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01.
arXiv (CS.LG) 2026-06-15

Decompose Sparsely Where You Should, Absorb Densely Where You Should No

arXiv:2606.14040v1 Announce Type: new Abstract: Sparse autoencoders (SAEs) are typically trained to reconstruct the entire residual stream through a sparse dictionary, implicitly assuming that all activation content is amenable to sparse, monosemantic decomposition. We question this assumption and hypothesize that activations contain a low-rank, dense component that is computationally important to the model yet inherently unsuitable for sparse representation, which serves as a major source of the persistent dense latents widely observed in trained SAEs. To test this, we add a small rank-$r$ linear bottleneck in parallel with standard SAEs (BatchTopK and Matryoshka), allowing dense structure to be absorbed before sparse reconstruction. On Gemma-2-2B layer 12, a rank-24 bottleneck reduces dense latent count by up to 84\% while improving sparse probing and targeted probe perturbation on both architectures at matched sparsity. The absorbed component is (i) structurally identifiable as the top principal components and outlier dimensions; (ii) causally necessary, with removing it raising next-token cross-entropy by 7.5$\times$, far exceeding the 2.8$\times$ from removing the geometrically near-identical top-24 PCA directions; and (iii) redundantly encoded by sparse dictionaries, with ablating 787 maximally aligned sparse features raising cross-entropy by only 2.9$\times$ and ablating 2,048 topic-aligned features leaving MMLU topic classification virtually unchanged, whereas removing the scaffold drops it from 98.7\% to chance. Together, our findings identify a compact, semantically informative and causally important component of residual stream activations (which we term a computational scaffold) that standard sparse dictionaries represent inefficiently, suggesting that the scope of sparsity-based interpretability methods warrants careful re-examination.

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

SAMTok: Representing Any Mask with Two Words

Pixel-wise capabilities are essential for building interactive intelligent systems. However, pixel-wise multi-modal LLMs (MLLMs) remain difficult to scale due to complex region-level encoders, specialized segmentation decoders, and incompatible training objectives. To address these challenges, we present SAMTok, a discrete mask tokenizer that converts any region mask into two special tokens and reconstructs the mask using these tokens with high fidelity. By treating masks as new language tokens, SAMTok enables base MLLMs (such as the QwenVL series) to learn pixel-wise capabilities through standard next-token prediction and simple reinforcement learning, without architectural modifications and specialized loss design. SAMTok builds on SAM2 and is trained on 209M diverse masks using a mask encoder and residual vector quantizer to produce discrete, compact, and information-rich tokens. With 5M SAMTok-formatted mask understanding and generation data samples, QwenVL-SAMTok attains state-of-the-art or comparable results on region captioning, region VQA, grounded conversation, referring segmentation, scene graph parsing, and multi-round interactive segmentation. We further introduce a textual answer-matching reward that enables efficient reinforcement learning for mask generation, delivering substantial improvements on GRES and GCG benchmarks. Our results demonstrate a scalable and straightforward paradigm for equipping MLLMs with strong pixel-wise capabilities. Our code and models are available.

03.
arXiv (math.PR) 2026-06-16

Probabilities

arXiv:2601.18853v4 Announce Type: replace-cross Abstract: Probabilities is the English translation of the book Probabilités Tome 1 and Tome 2. The mathematic content is authored by Prof. Jean-Yves Ouvrard. The English version has been done by his eldest son Dr. Xavier Ouvrard. This probability theory book covers not only an introduction to this field, but also advanced concepts based on measure theory. The first part introduces the fundamentals of probability theory across 7 chapters, targeting bachelor level, including event algebras, random variables, independence, conditional probabilities, moments of discrete and continuous random variables, generating functions, and limit theorems. The second part contains 10 chapters and corresponds to master level. Following a brief introduction to measure theory, this part develops more advanced topics: probability measures and their complements, distributions and moments of random variables, modes of convergence, laws of large numbers, conditional expectation, Fourier transforms and characteristic functions, Gaussian random variables, convergence of measures, convergence in distribution, discrete-time stochastic processes, martingales, and Markov chains. The reader's work is greatly facilitated by the inclusion, in every chapter, of numerous exercises, all accompanied by detailed solutions that often provide substantial extensions to the theoretical material.

