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01.
arXiv (CS.LG) 2026-06-12

When to Align, When to Predict: A Phase Diagram for Multimodal Learning

arXiv:2606.11190v2 Announce Type: replace Abstract: Cross-modal alignment (CA) and cross-modal prediction (CP) are the dominant paradigms for multimodal representation learning, yet there is no systematic understanding of when each succeeds, when each fails, and when cross-modal training helps at all – a gap that leaves practitioners, especially in scientific domains like biomedicine or astrophysics, with heterogeneous instruments and multiple levels of organization and measurement, unable to diagnose why standard methods underperform the best single modality. We develop a unified linear framework that addresses both questions. Under a spiked signal-plus-noise model with structured cross-modal nuisance correlation, we derive separation ratios for both objectives that expose complementary failure modes: alignment whitens each modality and fails when nuisance is strongly correlated across views; prediction encodes whatever is cross-predictable through a one-sided whitening, with recovery governed by source-modality quality. The resulting phase diagram partitions multimodal problems into four regimes: Both, CA only, CP only, and Neither. We present a data-driven procedure to locate real-world datasets in this diagram using a small labeled subsample, identifying the preferred objective and prediction direction before any cross-modal training. Experiments on synthetic data, stereo-vision benchmarks, image-caption pairs, and real astrophysical data validate the predictions in the nonlinear regime, including the Neither regime where cross-modal training is actively harmful. Our framework lets practitioners diagnose their multimodal problem and choose the right objective before committing to training. Code to reproduce the results is available at https://github.com/IlayMalinyak/mm_align_vs_pred.

02.
PLOS Computational Biology 2026-06-01

Histology-informed spatial domain identification through multi-view graph convolutional networks

作者:

by Huihui Zhang, Jiaxing Chang, Zirong Li, Yue Sun, Pinli Hu, Haoxiu Wang, Hang Yang, Yonglin Ren, Xingtan Zhang, Zehua Chen, Kok Wai Wong, Haojing Shao Identifying spatial domains is crucial in spatial transcriptomics, yet effectively integrating gene expression, spatial location, and histology remains challenging. We present STESH, a Spatial Transcriptomics clustering method that combines Expression, Spatial information and Histology. STESH extracts histological features using a convolutional neural network and generates expression, histology, spatial, and collaborative convolution modules for a multi-view graph convolutional network with a decoder and attention mechanism. We evaluated STESH on multiple tissue types and technology platforms. STESH consistently outperformed ten state-of-the-art methods, achieving superior clustering accuracy with the highest scores in adjusted Rand index, normalized mutual information, and Fowlkes-Mallows index.

03.
arXiv (CS.LG) 2026-06-16

Dynestyx: A Probabilistic Programming Library for Dynamical Systems

arXiv:2606.16985v1 Announce Type: cross Abstract: State-space models (SSMs) are the standard formalism for Bayesian treatment of dynamical systems, with natural applications in statistics, signal processing, and machine learning. Despite their importance in both theory and application, dynamical systems have proven difficult to incorporate in modern probabilistic programming languages (PPLs), making state-of-the-art methods less accessible to practitioners and introducing friction in following the "Bayesian workflow." We introduce dynestyx, a probabilistic programming library with first-class support for SSMs, including state-of-the-art methods in the estimation of both states and parameters. Through a single, unified interface, users may specify arbitrary priors for discrete-time or continuous-time dynamical systems, perform inference over mixed-effect data, and make state and parameter estimates with principled uncertainty quantification.

04.
Nature (Science) 2026-06-11

‘Footballers are not superheroes’: we must tackle the mental and physical pressures of elite sport

作者:

As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge. As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge.

05.
medRxiv (Medicine) 2026-06-24

Cognitive-emotional responses to ultrasonic neuromodulation of anterior cingulate cortex

