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Selective Test-Time Compute Scaling for Click-Through Rate Prediction via Uncertainty-Triggered Feature Path Exploration

arXiv:2605.24989v1 Announce Type: cross Abstract: Scaling test-time compute has proven highly effective for language models, yet this opportunity remains largely unexplored for industrial Click-Through Rate (CTR) prediction. CTR models suffer from a fundamental asymmetry: feature combinations well-represented in training yield confident predictions, while sparsely observed ones produce unreliable outputs. Existing training-phase solutions such as adaptive gating learn a fixed selection function subject to the same sparsity, offering no per-instance recourse at deployment.We propose UTTSI (Uncertainty-Triggered Test-Time Selective Inference), a training-free model-agnostic framework that scales inference depth proportionally to per-instance uncertainty. A dual-signal estimator combining model logit confidence with a data-level frequency prior distinguishes epistemic uncertainty from aleatoric ambiguity. Every instance undergoes adaptive feature filtering to remove unreliable embeddings; uncertain instances additionally receive stochastic feature-path explorations whose predictions are aggregated via consistency-weighted ensembling. Confident instances bypass exploration entirely, keeping average overhead at approximately $2.8\times$ base model cost with worst-case latency unchanged.Experiments on four datasets with three backbone architectures demonstrate consistent, statistically significant gains over all training-phase baselines. A seven-day online A/B test further confirms a 5.3% relative CTR gain ($p
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FDX1 as a predictive biomarker and therapeutic target for lymph node metastasis in gastric cancer

Clin Exp Med. 2026 May 10. doi: 10.1007/s10238-026-02160-0. Online ahead of print.

ABSTRACT

The prognostic values of cuproptosis-related genes (CRGs) in gastric cancer with lymph node metastasis (GCLM), especially in the tumor immune microenvironment (TIME), remain unclear. We analyzed the expression, mutation, immunity, drug sensitivity, and prognostic value of CRGs in GCLM using TCGA and GEO cohorts. Consensus clustering was performed to identify CRG subtypes, with differences characterized by multi-omics analysis. A CRG-based prognostic risk score and immune score were constructed for individualized assessment, and the role of CRGs was validated through in vitro and in vivo experiments. Consensus clustering revealed that CRGs were significantly enriched in biological processes related to mitosis and energy metabolism, as well as in immune-related and cancer-associated pathways. Four distinct CRG subtypes were identified, showing marked differences in expression profiles, prognosis, genetic alterations, TIME, and chemotherapeutic drug sensitivity. We developed an exploratory CRG-based prognostic risk score for preliminary individualized assessment, and the functional relevance of CRGs in GCLM was further validated through in vitro experiments. Among these, FDX1, LIAS, DLAT, MTF1, and GLS were identified as key determinants of overall survival in patients with GCLM, with FDX1 emerging as a potential independent prognostic factor. Notably, upregulation of FDX1 significantly suppressed lymph node metastasis of gastric cancer cells in a mouse popliteal lymph node metastasis model. Our data uncovers FDX1 might be a potential favorable prognostic factors in GCLM patients. These findings may improve our understanding of CRGs in GCLM and provide new in-sights for assessing prognosis and developing more effective treatment strategies.

PMID:42107026 | DOI:10.1007/s10238-026-02160-0

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Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling

Discov Oncol. 2026 Apr 11. doi: 10.1007/s12672-026-04951-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Chromosome 8 open reading frame 33 (C8orf33) has been noted as a potential oncogenic factor in several cancers, but its biological roles and regulatory mechanism in HCC microenvironment remain unknown.

METHODS: We integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) to characterize the expression landscape of C8orf33. We then performed C8orf33 loss-of-function studies in HCC cell lines, including in vitro phenotypic assays and subcutaneous xenografts.

RESULTS: C8orf33 was broadly overexpressed and associated with unfavorable prognosis across multiple Cancers. In HCC, higher C8orf33 aligned with advanced stage and shorter overall survival. C8orf33 knockdown reduced proliferation and migration, impaired tumorigenic capacity, and increased apoptosis. ScRNA-seq analyses identified a malignant population of Epi3 with high C8orf33 expression. Cell-cell communication analysis suggested that C8orf33-high Epi3 state was associated with an enriched MIF-CD74/CXCR4/CD44 signaling program toward macrophage populations with M2-like features. ST analyses further confirmed the colocalization of C8orf33 with malignant features in tumor cores. In Huh7 cells, C8orf33 knockdown was accompanied by reduced mRNA and protein levels of MIF and its receptor components. Consistently, xenografts derived from C8orf33-silenced cells showed lower expression of these MIF-axis components and reduced infiltration of CD163 and CD206-positive macrophages.

CONCLUSION: These results support a tumor-promoting association of C8orf33 in HCC and suggest a potential link to macrophage-associated immunomodulatory features, nominating C8orf33 as a candidate biomarker and therapeutic target.

PMID:41965457 | DOI:10.1007/s12672-026-04951-z

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Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling

Discov Oncol. 2026 Apr 11. doi: 10.1007/s12672-026-04951-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Chromosome 8 open reading frame 33 (C8orf33) has been noted as a potential oncogenic factor in several cancers, but its biological roles and regulatory mechanism in HCC microenvironment remain unknown.

