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01.
medRxiv (Medicine) 2026-06-15

Instrumental Activities of Daily Living in Older Adults with Epilepsy: A Cross-Sectional and Longitudinal Multicenter Study

Objective: Instrumental activities of daily living (IADLs) represent a critical but understudied measure of day-to-day function in persons with epilepsy(PWE). In the multicenter Brain Aging and Cognition in Epilepsy (BrACE) study of PWE aged greater than or equal to 55 years, we examined the proportion, clinical correlates, epilepsy-related predictors, and longitudinal trajectory of IADL impairment. Methods: IADLs were assessed using the Functional Activities Questionnaire (FAQ; range=0 to 30; higher=more impaired); a FAQ greater than or equal to 2 defines MCI-level impairment, and a FAQ greater than or equal to 5 defines dementia-level functional impairment. Multivariable logistic regression identified predictors of baseline function. Global cognition (Montreal Cognitive Assessment [MoCA]), individual cognitive measures, and quality of life (QOL) were compared between the impaired and unimpaired groups. Linear regression evaluated predictors of longitudinal functional decline. Results: Of 57 participants (mean age=66.6 years; female=52.6%), 38.6% (n=22) had MCI-level functional impairment and 17.5% (n=10) had dementia-level functional impairment. In univariate analyses, worse FAQ scores were associated with lower education, higher area deprivation index, early-onset epilepsy (EOE less than 60 years), antiseizure medication polytherapy, and epilepsy localization. In multivariable analysis, temporal lobe epilepsy (OR=4.46, 95% CI=1.09, 21.83,p=0.047), EOE(OR=7.14, 95% CI=1.16, 59.97, p=0.046), and lower education(OR=0.70,95% CI=0.49, 0.93, p=0.025) remained independently associated with baseline MCI-level functional-impairment. Lower education (OR=0.55,95% CI=0.29, 0.84, p=0.021) was the only factor associated with dementia-level IADL-impairment. IADL-impaired participants demonstrated lower verbal memory scores (adjusted p=0.041) and MoCA scores (adjusted p

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

Evaluation of Alternative-Based Information Systems for Deliberative Polling using an Agentic Simulator

arXiv:2606.11692v1 Announce Type: cross Abstract: Deliberative polling promises to improve collective decision-making by exposing shareholders to a broad range of arguments before they vote. Yet ensuring that every voter encounters a representative sample of the reason space, the coverage problem, remains an open challenge, particularly at scale and in adversarial or strategically motivated electorates. This paper introduces a way of evaluating solutions using the LLM-based Agentic Bipolar Argumentation Simulator, grounded in a framework which formalises a poll as a six-tuple of endorsing and opposing justifications, attack and enhance relations, and shareholder- and relation-weights. ABAS simulates N autonomous shareholder agents, each assigned a latent opinion according to desired distributions in [-1, 1], who sequentially vote, choose or author justifications, and optionally submit argumentation-graph links. The simulator implements recommendations that rank existing justifications by their observable endorsement mass. It evaluates the mechanism's success by coverage, namely the fraction of the corpus reason-tag set represented in the K recommendations presented to each shareholder, as a solution to the NP-hard Subsuming Justification Problem. Reported experiments characterise how creativity rate (pown), recommendation size (K), argumentation density (plinks), and population size (N) affect coverage and corpus diversity. In an authenticated electorate where Sybil attacks are impossible and only the relation graph is gameable, we stress-test the scoring with coordinated strategic voting attacks: a tag-flood attack collapses coverage, while author-count relation weighting through a reversed-PageRank rule resists the flood markedly better than uniform weights.

