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01.
arXiv (CS.AI) 2026-06-24

IV-CoT: Implicit Visual Chain-of-Thought for Structure-Aware Text-to-Image Generation

arXiv:2606.24849v1 Announce Type: cross Abstract: Unified multi-modal large language models (MLLMs) have achieved strong text-to-image generation quality, but still struggle with structure-aware prompt following, where object counts, spatial relations, attribute bindings, and coarse layouts must be preserved. We attribute this limitation in part to the entanglement of structural planning and appearance rendering within a single conditioning stream. To address this issue, we propose Implicit Visual Chain-of-Thought (IV-CoT), a latent visual reasoning framework for query-conditioned image generation. IV-CoT decomposes the visual conditioning queries into a structural-to-semantic cascade, where structural queries first form a latent visual plan and semantic queries then render appearance conditioned on this plan. To guide the structural queries, we introduce training-only sketch supervision, which encourages them to capture structure from sketches without requiring sketch extraction or intermediate decoding at inference time. IV-CoT performs implicit CoT reasoning in a single forward pass and achieves superior results on GenEval and T2I-CompBench. Visualizations and analyses demonstrate that the learned structural and semantic queries play complementary roles in structure-aware generation.

02.
Nature Medicine 2026-06-12

The Hong Kong Genome Project is a flagship initiative for precision medicine in Chinese populations

Authors: Unknown Author

The Hong Kong Genome Project established a genome sequencing database that provides improved diagnoses for patients and more efficient, population-tailored carrier status screening. Actionable pharmacogenomic variants were identified in almost all participants, informing drug prescriptions. This work establishes a genomic resource and a transferable model for equitable precision medicine in underrepresented populations worldwide.

03.
arXiv (CS.LG) 2026-06-11

Bypassing Prompt Guards in Production with Controlled-Release Prompting

arXiv:2510.01529v4 Announce Type: replace Abstract: Ball et al. recently established that prompt filtering for AI alignment faces a fundamental barrier: under standard cryptographic assumptions, no filter running significantly faster than the protected model can universally distinguish adversarial prompts from benign ones. We investigate whether this impossibility result translates to real-world vulnerabilities in deployed large language model (LLM) systems. We answer affirmatively by introducing controlled-release prompting, a practical instantiation of the theoretical framework that exploits the resource asymmetry between lightweight input filters and the main models they protect. Unlike the theoretical construction, our attack does not require model modification: it generates malicious prompts that are indecipherable by any bounded filter yet remain tractable to the target LLM. We find our attack to be successful on four major chat platforms (Google Gemini, DeepSeek Chat, xAI Grok, and Mistral Le Chat) where baseline methods fail. Additionally, we apply our attack to extract copyrighted data from Gemini. Finally, we provide a systematic evaluation of 14 open-weight prompt guard models, revealing that even reasoning-capable filters cannot reliably detect our attack without incurring prohibitive resource overhead.

04.
arXiv (CS.CV) 2026-06-18

Geometry-Aware Dataset Condensation for Diffusion Model Training

Dataset condensation aims to construct compact datasets from real data via synthesis or selection. However, existing approaches are ill-suited for diffusion model training: synthetic data generation often yields low-fidelity samples unsuitable for authentic modeling, while real subset selection typically fails to preserve the distributional geometry required by diffusion likelihood objectives. To address this, we propose to reformulate real subset selection as a geometry-aware distribution alignment problem. By incorporating one-sided partial optimal transport, our method selectively aligns a compact subset with the full data distribution while allowing unmatched mass in low-density regions, ensuring the preserved geometric structure necessary for effective diffusion model training. To further ensure distributional fidelity, we complement geometric alignment with lightweight feature-statistics and semantic consistency regularization. An efficient two-stage discrete optimization strategy is proposed to achieve this alignment objective. Extensive experiments across diffusion variants, subset sizes, image resolutions, and training rounds show that our method achieves superior fidelity and distributional coverage in diffusion model training. Codes are available at https://github.com/2018cx/GADC.

