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01.
medRxiv (Medicine) 2026-06-16

Care Delivery Gap framework: a proof-of-concept patient-reported measure of guideline-referenced care-process omissions in sickle cell disease

Abstract Background:Sickle cell disease (SCD) is concentrated in sub-Saharan Africa, where delivery of guideline-referenced care remains challenging. Current evaluation approaches rely largely on access indicators and clinical outcomes, which do not directly measure care delivery. We developed the Care Delivery Gap (CDG) framework, a patient-reported approach for identifying care-process omissions, and conducted a proof-of-concept study to assess feasibility and explore variation across income strata. Methods: We conducted a cross-sectional framework-development study involving a proof-of-concept sample of 52 individuals with SCD or caregivers recruited through clinics and moderated SCD communities across Africa, North America, and Europe between June 2025 and March 2026. The CDG framework assessed patient-reported omissions in specialist involvement, follow-up continuity, cardiovascular screening, and biochemical surveillance. Analyses were descriptive. Results: Substantial multi-domain care-process omissions were identified despite high reported healthcare engagement. Across geographic income strata, cardiovascular screening was reported by 4/35 (11%) LMIC versus 16/17 (94%) HIC participants, and regular follow-up within the preceding 12 months by 14/35 (40%) versus 16/17 (94%), respectively. High CDG scores, representing 1 omissions across three or four domains, occurred in 20/35 (57%) LMIC compared with 1/17 (6%) HIC participants. Similar disparities were observed across specialist review and vitamin B12 surveillance domains. Conclusion: A structured patient-reported framework identified multi-domain omissions in guideline-referenced SCD care, including among individuals reporting healthcare access. The divergence between access indicators and reported care delivery suggests that service contact alone may not reflect care quality. The framework provides a feasible foundation for future process-level quality measurement in high-burden settings.

02.
PLOS Medicine 2026-05-08

Climate change and non-communicable diseases: An invisible syndemic

by Gokul Parameswaran, Sadeer Al-Kindi, Sanjay Rajagopalan Climate change accelerates non-communicable diseases (NCDs) through cascading environmental disruptions and is attributed to driving increased NCD-related mortality. Yet this syndemic remains invisible and underfunded. We detail why addressing the climate-NCD intersection is critical for improving health. In this Perspective, Sanjay Rajagopalan and colleagues discusses how climate change accelerates non-communicable diseases (NCDs) and exacerbates NCD-related mortality, and calls for greater visibility and funding to address this syndemic and improve human health.

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

From Noise to Order: Learning to Rank via Denoising Diffusion

arXiv:2602.11453v3 Announce Type: replace-cross Abstract: Learning-to-rank (LTR) methods have traditionally been limited to discriminative machine learning approaches that model the probability of the document being relevant to the query given some feature representation of the query-document pair. We propose an alternative denoising diffusion-based generative approach to LTR that instead models the full joint distribution over features and relevance labels. While in discriminative LTR, an over-parameterized ranking model may find different ways to fit the training data, we posit that candidate solutions that can explain the full data distribution under the generative setting maybe better at estimating relevance. Thus, we propose DiffusionRank that extends TabDiff, an existing diffusion model for tabular datasets, to create generative alternatives to classical discriminative pointwise and pairwise LTR objectives. Our work demonstrates improvements from DiffusionRank over discriminative counterparts on four standard LTR datasets and points to a rich space for future exploration to leverage ongoing advancements in deep generative models for LTR. Our code is publicly available at https://github.com/sadjadeb/DiffusionRank.

04.
arXiv (quant-ph) 2026-06-16

Comparative Performance Analysis of NIST PQC Standards: From STM32 Software Limitations to FPGA-SoC Acceleration

arXiv:2606.15744v1 Announce Type: new Abstract: The rapid advancement of quantum computing poses a significant threat to classical public-key cryptographic systems, necessitating the transition to Post-Quantum Cryptography (PQC). This study investigates the implementation challenges of NISTstandardized signature schemes on resource-constrained embedded hardware. We present a comparative analysis of SPHINCS+ and CRYSTALS-Dilithium on an ARM Cortex-M4 (STM32F407G) microcontroller. Our findings reveal that SPHINCS+ is practically unusable in this software-only environment, with impractical execution times. Furthermore, the reference Dilithium implementation failed to execute entirely on the MCU due to severe RAM and timing constraints. To overcome these hardware limitations, we integrated a hardware-accelerated Dilithium core onto a Xilinx Zynq-7000 ZedBoard SoC. By implementing a specialized Number Theoretic Transform (NTT) accelerator in the FPGA fabric, we achieved successful execution with performance rates for key generation and signature generation at millisecond levels. These results demonstrate that while pure software PQC is non-viable for standard microcontrollers, a hardware-software codesign approach provides the necessary efficiency for quantumresistant embedded systems.

