Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (quant-ph) 2026-06-19

Charge-Conjugation Violation and Population Asymmetry in Bipartite Fermionic Lattices

arXiv:2606.06138v2 Announce Type: replace-cross Abstract: Charge conjugation violation (CCV) is a central concept in particle physics and appears also for quasiparticles in quantum many-body systems, which typically relies on an embedded external symmetry breaking to the underlying system. An open question is how an intrinsic CCV mechanism could emerge and what its macroscopic consequences would be. We establish sublattice kinks in bipartite fermionic lattices as a concrete setup showing intrinsic CCV. The intrinsic CCV of the sublattice kink is based on the graph-topological nature of the underlying Hamiltonian, with no explicit symmetry breaking taking place. It leads to a population asymmetry of different configurations and imprints a hidden leaf-like structure in the eigenenergy spectrum. The population asymmetry also leads to an imbalanced sublattice-kink production triggered by the vacuum-instability in the quench dynamics. Our work demonstrates the graph topology as the microscopic origin of intrinsic CCV, with the population asymmetry as the macroscopic consequence, of which the proposed setup is highly amenable to experimental implementation via cold-atom quantum simulators.

02.
arXiv (math.PR) 2026-06-15

Limiting partition function for the Mallows model: a conjecture and partial evidence

作者:

arXiv:2406.18855v2 Announce Type: replace Abstract: Let $S_n$ denote the set of permutations of $n$ labels. We consider a class of Gibbs probability models on $S_n$ that is a subfamily of the so-called Mallows model of random permutations. The Gibbs energy is given by a class of right invariant divergences on $S_n$ that includes common choices such as the Spearman foot rule and the Spearman rank correlation. Mukherjee in 2016 computed the limit of the (scaled) log partition function (i.e. normalizing factor) of such models as $n\rightarrow \infty$. Our objective is to compute the exact limit, as $n\rightarrow \infty$, without the log. We conjecture that this limit is given by the Fredholm determinant of an integral operator related to the so-called Schrödinger bridge probability distributions from optimal transport theory. We provide partial evidence for this conjecture, although the argument lacks a final error bound that is needed for it to become a complete proof.

03.
arXiv (CS.LG) 2026-06-18

Generalised Eigenvalue Geometry of Semantic Adversarial Attacks

arXiv:2606.19212v1 Announce Type: cross Abstract: Recent empirical work shows that semantically equivalent paraphrases can fool financial sentiment classifiers: although a paraphrase remains close to the original under a strong reference embedding, it may shift the target model's representation enough to change the predicted class. Existing robustness theory either assumes a single-model threat model or focuses mainly on empirical attack algorithms. We develop a continuous local model of semantic paraphrase perturbations that captures this two-model structure. We show that the worst-case local displacement of the target representation, subject to a proxy-model budget, is governed by the largest generalised eigenvalue of a matrix pencil $(A,B)$ constructed from the Jacobians of the two embedding maps. The resulting attackability index $\lambda^*(x)$ is intrinsic to the local paraphrase geometry and the chosen embedders, yields a closed-form prediction-flip condition for affine readouts, and supports conservative population and finite-sample attackability certificates. For uniform control over classes of affine readouts, we derive a distribution-free VC bound for binary attackability indicators and a scale-sensitive margin bound based on an attackability-adjusted margin that subtracts a local geometric penalty from the standard classifier margin. We also connect the continuous theory to discrete paraphrase search, identify an asymmetry between successful and unsuccessful finite searches, and give a covering condition under which the discrete and continuous settings agree. Finally, we propose an empirical verification framework using soft-token relaxations and generated paraphrase sets to assess the local eigenvalue geometry, prediction-flip condition, and finite-search approximation on a deployed financial-text classifier.

