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01.
arXiv (quant-ph) 2026-06-25

Feasibility-driven QAOA with penalty scheduling

arXiv:2606.25117v1 Announce Type: new Abstract: Most available quantum algorithms address constrained optimization problems by treating constraints as soft penalty terms within a QUBO formulation. This approach requires careful adjustment of the penalty coefficients, which scales poorly with the number of constraints and lacks a proper strategy to balance feasibility and solution quality. In this work, we introduce two extensions of standard linear-ramp QAOA (lr-QAOA) tailored to problems with multiple heterogeneous constraints. We first construct $\Lambda$-lr-QAOA, in which each penalty term is assigned its own linear-ramp schedule, promoting penalty weights from external hyperparameters to internal variational parameters of QAOA, similarly to the objective and mixer parameters. By optimizing all schedules jointly in a single run, this approach eliminates nested penalty tuning and scales more efficiently to multiple constraints. The optimization is guided by a feasibility-driven loss function that pushes the quantum state towards high-quality feasible solutions. As a further refinement, we introduce piecewise-ramp QAOA, in which the linear ramps are replaced by two-segment piecewise schedules, enhancing the expressiveness of the Ansatz at the cost of a small parameter overhead independent of the circuit depth. We benchmark both methods on Earth-observation satellite mission planning tasks formulated as budget-constrained Maximum Weight Independent Set problems. Numerical results show that piecewise-ramp QAOA consistently outperforms lr-QAOA and $\Lambda$-lr-QAOA across circuit depths and system sizes. Furthermore, both $\Lambda$-lr-QAOA and piecewise-ramp QAOA exhibit a high feasibility rate, which is crucial in industrial applications. Our analysis highlights an intrinsic feasibility-optimality trade-off, which we address by introducing a filtered variant of the loss providing a single hyperparameter to tune this balance.

02.
arXiv (CS.CV) 2026-06-15

SMART: Scalable Mesh-free Aerodynamic Simulations from Raw Geometries using a Transformer-based Surrogate Model

Machine learning-based surrogate models have emerged as more efficient alternatives to numerical solvers for physical simulations over complex geometries, such as car bodies. Many existing models incorporate the simulation mesh as an additional input, thereby reducing prediction errors. However, generating a simulation mesh for new geometries is computationally costly. In contrast, mesh-free methods, which do not rely on the simulation mesh, typically incur higher errors. Motivated by these considerations, we introduce SMART, a neural surrogate model that predicts physical quantities at arbitrary query locations using only a point-cloud representation of the geometry, without requiring access to the simulation mesh. The geometry and simulation parameters are encoded into a shared latent space that captures both structural and parametric characteristics of the physical field. A physics decoder then attends to the encoder's intermediate latent representations to map spatial queries to physical quantities. Through this cross-layer interaction, the model jointly updates latent geometric features and the evolving physical field. Extensive experiments show that SMART is competitive with and often outperforms existing methods that rely on the simulation mesh as input, demonstrating its capabilities for industry-level simulations.

03.
arXiv (CS.CL) 2026-06-17

Olmo Hybrid: From Theory to Practice and Back

Recent work has demonstrated the potential of non-transformer language models, especially linear recurrent neural networks (RNNs) and hybrid models that mix recurrence and attention. Yet there is no consensus on whether the potential benefits of these new architectures justify the risk and effort of scaling them up. To address this, we provide evidence for the advantages of hybrid models over pure transformers on several fronts. First, theoretically, we show that hybrid models do not merely inherit the expressivity of transformers and linear RNNs, but can express tasks beyond both, such as code execution. Putting this theory to practice, we train Olmo Hybrid, a 7B-parameter model largely comparable to Olmo 3 7B but with the sliding window layers replaced by Gated DeltaNet layers. We show that Olmo Hybrid outperforms Olmo 3 across standard pretraining and mid-training evaluations, demonstrating the benefit of hybrid models in a controlled, large-scale setting. We find that the hybrid model scales significantly more efficiently than the transformer, explaining its higher performance. However, its unclear why greater expressivity on specific formal problems should result in better scaling or superior performance on downstream tasks unrelated to those problems. To explain this apparent gap, we return to theory and argue why increased expressivity should translate to better scaling efficiency, completing the loop. Overall, our results suggest that hybrid models mixing attention and recurrent layers are a powerful extension to the language modeling paradigm: not merely to reduce memory during inference, but as a fundamental way to obtain more expressive models that scale better during pretraining.

