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01.
medRxiv (Medicine) 2026-06-15

Socioeconomic inequalities in smoking prevalence and intensity in Germany: A repeated cross-sectional analysis from 1998 to 2024

Background: Smoking inequalities by socioeconomic status have widened consistently in Germany, but sex-specific trends after 2013 and inequalities in daily cigarette consumption among smokers (intensity) are unknown. We analyzed trends in absolute and relative socioeconomic inequalities in smoking prevalence and intensity among German adults across three decades. Methods: We used 14 waves (1998-2024) of population-representative cross-sectional data from the German Socio-Economic Panel to estimate sex-specific trends in smoking prevalence and intensity in adults aged 25-64. Inequalities were quantified across strata of education, occupation, and equivalized household income using the absolute and relative concentration index with 95% bootstrap confidence intervals. Results: Overall smoking prevalence declined from 35.05% (CI: [33.90%, 36.20%] in 1998 to 22.19% (CI: [21.15%, 23.24%]) in 2024, and mean intensity from 17.49 (CI: [17.09,17.90]) to 13.33 (CI: [12.88, 13.79]) cigarettes/day. Over this period sex-differences in both outcomes narrowed almost completely. Absolute and relative inequalities in smoking prevalence widened across all SES dimensions, particularly for education and occupation. By 2024, inequalities were larger among women than men driven by a stagnating or rising smoking prevalence among low-SES women at least until 2018 alongside continued declines in higher-SES women and for men. Inequalities in smoking intensity, particularly related to income, were generally smaller than those in prevalence. Conclusion: Socioeconomic smoking inequalities in Germany widened from 1998 to 2024 primarily driven by reductions among higher-SES groups and increases in low-SES women. However, recent reductions in low-SES women may indicate a new phase in the smoking epidemic. Health equity considerations should be integrated into a targeted German tobacco control strategy.

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

No One Knows the State of the Art in Geospatial Foundation Models

Geospatial foundation models (GFMs) have been proposed as generalizable backbones for disaster response, land-cover mapping, food-security monitoring, and other high-stakes Earth-observation tasks. Yet the published work about these models does not give reviewers or users enough information to tell which model fits a given task. We argue that nobody knows what the current state of the art is in geospatial foundation models. The methods may be useful, but the GFM literature does not standardize evaluations, training and testing protocols, released weights, or pretraining controls well enough for anyone to compare or rank them. In a 152-paper audit, we find 46 cross-paper disagreements of at least 10 points for the same model, benchmark, and protocol; 94/126 papers with extractable pretraining data use a configuration no other paper uses; and 39% of GFM papers release no model weights. This lack of community standards can be solved. We propose six concrete expectations: named-license weight release, shared core evaluations, copied-versus-rerun baseline annotations, variance reporting, one shared evaluation harness, and data-vs-architecture-vs-algorithm controls. These gaps are a coordination failure, not a fault of any individual lab; the authors of this paper, like many others in the GFM community, have contributed to them. Rather than just critiquing the community, we aim to provide concrete steps toward a shared understanding of how to innovate GFMs.

03.
arXiv (quant-ph) 2026-06-19

Exploiting More Than Symmetry in Variational Quantum Machine Learning

arXiv:2606.20316v1 Announce Type: new Abstract: The success of variational quantum learning models crucially depends on choosing parametrizations that reflect the structure of the problem at hand. Symmetries provide one of the clearest such structures: whenever transformations of the input leave the desired outcome unchanged, this invariance should be built into the model rather than discovered during training. However, imposing a symmetry does not by itself determine a useful ansatz. Even within the symmetry-preserving space, one must decide where the trainable degrees of freedom should be placed. In this work, we study this remaining design freedom in equivariant variational quantum circuits. Building on symmetry-based parameter sharing, we disentangle two architectural choices: how much symmetry should be enforced, and which symmetry-respecting interactions should be trainable. Using Tic-Tac-Toe as a fully enumerable and structurally transparent test case, we find that suitable subgroups preserve most of the generalization benefit. By contrast, the dominant gains arise from gates acting directly on decisive task motifs. Thus, symmetry defines the admissible design space, while effective ansatze require an additional task-informed choice of trainable interactions.

