Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

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

AfroScope: A Framework for Studying the Linguistic Landscape of Africa

Language Identification (LID), the task of determining the language of a given text, is a fundamental preprocessing step that shapes the reliability of downstream NLP applications. While recent work has expanded African LID, existing systems remain limited in both language coverage and fine-grained discrimination among closely related languages and varieties. We introduce AfroScope, a unified framework for African LID that includes AfroScope-Data, a dataset covering 640 languages, and AfroScope-Models, a suite of strong LID models with broad African language coverage. To address persistent confusions among closely related languages, we propose a hierarchical classification approach that leverages AfroScope-Mirror, a specialized embedding model for targeted disambiguation, improving macro-F1 by 1.57 points on the confusable subset compared to our best base model. We further analyze cross-lingual transfer and domain effects, showing how language-family structure, script compatibility, and domain coverage shape LID performance. We position African LID as an enabling technology for large-scale measurement of Africa's linguistic landscape in digital text, and release AfroScope-Data and AfroScope-Models online.

02.
Nature (Science) 2026-06-10

Mitochondria directly interact with the nuclear pore complex

Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5. Here we identify direct interactions between mitochondria and nuclear pores. Using two unbiased proteomic screens, GST pulldown and BioID, we found that VDAC1 was the top mitochondrial candidate that interacts with the filamentous nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knockout, RANBP2 truncation or site-directed mutagenesis of RANBP2–VDAC1 interacting amino acids resulted in reduced mitochondria–nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in the levels of the nuclear phosphoproteome and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. Moreover, deletion of the RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the nuclear pore complex, a phenomenon critical for regulation of nuclear energetics and cellular differentiation. Undoubtedly, additional roles of this interaction remain to be revealed. Mitochondria interact directly with the nuclear pore complex via VDAC1–RANBP2 binding to sustain nuclear ATP levels.

03.
PLOS Computational Biology 2026-06-15

A multilevel hierarchical framework for quantification of experimental heterogeneity in population snapshot data

by David J. Warne, Xiangrun Zhu, Thomas P. Steele, Stuart T. Johnston, Scott A. Sisson, Matthew Faria, Ryan J. Murphy, Alexander P. Browning Biological systems exhibit substantial heterogeneity: that is, variation in specific characteristics of individuals within a population. As a result, it is of critical importance to appropriately account for biological heterogeneity when calibrating mathematical models to infer cellular processes and predict behaviour. Recent approaches consider ordinary differential equations with random parameters to quantify heterogeneity in dynamical processes of cells. In this setting, statistical inference is performed to characterise the distribution of these random parameters within a cell population. One significant limitation of this approach is the tacit assumption that there are no substantial deviations in these distributions across experimental replicates. In this work, we propose a flexible Bayesian hierarchical differential equation modelling framework that quantifies and distinguishes both inter-experimental heterogeneity (heterogeneity between experimental replicates) and intra-experimental heterogeneity (biological heterogeneity within replicate populations). We consider two recent studies that employ mathematical models to interpret flow cytometry snap-shot data and quantify heterogeneity in nano-particle cell interactions and cell internalisation processes. Using simulation data, we demonstrate that substantial inaccuracy in the inferred dynamics can arise when experimental heterogeneity is not accounted for. By contrast, our hierarchical approach is robust to variability in inter-experimental and intra-experimental heterogeneity and our method simplifies to previous methods when inter-experimental heterogeneity is negligible. Our approach is flexible and widely applicable to applications involving replicate populations and snapshot data. We provide open-source implementations of our methods on GitHub.

04.
arXiv (CS.AI) 2026-06-16

GAS-Leak-LLM: Genetic Algorithm-Based Suffix Optimization for Black-Box LLM Jailbreaking

arXiv:2606.15788v1 Announce Type: cross Abstract: Large Language Models (LLMs) constitute pivotal components within the AI-dominated information technology ecosystem. To mitigate risks associated with harmful or policy-violating outputs, commercial systems employ advanced alignment strategies and multi-layered content moderation mechanisms. Despite these safeguards, recent research has demonstrated that LLMs remain vulnerable to adversarial manipulation, particularly through jailbreaking and prompt injection techniques. In this work, we propose GAS-Leak-LLM a novel jailbreaking attack based on a genetic algorithm that systematically evolves adversarial suffix to bypass safety constraints. Operating in a strict black-box setting, our method requires no access to model parameters or internals, thereby reflecting realistic threat scenarios in deployed systems. Through the iterative application of selection, mutation, and crossover heuristics, the framework systematically explores the discrete prompt space to identify high-fitness adversarial suffixes. Empirical findings reveal critical shortcomings in existing safety enforcement mechanisms and confirm the effectiveness and practical viability of the proposed attack.

