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

SpheriCity: Designing Trustworthy Conversational AI for Sustainability Decision Support

Authors:
Ahmed Qayyum↗Madison Werner↗Kathryn Youngblood↗Jenna R. Jambeck↗Tahiya Chowdhury↗

arXiv:2606.13854v1 Announce Type: cross Abstract: We present SpheriCity, an expert-grounded conversational prototype designed to support trustworthy knowledge sensemaking from sustainability reports. City-level circularity assessment reports contain rich information about materials, infrastructure, and policy interventions, yet their length and heterogeneous structure make cross-document synthesis and comparison difficult for practitioners and researchers working on circular economy initiatives. While large language models (LLM) promise faster knowledge access and synthesis, their opaque reasoning, hallucinations, and lack of source transparency introduce risks for trust and interpretability, and require verification in high-stakes sustainability contexts. SpheriCity addresses these challenges through a provenance-first conversational agent that foregrounds evidence traceability, structured synthesis, and interaction scaffolds to support exploratory querying and cross-document synthesis across sustainability reports. We conducted a formative expert review with six sustainability experts using representative queries spanning cross-city comparison, policy summarization, and recommendation-oriented tasks. Experts evaluated responses across dimensions and provided qualitative reflections on the system's usefulness for sustainability knowledge work. Our results reveal that transparent sourcing, contextual explanation, interpretability, and alignment with expert workflow strongly shape expert trust and judgments of system usefulness. This work contributes (1) a conversational prototype for sustainability knowledge sensemaking, (2) an expert-grounded evaluation framework for assessing AI responses in high-stakes knowledge domains, and (3) design insights into how provenance, uncertainty communication, and integration in workflow influence expert users' trust in AI assistance for sustainability decision support.

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02.
arXiv (CS.AI) 2026-06-17

How Inference Compute Shapes Frontier LLM Evaluation

Authors:
Jessica McFadyen↗Ole Jorgensen↗Harry Coppock↗Kevin Wei↗Cozmin Ududec↗

arXiv:2606.17930v1 Announce Type: new Abstract: AI evaluations are shifting toward harder tasks that benefit from longer trajectories involving tool use and iterative problem solving. As a result, performance is increasingly sensitive to the amount and allocation of compute available at test time ("inference compute"). Yet many evaluations still report performance at a single restrictive budget, meaning that low scores may reflect the evaluation setup rather than the model's underlying capability. To test this, we evaluate up to 12 frontier language models on seven challenging benchmarks spanning software engineering, mathematics, medicine, and cybersecurity. We use a controlled setup combining three simple inference-scaling interventions: larger token budgets, context compaction, and repeated submission attempts, guided either by the model itself or by minimal correctness feedback. We find three main results. First, larger token budgets substantially improve performance on benchmarks across multiple domains, including cybersecurity, FrontierMath, Humanity's Last Exam, and TerminalBench. Second, fixed-budget evaluations can increasingly understate frontier capability as models advance. Newer models reach higher performance at large budgets, where they unlock harder tasks and solve them more reliably. Third, benchmarks differ in which inference-scaling methods help most: repeated submission broadly improves performance, but the value of larger token budgets, external feedback, and parallel attempts varies by benchmark. Overall, our results show that benchmark scores are protocol-dependent. We therefore argue that evaluations should report capability as a function of inference-time compute, specify protocol choices explicitly, and compare model generations over a large shared compute range at matched budgets, especially in safety- or policy-relevant settings.

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03.
arXiv (CS.AI) 2026-06-18

NeSyCat Torch: A Differentiable Tensor Implementation of Categorical Semantics for Neurosymbolic Learning