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

VideoMDM: Towards 3D Human Motion Generation From 2D Supervision

We introduce VideoMDM, a diffusion-based framework that trains 3D human motion priors directly from accurate 2D poses extracted from monocular videos, without any 3D ground truth. A pretrained 2D-to-3D lifter provides approximate 3D pose sequences that serve as a noisy teacher: these are diffused, denoised by the model in 3D, and supervised in 2D by reprojecting the prediction and comparing against accurate keypoints. We show that, under mild assumptions, a depth-weighted 2D reprojection loss is equivalent in expectation to direct 3D supervision, and we adapt standard 3D motion regularizers - velocity consistency and over-parameterized representation alignment - to this 2D setting. Unlike methods that lift 2D to 3D only at inference, VideoMDM learns a coherent 3D motion manifold during training. On HumanML3D it nearly closes the gap to fully 3D-supervised MDM (FID 0.88 vs 0.54); On real video datasets Fit3D and NBA the method learns to generate motions consistently preferred by humans, with strong quantitative results.

05.
arXiv (CS.AI) 2026-06-19

BIM-Edit: Benchmarking Large Language Models for IFC-Based Building Information Modeling

arXiv:2606.20146v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly applied to computer-aided design (CAD) to generate design artifacts from textual instructions. In engineering practice, this requires more than creating new geometry, models must also understand existing scenes, edit them correctly, and preserve semantics and relations. However, many CAD benchmarks focus on creating new models rather than editing existing ones, and mostly evaluate geometric correctness. We introduce BIM-Edit, a benchmark for evaluating LLMs on natural-language editing of Building Information Models (BIM) represented in the Industry Foundation Classes (IFC) format. BIM provides a challenging testbed because building models encode geometry together with semantic and relational structure. BIM-Edit contains 324 editing tasks spanning 11 realistic building models and 36 synthetic scenes. Tasks are expressed using three instruction categories - direct, spatial, and topological - covering both explicit and scene-grounded edits. We evaluate outputs along three dimensions: geometric accuracy, semantic validity, and topological consistency. Across evaluated LLMs, the best-performing model achieves only 49.5% average score across the three metrics, and no model fully solves more than 3.4% of tasks. These results demonstrate a substantial gap between current LLM capabilities and the requirements of structured engineering design workflows.

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

Brain-IT-VQA: From Brain Signals to Answers

Decoding visual content from fMRI signals recorded while a person views images, and specifically answering questions about the seen images, is a long-standing challenge. While significant progress has been made in recent years in visual question answering (VQA) from fMRI, performance remains limited. Moreover, although recent models can make increasingly accurate predictions, they have rarely been used as tools for understanding the structure of visual representations in the brain. We present Brain-IT-VQA, a framework for visual question answering from fMRI. Building on the Brain Interaction Transformer (Brain-IT), our method decodes language tokens from brain activity and integrates them with a language model to answer visual questions. Our model substantially outperforms previous fMRI-based captioning and VQA approaches. We further introduce NSD-VQA, a new dataset and benchmark for visual question answering from fMRI. Unlike existing image-fMRI VQA datasets, which typically provide only a few broad and weakly controlled questions per image, NSD-VQA provides on average 20 question-answer pairs per image across 20 controlled question categories that disentangle multiple levels of visual understanding. This enables more reliable and interpretable evaluation despite limited fMRI test data. Together, Brain-IT-VQA and NSD-VQA provide both a strong predictive framework and a tool for studying brain representations. Using this benchmark, we quantify which forms of visual and semantic information can be reliably decoded from fMRI responses to natural images. We further analyze the contributions of different brain regions across question types.

