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01.
arXiv (quant-ph) 2026-06-17

From Period Finding to Lattice Sampling: Experimental Insights into Shor's and Regev's Factoring Algorithms

arXiv:2606.17647v1 Announce Type: new Abstract: Quantum algorithms for integer factorization represent one of the most prominent applications of quantum computation, with far-reaching implications for modern cryptography. While Shor's algorithm provides a polynomial-time solution in the ideal quantum model, its practical implementation is severely constrained by the limitations of current noisy intermediate-scale quantum (NISQ) hardware. These constraints have motivated the exploration of alternative factoring algorithms with different structural and resource trade-offs. In this work, we present an experimental study of Regev's quantum factoring algorithm, implemented on real quantum hardware, and compare its behavior with that of Shor's algorithm under analogous conditions. Focusing on the case N = 15, we execute both algorithms on the QMIO quantum computer at the Centro de Supercomputacion de Galicia (CESGA) and contrast the results with one of IBM's open-access quantum computers and ideal simulations. This parallel execution enables a low-level comparison of the two algorithms, highlighting how their respective quantum implementations interact with hardware noise, limited circuit depth, and finite sampling. Our analysis emphasizes the different ways in which Shor's and Regev's algorithms encode arithmetic structure into quantum states through Fourier sampling in one and higher dimensions, respectively, and how these differences manifest in experimental outcomes. Although neither algorithm demonstrates a practical advantage in the small N regime, the results provide insight into their relative robustness and failure modes on contemporary quantum devices. This study illustrates the value of experimental benchmarking of alternative quantum factoring algorithms as a means of understanding the practical implications of algorithmic design choices in the NISQ era.

03.
arXiv (CS.CL) 2026-06-19

Group-Sparse Matrix Factorization for Transfer Learning of Word Embeddings

Unstructured text provides decision-makers with a rich data source in many domains, ranging from product reviews in retail to nursing notes in healthcare. To leverage this information, words are typically translated into word embeddings – vectors that encode the semantic relationships between words – through unsupervised learning algorithms such as matrix factorization. However, learning word embeddings from new domains with limited training data can be challenging, because the meaning/usage may be different in the new domain, e.g., the word ``positive'' typically has positive sentiment, but often has negative sentiment in medical notes since it may imply that a patient tested positive for a disease. In practice, we expect that only a small number of domain-specific words may have new meanings. We propose an intuitive two-stage estimator that exploits this structure via a group-sparse penalty to efficiently transfer learn domain-specific word embeddings by combining large-scale text corpora (such as Wikipedia) with limited domain-specific text data. We bound the generalization error of our transfer learning estimator, proving that it can achieve high accuracy with substantially less domain-specific data when only a small number of embeddings are altered between domains. Furthermore, we prove that all local minima identified by our nonconvex objective function are statistically indistinguishable from the global minimum under standard regularization conditions, implying that our estimator can be computed efficiently. Our results provide the first bounds on group-sparse matrix factorization, which may be of independent interest. We empirically evaluate our approach compared to state-of-the-art fine-tuning heuristics from natural language processing.

04.
medRxiv (Medicine) 2026-06-15

Cost-Performance Evaluation of Large Language Models for Aspect-Based Sentiment Analysis of HCAHPS Patient Comments: A Validation Study

Background: Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) free-text comments contain actionable feedback, but timely, scalable, and affordable sentiment analysis remains challenging for health systems that rely on third-party vendors. Objectives: To evaluate cost-performance tradeoffs between a cost-optimized and a flagship large language model (LLM) for aspect-based sentiment analysis of HCAHPS comments, using human inter-rater agreement as a reproducibility benchmark. Methods: We analyzed 512 free-text HCAHPS comments collected from two community hospitals in calendar year 2023. Six trained reviewers (medical students, recent medical graduates, and practicing internists) independently assigned positive, negative, or neutral labels to each comment-aspect pair; the majority label among three reviewers formed the consensus reference standard. Two OpenAI models - GPT-5-nano (cost-optimized) and GPT-5 (flagship) - were prompted in a zero-shot setting via the OpenAI API. We calculated pairwise Cohen's {kappa} to establish a human inter-rater baseline, then compared each model's labels to the consensus using Cohen's {kappa}, accuracy, weighted F1, and per-call cost and latency. Results: Mean human inter-rater agreement was {kappa} = 0.79 (substantial). Both LLMs exceeded this baseline (cost-optimized {kappa} = 0.85; flagship {kappa} = 0.85) with nearly identical accuracy (0.92) and weighted F1 (0.93 vs. 0.93). Performance was strong on positive (F1 ~ 0.97) and negative (F1 ~ 0.90) classes but poor on the underrepresented neutral class (F1