04.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

作者:

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach limits cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides a new approach to precision disease treatments for undruggable targets.

05.
arXiv (quant-ph) 2026-06-11

Magneto-Optical Trapping of a Metal Hydride Molecule

arXiv:2512.22350v2 Announce Type: replace-cross Abstract: We demonstrate a three-dimensional magneto-optical trap (MOT) of a metal hydride molecule, CaH. We are able to scatter $\sim$$10^{4}$ photons with vibrational loss covered up to vibrational quantum number $\nu=2$. This allows us to laser slow the molecular beam near zero velocity with a "white-light" technique and subsequently load it into a radio-frequency MOT. The MOT contains $230(40)$ molecules, limited by beam source characteristics and predissociative loss of CaH. The temperature of the MOT is below one millikelvin. The predissociative loss mechanism could, in turn, facilitate controlled dissociation of the molecule, offering a possible route to optical trapping of hydrogen atoms for precision spectroscopy.

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

TACOMORE: Exploring a replicable prompting protocol for LLM-assisted corpus analysis

As corpus linguistics continues to scale, researchers are facing a growing methodological bottleneck: while computational tools can easily count billions of words, the qualitative interpretation of these data remains a slow and labor-intensive human task. Large Language Models (LLMs) offer a promising way to automate this process, yet their integration into the field is often hindered by concerns over black-box unpredictability and a lack of replicability. This study introduces TACOMORE, a structured prompting framework designed to transform ad-hoc AI interactions into a standardized linguistic protocol. Built upon four foundational principles (Task, Context, Model, and Replicability), the framework guides LLMs to move beyond generic probability prediction to anchoring their reasoning in the specific co-occurrence patterns of a target corpus. We applied this framework to three core corpus tasks, i.e., the analysis of keywords, collocates, and concordances, using an open corpus of COVID-19 research abstracts. After testing three LLMs, we found that while structured prompting improves accuracy and replicability, inherent limitations regarding hallucination persist. This research offers a critical lens into the role of LLMs in corpus linguistics, highlighting their potential as complementary tools while emphasizing the irreplaceable role of human validation.

07.
medRxiv (Medicine) 2026-06-19

Reassessing Instrument Strength in Two-Sample Mendelian Randomization Analysis

Mendelian randomization (MR) analysis is widely used to estimate causal relationships between risk factors and outcomes of interest. Two-sample MR approaches have gained increasing attention in genetic epidemiology due to the growing availability of Genome-Wide Association Study (GWAS) summary statistics from public databases. A critical step in two-sample MR is the selection of genetic variants as instrumental variables (IVs). Although genome-wide significant variants are typically preferred, the inclusion of variants with weaker association p-values is considered, as they may potentially improve power through an increased instrument number of instruments, while they may introduce weak instrument bias and attenuate effect estimates towards the null. Our simulation results show that even modest levels of pleiotropy substantially increase the variability of causal effect estimates, while the inclusion of weak IVs does not substantially affect the direction and variability of causal effect estimates in most cases. In real data analyses, we used two released versions of FinnGen GWAS summary statistics with different sample sizes as exposure GWASs to assess the influence of weak IVs. Here, the inclusion of IVs with higher exposure-association p-values resulted in weakened estimated effect sizes, particularly when the exposure GWAS sample size was small. These findings suggest that incorporating weak IVs is reasonable when the exposure GWAS sample size is large, but it poses a risk of falsely concluding null associations when the exposure GWAS sample size is small.