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

SkillJuror: Measuring How Agent Skill Organization Changes Runtime Behavior

arXiv:2606.11543v1 Announce Type: new Abstract: Agent Skills augment large language model (LLM) agents with procedural knowledge at inference time, but current benchmarks rarely distinguish what a Skill says from how it is organized. We study this distinction through Progressive Disclosure, where a concise root file points agents to supporting resources on demand, and compare it with a normalized flat baseline. We present SkillJuror, a framework for evaluating Skill writing paradigms through semantically controlled variants, matched multi-trial evaluations, and trajectory evidence while holding task knowledge fixed. In an 82-task SkillsBench study, Progressive Disclosure changes runtime behavior before aggregate outcomes: distinct Skill resources touched per trajectory rise from 1.18 to 3.85, and effective uptake events rise from 1.33 to 3.92. It also yields 17 additional verifier-passing trials out of 410 matched trials (+4.1%) over the normalized flat baseline. The benefit is task-dependent. Progressive Disclosure helps when supporting resources guide implementation, checking, or repair, but is weaker when success hinges on exact output conventions, numerical thresholds, or long artifact-generation pipelines. These results show that Skill organization is not mere presentation: it can change how agents search and apply procedural knowledge, while outcome gains depend on whether the exposed resources are actionable for the task. Code is available at https://github.com/zhiyuchen-ai/skill-juror.

07.
arXiv (quant-ph) 2026-06-11

Fisher geometry reshapes the effect of incompatibility in multiparameter quantum estimation

arXiv:2606.11343v1 Announce Type: new Abstract: Multiparameter quantum estimation faces two fundamental obstacles: sloppiness, i.e., anisotropy of the quantum Fisher information matrix (QFIM) that renders some parameter directions insensitive, and incompatibility, the non-commutativity of optimal measurements for different parameters. The trade-off bound $C_T$ captures their joint impact on precision, but it has remained unclear how the distribution of incompatibility across parameter planes affects its overall cost. Here we separate the total amount of incompatibility from its location. We introduce a dimensionless quantity $G_n^{(F)}$ that measures the alignment between the incompatibility distribution and the eigenvalues of the QFIM, and show how the Frobenius scale of the incompatibility contribution factorizes. We obtain a bound and prove the incompatibility cost lies between this bound and a rank-dependent multiple thereof. We also prove that at fixed sloppiness, or equivalently fixed Fisher volume, concentrating incompatibility into a single parameter plane reduces the optimized trade-off cost because the Fisher geometry can then be reshaped to allocate more Fisher area to that plane. A qutrit $SU(2)$ encoding numerically confirms that states with larger incompatibility strength can nevertheless incur a smaller cost if the matching factor $G$ is sufficiently small. Our results establish that the distribution of incompatibility relative to the Fisher eigenbasis is a central diagnostic for multiparameter estimation, beyond the total incompatibility strength.

08.
arXiv (quant-ph) 2026-06-24

Challenges in Barren Plateau Mitigation with Dynamic Parameterized Quantum Circuits

arXiv:2606.23751v1 Announce Type: new Abstract: Variational quantum algorithms (VQAs) are a promising paradigm for quantum advantage, yet their trainability is severely hampered by barren plateaus (BPs). Several works have proposed using dynamic parameterized quantum circuits (DPQCs) which intersperse unitary layers with parameterized CPTP maps (e.g. engineered dissipation, feedforward gadgets, or periodic resets), as a potential route around BPs. We unite this class of circuits into a formalization for DPQCs. We identify constraints on the nature and the structure of DPQCs if they are to prevent a significant number of parameters from becoming untrainable. We further show via purification and Pauli path analysis, a mechanism with which cost function anti-concentrates in DPQCs while still suffering from untrainability of a significant number of parameters. Our analysis reveals ways to design DPQCs that do not have an exponentially concentrated cost function, and our results suggest that BP mitigation via DPQCs is at least as hard as designing BP-free unitaries.

