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01.
arXiv (quant-ph) 2026-06-15

A new class of degenerate solutions to the massless Dirac equation and their potential applications in optical memories

arXiv:2606.14256v1 Announce Type: new Abstract: In this article, we present a novel class of degenerate solutions to the massless Dirac equation, corresponding to a wide variety of electromagnetic 4-potentials and fields, including both zero field and circularly polarized electromagnetic waves. An interesting property of these solutions is that the spin of the particles rotates in synchronization with the electric and magnetic fields of the electromagnetic waves. These results could be utilized for the development of optical memories based on materials supporting massless Dirac fermions, such as graphene.

02.
arXiv (quant-ph) 2026-06-15

The Bilateral Efficiency of Ethernet: Recalibrating Metcalfe and Boggs After Fifty Years

作者:

arXiv:2603.19406v2 Announce Type: replace-cross Abstract: In July 1976, Metcalfe and Boggs published their foundational paper on Ethernet in Communications of the ACM. Their efficiency model – E = (P/C)/(P/C + W*T) – measures the fraction of Ether time carrying good forward packets under contention. For fifty years this model has framed how the community thinks about Ethernet performance. We argue it is silent on the question that matters for modern intra-rack interconnect: bilateral transaction efficiency – the fraction of link time that produces committed agreements between sender and receiver. Metcalfe and Boggs themselves planted the seed in their EFTP "end-dally" protocol (Section 7.2.2), and the deeper anchor is older still: Abramson's Alohanet carried positive acknowledgments at the link layer – a bilateral mechanism Metcalfe consciously removed in 1973 to obtain Ethernet's simple, ACK-free packet format. The result is a fifty-year bilateral zigzag: Aloha (bilateral) to Ethernet (unilateral) to the EFTP end-dally (bilateral) to TCP (unilateral-with-bilateral-above). We formalize bilateral efficiency, connect it to the back-to-back Shannon channel with Perfect Information Feedback, and – scoping the claim explicitly to intra-rack distances of one meter or less – describe how the Open Aethernet link recovers mutual knowledge at the link layer. The correction to Table 1 is not a different set of numbers. It is a different question.

03.
arXiv (CS.CL) 2026-06-15

MedLatentDx: Latent Multi-Agent Communication for Cross-Hospital Rare-Disease Diagnosis

Rare diseases affect over $300$ million patients across more than $7{,}000$ conditions, yet no single hospital encounters enough cases of any one condition for reliable diagnosis. Cross-hospital collaboration could help by allowing a diagnosing institution to use distributed, case-specific diagnostic evidence, but privacy regulations restrict the transmission of identifiable clinical text across institutional boundaries. This setting raises two challenges: existing medical agent systems often rely on textual evidence exchange, while raw latent states such as hidden states and KV caches may still reveal prompt-derived clinical content. We introduce MedLatentDx, a latent multi-agent communication framework in which hospital agents keep private clinical records and retrieved cases local, and send compact latent KV blocks to a host agent for rare-disease diagnosis. MedLatentDx supports two deployment settings: same-backbone hospital agents use latent KV distillation, while hospitals with different LLM backbones use cross-family latent alignment. On CrossRare-Bench, a self-built large-scale rare-disease benchmark with hospital-level partitions, MedLatentDx improves cross-hospital diagnostic performance while reducing reconstructable clinical content relative to raw-latent communication baselines.

04.
arXiv (CS.CV) 2026-06-12

ViPER: Vision-based Packing-Aware Encoder for Robust Malware Detection

Visualization-based malware detection maps raw binary bytes to grayscale images and applies learned visual classifiers, providing an evasion-resistant and disassembly-free alternative to conventional analysis pipelines. However, executable packing remains a critical failure mode: packed binaries produce high-entropy images that obscure the structural patterns these models rely on. Because packing is also prevalent in benign software (e.g., for compression or copy protection), packing state alone is not a reliable indicator of maliciousness, and existing approaches do not address this challenge within a unified supervised framework. We present ViPER, a Vision-based Packing-Aware Encoder for Robust malware detection. ViPER builds on a LoRA-adapted ViT-B/14 backbone with a dual-head architecture that jointly learns malware classification and packing detection. A packing-aware gating mechanism conditions malware predictions on the inferred packing state, enabling distinct decision boundaries for packed and unpacked inputs. To address packing label skew during training, we employ frequency-weighted losses with stratified sampling over joint class-packing strata. Evaluated on 200,000 Windows PE byteplot images, ViPER achieves a balanced accuracy of 0.8521, ROC-AUC of 0.9260, and AUPR of 0.9279, outperforming representative state-of-the-art baselines across all primary metrics, while attaining a packing detection AUC of 0.9949.