The anterior cingulate cortex (ACC) is a key brain center involved in cognitive and emotional processing that is implicated in a variety of neuropsychiatric disorders including chronic pain and depression. Circuit-targeted diagnosis and treatment of these disorders will require the capacity to precisely modulate ACC subregions. Toward that end, we recently developed and validated a novel low-intensity transcranial focused ultrasound device that can noninvasively and directly modulate ACC subdivisions in humans with millimeter precision. Here we describe the subjective reports of 36 individuals diagnosed with either chronic pain or major depression who received repeated brief stimulation trials (807 active, 797 sham; duration 30s-3min) spanning the dorsoventral extent of the ACC. Sonication immediately altered cognitive-emotional states (odds ratio 5.6, active versus sham), eliciting a positive-valence experience more often than negative (29% versus 8%) in both diagnostic groups. Sham-adjusted response rate varied across ACC targets, with the largest effects (Cohen's d ~ 0.8) observed in pregenual and subgenual ACC in subjects with chronic pain and depression, respectively. These rapid trial-by-trial responses to ACC stimulation predicted subsequent improvements in pain and depression severity at 24 hours. Collectively, these findings reveal that transcranial ultrasound can robustly evoke immediate, target-specific, clinically meaningful changes in cognitive-emotional state, demonstrating the potential of ultrasonic neuromodulation as a tool for individualized probing of circuit function and dysfunction.

06.
arXiv (math.PR) 2026-06-17

Limit theorems for random Dirichlet series with summation over primes, with an application to Rademacher random multiplicative functions

arXiv:2508.15032v2 Announce Type: replace Abstract: It is shown that two conjectures put forward in the recent article Iksanov and Kostohryz (2025) are true. Namely, we prove a functional central limit theorem (FCLT) and a law of the iterated logarithm (LIL) for a random Dirichlet series $\sum_p \frac{\eta_p}{p^{1/2+s}}$ as $s\to 0+$, where $\eta_1$, $\eta_2,\ldots$ are independent identically distributed random variables with zero mean and finite variance, and $\sum_p$ denotes the summation over the prime numbers. As a consequence, an FCLT and an LIL are obtained for $\log \sum_{n\geq 1} \frac{f(n)}{n^{1/2+s}}$ as $s\to 0+$, where $f$ is a Rademacher random multiplicative function.

07.
arXiv (CS.AI) 2026-06-15

STaR-DRO: Stateful Tsallis Reweighting for Group-Robust Structured Prediction

arXiv:2604.09737v2 Announce Type: replace-cross Abstract: Structured prediction with large language models requires outputs that are label-accurate, ontology-constrained, structurally valid, and evidence-grounded under label imbalance and heterogeneous group difficulty. We present a unified framework for ontology-constrained generation. First, we introduce a modular prompt-engineering architecture combining XML-style structure, expert disambiguation rules, chain-of-thought reasoning, metadata-aware decision logic, schema contracts, and a self-validation gate. It targets recurrent in-context failures, including format drift, label ambiguity, evidence hallucination, and metadata-conditioned confusion. Second, we propose STaR-DRO, combining Tsallis mirror ascent, sparse entmax-style primal mapback, EMA-smoothed group-loss tracking, rescaled ascent signals, and bounded excess-only multipliers. Unlike conventional DRO, which relies on dense Shannon-entropy exponentiated-gradient updates, can introduce high-variance stochastic reweighting, assigns positive adversarial mass to groups that are not persistently hard, and incurs costs through simplex competition, STaR-DRO upweights only persistently hard groups without suppressing easier ones. We evaluate the framework on EPPC Miner, a clinically grounded high-stakes structured-prediction task requiring hierarchical label prediction and evidence-span extraction from patient-provider secure messages. Across 1B-70B Llama models, prompt engineering improves zero-shot extraction, yielding an average label F1 gain of +14.46 and a Span F1 gain of +17.40. Building on supervised fine-tuning, STaR-DRO further improves accuracy and robustness, increasing average label F1 by +1.08 and +2.20 while reducing mean groupwise validation cross-entropy by 21.3% and 14.8% relative to SFT and standard DRO, respectively. These results advance reliable automated communication mining for patient-centered clinical care analysis.

08.
arXiv (CS.AI) 2026-06-16

Few-shot Class-variable Incremental Audio Classification via Prototype Adaptation and Pseudo Class-variable Training

arXiv:2606.08898v2 Announce Type: replace-cross Abstract: In the task of few-shot class-incremental audio classification, the number of classes is assumed to always increase without considering the possibility of decrease. However, the number of classes generally increases or decreases in practice. In this paper, we investigate a problem of Few-shot Class-variable Incremental Audio Classification (FCIAC), in which the number of classes increases or decreases. We propose a FCIAC method using prototype adaptation and pseudo class-variable training. The model in our method consists of an encoder and a classifier. The classifier is initialized by a class-variable prototype adaptation network, whose structure dynamically changes with the change of classes. In addition, we design a pseudo class-variable training strategy to enhance the model's adaptability to changing classes. Experiments on three public datasets show that our method exceeds previous methods in average accuracy. The code is at: https://github.com/cgq2971-afk/FCIAC.

