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Joint impact of pathological burden and cognitive resilience on Alzheimer’s disease risk

Nature Medicine, Published online: 11 September 2026; doi:10.1038/s41591-026-04635-9

A 15-year cohort study shows that Alzheimer’s dementia risk is jointly shaped by Alzheimer’s pathology and cognitive resilience, with high resilience linked to lower risk, even under greater pathology.

MITF-SCD1 Lipid Metabolic Axis Prevents Ouabain-Induced Spiral Ganglion Neuron Ferroptosis and Hearing Loss

Ouabain triggers cochlear spiral ganglion neuron (SGN) ferroptosis and hearing loss via SCD1 downregulation. MITF directly activates Scd1 transcription, and the MITF–SCD1 axis mitigates SGN ferroptosis and hearing impairment in ototoxic ouabain and cisplatin models, revealing a lipid metabolic vulnerability and therapeutic target for sensorineural hearing loss.

Dear Algo: A Precision-First Agentic Intent Layer for Unified Search and Recommendation

arXiv:2608.15877v3 Announce Type: replace Abstract: Search and recommendation serve a shared discovery objective but encode intent differently. We study this boundary through Dear Algo on Threads, a deployed product where open-ended requests such as \emph{more NBA news} or \emph{less politics} steer subsequent feed recommendations rather than return a one-shot result list. Its agentic intent layer compiles explicit, inferred, negative, and compound intent into a grounded executable plan, then invokes conventional retrieval and optional semantic or multimodal reranking. The layer shares an intent-to-retrieval contract without requiring one model or serving path across search-like and recommendation-like modes. We evaluate Dear Algo under a precision-first objective. In a blinded audit of 300 public request-item pairs (296 evaluable), a strict categorical LLM-as-a-judge gate achieved 94.4\% exact-Relevant precision [88.8\%, 98.9\%]. Across 72 normalized request clusters, the full configuration produced 7.73 judge-qualified candidates per 20 slots versus 6.61 for an LLM-derived-query baseline, a gain of 1.11 [0.12, 2.12]. In a candidate-randomized serving-path study restricted to the reranker path's first 72 eligible hours, the user-weighted judge-Irrelevant share among judged admissions was 2.80\% versus 4.78\% off (-1.97 points [-3.02, -0.94]), while Exact-Relevant share was 2.24 points higher [0.08, 4.41]. Together, these studies show how explicit natural-language intent can be carried into feed recommendation under a precision-first evaluation framework

A bivalent molecular glue linking lysine acetyltransferases to oncogene-induced cell death

Chemically induced proximity of lysine acetyltransferases (KATs) with BCL6 reprograms epigenetic signaling to eliminate lymphoma tumors. Structural and mechanistic studies demonstrate that fortuitous protein-protein contacts convert proximity induction into targeted changes in chromatin, revealing a key mechanism by which small molecules can co-opt oncogenic transcriptional regulators to elicit malignant cell death.

Memorize Theorems, Not Instances: Probing SFT Generalization through Mathematical Reasoning

arXiv:2605.09270v2 Announce Type: replace-cross Abstract: Supervised Fine-Tuning (SFT) is widely used for task-specific adaptation, yet recent work shows it systematically undermines reasoning generalization. We argue the root cause is not memorization itself, but its target: vanilla SFT drives models to exploit and memorize spurious surface correlations in problem-solution pairs, leaving them brittle to superficial input variations. To address this, we propose Theorem-SFT, which reorients supervision toward explicit theorem application by teaching models how rules are invoked rather than what answers look like. Theorem-SFT yields consistent gains across benchmarks and model families: +8.8% on MATH (LLaMA3.2-3B-Instruct) and +20.27% on GeoQA (Qwen2.5-VL-7B-Instruct) without modality-specific re-training. Fine-tuning MLP layers alone matches full-layers performance, implicating feed-forward components as the primary locus of reasoning rules. Our findings reframe the debate: Generalization failures stem not from memorization as a mechanism, but from memorizing the wrong inductive targets.

