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01.
arXiv (quant-ph) 2026-06-16

Connecting entanglement growth with local integrals of motion in the disordered Fermi-Hubbard model

arXiv:2606.15481v1 Announce Type: new Abstract: Generically a quantum system initialized in an unentangled state will, under unitary dynamics, rapidly become entangled, a process closely related to information transport and to thermalization. Disorder can suppress the growth of entanglement and result in memory of initial conditions. In non-interacting systems this arises from localization of single-particle states, the occupancy of which is fixed by the initial condition. In interacting systems similar localized conserved quantities persist, but with the added feature that they are coupled, resulting in entanglement growth which is distinct from both non-interacting localized systems and from generic ergodic systems. The Fermi-Hubbard model has two degrees of freedom per site – charge and spin – and disorder may be present in both of these. We study the growth of entanglement in two scenarios – disorder in charge equal and unequal to that in spin, and determine the distinct contributions of charge and spin degrees of freedom by expanding the Hamiltonian in terms of a set of optimally localized conserved quantities with separate charge and spin character. We find that coupling between charge and spin is significantly weaker than charge-charge and spin-spin coupling. While this decoupling is present in all our results, it is only apparent when the strength of the disorder in the two sectors is different such that there is a separation between the characteristic timescales of the contributions to entanglement made by charge and by spin.

02.
arXiv (quant-ph) 2026-06-16

VQE as Initial State Preparation for QPE on Heisenberg Spin-Glass Hamiltonians

arXiv:2606.15061v1 Announce Type: new Abstract: Quantum Phase Estimation (QPE) is the quantum algorithmic workhorse for computing ground state energies of quantum Hamiltonians with quantum computers. Ground state energy calculation of physical systems is perhaps the most promising use case for quantum computing in terms of scientific and commercial value with a plausible path to outperformance of classical alternatives. This path, however, hinges on the availability of initial states for QPE with significant overlap with the true ground state. Using extensive (classical) numerical computations, we study whether the NISQ-era algorithm VQE (Variational Quantum Eigensolver) could be used to efficiently prepare high-overlap states of disordered fully-connected anisotropic Heisenberg spin glass quantum Hamiltonians with up to $15$ qubits. We find that (i) – consistent with widely held, but rarely numerically illustrated beliefs – VQE is generally unable to efficiently converge to the ground state for our Hamiltonians, which is a well-known issue with VQE due to a variety of factors including vanishing gradients and local minima; (ii) low energy states do not necessarily have large ground-state overlap, but there is typically a correlation between the two measures; (iii) adding more than three layers to the VQE ansatz neither improves overlap nor the energies found; and (iv) the best-found overlap scaling as a function of the Hamiltonian system size is not strongly exponentially decreasing, suggesting potential for VQE to be a heuristic state preparation algorithm for QPE.

03.
PLOS Computational Biology 2026-06-17

Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization

作者:

by Anyi Yang, Xingzhong Zhao, Xing-Ming Zhao, Yucheng T. Yang Reconstructing causality routes from genetic effects to complex phenotypes in particular cell types is crucial for understanding biological mechanisms underlying the brain-associated phenotypes including imaging-derived phenotypes (IDPs), and brain disorders and behaviors (DBs). Here, we develop a single-cell Mendelian randomization framework to infer cell type-specific causal relationships between gene expression and diverse brain-associated complex phenotypes by integrating single-cell expression quantitative trait loci (cis-eQTLs) and genome-wide association study findings. We identifiy a set of 254 and 217 cis-eQTL target genes (eGenes) that may have causal effects on 112 IDPs and 26 DBs in eight cell types, respectively. These causal eGenes exhibit strong cell type specificity and varied pleiotropy among different types of brain-associated phenotypes. Further integrative analysis reveals putative causality routes among cell type-specific causal eGenes and brain-associated complex phenotypes. Finally, we characterize the spatiotemporal expression patterns of these causal eGenes, and highlight the coordinated associations of the brain-associated phenotypes based on the expression of their causal eGenes. Overall, our study presents a large-scale analysis of the genetic effects of brain structures, disorders and behaviors, providing a catalog of cell type-specific causal eGenes.

