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cs.AI, q-bio.NC updates on arXiv.org
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GraphAHA: Graph-Based Adaptive Search with Heterogeneous Actions for Test-Time Code Generation
arXiv:2609.12757v1 Announce Type: cross Abstract: Test-time scaling improves code generation by spending additional inference budget (e.g., calls or tokens) on direct sampling, feedback-conditioned repair, and reasoning-guided implementation. Search-based methods can allocate this budget adaptively, but two challenges remain. First, tree-structured search treats each generation history as a separate state even when trajectories converge to the same program, duplicating evaluation and preventing
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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NBR1-Mediated Autophagic Degradation of YTHDF1 Curtails <em>FDX1</em> Translation to Drive Concurrent Multikinase Inhibitor Resistance and Cuproptosis Tolerance
Cancer Commun (Lond). 2026 Sep 11;46:0048. doi: 10.34133/cancomm.0048. eCollection 2026.ABSTRACTBackground: Cancer cells frequently acquire adaptive resistance to targeted therapies; however, strategies capable of concurrently overcoming treatment tolerance and reactivating cell death pathways are currently lacking. Here, we investigated the dual role of ferredoxin 1 (FDX1) in modulating both multikinase inhibitor (MKI) sensitivity and cuproptosis susceptibility in hepatocellular carcinoma (HCC)
NBR1-Mediated Autophagic Degradation of YTHDF1 Curtails <em>FDX1</em> Translation to Drive Concurrent Multikinase Inhibitor Resistance and Cuproptosis Tolerance
Cancer Commun (Lond). 2026 Sep 11;46:0048. doi: 10.34133/cancomm.0048. eCollection 2026.
ABSTRACT
Background: Cancer cells frequently acquire adaptive resistance to targeted therapies; however, strategies capable of concurrently overcoming treatment tolerance and reactivating cell death pathways are currently lacking. Here, we investigated the dual role of ferredoxin 1 (FDX1) in modulating both multikinase inhibitor (MKI) sensitivity and cuproptosis susceptibility in hepatocellular carcinoma (HCC), and sought to develop a therapeutic approach for reversing resistance. Methods: HCC models, both in vitro and in vivo, were employed to investigate the role of FDX1 in MKI resistance and cuproptosis evasion. Polysome profiling, SunTag translation reporters, CRISPR-Cas9 mutagenesis, and mass spectrometry were employed to delineate the underlying mechanisms. A codelivery nanoliposome system was engineered and tested in orthotopic HCC models. Results: Prolonged exposure to MKIs led to the down-regulation of FDX1 protein levels, resulting in MKI resistance and cuproptosis tolerance in HCC both in vitro and in vivo. Mechanistically, we found that MKIs inactivated protein kinase B (PKB, also known as AKT)-mechanistic target of rapamycin (mTOR) signaling, thereby suppressing the SET and MYND domain-containing protein 2 (SMYD2)-mediated methylation of YTH domain family protein 1 (YTHDF1) at lysine 515 (K515). Hypomethylated YTHDF1 was degraded via next to BRCA1 gene 1 protein (NBR1)-dependent autophagy, leading to the repression of N6-methyladenosine modification-dependent translation of FDX1 mRNA. FDX1 deficiency drove MKI resistance by reactivating AKT survival signaling while impairing cuproptosis through reduced divalent copper ions (Cu2+) to monovalent copper ions (Cu+) conversion and the loss of protein lipoylation. Additionally, restoring FDX1 expression through NBR1 knockdown or YTHDF1 overexpression overcame MKI resistance and resensitized HCC cells to cuproptosis. Finally, a nanoliposomal system, super cuproptosis detonator liposome, designed for the codelivery of NBR1 small interfering RNA, a copper ionophore, and sorafenib restored FDX1-dependent cuproptosis and exhibited marked anti-HCC efficacy, suppressing HCC growth in vivo. Conclusions: MKIs suppressed SMYD2-mediated YTHDF1 methylation at K515 via the inactivation of AKT-mTOR signaling. This led to the inhibition of FDX1 translation, resulting in AKT signaling reactivation and protein lipoylation impairment, effects that contributed to both MKI resistance and cuproptosis tolerance in HCC. Overcoming MKI resistance and resensitizing cells to cuproptosis by targeting NBR1-mediated YTHDF1 degradation using a nanoliposomal codelivery system represents a promising strategy for HCC treatment.
