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

LLM-Powered Multi-Agent System for Automated Crypto Portfolio Management

arXiv:2501.00826v3 Announce Type: replace-cross Abstract: Cryptocurrency portfolio management requires the fusion of heterogeneous multi-modal signals, including structured price and on-chain time series, unstructured news text, and technical indicators, under high-volatility and real-time constraints. While deep learning approaches show predictive capability, their opacity limits practical adoption, and single large language model (LLM) agents struggle to process the breadth of modality-specific inputs needed for robust decision-making. We propose a multi-agent system (MAS) framework in which three modality-specialised agents, a Crypto Agent for market dynamics, a News Agent for weekly news sentiment, and a Trading Agent for signal fusion and portfolio execution, decompose the task across three communication architectures: hierarchical, collaborative, and debate. We evaluate four capability configurations: zero-shot, chain-of-thought (CoT), retrieval-augmented generation (RAG), and skill-augmented. In a 52-week backtest over calendar year 2025 across the top 15 L1 blockchain native cryptocurrencies by market capitalisation as of January 2025, the best configuration, Hierarchical (Skill), achieves a cumulative return of 133.52% and a Sharpe ratio of 1.502, outperforming single-agent variants, passive benchmarks, and deep learning baselines. An ablation study identifies the Crypto Agent as the most critical component, with its removal reducing cumulative return by 42.57 percentage points. A cross-model comparison further shows that MAS outperforms the single-agent baseline under GPT-4o, GPT-5, and Claude Sonnet 4.5, suggesting that the benefit of multi-agent coordination is model-agnostic. Unlike black-box deep learning models, every portfolio decision is traceable to explicit agent reasoning, offering an interpretable and effective approach to multi-modal cryptocurrency portfolio management.

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

Whole-Brain Connectomic Graph Model Enables Whole-Body Locomotion Control in Fruit Fly

arXiv:2602.17997v3 Announce Type: replace Abstract: Animals perform coordinated whole-body movements under the control of neural systems shaped by brain-wide connectivity. The mapping of the whole-brain neural connections, or the connectomes, provides a natural graph for modeling sensorimotor information flow, yet its potential as a neural controller for embodied agents remains largely unexplored. Here, we introduce the Fly-connectomic Graph Model, which directly instantiates the whole-brain connectome of an adult Drosophila as a graph-structured neural controller for movements of a simulated biomechanical fruit fly via deep reinforcement learning. We achieve stable performance across diverse locomotion tasks, as well as better sample efficiency compared to both graph and non-graph baselines. Our results demonstrate a biologically informed way towards effective control policy design by translating whole-brain wiring principles into actionable architectural priors, while also improving the interpretability through dynamic information flow. This work also highlights the potential to bridge neuromechanics with embodied intelligence by providing a computational platform for investigating the sensorimotor transformation underlying animal behavior and a paradigm to advance the development of more nature-aligned intelligent systems.

03.
arXiv (CS.CL) 2026-06-12

CuMA: Aligning LLMs with Sparse Cultural Values via Demographic-Aware Mixture of Adapters

As Large Language Models (LLMs) serve a global audience, alignment must transition from enforcing universal consensus to respecting cultural pluralism. We demonstrate that dense models, when forced to fit conflicting value distributions, suffer from Mean Collapse, converging to a generic average that fails to represent diverse groups. We attribute this to Cultural Sparsity, where gradient interference prevents dense parameters from spanning distinct cultural modes. To resolve this, we propose \textsc{CuMA} (Cultural Mixture of Adapters), a framework that frames alignment as a conditional capacity separation problem. By incorporating demographic-aware routing, \textsc{CuMA} internalizes a Latent Cultural Topology to explicitly disentangle conflicting gradients into specialized expert subspaces. Extensive evaluations on WorldValuesBench, Community Alignment, and PRISM demonstrate that \textsc{CuMA} achieves state-of-the-art performance, significantly outperforming both dense baselines and semantic-only MoEs. Crucially, our analysis confirms that \textsc{CuMA} effectively mitigates mean collapse, preserving cultural diversity. Our code is available at https://github.com/Throll/CuMA.

