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01.
bioRxiv (Bioinfo) 2026-06-19

StickForStats: automated statistical assumption validation for reproducible computational biology

Reproducible computational biology depends on statistical decisions that routine workflows often skip: verifying that a differential-expression test's assumptions hold across all genes, that a strategy-comparison ANOVA is robust to non-normality, or that a meta-analysis is not distorted by publication bias. Surveys consistently find that fewer than 20% of published biomedical studies report checking these assumptions, and existing statistical software leaves validation to the analyst as an optional step. We present StickForStats, an open-source web platform that reframes assumption validation as a default precondition for every analysis. Its Guardian system–a middleware pipeline of eight validators (normality, variance homogeneity, independence, outliers, sample size, modality, linearity, homoscedasticity)–checks assumptions before execution and, on critical violations, reroutes to an appropriate nonparametric alternative with a documented decision trail. At genome scale, applying Guardian to a 91-sample synovial-sarcoma RNA-seq study (GSE271517) cascaded 90.6% of 27,221 genes to a rank-based test and flipped the differential-expression verdict for 553 genes–479 rescued from an under-powered t-test and 74 outlier-driven false positives rejected–materially changing the gene list a biologist would act on. The same automatic validation generalizes across domains: a CRISPR editing-strategy comparison (ANOVA F = 1122, with Guardian recommending Kruskal-Wallis H = 36.6), an ordinal correlation (Pearson r = 0.476 corrected to Spearman {rho} = 0.479), and a sixteen-trial clinical meta-analysis revealing severe publication bias (Egger's t = -5.78, p < 0.001); a complementary module extends the same validators to published manuscripts, checking claims against CONSORT, STROBE, ICH-E9, and JARS-Quant reporting standards. By making assumption validation automatic and transparent, StickForStats targets a tractable, under-served contributor to irreproducibility. The platform is MIT-licensed, validated against SciPy and R, and freely available at https://github.com/visvikbharti/stickforstats_new.

02.
medRxiv (Medicine) 2026-06-17

Reverse engineering of motor unit discharge in multiple sclerosis reveals heterogeneity of voluntary motor commands

Central nervous system injury causes motor deficits through derangement of excitatory, inhibitory, and/or neuromodulatory inputs to motoneurons, the three fundamental components of motor commands. Typically, study of pathologic neural control in humans is restricted to only one of the three. Chardon et al. (2024) presented a fundamentally new approach to comprehensively study all components by reverse engineering motor unit firing patterns. We apply their framework to motor unit firing patterns from 89 people with multiple sclerosis (MS) and 34 controls to study excitatory, inhibitory, and neuromodulatory contributions to pathologic motor output. Disruptions to all components are plausible in MS, a disease hallmarked by heterogeneity in nearly all aspects. Accordingly, we found abnormalities in MS for all three components. Notably, neuromodulation included both high and low extremes. Our results suggest that pathophysiology of motor commands in MS varies among patients, a finding fundamentally different from other studied populations showing relative consistency.

03.
arXiv (CS.LG) 2026-06-16

MARS: Efficient, Adaptive Co-Scheduling for Heterogeneous Agentic Systems

arXiv:2604.26963v2 Announce Type: replace-cross Abstract: Large language models (LLMs) are increasingly deployed as the execution core of autonomous agents rather than as standalone text generators. Agentic workloads induce a temporal shift from single-turn inference to multi-turn LLM-tool loops, and a spatial shift from chat-scale, GPU-only execution to repository-scale, GPU-CPU co-located execution. Consequently, coordinating heterogeneous resource demands of agentic execution has emerged as a critical system challenge. We design and implement MARS, an efficient and adaptive co-scheduling system that globally coordinates heterogeneous agentic workloads under coupled GPU-CPU resource pressure. By establishing holistic visibility across GPU inference and CPU tool execution via a unified information stream, an external control plane in MARS decouples admission from execution to prevent heterogeneous resource oversubscription. An internal agent-centric scheduler further minimizes the end-to-end critical path by prioritizing latency-sensitive continuations and adaptively retaining KV cache state only when warm resumption yields a latency benefit. Our evaluations show that MARS reduces end-to-end latency by up to 5.94x while maintaining nearly maximal system throughput. We further integrate MARS as the serving backend for the OpenHands coding agent framework, demonstrating its real-world effectiveness by accelerating end-to-end task completion time by up to 1.87x. Our source code is publicly available at https://github.com/Afterglow231/MARS_preview .