04.
arXiv (CS.CL) 2026-06-25

Scaling Laws for Agent Harnesses via Effective Feedback Compute

Agent harnesses shape language-model performance by controlling tool use, feedback, verification, memory, and repair. Yet raw test-time expenditure, such as tokens, tool calls, wall time, or cost, cannot distinguish useful feedback from redundant or unstable interaction. We introduce Effective Feedback Compute (EFC), a trace-level scaling coordinate for informative, valid, non-redundant, and retained feedback. We further define Estimated-EFC, NRS-EFC, harness efficiency $\eta$, and task-demand normalization for realistic traces and heterogeneous tasks. Across synthetic, real, held-out, and prospective evaluations, EFC-based coordinates outperform raw-compute baselines and SAS. Oracle-EFC/$D_{\mathrm{task}}$ reaches $R^2=0.99$ in controlled scaling, and NRS-EFC/$D_{\mathrm{task}}$ reaches $R^2=0.93$ on real traces where raw compute has near-zero or negative fit. Finally, \ours uses EFC as a companion control layer for existing harnesses, improving mean pass rate from $61.2\%$ to $68.2\%$ while reducing mean raw cost from $213.8$ to $85.1$ under matched settings. These results suggest that harness scaling depends on durable, task-sufficient feedback rather than raw computation alone.

05.
arXiv (quant-ph) 2026-06-16

Experimental quantum state learning with pairs of photons

arXiv:2606.16932v1 Announce Type: new Abstract: Tomography allows one to estimate the density matrix describing the state an ensemble of quantum systems are prepared in (for example, polarization tomography determines the polarization state of a beam of identically prepared photons). In general, it is not possible to uniquely decompose the density matrix into its pure state components. Agarwal et al. proposed a protocol which, for a mixture composed of any two pure states of a qubit (with arbitrary probabilities), allows an observer to infer not only the density matrix but the identity of those specific pure states and their weights - the additional requirement being that the qubits arrive in pairs, where both qubits in each pair are in the same state. We experimentally demonstrate this learning-from-pairs concept using photons in the polarization degree of freedom. We use tomography to measure a sequence of single photons and make use of their time-of-arrival information to 'pair up' the photons after the measurement. From here we are able to infer the photons' polarization states and their respective probabilities, and we demonstrate this for various different choices of polarization states and ratios. Finally, we investigate our ability to discriminate between two equal mixtures of distinct pairs of orthogonal polarization states. We find that on the order of approx. 10e4 photons is typically enough to achieve tomography fidelities of approximately 0.9999. This is sufficient to discriminate between two different preparations of the same mixed state, differing by angles of less than 5 degrees between the pure states used in the two preparations.

06.
arXiv (CS.LG) 2026-06-24

Closing the Loop: Formally Verified Law as a Reward Signal for Self-Improving Legal AI

arXiv:2606.23913v1 Announce Type: new Abstract: This article develops an architecture that creates a formally verifiable reward signal to train legal AI, adapting the LLM proposes, verifier disposes paradigm from mathematical AI to the distinctive demands of law. We present an architecture comprising LLM-driven autoformalization into a formal legal calculus extending Catala, a verification kernel, and explanation generation grounded in formal proof traces. For the computational components of law, the architecture provides provable correctness. For open-textured legal analysis, it provides structural guarantees: every required stage of the legal argument is addressed, argumentation is exercised at the correct stages and not omitted, and the deductive links between steps are valid. We demonstrate the architecture on procedural deadline calculations in German law, Commerce Clause analysis in U.S. constitutional law, and cross-jurisdictional sanction proportionality. We further show that the same architecture has a structural advantage for legal AI training: a deterministic external verifier supplies verifiable outcomes for legal problems and thereby closes the traditional reinforcement-learning loop gap in law.