03.
arXiv (CS.AI) 2026-06-12

HD-Prot: A Protein Language Model for Joint Sequence-Structure Modeling with Continuous Structure Tokens

arXiv:2512.15133v3 Announce Type: replace-cross Abstract: Proteins inherently possess a consistent sequence-structure duality. The abundance of protein sequence data, which can be readily represented as discrete tokens, has driven fruitful developments in protein language models (pLMs). A key remaining challenge, however, is how to effectively integrate continuous structural knowledge into pLMs. Current methods often discretize protein structures to accommodate the language modeling framework, which inevitably results in the loss of fine-grained information and limits the performance potential of multimodal pLMs. In this paper, we argue that such concerns can be circumvented: a sequence-based pLM can be extended to incorporate the structure modality through continuous tokens, i.e., high-fidelity protein structure latents that avoid vector quantization. Specifically, we propose a hybrid diffusion protein language model, HD-Prot, which embeds a continuous-valued diffusion head atop a discrete pLM, enabling seamless operation with both discrete and continuous tokens for joint sequence-structure modeling. It captures inter-token dependencies across modalities through a unified absorbing diffusion process, and estimates per-token distributions via categorical prediction for sequences and continuous diffusion for structures. Extensive results demonstrate that HD-Prot achieves competitive performance in unconditional sequence-structure co-generation, motif-scaffolding, protein structure prediction, and inverse folding tasks. Furthermore, our method can perform on par with state-of-the-art multimodal pLMs, despite being developed under limited computational resources (i.e., less than one-tenth the budget for modality extension fine-tuning). It highlights the viability of simultaneously estimating categorical and continuous distributions within a unified language model architecture, offering a promising alternative direction for multimodal pLMs.

04.
medRxiv (Medicine) 2026-06-22

Cumulative Metabolic Exposure to Hyperglycemia and Risk of Cardiovascular and Limb Events in Peripheral Artery Disease

Background: Although diabetes is a potent risk factor for the development of peripheral artery disease (PAD), the effect of cumulative metabolic exposure to hyperglycemia on risk of cardiovascular or limb events in patients with PAD remains unclear. Methods: The Peripheral Artery Disease: Long-term Survival (PEARLS) is a longitudinal registry of Veterans with newly diagnosed PAD identified using a natural language processing approach. Included patients had ankle brachial index [≤]0.9 or toe brachial index [≤]0.7, and no history of lower extremity revascularization or major amputation. Among patients with diabetes in this cohort, we assessed cumulative exposure to hyperglycema based on a 24-month rolling average of hemoglobin (Hgb) A1c values, categorized as [≤]7%, >7% to [≤]8%, and >8%. Multivariable Cox regression models evaluated the association between categories of HgbA1c, modeled as a time-varying exposure, and risk of cardiovascular (CV: myocardial infarction or stroke) and limb (chronic limb threatening ischemia [CLTI] or major amputation) events. Results: Among 45,109 patients with new diagnosis of PAD and pre-existing diabetes, the mean HgbA1c at baseline was 7.5%, with nearly one-third (30.4%) having HgbA1c >8%. The mean age was 70.4 years, 19.8% were Black and 4% were Hispanic. Patients with baseline HgbA1c >8% were younger and compared to those with HgbA1c [≤]7%, more likely to have coronary disease, kidney disease, and obesity. Over a median follow up of 4.2 years, 8,306 (18.4%) patients experienced a CV event, and 8,199 (18.2%) experienced a limb event. The adjusted association between HgbA1c and hazard of CV events was 12% higher in patients exposed to HgbA1c >7% to [≤]8% (HR 1.12; 95%CI: 1.05-1.18) and 38% higher in those exposed to HgbA1c >8% (HR 1.38; 95%CI: 1.30-1.46), compared to HgbA1c 7% to [≤]8% (HR 1.20; 95%CI: 1.13-1.28) and HgbA1c >8% (HR 1.60; 95%CI: 1.51-1.70), respectively when compared to HgbA1c [≤]7%. These findings were consistent in subgroups based on age and severity of PAD. Conclusions: Among diabetic patients with PAD, cumulatiave metabolic exposure to hyperglycemia is associated with a markedly increased risk of clinical events, especially limb events.