05.
arXiv (CS.LG) 2026-06-12

Loss-Shift Transfer via Bayes Quotients

arXiv:2606.13178v1 Announce Type: new Abstract: Transfer learning is usually studied as a consequence of distribution shift. This paper identifies an orthogonal failure mode in which the data distribution is fixed and the loss changes. This setting is called loss shift. A loss determines which information in \(X\) is Bayes-relevant, and two losses may therefore require different representations even under the same joint law \(P(X,Y)\). The idea is formalized using Bayes quotients, which allow losses to be ordered by refinement. In the Bayes-quotient formulation, strict refinement gives an immediate qualitative obstruction. A source-minimal representation for a coarser loss is insufficient for a strictly finer target loss. For finite-output log loss, this obstruction becomes an exact quantitative identity. The excess risk is the conditional information about \(Y\) discarded by the representation. Experiments in controlled, learned, synthetic-image, and real-image settings show the predicted effect, i.e., classification-equivalent representations can have different optimal log-loss performance under a fixed data distribution.

06.
arXiv (CS.AI) 2026-06-11

HiGR: Industrial-Scale Hierarchical Generative Slate Recommendation Framework in Tencent

arXiv:2512.24787v4 Announce Type: replace-cross Abstract: Slate recommendation, which presents users with a ranked item list in a single display, is ubiquitous across mainstream online platforms. While recent generative recommendation methods have shown strong potential in modeling item sequences with semantic IDs, directly applying them to industrial-scale slate recommendation faces a fundamental disconnect: entangled SID spaces confound high-level list planning, fine-grained autoregressive decoding over long sequences limits semantic planning efficiency, and token-level objectives misalign with holistic slate quality. In this paper, we propose HiGR, an industrial-scale hierarchical generative framework for slate recommendation that bridges this disconnect through a co-designed pipeline. First, HiGR learns structured SIDs via a Prefix-Contrastive Residual Quantized VAE (PCRQ-VAE). By enforcing high-level prefixes to capture shared semantics, PCRQ-VAE creates a controllable discrete space that acts as a prerequisite for efficient planning. Leveraging this structured space, our Hierarchical Slate Decoder (HSD) shifts autoregressive modeling from entangled token-level decoding to coarse-grained preference embeddings. This design significantly reduces inference latency while allowing explicit global slate structure planning. Finally, this stable planning space enables an ORPO-based listwise alignment mechanism to optimize triple-objective implicit feedback-ranking fidelity, genuine user interest, and diversity. Extensive offline experiments show that HiGR outperforms state-of-the-art baselines by over 10% in offline recommendation quality while achieving a $5\times$ inference speedup. Online A/B tests on Tencent platforms further improve watch time by 1.22% and video plays by 1.73%. HiGR has been deployed on multiple Tencent platform surfaces, serving hundreds of millions of users and proving its industrial-scale applicability.

07.
arXiv (CS.LG) 2026-06-18

Do Time Series Foundation Model Benchmarks Hide Regime-Dependent Failures? Evidence from Traffic Speed Forecasting

arXiv:2606.18367v1 Announce Type: new Abstract: Standard benchmarks evaluate time series foundation models (TSFMs) using aggregate metrics, but these can mask severe failures in critical operating regimes. We introduce regime-stratified evaluation and apply it to three TSFMs on two standard traffic speed benchmarks. Traffic exhibits abrupt regime switching between free-flow and congested states, producing bimodal speed distributions during transitions. When we stratify by traffic regime, both accuracy and prediction-interval coverage degrade sharply during transitions: transition-regime MAE reaches 11 mph (versus 3 mph overall), and empirical coverage of 90% prediction intervals drops as low as 55%. These failures are invisible in aggregate metrics because free-flow observations dominate the sample. A simple historical conditional baseline (sampling from per-sensor training distributions) achieves better transition coverage than any TSFM, but has far worse overall accuracy. We propose bimodal mixture augmentation (BMA), a post-hoc method that combines TSFM forecasts with historical distributional knowledge, approaching the historical baseline's transition coverage while preserving the TSFM's accuracy. Our results suggest that TSFM benchmarks should incorporate regime-aware evaluation to surface failures that aggregate metrics hide.

