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01.
arXiv (CS.LG) 2026-06-18

Identifying Structural Biases from Causal Mechanism Shifts

arXiv:2606.18834v1 Announce Type: new Abstract: Causal discovery methods commonly assume that all data is independently and identically distributed (i.i.d.) and that there are no unmeasured variables affecting the system. In practice, these assumptions are often violated, leading to inaccurate inference. In this paper, we study how to identify hidden confounding and selection biases from causal mechanism shifts. In particular, we show that structural biases lead to dependent mechanism shifts. That is, by considering for which variables the mechanisms change given data from different environments, we can tell which variables are unbiased, which are subject to hidden confounding, and which are undergoing selection bias. We formalize this into an empirically testable criterion based on mutual information, and show under which conditions it identifies structural biases. To tell which nodes are subject to what kind of bias, we introduce the StruBI algorithm. Experiments on synthetic and real-world data show that StruBI works well in practice, accurately recovering affected variable sets and types of biases, outperforming the state-of-the-art by a wide margin.

02.
arXiv (CS.CV) 2026-06-15

Memento: Reconstruct to Remember for Consistent Long Video Generation

Long-form video generation requires recurring subjects to remain consistent across various shots, viewpoints, motions, and scene transitions. Existing temporal decomposition methods improve scalability by generating videos shot by shot. However, they mainly focus on optimizing plausible next-shot continuations without verifying whether the historical memory preserves identity-critical subject evidence. Consequently, as generation proceeds, recurring subjects may be diluted, overwritten, or forgotten. In this paper, we propose Memento, a subject-reconstruction-guided framework that treats subject preservation as an explicit identity grounding problem, based on the premise that a memory bank faithfully preserving a subject should support reconstructing that subject from memory alone. Specifically, Memento jointly trains autoregressive next-shot generation with memory-based subject reconstruction, recovering target appearances using historical memory and global story captions. To disentangle long-range subject evidence from short-range cues, Memento introduces a dual-query memory mechanism, where one query retrieves identity-relevant memory and the other selects short-context keyframes for coherent continuation. Additionally, a subject-aware cinematic data pipeline provides precise reconstruction supervision via consistent, pronoun-free subject descriptions. Experiments demonstrate that Memento achieves state-of-the-art performance in long-term subject consistency, cross-shot coherence, and visual quality.

03.
medRxiv (Medicine) 2026-06-11

Effects of Resveratrol as an Adjunct to a Low-Calorie Diet in Postmenopausal Women with Obesity and Knee Osteoarthritis

Background. Obesity is a modifiable risk factor for osteoarthritis and may contribute to pain, functional impairment, inflammation, and cartilage degradation. Resveratrol has potential anti-inflammatory and chondroprotective effects, but its efficacy as an adjunct to dietary intervention remains unclear. Objective. This study evaluated whether resveratrol supplementation provides additional benefits when combined with a low-calorie diet in postmenopausal women with obesity and knee osteoarthritis. Methods. A total of 97 postmenopausal women with obesity and knee osteoarthritis were included in this randomized controlled clinical study. Participants received either a 10-day low-calorie diet alone or the same diet combined with 150 mg/day trans-resveratrol. Anthropometric parameters, body composition, biochemical markers, pain intensity, functional status, and urinary CTX-II were assessed at baseline and follow-up. Results. Both interventions were associated with reductions in body weight, BMI, waist and hip circumferences, fat mass, glucose, HOMA-IR, lipid parameters, hsCRP, VAS, WOMAC, LAI, and urinary CTX-II. Compared with diet alone, resveratrol supplementation did not provide additional benefits for anthropometric parameters, glucose metabolism, lipid profile, or WOMAC score. However, the resveratrol group showed a greater reduction in hsCRP and urinary CTX-II. The obesity class did not modify the treatment effect. Conclusion. A short-term low-calorie diet improved metabolic, inflammatory, and osteoarthritis-related parameters in postmenopausal women with obesity and knee osteoarthritis. The addition of resveratrol did not enhance weight loss or improve most metabolic outcomes but was associated with greater reductions in hsCRP and urinary CTX-II. These findings suggest a potential anti-inflammatory and cartilage-related effect of resveratrol, which requires confirmation in longer randomized trials.

