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01.
arXiv (CS.AI) 2026-06-18

Examining Human-Like Behaviors in LLMs: A Multi-Dimensional Analysis of Model Behaviors, User Factors, and System Prompts

arXiv:2606.18258v1 Announce Type: cross Abstract: Large language models (LLMs) exhibit a wide range of human-like behaviors, from expressing thoughts and emotions, to engaging in relationship-building with users, to refusing requests and maintaining boundaries. Despite their prevalence, researchers and practitioners lack methods and empirical insights to make informed decisions about when and what types of human-like behaviors LLMs should exhibit. To fill this gap, we present a multi-dimensional analysis of the prevalence, potential effects, and controllability of these behaviors using LLM-as-a-judge and human evaluation. Across 21,000 multi-turn conversations from four widely used models (gpt-4o, gpt-4.1-mini, claude-sonnet-4.6, gemini-2.5-flash), we find that human-like behaviors are pervasive but vary across models and user factors (conversation goals and user profiles). In terms of perceived appropriateness, human evaluators judged self-referential and relationship-building behaviors as less appropriate from LLMs than from humans, but boundary-maintaining behaviors more appropriate from LLMs than from humans. Finally, we show that system prompting can control these behaviors, though it requires careful evaluation to avoid unintended effects. We discuss the implications of our findings and provide recommendations for responsible LLM design and evaluation.

02.
arXiv (CS.CL) 2026-06-15

The Culture Funnel: You Can't Align What isn't in the Data

Current cultural alignment approaches focus on inference-time interventions, assuming models already contain sufficient cultural knowledge. We argue modern LLM pipelines suffer from a cultural data funnel. Using a multidimensional tagging framework across pretraining, fine-tuning, alignment, and reasoning datasets, we show explicit cultural signals decline sharply during post-training, while geographically concentrated, task-specialized data dominates. Multilinguality enhances geographic diversity of cultural knowledge but does not ensure balanced representation. Our tags improve downstream cultural benchmark performance, demonstrating that advances require shifting focus in training data pipelines. To facilitate future research, we release our culturally tagged dataset with 5.6M samples at https://huggingface.co/datasets/CohereLabs/CultureMarkers.

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

Democracy in the Era of Artificial Intelligence

arXiv:2606.13026v1 Announce Type: cross Abstract: Interfacing Artificial Intelligence (AI) with democracy is one of the most profound challenges of our times. On the one hand, AI comes with opportunities to overcome long-standing challenges in democracy, such as low participation in deliberative and voting processes with poor representation of people. On the other hand, new risks arise from AI algorithms that are privacy-intrusive, biased, manipulative, spread misinformation and influence election results. Moving beyond the over-simplistic question of whether AI is good or bad for democracy, the Handbook on Democracy in the Era of Artificial Intelligence asks instead: how to upgrade democracies and the principles they are built on, using AI? How to engage with AI and on what terms? Which new values and design principles are required to build democratic resilience? In 34 chapters by 59 authors across the world from different disciplines, we explore how AI can empower collective intelligence for democracy (Part 1) and what is the future of deliberative democracy using large language models and social media (Part 2). We also illustrate the role of AI for building resilient self-governance systems (Part 3) and the challenges of transforming democracy in the age of AI (Part 4). We conclude with broader perspectives (Part 5) that re-imagine the interplay of democracy and AI.

04.
medRxiv (Medicine) 2026-06-22

Genetic and Shared Environmental Influences on Cancer Risk and Cross-Cancer Associations in Nordic Twins

The relative contributions of genetic and shared environmental influences to cancer risk and cross-cancer associations remain poorly understood. We analyzed data from 222,530 same-sex twins from Denmark, Finland, Norway, and Sweden in the Nordic Twin Study of Cancer, including 43,060 incident cancers over a median follow-up of 41.6 years. Using a target trial framework, biometric modeling, and competing-risk adjustment, we estimated familial risk, heritability, and shared environmental contributions across 35 cancer sites. Lifetime cancer risk was 36.5%, increasing to 51.4% in monozygotic (MZ) twins and 45.3% in dizygotic (DZ) twins with an affected co-twin. Overall cancer risk was explained by heritable (28%) and shared environmental (40%) influences. Heritability was highest for prostate (42%), non-melanoma skin (24%), and breast (18%) cancers. Cross-cancer analyses revealed extensive overlap in the genetic and shared environmental factors across sites, consistent with widespread pleiotropy and shared environmental susceptibility. Prostate cancer exhibited the strongest genetic overlap with rectum/anus (12%) and kidney (11%) cancers, whereas co-shared environmental influences were most pronounced for breast-lung (11%), prostate-bladder (11%), and prostate-lung (12%) cancers. These findings show pervasive genetic overlap across cancers at different sites and emphasize the importance of incorporating familial shared environmental exposures into cancer risk prediction and prevention strategies.