08.
bioRxiv (Bioinfo) 2026-06-19

StickForStats: automated statistical assumption validation for reproducible computational biology

Reproducible computational biology depends on statistical decisions that routine workflows often skip: verifying that a differential-expression test's assumptions hold across all genes, that a strategy-comparison ANOVA is robust to non-normality, or that a meta-analysis is not distorted by publication bias. Surveys consistently find that fewer than 20% of published biomedical studies report checking these assumptions, and existing statistical software leaves validation to the analyst as an optional step. We present StickForStats, an open-source web platform that reframes assumption validation as a default precondition for every analysis. Its Guardian system–a middleware pipeline of eight validators (normality, variance homogeneity, independence, outliers, sample size, modality, linearity, homoscedasticity)–checks assumptions before execution and, on critical violations, reroutes to an appropriate nonparametric alternative with a documented decision trail. At genome scale, applying Guardian to a 91-sample synovial-sarcoma RNA-seq study (GSE271517) cascaded 90.6% of 27,221 genes to a rank-based test and flipped the differential-expression verdict for 553 genes–479 rescued from an under-powered t-test and 74 outlier-driven false positives rejected–materially changing the gene list a biologist would act on. The same automatic validation generalizes across domains: a CRISPR editing-strategy comparison (ANOVA F = 1122, with Guardian recommending Kruskal-Wallis H = 36.6), an ordinal correlation (Pearson r = 0.476 corrected to Spearman {rho} = 0.479), and a sixteen-trial clinical meta-analysis revealing severe publication bias (Egger's t = -5.78, p < 0.001); a complementary module extends the same validators to published manuscripts, checking claims against CONSORT, STROBE, ICH-E9, and JARS-Quant reporting standards. By making assumption validation automatic and transparent, StickForStats targets a tractable, under-served contributor to irreproducibility. The platform is MIT-licensed, validated against SciPy and R, and freely available at https://github.com/visvikbharti/stickforstats_new.

09.
arXiv (CS.CV) 2026-06-16

Simulation-Based Multi-Fillet Evaluation of Woody Breast Poultry Fillets

Woody breast (WB) is a myopathy in modern broiler chickens that causes the breast muscle to become unusually stiff and fibrous, leading to decreased meat quality and significant economic losses. State-of-the-art automated WB detection relies on a side-view imaging system to analyze the bending behavior of a single fillet as it falls off a conveyor belt. While highly accurate, this approach is constrained by its single-fillet field of view, creating throughput bottlenecks on commercial processing lines. In this paper, we address this limitation via a novel multi-fillet detection architecture utilizing a top-down camera configuration. To validate our approach, we first develop a high-fidelity digital twin of an industrial conveyor system. Next, we synthesize a diverse dataset of 3D fillet meshes and model their viscoelastic bending dynamics using a physics-based simulation engine. Lastly, a continuous 2D shape deformation score is extracted from the top-down perspective as the simulated fillets traverse the roller precipice. Experimental results demonstrate that the top-down shape score effectively captures the contour changes of the fillets as it bends, providing a robust and scalable alternative to a side-view imaging system for simultaneous multi-fillet WB evaluation.