04.
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.

05.
arXiv (quant-ph) 2026-06-19

Measuring Rényi entropy with an Echo Protocol

arXiv:2504.05237v3 Announce Type: replace Abstract: We present efficient and practical protocols to measure the second Rényi entropy, whose exponential is known as the purity. Our approach is based on expressing the purity in terms of transition probabilities generated by an echo-type forward-backward evolution sequence, making it applicable to quantum many-body systems. Notably, our approach does not rely on random-noise averaging, a feature that can be extended to protocols to measure out-of-time-order correlation functions, as we demonstrate. By way of example, we show that our protocols can be practically implemented in superconducting qubit-based platforms, as well as in cavity-QED trapped ultra-cold gases.

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

What sentiment analysis can't see: Measuring whether customers were helped, and what went wrong, across 70,000 support conversations

Most companies read their customer support data at scale using sentiment analysis, which measures how customers sound rather than whether they were satisfied with the result. We tested a richer alternative on 70,450 support conversations from a leading online fundraising platform: alongside tone, we used GPT-5.4 to estimate each customer's satisfaction and to flag whether they reported a concrete problem, then validated all three readings against the 1-to-5 ratings customers left on the conversations they rated. The satisfaction estimate tracked those ratings far better than sentiment did, correlating at 0.47 against 0.36 and flagging unhappy customers with far fewer false alarms. The structured read also sees what sentiment cannot: tone and satisfaction disagree in 44% of conversations, a single "Neutral" label hides everything from quietly satisfied customers to ones who quietly gave up, and the largest group of all is "tolerated friction," customers who are satisfied but still reporting a fixable problem, a standing issue that no sentiment-based dashboard can surface. The broader finding is that LLM-based annotation can capture far more than the tonality of a customer's language, offering strong potential for new business metrics grounded instead in the customer's state (whether they were satisfied) and the cause of their problem extracted directly from the raw textual data of interactions and feedback.

07.
arXiv (CS.AI) 2026-06-11

Improving Generalization and Data Efficiency with Diffusion in Offline Multi-agent RL

arXiv:2307.01472v2 Announce Type: replace Abstract: We present a novel Diffusion Offline Multi-agent Model (DOM2) for offline Multi-Agent Reinforcement Learning (MARL). Different from existing algorithms that rely mainly on conservatism in policy design, DOM2 enhances policy expressiveness and diversity based on diffusion model. Specifically, we incorporate a diffusion model into the policy network and propose a trajectory-based data-reweighting scheme in training. These key ingredients significantly improve algorithm robustness against environment changes and achieve significant improvements in performance, generalization and data-efficiency. Our extensive experimental results demonstrate that DOM2 outperforms existing state-of-the-art methods in all multi-agent particle and multi-agent MuJoCo environments, and generalizes significantly better to shifted environments {(in $28$ out of $30$ settings evaluated)} thanks to its high expressiveness and diversity. Moreover, DOM2 is ultra data efficient and requires no more than $5\%$ data for achieving the same performance compared to existing algorithms (a $20\times$ improvement in data efficiency).

08.
arXiv (CS.AI) 2026-06-19

Calibration Without Comprehension: Diagnosing the Limits of Fine-Tuning LLMs for Vulnerability Detection in Systems Software

arXiv:2606.20502v1 Announce Type: cross Abstract: Whether LLMs scoring well on vulnerability benchmarks genuinely reason about security or merely pattern-match on contaminated data remains unresolved. We present CWE-Trace, a framework for LLM vulnerability detection built from 834 manually curated Linux kernel samples spanning 74 CWEs. The framework enforces a strict temporal split (pre-2025 historical set / post-cutoff leakage-free set), preserves context-aware vulnerable–patched pairs, and introduces two diagnostic metrics: the Directional Failure Index (DFI) and Hierarchical Distance and Direction (HDD). We evaluate eight vanilla LLMs and 15 LoRA fine-tuned variants across non-targeted detection, targeted detection, and CWE classification. Our analysis yields two key results. First, data contamination provides no measurable advantage. Function-level analysis shows that 84% of nominally contaminated samples carry no usable memorization signal: vulnerable functions are absent or cross-mapped across datasets, and ~31% of contaminated samples carry CWE misclassification. Second, backbone directional priors dominate fine-tuning. Models exhibit stable, systematic failure modes (DFI ranging from -85.5 to +94.8 pp) that persist from historical to post-cutoff data and resist correction. Fine-tuning shifts the output threshold without changing the decision policy. This is calibration without comprehension: output distributions adapt to training data while the underlying security reasoning remains absent. The weakest backbone at binary detection (DeepSeek-R1) gains the most in coarse CWE classification, revealing that detection and understanding are decoupled capabilities. The best detection score reaches only 52.1% (+2.1 pp above chance); exact CWE ranking remains below 1.3% Top-1 accuracy, confirming that current LLMs lack reliable security reasoning for systems software, regardless of fine-tuning strategy.