05.
arXiv (CS.CV) 2026-06-11

CFCamo: A Counterfactual Detect-or-Abstain Framework for Camouflaged Object Detection

Vision-language reinforcement learning has recently shown strong target-present localization for camouflaged object detection (COD). Yet localization is only one side of the decision: when the agent faces an ordinary image with no camouflaged target, will it still claim that a camouflaged object exists? Standard COD training and evaluation data are positive-only, so agents optimized under this setting can acquire an over-detect bias, a task-specific form of object hallucination that standard COD evaluation leaves unmeasured. To quantify this target-absent behavior, we construct Counterfactual COD (CF-COD), a paired benchmark that removes the camouflaged target from each held-out COD evaluation image while preserving a plausible background. CF-COD evaluates whether a model detects the target on the original image and abstains on the target-absent counterfactual, summarized by Pair Accuracy (PA). We further introduce CFCamo, a paired counterfactual framework for COD with abstention. For training, CFCamo optimizes a Qwen3-VL-4B-Instruct agent with Counterfactual Sequence Policy Optimization (CSPO), which samples paired original-counterfactual rollouts and uses a Counterfactual Paired Reward (CPR) to couple original-image detection with counterfactual abstention. On CAMO-test, CFCamo improves S_alpha by +3.7 pp over the prior RL-based COD baseline; across CF-COD, it reaches 80.0-90.8% PA. Ablations show that removing counterfactual coupling reduces PA to 1.4-5.2% despite strong target-present COD scores, showing that target-present evaluation alone does not characterize detect-or-abstain behavior. Overall, these results indicate that CFCamo improves COD agents by coupling target-present detection with target-absent abstention, rather than merely strengthening target-present localization. Code and data are available at https://github.com/suhang2000/CFCamo.

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

Exploiting More Than Symmetry in Variational Quantum Machine Learning

arXiv:2606.20316v1 Announce Type: new Abstract: The success of variational quantum learning models crucially depends on choosing parametrizations that reflect the structure of the problem at hand. Symmetries provide one of the clearest such structures: whenever transformations of the input leave the desired outcome unchanged, this invariance should be built into the model rather than discovered during training. However, imposing a symmetry does not by itself determine a useful ansatz. Even within the symmetry-preserving space, one must decide where the trainable degrees of freedom should be placed. In this work, we study this remaining design freedom in equivariant variational quantum circuits. Building on symmetry-based parameter sharing, we disentangle two architectural choices: how much symmetry should be enforced, and which symmetry-respecting interactions should be trainable. Using Tic-Tac-Toe as a fully enumerable and structurally transparent test case, we find that suitable subgroups preserve most of the generalization benefit. By contrast, the dominant gains arise from gates acting directly on decisive task motifs. Thus, symmetry defines the admissible design space, while effective ansatze require an additional task-informed choice of trainable interactions.

07.
medRxiv (Medicine) 2026-06-17

Targeted Proteomic Profiling of Nasal Fluid from the Brain-Nose Interface

The brain-nose interface is an anatomical junction where olfactory neurons from the olfactory bulb traverse the cribriform plate into the nasal mucosa, providing minimally invasive access to the central nervous system (CNS). We hypothesized that nasal fluid from this region could enable detection of neurology-relevant proteins using targeted multiplex assays. Using nosecollect, a targeted nasal sampling device, nasal fluid proximal to brain-nose interface was collected from cognitively impaired patients, alongside matched cerebrospinal fluid (CSF) and plasma. After nasal sample-specific dilution optimization and intra-assay precision evaluation, all matrices were profiled with the Olink Target 96 Neurology and NUcleic acid Linked Immuno-Sandwich Assay CNS disease 120 (NULISAseq CNS Disease 120) panels. Nasal fluid showed technically repeatable detection (intra-assay coefficient of variation

