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01.
arXiv (CS.AI) 2026-06-16

Medical Heuristic Learning: An LLM-Driven Framework for Interpretable and Auditable Clinical Decision Rules

arXiv:2606.16337v1 Announce Type: new Abstract: Predictive modeling for clinical tabular data is central to clinical decision support and therefore requires not only strong predictive performance but also transparent decision logic. Although deep learning and tree-based ensemble methods can achieve high accuracy, their black-box nature remains a major obstacle to clinical deployment. This challenge is further compounded by common characteristics of medical data, including limited sample sizes, severe class imbalance, and feature evolution arising from changes in diagnostic criteria and clinical documentation. To address these issues, we propose Medical Heuristic Learning (MHL), an instantiation of the learning-beyond-gradients paradigm for clinical tabular prediction. Instead of relying on neural network weight updates, MHL uses a large language model (LLM)-driven workflow that integrates statistical probes, medical knowledge probes, rule synthesis, and code-level iterative refinement to optimize a deterministic and executable decision system. The resulting model is expressed not as opaque parameters, but as versioned pure-Python decision rules that are explicitly interpretable, fully auditable, and clinically grounded. MHL also supports continual learning by starting from previously validated rules and iteratively revising them using updated feature information under data drift or feature evolution. Comprehensive experiments on medical datasets show that MHL achieves performance comparable to state-of-the-art methods while maintaining strong behavior in small-sample and highly imbalanced settings. The results further indicate that this explicit rule update mechanism can help alleviate catastrophic forgetting under feature evolution. Overall, these findings suggest that non-gradient-based heuristic systems offer a transparent and adaptable alternative for high-stakes clinical decision support.

02.
arXiv (CS.CL) 2026-06-16

Vocabulary Dropout for Curriculum Diversity in LLM Co-Evolution

Co-evolutionary self-play, where one language model generates problems and another solves them, promises autonomous curriculum learning without human supervision. In practice, the proposer quickly converges to a narrow distribution of problems that satisfy the reward function. This diversity collapse renders the curriculum uninformative for the solver, stalling the co-evolutionary loop. We introduce vocabulary dropout, a random mask applied to the proposer's output logits during both policy training and curriculum generation, as a lightweight mechanism to sustain diversity. The mask is hard and non-stationary, preventing the proposer from locking into fixed token sequences. Training Qwen3-4B and Qwen3-8B on mathematical reasoning via R-Zero, we find that vocabulary dropout sustains proposer diversity across lexical, semantic, and functional metrics throughout training. It also yields solver improvements averaging +4.4 points at 8B, with the largest gains on competition-level benchmarks. Our findings suggest that explicit action-space constraints, analogous to the structural role that game rules play in classical self-play, can help sustain productive co-evolution in language. Vocabulary dropout is one simple instantiation of this principle.

03.
arXiv (CS.CV) 2026-06-11

ISAP-3D: Identity-Slot Aligned Part-Aware 3D Generation

Part-aware 3D generation aims to synthesize structured objects with semantically meaningful components, yet often suffers from structural ambiguity due to identity-layout entanglement. Existing methods either infer part identity and spatial layout implicitly, which can lead to unstable part allocation (e.g., slot swapping or part merging), or rely on strong layout conditions that are difficult to obtain in practice. We attribute this ambiguity to identity-slot permutation freedom: without explicit identity-slot alignment, the correspondence between semantic parts and generation slots is not identifiable during training, allowing multiple slot assignments to fit the same supervision and leading to inconsistent decomposition. Based on this insight, we argue that stable part-aware generation requires identity-aligned one-to-one slot modelling. We therefore propose an identity-slot aligned framework, ISAP-3D, which anchors each part with semantic identity tokens and performs identity-conditioned one-to-one layout prediction, followed by layout-conditioned geometry synthesis. Structured local-global conditioning maintains identity alignment across semantic, spatial, and geometric stages. We also construct a part-level dataset with a unified semantic protocol to enable learnable and consistent identity-slot alignment. Extensive experiments demonstrate improved structural stability, controllability, and robustness over state-of-the-art part-aware generation baselines.