PMID:42729649 | PMC:PMC13562797 | DOI:10.34133/cancomm.0048
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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Gut dysbiosis, metabolic signals, and pulmonary immune reprogramming: decoding the gut microbiota -immune axis in stroke-associated pneumonia
Front Immunol. 2026 Aug 27;17:1812306. doi: 10.3389/fimmu.2026.1812306. eCollection 2026.ABSTRACTStroke-associated pneumonia (SAP) is the most common infectious complication following acute stroke. The limited efficacy of conventional antimicrobial therapy suggests that SAP may be fundamentally a syndrome driven by dysregulated cross-system interactions. This review proposes the "gut microbiota-immune axis" (GMIA) as a comprehensive framework for the development of SAP and systematically discuss
Gut dysbiosis, metabolic signals, and pulmonary immune reprogramming: decoding the gut microbiota -immune axis in stroke-associated pneumonia
Front Immunol. 2026 Aug 27;17:1812306. doi: 10.3389/fimmu.2026.1812306. eCollection 2026.
ABSTRACT
Stroke-associated pneumonia (SAP) is the most common infectious complication following acute stroke. The limited efficacy of conventional antimicrobial therapy suggests that SAP may be fundamentally a syndrome driven by dysregulated cross-system interactions. This review proposes the "gut microbiota-immune axis" (GMIA) as a comprehensive framework for the development of SAP and systematically discusses the potential mechanisms by which post-stroke microbial-derived metabolic signals-including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, and endotoxins-drive systemic immune reprogramming, predisposing patients to SAP. Based on the GMIA, we highlight several promising intervention strategies, including dietary modulation, precision antibiotic use, probiotics, fecal microbiota transplantation (FMT), supplementation with microbial metabolites, and receptor-targeted therapies, and summarize the current clinical translation related to the GMIA. Future research directions require high-quality clinical trials that integrate multi-omics data from the microbiome with immune biomarkers and clinical parameters. Such an approach is essential for constructing validated risk stratification models and advancing the management of SAP from empirical anti-infective treatment toward a precision medicine model centered on GMIA-based immune modulation.
PMID:42724580 | PMC:PMC13560329 | DOI:10.3389/fimmu.2026.1812306
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Nature Biomedical Engineering
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Engineering inflammation-responsive proteins through nitric oxide-caged amino acids
Nature Biomedical Engineering, Published online: 31 August 2026; doi:10.1038/s41551-026-01782-9A protein engineering strategy enables nitric oxide-triggered reactivation of proteins using genetically encoded caged amino acids, allowing inflammation-localized control of protein activity, viral gene delivery and biosensing in vivo.
Engineering inflammation-responsive proteins through nitric oxide-caged amino acids
Nature Biomedical Engineering, Published online: 31 August 2026; doi:10.1038/s41551-026-01782-9
A protein engineering strategy enables nitric oxide-triggered reactivation of proteins using genetically encoded caged amino acids, allowing inflammation-localized control of protein activity, viral gene delivery and biosensing in vivo.-
cs.AI, q-bio.NC updates on arXiv.org
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FlowCPO: A Unified Divergence View of Preference Alignment for Flow Models
arXiv:2609.09905v1 Announce Type: cross Abstract: Preference alignment for flow and diffusion models now spans online reinforcement learning and offline preference optimization, but the relation between these methods remains unclear. In particular, existing forward-process alignment methods require fresh samples from the current model, while offline methods based on fixed preference pairs rely primarily on positive-only fine-tuning or DPO-style likelihood-ratio surrogates. We organize these app
FlowCPO: A Unified Divergence View of Preference Alignment for Flow Models
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Nature - Issue - nature.com science feeds
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Ancient proteins identify various Denisovan remains from Southwest China
Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-10976-9Identification and proteomic analysis of bone fragments and teeth from an excavation in Southwest China provide insight into the evolution and phenotype of Denisovans and fill a geographical gap in their documented distribution.
