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01.
arXiv (CS.AI) 2026-06-25

Project Auto-World: Towards Automated Benchmarking of Neural Relational Reasoners

arXiv:2606.24965v1 Announce Type: new Abstract: Reasoning about relational structures remains a significant challenge for neural models, particularly when they must systematically apply learned knowledge to problem instances that are harder than those seen in training. Progress is hampered by the difficulty of evaluating such generalization, since a priori, it is rarely clear what makes an instance hard. We study how this issue can be addressed by using large language models (LLMs) to automate benchmark generation, learning to produce increasingly challenging instances in an end-to-end manner. Concretely, given a world parametrized by Datalog rules, and an Edge Transformer as the reasoning evaluator, we use LLM-driven evolutionary search (based on FunSearch) and autonomous agentic search to discover sampling functions that yield hard problem instances. We also show that the Edge Transformer can be improved using this data such that it generalizes well to further data perturbations. Finally, we show that the same machinery can be applied to novel worlds proposed by LLMs, opening the door to autonomous research on neural relational reasoning.

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

Learning to Prompt: Improving Student Engagement with Adaptive LLM-based High-School Tutoring

LLMs can personalize education, although current static-prompt tutoring systems struggle to adapt to diverse academic disciplines. We develop and test a system with subject-aware prompting, based on 14 pedagogical features (e.g., tutor scaffolding, student understanding) extracted from raw transcripts. We first train a prompt routing model in a simulation environment, and then deploy it for online adaptation with actual high-school students. The simulation benchmark shows the router outperforming two static baselines ($0.694$ vs. $0.647$ and $0.64$, $p

03.
bioRxiv (Bioinfo) 2026-06-10

When batch correction corrupts gene expression: uncovering distortions in correlation structures

Batch correction is essential for integrating datasets and enabling population-level insights into health and disease. Embedding-based approaches are among the most widely used solutions, but here we highlight a critical, overlooked limitation: these methods can distort feature-to-feature (e.g., gene gene) relationships, potentially undermining downstream analyses. We investigate this issue and introduce a novel metric to quantify it.

04.
arXiv (quant-ph) 2026-06-17

An energy-based uncertainty principle and low-energy state preparation

作者:

arXiv:2603.15495v2 Announce Type: replace Abstract: Preparing low-energy states of many-body Hamiltonians is a central challenge in quantum computing, quantum complexity, and condensed matter physics. Existing approaches often get trapped in suboptimal states such as high-energy eigenstates or, more generally, low-variance states that resist further energy reduction. In this work, we explore a different perspective: instead of optimizing with respect to a single Hamiltonian, we leverage the fact that many systems admit families of Hamiltonians that share similar low-energy subspaces but differ at higher energies. We show that this redundancy can be turned into an algorithmic resource by establishing an energy-based uncertainty principle, which implies that these Hamiltonians cannot simultaneously admit low-variance states at higher energies. This suggests a simple strategy of alternating energy-lowering steps across such Hamiltonians, which we investigate numerically on several models. We also introduce a sparse variant where the uncertainty principle yields quadratically larger variance at higher energies, leading to more pronounced energy change. Overall, this work suggests a range of open questions at the interface of random matrix theory, local Hamiltonians and low-energy state preparation, aimed at understanding when such approaches are practical and how they can be analyzed rigorously.

05.
medRxiv (Medicine) 2026-06-22

Cumulative Metabolic Exposure to Hyperglycemia and Risk of Cardiovascular and Limb Events in Peripheral Artery Disease

