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01.
arXiv (CS.LG) 2026-06-17

Regularized Machine Learning for System Identification of Ship Free-Running Manoeuvres from CFD-Based Synthetic Data: A Comparative Study

arXiv:2606.17121v1 Announce Type: cross Abstract: This study investigates supervised machine learning techniques for identifying ship hydrodynamic coefficients from CFD-generated data from free-running simulations. Specifically, ordinary least squares and regularized regression methods are applied to Abkowitz-type manoeuvring models. Training and validation datasets are derived from URANS simulations of zig-zag and turning circle manoeuvres, which are validated against experimental benchmark data. The analysis evaluates the effects of coefficient set size, minimum training length required for predictive model training, and manoeuvre combinations on model performance. Results demonstrate the suitability of large-angle zig-zag manoeuvres for hydrodynamic system identification, provided that multicollinearity is addressed through appropriate coefficient selection, regression models, or input data variability. Larger coefficient sets offer greater model flexibility for variable conditions but are more prone to multicollinearity. Regularized regression techniques effectively mitigate multicollinearity and notably enhance prediction accuracy, as does incorporating more diverse manoeuvring data. Among tested models, Ridge regression provided the best compromise between computational efficiency and prediction accuracy.

02.
medRxiv (Medicine) 2026-06-16

Recurrence After Hepatic Hydatid Cyst Surgery: Scolicidal Agent Application Technique and the Effect of Cystopiliary Fistula

Objective: This study aimed to evaluate long-term outcomes in patients who underwent surgical treatment for hepatic hydatid cyst (HCC) disease and, in particular, to investigate the effect of scolicidal agent (SA) application method and the presence of cystobiliary fistula (CBF) on the development of recurrence. Materials and Methods: This single-center, retrospective study included 197 patients who underwent surgical treatment for HCC disease. Hypertonic saline was used as SA in all patients and was classified as intracystic or pericystic application according to the application method. The presence of CBF was evaluated according to intraoperative and postoperative findings. Patients were followed for 86 months, and the development of recurrence was identified by radiological methods. Comparisons were made between the groups with and without recurrence in terms of SA application method and the presence of CBF. Results: The median age of the patients was 38 years, and the median follow-up period was 86 months. SA application was performed into the cyst in 51.3% of the patients and around the cyst in 48.7%. The presence of CBF was detected in 49.7% of the patients. No statistically significant difference was found between the recurrent and non-recurrent groups in terms of SA application method (p = 0.344). Similarly, no significant relationship was found between the presence of CBF and the development of recurrence (p = 0.721). Conclusion: This study showed that the SA application method and the presence of CBF are not determinants of recurrence in HCC disease. It is thought that recurrence rates can be kept low with appropriate surgical technique and effective biliary tract management.

03.
arXiv (quant-ph) 2026-06-15

Universal Crossovers of Stabilizer Entropy Beyond Criticality

arXiv:2606.13810v1 Announce Type: new Abstract: Stabilizer Rényi entropy has emerged as a probe of nonstabilizerness in quantum many-body systems, but its scaling structure beyond critical points remains poorly understood compared with entanglement entropy. Recent field-theory approaches indicate that stabilizer entropy contains universal critical data and boundary-sensitive terms, raising the question of how these structures extend into massive and crossover regimes. We address this problem for a broad class of finite-range spin chains at Rényi index one-half. We derive exact finite-size formulas for both full periodic chains and finite intervals of the infinite chain, making the universal crossover from critical to noncritical behavior analytically accessible. In periodic geometry, the entropy obeys a volume law away from criticality and exhibits a universal finite-size crossover controlled by the competition between system size and correlation length. We also show that the large-scale SRE density develops a cusp across the field-tuned critical line, while the XX endpoint is governed by a distinct scaling regime associated with the saturation point. In the subsystem geometry, the interval entropy separates bulk critical behavior from boundary contributions generated by the way the finite region cuts the infinite chain. The crossover from critical to massive behavior is then encoded in boundary constants and universal functions controlled by the correlation length. Through exact stabilizer-entropy correspondences, the scaling theory extends to internal XY reductions, Finite-range spin chains, and Cluster–Ising representatives. Our results provide an exact lattice benchmark for the emerging QFT description of stabilizer entropy beyond isolated conformal points.

04.
arXiv (quant-ph) 2026-06-12

Intermediate State Formation of Topologically Associated Chromatin Domains using Quantum Annealing

arXiv:2505.23289v2 Announce Type: replace Abstract: Topologically Associating Chromatin Domains are spatially distinct chromatin regions that regulate transcription by segregating active and inactive genomic elements. Empirical studies show that their formation correlates with local patterns of epigenetic markers, yet the precise mechanisms linking 1D epigenetic landscapes to 3D chromatin folding remain unclear. Recent models represent chromatin as a spin system, where nucleosomes are treated as discrete-state variables coupled by interaction strengths derived from genomic and epigenetic data. Classical samplers struggle with these models due to high frustration and dense couplings. Here, we present a quantum annealing (QA) approach to efficiently sample chromatin states, embedding an epigenetic Ising model into the topology of D-Wave quantum processors. Rather than reconstructing exact TAD size distributions or insulation scores, our method reproduces statistical features, such as mean marker incidences and intra-/inter-nucleosome correlations, while generating configurations that exhibit TAD-like structural motifs. These results demonstrate QA as an alternative to explore the chromatin architecture and provide a foundation in epigenetic modeling.

