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01.
arXiv (CS.CV) 2026-06-17

CIAN: Multi-Stage Framework for Event-Enriched Image Captioning via Retrieval-Augmented Generation

Event-enriched image captioning describes not only visible content but also the broader context of events, including timing, location, and participants, capabilities missing in most pixel-bound models. We propose the Contextual Image-Article Narrator (CIAN), a multi-stage framework that enriches captions with external narratives. CIAN retrieves relevant articles using SigLIP, summarizes them to guide a Narrative Generation stage with a LoRA-fine-tuned Qwen model, and applies N-Gram-based Refinement for fluency and coherence. On the OpenEvents-V1 benchmark, CIAN achieves high retrieval performance (mAP 0.979) and improves caption quality, increasing CIDEr from 0.030 to 0.094. These results highlight the effectiveness of retrieval-augmented reasoning combined with linguistic refinement for generating context-aware, human-like captions.

02.
arXiv (CS.CL) 2026-06-19

Leverage Is Not Reach: A Control-Window Law for Single-Neuron Steering in Language Models

Aligned language models gate behaviors such as refusal and language routing through sparse feed forward neurons, yet no theory predicts when a single neuron intervention controls a behavior coherently rather than collapsing the output. We develop a budget normalized control window framework for single neuron steering. A dose along one write direction reduces to one control coordinate: the alignment between the residual stream and the write, driven along a universal saturation curve in units of a coherence budget set by the residual norm divided by the write norm. Coherent control exists when a behavior trigger lies below the collapse ceiling. The same coordinate governs benign mode switches and refusal; the ceiling follows from weights and one generic forward pass, while triggers are measured at rollout. On fifteen held out neurons, the predicted ceiling has mean absolute error 0.14, about 0.07 in bulk layers, and the committed open or closed verdict holds on eleven against a ten of fifteen majority baseline. Closed cases expose three failure modes rather than violations: collapse before trigger, too little depth to propagate, or a normalization that caps how far one neuron can push. The law explains why local gradient attribution anti predicts control: true controllers write off the readout axis and carry a near zero first order gradient. A forward only contrastive screen made precise by the window recovers controllers that attribution misses. On refusal, the hardest case, intervention success is typed, not scalar: coherent bypass and strict actionable reach separate, so a neuron can flip refusal in fluent, on task text with no actionable content, and genuine actionable reach appears only for three of six audited Llama pivots and only at later rollout horizons. Single neuron steering is therefore a budgeted, typed audit of controllability rather than a fixed dose anecdote.

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

Which Sections of a Research Paper Best Reveal Its Research Methods? Evidence from Library and Information Science

Research methods are essential carriers of knowledge contribution in academic papers. Automatic multi-label classification of research methods can support knowledge services such as method retrieval, review generation, and research intelligence analysis. While existing studies primarily rely on titles and abstracts, abstracts often provide only limited methodological information, whereas utilizing full-text content faces challenges related to excessive length and information redundancy. Therefore, this paper proposes a segment combination strategy by partitioning the full-text content according to its physical postion. Using an annotated corpus of 1,954 full-text articles from three representative journals in Library and Information Science (JASIST, LISR, and JDoc), we evaluate the classification performance of various segments and their combinations across multiple models. Experimental results indicate that methodological information is distributed unevenly within the full-text content, with the middle-to-late and final segments exhibiting greater discriminative power. Furthermore, integrating bibliographic metadata with cross-segment combination strategies effectively enhances classification performance.