09.
arXiv (CS.LG) 2026-06-18

Ensuring Trustworthy Online A/B Testing: Addressing Five Key Questions on CUPED

arXiv:2606.18750v1 Announce Type: cross Abstract: A/B testing has become the gold standard for data-driven decision-making in large-scale online experimentation, providing critical guidance for feature launch, pricing optimization, and user experience enhancement. To maximize statistical sensitivity, many technology companies routinely employ Controlled-experiment Using Pre-Experiment Data (CUPED), a technique that achieves substantial variance reduction while preserving the unbiasedness of estimating the average treatment effect. Despite its widespread adoption, several critical methodological and practical nuances of CUPED remain underexplored. This paper systematically addresses five frequently encountered yet overlooked questions regarding the application of CUPED. First, we provide a comparative analysis of various post-CUPED estimators to identify the optimal adjustment specification. Second, we evaluate the validity of regression-based adjustments and delineate robust variance estimation methods tailored for such frameworks. Finally, we extend our investigation to complex but common scenarios, including multi-arm experiments and two-stage sampling designs. Our findings reveal that in these settings, naive reliance on standard variance estimators can lead to severely misleading inferences. By offering rigorous theoretical insights and extensive experimental validation, this work deepens the conceptual understanding of CUPED. Notably, the recommended methodologies have been successfully deployed and integrated into ByteDance's experimentation platform.

10.
arXiv (CS.AI) 2026-06-18

Deep-Learning-Based Pixelated Microwave Filter Design and Characterization using Electro-Optical Electric-Field Measurements

arXiv:2606.18402v1 Announce Type: cross Abstract: Traditional microwave filter design typically relies on iterative parameter tuning and predefined topologies, which limits design space and increases development time. This study uses a deep learning approach combining convolutional neural networks with genetic algorithms to automate pixelated microwave filter synthesis. To validate the approach experimentally, both S-parameter and spatial electric-field measurements were analyzed. The synthesized low-pass filter demonstrated excellent agreement between simulated and measured performance, achieving a 7 GHz passband with over 20 dB suppression beyond 9.5 GHz. Electro-optical measurements, for the first time, revealed electric field patterns that resemble coupled transmission-lines or stub structures, providing insight into the emergent characteristics of AI-generated designs.

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

AutoSpecNER: A Fine-Grained Named Entity Recognition Dataset for Vehicle Specification Extraction

Vehicle advertisements contain rich specification information, but automotive NER resources remain limited. We introduce AutoSpecNER, an expert-annotated dataset for fine-grained entity recognition in vehicle listings. The dataset includes 659 advertisements from a popular car-selling website, with over 10,000 entities annotated across 15 categories, including MODEL, ENGINE_SPEC, and BATTERY_CAPACITY. Annotation quality was validated through inter-annotator agreement, achieving an average score of 91.5%. We benchmark rule-based extraction, fine-tuned transformer encoders, and large language models. DeBERTa achieves the best performance with a 90% micro-F1 score, outperforming the rule-based baseline (43%) and the strongest large language model (77.8%).

12.
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.

13.
arXiv (quant-ph) 2026-06-12

Relativistic Locality from Electromagnetism to Quantum Field Theory

arXiv:2412.11532v2 Announce Type: replace Abstract: Electromagnetism is the paradigm case of a theory that satisfies relativistic locality. This can be proven by demonstrating that, once the theory's laws are imposed, what is happening within a region fixes what will happen in the contracting light-cone with that region as its base. The Klein-Gordon and Dirac equations meet the same standard. We show that this standard can also be applied to quantum field theory (without collapse), examining two different ways of assigning reduced density matrix states to regions of space. Our preferred method begins from field wave functionals and judges quantum field theory to be local. Another method begins from particle wave functions (states in Fock space) and leads to either non-locality or an inability to assign states to regions, depending on the choice of creation operators. We take this analysis of quantum field theory (without collapse) to show that the many-worlds interpretation of quantum physics is local at the fundamental level. We argue that this fundamental locality is compatible with either local or global accounts of the non-fundamental branching of worlds, countering an objection that has been raised to the Sebens-Carroll derivation of the Born Rule from self-locating uncertainty.

