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01.
medRxiv (Medicine) 2026-06-24

Self-administered computerized cognitive training for cognitive deficits in individuals with metabolic syndrome: a randomized controlled trial

Background: Metabolic syndrome (MetS) has been associated with cognitive decline. Considering its increasing prevalence worldwide, the goal of this study was to evaluate the feasibility and efficacy of a short-term, self-administered computerized cognitive training programme in individuals with metabolic syndrome and low cognitive performances. Methods: Thirty six participants, aged 40-72 years (mean age: 57.8 years), were randomly assigned to the cognitive training or the passive control group. The cognitive training component of Long Lasting Memories (LLM) Care was used as an interactive software to enhance participants' cognitive functions. Up to 24 sessions, each lasting 45 minutes, were self-administered at home twice per week for 3 months. Thorough cognitive assessments with were performed at baseline (randomization), at the end of intervention, and 12 months after baseline. The primary outcome was performance at nine neuropsychological tests, and the secondary outcome was a self-reported questionnaire assessing everyday functional abilities. Primary analyses were performed employing mixed-effect models using the intention-to-treat principle. Results: Low adherence was observed in the study, as only 9 participants (50%) completed at least 8 sessions of the cognitive training programme (range 9-24 sessions, median 15 sessions). No statistically significant effect of the cognitive training programme on performance in neuropsychological tests or everyday functioning was found. At the end of the 3-month intervention programme, effect for visual memory enhancement in immediate ({beta} = 1.58, 95% CI = -1.84 to 4.99, Cohen's d = 0.39) and delayed recall ({beta} = 2.17, 95% CI = -1.68 to 6.01, Cohen's d = 0.45) was moderate in favour of the intervention group, and at 12-month follow-up, semantic verbal fluency gains for the intervention group were detected ({beta} = 2.78, 95% CI = -0.92 to 6.49, Cohen's d = 0.70), though with wide confidence intervals. Conclusions: Despite some small effects observed in memory and verbal fluency, cognitive training did not yield statistically significant improvements. The observed low adherence and limited benefits on mild cognitive deficits in mostly middle-aged individuals with MetS are likely associated with the self-administered and short-term nature of the computerized intervention. This highlights the need for more intensive and clinician-delivered approaches to enhance engagement. Registry: ClinicalTrials.gov, TRN: NCT05658354, Registration date: 08 December 2022. Keywords: Metabolic syndrome, cognitive deficits, cognitive training, computerized, adults

02.
arXiv (CS.LG) 2026-06-16

Spectral Analysis of Molecular Features: When Richer Features Do Not Guarantee Better Generalization

arXiv:2510.14217v2 Announce Type: replace Abstract: The spectral properties of feature embeddings offer critical insights into model generalization and representation quality. While deep learning models are widely used for molecular property prediction, kernel methods remain competitive in low-data regimes, yet their spectral behavior is largely unexplored. We present the first comprehensive spectral analysis of kernel ridge regression across diverse representations-including molecular fingerprints (ECFP), pretrained transformers, graph neural networks, and 3D descriptors-evaluated on QM9 and 3 MoleculeNet benchmarks. Surprisingly, richer spectral features do not consistently yield better generalization performance, contradicting common representation heuristics used in self-supervised learning (SSL). Across 4 spectral metrics, only ECFP-based kernels show a strictly positive correlation with performance. Transformer and global 3D representations exhibit mixed behavior, whereas local 3D representations show consistently negative correlations. Truncation analysis further emphasizes this disparity: for local 3D representations on thermodynamic targets, fewer than 2\% of eigenvalues (and occasionally as few as 0.02\%) are needed to recover 95\% of performance, whereas ECFP and transformer kernels require significantly more. By demonstrating a strong dependence on both task and representation, our results challenge the heuristic that richer spectra inherently improve generalization, providing new guidance for evaluating representations in SSL and in label-limited scientific tasks.