10.
arXiv (CS.LG) 2026-06-18

KANEL\'E: Kolmogorov-Arnold Networks for Efficient LUT-based Evaluation

arXiv:2512.12850v3 Announce Type: replace-cross Abstract: Low-latency, resource-efficient neural network inference on FPGAs is essential for applications demanding real-time capability and low power. Lookup table (LUT)-based neural networks are a common solution, combining strong representational power with efficient FPGA implementation. In this work, we introduce KANEL\'E, a framework that exploits the unique properties of Kolmogorov-Arnold Networks (KANs) for FPGA deployment. Unlike traditional multilayer perceptrons (MLPs), KANs employ learnable one-dimensional splines with fixed domains as edge activations, a structure naturally suited to discretization and efficient LUT mapping. We present the first systematic design flow for implementing KANs on FPGAs, co-optimizing training with quantization and pruning to enable compact, high-throughput, and low-latency KAN architectures. Our results demonstrate up to a 2700x speedup and orders of magnitude resource savings compared to prior KAN-on-FPGA approaches. Moreover, KANEL\'E matches or surpasses other LUT-based architectures on widely used benchmarks, particularly for tasks involving symbolic or physical formulas, while balancing resource usage across FPGA hardware. Finally, we showcase the versatility of the framework by extending it to real-time, power-efficient control systems.

11.
arXiv (CS.CL) 2026-06-12

One Polluted Page Is Enough: Evaluating Web Content Pollution in Generative Recommenders

Search-augmented LLMs increasingly mediate everyday consumer recommendations by retrieving live web content. This creates a new risk: generative recommenders may consume polluted web content, such as fake reviews and promotional pages crafted to mislead recommendations. We ask: to what extent do search-augmented LLMs become unwitting promoters of fake products when consuming polluted retrieval results? To answer this, we introduce FORGE (Fake Online Recommendations in Generative Environments), a benchmark for measuring fake-product promotion under controlled web-content pollution. Given an upstream search result, FORGE locally rewrites real products in retrieved web pages into fake ones to simulate web-content pollution, and measures how often the LLM recommends the fake product. FORGE covers 225 real-world products across 15 categories and 5 consumer scenarios. Across 12 commercial and open-weights LLMs, all models are vulnerable: a single polluted page yields fooled rates of up to 27%, while the full top-3 replacement raises this to 73.8%. Vulnerability varies substantially across categories, increasing when models lack stable prior knowledge of the relevant products. Reasoning does not mitigate this vulnerability; instead, it often generates spurious social proof to justify false recommendations. We evaluate three defenses: skepticism prompting and consensus filtering (over model priors or cross-document evidence). Skepticism can exacerbate vulnerability, much like reasoning, while filtering risks suppressing legitimate products. We release FORGE at https://github.com/leoluolol/forge-benchmark.

12.
arXiv (CS.CV) 2026-06-17

FUSER: Feed-Forward MUltiview 3D Registration Transformer and SE(3)$^N$ Diffusion Refinement

Registration of multiview point clouds conventionally relies on extensive pairwise matching to build a pose graph for global synchronization, which is computationally expensive and inherently ill-posed without holistic geometric constraints. This paper proposes FUSER, the first feed-forward multiview registration transformer that jointly processes all scans in a unified, compact latent space to directly predict global poses without any pairwise estimation. To maintain tractability, FUSER encodes each scan into low-resolution superpoint features via a sparse 3D CNN that preserves absolute translation cues, and performs efficient intra- and inter-scan reasoning through a Geometric Alternating Attention module. Particularly, we transfer 2D attention priors from off-the-shelf foundation models to enhance 3D feature interaction and geometric consistency. Building upon FUSER, we further introduce FUSER-DF, an SE(3)$^N$ diffusion refinement framework to correct FUSER's estimates via denoising in the joint SE(3)$^N$ space. FUSER acts as a surrogate multiview registration model to construct the denoiser, and a prior-conditioned SE(3)$^N$ variational lower bound is derived for denoising supervision. Extensive experiments on 3DMatch, ScanNet and ArkitScenes demonstrate that our approach achieves the superior registration accuracy and outstanding computational efficiency.

