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01.
medRxiv (Medicine) 2026-06-15

Identifying the risk profile of anemia subtypes and hemodynamic obstetric complications in relation to peripartum cardiomyopathy

Background: Peripartum cardiomyopathy (PPCM) is a leading cause of maternal mortality worldwide, with worse outcomes associated with African Ancestry and delayed presentation. However, the mechanisms underlying PPCM are incompletely understood. Objective: Use a large, nationwide cohort to explore associations between PPCM and underexplored perinatal risk factors and complications of childbirth. Methods: Public hospital discharge data were obtained from eleven U.S. states between 2003-2019. Delivery hospitalizations, patient characteristics and obstetric complications were identified using ICD-9 and -10 CM codes. Only cases with unique patient identifiers enabling readmission analysis were included. The primary outcome was incident PPCM coded between 30 days antepartum and 150 days postpartum. Results: Of 7,424,916 delivering patients, 5,488 patients were diagnosed with PPCM. Patients with PPCM had higher rates of anemia, anemia of chronic disease (ACD), iron deficiency anemia (IDA), sickle cell disease (SCD), sickle cell trait (SCT), red blood cell (RBC) transfusion, and postpartum hemorrhage (PPH) (p

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

Scalable Circuit Learning for Interpreting Large Language Models

arXiv:2606.16939v1 Announce Type: cross Abstract: A prominent research direction in mechanistic interpretability is learning sparse circuits over LLM components to reveal how they jointly produce model behavior. However, raw neurons are polysemantic, making learned circuits hard to interpret. Sparse autoencoder (SAE) features alleviate this, but their high dimensionality makes existing intervention-based circuit learning methods computationally prohibitive. We propose CircuitLasso, a scalable circuit-learning approach based on sparse linear regression. CircuitLasso recovers circuits whose structural accuracy matches that of state-of-the-art intervention-based methods on the benchmark data, at a fraction of the computational cost. For interpretability, CircuitLasso efficiently uncovers relationships among SAE features, showing how human-interpretable semantic features propagate through the model and influence its predictions. Finally, we validate the utility of our learned circuits by leveraging their insights to achieve comparable performance at substantially lower cost on a domain-generalization task.

03.
arXiv (CS.CV) 2026-06-15

ZipSplat: Fewer Gaussians, Better Splats

Feed-forward 3D Gaussian Splatting methods reconstruct a scene from posed or pose-free images in a single forward pass, yet current approaches predict one Gaussian per input pixel, tying the representation budget to camera resolution rather than scene complexity. A flat wall and a richly textured object thus produce equally many Gaussians despite very different geometric needs. We propose ZipSplat, a token-based feed-forward model that decouples Gaussian placement from the pixel grid. A multi-view backbone extracts dense visual tokens, and k-means clustering compresses them into a compact set of scene tokens. Cross- and self-attention refine these tokens, and a lightweight MLP decodes each into a group of Gaussians with unconstrained 3D positions. Because clustering is applied at inference, a single trained model spans the quality-efficiency curve without retraining. ZipSplat operates without ground-truth poses or intrinsics, yet sets a new state of the art on DL3DV and RealEstate10K with ${\sim}6{\times}$ fewer Gaussians than pixel-aligned methods, surpassing the best pose-free baseline by 2.1dB and 1.2dB PSNR, respectively. It further generalizes zero-shot to Mip-NeRF360 and ScanNet++, outperforming all comparable baselines. Our project page is at https://veichta.com/zipsplat.