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

Hierarchical Planning with Latent World Models

arXiv:2604.03208v2 Announce Type: replace Abstract: World models are a promising path to zero-shot embodied control through planning. However, existing world model planners struggle on long-horizon, multi-stage tasks: prediction errors compound and naive search is exponential in the planning horizon. Hierarchy mitigates both by decomposing tasks into shorter, tractable subproblems; yet prior hierarchical approaches either amortize control into task-specific policies (hierarchical RL) or assume low-dimensional states and known dynamics (classical hierarchical MPC). We present Hierarchical Planning with Latent World Models (HWM), an architecture and planning paradigm for hierarchical model predictive control (MPC) directly on visual world models trained solely via next-latent prediction. HWM learns world models at multiple temporal scales within a shared latent space, so predictions from the long-horizon model serve as subgoals for the short-horizon model via latent matching, without task-specific rewards, skill learning, or hierarchical policies. To keep long-horizon search tractable, HWM learns an action encoder that compresses primitive action chunks into latent macro-actions. On real-world Franka manipulation, HWM solves pick-and-place from a single goal image at 70% success vs. 0% for single-level planning. Across simulated push manipulation and maze navigation, HWM consistently improves performance on long-horizon tasks while requiring up to 3x less planning compute.

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

SoftSkill: Behavioral Compression for Contextual Adaptation

arXiv:2606.20333v1 Announce Type: new Abstract: Agent skills are commonly deployed as natural-language Markdown files that encode answer policies, evidence-use habits, and task procedures. These files are readable and portable, but they are consumed indirectly: for each task instance, a frozen language model must translate a long textual artifact into generation-time behavior. This paper asks whether a natural-language skill can instead initialize a compact continuous context object, refined by a trainable soft delta while the base model remains frozen. We propose SoftSkill, a frozen-backbone method that tunes such soft skills with next-token prediction and deploys them as latent behavioral priors at inference time. In our main single-round setting, a length-32 SoftSkill prefix on Qwen3.5-4B improves over no-skill prompting by 8.3 points on SearchQA, 42.1 points on LiveMath, and 1.3 points on DocVQA. Relative to SkillOpt, SoftSkill improves accuracy by 5.2 points on SearchQA and 12.5 points on LiveMath, while replacing hundreds to thousands of Markdown skill tokens with a few virtual tokens. We further study agentic execution as a harder boundary case, where sparse trajectory imitation provides useful signal but does not yet robustly compress long-horizon procedural behavior. More broadly, the results suggest that some task skills are better treated not as additional Markdown to be reinterpreted at inference time, but as compact latent controls over how a frozen model enters the task.

07.
Nature Biotechnology 2026-06-11

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

作者:

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in situ. In a human cancer metastatic colonization model, we applied large (80,000+) sgRNA panels across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes. We linked perturbations affecting long noncoding RNA covariation, microRNA–mRNA interactions and distinct amino acid-specific tRNA alterations to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, investigation of the tumor immune microenvironment indicated distinct, synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of perturbation responses in complex tissues, including small and large RNA regulation, tumor proliferation, migration, metastasis and immune interactions. In vivo CRISPR genetic perturbations are spatially mapped at scale.

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

Too long; didn't solve

arXiv:2604.07593v2 Announce Type: replace Abstract: Mathematical benchmarks consisting of a range of mathematics problems are widely used to evaluate the reasoning abilities of large language models, yet little is known about how their structural properties influence model behaviour. In this work, we investigate two structural length variables, prompt length and solution length, and analyse how they relate to model performance on a newly constructed adversarial dataset of expert-authored mathematics problems. We find that both prompt and solution lengths correlate positively with increased model failure across models. We also include a secondary, exploratory analysis of cross-model disagreement. Under a difficulty-adjusted normalised analysis, both variables retain weak negative associations with realised model separation, slightly stronger for prompt length. Overall, our main robust finding is that structural length is linked to empirical difficulty in this dataset.