05.
medRxiv (Medicine) 2026-06-22

Why drinking episodes escalate differently: Event-level pathways linking hazardous alcohol consumption and sexual risk

Background: Alcohol-involved drinking episodes vary in whether they involve hazardous alcohol consumption alone, near-miss sexual risk, or sexual risk behavior, but the within-event mechanisms underlying this variability remain unclear. Methods: Guided by syndemic theory, we conducted a qualitative event-level analysis using modified grounded theory among adults in the San Francisco Bay Area who reported hazardous alcohol consumption, defined as an Alcohol Use Disorder Identification Test score [≥]16. In-depth interviews elicited narratives of recent heavy drinking episodes and yielded 64 discrete drinking events across 22 participants. We focused on 35 events with evidence of within-event interaction between biopsychosocial and contextual factors. Using constant comparison, we identified escalation pathways, characterized interruption, and examined how events diverge into three outcomes: hazardous alcohol consumption only, hazardous alcohol consumption with near-miss sexual risk (when risk was plausible but not enacted), and hazardous alcohol consumption with sexual risk behavior. Results: Two primary escalation pathways emerged. Dose-driven escalation involved cumulative alcohol or substance exposure that progressively impaired awareness and self-regulation. Meaning-driven escalation involved prioritizing connection, intimacy, or belonging despite awareness of risk. Time-driven continuation extended exposure across contexts and amplified both pathways. Hazardous alcohol consumption-only events more often followed dose-driven pathways, whereas events involving sexual risk behavior more often followed meaning-driven pathways. Near-miss events occurred across both pathways and illustrated how interruption before the escalation constraint point, when the capacity to modify behavior became reduced, could redirect escalation before sexual risk behavior occurred. Across events with similar levels of intoxication narratives, outcomes diverged according to when the interruption occurred and whether it altered escalation. Conclusion: Hazardous drinking episodes diverge into different outcomes based on escalation pathways and the timing and effectiveness of interruption. Early and effective interruption before the escalation constraint point may represent a key target for harm-reduction strategies to prevent progression to sexual risk behavior.

06.
medRxiv (Medicine) 2026-06-16

Higher Population Coverage with Typhoid Conjugate Vaccine is Needed to Induce Herd Protection: Evidence from a Cluster-Randomized Trial in Urban Bangladesh

Introduction: A cluster randomized trial (CRT) in Bangladesh found that Vi-tetanus toxoid (Vi-TT) vaccine conferred 85% protection to vaccinees at 18 months of follow-up; however, it failed to confer significant herd protection to non-vaccinees. Methods: In the CRT, children aged 9 months to

07.
arXiv (CS.LG) 2026-06-12

Physics-Aware Auxiliary Losses Improve Out-of-Distribution Generalization of a GNN Synthesizability Filter

arXiv:2606.12651v1 Announce Type: new Abstract: Machine-learning drug-discovery pipelines increasingly rely on generative models that propose molecules far from the data used to train downstream synthesizability filters. Existing filters (SAScore, SCScore, RAscore, DeepSA) are purely statistical and degrade in exactly this out-of-distribution (OOD) regime. We ask whether cheap, closed-form physical priors, used as auxiliary supervision on a graph neural network (GNN), improve OOD generalization. We add two auxiliary losses to a GINE backbone: a topological complexity regression supervised by the Bertz index, and a strain-energy soft penalty supervised by MMFF94 force-field energy. On a 65,177-molecule corpus (HIV, Tox21, COCONUT) labeled by SAScore thresholds we reproduce a strong in-distribution baseline, then evaluate a 4-way ablation (baseline / +complexity / +strain / +both) on a single-source OOD split (train on drug-like HIV+Tox21, test on COCONUT natural products), repeated over 5 seeds with paired bootstrap confidence intervals. All three physics-aware variants give a small but statistically significant OOD improvement over the baseline (mean OOD AUC 0.9774): +complexity Delta = +0.0060 (95% CI [+0.0023, +0.0102]), +strain Delta = +0.0032 ([+0.0008, +0.0052]), +both Delta = +0.0066 ([+0.0038, +0.0093]); every interval excludes zero, and the combination is best. The variants are indistinguishable in-distribution, so the effect is visible only under OOD evaluation. We are explicit that the effects are modest, and we report a cautionary methodological finding: a single-seed version of this experiment produced a qualitatively different (non-monotone) story that did not survive multi-seed evaluation.