METHODS: We integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) to characterize the expression landscape of C8orf33. We then performed C8orf33 loss-of-function studies in HCC cell lines, including in vitro phenotypic assays and subcutaneous xenografts.

RESULTS: C8orf33 was broadly overexpressed and associated with unfavorable prognosis across multiple Cancers. In HCC, higher C8orf33 aligned with advanced stage and shorter overall survival. C8orf33 knockdown reduced proliferation and migration, impaired tumorigenic capacity, and increased apoptosis. ScRNA-seq analyses identified a malignant population of Epi3 with high C8orf33 expression. Cell-cell communication analysis suggested that C8orf33-high Epi3 state was associated with an enriched MIF-CD74/CXCR4/CD44 signaling program toward macrophage populations with M2-like features. ST analyses further confirmed the colocalization of C8orf33 with malignant features in tumor cores. In Huh7 cells, C8orf33 knockdown was accompanied by reduced mRNA and protein levels of MIF and its receptor components. Consistently, xenografts derived from C8orf33-silenced cells showed lower expression of these MIF-axis components and reduced infiltration of CD163 and CD206-positive macrophages.

CONCLUSION: These results support a tumor-promoting association of C8orf33 in HCC and suggest a potential link to macrophage-associated immunomodulatory features, nominating C8orf33 as a candidate biomarker and therapeutic target.

PMID:41965457 | DOI:10.1007/s12672-026-04951-z

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A Data-driven Approach for Biomarker Discovery based on U-centered Distance Correlation Network: Multi-omics Warning Signals for Non-small Cell Lung Cancer

Comb Chem High Throughput Screen. 2026 Mar 27. doi: 10.2174/0113862073445368260131002109. Online ahead of print.

ABSTRACT

INTRODUCTION/OBJECTIVE: Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Alterations in metabolic activities play important roles in NSCLC development, wherein related genes and metabolites interact with each other, involving multiple forms.

METHODS: To comprehensively understand the pathogenic mechanisms and improve the performance of clinical early, precise diagnosis, this study proposed a data-driven approach for biomarker discovery based on U-centered distance correlation network (DCN) to investigate NSCLC metabolism-related reactions. In DCN, changes in molecular relationships during NSCLC initiation and progression are measured using the t-statistics of U-centered distance correlation for network construction, in which prospective warning signals representing NSCLC onset can be identified without human intervention. Additionally, the network construction criterion in DCN can precisely and effectively capture both linear and nonlinear molecular relationships in simple and biologically relevant manners.

RESULTS: DCN was successfully employed to analyze NSCLC metabolism-related metabolomics and genomics datasets. Statistical analyses confirmed that compared with other algorithms, the gene and metabolite biomarker panels identified by DCN provided more reliable diagnostic capabilities for clinical NSCLC detection. Biological analyses revealed that disturbed energy metabolism and lipid metabolism occurred during tumor cell proliferation and growth in NSCLC patients.

DISCUSSION: The gene ASPA and metabolite aspartic acid were significantly decreased in NSCLC samples, suggesting that the corresponding amino acid metabolic activities were intricately linked to NSCLC progression.

CONCLUSION: These findings demonstrated that DCN can further facilitate NSCLC studies to improve clinical outcomes in patients.

PMID:41937706 | DOI:10.2174/0113862073445368260131002109

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A Data-driven Approach for Biomarker Discovery based on U-centered Distance Correlation Network: Multi-omics Warning Signals for Non-small Cell Lung Cancer

Comb Chem High Throughput Screen. 2026 Mar 27. doi: 10.2174/0113862073445368260131002109. Online ahead of print.

ABSTRACT

INTRODUCTION/OBJECTIVE: Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Alterations in metabolic activities play important roles in NSCLC development, wherein related genes and metabolites interact with each other, involving multiple forms.

METHODS: To comprehensively understand the pathogenic mechanisms and improve the performance of clinical early, precise diagnosis, this study proposed a data-driven approach for biomarker discovery based on U-centered distance correlation network (DCN) to investigate NSCLC metabolism-related reactions. In DCN, changes in molecular relationships during NSCLC initiation and progression are measured using the t-statistics of U-centered distance correlation for network construction, in which prospective warning signals representing NSCLC onset can be identified without human intervention. Additionally, the network construction criterion in DCN can precisely and effectively capture both linear and nonlinear molecular relationships in simple and biologically relevant manners.

RESULTS: DCN was successfully employed to analyze NSCLC metabolism-related metabolomics and genomics datasets. Statistical analyses confirmed that compared with other algorithms, the gene and metabolite biomarker panels identified by DCN provided more reliable diagnostic capabilities for clinical NSCLC detection. Biological analyses revealed that disturbed energy metabolism and lipid metabolism occurred during tumor cell proliferation and growth in NSCLC patients.

DISCUSSION: The gene ASPA and metabolite aspartic acid were significantly decreased in NSCLC samples, suggesting that the corresponding amino acid metabolic activities were intricately linked to NSCLC progression.