05.
arXiv (math.PR) 2026-06-19

The central heat trace on large compact classical groups

arXiv:2511.08288v2 Announce Type: replace-cross Abstract: We study the large-$N$ asymptotics of the central trace of the heat kernel on compact classical groups. For every classical family $G_N\subset \mathrm{GL}_N(\C)$, we prove a full large-$N$ asymptotic expansion, using a highest weights/partitions correspondence adapted to the large-rank regime, under which the eigenvalues of the Laplace–Beltrami operator stabilize as observables in the algebra of shifted symmetric functions. Then, we prove a random surface representation of the trace in terms of ramified coverings of the torus. We provide two independent applications: an explicit large-rank counting law for the Casimir spectrum, with exponential Hardy–Ramanujan-type growth in contrast with the polynomial behavior of Weyl's law at fixed rank, and a rigorous probabilistic formulation of the Yang–Mills/Hurwitz duality on a two-dimensional torus initiated by Gross and Taylor, completing a previous work of the authors. We also extend this duality to a Yang–Mills/Gromov–Witten duality by expressing the coefficients of the central heat trace as explicit functionals of the generating function of Gromov–Witten invariants.

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

CineOrchestra: Unified Entity-Centric Conditioning for Cinematic Video Generation

Cinematic video depicts multiple subjects acting or interacting at specific moments, captured with deliberate camera movement, and stitched together by shot transitions. Together, these elements demand a level of fine-grained control beyond current text-to-video models. Existing work addresses each axis in isolation: multi-subject personalization, temporal control, multi-shot synthesis, or camera control; no prior framework jointly integrates all four. We present CineOrchestra, a unified video diffusion model that controls subjects, events, cameras, and shot transitions simultaneously. Our key insight is that these heterogeneous cinematic elements share a fundamental structure: each is an entity acting over a specific temporal interval, which can therefore all be expressed through one shared structure of entity-centric conditioning primitives, augmented with reference images for visual entities. This formulation reduces the architectural challenge to a single positional encoding problem, which we solve with two parameter-free coordinated rotary embeddings: (a) an interval-sampled temporal RoPE that yields consistent attention behavior across events of dramatically varying duration, and (b) a 2D entity-temporal cross-attention RoPE that disambiguates per-entity conditions and routes each to its corresponding spatiotemporal region. On two new benchmarks, CineOrchestra outperforms six per-axis specialists on dense caption following and shot-transition timing, with consistent gains in a pairwise user study and component ablations.

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

Koshur Diacritizer: A Byte-Level Sequence-to-Sequence Model for Kashmiri Diacritic Restoration

Kashmiri, an Indo-Aryan language written in a modified Perso-Arabic script, frequently omits diacritic marks in digital text, creating ambiguity and challenging downstream NLP applications. We present Koshur Diacritizer, a ByT5-small byte-level sequence-to-sequence model for restoring diacritics in Kashmiri text. To support this task, we release a publicly available dataset of 23.7k aligned undiacritized diacritized Kashmiri sentence pairs. The proposed framework combines script-aware normalization, alignment validation, and skeleton-preserving inference to ensure reliable restoration while maintaining the original base-letter sequence. Experimental results on a held-out test set achieve a DERm of 0.2012 and a WER of 0.2159. Additionally, evaluation by a native Kashmiri linguistic expert yields a mean accuracy of 77.5%. The dataset, model, and source code are publicly released to provide a reproducible baseline for Kashmiri diacritic restoration and future low-resource language research.