08.
medRxiv (Medicine) 2026-06-15

Cost-Performance Evaluation of Large Language Models for Aspect-Based Sentiment Analysis of HCAHPS Patient Comments: A Validation Study

Background: Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) free-text comments contain actionable feedback, but timely, scalable, and affordable sentiment analysis remains challenging for health systems that rely on third-party vendors. Objectives: To evaluate cost-performance tradeoffs between a cost-optimized and a flagship large language model (LLM) for aspect-based sentiment analysis of HCAHPS comments, using human inter-rater agreement as a reproducibility benchmark. Methods: We analyzed 512 free-text HCAHPS comments collected from two community hospitals in calendar year 2023. Six trained reviewers (medical students, recent medical graduates, and practicing internists) independently assigned positive, negative, or neutral labels to each comment-aspect pair; the majority label among three reviewers formed the consensus reference standard. Two OpenAI models - GPT-5-nano (cost-optimized) and GPT-5 (flagship) - were prompted in a zero-shot setting via the OpenAI API. We calculated pairwise Cohen's {kappa} to establish a human inter-rater baseline, then compared each model's labels to the consensus using Cohen's {kappa}, accuracy, weighted F1, and per-call cost and latency. Results: Mean human inter-rater agreement was {kappa} = 0.79 (substantial). Both LLMs exceeded this baseline (cost-optimized {kappa} = 0.85; flagship {kappa} = 0.85) with nearly identical accuracy (0.92) and weighted F1 (0.93 vs. 0.93). Performance was strong on positive (F1 ~ 0.97) and negative (F1 ~ 0.90) classes but poor on the underrepresented neutral class (F1

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

Time Series Causal Discovery via Context-Conditioned and Causality-Augmented Pretraining

arXiv:2605.26759v2 Announce Type: replace Abstract: Causal discovery from time series is critical for many real-world applications, such as tracing the root causes of anomalies. Existing approaches typically rely on dataset-specific optimization, making it difficult to transfer their causal discovery capabilities to new time series governed by diverse causal mechanisms. In this paper, we propose PTCD, a novel Pretraining framework for Time-series Causal Discovery, which improves cross-task generalization through context-conditioned modeling and transferable causal augmentation. To model complex temporal causal dependencies, PTCD employs a dual-scale iterative attention mechanism to capture window-level causal relationships, and a Gaussian mixture with a context-level routing mechanism to handle heterogeneous exogenous distributions. To further address distribution shifts across causal graphs, PTCD adopts a pretraining paradigm on synthetic datasets that integrates intervention-based learning and a causal mixup strategy, promoting stable causal discovery and stronger generalization. Extensive experiments on multiple real-world out-of-distribution (OOD) datasets demonstrate that PTCD excels in both causal discovery and root cause identification.

10.
arXiv (CS.LG) 2026-06-11

Categorical Robustness Assessment for Machine Learning based Network Intrusion Detection Systems

arXiv:2606.12075v1 Announce Type: cross Abstract: Network Intrusion Detection Systems (NIDS) heavily utlize Machine Learning (ML) but ML models can be manipulated via adversarial attacks. These attacks add carefully crafted perturbations to network traffic data that leads to misclassifications. While prior work has demonstrated adversarial vulnerabilities in isolated settings, systematic cross-architecture as well as class and category of attack based comparisons under controlled attack conditions remain limited, leaving practitioners without clear guidance on which models to deploy in adversarial environments. This paper asks a simple question: what type of classifier architectures actually hold up when attackers try to manipulate the systems? We put three popular architectures through their paces: a 1D Convolutional Neural Network, a Long Short-Term Memory (LSTM) network, and a Random Forest (RF) ensemble. Using the ACI-IoT-2023 dataset (over 1.2 million samples spanning 12 attack types), we subject each model with FGSM and PGD adversarial attacks, which apply gradient-based perturbations in normalized feature space consistent with established adversarial ML evaluation protocols, at perturbation budgets ranging from $\epsilon=0.01$ to $\epsilon=0.1$. Surprisingly, Random Forest achieved near-perfect baseline accuracy (99.98\%), yet collapsed catastrophically under attack, dropping 73 percentage points at the smallest perturbation we tested. CNN, on the other hand, retained 95.5\% accuracy at $\epsilon=0.01$ and degraded gracefully as perturbations increased. LSTM fell somewhere in between. These findings flip the conventional wisdom where high baseline accuracy means nothing if a model shatters at the first sign of adversarial pressure. For practitioners deploying intrusion detection in adversarial environments, we recommend CNN-based architectures and provide scenario-specific deployment guidance.