04.
arXiv (CS.LG) 2026-06-25

Scalable Peptide Design via Memory-Efficient Equivariant Transformer

arXiv:2606.25006v1 Announce Type: new Abstract: Target-specific peptide design requires sequence and structure co-design under full atom geometric constraints. Latent generative frameworks offer an effective route for this problem by compressing fine grained atomic structures into block level latent representations and performing conditional generation in a compact latent space. However, the scalability of such systems depends heavily on the geometric backbone used throughout their encoding, decoding, and denoising components. We introduce MEET (Memory Efficient Equivariant Transformer), an E(3) equivariant backbone for scalable atomistic peptide modeling. MEET maintains coupled invariant scalar and equivariant vector feature streams, while reformulating geometric computation around memory efficient attention. It initializes vector features through global coordinate aggregation, incorporates pairwise distances through augmented query and key dot products, and injects covalent bond information through sparse bond adaptation. Integrated into a VAE and latent diffusion pipeline for full atom peptide generation, \model{} achieves linear memory scaling with atom count and improves generation quality over existing peptide design methods. Experiments on large scale AFDB derived datasets further show that the proposed backbone supports systematic model and data scaling, leading to better binding affinity, physical validity, and sample diversity.

05.
arXiv (CS.LG) 2026-06-25

The Gentle Collapse: Distributional Metrics for Continual Learning

arXiv:2606.25165v1 Announce Type: new Abstract: Accuracy degradation is the standard metric for Catastrophic Forgetting (CF), however, it records only whether forgetting occurred or not. It saturates at the extremes and collapses discretely at task boundaries, hiding the internal structure of what is being forgotten. We introduce six softmax-derived metrics spanning true-label rank (TLR), predictive confidence, and distributional divergence that characterize forgetting continuously, each normalized to [0, 1] with no modification to training. On CIFAR-100, these metrics carry information where accuracy does not: at 0% accuracy, the Confusion Margin spans an IQR of [0.32, 0.50] across classes that accuracy treats identically. We demonstrate that this richer signal is actionable in mitigating catastrophic forgetting. Per-sample metric scores used as loss weights reduce forgetting by 1.3 percentage points over uniform experience replay (ER) on CIFAR-100. Furthermore, the slope of a metric over a small window provides a stable sampling criterion: at a small-window size (e.g. 3 epochs), accuracy-trend degrades to 34.79% (std. = 2.32) while log-TLR achieves 41.07% (std. = 0.57). This gap is structural since reliable small-window trend estimation requires a continuous signal. On TinyImageNet, log-TLR trend sampling reduces forgetting by 7.7 percentage points over the ER baseline.

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

The Measurable Majority

arXiv:2606.23853v1 Announce Type: cross Abstract: This paper studies strict majority reasoning in finite electorates using so-called $social decision frames$: finite sets of voters equipped with distinguished families of coalitions interpreted as those voting blocs evaluated to form a strict majority. A coherence criterion for qualitative majority judgments is identified and shown to give an exact characterization for representability of strict majorities by finitely additive measures. In addition, a minimal natural logic for reasoning about strict majorities is shown to be sound and complete. These developments motivate examination of associated combinatorial questions concerning incoherence in finite families of sets; partial results and a conjecture are given. Finally, the results of this paper are applied to correct a classical representation theorem for weak qualitative probability structures due to Patrick Suppes and to establish a May-type characterization for ordinary strict majority rule for social decision frames.

