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01.
medRxiv (Medicine) 2026-06-12

Microbial etiology, antibiotic susceptibility profiles, and multidrug resistance of urinary tract infections at a secondary healthcare facility in Ghana

Background: Rising antibiotic resistance challenges empirical therapies for urinary tract infections (UTIs). This study evaluated the microbial etiology, susceptibility profiles, and multidrug resistance (MDR) patterns of uropathogens among outpatients at the Berekum Holy Family Hospital, Ghana. Methods: This cross-sectional study (February to August 2021) screened 263 symptomatic outpatients. Mid-stream urine samples underwent quantitative culture, biochemical identification, and antimicrobial susceptibility testing via the Kirby-Bauer disc diffusion method following the 2021 CLSI guidelines. Results: Significant bacteriuria prevalence was 22.8% (60/263). UTIs predominated in females (78.3%, 47/60; p = 0.1501) and individuals [≥]45 years (33.3%, 20/60). Gram-negative rods accounted for 90.0% of isolates, primarily Escherichia coli (26.7%), Citrobacter spp. (25.0%), and Enterobacter spp. (21.7%); Staphylococcus aureus (10.0%) was the only Gram-positive pathogen. Extreme phenotypic resistance was observed against piperacillin/tazobactam (98.3%), cefotaxime (93.3%), tetracycline (88.3%), and cefoperazone (85.0%). Conversely, highest therapeutic susceptibilities were retained by amikacin (78.3%), levofloxacin (61.7%), and gentamicin (58.3%). Conclusion: The high prevalence of MDR uropathogens against advanced beta-lactamase inhibitor combinations and cephalosporins necessitates an immediate re-evaluation of regional empirical protocols. Amikacin, levofloxacin, and gentamicin remain viable options prior to culture confirmation. These findings establish a crucial phenotypic baseline to guide localized prescribing policies and regional antimicrobial resistance tracking strategies.

02.
arXiv (CS.AI) 2026-06-12

From Verdict to Process: Agentic Reinforcement Learning for Multi-Stage Fact Verification

arXiv:2606.13262v1 Announce Type: new Abstract: Recent approaches combining Large Language Models (LLMs) with retrieval-augmented reasoning have shown promise for automated fact verification. To process complex claims, these verification pipelines typically execute multi-stage workflows that coordinate tightly coupled modules, including claim decomposition, evidence gathering, and verdict prediction. However, existing methods optimize individual stages in isolation or rely on fixed heuristics, which limits adaptive coordination among stages and can lead to suboptimal outcomes. In this work, we propose ProFact, an agentic reinforcement learning framework for end-to-end optimization of multi-stage fact verification trajectories. ProFact trains a unified policy to coordinate claim decomposition, evidence seeking, answer generation, and verdict prediction. To address the sparse and delayed supervision provided by final veracity labels, ProFact introduces process-aware rewards that provide stage-level learning signals throughout the verification process. Empirical evaluation shows that ProFact consistently outperforms strong baselines in both verification performance and inference efficiency. These results highlight the effectiveness of process-aware trajectory optimization for multi-stage fact verification.

03.
arXiv (CS.AI) 2026-06-12

Constructing Evaluation Datasets for Procedural Reasoning: Balancing Naturalness, Grounding, and Multi-Hop Coverage

arXiv:2606.12767v1 Announce Type: new Abstract: Evaluating procedural reasoning in AI-supported learning systems requires question-answer datasets that are both learner-like and grounded in the instructional knowledge the system is expected to use. We study how TMK-based question generation strategies affect dataset quality for procedural and multi-hop reasoning. We compare three strategies: strict generation from Task-Method-Knowledge (TMK) models, transcript-first generation with post-hoc TMK filtering, and TMK-aware generation that combines transcripts with structured guidance. To evaluate generated items, we introduce a grounding validation framework based on closed-set evidence units extracted from TMK models. The framework measures whether answers are supported by the underlying representation, whether questions are self-contained, and whether they target multi-hop procedural reasoning. Across 23 instructional topics and 690 generated question-answer pairs, strict TMK generation achieves the strongest overall quality, with 96.5% grounded questions and 92.6% usable questions. Transcript-first generation produces more learner-like questions but more context-dependent or weakly grounded items, while TMK-aware generation yields high raw multi-hop coverage but lower grounding. These results show that procedural richness and natural phrasing do not guarantee representational grounding, motivating explicit representation-aware validation for evaluation datasets in AI-supported learning.