07.
arXiv (quant-ph) 2026-06-15

An integrated ultrahigh vacuum cluster tool for diamond surface science and single nitrogen-vacancy center measurements

arXiv:2606.13961v1 Announce Type: new Abstract: We present a custom-designed ultrahigh vacuum (UHV) cluster tool developed for studying shallow nitrogen-vacancy (NV) centers in diamond, enabling in situ diamond surface preparation, characterization, and single NV center dynamics measurements within a single connected platform. The system combines a surface science chamber for controlled surface modification and analysis with a cryogenic confocal microscope chamber dedicated to NV spin and optical measurements. This integrated approach enables a direct correlation between diamond surface chemistry and the resulting NV spin and charge properties. The instrument provides a versatile platform for systematic studies of surface-induced decoherence mechanisms and charge dynamics for shallow NV centers, and establishes a pathway toward reproducible surface engineering for quantum sensing applications.

08.
arXiv (CS.CL) 2026-06-17

From Observation to Intervention: A Causal Audit of Expert Importance in Mixture-of-Experts Models

Interpretability methods routinely use population-level summary statistics over observed model behaviour to license claims about the effects of targeted interventions on specific computations; in Pearl's terms, they treat rung-1 associational evidence as if it supported rung-2 interventional conclusions, a move whose validity is rarely tested. We examine one concrete instance: the use of routing statistics in Mixture-of-Experts (MoE) pruning, where utilization rates, activation norms, and routing weight distributions are treated as predictors of which experts can be removed without functional cost. A token-level interventional audit across three high-redundancy MoE architectures (OLMoE-1B-7B-0924, Qwen1.5-MoE-A2.7B, DeepSeek-V2-Lite) finds no observational metric predicts causal expert importance in any model: across all 60 metric-layer combinations effect sizes stay below Cohen's $d = 0.23$, and no metric is reliably positive under our corrected, dual-test criterion. A per-token routing weight control, run with identical $n$, rules out insufficient power, recovering a signal whose CI excludes zero at OLMoE's final MoE layer ($d = +0.231$, 95\% CI $[+0.09, +0.37]$, $p = 0.0013$). Existing pruning methods succeed in this regime not by identifying dispensable experts but because early-layer redundancy renders most selection criteria interchangeable. Our results provide an explicit counterexample to the common inferential step from population-level observational summaries to token-level interventional claims about expert importance, and illustrate how interventional audits can calibrate the evidential standards for interpretability claims.

09.
arXiv (CS.AI) 2026-06-12

Structured vs. Unstructured Pruning: An Exponential Gap

arXiv:2603.02234v3 Announce Type: replace-cross Abstract: The Strong Lottery Ticket Hypothesis (SLTH) states that large, randomly initialized neural networks contain sparse subnetworks capable of approximating a target function at initialization without training, suggesting that pruning alone is sufficient. Pruning methods are typically classified as unstructured, where individual weights can be removed from the network, and structured, where parameters are removed according to specific patterns, as in neuron pruning. Existing theoretical results supporting the SLTH rely almost exclusively on unstructured pruning, showing that logarithmic overparameterization suffices to approximate simple target networks. In contrast, neuron pruning has received limited theoretical attention, despite its practical appeal for direct hardware speedups. In this work, we consider the problem of approximating a single bias-free ReLU neuron by pruning hidden units of a randomly initialized two-layer ReLU network, effectively isolating the intrinsic limitations of neuron pruning. We show that achieving an $\varepsilon$-approximation requires a starting network size of $\Omega(1/\varepsilon)$ for neuron pruning, whereas weight pruning succeeds with only $O(\log(1/\varepsilon))$ hidden units, revealing an exponential separation between the two approaches.

10.
arXiv (quant-ph) 2026-06-24

High-harmonic generation driven by temporal-mode quantum states of light

arXiv:2512.06602v2 Announce Type: replace Abstract: We develop a theoretical framework for high-harmonic generation (HHG) driven by quantum states of light based on a temporal-mode expansion of the electromagnetic field. This approach extends previous single plane-wave mode treatments to realistic pulse configurations and arbitrary multi-mode states of light, resolving conceptual inconsistencies arising from non-normalizable infinite plane waves and establishing consistency between analytical and numerical methods. We derive a correction factor that quantifies deviations from the diagonal approximation (in which the yield becomes a statistical average over classical-field simulations) both for the response of a single atom and in the many-atom regime. Our results confirms that the HHG spectrum for atoms driven by any quantum state of light in free space is accurately described by averaging semi-classical calculations over the Husimi distribution, with no observable genuine quantum effects in the spectrum. We also demonstrate that in the many-atom regime, the mean-field coherent-state approximation underlying this treatment does not preserve probabilities, although unitarity is restored by in the diagonal approximation. The absence of genuine quantum effects in the HHG yield is attributed to the large photon numbers ($\sim 10^{11}$) required to reach HHG intensities in free space, which render quantum fluctuations negligible. We discuss nanophotonic environments with ultrasmall mode volumes as potential platforms where few-photon strong-field processes could exhibit genuine quantum signatures.