Authors:
Daniel Romero Schellhorn↗Till Mossakowski↗Bj\"orn Gehrke↗

arXiv:2606.19279v1 Announce Type: new Abstract: Neurosymbolic semantics is fragmented: classical, fuzzy, probabilistic and neural systems each define truth by their own inductive rules. NeSyCat, extending ULLER, subsumes them under a single inductive definition of truth, parametric in a strong monad and an aggregation structure on truth-values. NeSyCat has so far lacked an account of predicates and functions learned by neural networks. We provide NeSyCat Torch as the missing link and interpret computational symbols via neural networks, implementing the framework in probabilistic programming and tensor-based backends. We use the distribution monad for reference semantics and metric evaluation, and complement it by a monad for numerically stable, differentiable training: the lazy log-tensor monad over the log-semiring. For efficient training in batches, we furthermore employ a batch monad. The axioms are the source code: written once in monad-based do-notation, monadic bind performs marginalisation, lazily pruning unneeded branches. On MNIST addition, our HaskTorch, JAX, and PyTorch implementations outperform LTN and DeepProbLog in speed and accuracy, while achieving nearly the accuracy of DeepStochLog. However, unlike DeepStochLog, we stay in a uniform framework that applies to many first-order NeSy approaches. Namely, the construction is parametric in the monad; instantiating it with, e.g., the Giry monad extends the approach to continuous probability (working out a neural representation here is left for future work).

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04.
bioRxiv (Bioinfo) 2026-06-11

OCOO-T : A SIMPLE AND SCALABLE VIRTUAL CELL MODEL FOR TRANSCRIPTIONAL PERTURBATION RESPONSE PREDICTION

Authors:
Zhao↗Lai↗Jiang↗An↗

Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

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05.
arXiv (CS.AI) 2026-06-19

Computational Identifiability

Authors:
Lucius E. J. Bynum↗Rajesh Ranganath↗Kyunghyun Cho↗

arXiv:2606.19361v1 Announce Type: cross Abstract: Identification conditions describe the computability of a target query or parameter of interest as a function of the type and amount of information available. In causal identification, this information is often expressed in the form of a causal graph, and data are observed or collected for some subset of variables in the graph. Target queries may be for a single effect alone or for a class of effects in a given model. The derivation of an identification algorithm then defines mathematically the process by which the desired causal effect(s) can be uniquely determined, theoretically, in expectation. Identifiability in expectation, or 'theoretical identifiability,' generally assumes asymptotic properties, infinite data, or other mathematically idealized conditions. In this paper, we explore a fundamental distinction between this theoretical, idealized notion of identifiability and a proposed alternative that is computation-bound. The framework we propose - 'computational identifiability' - is to instead define a finite computational search procedure for an empirical estimator. If this process finds an estimator empirically, within a desired error tolerance, then identifiability is satisfied, conditional on the specified assumptions of the search (i.e., a prior distribution over the parameters) and conditional on the search procedure itself. Through several experiments, we demonstrate how this framework allows us to answer fine-grained, practical identification questions, such as identification with small finite samples, with ambiguous graphical criteria, with mixed observational-interventional data, and across counterfactual data and estimands. Code is available at https://github.com/lbynum/metadentify.

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06.
Science (Express) 2026-06-11

Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle | Science

Authors: Unknown Author

The identification of the cancer cell of origin is a fundamental question in cancer biology. We used fluorescent lineage tracing of independent mouse skin stem cell populations, single cell transcriptomics, and Duplex sequencing, to identify the origin of chemically induced skin tumors. Tumors arose predominantly from Lgr6+ and / or Lrig1+ stem cells of the upper hair follicle, but only very rarely from the Lgr5 + and Krt19 + hair follicle bulge. Lgr6 + stem cells initiated by dimethylbenzanthracene responded to tumor promoter treatment resulting in clonal expansion of initiated cells carrying the canonical Hras Q61L mutation. Spontaneous mutations in Kras also clonally expanded, but did not generate tumors unless the Hras gene was deleted, thus revealing a competitive interaction between Hras and Kras pathways that influences clonal selection.

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

XAI-Grounded Explanation Generation for Speech Deepfake Detection with Training-Free Multimodal Large Language Models

Authors:
Yupei Li↗Qiyang Sun↗Xiaoliang Wu↗Chenxi Wang↗Berrak Sisman↗Bj\"orn W. Schuller↗

Speech deepfake detection (SDD) systems require trustworthy explanations for reliable decision-making. Existing explanation ways mainly fall into two categories. Traditional explainable AI (XAI), such as gradient-based attribution, produces low-level attribution signals tightly coupled with model decisions, and harder to be understood by human than natural language explanations. Meanwhile, large language model (LLM)-based explanation generation often produces generic and ungrounded descriptions due to the lack of heuristic evidence and task-specific supervision, stemming from limited grounded explanation datasets for SDD. We therefore propose a training-free explanation framework that integrates XAI evidence with multimodal LLMs to generate grounded and specific explanations. Using the PartialSpoof dataset, we construct a grounded explanation dataset and show that methods with XAI increase inside accuracy by over 45\%, verified through human evaluation and faithfulness checks.