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

SafeSpec: Fast and Safe LLM via Dynamic Reflective Sampling

arXiv:2606.19755v1 Announce Type: cross Abstract: Speculative inference accelerates large language model (LLM) decoding but provides no inherent safety guarantees. Existing safety defenses are largely incompatible with speculative inference: they either introduce additional computation or disrupt the draft-verify mechanism, negating acceleration benefits. This reveals a fundamental incompatibility between current safety methods and speculative decoding. We propose SafeSpec, a safety-aware speculative inference framework that integrates risk estimation directly into the verification process. SafeSpec attaches a lightweight latent safety head to the target model to jointly evaluate semantic validity and safety in a single forward pass. When unsafe generations are detected, SafeSpec applies rollback and safety-guided reflective multi-sampling to recover safe continuations rather than terminating generation. We model jailbreak attacks as distributional shifts over generative trajectories, where adversarial prompts increase the probability of harmful continuations without eliminating safe ones. Under this model, SafeSpec performs risk-aware trajectory recovery within the speculative decoding process. Across multiple models and adversarial benchmarks, SafeSpec achieves a substantially improved safety-efficiency trade-off. On Qwen3-32B, SafeSpec reduces attack success rates by 15% while preserving a 2.06x inference speedup on benign workloads, demonstrating that speculative acceleration and inference-time safety can be jointly optimized.

05.
arXiv (CS.LG) 2026-06-16

Sobolev Approximation by Fixed-Size Neural Networks with Arbitrary Accuracy

arXiv:2606.16975v1 Announce Type: cross Abstract: In this work, we investigate new activation functions for achieving arbitrary-accuracy Sobolev approximation by fixed-size neural networks. We first show that any function in $W^{2,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy, measured in the $W^{1,\infty}$-norm, by a fixed-size neural network using the Elementary Universal Activation Function ($\mathrm{EUAF}$). To extend this result to $W^{s,\infty}((a,b)^d)$ for $s\in\mathbb{N}$, we introduce a smooth activation $\mathrm{DUAF}_{\infty}$ from the family of Differentiable Universal Activation Functions ($\mathrm{DUAF}_n$). We prove that any function in $W^{s,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy in the $W^{s-1,\infty}$-norm by a fixed-size $\mathrm{DUAF}_{\infty}$-activated network. We further construct sigmoidal variants $\widetilde{\mathrm{DUAF}}_n$ and show that, for every $1\leq s\leq n$, fixed-size $\widetilde{\mathrm{DUAF}}_n$-activated networks still approximate any $f\in W^{s,\infty}((a,b)^d)$ with arbitrary accuracy in the $W^{s-1,\infty}$-norm. In all these results, the width and depth bounds are computed explicitly, and the proposed activations are elementary.

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

A Five-Plane Reference Architecture for Runtime Governance of Production AI Agents

作者:

arXiv:2606.12320v1 Announce Type: new Abstract: Enterprise security was built to govern data boundaries: the protected surface was data at rest and in transit, and the controls – access control, data-loss prevention, perimeter inspection – governed crossings of that boundary. Production AI agents dissolve this assumption. An agent reads context, calls tools, invokes connectors, and modifies systems of record on an enterprise's behalf, so risk moves inside the workflow, into sequences of individually-permitted actions that may transform a business process no one authorized. Existing policy engines do not extend to this regime: they evaluate request-time decisions against atomic principals, where agentic systems require stateful evaluation against composite principals whose authority attenuates through delegation chains. We present a reference architecture for the runtime governance of production agents, built from four composable primitives: a five-plane decomposition (a reasoning plane that adjudicates intent, and four enforcement planes – network, identity, endpoint, data – that realize the decision), stop-anywhere mediation, composite principals with capability attenuation, and audit as a structured evidence substrate. We define a taxonomy of six interruption primitives that generalize allow and deny, state and argue for four correctness invariants, and demonstrate the foreclosure of seven production-agent threats across five concrete workflows. A reference implementation of the policy-engine core supplies measured evidence: attenuation correctness and evidence reconstructability hold on every trial, adjudication runs in single-digit microseconds, and the audit substrate's tamper-evidence behaves exactly as designed. We are explicit about scope: the architecture governs delegated action, not model behavior, and a full-system evaluation against a live agent benchmark is the invited next step.

