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01.
arXiv (math.PR) 2026-06-12

On McDiarmid's Inequality under Dependence via Approximate Tensorization of Entropy

Authors:

arXiv:2606.12720v1 Announce Type: new Abstract: We argue that dependent versions of McDiarmid's inequality are a useful but underutilized tool in mathematical statistics, learning theory and theoretical computer science. To make this point, we first highlight that approximate tensorization of entropy (ATE) implies McDiarmid's via the Entropy Method. Second, we derive McDiarmid's inequality for non-isotropic Gaussian random vectors $X \sim \mathcal N(\mu, \Sigma)$ through ATE with a constant of the order of the condition number of $\Sigma$. We both independently obtain this ATE through a simple application of stochastic localization and also discuss how a more general ATE for the Gibbs sampler due to Ascolani et al., 2026 generalizes McDiarmid's-like concentration to strongly log-concave and log-smooth probability measures. We then apply the resulting concentration inequalities to resolve a question on the concentration of $\operatorname{sign}(X)$ posed by Simone Bombari, investigate Erdős-Rényi graphs under dependence and prove a Dvoretzky-Kiefer-Wolfowitz-type inequality for observations from a joint measure fulfilling ATE and continuous marginal CDFs. For the class of strongly log-concave and log-smooth measures, this result improves upon a prior Dvoretzky-Kiefer-Wolfowitz-type inequality for non-i.i.d. observations due to Bobkov and Götze, 2010, by establishing the expected $1/\sqrt{n}$-rate of convergence under weak dependence instead of $n^{-1/3}$.

02.
medRxiv (Medicine) 2026-06-23

Uptake of minimal intervention dentistry among Romanian dental professionals and trainees: an exploratory cluster and network analysis

Background Minimal intervention dentistry (MID) is promoted as a prevention-oriented approach to caries management, but its integration into routine practice remains uneven. Existing research often examines MID-related knowledge, attitudes, or practices separately, offering limited insight into how these dimensions co-occur within individuals or are conditionally associated. Methods This exploratory cross-sectional survey examined multidimensional MID uptake among 327 Romanian dental students, residents, and specialists from five university centers. Ten MID-related scores were analyzed, including nine formative composites and one single-item peer-norm indicator. K-means clustering examined uptake profiles, and Gaussian graphical model network analysis with stepwise BIC selection examined conditional associations among constructs. Results A two-cluster solution was highly reproducible but modestly separated (n = 144 vs n = 183; average silhouette width = 0.13; mean Jaccard similarities = 0.92 and 0.94). The profiles reflected broadly lower versus higher uptake across knowledge-, belief-, and practice-related dimensions, while perceived peer norms for hygiene instruction showed the opposite pattern. Profile membership was not clearly patterned by gender, age band, professional status, or clinical experience. The primary network included 14 non-zero edges out of 36 possible edges, all positive; the strongest partial association linked diagnostic knowledge to diagnostic methods used in practice (partial r = .22). Familiarity, diagnostic knowledge, and general practices occupied more interconnected positions descriptively, but limited centrality stability precluded interpreting them as intervention targets. Conclusions MID uptake in this sample was better represented as a continuum of modestly differentiated profiles than as sharply separated participant types. The findings provide an exploratory map of multidimensional MID uptake and may inform future survey validation, implementation research, and dental education studies. Because the study was cross-sectional, convenience-sampled, and based on self-report, findings should be interpreted as hypothesis-generating rather than causal or population-representative.

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

Rethinking RAG in Long Videos: What to Retrieve and How to Use It?

arXiv:2606.13141v1 Announce Type: new Abstract: Retrieval-augmented generation is moving beyond text into long, egocentric video, where systems must select query-relevant chunks across multiple modalities and temporal granularities. Yet progress in VideoRAG is limited by two gaps: existing benchmarks allow queries to be answered without the video, obscuring retrieval errors, and prior methods apply a single modality-granularity configuration per query, ignoring chunk-level variability. We address both by introducing V-RAGBench, a benchmark of $\langle$query, evidence chunk, answer$\rangle$ triplets that enables faithful, decoupled evaluation of retrieval and generation, and CARVE, a simple method that runs parallel retrievers across configurations and employs chunk-adaptive reranking to identify the winning configuration for each chunk. Each chunk then enters the generator under its winning configuration selected during retrieval, yielding an interleaved evidence form where the chunk-level decision propagates across both stages. CARVE outperforms eight recent VideoRAG baselines, with the chunks supplied to the generator interleaving multiple configurations rather than sharing a single one, a behavior unattainable by query-level methods.