Background: Although diabetes is a potent risk factor for the development of peripheral artery disease (PAD), the effect of cumulative metabolic exposure to hyperglycemia on risk of cardiovascular or limb events in patients with PAD remains unclear. Methods: The Peripheral Artery Disease: Long-term Survival (PEARLS) is a longitudinal registry of Veterans with newly diagnosed PAD identified using a natural language processing approach. Included patients had ankle brachial index [≤]0.9 or toe brachial index [≤]0.7, and no history of lower extremity revascularization or major amputation. Among patients with diabetes in this cohort, we assessed cumulative exposure to hyperglycema based on a 24-month rolling average of hemoglobin (Hgb) A1c values, categorized as [≤]7%, >7% to [≤]8%, and >8%. Multivariable Cox regression models evaluated the association between categories of HgbA1c, modeled as a time-varying exposure, and risk of cardiovascular (CV: myocardial infarction or stroke) and limb (chronic limb threatening ischemia [CLTI] or major amputation) events. Results: Among 45,109 patients with new diagnosis of PAD and pre-existing diabetes, the mean HgbA1c at baseline was 7.5%, with nearly one-third (30.4%) having HgbA1c >8%. The mean age was 70.4 years, 19.8% were Black and 4% were Hispanic. Patients with baseline HgbA1c >8% were younger and compared to those with HgbA1c [≤]7%, more likely to have coronary disease, kidney disease, and obesity. Over a median follow up of 4.2 years, 8,306 (18.4%) patients experienced a CV event, and 8,199 (18.2%) experienced a limb event. The adjusted association between HgbA1c and hazard of CV events was 12% higher in patients exposed to HgbA1c >7% to [≤]8% (HR 1.12; 95%CI: 1.05-1.18) and 38% higher in those exposed to HgbA1c >8% (HR 1.38; 95%CI: 1.30-1.46), compared to HgbA1c 7% to [≤]8% (HR 1.20; 95%CI: 1.13-1.28) and HgbA1c >8% (HR 1.60; 95%CI: 1.51-1.70), respectively when compared to HgbA1c [≤]7%. These findings were consistent in subgroups based on age and severity of PAD. Conclusions: Among diabetic patients with PAD, cumulatiave metabolic exposure to hyperglycemia is associated with a markedly increased risk of clinical events, especially limb events.

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

Online Dynamic Batching with Formal Guarantees for LLM Training

arXiv:2606.19989v1 Announce Type: cross Abstract: Modern LLM training breaks a core assumption behind offline batch samplers: the true training cost of a sample is only observable after preprocessing, augmentation, templating, tokenization, and multimodal visual-token expansion. Unless one pays for a preprocessing- and augmentation-dependent length cache, batch construction is therefore blind to the quantity that determines padding, memory use, and GPU saturation. We introduce Online Dynamic Batching (ODB), a DataLoader-side drop-in system that moves batch formation to this point of accurate observability while preserving DDP step alignment. We formalize this synchronization requirement as the Distributed Group Alignment Problem and prove deadlock-free bounded termination with default join-mode identity coverage and opt-in non-join sample-quota closure. ODB requires no model, optimizer, or attention-kernel changes and is released as online-dynamic-batching with lightweight trainer adapters. Across public 2B/8B Qwen3-VL runs on UltraChat/LLaVA/ShareGPT4o, ODB improves literal emitted-sample throughput vs. fixed-batch Standard by 1.58-2.51x on single-node Full FT/LoRA and 1.71-3.78x on two-node Full FT, with Standard-comparable quality; production MM-Mix reaches 4.43x. Against GMT/BMT offline token-budget oracles, ODB is within 15% on UltraChat/LLaVA and faster on high-CV ShareGPT4o: 2.24-2.39x single-node Full FT/LoRA and 3.06-3.69x two-node Full FT. Together, ODB occupies the online/drop-in regime for high-heterogeneity LLM fine-tuning: large throughput gains at Standard-comparable quality, formal DGAP guarantees, and no length-cache precompute or kernel rewrites.