03.
arXiv (quant-ph) 2026-06-19

Thermodynamic Value of XOR-Game-Induced Side Information in a Szilard Engine

arXiv:2605.12044v3 Announce Type: replace Abstract: We introduce a Szilard-type thermodynamic valuation of side-information channels induced by Bell-type correlations. In each round, a two-level working system is thermalized with a degenerate Hamiltonian, so that its physical microstate is a uniform classical bit. A trusted referee embeds this bit into a finite two-player XOR game, and a correlation resource produces a compressed controller bit. The controller uses only this compressed bit as side information for feedback. The construction is formulated first for arbitrary finite XOR games. The referee encoding makes the game-winning event equivalent to correct prediction of the physical microstate. Consequently, the induced side-information channel is binary symmetric, with success probability equal to the XOR-game winning probability of the supplied behaviour. The reversible Szilard feedback value is therefore fixed by the mutual information between the microstate and the controller record. Optimizing over local, quantum, and nonsignalling behaviour sets turns the corresponding game values into local, quantum, and nonsignalling thermodynamic ceilings. The construction is an effective-channel valuation, not a claim that Bell nonlocality is thermodynamic fuel. The controller receives only the compressed prediction bit, not the auxiliary variables that define the game. The thermodynamic costs of the referee, the correlation resource, and the preprocessing are not included. When controller-memory reset is included in a full cycle, the net work is non-positive, consistently with the second law.

04.
arXiv (CS.CL) 2026-06-18

LLM Parameters for Math Across Languages: Shared or Separate?

Large language models (LLMs) exhibit substantial cross-lingual variation in mathematical reasoning performance, but it remains unclear whether these differences reflect language-specific parameters or a shared mechanism that manifests differently by language. We present a cross-lingual mechanistic analysis of mathematical reasoning in LLMs, enabling us to localize and compare model parameters that support mathematical reasoning across languages. We find that the extracted math-associated parameters exhibit partial cross-lingual overlap, with the strongest overlap concentrated in intermediate model layers. We further observe that English consistently produces the largest set of math-relevant parameters, whereas lower-resource languages reveal smaller sets of relevant parameters. These results suggest that math-related behavior in multilingual LLMs is neither fully language-invariant nor fully language-specific, but instead exhibits partial cross-lingual parameter overlap with systematic language-dependent differences.

05.
arXiv (quant-ph) 2026-06-19

Matrix Product Operator Encodings of the Magnus Expansion and Dyson Series

arXiv:2605.21597v2 Announce Type: replace Abstract: We introduce a matrix product operator (MPO) encoding of the Magnus expansion and the Dyson series for one-dimensional quantum lattice models with time-dependent Hamiltonians. The MPO construction can be made accurate up to arbitrary order in the time step, it can be applied to both finite and infinite systems, and it can handle long-range interactions. The resulting MPO can be combined with state-of-the-art time evolution algorithms based on matrix product states, allowing for drastic improvements in simulating evolution under time-dependent Hamiltonians. Our MPO construction can also be used for the optimization of quantum circuits in the context of quantum simulation of time-dependent Hamiltonians.

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

OmniBioTwin: A System-of-Twinned-Systems Framework for Health Digital Twins

arXiv:2606.11264v1 Announce Type: cross Abstract: Health digital twins (HDTs) promise patient-specific modeling and decision support but current approaches remain structurally fragmented: monolithic models that address a single organ or task lack cross-scale fidelity, while system-level twins lack generalizable architectural frameworks. We propose OmniBioTwin, a System-of-Twinned-Systems (SoTS) framework that organizes HDTs as modular computational entities coupled through explicit interaction operators within a multi-layer network architecture. The framework comprises seven coordinated layers - spanning data integration, autonomous twin modeling, cross-scale coupling, temporal synchronization, and human-in-the-loop decision support. We demonstrate OmniBioTwin by instantiating a multiscale twin for glucagon-like peptide-1 (GLP-1) signaling pathways in Alzheimer's disease, illustrating how molecular, cellular, and organ-level twins can be composed and coupled within a unified system.

