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01.
medRxiv (Medicine) 2026-06-12

Cancer care disruption during the COVID-19 pandemic in Ontario, Canada: A sequential mixed-methods study

Introduction The COVID-19 pandemic profoundly disrupted healthcare delivery worldwide, with cancer care among the most affected services. Prior studies documented delays in referrals, reduced specialist access, and increased provider burden. However, the extent to which these experiences were reflected at the system level remains unclear. Objective To document cancer care experiences and examine whether these experiences were reflected in population-level health system indicators across Ontario, Canada. Methods We used an exploratory sequential mixed-methods design. Qualitative data were collected through focus groups and semi-structured interviews with 32 participants, including patients with cancer (n=8), caregivers (n=5), healthcare providers (n=14), and decision-makers (n=5) across two hospital settings in Ontario, Canada. Emergent themes informed the development of quantitative indicators. We then conducted a retrospective population-based analysis of linked administrative health databases for cancer patients in Ontario (n=87,786) to assess the prevalence of identified themes. Results Four themes emerged: (I) delays in diagnosis and screening; (II) disrupted access to primary care; (III) barriers to specialist and mental health services; and (IV) fragmented care for patients with multimorbidity. Quantitative findings corroborated major themes. Screening rates declined for cervical (64.8% to 57.5%) and breast cancer (64.5% to 57.2%). While in-person primary care shifted almost entirely to virtual modalities (8.5% to 95.4%), overall visit volumes remained stable. Specialist care showed uneven patterns, with increased oncology visits but declines in cardiology and mental health services. Patients with multiple comorbidities experienced the largest reductions in non-oncology specialist care. Conclusion The pandemic disrupted key components of cancer care, particularly screening, access to certain specialist services, and care for patients with complex needs. Integrating qualitative and quantitative evidence highlights areas of system vulnerability and underscores the need for coordinated, resilient cancer care capable of maintaining essential services during future crises.

03.
Science (Express) 2026-06-18

Dynamic asymmetric strain imprinted into substrates by an oxide thin film | Science

Authors: Unknown Author

In film-substrate systems, the substrate role is often considered to be limited to providing static mechanical constraints. Dynamic film-substrate interactions when a structural change in the film modifies the substrate are generally disregarded. Using combined X-ray and electron microscopies, we observed that the electrically induced filament in a VO 2 film created strong asymmetric strain in the underlying Al 2 O 3 substate. This asymmetric substrate strain fed back into the film and defined the filament expansion direction, revealing the importance of film-substrate dynamic interactions in determining film functionality. Furthermore, the strain imprint propagated at least tens of microns deep into the substrate, exceeding the film thickness more than 200 times, potentially enabling substrate functionalization as an active mechanical coupling media in 3D-integrated microelectronics architectures.

04.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

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

HairLRM: Strand-based Hair Modeling via Large Reconstruction Models

The fundamental limitation of traditional strand-based modeling is not simply data scarcity, but the ill-posedness of inferring complex 3D fields from 2D imagery without structural constraints. This unconstrained regression leads to catastrophic failures in resolving both global occlusion (e.g., in ponytails) and local directionality (e.g., in curls), resulting in over-smoothed, plausible-but-incorrect geometries. To resolve this, we integrate the strong geometric priors of Large Reconstruction Models (LRMs) into the strand generation pipeline. Using the LRM mesh as a structural anchor, we employ a novel Dual Orientation AutoEncoder to lift coarse geometry into high-fidelity strands. By resolving vector field singularities through latent-space optimization and surface-guided refinement, our method effectively disentangles complex topological structures, setting a new benchmark for robustness and accuracy in hair reconstruction.

06.
medRxiv (Medicine) 2026-06-17

Real-World Effectiveness and Safety of Avacopan in ANCA-Associated Vasculitis: A Systematic Literature Review and Meta-analysis

