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01.
arXiv (CS.LG) 2026-06-15

Adaptive Identification and Modeling of Clinical Pathways with Process Mining

arXiv:2512.03787v2 Announce Type: replace Abstract: Clinical pathways are specialized healthcare plans that model patient treatment procedures. They are developed to provide criteria-based progression and standardize patient treatment, thereby improving care, reducing resource use, and accelerating patient recovery. However, manual modeling of these pathways based on clinical guidelines and domain expertise is difficult and may not reflect the actual best practices for different variations or combinations of diseases. We propose a two-phase modeling method using process mining, which extends the knowledge base of clinical pathways by leveraging conformance checking diagnostics. In the first phase, historical data of a given disease is collected to capture treatment in the form of a process model. In the second phase, new data is compared against the reference model to verify conformance. Based on the conformance checking results, the knowledge base can be expanded with more specific models tailored to new variants or disease combinations. We demonstrate our approach using Synthea, a benchmark dataset simulating patient treatments for SARS-CoV-2 infections with varying COVID-19 complications. The results show that our method enables expanding the knowledge base of clinical pathways with sufficient precision, peaking to 95.62% AUC while maintaining an arc-degree simplicity of 67.11%.

02.
arXiv (CS.CL) 2026-06-18

Improve Large Language Model Systems with User Logs

Scaling training data and model parameters has long driven progress in large language models (LLMs), but this paradigm is increasingly constrained by the scarcity of high-quality data and diminishing returns from rising computational costs. As a result, recent work is increasing the focus on continual learning from real-world deployment, where user interaction logs provide a rich source of authentic human feedback and procedural knowledge. However, learning from user logs is challenging due to their unstructured and noisy nature. Vanilla LLM systems often struggle to distinguish useful feedback signals from noisy user behavior, and the disparity between user log collection and model optimization (e.g., the off-policy optimization problem) further strengthens the problem. To this end, we propose UNO (User log-driveN Optimization), a unified framework for improving LLM systems (LLMsys) with user logs. UNO first distills logs into semi-structured rules and preference pairs, then employs query-and-feedback-driven clustering to manage data heterogeneity, and finally quantifies the cognitive gap between the model's prior knowledge and the log data. This assessment guides the LLMsys to adaptively filter out noisy feedback and construct different modules for primary and reflective experiences extracted from user logs, thereby improving future responses. Extensive experiments show that UNO achieves state-of-the-art effectiveness and efficiency, significantly outperforming Retrieval Augmented Generation (RAG) and memory-based baselines. We have open-sourced our code at https://github.com/bebr2/UNO .

03.
arXiv (CS.LG) 2026-06-11

Restless bandits with imperfect binary feedback: PCL-indexability analysis and computation

arXiv:2606.11192v1 Announce Type: new Abstract: We study restless bandits with binary latent states and imperfect binary feedback, motivated by opportunistic spectrum access with sensing errors. For the associated belief-state model, we develop a partial conservation laws (PCL)-based analytical and computational framework for establishing indexability and evaluating the Whittle index, building on a verification theorem for real-state discounted restless bandits. The framework analyzes the stochastic dynamics via an associated deterministic skeleton, renewal decompositions, and combinatorics on words. It yields tractable expressions for discounted reward and resource metrics in several threshold regimes, enabling full verification of the PCL-indexability conditions there. For the remaining regime, where a complete analytic verification is not achieved in this paper, we derive efficient numerical schemes for computing the relevant marginal metrics and the marginal productivity (MP) index, which equals the Whittle index when those conditions hold. Extensive computational experiments provide strong evidence that these conditions also hold in that regime across broad parameter ranges and without the stringent parameter restrictions imposed in prior work. The experiments further show that theMP index policy typically outperforms standard benchmark policies, often by a substantial margin.

