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01.
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.

02.
arXiv (math.PR) 2026-06-12

Branching-selection particle systems and inverse first passage problems

Authors:

arXiv:2606.13487v1 Announce Type: new Abstract: A generalised inverse first passage problem asks whether, given a probability measure $p$ on $[0,\infty]$, one can find a boundary $b:[0,\infty]\to \mathbb{R}$ such that the stopping time:\[\tau:=\inf\left\{t:\Lambda\int_0^t \omega(W_s-b(s))ds \geq U\right\}\] has distribution $p$, where $U\sim Exp(1)$, $\Lambda\in(0,\infty)$ and $\omega$ is a monotonic decreasing function. We construct a branching-selection particle system whose hydrodynamic limit is governed by a free boundary problem and connect this to the generalised inverse first passage problem. In the $N$-particle system, particles move as independent Brownian motions, branch at a prescribed rate, and are removed at a rate proportional to their location relative to a position $b^N(t)$ which is a function of the empirical distribution. We identify the limit of $b^N$ as the solution of the inverse first passage problem.

03.
arXiv (CS.CL) 2026-06-24

Precision Recall Controllable Radiology Report Generation via Hybrid Natural Language and Clinical Reward Learning

Automated radiology report generation (RRG) has gained increasing attention because it can reduce the heavy workload of clinical report writing. However, most existing methods mainly optimize for natural language generation (NLG) metrics that focus on language fluency, while providing little control over clinically important factors such as precision and recall. As consequence, generated reports may be fluent but not well aligned with different clinical needs. To address this challenge, we propose a reinforcement learning framework for precision recall controllable RRG, where a control parameter explicitly adjusts the trade-off between clinical precision and recall during inference. This design allows the model to flexibly generate reports according to different clinical requirements. To ensure clinical correctness, we introduce a clinical reward into the training objective, which helps improve clinical efficacy (CE) beyond standard language-based optimization. In addition, we apply a group-relative training strategy that normalizes rewards within each training group, reducing reward variance and improving training stability. Extensive experiments on the MIMIC-CXR dataset show that our method consistently outperforms state-of-the-art approaches in both NLG and CE evaluation metrics, while providing reliable control over the CE precision recall trade-off.

04.
arXiv (CS.AI) 2026-06-11

From Uniform to Learned Graph Priors: Diffusion for Structure Discovery

arXiv:2606.11831v1 Announce Type: cross Abstract: Neural relational inference (NRI) methods discover interaction graphs from trajectories through variational reasoning on discrete potential edges. However, these methods typically rely on oversimplified, factorized graph priors. Such priors, typically nearing uniform distributions, treat edges as independent entities. This systemic misalignment does not match the real-world systems and yields diffuse and indecisive edge posteriors limiting the reliability of structural discovery. To address this, we propose Diff-prior, a diffusion-parameterized adaptive prior used to calibrate latent graph distribution rather than generate graphs. Our core insight is to reframe prior integration as a learnable denoising-style calibration that organizes scattered, uncertain edge posteriors into a more reliable overall structure which can be trained by the diffusion model. Diff-prior learns an adaptive structure prior that performs structured calibration on the edge posteriors during inference, guiding it towards a distribution closer to the underlying structure. The diff-prior operates before structural sampling and acts as a denoising calibrator directly on the encoder edge distribution, which provides a generic training paradigm over structured variables. Experiments on standard benchmarks validated our framework, and the results indicate that Diff-prior improves the performance of structure inference and generates more decisive edge posteriors across multiple NRI-family architectures. The code is available on https://github.com/Hardy158118/Diffprior.

05.
arXiv (CS.CL) 2026-06-11

Pass@K Policy Optimization: Solving Harder Reinforcement Learning Problems

Reinforcement Learning (RL) algorithms sample multiple n>1 solution attempts for each problem and reward them independently. This optimizes for pass@1 performance and prioritizes the strength of isolated samples at the expense of the diversity and collective utility of sets of samples. This under-utilizes the sampling capacity, limiting exploration and eventual improvement on harder examples. As a fix, we propose Pass-at-k Policy Optimization (PKPO), a transformation on the final rewards which leads to direct optimization of pass@k performance, thus optimizing for sets of samples that maximize reward when considered jointly. Our contribution is to derive novel low variance unbiased estimators for pass@k and its gradient, in both the binary and continuous reward settings. We show optimization with our estimators reduces to standard RL with rewards that have been jointly transformed by a stable and efficient transformation function. While previous efforts are restricted to k=n, ours is the first to enable robust optimization of pass@k for any arbitrary k