07.
arXiv (CS.AI) 2026-06-18

SwitchBraidNet: Quantisation-Aware Lightweight Architecture for Hybrid Brain-Computer Interface

arXiv:2606.18816v1 Announce Type: cross Abstract: Hybrid brain-computer interfaces (BCIs) that integrate motor imagery (MI) and steady-state visual evoked potentials (SSVEP) provide high-dimensional neural decoding but typically exceed the computational limits of embedded hardware. To address this, we propose SwitchBraidNet, a compact EEG classification architecture designed for low-power deployment. The model employs a dual-path temporal braid to extract multiscale oscillatory features, an adaptive squeeze-and-excitation spatial switch for electrode gating, and a log-variance readout layer for direct band-power encoding. Furthermore, through systematic quantisation-aware training on the OpenBMI dataset, we compared SwitchBraidNet against four established baselines across FP32, FP16, and INT8 precisions. Experimental results demonstrate superior efficiency and performance, achieving MI accuracy of 69.49% (FP16), SSVEP accuracy of 93.48% (FP32), and a hybrid information transfer rate of 64.82 bits/min (FP16). With an INT8 footprint of only 3.03 KB, SwitchBraidNet maintains high accuracy across varying numerical precisions, demonstrating its suitability for low-power embedded BCI deployment.

08.
arXiv (CS.LG) 2026-06-19

Critical Percolation as a Synthetic Data Model for Interpretability

arXiv:2606.20347v1 Announce Type: new Abstract: Neural networks learn features that reflect the hierarchical, multi-scale structure of natural data. Synthetic datasets used to evaluate interpretability methods typically lack this structure, limiting their value as realistic toy models. To close this gap, we introduce a family of synthetic datasets consisting of hierarchical functions defined on critical mean-field percolation clusters embedded in a high-dimensional data space. The percolation data consists of sparse, low-dimensional fractal clusters with a power-law size distribution. Latent variables modeling a taxonomic hierarchy generate each data point's target value. The data model is analytically tractable with known critical exponents that fix its properties without requiring hyperparameter tuning. We leverage a mapping between percolation clusters, random trees, and additive coalescence to propose an almost linear-time algorithm to jointly sample a random tree and its hierarchical latent decomposition, enabling data generation at arbitrary scale. Using probing experiments, we find that the model's ground-truth latent variables can be linearly decoded from neural network activations. Together, sparsity, self-similarity, power-law statistics, and analytical tractability make critical percolation a principled testbed for interpretability research.

09.
arXiv (CS.CL) 2026-06-12

Why Sampling Is Not Choosing: Intentionality, Agency, and Moral Responsibility in Large Language Models

Recent advances in large language models (LLMs) have prompted claims that such systems exhibit agency or qualify as moral agents. This paper argues that these attributions are misguided. We maintain that moral responsibility requires commitment-bearing agency grounded in intrinsic intentionality and self-attributed action, and that such agency constitutes the form of free will relevant to responsibility. Although LLMs generate coherent and normatively evaluable outputs, their operation is fully characterized by probabilistic input-output mappings learned from data. Their apparent intentionality is derived rather than intrinsic, and their outputs are neither owned as commitments nor guided by reasons. Variability introduced by stochastic sampling does not amount to choice or authorship. We address objections from the intentional stance, functionalism, compatibilism, and the presence of moral reasoning in model outputs, arguing that none suffice to establish genuine agency.