04.
arXiv (quant-ph) 2026-06-19

Progress on the Kretschmann-Schlingemann-Werner Conjecture

arXiv:2308.15389v4 Announce Type: replace Abstract: Given any pair of quantum channels $\Phi_1,\Phi_2$ such that at least one of them has Kraus rank one, as well as any respective Stinespring isometries $V_1,V_2$, we prove that there exists a unitary $U$ on the environment such that $\|V_1-({\bf1}\otimes U)V_2\|_\infty\leq\sqrt{2\|\Phi_1-\Phi_2\|_\diamond}$. Moreover, we provide a simple example which shows that the factor $\sqrt2$ on the right-hand side is optimal, and we conjecture that this inequality holds for every pair of channels.

06.
medRxiv (Medicine) 2026-06-11

Long-term exposure to PM2.5 components and lipid profiles in WTC Health Program general responders

Fine particulate matter (PM2.5) was found to be associated with elevated blood lipids, but fewer studies have examined the associations with specific constituents of PM2.5. We studied the associations between exposure to annual PM2.5 and its 14 constituents, and repeated blood lipid measurements among general responders enrolled in the World Trade Center Health Program between 2003 and 2019 (n = 44,876). We used generalized additive mixed effect models to investigate the single-pollutant associations with repeated measures of blood total cholesterol (TC), high and low-density lipoprotein (HDL-C and LDL-C) levels. We then used linear generalized weighted quantile sum regression with a random intercept for participant ID to account for the clustering of repeated measures and evaluate the combined associations with the component mixture. A decile increase in the mixture of 14 PM2.5 chemical components was associated with 0.375 mg/dL increase in TC levels (95% confidence Interval (CI): 0.174-0.577) and 0.302 mg/dL increase in LDL-C (95% CI: 0.063, 0.540). Lead, organic carbon, and iron were major drivers of both associations. Component-specific models also show higher TC and LDL levels associated with interquartile range increases in organic carbon (0.472, 95% CI [0.027, 0.918] and 0.648 95% CI [0.136, 1.160]) and iron exposure (1.081, 95% CI [0.630, 1.532] and 0.748, 95% CI [0.318, 1.178]). In conclusion, we found PM2.5 exposure to be associated with elevated lipid levels. The associations differed by PM2.5 composition, highlighting organic carbon, lead, and iron and major drivers. These findings are highly significant for a population exposed to extreme air pollution event and susceptible to lipid alterations that might trigger cardiovascular events.

07.
arXiv (CS.LG) 2026-06-15

Nonlinear Two-Time-Scale Stochastic Approximation: A Sharp Phase Transition and How to Beat It

arXiv:2606.14488v1 Announce Type: cross Abstract: Recent finite-time analyses of nonlinear two-time-scale stochastic approximation show that under contractive assumptions the slow iterate $Y_k$ with stepsizes $\beta_k=\Theta(k^{-1})$ and $\alpha_k=\Theta(k^{-a})$, $a\in(1/2,1)$, generally satisfies a mean-square rate of order $k^{-a}$; decoupled $k^{-1}$ rates require strong local linearity. We identify a sharp regularity-dependent boundary. In a rate-determining normal form where the slow drift contains a locally linear leakage and a nonlinear remainder of order $1+\rho$ ($\rho\in[0,1]$), the uncorrected recursion satisfies \[ \mathbb{E}\|Y_k\|^2 \le C\bigl(k^{-1}+k^{-a(1+\rho)}\bigr), \] and a matching scalar Gaussian lower bound shows that the slower term is unavoidable without modifying the update. Thus the decoupled $k^{-1}$ rate is guaranteed for the uncorrected recursion exactly when $a(1+\rho)\ge 1$. This lower bound concerns only the naive update; it is not an information-theoretic obstruction. We demonstrate this by equipping the normal-form recursion with an auxiliary online bias estimator \[ M_{k+1}=M_k+\gamma_k(R(X_k)-M_k),\qquad \beta_k\ll\gamma_k\ll\alpha_k, \] and subtracting $M_k$ from the slow update. Under the same stability, moment, and remainder assumptions, the corrected recursion achieves $\mathbb{E}\|\widetilde Y_k\|^2=O(k^{-1})$ for every $\rho\in[0,1]$, including regimes where the uncorrected update provably suffers the slower rate. Finally, we prove localized transfer theorems that extend the phase-transition mechanism to general nonlinear TTSA in fast-manifold coordinates. The proofs are non-asymptotic and rely on two Abel-transform cancellations: one for the locally linear fast-error leakage, and one for the tracked nonlinear bias.