09.
arXiv (CS.CV) 2026-06-11

Parameter-Efficient Adapter Tuning for Tabular-Image Multimodal Learning

作者:

Tabular-image multimodal learning aims to improve predictive modeling by jointly using structured tabular attributes and visual data. Although pretrained encoders provide strong modality-specific representations, full fine-tuning can be computationally expensive, while keeping encoders frozen may limit task-specific adaptation. We propose the Tabular-Image Adapter (TI-Adapter), a modality-specific adapter-based fine-tuning framework for efficient multimodal adaptation. TI-Adapter freezes the pretrained tabular encoder and learns an adapter after the extracted tabular embedding, while adapting the image branch with embedding-level and bottleneck-level adapters instead of full fine-tuning. Experiments on 20 tabular-image datasets show that TI-Adapter achieves competitive or better predictive performance than full fine-tuning while using substantially fewer trainable parameters. Ablation studies further demonstrate the importance of adapter placement for balancing performance and practical efficiency.

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

Natural-Language Temporal Grounding in Hour-Long Videos is a Search Problem: A Benchmark and Empirical Decomposition

Temporal grounding–returning the interval $[t_s, t_e]$ for a natural-language query over a video–is the language interface to long-form video, yet has been studied on short videos; the dynamics of hour-scale natural-language grounding remain underexplored. We take the position that at hour-scale, the binding constraint is search, not recognition: Video-LLMs are bottlenecked not by localizing a nearby event, but–given a natural-language query–by searching for the relevant region of a long video. To test this, we release ExtremeWhenBench, the first open hour-scale grounding benchmark (2,273 queries over 194 videos, mean 75.7 min, max 9 hr) with an open-form query distribution. Every open Video-LLM collapses while a frame-level retrieval baseline outperforms them; a failure taxonomy attributes 85% of failures to search; and a retrieve-then-ground hybrid recovers 6.7x over the monolithic Video-LLM–mirroring retrieve-then-read in open-domain QA.

11.
arXiv (CS.AI) 2026-06-17

Trust the Right Teacher: Quality-Aware Self-Distillation for GUI Grounding

arXiv:2606.18101v1 Announce Type: new Abstract: Graphical user interface (GUI) grounding requires vision-language models (VLMs) to identify small target elements in high-resolution screenshots and predict precise screen coordinates. On-policy self-distillation (OPSD) is a promising post-training approach for this coordinate-sensitive task, since it provides dense token-level teacher signals beyond hard coordinate labels. However, naive OPSD is not well suited to GUI grounding: OPSD evaluates the teacher on student-generated prefixes, the quality of coordinate-token teacher signals can degrade when the prefix has already deviated from the target coordinate, leading to unreliable teacher signal. To mitigate this, We propose quality-aware self-distillation for VLM-based GUI grounding, which improves coordinate-token teacher-signal quality through soft correctness-aware gating and teacher-probability scaling. The soft correctness-aware gate checks whether the teacher's current coordinate-token prediction can still be completed into the ground-truth box under the student-generated prefix. If not, the corresponding teacher signal is down-weighted. Teacher-probability scaling then uses the teacher's confidence as a lightweight factor to further calibrate the strength of the gated supervision. A key empirical finding is that neither component alone improves overall performance, whereas combining them consistently improves performance. This suggests that the two mechanisms play complementary roles: correctness-aware gating suppresses unreliable coordinate-token supervision, while teacher-probability scaling calibrates the strength of the remaining signals. Experiments across six GUI grounding benchmarks show that our method consistently improves the base model and outperforms strong baselines.

