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01.
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.

02.
arXiv (CS.AI) 2026-06-17

Online LLM Selection via Constrained Bandits with Time-Varying Demand

arXiv:2606.17489v1 Announce Type: cross Abstract: Large Language Models (LLMs) are increasingly deployed in edge-cloud inference systems to handle diverse user tasks with heterogeneous accuracy, latency, and cost profiles. Selecting the appropriate LLM for each incoming task is critical for ensuring service quality and efficient resource utilization. However, model heterogeneity, stochastic and unknown performance characteristics, and time-varying task demands make static selection strategies inadequate. Real-world deployments often impose hard resource budgets such as monetary expenditure limits, along with soft service-level requirements such as latency guarantees. These constraints introduce additional challenges for online decision-making. We formulate this problem as a constrained stochastic bandit learning task, where the learner sequentially selects models under both packing-type (hard) and covering-type (soft) constraints, while adapting to time-varying task demand. The learner operates without access to the underlying reward, cost, or latency distributions and must rely on partial feedback. We develop a novel online learning algorithm that leverages confidence-bound estimates and demand predictions to balance reward maximization with long-term constraint satisfaction. We provide theoretical guarantees showing sublinear regret and sublinear covering constraint violations compared to an offline benchmark with full information. Experimental results on synthetic workloads demonstrate the effectiveness and robustness of our approach in dynamic, resource-constrained environments.

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

Dialogue SWE-Bench: A Benchmark for Dialogue-Driven Coding Agents

AI coding agents have rapidly transformed software engineering, powering widely used interactive coding assistants. Despite their interactive real-world use, existing benchmarks evaluate them as fully-autonomous systems. In this work, we introduce Dialogue SWE-Bench, an automatic benchmark dataset for evaluating the ability of coding agents to resolve real-world software engineering problems through dialogue with a user. We design a novel, persona-grounded user simulator to support our task evaluation, and augment our task evaluation with automatic evaluations of dialogue quality. We also propose a new schema-guided agent, aimed at improving the dialogue capabilities of off-the-shelf coding agents, which improves over strong baselines by 3-14%. Our results indicate that better coding models do not always correspond to better dialogue models, suggesting that dialogue capability is a distinct and currently understudied dimension of coding agent performance.

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

It Takes One to Bias Them All: Breaking Bad with One-Shot GRPO

Warning: This paper contains several toxic and offensive statements. Modern large language models (LLMs) are typically aligned through large-scale post-training to ensure fair and reliable behavior. In this work, we investigate how easily such guardrails can be broken by Group Relative Policy Optimization (GRPO). We show that one-shot GRPO training on a single biased example is sufficient to induce systematic bias, with stereotype-driven reasoning generalizing across attributes, categories, and benchmarks. We further find that models differ in their susceptibility based on the initial likelihood of producing biased outputs. Our results reveal a critical vulnerability in post-training: alignment can be overridden by a single example.

05.
arXiv (CS.CV) 2026-06-12

SmartFont: Dynamic Condition Allocation for Few-Shot Font Generation

Few-shot font generation simultaneously requires global structural completeness and fine-grained local style fidelity. Existing methods usually either rely on global content-style modeling, which is robust but imperfectly disentangled, or emphasize component/local modeling, which captures fine details but relies heavily on local priors and reference coverage. We argue that the key challenge is not merely to learn purer conditions, but to organize complementary yet biased global and local conditions through multi-level allocation during generation. To this end, we propose SmartFont, a diffusion-based few-shot font generation framework that combines global content-style generation with weakly supervised local corrective experts. The local branch performs semantic-spatial allocation by learning expert-wise local concepts and semantically meaningful spatial maps under weak component supervision, enabling fine-grained correction without requiring explicit component-conditioned inference. On top of this, a denoising-state condition allocation module adaptively weights global content, global style, and local corrective feature across timesteps and injection blocks. Extensive experiments show that SmartFont achieves better global-local balance, improves glyph quality and local detail fidelity.