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

Federated Bilevel Performative Prediction

arXiv:2606.19734v1 Announce Type: new Abstract: Federated bilevel optimization is widely used for nested learning problems across distributed clients, such as federated hyperparameter tuning and meta-learning under privacy and communication constraints. Most existing formulations assume fixed client data distributions, which can be violated by performativity, where deployed decisions reshape client behavior and data collection, inducing client-specific, decision-dependent distribution shift. We study federated bilevel performative prediction, where both upper-level (UL) and lower-level (LL) objectives are evaluated under client-dependent, decision-dependent distributions. We formalize the federated bilevel performatively stable (FBPS) point under a decoupled-risk perspective and provide sufficient conditions for its existence and uniqueness. We then develop two federated methods to compute the FBPS solution: FBi-RRM, which converges linearly under a contraction condition, and FBi-SGD, a communication-efficient stochastic method based on federated hypergradient estimation with convergence guarantees under diminishing step sizes when sensitivities are sufficiently small. Experiments on strategic regression and meta strategic classification validate the predicted stability thresholds and demonstrate improved meta-generalization over non-performative baselines, and CNN-based classification further demonstrates the practical effectiveness of the proposed methods in nonconvex neural network settings.

09.
arXiv (CS.LG) 2026-06-16

Repeated Bilateral Trade: The Quest for Fairness

arXiv:2606.15369v1 Announce Type: new Abstract: We study repeated bilateral trade from a fairness perspective. At each round, a fresh seller-buyer pair arrives, and the platform posts a price before observing the traders' valuations. Trade occurs only if both agents accept the price. Rather than maximizing only the gain from trade, we consider platforms that seek balanced divisions of the generated surplus. We show that natural fairness desiderata lead to a one-parameter Rawls-to-Nash family of fair-gain objectives, obtained by aggregating the seller's and buyer's net gains through nonpositive Hölder means. Unlike the standard gain-from-trade objective and the Rawlsian fair-gain objective studied in prior work, our proposed objectives induce a new statistical structure in which expected rewards are recovered from threshold feedback through a two-dimensional singular-kernel integral identity. This leads to a nonstandard pure-exploration problem whose natural estimators are rectangular double sums with row-column dependence and singular weights. Assuming independent i.i.d. seller and buyer valuation sequences with arbitrary unknown marginals, we characterize the optimal learning rates for the whole Rawls-to-Nash family of fair-gain objectives, giving matching fixed-confidence sample-complexity and regret bounds up to polylogarithmic factors.

10.
arXiv (quant-ph) 2026-06-19

Nearest-neighbour gates are all you need: High-rate quantum low-density parity-check codes on a planar grid

arXiv:2606.19482v1 Announce Type: new Abstract: High-performance quantum low-density parity-check codes promise substantial reductions in the overhead of fault-tolerant quantum computation, but most constructions require long-range connectivity or qubit shuttling, both of which are difficult to realise in superconducting architectures. Here we introduce a family of quantum low-density parity-check codes that, for the first time, combines planar open-boundary layouts, finite-size advantages over surface codes, and syndrome extraction using only nearest-neighbour gates on a square grid of qubits. The key idea is to generate check-data connectivity dynamically: nearest-neighbour iSWAP walks both define the stabiliser supports and implement their measurement, avoiding the need for a long-range hardware graph. The resulting circuits achieve optimal constant-depth stabiliser measurement, independent of code size, and naturally remove leakage from the system by exchanging the role of check and data qubits at each syndrome extraction round. We find finite-size instances such as a [[323,14,15]] code, whose code-efficiency ratio is nearly an order of magnitude larger than that of rotated surface-code patches. At around 30 circuit qubits per logical qubit, the best directional tile-code layouts reduce the per-logical per-round logical error rate by up to a factor of 1000 relative to rotated surface-code memories. These results show that the advantages of quantum low-density parity-check codes can survive compilation into strictly planar nearest-neighbour circuits, bringing low-overhead fault-tolerant memories closer to near-term hardware.