05.
arXiv (CS.LG) 2026-06-16

FEnc$^2$: Unifying Data Packing for Efficient Private Inference via Convolution and Architecture-Aware Fragment Encoding

arXiv:2606.16359v1 Announce Type: cross Abstract: Fully Homomorphic Encryption (FHE) enables privacy-preserving machine learning but incurs extreme computational and memory overhead. These costs come not only from expensive low-level primitives, including Number Theoretic Transform (NTT), rotation, and key-switching, but also from inefficient ciphertext packing at the application level. Existing packing strategies typically preserve either neighboring data elements or feature grouping, but not both, leading to wasted ciphertext slots, excessive rotations, and inflated ciphertext counts. We propose FEnc2, a unified and principled fragment-based encoding framework for CKKS-based private convolutional neural network inference. FEnc2 optimizes slot utilization, rotation complexity, and ciphertext density through two components: 1)Conv-aware Encoding, which analytically selects an optimal fragment size to decouple spatial dependencies and jointly minimize inner-outer rotations across layers, and 2)Arch-aware Ct Compression, which restores ciphertext density after feature- or channel-reduction layers. Together, these transformations reshape encrypted workload structure and reduce homomorphic operations by one to two orders of magnitude. With full memory capacity utilized, i.e., at maximum batch size, FEnc2 achieves end-to-end latency speedups over the state-of-the-art Orion of up to 228.83x on GPU and 226.06x on CPU for LeNet on MNIST, and up to 4.55x on GPU and 9.43x on CPU for MobileNet on ImageNet. FEnc2 is hardware-agnostic yet architecturally transformative: by optimizing encrypted tensor layout before execution, it reduces ciphertext count and workload pressure on hardware, complementing primitive-level optimizations such as NTT and keyswitch accelerators. These results show that application-level data layout is a first-order architectural design dimension for encrypted inference and an important enabler for next-generation FHE systems.

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

Minimal Oversight: Uncertainty-Aware Governance for Delegated AI Systems

arXiv:2606.15563v1 Announce Type: new Abstract: AI systems increasingly delegate decisions to specialized models, evaluators, tools, and supervisory controllers. The central AI problem is no longer only model accuracy, but uncertainty-aware governance: how much autonomy to grant, which evidence should calibrate trust, what performance ceiling a delegated AI system can sustain, and when human intervention becomes necessary. We propose the Minimum Sufficient Oversight Principle (MSO), a variational principle for principled autonomy delegation: minimize governance burden on the Fisher information manifold subject to a delivery constraint. The resulting Euler-Lagrange solution yields a water-filling allocation of governed delegation across the task space. Building on a revealed-action governed delegation channel model, we prove a capacity theorem for stationary symbolwise review policies, derive a local first-order approximation relating workflow complexity to quality degradation, and give a drift-dominated autonomy-time scaling law linking intervention timing to effective capacity, complexity, and drift. Within this framework, masking appears as a structural AI-governance pathology: corrected performance can hide the competence signal needed to calibrate trust. Synthetic simulations and a semi-real reconstructed workflow support design prescriptions including upstream-first correction, sensitivity-based intervention, and explicit feasibility checks before autonomy is expanded. The result is a computable framework for uncertainty, planning, and oversight in delegated AI systems. A companion Python package is available at https://github.com/crbazevedo/delegation-lab.

07.
arXiv (CS.AI) 2026-06-17

Quantum Cinema: An Interactive Cinematic Exploration of Quantum Computing Hardware via Generative World Models

arXiv:2606.17102v1 Announce Type: cross Abstract: Quantum computing promises transformative advances across science and industry, yet the physical hardware that enables these computations remains invisible to the public: quantum processors operate inside sealed dilution refrigerators at temperatures near absolute zero, making direct observation impossible. This "imagination gap" between quantum computing's growing societal impact and the public's ability to visualize it represents a significant barrier to quantum literacy and workforce development. We present Quantum Cinema, an open-source, browser-based interactive application that closes this gap by transforming invisible quantum hardware into explorable, cinematic experiences using generative world models. Quantum Cinema guides users through a four-act narrative – from the foundational Nobel Prize-winning science of quantum entanglement, through curated video introductions to three major quantum computing architectures (trapped-ion, neutral-atom, and superconducting systems), into immersive three-dimensional generative worlds that make invisible quantum phenomena observable, and finally to interactive radar-chart comparisons grounded in real quantum device specifications. All three-dimensional environments are generated using WorldLabs' generative world model platform and are scientifically grounded in curated metrics from Amazon Web Services (AWS) Braket quantum hardware. Quantum Cinema requires no installation, no specialized hardware, and no quantum computing background. It is designed to serve two distinct communities: scholars and developers seeking to replicate or extend the platform, and educators, researchers, and science communicators seeking an intuitive tool for explaining quantum hardware to diverse audiences. This paper describes the system architecture, the generative world model pipeline, use cases for both communities, and directions for future work.