11.
arXiv (math.PR) 2026-06-18

A simple approach to the L{\o}kka-Zervos dichotomy for absolutely continuous dividend strategies

arXiv:2604.13302v3 Announce Type: replace-cross Abstract: We revisit the optimization problem solved in L{\o}kka & Zervos (2008), i.e., the maximization of dividends, in a Brownian risk model, with the possibility (not the obligation) of making capital injections. Following the approach introduced in Alvarez & Shepp (1998), Renaud & Simard (2021), Renaud et al. (2023), we consider instead absolutely continuous (AC) dividend strategies with an affine bound on the payment rates, while singular capital injections are still allowed. In addition, we incorporate a parameter for the cost of ruin or, said differently, a penalty at ruin in the performance function. We show that the solution is a so-called L{\o}kka-Zervos dichotomy: the surplus is never ruined by making bail-out payments, or no capital is injected and bankruptcy can occur; in either case, dividends are paid at full rate when the surplus is above a threshold. Our framework allows us to provide explicit conditions to express the dichotomy, either using the cost of capital injections or the cost of ruin as a criterion, which also exposes the underlying structure of the solution. In particular, for some values of the parameters, we show that it is optimal to liquidate. Moreover, we perform a numerical analysis highlighting the range of values generated under this AC affine-bound structure.

12.
bioRxiv (Bioinfo) 2026-06-16

AutoZyme: An Autonomous Agentic Framework to Optimize Bioinformatics Software

Performance bottlenecks in widely used genomics and bioinformatics software present a substantial and growing burden as biological datasets continue to increase in size and number. Relieving these bottlenecks relies largely on expert manual optimization and therefore remains difficult to scale. Here we present AutoZyme, an agentic framework for scientific software optimization. Given a target function, AutoZyme builds benchmarks, identifies bottlenecks, and iteratively tests code changes, retaining only those that improve runtime while preserving output. We evaluated AutoZyme on 45 functions, improving runtime without substantial memory increases in over 95% of cases considered. Across 38 functions from Seurat, Scanpy and related packages in genomics and bioinformatics, AutoZyme reduced runtime by a median of 8.52-fold, with the largest reductions exceeding 676-fold. The optimized functions are distributed through AutoZyme-Library as drop-in replacements for existing analysis pipelines. We also release AutoZyme as a reusable framework for optimizing additional user-specified packages and functions.

13.
arXiv (CS.CV) 2026-06-15

MirrorCheck: Efficient Adversarial Defense for Vision-Language Models

Vision-Language Models (VLMs) are increasingly susceptible to sophisticated adversarial attacks, including adaptive strategies specifically designed to bypass existing defenses. To address this vulnerability, we propose MirrorCheck, a robust and model-agnostic detection framework that operates effectively in both unimodal and multimodal settings. MirrorCheck leverages Text-to-Image (T2I) models to regenerate visual content from captions produced by the target model and assesses semantic consistency by comparing feature-space embeddings between the original and synthesized images. To enhance robustness against adaptive attacks, MirrorCheck introduces a stochastic defense strategy that randomly selects T2I generators and image encoders from a diverse model zoo. Additionally, we incorporate a novel One-Time-Use (OTU) perturbation applied to the selected encoder embeddings, regulated by a scaling factor, which decreases the effectiveness of adaptive attacks. Extensive experiments across multiple threat scenarios demonstrate that MirrorCheck consistently outperforms baseline methods, and maintains its utility even under strong adaptive adversarial conditions.