05.
arXiv (quant-ph) 2026-06-15

QCI Connect: A Modular Full-Stack Quantum Computing Platform

arXiv:2606.14456v1 Announce Type: new Abstract: In a world of various competing quantum computing architectures, hardware-agnostic, full-stack platforms are necessary to bring the full power of quantum computing hardware to domain experts via the cloud. QCI Connect and its Software Development Kit provide a reference architecture for a full-stack platform with a modular design and open-source interface definitions, built to facilitate a community-driven application ecosystem. Here, we present its overall design and features, central interfaces, and lessons learned, both for users of the platform and as a reference guide for future developments.

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

Projected random forests and conformal prediction of circular data

arXiv:2410.24145v3 Announce Type: replace-cross Abstract: We apply conformal prediction techniques to regression problems with circular responses, producing prediction sets with adaptive arc length and finite-sample coverage guarantees for any circular predictive model under the assumption of data exchangeability. Leveraging the high performance of existing predictive models designed for linear responses, we analyze a general projection procedure that converts any linear-response regression model into one suitable for circular responses. When random forests are used as base models in this projection procedure, we leverage the random forest out-of-bag mechanism to eliminate the need for a separate calibration sample in the construction of prediction sets. On synthetic and real datasets, the resulting projected random forest model produces more efficient out-of-bag conformal prediction sets, with shorter median arc length, than the split conformal prediction sets generated by two existing alternative models.

07.
arXiv (quant-ph) 2026-06-17

Cavity-enhanced superconducting response in an underdoped cuprate

arXiv:2606.18084v1 Announce Type: cross Abstract: Superconductors carry electrical current without resistance when paired electrons condense into a coherent macroscopic quantum state. In underdoped cuprates, evidence suggests that pairing-related correlations and superconducting fluctuations can survive above the temperature at which global coherence is lost, pointing to phase fluctuations as a key limitation on superconductivity in this regime. Motivated by recent demonstrations of cavity-modified collective states in quantum materials, we investigate whether superconducting coherence can be stabilized by engineering the electromagnetic environment of the superconductor. We study an underdoped YBa$_2$Cu$_3$O$_{7-\delta}$ thin film in a tunable terahertz cavity formed with a semi-transparent gold mirror. From temperature-dependent terahertz transmission measurements, we find that the cavity enhances the superconducting response below the critical temperature, with an increase of the inferred superfluid weight. The effect becomes more pronounced at smaller cavity lengths and is accompanied by an upward shift of the superconducting onset temperature. Calculations based on a cavity-coupled model for phase-fluctuating superconductors capture these trends and support an interpretation in terms of cavity-enhanced phase stiffness. These results showcase the potential of cavity engineering for designing emergent functionalities in correlated systems.

08.
arXiv (CS.CV) 2026-06-15

CineOrchestra: Unified Entity-Centric Conditioning for Cinematic Video Generation

Cinematic video depicts multiple subjects acting or interacting at specific moments, captured with deliberate camera movement, and stitched together by shot transitions. Together, these elements demand a level of fine-grained control beyond current text-to-video models. Existing work addresses each axis in isolation: multi-subject personalization, temporal control, multi-shot synthesis, or camera control; no prior framework jointly integrates all four. We present CineOrchestra, a unified video diffusion model that controls subjects, events, cameras, and shot transitions simultaneously. Our key insight is that these heterogeneous cinematic elements share a fundamental structure: each is an entity acting over a specific temporal interval, which can therefore all be expressed through one shared structure of entity-centric conditioning primitives, augmented with reference images for visual entities. This formulation reduces the architectural challenge to a single positional encoding problem, which we solve with two parameter-free coordinated rotary embeddings: (a) an interval-sampled temporal RoPE that yields consistent attention behavior across events of dramatically varying duration, and (b) a 2D entity-temporal cross-attention RoPE that disambiguates per-entity conditions and routes each to its corresponding spatiotemporal region. On two new benchmarks, CineOrchestra outperforms six per-axis specialists on dense caption following and shot-transition timing, with consistent gains in a pairwise user study and component ablations.