Ancient proteins identify various Denisovan remains from Southwest China
Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-10976-9
Identification and proteomic analysis of bone fragments and teeth from an excavation in Southwest China provide insight into the evolution and phenotype of Denisovans and fill a geographical gap in their documented distribution.-
Omics in Hepatocellular
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Integrated single-cell multi-omics characterization reveals lipid-associated macrophage-mediated immunosuppression in neoadjuvant immunotherapy of hepatocellular carcinoma
Nat Commun. 2026 Jul 31;17(1):9381. doi: 10.1038/s41467-026-75949-y.ABSTRACTHepatocellular carcinoma (HCC) is a cancer with high incidence and mortality rate. Although immune checkpoint inhibitors (ICIs) improved survival outcomes for HCC patients, limited objective response rate highlights the urgency of investigating determinants of immunotherapy. Here, we explore HCC resistance mechanisms following neoadjuvant αPD-1 immunotherapy by constructing a comprehensive multi-modal single-cell transcr
Integrated single-cell multi-omics characterization reveals lipid-associated macrophage-mediated immunosuppression in neoadjuvant immunotherapy of hepatocellular carcinoma
Nat Commun. 2026 Jul 31;17(1):9381. doi: 10.1038/s41467-026-75949-y.
ABSTRACT
Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality rate. Although immune checkpoint inhibitors (ICIs) improved survival outcomes for HCC patients, limited objective response rate highlights the urgency of investigating determinants of immunotherapy. Here, we explore HCC resistance mechanisms following neoadjuvant αPD-1 immunotherapy by constructing a comprehensive multi-modal single-cell transcriptomic atlas consisting of 14 HCC patients treated with αPD-1 from our cohort (ClinicalTrials.gov ID: NCT06571396) and 60 external HCC cases with heterogeneous treatment backgrounds. Supervised by clinical outcomes of our cohort, we identify positive and negative regulators of immunotherapy within the tumor immune microenvironment (TIME), especially lipid-associated macrophages (LAM) with increased lipid metabolic state in non-responders and characterized by C1QA, FABP1, and APOA1 expression. We further show the presence, exogenous inducements and immunosuppressive functions of LAM, along with regulation strategies of its lipid-associated condition, including lycopene and chiglitazar. Furthermore, we construct interaction networks of immune regulators across responders and non-responders, showing distinct ligand-receptor landscapes with intervention targets. We reveal the TIME components including immunosuppressive LAMs that influence immunotherapy outcomes, thus providing evidence and insights for exploring immune landscape and therapeutic strategies for HCC immunotherapy. ClinicalTrials.gov ID: NCT06571396.
PMID:42680737 | PMC:PMC13534469 | DOI:10.1038/s41467-026-75949-y
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cs.AI, q-bio.NC updates on arXiv.org
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When the Manual Lies: A Realistic Benchmark to Evaluate MCP Poisoning Attacks for LLM Agents
arXiv:2605.24069v1 Announce Type: cross Abstract: The rise of tool-using Large Language Model (LLM) agents, standardized by protocols like the Model Context Protocol (MCP), has unlocked unprecedented autonomous execution capabilities for LLM Agents by integrating external open-domain knowledge and tools. However, this interoperability introduces a covert attack surface targeting the agent's cognitive planning layer. This paper systematically investigates Tool Description Poisoning (TDP), a nove
When the Manual Lies: A Realistic Benchmark to Evaluate MCP Poisoning Attacks for LLM Agents
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cs.AI, q-bio.NC updates on arXiv.org
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Security in the Fine-Tuning Lifecycle of Large Language Models: Threats, Defenses,Evaluation, and Future Directions
arXiv:2605.25073v1 Announce Type: cross Abstract: Background: Fine-tuning is central to adapting pre-trained Large Language Models (LLMs) to downstream tasks, but its reliance on training data, parameter updates, and reusable components opens entry points for attackers. Threats have evolved from data poisoning and weight tampering to agent manipulation and interface exploitation, yet existing reviews lack a unified framework spanning the full fine-tuning lifecycle. Objective: This paper present
Security in the Fine-Tuning Lifecycle of Large Language Models: Threats, Defenses,Evaluation, and Future Directions
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cs.AI, q-bio.NC updates on arXiv.org
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Hide to Guide: Learning via Semantic Masking
arXiv:2605.25198v1 Announce Type: cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has become a powerful paradigm for improving language models on reasoning-intensive tasks, but its effectiveness is often limited by exploration. For example, models often fail on hard problems, leaving little useful reward signal. External expert traces offer a natural source of guidance, yet they may also expose reward-relevant content along the critical path to the verifier target, such as
Hide to Guide: Learning via Semantic Masking
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cs.AI, q-bio.NC updates on arXiv.org