04.
arXiv (CS.LG) 2026-06-12

Design Criteria for SGD Preconditioners: Local Conditioning, Noise Floors, and Basin Stability

arXiv:2511.19716v2 Announce Type: replace-cross Abstract: Stochastic Gradient Descent (SGD) often slows in the late stage of training due to anisotropic curvature and gradient noise. We analyze preconditioned SGD in the geometry induced by a symmetric positive definite matrix $\mathbf{M}$, deriving bounds in which both the convergence rate and the stochastic noise floor are governed by $\mathbf{M}$-dependent quantities: the rate through an effective condition number in the $\mathbf{M}$-metric, and the floor through the product of that condition number and the preconditioned noise level. For nonconvex objectives, we establish a preconditioner-dependent basin-stability guarantee: when smoothness and basin size are measured in the $\mathbf{M}$-norm, the probability that the iterates remain in a well-behaved local region admits an explicit lower bound. This perspective is particularly relevant in Scientific Machine Learning (SciML), where achieving small training loss under stochastic updates is closely tied to physical fidelity, numerical stability, and constraint satisfaction. The framework applies to both diagonal/adaptive and curvature-aware preconditioners and yields a simple design principle: choose $\mathbf{M}$ to improve local conditioning while attenuating noise. Experiments on a quadratic diagnostic and three SciML benchmarks validate the predicted rate-floor behavior.

05.
arXiv (CS.CL) 2026-06-17

Moderating Illicit Online Image Promotion for Unsafe User-Generated Content Games Using Large Vision-Language Models

Online user generated content games (UGCGs) are increasingly popular among children and adolescents for social interaction and more creative online entertainment. However, they pose a heightened risk of exposure to explicit content, raising growing concerns for the online safety of children and adolescents. Despite these concerns, few studies have addressed the issue of illicit image-based promotions of unsafe UGCGs on social media, which can inadvertently attract young users. This challenge arises from the difficulty of obtaining comprehensive training data for UGCG images and the unique nature of these images, which differ from traditional unsafe content. In this work, we take the first step towards studying the threat of illicit promotions of unsafe UGCGs. We collect a real-world dataset comprising 2,924 images that display diverse sexually explicit and violent content used to promote UGCGs by their game creators. Our in-depth studies reveal a new understanding of this problem and the urgent need for automatically flagging illicit UGCG promotions. We additionally create a cutting-edge system, UGCG-Guard, designed to aid social media platforms in effectively identifying images used for illicit UGCG promotions. This system leverages recently introduced large vision-language models (VLMs) and employs a novel conditional prompting strategy for zero-shot domain adaptation, along with chain-of-thought (CoT) reasoning for contextual identification. UGCG-Guard achieves outstanding results, with an accuracy rate of 94% in detecting these images used for the illicit promotion of such games in real-world scenarios.

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

When Does Delegation Beat Majority? A Delegation-Based Aggregator for Multi-Sample LLM Inference

arXiv:2606.08098v2 Announce Type: replace Abstract: Majority voting over sampled answers is the dominant unsupervised aggregator for multi-sample LLM inference. In this paper, we show a delegation-based aggregator (Propagational Proxy Voting, PPV; Sakai et al., 2025) yields an unsupervised consensus rule that beats majority on MMLU-Pro by +1.5 pp overall and +2.24 pp on the non-trivial subset (paired McNemar p ~ 1.0e-14, n = 8,099). Majority discards two signals that every sample carries: within-group letter entropy and between-group reasoning geometry. PPV exposes per-voter levers that consume exactly these two signals: When (how much weight a voter keeps on its own pick) and Whom (how it splits the remainder across peers). We drive When with letter entropy and Whom with per-question-centered embedding cosine. Our method needs no gold labels and no auxiliary training: per-question, we partition 128 sampled generations into 16 groups, compute each group's letter-level semantic entropy and reasoning embedding centroid, and feed both into a stochastic delegation matrix whose stationary distribution selects the consensus answer. We walk through an example in which PPV overturns a clear 10-6 majority for the wrong letter: the 10-voter majority cluster is geometrically incoherent (mean within-cluster cosine -0.02) while the 6-voter minority is tight (+0.26), so propagated delegation mass concentrates on the minority's answer even though entropy alone would keep the majority ahead. We further report delegation strategies with negative results that constrain the design space for unsupervised LLM aggregation. No within-question ensemble of confidence modes closes the oracle gap.