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

FEnc$^2$: Unifying Data Packing for Efficient Private Inference via Convolution and Architecture-Aware Fragment Encoding

arXiv:2606.16359v1 Announce Type: cross Abstract: Fully Homomorphic Encryption (FHE) enables privacy-preserving machine learning but incurs extreme computational and memory overhead. These costs come not only from expensive low-level primitives, including Number Theoretic Transform (NTT), rotation, and key-switching, but also from inefficient ciphertext packing at the application level. Existing packing strategies typically preserve either neighboring data elements or feature grouping, but not both, leading to wasted ciphertext slots, excessive rotations, and inflated ciphertext counts. We propose FEnc2, a unified and principled fragment-based encoding framework for CKKS-based private convolutional neural network inference. FEnc2 optimizes slot utilization, rotation complexity, and ciphertext density through two components: 1)Conv-aware Encoding, which analytically selects an optimal fragment size to decouple spatial dependencies and jointly minimize inner-outer rotations across layers, and 2)Arch-aware Ct Compression, which restores ciphertext density after feature- or channel-reduction layers. Together, these transformations reshape encrypted workload structure and reduce homomorphic operations by one to two orders of magnitude. With full memory capacity utilized, i.e., at maximum batch size, FEnc2 achieves end-to-end latency speedups over the state-of-the-art Orion of up to 228.83x on GPU and 226.06x on CPU for LeNet on MNIST, and up to 4.55x on GPU and 9.43x on CPU for MobileNet on ImageNet. FEnc2 is hardware-agnostic yet architecturally transformative: by optimizing encrypted tensor layout before execution, it reduces ciphertext count and workload pressure on hardware, complementing primitive-level optimizations such as NTT and keyswitch accelerators. These results show that application-level data layout is a first-order architectural design dimension for encrypted inference and an important enabler for next-generation FHE systems.

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

Imperfect Visual Verification for Code Edition : A Case Study on TikZ

arXiv:2606.15693v1 Announce Type: cross Abstract: LLMs have significantly advanced code generation, enabling the synthesis of functional programs. While recent systems achieve strong performance on many coding benchmarks, tasks involving programs such as TikZ that generate visual artifacts remain challenging, in particular on visual code customization. Unlike generation from scratch, customization requires localized, semantics-preserving edits: the model must locate relevant code, modify it according to the instruction, and preserve the remaining structure and rendering. Approaches based on post-hoc iterative refinement/correction where a verifier provides feedback to guide corrections, have shown promise. However, in the case of programs with a visual outcome such as in TikZ, where correctness is harder or likely impossible to formalize and evaluate automatically, deterministic verifiers do not exist. Hence, developers can only rely on imperfect verifiers. In this paper, we conduct an empirical study to answer:to what extent can iterative refinement remain effective when the verifier itself is unreliable?} We use TikZ as a focused case study that isolates the core difficulties of the problem (weak code structure, fine-grained visual semantics, and difficult feature localization) in a controlled and challenging setting. We define visual code customization as an iterative editing problem with an imperfect oracle, and introduce a framework for analyzing such iterative refinements. We conduct a large-scale study and evaluate multiple LLM-based and tool-augmented visual verifiers within iterative refinement pipelines, and perform extensive manual annotation of refinement trajectories to assess verifier behavior and feedback quality. Our findings show that even imperfect verifiers can determine with moderate accuracy whether visual instructions are applied to code, achieving F1-scores up to 0.815. Feedback improves iterative refinement, especially for weaker models, adding 11–20 perfect customizations for Qwen3-vl-30b-a3b-Instruct, while stronger models like Gemini-3 gain fewer improvements (+5) but benefit more from accurate verification that prevents premature acceptance. Feedback is effective only when it precisely identifies image issues, provides actionable guidance, addresses all relevant problems, and remains grounded in the original instruction.