09.
arXiv (CS.LG) 2026-06-19

Adaptive Distance-Aware Trunk Deep Operator Learning for Long-Span Roadway Bridges

arXiv:2606.20015v1 Announce Type: new Abstract: Long-span roadway bridges exhibit highly localized structural responses under vehicular loading, making repeated FE analysis computationally expensive for applications such as influence surface generation and structural digital twins. Existing SciML approaches struggle to accurately capture these localized responses. To address this challenge, this study proposes an adaptive-trunk DeepONet for localized structural response prediction in large-scale bridge systems. The framework dynamically constructs a load-dependent learning domain using a KNN strategy, allowing the network to focus on structural influence zones. The trunk network is further enhanced using distance-aware features that encode the geometric relationship between the load and structural nodes. A physics-based full-field reconstruction is incorporated through a stiffness-informed Schur complement formulation, enabling predictions at adaptive nodes to be extended to the entire structural domain. To enable scalable training, response data are generated using a reduced-order equivalent shell model that preserves the dominant global behavior while significantly reducing computational cost. The proposed framework is validated on both a benchmark bridge model and the real-world Mussafah Bridge. Results show that the method achieves FEM-level accuracy with relative errors below 5%, while reducing the total response evaluation time (including full-field reconstruction) by approximately 60x; excluding the post-processing reconstruction step, the AD-DeepONet inference is up to four orders of magnitude faster than FEM. In addition, the framework enables rapid generation of full-field responses, influence lines, and influence surfaces under arbitrary vehicular loading configurations, demonstrating strong potential for large-scale bridge analysis and digital twin applications.

10.
arXiv (CS.AI) 2026-06-24

Assessing Distribution Shift in Human Activity Recognition for Domain Generalization

arXiv:2606.24781v1 Announce Type: new Abstract: While the field of Human Activity Recognition (HAR) continues to draw interest from researchers and advance in important ways, some key challenges remain. One of the most difficult aspects of building HAR models that show good performance in real-world settings is dealing with data diversity from device and sensor heterogeneity, and contextual changes that are intrinsic to real-world applications. While data diversity in HAR has been well-acknowledged in the literature, there remains a gap in understanding the effect of various types of distribution shifts on HAR models and the domain generalization problem that arises. Towards that end, this paper systematically evaluates 4 different types of distribution shifts, including variations in device type, sensor placement, sampling rate, and user behavior. Quantifying their effects, we illustrate that diversity shifts predominantly define all types of shifts, indicating the existence of unique features that are not shared across different domains. We then introduce a uniform HAR-based distribution shift benchmarks and conduct a comprehensive evaluation of up to 28 domain generalization methods. Our analysis exposes the limitations of current domain generalization algorithms in achieving model generalizability, marginally outperforming the empirical risk minimization baseline. This work represents the first systematic exploration of domain generalization and adaptation concerning specific distribution shifts in sensor-based HAR, offering an open-source benchmark platform and datasets to spur further research.

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

Evaluation Metrics as Averaged Outcomes of Fair Gambles

arXiv:2401.14483v4 Announce Type: replace Abstract: In the current practices of machine learning, the evaluation of forecasts has become a cornerstone of scientific progress. A multitude of evaluation metrics have been suggested and used to qualify "good" forecasts. What do those metrics share? How are they related? In this work, we use a protocol borrowed from game-theoretic probability to show that a large part of evaluation metrics can be viewed as averaged outcomes of fair gambles. Intuitively, a fair gambler is one which a forecaster would expect to fail. Hence, the gambler's ability to gain disproves the quality of the forecast. Standard evaluation metrics are then variants of choices of such fair gambles. In particular, this choice is structured along two dimensions, one of which separates calibration-type and regret-type metrics. In particular, this framework sheds light on the relationship of calibration and regret showing a theoretical equivalence in their ability to evaluate when being scaled appropriately, but the incomparability of obtained scores.

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

Few-Shot Biomedical Relation Extraction with Large Language Models: A Viable Alternative to Supervised Learning?