07.
arXiv (CS.AI) 2026-06-16

User as Code: Executable Memory for Personalized Agents

作者:

arXiv:2606.16707v1 Announce Type: new Abstract: A personalized AI agent needs a user memory: a persistent model of who the user is, built across many conversations and consulted on each new one. Today this memory is almost always stored as unstructured text, a knowledge graph, or a flat store of facts, and consulted by retrieval – fetching the entries most similar to the current request. Such "bag-of-facts" memory recalls individual facts well, but because storing a fact and acting on it are separate steps, it struggles to resolve contradictions, aggregate over many records, or enforce rules. We argue that user memory should instead be executable. We introduce User as Code (UaC), a paradigm in which an agent's model of a user is a living software project: typed Python objects hold the user's state and ordinary Python functions encode the rules that govern it, so representing and reasoning about the user happen in one medium an interpreter can run. The enabling mechanism is a two-phase pipeline: an append-only log that never discards a fact, periodically checkpointed into typed code. This changes what memory can do. On standard long-term conversation benchmarks, UaC matches both a full-context upper bound and the strongest prior memory systems on recall (78.8% on LOCOMO). Its advantage emerges where representation matters most. On aggregate questions over a user's history – "how many international trips did I take last year?" – retrieval-based memory collapses (6-43%) while UaC stays near-perfect (99%), because the answer is a one-line computation over typed state rather than a search over text. And because its rules execute deterministically whenever the state changes, UaC can surface unsolicited, safety-critical alerts – such as a newly prescribed drug that conflicts with an allergy recorded months earlier – a capability query-driven memory cannot provide.

08.
arXiv (CS.LG) 2026-06-25

Efficient Adaptive Data Acquisition via Pretrained Belief Representations

arXiv:2606.25197v1 Announce Type: new Abstract: Learning effective policies for adaptive data acquisition remains challenging: posterior-based methods rely on surrogate models and posterior approximations that can be misspecified or biased, while direct policy-learning methods map from historical observations and fail to exploit available model representations, making learning harder. We introduce policy learning with belief representations (POLAR), based on the insight that optimal data acquisition depends on the observation history only through a sufficient belief state. Specifically, POLAR decouples representation learning from policy learning by leveraging pretrained predictive foundation models as belief-state encoders, training a policy head on top of their representations. This yields a simple, unified amortised policy learning framework for Bayesian experimental design, Bayesian optimisation, and active learning, differing only in the task-specific utility used to train the policy. Empirically, we find that POLAR outperforms state-of-the-art amortised methods across diverse tasks while requiring far fewer training samples, demonstrating a significant step in the scalability and efficiency of amortised data acquisition.

09.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

10.
arXiv (quant-ph) 2026-06-24

Controlled Chaos in 4D SCFTs

arXiv:2606.23785v1 Announce Type: cross Abstract: Chaotic dynamics play an important role in a number of physical systems. One of the qualitative hallmarks of this behavior is the appearance of a sufficiently "complex" spectrum of energy levels. This also makes it challenging to directly verify the onset of chaos in interacting quantum field theories. We present a class of 4D superconformal field theories (SCFTs) given by orbifolds of 4D $\mathcal{N} = 4$ Super Yang–Mills theory in which operator mixing in a controlled subsector is described by an effective spin chain in one spatial dimension with nearest neighbor interactions tuned by the marginal couplings of the SCFT. Tuning the marginal couplings results in a chaotic spectrum, while generically the spin chain exhibits Anderson localization. We diagnose the onset of chaos by analyzing the statistical distribution of eigenvalues of the dilatation operator, in particular properties such as eigenvalue level repulsion, spectral rigidity, and the spectral form factor. We also show that other diagnostics such as Krylov complexity sometimes do not faithfully capture this information. This structure defines a chaotic billiard in the target space of the stringy realization. We also comment on the large $N$ holographic dual description, where the controlled single spin chain approximation must be supplemented by multi-trace dynamics, i.e., the splitting and joining of multiple spin chains.