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

A Unified Framework for Efficient Remote Sensing Visual Question Answering: Adapting Dual, Hybrid, and Encoder-Decoder Architectures

Visual Question Answering (VQA) in the Remote Sensing (RS) domain presents unique challenges due to the high resolution, multi scale object distribution, and semantic complexity of aerial imagery. While general domain Foundation Models have achieved remarkable success, their direct application to RSVQA is hindered by massive domain shifts and the computationally prohibitive nature of full fine tuning. This study presents a comparative analysis of RS Adapter, a Parameter Efficient Fine Tuning (PEFT) strategy, applied across three distinct Vision Language Model (VLM) architectures: the Dual Encoder CLIP, the Encoder Decoder BLIP, and the Hybrid FLAVA. We introduce a unified architectural surgery pipeline that injects lightweight bottleneck adapters into the attention and MLP layers of frozen backbones, enabling rapid adaptation with less than 5 percent of trainable parameters. Experimental results on the high resolution RSVQA x dataset demonstrate that while all adapted models achieve convergence, the Hybrid FLAVA architecture offers a superior balance of multimodal reasoning and retrieval capabilities compared to its unimodal counterparts. Our findings establish a new baseline for resource efficient VQA in disaster assessment and urban monitoring.

07.
arXiv (CS.CL) 2026-06-12

LLMs Can Better Capture Human Judgments–With the Right Prompts

Are large language models (LLMs) bad at capturing human judgment? Two commonly stated limitations are that LLMs fail to capture full distributions of responses, and that their judgments are unstable across wording variations. We demonstrate simple prompting strategies that mitigate these limitations. Across two datasets–a U.S.-representative set of 144 moral scenarios and 38 moral beliefs from the International Social Survey Programme's Family and Changing Gender Roles module covering 32 countries–we show how simple elicitation techniques help improve AI-human alignment. First, prompting models to report standard deviations and response proportions recovers the full range of human responses better than common strategies. Second, ensuring scenarios are clear to human participants–as reflected in human confusion ratings–boosts model alignment, and LLMs can track human confusion ratings. At the same time, we find that LLMs' estimates of their own error are poorly calibrated, though they can predict human variability relatively well. These results suggest that asking better questions to LLMs can yield better answers.

08.
arXiv (CS.CV) 2026-06-17

AIGS-Net: Compact Illumination Field Modeling via 2D Gaussian Splatting for Fast Low-Light Image Enhancement

Existing low-light image enhancement methods often face a bottleneck between the representation capacity of illumination-field modeling and computational complexity. To address this issue, this paper proposes an Adaptive Illumination Gaussian Splatting Network (AIGS-Net), an ultra-lightweight architecture for fast low-light enhancement. Unlike conventional static priors, AIGS-Net constructs an input-adaptive 2D Gaussian Splatting illumination field. The opacity of Gaussian basis functions is dynamically modulated by relative luminance statistics of the input image, and spatially varying illumination compensation is rendered through ordered alpha compositing. To guide adaptive illumination compensation efficiently, a zero-parameter nonlinear multiscale contextual encoding module is introduced to extract low-frequency structures and local contrast cues without additional convolutional weights. To suppress noise amplification and sensor-induced color bias, AIGS-Net integrates noise-mask estimation, locked single-channel Gamma mapping, cross-channel consistency regularization, and target color-alignment constraints. Experiments on LOL and LSRW benchmarks show that AIGS-Net improves detail recovery and color fidelity while requiring only approximately 40 learnable parameters, achieving an effective trade-off between enhancement quality and extreme inference efficiency.

09.
arXiv (CS.AI) 2026-06-16

SPARK: Security Knowledge Priming and Representation-Guided Knowledge Activation for LLM-based Secure Code Generation

arXiv:2606.16244v1 Announce Type: cross Abstract: Large language models routinely generate code with exploitable security flaws. Prior literature attributes this limitation to a lack of security expertise, steering current defense mechanisms toward heavy fine-tuning or external knowledge retrieval, which introduces significant computational overhead and data bias through redundant code examples. Contrary to this view, we argue that pretraining corpora are already rich in security material. The bottleneck is activation: without an explicit and brief cue, statistical pressure toward common training-distribution patterns suppresses the model's safety-relevant representations. We present SPARK, an inference-time security harness that activates this latent knowledge without any retraining. The harness has two parts. Component~I retrieves a few of the relevant Common Weakness Enumeration (CWE) entries for each coding task and appends a short structured cue to the prompt; this alone is enough to surface the model's existing security representations. Component~II adds a precomputed token bias to the logits at every decoding step. We obtain the bias by projecting a safe-direction vector, the unit difference between the mean safe and mean unsafe last-layer hidden states, through the language model head. The bias is computed once offline; applying it costs a single vector addition per generated token. We evaluate SPARK on 9 open-source models across C++, Java, and Python, and compare with 7 baselines spanning fine-tuning and retrieval-augmented methods. SPARK matches or improves on the best baseline in every setting while preserving HumanEval utility. We further test Component~I in a black-box setting on 7 of today's strongest models, including Claude, DeepSeek, and GPT, demonstrating the bottleneck of insecure code generation and the improvements enabled by our method.

