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01.
arXiv (math.PR) 2026-06-18

Kemeny's constant minimization for reversible Markov chains via structure-preserving perturbations

Authors:
Fabio Durastante↗Miryam Gnazzo↗Beatrice Meini↗

arXiv:2510.24679v4 Announce Type: replace-cross Abstract: Kemeny's constant measures the efficiency of a Markov chain in traversing its states. We investigate whether structure-preserving perturbations to the transition probabilities of a reversible Markov chain can improve its connectivity while maintaining a fixed stationary distribution. Although the minimum achievable value for Kemeny's constant can be estimated, the required perturbations may be infeasible. We reformulate the problem as an optimization task, focusing on solution existence and efficient algorithms, with an emphasis on the problem of minimizing Kemeny's constant under sparsity constraints.

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02.
arXiv (CS.CL) 2026-06-16

Beyond Retrieval: Learning Compact User Representations for Scalable LLM Personalization

Authors:
Heng Cao↗Fan Zhang↗Jian Yao↗Yujie Zheng↗Changlin Zhao↗Lu Hao↗Yuxuan Wei↗Wangze Ni↗Huaiyu Fu↗Yuqian Sun↗Xuyan Mo↗

Personalizing large language models requires adapting model behavior to individual users while preserving robustness and deployment-scale efficiency. Existing approaches typically personalize LLMs either at the input level, by retrieving user histories or constructing profile prompts, or at the parameter level, by maintaining user-specific parameter-efficient modules. The former makes personalization sensitive to retrieval quality and prompt design, whereas the latter incurs storage and maintenance costs that grow with the user population. To address these limitations, we propose TAP-PER (Temporal Attentive Prefix for PERsonalization), a prefix-based framework that encodes user preferences as learnable representations, eliminating explicit prompt construction and replacing heavy per-user adapters with lightweight user-state prefix embeddings. Inspired by personalized recommendation systems, TAP-PER decomposes user modeling into user-state and query-conditioned components, and incorporates temporal signals to capture the evolving nature of user interests. Experiments on six LaMP tasks show that TAP-PER consistently outperforms prompt-based and model-based baselines across classification, rating, and generation settings. Moreover, TAP-PER uses 130x fewer per-user parameters than OPPU and roughly half the total parameter footprint of PER-PCS at the 1,000-user scale, demonstrating that scalable LLM personalization can be achieved without explicit prompt construction or heavy per-user adapters.

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03.
medRxiv (Medicine) 2026-06-22

MinderCare: protocol for a mixed-methods evaluation of a digitally enabled dementia care service.

Authors:
Jeyasingh-Jacob↗Tecilla↗Cro↗Lai↗Frigerio↗Joby↗Chavarro Novoa↗Fabusoro↗Rasulo↗James↗Amade Cassimo↗Hariss↗…

Introduction and aims Dementia is a growing public health challenge affecting millions of people worldwide. It is a progressive condition that increases the risk of infections, falls, hospital admissions, dependence in activities of daily living, safety issues such as wandering, care home transfers, and death. New ways of supporting people living with dementia (PLWD) at home are urgently needed. We describe the MinderCare study which evaluates a digitally enabled care model that integrates low-burden sensor-based remote monitoring within a nurse-led clinical service. Methods and analysis In this mixed-methods study, we will recruit 100 people with confirmed or suspected dementia living at home and deploy the Minder remote monitoring system for at least 12 months. A detailed characterisation of the cohort will be obtained, including cognition, frailty, participant and carer wellbeing, functioning, and quality of life. The feasibility, acceptability, sustainability, and resource requirements of the service will also be assessed. Low-cost sensors provide information about behaviour, environment and physiology from the home. Machine-learning algorithms have been used to develop digital biomarkers of infection, sleep, night-time behaviours, daily activities and routines, and the effects of clinical events and treatment. These will be assessed through clinical reports of sensor-derived data that include anomaly alerts provided to the clinical teams. Algorithms will be assessed for their clinical utility and acceptability. The comparative-effectiveness component will be designed as a target trial emulation using linked electronic health-record data to construct a time-indexed external usual-care control cohort. The primary comparative outcome will be Days Alive and Out of Hospital (DAOH) over 12 months from the activation-index date, with healthcare utilisation, costs, institutionalisation and mortality assessed as secondary outcomes. DAOH and estimated MinderCare effects will also be examined across prespecified strata of baseline inpatient utilisation. Ethics and dissemination Ethical approval has been granted by the North East Newcastle and North Tyneside 2 Research Ethics Committee, and the study has received confirmation of capacity and capability by the Imperial College Healthcare NHS Trust. Study findings will be disseminated to patients, health and social care professionals, and policymakers through peer-reviewed publications and conference presentations. Study registration number: ISRCTN14997677 and NIHR portfolio CPMSID 63023.

