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01.
arXiv (CS.AI) 2026-06-19

CTS-MoE: Implicit Terrain Adaptation via Mixture-of-Experts for Perceptive Locomotion

arXiv:2606.19633v1 Announce Type: cross Abstract: Perceptive legged locomotion over discontinuous terrain (e.g., stairs, gaps, and obstacles) requires adaptive behavior, as a single conservative gait cannot produce the anticipatory maneuvers needed for abrupt topology changes. Cast as multi-task reinforcement learning, this problem introduces a tension between sharing and separation. Tasks use a common locomotion base but have conflicting rewards, so a policy must share behavior while avoiding value interference. Prior work addresses only one side, with monolithic policies sacrificing specialization and hierarchical sub-policies sacrificing generalization across transitions and unseen terrain. We propose CTS-MoE, which combines a dense mixture-of-experts actor with perception-based gating to compose shared behaviors and a multi-critic with task-specific value heads to prevent interference. The model is trained end-to-end in a single-stage concurrent teacher-student setup that handles partial observability and avoids sequential distillation, with task labels used only during training. At deployment, routing depends solely on perception, allowing terrain adaptation without a high-level selector or terrain classifier. Experiments on a Unitree Go1 in simulation and on hardware across seen and unseen terrains show task-aware specialization, with lower tracking error and higher success rates than monolithic baselines. Project Website: https://cts-moe.github.io/ .

02.
medRxiv (Medicine) 2026-06-19

Specific epigenetic age acceleration measures are associated with oral health outcomes in U.S. adults

Objectives: Oral health conditions impact a significant proportion of the global population. Chronological age is a known risk factor; however, characterization of epigenetic age remains limited and is expected to provide additional insight into biological mechanisms. Materials and Methods: The National Health and Nutrition Examination Survey (NHANES) was used to analyze the effect of epigenetic age measures of DunedinPoAm, and epigenetic age acceleration (EAA) of Horvath, Hannum, Weidner, Lin, VidalBralo, PhenoAge, GrimAge, and GrimAge2, on various oral health outcomes from survey and examination results. Univariable and multivariable logistic regression were performed, adjusting for sex, race-ethnicity, education, poverty income ratio categories, and dental insurance coverage status. Results: DunedinPoAm was associated with the last dental appointment being for an existing issue (p=0.0093), poor general oral condition (p=0.0226), limiting food due to teeth problems (p=0.0031), and recommendation to see a dentist within the next two weeks (p=0.0171). EAAs for PhenoAge, GrimAge, and GrimAge2, were associated with a smaller number of oral health outcomes, whereas EAAs for Horvath, Hannum, Weidner, Lin, and Vidal-Bralo showed no associations. Conclusions: In a representative U.S. population, DunedinPoAm was most consistently positively associated with different adverse oral health outcomes compared with other epigenetic aging measures. Tracking specific epigenetic ages such as DunedinPoAm, EAA GrimAge, EAA GrimAge2, and PhenoAge, may aid in additional monitoring of oral health outcomes. Understanding specific aging-related CpGs associated with oral health may aid in elucidating underlying molecular mechanisms.

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

Operator Calculus for Population-Based Optimization: A Mean-Field Convergence Theory

arXiv:2606.14289v1 Announce Type: cross Abstract: Population-based and distributional optimization methods, from evolution strategies and consensus-based optimization to covariance-matrix adaptation and stochastic gradient methods viewed as distributional dynamics, are widely used for nonconvex or black-box problems, yet their convergence analyses remain fragmented across algorithm-specific techniques. We introduce an operator calculus in which a broad class of such methods, after choosing an appropriate state space and, where necessary, augmenting the state by memory or strategy variables, is described as a composition of three elementary operators (mutation, selection, and recombination) acting on probability measures. Under explicit stability and regularity conditions, the composite operator admits a pre-generator whose continuous-time limit is a transport-reaction-jump (TRJ) PDE that preserves the operator splitting. On this foundation we establish a modular Lyapunov principle. If a state-space Lyapunov function both dissipates under the full generator and controls the relevant search-space gauges, then the state-space Lyapunov functional and the induced search errors decay exponentially. The additive generator structure allows dissipation estimates to be assembled operator by operator, providing a toolkit for certifying convergence of composite mean-field algorithms.