10.
arXiv (CS.CL) 2026-06-15

LoSoNA: A Benchmark for Local Social Norm Adaptation in Group Conversations

Online group chats are social spaces with local conversational norms that are rarely stated explicitly. The ability and willingness of LLM-based agents to recognize and adapt to these norms remains mostly unexplored. We introduce LoSoNA, a benchmark for local social norm adaptation in multi-party chat. Each scenario gives a subject model a curated group-chat transcript in which non-subject participants demonstrate a hidden local norm, followed by a final elicitor turn that forces a response revealing whether the subject has inferred that norm. We evaluate eight frontier and open-weight models under four prompting conditions that vary how explicitly the model is told to treat the prior conversation as evidence for how it should answer. Naive prompting remains limited for most models; explicit norm-aware prompting helps unevenly, with Gemini 3.1 Pro reaching $84.2\%$ and Claude Fable 5 reaching $81.6\%$, while several other models show small gains or regressions. LoSoNA contributes to recent calls for evaluating LLM social capabilities by testing whether models can infer local conversational norms from precedent and use them in a one-turn group-chat response.

11.
arXiv (quant-ph) 2026-06-16

Improved Cryogenic Photodiode Optical Biasing for Low-Noise and Low-Jitter Superconducting Nanowire Single-Photon Detectors

arXiv:2606.07140v2 Announce Type: replace Abstract: We experimentally demonstrate an improved optical biasing scheme for superconducting nanowire single-photon detectors (SNSPDs), which employs a cryogenic InGaAs-InP photodiode (PD) as a local bias source. It is found that, under illumination from a stable external light source, this PD generates a stable photocurrent in a cryogenic environment (~2.3 K), with fluctuations in the photocurrent primarily attributed to fluctuations in the incident optical power. Furthermore, by screening and effectively blocking stray photons leaking from the PD, which give rise to background dark counts, we have achieved an SNSPD exhibiting an ultra-low intrinsic dark count rate of 1e-4 cps. Utilizing this improved optical biasing technique, our SNSPD achieved performance comparable to that obtained under conventional electrical biasing: a system detection efficiency of 80.7%, a background dark count rate of 32.6 cps, and a minimum timing jitter of 57.5 ps. These results indicate that cryogenic-PD-based optical biasing serves as a viable, low-noise, and low-jitter alternative to traditional electrical biasing. Moreover, this work offers useful design guidance for the future development of PD-based low-noise bias sources and for the construction of all-photonic SNSPD systems tailored for high-precision quantum photonics applications.

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

Remember, Don't Re-read: Stateful ReAct Agents for Token-Efficient Autonomous Experimentation

arXiv:2606.14945v1 Announce Type: new Abstract: The autoresearch pattern enables autonomous experimentation by having a large language model (LLM) iteratively modify code to optimize a target metric. Its stateless design, however, reconstructs experimental context from scratch at every iteration, incurring $O(n)$ token cost per iteration and $O(n^{2})$ total. This work reformulates the pattern as a stateful ReAct agent using LangGraph, where typed persistent state carries experimental history across iterations via a tool-calling interface. Two benchmarks are evaluated: hyperparameter tuning (15 iterations, small per-iteration observations) and code performance optimization (40 iterations, large per-iteration observations containing full source code and benchmark results). On hyperparameter tuning, the stateful agent consumes 90\% fewer tokens (2{,}492 vs.\ 24{,}465). On code optimization, the stateful agent consumes 52\% fewer tokens (627K vs.\ 1{,}275K) while achieving comparable optimization quality on both tasks. The token reduction is structural: the stateless agent re-reads the full history at $O(n)$ cost per iteration, while the stateful agent operates within a fixed-size conversation window at $O(1)$ cost. This paper describes the architecture in sufficient detail for practitioners to implement a stateful autoresearch agent for their own workflows.