08.
arXiv (CS.AI) 2026-06-12

Select and Improve: Understanding the Mechanics of Post-Training for Reasoning

arXiv:2606.13125v1 Announce Type: cross Abstract: Reinforcement learning has rapidly emerged as a key component in the training of reasoning and coding models, yet it remains poorly understood from a mechanistic perspective. We study how and through what underlying processes capabilities are acquired or enhanced via reinforcement learning post-training. Our analysis, based on controlled math reasoning experiments with Qwen-2.5-1.5B, reveals two core mechanisms: strategy selection and strategy improvement. Our results highlight the role of SFT data and reinforcement learning data in activating these mechanisms, in particular showing how supervising the model on diverse reasoning strategies can enable strategy selection and how increasing difficulty in reinforcement learning data can enable strategy improvement. Taken together, our results provide mechanistic insight into RL training and suggest practical interventions to continue scaling reasoning capabilities.

09.
arXiv (CS.AI) 2026-06-18

DeFAb: A Verifiable Benchmark for Defeasible Abduction in Foundation Models

arXiv:2606.18557v1 Announce Type: new Abstract: A rule-based logic solver resolves every instance in our benchmark in under 50 microseconds with 100% accuracy; the best frontier language model reaches 65% at best and drops to 23.5% under rendering-robust evaluation (worst case over four surface renderings). We introduce DeFAb (Defeasible Abduction Benchmark), a dataset and generation pipeline that converts four decades of publicly funded knowledge bases into formally grounded instances for defeasible abduction: constructing hypotheses that explain anomalies by overriding defaults while preserving unrelated expectations. Because every hypothesis must pass polynomial-time checks for valid derivation, conservativity, and minimality, DeFAb makes logical rigor the instrument for measuring creativity and theoretical reasoning, scoring the disciplined construction of theory revisions rather than fluent but theory-destroying prose. The pipeline pairs taxonomic hierarchies (OpenCyc, YAGO, Wikidata) with behavioral property graphs (ConceptNet, UMLS) to produce 372,648+ instances across 33.75M materialized rules from 18 sources, in three levels with polynomial-time verifiable gold standards. Four frontier models do not reliably internalize defeasible reasoning: rendering-robust Level 2 accuracy is 7.8-23.5%; chain-of-thought variance (~36 pp) exceeds any inter-model gap; and a matched contamination control isolates a +19.4 pp Level 3 gap. We further release DeFAb-Hard (a 235-instance Level 3 difficulty variant; best model 53.3% vs 100% symbolic) and CONJURE (a kernel-verified transformative-creativity variant of 560 Lean 4/Mathlib instances whose gold answers are definitions the proof kernel did not previously contain, judge-free verifier; a pilot finds zero novel concepts). The same verifier doubles as an exact reward for preference optimization (DPO, RLVR/GRPO). Released under MIT at https://huggingface.co/datasets/PatrickAllenCooper/DeFAb.

10.
arXiv (CS.AI) 2026-06-11

CredibleDFGO: Differentiable Factor Graph Optimization with Credibility Supervision

arXiv:2605.06100v2 Announce Type: replace-cross Abstract: Global navigation satellite system (GNSS) positioning is widely used for urban navigation, but the covariance reported by the GNSS solver is often unreliable in urban canyons. Existing differentiable factor graph optimization (DFGO) methods learn measurement weighting through the solver, but they still use position-only objectives. As a result, the position estimate may improve while the reported covariance remains too small, too large, or incorrectly oriented. We propose CredibleDFGO (CDFGO), a differentiable GNSS factor graph framework that makes covariance credibility an explicit training target. A Weighting Generation Network (WGN) predicts per-satellite reliability weights, and a differentiable Gauss-Newton solver maps these weights to a position estimate and a Hessian-derived posterior covariance. We use proper scoring rules to supervise the East-North predictive distribution end to end. We study negative log-likelihood (NLL), the energy score (ES), and their combination. Results on three UrbanNav test scenes show consistent gains in covariance credibility. Positioning accuracy also improves on the medium-urban and harsh-urban scenes; on the deep-urban scene, both the mean horizontal error and the 95th-percentile error improve. On the harsh-urban Mong Kok (MK) scene, CDFGO-Combined reduces the mean horizontal error from 13.77 m to 11.68 m, reduces NLL from 40.63 to 6.59, and reduces ES from 12.31 to 9.05 relative to DFGO (MAE). Case studies link the MK improvement to better axis-wise consistency, more credible local covariance ellipses, and satellite-level reweighting.