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

Towards Data-free and Training-free Compression for Speech Foundation Models Using Parameter Clustering

arXiv:2606.11836v1 Announce Type: cross Abstract: This paper presents a novel data-free and training-free compression approach for speech foundation models using channelwise clustering via k-means. More fine-grained, mixed sparsity pruning by layer-level varying number of parameter clusters is also explored. Experiments conducted on the LibriSpeech dataset suggest that when operating with pruning sparsity of 50% on HuBERT-large, consistent WER reductions of 27.73%/18.61% absolute (34.37%/21.91% relative) over the magnitude-based pruning were obtained on the test-clean and test-other subsets before fine-tuning and 0.19%/0.79% absolute (3.36%/4.62% relative) after fine-tuning with only 3 epochs. Similar WER reductions of 2.86%/5.02% absolute (59.21%/55.29% relative) were observed against magnitudebased pruning on Whisper-large-v3 at 10% sparsity, all with no significant WER increase relative to the uncompressed baseline.

08.
PLOS Medicine 2026-05-12

Social contact patterns in the United Kingdom following the COVID-19 pandemic: The Reconnect cross-sectional survey

by Lucy Goodfellow, Billy J. Quilty, Kevin van Zandvoort, W. John Edmunds Background Close-contact and respiratory infectious diseases are spread through social interactions. Measuring these interactions has transformed our ability to understand transmission and control these infections. Social contact patterns were disrupted during the COVID-19 pandemic and have been affected by wider demographic, cultural, and workplace changes since then. Methods and findings To estimate post-pandemic social contact patterns in the United Kingdom, we conducted a cross-sectional social contact survey from November 2024 to March 2025 on a nationally representative sample of participants. Interactions were captured by age, gender, and across socioeconomic status (SES) and ethnic groups. We calculated the mean number of daily contacts and contact matrices, stratified by variables of interest, using a negative binomial regression model weighted by age, gender, ethnic group, and weekday/weekend. 13,238 participants were recruited, 3,019 of whom were aged under 18 years old; survey response rates were 36% and 27% for adults and children, respectively. The mean number of daily contacts was 9.1 (95% confidence interval (CI): 8.7, 9.5); this figure was 13.8 (95% CI: 12.8, 14.9) for children, and 7.8 (95% CI: 7.4, 8.2) for adults. Higher numbers of contacts were positively associated with employment, household income, and educational qualifications held. Contact matrices showed high levels of age-assortativity, as well as inter-generational contacts in the home. Contacts were assortative between ethnic groups and SES in all settings; this effect was strongest between ethnic groups in the home, and between SES in the workplace. We constructed socially-stratified next-generation matrices for a novel respiratory pathogen, projecting that the majority White ethnic group would account for the largest share of new infections (76.7% (95% CI: 75.5, 77.9) of cases), but that per-capita infection risk would disproportionately affect minority ethnic groups, with the risk for the Black population being 2.27 (95% CI: 2.06, 2.51) times that of the White population. This study may be limited by the inherent recall biases and reporting fatigue involved with self-reporting contacts. Conclusions This study provides crucial data to inform post-pandemic mathematical models of infectious disease transmission, and allows ethnicity and SES to be incorporated in such models.

09.
arXiv (CS.AI) 2026-06-15

FPGA-Based Neural Network Accelerators for Space Applications: A Survey

arXiv:2504.16173v3 Announce Type: replace-cross Abstract: Space missions are becoming increasingly ambitious, necessitating high-performance onboard spacecraft computing systems. In response, field-programmable gate arrays (FPGAs) have garnered significant interest due to their flexibility, cost-effectiveness, and radiation tolerance potential. Concurrently, neural networks (NNs) are being recognized for their capability to execute space mission tasks such as autonomous operations, sensor data analysis, and data compression. This survey serves as a valuable resource for researchers aiming to implement FPGA-based NN accelerators in space applications. By analyzing existing literature, identifying trends and gaps, and proposing future research directions, this work highlights the potential of these accelerators to enhance onboard computing systems.