04.
arXiv (CS.CL) 2026-06-11

Litespark Inference For CPUs: Ultra-Fast SIMD Framework for Ternary (1.58-bit) Language Models

Large language models (LLMs) have transformed artificial intelligence, but their computational requirements remain prohibitive for most users. Standard inference demands expensive datacenter GPUs or cloud API access, leaving over one billion personal computers underutilized for AI workloads. Ternary models offer a path forward: their weights are constrained to {-1, 0, +1}, theoretically eliminating the need for floating-point multiplication. However, existing frameworks fail to exploit this structure, treating ternary models as dense floating-point networks. We address this gap with custom SIMD kernels that replace matrix multiplication with simple addition and subtraction operations, targeting the integer dot product instructions available on modern CPUs. Our implementation, Litespark-Inference, is pip-installable and integrates directly with Hugging-Face, achieving 18.15x higher throughput, 7.15x faster time-to-first-token and 6.03x memory reduction compared to standard PyTorch inference on Apple Silicon, with comparable or higher throughput speedups up to 95.81x on Intel and AMD processors.

05.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

06.
arXiv (CS.LG) 2026-06-17

Sum-of-Squares Degree Barriers for the Reweighted-Hinge Method in Robust Halfspace Learning: A Christoffel-Function Characterization

作者:

arXiv:2606.17215v1 Announce Type: new Abstract: A certificate that removes outliers sees the data only through its low-degree moments, and an adversary exploits exactly this, hiding corruption where the clean data already looks typical, in the blind spot no bounded-degree test resolves. That blind spot turns out to have an exact size: the Christoffel function of the clean marginal, the very quantity modern data analysis thresholds to detect outliers, here read from the adversary's side as the corruption a bounded-degree certificate cannot remove. We turn this inversion into the organizing principle of the reweighted-hinge approach to robustly learning $\gamma$-margin halfspaces under malicious noise (Shen, 2025; Zeng and Shen, 2025): the governing resource is the Sum-of-Squares degree of the outlier-removal certificate, and the resolution principle states that the maximal corruption mass which can hide at a center $c$ from a degree-$2t$ certificate is exactly the Christoffel function $\lambda_{t+1}(c)$ of the clean marginal. Three consequences follow, all against the certificate method (not information-theoretic). A margin-degree tradeoff: certifying the dense pancake to error $\epsilon$ costs SoS degree $\Omega(\log(1/\epsilon))$ or margin $\Omega(\sqrt{\log(1/\epsilon)}/\sqrt{d})$, explaining why the $\log(1/\epsilon)$ margin Shen (2025) records is forced, with a weighted-Chebyshev reduction making the threshold $2t=\Theta((|c|/s)^2)$ tight modulo one classical weighted-extremal estimate. A degree-$2$ outlier barrier: the resolution principle realized as an explicit instance on which degree $2$ is stuck at $\eta^{1/2}$ while degree $4$ escapes, locating the method's small breakdown rate in the degree, not the analysis. And a degree-$2t$ algorithm tracing the frontier $\eta^{1-1/2t}$ (recovering Shen (2025) at $t=1$), whose gain is an explicit constant, capped by the pancake density and shown unimprovable by the degree-$2$ barrier.

07.
arXiv (CS.AI) 2026-06-11

LSTM based IoT Device Identification

arXiv:2304.13905v2 Announce Type: replace-cross Abstract: While the use of the Internet of Things is becoming more and more popular, many security vulnerabilities are emerging with the large number of devices being introduced to the market. In this environment, IoT device identification methods provide a preventive security measure as an important factor in identifying these devices and detecting the vulnerabilities they suffer from. In this study, we present an end-to-end machine learning pipeline that identifies IoT devices in the Aalto university dataset (IoT devices captures) using Long Short-Term Memory (LSTM) networks. Raw network packet captures (PCAP) are processed into 25 engineered features, which are then arranged as sliding-window time-series sequences. We systematically evaluate sequence lengths from 2 to 20, reporting that performance improves approximately linearly up to length 6 and thereafter in a wave-like pattern, reaching its peak at length 18. On the final held-out test set with the optimal configuration, the model achieves an accuracy of 79.85% and a macro-averaged F1-score of 75.70% across 27 device classes.