11.
arXiv (quant-ph) 2026-06-25

A Short Note on the Generators of Controlled Quantum Gates

arXiv:2606.25789v1 Announce Type: new Abstract: We present the analytical generators for arbitrary multi-qubit controlled gates. Closed forms for the generating Hamiltonians are given for gates with both multiple control and target qubits, as well as for arbitrary control conditions. This allows us to go beyond gate-based simulations of quantum circuits and incorporate decoherence and other noise in simulations of quantum computers. We exemplify this by simulating the impact of a harmonic oscillator interacting with two qubits during the application of a controlled NOT gate.

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

Stochastic trace estimation with tensor train random vectors

arXiv:2606.15679v1 Announce Type: cross Abstract: Stochastic trace estimation is a standard tool for approximating the trace of a large-scale matrix available only through matrix-vector products. However, in tensor-structured settings, unstructured Gaussian or Rademacher test vectors may be prohibitively expensive to store and compute with, while cheaper rank-one tensor-product vectors can require sample complexities that grow exponentially with the tensor order. This work studies Gaussian random tensor train vectors as a structured alternative for stochastic trace estimation. We show that, with a suitable choice of the tensor train rank, random tensor train vectors recover dimension-independent guarantees for the Girard–Hutchinson estimator. In particular, a median-of-means variant with tensor train rank $r \geq d-1$ achieves the same dependence on the accuracy $\varepsilon$ and failure probability $\delta$ as the classical estimator based on unstructured Gaussian vectors. We further prove an oblivious subspace injection result for sketches formed from independent Gaussian random tensor train vectors: tensor train rank $r\geq d-1$ and $\mathcal{O}(\varepsilon^{-2}(k+\log(1/\delta)))$ samples suffice for a $k$-dimensional target subspace. Finally, we investigate the use of such sketches within the Nystr\"{o}m++ framework. We show that the resulting estimator can achieve the desired $\mathcal{O}(\varepsilon^{-1})$ sample complexity under an additional spectral-tail condition. These results provide clarififcation on both the potential and the limitations of random tensor train vectors in stochastic trace estimation.

13.
arXiv (CS.CV) 2026-06-24

Quantum CT via Dynamic Interval Encoding and Prior-Balanced QUBO Reconstruction

Quadratic unconstrained binary optimization (QUBO)-based quantum computed tomography (CT) casts reconstruction as a binary quadratic problem for quantum annealing and hybrid quantum–classical solvers. For grayscale CT, however, image encoding is constrained by the binary-variable budget: fixed global bit-plane encodings increase QUBO size and coupling complexity as gray-level precision improves, whereas low-bit encodings introduce quantization error. We propose a QUBO-based grayscale CT reconstruction framework that combines dynamic interval encoding with prior-balanced optimization. Each refinement round encodes active pixels only within local gray-level intervals around the current estimate, and a boundary-hit-guided update rule adaptively switches between search expansion and local refinement. To improve optimization stability, the method balances projection-domain data consistency and an edge-preserving quadratic prior before forming the final QUBO. Sparse-view and limited-angle fan-beam CT experiments show that the proposed method recovers structures and gray-level distributions more faithfully than the evaluated analytic, iterative, variational, and representation-based baselines. Expressivity analysis and ablation studies further indicate that the improvement mainly arises from effective gray-level representation through dynamic local encoding and more stable data-fidelity–prior coupling. Experiments on the D-Wave hybrid binary quadratic model (BQM) solver further demonstrate that the formulation is executable on a hardware-backed hybrid quantum–classical backend.