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

Sustainable Materials Discovery in the Era of Artificial Intelligence

arXiv:2601.21527v3 Announce Type: replace-cross Abstract: Artificial intelligence (AI) has transformed materials discovery, enabling rapid exploration of chemical space through generative models and surrogate screening. Yet current generative AI models for materials discovery, which now drive exploration of vast chemical and structural spaces, optimize candidates exclusively for structural stability and functional properties, with no integration of environmental assessment at any stage of the design loop. Prospective and ex-ante life cycle assessment methods exist and have been applied to emerging technologies, but they operate as standalone downstream analyses, not as active constraints within generative or active-learning pipelines. The result is that environmental feedback, even when produced, arrives after design decisions have been made rather than informing them. The disconnect between atomic-scale design and lifecycle assessment (LCA) reflects fundamental challenges: (i) data scarcity across heterogeneous sources, (ii) scale gaps from atoms to industrial systems, (iii) uncertainty in synthesis pathways, and (iv) the absence of frameworks that co-optimize performance with environmental impact. In this Perspective, we propose integrating upstream ML-assisted materials discovery with downstream LCA into the ML-LCA framework, comprising five components: information extraction for building materials-environment knowledge bases, harmonized databases linking properties to sustainability metrics, multi-scale models bridging atomic properties to lifecycle impacts, ensemble prediction of manufacturing pathways with uncertainty quantification, and uncertainty-aware optimization enabling simultaneous performance-sustainability navigation. Case studies spanning polymers, glass, photoresists, and cement demonstrate both necessity and feasibility while identifying material-specific integration challenges.

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

Electromagnetic Wightman functions and vacuum densities for a brane intersecting the AdS boundary

arXiv:2604.17583v2 Announce Type: replace-cross Abstract: We investigate the combined effects of a brane intersecting the AdS boundary and background gravitational field on the local characteristics of the electromagnetic vacuum. Two types of boundary conditions on the brane are considered, which are higher-dimensional generalizations of the perfect electric (PEC) and perfect magnetic (PMC) boundary conditions in Maxwell's electrodynamics. The brane-induced contributions to the Wightman functions of the vector potential and field tensor are explicitly extracted. Simple expressions in terms of elementary functions are provided. The behavior of the vacuum expectation values (VEVs) is mimicked by a scalar field with a negative effective mass squared determined by the radius of the AdS spacetime. The expectation values of the electric and magnetic fields squares and of the energy-momentum tensor are investigated as local characteristics of the vacuum state. The brane-induced contributions to these VEVs have opposite signs for the PEC and PMC conditions. For the PMC condition, this contribution is negative for the electric field squared and positive for the magnetic field squared. The VEV of the energy-momentum tensor has a nonzero off-diagonal component. The brane-induced vacuum energy density is positive for PMC condition, whereas the normal and parallel stresses change sign as functions of the distance from the brane. Unlike the problem involving a planar boundary in the Minkowski bulk, the vacuum energy-momentum tensor does not vanish in (3+1)-dimensional AdS spacetime.

07.
medRxiv (Medicine) 2026-06-16

Exercise Training Improves Skeletal Muscle Insulin Sensitivity and Reprograms the Adipose Transcriptome in Heavier Monozygotic Twins

Exercise training improves skeletal muscle insulin sensitivity, yet its effects on white adipose tissue remain incompletely understood. We investigated how adiposity and exercise training influence insulin-stimulated glucose uptake in skeletal muscle and abdominal subcutaneous adipose tissue (ASAT), alongside adaptations in gene expression and DNA-methylation. Ten monozygotic twin pairs discordant for BMI underwent [18F]FDG-PET/CT imaging of skeletal muscle (vastus lateralis, VL) and ASAT during a euglycemic-hyperinsulinaemic clamp before and after six months of exercise training. VL and ASAT biopsies were analyzed using mRNA-sequencing and reduced representation bisulfite sequencing. Exercise training improved whole-body and VL insulin sensitivity in leaner and heavier co-twins (p

08.
medRxiv (Medicine) 2026-06-15

Automated AI-Based Ventricular Subcompartment Segmentation and Volumetry in Idiopathic Normal Pressure Hydrocephalus