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

From Parameters to Feature Space: Task Arithmetic for Backdoor Mitigation in Model Merging

arXiv:2606.12498v1 Announce Type: cross Abstract: Model merging (MM) has gained significant attention as a cost-effective approach to integrate multiple task-specific models into a unified model. However, recent work reveals that MM is highly susceptible to backdoor attacks. Existing defenses based on task arithmetic often fail to eliminate backdoors without substantially degrading clean-task performance, owing to their reliance on direct parameter-space editing. To address this gap, we propose Linear Feature Path Minimization (LFPM), a backdoor mitigation framework for model merging, which introduces an anti-backdoor task vector into the backdoored merged model. Unlike prior approaches, LFPM formulates the backdoor robustness of the merged model from a unified feature-space perspective under the Cross-Task Linearity (CTL) framework, which leverages the approximate linearity of features across tasks. This perspective guides the optimization of the anti-backdoor task to suppress backdoors while preserving clean-task performance. Furthermore, we introduce an effective optimization mechanism based on gradient accumulation and loss path-integral, ensuring robust backdoor suppression along the interpolation path. Extensive experiments demonstrate that LFPM consistently exhibits strong robustness against backdoor attacks in both full fine-tuning and Parameter-Efficient Fine-Tuning (PEFT) settings.

05.
arXiv (CS.CV) 2026-06-16

MoECa: Aligning Feature Reuse with Expert Decomposition in Diffusion Transformers

Diffusion Transformers with Mixture-of-Experts (DiT-MoE) improve model capacity under sparse activation, but diffusion inference is still bottlenecked by redundant computation across timesteps. Existing caching methods mainly operate at the token level, which becomes suboptimal in DiT-MoE because each token update is internally decomposed into multiple routed expert branches. Our analysis shows that cross-timestep redundancy in DiT-MoE is better characterized at the expert-branch level than at the whole-token level. Based on this observation, we propose MoECa, a fine-grained caching framework that performs branch-level feature reuse across timesteps. MoECa further introduces expert-aware adaptive control and synchronized cache updates across MoE and attention paths to maintain stable intermediate states. Experiments on multiple DiT-MoE models show that MoECa consistently achieves a better speed-quality trade-off than prior caching methods, with up to 2.83$\times$ inference speedup and minimal quality degradation.

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

Fully Geometric Multi-Hop Reasoning on Knowledge Graphs with Transitive Relations

arXiv:2505.12369v2 Announce Type: replace Abstract: Multi-hop logical reasoning on knowledge graphs requires faithfully mapping the logical semantics to latent space. Current geometric embedding methods show to be useful on this task by mapping entities to geometric regions and logical operations to latent transformations. While a geometric embedding can provide a direct interpretability framework for query answering, current methods have only leveraged the geometric construction of entities, failing to map logical operations to pure geometric transformations and, instead, using neural components to learn these operations. On the other hand, purely neural-based methods outperform geometric methods, but they lack interpretability in the latent space. We introduce GeometrE, a geometric embedding method for multi-hop reasoning, that maps every logical operation to a purely geometric operation in the latent space. Additionally, we introduce a transitive loss function and show that, unlike existing methods, it can preserve the logical rule for all a,b,c: r(a,b) and r(b,c) -> r(a,c). Our experiments show that GeometrE outperforms current state-of-the-art geometric methods and remains competitive with existing neural-based methods on standard benchmark datasets.

07.
arXiv (math.PR) 2026-06-16

An Algebraic Matrix Spencer Theorem

arXiv:2606.16005v1 Announce Type: new Abstract: We develop an algebraic approach to matrix discrepancy based on the representation theory of finite-dimensional C$^*$-algebras. As an application, we resolve a substantial structured special case of the Matrix Spencer conjecture. In particular, we show that for every family of contractions $A_1,\ldots,A_n$ that are contained in a finite-dimensional $C^*$-algebra $\mathcal A$ with $dim_{\mathbb C} (\mathcal A) \lesssim n$, there exists signs $x\in\{\pm1\}^n$ such that $\|\sum_{i=1}^n x_i A_i\| \le O(\sqrt n)$. As a noteworthy special case, our main result also resolves the Group Spencer conjecture of (Bandeira'24). We furthermore prove that Matrix Spencer continues to hold for low-rank perturbations of matrix families coming from an $C^*$-algebra of small dimension.