14.
medRxiv (Medicine) 2026-06-17

Accounting for Human Movement to Improve Exposure-Health Models

Background. Current exposure-health models rely on averaged, residential-based environmental exposures, failing to account for human movement. This aggregation can lead to exposure misclassification and biased exposure-response estimates, potentially distorting our understanding of the true health effects of environmental conditions. We developed exposure disaggregation regression models that explicitly account for human movement when linking environmental exposures to health outcomes. Methods. By weighting pixel-level exposures according to distance from home as a simple proxy for human movement, our model linked disaggregated environmental exposures to individual-level health outcomes. Weights were either fixed a priori or derived from a latent distance-decay power parameter learned from the data. We additionally evaluated model performance under a nonlinear exposure-response relationship. Model performance was assessed across multiple sample sizes (N = 1,114; 50,000; and 100,000). A simulation study examined parameter recovery using bias, empirical standard error (EmpSE), and credible interval coverage. As a case study, Demographic and Health Surveys (DHS) data from Albania were used to link acute respiratory infection (ARI) outcomes among children under five to pixel-level NDVI within a 3 km buffer around DHS cluster centroids, and the proposed models were applied to these data. Results. Across all models (fixed-weight, learned-weight, and restricted cubic spline models), parameter recovery improved with increasing sample size. At N = 1,114, estimates were biased and imprecise, with incorrect effect direction for exposure-response parameters (e.g., learned-weight {beta}1 bias = - 0.79; EmpSE = 2.61; coverage = 0.88). In contrast, the models accurately recovered parameters at larger sample sizes, including the latent distance-decay parameter (bias = - 0.02; EmpSE = 0.15; coverage = 0.95 at N = 100,000), demonstrating their ability to reliably learn movement-based exposure weights when sufficient data were available. Conclusion. Instead of relying on arbitrarily-sized buffers, this statistical framework provides a novel method for studying environmental exposure-health relationships whilst accounting for human movement. With sufficiently large sample sizes, it can accurately estimate the influence of disaggregated environmental exposures on individual-level health and help address exposure misclassification arising from residential-only metrics. This methodological framework remains scalable, interpretable, and adaptable to other exposures and outcomes, offering a foundation for future work that integrates richer mobility-informed exposure-health research.

15.
arXiv (quant-ph) 2026-06-11

Circulators Based on Coupled Quantum Anomalous Hall Insulators and Resonators

arXiv:2505.07770v2 Announce Type: replace Abstract: Integrated plasmonics is advancing rapidly, enabling a wide range of functionalities to be incorporated onto a single chip. Applications span information processing, computation, quantum sensing, and dark-matter detection. This progress has driven the development of integrated non-reciprocal devices, which are essential for preventing unwanted feedback that can degrade system performance. While non-reciprocal devices have been realized in edge magnetoplasmon materials via classical interference effects, their operation is often limited by the input power range. Here, we demonstrate that topological circulators utilizing asymmetric coupling offer improved input power range, isolation, and insertion loss. In this configuration, we demonstrate the coupling between a chiral edge magnetoplasmonic resonator and a pair of LC resonators is well described by an effective non-Hermitian two-site Hatano-Nelson model with asymmetric directional couplings, resulting in nonreciprocal behavior. The coherent photon-plasmon interaction enables a circulator with up to 50 dB of isolation across a broad range of excitation power. These results suggest that magnetic topological insulators provide a promising platform for realizing asymmetric non-Hermitian couplings at radio frequencies and for exploring regimes of strong directional suppression and possible exceptional-point physics. More broadly, they highlight the potential of topological-material-based microwave devices for future integration with superconducting quantum information platforms.

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

Cross-Modal Registration Between 3D and 2D Fingerprints via Pose-Aware Unwrapping and Point-Cloud Fusion

Three-dimensional (3D) fingerprints preserve global finger geometry and local ridge structure while avoiding contact-induced deformation, but they remain difficult to integrate with legacy two-dimensional (2D) fingerprint systems. This paper addresses the intermediate stage between 3D acquisition and cross-modal matching, and presents a unified framework for 3D fingerprint preprocessing and registration across contactless and contact-based 2D modalities. The framework combines four components: 1) a nonparametric visualization and unwrapping method that converts a 3D fingerprint point cloud into a rolled-equivalent 2D representation without relying on a global finger-shape model; 2) a point-cloud fusion pipeline that registers and mosaics multiple partial 3D captures into a more complete fingerprint model; 3) an ellipse-based pose normalization method for canonical finger alignment; and 4) a pose-aware cross-modal registration strategy that improves compatibility between 3D fingerprints and both contactless and contact-based 2D fingerprints. Experiments on a self-collected multimodal fingerprint database containing 150 fingers show that the proposed framework achieves ridge-level 3D registration accuracy, robust pose estimation, and consistent gains in 2D compatibility. In particular, the 3D fusion error is concentrated around 0.09 mm, contactless 2D–3D registration reaches ridge-scale projection accuracy, and pose-aware unwrapping improves genuine matching scores relative to generic 3D unwrapping. These results support the use of 3D fingerprints as an effective geometric bridge across heterogeneous fingerprint modalities. The baseline implementation has been publicly released at https://github.com/XiongjunGuan/3DFpVisual.