10.
arXiv (math.PR) 2026-06-12

Stochastic dominations for FK percolation and sharp thinning thresholds for the Ising energy field

arXiv:2606.13648v1 Announce Type: new Abstract: At first glance, one would imagine that the energy field of the Ising model, the set of edges whose endpoints share the same spin, is stochastically monotone as a function of the coupling constants. However, this is not generally the case. In this paper, we introduce two weaker notions of stochastic domination that make this result true: $p$–weak and $p$–weak$^\dagger$ domination. Both of these notions depend on a parameter $p$ and we find the optimal values $p$ and $p^\dagger$ so that these dominations hold. One of the key ingredient to obtain some of the results is a new stochastic domination relating FK percolations with different parameters $q,\tilde{q}\geq 1$ that is of independent interest.

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

OQMD: Single-Qubit Rotation Control Improves Low-CNOT Multiclass Quantum Classification

arXiv:2606.14088v1 Announce Type: new Abstract: Near-term variational classifiers incur substantial error and latency from two-qubit gates, yet practitioners often assume that additional entangling depth is the default route to higher accuracy. This work studies Optimal Quantum Measurement Decoding (OQMD): optimizing how quantum outcomes are mapped to classical labels by training a readout layer before measurement, jointly with the variational circuit, without adding CNOTs. Experiments use trainable triple single-qubit rotations as one concrete, hardware-native realization of OQMD; other single-qubit parametrizations fit the same classical outer loop. On the Iris benchmark with a 30-point stratified test split, the best observed 0-CNOT configuration with OQMD reaches 83.33\% accuracy, with a 96\% at 9 CNOTs, exceeding the best 18-CNOT controls (56.67\%) and the best 18-CNOT configuration with OQMD (66.67\%) under a common protocol. A six-point CNOT-depth series from 0 to 18 (fixed optimizer, iteration budget, random-seed count, and ZXZ readout) shows that the highest raw scores need not occur at the largest template, so aggregate complexity is not summarized by CNOT count alone. Because run-level accuracies are discrete and non-Gaussian, we emphasize best-observed scores and, where a global comparison of pooled runs is required, Mann–Whitney $U$ tests rather than parametric tests on means. Across architectures, OQMD shows statistically consistent but magnitude-dependent gains: large peak lifts on minimal circuits coexist with a small pooled mean shift on complex 18-CNOT runs ($p\approx 0.03$) that is not ``universal'' in the sense of uniformly large practical effects.%

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

Robust Pretty Good Measurement via Hybrid Classical-Quantum Pseudoinverse Approximation and Circuit-Level Realization

arXiv:2606.13150v1 Announce Type: new Abstract: Pretty Good Measurement (PGM) is a near-optimal strategy for quantum state discrimination, but its practical realization becomes unstable when the ensemble operator is singular or ill-conditioned. We introduce a numerically robust PGM formulation based on the Moore-Penrose pseudoinverse, replacing the standard inverse square root with a threshold-regularized variant that remains well-defined across different spectral regimes. We develop a hybrid classical-quantum framework that combines pseudoinverse-based spectral preprocessing with quantum circuit realizations using block-encoding and spectral-transformation techniques. The framework incorporates support awareness, yielding physically meaningful measurement operators even in rank-deficient cases, and employs oblivious amplitude amplification to improve circuit-level success probabilities. Extensive numerical and circuit-level simulations show close agreement between theoretical predictions and quantum circuit outputs. Experiments on synthetic and real datasets, including ill-conditioned and degenerate scenarios, demonstrate stable discrimination performance where standard PGM becomes numerically unstable. The results establish a practical hybrid classical-quantum framework for robust quantum state discrimination and extend previous circuit-based implementations of the PGM testing stage toward pseudoinverse-aware measurement design.