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

On the Redundancy of Timestep Embeddings in Diffusion Models

Authors:
Jos\'e A. Ch\'avez↗

arXiv:2606.20416v1 Announce Type: new Abstract: Diffusion models rely heavily on explicit timestep embeddings to modulate the denoising process across various noise scales. In this work, we challenge the necessity of these temporal signals by analyzing their impact on U-Net and Diffusion Transformer architectures. Beyond empirical evidence, we provide a theoretical framework demonstrating that, under certain conditions, the global minimizer of the diffusion training objective can be achieved without explicit timestep conditioning. Our findings reveal a surprising robustness when timestep embeddings are completely removed. Extensive ablation studies on the CelebA and CIFAR-10 datasets show that these time-agnostic models can maintain high structural fidelity and even surpass their conditioned counterparts in competitive metrics, including FID, precision, and recall. Our analysis suggests these architectures can implicitly infer noise scales from the corrupted input under specific assumptions, rendering explicit temporal conditioning redundant. This study challenges long-standing temporal conditioning paradigms and paves the way for more efficient and structurally focused generative architectures.

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09.
arXiv (CS.AI) 2026-06-17

Any2Any: Efficient Cross-Embodiment Transfer for Humanoid Whole-Body Tracking

Authors:
Ming Yang↗Tao Yu↗Feng Li↗Hua Chen↗

arXiv:2605.23733v2 Announce Type: replace-cross Abstract: Whole-body tracking (WBT) models have become a key foundation for humanoid robots, enabling them to imitate diverse motions with high fidelity. Training such models from scratch requires large-scale data and computation, making rapid deployment on new humanoid platforms costly. This raises a natural question: Can pretrained WBT models transfer across embodiments with minimal adaptation? To answer this question, we propose Any2Any, a paradigm that efficiently transfers an existing WBT specialist to a new humanoid embodiment with only a small amount of data and compute. Any2Any first performs kinematic alignment between source and target humanoids, aligning their input and output spaces so that the pretrained source policy can be meaningfully reused on the target embodiment.Any2Any then performs dynamics adaptation by applying lightweight parameter-efficient fine-tuning (PEFT) components to selected dynamics-sensitive modules, preserving useful behavioral priors while enabling targeted adaptation to the target robot. Extensive experiments on multiple humanoid platforms and pretrained backbones show that Any2Any substantially accelerates convergence and reduces training cost compared with training from scratch, while achieving competitive or superior tracking performance. Notably, using only 1% of the compute and data required for full training, Any2Any successfully transfers Sonic models pre-trained on Unitree G1 to LimX Oli and LimX Luna. These results suggest that pretrained WBT specialists can be efficiently reused across embodiments, providing a scalable path toward deploying humanoid whole-body control on new robots.

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

Acquisition state behaves as a structured, measurable variable governing lung-nodule AI: kernel-driven measurement instability and noise-driven detection fragility, invisible to DICOM metadata

Authors:
Daniel Soliman↗

AI governance for medical imaging is formalizing: the 2026 ACR-SIIM Practice Parameter recommends local acceptance testing and ongoing drift monitoring, and the ACR Assess-AI registry monitors AI outputs using DICOM metadata for context. We argue that a necessary, currently unmonitored layer sits beneath output metrics: whether incoming studies remain within the acquisition envelope a model was validated on. Using a LUNA16-trained MONAI RetinaNet lung-nodule detector, we test whether acquisition state behaves as a structured, measurable variable. On real paired CT differing only in reconstruction kernel (NLST B30f vs B80f), kernel alone shifted AI-measured diameter and flipped a Fleischner size category in 5.2% (8 of 155) of nodules at fixed patient and acquisition, while detection confidence was unchanged (Wilcoxon p=0.22). Under controlled LIDC-IDRI perturbations the effects dissociated by axis: the noise axis degraded detection confidence (p=5.9e-32, concentrated in nodules under 6 mm) but not measurement, while the frequency/kernel axis corrupted measurement (p=8.6e-13) but not detection. A 4-feature pixel fingerprint recovered reconstruction identity (patient-level AUC about 0.95 on real CT, 0.995 on a QIBA phantom) where the ConvolutionKernel DICOM tag was uninformative (identical labels across reconstructions). The kernel axis transported across four manufacturers (leave-one-vendor-out AUC 0.94-0.98, matching the within-vendor ceiling). Acquisition state thus maps to distinct AI failure modes, frequency content to measurement reliability and noise to detection sensitivity, and is not recoverable from metadata. Acquisition-aware, input-side validation is the missing layer for the acceptance-testing and drift-monitoring requirements now entering imaging-AI accreditation.