08.
arXiv (CS.CV) 2026-06-16

GRACE: Boosting Video MLLMs with Grounded Action-Centric Evidence for Viewer Sentiment Prediction

Viewer sentiment prediction in video advertisements aims to infer the latent affective response evoked in the audience. To bridge the gap between what is shown and what is felt, models must deduce hidden viewer emotions from explicit visual narratives, concrete character-object interactions, and visible textual cues. However, standard Multimodal Large Language Models (MLLMs) typically rely on holistic frame representations, which leave these fine-grained, affect-relevant events implicit and complicate precise emotional reasoning. To address this, we propose a grounded action-centric evidence augmentation framework that enhances video MLLMs' clue extraction and comprehension by introducing explicit event structure and localized visual evidence. Our method extracts temporally ordered subject-verb-object (SVO) triplets and auxiliary visible textual cues from action-centric video descriptions, grounds subject and object entities as visual entity crops, and then enables the MLLM to perform clue-enhanced emotional reasoning based on these extracted structured clues. In this way, action triplets specify "what happens", while grounded visual entity crops anchor "who or what participates in each event" to concrete visual evidence. Experiments on the Pitts dataset show consistent improvements over Qwen2.5-VL and Qwen3-VL baselines. Ablation studies, cross-dataset evaluation on AdsQA, and transfer experiments on an emotion-focused TVQA subset further support the effectiveness and generalization of our approach.

09.
Science (Express) 2026-06-04

Long-range extended chains arising from polymerization-driven spontaneous assembly | Science

作者: 未知作者

A central challenge for conjugated polymers is to achieve long-range order while remaining solution-processable, which is essential for matching the electrical performance of their counterparts of crystalline inorganic semiconductors. Here we show that n-doped poly(benzodifurandione) (n-PBDF) can undergo polymerization-driven spontaneous assembly (PSA), in which chain growth, chemical doping, and structural ordering are intrinsically coupled, yielding long-range chain extension over hundreds of nanometers. We reveal that the spontaneously formed n-PBDF nanoribbons arise from a self-initiated, convergent growth mechanism driven by cooperative monomer–polymer interactions and stabilized by proton-coupled duplex chains and the polymer’s intrinsic polyelectrolyte character. With long-range extended chains in the nanoribbons, the aligned n-PBDF thin films demonstrate metallic-level conductivity (>10 4 Siemens per centimeter).

10.
medRxiv (Medicine) 2026-06-19

A soluble bi-specific fusion protein for the improved expansion of human CD8+ CAR-T cells

The success of Chimeric Antigen Receptor (CAR) T cell therapy is heavily dependent on the quality of the final cellular product. Current expansion protocols often rely on reagents that require removal from cell culture media, posing logistical challenges in manufacturing, and can also lead to terminal differentiation. Here, we evaluate the use of a soluble, bead-free T cell activator, T cell expansion protein (T-CEP), as a streamlined alternative for generating potent CAR-T cells. Human T cells were activated with T-CEP or known T cell activators (Dynabeads and TransAct) and transduced with either CD19 or interleukin-13 (IL-13) mutein (tetravariant-13; TV-13)-based CAR lentiviral vectors. Our results demonstrate that T-CEP supports robust CAR-T cell expansion and achieves transduction efficiencies comparable to commercial reagents for both types of CAR-T cells. Notably, T-CEP significantly favored the expansion of CD8+ T cells, yielding an enhanced CD27+ phenotype and a lower CD4:CD8 ratio compared to TransAct. Cytotoxicity assays confirmed that T-CEP-expanded CAR-T cells possess cytolytic function equivalent to commercial reagents for both CARs, while exhibiting lower levels of inflammatory cytokine secretion. In summary, T-CEP represents a competitive alternative to existing expansion agents, as it does not require its removal during CAR-T manufacturing and generates a CD8+ dominant, less-differentiated phenotype without compromising efficacy.