Purpose In idiopathic normal pressure hydrocephalus (iNPH), longitudinal monitoring of ventricular size is important for diagnosis and treatment follow-up. This study aimed to validate a fully automated AI model for CT ventricular volumetry with subcompartments and to compare AI-derived volume changes with routine radiology assessments. Methods This retrospective, single-center study included 88 patients with iNPH and 456 non-contrast-enhanced head CT examinations. The model was trained on 38 manually labeled CT scans with 12 ventricular subcompartments. Outcomes included segmentation accuracy, correspondence between AI-derived longitudinal ventricular volume changes and radiology report categories (decreased, unchanged, increased), radiologist detection thresholds for ventricular change, and paired pre- and postoperative volume changes in 22 patients with ventriculoperitoneal shunt. Results Mean segmentation accuracy was high (Dice, 0.83). 91% of 100 segmentations were rated as excellent by an expert neuroradiologist. AI-derived ventricular volume changes corresponded well to radiology report categories (median total ventricular volume changes of -17% in cases reported as decreased, 0% in unchanged cases, and +22% in increased cases; all p < 0.001). Radiologists reported ventricular volume change in 50% of cases at an AI-measured relative volume change of +/-6%, and in 90% of cases at +21% for enlargement and -18% for decrease. After shunt placement, ventricular volume decreased by -8% (median), with the largest relative reductions observed in the right temporal and occipital horns. Conclusions Automated AI-based ventricular segmentation on CT enables accurate and reproducible assessment of ventricular volume changes in iNPH and complements routine radiological evaluation for longitudinal and postoperative monitoring.

09.
arXiv (quant-ph) 2026-06-17

Pulse-optimised circuit elements for scalable and noise-resilient quantum chemistry

arXiv:2606.17357v1 Announce Type: new Abstract: Useful chemistry calculations on near-term quantum processors are hindered by current algorithmic runtimes. We develop a methodology to significantly reduce these runtimes. Typically, variational quantum eigensolver (VQE) algorithms are implemented as sequences of primitive gates. Our methodology instead relies on gradient-ascent pulse engineering to construct hardware-tailored pulses for the direct implementation of VQEs. As problem sizes increase, it quickly becomes intractable to optimise a pulse that implements an entire VQE ansatz circuit. However, leading VQEs are constructed in a modular fashion. A problem-tailored VQE is assembled from parameterised circuit elements that simulate hopping between two or four electronic spin orbitals. We show that these circuit elements can be implemented more efficiently using hardware-tailored pulses. We numerically demonstrate our methodology on a silicon spin-qubit quantum processor. We find that common circuit elements, known as single- and double-qubit excitations, can be implemented in less than 289 ns and 927 ns, respectively. Compared with conventional gate-based implementations, our pulse-accelerated qubit excitations provide a scalable approach for faster and therefore more noise-robust quantum chemistry simulations by reducing VQE runtimes by up to a factor of 15.3.

10.
medRxiv (Medicine) 2026-06-15

International Consensus Guideline on Management of Genitourinary Adverse Events Associated with Prostate Cancer Radiotherapy

Purpose/Objective: Genitourinary (GU) adverse events (AEs) are common during and after pelvic radiation therapy (RT) for prostate cancer and can substantially impact quality of life. We convened an international committee to establish consensus in the prevention, mitigation, and management of radiation-related acute and late GU AEs, as there are no relevant evidence-based consensus guidelines to inform treating providers. Materials/Methods: A systematic evidence review focused on mitigation and management of radiation-related acute and late GU AEs was performed in PubMed, Embase and Cochrane. The following topics were addressed: management of acute GU AEs in the intact and post-operative settings; RT techniques; bladder outlet obstruction procedures; and indications for urology referral or hyperbaric oxygen therapy (HBO). Evidence-based consensus recommendations were developed using a Delphi process. We highlight the current state of evidence and evidence gaps worthy of future study. Results: Consensus was reached for 31 key questions. For management of lower urinary tract symptoms (LUTS), most evidence comes from trials in patients without cancer and not undergoing RT. A consensus algorithm for medical management of acute GU AEs was developed with the following highlights: (a) alpha blockers as 1st-line for obstructive symptoms in the intact setting, (b) anti-spasmodics as 1st -line for irritative symptoms in the intact setting, and (c) anti-spasmodics as 1st -line in the post-operative setting. The consensus algorithm provides an ordered list of medications to offer if 1st -line options afford inadequate relief. For RT fractionation, randomized clinical trial (RCT) data are available. 40% of panelists rarely or never use standard fractionation over moderate hypofractionation for patients with baseline LUTS, but most consider moderate hypofractionation over SBRT for AUA IPSS > 15. For patients with severe obstructive LUTS (most commonly AUA IPSS >20), the panel recommends a prophylactic bladder outlet obstruction procedure and, if obstructive symptoms improve, consideration of moderate hypofractionation or SBRT, based on retrospective data. There is one RCT supporting use of HBO for late radiation cystitis. Conclusions: The consensus guideline synthesizes available evidence and expert opinion across key clinical decision points to provide practical guidance in the prevention, mitigation, and management of radiation-related acute and late GU AEs in prostate cancer RT. Envisioned as a living document with periodic updates, this guideline serves as a resource for practicing radiation oncologists by outlining expert-derived consensus recommendations of evidence-based care in areas where high-quality data is limited.