12.
arXiv (quant-ph) 2026-06-19

Exclusion Statistics as a Thermodynamic Resource in Quantum Heat Engines

arXiv:2606.19310v1 Announce Type: cross Abstract: The maximum power extractable from a quantum thermoelectric heat engine operating with free fermion carriers is bounded by the universal Whitney limit, $P_{fermion}^{\max} \simeq 0.0321\pi^2 k_B^2(T_L-T_R)^2/h$. We demonstrate that this bound is not fundamental to quantum heat engines but is instead an artifact of fermionic statistics. Within the nonlinear Landauer-B\"{u}ttiker framework, a bosonic working medium yields a strictly enhanced universal maximum power, $P_{boson}^{\max} = (\ln 2)^2\, k_B^2(T_L-T_R)^2/h$, exceeding the fermionic limit by a factor of $(\ln 2)^2/(0.0321\pi^2) \approx 1.52$. We propose magnon transport through a ferromagnetic spin chain as an experimentally viable bosonic realization. Incorporating Haldane fractional exclusion statistics with parameter $g$ provides a continuous interpolation between the bosonic ($g = 0$) and fermionic ($g = 1$) limits, revealing a monotonic enhancement of maximum power for $g < 1$ at reduced bias cost. These results establish quantum statistical exclusion as a previously unrecognized and independently tunable thermodynamic resource, opening performance regimes inaccessible to conventional carrier-engineering approaches.

13.
arXiv (quant-ph) 2026-06-17

Coupled-Mode Equations with Arbitrary Mode Combinations for Kinetic-Inductance Superconducting Traveling-Wave Parametric Devices: Theory and Experimental Validation

arXiv:2606.17264v1 Announce Type: cross Abstract: The coupled-mode equations (CMEs) have proven very successful in describing parametric processes in nonlinear optics. More recently, the same formulation has been used to model microwave superconducting parametric amplifiers and frequency multipliers. However, when applied to the microwave regime, not all assumptions remain valid and losses play a more dramatic role. Here, we revisit the CMEs applied to traveling-wave superconducting amplifiers to include losses and provide a formulation that enables their systematic derivation for any combination of traveling waves. As examples, we discuss the impact of unwanted harmonics and intermodulation products on parametric amplification, as well as harmonic generation. We verify that, if not properly accounted for, device performance can deviate considerably from the ideal case. Furthermore, using a superconducting CPW-based artificial transmission line and combining an independent experimental determination of its nonlinear parameter $I'_*$ with simulations of its linear properties, we obtain a parameter-free validation of this formulation. The nonlinear parameter was determined to be $I'_* \approx 27$ mA which, surprisingly, scales with the theoretical depairing current and not with the much smaller critical current of the device. For the validation, we measured multiple-harmonic generation and found excellent agreement between theory and experiment. The fact that $I'_* \gg I_C$ has direct implications for device design.

14.
arXiv (CS.LG) 2026-06-15

Free Heavy-Tailed Lunch for Muon: A Theoretical Justification of Empirical Success

arXiv:2606.14560v1 Announce Type: cross Abstract: Non-Euclidean optimisation methods with matrix-valued updates, such as Muon and Scion, have recently shown strong empirical performance for training Transformer models, yet their theoretical advantages over Euclidean methods remain poorly understood. We address this gap in the heavy-tailed non-convex regime, where stochastic gradients have bounded $p$-th central moments, $p \in (1,2]$. We show that certain non-Euclidean methods achieve optimal sample complexity under stronger stationarity measures, while Euclidean methods incur additional dimension-dependent costs. As a consequence, for $m \times n$ matrices, Muon finds an $\varepsilon$-stationary point in nuclear norm within $\mathcal{O}\left(\min\{m, n\} \frac{\Delta_1 L}{\varepsilon^2} \left(\frac \sigma \varepsilon \right)^{\frac p {p-1}}\right)$ samples, absorbing heavy-tailed noise without extra dimension dependence, unlike Euclidean methods. We further prove this sample complexity, including its dimension dependence, is optimal for all first-order methods under nuclear-norm stationarity. Experiments on large language models support our theory. Surprisingly, our results suggest that other Schatten geometries beyond the spectral geometry of Muon can perform competitively in certain settings.