07.
arXiv (CS.CV) 2026-06-19

MMD-SLAM: Structure-Enhanced Multi-Meta Gaussian Distribution-Guided Visual SLAM

3D Gaussian Splatting (3DGS) has significantly boosted novel view synthesis and high-fidelity scene reconstruction, expanding the potential of 3DGS-based Visual Simultaneous Localization and Mapping (SLAM) methods. However, most existing systems fail to fully exploit the underlying structural information, which limits rendering quality and often leads to inconsistent maps. To address these limitations, we propose MMD-SLAM, a structure-enhanced Visual SLAM framework that leverages the Atlanta World (AW) assumption to guide a Multi-Meta Gaussian representation for photorealistic mapping. First, we introduce a point-line fusion strategy for pose optimization, where 3D line segments are incorporated to improve tracking robustness and provide additional constraints for mapping. Second, we design a Multi-Meta Gaussian representation with dominant directions, explicitly encoding structural priors from the AW hypothesis. Finally, we propose a Gaussian evolution strategy that adapts to scene geometry and incorporates structural cues into global optimization. Extensive experiments demonstrate that these innovations enable MMD-SLAM to achieve state-of-the-art performance in both tracking accuracy and mapping quality. e.g., our method achieves a 48.56% reduction in ATE RMSE on ScanNet and a 5.71% improvement in PSNR on Replica, compared with MonoGS.

08.
arXiv (quant-ph) 2026-06-19

Quantifying Entanglement via Quantum Wasserstein Distances

arXiv:2606.04969v2 Announce Type: replace Abstract: We propose a bipartite entanglement measure defined as the minimal order-1 quantum Wasserstein distance from a state to the set of separable states. Owing to the universal data-processing inequality of the Wasserstein metric, the measure satisfies all fundamental axioms within a single geometric framework. A Lipschitz dual formulation yields explicit lower bounds for pure and mixed states, a sharp constant for two-qubit systems, and an expected value for Haar-random pure states. We further establish a quantitative connection to entanglement witnesses: any negative witness expectation value certifies a lower bound, and the dual variational bound is exactly the maximal violation achievable by a Lipschitz-1 witness. The approach naturally provides subadditivity, trace-distance estimates, and bounds on local observables, while pointing toward large-deviation conjectures. This work introduces a framework at the interface of entanglement theory, optimal transport, and experimental entanglement detection.

10.
arXiv (CS.AI) 2026-06-17

DiagFlowBench: Evaluating How Language Models Handle Off-Procedure Inputs in Grounded Diagnostic Dialogue

arXiv:2606.17904v1 Announce Type: new Abstract: Language models increasingly serve as advisory systems in maintenance operations. To prevent hallucination, recent systems ground these models in procedural documentation to constrain them to approved steps. In practice, however, operator queries frequently stray from this path, requiring models to recognise out-of-scope inputs mid-conversation, a dynamic that current benchmarks rarely prioritise. We introduce DiagFlowBench, a dataset of 50 industrial diagnostic flowcharts from a consumer manufacturer converted into 1,676 multi-turn conversations that contrast compliant with out-of-scope utterances. Evaluating a panel of ten commercial and open-weight models reveals high variability in abstention rates, with models commonly selecting a real but contextually inadequate step rather than fabricating facts. The inherent plausibility and authority of this mapped but wrong advice exposes a challenging vulnerability for grounding systems.

11.
arXiv (quant-ph) 2026-06-17

Optimality Condition for the Petz Map

arXiv:2410.23622v5 Announce Type: replace Abstract: In quantum error correction, the Petz map serves as a perfect recovery map when the Knill-Laflamme conditions are satisfied. Notably, while perfect recovery is generally infeasible for most quantum channels of finite dimension, the Petz map remains a versatile tool with near-optimal performance in recovering quantum states. This work introduces and proves, for the first time, the necessary and sufficient conditions for the optimality of the Petz map in terms of entanglement fidelity. In some special cases, the violation of this condition can be easily characterized by a simple commutator that can be efficiently computed. We provide multiple examples that substantiate our new findings.