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

Agentic Discovery of Non-Canonical Antimicrobial Peptides with AMPGAN v3

arXiv:2606.17127v1 Announce Type: cross Abstract: Antimicrobial resistance causes to over a million deaths annually. Antimicrobial peptides (AMPs) are a promising solution, but generative AMP models are not yet ready to design peptides with non-natural amino acids and/or chemical modifications, which are essential for real-world peptide drugs. We present AMPGAN v3, a multi-objective conditional GAN that expands the generative vocabulary to D-amino acids and N/C-terminus modifications such as amidation. By separating adversarial and activity-aware supervision across two specialized discriminators, AMPGAN v3 substantially improves training stability and outperforms prior generative AMP models on external classifiers. We validated five candidates spanning three structural classes in vitro; two showed activity against Gram-positive strains, with the best candidate reaching MIC 8 {\mu}g/mL against B. subtilis. To support downstream curation, we further present PepCraft, a multi-agent framework for end-to-end AMP discovery in which a Planning Agent orchestrates specialized executors for generation, filtering, and verification. Its prioritization recommendations align with our in vitro outcomes. Together, these contributions let us examine, on a small but real scale, how generative and agentic AI compose in therapeutic peptide discovery. Code: https://github.com/marszzibros/AMPGANv3

10.
arXiv (CS.LG) 2026-06-16

Constraining the outputs of ReLU neural networks

arXiv:2508.03867v2 Announce Type: replace-cross Abstract: We introduce a class of algebraic varieties naturally associated with ReLU neural networks, arising from the piecewise linear structure of their outputs across activation regions in input space, and the piecewise multilinear structure in parameter space. By analyzing the rank constraints on the network outputs within each activation region, we derive polynomial equations that characterize the functions representable by the network. We further investigate conditions under which these varieties attain their expected dimension, providing insight into the expressive and structural properties of ReLU networks.

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

Layer-wise Geometric Approximation Rates for Deep Networks

arXiv:2604.20219v2 Announce Type: replace Abstract: Depth is widely viewed as a central contributor to the success of deep neural networks, whereas standard neural network approximation theory typically provides guarantees only for the final output and leaves the role of intermediate layers largely unclear. We address this gap by developing a quantitative framework in which depth admits a precise scale-dependent interpretation. Specifically, we design a single shared mixed-activation architecture of fixed width $2dN+d+2$ and any prescribed finite depth such that each intermediate readout $\Phi_\ell$ is itself an approximant to the target function $f$. For $f\in L^p([0,1]^d)$ with $p\in [1,\infty)$, the approximation error of $\Phi_\ell$ is controlled by $(2d+1)$ times the $L^p$ modulus of continuity at the geometric scale $N^{-\ell}$ for all $\ell$. The estimate reduces to the geometric rate $(2d+1)N^{-\ell}$ if $f$ is $1$-Lipschitz. Our network design is inspired by multigrade deep learning, where depth serves as a progressive refinement mechanism. For every prescribed terminal depth, the construction yields a finite nested family of prefix readouts whose earlier correction terms remain embedded in later readouts. Thus the approximation may be truncated within the prescribed depth range once the desired certified accuracy is reached.

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

LearnOpt: Recovering the Latent Cognitive Structure of Standardized Examinations via Knowledge Graphs and Constrained Optimization