17.
bioRxiv (Bioinfo) 2026-06-18

Predicting optimal growth temperatures of bacteria using learned structural information from a single protein

Temperature is a fundamental determinant of bacterial physiology and ecology. Optimal growth temperature (OGT) is highly variable across species, contributing to differences in where and when species are most likely to thrive. Although the OGTs for most bacteria remain unknown, the increasing availability of genomes from uncultivated and cultivated taxa has made it advantageous to build genomic, cultivation-independent models to infer OGT. However, pre-existing genomic models often lack the generalizability and mechanistic grounding required for robust inferences of OGT. We propose a novel framework for predicting bacterial OGT which uses learned protein structural signatures of thermal adaptation. We hypothesize that biophysical tradeoffs which dictate enzymatic functions across variable temperatures provide a more robust empirical basis for OGT prediction than broad genomic features. Our OGT-predicting model, ROSEATE, is based on a single gene, adenylate kinase (ADK), that encodes for a ubiquitous enzyme essential for energy homeostasis. ROSEATE uses high-dimensional latent space encoding via MSA Transformer, a protein language model which embeds ADKs in a manner which preserves biophysical information about embedded proteins. We show that the accuracy of the ROSEATE model is on par with other genome-based models, has a high degree of phylogenetic generalizability, and the ESM embeddings effectively capture key temperature-adaptive enzyme characteristics derived from AlphaFold structures. Because ROSEATE is based on analyses of a single ubiquitous protein, it can be used with metagenomic data to infer the community-level variation in bacterial OGTs. We demonstrate this feature of ROSEATE by reconstructing ADK sequences from over 500 environmental and host-associated metagenomes, successfully distinguishing community-wide thermal preferences across diverse habitats, from polar oceans to mammalian guts. By transitioning from genomic proxies to informationally dense protein structural features, this work provides an efficient, interpretable tool for predicting bacterial OGTs across taxa and whole communities.

18.
arXiv (CS.LG) 2026-06-16

Finite Resources False Discovery Rate Control in Structured Hypothesis Spaces

arXiv:2606.15393v1 Announce Type: cross Abstract: Scientific discovery relies on large-scale hypothesis testing. However, the capacity to identify true discoveries while controlling false discovery faces major challenges: obtaining relevant reference data (the null distribution) is resource-intensive, leaving finite-data uncertainty, and the procedure should account for the inherent structure in the hypothesis space, when such structure exists. Here, we present a framework for controlling the false discovery rate both when each hypothesis is evidenced only by a finite count of null draws, leaving its p-value uncertain, and when the hypothesis space carries arbitrary structure, requiring only that the structure be represented through a suitable reproducing kernel. We present two decision rules that are both robust to structural mis-specification, yet offer a distinct trade-off between exact FDR control and statistical power. The first rule guarantees exact FDR control; the second maximizes power by adapting mirror-statistic control into count space, utilizing an analytical framework to assess FDR control when exact mirror symmetry is relaxed. Furthermore, the tractability gained by the RKHS framework allows us to directly investigate finite-data uncertainties, which we leverage to suggest a policy for the efficient allocation of null distribution samples.

19.
arXiv (CS.LG) 2026-06-18

Measurement noise limits the advantage of nonlinear models over linear models in biomedical prediction

arXiv:2606.18420v1 Announce Type: new Abstract: On biomedical tabular data, flexible models such as deep networks, gradient-boosted trees, and kernel methods are repeatedly matched or beaten by linear and logistic regression given the same features. The usual reaction is to treat this as a model-side shortfall, to be fixed with more data, a better architecture, or tuning, on the assumption that the nonlinear structure is there and the model has failed to capture it. We argue that these fixes cannot help when the binding limit is the measurement rather than the model, as it frequently is in biomedicine. Additive noise blurs the population-optimal predictor, and because blurring removes a function's fine, rapidly varying detail before its broad shape, it erases nonlinear structure faster than linear structure. A degree-$k$ interaction is attenuated by the $k$-th power of feature reliability, while the linear part is attenuated only once. At the reliabilities typical of biomedical measurement, the nonlinear advantage can vanish even when the underlying biology is strongly nonlinear, and what the noise removes cannot be recovered by a larger cohort or a more flexible model, only by better measurement. The nonlinearity is hidden, not absent, and a tie between linear and flexible models is not by itself a verdict on the biology. These pieces are classical, drawn from measurement-error statistics, psychometrics, and Gaussian analysis, and we assemble them into an exact excess-risk identity. Measurement reliability is one of three conditions, alongside sample size and feature representation, that must align for a flexible model to help, and together they leave only a narrow window that most biomedical tasks fall outside. Across 140 UK Biobank tasks, the gap between flexible and linear models, where it exists, carries the predicted noise signature, and the three conditions can be separated by intervention but not by a benchmark alone.