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

Shepherd: Enabling Programmable Meta-Agents via Reversible Agentic Execution Traces

arXiv:2605.10913v3 Announce Type: replace Abstract: As LLM agent systems take on more complex tasks, they increasingly rely on meta-agents: higher-order agents that create, operate on and manage other agents. Meta-agent operations such as coordinating agents, halting risky actions before execution, or repairing failed runs, require runtime manipulation of agentic execution. Yet existing agentic substrates make this difficult: they expose only transcripts and environment snapshots, forcing meta-agents to build ad hoc tooling to reconstruct and operate over full execution state. Therefore, we introduce Shepherd, a Python substrate grounded in functional programming principles, where an agent's execution is itself a first-class object that a meta-agent can easily inspect and transform. Every model action, tool call, and environment change becomes a structured event in a reversible, Git-like execution trace, where any past state can be reverted 5x faster than docker commit and fork. Three example use cases show Shepherd's versatility: (1) a supervisor meta-agent prevents conflicts among parallel coding agents, lifting pair-coding pass rate from 28.8% to 54.7% on CooperBench; (2) a counterfactual optimization meta-agent repairs agent workflows by proposing edits and replaying runs from the point of changed behavior, outperforming MetaHarness on Terminal-Bench 2.0 by 12.8% with 58% lower wall-clock; (3) a training meta-agent picks fork points during rollouts to improve credit assignment in long-horizon agentic RL, doubling GRPO's uplift on Terminal-Bench 2.0. We open-source Shepherd to enable principled and efficient operations over agentic execution for both users and meta-agents.

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

Repurposing a Speech Classifier for Guided Diffusion-Based Speech Generation

arXiv:2606.20457v1 Announce Type: cross Abstract: Classifier guidance is a way to control diffusion generation by using a noise-conditioned classifier to steer the sampling process toward a target class. One drawback of classifier guidance is that it requires two separately trained models: a classifier and a diffusion model. We therefore study a more compact alternative in which a conventionally trained speech classifier is repurposed as the backbone for diffusion generation. Starting from a frozen noise-conditioned classifier in log-Mel space, we attach a lightweight subnetwork that reuses intermediate classifier representations and train only this subnetwork under a Denoising Score Matching objective. Our work shows that a pretrained classifier can be repurposed for conditional generation, providing an appealing bridge between discriminative modeling and conditional speech synthesis resulting in high speech quality within a single-backbone model, with reduced memory footprint and computational cost.

13.
medRxiv (Medicine) 2026-06-18

MOSAIC: Methylation-Oriented Site Analysis and Information Classifier for Robust Epigenomic Classification of Acute Leukemia in Clinical Cohorts with Variable Tumor Purity

DNA methylation-based classification offers a rapid diagnostic complement to conventional molecular workflows in acute leukemia. Existing classifiers are trained on array-derived reference cohorts whose construction favors specimens with adequate tumor content, leaving clinically relevant low-purity specimens underrepresented and classifier robustness in this regime uncharacterized. On held-out low-purity specimens, existing classifiers were concordant with expert pathology in only 7 of 10 (MARLIN) and 5 of 10 (ALMA) cases, motivating a classifier built to maintain accuracy at low tumor purity. We developed MOSAIC (Methylation-Oriented Site Analysis and Information Classifier), a neural network classifier built to maintain accuracy across the full range of tumor purities encountered in clinical practice. MOSAIC is a neural network trained on publicly available array-based methylation data augmented with native methylation calls from Oxford Nanopore sequencing. MOSAIC was evaluated on low-purity specimens held out entirely from training. On these held-out low-blast leukemia specimens, all below 25% blasts and including a case at 1.4%, MOSAIC was concordant with expert pathology in every case, recovering the correct subtype where diluted disease signal would otherwise be mistaken for normal or unrelated tissue. Gradient-based saliency analysis showed that the network relies on a partially distinct set of discriminative CpG probes when classifying low-blast specimens. MOSAIC demonstrates that augmenting training with clinically representative clinical specimens yields methylation-based leukemia classification that maintains effectiveness under the variable tumor purity of real clinical cohorts.