08.
arXiv (math.PR) 2026-06-16

Free energy of non-convex multi-species spin glasses with centered Ising spins

arXiv:2606.16636v1 Announce Type: new Abstract: We identify the limit free energy of all multi-species spin glasses with centered $\pm 1$ spins. The result was previously known only under a convexity assumption on the covariance function of the Hamiltonian. We also obtain a one-species reduction of the formula for balanced multi-species models.

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

SwitchBraidNet: Quantisation-Aware Lightweight Architecture for Hybrid Brain-Computer Interface

arXiv:2606.18816v1 Announce Type: cross Abstract: Hybrid brain-computer interfaces (BCIs) that integrate motor imagery (MI) and steady-state visual evoked potentials (SSVEP) provide high-dimensional neural decoding but typically exceed the computational limits of embedded hardware. To address this, we propose SwitchBraidNet, a compact EEG classification architecture designed for low-power deployment. The model employs a dual-path temporal braid to extract multiscale oscillatory features, an adaptive squeeze-and-excitation spatial switch for electrode gating, and a log-variance readout layer for direct band-power encoding. Furthermore, through systematic quantisation-aware training on the OpenBMI dataset, we compared SwitchBraidNet against four established baselines across FP32, FP16, and INT8 precisions. Experimental results demonstrate superior efficiency and performance, achieving MI accuracy of 69.49% (FP16), SSVEP accuracy of 93.48% (FP32), and a hybrid information transfer rate of 64.82 bits/min (FP16). With an INT8 footprint of only 3.03 KB, SwitchBraidNet maintains high accuracy across varying numerical precisions, demonstrating its suitability for low-power embedded BCI deployment.

10.
arXiv (quant-ph) 2026-06-19

Measuring Rényi entropy with an Echo Protocol

arXiv:2504.05237v3 Announce Type: replace Abstract: We present efficient and practical protocols to measure the second Rényi entropy, whose exponential is known as the purity. Our approach is based on expressing the purity in terms of transition probabilities generated by an echo-type forward-backward evolution sequence, making it applicable to quantum many-body systems. Notably, our approach does not rely on random-noise averaging, a feature that can be extended to protocols to measure out-of-time-order correlation functions, as we demonstrate. By way of example, we show that our protocols can be practically implemented in superconducting qubit-based platforms, as well as in cavity-QED trapped ultra-cold gases.

11.
arXiv (CS.LG) 2026-06-19

Performance Analysis and Optimization of 3D Generative Diffusion Models across GPU Architectures

arXiv:2606.19365v1 Announce Type: new Abstract: Diffusion models have become essential for high-fidelity 3D MRI synthesis, yet their deployment remains constrained by substantial GPU resource demands arising from hundreds of U-Net evaluations per sample and a highly heterogeneous kernel behavior. This paper performs a comprehensive performance analysis of the state-of-the-art medical diffusion model, Med-DDPM, across three generations of NVIDIA architectures to study kernel-level runtime breakdowns, instruction-mix characteristics, memory system utilization, warp-level activities, and profiler priority-score estimates. We show that training is overwhelmingly dominated by cuDNN convolution and implicit-GEMM kernels, with inefficiencies arising from memory-access patterns, tensor-layout conversions, and limited Tensor Core utilization. Guided by these insights, we evaluate two architecture-aware optimizations TF32 Tensor Core activation and a 3D channels-last layout and demonstrate that they reduce SM cycles by up to 100x, cut dynamic instructions by 100x, raise Tensor Core utilization from 1.45 to 9.98x, and increase IPC by 7% on A100, all without degrading synthesis quality.