11.
medRxiv (Medicine) 2026-06-16

Investigating naming error patterns after non-invasive brain stimulation and language treatment in persons with aphasia

Abstract Background: Transcranial direct current stimulation (tDCS) paired with behavioral language therapy can improve naming in persons with aphasia (PWA), yet naming errors persist. Little is known about how naming error patterns change after non-invasive brain stimulation is combined with language treatment. Aims: To examine whether right cerebellar tDCS plus computerized aphasia therapy changes the types of naming errors in people with chronic aphasia across timepoints, and to determine whether effects differ by cerebellar tDCS polarity (anode vs. cathode). Methods and Procedures: In a randomized, double-blind, sham-controlled, within-subject crossover study, we retrospectively analyzed behavioral data from 24 individuals with post-stroke aphasia. Each participant completed two 15-session intervention periods (3-5 sessions/week) with active cerebellar tDCS + computerized aphasia therapy and sham + computerized aphasia therapy, separated by a two-month washout. General linear models (GLMs) assessed longitudinal changes in six error types (semantic, phonological real word, phonological nonword, no response, mixed, unrelated) on an untrained picture naming task (Philadelphia Naming Test; PNT) and a trained task (Naming 80; N80). Additional GLMs evaluated polarity effects with 2 (Group: anode vs. cathode) x 2 (Treatment) interactions, and treatment-order effects with 2 (Group: tDCS-first vs. sham-first) x 2 (Treatment) interactions. Outcomes and Results: Active cerebellar tDCS did not significantly change error types for trained items (N80). For untrained items (PNT), active tDCS reduced several error types relative to sham, with the clearest and most durable reduction in phonological nonword errors; more moderate reductions occurred for phonological real word and unrelated errors. Mixed errors showed a marginally opposite pattern, tending to increase after tDCS and decrease after sham. Polarity analyses indicated broadly similar effects across anodal and cathodal stimulation overall, but only the anode group showed a reliable treatment effect for phonological nonword errors on the PNT. Treatment-order analyses revealed no significant order effects. Conclusions: Our results indicate a shift in naming error types, particularly after tDCS treatment for the untrained naming task (PNT). These findings may help guide the course of treatment approaches of those with aphasia and what error naming pattern types may show changes post stroke when combining non-invasive brain stimulation and computerized aphasia therapy. Clinical Trial Registration: Cerebellar Transcranial Direct Current Stimulation and Aphasia Treatment [NCT02901574] Keywords: aphasia, naming errors, non-invasive brain stimulation, cerebellar tDCS, computerized aphasia treatment

12.
medRxiv (Medicine) 2026-06-18

Hospital-Level Variation in Antenatal Corticosteroids for Late Preterm Births

Objective: To determine whether and to what extent hospitals across the United States vary in their use of late-preterm steroids using a novel data set in which the timing of steroid administration relative to delivery can be observed. Methods: This was a retrospective cohort study of singleton births with known gestational ages identified in the Premier Healthcare Database from 2015 to 2022. The primary variable of interest was hospital-level adoption of antenatal corticosteroids for late-preterm singleton deliveries, calculated as the proportion of late-preterm singleton births (34-36 completed weeks of gestation) with any betamethasone exposure during the same late-preterm period. Hospital adoption was defined as the weighted average rate of ALPS administration among late-preterm infants across the entire post-period. Hospitals were ranked by their late-preterm steroid adoption rates and categorized by quartile based on the empirical distribution. Temporal trends were assessed using annual hospital-level adoption rates and visualized using time-series plots and distributional plots. A logistic regression model was constructed to determine hospital characteristics associated with being a highest-quartile adopting hospital. Results: The analysis cohort included 728 hospitals and 5,452,791 births, of which 361,006 (6.6%) were singleton late preterm births. Hospital steroid exposure rates ranged from 0 to 82% and were categorized into quartiles based on overall exposure rate, with cutoffs at 20.6%, 29.8%, and 40.1%. Median exposure rates increased progressively across quartiles from 14.1% (IQR 9.3-17.4%) in the lowest adopting hospitals (Q1) to 47.6% (IQR 43.7-53.2%) in the highest adopting hospitals (Q4), with substantial within-quartile variation. In the multivariable model, urban location was a strong predictor of high adoption after adjustment (aOR 2.05; 95% CI 1.11-3.83, p=0.02). Compared to Midwest hospitals, Southern hospitals had significantly lower odds of being high adopters (aOR 0.37; 95% CI 0.20-0.69, p