Towards generalizable seizure monitoring: EpiVLM for cross-environment detection and classification

npj Digital Medicine, Published online: 26 May 2026; doi:10.1038/s41746-026-02810-3

Towards generalizable seizure monitoring: EpiVLM for cross-environment detection and classification

Schema-Aware Planning and Hybrid Knowledge Toolset for Reliable Knowledge Graph Triple Verification

arXiv:2604.04190v1 Announce Type: new Abstract: Knowledge Graphs (KGs) serve as a critical foundation for AI systems, yet their automated construction inevitably introduces noise, compromising data trustworthiness. Existing triple verification methods, based on graph embeddings or language models, often suffer from single-source bias by relying on either internal structural constraints or external semantic evidence, and usually follow a static inference paradigm. As a result, they struggle with complex or long-tail facts and provide limited interpretability. To address these limitations, we propose SHARP (Schema-Hybrid Agent for Reliable Prediction), a training-free autonomous agent that reformulates triple verification as a dynamic process of strategic planning, active investigation, and evidential reasoning. Specifically, SHARP combines a Memory-Augmented Mechanism with Schema-Aware Strategic Planning to improve reasoning stability, and employs an enhanced ReAct loop with a Hybrid Knowledge Toolset to dynamically integrate internal KG structure and external textual evidence for cross-verification. Experiments on FB15K-237 and Wikidata5M-Ind show that SHARP significantly outperforms existing state-of-the-art baselines, achieving accuracy gains of 4.2% and 12.9%, respectively. Moreover, SHARP provides transparent, fact-based evidence chains for each judgment, demonstrating strong interpretability and robustness for complex verification tasks.

CREBench: Evaluating Large Language Models in Cryptographic Binary Reverse Engineering

arXiv:2604.03750v1 Announce Type: cross Abstract: Reverse engineering (RE) is central to software security, particularly for cryptographic programs that handle sensitive data and are highly prone to vulnerabilities. It supports critical tasks such as vulnerability discovery and malware analysis. Despite its importance, RE remains labor-intensive and requires substantial expertise, making large language models (LLMs) a potential solution for automating the process. However, their capabilities for RE remain systematically underexplored. To address this gap, we study the cryptographic binary RE capabilities of LLMs and introduce \textbf{CREBench}, a benchmark comprising 432 challenges built from 48 standard cryptographic algorithms, 3 insecure crypto key usage scenarios, and 3 difficulty levels. Each challenge follows a Capture-the-Flag (CTF) RE challenge, requiring the model to analyze the underlying cryptographic logic and recover the correct input. We design an evaluation framework comprising four sub-tasks, from algorithm identification to correct flag recovery. We evaluate eight frontier LLMs on CREBench. GPT-5.4, the best-performing model, achieves 64.03 out of 100 and recovers the flag in 59\% of challenges. We also establish a strong human expert baseline of 92.19 points, showing that humans maintain an advantage in cryptographic RE tasks. Our code and dataset are available at https://github.com/wangyu-ovo/CREBench.

Gram-Anchored Prompt Learning for Vision-Language Models via Second-Order Statistics

arXiv:2604.03980v1 Announce Type: cross Abstract: Parameter-efficient prompt learning has become the de facto standard for adapting Vision-Language Models (VLMs) to downstream tasks. Existing approaches predominantly focus on aligning text prompts with first-order visual features (i.e., spatial feature maps). While effective for fine-grained semantic discrimination, we argue that relying solely on first-order information is insufficient for robust adaptation, as these spatially entangled features are highly susceptible to domain shifts and local noise. In this work, we propose \textbf{Gram-Anchored Prompt Learning (GAPL)} for Vision-Language Models via Second-Order Statistics, a framework that synergizes local semantic alignment with global structural consistency. Methodologically, we introduce an additional second-order statistical stream via \textbf{Gram matrices} that augments the standard first-order spatial interaction. By anchoring prompts to these second-order priors, our approach enables language representations to dynamically adapt to statistical distribution shifts across diverse domains. Extensive experiments indicate the effectiveness of the second-order features, and show compelling performances of GAPL on various benchmarks.

DVM: A Bytecode Virtual Machine Approach for Dynamic Tensor Computation

arXiv:2603.24239v2 Announce Type: replace-cross Abstract: Dynamism is common in AI computation, e.g., the dynamic tensor shapes and the dynamic control flows in models. Due to the long compilation time, existing runtime compilation damages the model efficiency, while the offline compilers either suffer from the long compilation time and device memory footprint to cover all the possible execution instances of a dynamic model, or sacrifice optimization opportunities for usability. In this paper, we rethink the feasibility of runtime compilation for dynamic models and identify that the key for it to work is to speed up the compilation or hide the compilation overhead. To do this, we propose a real-time compiler, DVM. In DVM, we design a runtime operator compiler based on a bytecode virtual machine to perform effective and efficient compilation for each dynamic operator instance given its input. Specifically, instead of compiling programs into machine code, we encode the operator program into bytecode on the CPU and decode the bytecode into virtual instructions for direct execution on the NPU. Based on the runtime operator compiler, we further propose an operator fuser, which performs symbol-deduction-based fusion on static graphs and runtime fusion on dynamic graphs. Both pattern- and stacking-based fusion are supported to increase fusion opportunities. Evaluation on operators, subgraphs, and models shows that, compared with TorchInductor, PyTorch-eager and MindSpore-graph-O0, we are up to 11.77$\times$ better in terms of the operator/model efficiency and up to 5 orders of magnitude faster in terms of the maximum compilation time.