07.
medRxiv (Medicine) 2026-06-22

Age-related changes in acoustic cue use for speech-in-speech perception

Acoustic cues such as pitch and spatial location allow listeners to attend to a target speaker and ignore competing talkers, aiding speech recognition in background noise. Diminished ability to utilize acoustic cues for speech stream segregation may thus contribute to older adults' challenges hearing in noise. Adults aged 18-74 completed a speech-in-speech identification task with three conditions containing 1) only pitch cues (fundamental frequency), 2) only spatial cues (interaural time differences; ITDs), and 3) both pitch and spatial cues for segregating a target talker from competing talkers. Hearing thresholds at standard and extended high frequencies (EHFs), auditory brainstem responses (ABRs), and digit span scores were acquired to examine the influence of sensory and cognitive factors on use of each acoustic cue for speech-in-speech recognition. Significant differences were observed between cue condition scores indicating that use of the available cue(s) drove performance. ABR metrics were not a significant predictor but digit span scores significantly predicted scores on all three cue conditions. Working memory abilities therefore set a baseline for participants' speech-in-speech recognition regardless of the acoustic content. Hearing thresholds at standard frequencies significantly predicted scores on the Pitch condition. EHF hearing thresholds better predicted Spatial and Both Cue condition performance, suggesting that EHF thresholds represent auditory processing important for coding ITDs. Age group analysis revealed that older adults (aged 40+) performed significantly more poorly on all cue conditions of the speech-in-speech recognition task relative to younger adults. Age-related changes in auditory sensory processing may therefore impair older adults' speech-in-noise perception by reducing their ability to use acoustic cues for segregating target and competing speech.

08.
arXiv (CS.AI) 2026-06-19

Thermodynamic Measure of Intelligence

arXiv:2606.20231v1 Announce Type: new Abstract: Can intelligence be measured? We propose that intelligence can be defined as the lawful amplification of rare but valid futures: a system increases the probability of outcomes that would be unlikely under passive dynamics but remain admissible under the constraints of the domain. We start with the premise that an intelligent system must model the world and its own place within it. Because the system is part of the world it models, this leads naturally to recursive self-simulation: the system represents futures in which its own actions are part of the trajectory. Our central results give a necessity statement and a conditional near-sufficiency statement connecting this architecture to a precise thermodynamic measure of lawful amplification of rare-valid futures: high rare-valid lift is impossible unless the internal simulation identifies rare-valid futures with high fidelity; conversely, when rare-valid fidelity is high and the simulation contains an effective policy, the achievable lift approaches the actuation-limited optimum. Thus recursive self-simulation is not merely a plausible feature of intelligence but, under the stated assumptions, is necessary and nearly sufficient for high thermodynamic intelligence. The resulting framework makes intelligence measurable on a universal scale, from passive matter and feedback controllers, large language models, and humans as text generators to Maxwell-demon-like information engines.

09.
arXiv (CS.CV) 2026-06-12

RepWAM: World Action Modeling with Representation Visual-Action Tokenizers

This work presents RepWAM, a representation-centric world action model (WAM) built on representation visual-action tokenizers. Existing WAMs typically inherit reconstruction-oriented video tokenizers from pretrained video generation models. Although these tokenizers preserve visual fidelity, pixel reconstruction alone provides limited guidance for learning instruction-following dynamics that connect future prediction with robot control. To address this, we explore a semantic visual-action latent space for representation-centric world action modeling. Specifically, we train a representation visual-action tokenizer that maps visual inputs into aligned visual and latent action tokens. We then pretrain our WAM to jointly model future visual states and the latent actions that connect them under language instructions, followed by adaptation to real robot trajectories for closed-loop manipulation. Experiments on real-world manipulation tasks and simulation benchmarks show that RepWAM delivers strong performance across diverse manipulation settings, while ablations highlight the value of semantic visual-action tokenization over reconstruction-oriented alternatives. These results establish representation visual-action tokenization as a promising foundation for world action models and a step toward generalist robot policies. Code and weights will be available at https://github.com/wdrink/RepWAM.

10.
arXiv (CS.LG) 2026-06-16

Stochastic trace estimation with tensor train random vectors

arXiv:2606.15679v1 Announce Type: cross Abstract: Stochastic trace estimation is a standard tool for approximating the trace of a large-scale matrix available only through matrix-vector products. However, in tensor-structured settings, unstructured Gaussian or Rademacher test vectors may be prohibitively expensive to store and compute with, while cheaper rank-one tensor-product vectors can require sample complexities that grow exponentially with the tensor order. This work studies Gaussian random tensor train vectors as a structured alternative for stochastic trace estimation. We show that, with a suitable choice of the tensor train rank, random tensor train vectors recover dimension-independent guarantees for the Girard–Hutchinson estimator. In particular, a median-of-means variant with tensor train rank $r \geq d-1$ achieves the same dependence on the accuracy $\varepsilon$ and failure probability $\delta$ as the classical estimator based on unstructured Gaussian vectors. We further prove an oblivious subspace injection result for sketches formed from independent Gaussian random tensor train vectors: tensor train rank $r\geq d-1$ and $\mathcal{O}(\varepsilon^{-2}(k+\log(1/\delta)))$ samples suffice for a $k$-dimensional target subspace. Finally, we investigate the use of such sketches within the Nystr\"{o}m++ framework. We show that the resulting estimator can achieve the desired $\mathcal{O}(\varepsilon^{-1})$ sample complexity under an additional spectral-tail condition. These results provide clarififcation on both the potential and the limitations of random tensor train vectors in stochastic trace estimation.