04.
arXiv (CS.AI) 2026-06-17

DRFLOW: A Deep Research Benchmark for Personalized Workflow Prediction

arXiv:2606.18191v1 Announce Type: new Abstract: Deep research (DR) systems are increasingly used for complex information-seeking tasks, but existing works mainly focus on generating reports and summaries. In contrast, many enterprise tasks instead require an agent to identify concrete workflows which is a sequence of action-steps. For example, rather than summarizing budgeting policies, an agent should be able to determine the steps needed to answer a question such as: "How do I request new headcount given a fixed budget?". Therefore, we introduce DRFLOW, a benchmark for evaluating personalized workflows predicted by agents from heterogeneous sources. Each task requires the agent to identify relevant evidence from scattered sources, then use that evidence to predict the correct action-step sequence for the user's task. DRFLOW contains 100 tasks across five domains, with 1,246 reference workflow steps grounded in more than 3,900 sources. We define seven diagnostic metrics covering factual grounding, step recovery, structural ordering, condition resolution, and personalization. We further present DRFLOW-Agent (DRFA), a workflow-oriented reference agent to predict personalized workflow. We show that although DRFA improves over strong baseline agents (upto 10.02% average F1 score), there is substantial room for improvement remains across these workflow metrics, indicating that predicting complete and correct personalized workflows remains a challenging frontier for deep research.

05.
arXiv (quant-ph) 2026-06-12

Simple analytical flux-tuned iSWAP pulses for leakage suppression

arXiv:2606.13052v1 Announce Type: new Abstract: Fast, high-fidelity two-qubit gates are a key requirement for fault-tolerant quantum computation. Tunable coupler architectures provide a flexible approach for implementing entangling gates through flux control with large on-off ratios, but fast flux modulation can induce diabatic transitions and population leakage to non-computational states, limiting gate performance. Here we present an analytical flux control method enabling derivative removal by adiabatic gate ($\Phi$-DRAG) for suppressing leakage in flux tunable two-qubit gates. We show that $\Phi$-DRAG differs fundamentally from conventional microwave implementations and derive modified flux modulation protocols that suppress leakage below $10^{-4}$ for fast entangling gates. The method remains effective across a range of asymmetry between qubit anharmonicities and different circuit parameters, enabling high-fidelity two-qubit gates within the fifteen nanosecond range.

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

Creating squeezed and non-classical collective motional many-body states through stroboscopic Rydberg dressing

arXiv:2606.17849v1 Announce Type: cross Abstract: Realizing conditional quantum operations, e.g., quantum gates, for quantum computing and simulation requires controlled interactions between particles. Often, these interactions depend on the interparticle distance, and accordingly, an uncertainty of the relative particle position may translate into gate infidelities. We consider here a quantum computing platform based on an array of neutral atoms and present a method that allows to reduce the uncertainty of all interatomic distances. Our approach exploits the coupling between atomic motion and stroboscopically excited atomic Rydberg states. It allows to collectively squeeze the modes corresponding to interatomic displacements, thereby reducing distance fluctuations down to a fraction of the motional vacuum state. Furthermore, the method permits the creation of non-classical states with substantial Wigner negativity. These correlated states may allow reducing motional decoherence, increasing gate fidelity, and potentially yield a resource for quantum-enhanced metrology.

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

Region-Adaptive Sampling for Diffusion Transformers

Diffusion models (DMs) have become the leading choice for generative tasks across diverse domains. However, their reliance on multiple sequential forward passes significantly limits real-time performance. Previous acceleration methods have primarily focused on reducing the number of sampling steps or reusing intermediate results, failing to leverage variations across spatial regions within the image due to the constraints of convolutional U-Net structures. By harnessing the flexibility of Diffusion Transformers (DiTs) in handling variable number of tokens, we introduce RAS, a novel, training-free sampling strategy that dynamically assigns different sampling ratios to regions within an image based on the focus of the DiT model. Our key observation is that during each sampling step, the model concentrates on semantically meaningful regions, and these areas of focus exhibit strong continuity across consecutive steps. Leveraging this insight, RAS updates only the regions currently in focus, while other regions are updated using cached noise from the previous step. The model's focus is determined based on the output from the preceding step, capitalizing on the temporal consistency we observed. We evaluate RAS on Stable Diffusion 3 and Lumina-Next-T2I, achieving speedups up to 2.36x and 2.51x, respectively, with minimal degradation in generation quality. Additionally, a user study reveals that RAS delivers comparable qualities under human evaluation while achieving a 1.6x speedup. Our approach makes a significant step towards more efficient diffusion transformers, enhancing their potential for real-time applications.