13.
medRxiv (Medicine) 2026-06-18

Early-life Urban Environment, Nutrition, and Pubertal Timing in Southern Europe: An Exposome Analysis

Background: Urban environmental and lifestyle factors during early life may influence pubertal timing, but the combined effects of multiple environmental exposures within an exposome analytical framework remain poorly understood. Objective: To examine the association between early-life urban environmental exposures and pubertal timing, and to explore whether these exposures interact with early-life nutritional factors, namely breastfeeding duration and childhood diet quality. Methods: Data from two European population-based birth cohorts were analysed: Generation XXI (G21, Portugal; n=5263; 51.5% girls) and INfancia y Medio Ambiente (INMA, Spain; n=1019; 50.1% girls). Urban environmental exposures including indicators of air pollution, traffic, built environment, and natural spaces were estimated at 4 early-life stages at both cohorts: pregnancy (INMA only), birth, 1 year, and 4-5 years of age. Pubertal development timing was assessed using Tanner staging and/or the Pubertal Development Scale (PDS), and age at menarche was self-reported. Exposome-Wide Association Study (ExWAS) models and unsupervised clustering followed by ordinal logistic regression models were used to examine single- and multi-exposure associations, respectively. Regression models were fitted adjusting for relevant child characteristics, maternal factors, and household socioeconomic conditions, and corrected for multiple testing. Results: Individuals living in more unfavourable urban environments characterised by higher building density, air pollution, and lower access to natural spaces showed earlier pubertal timing according to multiple outcomes, across multiple early-life exposure periods, and in both cohorts. In the G21 cohort, these environmental profiles were associated with earlier age at menarche, particularly for exposures at 1-1.5 and 4-5 years (e.g., 1-1.5y: {beta}=-0.172, FDR-adjusted p-value=0.041), while in the INMA cohort, boys exposed to more unfavourable environmental profiles showed more advanced pubertal development, also particularly for exposures at 1-1.5 and 4-5 years of age (e.g., 1-1.5y; {beta}=0.572, FDR-adjusted p-value=0.008). Among environmental domains, air pollution and traffic were the factors most consistently associated with pubertal timing. Regarding early-life nutritional factors, longer duration of exclusive breastfeeding was associated with a lower Tanner stage among girls in G21. No significant interactions between breastfeeding duration and environmental exposure clusters were observed. Conclusion: Early-life urban environmental exposures, particularly air pollution and traffic, may influence pubertal timing. Exclusive breastfeeding may have a protective role against earlier pubertal development. These findings highlight the importance of improving urban environmental conditions and promoting breastfeeding to support healthy developmental trajectories.

14.
medRxiv (Medicine) 2026-06-15

Recruitment, Retention Approaches and Community Engagement in the THRIVE pilot Trial: Lessons Learned from a Food is Medicine Trial

Background: Recruitment of underrepresented populations, including Black and Hispanic populations, for Food is Medicine (FIM) and cardiovascular trials, may pose significant challenges. Methods: We implemented a multi-component recruitment approach for the THRIVE (AdapTive personalized dietitian coacHing and messaging with pRoduce prescrIptions to improVE healthy dietary behaviors) pilot trial to engage primarily Black and Hispanic adults in a Food is Medicine for hypertension intervention. The recruitment approaches included community engagement at approximately 40 community events (cultural festivals and neighborhood gatherings); partnerships with 8 community and faith-based service hubs and food distribution sites; recruitment through safety net primary care clinics, digital outreach via the study website, and social media campaigns; and direct recruitment at places of worship. We report lessons learned from the community engagement process, recruitment efficiency, representativeness, and retention outcomes. Results: Within 6 months, the enrollment target was exceeded by 40%, with an accrual index of 1.04. Over 1,000 individuals were reached through the direct-to-community engagement process, while faith-based partnerships engaged about 900 adults. There were 2,673 visits to the study webpage, and social media achieved 12,259 impressions with 399 clicks. About 95% of participants resided within 10 miles of the faith-based recruitment sites. Face-to-face engagement at the food distribution sites within faith-based organizations or community service hubs outperformed digital methods. Faith leader endorsements and follow-up in-person meetings (following unsuccessful email outreach) dramatically increased recruitment. Regarding retention, pre-randomization attrition was 6%, and 82% of participants completed the study. Conclusion: Culturally tailored, community-engaged recruitment grounded in faith-based and local community partnerships, was highly effective in engaging Black and Hispanic populations in this FIM cardiovascular trial. This provides a replicable model for implementing equitable and sustainable cardiovascular health interventions.