04.
arXiv (CS.AI) 2026-06-16

Phys-JEPA: Physics-Informed Latent World Models for Multivariate Time-Series Forecasting

arXiv:2606.16076v1 Announce Type: cross Abstract: Multivariate forecasting in physical systems requires models that predict coupled temporal variables while preserving meaningful state evolution. Deep forecasters can fit temporal correlations, and physics-informed models can regularize predictions with scientific constraints, but these directions are often connected only at the decoded-output level. As a result, the hidden predictive state that generates future trajectories may remain statistically useful but physically unstructured. We introduce Phys-JEPA, a physics-informed joint-embedding predictive architecture for multivariate time-series forecasting. Phys-JEPA learns a latent world model in which predictive states are decomposed into physical and residual components, and physical consistency is imposed directly on latent states and latent transitions rather than only on decoded forecasts. This formulation uses known physical variables to organize the representation space while retaining residual capacity for unresolved dynamics. On Jena Climate 2009–2016, Phys-JEPA reduces aggregate MSE from 0.12482 to 0.12273 and temperature MSE from 0.01892 to 0.01831 at H=24. On Traffic, full Phys-JEPA improves aggregate MSE over the supervised baseline across all tested horizons, reducing H=192 MSE from 0.800784 to 0.773873. On Electricity, the best variant depends on horizon: static latent consistency is strongest at H=24 and H=48, while full Phys-JEPA gives the best aggregate and target-variable MSE at H=192. These initial results suggest that moving physics-informed learning from output space to latent predictive state space is a promising direction for interpretable temporal world models.

05.
arXiv (math.PR) 2026-06-16

Logarithmic Large Deviations for Heavy-Tailed Sums

arXiv:2606.16487v1 Announce Type: new Abstract: We establish logarithmic large-deviation bounds for sums of independent nonnegative random variables with regularly varying tails. The normalization is chosen at the extreme-value scale and the speed is $\log n$. In contrast with Cramér's theorem, the resulting rate function is determined only by the tail index. The proof transfers a maximum large-deviation principle to sums in the one-big-jump region.

06.
medRxiv (Medicine) 2026-06-24

Differential COVID-19 Outcomes Across Lysosomal Disorders

Background Lysosomal disorders (LDs) are a heterogeneous group of rare inherited disorders characterized by multi-system involvement and high comorbidity burden, which raises concerns about severe COVID-19 outcomes. Conversely, because SARS-CoV-2 relies on endolysosomal pathways for cellular entry and replication, certain LDs may exert a protective effect against viral pathogenesis. Prior clinical evidence investigating LDs and severe SARS-CoV-2 infection has been limited by small sample sizes and inconsistent findings. Therefore, to resolve these conflicting biological hypotheses and estimate population-level outcomes, we conducted a large-scale retrospective cohort study using nationwide U.S. harmonized electronic health record data from the National Clinical Cohort Collaborative (N3C). This design utilized longitudinal records starting January 1, 2018, to evaluate COVID-19 infections captured between January 1, 2020, and July 11, 2024. Results The study included 16,380 individuals, comprising 5,460 patients with lysosomal disorders and 10,920 matched controls. Patients with LDs had significantly higher odds of COVID-19 hospitalization compared with controls (OR = 1.86, 95% CI: 1.70-2.04). Elevated odds were observed across the evaluated categories, but varied substantially. Notably, neurodegenerative LDs such as neuronal ceroid lipofuscinosis (OR = 9.32) and metachromatic leukodystrophy (OR = 2.33) remained associated with hospitalization after adjustment for comorbidities. Contrarily, the elevated odds for Fabry disease and Gaucher disease were no longer significant after adjustment. Mortality among hospitalized patients with LDs was comparable to that of matched controls (one-year survival: 82.1% vs 82.0%), suggesting that LD status does not independently worsen survival once hospitalization occurs. Conclusions Patients with LDs were at an increased odds of COVID-19 hospitalization, driven by a combination of elevated comorbidity burden and disorder-specific effects, which vary significantly across LD categories. This study clarifies that excess risk is concentrated in the transition to hospitalization. These patients may thus require personalized clinical care to mitigate the negative consequences of COVID-19.