09.
arXiv (quant-ph) 2026-06-16

Adaptively secure unitary designs with constant non-Clifford cost

arXiv:2510.08129v2 Announce Type: replace Abstract: Randomness is a fundamental resource in quantum information, with crucial applications in cryptography, algorithms, and error correction. A central challenge is to construct unitary $k$-designs that closely approximate Haar-random unitaries while minimizing the costly use of non-Clifford operations. In this work, we present a protocol able to generate unitary $k$-designs on $n$ qubits, secure against any adversarial quantum measurement, with a system-size-independent number of non-Clifford gates. Our construction applies a $k$-design only to a subsystem of size $\Theta(k)$, independent of $n$. This ``seed'' design is then ``diluted'' across the entire $n$-qubit system by sandwiching it between two random Clifford operators. The resulting ensemble forms an $\varepsilon$-approximate unitary $k$-design on $n$ qubits. We prove that this construction achieves full quantum security against adaptive adversaries using only $\tilde{O}(k^2 \log\varepsilon^{-1})$ non-Clifford gates. If one requires security only against polynomial-time adaptive adversaries, the non-Clifford cost decreases to $\tilde{O}(k + \log^{1+c} \varepsilon^{-1})$. This is optimal, since we show that at least $\Omega(k)$ non-Clifford gates are required in this setting. Compared to existing approaches, our method significantly reduces non-Clifford overhead while strengthening security guarantees to adaptive security as well as removing artificial assumptions between $n$ and $k$. These results make high-order unitary designs practically attainable in near-term fault-tolerant quantum architectures.

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

Constrained hybrid modelling to predict microbial dynamics and organic matter turnover in soil systems

arXiv:2606.20329v1 Announce Type: new Abstract: Soil microorganisms control organic matter cycling and largely determine how soil systems can cope with and mitigate climate change and environmental threats. Representing microbial dynamics in process-based soil models is therefore critical to predict carbon cycling in soils, albeit highly challenging to inform from data. One promising approach to improve their parametrisation is the integration of genomic data, yet modelling the complex and unknown relationship between genomes and the processes the microbes are driving is an unsolved problem. In this work, we present the first hybrid modeling framework for deriving biokinetic parameter values of a process-based soil organic matter turnover model from metagenome-inferred functional traits based on DNA sequencing data. Our model predicts biokinetic parameters of the process-based model from genomic trait data with a neural network and integrates constraints from ecological theory and literature to ensure realistic behavior, even of non-observed state variables. We evaluate our method on synthetic genomic trait datasets of varying complexity and on real data, showing that our approach improves performance over multiple baselines and learns the dynamics of unmeasurable components of the process-based model effectively, even for small training datasets.

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

Smarter Saboteurs, Better Fixers: Scaling & Security in Linear Multi-Agent Workflows

arXiv:2606.12709v1 Announce Type: cross Abstract: As LLM-based multi-agent systems (MAS) are deployed in the wild, the resilience of their collaboration structures against adversarial compromise becomes a critical safety concern. Attackers may leverage prompt-injection or jailbreaking to sabotage individual agents within MAS workflows, but the interaction between model scaling and system-level resilience remains poorly understood. This paper investigates how model scale affects the security of linear multi-agent workflows. Our experiments across scales of two open-weight model families on the HumanEval benchmark reveal a compliance-correction symmetry: larger models are far more likely to faithfully execute malicious instructions, with the control-to-malicious performance drop reaching 53.7pp at 27B in uncorrected pipelines. However, appending a lightweight terminal Fixer stage collapses this to 0.6pp and restores statistical parity with control-level performance, demonstrating that strictly linear collaboration structures can be viable and resilient to adversaries at this scale, and suggesting that the brittleness previously attributed to linear topology may stem from a lack of correction.