11.
arXiv (CS.LG) 2026-06-24

HyMaTE: A Hybrid Mamba and Transformer Model for EHR Representation Learning

arXiv:2509.24118v2 Announce Type: replace Abstract: Electronic health Records (EHRs) have become a cornerstone in modern-day healthcare. They are a crucial part for analyzing the progression of patient health; however, their complexity, characterized by long, multivariate sequences, sparsity, and missing values poses significant challenges in traditional deep learning modeling. While Transformer-based models have demonstrated success in modeling EHR data and predicting clinical outcomes, their quadratic computational complexity and limited context length hinder their efficiency and practical applications. On the other hand, State Space Models (SSMs) like Mamba present a promising alternative offering linear-time sequence modeling and improved efficiency for handling long sequences, but focus mostly on mixing sequence-level information rather than channel-level data. To overcome these challenges, we propose HyMaTE (A Hybrid Mamba and Transformer Model for EHR Representation Learning), a novel hybrid model tailored for representing longitudinal data, combining the strengths of SSMs with advanced attention mechanisms. By testing the model on predictive tasks on multiple clinical datasets, we demonstrate HyMaTE's ability to capture an effective, richer, and more nuanced unified representation of EHR data. Additionally, the interpretability of the outcomes achieved by self-attention illustrates the effectiveness of our model as a scalable and generalizable solution for real-world healthcare applications. Codes are available at: https://github.com/healthylaife/HyMaTE.

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

TrustErase: Auditable Instant Machine Unlearning with Passport-Embedded Representations

arXiv:2606.17122v1 Announce Type: cross Abstract: The demand for privacy-compliant AI has amplified the need for machine unlearning; yet, existing retraining or distillation-based methods remain unverifiable and computationally costly. We introduce TrustErase, a verifiable, data-free unlearning framework leveraging passport-embedded representations for instant, modular, and auditable forgetting. By treating passports as cryptographic keys within parameter-efficient adaptation layers, TrustErase enables the removal of specific classes or datasets through simple deactivation, without retraining, fine-tuning, or access to the original data. A singular value based decomposition conceals passports within model weights, ensuring that unlearning actions remain transparent and provably compliant. Evaluations on MNIST, CIFAR10 and CIFAR100 show that TrustErase matches or exceeds state-of-the-art benchmarks such as DELETE, L2UL, and Boundary Shrink, while operating in a strictly data-free regime. Ultimately, TrustErase establishes a new paradigm for trustworthy, accountable, and instantly forgettable AI systems.

13.
arXiv (CS.CV) 2026-06-18

Semantic Robustness Certification for Vision-Language Models

Vision-language models (VLMs) are now widely used in downstream tasks. However, real-world applications often expose VLMs to distribution shifts induced by semantic variation (e.g., shape, size, and style). Robustness certification determines if a model's prediction changes when transformations are applied to its input. While most certification frameworks study geometric or pixel-level transformations over inputs, this work proposes a novel framework that enables certifying VLM robustness under semantic-level transformations. Leveraging the open-vocabulary capability of VLMs, we use text prompts as semantic proxies to construct transformations parameterized by an extent that controls the degree of semantic variation. By characterizing the VLM decision boundary in closed form, our framework quantitatively certifies extent intervals for which the predicted class remains unchanged under the semantic transformation. Our framework is the first to certify VLM robustness under semantic-level variations without requiring additional data for each variation, making it practical to apply. Experiments on both synthetic and real-world data show that our framework enables certifying robustness under diverse semantic variations across scenarios.

14.
arXiv (CS.CL) 2026-06-11

Short Chains, Deep Thoughts: Balancing Reasoning Efficiency and Intra-Segment Capability via Split-Merge Optimization

While Large Reasoning Models (LRMs) have demonstrated impressive capabilities in solving complex tasks through the generation of long reasoning chains, this reliance on verbose generation results in significant latency and computational overhead. To address these challenges, we propose CoSMo (Consistency-Guided Split-Merge Optimization), a framework designed to eliminate structural redundancy rather than indiscriminately restricting token volume. Specifically, CoSMo utilizes a split-merge algorithm that dynamically refines reasoning chains by merging redundant segments and splitting logical gaps to ensure coherence. We then employ structure-aligned reinforcement learning with a novel segment-level budget to supervise the model in maintaining efficient reasoning structures throughout training. Extensive experiments across multiple benchmarks and backbones demonstrate that CoSMo achieves superior performance, improving accuracy by 3.3 points while reducing segment usage by 28.7\% on average compared to reasoning efficiency baselines.