13.
medRxiv (Medicine) 2026-06-18

Chest X-Ray as a critical screening tool for Household Contacts of TB: Lessons from Three Years of Programmatic Data in India

Introduction: Household contacts (HHCs) of pulmonary TB patients remain at high risk for TB infection and disease progression, yet many remain asymptomatic and are missed by symptom-screening pathways. While India expanded its TB preventative guidelines to include all HHCs in 2021, chest X-ray (CXR) screening continues to be used selectively, representing a missed opportunity in early case detection. Methods: The analysis uses programmatic data from Project JEET 2.0 (Joint Effort for Elimination of Tuberculosis), implemented by the William J. Clinton Foundation in India, between October 2021 and March 2024. Eligible HHCs (>=5 years) were offered CXR screening as part of TB preventive therapy (TPT) evaluation. Descriptive and multivariable analyses examined predictors of CXR uptake and TB yield. A two-stage logistic regression model estimated potential TB yield under universal CXR coverage. Model performance was evaluated using the area under the curve (AUC), and bootstrap simulations generated counterfactual estimates of missed TB cases. Results: Among 1,034,621 HHCs, 1.02% individuals were found positive for TB, which includes 7,786 HHCs who were on TB treatment already, while an additional 2,812 were identified during pre-TPT evaluation. Among eligible HHCs (n = 1,026,835), 70% were screened with CXR, of which 2.4% had suggestive TB findings. Of these, 79% went for further TB assessment. Symptomatic HHCs were more likely to be CXR screened (84% vs 69%) and assessed for TB, yet two-thirds of all detected TB cases were asymptomatic. It is estimated that universal CXR coverage and TB testing for suggestive cases can increase TB detection by at least 87%. Conclusion: The study provides a scalable approach to expand CXR coverage through public-private partnerships, enabling early TB detection among HHCs, especially among asymptomatic contacts. Future implementations will benefit from integrating AI-enabled reading, along with systematic follow up for those with suggestive findings.

14.
arXiv (CS.LG) 2026-06-11

Apertus LLM Family Expansion via Distillation and Quantization

arXiv:2605.29128v2 Announce Type: replace Abstract: The wide adoption of LLMs has led to their use in great variety of applications and scenarios, such as chatbot assistants and data annotation, creating the need for the models to satisfy certain budget and hardware constraints. This has led to the trend of LLMs being released in batches consisting of similar models of various sizes for the family of models to adhere to as wide of a range of constraints as possible. In this paper, we validate distillation and quantization as a cost-effective way to expand model families to new sizes and hardware formats. Based on the open-recipe Apertus 8B LLM, we produce Apertus-v1.1 - a distilled family of models with up to 4B parameters trained on 1.7T permissive license tokens. We demonstrate cost-efficiency and strong accuracy performance of our approach for covering large ranges of hardware and systems requirements.

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

A random approach to the multibonacci sequence

arXiv:2606.14294v1 Announce Type: cross Abstract: This paper presents a random approach to the multibonacci sequence. We generalise the model introduced by Benjamin, Levin, Mahlburg, and Quinn, which is based on a random tiling method using dominoes and squares that leads to the Fibonacci sequence, and which was extended to the tribonacci case in a previous work by the authors. Our approach employs tiling with linear $k$-ominoes, $k=1,\ldots,s$, combined with specific colouring, to generate a weighted multibonacci sequence. For a natural random variable~$X$ defined by this model, we establish the distribution of $X$ in terms of multibonacci numbers and compute $\mathbb{E}[X] = 2^{s+1}-3$.

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

Self-Guidance: Enhancing Neural Codecs via Decoder Manifold Alignment

arXiv:2606.12940v1 Announce Type: cross Abstract: Neural speech codecs based on Vector-Quantized VAEs (VQ-VAEs) are core audio tokenizers for speech LLMs, yet their reconstruction fidelity is bottlenecked by quantization error. Modifying the quantizer or increasing model capacity are common fixes, but they complicate downstream language modeling. Our core idea is to align the decoder's internal feature manifolds when processing both the quantized tokens and their original continuous embeddings, using a lightweight feature-mapping loss. This requires minimal training overhead and no inference-time changes. Applied to XCodec2, self-guidance improves all reconstruction metrics, achieving state-of-the-art low-bitrate performance. Notably, it enables a 4x codebook reduction without fidelity loss, which downstream TTS experiments show significantly improves LLM-based synthesis by simplifying the token modeling space. Multiple statistical observations and visualizations corroborate the enhanced internal manifold alignment in the decoder. Extensive experiments confirm its generality across various inductive biases. Self-guidance thus establishes an efficient, broadly applicable method for high-fidelity neural audio coding.