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

Localized Kernel Projection Outlyingness: A Two-Stage Approach for Multi-Modal Outlier Detection

arXiv:2510.24043v4 Announce Type: replace Abstract: This paper presents Two-Stage LKPLO, a novel multi-stage outlier detection framework that overcomes the coexisting limitations of conventional projection-based methods: their reliance on a fixed statistical metric and their assumption of a single data structure. Our framework uniquely synthesizes three key concepts: (1) a generalized loss-based outlyingness measure (PLO) that replaces the fixed metric with flexible, adaptive loss functions like our proposed SVM-like loss; (2) a global kernel PCA stage to linearize non-linear data structures; and (3) a subsequent local clustering stage to handle multi-modal distributions. Comprehensive 5-fold cross-validation experiments on 10 benchmark datasets, with automated hyperparameter optimization, demonstrate that Two-Stage LKPLO achieves state-of-the-art performance. It significantly outperforms strong baselines on datasets with challenging structures where existing methods fail, most notably on multi-cluster data (Optdigits) and complex, high-dimensional data (Arrhythmia). Furthermore, an ablation study empirically confirms that the synergistic combination of both the kernelization and localization stages is indispensable for its superior performance. This work contributes a powerful new tool for a significant class of outlier detection problems and underscores the importance of hybrid, multi-stage architectures.

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

Contrastive-Difference CKA Reveals Concept-Specific Structural Alignment Across Language Model Architectures

作者:

Do different LLM architectures encode high-level concepts in structurally compatible ways? We systematically characterize a geometric-functional universality dissociation: across multiple concept domains and architectural families, moderate geometric convergence coexists with near-perfect functional transfer. Using contrastive-difference CKA (CKA_Delta), a training-free diagnostic that computes kernel alignment on per-sample contrastive differences, we isolate concept-specific convergence from generic similarity – achieving significant discrimination where standard CKA cannot. The dissociation replicates across all six concept domains we test (five with p =70B models. We position CKA_Delta as a practical regime classifier and architectural outlier detector (Gemma: d = 1.08, AUC = 0.79) rather than an absolute transfer-accuracy predictor, providing a training-free diagnostic for cross-architecture concept monitoring.

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

Decision-Driven Geosteering Under Uncertainty: A Unified Framework for Sequential Decision Optimization

arXiv:2606.17331v1 Announce Type: new Abstract: Geosteering requires navigating a well trajectory through an unknown geological configuration, while sequentially updating decisions based on indirect measurements acquired during drilling. This work presents an uncertainty-aware geosteering framework that tightly integrates particle filtering for probabilistic subsurface interpretation with value-based reinforcement learning for sequential decision-making. Geological uncertainty ahead of the drill bit is represented explicitly through a particle filter (PF), enabling belief-informed control rather than deterministic trajectory correction. The framework couples PF belief updates with belief-informed decision policies and evaluates three decision-making options that operate under identical uncertainty representations: an interpretable Approximate Dynamic Programming (ADP) scheme, a Deep Q-learning baseline, and a Dual Deep Reinforcement Learning (Dual DRL) architecture trained with a target Q-network scheme for stability, using a dueling (value/advantage) decomposition for Q-value parameterization. Beyond final placement performance, we assess policy behavior using stability-oriented metrics that quantify steering smoothness over time, providing additional operational insight into how decision policies respond as uncertainty evolves. The framework is integrated with an API for validation within an industrial geosteering simulator under realistic measurement noise and drilling constraints. Using identical geological realizations, operational limits, and reward definitions across methods, the experiments provide a controlled and high-fidelity evaluation of how alternative decision policies behave throughout the drilling process, rather than evaluating performance solely from the final well trajectory.