10.
arXiv (quant-ph) 2026-06-11

Quest for quantum advantage: Monte Carlo wave-function simulations of the Coherent Ising Machine

arXiv:2501.02681v2 Announce Type: replace Abstract: The Coherent Ising Machine (CIM) is a quantum network of optical parametric oscillators (OPOs) intended to find ground states of the Ising model. This is an NP-hard problem, related to several important minimization problems, including the max-cut graph problem. In order to enhance its potential performance, we analyze the coherent coupling strategy for the CIM in a highly quantum regime. To explore this limit, without assuming gaussianity, we employ accurate numerical simulations. Due to the inherent complexity of the system, the maximum network size is limited. While master equation methods can be used, their scalability diminishes rapidly for larger systems. Instead, we use Monte Carlo wave-function methods, which scale as the wave-function dimension, and use large numbers of samples. These simulations involve Hilbert spaces exceeding $10^{7}$ dimensions. To evaluate success probabilities, we use quadrature probabilities. We demonstrate the potential for quantum computational advantage by reducing the time required to reach maximum success probability in a low-dissipation regime enabled by initial quantum superpositions and entanglement. Furthermore, we demonstrate that tailored time-dependent couplings can amplify these quantum effects. Comparisons with classical CIM models give evidence that quantum tunneling effects in this strong coupling limit can overcome trapping in false minima. This can greatly increase success rates, indicating a potential for quantum advantage. Finally, we perform a coherence analysis based on the state purity to examine the role of quantum coherence in CIM performance and to determine how state purity correlates with improved optimization outcomes.

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

Precision Physical Activity Prescription via Reinforcement Learning for Functional Actions

arXiv:2605.19208v2 Announce Type: replace-cross Abstract: Physical activity (PA) plays an important role in maintaining and improving health. Daily steps have been a key PA measure that is easily accessible with common wearable devices. However, methods are lacking to recommend a personalized optimal distribution of daily steps over a period of time for the best of certain health biomarkers. In this paper, we fill this void based on the data from the All of Us Research Program which includes months of step counts as well as repeated measurements of key health biomarkers. We develop a new offline reinforcement learning (RL) algorithm to learn personalized and optimal PA distributions associated with cardiometabolic risk, where the action is a function representing the daily step distribution over a period of time. Simulation studies demonstrate the advantage of the proposed approach over existing continuous-action RL methods. The learned optimal policy from the All of Us data generally suggests people take more daily steps and also follow a more consistent pattern of PA over time while offering tailored recommendations for subgroups in blood glucose level, body mass index, blood pressure, age, and sex.

12.
arXiv (CS.AI) 2026-06-17

StepGuard: Guarding Web Navigation via Single-Step Calibration

arXiv:2606.17871v1 Announce Type: new Abstract: Web navigation requires agents to follow natural language goals, interact with web pages, and produce accurate answers. While recent advances leverage vision-language models and reinforcement learning, existing methods still suffer from single-step fragility due to reward misalignment and error propagation. To tackle the reward entanglement, we design Dynamic Dual-Policy Optimization (DDPO), which dynamically switches between a navigation-first mode for exploration and an answer-first mode for question-answering to mitigate reward conflict. To calibrate the single-step error, we propose Confidence-Guided Adaptive Navigation Reflection (CANR), a mechanism that estimates per-step confidence, triggers reflection only when necessary, and uses contrastive rewards to encourage self-correction to calibrate the single-step inaccuracy. With the above as the main components, we finally develop our StepGuard, a new framework of Guarding Web Navigation via Single-Step Calibration. Experiments demonstrate that our approach significantly improves navigation and answer accuracy, setting new state-of-the-art performance on standard web navigation benchmarks.