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

Non-frontal face recognition using GANs and memristor-based classifiers

Face recognition systems have advanced significantly through deep learning techniques, delivering high performance and robustness in complex scenarios. However, these approaches incur substantial computational overhead, limiting their in situ applicability in resource-constrained platforms such as drones, where they can address challenges including non-frontal facial imagery. Memristor-based neuromorphic systems have emerged as a compelling approach for edge AI applications, combining biologically inspired processing with efficient and scalable computation. In this work, we propose a facial recognition framework that addresses non-frontal pose variations by integrating lightweight generative adversarial network (GAN)-based pose frontalisation with memristor-based neuromorphic recognition. The experimental results on two datasets demonstrate the effectiveness of combining adversarial learning with memristive technology, achieving up to 96% identification accuracy. The proposed approach alleviates the computational bottlenecks of conventional AI and offers a scalable, efficient solution for face recognition in dynamic real-world environments.

13.
arXiv (CS.CV) 2026-06-17

Looped World Models

Current world models face a fundamental tension: faithful long-horizon simulation demands deep computation, but deeper models are expensive to deploy and prone to compounding errors. We resolve this by introducing Looped World Models (LoopWM), which are the first looped architectures for world modelling. Our method iteratively refines latent environment states through a parameter-shared transformer block. This yield up to 100x parameter efficiency over conventional approaches with adaptive computation that automatically scales depth to match the complexity of each prediction step. Orthogonal to scaling model size and training data, LoopWM establishes iterative latent depth as a new scaling axis for world simulation, which might significantly push the community forward.

14.
arXiv (CS.CV) 2026-06-12

Multi-Label Test-Time Adaptation with Bayesian Conditional Priors

Multi-label recognition with frozen Vision-Language Models (VLMs) is brittle under distribution shift: standard zero-shot inference scores labels independently, ignoring co-occurrence structure and producing incoherent label sets where dominant concepts suppress weaker but compatible labels. We introduce Bayesian Conditional Priors (BCP) Estimation, a gradient-free test-time adaptation method that injects label dependency without tuning the backbone. BCP views zero-shot logits as a proxy for marginal posteriors under a fixed image-text likelihood and attributes shift-induced errors mainly to a mismatched label prior. For each test image, it selects a high-confidence anchor label and applies an anchor-conditioned Bayesian refinement. This update is closed-form in logit space and admits a pointwise mutual information (PMI) interpretation, explicitly promoting compatible labels and suppressing incompatible ones. BCP operates without target annotations by estimating anchor-conditioned priors online from the unlabeled test stream via lightweight second-order co-occurrence statistics, adding negligible overhead beyond a single forward pass. Across standard multi-label benchmarks and multiple CLIP backbones, BCP consistently outperforms strong TTA baselines, e.g., improving RN50 average mAP from 57.31 to 69.22 and ViT-B/16 from 62.61 to 71.79.

15.
arXiv (CS.AI) 2026-06-11

SVoT: State-aware Visualization-of-Thought for Spatial Reasoning via Reinforcement Learning

arXiv:2606.11770v1 Announce Type: new Abstract: Spatial reasoning remains a challenge for Multimodal Large Language Models (MLLMs), as it requires reliable multi-hop inference over both intermediate states and state transitions. Current studies often leave intermediate states unverified and treat state transitions as implicit processes, which limits reliability in multi-hop spatial reasoning. To address this, we propose State-aware Visualization-of-Thought (SVoT), a reinforcement learning framework that generates interleaved, verifiable intermediate states and visualizations. SVoT integrates transition reasoning chains into the generation processes, enabling the model to verify action preconditions and effects through interleaved textual and visual reasoning. We train SVoT via Group Relative Policy Optimization (GRPO), instantiating verification through reward design and evaluating the efficacy of different fine-grained rewards. As existing benchmarks reduce state transitions to single-variable updates, substantially simplifying the problems, we establish five domains by extending classical environments and introducing two novel domains, Pacman and Gather, that require multi-object interactions and numerical reasoning. These domains support systematic evaluation of multi-hop spatial reasoning with quantitative verification of generated intermediate states and transition reasoning. SVoT with transition-aware supervision achieves state-of-the-art performance across the introduced domains, yielding up to a 65% absolute accuracy gain on out-of-distribution test sets.