10.
arXiv (CS.LG) 2026-06-12

The Urysohn Machine: A Metric-Topological Model of Computation

作者:

arXiv:2508.14143v2 Announce Type: replace Abstract: We introduce the Urysohn Machine, an effective model of classification-oriented computation in which metric separation, frontier structure, and contraction are explicit parts of the computational state. Its basic object is a Urysohn Triple: a support region, a target partition, and a separating classifier stored in a reusable Metric Library. The topological foundation is a constructive Urysohn Realization theorem for finite simplicial settings. It builds separators from dyadic ladders of nested polyhedral regions and equips their frontiers with a chain-level calculus: frontiers are cycles, and shells between levels have boundaries given by differences of frontiers. This construction yields two related complexity measures: decision-boundary width, the geometric measure of a single classifier's boundary, and Urysohn width, the total frontier mass represented by a library or realization. We prove an Amortized Separation Theorem showing that approximating a boundary of width to accuracy requires a number of simple basis triples proportional to boundary width and inversely proportional to resolution, under explicit boundary-footprint assumptions. We also introduce a contrastive separation operator whose graph-cut functional consistently estimates decision-boundary width from sampled metric data, while its Laplacian spectrum certifies class-component structure and conductance. Finally, we analyze the dynamic Urysohn ladder and prove four guarantees: separability under quotient collapse, stability of committed frontiers, bounded capacity under contraction, and scalability with quotient distance. Together, these results give a metric-topological account of classification complexity, amortized inference, and compositional reuse that preserves classical computability while exposing geometric structure hidden by purely symbolic descriptions.

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

GLACIER: A Multimodal Student-Teacher Foundation Model for Molecular Property Prediction

arXiv:2606.11382v1 Announce Type: new Abstract: Deep learning models facilitate the discovery of molecules with tailored properties among billions of candidate compounds. However, the computational burden to develop and deploy state-of-the-art models continuously increases, limiting their scalability. Most large-scale models are unimodal in nature and overlook the potential to leverage complementary molecular data modalities. To address these shortcomings, this paper introduces the Graph-Language Alignment for Chemical Inference and Exploration using Representations (GLACIER) model, a student-teacher framework that integrates molecular graphs, SMILES strings, and physicochemical descriptors to learn rich molecular embeddings. Our framework consists of three stages: (1) we pretrain three student encoders on 100,000 drug-like molecules: a message-passing neural network for molecular graphs, a transformer-based encoder for SMILES strings, and a multilayer perceptron for physicochemical descriptors, (2) we fuse these student modalities using a novel Finsler geometry-aware module, and (3) distill complementary knowledge from large teacher models, including MiniMol and MolFormer, into a single lightweight model via contrastive learning. We demonstrate that GLACIER is a robust framework that delivers high predictive performance and computational efficiency in complex molecular property prediction tasks. Our code is publicly available at https://github.com/eemokey/glacier.

12.
arXiv (CS.AI) 2026-06-15

SkillAudit: Ground-Truth-Free Skill Evolution via Paired Trajectory Auditing

arXiv:2606.14239v1 Announce Type: new Abstract: Agent skills are structured procedural packages that guide frozen LLM agents in specialized workflows. Skills rarely remain sufficient after deployment: edge cases, API changes, and deployment constraints become visible only through use, making skill evolution a practical necessity. Existing methods depend on privileged feedback such as held-out validation scores, hidden test outcomes, or environment rewards – signals often unavailable when a practitioner has only a task description and workspace data. We introduce SkillAudit, a framework for evolving agent skills without ground-truth feedback. The key idea is paired trajectory auditing: at each iteration, the same task is executed with and without the candidate skill, isolating how the skill changes agent behavior without external labels. To turn behavioral differences into edit guidance, SkillAudit uses Process-Aligned Contrastive Evaluation (PACE), a cluster of evaluators that maps trajectory divergences to diagnostic signals linked to specific passages in the skill document. A structural verifier, compiled once from the task specification and then fixed, checks task constraints and rolls back harmful updates. SkillAudit routes edits through two pipelines: Refine removes noisy or irrelevant guidance from broadly useful skills, while Repair replaces passages that conflict with the task. Across 89 containerized tasks spanning 8 professional domains, SkillAudit achieves 73.9% average task reward, outperforming an agent without skills (40.9%) and the static expert skill (56.7%). These gains are obtained without accessing hidden tests, reference solutions, or external scoring functions during evolution.

