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01.
medRxiv (Medicine) 2026-06-12

Integrative Mechanisms of Early Clinical and Research Training (ECART) in Orthopaedic Medical Education: A Qualitative Single-Case Study

Background: Early clinical exposure and student participation in research are important components of medical training. They may support learning motivation, evidence literacy, and self-directed learning. In many programmes, however, clinical training and research training remain separated. Few studies have explained, within a real teaching team, how learners turn clinical phenomena into researchable questions and how research participation can reshape their clinical understanding. Early Clinical and Research Training (ECART) is a clinical-research integration approach developed by an orthopaedic team at the Second Hospital of Shandong University. Methods: We conducted a theory-informed, interpretivist qualitative single-case study. The case was an orthopaedic clinical-research team at the Second Hospital of Shandong University. Participants included medical undergraduates, academic degree graduate students, professional degree graduate students, clinical teachers, and research platform leads. We used purposive sampling with maximum variation. Data were collected through semi-structured interviews and de-identified teaching documents. Data were analysed using the framework method and were interpreted with a Context-Activity-Mechanism-Outcome (CAMO) logic. Results: The analysis showed that ECART was not simply early entry into the clinic or early entry into the laboratory. It was a team-based learning process centred on real medical problems. Four themes were identified. First, early clinical exposure helped learners make real problems visible and nameable, rather than merely increasing exposure. Second, clinical-research connection followed different pathways. Professional degree graduate students often started from clinical uncertainties in residency training and case management, and moved toward evidence-informed small projects. Academic degree graduate students often started from literature gaps, experimental findings, and mechanistic hypotheses, and then used clinical feedback to calibrate meaning. Third, research training, through literature reading, group meetings, experimental design, data review, and mentor questioning, helped learners move from completing tasks to explaining problems. Fourth, sustained ECART depended on a tiered team ecology formed by clinical teachers, research mentors, research platforms, and senior peers. Based on these findings, we refined the ECART programme theory: real medical problems are translated through explanation, searching, experimentalisation, and feedback-based reinterpretation into research questions that learners can understand, discuss, and test. This process supports problem formation, evidence awareness, mechanistic reasoning, translational judgement, and career clarification. Conclusion: ECART is best understood as a clinical-research integrated learning ecology that emerges from real team practice, rather than as a fixed standardised course. Its educational value lies in a recurring cycle of real problems, research translation, multi-source feedback, and clinical reinterpretation. This framework may inform the design, evaluation, and contextual adaptation of clinical-research integration pathways in medical education.

02.
arXiv (CS.LG) 2026-06-15

Graph Diffusion Residuals for Control-Function Instrumental Variables

arXiv:2606.14636v1 Announce Type: new Abstract: Control-function instrumental variable estimators need a first-stage residual, not merely a first-stage prediction. High-capacity first stages can interpolate treatment and leave too little residual information for the outcome equation. We study Adaptive Anisotropic Instrumental Heat Flow (A-IHF), a deterministic graph-diffusion residual extractor for flexible control functions. A-IHF treats treatment as a signal on a graph of first-stage features, uses pilot diffusion to detect large treatment jumps, attenuates conductance across those jumps, and computes the generated control with a sparse graph resolvent. Its observational selection rule uses only $(Z,X)$, combining graph generalized cross-validation, roughness, residualized-treatment relevance, and graph-admissibility filtering. The analysis decomposes error into structural leakage, residual attenuation, and residualized treatment variation, yielding finite-sample bounds, graph-admissibility rates under latent piecewise-smooth geometry, and finite-path selection calibration. Across 54 synthetic benchmark cells with tuned graph, kernel, tree, boosting, series, and neural control-function baselines, guarded observational A-IHF has the lowest average structural-response MSE; the A-IHF family beats the best non-A-IHF baseline in 32 cells. Performance is strongest when the graph captures piecewise-smooth first-stage structure.

03.
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.