Biomedical relation extraction (BioRE) is a key step in transforming biomedical literature into structured knowledge. However, most existing approaches rely on supervised models trained on costly annotated datasets, limiting their scalability and adaptability across relation types and domains. We investigate few-shot BioRE using prompt-based learning with large language models (LLMs) and compare two task formulations: pairwise classification, which predicts relations for individual entity pairs, and joint generation, which extracts multiple relations in a single model call. Experiments on the BioREDirect dataset reveal a clear precision-recall trade-off. Pairwise classification achieves higher recall, whereas joint generation is more precise and computationally efficient. The best-performing model achieves a micro-F1 score of 0.44, substantially outperforming previous few-shot results (0.34) while remaining below the supervised baseline (0.56). Much of this gap is attributable to a single ambiguously defined relation type. When evaluated using macro-F1, which better captures performance across relation types in an imbalanced setting, prompt-based approaches outperform the supervised baseline (0.45 vs. 0.38), particularly on rare relation types. These findings highlight the potential of LLMs for BioRE in low-resource settings and underscore the importance of well-defined relation schemas.

13.
arXiv (CS.LG) 2026-06-24

Experiments with Optimal Model Trees

arXiv:2503.12902v4 Announce Type: replace Abstract: Model trees provide an appealing way to perform interpretable machine learning for both classification and regression problems. In contrast to ``classic'' decision trees with constant values in their leaves, model trees can use linear combinations of predictor variables in their leaf nodes to form predictions, which can help achieve higher accuracy and smaller trees. Typical algorithms for learning model trees from training data work in a greedy fashion, growing the tree in a top-down manner by recursively splitting the data into smaller and smaller subsets. Crucially, the selected splits are only locally optimal, potentially rendering the tree overly complex and less accurate than a tree whose structure is globally optimal for the training data. In this paper, we empirically investigate the effect of constructing globally optimal model trees for classification and regression with linear support vector machines at the leaf nodes. To this end, we present mixed-integer linear programming formulations to learn optimal trees, compute such trees for a large collection of benchmark data sets, and compare their performance against greedily grown model trees in terms of interpretability and accuracy. We also compare to classic optimal and greedily grown decision trees, random forests, and support vector machines. Our results show that optimal model trees can achieve competitive accuracy with very small trees. We also investigate the effect on the accuracy of replacing axis-parallel splits with multivariate ones, foregoing interpretability while potentially obtaining greater accuracy.

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

SARLO-80: Worldwide Slant SAR Language Optic Dataset 80cm

arXiv:2606.20523v1 Announce Type: cross Abstract: Multimodal foundation models have advanced rapidly thanks to large optical benchmarks, but comparable resources for synthetic aperture radar (SAR) remain limited. Existing SAR–optical datasets largely rely on low-resolution, intensity-only Ground Range Detected~(GRD) products and do not preserve complex-valued SAR measurements or native acquisition geometry, which restricts physically grounded multimodal learning. In particular, large-scale public datasets combining very-high-resolution (VHR) SAR SLC, aligned optical imagery, and natural-language descriptions are still lacking. We present a VHR SAR–optical–text dataset built from open-access Umbra spotlight acquisitions distributed as Sensor Independent Complex Data (SICD). From around 2,500 worldwide scenes (VV/HH, 20cm–2m native resolution), we standardize all SAR data to an 80cm slant-range grid via band-limited FFT resampling and tile the imagery into 1024 by 1024 patches. For each SAR patch, we retrieve a high-resolution optical tile and warp it into the SAR grid using local coordinate correspondences for local pixel-level alignment. We further generate three caption variants (SHORT/MID/LONG) per sample to support vision–language training and evaluation. Our dataset contains 119,566 triplets (complex and amplitude slant-range SAR patch, aligned optical patch, natural-language description) covering 257 locations across 72 countries and a broad range of land types and infrastructures. We release fixed train/validation/test splits and the full preprocessing and baseline code to enable reproducible benchmarks for multimodal alignment on cross-modal retrieval and conditional generation in native SAR geometry. The dataset is publicly available on the Hugging Face Hub at https://huggingface.co/datasets/ONERA/SARLO-80.