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11.
medRxiv (Medicine) 2026-06-17

Perceptions of aging well among older adults with heart failure: insights from a qualitative study

Authors:
Reid↗R.-J↗Ofosu↗Goyal↗De Main↗Lambert↗W. M↗Navarro-Millan↗Sterling↗M. R↗Rajan↗Soroka↗…

Background: Heart failure (HF) is a prevalent and often debilitating cardiovascular condition among older adults, frequently accompanied by multimorbidity, functional limitations, and the need to age in place. Traditional models of successful aging emphasize disease absence and preserved function, yet most individuals with HF live with ongoing symptoms and chronic health challenges. How older adults with HF define aging well, particularly across different socioeconomic contexts, remains underexplored. Objectives: To explore how older adults with HF conceptualize aging well and to identify perceived facilitators and barriers across more and less resourced New York City neighborhoods. Methods: We conducted semi-structured interviews with 20 adults diagnosed with HF residing in Manhattan and Brooklyn neighborhoods classified by 2019 United States Census data. Interviews were guided by Rowe and Kahn's model. Transcripts were analyzed using an inductive-deductive thematic approach and interpreted in alignment with the Healthy People 2030 framework. Results: Participants had a mean age of 69 years; 50% identified as Black and 50% were women. Despite functional limitations, 65% reported aging well. Five themes emerged: maintaining physical function, maintaining cognitive function, sustaining social relationships, avoiding pain, and promoting overall well-being. Avoiding pain and promoting well-being extended beyond traditional models. Neighborhood context shaped priorities, with financial stability emphasized in more affluent areas and social cohesion prioritized in less affluent communities. Conclusions: Older adults with HF frequently perceive themselves as aging well despite chronic illness, reframing successful aging beyond disease avoidance. These findings support a patient-centered, place-informed model of aging well with implications for healthcare delivery and policy.

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12.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

Authors:
Hosseini↗Sharma↗

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

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13.
arXiv (CS.CV) 2026-06-11

OpenMedReason: Scientific Reasoning Supervision for Medical Vision-Language Models

Authors:
Negin Baghbanzadeh↗Pritam Sarkar↗Michael Colacci↗Abeer Badawi↗Adibvafa Fallahpour↗Arash Afkanpour↗Leonid Sigal↗Ali Etemad↗Elham Dolatabadi↗

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.

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14.
medRxiv (Medicine) 2026-06-22

Study protocol: Feasibility and clinical implications of real-time cerebral autoregulation monitoring in major noncardiac surgery with the Medtronic Cotrending algorithm (AUTOREGULATE-NONCARDIAC-COTRENDING)