15.
bioRxiv (Bioinfo) 2026-06-18

Metrics for Evaluating Biological AI Model Predictive Accuracy at the Data-Substrate Level

Authors:

Reports in the biological literature disagree on whether a given model can predict a biological outcome from a given data sample — one study finding a model capable, another, on the same kind of data, finding it is not. This is particularly a challenge in relation to LLMs–where the models are large and opaque, with weights and training data inaccessible.textbf{ }Such disagreements cannot be settled by directly inspecting the model. To address this challenge, we considertextbf{ }an alternative approach: assessing whether the data sample is adequate to support the prediction asserted. For a given dataset, its substrate — the underlying structure of the data — determines what any model can recover, independent of architecture or capacity. At the same time, predicting the present state of a biological process and predicting the direction of its future change are different tasks; the second is supportable among AI models only where the data encode direction as determinable from the state — a property we call encoding — and is unsupportable where the same observed state precedes change in opposite directions — a property we call non-identifiability, in the informational rather than the statistical sense. We introduce two generic metrics, Predictive Blindness Risk (PBR) and Prediction Indeterminacy Measure (PIM), that evaluate a data substrate for predictive accuracy directly — without access to model weights, architecture, or training data — and locate the regions of a data substrate where a predictive claim can be supported and where it cannot. Using human biological subjects, we employ the Yale Brain Metastases Longitudinal Data (1,430 human subjects; 11,892 MRI studies; four sequences) and show that direction of change was non-identifiable across regions encompassing the majority of transitions; a nonlinear AI model gained essentially nothing over majority-direction prediction there while recovering direction near-perfectly where the state encoded it; and model accuracy tracked data-substrate resolvability continuously (Spearman {rho} = -0.95 to -1.00). The metrics adjudicate, before any model is trusted and from the data alone, where claims of predictive accuracy — of state, or of the law of change — can be supported.

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

Towards Fast GNN Surrogates for CO2 Migration in Complex Geological Formations

arXiv:2606.17180v1 Announce Type: new Abstract: This chapter discusses how a data-driven machine learning approach can reproduce key aspects of the physical behavior of multiphase flows in complex geological formations. We propose an end-to-end graph neural surrogate tailored to CO$_2$ plume migration forecasting in geological storage. The method is evaluated on the SPE11A benchmark, a well-known industry test case designed to assess CO$_2$ storage scenarios and characterized by sharp gas-water interfaces, strong advective transport, and rapid convective mixing with fingering development. The benchmark is reformulated as a graph in which nodes represent computational cells and edges encode transmissibility-based interactions enriched with geometric attributes. Directional transport arising from grid geometry, permeability contrasts, and geological heterogeneity is captured through an anisotropic message-passing mechanism, where interaction weights are computed via geometry-conditioned edge embeddings, biasing message aggregation toward physically relevant transport directions. Temporal evolution is modeled in latent space using an autoregressive residual formulation trained with multi-step supervision. The proposed model produces competitive forecasts of gas saturation and liquid-phase density, which are key indicators for CO$_2$ storage monitoring, with cumulative errors that remain moderate over extended forecasting horizons.

17.
medRxiv (Medicine) 2026-06-22

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort

Expanded short tandem repeats contribute to a broad spectrum of neurodegenerative diseases, yet their roles in Parkinson's disease (PD) and parkinsonism remain incompletely characterized, especially across diverse ancestries. We analyzed short-read whole-genome (WGS) and clinical exome sequencing (CES) data from 38,365 individuals (28,861 WGS; 9,504 CES), encompassing 23,242 patients with PD, 4,729 patients with atypical parkinsonism and 10,394 healthy controls from 11 genetic ancestries. To determine carrier frequencies and characterize repeat structures across diverse ancestries, we genotyped 12 established pathogenic loci where normal, intermediate, and pathogenic alleles can be reliably differentiated using short-read sequencing data. Additionally, we conducted threshold-based associations to determine the minimum threshold associated with increased PD risk in 15,995 individuals (8,591 PD, 7,404 controls) of European ancestry. Pathogenic repeat expansions were detected in 62 patients (56 PD and 6 atypical parkinsonism) and 5 controls across seven loci (AR, ATXN1, ATXN2, ATXN3, CACNA1A, HTT and THAP11), spanning seven ancestries. Among these, ATXN2 expansions were the most frequently observed in PD and were present in African, East Asian, European and Middle Eastern ancestries. Additionally, intermediate ATXN2 repeat expansions exhibited a strong, length-dependent association with PD risk in the European population, with individuals with [&ge;]32 repeats having a more than four-fold increased risk (odds ratio 4.25, 95% confidence interval 1.80-12.05). Overall, >92% of expanded alleles harbor CAA interruptions within the CAG tract. Pathogenic expansions at other loci, such as ATXN3 and THAP11, showed more ancestry-specific distributions. Clinically, individuals with pathogenic ATXN2 and ATXN3 expansions most often presented with typical PD features but frequently showed earlier disease onset and a strong family history of PD. This large-scale, multi-ancestry study comprehensively maps the genetic landscape of pathogenic and intermediate repeat expansions in PD. Our findings confirm a length- and structure-dependent risk association for ATXN2 with PD in the European population, and highlight the pleiotropic effects of repeat expansions across the parkinsonian spectrum.