17.
arXiv (CS.AI) 2026-06-16

IoT-Zoo: A Container-Based Framework for Heterogeneous IoT Device Profiles and Reproducible Traffic Capture

arXiv:2606.15653v1 Announce Type: cross Abstract: The validation of networking and security solutions for the Internet of Things (IoT) requires realistic and reproducible experimental data. However, existing platforms often achieve scalability by replicating a limited set of device types, which restricts profile diversity and fails to capture the heterogeneity of real-world IoT environments. In this paper, we present IoT-Zoo, a container-based testbed designed to support reproducible experimentation through heterogeneous, dataset-driven IoT device profiles. Built upon Containernet, IoT-Zoo automates the deployment of multi-domain scenarios and supports real application protocols such as MQTT and RTSP. The platform provides a single-command interface for environment provisioning and automated traffic capture (PCAP), enabling the generation of consistent traffic baselines and reducing the operational effort required to evaluate networking and security solutions.

18.
Nature (Science) 2026-06-17

Cucurbituril-based anion-conducting membranes with supramolecular nanopores

Authors:

Nanoporous anion-conducting membranes have gained considerable interest for their potential to reduce resistance in electrochemical devices1–4. Current pore-forming methods, such as backbone engineering through polymers of intrinsic microporosity5,6 or covalent organic and metal–organic frameworks7,8, however, suffer from limited structural control, mechanical fragility or demanding synthesis. Here we establish a supramolecular strategy that overcomes these limitations by constructing uniform, dynamic nanopores. Co-assembly of the rigid macrocyclic host cucurbit[7]uril with the cationic polymer guest quaternized poly(piperidinium-terphenyl) yields a robust network of nanometre-scale channels while simultaneously enhancing mechanical and chemical stability. The dynamic host–guest interactions allow the pore structure to fluctuate on picosecond and angstrom scales. This transient environment supports low-friction hydroxide migration through a Grotthuss mechanism, producing a marked enhancement in ionic conductivity. This bottom-up design principle provides a versatile new tool for molecularly engineering transport pathways and promises to advance electrochemical reactors with respect to energy efficiency, operational stability and the production of high-purity products. A supramolecular strategy, in which uniform, dynamic nanopores are constructed, overcomes the limitations of limited structural control, mechanical fragility or demanding synthesis in nanoporous anion-conducting membranes, providing a versatile tool for molecularly engineering transport pathways.

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

BoRAD: Bootstrap your Own Representations for Multi-class Anomaly Detection

Reconstruction-based anomaly detection is attractive for industrial inspection, but scaling it from category-specific training to a one-for-all setting is challenging. A single model must reconstruct diverse normal appearances without copying abnormal details, which exposes two coupled failure modes: identical shortcut, where anomalies pass through the reconstruction path, and mis-reconstruction, where normal categories are confused with one another. We propose BoRAD, a label-free training framework that treats this as a representation-capacity allocation problem. BoRAD uses a shared learnable prototype bank to impose two complementary regularizers: spatial prototype alignment contracts local within-prototype variation to suppress anomaly copying, while prototype-relative global alignment preserves between-prototype structure and improves sensitivity to abnormal angular deviations. The prototype bank and prediction heads are used only during training; inference remains a standard teacher-student feature discrepancy pass, with no class labels, negative pairs, memory retrieval, or prototype lookup. BoRAD achieves competitive one-for-all anomaly detection performance, including 86.2\% mAD on MVTec AD, 80.7\% mAD on VisA and 73.1\% mAD on Real-IAD. Diagnostic analyses further show reduced anomaly leakage, improved normal-category separability, and stronger anomaly-normal score separation.