14.
medRxiv (Medicine) 2026-06-22

Rare loss-of-function variants in POLD1, PMS1 and FAN1 modify age at onset of motor symptoms in Huntington's disease

Huntington's disease is a rare neurodegenerative disease whose primary risk factors are inherited expansions of a CAG repeat tract in the HTT gene. Somatic expansion of these tracts leads to neuronal toxicity, neuronal death and clinical disease progression. To identify genetic factors with a major impact on disease onset and progression, we genome sequenced 18,825 individuals for the ENROLL-HD study. Our results show rare inactivating mutations in three genes, all involved in DNA damage repair, are major determinants of age of onset for motor symptoms (n=10,610) and other clinical manifestations. Heterozygote carriers of predicted loss-of-function (pLoF) variants in POLD1 and PMS1 developed motor symptoms an average 20 years (n=3; P=1x10-5) and 7 years (n=6; P=2x10-3) later than non-carriers, respectively. Conversely, heterozygote carriers of pLoF variants in FAN1 (n=30) developed symptoms 10 years earlier (P=2x10-10). Our findings highlight therapeutic strategies and help predict age of onset for at-risk individuals.

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

HULFSynth : An INR based Super-Resolution and Ultra Low-Field MRI Synthesis via Contrast factor estimation

We present an unsupervised single image bidirectional Magnetic Resonance Image (MRI) synthesizer that synthesizes an Ultra-Low Field (ULF) like image from a High-Field (HF) magnitude image and vice-versa. Unlike existing MRI synthesis models, our approach is inspired by the physics that drives contrast changes between HF and ULF MRIs. Our forward model simulates a HF to ULF transformation by estimating the tissue-type Signal-to-Noise ratio (SNR) values based on target contrast values. For the Super-Resolution task, we used an Implicit Neural Representation (INR) network to synthesize HF image by simultaneously predicting tissue-type segmentations and image intensity without observed HF data. The proposed method is evaluated using synthetic ULF-like data from generated from standard 3T T$_1$-weighted images for qualitative assessments and paired 3T-64mT T$_1$-weighted images for validation experiments. WM-GM contrast improved by 52% in synthetic ULF-like images and 37% in 64mT images. Sensitivity experiments demonstrated the robustness of our forward model to variations in target contrast, noise and initial seeding.

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

Against probability: A quantum state is more than a list of probability distributions

arXiv:2601.18872v2 Announce Type: replace Abstract: The state of a quantum system can be represented by listing the outcome probabilities for a tomographically complete set of measurements. Such representations appear throughout physics, for example, in quantum field theory via correlation functions and in quantum foundations within generalized probabilistic frameworks. In this paper, we show a no-go result: To enable useful statements, the probability representation must be topologically robust$\unicode{x2014}$preserving the notion of closeness between states. Yet, a topologically robust probability representation cannot simultaneously retain other essential structure, such as the subsystem structure.

17.
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.

18.
arXiv (CS.LG) 2026-06-15

Multidimensional Bayesian Active Machine Learning of Working Memory Task Performance

arXiv:2510.00375v2 Announce Type: replace Abstract: While adaptive experimental design has outgrown one-dimensional, staircase-based adaptations, most cognitive experiments still control a single factor and summarize performance with a scalar. We show a validation of a Bayesian, two-axis, active-classification approach, carried out in an immersive virtual testing environment for a 5-by-5 working-memory reconstruction task. Two variables are controlled: spatial load L (number of occupied tiles) and feature-binding load K (number of distinct colors) of items. Stimulus acquisition is guided by posterior uncertainty of a nonparametric Gaussian Process (GP) probabilistic classifier, which outputs a surface over (L, K) rather than a single threshold or max span value. In a young adult population, we compare GP-driven Adaptive Mode (AM) with a traditional adaptive staircase Classic Mode (CM), which varies L only at K = 3. Parity between the methods is achieved for this cohort, with an intraclass coefficient of 0.755 at K = 3. Additionally, AM reveals individual differences in interactions between spatial load and feature binding. AM estimates converge more quickly than other sampling strategies, demonstrating that only about 30 samples are required for accurate fitting of the full model.