15.
arXiv (CS.CV) 2026-06-18

Recognizing and Reconstructing a Multi-Unit Floor Plan

Digital twins have a major potential to form a significant part of urban management in emergency planning, as they allow more efficient designing of the escape routes, better orientation in exceptional situations, and faster rescue intervention. Nevertheless, creating the twins still remains a largely manual effort, due to a lack of 3D-representations, which are available only in limited amounts for some new buildings. Thus, in this paper we aim to synthesize 3D information from commonly available 2D architectural floor plans. We propose two novel pixel-wise segmentation methods based on the MDA-Unet and MACU-Net architectures with improved skip connections, an attention mechanism, and a training objective together with a reconstruction part of the pipeline, which vectorizes the segmented plans to create a 3D model. The proposed methods are compared with two other state-of-the-art techniques and several benchmark datasets. On the commonly used CubiCasa benchmark dataset, our methods have achieved the mean F1 score of 0.86 over five examined classes, outperforming the other pixel-wise approaches tested. We have also made our code publicly available to support research in the field.

16.
arXiv (CS.CL) 2026-06-19

DeFrame: Debiasing Large Language Models Against Framing Effects

As large language models (LLMs) are increasingly deployed in real-world applications, ensuring their fair responses across demographics has become crucial. Despite many efforts, an ongoing challenge is hidden bias: LLMs appear fair under standard evaluations, but can produce biased responses outside those evaluation settings. In this paper, we identify framing – differences in how semantically equivalent prompts are expressed (e.g., "A is better than B" vs. "B is worse than A") – as an underexplored contributor to this gap. We first introduce the concept of "framing disparity" to quantify the impact of framing on fairness evaluation. By augmenting fairness evaluation benchmarks with alternative framings, we find that (1) fairness scores vary significantly with framing and (2) existing debiasing methods improve overall (i.e., frame-averaged) fairness, but often fail to reduce framing-induced disparities. To address this, we propose a framing-aware debiasing method that encourages LLMs to be more consistent across framings. Experiments demonstrate that our approach reduces overall bias and improves robustness against framing disparities, enabling LLMs to produce fairer and more consistent responses.

17.
medRxiv (Medicine) 2026-06-16

Physiological Aging of the Respiratory System (PARS): from development to application

Background: Aging has a critical role in lung changes and the outcome of lung disease. Several lung aging equations have been proposed to measure deviation from physiological aging of the respiratory system. In this study, we aimed to develop a single measure of accelerated lung aging and show its application as a measure of lung aging. Method: We used a pre-bronchodilator pulmonary function test (PFT) from NHANES adult participants recruited from 2007 to 2011. We applied Klemera-Dubal Method (KDM) to four PFT measurements, FEV1, FVC, FEF25-75, and PEF, to calculate a measure of lung biological aging. Physiological Aging of the Respiratory System (PARS) was calculated from the residual method vs. chronological age. We tested the construct validity of PARS by measuring its association with risk factors of lung health. The prognostic validity was measured using a survival analysis. Sampling weights were applied to all analyses. Results: In 14,123 adult participants, the mean (SD) of accelerated lung age (PARS) was 0 (8.2) years. Participants with a history of asthma and emphysema had 4- and 10-year higher PARS. Cigarette smoking, lower socioeconomic status, black race, higher serum cadmium, and lower serum selenium and magnesium were associated with higher PARS. During 116 months of follow-up, PARS was associated with a higher mortality (HR = 1.06, 95%CI: 1.05-1.07 per year). Females with higher PARS had a higher risk of death (P for interaction < 0.001). Results were consistent across different subgroups and sensitivity analyses. Conclusion: PARS is a noninvasive lung aging marker and can be applied as a single measure of lung accelerated aging in the adult population. Its strong construct and predictive validity support its future application among different populations with and without lung disease.