04.
arXiv (CS.LG) 2026-06-19

A fast direct solver based neural network for solving PDEs

arXiv:2606.19895v1 Announce Type: cross Abstract: The matrices arising from large scale $N$-body problems can be efficiently represented using hierarchical matrices, whose key idea is that the admissible off-diagonal sub-matrices can be well approximated by low-rank matrices across a hierarchy of matrix partitions. HODLR (Hierarchical Off-Diagonal Low-Rank) matrices are a subclass of hierarchical matrices in which all off-diagonal submatrices at every level of a recursive binary partition are low-rank. In this article, we present a neural network that learns the inverse operation of HODLR matrices based on the fast direct solver for HODLR matrices developed by Ambikasaran and Darve (2013). We further extend the architecture to learn nonlinear solution operators associated with PDEs by replacing some of the linear layers with deep sub-networks. We demonstrate the performance of the proposed architecture by performing a comprehensive set of experiments that include (i) solving a linear problem such as the Fredholm integral equation of the second kind, (ii) solving PDEs such as the nonlinear Schrödinger equation, Burgers' equation, and the steady-state Darcy's flow equation, (iii) generalization study across varying parameter values, (iv) comparing the inference time of the proposed network with the run time of a classical numerical solver, and (v) comparing the proposed network with some of the existing neural operator learning networks.

05.
medRxiv (Medicine) 2026-06-15

Data-Driven Stochastic Model for Detecting Patientswith Alzheimer's Disease

Alzheimer s disease (AD) is a critical neurological disorder that causes the brain to shrink and leads to the eventual death of brain cells, adversely affecting a person s ability to function. AD is a fast-growing disease in the United States and was the fifth leading cause of death among Americans 65 years of age or older in 2023. In the United States 6.9 million people aged 65 or older were diagnosed with AD, along with a high rate of undiagnosed patients. Thus, the objective of our study is to develop a real data-driven predictive model to identify a patient with AD based on eight risk factors: Age, Gender, ADAS-Cog13, Entorhinal, Fusiform, Intracranial Volume (ICV), Amyloid-Beta, and Tau Protein, with a high degree of accuracy. The quality of the model was evaluated using well-established and sophisticated statistical measures: the area under the receiver operating characteristic curve, calibration plot, Hosmer-Lemeshow goodness-of-fit test, and K-fold cross-validation. If a patient is given information on the above risk factors, our proposed binary logistic regression model can classify the patient as having AD or not with at least 98% accuracy.

06.
medRxiv (Medicine) 2026-06-17

Menopausal symptoms in peri- and postmenopausal women: systematic review and meta-analysis of prevalence, incidence, comorbidities, and clinical outcomes

Introduction: The global epidemiology of menopausal symptoms among middle-aged and elderly women remains unclear. Methods: Data on prevalence, comorbidities, incidence and outcomes of menopausal symptoms published up until March 1st 2019 were searched in PubMed, Embase and Cochrane databases. We used a random-effects model to compute point estimates of prevalence for 24 types of menopausal symptoms. We narratively summarized the patterns of the comorbidities, incidence and outcomes of menopausal symptoms due to limited data. Results: A total of 239 studies (n{approx}2.5 million middle-aged and elderly women) from 56 countries and regions were included in the analysis. The global pooled prevalence analysis revealed that hot flashes (48%) and night sweats (30%) were highly prevalent, alongside psychological symptoms like insomnia (47%), irritability (46%), anxiety (39%), and depression (30%). Physical symptoms including joint aches/pain (50%), backache (47%), and tiredness (61%) were also commonly reported. Heat intolerance showed the highest prevalence (76%), while symptoms like urinary incontinence (24%) and poor appetite (8%) were less frequent. These findings highlight the diverse and widespread impact of menopause on women globally, with significant variations across symptom types. Africa showed the highest pooled prevalence across a series of symptoms, compared with other continents. We observed high prevalence in developing countries, especially for psychological and physical symptoms; significant intra-Asian variation in vasomotor symptoms; hypertension and obesity as the most common comorbidities; joint pain, urinary incontinence, and vasomotor symptoms as the most incident complaints; and positive associations with cardiovascular disease in the psychological (depression and insomnia) and physical (joint pain) domains. Conclusion: This study highlights the global burden of menopausal symptoms, with significant differences across continents. The findings call for more inclusive research on underrepresented groups (particularly in Africa) and further investigation into drivers of this marked global heterogeneity in prevalence of menopausal symptoms and their comorbidities, incidence and outcomes.