08.
bioRxiv (Bioinfo) 2026-06-11

A high-quality chromosome-scale reference genome assembly for Asparagus racemosus var. CIM-Shakti (Shatavari), a medicinal plant of Ayurvedic importance

Asparagus racemosus Wild., commonly known as Shatavari, is an important medicinal plant in Ayurveda and is valued for its steroidal saponins, particularly shatavarin compounds, which contribute to its adaptogenic, galactagogue, immunomodulatory, and therapeutic properties. Despite its medicinal and economic importance, genomic resources for this species have remained limited, restricting molecular breeding, pathway discovery, and comparative evolutionary studies within Asparagaceae. Here, we report a high quality chromosome scale reference genome assembly of A. racemosus var. CIM Shakti generated using PacBio HiFi long read sequencing and Omni C chromatin conformation scaffolding. The pseudo haploid assembly spans 817 Mb across 53 scaffolds, with a scaffold N50 of 98.50 Mb, L50 of 5, and a largest scaffold of 113.80 Mb. Ten major chromosome scale pseudomolecules were resolved, corresponding to the haploid chromosome complement of A. racemosus. The assembly showed high gene space completeness, with BUSCO completeness of 99.8% against the Eukaryota dataset and 98.0% against the Embryophyta dataset. BlobToolKit profiling further supported assembly quality, with GC content of approximately 39 to 40% and no major evidence of contamination. EDTA based repeat annotation identified 580.93 Mb of interspersed repetitive elements, accounting for 71.06% of the 817.57 Mb genome assembly. The repeat landscape was dominated by LTR retrotransposons, particularly Gypsy elements, which accounted for 25.01% of the assembly, followed by unclassified LTR elements at 26.58% and Copia elements at 4.84%. Structural and functional annotation identified 29,199 protein coding genes represented by 29,199 transcript models, 138,433 exons, and 125,201 CDS features. The annotation was structurally robust, with an average gene length of 4,605.1 bp, 4.74 exons per transcript, and 97.80% of transcripts containing multiple exons. The CIM Shakti reference genome provides a foundational genomic resource for investigating steroidal saponin biosynthesis, sex chromosome evolution, repeat driven genome expansion, and comparative genomics in Asparagaceae. This assembly will support future studies on medicinal trait improvement, conservation genomics, and genomics assisted breeding of climate resilient Shatavari cultivars.

09.
arXiv (CS.AI) 2026-06-17

Cluster-Aware Dual-Level Test Specification Generation for Large-Scale Automotive Software Requirements

arXiv:2606.17197v1 Announce Type: cross Abstract: Generating test specifications that satisfy Automotive SPICE SWE.6 requirements becomes increasingly challenging and time-consuming as projects scale to thousands of requirements. Because this manual process often consumes weeks of engineering effort, automation becomes a critical necessity. However, standard Large Language Model (LLM) approaches struggle at scale: processing requirements individually discards vital inter-requirement dependencies, while feeding entire corpora at once exceeds context-window limits, leading to incomplete integration coverage and redundant test cases. This paper presents a novel "Cluster-then-Summarize" pipeline that addresses these limitations through three-stages. Requirements are embedded using sentence transformers and grouped using UMAP dimensionality reduction followed by HDBSCAN density-based clustering. This grouping utilizes an automatic minimum cluster size selection driven by a quality criterion combining normalized Silhouette and Calinski-Harabasz scores. A multi-level map-reduce summarization algorithm then distills each cluster into concise, domain-conformant descriptions while preserving quantitative thresholds and safety integrity levels. The pipeline exploits the derived cluster topology to generate test specifications at two levels: individual requirement verification and cluster-level integration tests that verify cross-requirement feature behavior. A nearby-cluster context mechanism provides bounded cross-feature awareness during each LLM call, and Retrieval-Augmented Generation grounds all outputs in ISO 26262 and ASPICE standards. Evaluation on automotive requirement datasets of varying scale demonstrates that the cluster-aware approach improves integration test coverage and maintains summarization fidelity compared to baseline methods while scaling efficiently to thousands of requirements.