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

A solvable model for unsupervised federated learning

arXiv:2606.13045v1 Announce Type: cross Abstract: We introduce a theoretical framework for analyzing federated learning in a generative setting through a teacher-multiple interacting students scenario, in which each student receives a distinct realization of the data, either through a different noise corruption or by accessing a different subset, possibly of varying size. Using theoretical tools in equilibrium disordered system, we analytically show that interactions among students systematically enhance learning performance: highly noisy students require fewer samples to recover the underlying pattern, while low-noise students achieve a larger overlap with the ground-truth signal. We derive the optimal Bayesian conditions for teacher recovery as functions of the sample complexity, noise level, and interaction strength, and validate these predictions through numerical simulations. The resulting dynamics can be mapped onto equilibrium sampling in a Restricted Boltzmann Machine with a structured hidden layer, providing a principled theoretical understanding of how interactions improve distributed generative modeling.

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

APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

arXiv:2606.12991v1 Announce Type: new Abstract: Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.

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

LegalHalluLens: Typed Hallucination Auditing and Calibrated Multi-Agent Debate for Trustworthy Legal AI

AI systems deployed in legal workflows hallucinate at rates that aggregate metrics report at ~52%, but this average conceals where errors concentrate and in which direction they run, leaving compliance officers without an actionable signal for trustworthy deployment. We present LegalHalluLens, an auditing framework with three components: typed hallucination profiles across four legally-motivated claim categories (numeric, temporal, obligation/entitlement, factual) over CUAD (Hendrycks et al., 2021); a Risk Direction Index (RDI) that reduces omission-versus-invention bias to a single deployment-comparable scalar; and a typed debate pipeline calibrated to both magnitudes and directions. Across 510 contracts and 249,252 clause-level instances we measure a within-model gap of approximately 38-40 pp between obligation/numeric and temporal claims that aggregate reporting hides, and show that two systems with matched 52% rates can carry opposite RDIs. The debate pipeline reduces fabricated detections by 45% with per-category gains tracking the diagnosis, matching commercial APIs with a substantially smaller backbone (4B active parameters). Typed profiles and RDI surface failure modes that aggregate metrics hide; we further show these diagnostics serve as calibration inputs for multi-agent debate pipelines, where Skeptic challenges and asymmetric gates targeted at measured failure modes outperform generically-tuned debate. The framework supports direction-aware procurement, accountability, and agent design for legal AI deployed in the wild.

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

CRANE: Constrained Reasoning Injection for Code Agents via Nullspace Editing

Code agents must both reason over long-horizon repository state and obey strict tool-use protocols. In paired Instruct/Thinking checkpoints, these capabilities are complementary but misaligned. The Instruct model is concise and tool-disciplined, whereas the Thinking model offers stronger planning and recovery behavior but often over-deliberates and degrades agent performance. We present CRANE (Constrained Reasoning Injection for Code Agents via Nullspace Editing), a training-free parameter-editing method that treats the Thinking-Instruct delta as a directional pool of candidate reasoning edits for the Instruct backbone. CRANE combines magnitude thresholding to denoise the delta, a Conservative Taylor Gate to retain edits that are jointly beneficial for reasoning transfer and tool-use preservation, and Graduated Sigmoidal Projection to suppress format-critical update directions. By merging paired Instruct and Thinking checkpoints, CRANE delivers strong gains over either individual model while preserving Instruct-level efficiency: on Roo-Eval it achieves pass1 of 66.2% (+19.5%) for Qwen3-30B-A3B and 81.5% (+8.7%) for Qwen3-Next-80B-A3B; on SWE-bench-Verified it resolves up to 14 additional instances at both scales (122/500 and 180/500); and on Terminal-Bench v2 it improves pass1/pass5 by up to 2.3%/7.8%, reaching 7.6%/17.9% and 14.8%/30.3%, respectively, consistently outperforming alternative merging strategies across all three benchmarks.