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

Scalable Production Scheduling: Linear Complexity via Unified Homogeneous Graphs

arXiv:2604.23841v2 Announce Type: replace-cross Abstract: Efficiently solving the Job Shop Scheduling Problem in real-world industrial applications requires policies that are both computationally lean and topologically robust. While Reinforcement Learning has shown potential in automating dispatching rules, existing models often struggle with a scalability bottleneck caused by quadratic graph complexity or the architectural overhead of heterogeneous layers. We introduce a unified graph framework that employs feature-based homogenization to project distinct node roles into a shared latent space. This allows a standard homogeneous Graph Isomorphism Network to capture complex resource contention with linear complexity, ensuring low-latency inference for large-scale industrial applications. Our empirical results demonstrate that our framework achieves state-of-the-art performance while exhibiting consistent zero-shot generalization. We identify the job-to-machine ratio as the primary driver of policy effectiveness, rather than absolute problem size. Based on this, we propose a hypothesis of structural saturation, demonstrating that policies trained on critically congested instances ($\mathcal{J} \approx \mathcal{M}$) learn scale-invariant resolution strategies. Agents trained at this saturation point internalize invariant conflict-resolution logic, allowing them to treat massive rectangular instances as a sequential concatenation of saturated sub-problems. This approach eliminates the need for expensive scale-specific retraining and prevents overfitting to statistical shortcuts, providing a robust and efficient pathway for deploying RL solutions in dynamic production environments.

20.
bioRxiv (Bioinfo) 2026-06-11

DivQuant: Estimation of Species Richness and Entropy from Small Samples

Estimating diversity properties of discrete distributions from a small observed sample is a fundamental problem in algorithmic statistics that has applications in many fields, in particular bioinformatics, but also in ecology or linguistics. The two most common diversity measures are the number of distinct elements in a multiset, also referred to as species richness in ecology or alpha diversity in microbial analysis, and the Shannon entropy, also referred to as evenness. Estimating these properties from a small sample is particularly challenging for distributions with many rare elements. Thus, many estimators have been proposed in the past that, in practice, work well for different types of distributions. We present DivQuant, an optimization-based, extrapolating richness and entropy estimator with three contributions. First, we formulate the upsampling problem as a convex quadratic program with a Neyman {chi}2 objective. Unlike the linear program of its predecessor RichnEst, DivQuant admits confidence intervals via {chi}2 test inversion that are empirically well-calibrated. Second, we replace RichnEst's fixed-threshold fingerprint truncation with the rare/abundant fingerprint split of Valiant and Valiant, which strongly reduces problem size and preserves enough degrees of freedom for the confidence-interval program to remain valid and feasible. Third, we plug the optimal population fingerprint returned by the program into Shannon's entropy formula to obtain an entropy estimate. DivQuant attains close-to-nominal 95% confidence intervals in essentially all tested regimes, including six simulated distribution families, Tara Oceans microbiome data, and 10X Genomics scRNA-seq data, while competing state-of-the-art methods (RichnEst, iNext, PreSeq) miss the true richness in up to 80% of instances, well above the nominal 5%. In addition, DivQuant outperforms classical asymptotic entropy estimators (Miller-Madow, CAE) and the extrapolating iNext estimator. Running times remain competitive, with DivQuant typically completing in seconds. DivQuant is available as a command-line tool at https://gitlab.com/rahmannlab/divquant.