08.
arXiv (quant-ph) 2026-06-12

Driven-dissipative entanglement of distant giant atoms

arXiv:2606.13375v1 Announce Type: new Abstract: Quantum interconnects distribute entanglement via controlled light-matter interactions for quantum computing and sensing applications. Many entanglement generation schemes use coherent, reversible interactions that require precisely calibrated pulses to execute. In contrast, driven-dissipative protocols use a continuous-wave drive in the presence of correlated dissipation to stabilize entanglement in protected (dark) states. However, the same dissipation that generates the entanglement also limits its utility once the stabilization protocol ends. Here, we engineer a superconducting system of two giant artificial atoms coupled sequentially to a waveguide, with tunable individual and correlated dissipation enabled by interference between coupling points. Continuously driving the atoms through the waveguide exploits correlated dissipation to generate remote entanglement. We then tune the qubit frequencies in situ to suppress individual dissipation and thereby preserve the entanglement, achieving a Bell-state fidelity F = 0.89 +/- 0.02. This demonstration indicates that the driven dissipation of giant atoms is a viable approach for distributing entanglement across quantum networks.

09.
bioRxiv (Bioinfo) 2026-06-11

STITCH links cellular morphology and gene expression in spatial transcriptomics

In situ spatial (ISS) sequencing can uncover co-variation between cellular morphology and gene expression in vivo. However, a principled and interpretable mathematical representation of morphology has not yet been applied in this context. In particular, current deep learning-based representations of cell images confound a cell's shape with its size. We present an interpretable representation of cellular boundary contours, based on tangent principal component analysis (TPCA) in a Kendall shape manifold, that captures size-independent contour shape features. This approach successfully recovers shape-perturbing genes in an RNAi screen than a previous metric geometry-based approach. We build on TPCA to develop STITCH (Shape-TranscriptomIc Correlation and Harmonization), an approach to reveal covariation between cell morphology with gene expression in ISS datasets. In a Xenium dataset, STITCH outperforms a deep learning-based approach in both recovering the layered organization of keratinocytes and a spatial gradient in nuclear eccentricity. Across samples in a melanoma CosMx dataset, STITCH reproducibly associates elongated and triangular fibroblasts with proximity to malignant cells and myofibroblast-like transcriptional program. Finally, STITCH independently recovers a known link between mesenchymal-like malignant cell states and increased cell area in two melanoma cohorts. STITCH can thus yield interpretable morphology-transcriptome relationships across cell types, patients, and spatial transcriptomics platforms.

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

Gradual Fine-Tuning for Flow Matching Models

arXiv:2601.22495v2 Announce Type: replace Abstract: Fine-tuning flow matching models is a central challenge in settings with limited data, evolving distributions, or computational constraints. While recent work has produced significant advances, particularly in the area of reward-based fine-tuning, current methods fail to demonstrate both theoretical correctness as well as strong empirical results in terms of stability, efficiency, and diversity preservation. In this work, we propose Gradual Fine-Tuning (GFT), a simple yet principled annealing-based framework for fine-tuning flow generative models when only samples from the target distribution are available. For stochastic flows, GFT defines a temperature-controlled sequence of intermediate objectives that smoothly interpolate between the pretrained and target drifts, provably approaching the true target as the temperature approaches zero. We analytically demonstrate that sample generation after GFT can be made substantially more efficient with the use of arbitrary (e.g., optimal transport) couplings, as well as by utilizing few-step inference methods. Empirically, GFT significantly improves convergence stability, while maintaining or improving generation quality, training speed, and generation diversity compared to other fine-tuning methods. Our results position GFT as a simple yet theoretically grounded and practically effective alternative for scalable adaptation of flow matching models under distribution shift.