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

T-Mem: Memory That Anticipates, Not Archives

Long-term memory is essential for conversational agents to remain coherent across extended dialogues, follow through on commitments made many sessions earlier, and adapt their behaviour to each user. Current LLM-backed long-term conversational memory, however, is reachability-bounded by the similarity between a query and stored content, both lexical and dense-vector. The approach is effective when query and memory share surface features such as wording or named entities (we call this descriptive). But it misses another, equally valuable class of cases, where query and memory do not share surface features and are tied only by a latent semantic arc (associative). On this regime prevailing long-term memory systems collectively fail. Covering this other half is what allows an assistant, for the first time, to actively draw on past dialogue as a semantic asset. On the memory side, this is the engineering counterpart of what cognitive science calls episodic future thinking: rehearsing past experience for the future contexts under which it will need to be found. We call these write-time rehearsals triggers. We propose T-Mem, the first long-term conversational memory architecture that covers both descriptive and associative recall. At each of two evidence granularities, single facts and full exchanges, T-Mem instantiates one descriptive trigger family and one associative trigger family, so that every memory remains reachable from both surface-similar and relevance-bound queries. As empirical validation, T-Mem reaches state-of-the-art on both LoCoMo and LoCoMo-Plus.

14.
arXiv (CS.LG) 2026-06-19

FlexLAM: Resolving the Bottleneck Trade-off in Latent Action Learning

arXiv:2606.19408v1 Announce Type: new Abstract: Latent actions provide a compact interface between action-free video and downstream decision-making, yet existing Latent Action Models (LAMs) force every transition through a fixed-capacity bottleneck. We identify a bottleneck trade-off: overly tight codes can discard transition cues needed for action alignment, while overly loose codes preserve additional transition variation that must be resolved when alignment labels are scarce or narrowly distributed. FlexLAM replaces this fixed capacity with variable-length latent actions trained by nested dropout, yielding prefix-valid codes that capture compact transition structure first and add detail only when needed, without new architectures or losses. A single FlexLAM matches or surpasses separately trained fixed-capacity LAMs at every evaluated token budget under standard scarce-label supervision and under a low-return single-task alignment stress test, indicating that FlexLAM is not merely adjustable at inference time but learns a better latent-action interface at the same token budgets. The same model supports inference-time token-budget adjustment without retraining, and FlexLAM improves Ego4D transition reconstruction. These results suggest that variable-length latent actions are an architecture-free, drop-in upgrade to the fixed-capacity bottleneck in latent action models, latent-action world models, and video-pretrained action interfaces.

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

LSTM-Based Detection of Structural Breaks in Property Insurance Loss Reserving: A Climate-Informed Approach

arXiv:2606.11463v1 Announce Type: cross Abstract: Accurate loss reserving is foundational to insurer solvency, yet accelerating climate driven catastrophes systematically violate the stability assumptions on which traditional actuarial methods depend. This white paper presents a research program testing whether Long Short Term Memory (LSTM) neural networks can detect and adapt to these structural breaks faster and more accurately than Chain Ladder, Bornhuetter Ferguson, and Cape Cod methods. Using 15 plus years of regulatory development triangle data from Florida and Louisiana, enriched with NOAA hurricane intensity indices and sea surface temperatures, we hypothesize a targeted improvement of 15, 20% in reserve accuracy for catastrophe exposed years, a threshold grounded both in the prior neural network reserving literature and in the formal convergence results developed here. Beyond empirical validation, we develop a theoretical framework grounding LSTM structural break detection in probabilistic terms, providing formal performance guarantees that compensate for the limited number of catastrophe events in the test period. We document the research design, methodology, expected contributions, and a candid assessment of limitations.