04.
arXiv (CS.LG) 2026-06-12

GEMSS: A Variational Bayesian Method for Discovering Multiple Sparse Solutions in Classification and Regression Problems

arXiv:2602.08913v2 Announce Type: replace Abstract: High-dimensional, underdetermined and highly correlated systems are common in data science practice, especially when analyzing physical measurements. In such settings, feature selection poses a fundamental challenge because multiple distinct sparse subsets may explain the response equally well. Their identification is crucial not only for predictive modeling but also for generating domain-specific insights into the underlying mechanisms. Yet, conventional methods typically isolate a single solution, obscuring the full spectrum of plausible explanations. This work introduces GEMSS (Gaussian Ensemble for Multiple Sparse Solutions), a variational algorithm designed to simultaneously discover multiple, diverse sparse feature combinations. The method employs a structured spike-and-slab prior for sparsity, a mixture of Gaussians to approximate the intractable multimodal posterior, and a Jaccard-based penalty to further control solution diversity. A single objective function is optimized via stochastic gradient descent. The method is tested on 128 comprehensive experiments by a novel benchmarking framework designed to generate artificial problems with multiple sparse solutions of equal predictive properties. This allows us to measure the retrieval of ground truth features rather than only evaluating predictive performance – characteristics more fitting to our practical needs. A comparative analysis shows that GEMSS consistently outperforms five prominent feature selection methods adapted through the ALFESE framework. Finally, we demonstrate practical usability through 3 challenging real-world datasets from metabolomics and physical chemistry: GEMSS successfully isolates multiple distinct yet quality solutions. GEMSS is available as a PyPI package 'gemss'. The corresponding repository github.com/kat-er-ina/gemss/ includes the full codebase and a free, no-code application GEMSS Explorer.

05.
arXiv (CS.CL) 2026-06-18

Continual Adaptation for Pacific Indigenous Speech Recognition

Speech foundation models struggle with low-resource Pacific Indigenous languages because of severe data scarcity. Furthermore, full fine-tuning risks catastrophic forgetting. To address this gap, we present an empirical study adapting models to real-world Pacific datasets. We investigate the impact of data volume, adaptation strategies, and representational drift on speech foundation models for various Pacific languages. Additionally, we analyze a continual learning framework for sequential language acquisition. Empirical results across three distinct Pacific Indigenous languages demonstrate that adapting to these linguistically distant languages induces severe internal representational drift. Consequently, these models face a strict plasticity and stability dilemma. While LoRA adapts well initially, it suffers from catastrophic forgetting during sequential learning. Ultimately, this study highlights the urgent need for robust adaptation strategies tailored to underrepresented languages.

06.
bioRxiv (Bioinfo) 2026-06-10

HOMED enables hierarchical and multimodal optimization of DNA methylation deconvolution across tissues

Cellular heterogeneity is a major confounder in bulk DNA methylation data for epigenome-wide association studies. Existing reference-based DNAm deconvolution methods often ignore hierarchies among related cell types and may generalize poorly across datasets due to limited variability in reference profiles. We developed HOMED (Hierarchically Optimized Methylation Deconvolution), a framework that integrates cell-lineage hierarchies, single-cell RNA sequencing-guided deconvolution, and paired bulk RNA-seq/DNAm data for CpG signature optimization. Across simulated and real peripheral blood mononuclear cell, lung, and placental datasets, HOMED consistently yielded the highest PCCs and lowest RMSEs, outperforming existing scRNA-seq-guided DNAm deconvolution methods, improving accuracy, resolution, and cross-tissue generalizability.

07.
arXiv (CS.AI) 2026-06-16

Scalable Circuit Learning for Interpreting Large Language Models

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

08.
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.

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

NetCause: Counterfactual Learning for Root Cause Analysis in Large-Scale Networks

arXiv:2606.13543v1 Announce Type: cross Abstract: Can a learned model capture how faults propagate through a large-scale network and use this knowledge to causally attribute customer impact to its underlying root cause? Existing root cause analysis techniques often rely on static rules, correlation heuristics, or topology-local reasoning, which struggle to generalize in dynamic environments where faults propagate across complex physical and logical dependencies. We present NetCause, a self-supervised learning-based framework that models network incidents as graph-temporal processes and uses counterfactual simulation to rank candidate root causes. This approach produces an interpretable ranking of root cause hypotheses and integrates naturally with operator-defined mitigation and remediation actions. We train the model on over 1,500 incidents collected over six months from a leading cloud provider's production network and evaluate it on 31 expert-labeled incidents. NetCause consistently improves root cause ranking quality in the regime most relevant to operational decision-making, achieving a 16.1% accuracy improvement over a rule-based heuristic baseline. While training is computationally intensive, inference is lightweight, requiring only seconds of GPU runtime per incident (well below typical telemetry collection latencies).