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

Graphical Causal Reasoning for Root Cause Analysis in Cloud Networks

arXiv:2606.13532v1 Announce Type: cross Abstract: Cloud-computing relies on large-scale networks which are inherently complex systems. In this paper, we present a novel approach to root cause analysis (RCA) of cloud network incidents, leveraging graph-based causal discovery techniques. Our method addresses the limitations of rule-based automation by introducing a spatiotemporal grouping strategy and an automation ontology to reduce the dimensionality of the problem. We construct a causal graph from binary time series data using bivariate Granger causality and conditional independence tests. For inference, we introduce a probabilistic method that assigns edge-specific conditional probabilities as a function of time lag, allowing for interpretable, time-aware root cause scoring via causal graph traversal. We evaluated the system using a labeled dataset of 35 production incidents from a major cloud provider. The model successfully recalled the correct root cause in 85.7% of incidents and produced an exact match in 74.3%. In production, the deployed system has been used in over 800 real-world incidents, with positive qualitative feedback from network engineers. These results highlight the practicality of a data-driven, causal approach to RCA in dynamic and large-scale operational environments.

12.
arXiv (CS.CV) 2026-06-16

SLUM-i: Semi-supervised Learning for Urban Mapping of Informal Settlements and Data Quality Benchmarking

Rapid urban expansion has fueled the growth of informal settlements in major cities of low- and middle-income countries, with Lahore and Karachi in Pakistan and Mumbai in India serving as prominent examples. However, large-scale mapping of these settlements is severely constrained not only by the scarcity of annotations but by inherent data quality challenges, specifically high spectral ambiguity between formal and informal structures and significant annotation noise. We address this by introducing a benchmark dataset for Lahore, constructed from scratch, along with companion datasets for Karachi and Mumbai, which were derived from verified administrative boundaries, totaling approximately 900 $km^2$ of urban area. This collection is supplemented by four cities from prior literature across Sub-Saharan Africa and Latin America, with comprehensive data quality assessments provided for each city. We also propose a semi-supervised segmentation framework designed to mitigate the class imbalance and distribution mismatch inherent in standard semi-supervised learning pipelines. Our method integrates a Class-Aware Adaptive Thresholding mechanism that dynamically adjusts confidence thresholds to prevent minority class suppression, and a DINOv2-based unlabeled pool filter that removes out-of-distribution tiles prior to training to reduce covariate shift. Extensive experiments across seven cities spanning three continents, repeated over five random seeds, demonstrate gains of up to +5.9 pp mIoU over state-of-the-art semi-supervised baselines, with both components being architecture-agnostic and adding no inference overhead.

13.
arXiv (CS.CV) 2026-06-16

Gen-VCoT: Generative Visual Chain-of-Thought Reasoning via Diffusion-Based RGB Intermediate Representations

Multimodal large language models (MLLMs) excel at visual reasoning but rely on text-based chain-of-thought (CoT), lacking interpretable visual intermediates. Existing methods use opaque tokens or external tools, missing key properties. We propose Gen-VCoT, a framework using expert vision models to generate RGB images as reasoning intermediates. It has three stages: visual grounding (SAM segmentation), geometric reasoning (Marigold depth maps), and semantic reasoning (Qwen2-VL integration). An adaptive router selects reasoning depth. Evaluations show Gen-VCoT improves spatial (25% better) and depth (50% better) questions, but may hurt simple factual queries. Text CoT outperforms visual intermediates on CLEVR (91.2% vs 62.5%), showing task-dependent optimal representations. Gen-VCoT establishes a new paradigm for interpretable multimodal reasoning.