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

Excited-State Quantum Chemistry on Qumode-Based Processors via Variational Quantum Deflation

arXiv:2604.13457v3 Announce Type: replace Abstract: Variational quantum algorithms on bosonic quantum processors are an emerging paradigm for quantum chemistry calculations, exploiting the natural alignment between molecular structure and harmonic oscillator-based hardware. We introduce the qumode-based variational quantum deflation framework (QumVQD) for finding both electronic and vibrational excited state energies on qumode-based architectures. We validate the approach through electronic structure calculations on H$_{2}$ and linear H$_{4}$, where we introduce Hamming-weight filtering of the Fock basis to enforce particle number conservation and eliminate spurious eigenstates by reducing the required Hilbert space, which reduces the required number of qumodes in turn. We achieve agreement with full configuration interaction (FCI) using the STO-3G basis set within the chemical accuracy threshold at most points along the potential energy surfaces. Extending to the vibrational structure, we combine QumVQD with an existing Hamiltonian fragmentation approach based on Cartan subalgebra, allowing us to compute the vibrational eigenenergies of CO$_{2}$ and H$_{2}$S to spectroscopic accuracy with per-fragment circuits that scale as $O(N)$ in single-qumode gates and $O(N^2)$ in beam-splitter gates for $N$ qumodes. For the case of CO$_{2}$, we get total gate counts more than an order of magnitude smaller than those reported for qubit-based vibrational algorithms at this system size. These results demonstrate that bosonic quantum devices are a viable platform for excited-state quantum chemistry, particularly for vibrational problems where qubit-based methods incur substantial boson-to-qubit mapping overhead.

17.
bioRxiv (Bioinfo) 2026-06-12

DNA Compression with Genomic Language Models: Tokenization, Benchmarking, and an Information-Content Map

Lossless compression and probabilistic sequence modeling are two faces of the same coin: a model that assigns high probability to a sequence can encode it in few bits via arithmetic coding. We exploit this duality to evaluate genomic language models as compressors of DNA, using compression primarily as an objective probe of generative sequence modeling rather than as a deployable storage system. We release DNAGPT2, a family of ten GPT-2-small models pretrained for one epoch on a single A40 using the DNABERT2 multi-species corpus that differ only in byte-pair encoding vocabulary size. Coupled with arithmetic coding, the best model reaches 1.47 bits per base (bpb) on the T2T human genome, fourth in the Cobilab compression benchmark and ahead of every general-purpose compressor. Our results suggest that NLP-style tokenization choices may be suboptimal for DNA: a 32-token BPE vocabulary compresses better than larger vocabularies. We also find that, in this benchmark, published long-context genomic LMs underperform a much shorter-context BPE GPT-2; we discuss in Section 5 that this is not a controlled context-length ablation, since the compared models also differ in architecture, training data, parameter count, and tokenization. Finally, we compute a per-nucleotide information-content map of the human genome and show that exons, introns, intergenic regions, and Alu repeats have statistically distinct information profiles.

18.
arXiv (CS.CV) 2026-06-12

LatentLens: Revealing Highly Interpretable Visual Tokens in LLMs

Transforming a large language model (LLM) into a vision-language model (VLM) can be achieved by mapping the visual tokens from a vision encoder into the embedding space of an LLM. Intriguingly, this mapping can be as simple as a shallow MLP transformation. To understand why LLMs can so readily process visual tokens, we need interpretability methods that reveal what is encoded in the visual token representations at every layer of LLM processing. In this work, we introduce LatentLens, a novel approach for mapping latent representations to descriptions in natural language. LatentLens encodes a large text corpus and stores contextualized token representations for each token in that corpus. Visual token representations are then compared to these contextualized representations and the top-nearest neighbor representations serve as descriptions of the visual token. We evaluate this method on 15 different VLMs, showing that commonly used methods, such as LogitLens, substantially underestimate the interpretability of visual tokens. With LatentLens instead, the majority of visual tokens are interpretable across all studied models and all layers. Qualitatively, we show that the descriptions produced by LatentLens are semantically meaningful and provide more fine-grained interpretations for humans compared to individual tokens. More broadly, our findings contribute new evidence on the alignment between vision and language representations and open up new directions for analyzing the latent representations of LLMs.