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

ComAct: Reframing Professional Software Manipulation via COM-as-Action Paradigm

Existing computer-use agents remain fundamentally limited in professional software manipulation: GUI-based agents suffer from fragile visual grounding and long-horizon error accumulation, while API-basedapproaches struggle with heterogeneous protocols and inaccessible commercial interfaces. In this work,we identify the Component Object Model (COM) as a unified executable abstraction, proposing COM-as-Action: a new paradigm that reframes professional software interaction as deterministic program synthesisrather than sequential visual control. To validate this paradigm in the most demanding environments, weintroduce ComCADBench, the first benchmark for agents operating real industrial CAD software. Ourexperiments reveal a substantial paradigm gap: frontier proprietary models achieve near-zero successunder GUI-based interaction, whereas COM-based execution yields substantial immediate gains. Tobridge the remaining gap between syntactic correctness and geometric accuracy, we develop ComActor, aself-correcting agent trained through a progressive three-stage framework, alongside ComForge, a scalableplatform for large-scale training in Windows containers. Extensive experiments show that ComActorachieves state-of-the-art performance on ComCADBench, with strong resilience in long-horizon taskswhere baselines collapse, and generalizes to external CAD benchmark.

07.
arXiv (CS.CV) 2026-06-15

Mirage Probes: How Vision Models Fake Visual Understanding

Vision-language models (VLMs) can answer image-based questions confidently, and often correctly, even when no image is provided. This mirage behavior inflates benchmark scores without reflecting visual grounding. Prior work treats this as a single failure mode. We argue it is two. Using Mirage Probes, a contrastive probing framework that pairs paraphrased question variants with matched mirage and non-mirage labels on the same image, we show that mirage behavior is linearly decodable from internal activations across residual stream, MLP, post-attention, and attention-head sites in two open-source VLMs. We demonstrate that a Naive Bayes text baseline cannot recover this signal, ruling out surface lexical confounds. Cross-benchmark separability patterns, together with a novel Prior Harnessing Index (PHI) measuring how much a model can answer from text alone, expose two distinct regimes: textual biases, where the model answers from language priors without engaging visual representations, and spurious images, where it constructs false visual content in latent space and answers as if grounded. The distinction has direct mitigation consequences: text-distribution cleaning can address the first regime but cannot reach the second, since spurious-image mirages live in the model's visual representations rather than its text. Faithful visual grounding will require interventions at the representational level.

08.
arXiv (CS.AI) 2026-06-25

Weight Space Representation Learning via Neural Field Adaptation

arXiv:2512.01759v3 Announce Type: replace-cross Abstract: We investigate the potential of weights to serve as effective representations, focusing on neural fields. Our key insight is that constraining the optimization space through a pre-trained base model and low-rank adaptation (LoRA) can induce structure in weight space. Across reconstruction, generation, and analysis tasks on 2D and 3D data, we find that multiplicative LoRA weights achieve high representation quality while exhibiting distinctiveness and semantic structure. When used with latent diffusion models, multiplicative LoRA weights enable higher-quality generation than existing weight-space methods.

09.
arXiv (CS.LG) 2026-06-24

Task Vector Bases: A Unified and Scalable Framework for Compressed Task Arithmetic

arXiv:2502.01015v5 Announce Type: replace Abstract: Task arithmetic, representing downstream tasks through linear operations on task vectors, has emerged as a simple yet powerful paradigm for transferring knowledge across diverse settings. However, maintaining a large collection of task vectors introduces scalability challenges in both storage and computation. We propose Task Vector Bases, a framework compressing $T$ task vectors into $M < T$ basis vectors while preserving the functionality of task arithmetic. By representing each task vector as a structured linear combination of basis atoms, our approach supports standard operations such as addition, negation, as well as more advanced arithmetic ones. The framework is orthogonal to other efficiency-oriented improvements in task arithmetic and can be used in combination with them. We provide theoretical analysis showing that basis compression retains addition generalization guarantees and enables principled unlearning, with error bounds depending on reconstruction quality. Empirically, our proposed basis construction methods consistently outperform heuristic basis construction baselines and, in some cases, even surpass the performance of full task vector collections across diverse downstream applications while reducing storage and computational requirements. The code is available at https://github.com/uiuctml/TaskVectorBasis.