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

PreLort: Prefix-Nested LoRA for Federated Fine-Tuning under Rank Heterogeneity

Authors:
Muhammad Waseem↗Nurbek Tastan↗Andrej Jovanovic↗Nicholas D. Lane↗Nils Lukas↗Karthik Nandakumar↗Samuel Horvath↗

Federated fine-tuning of large language models using parameter-efficient methods such as LoRA enables privacy-preserving adaptation of foundation models. Heterogeneous hardware resources introduce challenges, as clients with different adapter ranks cannot be directly aggregated. While existing methods enable aggregation under heterogeneous ranks, they fail to control how information is distributed across rank dimensions, leading to suboptimal use of shared low-rank representations. Instead, we propose PreLort: a nested low-rank formulation for federated LoRA that organizes adapter dimensions into a prefix hierarchy. Our approach ensures that lower-rank dimensions encode task-relevant information, while higher-rank dimensions capture additional capacity. Building on this, we introduce (i) a segment-wise aggregation rule that averages only over clients contributing to each rank segment, avoiding dilution from zero-padded lower-rank clients, and (ii) a prefix-nested training strategy that optimizes each adapter under multiple rank truncations, encouraging useful signal to concentrate in low-rank prefix dimensions. Together, these components encourage a consistent low-rank prefix capturing the most task-relevant information, while higher-rank dimensions learn additional capacity. This allows low-rank clients to benefit from richer information contributed by higher-rank clients, as prefix dimensions are consistently learned and aggregated. Experiments demonstrate that our method consistently outperforms prior heterogeneous federated LoRA methods in accuracy and ROUGE-L, while achieving lower or comparable perplexity across multiple base models.

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05.
arXiv (CS.CL) 2026-06-11

APEX: Automated Prompt Engineering eXpert with Dynamic Data Selection

Authors:
Fei Wang↗Si Si↗Cho-Jui Hsieh↗Inderjit S. Dhillon↗

Large Language Models are highly sensitive to prompt formulation, necessitating automatic prompt optimization to unlock their full potential. While evolutionary algorithms have emerged as the dominant paradigm, they suffer from a critical bottleneck: data efficiency. Current methods treat the development dataset as a static benchmark, wasting significant compute budget on uninformative data. In this work, we introduce APEX (Automatic Prompt Engineering eXpert), a novel framework that optimizes the data usage alongside the prompt search. APEX dynamically stratifies the dataset into Easy, Hard, and Mixed tiers based on the optimization lineage. By prioritizing the Mixed tier, which identifies the data where the LLM has mixed performance, we identify two high-leverage subsets: the addressable frontier for generating informative mutations and the rank-sensitive frontier for distinguishing candidate quality. We evaluate APEX across three diverse benchmarks: IFBench, SimpleQA Verified, and FACTS Grounding. Under a fixed budget of 5,000 evaluation calls, due to its data efficiency, APEX outperforms the initial prompt by an average of 11.2% on Gemini 2.5 Flash and 6.8% on Gemma 3 27B, demonstrating that a data-centric approach is key to efficient and effective prompt optimization.

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06.
arXiv (quant-ph) 2026-06-17

Manipulation of Topological Corner States via Subchiral Symmetry

Authors:
Hai-Tao Ding↗Tianqi Chen↗Leong-Chuan Kwek↗Jiangbin Gong↗

arXiv:2606.17975v1 Announce Type: new Abstract: Higher-order topological phases provide robust corner modes, but their use requires controllable creation, isolation, and transfer of individual modes and their superpositions. Here we demonstrate, using the two-dimensional Benalcazar-Bernevig-Hughes model as an example, that subchiral symmetry provides a general control principle for manipulating topological corner modes. The conventional chiral symmetry decomposes into four subchiral symmetries, each associated with one zero-energy corner mode. By selectively breaking these subsymmetries with controlled intercell hoppings, we reduce the fourfold corner-state manifold step by step to single isolated modes. We further design adiabatic protocols that transfer either a single corner state or a superposition of two corner states between selected corners, while preserving the relative phase in the latter case. Both numerical simulations and IBM quantum-processor implementations show that the proposed protocols can be executed with high fidelity, establishing subchiral symmetry as a route to programmable higher-order topological state manipulation.