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

Multi-Agent Reasoning with Adaptive Worker Allocation for Stance Detection

Stance detection requires identifying an author's position toward a target, often from short-form texts where stance is implicit, indirect, or rhetorically framed. Although large language models (LLMs) achieve strong performance on this task, single-pass prompting can be brittle when multiple interpretations are plausible. Existing aggregation strategies, such as majority voting or self-consistency, improve robustness by combining labels, but they discard the intermediate reasoning needed to resolve conflicting interpretations. We introduce a multi-agent reasoning framework with adaptive worker allocation for stance detection that shifts aggregation from label-level voting to reasoning-level synthesis. The framework employs a Manager-Worker architecture in which a Manager adaptively allocates a variable number of Worker agents based on input complexity. Each Worker analyzes the input from a distinct perspective and produces a reasoning-only explanation without emitting a stance label; the Manager then synthesizes these explanations to produce the final prediction. We evaluate the proposed framework on SemEval-2016, P-Stance, and COVID-19 Stance using Llama, Mistral, and Gemini. Results show that the framework yields the largest gains on implicit and context-dependent stance cases, achieving 86.07 Macro-F1 on COVID-19 and 82.90 on SemEval-2016, while remaining competitive on more explicit stance datasets such as P-Stance. These findings suggest that adaptive reasoning-level aggregation is most beneficial when stance cannot be reliably inferred from surface cues alone.

13.
arXiv (CS.CL) 2026-06-11

On The Effectiveness-Fluency Trade-Off In LLM Conditioning: A Systematic Study

Controlling the output of Large Language Models (LLMs) is a central challenge for their reliable deployment, yet a clear understanding of the involved trade-offs remains elusive. Current approaches to conditioning are often evaluated with a narrow focus on their effectiveness at injecting or removing a target concept, neglecting generation quality. We systematically investigate a range of conditioning methods in both injection and removal scenarios. We find that efficient steering methods frequently achieve conditioning at a steep cost to fluency. Furthermore, we identify a critical yet previously overlooked interaction with the training paradigm: activation steering methods are far less effective on instruction-tuned models than on their base counterparts. Simple prompting and full-fledged supervised fine-tuning, on the other hand, are viable options for concept injection, but are not as good at concept removal. Finally, cheaply computed textual metrics highly correlate to costly LLM-as-judge scores, and provide insights on the behavior of conditioning methods.

14.
bioRxiv (Bioinfo) 2026-06-11

Sequence-Based Therapeutic Peptide Classification with Augmented Negative Sampling

Therapeutic peptides offer high target specificity, low toxicity, and the ability to modulate protein-protein interactions, yet experimental functional characterization remains costly and slow. Computational prediction of therapeutic function directly from sequence could accelerate peptide screening and enable generative design pipelines, but requires reliable discrimination between therapeutic and non-therapeutic peptides. Existing multi-label predictors cover few functions, rely on limited datasets, and exhibit high glspl{fpr}, limiting their practical utility. We present a lightweight CNN classifier trained on the most comprehensive therapeutic peptide database to date (54,655 peptides, 48 functional categories). A key contribution is a statistically motivated negative sampling strategy using Markov models to generate diverse synthetic decoys at multiple difficulty levels. When evaluated on this controlled decoy benchmark, the FRP is reduced from over 60% for previous models to 2.1% for our approach. Our fine-tuned five-model ensemble achieves 78.9% Micro F1 and 54.6% Macro F1 while requiring only amino acid sequences as inputs. Analysis using a sparse L1-constrained variant of our model shows that convolutional filters capture conserved functional motifs and statistically improbable non-therapeutic patterns, with downstream layers combining these signals, providing mechanistic evidence that the network learns biologically meaningful structure. In a generalization task on the TPpred-LE benchmark, our model achieves 55.3% Micro F1 and 38.6% Macro F1, comparable to TPpred-LE trained on its native dataset (57.9%/38.1%) while predicting four times more therapeutic functions with four times fewer parameters. Code and models will be made available at https://github.com/terra-quantum-public/tq-therapep-ai.