14.
arXiv (CS.LG) 2026-06-12

ResidualPlanner+: a scalable matrix mechanism for marginals and beyond

arXiv:2305.08175v5 Announce Type: replace-cross Abstract: Noisy marginals are a common form of confidentiality protecting data release and are useful for many downstream tasks such as contingency table analysis, construction of Bayesian networks, and even synthetic data generation. Privacy mechanisms that provide unbiased noisy answers to linear queries (such as marginals) are known as matrix mechanisms. We propose ResidualPlanner and ResidualPlanner+, two highly scalable matrix mechanisms. ResidualPlanner is both optimal and scalable for answering marginal queries with Gaussian noise, while ResidualPlanner+ provides support for more general workloads, such as combinations of marginals and range queries or prefix-sum queries. ResidualPlanner can optimize for many loss functions that can be written as a convex function of marginal variances (prior work was restricted to just one predefined objective function). ResidualPlanner can optimize the accuracy of marginals in large scale settings in seconds, even when the previous state of the art (HDMM) runs out of memory. It even runs on datasets with 100 attributes in a couple of minutes. Furthermore, ResidualPlanner can efficiently compute variance/covariance values for each marginal (prior methods quickly run out of memory, even for relatively small datasets). ResidualPlanner+ provides support for more complex workloads that combine marginal and range/prefix-sum queries (e.g., a marginal on race, a range query on age, and a combined race/age tabulation that answers age range queries for each race). It even supports custom user-defined workloads on different attributes. With this added flexibility, ResidualPlanner+ is not necessarily optimal, however it is still extremely scalable and outperforms the prior state-of-the-art (HDMM) on prefix-sum queries both in terms of accuracy and speed.

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

PIGEON: VLM-Driven Object Navigation via Points of Interest Selection

Object navigation in unseen indoor environments requires agents to perform semantic search under partial observability. Vision-language models (VLMs) provide strong semantic-spatial priors for this task, but how to interface them with robot navigation remains challenging: dense VLM inference is expensive, while abstracting environments into symbolic memories often separates high-level reasoning from the raw visual evidence that supports it. We propose we propose PIGEON (Point of Interest Guided Exploration for Object Navigation), a VLM-driven framework that formulates object navigation as raw-observation-grounded sparse decision problem. PIGEON introduces Points of Interest (PoIs) as sparse visual decision units that couple geometrically executable waypoints with raw egocentric observations. Rather than using VLMs as dense controllers or restricting them to frontier ranking, PIGEON enables VLMs to select among task-critical PoIs, including exploration frontiers, suspected target objects, traversable stairs, and floor-level summaries, while low-level planners execute continuous motion between them. This PoI interface further makes high-level navigation decisions verifiable, allowing us to develop an RLVR pipeline that improves local VLMs without manual Chain-of-Thought annotations. Extensive experiments on Habitat ObjectNav benchmarks show that PIGEON achieves state-of-the-art zero-shot performance, scales consistently with foundation model capacity, and transfers to Active Embodied Question Answering with only prompt modifications. Real-world deployments on physical robots further demonstrate its robustness and efficiency.

16.
arXiv (quant-ph) 2026-06-12

Interference of critical dynamics associated with zero modes

arXiv:2606.13200v1 Announce Type: new Abstract: We study the interference of critical dynamics associated with zero modes (ICDZM) in the generalized Creutz ladders using closed quench paths that pass through two critical points successively. By reading out the final zero-mode transfer probability, we find rich ICDZM interference patterns dependent on the quench path. In particular, when the closed path links two topologically nontrivial phases, the ICDZM pattern may either vanish or exhibit period doubling. Within the framework of WKB analysis, this phenomenon is well clarified by the interference phase accumulated in the quench procedure. We also demonstrate that the zero-mode transfer probability can be detected by the deviation of the boundary particle number from its initial fractional value, which arises from the blending of bulk modes in the critical dynamics. As an edge defect, the zero-mode transfer probability captures both the ICDZM oscillation and the known anomalous defect production in a non-closed quench path. These results identify ICDZM and the corresponding edge defect as probes for critical dynamics associated with topological zero modes.