14.
bioRxiv (Bioinfo) 2026-06-24

An atlas-scale generative model for unified representation learning of bulk RNA-seq data

Public bulk RNA-seq repositories contain hundreds of thousands of samples, creating opportunities for large-scale representation learning, but integration across studies remains challenging because of heterogeneous annotations, experimental protocols, and technical variation. While pre-trained foundation models are now widely available for single-cell RNA-seq, comparable resources for bulk RNA-seq remain scarce, motivating a model that learns a unified, tissue-aware representation directly from bulk data. We trained a supervised variational autoencoder (VAE) on a compendium of 118,263 bulk RNA-seq samples that we assembled from TCGA, GTEx, and ARCHS4 and mapped to 42 tissue categories. The model classifies tissue of origin at 94.9% balanced accuracy (weighted F1 96.2%) and compresses 16,115 genes into a 121-dimensional latent space. Tissue identity is the primary organizing axis of the latent space, while source effects remain secondary. To assess the impact of data volume, we constructed training sets at three different scales (38K, 75K, and 118K samples). Our results demonstrated that reconstruction fidelity improved incrementally with each expansion of the dataset, but with diminishing returns. We validated the model on an independent cohort of 734 paediatric tumour samples from TARGET, achieving 84.6% agreement with the expected tissue of origin. The trained model and code are available at GitHub (https://github.com/BIMSBbioinfo/flexynesis_tissue_vae_manuscript) with an interactive web application.

15.
arXiv (CS.LG) 2026-06-18

Diffusion-Proof: Recipe for Formal Theorem Proving Beyond Auto-Regressive Generation

arXiv:2606.19315v1 Announce Type: new Abstract: Enhancing the formal math reasoning capabilities of Large Language Models (LLMs) has become a key focus in both mathematical and computer science communities in recent years. While significant progress has been made in using state-of-the-art Auto-Regressive (AR) LLMs for formal theorem proving, these models suffer from inherent limitations. Their next-token prediction generation methods may yield suboptimal performance due to the challenges of long-range coherence and the compounding of errors over long sequences. Recent advancements in diffusion LLMs (dLLMs), which generate text through iterative denoising of a multi-token block, offer a promising alternative. However, the application of dLLMs to formal mathematics, where maintaining long-range coherence is critical, remains largely understudied. To address the challenges above, we propose **Diffusion-Proof**, to the best of our knowledge, the first framework to train and apply dLLMs for formal theorem proving. Our frameworks contain training and inference methods for two models. The first one is *dLLM-Prover-7B*, which performs whole-proof writing with long-range coherent tactic usage. The second one is *dLLM-Corrector-7B*, which is a novel large block diffusion-based correction model. It leverages the in-filling capabilities of dLLMs to perform local proof correction using bi-directional information. Extensive experiments demonstrate that **Diffusion-Proof** relatively significantly outperforms the AR LLM baseline trained under the same dataset. **Diffusion-Proof** achieves an absolute improvement of **1.61%** on ProofNet-Test and **6.14%** on MiniF2F-Test benchmarks compare to the baseline. Notably, **Diffusion-Proof** successfully resolves one IMO problem that more advanced thinking model DeepSeek-Prover-V2-7B could not solve, showcasing the unique advantage of dLLMs in formal theorem proving.