15.
arXiv (quant-ph) 2026-06-24

Wavelet Matrix Product States for Quantum Fields

arXiv:2606.23823v1 Announce Type: new Abstract: We introduce a variational method to solve continuum quantum models with discrete tensor network techniques. The method leverages wavelet matrix product states (wMPS): matrix product states built on top of sufficiently regular ($N\geq 6$) Daubechies scaling functions. These states live in the continuum field theory Fock space, have finite energy density, and can be optimized with standard algorithms, without restriction to free theories. Further, exploiting the multi-resolution analysis built into wavelets, and its quantum circuit description, we can iteratively refine wMPS to obtain accurate approximations at arbitrarily fine length-scales. We showcase the efficiency of the method on the Lieb-Liniger model, computing energy density and correlation functions.

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

VitalAgent: A Tool-Augmented Agent for Reactive and Proactive Physiological Monitoring over Wearable Health Data

arXiv:2605.29483v2 Announce Type: replace Abstract: Wearable devices enable continuous monitoring of physiological signals such as ECG and PPG, but existing mHealth systems are largely limited to task-specific prediction pipelines or reactive question answering over static summaries. They lack the ability to support temporal reasoning, persistent physiological context, and proactive monitoring over long-term signal streams. We propose VitalAgent, a tool-augmented agentic framework for ECG/PPG-based mHealth that supports both reactive question answering and proactive monitoring. VitalAgent is built on a longitudinal physiological memory and a tool-augmented reasoning interface that enables dynamic computation over raw signals. We further introduce VitalBench, a longitudinal physiological monitoring benchmark dataset comprising 1,862 QA pairs for reactive question answering and 90.2 hours of continuous ECG/PPG recordings for proactive monitoring, covering cardiac, physical activity, and stress-related tasks. Experiments demonstrate that VitalAgent achieves over 25% improvement over prompt-based and ReAct baselines in reactive evaluation and supports proactive alert monitoring over long-term physiological signals, highlighting the importance of dynamic tool use and long-term physiological monitoring.

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

Stitching and dimensionality effects on large artificially generated volume datasets

Generating large images via deep learning requires patching input data to accommodate hardware memory limitations, then assembling output patches, a process that can introduce stitching artifacts when neighboring patches do not align at borders. While these artifacts are known to affect segmentation tasks, their impact on generative models for style-transfer remains poorly understood. We investigated three stitching approaches and two patch dimensionalities (2D vs 3D) using cycleGAN models trained on cryo-electron microscopy datasets. We evaluated both perceptual quality and performance on downstream mitochondria segmentation. Our key findings reveal that: (1) FID scores fail to detect subtle stitching artifacts that significantly impact downstream segmentation performance, (2) 3D models with artifact-free stitching marginally outperform 2D models on downstream tasks, though the improvement barely justifies the computational cost, and (3) 2D models train more stably due to larger batch sizes. Additionally, we demonstrate that ensembling predictions from three orthogonal directions can improve low-quality volumes but provides no benefit for high-quality outputs. These results demonstrate that maximizing generative model performance on large scientific datasets requires careful consideration and mitigation of stitching artifacts, and that perceptual metrics alone are insufficient for evaluating domain adaptation quality in biomedical imaging.