18.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.

19.
arXiv (CS.CV) 2026-06-25

Privacy-Aware Visual Language Models

As Visual Language Models (VLMs) become increasingly embedded in everyday applications, ensuring they can recognise and appropriately handle privacy-sensitive content is thus essential to protect users. To this end, we conduct a comprehensive evaluation of twelve state-of-the-art VLMs and identify limitations in their understanding of visual privacy. However, existing privacy-related datasets often suffer from label inconsistencies, limiting their reliability. To address this, we introduce two compact, high-quality benchmarks, PrivBench and PrivBench-H, that focus on commonly recognised visual privacy categories aligned with the General Data Protection Regulation (GDPR). Additionally, we present PrivTune, an instruction-tuning dataset specifically curated to improve privacy sensitivity. We obtain multiple Privacy VLMs by fine-tuning off-the-shelf VLMs on only a few hundred samples from PrivTune, which leads to substantial gains on all benchmarks, surpassing even GPT-4, while maintaining strong performance on other tasks. Our findings show that privacy-awareness in VLMs can be substantially improved with minimal data and careful dataset design, setting the stage for safer, more privacy-aligned AI systems.

20.
arXiv (CS.LG) 2026-06-25

KIGNet: Physics-Motivated Multi-Graph Representation Learning for Explainable Jet Tagging

arXiv:2512.07420v3 Announce Type: replace-cross Abstract: Jet identification plays a central role in analyzing data from high-energy collider experiments. While deep learning has improved jet classification, it often lacks interpretability. We introduce the Kinematic Interaction Graph Network (KIGNet), a graph neural network that integrates kinematic variables into jet classification by constructing four graph representations per jet, each weighted by a distinct variable: angular separation ($\Delta$), relative transverse momentum ($k_T$), momentum fraction ($z$), and invariant mass squared ($m^2$). Three of these ($\Delta$, $k_T$, $z$) are motivated by the Lund jet plane, grounded in perturbative QCD factorization; the fourth ($m^2$) adds complementary mass-scale sensitivity for heavy-flavor identification. Using Gradient-weighted Class Activation Mapping (Grad-CAM), we determine which variables dominate classification. Angular separation and relative transverse momentum account for about 76% of the total Grad-CAM attribution (40.72% and 35.67%), with momentum fraction and invariant mass contributing the remaining 24%. This hierarchy is consistent with the soft-collinear structure of QCD radiation in the training data, showing that the network learns physically interpretable representations rather than spurious correlations. On the JetClass dataset, KIGNet achieves a macro-accuracy of 95.07%, macro-AUC of 96.61%, and macro-AUPR of 81.52%, relative improvements of 2.45%, 3.40%, and 19.11% over the state-of-the-art baseline. On the Aspen Open Jets dataset of real CMS collision data, KIGNet produces substantially more structured latent representations than the baseline, reducing the Davies-Bouldin Index by 52.15% ($0.8395 \rightarrow 0.4017$) and increasing the Dunn Index by 42.33% ($0.0189 \rightarrow 0.0269$), confirming that physics-informed kinematic encoding generalizes beyond idealized simulation to experimental detector conditions.

21.
medRxiv (Medicine) 2026-06-18

Evaluating Deep-Learning Based Quantification of Breast Arterial Calcification on Mammography for Cardiovascular Risk Assessment

Purpose: To develop and evaluate a deep learning model for automated quantification of breast arterial calcification (BAC) on screening mammography and to assess whether AI-derived BAC burden predicts major adverse cardiovascular events (MACE) in women. Methods: In this retrospective study, 202,006 women who underwent screening mammography without history of MACE were included. A BAC segmentation model was trained on an expert-annotated dataset using a multi-task U-Net with a ResNet-18 encoder to detect and segment BAC. BAC burden was quantified as area (mm{superscript 2}) from model-generated masks using DICOM pixel spacing and categorized by tertiles into low, intermediate, and high. The PREVENT score and incident MACE were identified from electronic health records. Cox proportional hazards models were developed to evaluate AI-derived BAC burden and PREVENT score alone, and combined models for 5 - and 10-year cardiovascular risk prediction. Results: Among 202,006 women (mean age 54.8{+/-}11.7 years), 23.1% had AI-detected BAC, and 7,701 (3.8%) developed incident MACE during a median follow - up of 7.5 years. On the geographically held-out test set, the BAC model achieved an AUROC of 0.97, Dice score of 0.6678, and Pearson correlation of 0.961 between AI-derived and manually annotated BAC burden. BAC burden increased with age and was higher among women who developed MACE. Five - year MACE incidence increased across BAC categories from 1.5% in women without BAC to 6.9% in those with high BAC burden. BAC burden alone showed modest prediction of MACE, with 5-year and 10-year AUROCs of 0.661 and 0.650, respectively, while PREVENT achieved AUROCs of 0.781 and 0.771. Adding BAC to PREVENT produced minimal improvement in discrimination. Conclusion: Deep learning-based BAC quantification from routine mammography is feasible, accurate, and associated with future cardiovascular risk. Although BAC added little to PREVENT for overall discrimination, it may serve as a scalable opportunistic imaging biomarker to identify women at elevated cardiovascular risk and support preventive care.