10.
arXiv (CS.CL) 2026-06-19

SIGMA: Search-Augmented On-Demand Knowledge Integration for Agentic Mathematical Reasoning

Solving mathematical reasoning problems requires not only accurate access to relevant knowledge but also careful, multi-step thinking. However, current retrieval-augmented models often rely on a single perspective, follow inflexible search strategies, and struggle to effectively combine information from multiple sources. We introduce SIGMA (Search-Augmented On-Demand Knowledge Integration for AGentic Mathematical reAsoning), a unified framework that orchestrates specialized agents to independently reason, perform targeted searches, and synthesize findings through a moderator mechanism. Each agent generates hypothetical passages to optimize retrieval for its analytic perspective, ensuring knowledge integration is both context-sensitive and computation-efficient. When evaluated on challenging benchmarks such as MATH500, AIME, and PhD-level science QA GPQA, SIGMA consistently outperforms both open- and closed-source systems, achieving an absolute performance improvement of 7.4%. Our results demonstrate that multi-agent, on-demand knowledge integration significantly enhances both reasoning accuracy and efficiency, offering a scalable approach for complex, knowledge-intensive problem-solving. We will release the code upon publication.

11.
arXiv (CS.CV) 2026-06-18

OneCanvas: 3D Scene Understanding via Panoramic Reprojection

Existing approaches to 3D scene understanding in Vision-Language Models (VLMs) either rely on complex, model-specific geometry encoders or large training budgets in pursuit of spatial reasoning. Instead, OneCanvas aggregates patch features from all views onto a single equirectangular panoramic canvas. Namely, each patch is unprojected to a 3D world coordinate using its depth and camera pose, then placed on the canvas at the continuous longitude and latitude of that point as seen from the canvas origin, with no rasterization or aggregation across overlapping views. A 3D position embedding of the patch's metric coordinates is added to its feature, restoring the depth lost when collapsing the world position to an angular canvas coordinate. Patches from all frames thus share one spatial coordinate system with no fusion or major architectural modifications of the backbone. The pretrained VLM consumes this representation as if it were an ordinary image. Because the canvas can be centered on any pose of interest, the same representation directly supports situated reasoning from a specific viewpoint, a common requirement in robotics and embodied AI. Thanks to this representation, we can also introduce a spatial pretraining curriculum: by procedurally placing patch features of objects, drawn from real images, at chosen 3D world positions on an otherwise empty canvas, we generate on-the-fly supervision spanning a broad range of spatial reasoning tasks, with answer distributions controlled to reduce spatial reasoning shortcuts. OneCanvas achieves state-of-the-art accuracy on SQA3D and VSI-Bench, and generalizes to out-of-distribution data on SPBench, using an order of magnitude less training compute than the strongest competing methods.

12.
arXiv (CS.LG) 2026-06-19

Recurrent neural networks approximate continuous functions

arXiv:2606.20325v1 Announce Type: new Abstract: Classical approximation theorems ask for a new neural network whenever the target accuracy is improved. This paper studies the opposite possibility: can the network be chosen once and for all, and can accuracy be bought only by letting it run longer? We prove that this is possible for every continuous function on [-1,1]. More precisely, each such function is uniformly approximated by the time evolution of a single ReLU recurrent neural network with fixed weights and fixed hidden dimension. The mechanism behind the construction is a new intermediate model, the Turing machine with neural units (TMNU). This model retains the algorithmic freedom needed to implement polynomial approximation schemes, while remaining rigid enough to be simulated by RNNs with explicit bounds on hidden dimension and weight magnitude. The resulting convergence rates reflect the underlying polynomial approximation rates. We complement the construction with minimax lower bounds showing that runtime is not merely a proof artifact, but an unavoidable resource in this fixed-network approximation paradigm.

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

Anomalies in Multivariate Time Series Benchmarks Are Mostly Univariate

arXiv:2606.02670v3 Announce Type: replace-cross Abstract: Many recent multivariate time series anomaly detection (MTSAD) models incorporate cross-channel modeling, under the implicit assumption that the structure of anomalies may be spread across multiple channels. We evaluate this assumption on eight widely used public benchmarks by introducing a per-segment diagnostic framework that flags, for each labeled anomaly, whether at least one channel deviates individually from its normal history, whether the cross-channel correlation structure changes, or both. The framework shows that no cross-channel rupture occurs without an accompanying univariate deviation across a range of reasonable thresholds. A complementary metric also reveals that on six of the eight benchmarks, at least half of the labeled anomaly segments deviate univariately on 89% to 100% of their timesteps, reaching 100% on three of these datasets. To verify that our framework captures cross-channel structure when present, we construct synthetic data of phase-shifted sinusoidal channels with shared noise. Each anomalous segment is altered through one of two channel-wise corruptions that preserve the per-channel marginal distribution while breaking cross-channel structure, and our framework correctly characterizes these segments as cross-channel-only. On these data, channel-dependent (CD) models successfully exploit the cross-channel signal whereas channel-independent (CI) ones fail. The CI/CD comparison of a recent SOTA detector on real benchmarks further confirms that CD modeling brings no measurable gain. We conclude that current MTSAD benchmarks are unsuitable for validating cross-channel modeling capabilities, and we call for the development of more structurally diverse evaluation sets. The code for this study is publicly available.