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

fARfetch: Enabling Collocated AR-HRC in Large Visually Diverse Environments with VLM-Driven AR Content Adaptation

Augmented Reality (AR) can improve collocated human-robot collaboration by making robot state and intent visible and enabling intuitive control, yet large, visually diverse environments like the outdoors challenge both interaction and content legibility, especially at long distances and beyond visual line of sight. We present fARfetch, an AR-HRC system that integrates (i) shared semantic environment mapping across an AR headset and robot that visualizes detected landmarks in AR to support landmark-grounded go-to commands, (ii) a context-aware world-in-miniature representation of the shared environment for fine-grained path authoring, and (iii) vision-language-model driven AR view management that jointly adapts virtual content color, size, and orientation to maintain legibility in large visually diverse environments. We implement fARfetch with a Meta Quest 3 headset and Unitree Go2 quadruped robot, and conduct a within-subjects user study (N=13) on a real-world large-scale (30.5m) outdoor inspection task. fARfetch yielded significantly faster completion times than a non-AR baseline (66%) and significantly lower workload in mental demand (-43%), temporal demand (-34%), and frustration (-66%). A custom legibility survey indicated fARfetch effectively maintained virtual content legibility in the large outdoor environment.

17.
arXiv (CS.AI) 2026-06-24

SemChunk-C: Semantic Segmentation for C Code

arXiv:2606.23697v1 Announce Type: cross Abstract: Semantic segmentation of code written in a C-family language remains a challenging problem, due to the language's complex syntax, macro expansion, and irregular structural patterns. Existing chunking methods, such as fixed-sized windows, heuristic splitting, and syntax-based tools, often fail to capture meaningful functional units, limiting the efficacy of retrieval and other downstream LLM driven tasks. In this paper, we address the problem of chunking in C-related languages. First, we define a set of code chunk categories. Second, we train an LLM-based classifier to a) identify chunk boundaries, and b) assign each chunk a descriptive functional attribute (a category), which can be useful for downstream tasks. By leveraging the LLM's ability to capture semantic context within the code, we assume flexible chunk boundaries, allowing to adapt to the specific structure and context of each instance. Third, we introduce SemChunk-C, a family of lightweight language models for semantic chunking of C-related files (.c, .cpp, .h, .cs, etc.). These models are based on the first four Ettin encoders [1] with 17M, 32M, 68M, and 150M parameters. Despite their relatively small size, they are capable of identifying cohesive code units, such as data structures, interface blocks, and other components. Furthermore, we demonstrate the robustness of our approach on real-world code, including challenging constructs such as nested definitions and macros. We test our approach on various datasets, and show that it achieves high boundary accuracy and semantic coherence, matching or outperforming chunkers that are based on much larger code-oriented LLMs. We also validate the improved performance of the downstream tasks on a few curated benchmarks.

18.
arXiv (CS.AI) 2026-06-17

Memory as a Wasting Asset: Pricing Flash Endurance for Embodied Agents, and the Limits of Doing So

arXiv:2606.18144v1 Announce Type: new Abstract: A robot's flash endurance is a non-renewable stock: every persisted write spends one of a few thousand program/erase cycles and never refills, yet no fielded robot memory system prices which memories are worth an erase cycle. We treat embodied memory as depreciating capital and price that stock with a single endurance shadow price $\eta$, which makes cost-minimizing placement across a RAM / on-board NVM / cloud hierarchy a threshold in a wear-augmented per-byte index. The index is cost-optimal whatever the sign of the value-write association $\chi$; only when $\chi > 0$ does the optimum turn non-monotone, sending a robot's most valuable memories off its flash. The pivot is thus empirical, and we measure $\chi$ on real robot logs at a pre-specified gate: its sign is a property of the deployment regime – positive on recurrent long-horizon manipulation ($\hat{\chi} \approx +1.0 \times 10^{-3}$, replicated at full power), null on a shorter-horizon suite, and negative on non-recurrent teleoperation. Two boundaries scope the result. The endurance budget is dormant on premium 3,000-P/E TLC at datasheet prices and binding on the commodity QLC/eMMC ($\sim$1,000 P/E) that cheaper edge robots run. And where it binds, a learned wear-aware controller only ties price-based routing on task value, because realized value is tier-invariant across RAM, NVM, and cloud: the rent governs device lifetime and cost, not task performance. Whether wear-aware placement improves task value remains open – $\chi$ is measured against a value proxy, and the non-monotone optimum, while proven, is not yet observed in data.