Authors:
Gross↗Schindler↗Vogt↗A. P↗Pietsch↗Filipovic↗Steiner↗L. A↗Wanner↗P. M↗

Background: Perioperative hypotension is associated with postoperative organ injury. However, trials of hypotension avoidance have not found meaningful improvements in postoperative cardiovascular, renal, neurological or functional outcomes. One possible explanation is that organ perfusion depends on patients individual autoregulatory ranges. Hence, technology enabling monitoring of the autoregulatory status of vital organs, e.g. the brain, could provide a physiologic basis for personalising of blood pressure targets. However, current established methodologies for monitoring cerebral autoregulation in noncardiac surgery, e.g. the cerebral oximetry index (COx), are limited by performance and usability. The Medtronic Cotrending algorithm has been developed to provide automated, near real-time assessment of cerebral autoregulation. While feasibility was demonstrated in cardiac surgery, its applicability in major noncardiac surgery remains unknown. This study aims to evaluate the technical feasibility and clinical implications of Cotrending-based cerebral autoregulation monitoring in major noncardiac surgery. Objectives: Primary objective: To evaluate the technical feasibility of using the Medtronic Cotrending algorithm to monitor intraoperative cerebral autoregulation in real-time during major noncardiac surgery, drawing comparisons to the COx algorithm. Secondary objectives: to investigate the potential clinical implications of Cotrending-based cerebral autoregulation monitoring. Design: Single-centre, prospective cohort study. Setting: Swiss tertiary care centre Patients: Patients enrolled in AUTOREGULATE-NONCARDIAC who were monitored intraoperatively with the Medtronic INVOS(TM) 5100 near-infrared spectroscopy (NIRS) system. Outcomes: Technical feasibility outcomes include success rate of determination of the lower limit of cerebral autoregulation, intraoperative uptime, time to first estimate of the lower limit of cerebral autoregulation, sensitivity to external factors and to data artefacts; agreement of Cotrending-derived lower limit of cerebral autoregulation with COx-derived lower limit of cerebral autoregulation. Conclusions: N/A Trial registration: Clinicaltrials.gov NCT07630129

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15.
medRxiv (Medicine) 2026-06-12

Opportunistic CKD Screening in Hospitalized Patients

Authors:
Segal↗Levy↗Ghosheh↗Wolak↗Ben-Dov↗

Background. Chronic kidney disease (CKD) affects 10-13% of adults worldwide but remains largely undiagnosed until advanced stages. Hospitalization provides an opportunity for early detection through opportunistic urine albumin-to-creatinine ratio (UACR) measurement. Methods. We conducted a prospective three-arm study of opportunistic CKD screening in general internal medicine wards at Hadassah Mt. Scopus (MS), Hadassah Ein Kerem (EK), and Shaare Zedek Medical Center (SZMC) in Jerusalem (Protocol HMO-23-0300). Adult inpatients without known CKD or recent UACR were enrolled. Pathological UACR was defined as [≥]30 mg/g. Confirmed CKD required two pathological measurements [≥]90 days apart (KDIGO-compatible). eGFR was computed using the 2021 CKD-EPI race-free equation. Pooled proportions were estimated by fixed-effects logit meta-analysis; odds ratios by DerSimonian-Laird random-effects models. Results. A total of 158 patients were enrolled (MS n=50, EK n=57, SZMC n=51). Pathological first UACR was identified in 43/158 patients (27.2%; 95% CI 21.3-34.1%; I2=0% across centers). Of 24 patients with a second UACR available, 14 (58%) confirmed CKD, yielding a pooled confirmed-CKD rate of 8.9% of all screened patients. In-hospital mortality was significantly higher among patients with pathological UACR (9.3% vs ~2%; Fisher's exact p=0.012). In per-center multivariate logistic regression, three predictors reached pooled significance: BUN (OR 1.10 per mg/dL, 95% CI 1.04-1.17, p=0.002, I2=0%), heart failure (OR 3.21, 95% CI 1.34-7.70, p=0.009, I2=0%), and diabetes mellitus (OR 2.54, 95% CI 1.11-5.82, p=0.028, I2=17%). Cardiac/vascular admissions had the highest pathological UACR rate (~42%); GI/hepatic admissions had 0%. Conclusions. Opportunistic inpatient UACR screening identifies previously unrecognized CKD in approximately 9% of general internal medicine patients, with consistent results across three independent centers. BUN elevation, heart failure, and diabetes are the strongest independent predictors. Pathological UACR carries significant short-term mortality risk, supporting integration of routine screening into inpatient care pathways.