18.
bioRxiv (Bioinfo) 2026-06-18

A Two-Stage Interpretable Framework for Predicting Plant-Derived Small RNA Targets on Human 3'UTRs

作者:

Can plant-derived small RNAs target human mRNA 3'UTRs via complementary base pairing and produce experimentally detectable regulatory effects? This question concerns not only the fundamental feasibility of cross-kingdom RNA regulation but also the technological pathway for screening plant-derived active small nucleic acids. Existing miRNA target prediction tools are predominantly designed for endogenous miRNA-mRNA systems, exhibiting notable limitations when applied to cross-species small RNA inputs and small-sample wet-lab experimental adaptation. In this study, we developed a two-layer prediction framework, MetaLulu-AI. The first layer builds upon publicly available human miRNA-mRNA 3'UTR interaction data, utilizing XGBoost to learn foundational binding rules on human 3'UTRs based on 41 interpretable computational features, including seed region pairing types, local context sequence composition, site positioning, and RNA secondary structures. The second layer is tailored to the experimental system of plant-derived small RNAs and human target genes. It introduces 40 experimental samples using significant changes in endogenous protein expression as the regulatory standard (determined by Western blot or ELISA 48 hours post-transfection of small RNAs via Lipo3000). Using 52-dimensional computational features and the optimal transcript scores from the first layer as inputs, this layer employs TabPFN for experimental label adaptation. The first-layer dataset consists of 38,752 training samples, 5,536 validation samples, and 11,073 testing samples (totaling 55,361), with a positive-to-negative sample ratio of approximately 1:5.4. On the randomly split test set, the model achieved an AUC of 0.9686, a recall of 0.8523, a precision of 0.8080, and an accuracy of 0.9452 (at a decision threshold of 0.4797). Group-based splitting revealed that the model maintains high discriminative power for unseen genes (AUC = 0.9541), though its generalization ability for completely unseen miRNAs decreases (AUC = 0.7390). For the 40 experimental samples in the second layer, the TabPFN model achieved an average AUC of 0.7406 {+/-} 0.092 across ten repeated 70/30 random splits, outperforming the baseline of directly using the first-layer scores (0.3563 {+/-} 0.149); the average AUC in a 5-fold cross-validation was 0.770 {+/-} 0.177. SHAP analysis demonstrated a clear divergence in the discriminative basis of the two models: the first layer relies more heavily on the thermodynamics of the small RNA itself and the quality of canonical seed sites, whereas the second layer focuses more on the local UTR environment and statistical site features. Although the current second-layer results are constrained by sample size and gene coverage, this framework serves as a preliminary observation of the adaptation mechanism for cross-kingdom regulation experiments, and motivating future large-scale validation. Under stricter leave-one-gene-out and leave-one-small-RNA-out evaluation, the adapter exceeded the first-layer score baseline but only matched the majority-class baseline, underscoring that entity-level generalization is not yet established.

19.
medRxiv (Medicine) 2026-06-17

Menopausal symptoms in peri- and postmenopausal women: systematic review and meta-analysis of prevalence, incidence, comorbidities, and clinical outcomes

Introduction: The global epidemiology of menopausal symptoms among middle-aged and elderly women remains unclear. Methods: Data on prevalence, comorbidities, incidence and outcomes of menopausal symptoms published up until March 1st 2019 were searched in PubMed, Embase and Cochrane databases. We used a random-effects model to compute point estimates of prevalence for 24 types of menopausal symptoms. We narratively summarized the patterns of the comorbidities, incidence and outcomes of menopausal symptoms due to limited data. Results: A total of 239 studies (n{approx}2.5 million middle-aged and elderly women) from 56 countries and regions were included in the analysis. The global pooled prevalence analysis revealed that hot flashes (48%) and night sweats (30%) were highly prevalent, alongside psychological symptoms like insomnia (47%), irritability (46%), anxiety (39%), and depression (30%). Physical symptoms including joint aches/pain (50%), backache (47%), and tiredness (61%) were also commonly reported. Heat intolerance showed the highest prevalence (76%), while symptoms like urinary incontinence (24%) and poor appetite (8%) were less frequent. These findings highlight the diverse and widespread impact of menopause on women globally, with significant variations across symptom types. Africa showed the highest pooled prevalence across a series of symptoms, compared with other continents. We observed high prevalence in developing countries, especially for psychological and physical symptoms; significant intra-Asian variation in vasomotor symptoms; hypertension and obesity as the most common comorbidities; joint pain, urinary incontinence, and vasomotor symptoms as the most incident complaints; and positive associations with cardiovascular disease in the psychological (depression and insomnia) and physical (joint pain) domains. Conclusion: This study highlights the global burden of menopausal symptoms, with significant differences across continents. The findings call for more inclusive research on underrepresented groups (particularly in Africa) and further investigation into drivers of this marked global heterogeneity in prevalence of menopausal symptoms and their comorbidities, incidence and outcomes.