14.
arXiv (CS.AI) 2026-06-16

From Tokens to Regions: CUDA-Sensitive Instruction Tuning for GPU Kernel Generation

arXiv:2606.16231v1 Announce Type: cross Abstract: High-performance CUDA kernels are essential for scalable AI systems, while Large Language Models (LLMs) still struggle to generate correct kernels due to strict and implicit execution constraints. Existing LLM-based approaches either rely on costly agentic or reinforcement-learning (RL) pipelines, or adopt supervised fine-tuning (SFT) objectives that fail to explicitly model CUDA sensitivity, namely code tokens or regions tightly coupled with execution constraints. In this work, we investigate CUDA sensitivity from the perspective of token confidence patterns, showing that CUDA sensitivity appears at both token and region levels, where most CUDA-sensitive tokens are predicted with high confidence, while a smaller low-confidence subset forms regions corresponding to execution-critical structures. These findings suggest that effective CUDA kernel generation should both leverage high-confidence CUDA-sensitive tokens and preserve low-confidence CUDA-sensitive regions. Building on these insights, we propose \underline{CUDA-\underline{Se}nsitive Instruction \underline{T}uning (CuSeT)}, a low-cost post-training method within a simple SFT framework. CuSeT follows the principle of ``from tokens to regions'' by combining adaptive token-level masking with region-aware sample reweighting. Experiments show that CuSeT consistently improves functional correctness across multiple model families and scales, outperforming standard SFT and advanced SFT variants, while achieving competitive performance against frontier CUDA kernel generation models with substantially lower inference cost.

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

SpatialWorld: Benchmarking Interactive Spatial Reasoning of Multimodal Agents in Real-World Tasks

Spatial reasoning is a foundational capability for multimodal large language models (MLLMs) to perceive and operate within the physical world. However, existing benchmarks predominantly rely on passive evaluation (e.g., static VQA) or simulator-specific pipelines, failing to assess general interactive spatial understanding. We introduce SpatialWorld, a unified benchmark designed specifically for evaluating the interactive spatial understanding of multimodal agents in complex real-world tasks. Integrating eight heterogeneous simulation backends under a shared, simulator-agnostic protocol, SpatialWorld features 760 human-annotated tasks across diverse domains (e.g., household routines, travel, social collaboration). Agents must solve tasks under vision-only partial observability, actively gathering egocentric visual evidence and expressing decisions via a unified, text-based action interface native to MLLMs. For reliable evaluation, each task includes a human-validated initial state, a reference trajectory, and a terminal-state verifier. Evaluating 15 advanced agents reveals that robust spatial task solving remains challenging: the strongest model, GPT-5, achieves an average task success rate (TSR) of only 17.4%, while the leading open-source model, Qwen-3.5, reaches 14.1%. Further analysis exposes a clear mismatch between task success and execution efficiency, alongside substantial domain-specific performance variations. These bottlenecks in active exploration and long-horizon planning position SpatialWorld as a rigorous testbed for future spatial agents.