15.
medRxiv (Medicine) 2026-06-11

Development of iADJUST: a theory-informed, patient co-designed digital psychological intervention for adjustment in chronic kidney disease

Background: Psychological distress is common in chronic kidney disease (CKD) and is associated with reduced quality of life, treatment non-adherence, and worse clinical outcomes. Distress in CKD is also linked to difficulties adjusting to the demands of illness management. Despite this, psychological support remains inconsistently integrated within kidney care pathways, and existing interventions often lack clear theoretical specification and explicit targeting of mechanisms underpinning adjustment to CKD. Objectives: To describe the systematic development of iADJUST, a theory-informed patient co-designed digital psychological intervention targeting key cognitive and behavioural mechanisms involved in adjustment to CKD. Methods: Intervention development was guided by the Medical Research Council framework for complex interventions. A structured, iterative process integrated empirical evidence, psychological theory, and patient and public involvement and engagement. The Common-Sense Model of Self-Regulation and cognitive behavioural theories informed the identification of modifiable maintaining mechanisms associated with adjustment to CKD. Intervention components were mapped onto these mechanisms and refined through co-design with people living with CKD. Results: iADJUST is a six-session self-guided digital psychological intervention delivered over 12 weeks and supplemented by therapist contact. The intervention targets illness-related uncertainty, fatigue-related activity dysregulation, catastrophic what-if thinking, self-critical evaluation, and behavioural withdrawal. It integrates psychoeducation, cognitive and behavioural strategies, maintenance planning, and elements from acceptance and commitment therapy and compassion-focused approaches. Content is delivered through video, audio, and guided tasks and activities. Conclusion: iADJUST provides a theory-informed, evidence-based psychological intervention for CKD explicitly mapping intervention components to maintaining cognitive and behavioural mechanisms implicated in adjustment. Feasibility evaluation is underway.

16.
arXiv (quant-ph) 2026-06-19

Nearest-neighbour gates are all you need: High-rate quantum low-density parity-check codes on a planar grid

arXiv:2606.19482v1 Announce Type: new Abstract: High-performance quantum low-density parity-check codes promise substantial reductions in the overhead of fault-tolerant quantum computation, but most constructions require long-range connectivity or qubit shuttling, both of which are difficult to realise in superconducting architectures. Here we introduce a family of quantum low-density parity-check codes that, for the first time, combines planar open-boundary layouts, finite-size advantages over surface codes, and syndrome extraction using only nearest-neighbour gates on a square grid of qubits. The key idea is to generate check-data connectivity dynamically: nearest-neighbour iSWAP walks both define the stabiliser supports and implement their measurement, avoiding the need for a long-range hardware graph. The resulting circuits achieve optimal constant-depth stabiliser measurement, independent of code size, and naturally remove leakage from the system by exchanging the role of check and data qubits at each syndrome extraction round. We find finite-size instances such as a [[323,14,15]] code, whose code-efficiency ratio is nearly an order of magnitude larger than that of rotated surface-code patches. At around 30 circuit qubits per logical qubit, the best directional tile-code layouts reduce the per-logical per-round logical error rate by up to a factor of 1000 relative to rotated surface-code memories. These results show that the advantages of quantum low-density parity-check codes can survive compilation into strictly planar nearest-neighbour circuits, bringing low-overhead fault-tolerant memories closer to near-term hardware.

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

An expressivity analysis of hierarchical modelling in deep transformers via bounded-depth grammars

Deep neural networks are widely believed to derive their expressive power from their ability to form hierarchical representations, capturing progressively more abstract and compositional features across layers. In language modeling, transformers have emerged as the dominant architecture, with early layers capturing local syntactic patterns and later layers encoding more complex clause-level dependencies. While this intuition has shaped model design, there remains a lack of rigorous theoretical work demonstrating how deep transformers represent such hierarchical structures. In this work, we analyze the expressiveness of deep transformer models through the formal lens of bounded-depth, non-recursive context-free grammars. For this class of grammars, we explicitly construct transformers with positional attention whose depth grows linearly with grammar depth, while the neuron count scales with the number of derivation-tree shapes and quadratically with the number of production rules. Our theoretical results support the linear representation hypothesis by demonstrating that these architectures possess the structural capacity to encode abstract grammatical states into low-dimensional, linearly separable subspaces within the residual stream.