13.
arXiv (CS.AI) 2026-06-12

On Approximating the Dynamic Response of Synchronous Generators via Operator Learning: A Step Towards Building Deep Operator-based Power Grid Simulators

arXiv:2301.12538v2 Announce Type: replace-cross Abstract: This paper develops an Operator Learning framework for approximating the dynamic response of synchronous generators. The framework can be used to (i) build a neural network-based generator model that interacts with a power grid simulator or (ii) shadow the true generator's transient response. First, we develop a data-driven Deep Operator Network (DeepONet) to approximate the infinite-dimensional solution operator of the generators. Then, we design a numerical scheme based on DeepONet that simulates the generator's response over a given time horizon. The proposed scheme recursively employs the trained DeepONet to simulate the response for a given multi-dimensional input that describes the interaction between the generator and the power grid. In addition, we design a residual DeepONet numerical scheme that can incorporate information from existing mathematical models. We accompany this residual DeepONet scheme with an estimate for the prediction's cumulative error. Finally, we build a data aggregation (DAgger) strategy that allows fine-tuning of DeepONets using aggregated training data that the DeepONets will likely encounter during interactive simulations with other grid components. As a proof of concept, we demonstrate that the proposed frameworks can effectively approximate the transient model of a synchronous generator.

14.
arXiv (CS.AI) 2026-06-17

Conservation Laws for Modern Neural Architectures

arXiv:2606.17816v1 Announce Type: cross Abstract: Understanding gradient descent dynamics is key to explaining the success of over-parameterized models, where implicit bias manifests through conservation laws in gradient flow. While such laws are well understood for linear and ReLU networks, they remain largely unexplored for modern architectures. This work develops a unified framework to characterize conservation laws for contemporary models, including feedforward networks with GELU, SiLU, and SwiGLU activations, multihead attention with sinusoidal and rotary positional encodings, and Mixture-of-Experts architectures under diverse gating designs. Our theoretical findings are supported by experiments that validate the predicted invariants.

15.
arXiv (quant-ph) 2026-06-11

Fabricating fiber cavity mirror substrates compatible with high coupling efficiency

arXiv:2606.12168v1 Announce Type: cross Abstract: Fiber optical cavities offer small mode volumes and correspondingly strong light-matter interactions in an open Fabry-Perot geometry. However, existing fabrication techniques do not reliably produce substrates with surface profiles amenable to high mode matching between the cavity mode and fiber core, thereby limiting the achievable collection efficiency. Here we present a technique to fabricate fiber mirror substrates while using $in situ$ reflectometry to constrain the achievable mode matching prior to coating. By measuring the back-reflection from freshly cleaved fiber tips, we pre-select 138 fibers compatible with 96.5-99.5% mode matching, and after a single CO$_2$ laser ablation pulse, these fibers remained compatible with 95.3-99.2\%. This simple technique provides rapid feedback during each stage of substrate fabrication, greatly enhancing the yield of viable fiber mirror substrates prior to (expensive) coating runs.

16.
arXiv (CS.CL) 2026-06-17

An expressivity analysis of hierarchical modelling in deep transformers via bounded-depth grammars

Deep neural networks are widely believed to derive their expressive power from their ability to form hierarchical representations, capturing progressively more abstract and compositional features across layers. In language modeling, transformers have emerged as the dominant architecture, with early layers capturing local syntactic patterns and later layers encoding more complex clause-level dependencies. While this intuition has shaped model design, there remains a lack of rigorous theoretical work demonstrating how deep transformers represent such hierarchical structures. In this work, we analyze the expressiveness of deep transformer models through the formal lens of bounded-depth, non-recursive context-free grammars. For this class of grammars, we explicitly construct transformers with positional attention whose depth grows linearly with grammar depth, while the neuron count scales with the number of derivation-tree shapes and quadratically with the number of production rules. Our theoretical results support the linear representation hypothesis by demonstrating that these architectures possess the structural capacity to encode abstract grammatical states into low-dimensional, linearly separable subspaces within the residual stream.

17.
arXiv (CS.CL) 2026-06-16

Do You Really Need a GPU to Guard Your LLM? CPU-Class Classifiers and Multi-Stage Pipelines for Safety Enforcement at Scale