19.
PLOS Computational Biology 2026-06-18

Ten simple rules for turning your qualifying exam into an NIH-style fellowship proposal: A guide for graduate students

by Courtney Peña-Lima, Cameron S. Bader, Brendan K. Ball, Troy C. Dildine, Mekhala V. Dissanayake, Iris van ‘t Erve, Albina Ibrayeva, Amy Nippert, M.K. Quinn, Chelse Spinner, Samuel Thompson, Antonio Tomasso, Crystal M. Botham Qualifying exams, often referred to as “quals” or candidacy exams, are an important milestone in doctoral programs. Although the style of quals varies greatly by program and institution, it is usually a proposal that requires students to develop research ideas as well as their scientific writing skills. Many quals are modeled after funding mechanisms that graduate students can apply to and on a topic that the student will pursue in their dissertation. This paper offers graduate students a step-by-step guide on how to turn their quals into a fellowship-style research proposal, using National Institutes of Health (NIH) mechanisms as a benchmark, as this is the norm within US research institutions. This paper will be most useful for students who have completed or are in the process of completing proposal-based qualifying exams, usually in the second year of a doctoral program.

20.
medRxiv (Medicine) 2026-06-12

Design, Implementation, and Evaluation of a Shadowing Program for Medical Students in the Basic Sciences Phase

Introduction Shadowing, as an educational method based on active observation, can foster a realistic understanding of professional roles and enhance the communication skills of medical students. This study aimed to design, implement, and evaluate a shadowing program for basic sciences medical students. Methods This development study was conducted based on the ADDIE model in five phases. The study population consisted of 799 medical students in semesters 2 to 5. The stages included Analysis (determining needs through literature review and expert panels), Design (specifying learning environments and evaluation methods), Development (preparing guides and educational tools), Implementation (within the Medical Ethics course), and Evaluation (using questionnaires and reflection forms). Findings This study aimed to design and evaluate an educational shadowing program based on the ADDIE model. In the Analysis phase, the profiles of 799 students and learning objectives were determined. In the Design phase, a structured program for four types of shadowing was designed. In the Development phase, all guides and educational tools were prepared. In the Implementation phase, the program was carried out with complete coverage and adherence to ethical considerations. Finally, the program evaluation showed that "Motivation to become a good physician" (3.75-3.95) and "Enhancing empathy" (3.50-3.94) received the highest scores, while "Increasing understanding of the basic science-clinical connection" (2.53-2.89) and "Willingness to attend on holidays" (1.87-2.31) received the lowest scores. Conclusion The findings indicate that implementing the shadowing program is an effective method for strengthening the professional attitudes and academic motivation of medical students. However, the program did not significantly improve students perception of the basic science-clinical connection, indicating a need for curricular refinement. The continuation and extension of this program to other levels and fields of medical sciences are recommended.

21.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

22.
arXiv (CS.CV) 2026-06-11

OpenMedReason: Scientific Reasoning Supervision for Medical Vision-Language Models

High-stakes clinical use of large vision-language models (LVLMs) requires reasoning that is grounded in visual evidence and clinical knowledge, not just correct final answers. We introduce OpenMedReason, a large-scale, open multimodal medical reasoning corpus comprising approximately 450K image-question-answer instances whose reasoning traces are primarily derived from curated biomedical, human-authored scientific articles. OpenMedReason provides high-fidelity supervision beyond synthetic chains of thought, covering diverse medical domain vision modalities such as radiological scans, microscopic images, visible light photographs, charts, and others. We complement it with OpenMedReason-Bench, a held-out benchmark that allows fine-grained evaluation of LVLMs along three complementary axes of capability, including perception, medical knowledge, and rationale, enabling diagnostic evaluation beyond final-answer accuracy. OpenMedReason is a rich training resource that exhibits its effectiveness in both supervised fine-tuning (SFT) and reinforcement-based alignment. Training with OpenMedReason yields a 20% average improvement in VQA accuracy over the base model and achieves performance within 4.2% of the strongest comparable-scale medical LVLMs. Fine-grained performance analysis confirms that the gains are not concentrated in any single axis: OpenMedReason improves perception, medical knowledge, and rationale jointly, and its reasoning traces are preferred over those of the base model in 86.1% of pairwise comparisons. We release the code and dataset at huggingface.co/datasets/neginb/OpenMedReason.