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

SSMNBench: Diagnosing Image-based Cross-View Human-Object Understanding via Single-View Sufficiency and Multi-View Necessity

Multimodal Large Language Models (MLLMs) have shown remarkable progress in single-image perception, yet their ability to reason about complex cross-view human-centric scenes remains largely unverified. Current multi-view benchmarks evaluate models using a fixed "bag of frames" and thus conflate a model's robustness to visual distraction with its genuine ability to fuse fragmented cross-view evidence. To address this issue, we introduce SSMNBench, a diagnostic benchmark comprising 3,300 curated QA pairs for cross-view human and human-object understanding. SSMNBench uniquely categorizes tasks into Single-View Sufficiency (SVS) and Multi-View Necessity (MVN). By systematically perturbing view availability across 17 state-of-the-art MLLMs, critical limitations are revealed: models suffer from severe "distraction degradation" when presented with redundant views (SVS), and fail to integrate fragmented geometric evidence across cameras (MVN). Our evaluations demonstrate that modern MLLMs rely on multiple single-image semantic averaging and view preference rather than genuine cross-view synthesis. By exposing these fundamental vulnerabilities, SSMNBench provides a rigorous diagnostic framework to drive the advancement of future cross-view-aware multimodal architectures. The code is available at: $ \href{https://github.com/gtc-gh/SSMNBench}{SSMNBench} $

18.
arXiv (CS.AI) 2026-06-24

ATHENA: Agentic Team for Hierarchical Evolutionary Numerical Algorithms

arXiv:2512.03476v3 Announce Type: replace-cross Abstract: Progress in computational science depends on complex numerical workflows that must faithfully encode physical laws, yet translating conceptual insight into reliable code remains a major bottleneck. Although large language models can generate isolated code fragments, they lack the structured reasoning required to design, verify, and iteratively refine complete scientific pipelines. Here we introduce ATHENA, an agentic framework explicitly designed to emulate scientific research modeled as a knowledge-driven contextual bandit process. Its core loop separates conceptual policy from numerical realization through expert-derived conceptual scaffolding, enabling principled diagnosis, reformulation, and repair of computational strategies. Across scientific computing and scientific machine learning tasks, ATHENA autonomously derives and correctly applies exact analytical solutions, constructs stable numerical solvers, diagnoses ill-posed formulations, and orchestrates hybrid symbolic-numeric workflows. Quantitatively, ATHENA matches and frequently surpasses the accuracy of expert-authored reference solutions reported in the literature on canonical benchmarks. By reframing computation as an object of agentic reasoning, our framework enables autonomous orchestration of heterogeneous algorithms across scientific domains.

19.
medRxiv (Medicine) 2026-06-16

Development and reliability and validity test of the Questionnaire on Knowledge, Attitude and Practice of ICU Nurses on Blood Oxygen Saturation Management in Mechanically Ventilated Patients

Objective: A questionnaire on the knowledge, attitude and practice of ICU nurses regarding the management of blood oxygen saturation in patients with mechanical ventilation was compiled, and its reliability and validity were tested. Method: Drawing upon the knowledge-attitude-practice theory, the initial questionnaire draft was developed through literature review and consultation with Delphi experts. Employing convenience sampling, 32 nurses from the General ICU of Wuxi Second People's Hospital were surveyed between 1 August 2025 and 27 September 2025, enabling item screening and assessment of reliability and validity.The full version of the developed questionnaire is provided as Supporting Information (S1 File). All items are published under a CC BY 4.0 license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Result: A questionnaire on the knowledge, attitude and practice of ICU nurses regarding the management of blood oxygen saturation in mechanically ventilated patients was finalised, comprising 26 items: 11 in the knowledge dimension, 6 in the attitude dimension and 9 in the behaviour dimension. The overall Cronbach's coefficient for the questionnaire was 0.88, with dimension-specific coefficients of 0.787, 0.722, and 0.781 respectively. The Spearman-Brown coefficient for the entire questionnaire was 0.967, while dimension-specific coefficients were 0.796, 0.666, and 0.728 respectively. The content validity index at the questionnaire level (S-CVI) was 0.886, and the item-level content validity index (I-CVI) ranged from 0.913 to 0.967. 0.728. The questionnaire's level content validity index (S-CVI) was 0.886, and the item level content validity index (I-CVI) ranged from 0.913 to 1.00. Conclusion: The questionnaire on knowledge, attitude and practice of blood oxygen saturation management in mechanically ventilated patients demonstrates good reliability and validity. It may serve as an assessment tool for intensive care unit nurses regarding their knowledge, attitude, and practices concerning blood oxygen saturation management in mechanically ventilated patients, thereby establishing a foundation for developing targeted intervention strategies in future practice.