09.
arXiv (math.PR) 2026-06-11

Percolation on hierarchical lattices

arXiv:2606.11503v1 Announce Type: new Abstract: We consider independent Bernoulli percolation on top of sequences of hierarchical graphs. Given a graph $G_{1}$ with two distinguished vertices $a_{1}$ and $b_{1}$, the hierarchical graph with seed $G_{1}$ is the sequence $\big( G_{k} \big)_{k \geq 1}$ resulting from the inductive procedure, where the graph $G_{k+1}$ is obtained from $G_{k}$ by replacing each of its edges with a copy of $G_{1}$, attached by the vertices $a_{1}$ and $b_{1}$. We prove that, under sharp hypotheses, percolation on these graphs presents a unique phase transition. Second, we establish the existence of several critical exponents in this context, such as the critical exponents for the correlation length $\nu$, the surface tension $\mu$, the one-arm exponent $\alpha_{1}$. Several results are also obtained for their infinite counterpart $G_\infty$, which is the Benjamini-Schramm limit of $G_k$: uniqueness of the infinite cluster, continuity of $\theta(p)$, existence of the percolation-probability exponent $\beta$ and scaling relations for the critical exponents $\alpha_1$, $\nu$ and $\beta$. Furthermore, we analyze noise sensitivity for crossing functions in $G_{k}$ and establish sharp noise sensitivity in this setting. Finally, we propose a setup where it is possible to verify the locality hypothesis, stating that the critical threshold for percolation is a local property, while critical exponents are determined by the global geometry of the graph. As a consequence of the techniques developed here, we also provide a necessary and sufficient condition for the existence of a unique fixed point for the map $p \mapsto \mathbb{E}_p[g]$ in $(0,1)$, where $g:\{0,1\}^n \to \{0,1\}$ is a nontrivial monotone Boolean function.

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

GeoDial: A Multimodal Conversational Tutoring Dataset for Geometry Problem-Solving with Visual Tutor Turns

arXiv:2606.12419v1 Announce Type: cross Abstract: Several educational domains rely heavily on diagrams and visual cues, yet most existing tutoring datasets are limited to text-only interactions. This limits the development of AI tutors that can teach in visually grounded ways used by human instructors. Thus, we introduce GeoDial, a multimodal tutoring dataset of over 1.3K teacher-student dialogs in the domain of geometry collected from experienced math teachers, where instructional turns are explicitly grounded in diagram highlights. We propose a scalable annotation protocol that integrates dialog acts, visual highlighting, and feedback, enabling fine-grained supervision of both language and visual tutoring behavior. To illustrate the challenges posed by this setting, we fine-tune several vision-language models on GeoDial and evaluate their ability to generate tutoring utterances and diagram highlights. While supervised fine-tuning substantially improves the quality of generated dialog, it struggles to produce accurate diagram highlights, revealing a key limitation of current methods and highlighting the need for approaches that more effectively integrate visual reasoning with pedagogical interaction.

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

Rhythm of the Deep: A Computational-Linguistic Test of Duality of Patterning in Sperm Whale Codas

Human language has often been described as combining structure at two levels: lower-level units combine into larger units, which then combine into larger sequences. We test for this design feature, duality of patterning, in sperm whale codas using 1,483 codas from the Dominica Sperm Whale Project. Because acoustic similarity can imitate symbolic structure, we treat the problem as computational-linguistic structure discovery from continuous audio rather than as a direct claim about language or meaning. We use a consensus of frozen audio encoders, held-out structural tests, per-statistic nulls, and acoustic-null recoverability gates. The evidence supports a narrow two-tier architecture. At the lower tier, clicks compose into codas not by a stable ordered rule, but by which clicks are present together with their inter-click rhythm. At the upper tier, coda tokens show bout-level sequential dependence, with an NSB second-order transfer-entropy lift of 0.132 bits (p = 0.002). Under tempo scaling, encoder-derived click identity is strongly rate-bound, while coda identity remains substantially more stable, yielding a measurable abstraction gradient across the click-to-coda step. Rhythm-only baselines recover substantial lower-tier structure but fail to reproduce the upper-tier sequential-dependence signal. We do not claim language, semantics, perception, or human-like phonemes. Instead, we report representation-level evidence for a duality-of-patterning-like architecture whose lower tier is rhythmic rather than segmental, and provide a portable null-controlled framework for testing combinatorial structure in induced acoustic token systems.

12.
medRxiv (Medicine) 2026-06-22

A Plasmodium vivax controlled human infection and transmission model to evaluate interventions across the life cycle