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

Priors Persist Through Suppression: A Stroop Paradigm for Lexical Override

作者:

Glossaries, technical specifications, and system prompts routinely ask language models to use familiar words in unfamiliar ways. When this works, the local rule does not install the new meaning on top of the old one; the pretrained prior keeps operating underneath, and its strength still shows through. We test this with a Stroop-style paradigm: a remapping rule (doctor means forest) pitted against the query word's lexical-prior distractor (hospital), with matched neutral controls. Across 11 open-weight models spanning four families and 1B-9B parameters, lexical-prior strength predicts interference even after item-level controls for answer prior, frequency, tokenization, and prompt wording. Activation patching on five aligned models locates a source-position triplet (definition subject, definition target, query word) that nearly fully recovers the conflict effect (aggregate $R \in [0.92, 1.06]$); a definition-target swap shows the triplet performs binding rather than identity matching. Dissociation experiments isolate target preservation as the binding-specific signature: distractor suppression occurs under matched, swap, and item-mismatched conditions alike, whereas target logit collapse occurs only when the definition-target position is corrupted. Behavior and mechanism converge on the same channel: the prior's strength both predicts which overrides fail and marks where the causal repair lands.

10.
arXiv (CS.CV) 2026-06-25

VolSplat: Rethinking Feed-Forward 3D Gaussian Splatting with Voxel-Aligned Prediction

Feed-forward 3D Gaussian Splatting (3DGS) has emerged as a highly effective solution for novel view synthesis. Existing methods predominantly rely on a pixel-aligned Gaussian prediction paradigm, where each 2D pixel is mapped to a 3D Gaussian. We rethink this widely adopted formulation and identify several inherent limitations: it renders the reconstructed 3D models heavily dependent on the number of input views, leads to view-biased density distributions, and introduces alignment errors, particularly when source views contain occlusions or low texture. To address these challenges, we introduce VolSplat, a new multi-view feed-forward paradigm that replaces pixel alignment with voxel-aligned Gaussians. By directly predicting Gaussians from a predicted 3D voxel grid, it overcomes pixel alignment's reliance on error-prone 2D feature matching, ensuring robust multi-view consistency. Furthermore, it enables adaptive control over density based on 3D scene complexity, yielding more faithful Gaussians, improved geometric consistency, and enhanced novel-view rendering quality. Experiments on widely used benchmarks demonstrate that VolSplat achieves state-of-the-art performance, while producing more plausible and view-consistent results. The video results, code and trained models are available on our project page: https://lhmd.top/volsplat.

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

Difference-Making without Making a Difference

arXiv:2606.24832v1 Announce Type: new Abstract: Over a series of seven papers, Andreas & Günther have introduced seven definitions of actual causation and have classified them as belonging to three different, competing, types of accounts: factual difference-making, counterfactual difference-making, and regularity-based. I show that their most recent - factual difference-making - definition instantiates all three types, thereby proving that these are distinctions without a difference. I further compare their novel account to the other six accounts on several crucial examples, revealing that this undermines all seven of their accounts.

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

Beyond Native Success: Auditing Deployment-Interface Exposure of CLIP Backdoors

Contrastive Language-Image Pre-training models are widely reused across downstream interfaces, including feature extraction, retrieval, reranking, and selection. Existing CLIP backdoor, however, usually validate attacks on a small attack-native task, leaving unclear whether the same poisoned checkpoint remains exposed, weakens, or becomes not applicable when reused through other interfaces. We introduce DIFE, a Deployment-Interface Footprint Evaluation framework that audits backdoored CLIP checkpoints across deployment interfaces. DIFE makes various evaluations comparable by specifying each interface's component readout, trigger channel, target event, reference condition, and metric. DIFE also introduces effective-footprint diagnosis to identify the reusable CLIP component or component combination that carries exposure and explains where risk transfers. Auditing reproduced CLIP backdoors with DIFE reveals a structured landscape: native success is not a checkpoint-level risk certificate, exposure follows component footprints, text-side poisoning does not yield textual-encoder control, and some coupled attacks remain mechanism-bound. This audit reveals a import gapin existing CLIP backdoors: a textual encoder that itself becomes a reusable carrier of adversarial behavior. We therefore introduce BadTextTower to fill this gap. BadTextTower produces strong text-conditioned retrieval, reranking, and selection exposure while leaving visual-only reuse nearly clean.