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

Residual-Space Evolutionary Optimization via Flow-based Generative Models

arXiv:2606.20084v1 Announce Type: new Abstract: Data editing with generative methods typically requires differentiable objectives and gradient-based search. However, these assumptions break down in flow-based settings, where edits are performed through forward and backward integration and often involve non-differentiable or black-box objectives. We introduce residual-space evolutionary optimization, a model-agnostic framework that addresses this gap by combining flow-based generative editing with evolutionary algorithms. Building on the observation that conditional flow matching (CFM) can disentangle condition-controlled factors from instance-specific residuals, our framework directly operates in residual space and separates two complementary search regimes: self-pollination performs local exploitation through feature-preserving residual refinement, and cross-pollination promotes broader exploration by recombining residuals across heterogeneous samples. As a proof of concept, we validate on MorphoMNIST, a benchmark dataset for counterfactual generation, and on crystal data, demonstrating that this exploration–exploitation decomposition provides a useful mechanism for balancing target alignment, instance preservation, and diversity, and extends beyond images to real-world scientific domains.

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

Pareto Q-Learning with Reward Machines

arXiv:2606.19134v1 Announce Type: cross Abstract: We present Pareto Q-Learning with Reward Machines (PQLRM), a multi-objective reinforcement learning algorithm for tasks whose reward structure is specified by a set of reward machines (RMs). PQLRM combines Pareto Q-Learning (PQL), which maintains sets of vector-valued Q-estimates to approximate the Pareto front, with enhancements from Q-Learning with Reward Machines (QRM), which exploits the factored automaton structure of the reward signal. This yields a multi-policy algorithm that remains sample-efficient under non-Markovian, RM-encoded rewards. Experimental trials show that PQLRM converges faster than a naive PQL baseline applied to the cross-product MDP and can synthesize Pareto-optimal policies that QRM cannot.

15.
medRxiv (Medicine) 2026-06-22

An integrated AI-microfluidic platform reveals the broad persistence and developmental potential of rare sperm in non-obstructive azoospermia

Non-obstructive azoospermia (NOA) represents the most severe form of male infertility, severely limiting a patient's prospects for biological fatherhood when surgical retrieval fails. However, the true biological limits of NOA remain obscured by the inherent limitations of conventional gamete recovery protocols: standard centrifugation frequently causes substantial cell loss, masking extremely rare sperm, while surgical interventions are constrained by spatial sampling biases. Here we report SpermSeek, an integrated AI-guided microfluidic platform for real-time, non-destructive isolation of single sperm directly from semen. Operating at scalable throughput (0.36 mL/h), the system achieves 98.3% detection precision and a 95.5% target encapsulation efficiency, suppressing background debris. In a 59-patient NOA cohort, SpermSeek detected morphologically identifiable sperm in 64.4% (38/59) of cases, spanning diverse genetic etiologies, including AZFb/c microdeletions, and severe histopathological phenotypes, such as Sertoli-cell-only syndrome (SCOS). Notably, among a sub-cohort of 41 patients who remained consistently sperm-negative despite prior medical or micro-TESE interventions, our platform identified gametes in 53.7% (22/41) of these cases. Comprehensive safety profiling in healthy human donors and wild-type mice confirmed that processed sperm retain high DNA integrity and epigenomic concordance (r=0.98), supporting transgenerational developmental stability in mice. Furthermore, in a 26-patient validation cohort, SpermSeek recovered rare sperm in 11 cases. Utilizing gametes from a subset (n=5), we demonstrated their capacity to support early human embryogenesis, yielding high-quality cleavage-stage embryos with confirmed genomic euploidy. This work establishes a highly sensitive framework for re-examining the biological limits of human spermatogenesis, laying the foundation to expand autologous reproductive options for patients refractory to conventional retrieval protocols.