20.
medRxiv (Medicine) 2026-06-18

Distinct Neuronal, Proliferative, and Secretory Pathways are Perturbed in Cancer Survivors with Depressive Symptoms

Introduction Depression is highly prevalent among cancer survivors and may be biologically distinct, although clinical studies investigating these mechanisms remain limited. Thus, the aims of this study were to (1) identify perturbed biological pathways associated with depressive symptom severity in cancer survivors, and (2) investigate whether these pathways are common or distinct to those perturbed in an age-matched non-cancer cohort. Methods We analyzed cross-sectional self-reported and transcriptomic data from the Multi-Ethnic Study of Atherosclerosis (PHD #39341). Cancer survivors and an age-matched non-cancer cohort (target ratio 1:2) were identified. The 20-item Center for Epidemiologic Studies Depression Scale (CES-D) was used to split participants into low (CES-D

21.
Nature (Science) 2026-06-24

Alternate RNA decoding results in stable and abundant proteins in mammals

作者:

Amino acid substitutions may substantially alter protein stability and function1,2. However, the contribution of substitutions that arise from alternate translation (deviations from the genetic code) is unknown. Here to address this issue, we analysed deep proteomic, transcriptomic and genomic data from more than 1,000 human samples, including 6 cancer types and 26 healthy human tissues. This global analysis identified 60,803 fragmentation spectra corresponding to 8,746 unique substitutions in proteins derived from 1,767 genes, including 1,955 confidently localized sites. Some substitutions were shared across samples, whereas others exhibited strong tissue-type and cancer specificity. Notably, products of alternate translation were more abundant than their canonical counterparts for hundreds of proteins, which suggests that there is sense-codon recoding. Recoded proteins included transcription factors, proteases, signalling proteins and proteins associated with neurodegeneration. Mechanisms that contribute to substitution abundance included protein stability, codon frequency, codon–anticodon mismatches and RNA modifications. We also characterized how alternatively translated proteoform ratios vary across protein domains, tissue types and cancers. These ratios were positively associated with intrinsically disordered regions and genetic polymorphisms in the gnomAD database, although the polymorphisms could not account for the substitutions. The sequence, relative abundance and the tissue specificity of alternatively translated proteins were conserved between humans and mice. These results demonstrate the contribution of alternate translation to the diversification of mammalian proteomes and its association with protein stability, tissue-specific proteomes and disease. Alternate RNA decoding, an understudied process, leads to peptide sequence modifications that can have substantial functional effects on protein stability, tissue-specific proteomes and disease.

22.
medRxiv (Medicine) 2026-06-10

Assessment of the accuracy of lung lesions diagnosis in adolescents with osteosarcoma using artificial intelligence

Background. Lung metastases in osteosarcoma (OS) are the main cause of the death. The accuracy of the diagnosis of nodules by computed tomography (CT) of the lungs is critically important for determining the disseminated stage of the disease and planning surgical treatment. The use of artificial intelligence (AI) in the search for lung nodules increases the accuracy of diagnosis and reduces the chance of missing metastases. Objective: to evaluate the accuracy of lung nodules diagnosis in adolescents with OS using AI. Methods. A retrospective assessment of CT scans of adolescents with OS was performed. A pathological nodule with an average size of [≥]4 mm was considered a target finding. The diagnostic accuracy of an AI algorithm previously trained on an adult dataset was evaluated, and the number of false positives (FP) and false negatives (FN) was determined. Sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, and F1-measure were calculated. Based on the obtained results, the effectiveness of the algorithm was assessed. Results. 248 CT scans of adolescents with OS were evaluated. The following results were obtained: in 5 cases, the AI algorithm showed a FP result (2.02%), in 34 cases, it showed a FN result (13.71%), and in 209 cases, a correct result (both true positive and true negative) (84.27%). The diagnostic accuracy of the algorithm was 0.843 (95% CI 0.794-0.887). The application of the AI algorithm in the practice of an X-ray doctor in a specific clinical task would allow to increase the sensitivity from 0.805 to 0.891, while ensuring an absolute decrease in the number of FN results by 8.59% and a relative decrease by 44%. Conclusion. The obtained results confirm the practical value of the application of the AI algorithm and justify the implementation of AI-assisted systems in the diagnostic protocols for lung metastases in adolescents with OS.