Background Plasmodium vivax is an underappreciated cause of malaria disease burden. No reproducible and standardized full life-cycle controlled human malaria infection (CHMI) model to accelerate development of novel interventions is available. Methods This transmission-CHMI trial was conducted in Nijmegen, Netherlands. Healthy, malaria-naive adults were sequentially enrolled into three cohorts of four and inoculated with the asexual blood-stage isolate PvW1. Primary endpoint was proportion of oocyst-positive laboratory-reared Anopheles stephensi mosquitoes. The sequential design allowed for adaptations between cohorts. At parasitemia >10 parasites/microL or symptom onset, participants received oral gametocyte-sparing treatment (GST): mepacrine (Cohort 1 and 3; 100 mg at 0, 8 16 hours, then once daily for 3 days) or piperaquine (Cohort 3; 480 mg single-dose). Transmission was assessed by direct skin feeding (DSF) and membrane feeding assay (DMFA) with and without enrichment of gametocytes. End-of-study treatment was atovaquone-proguanil (1000/400 mg once daily for 3 days). The trial was registered: NL-OMON57011. Findings Participants were enrolled between September 17, 2024 and March 25, 2025, all (12/12) developed parasitemia and transmitted PvW1 to mosquitoes. No serious adverse events occurred. Most adverse reactions were related to malaria. Mepacrine and piperaquine reduced asexual parasitemia while preserving gametocytemia and transmission. Peak transmission occurred within 3 days after GST and depended on the parasite developmental cycle, with highest gametocyte-infectivity ~48 h post ring-stage. In Cohort 3, mosquito infection reached 100% in all transmission assays. Median peak oocyst counts were 24 (IQR: 14-31) for DSF, 17 (12-19) for DMFA, and 150 (116-199) for enriched DMFA. A two-fold increase in pre-GST maximal parasitemia was associated with 20 additional oocysts (95% CI 8,6-32) in enriched DMFA. Sporozoites were viable in primary human hepatocytes. Interpretation A PvW1 transmission-CHMI is reproducible and safe, enabling P. vivax sporozoite production, relapse models and evaluation of transmission-blocking interventions.

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

Hubs or Fringes: Pretraining Data Selection via Web Graph Centrality

The performance of modern language models depends critically on pretraining data composition. Yet existing data selection methods rely on auxiliary classifiers for document scoring or mixture optimization, adding computational overhead and dependence on labeled data. We propose WebGraphMix, a lightweight data selection framework that computes structural centrality scores over the Common Crawl host-level web graph and uses them to vary the proportion of central versus peripheral documents in the pretraining mixture. We hypothesize that central hosts expose models to reusable abstractions, while peripheral hosts encode specialized, long-tail knowledge. WebGraphMix computes centrality scores efficiently at web scale, requiring no model training, labeled data, or downstream supervision. We integrate WebGraphMix into the DataComp-LM pipeline and train models at 400M and 1B parameter scales with 8B and 28B tokens respectively, evaluating on 23 tasks ranging from factual knowledge to symbolic reasoning. Our experiments show that central and peripheral web regions encode complementary capabilities. Mixture combining both at a ratio of 1:1 achieves 41.4% on average, compared to 39.8% for uniform sampling. Combining structural scores with document-level quality classifier scores further improves performance to 43.8%. These findings demonstrate that web graph topology is a meaningful axis for pretraining data curation, capturing information that is largely orthogonal to existing content-based approaches.

14.
Nature (Science) 2026-06-10

A thalamus–brainstem attractor network drives history-biased decisions

作者:

Natural environments often change gradually, making it adaptive to bias decisions on the basis of the recent past — a phenomenon known as serial dependence1–3. Large-scale recordings during behaviour have identified that serial dependence is a common motif for decision-making, with neural representations of past experiences found throughout the brain4–11. However, it remains unclear whether this bias arises from dedicated neural circuits with history-specific computations. Using whole-brain, cellular-resolution imaging in zebrafish performing memory-guided evasive manoeuvres12–14, we identified a hierarchical circuit that maintains past information and biases future choices. Discrete attractors in the dorsal thalamus encoded the position of the most recent obstacle, maintaining a categorical memory via persistent activity lasting 10–20 s. Optogenetic manipulation of the dorsal thalamus abolished or imposed serial bias. A downstream hindbrain integrator received input from the thalamus and combined it with current sensory cues to produce graded responses reflecting multi-trial history. Leveraging a comprehensive brain atlas in zebrafish15, we constructed a whole-brain computational model that recapitulated behaviour and also predicted a key role for heterogeneous inhibitory subtypes in enabling flexible state transitions. This attractor–integrator architecture reveals a hierarchical and modular computation that unifies robust memory retention with flexible sensory integration, providing a general principle for history-biased decisions. Whole-brain, cellular-resolution imaging reveals a hierarchical thalamus–brainstem attractor network that encodes recent history and shapes behavioural bias in zebrafish.