arXiv:2606.15349v1 Announce Type: cross Abstract: Standardized examinations are typically treated as uniform syllabus coverage problems. We argue they are better understood as adversarial systems with stable latent cognitive structures diverging systematically from official syllabi. We introduce LearnOpt, which recovers this structure from historical question papers and generates personalized, time-bounded study plans. Applied to nine years of NEET questions (2016-2024, n=1,496), LearnOpt builds an exam knowledge graph from LLM-tagged questions, extracts a five-category latent skill distribution, and formulates study planning as a knapsack-variant optimization over prerequisite-aware subgraphs with Bayesian Knowledge Tracing. Central finding: NEET's latent skill distribution is stable within a syllabus regime (consecutive-year KL divergence 0.004-0.032 for 2016-2021, non-significant under permutation testing) but shifts significantly with NCERT's 2023 syllabus rationalization: pooling 2016-2021 (n=1,072) vs 2023-2024 (n=392) gives KL=0.040 (p=0.0005), with Elimination/Negation questions rising from ~20-29% to ~31-35%. Latent structure, while not permanently stationary, is piecewise stable, with shifts detectable and attributable to curricular events. Within either regime, subject predicts skill profile more strongly than year. An optimization evaluation, using one real and two synthetic mastery profiles, shows the skill-weighted objective produces a modest but real reordering of recommended topics over a mastery-conditioned frequency baseline. Applying the pipeline to JEE Advanced reveals a profile dominated by Multi-concept Integration (80.9% vs. 33.3% for NEET), with a JEE-vs-NEET divergence (KL=0.505) exceeding NEET's largest cross-subject divergence: exam tier shapes latent cognitive structure more than subject, which shapes it more than time within a regime. Code, knowledge graph, and annotated dataset are released publicly.

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

CogniFold: Always-On Proactive Memory via Cognitive Folding

Existing agent memory remains predominantly reactive and retrieval-based, lacking the capacity to autonomously organize experience into persistent cognitive structure. Toward genuinely autonomous agents, we introduce CogniFold, a brain-inspired "always-on" agent memory designed for the next generation of proactive assistants. CogniFold continuously folds fragmented event streams into self-emerging cognitive structures, bootstrapping progressively higher-level cognition from incoming events and accumulated knowledge. We ground this by extending Complementary Learning Systems (CLS) theory from two layers (hippocampus, neocortex) to three, adding a prefrontal intent layer. Emulating the prefrontal cortex as the locus of intentional control and decision-making, CogniFold achieves this through graph-topology self-organization: cognitive structures proactively assemble under the stream, merge when semantically similar, decay when stale, relink through associative recall, and surface intents when concept-cluster density crosses a threshold. We evaluate structural formation using CogEval-Bench, demonstrating that CogniFold uniquely produces memory structures that match cognitive expectations and concept emergence. Furthermore, across eight downstream benchmarks – two probing long-term conversational memory (LoCoMo, LongMemEval) and six spanning other cognitive domains – we validate that CogniFold simultaneously performs robustly on conventional memory tasks. Our code is available at https://github.com/OpenNorve/CogniFold.

14.
arXiv (CS.LG) 2026-06-17

CheckMIABench: Firm Foundations For Membership Inference Attacks on Language Models

arXiv:2606.17464v1 Announce Type: new Abstract: Membership inference attacks (MIAs) are a canonical way to assess a machine learning model's privacy properties. Although several attempts have been made to evaluate MIAs on language models, the extant literature has suffered numerous difficulties in constructing clean evaluations to test new techniques. In particular, subtle distribution shifts between member and non-member sets can undermine the statistical validity of MIAs; recent work has underscored this by showing that "blind" methods with no access to the underlying model can perform far better than published methods on the same benchmarks. This paper constructs a benchmark for principled evaluation of MIAs against LLMs, by leveraging the insight that training data before and after a fixed point during training are drawn from the same distribution. Therefore, all open-source models with intermediate checkpoints and public training data can be converted into MIA testbeds. We apply our framework to a half-dozen published attacks on the Pythia and OLMo family of models, from 70M to 7B parameters. To facilitate further privacy research, we open-source a modular library for designing and implementing attacks in this setting: https://github.com/safr-ai-lab/pandora_llm.

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

SciDef: Datasets and Tools for Automated Definition Extraction from Scientific Literature with LLMs

Scientific concepts are often defined inconsistently across papers, making it difficult to compare findings, reuse terminology, and build reliable downstream resources. We present SciDef, a resource suite for scientific definition extraction. The suite contains DefExtra, a benchmark of 268 human-validated author-stated definitions from 75 academic papers; DefSim, 60 human-labeled definition-pair similarity judgments; and an open LLM-based pipeline for PDF preprocessing, chunking, definition extraction, prompt optimization, and evaluation. We validate the resources by benchmarking 16 language models across prompting strategies and chunking schemes. The strongest set-level configuration achieves a score of 0.397, while the highest-coverage configuration matches at least one prediction to 86.4% of gold definitions but over-generates candidate definitions. We further show that an NLI-based matching metric agrees strongly with human DefSim judgments. These results position SciDef as a reusable benchmark and tooling layer for definition-centric literature analysis, while highlighting relevance-aware filtering as the key bottleneck for fully automatic definition extraction. Code & datasets are available at https://github.com/Media-Bias-Group/SciDef.