Background: The efficacy and safety of avacopan in ANCA-associated vasculitis (AAV) has been established in randomized trials of of avacopan as a glucocorticoid (GC) sparing therapy. However, real world evidence (RWE) has an important role in confirming effectiveness and evaluating safety in more generalizable settings. This study aimed to synthesize RWE on the effectiveness and safety of avacopan in adults with AAV. Methods: A systematic literature review and meta analysis of non interventional real world studies was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Eligible studies included adults with AAV treated with avacopan in routine clinical practice. Pooled estimates of effectiveness and safety outcomes were calculated using random effects meta-analyses. Primary outcomes included remission at 6 and 12 months and sustained remission at 12 months. Secondary outcomes included relapse, GC use and dosing, hepatotoxicity, infections, and treatment discontinuation. Exploratory outcomes included changes in estimated glomerular filtration rate (eGFR) and dialysis related endpoints. Results: A total of 71 studies were included and contributed to quantitative analyses. Pooled remission for patients on avacopan was 87% (95% CI: 75%-94%) at 6 months and 93% (95% CI: 86%-97%) at 12 months, and sustained remission was 86% (95% CI: 74%-93%) at 12 months. Relapse at 12 months was low (7%; 95% CI: 4%-11%). GC use was 36% at both 6 and 12 months. Improvements in eGFR were observed at 6 months (18 mL/min/1.73 m2) and 12 months (18 mL/min/1.73 m2), and dialysis liberation was 66% in a limited subset. Among avacopan patients, 11% experienced any hepatotoxicity, including 7% with serious (defined as directly reported or requiring hospitalization) hepatotoxicity, while 7% experienced serious (defined as directly reported or requiring hospitalization) infection. Conclusions: In real world clinical practice, avacopan is associated with high remission rates, low relapse rates, and a consistent GC sparing effect, with effectiveness comparable to standard of care regimens. Findings support its clinical use with appropriate safety monitoring; however, the observed heterogeneity in hepatotoxicity and the limited comparative effectiveness evidence highlight areas requiring further investigation.

07.
arXiv (quant-ph) 2026-06-24

A Hybrid Quantum-Classical Approach for Melt Pool Prediction in Laser Powder Bed Fusion

arXiv:2606.23719v1 Announce Type: new Abstract: Laser powder bed fusion (LPBF) is a promising additive manufacturing technique that suffers from quality assurance concerns. Predicting melt pools from process parameters is crucial for assessing quality prior to manufacturing but remains a difficult problem because of the complex physical processes underlying LPBF. Quantum computers present a new computing paradigm, providing a new approach to information processing using quantum entanglement and superposition. This paper presents a practical demonstration of a hybrid quantum-classical model that leverages quantum computing to improve process parameter feature extraction with a quantum feature encoder. To make the quantum approach computationally feasible for large datasets, we first employ a clustering algorithm to reduce the number of expensive quantum computations. These quantum features are then processed by a classical neural network to predict the melt pool morphology, allowing for more accurate predictions of melt pools. We demonstrate the method using a quantum simulator, analyze the effect of measurement shot noise on the predictive performance of the network, and verify the results using quantum hardware. Finally, by examining which quantum features are most important, we provide insights that can inform the future design of more effective quantum encoding circuits. Ultimately, the performance improvement over purely classical networks validates the hybrid approach, demonstrating an engineering application of quantum computing using noisy and intermediate scale quantum (NISQ) devices.

08.
arXiv (CS.CV) 2026-06-15

SED:Lightweight Saliency prediction for Event-based data via Distillation

Event-based saliency prediction has gained attention recently, as combining event cameras with saliency estimation can act as an upstream stage that naturally improves the efficiency of downstream eventbased perception at the edge. However, current approaches are either neuromorphic, underperforming on event-based saliency benchmarks, or too heavy for resource-constrained edge applications due to their reliance on transformers or 3D convolutions. Drawing inspiration from efficient convolutional modules, SED and aiming to exploit the temporal information in event data, we propose a lightweight network, trained through knowledge distillation, built on a Depthwise Spatio-Temporal Block (DSTconv) – a factorization of the 3D depthwise separable convolution. Relative to its teacher, our model reduces the model size from 180 MB to 0.32 MB (562x) and the parameter count from 45M to 81k (554x), while matching or outperforming it on the N-DHF1K and N-UCF Sports datasets. Moreover, it generalizes strongly beyond its training distribution, transferring from synthetic to real event data where a model trained from scratch fails.