20.
bioRxiv (Bioinfo) 2026-06-19

Simulation-based Bayesian deep learning enables uncertainty-aware tumor fraction estimation in cell-free DNA

Background: Estimating tumor fraction from whole-genome cell-free DNA sequencing is critical for liquid biopsy, but is hampered by weak signals and baseline noise at low tumor fractions. Existing computational methods often require matched controls or large labeled datasets for training and lack uncertainty quantification. To address these gaps, we developed purNPE, a Bayesian deep-learning framework trained without labeled cancer cell-free DNA samples. Specifically, purNPE leverages a two-part generative model: one component simulates diverse tumor copy-number profiles based on evolutionary genealogies, while a second, data-driven component learns and replicates realistic sequencing background patterns from cancer-free cell-free DNA. By training a Neural Posterior Estimator on synthetic tumor profiles augmented with learned noise, purNPE performs amortized inference in milliseconds without needing a reference sample set at inference. Results: In a real-world pan-cancer cohort, purNPE achieved comparable performance with existing methods against orthogonal mutant-allele-fraction validation (MAE = 0.066). In silico and semi-synthetic experiments suggested analytical sensitivity around 1% tumor fraction under the evaluated conditions and showed strong classification accuracy in low tumor fractions (AUC = 0.98 for TF [&le;] 3% versus controls). Conclusions: This work provides a framework for using simulation-based inference to derive calibrated, uncertainty-aware TF estimates, offering a potential alternative to traditional data-dependent methods.

21.
arXiv (CS.AI) 2026-06-12

Real-Time Execution with Autoregressive Policies

arXiv:2606.13355v1 Announce Type: cross Abstract: Real-time execution, enabled by asynchronous inference that ensures both smooth action trajectories and fast reactivity, is critical for realistic deployments of large-scale Vision-Language-Action models. However, recent work on real-time execution primarily focuses on variants of diffusion policies, even though it is more critical for autoregressive policies given their slower rollout speed in synchronous inference. In contrast, we demonstrate that autoregressive policies can achieve real-time execution by adjusting the tokenization horizon and applying constrained decoding, thereby guaranteeing strict latency bounds that enable multi-trajectory decoding to maximize performance. Across simulated and real-world environments, we find that the autoregressive policy consistently outperforms its equivalent-level flow-matching policy counterpart while achieving significantly improved task completion speeds from synchronous inference. Coupled with the inherent advantages of autoregressive policies, such as faster convergence and better generalizability in instruction-following, these results confirm that autoregressive policies can remain a competitive policy type supporting real-time execution.

22.
bioRxiv (Bioinfo) 2026-06-11

A Deep Hypergraph Learning Model for Predicting Antimicrobial Combination Effects Across Bacterial Targets

Antimicrobial resistance (AMR) creates an urgent need for efficient strategies to identify effective antibacterial combinations. Combination therapy, including antimicrobial peptides (AMPs) paired with conventional antibiotics, is a promising approach, but exhaustive experimental screening across drug pairs and bacterial targets is impractical. This study introduces a hybrid GCN-based hypergraph neural network (HGNN) for predicting antimicrobial-agent combination outcomes against bacterial targets. Each antimicrobial-agent-antimicrobial-agent-bacterium triplet is represented as a ternary hyperedge, enabling the model to learn context-dependent interaction patterns. The framework integrates SMILES-derived molecular graph embeddings for antimicrobial agents, including conventional antibiotics and AMPs, with taxonomy-derived bacterial representations. The prediction task was formulated as a three-class classification problem: synergy, antagonism, and non-interaction. The non-interaction class included experimentally verified indifferent records and synthetic presumed non-interaction triplets generated by negative sampling. Model development used drug-pair-grouped splitting, five-fold grouped cross-validation within the training/validation partition, and final evaluation on a held-out test set. On the held-out three-class test set, the selected GCN-based HGNN achieved an accuracy of 0.83, weighted F1-score of 0.84, macro F1-score of 0.80, and ROC-AUC of 0.95. Per-class evaluation showed accuracies of 0.80 for synergy, 0.92 for antagonism, and 0.85 for non-interaction. Pair-type analysis showed strong performance across AMP-AMP, AMP-conventional antibiotic, and conventional antibiotic-conventional antibiotic combinations. These findings suggest that hypergraph-based representation learning can support computational prioritization of antimicrobial combinations for experimental follow-up. Further studies will be needed to improve model interpretability and to perform prospective validation of predicted synergistic combinations.