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

GraphPO: Graph-based Policy Optimization for Reasoning Models

Reinforcement Learning with Verifiable Rewards (RLVR) has become a standard paradigm for enhancing the capability of large reasoning models. RLVR typically samples responses independently and optimizes the policy using from final answers. This paradigm has two limitations. First, independently responses often contain similar intermediate reasoning steps, causing redundant exploration and wasted computation. Second, sparse final-answer rewards make it hard to identify useful steps. Tree-based methods partly address this problem by sharing prefixes and comparing branches from the same prefix to provide fine-grained signals. However, tree branches are still expanded independently. When different branches reach similar reasoning states, they cannot share information and repeat similar exploration. Moreover, tree-based methods ignore such dispersion and only perform local comparisons within separate branches, which can lead to higher variance in advantage estimation. To address this challenge, we propose GraphPO (Graph-based Policy Optimization), a novel RL framework that represents rollouts as a directed acyclic graph, with reasoning steps as edges and semantic states summarized from the reasoning paths as nodes. GraphPO merges semantically equivalent reasoning paths into equivalence classes, allowing them to share suffixes and reallocating budget away from redundant expansions to diverse exploration. Furthermore, we assign efficiency advantages to incoming edges and correctness advantages to outgoing edges, thereby improving inference efficiency while deriving process supervision from outcome. Theory shows that GraphPO reduces advantage-estimation variance and enhances reasoning efficiency. Experiments on three LLMs across reasoning and agentic search benchmarks show that GraphPO consistently outperforms chain- and tree-based baselines with the same token budgets or response budgets.

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

FM-Agent: Scaling Formal Methods to Large Systems via LLM-Based Hoare-Style Reasoning

arXiv:2604.11556v2 Announce Type: replace-cross Abstract: LLM-assisted software development has become increasingly prevalent, and can generate large-scale systems, such as compilers. It becomes crucial to strengthen the correctness of the generated code. However, automated reasoning for large-scale systems remains challenging due to code complexity. Hoare logic offers an approach to decomposing a large system into smaller components and reasoning about them separately (i.e., compositional reasoning). However, existing works still struggle to scale, because Hoare logic requires writing formal specifications for each function, imposing a heavy human burden. The problem is exacerbated when code is generated by LLMs, as developers lack a deep understanding of each function's expected behavior. This paper presents FM-Agent, the first framework that realizes automated compositional reasoning for large-scale systems. Leveraging LLMs, FM-Agent introduces a top-down paradigm to automatically generate function-level specifications. Specifically, FM-Agent derives the specification of a function from how its callers expect the function to behave, so the generated specifications can reflect the developer's intent of a function even if the implementation is buggy. Developers' intent is usually expressed in natural language, while existing verifiers only support formulas. Therefore, FM-Agent generalizes Hoare-style inference to reason about functions against natural-language specifications. Finally, to confirm bug existence and explain bug causes, FM-Agent automatically generates test cases to trigger potential bugs. In our evaluation, FM-Agent successfully reasons about large-scale systems within 2 days, each of which has up to 143k LoC. These systems have already been tested by their developers, but FM-Agent still finds 522 newly discovered bugs. These bugs can cause serious consequences, including system crashes and incorrect execution results.

18.
arXiv (CS.CL) 2026-06-12

S-GBT: Smooth Growth Bound Tensor for Certified Robustness Against Word Substitution Attacks in NLP

Despite recent progress in Natural Language Processing (NLP), models remain vulnerable to word substitution attacks. Most existing defenses focus on first order sensitivity and measure how much the output changes when the input is slightly perturbed. However, they ignore how this sensitivity evolves, which is described by curvature. When gradients vary sharply, models can still fail. This paper introduces the Smooth Growth Bound Tensor (S-GBT), a second order method that bounds the Hessian element-wise, for which we provide formal theoretical proofs on the resulting robustness bounds. A regularization term is added during training to minimize these bounds. This yields tighter certified robustness against word substitution attacks. The change in the output under word substitution is bounded by both a linear term and a quadratic term. S-GBT is derived for two architectures: Long Short-Term Memory (LSTM) and Convolutional Neural Networks (CNN). The method is integrated directly into the training objective. Its effectiveness is evaluated on multiple benchmark datasets. The results show that combining first and second order regularization improves certified robust accuracy by up to 23.4% compared to prior methods, while clean accuracy remains competitive. These findings indicate that controlling both the gradient and its variation is a promising direction for building more robust models.