09.
arXiv (CS.LG) 2026-06-24

Stochastic Expectation Maximization for Robust State-Space Radio Interferometric Imaging

arXiv:2606.23944v1 Announce Type: cross Abstract: State–space models provide a flexible framework for analyzing dynamical systems, yet they often rely on Gaussian assumptions that fail to capture heavy-tailed or outlier-prone measurement noise. We propose a robust estimation scheme for linear state–space models subject to compound-Gaussian noise, as encountered for instance in radio interferometry affected by radio-frequency interference (RFI). The method relies on a Stochastic Approximation Expectation–Maximization (SAEM) algorithm in which the standard E-step is replaced by Monte Carlo sampling of the latent states and noise texture through closed-form Gibbs updates, enabling tractable inference despite the heavy-tailed likelihood. Numerical experiments show that the proposed method significantly improves reconstruction fidelity and robustness to RFI, outperforming a Gaussian EM algorithm and even an oracle RTS smoother. These results highlight the benefits of heavy-tailed state–space modeling and SAEM-based inference in interference-dominated imaging scenarios.

10.
arXiv (CS.AI) 2026-06-18

Code-Augur: Agentic Vulnerability Detection via Specification Inference

arXiv:2606.18619v1 Announce Type: cross Abstract: The advent of agentic vulnerability detection is already becoming a watershed moment for software security. Audits conducted entirely by autonomous LLM agents are uncovering critical vulnerabilities in fundamental software underpinning digital society. Many of these vulnerabilities remained masked for years, surfacing only now with AI agents. Yet the reasoning behind these discoveries remains alarmingly opaque and unvalidated. What assumptions did the agent make about a function's inputs when it deemed that function to be secure? Failures in reasoning and incorrect assumptions can lead to missed vulnerabilities and reduce trust in agentic analysis. We propose a security-specification-first paradigm that (1) exposes the agent's tacit assumptions explicitly as security specifications and (2) continuously refines those specifications via runtime falsification. We realize our approach in Code-Augur, a novel harness for agentic vulnerability detection. Given a codebase, Code-Augur analyzes each component of the system for vulnerable code. When it deems a component to be secure, it commits the local invariants behind that judgment as in-source assertions. In parallel, Code-Augur leverages a guided fuzzer to attempt to falsify those assumptions. When the fuzzer triggers an assertion, this either reveals a genuine vulnerability or a flawed specification to refine. In both cases, this process grounds the agent's understanding, aligning its view of code intent with how the code actually behaves. On real-world subjects, Code-Augur effectively leverages security specifications to detect more vulnerabilities than other state-of-the-art agents. Additionally, Code-Augur found 22 new vulnerabilities in key open-source projects. Compared to curated specialized models like Claude Mythos, Code-Augur offers effective agentic vulnerability detection built on widely available LLMs like Sonnet and DeepSeek.

12.
arXiv (quant-ph) 2026-06-15

Synchronization of Quasi-Particle Excitations in a Quantum Gas with Cavity-Mediated Interactions

arXiv:2504.17731v2 Announce Type: replace-cross Abstract: Driven-dissipative quantum systems can undergo transitions from stationary to dynamical phases, reflecting the emergence of collective non-equilibrium behavior. We study such a transition in a Bose-Einstein condensate coupled to an optical cavity and develop a cavity-assisted Bragg spectroscopy technique to resolve its collective modes. We observe dissipation-induced synchronization at the quasiparticle level, where two roton-like modes coalesce at an exceptional point. This reveals how dissipation microscopically drives collective dynamics and signals a precursor to a dynamical phase transition.

13.
arXiv (CS.AI) 2026-06-19

How Transparent is DiffusionGemma?

arXiv:2606.20560v1 Announce Type: cross Abstract: LLM reasoning transparency is a critical affordance for understanding model decisions, mitigating misuse and misalignment, and debugging surprising model behaviors. However, DiffusionGemma performs a larger fraction of its computation in a continuous latent space; does this make its reasoning less transparent? We study this question by decomposing transparency into two components: variable transparency, whether we understand intermediate snapshots of a model's computational state; and algorithmic transparency, whether we can use these snapshots to reconstruct the process by which the model arrived at its outputs. Naively, DiffusionGemma has poor variable transparency: its opaque serial depth, the amount of serial computation that occurs in between interpretable model states, seems at first 28.6X higher than the corresponding autoregressive Gemma 4 model. However, we show that we can map the information flowing between denoising steps through an interpretable token bottleneck with no decrease in downstream performance. Treating these intermediate states as interpretable reduces the opaque serial depth to just 1.1X that of Gemma 4. Algorithmic transparency is harder for diffusion models than for autoregressive models because all token predictions in the canvas can change at every denoising step, giving the model the power to implement complicated distributed algorithms during the denoising process. To begin bridging this gap, we conduct a suite of interpretability case studies, uncovering initial evidence of novel diffusion-specific phenomena such as non-chronological reasoning, token and sequence smearing, and intermediate-context reasoning. Finally, we test monitorability, a key application of transparency that measures whether model outputs are useful for downstream tasks. We find that DiffusionGemma is similarly monitorable to Gemma 4.