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

Discovery under Hypothesis Redundancy: A Geometric Theory of Discovery Bottlenecks

arXiv:2606.14386v1 Announce Type: cross Abstract: Scientific discovery saturates when new hypotheses cease to provide independent information, even if the nominal hypothesis space remains large. We study hybrid discovery systems that combine structured local search with LLM-generated non-local proposals and pose the Search Compression Hypothesis: non-local exploration helps only when three geometric conditions co-occur: spectral compression, orthogonal escape from the explored span, and residual signal alignment with the target. We formalize these conditions, derive necessary conditions for hybrid advantage, and test the mechanism in controlled synthetic environments, large-scale A-share factor discovery, and symbolic-regression benchmarks; a public tabular operational sanity check tests the associated budget-allocation implication. Signal-planting and directed-versus-random experiments show that novelty alone is insufficient: random orthogonal jumps expand coverage but do not improve yield without predictive alignment. Across compression sweeps, real factor archives, and LLM-SRBench tasks, hybrid gains concentrate in weakly represented but target-bearing directions and vanish as the hypothesis space approaches full rank. The framework turns LLM-guided discovery from generic novelty search into a diagnostic procedure for deciding when directed non-local exploration is warranted.

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

Damage-TriageFormer: A Foundation-Model Framework for Typology-Based Building Damage Assessment from Mono-Temporal Imagery

Decision-relevant building damage assessment is critical for prioritizing resources and recovery after a disaster, yet most automated methods either flatten damage into a single severity scale (no damage, minor, major, destroyed) or require paired pre- and post-event imagery that is often unavailable for emerging hazards. This paper presents Damage-TriageFormer, a single-image, post-event, footprint-conditioned model that produces a damage typology rather than a severity scale. We contribute: (1) DamageTriage-Bench, a new benchmark built from NOAA Emergency Response Imagery across Hurricane Michael (2018), Hurricane Helene (2024), and the 2025 Los Angeles wildfire complex, with five typology classes that distinguish roof damage from structural damage and, within each, partial from total extent; and (2) Damage-TriageFormer, which extends a DINOv3 ViT-L backbone with a Simple Feature Pyramid for higher-resolution instance pooling, a two-stage gated damage head, and an auxiliary severity-regression objective. Our model achieves macro F1 of 0.624 on validation and 0.619 on a held-out stratified test set, performing strongest where operational triage needs it most, with per-class F1 of 0.91 and 0.84 on undamaged buildings and total structural collapse, respectively. While the rare Total Roof Damage class remains difficult due to its limited examples and an inherently ambiguous label boundary, our results show that single-image post-event imagery can support actionable building damage typing, enabling targeted emergency response and resource allocation without a pre-event reference.

12.
arXiv (CS.AI) 2026-06-19

PSCT-Net: Geometry-Aware Pediatric Skull CT Reconstruction via Differentiable Back-Projection and Attention-Guided Refinement

arXiv:2606.19867v1 Announce Type: cross Abstract: Computed Tomography (CT) is essential for diagnosing pediatric craniofacial abnormalities, yet poses radiation risks to developing anatomies. Reconstructing 3D CT from sparse bi-planar X-rays offers a low-dose alternative but is severely ill-posed. Existing methods employ geometry-agnostic feature lifting, naively projecting 2D features into 3D without explicit spatial modeling, causing depth ambiguity and degraded osseous boundaries. We present PSCT-Net, a geometry-aware framework with differentiable back-projection. Differentiable back-projection establishes a spatially faithful volumetric prior, alleviating depth ambiguity. An Attention-Guided Projection (AGP-3D) module then learns non-linear voxel-wise correspondences between 2D regions and 3D locations. A Bidirectional Mamba (BiM-3D) module captures long-range volumetric dependencies with linear complexity. We further curate a private institutional pediatric skull CT cohort, PedSkull-CT, comprising normal and pathological cases for internal evaluation, addressing the gap in adult-centric, trunk-focused datasets.