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NSR-Boost: A Neuro-Symbolic Residual Boosting Framework for Industrial Legacy Models
arXiv:2601.10457v3 Announce Type: replace Abstract: Although the Gradient Boosted Decision Trees (GBDTs) dominate industrial tabular applications, upgrading legacy models in high-concurrency production environments still faces prohibitive retraining costs and systemic risks. To address this problem, we present NSR-Boost, a neuro-symbolic residual boosting framework designed specifically for industrial scenarios. Its core advantage lies in being ``non-intrusive''. It treats the legacy model as a
NSR-Boost: A Neuro-Symbolic Residual Boosting Framework for Industrial Legacy Models
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cs.AI, q-bio.NC updates on arXiv.org
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Bridging the Semantic-Action Gap in Visual Token Pruning for Efficient VLA Inference
arXiv:2511.16449v5 Announce Type: replace-cross Abstract: Vision-Language-Action (VLA) models have shown great potential for embodied AI by integrating visual perception, language understanding, and action execution. In real-time deployment, these models must process continuous visual streams, incurring substantial computational overhead. Visual token pruning -- a mainstream technique for accelerating Vision-Language Models (VLMs) by retaining salient tokens while discarding redundant ones -- o
Bridging the Semantic-Action Gap in Visual Token Pruning for Efficient VLA Inference
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Nature - Issue - nature.com science feeds
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A pathogen lncRNA secreted into rice sequesters a host miRNA for virulence
Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10572-xA fungal long non-coding RNA from Magnaporthe oryzae translocates into rice cells to sequester a host microRNA that normally represses PKR1, a negative immunity regulator, thereby facilitating infection and revealing a widespread RNA-based pathogen–host interaction mechanism.
A pathogen lncRNA secreted into rice sequesters a host miRNA for virulence
Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10572-x
A fungal long non-coding RNA from Magnaporthe oryzae translocates into rice cells to sequester a host microRNA that normally represses PKR1, a negative immunity regulator, thereby facilitating infection and revealing a widespread RNA-based pathogen–host interaction mechanism.-
(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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Effect of the Maxing Huoqiao granule on nonsevere community-acquired pneumonia: A multicenter, double-blind, placebo-controlled randomized trial
Pharmacol Res. 2026 Apr 9:108186. doi: 10.1016/j.phrs.2026.108186. Online ahead of print.ABSTRACTCommunity-acquired pneumonia (CAP) remains a major global public health challenge with substantial morbidity and mortality. Although preclinical studies suggest that Maxing Huoqiao (MXHQ) granule may have therapeutic potential for pneumonia, high-quality clinical evidence is still limited. We conducted a multicenter, double-blind, randomized, placebo-controlled trial at two tertiary hospitals in Chin
Effect of the Maxing Huoqiao granule on nonsevere community-acquired pneumonia: A multicenter, double-blind, placebo-controlled randomized trial
Pharmacol Res. 2026 Apr 9:108186. doi: 10.1016/j.phrs.2026.108186. Online ahead of print.
ABSTRACT
Community-acquired pneumonia (CAP) remains a major global public health challenge with substantial morbidity and mortality. Although preclinical studies suggest that Maxing Huoqiao (MXHQ) granule may have therapeutic potential for pneumonia, high-quality clinical evidence is still limited. We conducted a multicenter, double-blind, randomized, placebo-controlled trial at two tertiary hospitals in China to evaluate the clinical efficacy of MXHQ as adjunctive therapy and to explore its potential mechanisms in adults with nonsevere CAP receiving standard moxifloxacin treatment. A total of 96 patients were enrolled and randomized (1:1:1) to receive standard-dose MXHQ, low-dose MXHQ, or placebo in addition to moxifloxacin for 7 days, with a 14-day follow-up. The primary endpoint was clinical cure, defined as composite recovery of major respiratory symptoms, lung rales, and fever; secondary endpoints included symptom relief, radiographic improvement, and safety. Compared with placebo, standard-dose MXHQ was associated with a higher day-14 clinical cure rate (30.78% vs. 68.97%; RR = 0.45, 95% CI = 0.24-0.83; P < 0.01). Furthermore, the standard-dose intervention was correlated with a shorter time to relief and recovery of cough and sputum (P < 0.05), as well as improvements in symptom scores (P < 0.05) and promoting lesion absorption on chest CT (P < 0.05). Low-dose MXHQ showed no significant clinical benefit, whereas safety profiles were comparable across all groups. Transcriptomic analyses of peripheral blood mononuclear cells, complemented by a Streptococcus pneumonia animal model, indicated that the clinical benefits of MXHQ are linked to the modulation of inflammation and innate immunity. These omics and in vivo observations suggest a potential mechanism underlying the protective effects of MXHQ against inflammatory injury and promotion of tissue repair, involving the regulation of anti-inflammatory mediators and tissue repair-related factors. (Chictr.org.cn, ID Number: ChiCTR2400082095).