LatentPilot: Scene-Aware Vision-and-Language Navigation by Dreaming Ahead with Latent Visual Reasoning

arXiv:2603.29165v1 Announce Type: cross Abstract: Existing vision-and-language navigation (VLN) models primarily reason over past and current visual observations, while largely ignoring the future visual dynamics induced by actions. As a result, they often lack an effective understanding of the causal relationship between actions and how the visual world changes, limiting robust decision-making. Humans, in contrast, can imagine the near future by leveraging action-dynamics causality, which improves both environmental understanding and navigation choices. Inspired by this capability, we propose LatentPilot, a new paradigm that exploits future observations during training as a valuable data source to learn action-conditioned visual dynamics, while requiring no access to future frames at inference. Concretely, we propose a flywheel-style training mechanism that iteratively collects on-policy trajectories and retrains the model to better match the agent's behavior distribution, with an expert takeover triggered when the agent deviates excessively. LatentPilot further learns visual latent tokens without explicit supervision; these latent tokens attend globally in a continuous latent space and are carried across steps, serving as both the current output and the next input, thereby enabling the agent to dream ahead and reason about how actions will affect subsequent observations. Experiments on R2R-CE, RxR-CE, and R2R-PE benchmarks achieve new SOTA results, and real-robot tests across diverse environments demonstrate LatentPilot's superior understanding of environment-action dynamics in scene. Project page:https://abdd.top/latentpilot/

Screening of Hepatocellular Carcinoma in Hepatic Cirrhosis Patients by a Novel Blood-Based Multi-Omics Test

Technol Cancer Res Treat. 2026 Jan-Dec;25:15330338261435022. doi: 10.1177/15330338261435022. Epub 2026 Mar 23.

ABSTRACT

IntroductionHepatocellular carcinoma (HCC) screening in patients with hepatic cirrhosis (HC) relies on ultrasound and alpha-fetoprotein (US + AFP), which has limitations in sensitivity, particularly for early-stage HCC detection. This study aims to evaluate the performance of a novel multi-omics blood test, HCCscreen, with its individual components (methylation, AFP, Des-γ-Carboxy Prothrombin (DCP), mutations) and the standard US + AFP for HCC screening in a hepatic cirrhotic population.MethodsA total of 5078 patients with known high-risk for HCC were recruited. A prospective screening study was conducted on 650 patients with hepatic cirrhosis identified by ultrasound. Blood samples were collected from all patients before the confirmation of diagnosis by imaging and/or pathological examinations. The performance of HCCscreen, individual markers and US + AFP were calculated and compared. Statistics was performed with Graphpad Prism 5.0.ResultsHCCscreen exhibited a sensitivity of 86.3% at a specificity of 81.3%, with a positive predictive value (PPV) of 28.2% and a negative predictive value (NPV) of 98.6%. The positive likelihood ratio (LR+) was 4.61 and the negative LR (LR-) was 0.17. The positive detection rate (PDR) for all markers increased with more advanced HCC stages, whether Barcelona Clinic Liver Cancer (BCLC) or clinical staging. Among the single-omics, methylation showed the highest PDR, followed by AFP, DCP and mutations. HCCscreen demonstrated superior overall performance with an AUC of 0.87, outperforming individual markers like methylation (AUC = 0.76), AFP (AUC = 0.83), and DCP (AUC = 0.77). Crucially, HCCscreen's PDR was significantly higher than US + AFP in early-stage HCC (BCLC-0 and clinical stage I). Furthermore, while AFP's PDR varied significantly by sex, HCCscreen's performance remained consistent across all demographics. Correlation analysis revealed a significant association only between the HCCscreen score and the methylation score.ConclusionsThe multi-omics approach of HCCscreen significantly enhances early HCC detection in patients with hepatic cirrhosis compared to both its individual components and the current standard of US + AFP. Its robust and consistent performance across patient demographics underscores its potential as a superior tool for population-wide early HCC screening.

PMID:41869803 | PMC:PMC13009828 | DOI:10.1177/15330338261435022

Screening of Hepatocellular Carcinoma in Hepatic Cirrhosis Patients by a Novel Blood-Based Multi-Omics Test

Technol Cancer Res Treat. 2026 Jan-Dec;25:15330338261435022. doi: 10.1177/15330338261435022. Epub 2026 Mar 23.