13.
medRxiv (Medicine) 2026-06-22

Age-related changes in acoustic cue use for speech-in-speech perception

Authors:

Acoustic cues such as pitch and spatial location allow listeners to attend to a target speaker and ignore competing talkers, aiding speech recognition in background noise. Diminished ability to utilize acoustic cues for speech stream segregation may thus contribute to older adults' challenges hearing in noise. Adults aged 18-74 completed a speech-in-speech identification task with three conditions containing 1) only pitch cues (fundamental frequency), 2) only spatial cues (interaural time differences; ITDs), and 3) both pitch and spatial cues for segregating a target talker from competing talkers. Hearing thresholds at standard and extended high frequencies (EHFs), auditory brainstem responses (ABRs), and digit span scores were acquired to examine the influence of sensory and cognitive factors on use of each acoustic cue for speech-in-speech recognition. Significant differences were observed between cue condition scores indicating that use of the available cue(s) drove performance. ABR metrics were not a significant predictor but digit span scores significantly predicted scores on all three cue conditions. Working memory abilities therefore set a baseline for participants' speech-in-speech recognition regardless of the acoustic content. Hearing thresholds at standard frequencies significantly predicted scores on the Pitch condition. EHF hearing thresholds better predicted Spatial and Both Cue condition performance, suggesting that EHF thresholds represent auditory processing important for coding ITDs. Age group analysis revealed that older adults (aged 40+) performed significantly more poorly on all cue conditions of the speech-in-speech recognition task relative to younger adults. Age-related changes in auditory sensory processing may therefore impair older adults' speech-in-noise perception by reducing their ability to use acoustic cues for segregating target and competing speech.

14.
arXiv (CS.AI) 2026-06-11

From Consumption to Reflection: Designing Human-AI Relations for Stable Reasoning

arXiv:2606.11195v1 Announce Type: cross Abstract: Large language models (LLMs) have transformed how humans access information, but not how we reason with it. Their fluency accelerates consumption while bypassing the slow, reflective processes that underpin sound judgment. This paper introduces Relational Reflective Intelligence (RRI), an inference-time governance layer that operationalizes reflection through auditable reasoning loops. RRI operates not inside the model but around it, providing a practical structure for stable, auditable reasoning between humans and LLMs. The core premise is that LLMs inherit cognitive vulnerabilities similar to those that shape human thought: reliance on intuitive shortcuts, confusion between representation and reality, and a preference for coherence over falsification. When humans and models share these tendencies, their errors compound. We refer to this as relational drift, a failure that arises from interaction rather than from the model alone. Addressing this requires a shift from modeling relations between words to structuring relations between model outputs and human reasoning. RRI provides this missing layer through three components: the Rose-Frame, which identifies likely breakdowns in reasoning; the Architect's Pen, which introduces targeted reflection steps at critical moments; and an inference-time workflow that embeds these steps without retraining the model. Together, these elements transform human-AI interaction into a joint reasoning system with explicit checkpoints, conflict surfacing, and an auditable trail of assumptions. Rather than making machines think like humans or forcing humans to reason like machines, RRI creates a structured interaction in which both compensate for each other's limitations. It reframes AI safety as a cognitive architecture problem, where reliable decisions depend on embedding reflection directly into the interaction process.

15.
arXiv (CS.CV) 2026-06-25

MIMFlow: Integrating Masked Image Modeling with Normalizing Flows for End-to-End Image Generation

Normalizing Flows (NFs) are powerful generative models capable of exact density estimation and sampling. However, their strict invertibility often forces the model to exhaust its capacity on low-level pixel details, hindering the capture of high-level semantic structures. While Masked Image Modeling (MIM) has excelled in representation learning, its integration into generative pipelines has remained largely modular and disjointed. In this paper, we propose MIMFlow, a unified end-to-end framework that jointly optimizes latent semantics, pixel reconstruction, and generative flow. By employing a VAE encoder to infer semantic latent from masked images, MIMFlow achieves a principled decoupling of the generative task: the Normalizing Flow focuses on modeling a simplified, low-frequency semantic manifold, while a specialized decoder handles high-frequency synthesis. This design effectively resolves the inherent capacity bottleneck of NFs, allowing the model to prioritize global structural coherence over redundant noise. Empirical results on ImageNet 256$\times$256 show that MIMFlow-L reaches 71.3\% linear probing accuracy and an FID of 2.50. Despite using only 128 tokens (50\% fewer than standard models), it yields a 32.8\% performance gain over similar-scale NF baselines. Our code is available at https://github.com/MCG-NJU/MIMFlow.