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

Charting the Future of Scholarly Knowledge with AI: A Community Perspective

arXiv:2509.02581v2 Announce Type: replace-cross Abstract: Despite the growing availability of tools designed to support scholarly knowledge extraction and organization, many researchers still rely on manual methods, sometimes due to unfamiliarity with existing technologies or limited access to domain-adapted solutions. Meanwhile, the rapid increase in scholarly publications across disciplines has made it increasingly difficult to stay current, further underscoring the need for scalable, AI-enabled approaches to structuring and synthesizing scholarly knowledge. Various research communities have begun addressing this challenge independently, developing tools and frameworks aimed at building reliable, dynamic, and queryable scholarly knowledge bases. However, limited interaction across these communities has hindered the exchange of methods, models, and best practices, slowing progress toward more integrated solutions. This manuscript identifies ways to foster cross-disciplinary dialogue, identify shared challenges, categorize new collaboration and shape future research directions in scholarly knowledge and organization.

14.
arXiv (math.PR) 2026-06-17

Non-asymptotic Tail Bounds for the Kostlan–Shub–Smale Field: Tensor PCA and Spherical $k$-Spin Complexity

arXiv:2606.17665v1 Announce Type: cross Abstract: This paper builds a hierarchy of explicit, non-asymptotic tail bounds for the supremum of the Kostlan–Shub–Smale (KSS) random field on the sphere, and applies it to two problems: Spiked Tensor PCA and the landscape of the spherical $k$-spin model. For Tensor PCA, we study the non-asymptotic statistical limits of estimating a rank-$R$ symmetric signal tensor of order~$k\ge 3$ and dimension~$d\ge 3$ from a single Gaussian observation at signal-to-noise ratio~$\lambda$, through the profile maximum likelihood estimator, the MLE restricted to normalized rank-$R$ tensors of coherence at least~$\kappa$. Our analysis uses a single reduction: a deterministic geometric inequality (the Tube Method) and a rank-reduction step bound the estimation error by the supremum of the canonical KSS field, which the Kac–Rice formula turns into a Gaussian integral against the expected absolute characteristic polynomial of a shifted Gaussian Orthogonal Ensemble, controlled in turn by the four explicit tail bounds of our hierarchy (three from a Mehta–Fyodorov representation, one from a Ben Arous–Dembo–Guionnet large deviation). The same reduction yields two results, each with explicit constants. For estimation, a finite-$(k,d)$ error bound recovers the asymptotically optimal rate~$\sqrt{d\log k}$ of Perry, Wein and Bandeira, with explicit dependence on the rank~$R$ and the coherence~$\kappa$. For the landscape, a two-sided non-asymptotic bracketing of the annealed complexity of the spherical $k$-spin Hamiltonian recovers the Auffinger–Ben Arous–\v{C}ern\'y complexity function in the high-dimensional limit.

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

MetaboNet-Bench: A Multi-modal Benchmark for Glucose Forecasting in Type 1 Diabetes

arXiv:2606.18640v1 Announce Type: new Abstract: Glucose forecasting algorithms are an important aspect of glycemic control management in type 1 diabetes. So far, the research community has developed numerous algorithms and models for forecasting. However, it is well-recognized that the lack of standardized model performance evaluation benchmarks makes fair comparison difficult and hinders further innovation, and thus benchmark standardization is in urgent need. Furthermore, many published glucose forecasting algorithms are limited to CGM data alone, ignoring other multimodal signals such as insulin dosing and carbohydrate intake. Here, we introduce MetaboNet-Bench, a benchmark for multimodal glucose forecasting for patients with type 1 diabetes that provides an extensible open-source evaluation framework for comparison of glucose forecasting algorithms that leverage glucose, insulin, and carbohydrate data. We then demonstrate its utility by benchmarking several recently published glucose forecasting models and a custom multimodal time-series model, representing different model architectures. The results show that the benefit of adding data modalities is conditioned on the complexity of the model and that incorporating more clinical metrics helps identify meaningful gaps to fill for future research.