18.
arXiv (CS.AI) 2026-06-16

Cordyceps: Covert Control Attacks on LLMs via Data Poisoning

arXiv:2605.26595v2 Announce Type: replace-cross Abstract: Large language models (LLMs) are often fine-tuned on uncurated text datasets that adversaries can poison. Existing poisoning attacks primarily rely on fixed trigger phrases that defenses such as outlier detection, clean-data regularization, or online monitoring can neutralize. In this paper, we propose a data poisoning method that teaches an LLM an information hiding scheme reliably and stealthily through semantic associations between shared knowledge such as facts or concepts and attacker-chosen phrases. The induced hiding scheme can encode and decode arbitrary malicious instructions, thus revealing a new and subtle poisoning-induced vulnerability: covert control attacks. We precisely characterize covert control attacks and evaluate them across $5$ LLMs, $3$ backdoor defenses, and $4$ prompt injection defenses. With a small poisoned fraction, covert control attacks outperform heuristic-based prompt injection attacks in average attack success rate by about $40\%$ relative to clean fine-tuned models. They also circumvent defenses based on detection and fine-tuning, maintaining up to $93\%$ attack success rate after backdoor defenses and up to $98\%$ after prompt injection defenses.

19.
arXiv (CS.LG) 2026-06-15

Minimum Distance Summaries for Robust Neural Posterior Estimation

arXiv:2602.09161v2 Announce Type: replace-cross Abstract: Simulation-based inference (SBI) enables amortized Bayesian inference by first training a neural posterior estimator (NPE) on prior-simulator pairs, typically through low-dimensional summary statistics, which can then be cheaply reused for fast inference by querying it on new test observations. Because NPE is estimated under the training data distribution, it is susceptible to misspecification when observations deviate from the training distribution. Many robust SBI approaches address this by modifying NPE training or introducing error models, coupling robustness to the inference network and compromising amortization and modularity. We introduce minimum-distance summaries, a plug-in robust NPE method that adapts queried test-time summaries independently of the pretrained NPE. Leveraging the maximum mean discrepancy (MMD) as a distance between observed data and a summary-conditional predictive distribution, the adapted summary inherits strong robustness properties from the MMD. We demonstrate that the algorithm can be implemented efficiently with random Fourier feature approximations, yielding a lightweight, model-free test-time adaptation procedure. We provide theoretical guarantees for the robustness of our algorithm and empirically evaluate it on a range of synthetic and real-world tasks, demonstrating substantial robustness gains with minimal additional overhead.

20.
arXiv (math.PR) 2026-06-18

Very large cliques in a scale-free random graph

arXiv:2606.18722v1 Announce Type: new Abstract: In this short article we consider a preferential attachment random graph model with edge steps, studied by Alves, Ribeiro and Sanchis. Starting with an initial graph $\mathbb{G}_1$ formed by a vertex with a self-loop attached to it, the model evolves as follows. At every subsequent (discrete) time step, either with probability $p$ we add a vertex to the graph and connect it to exactly one of the older vertices selected with probability proportional to its degree, or with probability $1-p$ we add one edge between two existing vertices, both selected (independently) with probability proportional to their degrees. Let $\omega(\mathbb{G})$ be the clique number of a graph $\mathbb{G}$, i.e.\ the number of vertices in a largest complete subgraph of $\mathbb{G}_{}$. Alves, Ribeiro and Sanchis showed that, for any given $\varepsilon>0$, we have $\omega(\mathbb{G}_{2t})\geq t^{\frac{1-p}{2-p}(1-\varepsilon)}$ with high probability (i.e.\ with probability tending to $1$ as $t\rightarrow \infty$). Here we strengthen this bound by showing that, for any function $f:\mathbb{N}\mapsto \mathbb{N}$ that satisfies $f(t)\rightarrow \infty$ as $t\rightarrow \infty$, with high probability \[\omega(\mathbb{G}_{2t}) = \Omega\left(t^{\frac{1-p}{2-p}}\Big(\log^{\frac{1}{2-p}}(t)f(t)\Big)^{-1}\right).\]

21.
arXiv (CS.AI) 2026-06-16

Adaptive inference and function vectors in deep transformers

arXiv:2606.16694v1 Announce Type: cross Abstract: Transformers are widely used as a general-purpose substrate for learning complex correlations between a large collection of coupled variables, but their internal mechanisms have remained mysterious. We introduce a theory of a deep transformer as a mean-field interacting system that implements distributed inference, subject to constraints on communication, locality and depth. We show that such a system can exploit internal state representations ('function vectors') to infer a latent context variable at increasingly finer scales over its layers. In an in-context regression task, the theory predicts a non-trivial relationship between non-Gaussian, hierarchical structure in the latent context variable, and transformer depth. Predictions are tested using constrained linear attention transformers and demonstrate adaptive inference in deep architectures. Feedforward blocks and depth enable transformers to implement a much richer class of in-context learning algorithms than previously described.