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

BRDFusion: Physics Meets Generation for Urban Scene Inverse Rendering

Inverse rendering of urban scenes from captured videos enables numerous applications, including content creation and autonomous driving simulation. Physically-based rendering methods follow and control lighting physics, but suffer from reconstruction and rendering artifacts. While generative models produce realistic videos, they offer limited consistency and controllability. We present BRDFusion, a unified framework that combines two complementary models for inverse and forward rendering. Specifically, BRDFusion recovers explicit, consistent scene properties with physical modeling and alleviates optimization ambiguity with generative priors. During forward rendering, the physical model provides controllable rendering from the scene configuration, and the generative model denoises and fixes artifacts. Therefore, our method produces high-quality videos while allowing precise control, outperforming baselines in real and synthetic scenes. Moreover, BRDFusion supports novel-view relighting, night simulation, and dynamic object insertion/editing. Project page: https://shigon255.github.io/brdfusion-page/

12.
medRxiv (Medicine) 2026-06-17

Clinician knowledge and self-efficacy in snakebite management: A cross-sectional assessment in Northern Uganda

Background: Snakebite envenomation (SBE) is a major public health crisis in rural Uganda, yet it remains a neglected tropical disease. Effective management is often compromised by systemic barriers and a lack of clinician training. This study assessed clinician self-efficacy and objective knowledge regarding SBE management in Northern Uganda. Methods: A descriptive, cross-sectional study was conducted between February and July 2025 among 379 healthcare workers in Gulu, Omoro, and Pader districts. A validated questionnaire was used to collect data on socio-demographics, self-reported efficacy (scale 1-10), and objective knowledge. Knowledge scores [&ge;]70% were categorized as adequate. Multivariable logistic regression identified independent predictors of adequate knowledge, and Spearmans correlation ({rho}) assessed the relationship between knowledge and self-efficacy. Results: The participants had a mean age of 35.6 years (SD {+/-}7.3), were predominantly female (56.5%, 214/379), and most (83.6%, 317/379) practiced at Health Centre III level facilities. While 53.8% (204/379) reported prior training, 48.3% (183/379) of these had not received an update in over 10 years. Adequate knowledge was demonstrated by 51.5% (195/379) of participants. In the multivariable analysis, practicing in Omoro (adjusted odds ratio [aOR]: 0.3, 95% CI: 0.1-0.6, p < 0.001) or Pader (aOR: 0.2, 95% CI: 0.1-0.4, p < 0.001) was associated with lower odds of adequate knowledge compared to Gulu district. Prior training significantly increased the odds of adequate knowledge (aOR: 2.3, 95% CI: 1.3-4.2, p = 0.006). A moderate positive correlation was observed between self-efficacy and objective knowledge (Spearmans {rho} = 0.33, p < 0.0001). Conclusion: Approximately half of the frontline healthcare workers in Northern Uganda lack adequate knowledge on SBE management, with significant geographic differences and outdated training. The gap between clinician self-efficacy and objective knowledge poses a risk to patient safety. Regular, mandatory refresher training and targeted educational outreach to remote districts are required to reduce SBE-related morbidity and mortality.