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

Can I Buy Your KV Cache?

arXiv:2606.13361v1 Announce Type: new Abstract: Right now, across the world, AI agents are repeating the same absurd act: to read one document, they each recompute it from scratch. Every agent re-runs prefill, the most compute-intensive step a large model takes, over identical text, only to rebuild a key-value (KV) cache identical to the one the agent before it just built. The same answer, computed a million times. We make a proposal that is almost offensively simple: compute it once. Let a publisher precompute a document's KV cache, and let every other agent buy the right to load it and skip prefill. It works, and it is token-exact: loading a precomputed KV and continuing matches prefilling from scratch (24/24 greedy tokens, and at the logits level), with no accuracy cost. On Qwen3-4B, reuse is 9-50x cheaper in compute than prefill, and the gap widens with length (prefill's attention scales with L^2), so a single reuse already pays it back. Then the part that matters: where the KV lives. Shipping it fails, because KV is nearly incompressible, so per-load egress costs more than the prefill it saves. Hosting it provider-side, exactly as production prompt-caching works, removes egress entirely. The size of the prize is set by our measured compute saving: serving one hot 3774-token document to 80M agents costs ~$1.5M to re-prefill but only ~$0.03M of reuse compute (49.7x less). The 0.1x cache-read tariff APIs charge passes a 10x discount to users while sitting inside this measured envelope, so the 10x is a floor that the measured ~50x compute saving clears, and the gap to the physical ~50x is provider margin: millions of dollars per popular document. We frame the resulting agent-native prefill CDN and leave lossless KV compression and a cross-party payment layer as the open problems.

18.
medRxiv (Medicine) 2026-06-24

A Systematic Review of Sex Differences in Postoperative Nausea and Vomiting

Background: Postoperative nausea and vomiting (PONV) is a common consequence of anaesthesia, affecting up to 30% of postoperative patients. Female sex is one of the strongest risk factors for PONV, yet no dedicated analysis has examined how this association varies across surgical settings and timepoints. This systematic review and meta-analysis aimed to quantify sex differences in PONV incidence across different surgical contexts. Methods: A systematic search was conducted using PRISMA guidelines across Medline and Embase from inception to September 1, 2025. Eligible studies were observational cohort studies (n[≥]500) of adult patients that conducted multivariate regression analyses including sex as a variable. Two reviewers independently screened, extracted data, and assessed risk of bias using ROBINS-E. A random-effects meta-analysis was performed. Subgroup analyses and multiple sensitivity analyses were completed. Results: From 4620 identified studies, 23 met the inclusion criteria, including 462,828 patients across various surgical settings and specialties (52% female). The pooled incidence of PONV was 21% (95% CI[16-27%]), with high heterogeneity (I2=99.9%). Meta-analysis confirmed females had a higher risk of developing PONV compared to males (pooled OR=2.40, 95% CI[2.06-2.79], I2=93.1%, p