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

Provably Efficient Regularized Online RLHF with Generalized Bilinear Preferences

arXiv:2602.23116v3 Announce Type: replace Abstract: We consider the problem of regularized best-response max-regret minimization in online RLHF under general preferences and bandit feedback. While various regularizers are utilized to robustify alignment, known polylogarithmic regret guarantees remain heavily specific to KL. To investigate whether such fast rates extend beyond KL, we adopt the Generalized Bilinear Preference Model (GBPM) – capturing intransitive preferences over $d$-dimensional item-wise features via a rank-$2r$ skew-symmetric matrix – to isolate the impact of generic regularization. Crucially, under GBPM, we prove that the dual gap of any greedy policy is bounded by the squared estimation error, derived using only strong convexity and skew-symmetry. Under a feature coverage assumption, we establish a generic polylogarithmic regret of $\tilde{\mathcal{O}}(\eta d^4 C_{\min}^{-1} (\log T)^2 \wedge d^2 C_{\min}^{-1/2} \sqrt{T})$ with Greedy Sampling, and a dimension-wise improved regret (for well-conditioned arm-sets) of $\tilde{\mathcal{O}}(C_{\min}^{-2} \sqrt{\eta r T} \wedge r^{1/3} C_{\min}^{-4/3} T^{2/3})$ with Explore-Then-Commit, where $\eta^{-1}$ is the regularization coefficient, $T$ is the time horizon, and $C_{\min}$ is an arm-set dependent quantity. This demonstrates that ``fast'' regrets are not KL-specific, but rather a fundamental consequence of generic strongly convex geometry.

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

Hidden Degradation Costs in Energy-Cost-Only HEMS Optimisation: Study on Battery and PV Sensitivity

arXiv:2606.16051v1 Announce Type: cross Abstract: Residential battery energy storage systems (BESS) are increasingly deployed alongside photovoltaic (PV) generation to reduce household energy costs under volatile time-of-use (TOU) tariffs. Model predictive control (MPC) is a widely adopted optimisation strategy for home energy management systems (HEMS), typically formulated to minimise net energy cost, subject to physical and operational constraints. However, battery degradation is rarely embedded in the optimisation objective, meaning its cost is unquantified and aggressive; high-cycle-count strategies could incur significant losses once deployed to physical systems. This paper presents a receding-horizon mixed-integer linear programming (MILP) baseline for a UK residential HEMS, using demand data from the REFIT dataset. A 3 by 3 sensitivity study is conducted across three battery sizes and three PV array sizes, with post-hoc degradation cost estimated using the Naumann stress model and rainflow cycle counting. Results show that degradation remains constant for each battery size and can exceed energy cost savings by up to 1,060 %. These results demonstrate that energy-cost-only optimisation systematically underestimates the true system cost, motivating a degradation-aware control formulation.

09.
bioRxiv (Bioinfo) 2026-06-11

HoloCell: A Generative Foundation Model for Holistic Cellular Modeling

Single-cell multi-omics technologies have recently advanced to enable the profiling of epigenomic, transcriptomic, and proteomic layers within individual cells, offering new opportunities to characterize cellular states as integrated biological systems. However, developing a unified framework that can seamlessly integrate diverse omics modalities and remain robust to heterogeneous modality missingness remains challenging. Here we present HoloCell, to our knowledge the first generative foundation model for joint representation learning and generative modeling across all three major single-cell omics modalities, i.e., epigenomics, transcriptomics, and proteomics. HoloCell contains over 860 million parameters and is pretrained on the Human-Multi-Omics-Corpus, which comprises approximately 468 million single-cell profiles across these three omics layers, corresponding to over 425 billion tokens. HoloCell introduces a simple yet biologically grounded hierarchical tokenization strategy that encodes cis-regulatory elements, genes, and proteins as structured tokens within a shared modeling framework. We evaluated HoloCell across single-omics representation learning, paired multi-omics integration, unpaired multi-omics alignment, and cross-modal generation via iterative diffusion and remasking, demonstrating its superior performance and flexibility across diverse omics tasks. From a representation perspective, HoloCell provides a unified digital mapping of cellular states across multiple omics layers, capturing cell heterogeneity as an integrated system. From a generation perspective, its iterative diffusion and remasking framework accounts for the inherently unordered nature of biological features, enabling in silico simulation of multi-omics information flow. Together, these capabilities position HoloCell as a versatile foundation model toward the emerging concept of a virtual cell, offering both systematic characterization and generative simulation of cellular systems within a unified framework.