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

Cross-Dataset Bloom Question Classification: Supervised Models and Prompted LLMs

Automatic Bloom's taxonomy classification of assessment questions can substantially reduce instructor workload, but labeling is subjective and teacher-dependent. Prior machine learning (ML) and deep learning (DL) approaches reported strong within-dataset results, yet were rarely evaluated in cross-dataset settings, leaving real-world generalizability unclear; meanwhile, LLM effectiveness for Bloom question classification has not been systematically studied. We evaluated the cross-dataset generalization of existing ML/DL methods and assessed LLMs with multiple prompting strategies on five datasets; the best prompting strategy combined in-context examples with course-specific action verbs. Supervised ML/DL models degraded substantially on unseen datasets, whereas LLMs were more stable, suggesting a robust alternative across diverse educational contexts. Based on the best prompting strategy, we also presented a lightweight UI that supports instructors in automatically classifying large question banks; a usability study indicated low workload and high usability.

17.
arXiv (CS.CL) 2026-06-15

SIMMER: Benchmarking Latent Failures in LLM Executable Planning with a World Model

Large language models (LLMs) are increasingly deployed as planners for autonomous agents in household environments. While existing benchmarks evaluate whether LLM-generated plans execute successfully, they overlook a critical type of failure: latent failures. Unlike immediate failures that trigger instant feedback at execution time and enable timely correction, latent failures do not immediately halt plan execution but silently compromise goal achievement. In severe cases, they cause irreversible harm. To address this gap, we introduce SIMMER, a benchmark for evaluating latent failures in LLM planning through a human-curated symbolic world model grounded in the kitchen domain. SIMMER defines a world model comprising 77 actions, 262 unique objects, and approximately 46,800 possible interactions that are semantically realistic, derived from real-world cooking scripts. It then leverages a state machine executor that validates plans against the world model and detects immediate precondition violations, latent hazards, and irreversible failures. Experiments across six LLMs show that even frontier models achieve at most 17% error-free plans. Moreover, up to 56% of plans contain latent failures, the majority of which lead to irreversible consequences. We further demonstrate that explicit state reasoning via counterfactual foresight simulation can reduce latent failures by up to 72% and irreversible cases by up to 75%, suggesting a promising direction for more robust LLM planners.

18.
arXiv (quant-ph) 2026-06-19

Exact Markovian Dissipation Requires Singular Energy Resources

arXiv:2606.19510v1 Announce Type: new Abstract: The Gorini–Kossakowski–Lindblad–Sudarshan (GKLS) equation describes irreversible quantum dynamical semigroups. We show that this description cannot be exact under physically regular energy conditions. We prove that the open-system survival probability under physically regular energy conditions has sublinear decay, whereas any dissipative GKLS semigroup has a linear short-time decay. Hence exact Markovian dissipation requires singular energy resources: an unbounded-below total Hamiltonian or infinite initial energy, and a divergent interaction-energy moment. Therefore, a dissipative time-independent GKLS equation should be regarded as an effective description rather than the exact reduced dynamics of a Hamiltonian dilation satisfying physically regular energy conditions.

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

The Initial Exploration Problem in Knowledge Graph Exploration

arXiv:2602.21066v2 Announce Type: replace Abstract: Knowledge Graphs (KGs) enable the integration and representation of complex information across domains, but their semantic richness and structural complexity create substantial barriers for lay users without expertise in semantic web technologies. When encountering an unfamiliar KG, such users face a distinct orientation challenge: they do not know what questions are possible, how the knowledge is structured, or how to begin exploration. This paper identifies and theorises this phenomenon as the Initial Exploration Problem (IEP). Drawing on theories from information behaviour and human-computer interaction, including ASK, exploratory search, information foraging, and cognitive load theory, we develop a conceptual framing of the IEP characterised by three interdependent barriers: scope uncertainty, ontology opacity, and query incapacity. We argue that these barriers converge at the moment of first contact, distinguishing the IEP from related concepts that presuppose an existing starting point or information goal. Analysing KG exploration interfaces at the level of interaction primitives, we suggest that many systems rely on epistemic assumptions that do not hold at first contact. This reveals a structural gap in the design space: the absence of interaction primitives for scope revelation, mechanisms that communicate what a KG contains without requiring users to formulate queries or interpret ontological structures. In articulating the IEP, this paper provides a theoretical lens for evaluating KG interfaces and for designing entry-point scaffolding that supports initial exploration.