14.
arXiv (CS.CV) 2026-06-15

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

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

15.
arXiv (math.PR) 2026-06-25

Haagerup property and group-invariant percolation

arXiv:2303.17429v3 Announce Type: replace-cross Abstract: Let $\mathcal G$ be the Cayley graph of a finitely generated, infinite group $\Gamma$. We show that $\Gamma$ has the Haagerup property if and only if for every $\alpha\alpha\mathrm{deg}_{\mathcal G}(g)$ for every vertex $g$ and with the two-point function $\tau(g,h)=\mathbb P\big[g\leftrightarrow h\big]$ vanishing as $d(g,h)\to\infty$. On the other hand, we show that $\Gamma$ has Kazhdan's property (T) if and only if there exists a threshold $\alpha^*\alpha^*\mathrm{deg}(o)$ implies that the two-point function is uniformly bounded away from zero. These results in particular answer questions raised by Lyons (J. Math. Phys. 41. 1099-1126 (2000)) about characterizations of properties of groups beyond amenability through group-invariant percolations. The method of proof is new and is based on a construction of percolations with suitable dependence structures built from invariant point processes on spaces with measured walls. This construction furthermore leads to quantitative bounds on the two-point functions, exhibiting in particular exponential decay of the two-point function in several prominent examples of Haagerup groups, including co-compact Fuchsian groups, co-compact discrete subgroups of $\mathrm{Isom}(\mathbb H^n)$ and lamplighters over free groups. This method also allows us to extend the aforementioned characterization of property (T) to the setting of relative property (T) and provide an application to Bernoulli percolation at the uniqueness threshold.

16.
arXiv (quant-ph) 2026-06-11

Strong-field control of the $Z$-boson resonance in $e^+e^-$ collisions

arXiv:2606.09394v2 Announce Type: replace-cross Abstract: Resonant $Z$-boson production is a cornerstone of precision electroweak physics, with its vacuum line shape set by the $Z$ mass, width, and collision kinematics. We show that a strong laser field can significantly alter this picture. By treating the field nonperturbatively, we find that laser dressing of the incoming fermions alters the effective collision kinematics and opens laser-photon exchange channels, including multiphoton processes, in $e^{+}e^{-}$ collisions. As a result, the $Z$-resonance profile develops distinct intensity-dependent regimes, evolving from the vacuum limit to saturation at intermediate field strengths and to an approximately quadratic enhancement at higher intensities. Additionally, the polarization composition of the produced $Z$ bosons is redistributed. In particular, at high intensities the laser-induced contribution can compensate the intrinsic chiral asymmetry of the electroweak interaction, leading to nearly parity-balanced $Z$-boson production. Our results identify that strong classical fields can dynamically control electroweak resonance phenomena, opening a bridge between strong-field QED and high-energy collider physics.

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

DiffMath: Symbol- and Graph-Aware Latent Diffusion Transformer for Handwritten Mathematical Expression Generation

Handwritten Mathematical Expression Generation (HMEG) is challenging due to the complex two-dimensional layouts and long-range structural dependencies of mathematical expressions. Existing methods typically rely on explicit spatial supervision, such as symbol-level bounding boxes, which incurs high annotation costs and limits scalability. In this work, we propose DiffMath, a symbol- and graph-aware latent diffusion framework that leverages the hierarchical structure inherent in LaTeX as a structural prior, eliminating the need for positional supervision. First, we design a Relational Abstract Syntax Tree (RelAST), a generation-oriented representation that distills MathML trees into compact triplet sequences [S, R, D], where each token directly encodes a symbol identity, spatial relation, or nesting depth. Second, we introduce MathVAE, which learns structure-preserving latent representations through symbol-aware and relation-aware perceptual regularization, ensuring that the latent space captures both character semantics and spatial topology. Third, MathDiT performs conditional denoising in this structured latent space, further guided by a global symbol-count prior via Adaptive Layer Normalization (AdaLN) to improve structural coherence. Experiments show that DiffMath produces structurally consistent handwritten expressions, achieves superior performance over existing methods, and improves the accuracy of downstream OCR models through synthetic data augmentation.

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

LLMs Can Better Capture Human Judgments–With the Right Prompts

Are large language models (LLMs) bad at capturing human judgment? Two commonly stated limitations are that LLMs fail to capture full distributions of responses, and that their judgments are unstable across wording variations. We demonstrate simple prompting strategies that mitigate these limitations. Across two datasets–a U.S.-representative set of 144 moral scenarios and 38 moral beliefs from the International Social Survey Programme's Family and Changing Gender Roles module covering 32 countries–we show how simple elicitation techniques help improve AI-human alignment. First, prompting models to report standard deviations and response proportions recovers the full range of human responses better than common strategies. Second, ensuring scenarios are clear to human participants–as reflected in human confusion ratings–boosts model alignment, and LLMs can track human confusion ratings. At the same time, we find that LLMs' estimates of their own error are poorly calibrated, though they can predict human variability relatively well. These results suggest that asking better questions to LLMs can yield better answers.