22.
arXiv (CS.CV) 2026-06-24

DDStereo: Efficient Dual Decoder Transformers for Stereo 3D Road Anomaly Detection

Stereo-based 3D object detection still faces two critical safety challenges: real-time performance and open-set generalization. Existing stereo 3D methods typically achieve twice the accuracy of monocular methods but suffer from significantly lower inference speeds, making them unsuitable for real-time applications. Meanwhile, recent advances in open-world detection have introduced open-set and open-vocabulary algorithms in monocular 2D and 3D settings, yet stereo-based open-set detection remains largely unexplored. To bridge this gap, we propose DDStereo, a novel Dual-Decoder Stereo Transformer for real-time open-set 3D object detection. DDStereo features two lightweight decoder branches: one for open-set foreground 2D detection and the other for 3D attribute regression. These decoders share object-level queries to achieve unified target-level alignment. To enhance inference efficiency, we designed a compact disparity feature extractor and a streamlined decoder architecture. Experiments on public stereo 3D benchmarks demonstrate that DDStereo achieves state-of-the-art accuracy under both closed-set and open-set protocols. Notably, our method surpasses existing stereo 3D detectors in inference speed and, for the first time, achieves real-time performance comparable to monocular approaches.

24.
Nature (Science) 2026-06-10

SIRT7 regulates dosage compensation and safeguards the female X chromosome

Sirtuins are deacetylases implicated in stress responses and longevity in mammals1,2. Although their differential impact on disease for the two sexes has been noted3–7, the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7−/− female mice have decreased fitness throughout their lifespan. Notably, SIRT7 preferentially localizes to the sex chromosomes. In female individuals, SIRT7 loss affects X-chromosome inactivation, the first arm of dosage compensation that equalizes X-linked gene expression between males and females8–10. Xist is overexpressed and gene silencing becomes more efficient. However, SIRT7 loss has greatest impact on the active X (Xa) chromosome. The Xa chromosome becomes hyperacetylated at Lys36 of histone H3, structurally disorganized, prone to DNA damage and overexpressed. Increased Xa-chromosome expression leads to genome imbalance and augmented X-chromosome upregulation—the second arm of dosage compensation that balances X-chromosome versus autosomal gene expression. These data reveal an essential crosstalk between sirtuins and the sex chromosomes, with SIRT7 safeguarding X-chromosome integrity and dosage balance with autosomes. We propose that the sex bias in SIRT7 biology can be explained in part by unequal effects on the sex chromosomes. SIRT7 safeguards X-chromosome integrity and dosage balance with autosomes.

25.
arXiv (CS.AI) 2026-06-24

Diffusion Integrated Gradients: Controllable Path Generation for Flexible Feature Attribution

arXiv:2606.22314v2 Announce Type: replace-cross Abstract: Path-based attribution methods such as Integrated Gradients (IG) are widely adopted for their strong axiomatic properties and effectiveness in attributing model predictions to input features by integrating gradients along a path from a baseline to the input. However, the choice of the attribution path largely affects the quality of explanations, and existing approaches rely on fixed or hand-crafted paths that often produce noisy or distorted attributions. To address this limitation, we propose Diffusion Integrated Gradients (DiffIG), a novel method that reformulates path generation as a conditional generative modeling problem. DiffIG first trains a diffusion model to learn a distribution over paths generated from a Stick-Breaking Process, then employs guided sampling to embed user guidance during the sampling procedure. We demonstrate that DiffIG quantitatively matches or outperforms existing path-based methods, achieving perceptually aligned explanations. This work introduces a new generative perspective for flexible, inference-time controllable Explainable Artificial Intelligence (XAI) methods.