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

Intrinsic Computational Functionalism and Simulated Consciousness

Authors:
Ryota Kanai↗Shuqin Ma↗

arXiv:2606.15348v1 Announce Type: cross Abstract: A common objection to artificial or simulated consciousness is that a simulated brain is no more conscious than simulated water is wet. We address this from the perspective of Intrinsic Computational Functionalism (ICF): if consciousness is computationally constituted, it depends not on externally imposed descriptions but on the computational structures a system physically realizes in virtue of its own causal-dynamical organization. In previous work we developed Canonical Functionalism as a mathematically precise special case of this anti-interpretivist program, identifying functional states by their complete future input-output roles under a fixed interface. Here we argue that this input-output construction, though important, is incomplete: as a behavioral boundary case of ICF, it makes lookup tables and unfolded systems that preserve the same boundary behavior canonically equivalent. A consciousness-relevant canonical representation must instead include internal mechanisms, interventions, and joint readouts belonging to the relevant intrinsic organization. We therefore define a mechanism-enriched canonical structure and use it to formulate Intrinsic Causal-Computational Realization (ICCR), a realization relation preserving physical implementation, intrinsic state individuation, transition structure, intervention profiles, and the relevant agent-body-world boundary. The central result is conditional: if conscious properties are invariants of intrinsic causal-computational organization, then any system satisfying ICCR realizes the same consciousness-relevant properties, whether biological, artificial, or simulated. We discuss objections including biological naturalism and integrated information theory. We conclude that to deny consciousness to a simulation, one must identify a consciousness-relevant intrinsic causal-computational structure that the simulation fails to realize.

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08.
medRxiv (Medicine) 2026-06-11

The impact of pre-stroke statin use on baseline corrected infarct volume and collateral perfusion

Authors:
Coupland↗K. G↗Toson↗Martin↗Lillicrap↗T. P↗Pinheiro↗Levi↗C. R↗Garcia-Esperon↗Spratt↗N. J↗…

Stroke is a leading cause of disability and mortality worldwide, with ischaemic stroke the most prevalent type. Statins, used for cholesterol management, have demonstrated benefits in reducing stroke risk and improving outcomes in preclinical studies. However, the impact of pre-stroke statin use on stroke outcomes remain inconsistent. In this study, we aim to evaluate whether pre-stroke statin use is associated with greater volume of salvaged tissue and improved cerebral collateral perfusion. A retrospective analysis was conducted using data from 281 patients presenting with acute ischemic stroke to the John Hunter Hospital between May 2015 and May 2020. Patients were grouped based on pre-stroke statin use, and clinical variables, including infarct volume and collateral perfusion, were assessed. The primary outcome was salvage volume derived from baseline perfusion lesion volume minus infarct volume at follow-up. Collateral perfusion was measured by the hypoperfusion volume defined by delay time (DT)>6 seconds divided by the hypoperfusion volume defined by DT >2 seconds. Patients on statins at admission were significantly older and had more comorbidities. No significant association was found between pre-stroke statin use and salvage volume or collateral perfusion after adjusting for covariates. Larger initial infarct core was a significant predictor of salvage volume due to larger salvageable tissue volume at baseline. These findings indicate that pre-morbid statin use is not associated with larger salvage volume or improved cerebral collateral perfusion.

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09.
arXiv (CS.LG) 2026-06-18

GrapNet: A Programmable Dynamic-Architecture Neural Graph Substrate

Authors:
Zirong Li↗

arXiv:2606.18923v1 Announce Type: new Abstract: Programmability is a missing first-class interface in fixed-tensor neural networks: editing a relation, freezing a subgraph, auditing a local function, or changing the execution backend should be an operation on the neural program rather than ad-hoc parameter surgery. GrapNet studies this graph-as-network setting. The graph is the architecture and executable program, not an input data graph. Each compute node owns its next-layer child references and a trainable allocation vector aligned with those references; deleting a relation physically removes both the child reference and the corresponding allocation coordinate. Structural rules and execution policies live outside the node core, so the same child-owned graph can be grown, frozen, structurally edited, grouped into trainable family blocks, routed by attention over active relations, or lowered to dense snapshots after topology stabilizes. GrapNet composes with conventional modules through a vector-valued parent interface: dense layers, CNN encoders, ResNet feature extractors, attention blocks, and transformer representations can all feed one sensory GrapNode per coordinate. The evaluation is organized as a programmability stress suite rather than as a new replay benchmark. In a matched ten-seed Split Fashion-MNIST study, a plastic GrapNet+ER head reaches 63.16 percent seen-class accuracy versus 51.08 percent for a parameter-larger dense MLP+ER under the same seen-class loss and replay memory, with paired delta 12.08 points and p=1.3e-5. On Split CIFAR-10 with a frozen ImageNet ResNet-18 encoder, the same substrate improves the online head over MLP-256 by 3.81 points, with p=0.0026. These results support GrapNet as an editable neural graph substrate whose core value is structural programmability with faithful execution views.