21.
medRxiv (Medicine) 2026-06-15

Two Blood-based Endotypes Reveal Divergent Clinical Outcomes of Fibrotic Hypersensitivity Pneumonitis

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an antigen-driven, life-threatening interstitial lung disease characterized by heterogeneous radiologic features, clinical outcomes, and treatment responses. Objectives: To identify blood-based fHP endotypes that inform mechanism, prognosis and therapeutic response. Methods: We performed integrative analyses of multi-compartment transcriptomic data derived from whole blood, peripheral blood mononuclear cells, bronchoalveolar lavage, and surgical lung biopsies, alongside circulating plasma proteomics. Multiple clustering algorithms were cross-compared to ensure robustness and reproducibility of endotypes identification. Immune cell composition was inferred using bulk RNA-seq deconvolution and annotated with BAL single-cell RNA-seq. Pathway activities were characterized using Gene Set Enrichment Analysis. Transplant-free survival (TFS) was evaluated for endotype and corticosteroid exposure by Kaplan-Meier methods, with hazard ratios analyzed using multivariable Cox proportional hazards models. Results: Two molecular endotypes, lymphocytic-associated (L-fHP) and non-lymphocytic-associated (N-fHP), were identified and validated. L-fHP showed enrichment of adaptive immune signaling and lymphocyte predominance, whereas N-fHP demonstrated myeloid-cell activation with neutrophil and macrophage predominance. Corticosteroid exposure was associated with worse TFS in L-fHP but not in N-fHP after adjusting for age, sex, and baseline pulmonary function. Compared to L-fHP, N-fHP had poorer baseline pulmonary function, faster 12-month FVC decline, and shorter TFS. N-fHP also exhibited elevated neutrophil-associated markers, including matrix metalloproteinase-9, across paired transcriptomic and proteomic datasets, supporting a neutrophil-driven, cross-compartment disease process. Conclusion: Multi-omic, multi-compartment analysis identifies two reproducible fHP endotypes with distinct clinical outcomes and corticosteroid responses, supporting a precision medicine approach beyond current clinical and radiologic classification.

22.
arXiv (CS.CV) 2026-06-24

Flood Mapping from RGB imagery using a Vision Foundation Model

Timely, high-resolution maps of flood extent around settlements are essential for emergency response and damage assessment. We consider airborne RGB imagery for flood mapping as it can be collected rapidly at low cost. To produce flood maps, deep learning models for water segmentation are often used. CNN based and small vision transformer models are used. However, they need much data for adaptation to a change of scenery, i.e., another flooding event. Vision foundation models or large vision transformers are known to generalize across domains. Recently, foundation models for Earth observation became available. They are pretrained on satellite data, whose spatial resolution, viewing geometry, and radiometry differ from nadir RGB imagery. Thus, adaptation is required. We investigate how a satellite-pretrained Earth observation foundation model can be adapted to centimeter-scale floodwater mapping from RGB imagery. Specifically, we fine-tune a model we call Prithvi-2.0-UPN consisting of the Prithvi-EO-2.0-600M Vision Transformer combined with a UPerNet decoder for binary water segmentation on two RGB datasets (BlessemFlood21, NeuenahrFlood). In a first experiment we observe that Prithvi-2.0-UPN reaches state-of-the-art results on BlessemFlood21 and NeuenahrFlood, when trained on their datasets. In a second experiment we show that Prithvi-2.0-UPN performs better than state-of-the-art baseline models for transfer to a new flood event (trained on BlessemFlood21, tested on NeuenahrFlood) in a zero-shot setting. However, the performance indicates room for improvement. In this respect, we investigate in a third experiment how performance improves when further fine-tuning the models with small shares of NeuenahrFlood training data: Prithvi-2.0-UPN improves the fastest and reaches almost the performance level when fully trained on NeuenahrFlood, indicating transfer capabilities.