10.
arXiv (CS.AI) 2026-06-12

Different Layers, Different Manifolds: Module-Wise Weight-Space Geometry in Transformer Optimization

arXiv:2606.13276v1 Announce Type: cross Abstract: Weight-space geometry plays a central role in neural network optimization, yet manifold constraints are often applied uniformly across all weight matrices. In this work, we ask whether different transformer modules prefer different manifold geometries. We study Manifold Muon for GPT-2 pretraining and compare layer-wise assignments of Stiefel and DGram constraints across attention and MLP blocks. Our results show a clear asymmetry: constraining attention layers with Stiefel geometry while assigning DGram geometry to MLP layers gives the best performance among the tested configurations, whereas the inverted assignment and all-DGram configuration become unstable under the shared hyperparameter setting. We trace this failure to singular value growth in DGram-constrained attention weights, which can amplify attention logits and induce softmax saturation. These findings suggest that symmetry-aware and geometry-aware optimization for transformers should be module-specific rather than uniform.

11.
arXiv (CS.CV) 2026-06-18

SAMA: Semantic Anchor-aligned Augmentation for Unified Low-Resource Multimodal Information Extraction

Multimodal Information Extraction (MIE)-covering tasks such as Multimodal Named Entity Recognition (MNER), Relation Extraction (MRE), and Event Extraction (MEE)-is essential for understanding multimedia content but remains constrained by severe data scarcity. Although data augmentation is a promising remedy, existing approaches are impeded by coarse cross-modal alignment and fragmented, task-specific designs that fail to exploit shared semantic knowledge. To overcome these limitations, we introduce Semantic Anchor-aligned Multimodal Augmentation (SAMA), a unified framework for generating high-fidelity, task-aware synthetic data. SAMA constructs structured semantic anchors from ground-truth labels to guide a Collaborative Multi-Experts Multimodal Large Language Model (CME-MLLM), which integrates a Universal Adapter for shared semantics with Task-Specific Adapters to produce diverse yet constraint-compliant textual samples. For image synthesis, SAMA employs an Anchor-Preserving Diffusion mechanism that uses anchor-weighted prompts and latent conditioning to maintain critical semantic anchors while diversifying visual contexts. To eliminate the need for manual verification, SAMA further introduces a Dual-Constraint Filtering module that selects synthetic samples based on both cross-modal consistency and anchor fidelity. Extensive experiments across benchmark datasets for MNER, MRE, and MEE demonstrate that SAMA consistently outperforms state-of-the-art augmentation baselines under both fully supervised and low-resource settings, underscoring its versatility, robustness, and effectiveness.

12.
arXiv (CS.LG) 2026-06-24

Learning the Koopman Operator using Attention Free Transformers

arXiv:2606.23957v1 Announce Type: new Abstract: Learning Koopman operators with autoencoders enables linear prediction in a latent space, but long-horizon rollouts often drift off the learned manifold, leading to phase and amplitude errors on systems with switching, continuous spectra, or strong transients. We introduce two complementary components that make Koopman predictors more robust. First, we add an attention-free latent memory (AFT) block that aggregates a short window of past latents to produce a corrected latent before each Koopman update. Unlike multi-head attention, AFT operates in linear time and adds only $\approx$30k parameters ($3d^2 + T^2$, fewer than matched multi-head attention), yet captures the local temporal context needed to suppress error divergence. Second, we propose dynamic re-encoding: lightweight, online change-point triggers (EWMA, CUSUM, and sequential two-sample tests) that detect latent drift and project predictions back onto the autoencoder manifold. Across three benchmark systems – Duffing oscillator, Repressilator, IRMA – our model consistently reduces error accumulation compared to a Koopman autoencoder and matched-capacity multi-head attention. We also compare against GRU and Transformer autoencoders, evaluated both from initial conditions and with a 50-step context, and find that Koopman+AFT (with optional re-encoding) attains markedly lower long-horizon error while maintaining lower inference latency. We report improvements over horizons up to 1000 steps, together with ablations over trigger policies. The result is a fast, compact predictor that stays on the learned manifold over long horizons.