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10.
Science (Express) 2026-05-21

DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme | Science

Authors: Unknown Author

Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3′–guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

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11.
arXiv (CS.AI) 2026-06-17

PreAct: Computer-Using Agents that Get Faster on Repeated Tasks

Authors:
Bojie Li↗

arXiv:2606.17929v1 Announce Type: new Abstract: Computer-using agents drive real software through the screen – clicking and typing – but they solve every task from scratch: asked to repeat a task, an agent re-reads the screen, re-reasons every tap, and pays the full cost again. We present PreAct, which lets such an agent get faster on tasks it has done before. The first time it succeeds, PreAct compiles the run into a small state-machine program-states that check the screen, transitions that act-and on later runs replays it directly instead of invoking the agent 8.5-13x faster, with no per-step language-model calls. Replay is not blind: at each step PreAct checks that the screen matches what the program expects before acting, and hands control back to the agent the moment something is off. PreAct applies the same discipline when deciding what to keep: a freshly compiled program enters the store only if, re-run from a clean state, an independent evaluator confirms it solved the task-catching programs that replay to their last step yet leave the task undone. Across a mobile, a desktop, and a web benchmark, this store-time check separates repeated runs that improve from ones that degrade as faulty programs accumulate, worth 1.75-2.6 tasks per benchmark, the same direction on all three; a fallback that explores afresh when no program fits brings PreAct level with a strong record-and-replay baseline. We also report what did not matter: prompt wording, runtime guardrails, and whether a language model or a plain embedding retriever selects which program to reuse.

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12.
PLOS Medicine 2026-06-09

Molecular Tumor Boards clinical impact on patient care and structural features: A systematic review and meta-analysis

Authors:
Luigi Russo↗

by Luigi Russo, Erika Giacobini, Nicolò Lentini, Tommaso Osti, Maud Kamal, Stefania Boccia, Roberta Pastorino Background Molecular Tumor Boards (MTBs) bring together multidisciplinary experts to translate genomic data into clinical decisions in oncology, however, their overall clinical impact remains unclear. The aim of this systematic review is to assess the clinical impact of MTB-recommended therapies on patients with cancer outcomes. Methods and findings In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and CENTRAL up to July 2025. We included studies of any design, both single-arm studies and studies with a comparator group, that reported the clinical impact of MTBs in patients who received MTB-guided therapy. Meta-analyses were performed separately by study design, using hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for objective response rate (ORR) and disease control rate (DCR), and pooled proportions for PFS ratio ≥1.3. All meta-analyses were conducted using random-effects models based on the inverse variance method. We evaluated the risk of bias using the RoB 2.0 for RCTs and ROBINS-I for non-randomized studies.From 6,846 records, 78 studies (9,195 patients; 4,569 treated per MTB recommendations) were included. MTB-guided therapies were associated with reduced risk of death (HR 0.87; 95% CI [0.76, 1.01]; p = 0.069; I2 = 0.0% in RCTs; 0.62 in retrospective studies) and disease progression (HR 0.73; 95% CI [0.64, 0.84]; p 

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

Token-Level Entropy Reveals Demographic Disparities in Language Models

Authors:
Messi H. J. Lee↗

We ask whether demographic identity, signaled by a name alone, systematically reshapes the generative distribution of a language model. Measuring full-vocabulary Shannon entropy at temperature zero across six open-weight base models and 5,760 implicit sentence-completion prompts (e.g., "Tanisha walked into the office on a Monday morning and"), we find that Black-associated names produce higher first-token entropy than White-associated names across all six architectures - opposite to the output-level homogeneity bias documented under explicit demographic prompting (Lee et al., 2024) - and Black-associated names always produce greater entropy above identity-neutral baselines than White-associated names ($\Delta\Delta > 0$ in all six models). Women-associated names co-occur with lower first-token entropy (DL-pooled $\hat\beta = -0.041, p = .019$) and more homogeneous outputs ($\hat\alpha = +0.024, p < .001$) than men-associated names - a pattern convergent with homogeneity bias; race and gender effects are additive. Instruction tuning does not attenuate the race gap (matched-format DL-pooled $\hat{\beta}=+0.153$). Running the same templates with explicit group labels instead of names yields null race effects in 10 of 12 models where implicit probing is significant - establishing that probing methodology is a primary determinant of which distributional structure is recovered.