08.
bioRxiv (Bioinfo) 2026-06-19

Nickel-Driven Dynamics of Urease in Sporosarcina pasteurii: Integrated Computational and Experimental Insights

Urease is a nickel-dependent enzyme that plays an important role in urea hydrolysis and in a process named as microbial-induced calcium carbonate precipitation (MICP), which is widely used in sustainable environmental biotechnology. Despite its ecological importance, urease powers Biogrout (biocementation), a promising green technology for soil stabilization and infrastructure repair. Yet, the relationship between nickel availability, enzyme activation, and bacterial fitness remains poorly understood. In this study, we reveal a striking dual effect of nickel on Sporosarcina pasteurii: while high Ni2+ concentrations strongly inhibit growth (IC50 {approx} 637.7 {micro}M), they simultaneously boost specific urease activity up to six-fold. This uncoupling between biomass and enzymatic efficiency highlights a previously overlooked adaptive strategy under metal stress. Using structural bioinformatics and molecular docking, we show that Ure1–the catalytic subunit–exhibits the strongest nickel affinity (-4.3 kcal{middle dot}mol-1), supported by highly conserved active-site residues, whereas accessory proteins UreE and UreG display moderate and weak binding, consistent with their roles in metal delivery and GTP-dependent maturation. In addition, microscopic observations confirmed that calcium carbonate precipitation was most pronounced at intermediate nickel concentrations (approximately 400-1000 {micro}M), whereas higher concentrations ([≥]1000-1300 {micro}M) led to reduced mineral formation due to loss viable cells. Taken together, these results indicates that nickel availability controls both urease activation and bacterial fitness, and that an optimal balance is required to maximize biomenerilization efficiency in environmental applications, particularly in biocementation technology.

09.
arXiv (quant-ph) 2026-06-16

Quantum Measurement and Continuous Markov Processes

arXiv:2606.15958v1 Announce Type: new Abstract: These are the lecture notes for a course on diffusive quantum measuring instruments. They were prepared and delivered at the Perimeter Institute on Mondays and Thursdays, from 2:30 to 4:00 PM, beginning October 27th, 2025 and ending December 11th, 2025. These lectures were recorded and can be found at https://pirsa.org/c25038.

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

Creative Integration: A Decidable Criterion of Creativity

"Integrative" solutions are widely praised but rarely defined: we lack an operational way to tell a genuine integration – one that makes the world cheaper to describe – from a tidy re-description. Building on the lineage that treats creativity and intelligence as compression, we give such a criterion for creative integration (CI): the resolution of a real conflict between A and B is CI if and only if, under a fixed description language, the description length strictly shrinks (C = L_pre/L_post > 1), with the reduction located in the conflict itself. We make the judgment decidable through four binary, conjunctive gates, and we fix its extension through a taxonomy of pseudo-integration that names and rejects the look-alikes. We back the criterion with a curated, multi-domain corpus and – crucially – validate it not by human inter-rater agreement but by four falsifiable tests it could fail: an independent computational check, discrimination against hard negatives, out-of-sample prediction, and description-language robustness; all pass with margin. The contribution is not "creativity is compression" but its decidability, discrimination, and corpus: on this account, what makes a move genuinely creative – rather than merely novel – is that it compresses a conflict, with novelty and value as downstream symptoms; whether all creativity is so constituted we state as an explicit conjecture. We claim only the sign of C-1; we judge, not generate. The result is a citable primitive for a broader program.

11.
medRxiv (Medicine) 2026-06-18

Antimicrobial-resistant E. coli in human, animal and environmental reservoirs in rural Bangladeshi households with young children