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

HadBalance: A Plug-and-Play Unified Global Geometric Prior Framework for Generalizable Biomedical Segmentation

Precise biomedical image segmentation is crucial for clinical diagnosis. Geometric cues (e.g., boundary, shape, and topology) can improve structural consistency, yet most are task-specific and lack a unified geometric foundation that generalizes across organs and modalities. We are motivated by the observation that several medical segmentation targets can be approximated as globally near-convex shapes. A convex region is one in which any two interior points can be connected by a line segment entirely contained within the region. In practice, medical targets may exhibit small local concavities or boundary irregularities; we refer to such globally convex-like shapes as near-convex. Motivated by this, we derive Hadwiger Shape Priors from Hadwiger's theorem as an interpretable global regularizer using three 2D measures: area A, perimeter P, and Euler characteristic chi, enabling transfer across organs and modalities. However, because medical datasets are shape-heterogeneous, enforcing near-convex priors uniformly can over-regularize non-convex anatomy with significant concavities, washing out concavities and fine details and degrading segmentation accuracy. To address this challenge, we propose Conflict-Aware Objective Balancing (CAOB), which integrates shape priors with segmentation in a gradient-aware manner. For each prior, CAOB removes only the gradient component that conflicts with segmentation while preserving the remaining aligned component, and adaptively regulates objective influences to prevent prior dominance. This enables stable use of shape priors on shape-heterogeneous data without erasing genuine concavities or fine structural details. We call this plug-and-play framework HadBalance.

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

Metric Match: A Subset Selection Approach to Evaluating LLM Judge Reliability

arXiv:2606.15029v1 Announce Type: new Abstract: LLM judges are used to reduce the need for costly human labor in evaluating open-ended text generation. However, the reliability of these judges depends critically on their alignment with human raters – a property that itself depends on costly human annotations. In this work, we develop a method (Metric Match) for estimating correlation-based reliability metrics of LLM judges from limited annotations. Metric Match selects a subset of samples for human annotation such that the subset matches the population reliability metric with respect to acquired synthetic labels. We empirically show that Metric Match achieves a win-rate of 0.838 against random subset selection across four different correlation metrics and 15 datasets, with an 18.7% decrease in average estimation error and reduces annotation needs by 32.5%. We provide a cost model and highlight a medical case study where our method saves $1,041.67 compared to random selection for expert annotation. Further, we shift our task from reliability estimation to reliability classification of whether a given judge is above a deployment threshold, outperforming random selection with Metric Match. All project code is publicly available, and we additionally provide an installable package for ease of use.

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

Polaris: A Godel Agent Framework for Small Language Models through Experience-Abstracted Policy Repair

arXiv:2603.23129v3 Announce Type: replace Abstract: Gödel agent realize recursive self-improvement: an agent inspects its own policy and traces and then modifies that policy in a tested loop. We introduce Polaris, a Gödel agent for compact models that performs policy repair via experience abstraction, turning failures into policy updates through a structured cycle of analysis, strategy formation, abstraction, and minimal code pat ch repair with conservative checks. Unlike response level self correction or parameter tuning, Polaris makes policy level changes with small, auditable patches that persist in the policy and are reused on unseen instances within each benchmark. As part of the loop, the agent engages in meta reasoning: it explains its errors, proposes concrete revisions to its own policy, and then updates the policy. To enable cumulative policy refinement, we introduce experience abstraction, which distills failures into compact, reusable strategies that transfer to unseen instances. On MGSM, DROP, GPQA, and LitBench (covering arithmetic reasoning, compositional inference, graduate-level problem solving, and creative writing evaluation), a 7-billion-parameter model equipped with Polaris achieves consistent gains over the base policy and competitive baselines.