20.
arXiv (math.PR) 2026-06-11

Feynman–Kac formula for the heat equation with a one-center point interaction in $d=3$

arXiv:2606.11677v1 Announce Type: new Abstract: We study Schrödinger operators with a one-center point interaction, formally defined by \begin{align*} -\Delta_\alpha=-\Delta+\alpha\,\delta_0(\cdot), \end{align*} for $\alpha\in\mathbb{R}$, and the associated heat equation \begin{align} \partial_t u=\tfrac{1}{2}\Delta_{\alpha} u,\quad u(0,x)=u_0(x)\in C_c^{\infty}(\mathbb{R}^3\setminus\{0\}).\label{eq:HEapp} \end{align} Here $\Delta$ denotes the Laplacian (self-adjoint on $L^2(\mathbb{R}^3)$) and $\delta_x$ the Dirac measure at $x$. The operator $-\Delta_\alpha$ can be realized either as a self-adjoint extension of $-\Delta|_{C_0^{\infty}(\mathbb{R}^3\setminus\{0\})}$ in $L^2(\mathbb{R}^3)$, or as the norm-resolvent limit of $-\Delta+\lambda_\varepsilon V(\cdot/\varepsilon)$ for suitable $\lambda_\varepsilon$ and $V:\mathbb{R}^3\to\mathbb{R}$. In this paper we construct, for each $t>0$ and $x\in\mathbb{R}^3\setminus\{0\}$, a probability law on path space and a normalizing function $G_t^\alpha(x)$ giving the following probabilistic representation of the solution to the associated equation: \begin{align*} u(t,x)=G_t^\alpha(x)\,\mathbb{E}\bigl[u_0\bigl(W^{t,x}(t)\bigr)\bigr], \end{align*} where $\{W^{t,x}(s):0\le s\le t\}$ is a continuous process depending on $(t,x,\alpha)$. The result provides a Feynman–Kac type formula for the heat equation with a one-point interaction in three dimensions.

21.
bioRxiv (Bioinfo) 2026-06-18

segSHAPE: RNA secondary structure prediction from nanopore direct RNA sequencing

RNAs adopt complex structures that regulate key biological processes, making accurate structure prediction essential. Chemical probing coupled with Nanopore direct RNA sequencing (DRS) offers a route to single-molecule structural inference, but current tools are limited by inaccurate signal-to-sequence alignment, which degrades modification-rate estimation and downstream structure prediction. Here we introduce segSHAPE for RNA secondary structure prediction from Nanopore DRS data (both RNA002 and RNA004 chemistries), a probe-agnostic framework that improves signal alignment using prior information of basecalling and per-read signal baseline shift correction, learns position-specific k-mer raw signal parameters, and estimates per-nucleotide modification rates with an unsupervised anomaly detector. On three public RNA002 DRS datasets spanning different chemical probes (AcIm, NAI-N3) and RNAs from 421 to 1552 nt, segSHAPE achieves the highest F1 score and Matthews correlation coefficient (MCC) on all RNAs, exceeding the strongest baseline by 3.4 to 5.8 percentage points in MCC. It additionally captures the ligand-induced conformational change of the thiamine pyrophosphate (TPP) riboswitch RNA directly from RNA002 DRS data using the DEPC probe. On a public RNA004 DRS dataset, segSHAPE improves over the sm-PORE-cupine baseline by 17 ROC-AUC points in modification rate estimation and by 6.7 MCC points in structure prediction. These results establish segSHAPE as a unified, probe-agnostic pipeline for RNA structure prediction from Nanopore DRS data.

22.
medRxiv (Medicine) 2026-06-19

Performance of family history-based colorectal cancer screening criteria by race and age at diagnosis in the Disparities and Cancer Epidemiology (DANCE) study

Importance: Family history (FH) and age are the primary criteria employed for early colorectal cancer (CRC) risk stratification. We evaluated how well these criteria identify individuals diagnosed with CRC across age and racial groups. Objective: To evaluate the performance of FH and age based screening criteria for identifying individuals with CRC, with attention to differences by race and age at diagnosis. Design, Setting, and Participants: This case control and case only analysis used data from the Disparities and Cancer Epidemiology (DANCE) cohort, a population based study of invasive CRC cases diagnosed from 2013 to 2022, recruited through the Metropolitan Detroit Cancer Surveillance System and the Louisiana Tumor Registry. Analyses included 1,158 non-Hispanic Black (NHB) and non-Hispanic White (NHW) CRC cases and 1,434 cancer-free controls from the Inflammation Health and Lung Epidemiology (INHALE) study, enrolled from the same Detroit catchment area. Data were analyzed in 2025. Exposures: Self reported cancer FH among first-degree (FD) relatives and grandparents, summarized into three FH-based screening criteria: at least one FD relative with CRC (colon early-screening criterion), any FH of Lynch syndrome related cancers, and meeting NCCN criteria for Lynch syndrome genetic testing. Main Outcomes and Measures: Proportion of cases meeting each FH based screening criterion stratified by race and age at diagnosis (