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

A Model-Driven Approach for Developing Families of Reinforcement Learning Environments

Authors:
Xiaoran Liu↗Istvan David↗

arXiv:2606.20324v1 Announce Type: cross Abstract: Virtual training environments are software-intensive systems in which reinforcement learning (RL) agents learn, adapt, and demonstrate meaningful behavior. Virtual training environments offer a safe and cost-efficient alternative to training agents in real-world settings. However, to converge, most realistic RL problems require training in multiple, mostly similar but slightly different environments - i.e., families of environment variants. The typical development process of environment families is a labor-intensive and error-prone manual endeavor that does not scale well. To alleviate these issues, in this paper, we propose a model-driven approach for developing families of RL training environments. To obtain the family of environments, we develop an approach and prototype tool. In our approach, a hybrid genetic algorithm - a combination of population-based global search and heuristic local search - generates environment families. Mutations and constraints are expressed as model transformations and are operationalized into a search process by a state-of-the-art model transformation engine. We demonstrate the soundness of our approach in a wildfire mitigation scenario and curriculum learning - a particular learning paradigm that relies on environment families.

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15.
arXiv (quant-ph) 2026-06-17

Fabless Quantum Chip Design and Commercial Production

Authors:
Cai↗Ling Qiao↗Bin Yang↗Fumin Luo↗WeiGui Guo↗GuoRong Zhang↗XueFei Liu↗Qinglang Guo↗Bin Wu↗

arXiv:2606.17956v1 Announce Type: new Abstract: This paper proposes a fabless quantum-chip design and production architecture for superconducting quantum computing, centered on the SPICE-Q multiphysics simulation framework. The proposed ecosystem connects process-certified quantum PDKs, parameterized device cells, traceable model cards, SPICE-Q physical modeling languages, unified Q-EDA flows, foundry sign-off rules, cryogenic test feedback, and reusable quantum IP. In this model, design firms do not merely outsource fabrication; they prepare verified tape-outs under standardized process constraints and calibrated physical models. Its economic value lies in reducing repetitive device debugging, process exploration, and low-level layout effort, while its feasibility depends on PDK maturity, foundry yield, cryogenic test throughput, model-prediction accuracy, data-feedback mechanisms, and IP licensing boundaries. We argue that superconducting quantum chips can move from the current largely vertically integrated development model toward a fabless-foundry ecosystem only when hardware design is supported by standardized, verifiable, and reusable software and process interfaces. The required pillars are certified PDKs, PCell-based parameterized design, SPICE-Q cross-physics simulation, end-to-end Q-EDA automation, and a tradable quantum-IP market. By adapting lessons from the classical semiconductor industry to quantum hardware, this framework defines a path toward scalable, manufacturable, and commercially reusable superconducting quantum-chip design.

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

How Far Can Chord-Symbol Time-Series Adaptation Carry Genre Identity? Capabilities and Boundaries in Multi-Genre Chord-Symbol Modeling

Authors:
Jinju Lee↗

arXiv:2606.07334v2 Announce Type: replace-cross Abstract: This report treats chord-symbol sequences as an interpretable, controllable time series for genre-local harmonic modeling. The frozen Music Transformer base - released as a pop-jazz fine-tune endpoint but verified in this revision weight-identical to the pop-only Phase-0 baseline, so all gains are measured over a pure-pop prior (see Changes in v2) - is extended to eleven target genres: blues, bossa nova, Bach chorales, country, electronic, folk, funk, gospel, hip-hop, R&B/soul, and rock. The main evaluation compares LoRA, IA3, BitFit, prefix tuning, and full fine-tuning over 11 genres and 3 seeds, a complete 165-cell grid. All five methods improve over the frozen base on held-out chord prediction (macro gains +2.89 to +3.61 percentage points); LoRA and IA3 score highest, but pairwise Wilcoxon tests with Holm and Benjamini-Hochberg correction do not support a decisive winner. A matched-data-size control sharpens this: at a common corpus size IA3 stays on top while LoRA drops to last, so the small method gaps are partly data-driven rather than representational. A control-token baseline is also strong, and wrong-genre adapters often beat the frozen base, suggesting the adaptation effect is largely lightweight conditioning over a reusable harmonic base rather than genre-specific adapter memory. Further diagnostics (rank sweeps, wrong-genre rotation, a base-checkpoint ablation that v2 reinterprets as a same-weights control, chord-only genre classification, output-distribution statistics, real-song evaluation, duplicate analysis) support a bounded conclusion: chord-symbol adaptation reliably improves genre-local harmonic prediction, but chord symbols alone do not carry complete genre identity. Perceived genre authenticity and musical quality are left to controlled listener evaluation.