15.
arXiv (CS.LG) 2026-06-11

Finding Multiple Interpretations in Datasets

arXiv:2606.12277v1 Announce Type: new Abstract: In this paper, we propose an approach to finding sets of similar-performing models (in terms of loss/accuracy measurements) with highly different context-aware characteristics. Through experiments on the METABRIC dataset, we show that the proposed method finds multiple models with highly different gene expressions than those found by the control methodology without performance penalties. We argue that the proposed methodology is important whenever one aims to analyze any global characteristic of a model to extract insight into the underlying phenomenon being studied.

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

The Art of Mixology: Mixup-based Obfuscation for Privacy-Preserving Split Learning in Large Language Models

Split learning provides a practical paradigm for resource-constrained users to train Large Language Models (LLMs) by offloading computation-intensive layers to a server while keeping raw data local. However, existing privacy-preserving split learning methods still face a difficult trade-off among utility, privacy, efficiency, and stability. Specifically, these methods often suffer from substantial utility degradation, remain vulnerable to advanced data reconstruction attacks, incur prohibitive computational and communication overhead, or exhibit unstable performance across different tasks. In this paper, we propose MIXGUARD, a novel mixup-based privacy-preserving split learning framework for LLMs. MIXGUARD introduces token-level obfuscation, representation-level obfuscation, and adaptive gradient perturbation mechanisms, which operate jointly to preserve useful learning signals while preventing privacy leakage to the server. Technically, MIXGUARD first constructs a lightweight calibration model on a public dataset to refine the approximated target representation, and then applies this model during privacy-preserving fine-tuning on private data. We conduct extensive experiments on four classification tasks and four text generation tasks across multiple LLM families, model sizes, architectures, and fine-tuning strategies. The results show that MIXGUARD preserves model utility comparable to non-split training baselines, consistently achieves stronger privacy protection than existing split learning defense methods against state-of-the-art data reconstruction attacks, and remains robust under adaptive attack settings.

17.
arXiv (CS.CV) 2026-06-18

Cosmos 3: Omnimodal World Models for Physical AI

We introduce Cosmos 3, a family of omnimodal world models designed to jointly process and generate language, image, video, audio, and action sequences within a unified mixture-of-transformers architecture. By supporting highly flexible input-output configurations, Cosmos 3 seamlessly unifies critical modalities for Physical AI – effectively subsuming vision-language models, video generators, world simulators, and world-action models into a single framework. Our evaluation demonstrates that Cosmos 3 establishes a new state-of-the-art across a diverse suite of understanding and generation tasks, demonstrating omnimodal world models as scalable, general-purpose backbones for embodied agents. Our post-trained Cosmos 3 models were ranked as the best open-source Text-to-Image and Image-to-Video models by Artificial Analysis, and the best policy model by RoboArena at the time the technical report was written. To accelerate open research and deployment in Physical AI, we make our code, model checkpoints, curated synthetic datasets, and evaluation benchmark available under the Linux Foundation's OpenMDW-1.1 License at https://github.com/nvidia/cosmos and https://huggingface.co/collections/nvidia/cosmos3. The project website is available at https://research.nvidia.com/labs/cosmos-lab/cosmos3.

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

N(CO)$^2$: Neural Combinatorial Optimization with Chance Constraints to Solve Stochastic Orienteering

arXiv:2606.18514v1 Announce Type: cross Abstract: Neural combinatorial optimization (NCO) offers a promising alternative to traditional heuristic-based methods for solving complex graph optimization problems by proposing to learn heuristics through data. This class of problems frequently arises in automation, as it can be used to model a variety of applications. While NCO has been extensively studied for deterministic combinatorial optimization problems, there are only a few works that aim to solve stochastic combinatorial optimization problems. In this work, we present N(CO)$^2$: Neural Combinatorial Optimization with Chance cOnstraints to solve the Stochastic Orienteering Problem (SOP) without the use of hand-crafted heuristics. By integrating a reinforcement learning (RL) framework, the model optimizes path selection under uncertainty, effectively balancing exploration and exploitation. Empirical results demonstrate that our method generalizes well across diverse SOP instances, achieving competitive performance compared to the state-of-the-art mixed-integer linear program (MILP) for the task. The proposed approach reduces human effort in heuristic design while enabling adaptive and efficient decision-making in uncertain environments.