14.
arXiv (CS.LG) 2026-06-11

Family-Aware Residual Architecture for Predicting Quantum Circuit Simulation Performance

arXiv:2606.11620v1 Announce Type: cross Abstract: Approximate tensor-network simulators enable classical simulation of quantum circuits beyond the reach of exact methods, but selecting optimal approximation parameters – such as bond dimension thresholds – remains a costly trial-and-error process. We present a family-aware neural architecture that predicts both the minimum approximation threshold required to achieve target fidelity and the expected wall-clock runtime for quantum circuit simulation, given only the circuit's OpenQASM description and execution context. Our key insight is that quantum circuits from different algorithmic families (e.g., QFT, Grover, VQE) exhibit fundamentally distinct simulation cost profiles due to their differing entanglement structures. We employ family-conditioned residual corrections – additive, family-specific adjustments atop a shared backbone, drawing on established conditional computation techniques – enabling the model to capture both universal circuit properties and algorithmic nuances. The architecture incorporates a pretrained family classifier (97.5% accuracy) and domain-informed algorithm fingerprint features derived from gate-composition heuristics. Evaluated on circuits spanning 7–130 qubits across 10 algorithm families, our system achieves 79.5% exact threshold accuracy (91.2% within one rung) and $R^2 = 0.82$ runtime correlation, with inference completing in approximately 50 ms – replacing trial-and-error simulation runs that may take minutes to hours. Ablation studies confirm that family-aware modeling provides the single largest performance improvement (+3.2 percentage points), validating the hypothesis that algorithm family is a first-class feature for simulation cost prediction.

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

Which Models Are Our Models Built On? Auditing Invisible Dependencies in Modern LLMs

Modern LLM training pipelines increasingly rely on other models to generate data, filter corpora, judge outputs, and guide development decisions. These dependencies are recursive: a model may depend on an upstream artifact whose own dependencies are documented only in separate releases and artifacts. As a result, the full dependency structure is fragmented across heterogeneous public artifacts, with complexity and recursive depth far outpacing humans' ability to trace. We introduce ModSleuth, an agentic system that recursively reconstructs LLM dependency graphs from public artifacts with source-grounded evidence. We find that the primary challenge is no longer information extraction, but defining what constitutes a dependency and reconciling artifact references across inconsistent documentation. We address these challenges through a formalization that distinguishes direct and indirect dependencies, represents heterogeneous pipeline roles through operation-centered relationships, and resolves artifact identities across names, versions, and repositories. Applying ModSleuth to four public-artifact-rich LLM releases, we recover 1,060 source-verified dependencies and construct large-scale dependency graphs of modern LLM development. These graphs reveal multi-hop license obligations, train-evaluation coupling, discrepancies between released and training-time artifacts, and documentation inconsistencies that would otherwise be difficult to uncover. We release ModSleuth and the resulting dependency graphs to support transparent analysis of the increasingly complex ecosystems underlying modern LLMs.

16.
arXiv (CS.CL) 2026-06-11

Context-Driven Incremental Compression for Multi-Turn Dialogue Generation

Modern conversational agents condition on an ever-growing dialogue history at each turn, incurring redundant attention and encoding costs that grow with conversation length. Naive truncation or summarization degrades fidelity, while existing context compressors lack cross-turn memory sharing or revision, causing information loss and compounding errors in long dialogues. We revisit the context compression under conversational dynamics and empirically present its fragility. To improve both efficiency and robustness, we introduce Context-Driven Incremental Compression (C-DIC), which treats a conversation as interleaved contextual threads and stores revisable per-thread compression states in a single, compact dialogue memory. At each turn, a lightweight retrieve, revise, and write-back loop shares information across turns and updates stale memories, stabilizing long-horizon behavior. In addition, we adapt truncated backpropagation-through-time (TBPTT) to our multi-turn setting, learning cross-turn dependencies without full-history backpropagation. Extensive experiments on long-form dialogue benchmarks demonstrate superior performance and efficiency of C-DIC; notably, C-DIC shows stable inference latency and perplexity over hundreds of dialogue turns, supporting a scalable path to high-quality dialogue modeling.