20.
arXiv (CS.AI) 2026-06-11

WeaveBench: A Long-Horizon, Real-World Benchmark for Computer-Use Agents with Hybrid Interfaces

arXiv:2606.09426v2 Announce Type: replace Abstract: Computer-use agents (CUAs) increasingly operate in runtimes that combine visual desktop control, command-line execution, code editing, browsers, and external tools. Existing benchmarks, however, often evaluate these interfaces as separable capabilities, leaving long-horizon cross-interface orchestration under-tested. Thus, we introduce WeaveBench, a long-horizon hybrid-interface benchmark with 114 tasks across 8 real-world work domains, grounded in real user requests and publicly verifiable artifacts. Each task requires agents to combine GUI observations/actions with CLI/code operations within a single trajectory. We evaluate these tasks on a real Ubuntu desktop inside deployed CLI-agent runtimes, augmented with a minimal desktop-control plugin. We also propose a companion trajectory-aware judge that inspects deliverables, files, screenshots, logs, and action traces, while detecting shortcut behaviors such as fabricated visual evidence or hard-coded metrics. Across frontier model-runtime pairings, the best PassRate reaches only 41.2%, showing the benchmark remains far from saturated. The trajectory-aware judge further reveals that outcome-only grading substantially overestimates agent performance. Overall, WeaveBench exposes a critical gap in CUA evaluation and provides an effective testbed to measure whether agents can orchestrate GUI, CLI, and code operations across long-horizon real-world tasks.

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

SPRI: SVD-Partitioned Residual Initialization for Data-Constrained MoE Upcycling

arXiv:2606.16456v1 Announce Type: cross Abstract: Mixture-of-Experts (MoE) models enable efficient scaling, but training them from scratch remains prohibitively expensive. MoE upcycling mitigates this cost by converting pretrained dense models into sparse MoE models. However, existing upcycling methods typically rely on large-scale continued training and often perform poorly under data-constrained supervised adaptation, due to either homogeneous experts or overly disruptive perturbations to pretrained parameters. In this setting, effective upcycling must leverage pretrained weight structure while introducing sufficient diversity among routed experts. To this end, we propose SVD-Partitioned Residual Initialization (SPRI), which distributes SVD-partitioned residuals derived from pretrained feed-forward network (FFN) weights across routed experts, introducing controlled expert diversity grounded in pretrained spectral structure. We further introduce a two-stage training strategy to improve adaptation stability. We evaluate SPRI on multilingual speech-to-text translation, where limited supervised data challenges MoE upcycling and multiple target languages provide natural routing heterogeneity. On CoVoST2 across 15 En-to-XX directions, SPRI improves average BLEU and COMET over fully fine-tuned dense models by 2.58 and 3.32 points, respectively, and outperforms the prior best MoE upcycling baseline by 3.39 BLEU and 4.34 COMET points.

22.
medRxiv (Medicine) 2026-06-16

Comparative Effectiveness and Safety of Prophylactic Vasopressors for Preventing Post-induction Hypotension in the Elderly: A Systematic Review and Network Meta-analysis