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

The MAMA-MIA Challenge: Advancing Generalizability and Fairness in Breast MRI Tumor Segmentation and Treatment Response Prediction

arXiv:2603.01250v2 Announce Type: replace-cross Abstract: Breast cancer is the most frequently diagnosed malignancy among women worldwide and a leading cause of cancer-related mortality. Dynamic contrast-enhanced magnetic resonance imaging plays a central role in tumor characterization and treatment monitoring, particularly in patients receiving neoadjuvant chemotherapy. However, existing artificial intelligence models for breast magnetic resonance imaging are typically developed and evaluated using heterogeneous datasets, study populations, and assessment protocols, making direct comparison difficult and limiting understanding of model robustness across institutions and clinically relevant patient subgroups. The MAMA-MIA Challenge was designed to address these challenges by providing a standardized benchmark for the joint evaluation of primary tumor segmentation and prediction of pathologic complete response using pre-treatment magnetic resonance imaging only. The training cohort comprised 1,506 patients from multiple institutions in the United States, while evaluation was conducted on an external test set of 574 patients from three independent European centers to assess cross-continental and cross-institutional generalization. A unified scoring framework combined predictive performance with subgroup consistency across age, menopausal status, and breast density. Twenty-six international teams participated in the final evaluation phase. Results demonstrate substantial performance variability under a common external evaluation framework and reveal trade-offs between overall accuracy and subgroup fairness. The challenge provides standardized datasets, evaluation protocols, and public resources to promote the development of robust and equitable artificial intelligence systems for breast cancer imaging.

23.
arXiv (CS.AI) 2026-06-24

When Preferences Fail to Become Incentives: A Utility-Behavior Gap in Large Language Models

arXiv:2606.22974v2 Announce Type: replace Abstract: Recent work on preference elicitation in large language models (LLMs) has demonstrated that, when given a series of choices between two outcomes, LLMs reveal a coherent, model-specific utility structure. Notably, this structure often includes preferences that the models' trainers did not intend, such as valuing people of some nationalities above others, raising the possibility that LLMs might be forming emergent, misaligned goals, which, if true, would have major safety implications. However, the choice paradigms in which these preferences are observed are not reflective of real-world situations in which misaligned behavior would be a practical concern. Therefore, we design an experimental paradigm to probe whether these preferences serve as motivations for LLM behavior in realistic scenarios. First, we reproduce prior findings on consistent preference elicitation. Next, we create a set of common writing tasks - essays, grant proposal abstracts, incident postmortems, and translations - where quality can be assessed by a blind, independent LLM judge panel. Then, we demonstrate that LLMs can be motivated via direct exhortation and other explicit cues to modulate their output quality on these tasks. Finally, we probe whether utilities inferred from explicitly reported preferences can shift output quality on these tasks by offering LLMs high-utility incentives for high-quality outputs. In all tasks, across all models tested, offering LLMs outcomes that they report in the choice paradigm as being highly preferred does not lead them to create higher quality outputs than offering them dispreferred outcomes, or even no outcomes at all. We conclude that the existence of coherent preferences as demonstrated in choice paradigms should not be taken as evidence that those preferences have incentive value for the models or affect their behavior in other contexts.

24.
medRxiv (Medicine) 2026-06-15

The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease

Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.

25.
arXiv (CS.CL) 2026-06-17

A Recipe for Long-Context Reasoning in Large Language Models via On-Policy Optimization and Distillation

Existing approaches to post-train models for long-context tasks face complementary limitations: (i) supervised fine-tuning (SFT) provides stable supervision but suffers from exposure bias; (ii) reinforcement learning methods such as Group Relative Policy Optimization (GRPO) train on model-generated trajectories but struggle with long-horizon credit assignment and sparse rewards; and (iii) on-policy distillation (OPD) provides dense token-level guidance but does not directly optimize task rewards. We study these complementary strategies for long-context alignment and derive a recipe that combines GRPO with OPD-style teacher guidance: the student learns from its own rollouts using outcome-level rewards, while a stronger teacher provides dense token-level regularization in place of the standard reference policy. This is especially useful when process-level supervision is difficult to obtain. To support this study, we introduce LongBlocks, a synthetic multilingual dataset spanning multi-hop reasoning, contextual grounding, and long-form generation. Through controlled ablations, we isolate the roles of cold-start initialization, teacher anchoring, and data mixing, showing that our recipe yields a more stable and effective path to long-context reasoning than GRPO or OPD while preserving short-context capabilities.