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

Continuous Audio Thinking for Large Audio Language Models

Large audio language models (LALMs) have shown impressive capabilities on diverse audio understanding tasks, ranging from speech transcription to music analysis. However, because LALMs are typically trained to produce text-aligned responses, their hidden states are progressively shaped for text generation rather than for preserving acoustic information. As a result, the diverse acoustic content that audio carries, such as phonetic detail, prosody, sound events, affect, and pitch, is lost along the way and difficult to leverage in the response. We introduce Continuous Audio Thinking (CoAT), a framework that equips audio language models with a continuous latent workspace for organizing acoustic information prior to response generation, grounded by distillation from audio experts. Within the thinking space, the model can utilize the rich acoustic information provided by expert distillation when generating its response. Furthermore, the proposed continuous thinking block can be processed in a single prefill, so CoAT does not require additional autoregressive decoding cost over the baseline. Across three LALMs, Qwen2-Audio, Qwen2.5-Omni-7B, and Audio Flamingo~3, performance gains on a broad benchmark suite spanning audio reasoning, audio understanding, music classification, speech emotion, and speech transcription demonstrate the effectiveness of CoAT. Further analysis confirms that the auxiliary supervision propagates from the thinking positions to the model's textual responses.

19.
bioRxiv (Bioinfo) 2026-06-16

MetaPilot: genome-aware adaptive search-space refinement for unified DDA and DIA metaproteomics

Metaproteomic peptide identification is constrained by the structure and size of the protein search space. Pooled gene catalogues provide coverage but obscure genome-level evidence, and current workflows for data-dependent (DDA) and data-independent (DIA) acquisition diverge in their database strategies. We present MetaPilot, a genome-aware workflow that uses conserved marker-protein evidence to rank candidate genomes from MGnify catalogues and construct adaptive, sample-specific search spaces. Applied to paired DDA/DIA datasets of defined mixtures and fecal samples, MetaPilot adapted genome selection to community complexity and reproduced published peptide evidence while expanding the detectable peptide space. In DDA-independent reanalysis of Orbitrap human gut DIA data, MetaPilot identified 24.4% more peptides than the published DDA-derived library and 2.06-fold more than the matched DDA-assisted DIA search. On timsTOF DIA-PASEF mouse intestinal data, it outperformed uMetaP by 41.8~119.7%, enabling genome-resolved functional interpretation without DDA-PASEF input.

20.
bioRxiv (Bioinfo) 2026-06-10

HOMED enables hierarchical and multimodal optimization of DNA methylation deconvolution across tissues

Cellular heterogeneity is a major confounder in bulk DNA methylation data for epigenome-wide association studies. Existing reference-based DNAm deconvolution methods often ignore hierarchies among related cell types and may generalize poorly across datasets due to limited variability in reference profiles. We developed HOMED (Hierarchically Optimized Methylation Deconvolution), a framework that integrates cell-lineage hierarchies, single-cell RNA sequencing-guided deconvolution, and paired bulk RNA-seq/DNAm data for CpG signature optimization. Across simulated and real peripheral blood mononuclear cell, lung, and placental datasets, HOMED consistently yielded the highest PCCs and lowest RMSEs, outperforming existing scRNA-seq-guided DNAm deconvolution methods, improving accuracy, resolution, and cross-tissue generalizability.

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

CaReTS: A Multi-Task Framework Unifying Classification and Regression for Time Series Forecasting

arXiv:2511.09789v2 Announce Type: replace Abstract: Recent advances in deep forecasting models have achieved remarkable performance, yet most approaches still struggle to provide both accurate predictions and interpretable insights into temporal dynamics. This paper proposes CaReTS, a novel multi-task learning framework that combines classification and regression tasks for multi-step time series forecasting problems. The framework adopts a dual-stream architecture, where a classification branch learns the stepwise trend into the future, while a regression branch estimates the corresponding deviations from the latest observation of the target variable. The dual-stream design provides more interpretable predictions by disentangling macro-level trends from micro-level deviations in the target variable. To enable effective learning in output prediction, deviation estimation, and trend classification, we design a multi-task loss with uncertainty-aware weighting to adaptively balance the contribution of each task. Furthermore, four variants (CaReTS1–4) are instantiated under this framework to incorporate mainstream temporal modelling encoders, including convolutional neural networks (CNNs), long short-term memory networks (LSTMs), and Transformers. Experiments on real-world datasets demonstrate that CaReTS outperforms state-of-the-art (SOTA) algorithms in forecasting accuracy, while achieving higher trend classification performance.