14.
arXiv (CS.AI) 2026-06-24

ARIA: Adaptive Region-Based Importance Allocation for Conditional Diffusion Distillation

arXiv:2606.23898v1 Announce Type: cross Abstract: Distilling conditional diffusion models aims to transfer the behavior of a large teacher to a smaller student while preserving alignment across conditioning inputs. Unlike recognition tasks, knowledge distillation in conditional diffusion often struggles to transfer knowledge beyond the training distribution, since the predicted noise strongly depends on the conditioning signal. As a result, effective distillation requires exploring a large conditioning space. In practical settings, this creates a major bottleneck. Paired image-condition data may be limited, and generating synthetic images for every available condition is often computationally infeasible, while the pool of conditions, such as text prompts, can be extremely large. Recent work addresses this issue by switching conditions during training, exposing the student to a broader conditioning space without changing the distillation objective. Yet this raises a complementary question: once a large conditioning corpus is available, how should the training effort be allocated? In this work, we introduce ARIA, a framework that adaptively allocates training effort across coarse regions of the conditioning space. By maintaining online estimates of teacher-student discrepancy at the region level, ARIA focuses updates where misalignment persists while preserving the original distillation objective. Empirically, ARIA improves over RC across most architectures and settings, with the clearest gains observed in unseen and underrepresented regimes. We also provide a theoretical analysis showing that the proposed tracking mechanism follows the evolving discrepancy during training under bounded variance and drift assumptions.

15.
arXiv (CS.AI) 2026-06-12

Arbor: Tree Search as a Cognition Layer for Autonomous Agents

arXiv:2606.12563v1 Announce Type: new Abstract: Arbor is a multi-agent framework that introduces structured tree search as a cognition layer for autonomous agents operating in large, stateful action spaces. Prior autonomous optimization systems operate on isolated targets with stateless evaluation. Arbor instead maintains an explicit search tree of scored hypotheses that serves as the shared working memory across agents, evolving with every measurement, treating failures as diagnostic signal that reshapes subsequent exploration, and expanding as prior successes shift the bottleneck distribution. We validate Arbor on full-stack LLM inference optimization, a domain where achieving peak performance has historically required coordinated effort from engineering teams across the application, framework, compiler, kernel, and hardware stack. Arbor pairs an Orchestrator agent, which drives optimization by delegating to Domain Specialists across the inference stack, with a Critic agent that safeguards stability through root-cause analysis, introspection, and measurement validation – a checks-and-balances architecture where neither agent can unilaterally drive the system. Agent capabilities are decomposed into hard skills (domain expertise) and soft skills (coordination protocols that determine how contributions compose), enabling fully autonomous multi-day campaigns. Arbor achieves up to 193% inference throughput-latency Pareto improvement over vendor-optimized baselines, while a single agent without the harness plateaus at +33% throughput improvement and crashes irrecoverably within hours. Arbor generalizes to multiple generations of hardware platform, and run-to-run variance is within 2 percentage points demonstrating that the method is hardware-agnostic and reproducible.

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

Large-Language-Model Discovery of Quantum LDPC Codes through Structured Concept Evolution

arXiv:2606.24808v1 Announce Type: cross Abstract: Quantum computers could outperform classical machines on important problems, but only if the errors that pervade quantum hardware can be corrected at scale. Quantum low-density parity-check (qLDPC) codes offer a promising route to this goal by combining sparse parity checks with finite encoding rate and growing distance, but their construction remains a challenging discrete design problem. Here we introduce structured concept evolution (SCE), a search framework that pairs a large language model with a structured algebraic mutation grammar to discover lifted-product code families, a class of CSS qLDPC codes. Instead of asking the LLM to design codes from first principles, SCE evolves structured concepts consisting of algebraic specifications paired with executable programs that realize them, using hierarchical mutations that modify the group algebra, protograph geometry, or base space. Running SCE, we discover a diverse set of competitive code families, ranging from abelian constructions to families over non-abelian groups beyond those underlying standard designs such as bivariate-bicycle codes, and characterize them under code-capacity depolarizing noise with BP+OSD decoding. These results are obtained with lightweight models (GPT-5.4-mini and GPT-5.4-nano).