19.
bioRxiv (Bioinfo) 2026-06-11

Tumour evolution as ground truth for cancer whole-genome sequencing

Cancer genomes are shaped by evolutionary processes that couple mutagenesis, clonal selection, chromosomal instability, spatial growth and treatment response into structured genomic patterns, yet current benchmarking strategies largely ignore this evolutionary dependency. Here, we present SCOUT, a large-scale synthetic whole-genome sequencing resource of over 200 samples, designed for systematic benchmarking of tumour genomic analysis and evolutionary inference under controlled evolutionary ground truth. Unlike conventional task-specific simulations, SCOUT models tumour evolution as a latent generative process that simultaneously shapes mutations, copy-number alterations, variant allele frequencies, mutational signatures and clonal architectures. SCOUT recapitulates key features of solid and haematological malignancies, including driver mutations, chromosomal instability, intratumour heterogeneity, spatial sampling and treatment-associated evolutionary dynamics in tumour and matched-normal longitudinal and multi-region sequencing designs. Using SCOUT, we benchmarked widely used methods for somatic variant detection, copy-number analysis, mutational signature inference and tumour evolutionary reconstruction. Across analytical tasks, performance deteriorated in low-purity, highly subclonal and structurally complex tumours, while spatial sampling bias and hypermutation generated spurious evolutionary signals that confounded tumour interpretation across multiple inference layers. Evolutionary simulations further distinguished lineage-restricted genetic bottlenecks from multi-lineage resistance dynamics associated with tumour plasticity. Tumour purity consistently exerted a stronger effect on inference accuracy than sequencing depth. Together, our results establish evolutionary ground truth as a prerequisite for reproducible benchmarking and biologically interpretable analysis of cancer whole-genome sequencing data.

20.
bioRxiv (Bioinfo) 2026-06-19

Perturbation Curve models continuous transcriptional response trajectories and improves prediction of genetic modulations

Single-cell CRISPR screens, Perturb-seq, have revolutionized functional genomics by revealing biological causality. However, although perturbation assignments are typically represented as discrete labels, the cell-level effective strength of perturbations is often continuous and diverse. Current analytical frameworks struggle to decouple the variability in perturbation strength from the diversity of downstream responses. Here, we present Perturbation Curve (PertCurve), a nonlinear, curve-based computational framework that models the trajectories of transcriptomic responses by explicitly incorporating diverse perturbation magnitudes and strengths. By ordering cells by perturbation strength, we demonstrate that PertCurve accurately recapitulates the response magnitudes and reveals the distinct modularity and asynchrony patterns of downstream gene behaviors. These patterns are categorized into archetypes, including proportional, sensitive, and threshold responses. By applying this framework across CRISPRi/a modalities, we identify universal response patterns in viral infection, apoptosis, and proliferation genes, and reveal previously overlooked context-specific regulatory features in cell differentiation. Finally, incorporating PertCurve into perturbation prediction models and evaluation metrics enhances predictive performance, delivering actionable insights for refining established models.

21.
arXiv (CS.CL) 2026-06-17

Nothing from Something: Can a Language Model Discover 0?

AI systems based on artificial neural networks are being developed with aspirations of pushing the boundary of human mathematical knowledge. A key question for these systems is how much they can reach beyond their training data. Mathematical discovery requires a strong form of out of distribution generalization; the ability to hypothesize genuinely new - and potentially logically more powerful - mathematical structures. It has been hypothesized that language abilities support such generalizations in human cognition. In this work, we use simple arithmetic as a case study for examining how modern AI models could expand their mathematical horizons, evaluating whether these models can independently discover the concept of "zero". We show that We show that (1) language models of a GPT-2 size are unable to perform this generalization at test time regardless of language pretraining, but (2) models can improve substantially after training on tens or hundreds of examples of zero. Additionally, we find that language pretraining reduces the number of required examples by approximately $50\%$, showing that language abilities can scaffold mathematical discovery in neural models.

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

"Is This Not Enough?": Asymmetries in Institutional Accountability and Collective Sensemaking in the Case of Canada's Algorithmic Visa Triage System

arXiv:2606.13071v1 Announce Type: cross Abstract: This paper examines how algorithmic accountability in Canada's visa system is articulated institutionally and experienced by applicants across borders. We analyzed Immigration, Refugees and Citizenship Canada (IRCC)'s Algorithmic Impact Assessment (AIA) for the temporary resident visa (TRV) triage system using the algorithmic decision-making adapted for the public sector (ADMAPS) framework and analyzed Reddit discussions among applicants using a mixed-methods approach. We show that while institutional artifacts emphasize transparency, procedural safeguards, and bounded impacts, applicants engage in collective sensemaking to interpret opaque decisions, often relying on peer knowledge amid uncertainty. We identify three asymmetries between how institutional accountability is structured and how people perceive the process: epistemic asymmetry in access to decision logic, jurisdictional asymmetry in exposure shaped by geopolitical positioning, and temporal–relational asymmetry in how waiting and uncertainty are experienced. We emphasize why it is important to shift attention from institutional design to the uneven distribution of experiences with public-sector algorithmic governance. Together, these contributions demonstrate how algorithmic governance systems in the context of transnational migration produce structured asymmetries not captured by institutional disclosure frameworks, and how extending ADMAPS can account for those uneven translations of accountability.