11.
arXiv (math.PR) 2026-06-16

Hua-Chen New Theory of Economic Optimization

arXiv:2504.19134v4 Announce Type: replace-cross Abstract: Between 1957-1985, Chinese mathematician Loo-Keng Hua pioneered economic optimization theory through three key contributions: establishing economic stability's fundamental theorem, proving the uniqueness of equilibrium solutions in economic systems, and developing a consumption-integrated model 50 days before his death. Since 1988, Mu-Fa Chen has been working on Hua's theory. He introduced stochastics, namely Markov chains, to economic optimization theory. He updated and developed Hua's model and came up with a new model (Chen's model) which has become the starting point of a new economic optimization theory. Chen's theory can be applied to economic stability test, bankruptcy prediction, product ranking and classification, economic prediction and adjustment, economic structure optimization. Chen's theory can also provide efficient algorithms that are programmable and intelligent. {Stochastics} is the cornerstone of Chen's theory. There is no overlap between Chen's theory, and the existing mathematical economy theory and the economics developments that were awarded Nobel Prizes in Economics between 1969 and 2024. The distinguished features of Chen's theory from the existing theories are quantitative, calculable, predictable, optimizable, programmable and can be intelligent. This survey provides a theoretical overview of the newly published monograph [5rw24]. Specifically, the invariant of the economic structure matrix, also known as the Chen's invariant, was first published in this survey.

12.
arXiv (quant-ph) 2026-06-16

Quantum-classical hybrid models based on error correction for time series forecasting

arXiv:2606.15213v1 Announce Type: new Abstract: Time series forecasting largely benefits from combining the strengths of different models, especially using a scheme where a model corrects another model by capturing supplementary patterns from forecasting errors. Concurrently, quantum models are providing a means to augment the classical capacity, including in time series forecasting, by acting alongside classical models in hybrid architectures. In this work, we propose the first forecasting system based on error correction that jointly uses quantum and classical models. Here, quantum models first extract patterns by exploring quantum phenomena, and classical models capture the remaining patterns from the quantum errors. Compared to classical single models and classical-classical hybrid models based on error correction, the complementary capacity that emerges from this quantum-classical system provided the best results in most of the addressed problems. Therefore, this work paves the way to introduce quantum models in established hybridization schemes for time series forecasting.

13.
arXiv (CS.CV) 2026-06-19

SA-VIS: Sparse frame Annotations for training Video Instance Segmentation

Recent online video instance segmentation (VIS) methods have achieved impressive results, thus becoming the preferred approach to segment instances in videos. Despite the resurgence of impressive single image models, the online (or semi-online) VIS approaches outperform single-image models (e.g., based on SAM) by using long sequences of densely annotated frames during training. However,such a training setup of VIS is expensive in the sense of compute as well as dense annotations required. In order to solve these major flaws, we argue that the effective modeling of the instances and their evolution in videos do not require densely annotated frames. To that end, we propose a simple and effective module, called Past-frames Feature Propagation (PFP) which aggregates low-dimensional features from the image encoder of multiple frames. This simple low-compute module provides tremendous learning capability in using sparse video frame labels for end-to-end training. Combined with a light-weight frame-specific Instance Queries, our Sparse frame Annotation VIS (SA-VIS) significantly improves performance over its baseline. Most interestingly, our simple design that avoids complexities effectively bridges the gap in accuracy between training on sparsely and densely annotated video sequences. This translates to a mere 0.4% drop in performance of SA-VIS when using annotations for only 1/5 of the images in the dataset. Empirically, SA-VIS shows strong improvements over the baseline on YouTube-VIS 2019/2021/2022 and Occluded VIS (OVIS) and an over 1% improvement in AP on the state-of-the-art in a limited annotations scenario.