PMID:41966499 | DOI:10.1016/j.phrs.2026.108186
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cs.AI, q-bio.NC updates on arXiv.org
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Talk to Right Specialists: Iterative Routing in Multi-agent Systems for Question Answering
arXiv:2501.07813v2 Announce Type: replace-cross Abstract: Retrieval-augmented generation (RAG) agents are increasingly deployed to answer questions over local knowledge bases that cannot be centralized due to knowledge-sovereignty constraints. This results in two recurring failures in production: users do not know which agent to consult, and complex questions require evidence distributed across multiple agents. To overcome these challenges, we propose RIRS, a training-free orchestration framewo
Talk to Right Specialists: Iterative Routing in Multi-agent Systems for Question Answering
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cs.AI, q-bio.NC updates on arXiv.org
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From Multi-Agent to Single-Agent: When Is Skill Distillation Beneficial?
arXiv:2604.01608v1 Announce Type: new Abstract: Multi-agent systems (MAS) tackle complex tasks by distributing expertise, though this often comes at the cost of heavy coordination overhead, context fragmentation, and brittle phase ordering. Distilling a MAS into a single-agent skill can bypass these costs, but this conversion lacks a principled answer for when and what to distill. Instead, the empirical outcome is surprisingly inconsistent: skill lift ranges from a 28% improvement to a 2% degra
From Multi-Agent to Single-Agent: When Is Skill Distillation Beneficial?
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cs.AI, q-bio.NC updates on arXiv.org
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SleepVLM: Explainable and Rule-Grounded Sleep Staging via a Vision-Language Model
arXiv:2603.26738v2 Announce Type: replace-cross Abstract: While automated sleep staging has achieved expert-level accuracy, its clinical adoption is hindered by a lack of auditable reasoning. We introduce SleepVLM, a rule-grounded vision-language model (VLM) designed to stage sleep from multi-channel polysomnography (PSG) waveform images while generating clinician-readable rationales based on American Academy of Sleep Medicine (AASM) scoring criteria. Utilizing waveform-perceptual pre-training
SleepVLM: Explainable and Rule-Grounded Sleep Staging via a Vision-Language Model
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cs.AI, q-bio.NC updates on arXiv.org
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Ran Score: a LLM-based Evaluation Score for Radiology Report Generation
arXiv:2603.22935v1 Announce Type: new Abstract: Chest X-ray report generation and automated evaluation are limited by poor recognition of low-prevalence abnormalities and inadequate handling of clinically important language, including negation and ambiguity. We develop a clinician-guided framework combining human expertise and large language models for multi-label finding extraction from free-text chest X-ray reports and use it to define Ran Score, a finding-level metric for report evaluation.
Ran Score: a LLM-based Evaluation Score for Radiology Report Generation
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cs.AI, q-bio.NC updates on arXiv.org
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PaLMR: Towards Faithful Visual Reasoning via Multimodal Process Alignment
arXiv:2603.06652v1 Announce Type: cross Abstract: Reinforcement learning has recently improved the reasoning ability of Large Language Models and Multimodal LLMs, yet prevailing reward designs emphasise final-answer correctness and consequently tolerate process hallucinations--cases where models reach the right answer while misperceiving visual evidence. We address this process-level misalignment with PaLMR, a framework that aligns not only outcomes but also the reasoning process itself. PaLMR
PaLMR: Towards Faithful Visual Reasoning via Multimodal Process Alignment
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cs.AI, q-bio.NC updates on arXiv.org
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Not All Candidates are Created Equal: A Heterogeneity-Aware Approach to Pre-ranking in Recommender Systems
arXiv:2603.03770v1 Announce Type: cross Abstract: Most large-scale recommender systems follow a multi-stage cascade of retrieval, pre-ranking, ranking, and re-ranking. A key challenge at the pre-ranking stage arises from the heterogeneity of training instances sampled from coarse-grained retrieval results, fine-grained ranking signals, and exposure feedback. Our analysis reveals that prevailing pre-ranking methods, which indiscriminately mix heterogeneous samples, suffer from gradient conflicts