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

Resonant Minds: Closed-Loop Social Avatars with Theory of Mind

Creating lifelike digital humans with genuine social intelligence requires unifying cognitive reasoning and multimodal generation within a coherent framework. Current approaches treat these as separate tasks: Large Language Models excel at dialogue but lack embodied expression, while diffusion-based talking head models achieve visual fidelity but ignore social cognition. To bridge this gap, we propose a closed-loop dual-agent framework integrating perception, social reasoning, and expression into a continuous interaction cycle. The perception module analyzes partners' multimodal behaviors from video, while the social reasoning module infers hidden mental states through Theory of Mind and selects responses via an ensemble mechanism. The expression module then generates emotion-controllable videos that jointly synthesize speaker speech and facial expressions with listener reactive behaviors, capturing bidirectional dynamics absent in prior work. We further construct a hierarchical Persona-Scenario dataset with psychologically grounded personas and private social goals to support evaluation under information asymmetry. Experiments on this dataset demonstrate competitive or superior performance on both dialogue quality and video generation metrics. Notably, our method surpasses even the full-information Script mode on key dialogue quality dimensions, suggesting that explicit mental state inference under uncertainty can elicit more thoughtful dialogue than unrestricted information access. Project page: https://resonantminds.github.io/.

17.
arXiv (CS.AI) 2026-06-19

Cost-Optimal LLM Routing with Limited User Feedback under User Satisfaction Guarantees

arXiv:2606.19376v1 Announce Type: cross Abstract: Inference costs for large language model (LLM) applications are rapidly growing, driven by surging demand and rising infrastructure cost. Users expect high-quality responses, and in commercial settings this is formally codified in Service Level Agreements (SLAs), creating a fundamental tension between cost and quality. Recent progress on cost-aware LLM request routing has shown potential to resolve this tension, but existing approaches rely on complete feedback signals, offline training, extensive per-workload tuning, and most lack SLA guarantees or inference-time adaptivity. We introduce SLARouter, an online routing algorithm that learns a cost-optimal policy from the sparse, one-sided user feedback available in production systems. SLARouter provides theoretical guarantees for both cost optimality and strict SLA compliance. Experiments across a wide range of LLM benchmarks show that SLARouter satisfies SLA constraints without the need for per-benchmark tuning, reducing operating cost by up to 2.2x over existing baselines.

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

Business as Rulesual: A Benchmark and Framework for Business Rule Flow Modeling with LLMs

Extracting structured procedural knowledge from unstructured business documents is a critical yet unresolved bottleneck in process automation. While prior work has focused on extracting linear action flows from instructional texts, such as recipes, it has insufficiently addressed the complex logical structures, including conditional branching and parallel execution, that are pervasive in real-world regulatory and administrative documents. Furthermore, existing benchmarks are limited by simplistic schemas and shallow logical dependencies, restricting progress toward logic-aware large language models.To bridge this Logic Gap, we introduce BREX, a carefully curated benchmark comprising 409 real-world business documents and 2,855 expert-annotated rules. Unlike prior datasets centered on narrow service scenarios, BREX spans over 30 vertical domains, covering scientific, industrial, administrative, and financial regulations. We further propose ExIde, a structure-aware reasoning framework that investigates five distinct prompting strategies, ranging from implicit semantic alignment to executable grounding via pseudo-code generation. This enables explicit modeling of rule dependencies and provides an out-of-the-box framework for different business customers without finetuning their own large language models. We benchmark ExIde using 13 state-of-the-art large language models. Our extensive evaluation reveals that executable grounding serves as a superior inductive bias, significantly outperforming standard prompts in rule extraction. In addition, reasoning-optimized models demonstrate a distinct advantage in tracing long-range and non-linear rule dependencies compared to standard instruction-tuned models.