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

PIVOT: Bridging Black-Scholes Implied-Volatility and Price Objectives via Differentiable Jäckel Operator

arXiv:2606.17065v1 Announce Type: cross Abstract: Modern option-learning systems operate in two coordinates: price space, where markets quote and no-arbitrage constraints are most naturally enforced, and implied volatility (IV) space, where volatility surfaces are smoothed, regularized, and evaluated. The bottleneck is interface, not approximation: Jäckel's seminal "Let's Be Rational" (LBR) solver already inverts the Black-Scholes price to machine precision efficiently. What is missing is a differentiable layer that preserves LBR in the forward pass and avoids backpropagating through its branch logic. Such a layer must also confront the unavoidable singularity of the inverse map in the low-vega regime, where the sensitivity 1/vega diverges as vega -> 0. We close this gap with PIVOT, the Price-Implied-Volatility Objective Translator. PIVOT keeps the LBR forward pass intact and supplies the backward pass by implicit differentiation through the smooth Black-Scholes/Black-76 price map, with an explicit gating contract: invalid domains return NaN, well-conditioned rows receive the exact 1/vega gradient, and low-vega rows are attenuated rather than silently regularized. On a single H100, a fused Triton kernel reaches 1.79e9 IV/s at machine precision (9.3e-14 max relative error vs. the reference C solver); end-to-end label generation sustains 48.9M/s on synthetic chains and 16.6M/s on SPX OptionMetrics. In a HyperIV-style one-day reproduction on SPX, PIVOT-augmented objectives Pareto-dominate the baselines, reducing held-out price MAE by up to 43.4% and the strongest three-seed gated objective improving price MAE by 38.8% and IV MAE by 21.3% jointly; cross-asset results on RUT, VIX, and NDX show directional price-MAE gains of 40.1%, 24.2%, and 16.7%, while an ungated IV-roundtrip control collapses to a degenerate near-zero surface, confirming the gate as a correctness contract rather than a tuning knob.

14.
arXiv (CS.LG) 2026-06-16

Spectral Analysis of Molecular Features: When Richer Features Do Not Guarantee Better Generalization

arXiv:2510.14217v2 Announce Type: replace Abstract: The spectral properties of feature embeddings offer critical insights into model generalization and representation quality. While deep learning models are widely used for molecular property prediction, kernel methods remain competitive in low-data regimes, yet their spectral behavior is largely unexplored. We present the first comprehensive spectral analysis of kernel ridge regression across diverse representations-including molecular fingerprints (ECFP), pretrained transformers, graph neural networks, and 3D descriptors-evaluated on QM9 and 3 MoleculeNet benchmarks. Surprisingly, richer spectral features do not consistently yield better generalization performance, contradicting common representation heuristics used in self-supervised learning (SSL). Across 4 spectral metrics, only ECFP-based kernels show a strictly positive correlation with performance. Transformer and global 3D representations exhibit mixed behavior, whereas local 3D representations show consistently negative correlations. Truncation analysis further emphasizes this disparity: for local 3D representations on thermodynamic targets, fewer than 2\% of eigenvalues (and occasionally as few as 0.02\%) are needed to recover 95\% of performance, whereas ECFP and transformer kernels require significantly more. By demonstrating a strong dependence on both task and representation, our results challenge the heuristic that richer spectra inherently improve generalization, providing new guidance for evaluating representations in SSL and in label-limited scientific tasks.

15.
PLOS Computational Biology 2026-06-22

Ten simple rules for making the supplement increase your paper’s impact

Authors:

by Volker Grimm, Uta Berger, Stefano Mammola Have you ever lost hours navigating supplementary materials—clicking between the main text and dozens of auxiliary files only to encounter broken links, illegible figures, and undefined variables and acronyms? If so, you’re not alone. What should support scientific communication has instead become an obstacle: supplementary information (SI) increasingly suffers from inconsistent formatting, poor accessibility, and fragmented organization that impedes rather than advances understanding. This is disheartening since the SI, if used effectively, has the power to enhance transparency, credibility, and reproducibility of research. Therefore, we propose 10 simple rules to help authors design SI that genuinely increase the impact of their research. The rules emphasize treating SI with the same care as the main text, using it strategically to support the scientific narrative while preserving clarity and focus. Key recommendations include creating a single, well-structured, self-contained SI master document; ensuring explicit cross-referencing between the main text and SI; making SI machine-readable; and avoiding the misuse of SI as a substitute for proper data repositories. We also highlight the importance of creativity in choosing appropriate formats and strict adherence to journal-specific guidelines. Finally, when available, we advocate the use of standardized templates to improve consistency, readability, and reuse across studies. By following these rules, authors can substantially increase the scientific impact of their work while at the same time contributing to more sustainable research practices.