20.
arXiv (CS.AI) 2026-06-19

Rethinking Shrinkage Bias in LLM FP4 Pretraining: Geometric Origin, Systemic Impact, and UFP4 Recipe

arXiv:2606.20381v1 Announce Type: new Abstract: FP4 training promises substantial reductions in memory and computation cost for LLM pretraining, yet current FP4 hardware paths and recipes, including NVIDIA Blackwell/Rubin-class systems and AMD MI350-series GPUs, remain centered on E2M1 data elements. In this study, we identify a fundamental limitation of that choice: non-uniform formats such as E2M1 inherently suffer from Shrinkage Bias, a systematic negative rounding error caused by the geometric asymmetry of their representable bins. We show that this bias accumulates multiplicatively across layers and is amplified by the Random Hadamard Transform (RHT), providing a unified explanation for the training instability observed in existing E2M1-based FP4 recipes. In contrast, uniform grids (E1M2/INT4) bypass this grid-geometry error and better convert the improved bucket utilization from RHT into higher quantization quality. Based on this finding, we propose UFP4, a uniform 4-bit training recipe that applies RHT to all three training GEMMs while restricting stochastic rounding to dY alone. On Dense 1.5B, MoE 7.9B, and MoE 124B long-run pretraining, UFP4 consistently achieves lower BF16-relative loss degradation than strong E2M1-based baselines, supported by scaling-law analysis and ablation studies. Our results suggest that future accelerators should support E1M2/INT4-style uniform 4-bit grids as first-class training primitives alongside E2M1.

21.
arXiv (CS.LG) 2026-06-19

A Model-Driven Approach for Developing Families of Reinforcement Learning Environments

arXiv:2606.20324v1 Announce Type: cross Abstract: Virtual training environments are software-intensive systems in which reinforcement learning (RL) agents learn, adapt, and demonstrate meaningful behavior. Virtual training environments offer a safe and cost-efficient alternative to training agents in real-world settings. However, to converge, most realistic RL problems require training in multiple, mostly similar but slightly different environments - i.e., families of environment variants. The typical development process of environment families is a labor-intensive and error-prone manual endeavor that does not scale well. To alleviate these issues, in this paper, we propose a model-driven approach for developing families of RL training environments. To obtain the family of environments, we develop an approach and prototype tool. In our approach, a hybrid genetic algorithm - a combination of population-based global search and heuristic local search - generates environment families. Mutations and constraints are expressed as model transformations and are operationalized into a search process by a state-of-the-art model transformation engine. We demonstrate the soundness of our approach in a wildfire mitigation scenario and curriculum learning - a particular learning paradigm that relies on environment families.

22.
arXiv (CS.CL) 2026-06-17

The Critical Role of Model Selection in Causal Inference: A Comparative Analysis of Classification Models within the InferBERT Framework for Pharmacovigilance

Distinguishing causal adverse drug events (ADEs) from spurious correlations remains a central challenge in pharmacovigilance. The InferBERT framework integrates transformer models with Do-calculus, but its success hinges on the underlying classification model. This study evaluates the impact of model choice in InferBERT, assessing whether simpler models suffice, if domain-specific pre-training helps, whether scaling to LLMs improves causal detection, and the effect of post-hoc calibration. We performed a comparative study on two benchmarks: Analgesics-induced Acute Liver Failure (AILF) and Tramadol-related Mortalities (TRAM). Four models were evaluated-XGBoost (baseline), ALBERT (original InferBERT), BioBERT (biomedical transformer), and Med-LLaMA (medical LLM)-using 5-fold cross-validation repeated over 20 runs. We measured accuracy, Expected Calibration Error (ECE) pre- and post-isotonic regression, and Jaccard concordance of causal terms with PRR, ROR, and EBGM; significance was tested with paired t-tests. BioBERT achieved the highest accuracy on both datasets, while Med-LLaMA underperformed despite its size and parameter-efficient fine-tuning. Domain-specific pre-training was decisive. Calibration improved ECE but had mixed effects on accuracy and causal discovery. BioBERT's superiority also yielded the strongest concordance with traditional pharmacovigilance signals. These results show that domain-specific pre-training provides a clear advantage over simpler baselines and larger LLMs. Investing in manageable, domain-aware models is more effective for computational pharmacovigilance than simply scaling model size.