23.
medRxiv (Medicine) 2026-06-18

Effectiveness and Safety of Bempedoic Acid Across Clinically Relevant Subgroups: Insights from the CLEAR Taiwan Study

Background Despite available lipid-lowering therapies (LLT), many patients fail to achieve low-density lipoprotein cholesterol (LDL-C) targets. This gap persists across clinically relevant subgroups. Bempedoic acid has demonstrated effective LDL-C lowering with a favorable safety profile in the CLEAR Taiwan study; however, its effects across subgroups in Asian populations remains limited. Methods The phase IV CLEAR Taiwan study (NCT06925100) enrolled patients with inadequately controlled hypercholesterolemia who received bempedoic acid for 12 weeks in addition to background LLT. This analysis evaluated changes in lipid parameters, high-sensitivity C-reactive protein (hsCRP), and safety outcomes in clinically relevant subgroups, including cardiovascular risk, diabetes, age, statin tolerance, and sex. Results A total of 180 patients were included. Bempedoic acid achieved significant LDL-C reductions in all subgroups. Numerically greater LDL-C reductions were observed in primary prevention, statin-intolerant, younger (< 65 years), and female patients, while comparable reductions were observed across diabetes status. Reductions in non-high-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B were consistent with LDL-C findings. Significant decreases in hsCRP were observed in all subgroups, with numerically greater reductions in patients aged < 65 years and those without diabetes. Bempedoic acid was well tolerated, with a low incidence of adverse events and no new safety signals identified. Changes in liver enzymes, renal function, and uric acid were minimal within subgroups. Conclusion Subgroup analyses from the CLEAR Taiwan study demonstrate consistent efficacy and safety of bempedoic acid across clinically relevant subgroups and support its use as a flexible option to address residual gaps in lipid management.

24.
arXiv (CS.AI) 2026-06-16

Rescaling Confidence: What Scale Design Reveals About LLM Metacognition

arXiv:2603.09309v2 Announce Type: replace Abstract: Verbalized confidence, in which LLMs report a numerical certainty score, is widely used to estimate uncertainty in black-box settings, yet the confidence scale itself (typically 0–100) is rarely examined. We show that this design choice is not neutral. Across six LLMs and three datasets, verbalized confidence is heavily discretized, with more than 78\% of responses concentrating on just three round-number values. To investigate this phenomenon, we systematically manipulate confidence scales along three dimensions: granularity, boundary placement, and range regularity, and evaluate metacognitive sensitivity using $meta-d'$. We find that a 0–20 scale consistently improves metacognitive efficiency over the standard 0–100 format, while boundary compression degrades performance and round-number preferences persist even under irregular ranges. These results demonstrate that confidence scale design directly affects the quality of verbalized uncertainty and should be treated as a first-class experimental variable in LLM evaluation.

25.
arXiv (math.PR) 2026-06-17

Time and Killed Resolvents in Reflected Optimal Stopping with a Max Payoff

arXiv:2606.18214v1 Announce Type: cross Abstract: We study infinite-horizon optimal stopping for normally reflected two-dimensional diffusions in the positive quadrant with max payoff \(G(x_1,x_2)=x_1\vee\alpha x_2\). The non-smooth payoff produces a singular stopping-gain measure on the kink set \(\Delta=\{x_1=\alpha x_2\}\). We prove $\displaystyle \Gamma^\Delta(dx) = -\frac{n^\top a(x)n}{2\sqrt{1+\alpha^2}}\,\sigma_\Delta(dx)$, with $n=(1,-\alpha)$, so the diagonal component is non-positive and strictly negative under local ellipticity. This implies that every interior kink point lies in the continuation region. We further show that the correct value representation uses the resolvent killed at first entry into the stopping set, $\displaystyle V=G-R_r^{\mathcal C}\Gamma$, and give a closed-form reflected Brownian counter-example showing that the unrestricted reflected resolvent is generally wrong. A reflected Brownian benchmark and numerical experiments illustrate the local-time, resolvent-gap, and diagonal-avoidance mechanisms.