13.
arXiv (quant-ph) 2026-06-16

Experimental Observation of Dynamical Phase Transitions in a Dephased Photonic Quantum Walk

arXiv:2606.15935v1 Announce Type: new Abstract: Dynamical phase transitions in open quantum systems govern how non-equilibrium states relax toward a stationary state. We study these transitions experimentally using a discrete-time photonic quantum walk on a three-node graph. A tunable synthetic gauge flux and calibrated dephasing allow us to control time-reversal symmetry and the detailed balance properties of the effective Markovian dynamics. With detailed balance, we observe a first-order dynamical phase transition marked by a crossing of real Liouvillian eigenvalues. When detailed balance is broken, we observe a second-order dynamical phase transition at an exceptional point where eigenvalues and eigenvectors coalesce. By progressively reducing the dephasing strength, we track the crossover toward the quantum-coherent regime and determine that the transitions persist down to a finite threshold. Our results link Liouvillian spectral topology to relaxation criticality and demonstrate a controllable platform for engineered dissipative dynamics.

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

An Improved Generative Adversarial Network for Micro-Resistivity Imaging Logging Restoration

An improved GAN-based imaging logging image restoration method is presented in this paper for solving the problem of partially missing micro-resistivity imaging logging images. The method uses FCN as the generative network infrastructure and adds a depth-separable convolutional residual block to learn and retain more effective pixel and semantic information; an Inception module is added to increase the multi-scale perceptual field of the network and reduce the number of parameters in the network; and a multi-scale feature extraction module and a spatial attention residual block are added to combine the channel attention. The multi-scale module adds a multi-scale feature extraction module and a spatial attention residual block, which combine the channel attention mechanism and the residual block to achieve multi-scale feature extraction. The global discriminative network and the local discriminative network are designed to gradually improve the content and semantic structure coherence between the restored parts and the whole image by playing off each other and the generative network. According to the experimental results, the average structural similarity measure of the five sets of imaged logging images with different sizes of missing regions in the test set is 0.903, which is an improvement of about 0.3 compared with other similar methods. It is shown that the method in this study can be used for the restoration of micro-resistivity imaging log images with good improvement in semantic structural coherence and texture details, thus providing a new deep learning method to ensure the smooth advancement of the subsequent interpretation of micro-resistivity imaging log images.

16.
bioRxiv (Bioinfo) 2026-06-18

Looking beyond stereotyped neuron structures reveals links between beading and morphological rearrangements in aging phenotypes.

Understanding how neuronal morphology changes during aging and acute stress is essential for elucidating mechanisms of neurodegeneration. The highly branched PVD neuron of Caenorhabditis elegans provides a powerful model for studying dendritic remodeling and degeneration-associated phenotypes such as dendritic beading. However, the complexity of this arbor presents substantial challenges for automated segmentation and quantitative analysis. In this study, we adapted a convolutional neural network (CNN)-guided region growing framework for automated dendrite tracing, coupled with two topology-based algorithms for categorizing dendritic segments by branching degree. The segmentation algorithm achieved high accuracy relative to manual tracing, with a median Dice coefficient of 0.82, while reducing analysis time by approximately tenfold. Automated dendrite categorization demonstrated strong agreement with manual annotations across branching orders, though position-based mapping performance declined with age due to progressive morphological distortion. Leveraging this platform, we investigated mechanistic differences in dendritic beading patterns observed during aging and cold shock. Consistent with prior work, aging was associated with decreased inter-bead spacing, whereas cold shock produced increased bead dispersion with stress severity. Structural analysis revealed that these trends were not driven by dendritic pruning or reduced arbor complexity. Instead, while a traditional anatomically unflexible paradigm falsely implicated lower-degree dendrites as highly vulnerable, our branching-informed framework revealed that age-dependent beading is fundamentally dictated by a segments history of successive branching events. Conversely, acute cold shock triggered systemic beading that expanded across all dendritic orders in a severity-dependent manner. Together, these findings demonstrate that chronic aging and acute stress engage distinct degenerative pathways (compartment-specific lineage vulnerability versus global architectural collapse) rather than gross morphological loss, as well as highlighting the need for paradigms that enable reliable analysis of changing morphologies.