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

Trust Region On-Policy Distillation

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.

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

Quantum Energy Teleportation under Equilibrium and Nonequilibrium Environments

arXiv:2511.01518v3 Announce Type: replace Abstract: Quantum energy teleportation (QET), implemented via local operations and classical communication, enables carrier-free energy transfer by exploiting quantum resources. While QET has been extensively studied theoretically and validated experimentally in various quantum platforms, enhancing energy output for mixed initial states, as the system inevitably interacts with environments, remains a significant challenge. In this work, we study QET performance in a two-qubit system coupled to equilibrium or nonequilibrium reservoirs. We derive an analytical expression for the energy output in terms of the system Hamiltonian eigenstates, enabling analysis of energy output for mixed states. Using the Redfield master equation, we systematically examine the effects of qubit detuning, nonequilibrium temperature difference, and nonequilibrium chemical potential difference on the energy output. We find that the energy output for mixed states often follows that of the eigenstate with the highest population, and that nonequilibrium environments can enhance the energy output in certain parameter regimes.

17.
medRxiv (Medicine) 2026-06-12

Effect of tenofovir on the outcomes of COVID-19 in persons with chronic hepatitis B: a nationwide cohort study in Sweden.

Background: Patients with chronic hepatitis B (CHB) may have an increased risk of severe COVID-19. Tenofovir has been hypothesized to confer protection against severe disease, but evidence is inconclusive. We evaluated the risk of severe COVID-19 among CHB patients treated with tenofovir compared with other nucleos(t)ide analogues (NAs). Methods and findings: In this nationwide, registry-based cohort study, we included all adults with CHB and laboratory-confirmed COVID-19 in Sweden between February 2020 and July 2022. Data from national health and socioeconomic registers were linked using unique personal identification numbers (PINs). Patients with HIV, hepatitis C, or hepatitis D coinfection were excluded. Exposure was defined as tenofovir versus other NA therapy. The primary outcome was severe COVID-19, defined as hospitalization >2 days or death within 30 days of diagnosis. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI), controlling for age, sex, comorbidities, vaccination, socioeconomic status, and region of birth. Among 5,877 CHB patients with COVID-19, 672 were receiving NA therapy (437 tenofovir, 235 other NAs). Severe COVID-19 occurred in 8.0% of tenofovir-treated patients and 14.5% of those receiving other NAs (unadjusted OR 0.52; 95% CI, 0.31-0.85). After adjustment, the association was attenuated and no longer significant (aOR 0.72; 95% CI, 0.39-1.31). Older age, comorbidities, and unvaccinated status were strongly associated with severe disease. Conclusions: The apparent protective effect of tenofovir against severe COVID-19 in unadjusted analyses was largely explained by confounding factors. The risk of severe disease was primarily driven by age, comorbidities, and vaccination status. Prevention of severe COVID-19 in patients with CHB should instead focus on vaccination and management of comorbidities.

18.
arXiv (CS.CV) 2026-06-16

Track2View: 4D-Consistent Camera-Controlled Video Generation via Paired 3D Point Tracks

Re-rendering an existing video from a novel camera viewpoint requires the output to follow the prescribed camera trajectory while preserving the appearance and dynamics of the original scene across every frame. Existing methods rely on per-frame pose embeddings, noisy point-cloud renderings, or implicit learned correspondences, none of which provides an explicit, temporally continuous link between source and target pixels. We propose Track2View, which conditions a video diffusion transformer on paired 3D point tracks: sparse trajectories of scene points projected into both the source and target camera views. These tracks provide explicit spatiotemporal correspondences that are temporally continuous by construction, encoding what content should appear where and when. At the core of Track2View is a dual-view track conditioner that transfers visual context from source to target view through parameter-free geometric operations and learned temporal aggregation, ensuring generalization to arbitrary camera trajectories without memorizing specific motions. We further introduce a data curation pipeline that extracts one-to-one track correspondences by running a 3D point tracker on temporally concatenated multi-camera view pairs. On a 400-video benchmark spanning static and dynamic scenes, Track2View achieves state-of-the-art results across visual quality, view synchronization, and camera accuracy, reducing rotation error by 30-65% and translation error by 61-72% relative to leading baselines. Project page is available at this https URL: https://qjizhi.github.io/track2view