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

Experimental Characterization and Modeling of Measurement-Induced State-Transitions in a Fluxonium Superconducting Qubit

arXiv:2606.17866v1 Announce Type: new Abstract: Superconducting qubits are most often measured using dispersive readout, which, ideally, implements a projective quantum non-demolition (QND) measurement. While a larger readout drive can increase the signal and, thus, reduce discrimination errors in the readout, strong microwave drives may also cause non-QND errors by driving the qubit to a state outside the computational subspace. In this work, we experimentally characterize measurement-induced state transitions (MIST) in a fluxonium qubit over its full external flux range. We further numerically calculate the MIST errors, and find that the theory accurately predicts eleven experimentally identified regions with increased MIST. In addition to transitions to higher fluxonium levels, we also find that, at certain flux points, MIST errors are dominated by transitions that include the transmission-line-like array modes of the fluxonium's superinductor. The excellent match between theory and experiment validates that the models accurately predict the occurrence of MIST in these systems, and further highlights the influence of array modes in fluxonium readout.

18.
medRxiv (Medicine) 2026-06-11

Ferritin across long-term conditions in England: cross-sectional primary care study

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (

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

Task-Aware Structured Memory for Dynamic Multi-modal In-Context Learning

Multi-modal large language models (MLLMs) depend on in-context learning (ICL) for rapid task adaptation, but their scalability is severely limited by finite context windows and the growing cost of key-value (KV) caches in long multi-modal sequences. Existing memory compression approaches typically rely on rigid token removal or sample-dependent importance estimation, which introduces bias, disrupts semantic structure, particularly for visual representations, and yields static memories that cannot adapt to new queries. We introduce TASM (Task-Aware Structured Memory), a training-free framework that addresses these limitations through task-aware, structure-preserving, and dynamically accessible memory construction. TASM employs task-vector guided compression to replace sample-specific signals with a task-level direction that captures shared relevance across demonstrations. To preserve the underlying manifold, it applies semantics-aware token merging via bipartite graph matching, aggregating tokens without destructive pruning. Finally, TASM structures memory into a hierarchy comprising a compact Core Memory and a Latent Bank, facilitating query-adaptive dynamic retrieval. Evaluations confirm TASM maintains high performance under heavy compression, effectively balancing efficiency with adaptability.

20.
arXiv (CS.AI) 2026-06-12

A Tutorial on World Models and Physical AI

作者:

arXiv:2606.12783v1 Announce Type: new Abstract: World modeling is emerging as a central principle for building intelligent systems capable of prediction, reasoning, and decision making. A central distinction can be drawn between explicit world models, which learn structured dynamics for rollout-based reasoning and planning, and implicit world models, which encode predictive structure within scalable learned representations. These complementary paradigms provide a foundation for physical AI in domains such as robotics and autonomous driving, enabling intelligence beyond reactive control under real-world constraints. Recent foundation models further suggest a pathway toward unified systems integrating perception, prediction, and action. Despite rapid progress, major challenges remain in hierarchical reasoning, long-horizon planning, and autonomous goal formation, which are critical for advancing toward artificial general intelligence. This tutorial presents a coherent framework in which diverse world modeling approaches are unified through shared predictive structure and differentiated by how such structure is represented and exploited.

21.
arXiv (quant-ph) 2026-06-19

Asymmetric and chiral dynamics of two-component anyons with synthetic gauge flux

arXiv:2512.19139v3 Announce Type: replace-cross Abstract: In this work, we investigate the non-equilibrium dynamics in a one-dimensional two-component anyon-Hubbard model, which can be mapped to an extended Bose-Hubbard ladder with density-dependent hopping phase and synthetic gauge flux. Through numerical simulations of two-particle dynamics and the symmetry analysis, we reveal the asymmetric transport with broken inversion symmetry and two dynamical symmetries in the expansion dynamics. The expansion of two-component anyons is dynamically symmetric under spatial inversion and component flip, when the sign of anyonic statistics phase or the signs of gauge flux and interaction are changed. In the non-interacting case, we show the dynamical suppression induced by both the statistics phase and gauge flux. In the interacting case, we demonstrate that both chiral and antichiral dynamics can be exhibited and tuned by the statistics phase and gauge flux. The dynamical phase regimes with respect to the chiral-antichiral dynamics are obtained. These findings highlight the rich dynamical phenomena arising from the interplay of anyonic exchange statistics, synthetic gauge fields, and interactions in multi-component anyons.