17.
arXiv (math.PR) 2026-06-24

Strong duality for the GROW criterion

arXiv:2606.24768v1 Announce Type: cross Abstract: This paper presents general strong duality results when testing hypotheses by betting against them. A bet is an e-variable for a composite null hypothesis $\mathcal{P}$: a nonnegative random variable $X$ whose expected value is at most one under every $\P \in \Pcal$. Following Kelly, Breiman, Cover, Shafer, Grünwald and others, we study a natural minimax log-optimality criterion: given a composite alternative $\Qcal$, we characterize the ``GROW value'' $\sup_{X} \inf_{\Q} \E_{\Q}[\log X]$. This paper generalizes the results of [larsson2025numeraire] from (arbitrary $\Pcal$ and) simple $\Qcal$ to arbitrary $\Qcal$. We identify a weak-$*$ joint information projection pair between arbitrary $\Pcal$ and $\Qcal$ that always exists and show that the GROW value for bounded e-variables always equals the relative entropy of this pair, without any restrictions on $\Pcal$ or $\Qcal$. We also prove a similarly general strong duality for the REGROW criterion with bounded e-variables and arbitrary bounded offsets. Under various assumptions our results extend to unbounded e-variables, and examples show that without any assumptions such extensions fail. Our results are analogous to those in[larsson2026complete], swapping tests for bounded e-variables, minimax risk for the GROW criterion, and total variation for relative entropy.

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

REALM: A Unified Red-Teaming Benchmark for Physical-World VLMs

Vision-language models (VLMs) are increasingly used as perception-reasoning backbones for embodied intelligence in safety-critical physical systems, where perception or reasoning errors can lead to unsafe decisions or actions. Although many red-teaming methods have been developed to probe VLM vulnerabilities, their evaluation remains fragmented across datasets, metrics, and threat models, making direct comparison difficult and obscuring whether observed differences arise from stronger attacks, more vulnerable models, or incompatible evaluation settings. Existing chatbot-centric red-teaming benchmarks mainly standardize jailbreak and content-safety evaluation, but they do not systematically capture physically grounded functional failures or cover red-teaming methods that target physical-world VLMs. This raises the key challenge of comparing diverse attack methods under a unified protocol while targeting the same scenario-specific failures. We introduce REALM, to our knowledge the first unified red-teaming benchmark for physical-world VLMs. REALM integrates 12 red-teaming methods, 3 model-agnostic defenses, and 13 VLMs under a practical black-box threat model with shared datasets and metrics. To align adversarial objectives across attack families, REALM introduces an agentic target-generation pipeline that constructs shared, scenario-specific, and physically grounded attack objectives for each scene, enabling fair comparison of diverse red-teaming methods under aligned adversarial goals. Our evaluation shows that text and typographic injection attacks induce the most failures, multimodal co-optimization yields the strongest visual-perturbation transfer, single-pass attacks approach iterative methods at much lower cost, and model scale alone does not confer adversarial robustness. Code is available at https://github.com/UCF-ML-Research/REALM.

19.
arXiv (CS.AI) 2026-06-15

Active Inference for Adaptive Traffic Signal Control in Noisy Nonstationary IoT Environments

arXiv:2606.13698v1 Announce Type: cross Abstract: Urban traffic signal control at IoT-instrumented intersections must remain effective under sensor occlusion, weather attenuation, and nonstationary demand. Conventional controllers degrade under these conditions, and learned policies remain difficult to audit. To address these challenges, we propose an active inference controller for a four-arm signalized intersection that dynamically selects phases by minimizing expected free energy (EFE) over Gaussian beliefs about per-direction congestion levels, yielding a fully traceable decision pipeline. We benchmark the controller in a SUMO traffic simulator against a rule-based heuristic and a deep Q-network (DQN) across four scenarios that progressively increase noise and nonstationarity, spanning sensor occlusion, adverse weather, and stochastic accidents. Across 100 independent random evaluations per scenario, active inference attains the lowest idle times and CO2 emissions in the noisiest scenarios (56,977 s and 29.12 kg vs. 71,741 s and 30.56 kg for DQN). These gains come at a modest cost in bus priority service rate and phase switch frequency.