22.
bioRxiv (Bioinfo) 2026-06-11

Robust semi-supervised scRNA-seq integration from virtual adversarial learning

Single-cell RNA sequencing integration methods that rely solely on transcriptomic data often struggle to preserve fine-grained distinctions between closely related cell subtypes. As a result, cell populations that are separable in the raw data may become over-mixed after integration, reducing biological resolution and interpretability. Incorporating marker gene information can potentially address these issues; however, the variability and complexity of available marker sets limit their effective application. To address this, we introduce scCRAFT+, a semi-supervised integration model that innovatively incorporates marker gene information through Virtual Adversarial Training (VAT). By jointly optimizing marker-derived supervision and transcriptome-wide representations, VAT enforces local prediction smoothness among transcriptionally similar cells, improving robustness to noisy marker annotations while enhancing both integration quality and cell type auto-annotation. This targeted approach significantly enhances annotation accuracy and robustness, particularly when faced with incomplete or incorrect marker gene sets. Benchmarking shows that scCRAFT+ achieves consistently stronger performance than current unsupervised and supervised integration approaches, resulting in improved integration quality and biologically meaningful sub-cell type auto-annotations.

23.
medRxiv (Medicine) 2026-06-22

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

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

24.
bioRxiv (Bioinfo) 2026-06-22

Drug-Prot: A query system for statistical inference of drug effects and interactions in dynamic proteomic networks

Understanding drug effects and drug-drug interactions is essential for developing combination therapies. We present Drug-Prot, a computational framework that leverages large-scale perturbation proteomics to quantify causal drug effects, drug-drug interactions, and dynamic protein relationships. Using data from 63 single drugs and 59 drug combinations applied to 18 breast cancer cell lines at 6, 24, and 48 hours, Drug-Prot estimates drug effects on protein expression and reconstructs directed temporal protein dependency networks. The publicly available software enables targeted analyses of user-defined protein sets, substantially reducing the multiple-testing burden. Through an interactive web application, users obtain corrected p-values for single-drug and combination effects, directed temporal dependency networks, and downloadable results without requiring access to the underlying proteomic dataset. As a use case, we apply invariance-regularized Random Forests to triple-negative breast cancer cell lines to identify proteins associated with drug response. Querying these proteins in Drug-Prot reveals drug-specific and interaction effects at the protein-network level, illustrating how the framework links candidate causal protein features to actionable drug combinations.

25.
arXiv (CS.CL) 2026-06-11

Factions Within, Uncertain Across: Within-Document Reader Sub-Groups in Social Highlighting

When many people highlight the same document, is the crowd a single consensus, or is it internally structured into reader sub-groups that mark different things – and is that structure a stable property of a reader or of the document? Building on prior work showing an individual's within-document highlighting signal is a whisper while individuality lives in selection, we ask the group-level question on a co-readership platform using a margin-preserving curveball null. Experiment 1: within a document, readers form strong sub-groups – pairs agree far beyond what shared salience, mark density, and sentence popularity predict (nearest-neighbour agreement z=+6.3, significant in 88% of documents). Under an eight-block region-preserving null, shared engagement with the same coarse regions of the document accounts for about 40% of this excess; the majority survives as finer reader-specific agreement (z=+3.6, 77% significant). So the within-document crowd is, in a descriptive sense, factional. Experiment 2: is that grouping a stable reader trait? Here we are honest about power. The cross-document split-half reproducibility of a pair's agreement is near zero pooled (+0.078 and 0.000 in two separately drawn samples), and a power calibration shows the test is informative only for pairs that co-read many documents. In the only informative high-overlap subset (k>=4), point estimates are positive but small-sample, imprecise across the separately drawn samples, never significant, and attenuate under the region-preserving null. We therefore leave cross-document stability unresolved: the data is consistent with anything from situational grouping to a weak-to-moderate stable reader trait. The crowd is factional within a document; whether its factions follow the reader across documents is, honestly, beyond our reach.