08.
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.

09.
medRxiv (Medicine) 2026-06-15

Non-Parametric Ancestry Adjustment for Polygenic Scores

Modern polygenic risk scores (PRS) exhibit shifts correlated with ancestry, leading to erroneous predictions for non-European individuals when models are trained on predominantly European cohorts. Such shifts arise from, among other factors, (1) algorithmic limitations in the ability of PRS model training to detect causal variants, rather than nearby variants with ancestry-dependent correlations to the causal one, (2) under-representation of alleles with higher prevalence in non-European populations in the association study training, and (3) gene-by-environment interactions where the environment is correlated with genetic ancestry. Current ancestry-adjustment methodologies often discretize individuals into population categories and apply a simple affine mapping to reduce these genetic ancestry biases. However, such approaches provide suboptimal adjustments, particularly for admixed individuals. In this work, we introduce a detailed theoretical characterization of ancestry-dependent biases and propose novel methods based on non-parametric neighborhood techniques that provide more accurate empirical results and admit statistical consistency guarantees. Extensive experiments using the UK Biobank demonstrate the effectiveness of the proposed methods.

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

Benchmarking Large Language Models for Safety Data Extraction

Accurate extraction of structured information from Safety Data Sheets (SDS) remains challenging in industrial safety due to heterogeneous document formats and the limitations of traditional rule-based methods. This study benchmarks state-of-the-art Large Language Models (LLMs) for automated SDS data extraction, comparing text-based and multimodal processing pipelines. We systematically evaluate four models: Gemini 1.5 Pro, GPT-4o, Claude 3.7 Sonnet, and Llama 3.1-70B, across three prompting strategies: zero-shot, few-shot, and chain-of-thought. The evaluation framework assessed accuracy, latency, and cost across more than 50,000 extracted data fields. Results show that text-based extraction consistently outperforms multimodal processing across all metrics. Gemini 1.5 Pro combined with a Chain-of-Thought prompt achieved the highest accuracy (84%), outperforming GPT-4o (81%) and Claude 3.7 Sonnet (79%). However, no model surpassed the 90% accuracy threshold commonly required for reliable real-world deployment. These findings indicate that general-purpose LLMs are not yet robust enough for unsupervised industrial use, though performance suggests strong potential with task-specific fine-tuning. Future research should focus on domain-adapted training, model calibration, and the integration of Human-in-the-Loop verification to ensure safety-critical reliability.

11.
medRxiv (Medicine) 2026-06-16

Risk beliefs, intensive digital information and demand for a new preventative health product in public clinics: Evidence from an experiment in Zimbabwe.

Demand for preventative health care is weak in low-income settings. In a field experiment in a low-income, high-risk setting, we evaluated whether demand for a new bio-medical preventative health product, offered free at public health clinics, responds to digital feedback-based intensive information on health risks and benefits of prevention along with a clinic referral enabling access to the product. In our sample of women aged 18-24 years, we find a large correction in risk beliefs sustained six months after the intervention. Against a background of very low baseline usage, within six months we find a 5.8 percentage point increase in take up of the prevention method, a level of uptake which is very large relative to the control group. Reassuringly, there is no meaningful difference in up-take amongst baseline high- risk and low-risk individuals.

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

Conditional Multi-Event Temporal Grounding in Long-Form Video

Multimodal large language models have made rapid progress in video temporal grounding, yet real-world applications routinely require localizing every event that satisfies compositional temporal and spatial conditions. Existing benchmarks fall short: they localize only a single moment per query, count without temporal conditions, or treat grounding and counting as disjoint tasks. We introduce CoMET-Bench for Conditional Multi-Event Temporal Grounding in long-form video, comprising 2789 queries over 600 videos averaging 33.8 minutes across five real-world domains, with each query composed from 4 temporal conditions, 3 spatial conditions, and a dedicated negative-query subset. We further propose a unified evaluation protocol jointly measuring counting, grounding, and negative-query recognition, including a new Rejection-F1 metric that prevents trivial gaming by lazy "always-empty" models. Benchmarking a broad suite of MLLMs, agent-based, and grounding-specialized methods reveals that existing approaches remain far from solving this task. Building on these findings, we propose CoMET-Agent, a training-free agentic framework that reformulates the task as structured search-and-aggregate, improving F1@0.5 by 6.1% over GPT-5 purely through structural reasoning. Failure analysis further surfaces three open directions: fine-grained entity tracking, position-uniform retrieval, and causal event pairing.