19.
arXiv (CS.CL) 2026-06-12

MARD: Mirror-Augmented Reasoning Distillation for Mechanism-Level Drug-Drug Interaction Prediction

Mechanism-level drug-drug interaction (DDI) prediction requires identifying which enzyme or pharmacodynamic axis is implicated, in which direction, and with which evidence – not merely whether two drugs interact. We introduce a reproducible mechanism-level DDI labelling and evaluation protocol with a structured 7-family/147-subtype taxonomy, leakage-safe cold-split protocols, and auditable reasoning metrics for evaluating pharmacological prediction beyond flat interaction classification. We propose a pipeline that produces a 7B reasoning MARD (Mirror-Augmented Reasoning Distillation), combining three training innovations: a single-token KL divergence on direction tag that ties the model's prediction, per-loss PRM-weighted DPO with programmatic hard negatives, and a leakage-safe mechanism-aware retrieval channel. Process-reward step labels are automatically verifiable against DrugBank-structured fields, requiring no human or LLM judges. On the April-2026 DrugBank release, our MARD-7B is the only system in a 32-system comparison whose accuracy survives drug-pair novelty, beating the best baseline by +13.9 pp and GPT-4o by +6.7 pp at ~1% of frontier API cost. Further analysis reveals an anti-memorisation signature where accuracy improves on rarely seen drugs, suggesting that gain comes from structured pharmacological reasoning rather than drug-frequency memorisation. We release corpus, DDI-PRM, retrieval index, and training code.

20.
medRxiv (Medicine) 2026-06-16

Prevalence and Correlates of Ideal Cardiovascular Health among Ugandan Adolescents: A Cross-Sectional Study

Introduction: Cardiovascular disease (CVD) risk factors often emerge during adolescence and track into adulthood, yet data on cardiovascular health (CVH) in sub-Saharan Africa remain limited. We assessed the prevalence and correlates of ideal CVH among Ugandan adolescents. Methods: We analysed baseline data of adolescents enrolled in a cluster-randomised controlled trial being conducted in urban (Kampala) and rural (Jinja) districts of Uganda. In this study, Ideal CVH was defined as meeting "ideal" status of 5-7 of the American Heart Association's Life's Simple 7 metrics. Random-effects logistic regression was used to identify factors associated with ideal CVH, accounting for village-level clustering. Results: We recruited 1316 participants with a mean age of 13.2 years, of whom 58.1% were female. Overall, the prevalence of ideal CVH was 66.8% (95% CI: 64.2% - 69.3%). The prevalence was higher in Jinja (74.4%, 95%CI: 70.9% - 77.7%) than Kampala (59.6%, 95%CI: 55.8%-63.2%) and the difference was evident (p

21.
arXiv (quant-ph) 2026-06-12

Asymmetric quantum steering harvested near a Lorentz-violating BTZ black hole

arXiv:2606.12766v1 Announce Type: cross Abstract: We investigate the harvesting of quantum steering and its directional asymmetry between two Unruh-DeWitt detectors in a Lorentz-violating BTZ black hole spacetime. Since the detectors are located at different radial positions outside the black hole, they experience inequivalent local environments induced by gravitational redshift, causing Alice to undergo stronger effective thermal noise than Bob. Remarkably, we uncover a counterintuitive phenomenon in which the detector subjected to a higher effective temperature exhibits stronger steerability than the other one, revealing a nontrivial inversion of thermal intuition in curved spacetime. Furthermore, quantum steering survives only within a finite window of detector energy gaps and reaches its maximum within an optimal regime. We find that Lorentz violation suppresses steering most strongly near this optimal energy gap, indicating an enhanced sensitivity of maximal correlation extraction to symmetry breaking effects. Our results demonstrate that Lorentz violation acts as a geometric constraint on the quantum information capacity of spacetime, simultaneously restricting both the strength and the directionality of quantum correlations.

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

Learning Earthquake Wave Arrival Time Picking from Labels with Inaccuracies

arXiv:2606.15377v1 Announce Type: cross Abstract: Inaccurately labeled training data, or "label noise", poses a significant threat to the integrity of supervised machine learning models. This corruption directly degrades performance by teaching the model erroneous mappings between features and labels, which leads to poor generalization and reduced accuracy on properly labeled validation and test data. Current seismological applications mainly rely on large-scale training sets or data augmentation to reduce the label-noise impact, which can be labor-intensive and costly. Here, we introduce a Label Noise-Contrastive Robust Learning (LaNCoR) approach that can effectively handle noisy labels in seismic signal processing tasks, without requiring large-scale training datasets. In this approach, the input waveform feature and label representation distributions are aligned in the feature space to correct mislabeling and reduce its impact on the training process. We present LaNCoR's performance on the task of P-phase arrival-time picking of real microseismic data using two baseline models and training approaches. Our results indicate that LaNCoR can improve performance by up to 28.8% across performance metrics. This approach holds great promise for model training in seismology and geosciences.