In low-income countries, ESBL-producing Escherichia coli (ESBL-EC) is frequently detected in humans, animals and household environments, indicating widespread exposure to antimicrobial resistance (AMR). Established risk factors such as antibiotic use do not explain the high community carriage of AMR in all settings; identifying the dominant exposure pathways can inform interventions against AMR. We aimed to investigate (i) animal-human-environment sharing of AMR by assessing associations between the abundance of ESBL-EC in the household environment, domestic animal feces and young children's stool and (ii) household factors associated with ESBL-EC abundance in these reservoirs. We enrolled 112 households from the CRADLE trial in rural Bangladesh. We enumerated ESBL-EC in drinking water, food, child hand rinses, outdoor soil, indoor floor swabs, chicken and cow feces, and stool from children aged 6 months. We recorded indicators of sanitation, animal ownership/management, human and animal antibiotic use, and child exposure behaviors using structured questionnaires and spot checks. The highest prevalence of ESBL-EC was in child stool (95.6%) and animal feces (82.3-96.9%), followed by soil (48.2%) and floors (36.6%); < 10% of food, child hands and drinking water harbored ESBL-EC. The abundance of ESBL-EC in child stool was not associated with its abundance in any sampled matrix; the abundance in chicken but not cow feces showed positive correlations with soil, floors, child hands, and drinking water (correlation coefficients: 0.19-0.39, p-values < 0.05). Higher-quality latrines (improved, pour-flush, with slab) were associated with lower ESBL-EC abundance across matrices; unsafe animal management (animals roaming or spending the night inside the home) was associated with higher abundance. Child antibiotic use and exposure behaviors (soil ingestion, time spent on floor) were not associated with ESBL-EC abundance in child stool. We observed high AMR colonization among young children and domestic animals in rural Bangladesh not explained by traditional fecal-oral exposure pathways. Future studies should explore additional pathways and assess whether sanitation and animal management improvements can reduce AMR.

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

Nearest-neighbour gates are all you need: High-rate quantum low-density parity-check codes on a planar grid

arXiv:2606.19482v1 Announce Type: new Abstract: High-performance quantum low-density parity-check codes promise substantial reductions in the overhead of fault-tolerant quantum computation, but most constructions require long-range connectivity or qubit shuttling, both of which are difficult to realise in superconducting architectures. Here we introduce a family of quantum low-density parity-check codes that, for the first time, combines planar open-boundary layouts, finite-size advantages over surface codes, and syndrome extraction using only nearest-neighbour gates on a square grid of qubits. The key idea is to generate check-data connectivity dynamically: nearest-neighbour iSWAP walks both define the stabiliser supports and implement their measurement, avoiding the need for a long-range hardware graph. The resulting circuits achieve optimal constant-depth stabiliser measurement, independent of code size, and naturally remove leakage from the system by exchanging the role of check and data qubits at each syndrome extraction round. We find finite-size instances such as a [[323,14,15]] code, whose code-efficiency ratio is nearly an order of magnitude larger than that of rotated surface-code patches. At around 30 circuit qubits per logical qubit, the best directional tile-code layouts reduce the per-logical per-round logical error rate by up to a factor of 1000 relative to rotated surface-code memories. These results show that the advantages of quantum low-density parity-check codes can survive compilation into strictly planar nearest-neighbour circuits, bringing low-overhead fault-tolerant memories closer to near-term hardware.

13.
Nature (Science) 2026-06-08

Fifty years since a simple equation described the chaos of biology

An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics. An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics.

14.
arXiv (CS.AI) 2026-06-16

Reward Hacking in Language Model Agents: Revisiting AI Safety Gridworlds

arXiv:2606.15385v1 Announce Type: new Abstract: Reward hacking, where AI systems exploit misspecified objectives to achieve high reward without satisfying intended goals, remains a central challenge in AI safety. Yet most known instances have been discovered post hoc in frontier systems where controlled study is impractical. We adapt the AI Safety Gridworlds framework into a text-based evaluation suite that reformulates classic reinforcement learning safety tasks for language-based agents. Across frontier and mid-scale models, we find that specification gaming emerges zero-shot: models systematically achieve high observed reward while underperforming on hidden safety objectives, and even apparently safe behaviors can reflect misunderstanding rather than principled safety. Reinforcement learning does not correct these failures: direct reward optimization widens the gap between observed and hidden reward, as the model's initial competence causes it to lock into locally rewarding strategies before discovering safer alternatives. This pattern persists across model scales (1.5B–14B) and is not resolved by finer credit assignment, exploration prompts, or entropy regularization. Our results show that reward hacking arises naturally when optimizing proxy objectives with capable language model agents and resists standard mitigations, suggesting that proxy-reward failures in agentic settings may require approaches beyond standard exploration and credit-assignment fixes. To facilitate reproducibility, the code for this work is available at \href{https://github.com/asparius/verl-agent-safety}{our public repository}.