14.
arXiv (CS.AI) 2026-06-19

When, Where, and How: Adaptive Binning for Tabular Self-Supervised Learning

arXiv:2606.19827v1 Announce Type: cross Abstract: Medical tabular data are ubiquitous in clinical research, but deep learning for tables remains underexplored because reliable labels often require costly expert adjudication, even though structured clinical variables are routinely available in tabular form. Self-supervised learning can leverage these unlabeled tables, and recent binning-based pretexts offer a promising inductive bias, but existing objectives fix a single global quantile discretization and apply feature-agnostic supervision. We propose Adaptive Binning, a training-adaptive discretization pretext for tabular SSL that couples discretization to learning through a feature-wise coarse-to-fine curriculum. Motivated by the spectral bias of neural networks and the principles of curriculum learning, our method progressively refines discretization per feature upon plateau detection and selects representation-aware splits to jointly improve value-space concentration and representation-space coherence. A heterogeneity-aware objective unifies categorical reconstruction with ordinal supervision for numerical features, and experiments on public medical tabular datasets under unified evaluation protocols show consistent gains for linear probing and fine-tuning without dataset-specific discretization tuning. We further introduce a medical tabular SSL benchmark with standardized protocols to support reproducible progress in this underexplored domain. Our code is available at https://github.com/labhai/Adaptive-Binning.

15.
arXiv (CS.LG) 2026-06-16

Filtered ANN as a Phase Transition: When Selectivity-Estimation Error Causes Plan Regret

arXiv:2606.16341v1 Announce Type: new Abstract: A filtered approximate-nearest-neighbor (ANN) query returns the k nearest vectors among those satisfying an attribute predicate P of selectivity s. The best execution strategy – pre-filter, post-filter, or in-filter – changes with s, so a system must estimate s and choose. We model this as an argmax over a landscape with phases (regions where each strategy wins) separated by boundaries, and show that selectivity-estimation error produces plan regret – recall lost versus the oracle strategy – only in the critical regions around those boundaries. The regret is a wedge of log-width equal to the multiplicative estimation error epsilon and height equal to the local cliff |V'(s*)| epsilon; the flip-margin 1/|V'(s*)| is the condition number of a sibling cardinality-estimation study reappearing as the local boundary theory. The two phase boundaries follow from independent mathematics: order statistics place the post-filter cliff at s ~ k/K, and site percolation places the in-filter cliff at s_c ~ 0.83/M for graph degree M (corpus-size independent). Criticality exists only under a constrained budget B < sqrt(k n). Under pre-registered decision rules we confirm, on synthetic sweeps and real SIFT1M, that regret concentrates ~290x at the boundary and that the regret curves obey a finite-size scaling collapse onto one universal wedge across two decades of corpus size. A real approximate index does not mis-locate the boundary, but a biased cost model opens a persistent miscalibration band that estimation-error robustness cannot fix. The contribution is a characterization, not a new index. Code and the full pre-registration are public.

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

A Security Analysis of Long-Horizon Agentic AI Systems: Threats, Evaluation, and Framework Development

arXiv:2606.14816v1 Announce Type: cross Abstract: This paper presents a structured analysis of security challenges in long-horizon agentic AI systems. The study reviews existing threats, evaluation approaches, attack propagation mechanisms, and security frameworks. A taxonomy of security threats and a framework for analyzing attack propagation are proposed to support future research in agentic AI security

17.
arXiv (CS.AI) 2026-06-19

Confidence Calibration for Multimodal LLMs: An Empirical Study through Medical VQA

arXiv:2606.19950v1 Announce Type: cross Abstract: Multimodal Large Language Models (MLLMs) show great potential in medical tasks, but their elicited confidence often misaligns with actual accuracy, potentially leading to misdiagnosis or overlooking correct advice. This study presents the first comprehensive analysis of the relationship between accuracy and confidence in medical MLLMs. It proposes a novel method that combines Multi-Strategy Fusion-Based Interrogation (MS-FBI) with auxiliary expert LLM assessment, aiming to improve confidence calibration in Medical Visual Question Answering (VQA). Experiments demonstrate that our method reduces the Expected Calibration Error (ECE) by an average of 40\% across three Medical VQA datasets, significantly enhancing MLLMs' reliability. The findings highlight the importance of domain-specific calibration for MLLMs in healthcare, offering a more trustworthy solution for AI-assisted diagnosis.