23.
bioRxiv (Bioinfo) 2026-06-21

Expanding the GUSome: Structure-guided identification and characterization of gut microbial β-glucuronidases

The gut microbiome-encoded {beta}-glucuronidase (GUS) enzymes have a significant effect on human physiology through their deglucuronidation activity on endogenous and exogenous glucuronides. GUS activity also significantly influences the pharmacokinetics, efficacy and toxicity of various drugs including chemotherapeutic drugs. Given their crucial role in drug metabolism, GUS enzymes have emerged as promising targets for therapeutic intervention. Here, we have identified and characterized 79 unique GUS enzymes through a structure-guided approach. Structural modelling of these GUS enzymes revealed a conserved core and active-site residues with significant variations in the number and nature of the C-terminal domains. A new classification system based on the number and type of additional C-terminal domains is presented for the GUS proteins. Further, GUS enzymes have been categorized into different loop categories linked to their substrate preferences. The relationship between domain architecture and loop-type is explored by sequence similarity network analysis. We could successfully express, purify and validate GUS processing capability of a panel of identified GUS proteins. The nature of oligomer organization has been deciphered by SEC and DLS studies. Further, we have identified additional GUS enzymes capable of processing SN-38G, glucuronidated form of anticancer drug, irinotecan. These newly identified GUS enzymes will offer valuable insights into gut microbial GUS diversity and their role in understanding the population-specific drug-induced adverse effects on human health.

24.
PLOS Computational Biology 2026-06-15

A multilevel hierarchical framework for quantification of experimental heterogeneity in population snapshot data

by David J. Warne, Xiangrun Zhu, Thomas P. Steele, Stuart T. Johnston, Scott A. Sisson, Matthew Faria, Ryan J. Murphy, Alexander P. Browning Biological systems exhibit substantial heterogeneity: that is, variation in specific characteristics of individuals within a population. As a result, it is of critical importance to appropriately account for biological heterogeneity when calibrating mathematical models to infer cellular processes and predict behaviour. Recent approaches consider ordinary differential equations with random parameters to quantify heterogeneity in dynamical processes of cells. In this setting, statistical inference is performed to characterise the distribution of these random parameters within a cell population. One significant limitation of this approach is the tacit assumption that there are no substantial deviations in these distributions across experimental replicates. In this work, we propose a flexible Bayesian hierarchical differential equation modelling framework that quantifies and distinguishes both inter-experimental heterogeneity (heterogeneity between experimental replicates) and intra-experimental heterogeneity (biological heterogeneity within replicate populations). We consider two recent studies that employ mathematical models to interpret flow cytometry snap-shot data and quantify heterogeneity in nano-particle cell interactions and cell internalisation processes. Using simulation data, we demonstrate that substantial inaccuracy in the inferred dynamics can arise when experimental heterogeneity is not accounted for. By contrast, our hierarchical approach is robust to variability in inter-experimental and intra-experimental heterogeneity and our method simplifies to previous methods when inter-experimental heterogeneity is negligible. Our approach is flexible and widely applicable to applications involving replicate populations and snapshot data. We provide open-source implementations of our methods on GitHub.

25.
arXiv (CS.CL) 2026-06-12

Language Model Circuits Are Sparse in the Neuron Basis

The high-level concepts that a neural network uses to perform computation need not be aligned to individual neurons (Smolensky, 1986). Language model interpretability research has thus turned to techniques which decompose the neuron basis into more interpretable units of model computation, such as sparse autoencoders (SAEs). However, not all neuron-based representations are uninterpretable. For the first time, we empirically show that MLP neurons are as sparse a feature basis as SAEs. We use this finding to develop an end-to-end gradient-based attribution pipeline for circuit tracing on the MLP neuron basis, which surfaces causally effective neurons on a variety of tasks. On a standard subject-verb agreement benchmark (Marks et al., 2025), a circuit of $\approx 10^2$ MLP neurons is enough to control model behaviour. On the multi-hop city-state-capital task from (Lindsey et al., 2025), we find a circuit in which small sets of neurons encode specific latent reasoning steps (e.g. mapping a city to its state), and can be steered to change the model's output. This work thus advances automated interpretability of language models without imposing additional training costs.