23.
arXiv (CS.CL) 2026-06-19

Creating Multilingual Mental Health Dialogue Datasets: Limits of Persona-Based Localization via Nationality and Language

AI and large language models (LLMs) have emerged as promising tools to address global mental health challenges. Despite the global nature of these challenges, there remains a critical shortage of high-quality datasets for training and evaluating such systems. To mitigate this gap, researchers increasingly generate synthetic clinical personas to simulate user data and test digital mental health support systems. However, most validated personas rely on English-centric contexts. This paper investigates whether similar persona-based methods can be used to generate multilingual mental health datasets. We modified nationality and language parameters in personas to generate clinical dialogues in Mandarin, Bengali, and Hindi. We then examined how different LLMs perform when evaluating the depression severity of these generated multilingual datasets against the baseline in English. Our findings indicate that just adding nationality and language parameters in personas might not be adequate, as it can introduce clinical inconsistency across languages. LLM judge models often exhibit inaccuracies in assessing depression severity in non-English texts, with performance varying across different models. This exposes the systemic limitations of applying English-centric personas to multilingual contexts. Ultimately, our work highlights the urgent need for culturally responsive data generation to ensure equitable mental health systems globally.

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

Structural MRI Synthesis for Alzheimer's Disease via Conditional Diffusion on Anatomical Masks

arXiv:2606.18354v1 Announce Type: cross Abstract: Recent advances in generative machine learning models have significantly improved medical imaging, offering promising solutions for data augmentation, privacy preservation, and improved model generalization. However, synthesizing high-quality structural MRI data for Alzheimer's Disease (AD) remains challenging due to the subtle, region-specific, and progressive anatomical changes associated with neurodegeneration. In this paper, we extend the Med-DDPM conditional diffusion model – originally designed for brain tumor synthesis – to generate 3D structural MRIs specifically tailored to AD. We adopted Med-DDPM due to its established stability and structural fidelity compared to other generative models, which makes it particularly suitable for capturing the subtle anatomical changes characteristic of AD. Our approach conditions the diffusion process on anatomical segmentation masks derived from the ADNI dataset, incorporating key AD-relevant brain structures into the generation process. We systematically evaluate the quality and utility of the synthetic images by training segmentation models on real, synthetic, and hybrid (mixed) datasets. Experimental results demonstrate that segmentation models trained exclusively on synthetic data achieve comparable Dice scores (0.6532) to those trained on real data (0.6513), while exhibiting significantly enhanced recall. Notably, models trained on hybrid datasets (mixing real and synthetic images) outperform both real and synthetic-only baselines, achieving a Dice score of 0.7244. These findings underscore the successful use of conditional diffusion models for generating anatomically accurate, AD-specific synthetic MRIs, and highlight their potential for enhancing training data availability, improving diagnostic accuracy, and promoting research reproducibility in neuroimaging studies.

25.
arXiv (CS.CL) 2026-06-12

Agentic MPC for Semantic Control System Resynthesis

While MPC effectively handles structured, diverse, and low-level specifications, it lacks the capability to dynamically incorporate high-level contextual information such as social norms, user intent, or natural language instructions. To address this limitation, this manuscript introduces an agentic MPC framework that enables context-aware, semantically adaptive control synthesis by integrating with large language model-based agents. The agent interprets heterogeneous inputs, including natural language messages, environmental observations, and external knowledge, to resynthesize the control specifications. The effectiveness of the framework is demonstrated in an autonomous driving scenario, where the system aligns with personal preferences or responds to social situations such as emergency vehicle yielding.