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

Empirical Study of Pop and Jazz Mix Ratios for Genre-Adaptive Chord Generation

Authors:

arXiv:2605.04998v2 Announce Type: replace-cross Abstract: This revision updates a pop-to-jazz chord-generation rehearsal study. Best-epoch metrics still show that modest pop rehearsal preserves pop accuracy while improving jazz prediction, but v2 corrects released-checkpoint selection: the released F1 equals Phase 0, F2 had a transcription error, and ft-pop80-v2 restores a hash-distinct jazz-adapted F1 across 3 seeds.

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

BrainDINO: A Brain MRI Foundation Model for Generalizable Clinical Representation Learning

Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis. Code is available at https://github.com/mclwu22/BrainDINO

18.
arXiv (quant-ph) 2026-06-19

Quantum Dynamics from Lax Pair Theory: A Reconstruction from Spectrum Preservation

arXiv:2606.19664v1 Announce Type: new Abstract: We reconstruct unitary quantum dynamics from a minimal axiomatic foundation built on Hilbert-space observables and isospectral evolution. The only dynamical assumption is that physical time evolution is a continuous one-parameter flow of Hermitian observables that preserves their spectra, i.e. the possible outcomes of measurement. We show that this assumption is already sufficient to force the Lax form of quantum dynamics. The Heisenberg equation, the time-dependent and time-independent Schrödinger equations, conservation laws, and good quantum numbers then follow as theorems rather than postulates. In this formulation, Lax pair theory supplies the missing dynamical bridge between the measurement structure of a Hilbert space and standard quantum evolution: the Hamiltonian is not assumed, but emerges as the generator required for an isospectral observable flow.

19.
medRxiv (Medicine) 2026-06-24

Using outlier detection methods to incorporate highly heterogeneous infection rates into compartment models

Superspreading events (SSEs) produce extreme, rare bursts of disease transmission that standard compartment models, which assume population homogeneity, fail to capture. This inability to model heterogeneity in transmission rates can result in biased estimates of transmissivity. To address this limitation, we present a modular framework that treats SSEs as statistical outliers in case count time series and incorporates them into SIR-type models via pulse terms that transfer SSE cases directly from susceptible to infected compartments. This separation isolates anomalous SSE-driven transmission from background spread, which reduces bias when estimating mean transmission rates. We validate the approach on synthetic data generated by a stochastic model with embedded SSEs, demonstrating accurate recovery of the true non-SSE transmission parameter. We then apply the method to COVID-19 outbreaks in Hong Kong and the German district of Gutersloh, showing improved model fits and more robust estimates of background transmissivity both for a period with constant transmission and for a period with temporally structured NPI-driven heterogeneities. The framework's interchangeable outlier-detection, compartment, and SSE modules make it adaptable to diverse diseases and data contexts.

20.
arXiv (CS.AI) 2026-06-16

Relational Structural Causal Models

arXiv:2606.14892v1 Announce Type: new Abstract: An artificial intelligence must have a model of its environment that is causal, supporting reasoning about interventions and counterfactuals, and also combinatorial, supporting generalization to unseen combinations of objects. In this work, we formally study when and how such a model can be learned. We develop relational structural causal models, extending structural causal models (Pearl 2009) to settings where objects and their relations vary. First, we show how answers to not only causal but also observational queries about unseen combinations of objects can not be identified without further assumptions. To enable such identification–including in the presence of unobserved confounding–we define relational causal graphs and derive symbolic identification criteria. Finally, we propose relational neural causal models, a provably correct approach that outperforms non-relational baselines on simulated traffic scenes with varying cars, signals, and pedestrians.