16.
arXiv (CS.CL) 2026-06-17

ALAS: An Automatic Latent Alignment Score for Audio Language Models

Large Language Models (LLMs) are extended into Speech-LLMs, and the quality of the audio–text alignment they learn affects most downstream Spoken Language Understanding (SLU) behavior. Yet despite a growth of fusion strategies, there is no standard way to measure how well a Speech-LLM internally binds audio frames to text tokens. We introduce ALAS (Automatic Latent Alignment Score), a model and task-agnostic metric that probes the LLM's per-layer hidden states, scoring the cross-modal cosine similarity between audio and text representations against a Whisper-derived reference. ALAS needs only a frozen forward pass and an off-the-shelf ASR reference, with no training or fitted classifier, and is calibrated to an interpretable uniform baseline comparable across tasks. Applying ALAS to four open-source Speech-LLMs (AF3, Qwen2-Audio, Qwen-Omni, SALMONN) across emotion recognition (IEMOCAP), open-ended SQA (LibriSQA), and multi-choice audio understanding (MMAU-speech), we find that the depth and strength of alignment reflect each model's audio-encoder design and the acoustic-versus-semantic demands of the task, and that ALAS tracks but does not duplicate task accuracy, exposing models that score well without genuinely grounding in the audio. We release ALAS as an open-source library so that practitioners can probe their own Speech-LLMs or try it on new tasks.

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

A Survey on Long-Term Memory Security in LLM Agents: Attacks, Defenses, and Governance Across the Memory Lifecycle

The emergence of writable, cross-session persistent memory in LLM agents introduces a qualitatively different threat landscape from conventional input-centric security concerns, characterized by three properties: persistence, statefulness, and propagation. To systematically characterize this landscape, we propose a Memory Lifecycle Framework that organizes attacks, defenses, and their cross-phase dependencies along two axes: six lifecycle phases (Write, Store, Retrieve, Execute, Share & Propagate, Forget & Rollback) and four security objectives (Integrity, Confidentiality, Availability, Governance). This analysis in turn exposes the need for formal security guarantees at the system level, motivating Verifiable Memory Governance(VMG), a framework of five architectural primitives that specifies what verifiable mechanisms a long-term-memory system must provide to maintain auditable, recoverable control over its memory state. Our analysis indicates that robust Long-Term Memory (LTM) security cannot be retrofitted at retrieval or execution time alone, but must be anchored in storage-time provenance, versioning, and policy-aware retention from the outset.

18.
bioRxiv (Bioinfo) 2026-06-11

DivQuant: Estimation of Species Richness and Entropy from Small Samples

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

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

Probe-and-Refine Tuning of Repository Guidance for Coding Agents

arXiv:2606.20512v1 Announce Type: cross Abstract: LLM-based coding agents need higher-level operational knowledge about a repository (which files house which subsystems, how to run the test suite, which workflows have historically led to wrong fixes) that does not exist in the code itself. Engineers typically maintain \texttt{AGENTS.md} files to supply this context as instructions for coding agents, but whether they help is contested: recent studies disagree on whether LLM-generated guidance improves or harms agent performance. In this paper we show that how the guidance is produced is the decisive variable, and introduce probe-and-refine tuning: a procedure that uses synthetic bug-fix probes to iteratively diagnose and patch a repository's guidance file through single-shot LLM calls, with no agent loop or tool use during tuning. On SWE-bench Verified across four independent trials with Qwen3.5-35B-A3B at 200 steps, probe-and-refine achieves 33.0\,\% mean resolve rate vs.\ 28.3\,\% for the static knowledge base used to initialize it and 25.5\,\% for an unguided baseline ($p < 0.001$ for both probe-and-refine contrasts). The improvement comes from coverage rather than precision: refined guidance produces evaluable patches for 14.5 percentage points (pp) more instances while per-patch precision remains statistically constant ($\sim$59\,\%, $p = 0.119$), showing that improved guidance helps agents reach the correct file rather than improving the quality of the changes they make. Further, a step-budget experiment shows that guidance is what lets the agent use a larger step budget productively, and a cross-model experiment with NVIDIA-Nemotron-3-Nano-30B-A3B finds that the tuning loop degrades when the model cannot generate sufficiently diagnostic output, though per-patch precision remains constant even then.