19.
arXiv (quant-ph) 2026-06-19

Many-Body Protection of Topological Edge Memory in Strong Interacting Quenches

arXiv:2606.19437v1 Announce Type: cross Abstract: Quantum quenches drive edge states far from equilibrium, yet whether the memory of a topological initial state survives in a non-integrable, interacting system has remained largely unexplored. We study this question in the bond-alternating XXZ chain – an interacting Su–Schrieffer–Heeger model hosting symmetry-protected topological edge modes with markedly enhanced boundary magnetization – and analyze quenches across all combinations of single-particle and many-body initial and final Hamiltonians. The results organize by a single distinction as we rigorously establish in this work: whether the post-quench Hamiltonian is free or genuinely interacting. For a free post-quench Hamiltonian, the dynamics is solved exactly by a correlation-matrix approach; the boundary-mode return amplitude decays as $t^{-3/2}$, and initial interactions enter only through a dressed one-body density matrix. For a genuinely interacting post-quench Hamiltonian, finite-time stability bounds prove that away from local resonances the first-dimer magnetization remains stable on time windows growing as arbitrarily large powers of the inverse inter-dimer coupling. Matrix product state simulations across all four protocols show that interactions in the final Hamiltonian markedly extend finite-time boundary memory – with local suppression near the isotropic $SU(2)$ point – revealing a many-body protection mechanism in a non-integrable system where scrambling would otherwise wash out initial-state memory fast.

20.
PLOS Computational Biology 2026-06-22

TCRBinder: Unified pre-trained language model with paired-chain synergy for predicting T-cell receptor binding specificity

作者:

by Weihe Dong, Qiang Yang, Long Xu, Xiaokun Li, Kuanquan Wang, Suyu Dong, Gongning Luo, Xianyu Zhang, Tiansong Yang, Xin Gao, Guohua Wang Deciphering how human T cells recognise peptide-HLA (pHLA) complexes underpins next-generation vaccines and personalised immunotherapies, yet extreme sequence diversity and paired-chains interdependence still hamper reliable in silico prediction of T-cell receptor (TCR) specificity. To overcome these hurdles, we built TCRBinder, a paired-chain-aware deep model with a multi-branch encoder that routes each molecular component through dedicated transformer-based modules to capture contextual signals in both HLA pseudo-sequences and antigenic peptides while simultaneously processing the TCR α and β chains. This design captures the synergistic interaction between paired chains to emulate peptide-HLA-TCR (PHT) interactions and expose residue-level contact motifs. Across PHT and peptide-TCR (pTCR) benchmarks, the model delivered state-of-the-art performance (AUC-ROC = 0.911, AUPR = 0.791 for the PHT task) and remained superior on multiple independent datasets. We tracked the dynamics of clonal expansion and, in a large SARS-CoV-2 repertoire containing completely unseen peptides, improved the AUC-ROC by up to 16.3% over the leading alternatives. Moreover, TCRBinder provided mechanistic insights by pinpointing contact hotspots and quantifying residue contributions to binding probability. These capabilities position TCRBinder as a versatile tool for rational antigen discovery, immunotherapy stratification, and neoantigen vaccine design.

21.
arXiv (CS.CL) 2026-06-25

The cognitive, affective, and behavioral expression of self-stigma among people who use drugs in online substance use communities