21.
bioRxiv (Bioinfo) 2026-06-16

Better data, better trees: GenBank-GISAID deduplication and source-specific artifact masking in viral genomics

GenBank and GISAID are the primary repositories for viral genomic data, but integrating records across them remains a challenge. The same sequence could be made available in both databases without any cross-reference linking the two entries. Consequently, there is no systematic way to identify this redundancy, which compromises the compilation of representative, non-redundant large-scale datasets. In parallel, the growth of viral genomic data has increased the risk of systematic technical artifacts introduced during sequencing or assembly. These artifacts can inflate substitution rate estimates and degrade temporal signal, biasing evolutionary rate estimates. To address both challenges, here we present a formal, reproducible workflow integrating two newly developed complementary tools: G2G matcher for cross-repository harmonization and Lab-Specific Bias FILTer (LSBFILT) for masking of laboratory-specific artifacts. Using the Eastern/Central/South African (ECSA) chikungunya virus lineage as a proof-of-concept, we demonstrate that our integrated workflow restores temporal signal and provides a robust, curated dataset for downstream phylodynamic analyses. Critically, restricting masking of homoplastic sites to specific sequences reduces the substitution rate estimate from an inflated 8.517 x 10e-4; to 5.078 x 10e-4; substitutions/site/year and increases the coefficient of determination (R2) of the root-to-tip regression analysis from 0.353 to 0.677. By enabling systematic cross-repository harmonization and source-specific artifact masking, we provide the molecular epidemiological community with scalable tools to reconcile fragmented genomic data and reduce technical biases, fostering more accurate and reproducible phylogenetic analysis. G2G matcher is available at https://github.com/andrezaleite/G2G-Matcher, and LSBFILT at https://github.com/khourious/LSBFILT.

22.
PLOS Medicine 2026-06-09

Molecular Tumor Boards clinical impact on patient care and structural features: A systematic review and meta-analysis

Authors:

by Luigi Russo, Erika Giacobini, Nicolò Lentini, Tommaso Osti, Maud Kamal, Stefania Boccia, Roberta Pastorino Background Molecular Tumor Boards (MTBs) bring together multidisciplinary experts to translate genomic data into clinical decisions in oncology, however, their overall clinical impact remains unclear. The aim of this systematic review is to assess the clinical impact of MTB-recommended therapies on patients with cancer outcomes. Methods and findings In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and CENTRAL up to July 2025. We included studies of any design, both single-arm studies and studies with a comparator group, that reported the clinical impact of MTBs in patients who received MTB-guided therapy. Meta-analyses were performed separately by study design, using hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for objective response rate (ORR) and disease control rate (DCR), and pooled proportions for PFS ratio ≥1.3. All meta-analyses were conducted using random-effects models based on the inverse variance method. We evaluated the risk of bias using the RoB 2.0 for RCTs and ROBINS-I for non-randomized studies.From 6,846 records, 78 studies (9,195 patients; 4,569 treated per MTB recommendations) were included. MTB-guided therapies were associated with reduced risk of death (HR 0.87; 95% CI [0.76, 1.01]; p = 0.069; I2 = 0.0% in RCTs; 0.62 in retrospective studies) and disease progression (HR 0.73; 95% CI [0.64, 0.84]; p 

24.
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.

25.
bioRxiv (Bioinfo) 2026-06-20

A network approach to DNA methylation clocks

Biological age predicts health and lifespan better than chronological age, but remains difficult to measure. One leading molecular proxy for biological age is DNA methylation, which underlies age predictors known as "clocks". These clocks use penalized linear regression to predict chronological age from methylation levels using selected cytosine–guanine pairs (CpGs) along DNA. Although they predict chronological age within a few years and track mortality risk, there are several issues. Different clocks share a vanishingly small number of CpG sites, many of which show weak associations with age. Also, the clocks often do not transfer across methylation array platforms. This paper takes a network approach to better understand these issues. By using 12 public datasets from human blood, we build a co-methylation network of the sites that show the strongest age correlation. After pruning weak links, we find that it has a small number of large modules of covarying CpGs surrounded by many small modules and singleton sites. These modules are biologically interpretable, as they are associated with CpG island contexts and enriched for distinct Gene Ontology functions. We also map five established clocks onto this network (Horvath, Hannum, AltumAge, Skin & Blood, and Han) and find that they select some CpGs from the same module. This suggests that they are more similar than they appear. The network structure also suggests new ways to build clocks. A simple clock that retains one CpG per module matches the performance of established clocks. A second one, built from module-level principal components, outperforms all five established clocks in three validation cohorts and is transferable across array platforms (Illumina Infinium Methylation 450K or EPIC arrays). Overall, the network perspective shifts attention from individual CpG sites to modules of covarying sites. This perspective helps explain why DNA methylation clocks perform so well despite their differences and provides a more systematic approach for developing the next generation of aging biomarkers.