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

Compact graphs and quantum automorphisms

arXiv:2606.13928v1 Announce Type: new Abstract: Compact graphs are graphs for which the fractional automorphism polytope has no genuinely fractional vertices. This paper proposes a quantum analogue of this idea by evaluating the fundamental magic unitary of the quantum automorphism group on states, which we show to produce a closed convex set of doubly stochastic matrices sitting between the classical automorphism polytope and the full fractional automorphism polytope. Our main result is that the natural quantum analogue of compactness is classical, that is, a quantum compact graph is classically compact. We also relate this set to the quantum orbital algebra and obtain a hierarchy of classical and quantum compactness pseudo notions. The framework recovers familiar consequences of compactness through commutants and suggests quantum analogues of generous transitivity and distance-transitivity. We also isolate examples and open problems indicating where quantum symmetries may strictly refine the classical compactness theory.

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

Automated 3D Kinematic Monitoring for Circadian Activity and Anomaly Detection in Juvenile Fish

Precision aquaculture faces a "phenotyping bottleneck" in tracking high-resolution behavioral traits, as conventional methods cannot quantify instantaneous three-dimensional (3D) physical exertion. To address this, we present a high-throughput 3D behavioral phenotyping framework integrating deep learning object detection with binocular stereo vision for real-time monitoring of juvenile tilapia in high-density environments. The system automates non-contact body length estimation and reconstructs 3D swimming trajectories from absolute spatial coordinates. By eliminating 2D perspective distortions, this approach precisely quantifies 3D velocity and acceleration, marking the first estimation of true physical swimming speeds in free-roaming juveniles. Results show the framework successfully establishes circadian locomotor baselines, serving as an early warning system for physiological stress and providing an objective metric for fish vitality.

13.
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.

14.
PLOS Computational Biology 2026-06-08

Assessing the inference of single-cell phylogenies and population dynamics from CRISPR lineage recordings

by Julia Pilarski, Tanja Stadler, Sophie Seidel Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation, and death, which can be represented as a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters – cell division, differentiation, and death rates – from this tracking data remains challenging and needs to be systematically evaluated. We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvements as the recorder capacity increases. We observe more accurate phylogenetic reconstruction from sequential compared to random recordings, but no substantial improvement in phylodynamic inference when using the additional information contained in the order of edits. Overall, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division when appropriate models are used. However, we detect biases in the inferred rates of cell division and death under phylodynamic model misspecification, i.e., when fitting classic memoryless birth-death processes to synchronous cell divisions. Moreover, for scenarios when cells differentiate into distinct types, we demonstrate that Bayesian phylodynamic analysis of sparse end-point measurements can resolve these cell differentiation trajectories by lineage and time. Under prototypical dynamics, we recover cell type-specific division and death rates, and cell type transition rates in over 80% of simulations. Overall, this simulation study explores how much information on cellular development can be extracted from state-of-the-art genetic lineage tracing data using phylogenetic and phylodynamic methodology.

15.
Nature (Science) 2026-06-08

Fifty years since a simple equation described the chaos of biology

An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics. An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics.

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

Noise-Driven Escape from Metastable Phases explains Grokking in Deep Neural Networks

arXiv:2606.17120v1 Announce Type: new Abstract: Deep neural networks (DNNs) exhibit first order phase transitions under variations of the L2 regularization strength, with each transition marking the onset of a new learnable feature. Below a critical regularization strength, all features are in principle learnable, but coexisting metastable states, separated by energy barriers, can trap the network and impede convergence. A strength of DNNs is their ability to generalize. But many open questions remain, among them the origin of so called grokking: the abrupt, delayed onset of generalization after prolonged apparent overfitting. We show for linear DNNs that grokking is consistent with hysteresis in first-order L2 phase transitions: using L2 regularization to engineer deliberate trapping, we demonstrate that a model in a low-accuracy metastable state escapes only when SGD noise drives it across an energy barrier, with escape times following Arrhenius scaling. We reproduce grokking-like delayed convergence across two orders of magnitude in escape time by deliberately trapping models in metastable phases. Using sparse sub-sampling we also reproduce the canonical grokking curve where test error eventually approaches the final training error. Our work suggests that the number of metastable states equals the number of learnable features – one per singular value of the data covariance – the potential for hysteresis grows naturally with task complexity. We provide evidence that the same mechanism likely operates in general nonlinear DNNs. Our results provide routes toward more efficient learning schemes.