19.
Nature Medicine 2026-06-12

Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith−Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: −4.04, 95% confidence interval: −6.89 to −1.18, P = 0.006, Hedges’ g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 . Pramipexole, in patients with major depressive disorder, dysthymia or bipolar depression, reduced Snaith−Hamilton Pleasure Scale scores significantly compared to placebo.

20.
arXiv (quant-ph) 2026-06-17

Engineering entanglement and transport in interacting quantum walks with tailored potentials

arXiv:2606.17825v1 Announce Type: new Abstract: Controlling the interplay between particle propagation and quantum correlation generation is a central challenge in quantum transport. Here, we investigate two distinguishable continuous-time quantum walkers evolving on parallel one-dimensional lattices, interacting via distance-dependent potentials. While on-site interactions reproduce the typical bosonic behaviour, extending the interaction to a linear potential over multiple neighbors introduces controlled Bloch-like oscillations and shifts the bound-pair regime to stronger couplings. More generally, we explore a Coulomb-like interaction parameterized by strength, spatial scaling, and decay rate. This reveals a rich phase diagram including four distinct dynamical regimes: (i) a high-entropy, oscillatory regime akin to a linear potential; (ii) a strongly localized, bound-pair regime; (iii) a novel intermediate regime combining near-ballistic spreading with strong correlations; and (iv) a weakly interacting, free-propagation regime. Notably, regime (iii) achieves concurrent optimization of transport efficiency and entanglement, offering a sweet spot for correlated quantum dynamics. Our results provide a tool for designing interaction-engineered quantum walks with potential applications in quantum information processing and simulations.

21.
medRxiv (Medicine) 2026-06-24

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing

Rare diseases collectively affect 1 in 10 individuals, yet current genetic testing fails to identify a causal variant for most cases. At present, cytogenetic methods and/or sequencing approaches such as exome (ES) or short-read genome sequencing (srGS) represent the state-of-the-art for comprehensive clinical discovery of sequence and structural variants (SVs), including copy number variants, balanced SVs, complex SVs, and tandem repeats (TRs). Recently, long-read genome sequencing (lrGS), coupled with multiomics data, has presented great promise to resolve variation in genomic regions recalcitrant to characterization by srGS such as highly repetitive simple repeat sequences and segmental duplications. However, there are few guidelines to enable clinical interpretation of genetic variation in these highly repetitive genomic regions, and the enthusiasm of the field in adopting lrGS has made it difficult to assess the true added diagnostic yield of this technology due to widely variable and inconsistently applied analytic pipelines and variable degrees of pre-screening by ES or srGS. Here, we investigated the contribution of SVs to rare diseases using srGS as a front-line strategy when paired with highly sensitive SV discovery and evaluate the added diagnostic yield of incorporating lrGS for a subset of cases. Our srGS analysis encompassed 1,462 families (3,450 individuals) recruited through the Broad Institute Center for Mendelian Genetics and the Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) programs. Diagnostic SVs were identified in 5.4% of cases (79/1,462), of which 80% were uniquely detectable by srGS compared to standard cytogenetic techniques. For 96 families (including 10 families with a heterozygous variant observed in a known recessive gene of clinical relevance), we performed lrGS with methylation profiling, as well as long-read transcriptomic analyses in a subset of 20 trios. Analyses with lrGS yielded over 25,000 SVs per genome, 63% of which were not captured by srGS, along with an additional ~200 rare SNV/indels per genome not previously captured and 12 differentially methylated regions per genome. Among these, we identified only one diagnostic variant not interpreted by srGS, an apparently mosaic de novo SNV in CASK that was absent in the srGS callset due to allelic imbalance. No new diagnoses were supported by long-read transcriptomics or episignatures. In this well characterized rare disease cohort, the added diagnostic yield was thus 1.04% (1/96 families). Following a systematic literature review of prior lrGS studies, we find that most reported diagnoses were detectable by srGS and that our added diagnostic yield is consistent with those prior studies. These studies emphasize the significant impact of comprehensive SV discovery in rare disease cases and further demonstrate the power for increased discovery of novel genomic variation and episignatures from lrGS. Nonetheless, they also serve to temper expectations of dramatic diagnostic advances in rare disease patients until there is more extensive annotation of the functional and clinical impact of all coding and noncoding variation uniquely accessible to lrGS with extensive reference databases spanning highly repetitive genomic sequencing that could be enabled by this transformative technology.