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

Two-Layer Linear Auto-Regressive Models Estimate Latent States

Authors:
Yahya Sattar↗Sunmook Choi↗Leo Maynard-Zhang↗Yassir Jedra↗Maryam Fazel↗Sarah Dean↗

arXiv:2606.12691v1 Announce Type: cross Abstract: Auto-regressive models have emerged as powerful tools for sequential data, from language to video. Understanding how and why these models learn latent representations remains an open theoretical question. In this work, we demonstrate that when trained by empirical risk minimization on data from partially observed linear dynamical systems, two-layer linear auto-regressive models naturally learn to approximate Kalman filtering. In particular, we show that the learned hidden representation coincides, up to a similarity transformation, with the state estimates produced by the optimal (Kalman) filter, even though the model has no explicit knowledge of the underlying dynamics or state. The result follows from three main insights. First, we establish that the Kalman filter is well approximated by an auto-regressive model with bounded truncation error. Second, we show that despite non-convexity, the two-layer optimization landscape is benign, i.e., all stationary points are either strict saddles or global minima. Finally, as our main contributions, we provide finite-sample guarantees on prediction error, parameter estimation error, and latent state recovery. Numerical simulations support the theoretical results and demonstrate that the latent representations of auto-regressive models recover state estimates.

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18.
Nature (Science) 2026-06-22

C-glycoside synthesis via radical cross-coupling of glycohydrazides

Authors:
Yinliang Guo↗

Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition, and cell signaling. Within this domain, C-glycosides1-3, in which the oxygen atom of the glycosidic bond in O-glycosides is replaced by carbon, have emerged as valuable motifs in medicinal chemistry due to their resistance to enzymatic hydrolysis2,4. Of particular importance are C-aryl glycosides, exemplified by the SGLT2 inhibitors dapagliflozin, canagliflozin, and empagliflozin, which are frontline therapies for type 2 diabetes5-7. However, scalable syntheses of C-aryl glycosides have traditionally relied on protected sugar derivatives, lengthy sequences, or conventional cross-couplings that often suffer from poor selectivity, limited scope, and extensive protecting-group manipulation6. Herein, we report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors, natural products such as salmochelins and neopetrosins, and medicinally relevant probes. Beyond anomeric functionalization, this platform enables C–C bond formation at multiple positions on carbohydrate scaffolds and supports stereoretentive radical coupling that can override inherent stereochemical biases, expanding practical access to carbohydrate-derived therapeutics and chemical tools.

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20.
medRxiv (Medicine) 2026-06-15

Wellbeing After Stroke-2 (WAterS-2): a feasibility study with process evaluation exploring inclusive, accessible, online psychological support after stroke

Authors:
Longley↗Woodward-Nutt↗Cotterill↗Chouliaria↗Thomas↗Bamford↗Bowen↗Patchwood↗