13.
arXiv (CS.AI) 2026-06-18

SAGE: Retain-Aware Post-Hoc Sanitization of Final Unlearning Vector

arXiv:2606.18309v1 Announce Type: cross Abstract: Large Language Model (LLM) unlearning aims to remove undesirable knowledge or behaviors while preserving retained capabilities. Current unlearning methods all involve a trade-off between unlearning and retention. We have found that the retention activation bias can also be used to quantify the damage an unlearning method inflicts on retention, without considering the specific implementation of the unlearning process. This allows us to restore retention performance for any unlearning method using a post-hoc approach. Therefore, we propose a complementary post-hoc setting to sanitize the final update vector without rerunning the original unlearning pipeline. In this setting, we design SAGE, Spectral Activation-GEometry Sanitization, a source-agnostic correction for final unlearning updates. SAGE collects real module inputs from a small retain proxy, extracts their dominant activation geometry, and solves a source-anchored optimization objective in closed form, which suppresses update components aligned with high-energy retained directions while preserving the source method's forgetting carrier. Across multiple unlearning methods, model scales, and benchmarks, SAGE consistently relieves the retain-forget trade-off, identifying post-hoc sanitization of final vectors as a practical and underexplored axis for machine unlearning.

14.
medRxiv (Medicine) 2026-06-22

The direct economic impact of surgical non-response in orthopaedic hip, knee, and spine surgery for osteoarthritis: a cost-utility analysis

Background Annually, nearly 2 million hip, knee, and spinal inpatient surgeries are performed in Canada and the US for osteoarthritis (OA), costing over $37 billion in hospital expenditures. However, 15-30% of patients experience limited or no improvement, resulting in poor value for money. This study evaluated the one-year cost-utility of joint and spine procedures for OA by comparing non-responders to responders, considering various responder definitions. Methods Individual micro-costing data were collected for 1,175 elective hip, knee, and spine patients enrolled in the Longitudinal Evaluation in the Arthritis Program - Osteoarthritis (LEAP-OA) between 2014 and 2018. Quality-adjusted life years (QALYs) were derived using the SF-6D utility index. One-year incremental cost-utility ratios (ICURs) were calculated from the hospital perspective. Results Responder rates varied by definition, ranging from 78%-94% for hip replacements, 64%-90% for knee replacements, 60%-64% for spine fusions, and 50%-68% for spine decompressions. Corresponding ICURs were: $45,956-$51,773/QALY for responders versus $108,593-$485,762/QALY for non-responders for hip replacements; $54,831-$71,151/QALY for responders versus $200,486-$1,203,596/QALY for non-responders for knee replacements; $65,980-$74,422/QALY for responders versus $262,039-$729,686/QALY for non-responders for spine fusions; and $29,947-$42,168/QALY for responders versus $63,195-$662,586/QALY for non-responders for spine decompressions. Conclusions While surgical response rates were highly dependent on the responder definition, ICURs for non-responders were significantly higher than those for responders across all definitions. Beyond the negative impact on patients, there is a compelling economic argument for investment in improved pre-operative identification of patients at risk of surgical non-response. Such efforts could enable more personalized, value-based care pathways and reduce the provision of low-value surgical interventions.