19.
arXiv (CS.CV) 2026-06-16

teasr: training-efficient any-step diffusion transformer for real-world image super-resolution

Diffusion models excel in Real-World Image Super-Resolution (Real-ISR) due to their powerful generative priors but suffer from slow iterative sampling. Although existing one-step distillation methods accelerate inference, they typically require auxiliary teacher models that inflate training memory and restrict scalability to large-scale architectures. Furthermore, these fixed-step models lack the flexibility to trade off speed for quality. In this paper, we propose TEASR, a training-efficient any-step diffusion framework for Real-ISR that enables both one-step and multi-step restoration within a unified model. Our key idea is to perform self-adversarial distillation within a single diffusion model, eliminating the need for auxiliary teachers or discriminators. Specifically, we propose a timestep-aware rectification strategy that stabilizes one-step generation across noise levels. These two designs further enables the distillation of 20B-parameter diffusion models on a single GPU, significantly improving training efficiency. Moreover, we introduce a dual-branch diffusion transformer with decoupled timestep condition to separate the current noise state and the denoising target to enhance sampling quality. Extensive experiments demonstrate that TEASR supports seamless any-step sampling and consistently outperforms state-of-the-art methods across multiple datasets.

20.
medRxiv (Medicine) 2026-06-22

T Cell Receptor repertoire analysis reveals antigenic convergence and immunotherapeutic opportunities in Prostate Cancer

Background: The T-cell receptor {beta} (TCR{beta}) repertoire reflects antigen-driven adaptive immune responses and provides insight into tumor-immune interaction. In prostate cancer (PCa), the immunosuppressive tumor microenvironment limits effective T-cell activation, and the antigenic drivers shaping intratumoral TCR repertoires remains poorly defined. This study aimed to characterize matched tumor and peripheral TCR{beta} repertoires from treatment-naive PCa patients and to identify shared clonotypes and antigenic specificities associated with disease severity. Methods: Next-generation sequencing was used to profile TCR{beta} repertoires from matched tumor biopsies and peripheral blood mononuclear cells obtained from treatment-naive PCa patients. Repertoires clonality, diversity, and was assessed using established metrics. Antigenic convergence was evaluated using GLIPH2 to identify shared CDR3{beta} motifs and predicted tumor-associated antigen (TAA) recognition, followed by functional validation using IFN-{gamma} ELISpot and T-cell expansion assays. Results: Tumor-derived TCR{beta} repertoires displayed reduced richness and increased clonality compared with peripheral blood mononuclear cells, consistent with local antigen-driven expansion. High-grade tumors demonstrated greater interpatient clonotype sharing and motif-level convergence, indicative of recognition of common TAAs. GLIPH2 analysis associated expanded clonotypes with epitopes derived from prostate-specific G-protein coupled receptor (PSGR), prostate-specific membrane antigen (PSMA), and prostate-specific antigen (PSA). Functional validation confirmed that peptide pools containing PSGR- and PSMA-derived epitopes induced IFN-{gamma} production and antigen-specific T-cell proliferation in vitro. Conclusions: These findings reveal an oligoclonal, antigen-driven intratumoral TCR{beta} landscape and identify PSGR and PSMA as immunogenic, potentially actionable targets. Integration of TCR profiling with antigen discovery pipelines may support the development of TCR-based biomarkers and precision immunotherapeutic strategies in prostate cancer.

21.
arXiv (quant-ph) 2026-06-16

High-Order Hermite Optimization: Fast and Exact Gradient Computation in Open-Loop Quantum Optimal Control using a Discrete Adjoint Approach

arXiv:2505.09857v5 Announce Type: replace-cross Abstract: This work introduces the High-Order Hermite Optimization (HOHO) method, an open-loop discrete adjoint method for quantum optimal control. Our method is the first of its kind to efficiently compute exact (discrete) gradients when using continuous, parameterized control pulses while solving the forward equations (e.g. Schrodinger's equation or the Linblad master equation) with an arbitrarily high-order Hermite Runge-Kutta method. The HOHO method is implemented in QuantumGateDesign$.$jl (https://github.com/leespen1/QuantumGateDesign.jl), an open-source software package for the Julia programming language, which we use to perform numerical experiments comparing the method to Juqbox$.$jl (https://github.com/LLNL/Juqbox.jl). For realistic model problems we observe speedups up to 775x.