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

PointDiffusion: Diffusion-Based Scene Completion in the Point Cloud Domain

Reconstructing dense 3D scenes from sparse LiDAR point clouds is a fundamental challenge in autonomous driving, where latent diffusion models offer a promising solution. However, existing approaches rely on object-level autoencoders that collapse into unstable global representations at outdoor scale and suffer from ground truth data corrupted by odometry drift that systematically degrades supervision quality. Furthermore, multi-step diffusion inference incurs prohibitive latency for real-time deployment. We propose a novel multi-token Gaussian VAE with cross-attention pooling for stable scene-scale LiDAR compression, combined with an anchor-based ICP ground truth refinement pipeline that eliminates drift-induced noise from training supervision. Together, these components enable a scaffold-free single-step diffusion completion model that achieves an approximately 16x reduction in squared Chamfer distance on SemanticKITTI seq. 08 (0.396 m^2 to 0.024 m^2), surpasses LiDiff and ScoreLiDAR by 17-19% and 10-11%, respectively, and operates at 25-143x lower inference latency. Our results demonstrate that data quality dominates model design in this regime and that multi-token latent spaces provide a stable first stage for latent diffusion-based scene completion.

13.
PLOS Medicine 2026-05-14

Antibody fine specificity correlates with protection from malaria for the RTS,S vaccine in young African children: A post hoc analysis of a phase IIb randomised controlled trial

作者:

by Alessia Hysa, D. Herbert Opi, Joshua Waterhouse, Sandra Chishimba, Jessica L. Horton, Natalie Kingston, Hans J. Netter, David Wetzel, Michael Piontek, Gaoqian Feng, Jahit Sacarlal, Carlota Dobaño, Liriye Kurtovic, James G. Beeson Background The RTS,S/AS01 malaria vaccine was recently approved for implementation in children, but only provides modest and short-lived efficacy against malaria. RTS,S targets a portion of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP), comprising the central NANP-repeat region and C-terminal domain. Mechanisms of immunity and correlates of protection for the RTS,S vaccine are not well defined, hindering progress towards generating highly effective CSP-based vaccines. Methods and findings We investigated epitope specificity and cross-reactivity of vaccine-induced antibodies to six peptides representing CSP epitopes in the N-terminal and central NANP-repeat region. We evaluated antibody reactivity in preclinical mouse vaccine studies, among CSP-specific monoclonal antibodies (mAbs), and in a large RTS,S phase IIb clinical trial in young children 1–4 years old (n = 735).The preclinical mouse vaccine studies and CSP-specific mAbs were used to initially evaluate IgG responses to the six peptides. Mice immunised with the central NANP-repeat region had IgG with cross-reactivity to an epitope in the N-terminal region. Additionally, we demonstrated that a single CSP-specific mAb could display cross-reactivity to several CSP epitopes. Through post hoc quantification and analysis of antibody responses in the RTS,S phase IIb clinical trial, we found that a subset of children generated IgG with specificity for a short NANP-repeat epitope (NANP2; amino acid sequence: NANPNANP) and cross-reactivity to an N-terminal epitope (J1; amino acid sequence: KQPADGNPDPNANPN). Notably, children with high IgG responses to NANP2 and J1 had a significantly reduced risk of clinical malaria, compared to children with low responses (IgG to NANP2 (aHR: 0.838 (95% CI [0.716, 0.981]; p = 0.028)) and J1 (aHR: 0.718 (95% CI [0.611, 0.844]; p 

14.
arXiv (math.PR) 2026-06-15

Stationary measures for higher spin vertex models on a strip

作者:

arXiv:2309.04897v2 Announce Type: replace-cross Abstract: We introduce a higher spin vertex model on a strip with fused vertex weights. This model can be regarded as a generalization of both the unfused six-vertex model on a strip arXiv:2212.09111 and an 'integrable two-step Floquet dynamics' model introduced in arXiv:1711.08884. We solve for the stationary measure using a fused version of the matrix product ansatz and then characterize it in terms of the Askey-Wilson process. Using this characterization, we obtain the limits of the mean density along an arbitrary down-right path. It turns out that all these models share a common phase diagram, which, after an appropriate mapping, matches the phase diagram of open ASEP. This provides evidence for the universality of this phase diagram.