19.
arXiv (CS.LG) 2026-06-25

RN-D: Discretized Categorical Actors for On-Policy Reinforcement Learning

arXiv:2601.23075v2 Announce Type: replace Abstract: On-policy Reinforcement Learning (RL) remains a dominant paradigm for continuous control, yet standard implementations rely on Gaussian actors and relatively shallow MLP policies, often leading to brittle optimization when gradients are noisy, and policy updates must be conservative. In this paper, we revisit actor policy representation as a first-class design choice for on-policy RL. We study discretized categorical actors, which represent each action dimension as a distribution over discrete bins and induce a policy objective analogous to classification cross-entropy loss. Building on architectural advances from supervised learning, we further pair discretized categorical actors with regularized networks, yielding RN-D. Across diverse continuous-control benchmarks, we show that simply replacing the standard Gaussian actor with our proposed actor substantially improves performance, achieving state-of-the-art results within on-policy RL. We release our code at https://github.com/alwaysbyx/RND-RL.

20.
arXiv (CS.CV) 2026-06-16

Akasha 2: Hamiltonian State Space Duality and Visual-Language Joint Embedding Predictive Architectur

作者:

We present Akasha 2, a state-of-the-art multimodal architecture that integrates Hamiltonian State Space Duality (H-SSD) with Visual-Language Joint Embedding Predictive Architecture (VL-JEPA). The system leverages the Mamba-3 Selective State Space Model (SSM) augmented by a Sparse Mixture of Hamiltonian Experts (SMoE-HE) that enforces latent physical conservation laws through symplectic integration. For visual synthesis, we introduce Hamiltonian Flow Matching (HFM) and persistent 3D Gaussian Splatting (3DGS), enabling ultra-low latency (

21.
Nature (Science) 2026-06-24

A global map of seagrass ecosystems

Combining satellite imagery and machine learning has created the first comprehensive map of seagrass meadows, in a boost for the conservation of these crucial ecosystems. Combining satellite imagery and machine learning has created the first comprehensive map of seagrass meadows, in a boost for the conservation of these crucial ecosystems.

22.
arXiv (CS.AI) 2026-06-18

RODS: Reward-Driven Online Data Synthesis for Multi-Turn Tool-Use Agents

arXiv:2606.19047v1 Announce Type: new Abstract: Multi-turn tool-use RL is bottlenecked by the rapid depletion of informative samples in static datasets. We observe that the gradient signal in GRPO concentrates on tasks with the highest rollout reward variance, a consequence of the Popoviciu upper bound. Consequently, samples near the agent's capability boundary – where successes and failures are roughly balanced – contribute disproportionately large policy gradients. As training progresses, this boundary continuously shifts, which gradually depletes the pool of informative samples in a static dataset. We propose RODS (Reward-driven Online Data Synthesis) to resolve this depletion. RODS closes the loop between RL training and data generation by repurposing the progress reward variance as a practical, zero-cost boundary detector that requires no extra inference beyond the rollouts already computed for training. It continuously identifies such boundary samples, synthesizes new multi-turn variants matching their structural complexity (e.g., API topology and dependency depth) via a skill-aligned resampling pipeline, and manages a dynamic replay buffer that co-evolves with the policy. Starting from 400 human seeds and maintaining an active training pool of ~800 samples, RODS achieves comparable performance to a 17K-sample offline pipeline while requiring roughly 20x fewer trajectories, and improves over fixed-data RL and environment augmentation in our controlled setting.