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

Reinforcement Learning Foundation Models Should Already Be A Thing

arXiv:2606.18812v1 Announce Type: cross Abstract: Foundation models for language and vision are powered by internet-scale data, while structured domains (tabular prediction, time-series forecasting, graph learning, reinforcement learning) are not. The substitute is synthetic data, which shifts the burden from collection to prior design. Such priors already exist for many structured tasks: TabPFN and its successors solve tabular classification with a transformer pretrained on a synthetic Bayesian prior. We make two points. First, reinforcement learning is the conspicuous gap: sampling a synthetic MDP is as feasible as sampling a synthetic tabular dataset, yet no in-context RL work treats prior design as a primary objective. Second, MDPs admit a fixed-size sufficient statistic, independent of the episodes observed and tabular in shape, which makes them directly amenable to the attention-based architectures used for tabular foundation models, with a policy head replacing the supervised target. Together these define the agenda for an RL foundation model. As a proof of concept, we train one model entirely on synthetic MDPs and show that, with no task-specific tuning, it solves held-out tabular benchmarks in context, both online and offline: online, in far fewer episodes than UCB-VI and tabular Q-learning, and offline, competitively with VI-LCB.

18.
arXiv (quant-ph) 2026-06-24

Testing quantum-like markers in neural dynamics

arXiv:2508.21490v3 Announce Type: replace-cross Abstract: We propose two experiments for identifying quantum markers in neural data based on quantum variants of well-known equations for neural activity that describe electrical signal propagation on axonal arbors and dendrites. These include (i) testing if power spectra from subthreshold oscillations in neuronal cultures follow the classical Fitzgugh-Nagumo equations or a recently introduced quantum variant of them and (ii) testing if propagation statistics of electrical activity in axons follow the classical diffusive cable equation or a quantum variant of it.

19.
arXiv (math.PR) 2026-06-18

Metastability for the Curie-Weiss-Potts model with unbounded random interactions

arXiv:2505.11260v2 Announce Type: replace Abstract: We analyse the metastable behaviour of the disordered Curie–Weiss–Potts (DCWP) model subject to a Glauber dynamics. The model is a randomly disordered version of the mean-field $q$-spin Potts model (CWP), where the interaction coefficients between spins are general independent random variables. These random variables are chosen to have fixed mean (for simplicity taken to be $1$) and well defined cumulant generating function, with a fixed distribution not depending on the number of particles. The system evolves as a discrete-time Markov chain with single spin flip Metropolis dynamics at finite inverse temperature $\beta$. We provide a comparison of the metastable behaviour of the CWP and DCWP models, when $N \to \infty$. First, we establish the metastability of the CWP model and, using this result, prove metastability for the DCWP model (with high probability). We then determine the ratio between the metastable transition time for the DCWP model and the corresponding time for the CWP model. Specifically, we derive the asymptotic tail behavior and moments of this ratio. Our proof combines the potential-theoretic approach to metastability with concentration of measure techniques, the latter adapted to our specific context.

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

A unified complexity bound for logconcave sampling

arXiv:2606.12694v1 Announce Type: cross Abstract: We give a simple, unified, and nearly tight bound for sampling arbitrary logconcave distributions from a warm start using the In-and-Out algorithm along with exponential lifting. The main new ingredient in the analysis is an improved bound on the Poincaré constant of a lifted distribution. As a consequence, the resulting convergence rate is nearly tight for both constrained settings (e.g., Gaussian restricted to a convex body) and well-conditioned settings (e.g., strongly logconcave and smooth densities).