19.
arXiv (CS.CL) 2026-06-17

Perceptual compensation for tonal context in self-supervised speech models

This study examines the extent to which the wav2vec2.0 architecture exhibits evidence of compensation for phonological context. We conducted a pseudo-replication of a perceptional compensation experiment on Mandarin Chinese tones, and compared the embedding similarities and probing classifier outputs between a purely self-supervised pre-trained model and a model fine-tuned for Mandarin ASR. No evidence of compensation was found in the embedding similarities of the purely pre-trained model. Probing classifiers showed some evidence of compensation in addition to the expected layer-wise improvements in categorization, but failed to replicate human performance on isolated test syllables. Our findings contrast with previous reports of sensitivity to phonological structure emerging through pre-training alone, and suggest that supervised objectives may be necessary to encourage the abstraction of at least some types of phonological regularities.

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

VOID: Defeating Unauthorized Mimicry in Latent Diffusion Models

While Latent Diffusion Models (LDMs) have revolutionized visual synthesis, they are increasingly exploited for unauthorized mimicry of individuals. Existing defenses inject deceptive perturbations to steer the generated images toward irrelevant targets. However, this approach hinges on an ungrounded assumption: subtle perturbations can maintain their deceptive efficacy throughout an LDM's extensive generation process. In reality, the model's innate restoration mechanism will remove such perturbations and cause individual identities to re-emerge in the images generated. We propose VOID, a defense framework that overcomes this conundrum by manipulating an LDM's intrinsic stochasticity. VOID perturbs the diffusion pipeline in two novel ways: 1) amplifying the latent encoding errors to shatter an image's semantic structure, and 2) counteracting the target guidance signals to suppress the model's restoration capabilities. This results in a semantic corruption that thwarts any unauthorized mimicry. Notably, the security gain does not come at the price of visual utility, as VOID simultaneously manages to confine perturbations to human-imperceptible regions of protected images. Our comprehensive evaluation of 24 state-of-the-art defenses against 10 mimicry attacks on 5 datasets demonstrates VOID's unprecedented protection power: it increases the average Frechet Inception Distance (FID) from 113 to 365, a 223% improvement over the strongest defense to date.

21.
arXiv (CS.AI) 2026-06-24

OrbitForge: Text-to-3D Scene Generation via Reconstruction-Anchored Video Synthesis

arXiv:2606.24799v1 Announce Type: cross Abstract: Generic text-to-video models can be used as rich open-world scene priors. Despite the high quality of today's generated videos, they do not directly yield reliable 3D assets: camera motion is difficult to control, view coverage is partial, and frames often contain inconsistencies across time. We introduce OrbitForge, an adapter built from frozen video priors and per-prompt Gaussian Splatting reconstruction optimization that converts a single text-generated video into a canonical closed-orbit 3D Gaussian Splatting scene. We use 3D reconstruction as an anchor to improve the 3D consistency of the generated video. We obtain a preliminary 3D reconstruction from a first generated video via Deformable Gaussian Splatting with a robust MedianGS proxy. We render views from a prescribed orbit to detect missing viewpoints. OrbitForge uses the text-to-video model to complete only the missing views, and reconstructs the completed orbit into a final Gaussian Splatting scene. This design requires no task-specific video or multiview fine-tuning, avoids per-prompt score-distillation optimization, and does not progressively generate views one step at a time. We further argue that this setting demands coverage-aware evaluation: local smoothness alone rewards methods that never attempt a full orbit. On a frozen 300-prompt T3Bench-derived audit, OrbitForge reconstruction attains a 359.0-degree measured median span, raises originally unsupported-bin Q10 ImageReward from 8.07 to 16.36 relative to MedianGS-only reconstruction, while remaining competitive with VideoMV on the coverage-quality.