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

Pareto Q-Learning with Reward Machines

arXiv:2606.19134v1 Announce Type: cross Abstract: We present Pareto Q-Learning with Reward Machines (PQLRM), a multi-objective reinforcement learning algorithm for tasks whose reward structure is specified by a set of reward machines (RMs). PQLRM combines Pareto Q-Learning (PQL), which maintains sets of vector-valued Q-estimates to approximate the Pareto front, with enhancements from Q-Learning with Reward Machines (QRM), which exploits the factored automaton structure of the reward signal. This yields a multi-policy algorithm that remains sample-efficient under non-Markovian, RM-encoded rewards. Experimental trials show that PQLRM converges faster than a naive PQL baseline applied to the cross-product MDP and can synthesize Pareto-optimal policies that QRM cannot.

23.
bioRxiv (Bioinfo) 2026-06-16

DynamicDemiLog: A Single Sketch for Ultrafast Similarity, Frequency, and Cardinality Estimation

Probabilistic cardinality estimators (HyperLogLog), similarity sketches (MinHash), and frequency estimators (Count-Min Sketch) are fundamental approximate data structures that each target one primary problem. We present DynamicDemiLog (DDL), a sketch that unifies cardinality estimation, set similarity, containment, element frequency and composition in one tiny data structure built from a single pass over the input stream. Using an inverted index over 200,687 RefSeq sketches (159,567 organisms), DDL performs all-to-all sketch similarity comparison of the full database in 30 seconds (128 threads, indexed) - over 375x faster per query than Mash's brute-force all-to-all comparison of 91,282 sketches, or 31x faster without the index, at double the sketch resolution. DDL extends the LogLog register with a mantissa: each register stores a floating-point-encoded hash value consisting of an integer exponent (the leading-zero count) and a fractional mantissa (the sub-leading-zero bits), rather than the integer leading-zero count alone. This preserves enough hash information for meaningful register-by-register comparison - a property that standard 6-bit registers lack - while improving on LogLog's cardinality estimation machinery, including DynamicLogLog's early exit mask for high-throughput streaming. With a default 10 mantissa bits (16-bit registers, 2,048 buckets, 4 KB), DDL achieves a per-register false-match rate of 0.018% on unrelated random same-size sets (compared to 17.0% for LL6, a basic HyperLogLog implementation), enabling Weighted Kmer Identity (WKID), Average Nucleotide Identity (ANI), containment, and completeness estimation from register comparison alone. A 16-bit per-register observation counter provides element frequency information at trivial additional computation cost, and an additional byte tracks element composition (GC content, for biological data). Furthermore, DDL's high-specificity registers enable an inverted index structure (DDLIndex) that answers similarity queries against a database of N sketches in O(B + M) time, where M is the number of matching index entries, compared to O(NxB) for pairwise comparison.

24.
arXiv (CS.CV) 2026-06-15

Representation Forcing for Bottleneck-Free Unified Multimodal Models

Unified multimodal models (UMMs) aim to handle perception and generation in a single model. Yet existing UMMs still rely on a frozen, separately pretrained VAE for image generation, imposing a structural bottleneck. Naively removing it introduces a quality gap, as the model must learn both high-level structure and low-level details from raw pixels. In this paper, we propose Representation Forcing (RF), a technique that closes this gap by making representation prediction a native capability of the model. Concretely, RF forces the decoder to autoregressively predict visual representations as intermediate tokens before pixels; these tokens then stay in context to guide pixel diffusion within the same backbone. By turning representations from perception outputs into generation targets, RF eliminates the need for any external generative latent space. We find that RF benefits both understanding and generation. On image generation, our pixel-space model with RF matches state-of-the-art VAE-based unified models. On image understanding, pixel-space RF generally outperforms its VAE-based variant. Together, these results offer an effective step toward end-to-end, bottleneck-free UMMs.