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

Be Your Own Teacher: Steering Protein Language Models via Unsupervised Reward Optimization

arXiv:2606.18961v1 Announce Type: new Abstract: Protein language models (PLMs) have emerged as powerful tools for controllable biomolecular design, yet their post-training adaptation typically relies on costly wet-lab validation or curated preference datasets. To overcome this supervision bottleneck, we introduce unsupervised reward optimization of PLMs, a comprehensive framework for steerable protein generation without ground-truth labels. Our key insight is that task-agnostic rewards, which combine intrinsic model uncertainty with extrinsic semantic consistency informed by protein representation models, exhibit strong correlation with controllability measures across base models and temperature regimes. Building upon this discovery, we propose two offline algorithms: Soft Reward Optimization (SRO) and Binarized Reward Optimization (BRO), which effectively maximize the classical RLHF objective induced by these proxy rewards. Extensive experiments on compositional out-of-distribution prompts demonstrate that both methods significantly outperform competitive baselines (DPO, KTO), while approaching oracle performance across multiple sampling temperatures, model scales and protein families. Moreover, PLMs fine-tuned with unsupervised rewards can achieve consistently higher coverage compared to their base model in pass@k evaluations. By enabling self-improvement of PLMs through their own generated experience, our framework provides a scalable pathway toward controllable biomolecular design in settings where labeled preferences or experimental feedback are scarce or unavailable.

23.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.

24.
medRxiv (Medicine) 2026-06-18

Human Intuition vs. Computational Precision: Neurologists, Feature-based Models, and Deep Learning for Stroke Prognosis

Background: Prognostication in large vessel occlusion (LVO) stroke remains challenging. Although several prognostic models exist, their comparison to clinician performance, human-model interaction, and specific sources of human bias remain poorly understood. Methods: Using pre-treatment clinical and CT data from the MR CLEAN trial (n=500), six neurologists predicted three-month modified Rankin Scale (mRS) scores for 40 patients, both unaided and assisted by a validated feature-based model (MR PREDICTS). Human performance was benchmarked against MR PREDICTS and a multimodal, interpretable deep learning (DL) approach using raw imaging data. We explicitly assessed neurologists? ability to estimate model-required imaging features and identified systematic human biases. Models were additionally validated in a larger MR CLEAN trial cohort (n=404). Results: For predicting the full mRS distribution, standalone models achieved good ordinal agreement (MR PREDICTS quadratic weighted kappa (QWK) 0.51 [0.24 to 0.70]; DL model 0.49 [0.25 to 0.67]), significantly outperforming unaided neurologists (QWK 0.27 [0.10, 0.42]). Neurologists showed systematic overoptimism, predicting lower mRS scores than observed. Furthermore, there was poor accuracy in extracting imaging features. Raters? ASPECTS predictions deviated by 3.4 points from the confirmed scores, and collateral score accuracy was 44.6%. However, for predicting binary mRS (0-2 vs. 3-6), accuracy was comparable between unaided neurologists (64.17% [55.42% to 72.92%]) and models (MR PREDICTS 67.50% [52.50% to 82.50%]; DL model 63.16% [47.37% to 78.95%]). Model-assistance modestly improved and harmonized neurologists? predictions (QWK 0.41 [0.22 to 0.55]; binary accuracy 68.75% [58.33% to 78.34%]. Model performance remained robust in the larger cohort. Conclusions: Multimodal prognostic models outperform clinicians in predicting the full range of mRS outcomes, while human error in imaging assessment and systematic optimism bias are primary drivers of prognostic inaccuracy. End-to-end DL models eliminate human-input variability and hold strong potential as an automated second opinion to support prognostication and decision-making in acute LVO stroke.