15.
arXiv (CS.LG) 2026-06-17

Adaptable Method for Crystal Design across Diverse Constraints and Objectives with Pretrained Property Predictors

arXiv:2410.08562v5 Announce Type: replace-cross Abstract: Advanced crystal design can accelerate materials discovery across applications from photovoltaics to spintronics. Practical design must satisfy multiple properties and physical constraints, yet existing machine-learning-based approaches to such design often depend on large datasets, retraining, or task-specific generators. Here, we show that direct predictor-guided gradient optimization enables data-efficient, constraint-rich crystal design by combining off-the-shelf predictors with site-wise element masks, template initialization, and task-specific losses. In perovskites, it outperformed generative and Bayesian baselines under three targets – band gap, formation energy, and tolerance factor – and two hard constraints. DFT assessment further showed band-gap targeting competitive with a leading generative model despite using predictors trained on roughly one-tenth of the data. By flexibly combining pretrained predictors with application-oriented masks and custom losses, the same framework supported half-metal design. Such modularity could help researchers and engineers translate diverse application requirements directly into optimized candidate crystals with minimal computational cost.

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

DynamicPTQ: Mitigating Activation Quantization Collapse via Residual-Stream Dynamics

arXiv:2606.12487v1 Announce Type: new Abstract: Post-training quantization (PTQ) is essential for efficient large language model inference, but reliably quantizing activations remains challenging when weights, activations, and KV caches are all quantized to 4-bit precision. A key difficulty lies in massive activations, whose extreme values dominate the activation range and amplify quantization errors. State-of-the-art methods mainly mitigate massive activations through transformation-based smoothing, such as orthogonal rotations and affine scaling, but overlook the cross-layer dynamics of the residual stream. In this paper, we show that massive activations emerge and disappear in a phase-wise pattern across network depth, triggering large residual changes. These changes cause newly injected layer-wise updates to dominate the 4-bit quantization scale and weaken historical residual information. To characterize this behavior, we introduce Jump Ratio and Historical Feature SNR. This suggests that static transformation-based smoothing cannot fully resolve dynamic quantization instability caused by cross-layer residual changes. Based on this analysis, we propose DynamicPTQ, a Dynamic Post-Training Quantization policy for phase-aware mixed-precision activation quantization. DynamicPTQ identifies quantization-sensitive layers from residual-stream dynamics and assigns 8-bit activation precision only to these layers, while keeping weights, KV caches, and other activations in 4-bit precision. It can be directly integrated with strong PTQ baselines such as QuaRot, SpinQuant, and FlatQuant. Experiments on LLaMA-2 and LLaMA-3 show that DynamicPTQ consistently improves perplexity and zero-shot QA performance under W4A4KV4 quantization, while achieving 1.05 to 1.07 times throughput improvement with modest memory overhead. These results demonstrate a practical path toward robust low-bit LLM inference.

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

$\mu$VLA: On Recurrent Memory for Partially Observable Manipulation in VLA Models

arXiv:2606.12497v1 Announce Type: new Abstract: Vision-language-action (VLA) models predict chunks of future actions from the current observation, an assumption that fails under partial observability, where decisions depend on information no longer visible. Existing memory-augmented VLAs simultaneously introduce recurrence, retrieval, compression modules, auxiliary objectives, hierarchical memory, or task-specific architectural changes, so the contribution of recurrence itself remains entangled with surrounding machinery. We present a controlled isolation study of recurrence in a strong pretrained VLA backbone. Our formulation augments the transformer with a small set of learnable memory tokens carried across timesteps and updated through self-attention, trained end to end with truncated backpropagation through time, with no auxiliary losses and no architectural changes. We instantiate this as $\mu$VLA, a family of OpenVLA-OFT variants parameterized by memory width m, TBPTT length K, and the memory update rule (cross-step gradients or a detached EMA), so that recurrence is the only varying factor. On MIKASA-Robo, $\mu$VLA improves average success rate on five training tasks from 0.42 to 0.84 at the strongest setting and reaches 0.23 on held-out tasks with the same memory structure versus 0.07 for the memoryless baseline. On tasks requiring different memory structure, performance remains near baseline. On LIBERO, the strongest recurrent variant achieves 96.2% average success, indicating no regression under full observability. We interpret these results as a calibration of the capability envelope of minimal in-backbone recurrence, identifying the regime in which it is sufficient and the regime where additional memory structure is required. Demos and videos can be found in https://avanturist322.github.io/mu-vla/.