ABSTRACT

IntroductionHepatocellular carcinoma (HCC) screening in patients with hepatic cirrhosis (HC) relies on ultrasound and alpha-fetoprotein (US + AFP), which has limitations in sensitivity, particularly for early-stage HCC detection. This study aims to evaluate the performance of a novel multi-omics blood test, HCCscreen, with its individual components (methylation, AFP, Des-γ-Carboxy Prothrombin (DCP), mutations) and the standard US + AFP for HCC screening in a hepatic cirrhotic population.MethodsA total of 5078 patients with known high-risk for HCC were recruited. A prospective screening study was conducted on 650 patients with hepatic cirrhosis identified by ultrasound. Blood samples were collected from all patients before the confirmation of diagnosis by imaging and/or pathological examinations. The performance of HCCscreen, individual markers and US + AFP were calculated and compared. Statistics was performed with Graphpad Prism 5.0.ResultsHCCscreen exhibited a sensitivity of 86.3% at a specificity of 81.3%, with a positive predictive value (PPV) of 28.2% and a negative predictive value (NPV) of 98.6%. The positive likelihood ratio (LR+) was 4.61 and the negative LR (LR-) was 0.17. The positive detection rate (PDR) for all markers increased with more advanced HCC stages, whether Barcelona Clinic Liver Cancer (BCLC) or clinical staging. Among the single-omics, methylation showed the highest PDR, followed by AFP, DCP and mutations. HCCscreen demonstrated superior overall performance with an AUC of 0.87, outperforming individual markers like methylation (AUC = 0.76), AFP (AUC = 0.83), and DCP (AUC = 0.77). Crucially, HCCscreen's PDR was significantly higher than US + AFP in early-stage HCC (BCLC-0 and clinical stage I). Furthermore, while AFP's PDR varied significantly by sex, HCCscreen's performance remained consistent across all demographics. Correlation analysis revealed a significant association only between the HCCscreen score and the methylation score.ConclusionsThe multi-omics approach of HCCscreen significantly enhances early HCC detection in patients with hepatic cirrhosis compared to both its individual components and the current standard of US + AFP. Its robust and consistent performance across patient demographics underscores its potential as a superior tool for population-wide early HCC screening.

PMID:41869803 | PMC:PMC13009828 | DOI:10.1177/15330338261435022

Effect of a Digital-Driven Physician-Pharmacist Collaborative Model for Diabetes in Primary Health Care: Cluster Randomized Trial

Background: Evidence-based physician-pharmacist collaborative clinics have demonstrated significant short-term benefits for patients with type 2 diabetes (T2D), but their long-term effectiveness remains unclear, especially in primary health care settings. Objective: This study aimed to explore the long-term effectiveness and cost-effectiveness of a novel, digital-driven, multifaceted physician-pharmacist collaborative model for managing patients with T2D in underresourced settings. Methods: We conducted a 12-month cluster randomized controlled trial from May 2021 to December 2022 across 6 primary health care settings in China. Guided by the theory of planned behavior, the intervention involved routine therapy from physicians along with pharmaceutical interventions from pharmacists. These were delivered through a combination of face-to-face visits and mobile health care. The intervention group received 4 face-to-face visits and biweekly remote education sessions over the 12 months. We conducted intention-to-treat analyses to estimate differences in clinical and behavior indicators between the intervention and control groups. Primary outcomes included glycosylated hemoglobin and 10-year atherosclerotic cardiovascular risk. Data were analyzed using adjusted generalized estimation equations. Results: This study included 574 patients (291 in the intervention group and 283 in the control group). Over 12 months, patients in the intervention group had significant reductions in hemoglobin A1c (–2.57 vs –1.96, respectively; P<.001; 95% CI –1.027 to –0.238) and 10-year atherosclerotic cardiovascular risk (–1.35 vs 0.01, respectively; P<.001; 95% CI –1.690 to –0.630) compared with the control group. Substantial improvements were also observed in several secondary outcomes, including fasting blood glucose, 2-hour postprandial blood glucose, waist circumference, waist-to-hip ratio, blood pressure, triglyceride, and total cholesterol. Total diabetes-related costs decreased, and patient satisfaction improved significantly in the intervention group. There were no significant differences in BMI, high-density lipoprotein, or low-density lipoprotein. Conclusions: These findings suggest that the physician-pharmacist collaborative model could improve the long-term quality and efficiency of T2D management and reduce medical costs in underresourced areas globally. Patients with T2D, especially those with central obesity or high cardiovascular risk, may benefit more from collaborative clinics. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000031839; https://www.chictr.org.cn/showproj.html?proj=51910

Risk-adaptive therapy guided by dynamic ctDNA in nasopharyngeal carcinoma

Nature, Published online: 11 March 2026; doi:10.1038/s41586-026-10244-w

A clinical trial testing whether monitoring ctDNA clearance during treatment for nasopharyngeal cancer could be used to inform decisions about an individual’s subsequent therapeutic programme shows promising results.