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

Individual Control Barrier Functions-Guided Diffusion Model for Safe Offline Multi-Agent Reinforcement Learning

arXiv:2606.12640v1 Announce Type: new Abstract: Offline reinforcement learning allows control policies to be learned directly from data without online interaction, making it suitable for safety-critical tasks. Recent studies have applied diffusion models to offline reinforcement learning to leverage their strong capacity for modeling complex data distributions. However, existing approaches primarily focus on single-agent settings, leaving the safety challenges in multi-agent environments largely unexplored. In this work, we propose a safe offline multi-agent reinforcement learning algorithm that embeds neural individual control barrier functions into the diffusion model to enhance safety during trajectory generation, with control policies recovered through inverse dynamics. We evaluate our algorithm across diverse benchmarks, demonstrating substantial safety improvements while maintaining competitive rewards.

18.
arXiv (quant-ph) 2026-06-16

Finite-Dimensional Type I von Neumann Algebras in PyTorch: A GPU-Accelerated Framework for Random Block-Diagonal Operators

arXiv:2606.15882v1 Announce Type: cross Abstract: We present \texttt{torch\_vn\_algebra}, an open-source Python library built on PyTorch for numerical experiments with finite-dimensional Type I von Neumann algebras (direct sums of matrix algebras). The library provides: $\bullet$ a compact batched tensor representation $(B,C,k_{\max},k_{\max})$ that handles both Monte Carlo samples and multiple direct summands; $\bullet$ lazy evaluation of operators to avoid unnecessary memory allocation; $\bullet$ generation of random operators with arbitrary eigenvalue distributions (user-provided samplers) and various unitary ensembles (Haar, $\mathrm{SU}(n)$, COE, CSE, diagonal phases); $\bullet$ functional calculus via SVD (absolute value, square root, inverse, entropy) and a hybrid method for extreme eigenvalues (exact diagonalisation for $k_{\max}\le256$, otherwise power iteration); $\bullet$ three trace functionals (blunt, normalised subspace trace, and the von Neumann tracial state); $\bullet$ GPU-accelerated batched linear algebra for moderate-scale Monte Carlo studies (e.g., $2\times10^4$ samples of $100\times100$ operators). The library is validated against analytical expectations (Haar moments, trace properties). Performance benchmarks on a Tesla P100 GPU are presented and discussed. Limitations and future work are outlined. The code is open-source.

19.
arXiv (CS.CL) 2026-06-17

EComAgentBench: Benchmarking Shopping Agents on Long-Horizon Tasks with Distributed Hidden Intent

As LLM-based shopping agents enter production, existing benchmarks fail to capture how a shopper's requirements arrive: stated implicitly in the query, recorded in a profile, or revealed only when the right question is asked. Benchmarks that expose full intent upfront and grade only the final choice can neither pose this long-horizon challenge nor explain which requirement an agent missed. To address this gap, we introduce EComAgentBench, a benchmark of 662 tasks grounded in real Amazon products and reviews. Each task scatters these requirements across a visible query, a tool-gated profile, and scripted clarification; an agent must uncover hidden intent, verify candidates against attributes and review evidence, and commit to a single product within 100 tool calls. Moreover, typed, source-tagged rubrics grade every task, attributing each failure to a requirement and its source. Construction is automated yet reliable, with every answer fixed in code before any text is generated and every sample validated. Our evaluation of seven models reveals that even the strongest attains only 57.1% overall accuracy, and rubric satisfaction degrades from visible to hidden sources. Overall, we believe EComAgentBench will serve as a reproducible foundation for moving shopping agents from single-query search toward dependable assistance over long horizons.

20.
arXiv (CS.CL) 2026-06-11

Agentic Environment Engineering for Large Language Models: A Survey of Environment Modeling, Synthesis, Evaluation, and Application

Environments serve as interactive systems for large language model (LLM) based agents across diverse scenarios and play a crucial role in driving the continual evolution of model capabilities. Despite this importance, existing work lacks a systematic categorization and deep analysis. This paper systematically studies current researches on agentic environments from the perspective of the environment engineering lifecycle, covering their modeling, synthesis, evaluation and application. Specifically, the paper first introduces representative environments from the perspectives of eight attributes and eight domains, providing detailed analyses of their development paths and highlighting their core capabilities. Second, for automated environment synthesis, two paradigms are introduced, such as symbolic synthesis and neural synthesis. This paper also shows different environment evaluation methods in each paradigm. Thirdly, the corresponding environment applications from the perspective of agent-environment co-evolution are discussed. In specific, the paper characterizes the primary pathways for agent evolution in dynamic environments from four complementary perspectives: memory-centric experience evolution, orchestration-centric workflow evolution, trajectory-centric offline evolution, and exploration-centric online evolution. And three paradigms of environment evolution are identified, namely neural-driven, difficulty-driven, and scaling-driven approaches. At last, several promising future directions are discussed, including Environment-as-a-Service, Multi-agent Environments, and Neural-Symbolic Environments.