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16.
arXiv (CS.LG) 2026-06-11

DeepRHP: A Hybrid Variational Autoencoder for Designing Random Heteropolymers as Protein Mimics

Authors:
Shuni Li↗Zhiyuan Ruan↗Andy Shen↗Ivan Jayapurna↗Ting Xu↗Haiyan Huang↗

arXiv:2606.11651v1 Announce Type: new Abstract: Synthetic random heteropolymers (RHPs), consisting of a predefined set of monomers, offer an approach toward the design of protein-like materials. These RHPs, if designed appropriately, can mimic protein behavior and function. As such, there is a need for computational tools to efficiently guide RHP design. We bridge this gap by developing DeepRHP, a modified variational autoencoder (VAE) model under a semi-supervised framework. By equipping a classical VAE with an additional feature-based VAE, DeepRHP forces the latent space to capture structures of critical chemical features as well as individual RHP sequence patterns. In this sense, our method is versatile by allowing any relevant features to be incorporated in a hybrid manner. We demonstrate the effectiveness of DeepRHP by suggesting potential monomer compositions that stabilize membrane proteins (e.g. Aquaporin Z) in non-native environments and cross-validating our prediction with published results. The concordance between our model and true RHP function suggests strong potential in utilizing hybrid autoencoder architectures to guide RHP design for proteins and other biological compounds.

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17.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Authors:
Daisy Yi Ding↗

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

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

GitOfThoughts: Version-Controlled Reasoning and Agent Memory You Can Replay, Diff, and Merge

Authors:
Pavan C Shekar↗Abhishek H S↗Aswanth Krishnan↗

Large language model (LLM) reasoning is ephemeral: chains of thought vanish with the context window, pruned search branches leave no record, and memory buffers cannot be diffed, merged, or audited. Every other complex software process (code, infrastructure, data, experiments) is version-controlled; reasoning is not. We introduce GitOfThoughts, which stores an agent's reasoning tree as a git repository: every scored thought is a commit, scores are notes, outcomes are tags, and retrieval is "git log" over the agent's own history. This makes reasoning replayable, auditable, and mergeable across agents at near-zero engineering cost. We then ask the harder question: does memory, in any substrate, actually improve accuracy? Across five substrates (none, markdown, vector, graph, git), two benchmarks, two model scales, and pre-registered replications, the answer for novel problems is no. No memory format reliably helps, and a promising early result collapsed under its own pre-registered replication. Memory pays only above what we call the copyability threshold: when the retrieved case is a near-duplicate of the current problem (similarity >~ 0.8), accuracy jumps sharply; below it, nothing. The gain is answer retrieval, not method transfer: a 4.5x larger model doubles the near-duplicate payoff yet still cannot extract a transferable method from a worked example. The only general lever we find is test-time sampling. The case for git-as-substrate is therefore auditability, provenance, and mergeability at accuracy parity. We document a retracted result and a refuted hypothesis to model the evaluation standard we hold ourselves to.

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19.
arXiv (CS.AI) 2026-06-12

"Is This Not Enough?": Asymmetries in Institutional Accountability and Collective Sensemaking in the Case of Canada's Algorithmic Visa Triage System

Authors:
Dipto Das↗Matthew Tamura↗Syed Ishtiaque Ahmed↗Shion Guha↗

arXiv:2606.13071v1 Announce Type: cross Abstract: This paper examines how algorithmic accountability in Canada's visa system is articulated institutionally and experienced by applicants across borders. We analyzed Immigration, Refugees and Citizenship Canada (IRCC)'s Algorithmic Impact Assessment (AIA) for the temporary resident visa (TRV) triage system using the algorithmic decision-making adapted for the public sector (ADMAPS) framework and analyzed Reddit discussions among applicants using a mixed-methods approach. We show that while institutional artifacts emphasize transparency, procedural safeguards, and bounded impacts, applicants engage in collective sensemaking to interpret opaque decisions, often relying on peer knowledge amid uncertainty. We identify three asymmetries between how institutional accountability is structured and how people perceive the process: epistemic asymmetry in access to decision logic, jurisdictional asymmetry in exposure shaped by geopolitical positioning, and temporal–relational asymmetry in how waiting and uncertainty are experienced. We emphasize why it is important to shift attention from institutional design to the uneven distribution of experiences with public-sector algorithmic governance. Together, these contributions demonstrate how algorithmic governance systems in the context of transnational migration produce structured asymmetries not captured by institutional disclosure frameworks, and how extending ADMAPS can account for those uneven translations of accountability.