23.
arXiv (math.PR) 2026-06-19

Extremal representations of functions of matrices and applications to multivariate prediction

arXiv:2606.19359v1 Announce Type: cross Abstract: Motivated by two seminal results of multivariate prediction theory by Helson and Lowdenslager and by Wiener and Masani we prove extremal representations of functions of matrices and derive their prediction-theoretic consequences. We also sketch a way to obtain matricial inequalities from our results. The main goal of the paper is the computation of the infimum of a set of values of the form $tr(A \Delta A^*)$, where $\Delta$ is a given non-negative Hermitian $n \times n$ matrix and the choices for $A$ exhauste a certain set of $n \times n$ matrices. In particular, we focus on norm-bounded unit spheres with certain types of properties of unitary invariance, what allows an application of the theory of majorization.

24.
arXiv (CS.AI) 2026-06-12

Agents-K1: Towards Agent-native Knowledge Orchestration

arXiv:2606.13669v1 Announce Type: new Abstract: Current LLM-based research agents have advanced through agent orchestration, yet largely overlook scientific knowledge orchestration. Existing works often reduce papers to abstracts, surface mentions, and flat \texttt{cites} edges, omitting key entities, claims, evidence, mechanisms, and method lineages essential for scientific reasoning. To this end, we introduce Agents-K1, an end-to-end knowledge orchestration pipeline that converts raw documents into agent-native scientific knowledge graphs. Agents-K1 integrates three components under a unifying theoretical foundation: a multimodal parser whose five-module schema captures entities, multimodal evidence, citations, and typed inter-entity relations across the full paper rather than abstracts alone; a 4B information-extraction backbone trained with GRPO under a rule-based reward; and a graphanything CLI, a tri-source agent interface that unifies web search, multimodal graph retrieval, and cross-document traversal. On top of this, we process 2.46 million scientific papers across six subjects to produce Scholar-KG, of which we release a one-million-paper subset, and the full Scholar-KG is accessible via the SCP link below. The same pipeline can be extended to general-domain corpora and to schema-conformant data synthesis. Extensive experiments demonstrate that Agents-K1 achieves superior performance in scientific information extraction, knowledge graph construction, and multi-hop scientific reasoning.

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arXiv (CS.LG) 2026-06-16

A Penalty Approach for Differentiation Through Black-Box Quadratic Programming Solvers

arXiv:2602.14154v3 Announce Type: replace Abstract: Differentiating through the solution of a quadratic program (QP) is a central problem in differentiable optimization. Most existing approaches differentiate through the Karush–Kuhn–Tucker (KKT) system, but their computational cost and numerical robustness can degrade at scale. To address these limitations, we propose dXPP, a penalty-based differentiation framework that decouples QP solving from differentiation. In the solving step (forward pass), dXPP is solver-agnostic and can leverage any black-box QP solver. In the differentiation step (backward pass), we map the solution to a smooth approximate penalty problem and implicitly differentiate through it, requiring only the solution of a much smaller linear system in the primal variables. This approach bypasses the difficulties inherent in explicit KKT differentiation and significantly improves computational efficiency and robustness. We evaluate dXPP on various tasks, including randomly generated QPs, large-scale sparse projection problems, and a real-world multi-period portfolio optimization task. Empirical results demonstrate that dXPP is competitive with KKT-based differentiation methods and achieves substantial speedups on large-scale problems. Our implementation is open source and available at https://github.com/mmmmmmlinghu/dXPP.