20.
medRxiv (Medicine) 2026-06-17

A multistate model of frailty progression after severe infections in adults >=65 years in England: a matched-cohort study

Background Evidence on frailty progression following severe infections is limited. We compared rates of transition to greater frailty or death between adults with and without severe infection in England. Methods We conducted a matched-cohort study among adults aged [≥]65 years (1,452,117: median age 76 years, 45% male) in Clinical Practice Research Datalink Aurum (2006-2019). Adults with severe infection (hospitalised primarily due to infection) were matched on calendar time to individuals without severe infection on age, sex, and primary care practice. The admission date was used as index date and same was assigned to matched unexposed adults. We measured frailty using Electronic Frailty Index, a proportion of 36 health deficits in validated categories (Fit 0-0.12, Mild >0.12-0.24, Moderate >0.24-0.36, Severe >0.36). In a time-varying Markov multistate model, we focused on forward transitions from baseline or intermediate frailty states to higher states or death. For each transition, we used Cox regression to estimate cause-specific transition hazard ratios (HR) with 95% confidence intervals (CIs), comparing adults with and without severe infection. We adjusted for baseline frailty score, age, sex, deprivation, harmful alcohol use, smoking, and primary care infection history 5 years before index date. We estimated state occupancy probabilities, and expected length of stay (ELOS) in each state at year five among adults with and without severe infection. We explored effect modification by infection type. Results Across all transitions, severe infection was associated with higher adjusted hazards of transitioning to worsening frailty or death, HR, 95% CI: (fit to: mild[1.56, 1.54-1.58], moderate[2.51, 1.79-3.51], death[4.57, 4.50-4.65]; mild to: moderate[1.52, 1.50-1.53], severe[1.90, 1.43-2.52], death[2.67, 2.64-2.70]; moderate to: severe[1.40, 1.38-1.42], death[1.87, 1.85-1.90]; severe to death[1.48, 1.46-1.50]). Transition hazard ratios were strongest for lower respiratory tract infections, followed by sepsis, urinary tract infections, meningitis/encephalitis, gastroenteritis, and skin and soft tissue infections. At five years, adults with severe infection had higher probabilities of transitioning to greater frailty or death across all transitions and lower ELOS in each frailty state than those without severe infection. Interpretation Severe infections may accelerate frailty deterioration in older age. Prevention through vaccination, early detection, and prompt management may help mitigate this decline.

21.
arXiv (CS.LG) 2026-06-11

Understanding Sample Efficiency in Predictive Coding

arXiv:2605.11911v2 Announce Type: replace Abstract: Predictive Coding (PC) is an influential account of cortical learning. Much of recent work has focused on comparing PC to Backpropagation (BP) to find whether PC offers any advantages. Small scale experiments show that PC enables learning that is more sample efficient and effective in many contexts, though a thorough theoretical understanding of the phenomena remains elusive. To address this, we quantify the efficiency of learning in BP and PC through a metric called ``target alignment'', which measures how closely the change in the output of the network is aligned to the output prediction error. We then derive and empirically validate analytical expressions for target alignment in Deep Linear Networks. We show that learning in PC is more efficient than BP, which is especially pronounced in deep, narrow and pre-trained networks. We also derive exact conditions for guaranteed optimal target alignment in PC and validate our findings through experiments. We study full training trajectories of linear and non-linear models, and find the predicted benefits of PC persist in practice even when some assumptions are violated. Overall, this work provides a mechanistic understanding of the higher learning efficiency observed for PC over BP in previous works, and can guide how PC should be parametrised to learn most effectively.