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

MARIC: Multi-Agent Reasoning for Image Classification

Authors:
Wonduk Seo↗Minhyeong Yu↗Hyunjin An↗Seunghyun Lee↗

Image classification has traditionally relied on parameter-intensive model training, requiring large-scale annotated datasets and extensive fine tuning to achieve competitive performance. While recent vision language models (VLMs) alleviate some of these constraints, they remain limited by their reliance on single pass representations, often failing to capture complementary aspects of visual content. In this paper, we introduce Multi Agent based Reasoning for Image Classification (MARIC), a multi agent framework that reformulates image classification as a collaborative reasoning process. MARIC first utilizes an Outliner Agent to analyze the global theme of the image and generate targeted prompts. Based on these prompts, three Aspect Agents extract fine grained descriptions along distinct visual dimensions. Finally, a Reasoning Agent synthesizes these complementary outputs through integrated reflection step, producing a unified representation for classification. By explicitly decomposing the task into multiple perspectives and encouraging reflective synthesis, MARIC mitigates the shortcomings of both parameter-heavy training and monolithic VLM reasoning. Experiments on 4 diverse image classification benchmark datasets demonstrate that MARIC significantly outperforms baselines, highlighting the effectiveness of multi-agent visual reasoning for robust and interpretable image classification.

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21.
bioRxiv (Bioinfo) 2026-06-19

OmniPath Metabo: chemical structures, interactions and mechanisms to study the metabolome

Authors:
Schaul↗Bai↗Franken↗Lawrence↗Palacio-Escat↗Bottazzi↗Carreno↗Daley↗Gul↗Sahin↗Mananes↗Bohar↗…

Mechanistic and functional analysis of omics data largely relies on the incorporation of prior knowledge; however, connecting metabolomics data and knowledge is a major methodological challenge. This is largely driven by the diverse prior knowledge being fragmented across many databases requiring the merging of different database records across chemical structures, identifiers, and varying levels of structural specificity. Hence, this limits mechanistic interpretation and functional characterisation of the metabolome. Here, we present OmniPath Metabo, a comprehensive, harmonized, metabolome-centric database covering metabolites, lipids, food-derived compounds, and small molecule drugs, along with their associated receptors, transporters, enzymes, reactions, allosteric regulators, and disease associations. OmniPath Metabo harmonizes attributes using controlled vocabularies and ontologies, structures and built-in cheminformatics to map identifiers and track ambiguity. OmniPath Metabo is built directly from 40+ original resources and is freely accessible via an interactive web app and API at metabo.omnipathdb.org. OmniPath Metabo enables dynamic, context-specific construction of subnetworks to serve dedicated purposes, such as cell-cell communication or integrated multi-omics metabolite-driven regulation, connecting reactions, allosteric regulation, metabolite-receptor and metabolite-transporter interactions. Combining it with the over 170 other resources in OmniPath, it can be used for integrated networks of signaling, gene regulation, and metabolism. We showcase the application of OmniPath Metabo by analysing publicly available metabolomics data of lung cancer cell lines and metabolic footprints to mutational patterns. In summary, OmniPath Metabo transforms fragmented resources into a harmonised prior knowledge framework for a mechanistic and functional analysis of the metabolome.

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22.
arXiv (CS.LG) 2026-06-18

Learning to Annotate Delayed and False AEB Events: A Practical System for Extreme Class Imbalance and Asymmetric Label Noise

Authors:
Mengxiang Hao↗Xin Jiang↗Xinghao Huang↗Wenliang Su↗Zhiteng Wang↗Junjie Rao↗Xiaotian Yang↗Wei Liao↗Chengyu Han↗Gen Liang↗Yulun Song↗Zhitao Xu↗…

arXiv:2606.19186v1 Announce Type: cross Abstract: Autonomous Emergency Braking (AEB) optimization relies on accurately annotated real-world trigger events, particularly rare but critical delayed and false AEB triggers that expose system deficiencies. However, these minority samples comprise less than 5% of thousands of daily triggers, making manual annotation prohibitively expensive at scale. We present the first automated AEB annotation framework to address this problem. During development, we identified two fundamental challenges that severely impair delayed/false trigger annotation accuracy: (1) Extreme class imbalance where delayed/false triggers are overwhelmed by true triggers; (2) Asymmetric label noise where mislabeled majority samples (true triggers) suppress minority samples (delayed/false triggers) learning. To overcome these challenges, we propose two key innovations: (1) Specific data augmentation that synthesizes realistic samples by manipulating focal target attributes, transplanting ego-vehicle dynamics, and masking non-focal agents; (2) noise suppression using stable hardness estimation and probe-guided adaptive threshold to clean mislabeled true trigger samples. Crucially, we deploy our model as a practical annotation system with full-stack architecture, efficiently identifying critical delayed/false triggers from thousands of daily AEB events. Production results demonstrate 80% improvement in recall of delayed/false triggers and 50% reduction in manual workload. Beyond immediate gains, the system enables continuous self-improvement through accumulated high-quality annotations, establishing a necessary data foundation for on-vehicle AEB system optimization