23.
medRxiv (Medicine) 2026-06-22

Characteristics and Outcomes of Gene-Elusive Dilated Cardiomyopathy

Background and Aims Genetic testing in dilated cardiomyopathy (DCM) guides risk stratification and family screening. Likely pathogenic or pathogenic (LP/P) variants are identified in approximately one-third of patients, leaving many without a genetic diagnosis. Cohort studies suggest that "gene-elusive" patients have a lower risk of adverse events. This study aims to better characterise this group and identify factors associated with adverse outcomes. Methods Consecutive and unrelated DCM patients undergoing genetic testing and returning no LP/P variants were retrospectively recruited and compared to two control cohorts of DCM patients carrying LP/P variants in LMNA and TTN for a primary composite endpoint of end-stage heart failure (ESHF) or malignant ventricular arrhythmia (MVA). Results Among patients without prior MVA, the composite endpoint occurred in 36/423 (8.5%) gene-elusive, 14/39 (35.9%) LMNA and 11/100 (11%) TTN cardiomyopathy patients (log-rank p

24.
arXiv (CS.LG) 2026-06-15

Neural Slack Variables for Shape Constraints

arXiv:2606.13803v1 Announce Type: new Abstract: Enforcing functional inequality constraints such as monotonicity and convexity in neural networks is a fundamental challenge in many industrial and scientific applications. Classical one-sided penalty methods, along with primal-dual methods gated by complementary slackness, provide constraint gradients only at violated locations, resulting in fragile satisfaction. Architectures that guarantee feasibility by construction, on the other hand, remain largely limited to elementary cases and impose additional inductive biases. We introduce neural slack variables, a deep learning native primal-side approach that converts constraint enforcement into a regression problem by coupling the primary network with a jointly learned auxiliary network. The auxiliary network serves as a valid target for the primary network's constraint quantities, inducing feasibility and regularity. Neural slack variables achieve zero measured violations on dense-grid monotonicity and convexity test cases, where penalty and primal-dual baselines leave residual violations, and enable arbitrage-free learning of volatility surfaces, an open industrial challenge in quantitative finance.

25.
medRxiv (Medicine) 2026-06-23

Post Hoc Localization of Beam F3 Stimulation Targets: An MRI-Derived Geodesic Approach for Refined TMS E-Field Simulations

Background: Transcranial magnetic stimulation (TMS) targeting the left dorsolateral prefrontal cortex (dlPFC) is an established treatment option in major depressive disorder. One of the most common approaches for targeting the dlPFC is the Beam F3 method, which determines the stimulation site (F3Beam) as a function of external cranial measurements. Precise knowledge of the individual stimulation site is essential for imaging-based analyses of TMS effects. However, due to the method's reliance on individual anatomy, retrospective identification of F3Beam targets across cohorts is challenging, limiting the analysis of existing datasets. We developed a scalable method to reconstruct subject-specific F3Beam target locations for e-field simulations based on structural imaging. Methods: High-resolution three-dimensional (3D) T1-weighted MRI was used to generate individual scalp meshes via the ''Simulation of Non-Invasive Brain Stimulation'' (SimNIBS) software. Subject-specific anatomical distances and coordinates of interest were measured geodesically using a Python-based script to reconstruct the individual F3Beam targets. Validation included a retrospective comparison between digital geodesic measurements and manual cranial measurements in 20 patients and a prospective comparison with MR-visible scalp markers in 2 healthy controls. To assess the impact of our targeting algorithm on e-field simulations, volumetric e-field maps based on three potential targets (F3Beam, F3MNI, F3Geo) were generated in SimNIBS and compared using voxel-wise statistics in SPM12. Results: Retrospective analysis revealed a systematic bias towards higher in vivo measurements compared to digital geodesic measurements, though deviations in the final distances determining F3Beam (xBeam and yBeam) were minimal ({Delta}xBeam: 0.11 {+/-} 0.08 cm; {Delta}yBeam: 0.14 {+/-} 0.21 cm). Prospective validation demonstrated that F3Beam coordinates better matched in vivo coil positions than group-template-derived targets (F3MNI). Group-level analysis showed method-dependent clustering of coil positions with corresponding voxel-wise e-field differences. Conclusions: Individualized geodesic measurements may enable accurate, scalable and retrospective identification of Beam F3 targets and coil orientations. This approach may yield more accurate e-field simulations than group-template based targeting and provides a practical method for retrospective analysis of existing TMS treatment cohorts. This could be leveraged to identify response predictors or imaging-based biomarkers of treatment response.