20.
medRxiv (Medicine) 2026-06-11

Global population frequencies of NAT2 star alleles observed in three large biobanks

NAT2 is an important pharmacogene which encodes the N-acetyltransferase 2 enzyme that is involved in the metabolism of multiple medications, and variants in this gene can affect patient response to these medications. CPIC has published a clinical guideline for prescribing hydralazine using NAT2 genotypes. Just prior to the guideline, updated NAT2 star allele numbering and definitions were released, differing somewhat from the historical nomenclature. Clinical pharmacogenomic testing panels often test for the most common star alleles, so knowledge of the most common updated NAT2 star alleles is critical for the implementation of the CPIC NAT2/hydralazine guideline. We first determine NAT2 diplotype frequencies from UK Biobank (UKBB) 200k phased genomes, then analyzed allele, diplotype, and phenotype population frequencies from the All of Us Research program, PennMedicine BioBank (PMBB) and UKBB 500k datasets. We found that analyzing NAT2 diplotypes from phased data provides critical information for algorithms designed to predict diplotypes from unphased data. We observed that NAT2*5, *6, and *4 were the most common star alleles in that order, and the top 11 most frequent NAT2 star alleles were the same across all biobanks. However, differences in star allele frequencies across biogeographical populations were observed. The largest difference led to a higher frequency of NAT2 poor metabolizer phenotypes as compared to rapid and intermediate metabolizer phenotypes in all global populations except in the EAS population, where NAT2 poor metabolizers were in the minority.

21.
arXiv (CS.CV) 2026-06-18

PEFT-MedSAM: Efficient Fine-Tuning of Medical Foundation Models for Explainable Skin Lesion Segmentation

Automated segmentation of skin lesions using deep learning models for dermoscopic images can be very helpful in finding melanomas earlier than they would normally be detected. However, most deep learning methods available do not perform well. The aim of this paper is to present a parameter-efficient fine-tuning method called PEFT-MedSAM for adapting the Medical Segment Anything Model (MedSAM) to automatically segment dermoscopic skin lesions. The PEFT-MedSAM method uses only the lightweight mask decoder for training the model while keeping the pre-trained image encoder and prompt encoder frozen. The experiments performed on the ISIC 2018 benchmark dataset shows that PEFT-MedSAM obtains a dice coefficient of .9411 and an intersection over union value of .8918 when compared to both a fully trained U-Net baseline (.8715 dice coefficient) and zero-shot MedSAM inference (.8997 dice coefficient). The external validation of the model using PH2 dataset shows .9467 dice coefficient with +/- .0310 standard deviation. Supportive evidence for these claims include a p-value less than .0001 for Wilcoxon signed rank tests comparing the two datasets and bootstrap-estimated 95% confidence intervals of [.9364,.9447] that represent the estimated range of possible values for the average dice coefficient obtained by repeating the test. To increase clinical trustworthiness, we used Grad-CAM explainability along with a pointing game based evaluation methodology to evaluate the CNN baseline model on the validation set. The results showed that we had an accuracy rate of 98.27% on the validation set of 519 images and confirmed that the model classified regions containing skin lesions.

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

ESBMC-PLC+: A Unified IEC~61131-3 Formal Verification Framework as a PLCverif Successor

PLCverif is the most mature open-source platform for PLC formal verification, developed at CERN and in production use since 2019. Yet it has two fundamental limitations: no support for Ladder Diagram (LD) programs, the dominant PLC notation, and reliance on CBMC as its primary backend, which restricts verification to bounded proofs. The PLCverif authors themselves identified ESBMC as the appropriate backend improvement. Prior work established ESBMC-PLC (a textual LD frontend with k-induction) and ESBMC-GraphPLC (graphical PLCopen XML support); together, they cover LD with unbounded proofs but not Structured Text (ST), and graphical LD with timer/counter function blocks remains unverifiable. This paper presents ESBMC-PLC+, a unified framework that closes both gaps: (1) an ST/SCL frontend via the MATIEC IEC 61131-3 compiler, routing C-compiled ST to ESBMC with nondeterministic input modeling and YAML property injection; (2) function block state semantics for graphical LD, extending the DFS resolver to model TON/TOF/TP timers, CTU/CTD counters, and R_TRIG/F_TRIG edge triggers as persistent scan-cycle state variables in the GOTO IR. ESBMC-PLC+ is the first open-source PLC verification framework to support all three major IEC 61131-3 input formats via a single ESBMC backend, enabling k-induction-unbounded safety proofs. A feature comparison with PLCverif and experimental evaluation on 8 benchmark programs, including programs with up to 8 integer timers, shows that ESBMC-PLC+ matches PLCverif's input coverage while providing stronger guarantees. Against nuXmv's BDD backend, ESBMC-PLC+ is 400-2,000x faster on timer programs and completes proofs where nuXmv BDD times out at 120s.