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23.
arXiv (CS.LG) 2026-06-19

A Solver-Free Training Method for Predict-then-Optimize

Authors:
Beichen Wan↗Mo Liu↗

arXiv:2606.19587v1 Announce Type: cross Abstract: We propose a scalable method for training prediction (machine learning) models in the predict-then-optimize paradigm, where model outputs serve as coefficients for a subsequent linear optimization task. Directly minimizing the empirical decision regret is intractable for linear programming and combinatorial optimization since the decision mapping is piecewise constant, and the gradients are zero almost everywhere. While existing methods address this by smoothing the differentiation process, they suffer from scalability issues, since a computationally expensive solver call is required for every gradient evaluation. To address this, we propose a decision-focused learning pipeline based on a measure transformation principle, which yields a new surrogate loss that is completely optimization-solver-free during training. We establish theoretical guarantees, including Fisher consistency and excess risk bounds. Empirically, our method achieves decision quality competitive with state-of-the-art methods while reducing training time by orders of magnitude.

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

A CEFR-Inspired Classification Framework with Fuzzy C-Means To Automate Assessment of Programming Skills in Scratch

Authors:
Ricardo Hidalgo-Arag\'on↗Jes\'us M. Gonz\'alez-Barahona↗Gregorio Robles↗

arXiv:2604.00730v2 Announce Type: replace-cross Abstract: Context: Schools, training platforms, and technology firms increasingly need to assess programming proficiency at scale with transparent, reproducible methods that support personalized learning pathways. Objective: This study introduces a pedagogical framework for Scratch project assessment, aligned with the Common European Framework of Reference (CEFR), providing universal competency levels for students and teachers alongside actionable insights for curriculum design. Method: We apply Fuzzy C-Means clustering to 2008246 Scratch projects evaluated via Dr.Scratch, implementing an ordinal criterion to map clusters to CEFR levels (A1-C2), and introducing enhanced classification metrics that identify transitional learners, enable continuous progress tracking, and quantify classification certainty to balance automated feedback with instructor review. Impact: The framework enables diagnosis of systemic curriculum gaps-notably a "B2 bottleneck" where only 13.3% of learners reside due to the cognitive load of integrating Logic Synchronization, and Data Representation–while providing certainty–based triggers for human intervention.

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25.
arXiv (CS.CL) 2026-06-18

Trust Region On-Policy Distillation

Authors:
Xingrun Xing↗Haoqing Wang↗Boyan Gao↗Ziheng Li↗Yehui Tang↗

On-Policy Distillation (OPD) is a fundamental technique for efficient post-training of large language models (LLMs), with broad applications in agent learning, multi-task enhancement, and model compression. However, OPD training becomes unstable when the teacher and student distributions differ substantially, as teacher supervision on student-generated tokens may yield unreliable policy gradients and even cause optimization failure. This work addresses reliable on-policy token-level supervision through credit assignment strategies, and proposes Trust Region On-Policy Distillation, TrOPD. It features the following characteristics: 1) Trust-Region On-Policy Learning: TrOPD performs OPD only in regions where the teacher provides reliable supervision, mitigating the optimization difficulty of the K1 reverse-KL estimator under distribution mismatch. 2) Outlier Estimation: For outlier regions, we explore gradient clipping, masking, and forward-KL estimation to reduce the adverse effects of unreliable supervision. 3) Off-Policy Guidance: The student continues generation from teacher prefixes and uses forward KL to imitate off-policy guidance, encouraging on-policy exploration toward reliable regions. Experiments show that TrOPD consistently outperforms SoTA OPD baselines, including OPD, EOPD, and REOPOLD, across mathematical reasoning, code generation, and general-domain benchmarks.

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