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

Light Interaction: Training-Free Inference Acceleration for Interactive Video World Models

arXiv:2605.31158v3 Announce Type: replace-cross Abstract: Interactive video world models generate video chunk by chunk in response to user-controlled camera movements, enabling applications such as real-time game simulation, virtual scene navigation, and embodied AI training. However, scaling to long interactive trajectories is prohibitively expensive due to growing context memory, quadratic attention complexity, and repeated denoising steps. We present Light Interaction, a training-free inference acceleration framework for interactive video world models. Our key insight is that interaction naturally enables trajectory-dependent adaptive computation: retrieved spatial memory can be discarded during novel exploration, temporal context can be adjusted according to local latent dynamics, and early-step model outputs can be reused when the camera revisits familiar regions. Based on this insight, Light Interaction combines adaptive context management, denoising cache acceleration, and hardware-software co-designed 3D block sparse attention with fused Triton kernels. Evaluated on HY-WorldPlay and Matrix-Game-3.0, Light Interaction achieves up to 2.59x speedup without model retraining while maintaining competitive visual quality.

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

Uncertainty Quantification of Engineering Structures by Polynomial Chaos Expansion and Multivariate Active Learning

arXiv:2606.17233v1 Announce Type: new Abstract: In many engineering applications, a single high-fidelity model produces multiple quantities of interest (QoIs) under the same input parameters, e.g. finite element models of complex physical systems. To alleviate the high computational cost of direct model evaluations, surrogate models are widely used to construct efficient approximations of model responses. Naturally, the accuracy of surrogates strongly depends on the quality of the experimental design (ED). However, a single ED may not provide an adequate representation for all outputs simultaneously, especially when different outputs exhibit varying sensitivities to the input variables. A straightforward solution is to perform separate sampling for each output, but this results in increased sampling complexity and computational cost. From a statistical perspective, such an approach also ignores potential correlations among all outputs and may compromise data consistency. To address this issue, an adaptive sequential sampling method for constructing polynomial chaos expansion surrogate models is generalized for vector valued QoIs. The method sequentially selects new samples from a candidate pool based on their local contribution to the output variance, while balancing distance-based exploration of the input space and exploitation of aggregated variance information across all outputs. Its performance is compared with non-sequential Latin Hypercube Sampling through several numerical examples from engineering problems. Numerical results demonstrate that the proposed strategy improves both surrogate accuracy and stability, and provides a more reliable estimation of second-order statistics.

17.
medRxiv (Medicine) 2026-06-16

Fidelity-Derived Quantum Dissimilarity-Enhanced k-Nearest Neighbor Algorithm for Arterial Hypertension Prediction

We present a quantum-enhanced version of the classic k-Nearest Neighbors (kNN) classification algorithm, applied to the prediction of arterial hypertension. The traditional Euclidean distance metric of the kNN algorithm is replaced with a Fidelity-derived quantum dissimilarity measure to evaluate the similarity between data samples. We map classical real-world clinical and ECG-derived data features into quantum states via the Dense-Angle Encoding, which efficiently utilizes parameterized rotation gates to pack multiple features into minimal qubits while maintaining pure states. We evaluate the performance of the dissimilarity measure using both the noiseless state vector Simulator and the IBM Qiskit Estimator primitives. The quantum circuit demonstrates robust predictive capabilities comparable to the classical model. While it does not claim computational supremacy over the classical baseline, the framework proves that fidelity-based similarity is a physically meaningful and efficient approach for hybrid quantum classical classification.

18.
arXiv (quant-ph) 2026-06-15

Jones-matrix analysis of phase accumulation in a linear-optical multi-pass interferometer

arXiv:2606.14422v1 Announce Type: new Abstract: Quantum information science has traditionally relied on nonclassical resources, such as entangled photon pairs and squeezed states, to achieve measurement performance beyond classical limits. Here, we revisit the multi-pass photonic scheme reported in Nature 450, 393 (2007) to clarify the physical origin of the observed superresolution and the associated claim of supersensitivity. Using a rigorous Jones-matrix formalism, we show that the round-trip evolution of the HQMQ linear optics unit is equivalent to the product of two reflections in polarization space, resulting in an effective rotation operator. This equivalence reveals that the accumulated phase arises from coherent polarization-state rotation on the Poincare'e sphere. The resulting phase accumulation is interpreted geometrically as a progressive realignment of the polarization state during successive forward and backward propagations. To validate the theoretical model, a classical-wave implementation is experimentally conducted, analyzed, and compared with the corresponding Jones-matrix solution. Finally, the scaling behavior of the Fisher information is analyzed to examine the origin of the claimed supersensitivity. The results are further compared with a recently developed coherence de Broglie wavelength framework, which achieves identical superresolution through repeated coherent interactions in a cascaded interferometeric architecture.