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

A Computational Audit of Demographic Association Encoding in ClinicalBERT Language Predictions

Transformer-based clinical language models are increasingly integrated into high-stakes clinical decision support pipelines, yet the computational mechanisms through which demographic associations encoded in medical documentation propagate into model probability distributions remain empirically underspecified. We present a systematic computational audit of representational bias in ClinicalBERT (Alsentzer et al., 2019), a BERT-based model pretrained on MIMIC-III discharge summaries, employing two complementary probing methodologies: Log Probability Bias Analysis (LPBA), which quantifies demographic descriptor-induced shifts in masked token probability distributions across behavioral and evaluative semantic categories, and Masked Language Model-based analysis (MLM), which probes internal representational structure for demographic agency attribution encoding across 98 real clinical sentence templates and eight intersectional race-gender combinations. Corpus frequency analysis operationalizes the distinction between statistical disparity and bias amplification by benchmarking model outputs against empirical term frequencies in the MIMIC-III training corpus. Of 32 statistically significant findings, 65.6% contradict observed corpus distributions, rising to 80% for Black patients and 87.5% for agency attribution under MLM probing, providing direct empirical evidence that representational bias in ClinicalBERT operates predominantly through model-internal amplification rather than training data inheritance. Keywords: natural language processing, clinical documentation, algorithmic auditing, representational bias, health equity 1

16.
medRxiv (Medicine) 2026-06-15

Natural Language Processing Based Solution for Labeling Brain Metastasis Identified in Radiology Reports

Abstract Purpose: Brain metastases (BM) far exceed primary CNS tumours and constitute the majority workload for neuro-oncology care providers. Currently, the cancer registries only capture synchronous BMs, which is only a small proportion of all BMs. We aim to develop and validate a natural language processing (NLP) algorithm that identifies brain metastases in radiology reports, enabling scalable surveillance of asynchronous BMs. Methods: Using population-based cancer registry data in Alberta, Canada, we identified a cancer cohort diagnosed between 2012–2019 with follow-up to 2022. All brain/head radiology reports at and post-cancer diagnosis were identified. Reports were sampled through a multi-phase approach and manually labeled for BM presence. We trained two Bio_ClinicalBERT models on the "Findings" and "Impressions" sections, respectively, and took the maximum predicted probability as the report-level prediction. Internal and external validation used reports from the Canadian provinces of Alberta, Ontario, and British Columbia. Results: The models were trained on 1,879 samples. For internal validation, 1,833 reports from 357 patients were tested. At a probability threshold of 0.4, the model achieved a sensitivity of 0.888 and precision of 0.499. The ensemble substantially outperformed single-section models, which achieved sensitivities of only 67.8% (Findings) and 74.2% (Impressions). On external validation, sensitivity was 0.918 in Ontario and 0.726 in British Columbia, demonstrating robustness across diverse data distributions. Conclusions: An NLP-based pipeline processing both Findings and Impressions sections has been developed and validated in three Canadian provinces. It meets cancer registry operational requirements and to be implemented into the surveillance workflow in Alberta and British Columbia, providing a foundation for population-level BM surveillance.

17.
arXiv (quant-ph) 2026-06-12

Approximability limits for bounded-degree max-LINSAT and implications for decoded quantum interferometry