23.
arXiv (CS.AI) 2026-06-18

RTSGameBench: An RTS Benchmark for Strategic Reasoning by Vision-Language Models

arXiv:2606.18950v1 Announce Type: new Abstract: Modern Vision-Language Models (VLMs) often struggle with strategic reasoning, i.e., anticipating and influencing other agents' actions, under uncertainty in competitive and cooperative settings. Real-time strategy (RTS) games can be a natural testbed for diagnosing this limitation, as they demand coordination with allies, adaptation to opponents' strategy, and long-horizon planning under partial observability. However, existing RTS benchmarks offer limited evaluation scope, lack systematic competency diagnosis, and remain fixed in the pre-designed scenario coverage. To address these limitations, we present RTSGameBench, which is built on Beyond All Reason, a large-scale RTS game with an expanded battlefield that demands broader strategy diversity than the existing testbeds. The proposed benchmark provides evaluations through diverse gameplay across various matchup structures, diagnostic assessment via mini-games, each targeting an individual strategic competency, and extensible coverage via a self-evolving generation framework that converts free-form queries into new mini-games, improving over successive cycles. Additionally, for VLMs to operate in large-scale RTS games, we provide RTSGameAgent that manages units by an FSM with agentic memory. We empirically validate that multiple state-of-the-art VLMs do not perform well when matchups demand tighter coordination, multiagent coordination and when task scale increases.

24.
bioRxiv (Bioinfo) 2026-06-11

DivQuant: Estimation of Species Richness and Entropy from Small Samples

Estimating diversity properties of discrete distributions from a small observed sample is a fundamental problem in algorithmic statistics that has applications in many fields, in particular bioinformatics, but also in ecology or linguistics. The two most common diversity measures are the number of distinct elements in a multiset, also referred to as species richness in ecology or alpha diversity in microbial analysis, and the Shannon entropy, also referred to as evenness. Estimating these properties from a small sample is particularly challenging for distributions with many rare elements. Thus, many estimators have been proposed in the past that, in practice, work well for different types of distributions. We present DivQuant, an optimization-based, extrapolating richness and entropy estimator with three contributions. First, we formulate the upsampling problem as a convex quadratic program with a Neyman {chi}2 objective. Unlike the linear program of its predecessor RichnEst, DivQuant admits confidence intervals via {chi}2 test inversion that are empirically well-calibrated. Second, we replace RichnEst's fixed-threshold fingerprint truncation with the rare/abundant fingerprint split of Valiant and Valiant, which strongly reduces problem size and preserves enough degrees of freedom for the confidence-interval program to remain valid and feasible. Third, we plug the optimal population fingerprint returned by the program into Shannon's entropy formula to obtain an entropy estimate. DivQuant attains close-to-nominal 95% confidence intervals in essentially all tested regimes, including six simulated distribution families, Tara Oceans microbiome data, and 10X Genomics scRNA-seq data, while competing state-of-the-art methods (RichnEst, iNext, PreSeq) miss the true richness in up to 80% of instances, well above the nominal 5%. In addition, DivQuant outperforms classical asymptotic entropy estimators (Miller-Madow, CAE) and the extrapolating iNext estimator. Running times remain competitive, with DivQuant typically completing in seconds. DivQuant is available as a command-line tool at https://gitlab.com/rahmannlab/divquant.

25.
medRxiv (Medicine) 2026-06-10

Optimisation of steatotic liver disease screening algorithm for resource-poor settings using machine learning

Background The European Association for the Study of the Liver (ESAL) - Steatotic Liver Disease (SLD) screening algorithm involves two steps; initial screening with FIB-4 followed by referral for vibration-controlled transient elastography (VCTE) in patients likely to have significant fibrosis (SF). However, VCTE is not widely available in resource-limited settings. Aim To optimise the EASL SLD screening algorithm for resource-poor settings using machine learning (ML). Methods We analysed data from 964 adults aged [≥]35 years who underwent VCTE at a tertiary referral centre in Sri Lanka between November 2024 and 2025. Multiple ML models using different methods and variable combinations were trained on 80% of the dataset and tested on the remaining 20%. Best models were selected based on performance and externally validated using data from 430 patients who underwent VCTE before November 2024. Model performance was compared with the FIB-4 using confusion matrices. Results A Random Forest model incorporating age, AST, ALT, and platelet count separately, rather than using FIB-4, outperformed. The all-variable ML model showed the best predictive performance for SF, with accuracy of 77.2%, recall of 0.762, precision of 0.778, and AUC-ROC of 0.818. The variables used in the model, in descending order of feature importance, were AST, platelet count, BMI, ALT, age, diabetes mellitus, hypertension, dyslipidaemia, sex, family history, hypothyroidism, diabetes complication and smoking. External validation demonstrated 75.1% accuracy and an AUC of 0.779. When used as the first step of the SLD screening algorithm, the all-variable ML model identified 37 (17.1%) additional true positives and reduced false-negative diagnoses by 50% compared with FIB-4. Conclusions ML-based models were more effective than the FIB-4 score as the first-line screening tool for VCTE referral, substantially improving the identification of patients with significant fibrosis in this South Asian cohort.