Objectives: To develop a codebook for self-stigma across cognitive, affective, and behavioral domains, and to estimate the prevalence, co-occurrence, and temporal patterns of these indicators in Reddit posts by people who use drugs. Methods: We developed a ten-indicator codebook through consensus-based abductive coding spanning cognitive (self-labeling, pessimism/self-defeatism, deservingness/worthlessness), affective (shame, guilt/self-blame, despair/hopelessness), and behavioral (concealment, anticipated rejection, desire to quit, ambivalence) domains; two coders reached substantial agreement (Cohen's k = 0.72). We then scaled classification with a large language model validated against expert coding (k = 0.73, F1 = 0.80), analyzing 72,115 thread-initiating posts from 1,660 English-language users (2006-2025). Results: 3,838 posts (5.3%) from 1,228 users (74.0%) contained self-stigma; all ten indicators discriminated self-stigma posts (RR 3.6 to 86.2), led by self-labeling (56.0%) and despair/hopelessness (48.5%). Self-stigma was integrated: core and behavioral indicators were strongly associated at the user level (OR = 4.65, 95% CI 3.12-6.94, p < 0.001), and 87.0% of posts with behavioral indicators also contained a core indicator. Contrary to progressive models, behavioral indicators emerged earlier than core ones (desire to quit at median position 0.08 vs. shame at 0.38). Nine of ten indicators were stable across posting trajectories; only pessimism increased (OR = 1.62, 95% CI 1.25-2.10). Conclusion: Among people who use drugs online, self-stigma is an integrated phenomenon in which behavioral indicators rarely appear without internalized ones and often precede them. Most expressions remain stable over time, but pessimism about change deepens, marking a target for early digital intervention and showing that progressive stage models do not map directly onto textual disclosure.

22.
arXiv (CS.AI) 2026-06-19

PSCT-Net: Geometry-Aware Pediatric Skull CT Reconstruction via Differentiable Back-Projection and Attention-Guided Refinement

arXiv:2606.19867v1 Announce Type: cross Abstract: Computed Tomography (CT) is essential for diagnosing pediatric craniofacial abnormalities, yet poses radiation risks to developing anatomies. Reconstructing 3D CT from sparse bi-planar X-rays offers a low-dose alternative but is severely ill-posed. Existing methods employ geometry-agnostic feature lifting, naively projecting 2D features into 3D without explicit spatial modeling, causing depth ambiguity and degraded osseous boundaries. We present PSCT-Net, a geometry-aware framework with differentiable back-projection. Differentiable back-projection establishes a spatially faithful volumetric prior, alleviating depth ambiguity. An Attention-Guided Projection (AGP-3D) module then learns non-linear voxel-wise correspondences between 2D regions and 3D locations. A Bidirectional Mamba (BiM-3D) module captures long-range volumetric dependencies with linear complexity. We further curate a private institutional pediatric skull CT cohort, PedSkull-CT, comprising normal and pathological cases for internal evaluation, addressing the gap in adult-centric, trunk-focused datasets.

23.
arXiv (CS.CL) 2026-06-11

Measuring language complexity from hierarchical reuse of recurring patterns

We introduce the ladderpath index as a measure of language complexity grounded in algorithmic information theory. It counts the minimum steps needed to reconstruct a sequence through hierarchical reuse of repeated substructures, capturing an exactly computable but constrained form of algorithmic compressibility related to, but distinct from, Kolmogorov complexity. We apply the ladderpath approach to 21 parallel corpora from the Parallel Universal Dependencies dataset. The ladderpath index is approximately invariant across the languages, and varies much less than the corpus length. This is more pronounced when all corpora are mapped to a unified binary representation, providing evidence for the equi-complexity hypothesis from a representation-independent perspective. We also observe trade-offs between character inventory size and corpus length, and between vocabulary-level and corpus-level reconstruction complexity, supporting the trade-off hypothesis that total complexity is conserved and redistributed across linguistic levels. The reusable substructures identified by the ladderpath approach, without any linguistic input, overlap with words and morphological components attested in the natural vocabulary. The hierarchical reuse captured by the ladderpath approach parallels the chunking mechanisms proposed in cognitive science, where the human cognitive system compresses linguistic input into nested, reusable units under shared memory and processing constraints. This connection between cognitive chunking and the ladderpath approach provides a new interpretation for the equi-complexity and trade-off hypotheses, grounding both in the shared cognitive architecture that underlies language processing across human languages.

25.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.