21.
arXiv (CS.AI) 2026-06-25

Evaluating Scene-based In-Situ Item Labeling for Immersive Conversational Recommendation

arXiv:2604.09698v2 Announce Type: replace-cross Abstract: The growing ubiquity of Extended Reality (XR) is driving Conversational Recommendation Systems (CRS) toward visually immersive experiences. We formalize this paradigm as Immersive CRS (ICRS), where recommended items are highlighted directly in the user's scene-based visual environment and augmented with in-situ labels. While item recommendation has been widely studied, the problem of how to select and evaluate which information to present as immersive labels remains an open problem. To this end, we introduce a principled categorization of information needs into explicit intent satisfaction and proactive information needs and use these to define novel evaluation metrics for item label selection. We benchmark IR-, LLM-, and VLM-based methods across three datasets and ICRS scenarios: fashion, movie recommendation, and retail shopping. Our evaluation reveals three important limitations of existing methods: (1) they fail to leverage scenario-specific information modalities (e.g., visual cues for fashion, meta-data for retail), (2) they present redundant information that is visually inferable, and (3) they poorly anticipate users' proactive information needs from explicit dialogue alone. In summary, this work provides both a novel evaluation paradigm for in-situ item labeling in ICRS and highlights key challenges for future work.

22.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

23.
medRxiv (Medicine) 2026-06-16

Adherence to Red Reflex and Vision Screening Recommendations: A Deep Dive into Primary Care Implementation Gaps

Introduction: Early childhood vision screening is critical for detecting amblyopia and other vision-threatening conditions. Despite screening recommendations during well-child visits, rates remain low. Red reflex assessment is recommended to identify serious ocular pathology, yet its use in primary care is not well described. We examined rates and drivers of vision screening in pediatric primary care. Methods: We conducted a retrospective review of electronic health records for children 3 to 5 years attending well-child visits in 2022 in one of three representative primary care clinics within a university health system. Outcomes were documented red reflex and functional vision tests. We evaluated associations with patient demographics and clinic site using multivariable logistic regression Results: Among 1,003 visits, 21.1% (n=212) had a documented red reflex assessment, and 60.8% (n=610) a functional vision test. Younger children (ages 3 and 4 vs. 5 years) had higher odds of red reflex assessment [adjusted odds ratio (aOR) 9.00 and 8.64], and lower odds of a functional vision (aOR 0.47 and 0.59) test. Females had higher odds of red reflex assessment (aOR 1.53). Other/Multiracial children had lower odds of red reflex assessment than Non-Hispanic White children (aOR 0.48). Screening rates varied significantly by clinic site Conclusions: Visual function and red reflex assessment are inconsistently performed in pediatric primary care, with particularly low rates of red reflex documentation. Screening rates varied between clinics and were affected by age. These findings highlight missed opportunities for early detection of vision-threatening conditions and identify targets for improving adherence to pediatric vision screening recommendations

24.
arXiv (CS.AI) 2026-06-19

Rethinking Shrinkage Bias in LLM FP4 Pretraining: Geometric Origin, Systemic Impact, and UFP4 Recipe

arXiv:2606.20381v1 Announce Type: new Abstract: FP4 training promises substantial reductions in memory and computation cost for LLM pretraining, yet current FP4 hardware paths and recipes, including NVIDIA Blackwell/Rubin-class systems and AMD MI350-series GPUs, remain centered on E2M1 data elements. In this study, we identify a fundamental limitation of that choice: non-uniform formats such as E2M1 inherently suffer from Shrinkage Bias, a systematic negative rounding error caused by the geometric asymmetry of their representable bins. We show that this bias accumulates multiplicatively across layers and is amplified by the Random Hadamard Transform (RHT), providing a unified explanation for the training instability observed in existing E2M1-based FP4 recipes. In contrast, uniform grids (E1M2/INT4) bypass this grid-geometry error and better convert the improved bucket utilization from RHT into higher quantization quality. Based on this finding, we propose UFP4, a uniform 4-bit training recipe that applies RHT to all three training GEMMs while restricting stochastic rounding to dY alone. On Dense 1.5B, MoE 7.9B, and MoE 124B long-run pretraining, UFP4 consistently achieves lower BF16-relative loss degradation than strong E2M1-based baselines, supported by scaling-law analysis and ablation studies. Our results suggest that future accelerators should support E1M2/INT4-style uniform 4-bit grids as first-class training primitives alongside E2M1.

25.
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.