23.
arXiv (math.PR) 2026-06-18

Rigidity of infinite exchangeable sequences with Gaussian marginals

arXiv:2606.18654v1 Announce Type: new Abstract: We study infinite exchangeable sequences with Gaussian one-dimensional marginals. We formulate the conjecture that joint Gaussianity of a single pair of coordinates forces the entire sequence to be a Gaussian process. Although this conjecture remains open, we prove that joint Gaussianity of the first four coordinates is sufficient. We also establish the corresponding two-point criterion under the additional assumption that the directing measure is almost surely infinitely divisible.

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

MDForge: Agentic Molecular Dynamics Pipeline Design under Sparse Simulator Feedback

Molecular dynamics (MD) is the canonical in-silico method for atomistic molecular science, simulating molecular behavior from first-principle physics. Designing an MD pipeline for a new system requires substantial expert knowledge: running it on even one molecule is expensive, ruling out trial-and-error. We automate this expert pipeline-design process with an LLM agent. Unlike existing MD agents that orchestrate a predefined tool set, we treat pipeline design as open-ended code generation in which the agent's behavior is reshaped online by verbal reward. Specifically, we build MDForge, an LLM agent whose in-context update rule densifies the sparse reward via a multi-agent debate among physics experts. On three SAMPL host-guest binding free-energy benchmarks, MDForge automatically designs MD pipelines competitive with human experts. Deployed on a library of unseen candidate guests, its CB[7] pipeline discovers a novel binder that wet-lab competition NMR confirms is a high-affinity, picomolar CB[7] binder. Our data and code are available at https://github.com/Zehong-Wang/MDForge.

25.
bioRxiv (Bioinfo) 2026-06-11

A quantitative coordinate system for developmental dynamics

Quantitative comparison of morphogenesis across individuals remains a fundamental challenge, as developing embryos vary in shape, orientation and developmental tempo. Moreover, real-time three-dimensional imaging generates large, heterogeneous four-dimensional datasets that are difficult to directly align. As a result, developmental variability is typically described qualitatively rather than measured. Here we introduce STERN, a quantitative framework that learns continuous spatiotemporal representations of morphogenesis directly from in vivo 4D imaging data. By embedding embryos into a shared spatiotemporal space, STERN defines a quantitative developmental coordinate system that enables direct comparison of developmental trajectories across individuals without requiring explicit registration or staging. Applied to mouse embryogenesis, STERN reveals that embryos follow conserved developmental trajectories while progressing at distinct temporal rates, providing a quantitative measure of developmental heterochrony. Extending this framework to zebrafish neural crest light-sheet timelapse imaging, we further show that developmental order is preserved across distinct imaging views even with altered anatomical coverage, supporting the generality of the learned representation across vertebrate imaging contexts. Finally, in developing mouse hearts, where morphogenesis proceeds through subtle and continuously evolving structural changes, STERN resolves fine-scale developmental dynamics at minute-scale temporal resolution that are difficult to localize reproducibly using human experts or general-purpose multimodal AI. Together, these results establish a shared quantitative coordinate system for morphogenesis, in which developmental trajectories become directly comparable across individuals and developmental variability becomes a measurable property.