19.
medRxiv (Medicine) 2026-06-11

A continental-scale scenario modelling framework for evaluating infant RSV immunisation strategies across Europe

Background. The recent approval of long-acting monoclonal antibodies (la-mAbs) and a maternal vaccine (MV) in the EU enables universal RSV prevention in infants. Modelling studies are widely used to quantify the population-level impact of alternative immunisation strategies. However, existing assessments of new RSV immunisation products focus on national or sub-national settings. Methods. We developed an age-stratified, stochastic compartmental model of RSV transmission for 28 EU/EEA countries. It combines literature-based parameters on RSV natural history and product efficacy with country-specific demographic and contact patterns. After model calibration against age- and country-specific RSV hospitalisation rates, we designed scenarios for both la-mAbs and MV at four coverage levels, with and without catch-up immunisation for infants under six months at season onset. We then evaluated each scenario against a no-immunisation baseline. Results. At 95% coverage, the cross-country median reduction in RSV hospitalisations over one season in infants under 12 months is 29.9% for la-mAbs (country median range: 27.7-33.9%) and 22.4% for MV (20.0-25.6%), scaling linearly with coverage. Out of all averted hospitalisations, 78.3% (90% CI: [67.3, 92.7]%) are concentrated in infants aged 0-2 months for la-mAbs and 72.7% (90% CI: [61.4, 88.6]%) for MV. A catch-up campaign nearly doubles the overall reduction in RSV hospitalisations. Conclusions. Despite country-specific heterogeneities, impact of la-mAbs and MV is comparable across settings and herd-immunity effects are largely negligible. This supports harmonised European guidelines on coverage targets. Seasonal catch-up campaigns emerge as an effective lever to maximise the impact of immunisation programmes.

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

EMORSION: Examining the Impact of Audio Parameters on Emotional Responses and Immersion in Film

arXiv:2606.18266v1 Announce Type: cross Abstract: EMORSION is an exploratory proof-of-concept study examining how film audio design shapes audience emotion and immersion in acinema setting. Four film scenes were selected across the horror (2) and drama (2) genres, balanced between mainstream and independent productions. For each scene, multiple alternative audio mixes were created by systematically manipulating three core aspects of audio design, frequency (pitch), dynamics (loudness), and directionality (spatial placement). Three audience groups viewed the scenes, with each group exposed to one manipulated mix alongside a control mix for each scene. Audience responses were assessed through a triangulated multimodal framework combining self-reported emotion and immersion via a questionnaire, physiological measures including heart rate monitoring, and video-based motion tracking. The protocol successfully captured measurable, interpretable differences across audio conditions, indicating that even subtle changes in audio design can shape emotional perception and immersion. Unconventional mixes tended to produce greater variability in audience interpretation, while conventional immersive mixes were associated with stronger cross-audience agreement. These findings establish the feasibility of the EMORSION protocol and motivate larger-scale studies to characterise the role of specific audio parameters in shaping audience experience.

21.
medRxiv (Medicine) 2026-06-18

Maternal and fetal HLA heterozygosity in preeclampsia: Insights from a large multi-ancestry pregnancy cohort

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic human leukocyte antigen (HLA) region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4,770 PE, 8,020 controls; 10,808 maternal, 1,982 fetal, including 1,848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (>80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across class I loci showed a protective effect in preterm PE (OR=0.82, 95%CI:0.69-0.97), with a similar pattern for HLA-A heterozygosity (OR=0.78, 95%CI:0.64-0.96). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR=1.36, 95%CI:1.03-1.79) and preterm PE (OR=1.73, 95%CI:1.13-2.73). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE etiology.