RxnNano:Training Compact LLMs for Chemical Reaction and Retrosynthesis Prediction via Hierarchical Curriculum Learning

arXiv:2603.02215v1 Announce Type: cross Abstract: Chemical reaction prediction is pivotal for accelerating drug discovery and synthesis planning. Despite advances in data-driven models, current approaches are hindered by an overemphasis on parameter and dataset scaling. Some methods coupled with evaluation techniques that bypass fundamental challenges in reaction representation and fail to capture deep chemical intuition like reaction common sense and {topological atom mapping logic}. We argue that the core challenge lies in instilling these knowledge into the models. To this end, we propose a unified framework that prioritizes chemical understanding over scale through three key innovations: (1) a {Latent Chemical Consistency} objective that models reactions as movements on a continuous chemical manifold, ensuring reversible and physically plausible transformations; (2) a {Hierarchical Cognitive Curriculum} that trains the model through progressive stages, from syntax mastery to semantic reasoning, building robust chemical intuition; (3) {Atom-Map Permutation Invariance (AMPI)}, which force the model to learn invariant relational topology and balance multi-task learning. (4)and structured plan-based reasoning to improve the performance of the LLMs. Our compact {0.5B-parameter model}, \textbf{RxnNano} significantly outperforms fine-tuned LLMs ten times larger (>7B) and all the domain baselines, achieving a 23.5\% Top-1 accuracy improvement on rigorous benchmarks without test-time augmentation. https://github.com/rlisml/RxnNano.

Pailitao-VL: Unified Embedding and Reranker for Real-Time Multi-Modal Industrial Search

arXiv:2602.13704v1 Announce Type: cross Abstract: In this work, we presented Pailitao-VL, a comprehensive multi-modal retrieval system engineered for high-precision, real-time industrial search. We here address three critical challenges in the current SOTA solution: insufficient retrieval granularity, vulnerability to environmental noise, and prohibitive efficiency-performance gap. Our primary contribution lies in two fundamental paradigm shifts. First, we transitioned the embedding paradigm from traditional contrastive learning to an absolute ID-recognition task. Through anchoring instances to a globally consistent latent space defined by billions of semantic prototypes, we successfully overcome the stochasticity and granularity bottlenecks inherent in existing embedding solutions. Second, we evolved the generative reranker from isolated pointwise evaluation to the compare-and-calibrate listwise policy. By synergizing chunk-based comparative reasoning with calibrated absolute relevance scoring, the system achieves nuanced discriminative resolution while circumventing the prohibitive latency typically associated with conventional reranking methods. Extensive offline benchmarks and online A/B tests on Alibaba e-commerce platform confirm that Pailitao-VL achieves state-of-the-art performance and delivers substantial business impact. This work demonstrates a robust and scalable path for deploying advanced MLLM-based retrieval architectures in demanding, large-scale production environments.

WiSparse: Boosting LLM Inference Efficiency with Weight-Aware Mixed Activation Sparsity

arXiv:2602.14452v1 Announce Type: cross Abstract: Large Language Models (LLMs) offer strong capabilities but incur high inference costs due to dense computation and memory access. Training-free activation sparsity is a promising approach for efficient LLM inference, yet existing methods often rely solely on activation information and uniform sparsity ratios. This overlooks the critical interplay with weights and inter-block sensitivity variation, leading to suboptimal performance. We identify two key phenomena in modern LLMs: 1) less significant activations may align with highly important weights, and 2) sparsity sensitivity varies non-monotonically across model blocks. We propose Weight-aware Mixed-Granularity Training-free Activation Sparsity (WiSparse), which leverages both activation and weight information for adaptive sparsity allocation. Specifically, we introduce a weight-aware mechanism integrating activation magnitudes with precomputed weight norms to accurately identify salient channels. This is combined with a mixed-granularity allocation scheme: a global budget is distributed across blocks via evolutionary search to protect sensitive regions, then refined within blocks to minimize reconstruction error. We improve sparse kernels and demonstrate effectiveness on three representative models. Notably, at 50% sparsity, WiSparse preserves 97% of Llama3.1's dense performance, surpassing the strongest baseline by 2.23 percentage points while achieving a 21.4% acceleration in end-to-end inference speed. Our research advances the limits of training-free approaches for efficient LLM inference, pushing the boundaries of achievable speedup without training.
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