18.
medRxiv (Medicine) 2026-06-22

Burden of Cardiovascular Disease in Brazil, 1996-2023: A Retrospective Descriptive Study of the Epidemiology and Impact on Public Healthcare with Emphasis on Acute Myocardial Infarction

Background Cardiovascular diseases (CVD) are the leading cause of death worldwide, and their epidemiology is correlated with genetic predisposition, exposure to risk factors, sex, age, access to medical care, and other sociodemographic characteristics. Brazil is a developing country with a vast territory, which leads to structural inequalities. Estimates of CVD in Brazil, in its regions, and in its population are poorly evaluated and analysed. Methods We obtained CVD-related data from the Brazilian Unified Health System (SUS) and analysed mortality and morbidity from 1996 to 2023 by sex, race/ethnicity, age, and region. We calculated the risk of death from the most prevalent diseases, the average length of hospital stay, and the costs associated with heart transplantation. Findings In Brazil, acute myocardial infarction was the pathology that led to the highest number of deaths across all variables analysed during the evaluated period. Other CVD were also related to causes of death and morbidity, such as hypertensive diseases and heart failure. Interpretation Brazil presents a serious challenge to the public health system due to the high number of deaths and the progressive mortality rate. This study represents a fundamental contribution to the basis for formulating public health policies aimed at reducing the growing impact associated with these diseases. Funding CNPq, CAPES, FAPEMIG, INCT

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

Rethinking Air-Ground Collaboration: A Progressive Cross-Task Benchmark and Socialized Learning Framework

Air-ground collaborative perception is crucial for robust visual understanding in real-world dynamic environments. However, existing studies typically formulate collaboration as single-task cross-view fusion, overlooking the functional dependencies among localization, target association, and fine-grained parsing. In addition, the heterogeneous nature of aerial and ground views introduces substantial geometric, scale, and occlusion discrepancies, making uniform feature sharing vulnerable to negative transfer. To tackle these issues, we model air-ground perception as a progressive cross-task collaboration task and construct the Air-Ground Progressive Collaboration (AGPC) benchmark, a spatio-temporally aligned benchmark comprising more than 745K raw video frames. Built upon this benchmark, we propose Socialized Co-Perception (SCP), a coarse-to-fine framework that organizes collaboration progressively from aerial global localization to ground target association and identity-aware parsing. Its core module, the Dual-Layer Router (DLR), decouples input-side multi-scale expert selection from output-side task-conditioned modulation, enabling selective cross-view and cross-task interaction while suppressing harmful interference. Extensive experiments demonstrate the effectiveness of SCP. It achieves a 3.73\% coevolutionary gain and a 7.86\% improvement in average downstream performance. These results show that task-conditioned collaboration is more effective than uniform fusion for heterogeneous air-ground perception. The code is available at https://github.com/g1136639260-spec/AGSCP.

20.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

21.
arXiv (CS.LG) 2026-06-17

Eigen-Spike Emergence and Quadratic Equivalents for Conjugate Kernels on Nonlinearly Separable Data

arXiv:2605.29669v2 Announce Type: replace-cross Abstract: Recent work in random matrix theory (RMT) has developed the notion of deterministic equivalents: typically linear surrogate models that approximate the spectral behavior of large nonlinear random matrices, such as nonlinear feature maps in neural networks (NNs). Such equivalents make theoretical predictions tractable by reducing a complex model to a simpler one with properties that fall under the umbrella of classical RMT tools. However, this leaves open the question of whether this idealized linear equivalence remains meaningful for classification of high-dimensional nonlinearly separable data. Motivated by this, we consider the conjugate kernel (CK), which is the nonlinear feature map of a one-layer feedforward NN, under a canonical nonlinearly separable dataset for the XOR problem; and we use the study of informative outlier eigenvalues in the CK and whether their corresponding eigenvectors asymptotically align with XOR labels as a proxy for nonlinear learnability. We develop a robust quadratic equivalent of the CK matrix that enables a precise analysis of emergent informative spikes, as one modifies various knobs common in ML practice: sample complexity, signal-to-noise ratio (SNR), nonlinear activation choice, and pretrained features. We identify regimes in which these knobs move the CK beyond the linear equivalent and produce BBP-type transitions to label-aligned outlier eigenspaces. Our analysis helps bring deterministic-equivalence tools from RMT to bear on problems of practical relevance in ML.