18.
arXiv (CS.AI) 2026-06-19

Can In-Context Learning Support Intrinsic Curiosity?

arXiv:2606.19476v1 Announce Type: cross Abstract: Effective machine learning depends not only on how we model data, but also on what data we choose to collect. While large sequence models have revolutionized data modeling, the problem of automated data selection, or "intrinsic curiosity", remains a significant challenge. Classic approaches incentivize exploration by rewarding an agent based on its "learning progress", which measures how much a newly acquired observation improves a world model's predictive ability. However, evaluating these rewards traditionally requires expensive inner loops of gradient descent updates within each trajectory, rendering them computationally impractical at scale. In this work, we investigate whether the emergent in-context learning (ICL) capabilities of sequence models can eliminate this bottleneck by serving as immediate, update-free world models. Specifically, we evaluate whether an exploration policy can be trained to maximize learning progress, using solely the prediction errors and counterfactual context manipulations of an in-context learner. We first prove that in general Markov decision processes, this is in fact impossible in an unbiased way: the resulting intrinsic rewards either suffer from nuisance terms that bias their estimation of true learning progress, or they cannot be implemented using an in-context learner's prediction errors. Conversely, we prove a positive result for a broad subclass of non-temporal settings, encompassing active learning and Bayesian Experimental Design: here, ICL-derived rewards successfully bound and asymptotically converge to the true learning progress. We corroborate our theory with controlled experiments across continuous and symbolic environments, demonstrating that our ICL-driven framework successfully trains curious data-collection policies that explore optimally.

19.
arXiv (CS.CL) 2026-06-11

Dummy Backdoor as a Defense: Removing Unknown Backdoors via Shared Internal Mechanisms for Generative LLMs

Backdoor attacks pose a serious threat to the safety and reliability of Large Language Models (LLMs), as they cause models to behave normally on clean inputs while producing attacker-specified responses when hidden triggers are present. Removing such unknown backdoors is particularly challenging when the defender does not know the backdoor attack types or the internal mechanisms formed through backdoor training. In this work, we propose a simple but effective backdoor removal method based on shared internal mechanisms across different backdoors. First, we show that different backdoors with the same task (attack objective) induce similar trigger-activated changes in the internal activations. Motivated by this observation, our method intentionally embeds a backdoor with a known trigger (dummy backdoor) and then removes it through further fine-tuning on dummy-triggered inputs paired with clean responses. Since the dummy backdoor and the unknown backdoor can rely on shared internal mechanisms, removing the dummy backdoor also reduces the effect of the unknown backdoor. We evaluate our method on three backdoor attack types across multiple model families. Experimental results show that our method substantially reduces the attack success rate of the unknown backdoor while preserving model utility, outperforming representative existing defense methods in both backdoor removal effectiveness and utility preservation. These findings suggest that a defender-controllable backdoor can serve as a helpful proxy for mitigating unknown backdoors in generative LLMs.

20.
arXiv (CS.CV) 2026-06-16

Robust Spoofed Speech Detection via Temporal Pyramid Modeling

Spoofed speech detection is increasingly challenged by realistic synthesis, voice conversion, and replay attacks, with cross-dataset generalization remaining a major limitation. This work we propose a Temporal Pyramid Adapter that utilize parallel temporal convolutions with varying receptive fields to capture multi-scale spoofing cues, ranging from local artifacts to global prosodic irregularities. We also integrated self-supervised XLS-R representations combined with front-end adapters, including Mel, Sinc, and a Temporal Pyramid design for multi-scale temporal modeling. The proposed model is evaluated cross multiple benchmark including ASVspoof 2017, ASVspoof 2021 (DF/LA), PartialSpoof, DiffSSD, and multilingual HQ-MPSD datasets. Experimental results demonstrate that Temporal Pyramid model obtained AUC of 99.24% and a EER of 3.87% on the PartialSpoof database, which is significantly outperforming the base model and several SOTA baseline such as LCNN-BLSTM (9.87% EER) and TRACE (8.08% EER). Additionally, multilingual evaluations confirm that while spoofing artifact are independent from language. While self-supervised representations improve robustness, performance degrades under domain and language shifts, highlighting the need for better adaptation and calibration strategies.