22.
arXiv (CS.CL) 2026-06-19

EndoCoT: Scaling Endogenous Chain-of-Thought Reasoning in Diffusion Models

Recently, Multimodal Large Language Models (MLLMs) have been widely integrated into diffusion frameworks primarily as text encoders to tackle complex tasks such as spatial reasoning. However, this paradigm suffers from two critical limitations: (i) MLLMs text encoder exhibits insufficient reasoning depth. Single-step encoding fails to activate the Chain-of-Thought process, which is essential for MLLMs to provide accurate guidance for complex tasks. (ii) The guidance remains invariant during the decoding process. Invariant guidance during decoding prevents DiT from progressively decomposing complex instructions into actionable denoising steps, even with correct MLLM encodings. To this end, we propose Endogenous Chain-of-Thought (EndoCoT), a novel framework that first activates MLLMs' reasoning potential by iteratively refining latent thought states through an iterative thought guidance module, and then bridges these states to the DiT's denoising process. Second, a terminal thought grounding module is applied to ensure the reasoning trajectory remains grounded in textual supervision by aligning the final state with ground-truth answers. With these two components, the MLLM text encoder delivers meticulously reasoned guidance, enabling the DiT to execute it progressively and ultimately solve complex tasks in a step-by-step manner. Extensive evaluations across diverse benchmarks (e.g., Maze, TSP, VSP, and Sudoku) achieve an average accuracy of 92.1%, outperforming the strongest baseline by 8.3 percentage points. The code and dataset are publicly available at https://internlm.github.io/EndoCoT/.

23.
Nature Medicine 2026-06-08

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial

Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg−1) or tirzepatide plus placebo. At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16 weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63−86%)) and 36 of 51 (71% (57−81%)) participants experiencing an AE, respectively. Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0−10%)) participants in each arm. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier: NCT06445075 . In the phase 2 EMBRAZE study, participants receiving tirzepatide and apitegromab lost less lean mass compared to participants receiving tirzepatide and placebo.

24.
arXiv (math.PR) 2026-06-16

Plateau Gaps of Poisson Correctors Encode Metastable Reaction Rates

arXiv:2606.14789v1 Announce Type: cross Abstract: Metastable reaction rates are commonly inferred from transition-state fluxes, mean first-passage times, or fitted kinetic models. We show that they are directly encoded in the plateau gap of an occupation-time Poisson corrector. For a centered basin-occupation observable, the Poisson corrector develops metastable plateaus in the reactant and product basins, and their separation determines the forward and backward transition rates. This construction requires only the generator, stationary measure, and metastable partition, and therefore does not rely on a predefined transition-state surface. In overdamped and underdamped double-well dynamics, the plateau-gap rate recovers the Kramers, Grote-Hynes, and Pollak-Grabert-Hänggi hierarchy. The same corrector-martingale decomposition yields a reactive-noise density, revealing where stochastic forcing contributes to transitions in configuration or phase space. Thus, reaction rates and their fluctuation sources emerge from a single corrector field.

25.
arXiv (CS.AI) 2026-06-11

Exploration Structure in LLM Agents for Multi-File Change Localization

arXiv:2606.11976v1 Announce Type: cross Abstract: Software engineering tools increasingly rely on LLM based agents to localize files to change to resolve a software issue. Most AI agents explore repositories linearly, that is, visiting one directory or file per step. We postulate that this is a structural mismatch for changes that span several subsystems. We compare linear sequential exploration against non-linear, domain-scoped parallel agentic exploration. Using SWE Bench Pro as initial benchmark, we focus on ansible as an exemplar. We construct an approach for persistent-session evaluation of GitHub issues anchored at a single base commit. We compare our non-linear domain-agent file traversal system against a base LLM without direct repository access, a single agent Recursive Language Model (RLM) baseline with a persistent Python REPL and an external CLI baseline using Codex 5.5 High. Domain scoped parallel agent spawning with a small Haiku-class model achieves the highest micro F1 among Haiku class models by a large margin. Domain-agents is the second highest behind only the much larger Codex 5.5 High on our own expanded benchmark including over more recent PRs from 2025 and 2026. On the original, curated, 2020 SWE-bench Pro benchmark, a larger Sonnet plain LLM baseline attains higher micro F1 by predicting few files, leading to higher precision, but at significantly lower all gold recall. We also present three additional findings. First, documentation evolution is a latent dependency unresolved by any approach. Second, naive file system access can degrade localization driven by test-file over prediction. Lastly, forced multi-agent consultation does not measurably help and raises token cost substantially.