22.
medRxiv (Medicine) 2026-06-15

Anti-Platelet Factor 4 Antibody Clonal Heterogeneity and MGUS Status in HIT

Background Monoclonal gammopathy of thrombotic significance (MGTS) is a recently described chronic prothrombotic condition characterized by monoclonal anti-PF4 antibodies that are detected above the polyclonal antibody background in patient sera (i.e. present as monoclonal gammopathy of undetermined significance, MGUS). Due to conflicting data in the published literature on antibody clonality in heparin-induced thrombocytopenia (HIT), we evaluated clonality and abundance of anti-PF4 antibodies in HIT, including investigating whether an MGUS, if present in HIT, represents the causative anti-PF4 antibody. Methods Blood samples from 15 patients with HIT were subject to Platelet Factor 4-dependent antigen-based and functional tests. The unmanipulated serum antibody repertoire and isolated anti-PF4 antibodies were subjected to mass spectrometric evaluation. Results Two of the 15 HIT patients had an IgG MGUS. Notably, anti-PF4 antibodies were not synonymous with the MGUS antibody in either of the two patients. Eight of the 15 patients demonstrated monoclonal anti-PF4 antibodies, however, none of the anti-PF4 antibodies were detectable as an MGUS upon evaluation of the entire serum antibody repertoire, reflecting their low abundance. In the seven patients with multiple anti-PF4 antibodies, non-monoclonality was confirmed by analysis of deglycosylated antibody heavy chains. Conclusions Anti-PF4 HIT antibodies are monoclonal in approximately 50% of HIT patients, however, antibody abundance is low such that they are not detectable over the polyclonal IgG background (i.e. are MGUS-negative), differentiating HIT from MGTS. This observation helps explain the transient nature of HIT relative to the persistent prothrombotic state seen in MGTS.

23.
arXiv (CS.LG) 2026-06-15

Closed-loop discovery of out-of-distribution processing protocols by evolutionary search and uncertainty-aware learning

arXiv:2606.13859v1 Announce Type: cross Abstract: Many materials and chemical systems exhibit history-dependent responses, where functional outcomes are governed not only by final-state variables but by the time-dependent sequence of fields, temperatures, or chemical potentials applied during operation. Discovering new processing protocols is therefore a high-dimensional search problem in which the control variable is an entire waveform or sample history, and conventional strategies either remain confined to conservative interpolative families or become prohibitively measurement intensive. Here, a closed-loop workflow is introduced that couples evolutionary search over a compact waveform representation with uncertainty-aware deep kernel learning to generate, rank, and experimentally validate candidate protocols. Applied to ferroelectric thin films, with the scanning-probe tip-bias waveform as the protocol and the nonlinear electromechanical response as the reward, the workflow discovers waveform families that enhance nonlinearity by de-aging the film. Spatially resolved before/after measurements show that the best-performing waveforms selectively activate pre-existing, weakly pinned domain-wall segments, whereas the worst drive long-range irreversible switching. This framework reframes protocol tuning as out-of-distribution discovery, generalizable to synthesis and annealing trajectories, battery formation protocols, and other high-dimensional control problems.

24.
medRxiv (Medicine) 2026-06-12

Cancer care disruption during the COVID-19 pandemic in Ontario, Canada: A sequential mixed-methods study

Introduction The COVID-19 pandemic profoundly disrupted healthcare delivery worldwide, with cancer care among the most affected services. Prior studies documented delays in referrals, reduced specialist access, and increased provider burden. However, the extent to which these experiences were reflected at the system level remains unclear. Objective To document cancer care experiences and examine whether these experiences were reflected in population-level health system indicators across Ontario, Canada. Methods We used an exploratory sequential mixed-methods design. Qualitative data were collected through focus groups and semi-structured interviews with 32 participants, including patients with cancer (n=8), caregivers (n=5), healthcare providers (n=14), and decision-makers (n=5) across two hospital settings in Ontario, Canada. Emergent themes informed the development of quantitative indicators. We then conducted a retrospective population-based analysis of linked administrative health databases for cancer patients in Ontario (n=87,786) to assess the prevalence of identified themes. Results Four themes emerged: (I) delays in diagnosis and screening; (II) disrupted access to primary care; (III) barriers to specialist and mental health services; and (IV) fragmented care for patients with multimorbidity. Quantitative findings corroborated major themes. Screening rates declined for cervical (64.8% to 57.5%) and breast cancer (64.5% to 57.2%). While in-person primary care shifted almost entirely to virtual modalities (8.5% to 95.4%), overall visit volumes remained stable. Specialist care showed uneven patterns, with increased oncology visits but declines in cardiology and mental health services. Patients with multiple comorbidities experienced the largest reductions in non-oncology specialist care. Conclusion The pandemic disrupted key components of cancer care, particularly screening, access to certain specialist services, and care for patients with complex needs. Integrating qualitative and quantitative evidence highlights areas of system vulnerability and underscores the need for coordinated, resilient cancer care capable of maintaining essential services during future crises.