21.
bioRxiv (Bioinfo) 2026-06-12

Systematic functional annotation of thousands of BAHD acyltransferases in plant genomes using Protein Language Model and phylogenomic tools

The functional annotation of plant genes lags significantly behind their genomic annotation. Closing this gap requires thorough cataloging of reported protein activities alongside predictive methods that scale beyond sequence-similarity inference. Focusing on the BAHD acyltransferase enzyme family as a model, we assembled FuncZymeDB-BAHD, a large database of 2,705 LLM-retrieved and curated enzyme-acceptor-donor activities covering 336 BAHDs from 156 plant species, a 2-to-6-fold expansion over Swiss-Prot and prior compilations. We further developed FuncPred-OG, which maps queries to orthologous groups and previously characterized enzymes in FuncZymeDB-BAHD, returning hits with high evidence provenance. FuncPred-OG enabled functional prediction of over half of BAHDs across 85 plant proteomes, of which five novel predictions were validated via in vitro assays and recent studies. For the remaining BAHDs without FuncPred-OG annotation, we developed FuncPred-AI, where logistic-regression classifiers trained on protein language model embeddings achieved high Area-Under-the-Precision-Recall-curve (AUPR) scores and correct-hit rates up to 93%. FuncPred-AI yielded >1 probable donor/acceptor annotation for 99.9% (8894/8897) of BAHDs in our pan-plant dataset. Finally, the FuncPred workflow and datasets were deployed on a web portal for broader utilization, potentially reducing experimentalist efforts for selecting candidates from days to minutes. Overall, this framework provides a generalizable template for functional annotation of entire enzyme families.

22.
medRxiv (Medicine) 2026-06-18

Cost-effectiveness of a virtual fracture clinic versus traditional in-person fracture clinic care for adults with acute simple fractures: a protocol for a health economic evaluation within the RECITAL trial

ABSTRACT Introduction Traditional in-person fracture clinics are often overcrowded and inconvenient for patients. Virtual fracture clinics aim to address some of these concerns by improving the efficiency of the orthopaedic service and reducing unnecessary interventions while maintaining safety and quality of care. The RECITAL trial is a non-inferiority randomised controlled trial comparing follow-up care provided at a virtual fracture clinic for people with acute simple fractures to follow-up care provided at an in-person fracture clinic. This study describes the protocol for an economic evaluation of RECITAL where the primary aim is to investigate the cost-effectiveness of a virtual fracture clinic compared with traditional in-person fracture clinic care from a health system perspective. Methods and analysis The RECITAL trial recruited 312 participants with acute simple fractures and randomised them to receive follow-up care provided at a virtual fracture clinic or follow-up care provided at an in-person fracture clinic. We will conduct a within-trial analysis from a health system perspective (primary analysis), as well as a health service, patient and societal perspective. The economic evaluation will estimate the difference in the cost of resource inputs on an intention to treat basis used by participants in the two arms of the trial, allowing comparisons to be made between the in-person and virtual fracture clinics. Data for intervention costs and healthcare utilisation will be collected from trial records, hospital electronic medical records and district performance units. The results of the economic evaluation will be expressed in terms of incremental cost per utility weight gained at 12 weeks and will be plotted on a cost-effectiveness plane. Bootstrapping by resampling will be used to estimate 95% confidence intervals around costs and outcomes, and to calculate the confidence intervals around the incremental cost-effectiveness ratio. A cost-effectiveness acceptability curve (CEAC) will be plotted, which will provide information about the probability that an intervention is cost-effective, given the level of a decision makers willingness to pay for each additional outcome. Ethics and Dissemination The trail was approved by the SLHD Ethics Review Committee (RPAH Zone) (X23-0200 and 2023/ETH01038). The findings will be disseminated through a peer-reviewed journal and conference presentations. Trial registration number The trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ANZCTR; 12623000934640)

23.
medRxiv (Medicine) 2026-06-22

Development and validation of a risk prediction algorithm to estimate all-cause mortality among community-dwelling Canadians: the Mortality Population Risk Tool (MPoRT)