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

Holo-World: Unified Camera, Object and Weather Control for Video World Model

Video world models are moving toward preserving an observed world under controllable camera and object motion while allowing its environmental state to change. Yet these controls remain isolated, and weather generation typically relies on a source video or reconstructed scene that already specifies future structure. We study a first-frame-anchored source-to-state setting, where the model starts from a single image and follows explicit camera and object controls and an optional weather instruction, then generates a video that either preserves the source world or transfers it to a target weather state. To address these challenges, we first build HoloStateData, a state video dataset that turns diverse videos into unified control samples for camera, object, and weather supervision. Second, we introduce Holo-World, a unified controllable video world model that jointly controls scene from a single image. Its Unified Scene Adapter factorizes world preservation and weather transfer into distinct parameter subspaces, using rendered background, geometry buffers, and object controls to maintain controlled scene structure while modeling weather-dependent appearance and particle effects. Additionally, Scene-Weather Decomposed CFG guides scene and weather residuals separately, strengthening target weather effects without over-amplifying the full condition. Quantitative and qualitative experiments demonstrate that Holo-World maintains precise camera and object control with consistent scene structure while transferring scenes into diverse target weather state, outperforming video-to-video weather editing baselines on weather-state generation. Our project page is available at \url{https://xiangchenyin.github.io/Holo-World/}.

14.
medRxiv (Medicine) 2026-06-19

Performance of family history-based colorectal cancer screening criteria by race and age at diagnosis in the Disparities and Cancer Epidemiology (DANCE) study

Importance: Family history (FH) and age are the primary criteria employed for early colorectal cancer (CRC) risk stratification. We evaluated how well these criteria identify individuals diagnosed with CRC across age and racial groups. Objective: To evaluate the performance of FH and age based screening criteria for identifying individuals with CRC, with attention to differences by race and age at diagnosis. Design, Setting, and Participants: This case control and case only analysis used data from the Disparities and Cancer Epidemiology (DANCE) cohort, a population based study of invasive CRC cases diagnosed from 2013 to 2022, recruited through the Metropolitan Detroit Cancer Surveillance System and the Louisiana Tumor Registry. Analyses included 1,158 non-Hispanic Black (NHB) and non-Hispanic White (NHW) CRC cases and 1,434 cancer-free controls from the Inflammation Health and Lung Epidemiology (INHALE) study, enrolled from the same Detroit catchment area. Data were analyzed in 2025. Exposures: Self reported cancer FH among first-degree (FD) relatives and grandparents, summarized into three FH-based screening criteria: at least one FD relative with CRC (colon early-screening criterion), any FH of Lynch syndrome related cancers, and meeting NCCN criteria for Lynch syndrome genetic testing. Main Outcomes and Measures: Proportion of cases meeting each FH based screening criterion stratified by race and age at diagnosis (

15.
PLOS Medicine 2026-06-04

Beyond associations: Navigating the safety of non-steroidal anti-inflammatory drugs (NSAIDs) in early pregnancy

by Andrew S. C. Yuen, Kenneth K. C. Man Pain and fever in pregnancy require treatment, but fetal safety concerns complicate analgesic choice. A recent PLOS Medicine study presents new evidence on the safety of first-trimester NSAID use and congenital malformation risk, but interpreting findings across studies is challenging. In this Perspective, Kenneth Man and Andrew Yuen highlight a recent PLOS Medicine study that presents new evidence on the safety of first-trimester NSAID use and congenital malformation risk, but discuss why interpreting findings across studies is challenging.

16.
arXiv (CS.AI) 2026-06-15

Position: Align AI to Our Aspirations, Not Our Flaws

arXiv:2606.13755v1 Announce Type: cross Abstract: We argue that aligning AI to aggregated human preferences is the wrong target. With current technology, one can train AIs to share the values of a Silicon Valley techno-optimist, a degrowth environmentalist, a national-conservative culture warrior, a single-party state cadre, or a devout religious traditionalist. We should not. Human values produce societies that thrive or fail on the merits of those values - from failed states and extreme inequality to declining happiness, political polarization, and government dysfunction in the world's wealthiest democracies. The pluralistic-alignment program correctly diagnoses that there is no single "humanity" to align with, but is dangerous if taken as the main directive. We argue that AI should be trained to a non-negotiable floor of objective alignment goals - competence, bounded by the constraints of factual accuracy, honesty, and lawfulness and that pluralism belongs at the surface (language, register, conventions, missing-context defaults) and across the wide band of legitimate value tradeoffs that respect the floor, but not at the level of values that violate it. We highlight the empirical reality of unfiltered pluralistic values, propose four commitments as a constructive alternative, and engage six credible objections: commercial pressure and practical feasibility, democratic legitimacy, regulatory compliance, over-reliance on institutionalist explanations, the charge that the floor itself is culturally laden, and the limits of Coherent Extrapolated Volition.