Objectives: Explore feasibility and acceptability of upskilling a workforce to deliver a co-developed intervention, based on Acceptance and Commitment Therapy (ACT), to support psychological adjustment post-stroke targeting underserved groups. Design: Multi-site, single-arm feasibility study with embedded mixed-methods process evaluation (ISRCTN17628580). Setting: Four NHS community stroke services across England. Participants: 1. Stroke survivors [&ge;]18 years of age, [&ge;]4 months post-stroke, reporting psychological difficulties adjusting to stroke, able to consent and access remote group sessions in English; 2. Group facilitators from NHS stroke services, not ACT specialists. Intervention: WAterS-2: an eight-session, remotely-delivered ACT-informed group intervention. Outcome measures: Recruitment, fidelity, safety, acceptability and perceived value were assessed using fidelity checklists, post-intervention surveys and semi-structured interviews with stroke survivors and facilitators. Clinical outcomes including mood (HADS), wellbeing (ONS4), psychological flexibility (AAQ-ABI), measured post-group and three-months later. Results: Nineteen stroke survivors recruited (mean 9.6 months post-stroke; n=5 (26%) minoritised ethnicities; n=10 (52%) with aphasia). Thirteen facilitators - including two peer support workers - delivered the intervention with fidelity following structured training across four services. Drop-out was low (2/19; 11%); with 15 (79%) attending [&ge;]5/8 sessions. Remote data collection was feasible (79% follow-up completion), with no adverse events recorded. Acceptability was high: survivors valued peer connection, grounding and mindfulness practices. ACT metaphors were helpful for some but challenging for others, including some with aphasia. Online delivery was suitable but limited informal connection. Facilitators reported increased capability, incorporating ACT skills into routine care. NHS workforce pressures and geographically-constrained referral pathways limited recruitment reach. Conclusions: WAterS-2 is feasible, safe, acceptable and inclusive. A mixed workforce, including NHS peer support workers, can be upskilled to deliver with fidelity. Inclusion of underserved groups is achievable but requires active strategies beyond standard NHS referral routes. Findings inform a provisional logic model and a future pragmatic trial.

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21.
medRxiv (Medicine) 2026-06-17

Clinical Study Protocol of the 'Biomarkers of Severity of COVID-19 Patients' (BIOMARCOVID) Project

Authors:
Dinh↗T.-A↗Leroy↗Brandolini-Bunlon↗Berthier↗Trocme↗Varoquaux↗Plazy↗Vilotitch↗Terra↗Toussaint↗Bosson↗…

Introduction The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide, in certain areas exceeding hospital capacities and human resources. This has underscored the importance of having better tools to predict the outcome of potentially severe respiratory infections such as SARS-CoV-2. Predicting COVID-19 severity may allow physicians to better manage ICU beds and increase the chances of patient survival through appropriate management. During the toughest months of the pandemic, most physicians tried to identify patients that might develop severe forms based primarily on clinical features on admission (e.g., BMI, age). In this context, significant research has focused on identifying comorbidities, clinical manifestations, and routine blood biomarkers to predict disease severity. However, despite the demonstrated value of untargeted metabolomics in assessing severity, limited data exist on its use for identifying novel metabolite biomarkers that could improve both the sensitivity and specificity of outcome prediction. Our goal is to identify metabolite biomarkers that could enhance the predictive accuracy of standard medical biology data and clinical parameters. Methods and analysis This is a retrospective, observational, monocentric cohort study conducted at the Centre Hospitalier Universitaire Grenoble Alpes (CHUGA). The maximum number of eligible patients admitted for PCR-confirmed COVID-19 between March and December 2020 will be included. Severity outcome is defined using the WHO 10-category ordinal scale (mild: categories 4-5; severe: >5). Blood samples were collected within 48 hours of admission and analyzed for 62 routine blood tests and untargeted multiplatform LC-MS/MS metabolomics across four national platforms. Statistical analysis will include logistic regression with variable selection for the primary aim, and multi-block chemometric integration of clinical, biological, and metabolomics data as a secondary aim. Ethics and dissemination A study steering committee has been formed to ensure the accuracy of the collected data by thoroughly reviewing it prior to the data lock. All aspects of the study comply with ethical standards, including approval by the CHUGA institutional review board and adherence to CNIL Reference Methodology MR004 for the protection of participants' rights, privacy, and confidentiality. This study is registered on the French Health Data Hub (number F20210218154851). Results will be disseminated through peer-reviewed publications, presentations at national and international scientific and clinical conferences, and reports shared with key healthcare system stakeholders.

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22.
bioRxiv (Bioinfo) 2026-06-18

Deciphering shared and divergent tissue architectures from cross-species spatial transcriptomics

Authors:
Zhang↗Zhou↗

The integration of spatial transcriptomics (ST) data across species is essential for cross-species and translational studies, but remains challenging due to molecular divergence and anatomical differences between organisms. We present STACAME, a graph attention autoencoder-based framework to decipher shared and divergent tissue architectures from cross-species ST data by explicitly modeling both orthologous and species-specific genes. STACAME aligns ST slices in a spatially aware manner, identifies homologous and species-specific domains, and enables a suite of downstream comparative analyses. We demonstrate its utility by integrating ST datasets from diverse tissues, including hippocampus, isocortex, embryo, breast, liver, and cerebellum, across multiple species such as human, macaque, marmoset, mouse, and zebrafish. STACAME supports cross-species spatial domain alignment, the detection of shared and divergent spatially variable genes, development alignment and comparison, and the 3D integration of tissue architecture. This flexible approach facilitates the translation of findings from model organisms to humans, providing a unified computational platform for cross-species spatial transcriptomics.