CONCLUSION: These findings demonstrated that DCN can further facilitate NSCLC studies to improve clinical outcomes in patients.

PMID:41937706 | DOI:10.2174/0113862073445368260131002109

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Sparse but Critical: A Token-Level Analysis of Distributional Shifts in RLVR Fine-Tuning of LLMs

arXiv:2603.22446v1 Announce Type: cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has significantly improved reasoning in large language models (LLMs), yet the token-level mechanisms underlying these improvements remain unclear. We present a systematic empirical study of RLVR's distributional effects organized around three main analyses: (1) token-level characterization of distributional shifts between base and RL models, (2) the impact of token-level distributional shifts on sequence-level reasoning performance through cross-sampling interventions, and (3) fine-grained mechanics of these shifts at the token level. We find that RL fine-tuning induces highly sparse and targeted changes, with only a small fraction of token distributions exhibiting meaningful divergence between the base and RL policies. We further characterize the structure and evolution of these shifts through analyses of token entropy, positional concentration, and reallocation of probability mass. To assess the functional importance of these sparse changes, we conduct cross-sampling experiments that selectively swap token choices between the base and RL models with varying intervention budgets. We show that inserting only a small fraction of RL-sampled tokens into base generations progressively recovers RL performance gains, while injecting a similarly small number of base token choices into otherwise RL-generated sequences collapses performance to base levels, isolating a small set of token-level decisions directly responsible for RLVR's performance gains. Finally, we explore divergence-weighted variants of the advantage signal as a diagnostic intervention, finding that they can yield improvements over baselines. Together, our results shed light on the distributional changes induced by RLVR and provide a fine-grained, token-level lens for understanding RLVR fine-tuning as a targeted refinement process.
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An Accurate and Interpretable Framework for Trustworthy Process Monitoring

arXiv:2302.10426v3 Announce Type: replace Abstract: Trustworthy process monitoring seeks to build an accurate and interpretable monitoring framework, which is critical for ensuring the safety of energy conversion plant (ECP) that operates under extreme working conditions such as high pressure and temperature. Contemporary self-attentive models, however, fall short in this domain for two main reasons. First, they rely on step-wise correlations that fail to involve physically meaningful semantics in ECP logs, resulting in suboptimal accuracy and interpretability. Second, attention matrices are frequently cluttered with spurious correlations that obscure physically meaningful ones, further impeding effective interpretation. To overcome these issues, we propose AttentionMixer, a framework aimed at improving both accuracy and interpretability of existing methods and establish a trustworthy ECP monitoring framework. Specifically, to tackle the first issue, we employ a spatial adaptive message passing block to capture variate-wise correlations. This block is coupled with a temporal adaptive message passing block through an \textit{mixing} operator, yielding a multi-faceted representation of ECP logs accounting for both step-wise and variate-wise correlations. Concurrently, to tackle the second issue, we employ a sparse message passing regularizer to filter out spurious correlations. We validate the efficacy of AttentionMixer using two real-world datasets from the radiation monitoring network for Chinese nuclear power plants.
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β-hydroxybutyrate enhances the metabolic fitness of CAR T cells in cancer

β-hydroxybutyrate (BHB), the ketone body associated with a ketogenic diet, metabolically reprograms and fuels CAR T cells to achieve proliferation, cytokine production, and superior tumor control. These findings suggest that BHB supplementation may be a practical way to boost adoptive cancer immunotherapy.
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Tuning the sensitivity of mechanosensory receptors through histidine scanning

Histidine scanning represents a broadly applicable technique for the identification of critical interaction sites within TCRs and other mechanosensory receptors to enhance receptor signaling strength and augment therapeutic efficacy via the catch bond mechanism.
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ReportLogic: Evaluating Logical Quality in Deep Research Reports

arXiv:2602.18446v1 Announce Type: cross Abstract: Users increasingly rely on Large Language Models (LLMs) for Deep Research, using them to synthesize diverse sources into structured reports that support understanding and action. In this context, the practical reliability of such reports hinges on logical quality: whether the report's claims and arguments are explicitly supported and can be trusted as a basis for downstream use, rather than merely appearing fluent or informative. However, current evaluation frameworks largely overlook this requirement. To bridge this gap, we introduce ReportLogic, a benchmark that quantifies report-level logical quality through a reader-centric lens of auditability. Specifically, ReportLogic adopts a hierarchical taxonomy that evaluates whether readers can (1) trace an on-topic report structure with a unified analytical arc (Macro-Logic), (2) understand the progression with necessary context (Expositional-Logic), and (3) verify conclusions via explicit claim--support (Structural-Logic). Based on this taxonomy, we construct a human-annotated rubric-guided dataset and train an open-source LogicJudge for scalable evaluation. We further evaluate judge robustness via adversarial attacks, showing that off-the-shelf LLM judges are frequently influenced by superficial cues (e.g., verbosity), and reasoning modes can mask broken support relations. Overall, our results provide actionable guidance for building more robust logic evaluators and improving the logical reliability of LLM-generated reports.
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