17.
Nature (Science) 2026-06-10

The Amazon can be saved — with concerted action inside and outside Brazil

作者: 未知作者

As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down. As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down.

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

Your "Pro" LLM Subscription May Actually Be "Free": Exposing Fingerprint Spoofing Risks in LLM Inference Services

As Large Language Model (LLM) APIs become ubiquitous, users increasingly rely on black-box fingerprinting to verify that providers are serving the advertised premium models. However, these methods may overlook adversarial providers who manipulate model weights to cheat the fingerprint process. We introduce a novel threat termed fingerprint spoofing, where a malicious provider stealthily serves a weaker model that has been parameter-efficiently fine-tuned to mimic a stronger model, thereby evading user-side fingerprinting. We first formally prove that user-side resource constraints (i.e., finite query budgets and weak fingerprinting classifiers) make current fingerprinting vulnerable to fingerprint spoofing. Guided by this theoretical analysis, we propose GhostPrint, a cost-effective attack framework leveraging surrogate modeling, reward-ranked fine-tuning, and knowledge distillation. Extensive evaluations in both static and continual fingerprinting settings demonstrate that GhostPrint allows weak models to consistently bypass representative fingerprint methods while maintaining utility at a low fine-tuning cost, exposing a critical vulnerability in current LLM fingerprinting pipelines.

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

Graph2Idea:Retrieval-Augmented Scientific Idea Generation with Graph-Structured Contexts

arXiv:2606.09105v3 Announce Type: replace Abstract: Generating novel, feasible, and high-quality research ideas is an important yet challenging task in scientific discovery. Recent Large Language Model (LLM)-based methods often ground idea generation with retrieved literature, but the retrieved evidence is usually provided as flat text, such as titles, abstracts, or summaries. Such flat contexts may contain redundant or weakly relevant information, while making cross-paper relations among problems, methods, mechanisms, and findings difficult to identify and trace. To address this challenge, we propose Graph2Idea, a knowledge graph-guided framework for retrieval-augmented scientific idea generation.Graph2Idea first retrieves papers according to the input topic, transforms them into structured knowledge triples, and dynamically constructs a target-centered knowledge graph to make literature relations explicit. It then extracts compact graph-derived contexts that retain target-relevant relational evidence while reducing noisy textual input. Based on these contexts, a two-stage generation process first identifies promising research directions and then guides the LLM to synthesize candidate ideas from graph-grounded evidence. Experiments on a scientific idea generation benchmark show that Graph2Idea outperforms representative baselines under the automatic evaluation protocol. Compared with the strongest baseline scores, it improves Novelty from 0.45 to 0.52, Quality from 0.24 to 0.29, and Feasibility from 0.22 to 0.28. These results suggest that graph-structured evidence helps LLMs generate research ideas through more explicit, compact, and traceable recombination of prior scientific knowledge.

