n=51) or DBS (n=55) to yield individualized virtual brains with high fidelity to empirical functional connectivity (r=0.935). By constructing counterfactual estimations between pathological and healthy neural states within these personalized models, we predicted clinical responses (TI: AUPR=0.853; DBS: AUPR=0.915), substantially outperforming baselines. External and prospective validations (n=14, n=11) highlight the feasibility of clinical translation. Moreover, our framework provides state-dependent regional patterns linked to response, offering hypothesis-generating mechanistic insights.

Route-Induced Density and Stability (RIDE): Controlled Intervention and Mechanism Analysis of Routing-Style Meta Prompts on LLM Internal States

arXiv:2603.29206v1 Announce Type: new Abstract: Routing is widely used to scale large language models, from Mixture-of-Experts gating to multi-model/tool selection. A common belief is that routing to a task ``expert'' activates sparser internal computation and thus yields more certain and stable outputs (the Sparsity--Certainty Hypothesis). We test this belief by injecting routing-style meta prompts as a textual proxy for routing signals in front of frozen instruction-tuned LLMs. We quantify (C1) internal density via activation sparsity, (C2) domain-keyword attention, and (C3) output stability via predictive entropy and semantic variation. On a RouterEval subset with three instruction-tuned models (Qwen3-8B, Llama-3.1-8B-Instruct, and Mistral-7B-Instruct-v0.2), meta prompts consistently densify early/middle-layer representations rather than increasing sparsity; natural-language expert instructions are often stronger than structured tags. Attention responses are heterogeneous: Qwen/Llama reduce keyword attention, while Mistral reinforces it. Finally, the densification--stability link is weak and appears only in Qwen, with near-zero correlations in Llama and Mistral. We present RIDE as a diagnostic probe for calibrating routing design and uncertainty estimation.

SortedRL: Accelerating RL Training for LLMs through Online Length-Aware Scheduling

arXiv:2603.23414v1 Announce Type: cross Abstract: Scaling reinforcement learning (RL) has shown strong promise for enhancing the reasoning abilities of large language models (LLMs), particularly in tasks requiring long chain-of-thought generation. However, RL training efficiency is often bottlenecked by the rollout phase, which can account for up to 70% of total training time when generating long trajectories (e.g., 16k tokens), due to slow autoregressive generation and synchronization overhead between rollout and policy updates. We propose SortedRL, an online length-aware scheduling strategy designed to address this bottleneck by improving rollout efficiency and maintaining training stability. SortedRL reorders rollout samples based on output lengths, prioritizing short samples forming groups for early updates. This enables large rollout batches, flexible update batches, and near on-policy micro-curriculum construction simultaneously. To further accelerate the pipeline, SortedRL incorporates a mechanism to control the degree of off-policy training through a cache-based mechanism, and is supported by a dedicated RL infrastructure that manages rollout and update via a stateful controller and rollout buffer. Experiments using LLaMA-3.1-8B and Qwen-2.5-32B on diverse tasks, including logical puzzles, and math challenges like AIME 24, Math 500, and Minerval, show that SortedRL reduces RL training bubble ratios by over 50%, while attaining 3.9% to 18.4% superior performance over baseline given same amount of data.

Cerebra: A Multidisciplinary AI Board for Multimodal Dementia Characterization and Risk Assessment