Background: Post-induction hypotension is a predictable haemodynamic hazard in older adults undergoing general anaesthesia. Prevention remains divided among volume optimisation, anaesthetic dose reduction, rescue treatment after hypotension occurs and proactive vasoactive support. Methods: We searched PubMed, Embase, Web of Science, CENTRAL, CNKI, Wanfang and VIP from inception to 30 March 2026. Eligible studies were randomised trials of prophylactic vasoactive drugs given before, during or immediately after induction in older adults. The primary outcome was post-induction hypotension. Secondary outcomes were post-induction mean arterial pressure (MAP), systolic arterial pressure (SBP), heart rate (HR) and reported haemodynamic adverse events. Random-effects network meta-analysis was used, and confidence in network estimates was assessed using CINeMA principles. Results: Thirty-one trials including 2,821 participants were included in the revised network. Compared with placebo/control, all active agents favoured lower post-induction hypotension. The most favourable point estimates were observed for phenylephrine (odds ratio [OR] 0.17, 95% confidence interval [CI] 0.01 to 2.16) and metaraminol (OR 0.19, 95% CI 0.02 to 1.53), although both were imprecise. More precise reductions were observed for methoxamine (OR 0.23, 95% CI 0.13 to 0.43), norepinephrine (OR 0.25, 95% CI 0.13 to 0.47) and ephedrine (OR 0.34, 95% CI 0.19 to 0.63). Phenylephrine ranked highest for MAP support, norepinephrine ranked highest for SBP support, and ephedrine ranked highest for HR preservation. Global inconsistency was detected for SBP but not for hypotension incidence, MAP or HR, supporting cautious profile-based interpretation. Conclusions: Prophylactic vasopressor choice during induction should be guided by haemodynamic phenotype rather than ranking alone. In the revised network, active prophylaxis consistently favoured lower hypotension, but sparse nodes produced uncertainty. Norepinephrine retained a comparatively balanced profile when vasodilatory post-induction hypotension is anticipated, phenylephrine and related alpha-agonists provided stronger pressure support when HR and cardiac-output reserve are preserved, and ephedrine was most relevant when chronotropic support is desired. Keywords: general anaesthesia; induction; hypotension; norepinephrine; phenylephrine; ephedrine; network meta-analysis; older adults.

23.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

24.
arXiv (CS.CV) 2026-06-18

SMART: A Flexible, Interpretable, and Scalable Spatio-temporal Brain Atlas from High-Resolution Imaging Data

We introduce SMART, a framework for learning a flexible, interpretable, and scalable spatio-temporal brain atlas from longitudinal high-resolution 3D medical images. Existing approaches to spatio-temporal atlas construction rely on black-box generative models that lack flexibility, limit interpretability, and struggle to scale to high-dimensional data. SMART addresses these challenges by learning a continuous disease-time atlas that decouples global group-wise disease dynamics from their patient-specific anatomical manifestation. Guided by anatomically inspired priors, SMART models interpretable global trajectories of regional progression along a shared disease timeline through region-specific differential equations. Global trajectories are further personalized to individual anatomies via dense diffeomorphic displacements parameterized by a flexible and scalable multi-scale Neural Cellular Automata. Evaluated on five longitudinal MRI datasets in Alzheimer's disease (ADNI-1/GO/2, OASIS-3, AIBL; > 1,300 subjects), SMART produces anatomically meaningful predictions of disease progression and achieves state-of-the-art forecasting accuracy and improved temporal consistency over adversarial and diffusion baselines. Our approach establishes a new paradigm for flexible, interpretable, and scalable modeling of spatio-temporal change in high-dimensional medical image time-series.

25.
arXiv (CS.CV) 2026-06-16

Attention-Based Prototype Calibration for Multi-Rater Few-Shot Medical Image Segmentation

Few-shot medical image segmentation methods typically assume a single ground-truth annotation, overlooking systematic variability across expert raters commonly observed in clinical datasets. We propose an attention-based prototype calibration framework for few-shot multi-rater segmentation that models rater-specific deviations from a consensus representation in prototype space. A lightweight yet principled attention operator directly refines rater prototypes without modifying the backbone feature extractor, making the approach fully compatible with existing prototype-based few-shot segmentation methods. This design preserves semantic consistency while enabling personalized segmentation outputs with minimal computational overhead. Experiments on multi-rater medical imaging datasets demonstrate consistent improvements over baseline prototype approaches, highlighting the effectiveness of structured prototype calibration for modeling annotation variability. Our code is available at https://github.com/truong2710-cyber/JAPC.