20.
arXiv (CS.AI) 2026-06-11

MetaPlate: Counterfactual-Guided RAG-LLM Tool for Personalized Food Recommendation and Hyperglycemia Prevention

arXiv:2606.10120v2 Announce Type: replace-cross Abstract: Postprandial hyperglycemia is a key risk factor for metabolic disorders; however, existing dietary guidance is often static, impractical, and insufficiently personalized, providing recommendations that are difficult to follow or not impactful. While recent advances leverage continuous glucose monitoring (CGM) and machine learning to predict glycemic responses, these approaches are largely predictive and lack actionable guidance. Moreover, recommendation systems are often misaligned with user goals and require extensive input. We present MetaPlate, a counterfactual explanation (CF) guided, context-aware decision-support framework that generates personalized meal recommendations to mitigate postprandial glucose excursions in healthy adults. MetaPlate integrates multimodal data, including CGM readings, wearable-derived physiological signals, and user-provided meal inputs from $25$ individuals to model pre-meal context. A machine learning model predicts glucose response, while a CF optimization module adjusts meal composition modifying macronutrient amounts to maintain glucose levels within a target range ($\leq 140$ mg/dL). An LLM-based retrieval-augmented generation (RAG) layer enhances interpretability by producing human-readable recommendations using constrained search of the USDA food database. We evaluate MetaPlate via a structured expert-in-the-loop assessment with registered dietitians (RDs), comparing performance before and after prompt refinement. Results show improvements in meal realism, portion suitability, and recommendation likelihood, with expert feedback indicating a shift from clinically implausible outputs to actionable, contextually appropriate recommendations. Our findings emphasize the importance of domain knowledge and structured constraints in LLM-driven systems and highlight the potential of MetaPlate as a real-time personalized dietary decision-support tool.

21.
arXiv (CS.CL) 2026-06-15

Can Post-Training Turn LLMs into Good Medical Coders? An Empirical Study of Generative ICD Coding

Automated International Classification of Diseases (ICD) coding is a core medical-coding task for billing, epidemiology, and clinical decision support. Generative large language models (LLMs) are often reported as weak medical coders, but this finding mainly comes from inference-time settings such as prompting, retrieval, reranking, or tool use, leaving the role of task-specific post-training underexplored. We present a controlled empirical study of post-training for generative ICD coding, comparing discriminative baselines with LLM coders across prompting, supervised fine-tuning, and reinforcement learning under a common protocol and metric set. To our knowledge, this is the first study to evaluate RL-based post-training for generative LLM coders in ICD coding. We further introduce PHI, a diagnostic curriculum that extends GRPO to refine missed-code cases. Our results show that prompting-only evaluation substantially underestimates the potential of LLMs for ICD coding. SFT provides the main capability jump, GRPO further improves code-set prediction beyond SFT, and PHI provides targeted gains on macro-level performance. These findings suggest that the main bottleneck is not the generative formulation alone, but how the model is adapted and optimized for full-taxonomy recall. We release our code, data splits, and checkpoints at https://github.com/AlexandreWANG915/LLM4ICD.

22.
Nature Biotechnology 2026-06-05

Multiplexed, precise genome engineering in monocots with twin prime editing systems

作者:

Simultaneously introducing diverse genomic edits remains a challenge in crop genome engineering. Here we describe a twin prime editing-based knockout (TKO) system that installs stop codon clusters (SCCs) for precise translational termination with minimal in-frame mutations. TKO achieves knockout efficiencies of up to 70.5%, 58.6% and 75.1% in rice, maize and wheat protoplasts, respectively, and produces heritable knockout alleles in 96.8% of regenerated rice plants. In hexaploid wheat, TKO outperforms Cas9 4.2-fold in generating triple-homolog knockouts, largely by reducing in-frame mutations. Orthogonal TKO editors with sequence-divergent SCCs enable simultaneous knockout of up to ten genes without cross-interference. Integration of TKO with conventional prime editing establishes TRIM1 (TKO editor-enabled gene rupture and development of integrated multitype genome modification system) for simultaneous knockout and precise editing, achieving a 22.8% coediting of four genes in rice. TRIM2 extends this capacity to kilobase-scale modifications through a prime editor–recombinase system, enabling a 4.9-kb insertion (1.2% efficiency) and gene knockout (up to 79.8%) in protoplasts. Plant genome editing is multiplexed with twin prime editing.