19.
medRxiv (Medicine) 2026-06-18

Distinct Neuronal, Proliferative, and Secretory Pathways are Perturbed in Cancer Survivors with Depressive Symptoms

Introduction Depression is highly prevalent among cancer survivors and may be biologically distinct, although clinical studies investigating these mechanisms remain limited. Thus, the aims of this study were to (1) identify perturbed biological pathways associated with depressive symptom severity in cancer survivors, and (2) investigate whether these pathways are common or distinct to those perturbed in an age-matched non-cancer cohort. Methods We analyzed cross-sectional self-reported and transcriptomic data from the Multi-Ethnic Study of Atherosclerosis (PHD #39341). Cancer survivors and an age-matched non-cancer cohort (target ratio 1:2) were identified. The 20-item Center for Epidemiologic Studies Depression Scale (CES-D) was used to split participants into low (CES-D

20.
arXiv (CS.CV) 2026-06-18

EDoF-NeRF: extended depth-of-field neural radiance fields using a coded aperture camera

We propose a method for extending the depth-of-field (DoF) to construct high-fidelity neural radiance fields (NeRF) – an emerging technique for rendering photorealistic novel views from a dataset of images captured at different viewpoints, based on implicit neural representations. The trade-off between DoF and light quantity is inherent not only in conventional cameras but also in NeRF, since the datasets used by NeRF are captured by these cameras. To address this issue, we introduce a coded aperture placed at the camera pupil, preserving spatial frequency components under defocused conditions. We develop a camera model incorporating coded apertures into NeRF, allowing direct input of coded images and enabling the generation of novel views with an extended DoF. We validate the proposed method, termed extended DoF-NeRF (EDoF-NeRF), through simulations and experiments, demonstrating its superior performance compared to conventional aperture cameras.

21.
arXiv (quant-ph) 2026-06-11

A Geometric Family of Correlations Containing the Quantum Singlet

arXiv:2606.12045v1 Announce Type: new Abstract: We introduce a geometrically constrained hidden-variable framework that generates a family of correlations parametrized by a boundary function, within which the quantum singlet correlation appears as a particular member. Exact expressions for the correlation function are derived. Several structural results are established, including admissibility conditions, symmetry properties, a universal stationary point of the associated CHSH function, and an exact relation between the CHSH value at $\nu=\pi/4$ and a geometric contrast measure defined on the underlying hidden-variable distributions. Rather than treating the quantum singlet correlation as an isolated target to be reproduced, the present framework places it within a broader geometric structure of correlations. These results suggest the existence of a nontrivial geometric structure underlying the family of correlations and motivate the search for a principle capable of selecting the quantum singlet solution from within that family.

22.
arXiv (CS.LG) 2026-06-12

The Metric Picks the Winner: Evaluation Choice Flips Model Rankings for Drug-Response Prediction in Unseen Chemistry

arXiv:2606.12639v1 Announce Type: new Abstract: Predicting how a cell's transcriptome responds to a drug it has never seen is a core, hard problem in computational cell biology: recent benchmarks show complex models often fail to beat trivial baselines once test compounds are held out by chemistry. We study one cell line and assay, THP-1 cells profiled by DRUG-seq, scored by the active-compound weighted MSE(wMSE) of the VCPI prediction contest. We propose a staged approach: dumb baselines (untreated control and mean training-compound response) that the field keeps failing to beat; non-parametric retrieval (a Tanimoto-weighted average of a held-out compound's nearest training compounds); and a fusion stage combining a frozen chemistry embedding with retrieval-support features to predict the residual over the mean, with an uncertainty head and gene programs. On the released VCPI THP-1 drug-seq data (14,026 training compounds), under a Bemis-Murcko scaffold split, the model ranking inverts depending on the metric. Under an inverse-variance per-gene proxy, a regularized linear regression on Morgan fingerprints appears to win over the deep models, retrieval, and ChemBERTa – the textbook "simple baselines win" result. But under the contest's true active-set metric (per-(gene, compound) Mejia weights, validated against the official scorer; mean baseline 0.535 vs the organizers' 0.507 reference), that reverses: the deep models win, our fusion decoder significantly beats the linear fingerprint baseline (-0.012 wMSE, paired bootstrap p < 10^-4), and the proxy's winner becomes the worst chemistry-aware predictor. Picking the metric picks the winner – to our knowledge the first demonstration on real held-out drug chemistry of the metric-calibration effect established largely on genetic perturbation. We release a reproducible pipeline wired to the official scorer that emits a valid submission over the real 1064 x 12,995 grid.