23.
arXiv (quant-ph) 2026-06-24

Crystalline Spectral Form Factors

arXiv:2512.11054v3 Announce Type: replace Abstract: We investigate crystalline-like behavior of the spectral form factor in unitary quantum systems with extremely strong eigenvalue repulsion. Using a low-temperature Coulomb gas as a model of repulsive eigenvalues, we derive the Debye-Waller factor suppressing periodic oscillations of the spectral form factor and estimate the order of its singularities at multiples of the Heisenberg time. We also reproduce this crystalline-like behavior using perturbed permutation circuits and random matrix ensembles associated with Lax matrices. Our results lay a foundation for future studies of quantum systems that exhibit intermediate level statistics between standard random matrix ensembles and permutation circuits.

24.
medRxiv (Medicine) 2026-06-16

Care Delivery Gap framework: a proof-of-concept patient-reported measure of guideline-referenced care-process omissions in sickle cell disease

Abstract Background:Sickle cell disease (SCD) is concentrated in sub-Saharan Africa, where delivery of guideline-referenced care remains challenging. Current evaluation approaches rely largely on access indicators and clinical outcomes, which do not directly measure care delivery. We developed the Care Delivery Gap (CDG) framework, a patient-reported approach for identifying care-process omissions, and conducted a proof-of-concept study to assess feasibility and explore variation across income strata. Methods: We conducted a cross-sectional framework-development study involving a proof-of-concept sample of 52 individuals with SCD or caregivers recruited through clinics and moderated SCD communities across Africa, North America, and Europe between June 2025 and March 2026. The CDG framework assessed patient-reported omissions in specialist involvement, follow-up continuity, cardiovascular screening, and biochemical surveillance. Analyses were descriptive. Results: Substantial multi-domain care-process omissions were identified despite high reported healthcare engagement. Across geographic income strata, cardiovascular screening was reported by 4/35 (11%) LMIC versus 16/17 (94%) HIC participants, and regular follow-up within the preceding 12 months by 14/35 (40%) versus 16/17 (94%), respectively. High CDG scores, representing 1 omissions across three or four domains, occurred in 20/35 (57%) LMIC compared with 1/17 (6%) HIC participants. Similar disparities were observed across specialist review and vitamin B12 surveillance domains. Conclusion: A structured patient-reported framework identified multi-domain omissions in guideline-referenced SCD care, including among individuals reporting healthcare access. The divergence between access indicators and reported care delivery suggests that service contact alone may not reflect care quality. The framework provides a feasible foundation for future process-level quality measurement in high-burden settings.

25.
arXiv (CS.CL) 2026-06-15

SANA: What Matters for QA Agents over Massive Data Lakes?

Exploratory question answering (EQA) over data lakes requires an LLM agent to discover relevant sources, analyze retrieved data, and adapt its actions based on intermediate results. End-to-end accuracy alone cannot distinguish failures in search, planning, data analysis, or the agent's Action Policy: its decisions about what to do next and when to submit an answer. We present SANA (Search Agent Navigation Ablation framework), a diagnostic ablation framework that transforms EQA tasks into runtime profiles containing gold source sequence, sanitized subquestions, and execution records. SANA uses these profiles to construct idealized search, planning, and data-analysis tools, allowing each component to be ablated; the residual gap is diagnostic evidence for policy failures. To illustrate SANA as a reusable evaluation framework, we adapted two recent EQA benchmarks, LakeQA and KramaBench, and evaluated lightweight and mid-sized agents under fixed prompts, budgets, data lakes, and runtimes. Across both benchmarks, data analysis is a consistent bottleneck while planning is less so. Search is a major limitation in LakeQA's large data-lake setting, but less so for the smaller-scale KramaBench. SANA thus deconstructs end-to-end task accuracies into a diagnosis of where data-lake agents fail, and allows for systematic comparisons of progress in search, planning, data analysis, and agent design.