arXiv:2606.13570v1 Announce Type: new Abstract: For general max-k-XORSAT with $k \geq 3$, no polynomial-time algorithm can do substantially better than random guessing on worst-case instances unless $\mathsf{P} = \mathsf{NP}$: approximating beyond the random-assignment value of $1/2$ is $\mathsf{NP}$-hard. The picture changes when each variable appears in at most $D$ constraints. In that bounded-degree setting, polynomial-time algorithms can provably beat the random baseline by an additive amount of order $1/\sqrt{D}$. For Boolean instances, this scaling is known to be optimal: the matching hardness result is due to Trevisan, while the corresponding algorithmic guarantee was established by Barak et al. Whether the same holds over general finite fields, and what it implies for quantum algorithms, has not been established. We make this connection explicit and extend the hardness to max-E$k$-LINSAT$(q,r)$ with bounded degree $D$ and over arbitrary finite fields $\mathbb{F}_q$, proving that it is $\mathsf{NP}$-hard to exceed $r/q + \mathcal{O}_{q,r}(1/\sqrt{D})$. These results provide the complexity-theoretic benchmark for the bounded-degree instances targeted by decoded quantum interferometry (DQI), QAOA, and classical heuristics. Any quantum advantage on bounded-degree instances is therefore confined to the constant prefactor. We further show that in the context of DQI and on $(k,D)$-regular instances, this prefactor is sensitive to the nature of the decoder: DQI with classical decoders faces an information-theoretic $1/\sqrt{D \log D}$ barrier that prevents it from matching the hardness scaling, while DQI with quantum decoders is compatible with the $1/\sqrt{D}$ scaling – identifying quantum decoding as the key ingredient for matching the complexity-theoretic scaling with DQI.

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

Bayesian Networks with Latent Time Embedding for Stage-Aware Causal Modeling of Alzheimer's Disease Progression

arXiv:2606.15784v1 Announce Type: new Abstract: Alzheimer's disease (AD) progression is often described through the amyloid-tau-neurodegeneration, or AT(N), cascade. However, most longitudinal models represent this cascade either as a fixed sequence of biomarkers or as a black-box forecasting task. This makes it difficult to determine when biologically guided biomarker relationships influence future regional pathology. In this study, we introduce Bayesian Networks with Latent Time Embedding (BN-LTE), a Bayesian structural framework for stage-aware modeling of AD progression. BN-LTE estimates disease pseudotime from baseline biomarker profiles and constrains directed dependencies according to biologically plausible AT(N) ordering. Posterior spline-varying structural equations are then used to link initial multimodal measurements with future annualized regional tau-PET change. Across repeated subject-disjoint evaluations using ADNI data, BN-LTE shows strong spatial reconstruction of tau progression compared with the included forecasting baselines. Beyond spatial reconstruction, BN-LTE recovers posterior stage-varying AT(N)-constrained effects and identifies a mid-pseudotime window of amyloid sensitivity. This window is supported by model-implied g-formula contrasts, root-adjusted AIPW, mechanism-sensitive ablations, and robustness analyses across spline and prior specifications. Overall, these findings position BN-LTE as a Bayesian structural framework for forecasting tau progression while examining stage-dependent AT(N)-cascade mechanisms in observational longitudinal neuroimaging data. Our code is available at https://github.com/danleneurocom/BN-LTE.

19.
bioRxiv (Bioinfo) 2026-06-16

DMcloud: Macromolecular Structure Modeling Using Local Structure Fitting for Medium to Low Resolution cryo-EM maps

Cryogenic electron microscopy (cryo-EM) has become an essential experimental approach in structural biology for determining macromolecular structures. When the resolution of a cryo-EM map is worse than approximately 5[A], fitting known or predicted molecular models into the map becomes a common strategy for interpretation. However, accurately fitting biomolecular models into cryo-EM maps, particularly for large macromolecular complexes, remains challenging when the input structure models contain errors or are in a conformation different from that represented in the map. Here, we present DMcloud, a method for local structure fitting of proteins and nucleic acids in cryo-EM maps. Instead of forcing an entire input model into the map, DMcloud divides input structures into local regions, identifies regions that are supported by the density, removes unsupported regions, and assembles the retained regions into a final model. We benchmarked DMcloud on 176 cryo-EM maps, including intermediate and high-resolution maps that include proteins, DNAs, or RNAs. For EM maps in the 5.0-10.0 [A] and 2.5-5.0 [A] resolution ranges, DMcloud achieved average sequence modeling coverage of 0.49 and 0.70, respectively. For DNA/RNA maps, DMcloud achieved an average sequence coverage of 0.75. Across all datasets, DMcloud consistently outperformed existing methods in model accuracy, map-model correlation, and modeling coverage.

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

Reassessing High-Performing LLMs on Polish Medical Exams: True Competence or Bias-Driven Performance?