21.
arXiv (CS.CV) 2026-06-19

Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank

The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.

22.
arXiv (CS.AI) 2026-06-12

Transformer Field Theory: A Response-Theoretic Approach to Mechanistic Interpretability

arXiv:2605.25225v2 Announce Type: replace-cross Abstract: Mechanistic interpretability often studies Transformer behavior by intervening on internal activations through activation patching, causal tracing, path patching, and steering directions. This paper develops Transformer Field Theory: a response-theoretic framework in which the residual stream of a fixed forward pass is treated as a Transformer field over layer depth and token position. In this formulation, patching becomes a localized source insertion into the Transformer field, first-order sensitivity fields predict patch effects, Green functions describe downstream propagation, and patch selection is posed as an adjoint inverse problem. Empirically, we test the theory's forward response objects in GPT-2-style autoregressive Transformers. Localized Transformer-field interventions exhibit a bounded local linear regime; first-order sensitivities predict patch effects across layer-token sites; localized sources generate structured anisotropic Transformer-field propagation; high-sensitivity sites and sliced Green operators provide reduced response descriptions; and prompt-induced Transformer-field displacements partially transfer answer behavior. These results establish sensitivities, Transformer-field responses, and sliced Green operators as practical objects for organizing patching experiments, while providing the forward mathematical basis for patch-site inference and cross-scale response transfer.

23.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

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

Geometry-Consistent Endoscopic Representations for Image-Guided Navigation via Structured Foundation Model Adaptation

Accurate vision-based navigation in monocular endoscopy is difficult due to limited depth cues, weak tissue texture, non-rigid deformation, and substantial appearance variation across domains, all of which complicate pose estimation, depth prediction, and image-to-anatomy alignment. Although recent vision foundation models have shown promise, their learned representations often remain insufficiently geometry-consistent, hindering stable feature correspondence and limiting their reliability for downstream navigation tasks. We propose a unified framework for learning geometry-consistent and domain-robust image representations for monocular endoscopy. The framework combines a synthetic data pipeline that provides accurate geometric supervision with Hierarchy-Aware Geometry-Semantic Adaptation, a structured alternative to standard LoRA that inserts low-rank adapters selectively across the transformer hierarchy and couples them with layer-wise training objectives to encourage geometric correspondence in intermediate features and semantic consistency in deeper features. Experiments on public and proprietary datasets show improved geometric and semantic representation quality, leading to better performance on downstream navigation tasks including pose estimation and monocular depth estimation. The learned representations show favorable synthetic-to-real transfer on clinical bronchoscopy and provide a useful initialization for adaptation to sinus endoscopy and colonoscopy under limited supervision. The framework also shows favorable scaling with model size and training data. These results support hierarchy-aware, geometry-guided adaptation as a practical approach for endoscopic representation learning.

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

A Self Consistency Based Reranking for Narrative Question Answering

Narrative question answering (NQA) is a challenging task in natural language processing that requires models to understand long textual contexts, capture relationships across events, and generate coherent responses. Despite recent advances in pretrained language models, most existing approaches rely on a single decoding output during inference, making them sensitive to generation variability and often resulting in incomplete or inconsistent answers .To address this limitation, we propose a self-ensemble Self-Consistency-Based reranking framework for narrative question answering. The proposed method generates multiple candidate answers for each story-question pair and selects the final answer based on semantic agreement among the generated responses. This allows the model to explore diverse answer formulations while improving robustness through consensus-based selection without requiring modifications to the underlying architecture .The framework combines pretrained and fine-tuned language generation with multi-answer inference and similarity-based reranking. We evaluate the proposed approach on the NarrativeQA dataset using multiple models, including FLAN-T5 (Base and Small) and Pegasus-Large, under both baseline and fine-tuned settings .Experimental results demonstrate that the proposed method consistently improves performance across all models. In particular, FLAN-T5-Base achieves the best overall performance, improving from 82.32% to 86.66% (+4.34%) when combined with self-ensemble inference. Additionally, the largest improvement is observed with Pegasus-Large, which increases from 72.50% to 87.07% (+14.57%), highlighting the effectiveness of the proposed strategy.