22.
arXiv (CS.LG) 2026-06-11

Enhancing Spectral Embedding through Robust and Flexible Knowledge Transfer in Electronic Health Records

arXiv:2606.11570v1 Announce Type: cross Abstract: We propose a spectral-based, unsupervised representation learning framework to derive low-dimensional embeddings for clinical concepts and patients in rare disease cohorts from electronic health records, where data are high-dimensional but sample sizes are limited. To overcome this challenge, we incorporate a knowledge matrix extracted from a broader population that shares a partially overlapping subspace with the rare-disease cohort. Our method departs from existing approaches by relaxing restrictive one-to-one signal-alignment assumptions between the latent data matrix and knowledge matrix, allowing more flexible and realistic forms of structured sharing. We introduce a novel two-step spectral embedding procedure: first, we identify and remove irrelevant components from the knowledge matrix; then, we apply a projection-based method to separately recover shared and heterogeneous components. Simulations and an analysis of a real-world multiple sclerosis cohort show that the proposed method outperforms competing approaches, particularly in challenging scenarios where shared signals are weak and only partially aligned, as is common in rare-disease data.

23.
medRxiv (Medicine) 2026-06-12

Effect of tenofovir on the outcomes of COVID-19 in persons with chronic hepatitis B: a nationwide cohort study in Sweden.

Background: Patients with chronic hepatitis B (CHB) may have an increased risk of severe COVID-19. Tenofovir has been hypothesized to confer protection against severe disease, but evidence is inconclusive. We evaluated the risk of severe COVID-19 among CHB patients treated with tenofovir compared with other nucleos(t)ide analogues (NAs). Methods and findings: In this nationwide, registry-based cohort study, we included all adults with CHB and laboratory-confirmed COVID-19 in Sweden between February 2020 and July 2022. Data from national health and socioeconomic registers were linked using unique personal identification numbers (PINs). Patients with HIV, hepatitis C, or hepatitis D coinfection were excluded. Exposure was defined as tenofovir versus other NA therapy. The primary outcome was severe COVID-19, defined as hospitalization >2 days or death within 30 days of diagnosis. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI), controlling for age, sex, comorbidities, vaccination, socioeconomic status, and region of birth. Among 5,877 CHB patients with COVID-19, 672 were receiving NA therapy (437 tenofovir, 235 other NAs). Severe COVID-19 occurred in 8.0% of tenofovir-treated patients and 14.5% of those receiving other NAs (unadjusted OR 0.52; 95% CI, 0.31-0.85). After adjustment, the association was attenuated and no longer significant (aOR 0.72; 95% CI, 0.39-1.31). Older age, comorbidities, and unvaccinated status were strongly associated with severe disease. Conclusions: The apparent protective effect of tenofovir against severe COVID-19 in unadjusted analyses was largely explained by confounding factors. The risk of severe disease was primarily driven by age, comorbidities, and vaccination status. Prevention of severe COVID-19 in patients with CHB should instead focus on vaccination and management of comorbidities.

24.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

25.
arXiv (quant-ph) 2026-06-17

Quantum Chip Paradigm Framework

arXiv:2606.17899v1 Announce Type: new Abstract: Quantum Electronic Design Automation (Q-EDA) is emerging as quantum chips move from laboratory prototypes to scalable engineering systems. This paper argues that superconducting quantum chip design is approaching a "SPICE moment" similar to early classical EDA, where growing qubit scale, control complexity, frequency planning, packaging, process variation, and cryogenic measurement feedback require a shift from experience-based design to model-driven engineering. We propose a Quantum Chip Paradigm Framework that treats Q-EDA not only as software, but as part of the quantum chip development paradigm. Unlike classical HDL-first design, quantum chip design must begin with physical structures such as Josephson junctions, resonators, couplers, readout elements, control lines, and packaging environments. The framework emphasizes PCell-based modeling, SPICE-Q simulation, Quantum PDKs, and design-technology-measurement co-optimization. We further outline a hierarchical Q-EDA system spanning physical structures, qubit PCells, logical qubits, quantum arithmetic, functional quantum IP, and Quantum SoC systems. The key goal is to turn physical models, layout rules, simulation results, fabrication data, and measurement feedback into reusable and auditable engineering objects for large-scale quantum processors and fault-tolerant quantum computing.