22.
bioRxiv (Bioinfo) 2026-06-17

DesignMaster: A Multi-Conditional Diffusion Framework for Rational PROTAC Design

Motivation: Proteolysis-targeting chimeras (PROTACs) enable targeted protein degradation through ternary complex formation with E3 ubiquitin ligase. However, the rational design of PROTACs remains highly challenging due to limited structure-activity relationship data and the vast conformational diversity of linkers. Existing computational approaches can be broadly divided into structure-based ternary modelling methods and fragment-based linker generation models. Although these approaches have advanced PROTAC design, they typically neglect key physicochemical constraints and linker-length control during the generation process, causing the generated PROTACs to lack balanced structural properties required for effective ternary complex formation with drug-like characteristics. Results: To address these limitations, we propose DesignMaster, a diffusion-based generative framework that explicitly incorporates linker length and physicochemical properties as controllable conditioning signals. DesignMaster employs an E(3)-equivariant graph Transformer with a gated multi-condition fusion module to inject linker length and physicochemical constraints throughout the diffusion process, enabling fine-grained and constraint-aware molecular generation. Experiments on PROTAC-DB 2.0 and 3.0 demonstrate that DesignMaster outperforms state-of-the-art baselines, with a 3.2% improvement in validity and a 34.4% improvement in recovery. The Case study shows DesignMaster achieves a 51.78% reduction in RMSD when predicting the linker of PROTAC BCPyr targeting 6W7O, highlighting its potential for practical structure-guided PROTAC design. Availability: The source code and datasets are available at https://github.com/ABILiLab/DesignMaster.

23.
arXiv (math.PR) 2026-06-16

Balanced affine Motzkin paths: Pearson geometry and global endpoint asymptotics

arXiv:2601.17634v2 Announce Type: replace Abstract: We study endpoint distributions of balanced affine weighted Motzkin paths. In the balanced case, the generating-function equation has Pearson-type characteristic geometry. We show that this geometry controls the terminal-height law globally: the characteristic escape time determines the limiting cumulant generating function, the large-deviation rate function, and the ray-scale asymptotics. Thus the usual Gaussian window is only the local quadratic approximation to a global Pearson-driven profile. For finite sizes, we prove a uniform Daniels saddlepoint approximation in the one-dominant-singularity regimes and identify the exceptional antipodal case requiring a lattice/interference correction.

24.
arXiv (CS.CV) 2026-06-19

Pixel-Level Residual Diffusion Transformer: Scalable 3D CT Volume Generation

Generating high-resolution 3D CT volumes with fine details remains challenging due to substantial computational demands and optimization difficulties inherent to existing generative models. In this paper, we propose the Pixel-Level Residual Diffusion Transformer (PRDiT), a scalable generative framework that synthesizes high-quality 3D medical volumes directly at voxel-level. PRDiT introduces a two-stage training architecture comprising 1) a local denoiser in the form of an MLP-based blind estimator operating on overlapping 3D patches to separate low-frequency structures efficiently, and 2) a global residual diffusion transformer employing memory-efficient attention to model and refine high-frequency residuals across entire volumes. This coarse-to-fine modeling strategy simplifies optimization, enhances training stability, and effectively preserves subtle structures without the limitations of an autoencoder bottleneck. Extensive experiments conducted on the LIDC-IDRI and RAD-ChestCT datasets demonstrate that PRDiT consistently outperforms state-of-the-art models, such as HA-GAN, 3D LDM and WDM-3D, achieving significantly lower 3D FID, MMD and Wasserstein distance scores.

25.
arXiv (CS.CV) 2026-06-12

IterCAD: An Iterative Multimodal Agent for Visually-Grounded CAD Generation and Editing

Computer-Aided Design is pivotal in modern manufacturing, yet existing automated methods predominantly rely on open-loop, one-shot generation, creating a mismatch with iterative real-world practices. In this paper, we present IterCAD, a unified multimodal agent framework for closed-loop, interactive CAD generation and editing. We formulate the task as a multi-turn interaction between a multimodal agent and an executable CAD sandbox, covering three tasks: Drawing-to-Code, Text-to-Code, and Interactive Editing. To support this, we develop a data synthesis pipeline incorporating advanced industrial manufacturing features to generate standard-compliant multi-view engineering drawings, complex code-editing tasks, and high-fidelity interaction trajectories. We optimize the agent via progressive SFT followed by geometry-aware reinforcement learning with viable-prefix masking to enhance code executability and geometric fidelity. Finally, we introduce the IterCAD-Bench evaluation suite and propose the Chamfer Distance Tolerance-Recall (CD-TR) curve alongside its AUC-TR metric, establishing a survivor-bias-free standard that unifies code validity and geometric precision. Extensive experiments demonstrate that IterCAD achieves highly competitive performance across multiple benchmarks, significantly outperforming existing approaches in both code executability and geometric precision, while exhibiting superior capabilities in closed-loop iterative refinement.