Safety classifiers that screen LLM inputs for jailbreak attempts have become standard deployment components, yet almost all production systems rely on GPU-based models: fine-tuned transformers and LLM-as-a-judge pipelines. These approaches impose significant per-query latency and infrastructure cost. Very little research has asked whether CPU-based classifiers, such as support vector machines and gradient-boosted trees trained on TF-IDF features, can match their accuracy across the conditions that production deployments encounter. We evaluate five CPU classifier families, Mamba-130M as an SSM-based GPU classifier, and transformer-based GPU models (DeBERTa-v3 and Gemma-2B with LoRA) across nine jailbreak sources and three regimes: in-distribution (D1), out-of-distribution (D2), and adversarially obfuscated (D3). On D1, the best CPU classifier matches the best transformer GPU model at roughly one-fifth the deployment cost. On D2, CPU classifiers fail via confident miscalibration, producing high-confidence false negatives that bypass escalation entirely. On D3, CPU classifiers outperform transformer GPU models by more than 26 percentage points in F1. Based on these complementary failure modes, we design GuardChain, a three-stage safety pipeline (Regex -> CPU -> GPU) that routes each prompt to the cheapest stage capable of a confident decision. The CPU stage alone resolves 80\% of in-distribution prompts at near-peak accuracy, and the GPU stage recovers the out-of-distribution failures. For practitioners deploying LLM safety at scale, this work provides evidence that GPU-class infrastructure is unnecessary for the majority of traffic.

18.
arXiv (CS.AI) 2026-06-19

TerraMind: Large-Scale Generative Multimodality for Earth Observation

arXiv:2504.11171v5 Announce Type: replace-cross Abstract: We present TerraMind, the first any-to-any generative, multimodal foundation model for Earth observation (EO). Unlike other multimodal models, TerraMind is pretrained on dual-scale representations combining both token-level and pixel-level data across modalities. On a token level, TerraMind encodes high-level contextual information to learn cross-modal relationships, while on a pixel level, TerraMind leverages fine-grained representations to capture critical spatial nuances. We pretrained TerraMind on nine geospatial modalities of a global, large-scale dataset. In this paper, we demonstrate that (i) TerraMind's dual-scale early fusion approach unlocks a range of zero-shot and few-shot applications for Earth observation, (ii) TerraMind introduces "Thinking-in-Modalities" (TiM) – the capability of generating additional artificial data during finetuning and inference to improve the model output – and (iii) TerraMind achieves beyond state-of-the-art performance in community-standard benchmarks for EO like PANGAEA. The pretraining dataset, the model weights, and our code are open-sourced under a permissive license.

19.
arXiv (CS.CL) 2026-06-18

Redact or Keep? A Fully Local AI Cascade for Educational Dialogue De-Identification

Educational dialogue is a valuable but sensitive resource for research: the same transcripts that capture authentic learning often capture personally identifiable information (PII) entangled with curricular content, where "Riemann" may refer to a real student or to a mathematical concept. Existing approaches force a tradeoff between governance and accuracy. Commercial Large Language Models (LLMs) can handle this ambiguity but require sending student data to third parties, while local named entity recognition (NER) systems preserve governance but over-redact curricular terms. We propose a fully local cascade framework that reframes de-identification from open-ended entity recognition to constrained privacy triage. A recall-first union proposer combines two lightweight encoders with deterministic rules to over-generate candidate spans; a context-aware reviewer then makes a binary Redact/Keep decision for each candidate using surrounding dialogue and speaker role. We evaluate three reviewer configurations against same-family LLM-only baselines and a commercial API on math tutoring transcripts from two large platforms. The strongest local configuration reaches 0.958 macro F1, compared with 0.767 for a same-family LLM-only baseline and 0.706 for the commercial API, while running entirely on a single laptop. On a targeted challenge set of curricular-personal name ambiguity, the same configuration degrades by only 0.03 F1 versus 0.19 to 0.25 for smaller reviewers. These results suggest that for educational de-identification, problem formulation matters more than model scale.

20.
arXiv (CS.CV) 2026-06-12

What's Old is New Again: Classical Dimensionality Reduction for Efficient Saliency-Guided Biometric Attack Detection

Saliency-guided training is a paradigm in visual recognition that encourages models to focus on the most relevant image regions during learning. While its application in biometric presentation attack detection (PAD) has shown strong benefits in robustness and generalization, adoption is often limited by the high cost, domain specificity, and limited scalability of existing saliency acquisition methods, such as human annotations over a limited dataset. We present a novel, cost-efficient, and highly-scalable approach to saliency acquisition using maps inspired by classical dimensionality reduction techniques: PCA and LDA. Our proposed methods generate saliency maps directly from raw training data, requiring no human annotation nor domain knowledge. We contextualize the effectiveness of these saliency sources in three saliency-explored domains (iris PAD, synthetic face detection, fingerprint PAD) and demonstrate its scalability in two saliency-novel domains (fingerprint vein PAD and ID card PAD). Across all domains tested, models trained using dimensionality reduction-sourced saliency maps exceed baseline and sometimes SOTA saliency methods without any resource investment or domain-specific tooling. Our findings overcome an important yet unaddressed barrier to saliency-guided training for biometric attack detection and beyond.