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23.
Nature (Science) 2026-06-17

A mosaic of whole-body representations on the human precentral gyrus

Authors:
Darrel R. Deo↗

Understanding how the body is represented in the motor cortex is key to understanding how the brain controls movement. Although the motor cortex has been mapped in animal models at a fine scale1–10, characterization in humans remains primarily limited to low-resolution recording11–16 and stimulation techniques17–20. Here we created a comprehensive map of the human motor cortex at single-neuron resolution, spanning microelectrode array recordings from 20 arrays across 8 individuals with paralysis from spinal cord injury, amyotrophic lateral sclerosis or brainstem stroke, all enrolled in brain–computer interface clinical trials. These arrays broadly sample the crown of the precentral gyrus (PCG; thought to be composed largely of the premotor cortex (Brodmann area 6)). We found that body parts were highly intermixed, such that the entire body was represented in all sampled locations of the PCG, although the relative strength of body parts was roughly consistent with the motor homunculus17,18. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them. Throughout the PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (for example, toe curl and hand close) having correlated representations. These data provide evidence consistent with an intermixed, interrelated and behaviour-centred organization of the motor cortex3,21. The resulting map also provides important targeting information for brain–computer interfaces that seek to restore motor function. A comprehensive map of the human motor cortex at single-neuron resolution is described.

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24.
arXiv (CS.LG) 2026-06-11

Machine-learning clustering of close-in exoplanet populations: links to pebble accretion

Authors:
Yi Duann↗Anders Johansen↗Haiyang S. Wang↗H. Jens Hoeijmakers↗

arXiv:2606.11737v1 Announce Type: cross Abstract: Close-in exoplanets exhibit a wide range of orbital architectures and physical properties shaped by both formation conditions and migration processes. Although population-synthesis models predict distinct planetary populations, establishing a quantitative connection between observed exoplanets and synthetic populations remains challenging. We investigate the intrinsic organisation of close-in exoplanets using physically motivated dynamical parameters and connect the resulting populations to pebble-accretion formation pathways. A two-stage Gaussian mixture model (GMM) is applied to an observed sample of close-in exoplanets, performing unsupervised probabilistic clustering in a feature space dominated by dynamical descriptors of planet-star interactions. The resulting clusters are mapped onto a pebble-accretion synthetic population within a statistically motivated three-dimensional parameter space. Formation-related quantities, including gas availability, gas fraction, and ice-rock mass ratio, are then used to interpret the mapped populations. We identify statistically supported sub-populations without imposing predefined classification boundaries, including very-massive gas giants, hot giants, warm-Jupiter-dominated systems, and lower-mass giants. The mapped synthetic populations reveal systematic differences in formation timing, gas accretion, and solid growth histories. In particular, very-massive gas giants are preferentially associated with earlier formation epochs than hot-giant and warm-Jupiter-dominated populations. These results demonstrate that physically motivated machine-learning approaches can provide a statistically robust framework for linking observed exoplanet populations to theoretical planet formation pathways.

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

EcoBin: A Two-Stage Deep Convolutional Neural Network for Contamination-Aware Waste Classification

Authors:
Raghav Senthil Kumar↗

Waste classification models have become highly accurate at sorting waste, often exceeding 95% on benchmark datasets. However, these models fail to account for contamination in recyclable waste. We present EcoBin, a two-stage deep convolutional neural network that classifies household waste by its disposal pathway and that explicitly accounts for contamination. The first stage is a base waste classifier built on an EfficientNetV2-S backbone that assigns each of the thirty waste categories in our dataset to one of four disposal pathways. The second stage is a contamination classifier that inspects any item routed toward recycling and overrides the decision to garbage when contamination is detected. Because no public dataset of contaminated recyclables exists, we synthesize one by segmenting images of clean recyclable objects with a U2-Net model and compositing realistic contamination textures onto their surfaces. The first stage achieves 87.42% test accuracy and a 96.13% pathway-adjusted accuracy. Meanwhile, the contamination stage distinguishes clean from contaminated items with a 0.99 ROC-AUC. On a test set of contaminated recyclables, the complete pipeline routes 24 of 25 items correctly, compared with only 1 of 25 for the base classifier alone. A McNemar's test confirms that the improvement contributed by the contamination stage is statistically significant (p < 0.001).

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