23.
medRxiv (Medicine) 2026-06-15

Beyond the Apnea-Hypopnea Index: Physiological and Demographic Predictors of Excessive Daytime Sleepiness in Obstructive Sleep Apnea

Excessive daytime sleepiness (EDS) is a common but inconsistently predicted symptom of obstructive sleep apnea (OSA). OSA is typically diagnosed with polysomnography (PSG), and the current standard for severity assessment is the apnea-hypopnea index (AHI). AHI has many limitations, including its inability to explain physiological mechanisms or reflect variability in patient symptoms, such as EDS. This retrospective study aims to find physiological and demographic parameters that better predict EDS in patients with OSA and to evaluate whether these parameters outperform AHI using PSG data from the Mount Sinai Integrative Sleep Center. Clinical variables used to predict EDS included arousal index (AI), average oxygen desaturation during sleep, average heart rate during sleep, and AHI, along with demographic variables including age, sex, and BMI. Hypothesis tests, logistic regression models, and decision tree classifier models were performed on the data to discriminate sleepy from nonsleepy patients as determined by an Epworth Sleepiness Scale (ESS) score [≥] 10. AI and oxygen desaturation were found to be the most predictive physiological variables, and sex and BMI were found to be the most predictive demographic variables. The final decision tree model with these four variables outperformed the AHI in predicting EDS. These findings suggest that daytime sleepiness in OSA can be better explained by measures of apnea burden, oxygenation impairment, and patient demographics than by AHI alone, although these remain only modestly predictive. Future studies should focus on investigating more comprehensive physiological markers, multi-night sleep data, and more objective assessments of sleepiness.

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

Differentiable Packing of Irregular 3D Objects with Adaptive Container Estimation

Most existing approaches either fix the container in advance or optimize only a single container dimension through an outer search loop, leaving the remaining dimensions as a manual tuning problem. We present a differentiable packing framework that jointly optimizes all 6N object pose parameters and all three container side lengths inside a single gradient-based loop. The formulation combines six physics-inspired, differentiable loss terms computed directly on triangle meshes through axis-aligned bounding-box proxies. An adaptive squeezing mechanism periodically tightens the container whenever the overlap loss falls below a pair-count-scaled threshold, producing a large initial drop in container volume, followed by small refinements. All pairwise computations are written in tensor-broadcasting form, giving a 3.4 to 54 times speedup over a reference loop-based implementation. The pipeline is implemented in Python and PyTorch, with no physics engine, FFT library, or convex decomposition. On multiple object categories, the method produces containers that are 11 to 32 percent smaller than time-matched DBLF and simulated-annealing baselines at N =100, while running in under 4 minutes per instance on a single consumer GPU.

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

HiMPO: Hindsight-Informed Memory Policy Optimization for Less-Entangled Credit in Long-Horizon Agents

Long-horizon agents rely on memory mechanisms to compress interaction history, but optimizing memory writing faces a distinct credit assignment challenge: a memory update may be rewarded or penalized due to downstream tool failures, noisy observations, or reasoning errors rather than its own contribution. This causally entangled credit can lead agents to discard useful evidence or preserve irrelevant information. We propose HiMPO, a Hindsight-Informed Memory Policy Optimization framework for assigning less-entangled credit to memory-writing actions in long-horizon agents. HiMPO first estimates the local utility of a memory update by comparing the task-relevant information recoverable from the previous and updated memories under the same pre-write state. It then uses hindsight relevance as a bounded retrospective filter that attenuates memory credit when local utility is not supported by the target outcome. The resulting memory-specific advantage is applied only to memory tokens, while trajectory-level rewards optimize the rest of the agent behavior. Across judge-based open-domain tasks and objective compressive-memory QA, HiMPO improves over strong memory-based and RL-based baselines while preserving compressed-context efficiency. Controlled interventions further show that HiMPO reduces blame leakage from tool-induced errors and improves attribution fidelity of memory updates.