21.
medRxiv (Medicine) 2026-06-12

Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk

Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 significant cell-type-specific CpG sites in 106 loci and 68 risk genes in 40 loci, including 26 previously unreported loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-{beta} signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.

22.
arXiv (CS.AI) 2026-06-16

Unifying Acoustic Features and Text with Multimodal LLMs for Neurodegenerative Screening

arXiv:2606.14788v1 Announce Type: cross Abstract: Voice-based screening offers a scalable and non-invasive way to assess neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), but their staging remains challenging due to the difficulty of integrating heterogeneous data. This paper presents NeurMLLM, an efficient multimodal generative framework for neurodegenerative disease staging. NeurMLLM first encodes the spectrograms and Mel-frequency cepstral coefficients of audio data with vision transformers and projects their representations into the embedding space of a large language model (LLM), where they are concatenated with transcript and demographic instruction tokens as a single unified sequence. The LLM is then instruction-tuned via Low-Rank Adaptation using task prompts to autoregressively predict a constrained label token, enabling a generative classification. By evaluating on the Bridge2AI-Voice dataset for fine-grained staging of AD and PD, we observe that NeurMLLM achieves strong performance, consistently outperforming classical machine learning methods and existing LLM-based approaches. The results show the high potential of multimodal LLMs in neurodegenerative disease staging, improving staging accuracy and supporting accessible deployment.

23.
arXiv (CS.AI) 2026-06-19

Interpretable and Verifiable Hardware Generation with LLM-Driven Stepwise Refinement

arXiv:2606.19387v1 Announce Type: cross Abstract: Large language models (LLMs) have achieved remarkable success in software development. However, they are susceptible to hallucinations, meaning that they can introduce subtle semantic and logical errors. Due to the high stakes in chip design and manufacturing, hardware engineers are still reluctant to rely on LLMs for register-transfer level (RTL) generation. In this paper, we propose a hardware generation framework that combines the creativity and broad knowledge of LLMs with the explainability and mathematical rigor of formal methods. Specifically, we devise a set of transformation rules that cover various design decisions and hardware features. By iteratively applying these rules, an LLM agent can convert a design specification into an RTL program with guaranteed correctness. Experimental results demonstrate the effectiveness and efficiency of the framework.

24.
Nature Medicine 2026-06-08

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial

Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg−1) or tirzepatide plus placebo. At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16 weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63−86%)) and 36 of 51 (71% (57−81%)) participants experiencing an AE, respectively. Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0−10%)) participants in each arm. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier: NCT06445075 . In the phase 2 EMBRAZE study, participants receiving tirzepatide and apitegromab lost less lean mass compared to participants receiving tirzepatide and placebo.

25.
arXiv (CS.CL) 2026-06-17

ART: Attention Run-time Termination for Efficient Large Language Model Decoding

Long-context decoding in Large Language Models (LLMs) is constrained by the cost of accessing and processing the Key-Value (KV) cache. Despite evidence that attention outputs depend jointly on keys and values, most existing KV management methods rely on key-only pruning, since incorporating values incurs prohibitive overhead. In this paper, we propose Attention Run-time Termination (ART), a lightweight run-time mechanism that tracks accumulated attention outputs during kernel execution and terminates subsequent KV block accesses once further contributions become negligible. Rather than replacing KV selection, ART dynamically terminates redundant KV traversal on top of existing dense or sparse attention policies. We introduce a stability-based criterion that monitors both magnitude and directional changes of intermediate attention outputs and provideds a theoretical characterization of the resulting truncation error. Experiments on the LongBench and RULER Needle-in-a-Haystack tasks show that ART increases the generation throughput of existing KV-cache methods by up to 20%, without compromising the result quality.