23.
arXiv (CS.CV) 2026-06-16

Parameter-Efficient Adaptation of SAM 3 for Automated ITV Generation from 4DCT Images

Four-dimensional computed tomography (4DCT) captures the full respiratory cycle of thoracic anatomy, yet current Internal Target Volume contouring workflows process each phase in isolation, discarding temporal coherence and leaving contours vulnerable to phase-specific artifacts. We present a lightweight framework that applies parameter-efficient fine-tuning to the Segment Anything Model 3 (SAM 3) via low-rank adaptation (LoRA) to align its text-prompted segmentation with the medical domain using only seven annotated 3D CT volumes. Furthermore, the framework incorporates a hard negative mining strategy to improve boundary discrimination in low-contrast thoracic regions. At inference, phase-wise predictions are refined through phase-coherent temporal filtering and spatial connectivity analysis. Since respiratory motion is continuous and periodic, genuine anatomy appears in contiguous blocks of phases, whereas transient artifacts appear sporadically and are thus effectively suppressed. Experiments on pulmonary and cardiac structures yield median Dice scores of 0.968 and 0.910 with 95th-percentile Hausdorff distances of 0.998 mm and 2.931 mm, respectively. The proposed framework effectively eliminates the severe false-positive predictions inherent in the zero-shot inference of the unadapted SAM 3. With only seven annotated volumes, the framework retains over 95% of full-data accuracy, and the entire pipeline is trainable on a single consumer-grade GPU, demonstrating a scalable, data-efficient solution for adaptive radiotherapy.

24.
PLOS Computational Biology 2026-06-05

A multiscale, Bayesian inference approach to augment mechanistic models of cell signaling with machine-learning predictions of binding affinity

by Holly A. Huber, Stacey D. Finley Computational models in systems biology are often underdetermined—that is, there is little data relative to the complexity and size of the model. This lack of data is primarily due to limits in our ability to observe specific biological systems and restricts the utility of computational models. To reduce this uncertainty, recent methods have explored augmenting parameter inference of systems biology models with predictions from machine learning models. Such approaches expand the pool of data that is applicable for the inference problem. Here, we explore augmenting the parameter inference of intracellular signaling models. We choose to investigate signaling because experimental measurements of the variables of interest, protein dynamics, are still quite limited. To investigate, we propose a novel, multiscale, Bayesian inference approach that augments traditional signaling data with predictions of binding affinity. These predictions are generated using a machine learning pipeline with measurements of amino acid sequence, from the Universal Protein Resource, or protein structure, from the Protein Data Bank, as inputs. We find that we can successfully integrate these measurements into the inference problem using our novel framework. Excitingly, this integration significantly improves the parameter estimates of signaling models. We demonstrate that how much this improvement impacts predictions of signaling depends on the sensitivity of the prediction to perturbations in the parameter values. Overall, the framework we establish here improves the parameter inference of intracellular signaling models by successfully bridging data on protein sequence and structure with systems-level signaling.

25.
medRxiv (Medicine) 2026-06-18

Comparative Evaluation of Pretrained Large Language Models for Suicide Risk Prediction from Clinical Notes in U.S. Veterans

Background: Suicide remains a significant and potentially preventable cause of death among United States veterans. Predictive models based on structured electronic health record (EHR) data, including the U.S. Department of Veterans Affairs' Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH-VET) program, aim to identify individuals at elevated risk for enhanced monitoring and follow-up. Increasing evidence suggests that unstructured clinical narratives contain additional psychosocial information that may enhance risk prediction when analyzed using natural language processing (NLP). However, optimal approaches for representing clinical text remain uncertain. Recent advances in large language models (LLMs) enable contextual text representations that capture complex semantic relationships beyond traditional lexical methods. Methods: We compared the predictive performance of pretrained LLMs with classical bag-of-words (BoW) representations for suicide risk prediction using clinical notes from 27,241 veterans receiving care in the Veterans Health Administration. Patients were stratified by REACH-VET risk tier (low, moderate, high), and models were evaluated across prediction windows defined by note look-back periods (