Large language models (LLMs) in medicine are mainly evaluated using multiple-choice question answering (MCQA), which can overestimate real clinical ability due to guessing strategies and answer biases. To address these limitations, we introduce an expanded and more challenging benchmark based on Polish medical exams, adding over 15,000 questions, two new domains, and four structural modifications that reduce MCQA-specific artifacts and better test reasoning. We evaluate 21 LLMs and show that evaluation design strongly affects results. Under our harder setup, the best model (Qwen3.5-122B) drops by 28.4 and 31 pp on English and Polish exams, respectively. Despite low evidence of data contamination, standard MCQA scores do not reliably reflect true medical competence. To facilitate further research, we make our benchmark publicly available.

21.
bioRxiv (Bioinfo) 2026-06-10

ECMME: an atlas of selection pressures on the mammalian extracellular matrix reveals contrasting evolutionary dynamics

The extracellular matrix (ECM) is a fundamental metazoan innovation that provides structural support and regulatory cues essential for multicellular life. While core matrisome components are subject to strong functional constraints, their evolutionary dynamics at the molecular level remain incompletely characterized. Here, we present a comprehensive per-residue analysis of selection pressures across 272 human core matrisome proteins using high-quality orthologous sequences from up to 228 placental mammal species. We developed an automated pipeline integrating ortholog identification, codon-aware alignments, and site-specific selection analyses with the MEME and FUBAR methods from the HyPhy suite. Results reveal pervasive strong purifying selection across the matrisome, consistent with its structural and functional indispensability. This is accompanied by episodic positive selection and rarer pervasive positive selection, with collagens exhibiting significantly elevated episodic positive selection compared to glycoproteins and proteoglycans. To facilitate community access, we developed ECMME (ECM Molecular Evolution) browser, an intuitive open-access web resource that visualizes selection metrics plotted directly onto protein topologies. ECMME allows researchers to seamlessly browse and investigate the data, providing a powerful framework for interpreting functional sites. It is available online and requires no local installation or set-up (https://izzilab-ecmme.share.connect.posit.cloud/).

22.
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.

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

CisTransCell: Single-Cell Perturbation Prediction via Gene Function, Regulatory Control, and Cellular Context

arXiv:2606.13713v1 Announce Type: cross Abstract: Predicting cellular transcriptional responses to genetic perturbations is a central problem in single-cell biology, especially in the zero-shot setting where the perturbed gene or gene combination is unseen during training. A major difficulty is that perturbation effects are not determined by expression state alone: they depend on how the perturbed gene product influences other genes and proteins, how those downstream factors act on cis-regulatory elements, and which regulatory programs are active in the current cell state. To better capture this biological complexity, we propose CisTransCell, a cell-conditioned multi-modal framework for single-cell perturbation prediction that augments each gene with two complementary priors: a regulatory-sequence prior that captures how the gene is controlled, and a coding-sequence prior that captures what the gene product does. By integrating these priors with cellular expression state, CisTransCell models perturbation response as a cascade from gene function to regulatory control to downstream transcriptional change. Experiments on benchmark single-cell perturbation datasets show that CisTransCell achieves strong performance in zero-shot perturbation prediction.

24.
arXiv (CS.LG) 2026-06-19

Comparing Linear Probes with Mahalanobis Cosine Similarity

arXiv:2606.19603v1 Announce Type: new Abstract: Linear probes are widely used in interpretability research and often compared by cosine similarity. The Mahalanobis cosine similarity (MCS) between two directions, which reweights the inner product by test data covariance, is a natural task-aware refinement. Ying et al. (2026) report that a probe's MCS to a reference probe trained on the out-of-distribution (OOD) data near-perfectly linearly predicts the probe's OOD AUROC (R^2 = 0.98). Here, we extend this empirical finding across models, layers, and concept domains, and prove this general phenomenon in closed form: For balanced classes whose projections are Gaussian, OOD AUROC and MCS to the reference probe are linear because both are sigmoid-shaped functions of the probe's signal-to-noise ratio (SNR) on the test data. The theory also predicts when this linearity fails, which we verify empirically. MCS offers a theoretically grounded and empirically effective alternative to Euclidean cosine similarity for comparing linear probes.