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

Counting Trees from Satellite Imagery with Noisy Supervision

Counting individual trees is a fundamental task for environmental monitoring, yet remains largely unexplored with satellite imagery. At these resolutions, isolated trees may still be identifiable, but crown boundaries become ambiguous in dense forests, making the notion of an individual tree inherently ill-defined. Moreover, large-scale manual annotations of individual trees are prohibitively expensive. While scalable supervision can be derived from airborne LiDAR, the resulting annotations are noisy and difficult to exploit effectively. We address these challenges by formulating tree counting as a spatial density matching problem supervised through Unbalanced Optimal Transport. This formulation naturally accommodates both precise localization of isolate trees and robust density estimation in dense forests. We further introduce a self-correction mechanism that leverages transport residuals to progressively refine noisy supervision during training. We evaluate our approach on TinyTrees, a new benchmark spanning three continents and three satellite sensors, comprising over 215 million tree annotations (including 773K manually verified instances) across 23,000 sq.km. Our method consistently outperforms detection-based, regression-based, and transport-based distribution-matching baselines, demonstrating the effectiveness of unbalanced transport and reliability-aware supervision for large-scale tree counting from satellite imagery. Code, data and models are available at https://github.com/dgominski/treematch.

23.
arXiv (CS.LG) 2026-06-16

Learning Hybrid Biophysical Neuron Models with Neural ODEs

arXiv:2606.16693v1 Announce Type: cross Abstract: Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications – omitting channels or reducing morphological detail – introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.

24.
medRxiv (Medicine) 2026-06-15

Routine use of oral iron for people with heart failure and iron deficiency in primary care; retrospective cohort study

Aims: Iron deficiency is common among people with heart failure and associated with morbidity and mortality. While intravenous iron improves clinical outcomes, oral iron continues to be prescribed in routine practice despite limited evidence of benefit. Methods: We completed a retrospective primary care cohort study (2016 to 2021) to investigate the proportion of people with an incident diagnosis of heart failure who had iron deficiency identified (defined as ferritin

25.
arXiv (CS.CL) 2026-06-18

Rethinking Reward Supervision: Rubric-Conditioned Self-Distillation

Post-training of reasoning language models is commonly driven by supervised distillation and reinforcement learning with verifiable rewards. Distillation often relies on chain-of-thought annotations that are expensive to obtain and may themselves be noisy, incomplete, or partially incorrect; even when the final solution is correct, an imperfect rationale can interfere with learning. Reinforcement learning with verified rewards, on the other hand, typically compresses evaluative feedback into a scalar signal, obscuring which aspects of a response should be improved. We propose Rubric-Conditioned Self-Distillation, a framework that incorporates rubrics as structured, fine-grained feedback for on-policy self-distillation. Our method conditions the teacher model on criterion-level rubrics and uses it to provide token-level guidance on the student's own sampled trajectories. This design avoids treating a single reference rationale as the sole supervision target. Instead, rubrics specify what a strong response should satisfy, enabling more fine-grained credit assignment over the reasoning process than scalar reward optimization. We instantiate this framework with a two-stage pipeline that first learns to generate task-specific rubrics and then trains a rubric-guided reasoner. We evaluate on a diverse suite of science reasoning benchmarks and results show that rubric-conditioned self-distillation effectively converts rubric-level criteria into token-level guidance over the reasoning process, surpassing GRPO by 1.0 points and OPSD by 0.9 points on average.