arXiv:2603.21597v2 Announce Type: replace Abstract: Modern clinical practice increasingly depends on reasoning over heterogeneous, evolving, and incomplete patient data. Although recent advances in multimodal foundation models have improved performance on various clinical tasks, most existing models remain static, opaque, and poorly aligned with real-world clinical workflows. We present Cerebra, an interactive multi-agent AI team that coordinates specialized agents for EHR, clinical notes, and medical imaging analysis. These outputs are synthesized into a clinician-facing dashboard that combines visual analytics with a conversational interface, enabling clinicians to interrogate predictions and contextualize risk at the point of care. Cerebra supports privacy-preserving deployment by operating on structured representations and remains robust when modalities are incomplete. We evaluated Cerebra using a massive multi-institutional dataset spanning 3 million patients from four independent healthcare systems. Cerebra consistently outperformed both state-of-the-art single-modality models and large multimodal language model baselines. In dementia risk prediction, it achieved AUROCs up to 0.80, compared with 0.74 for the strongest single-modality model and 0.68 for language model baselines. For dementia diagnosis, it achieved an AUROC of 0.86, and for survival prediction, a C-index of 0.81. In a reader study with experienced physicians, Cerebra significantly improved expert performance, increasing accuracy by 17.5 percentage points in prospective dementia risk estimation. These results demonstrate Cerebra's potential for interpretable, robust decision support in clinical care.

Do Vision-Language Models Measure Up? Benchmarking Visual Measurement Reading with MeasureBench

arXiv:2510.26865v2 Announce Type: replace-cross Abstract: Reading measurement instruments is effortless for humans and requires relatively little domain expertise, yet it remains surprisingly challenging for current vision-language models (VLMs) as we find in preliminary evaluation. In this work, we introduce MeasureBench, a benchmark on visual measurement reading covering both real-world and synthesized images of various types of measurements, along with an extensible pipeline for data synthesis. Our pipeline procedurally generates a specified type of gauge with controllable visual appearance, enabling scalable variation in key details such as pointers, scales, fonts, lighting, and clutter. Evaluation on popular proprietary and open-weight VLMs shows that even the strongest frontier VLMs struggle with measurement reading in general. We have also conducted preliminary experiments with reinforcement finetuning (RFT) over synthetic data, and find a significant improvement on both in-domain synthetic subset and real-world images. Our analysis highlights a fundamental limitation of current VLMs in fine-grained spatial grounding. We hope this resource and our code releases can help future advances on visually grounded numeracy and precise spatial perception of VLMs, bridging the gap between recognizing numbers and measuring the world.

Integrated Machine Learning and Multi-Omics Identifies a Novel Molecular Signature for Improving the Prognosis of Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2026 Mar 11;13:574690. doi: 10.2147/JHC.S574690. eCollection 2026.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) exhibits significant molecular heterogeneity and complex immune microenvironment, which to some extent limits the accuracy of prognosis assessment and the formulation of individualized treatment strategies. This study aims to identify immune-derived molecular signatures based on multi-omics data and machine learning methods for the prognosis prediction and risk stratification of HCC.

METHODS: Based on weighted gene co-expression network analysis(WGCNA) and differential gene analysis,immune-derived molecular signature (IDMS) were screened in both single-cell and bulk transcriptomes. Prognostic model was constructed by multi-machine learning approachs. Subsequently, we investigated the differences in mutations, biological functions, and immune cell infiltration within the tumor microenvironment between the high- and low-risk groups.In addition, we comprehensively analyzed the drug sensitivity of IDMS and predicted potential drugs.

RESULTS: We identified seven hub genes at the single-cell and bulk transcriptome levels. Based on multiple machine learning, we constructed a prognostic model that demonstrated excellent performance in predicting overall survival for patients with HCC. IDMS -integrated normograms provide a promising and quantitative tool for clinical risk management.Notably, a significant difference in microsatellite instability (MSI) was observed between the high- and low-risk groups. This indicates that patients in the high-risk group might have a better response to immunotherapy. Additionally, we predicted potential drugs targeting to these risk subgroups.

CONCLUSION: Our research developed an IDMS that could serve as an effective tool for patient stratification management and prognosis prediction. This signature could provide a reference for immunotherapy for patients with HCC and improve their prognosis.

PMID:41847219 | PMC:PMC12991065 | DOI:10.2147/JHC.S574690

MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism

Cell Death Discovery, Published online: 11 March 2026; doi:10.1038/s41420-026-02990-7

MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism
❌