BACKGROUND: The risk of all-cause mortality can inform decision-making for chronic disease prevention. We developed a predictive algorithm to estimate the 5-year risk of death among community-dwelling adults. METHODS: We derived and validated the Mortality Population Risk Tool (MPoRT) using data from population health surveys in Canada (the Canadian Community Health Survey) and the United States (the National Health Interview Survey), survey years 2001 to 2011, linked to vital statistics. The outcome was death within five years of the survey response. The algorithm was developed using data from Ontario respondents using a Cox proportional hazards model, then modified and re-estimated to allow cross-national assessment in Canada and the United States. Twenty-three prespecified predictors were assessed: seven sociodemographic, six behavioural, and ten general health and chronic disease. RESULTS: 527,369 respondents aged 20 to 105 years were included in the Canadian and United States development and validation cohorts, with 43,758 deaths during 3.68 million person-years follow-up. The final sex-specific MPoRT algorithms each contained 21 variables, showing strong discrimination (C-statistic: females 0.874 [0.871–0.877]; males 0.867 [0.865–0.871]) and good calibration overall and in 246 of 247 subgroups. Discrimination was modestly attenuated (0.01 decrease in C-statistic) in cross-national validation between Canada and the United States, with good calibration across all 71 subgroups. INTERPRETATION: MPoRT accurately discriminated all-cause mortality using only self-reported data, enabling broad application without clinical measures. While validation outside North America is needed to confirm broader applicability, MPoRT is designed for straightforward recalibration using routinely available national mortality data. This supports targeted chronic disease prevention strategies at both the population and individual levels, though the limitations inherent to self-reported predictors should be considered when interpreting predictions.

24.
medRxiv (Medicine) 2026-06-18

Automated Airways Characterization and Assessment of Cystic Fibrosis from CT Imaging

Background Advancements in medical imaging have enabled non-invasive diagnosis and staging of cystic fibrosis (CF) using CT scans, revealing dilated airways, an increased number of visible airways, and airway generation splits in these patients. However, manual characterization of airways remains time-consuming and challenging due to the numerous structural changes, thereby limiting clinical feasibility. This study aims to develop an automated algorithm to characterize airways from segmented lung CT scans and apply this to a retrospective population. This approach reduces the time required to analyze images and obtain disease-staging results. Methods This framework consists of two stages. The first stage extracts and skeletonizes the airway tree from lung CTs, while the second stage measures lung features, including airway volumes, branch counts, generation splits, diameters, and cross-sectional areas. This permits comprehensive characterization for use in clinical assessment. Results The airways analysis was performed on 169 CT volumes ranging in age from 6 to 18 years of age, revealing substantial differences in detected airway branches, generation splits, and normalized airway volume between the control and CF groups. The framework also measures airway diameters and cross-sectional areas, revealing an increase in the number of small airways in cystic fibrosis patients, due to early bronchiectasis. These findings align with previous research and demonstrate the framework's ability to accurately quantify airway changes in patients with CF. Discussion The framework extracts entire airway trees, facilitating measurements of volume, branch count, diameters, and cross-sectional areas, which change with CF severity and/or treatment. However, partial lung atelectasis can limit the accuracy of airway detection in moderate-to-severe cases. Funding NIA U54 AG054345 and NIA R21 AG07857501

25.
arXiv (CS.CV) 2026-06-19

Single-Stage Hierarchical Rectification for Weakly Supervised Histopathology Segmentation

Existing weakly supervised semantic segmentation (WSSS) methods in computational pathology rely on a multi-stage paradigm: class activation map (CAM) generation, offline pseudo-mask refinement, and fully supervised retraining. While established, this decoupled approach presents fundamental limitations. The multi-stage process not only incurs high computational training costs but also suffers from error propagation: local texture biases in shallow CNN layers generate false-positive artifacts that subsequent refinement steps often fail to correct. To address these persistent challenges through a simple yet highly effective approach, we propose the Single-Stage Hierarchical Rectification (SSHR) framework. Rather than passively refining CAMs post-hoc, our method proactively purifies intermediate feature representations during the forward pass. We introduce a Hierarchical Feature Rectification Module (HFRM) that utilizes deep global semantic context to filter out local anomalies in shallow layers. This mechanism generates high-fidelity activation maps directly within a single training loop. Experiments on the LUAD-HistoSeg and BCSS datasets demonstrate that SSHR outperforms state-of-the-art multi-stage methods. Furthermore, SSHR reduces training duration by 2 to 5 times. This efficiency minimizes computational overhead and accelerates clinical translation for large-scale histopathology workflows. The code is available at: https://github.com/trongduc-nguyen/SSHR