23.
arXiv (CS.CL) 2026-06-12

Operadic consistency: a label-free signal for compositional reasoning failures in LLMs

Detecting LLM reasoning failures at inference time without ground-truth labels has motivated a wide range of confidence baselines, including self-consistency, semantic entropy, and P(True), built on within-question sampling and self-evaluation. Operad theory, the formalism for systems built by iterated substitution, suggests a complementary diagnostic: a model's direct answer to a compositional query should agree with the answer it produces by composing a stated decomposition of the same query. We instantiate this idea as operadic consistency (OC), a per-question signal. Across twelve instruction-tuned LLMs (4B to 671B parameters, open-weights and closed-source) on four multi-hop QA datasets, OC is strongly correlated with accuracy on every dataset (Pearson $r \in [0.86, 0.94]$, all $p \leq 0.0004$), and is the only signal we evaluate with $r \geq 0.85$ uniformly across all four datasets. Chain-of-thought self-consistency (CoT-SC; Wang et al., 2023) matches OC on HotpotQA and DROP ($r = 0.93, 0.87$) but drops to $r \approx 0.45$ on MuSiQue and StrategyQA. At the per-question level, OC contributes information beyond CoT-SC and semantic entropy on every dataset (cluster-robust $p \leq 10^{-16}$ for the OC coefficient), and the conclusion is robust to additionally controlling for constructed decomposition-aware baselines ($p \leq 10^{-13}$). The same signal yields selective-prediction improvements (accuracy at fixed coverage) over a tuned CoT-SC baseline at the equal-cost $K = 3$ budget (AUARC lifts of +0.086 to +0.096 and AUROC lifts of +0.092 to +0.164; 95% CIs exclude zero on every cell). On five frontier thinking models, where the decomposition is extracted from the model's own chain of thought, the same equal-cost comparison gives positive selective-prediction point-estimate lift on all 16 (dataset, budget, metric) cells tested, with 95% CIs excluding zero on 12 of the 16.

24.
medRxiv (Medicine) 2026-06-17

Efficacy of a Gamified Digital Platform for Substance Use Education and Overdose Prevention Among College Students: a Pilot and Feasibility Study

Background: For US young adults aged 18-25 in the 2018-2024 period, fentanyl was involved in 78.2% of the 44,020 unintentional or undetermined-intent overdose deaths, most often co-involving stimulants and other non-opioid substances. While fatal overdose rates in this age group have fallen to their lowest recorded level, emergency medical services-attended non-fatal overdose events have reached record highs, shifting the decisive variable toward bystander recognition and response. College students report near-universal alcohol education but minimal education on the substances actually driving overdose mortality. Methods: We conducted a single-group pre-post evaluation of the DopaGE Portal, a gamified, mastery-based digital platform covering cocaine, MDMA, benzodiazepines, and opioid overdose response, deployed at a public university (UNL) and a multi-campus volunteer network (TACO). Paired pre/post surveys (N=42) measured self-efficacy (7 items; primary), behavioral intentions, risk perception, and knowledge/attitudes on 5-point scales, plus four factual knowledge questions. Paired t-tests, exact McNemar tests, and Benjamini-Hochberg correction across eight primary tests were applied. Institutional naloxone distribution at UNL was tracked as an ecological behavioral outcome. A mandated high-school cohort (N=94) provided supplementary acceptability data. Results: Self-efficacy increased from 2.82 to 4.46 (d=2.00, 95% CI 1.46-2.55; adjusted p

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

Optimal Scheduling in a Question-Answering Forum of Knowledge Workers

arXiv:2606.19759v1 Announce Type: new Abstract: As individuals turn to the Internet to find answers to questions they may have, several Question Answering (QA) forums have evolved, where users knowledgeable in certain topics can contribute their expertise to answering these requests for information. While these are currently volunteer based, we consider a future version employing knowledge workers who are experts in certain topics. In such a system, the request-answer processes forming the queuing system may utilize schedulers that assign requests in different topics to the experts in the forum, who may be able to answer them according to their expertise levels in different topics. With this model, we calculate the capacity of the system for handling the requests while keeping the system stable, and design schedulers that achieve capacity. We also investigate how collaboration between experts in answering requests can potentially increase capacity.