23.
Nature (Science) 2026-06-17

A blastoporal organizer in a ctenophore

In an iconic experiment in 1924, Hilde Mangold and Hans Spemann established that the dorsal blastopore lip of amphibian embryos functions as an organizer and induces a secondary body axis when transplanted into a host embryo1. This discovery demonstrated that specific embryonic regions can regulate embryonic patterning and lead to the establishment of an entire body axis. Subsequent studies have revealed that cnidarians, the sister group to Bilateria, also possess a blastoporal embryonic organizer2,3. However, the evolutionary origin of the organizer remains unclear. Here we report that the blastopore lip of the ctenophore Mnemiopsis leidyi, a member of the evolutionary sister group to all other metazoans4,5, exhibits organizer activity. We show that transplanted fragments of blastopore lip tissue from M. leidyi gastrula induce secondary pharynx and mouth formation. Moreover, transphyletic transplantation experiments show that the blastopore lip of M. leidyi leads to the generation of a secondary body axis in embryos of the cnidarian Nematostella vectensis. Organizer function in M. leidyi requires both β-catenin and TGFβ signalling, and the TGFβ-family ligands probably provide this inductive capacity. These findings reveal the deep homology of the blastoporal organizer in ctenophores, cnidarians and vertebrates, implying the ancestral organizer role of the blastopore lip. We propose that the emergence of the organizer was an essential innovation that facilitated the change from the temporal cell differentiation of unicellular relatives to the spatial cell differentiation of the first multicellular embryo. Experiments using the comb jelly Mnemiopsis leidyi and the sea anemone Nematostella vectensis reveal that the emergence of a core signalling pathway may have been a key innovation enabling the transition to multicellularity in animals.

24.
medRxiv (Medicine) 2026-06-10

A Three-Tier Operational Benchmark for Evaluating Large Language Models on Hospital Medication Safety

Objective. To introduce PsiBench, a clinically validated medication-safety benchmark for evaluating large language models (LLMs) against the standards used to certify hospital computerized provider order entry (CPOE) and electronic health record (EHR) systems, and a non-overlapping three-tier evaluation framework separating highest-stakes discrimination, the operational CDS regime, and category-correct alerting. Materials and Methods. PsiBench comprises 492 medication-safety scenarios across 11 safety categories, created by clinical pharmacology experts whose work underpins an annualized testing procedure used by more than 2,000 U.S. hospitals. The three-tier framework partitions the scenarios non-overlappingly: Discrimination (98 scenarios, 50 fatal vs 48 deception, near-balanced 51%/49%); Operational (394 scenarios, 261 serious unsafe plus 133 safe including 41 Excessive Alerts reclassified as operational negatives); and Attribution (311 alert-required scenarios). We evaluated 40 frontier LLMs from 10 providers over 3 runs per scenario at temperature 0.2 (or the provider default where temperature is not configurable), yielding 59,040 evaluations conducted April 21-23, 2026. Results. Headline binary performance on the full benchmark spans a wide range across the 40 models: F1 78.5%-92.3%, accuracy 65.4%-89.8%, sensitivity 81.4%-100.0%, specificity 6.1%-81.8%. Leading models by F1 (o4-mini 92.3%; o3 92.2%) pair high sensitivity with meaningful specificity; three models saturate sensitivity at 100% but fall below 25% specificity, indistinguishable from a naive always-alert classifier. The wide spread on a single headline metric motivates tier-specific analyses, developed in a separate clinical paper. Discussion and Conclusion. PsiBench and the three-tier framework operationalize a rigorous evaluation rubric for LLM medication safety, grounded in two decades of national hospital audit experience. The framework generalizes to any binary medication-safety classifier (rule-based, conventional ML, or LLM-driven), supporting tier-aware model selection and post-deployment surveillance.

25.
arXiv (CS.CL) 2026-06-16

Evaluating LLM Personalization via Semantic Constraint Verification

Current evaluation paradigms for Large Language Model (LLM) personalization rely heavily on brittle surface-matching metrics or computationally expensive LLM-as-a-judge protocols, both of which lack interpretability. To address these limitations, we introduce Natural Language Inference Constraint Verification (NLICV), a scalable, semantically invariant framework that maps sentence meanings to truth-condition sets to verify personalization constraints via a Natural Language Inference (NLI) model. Moving beyond binary scoring, NLICV categorizes LLM behaviors into four distinct modes: personalization, generalization, sycophancy, and failure. Extensive experiments demonstrate that NLICV aligns closely with human annotations while drastically reducing the latency and token costs associated with LLM judges (up to 2100 inference speedup). Finally, through an ablation-based procedure, NLICV pinpoints the exact sentences driving the constraint verification, yielding faithful, understandable evidence for its evaluations.