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01.
arXiv (CS.CV) 2026-06-18

Show, Don't Ask: Generative Visual Disambiguation for Composed Image Retrieval with Turn-Valid Coverage

Composed image retrieval (CIR) uses a reference image and a text modification to search for a target image. However, such queries often describe several possible images rather than one exact target, making the user's intent ambiguous. Recent methods address this by using conformal prediction to estimate ambiguity and by asking users clarifying text questions. However, these methods have two limitations: their coverage guarantee only holds at the first interaction, and text questions are often insufficient for resolving fine-grained visual differences such as appearance, attributes, or viewpoint. We propose CLARA, a clarification framework that resolves ambiguity by showing users a small panel of visual alternatives. Instead of answering text questions, the user simply selects the prototype image closest to the intended target. This provides a direct visual signal and avoids relying on a model to predict the user's answer. To maintain valid conformal guarantees across multiple interaction rounds, CLARA reweights calibration using the likelihood ratio induced by the user's selection. The displayed prototypes are also constrained to represent the current candidate set and are snapped to real corpus images, ensuring that generated images cannot artificially improve coverage. Experiments on open-domain and fashion benchmarks show that CLARA matches single-turn state-of-the-art retrieval performance, maintains nominal coverage across interaction rounds, and finds the intended target in fewer rounds than strong text-question baselines. Its advantage is especially clear when ambiguity involves viewpoint or fine-grained attributes, where visual clarification is more effective than textual questioning.

02.
arXiv (CS.CV) 2026-06-17

NTIRE 2024 Challenge on Image Super-Resolution (x4): Methods and Results

This paper reviews the NTIRE 2024 challenge on image super-resolution ($\times$4), highlighting the solutions proposed and the outcomes obtained. The challenge involves generating corresponding high-resolution (HR) images, magnified by a factor of four, from low-resolution (LR) inputs using prior information. The LR images originate from bicubic downsampling degradation. The aim of the challenge is to obtain designs/solutions with the most advanced SR performance, with no constraints on computational resources (e.g., model size and FLOPs) or training data. The track of this challenge assesses performance with the PSNR metric on the DIV2K testing dataset. The competition attracted 199 registrants, with 20 teams submitting valid entries. This collective endeavour not only pushes the boundaries of performance in single-image SR but also offers a comprehensive overview of current trends in this field.

03.
arXiv (CS.LG) 2026-06-18

EfficientRollout: System-Aware Self-Speculative Decoding for RL Rollouts

arXiv:2606.18967v1 Announce Type: new Abstract: Reinforcement learning (RL) has become a representative post-training paradigm for LLMs, enabling strong reasoning and agentic capabilities. However, rollout generation remains a dominant latency bottleneck because autoregressive sampling decodes responses sequentially and a small number of long-tailed generations often determine completion time. Speculative decoding (SD) offers a natural way to address this bottleneck, as it is a well-established technique for serving fixed LLMs that reduces latency by rapidly drafting tokens and accepting them through parallel verification while preserving the target-model distribution. However, its practical speedups do not directly carry over to RL rollouts: (i) the evolving target policy makes any fixed drafter increasingly mismatched with the policy's output distribution; and (ii) active batch sizes shrink throughout rollout decoding, shifting decoding from compute-bound to memory-bound regimes where parallel verification can exploit underutilized compute. Therefore, accelerating RL rollouts requires both a drafter that remains effective under long, high-temperature generations from an evolving policy and system-aware use of SD that avoids compute-bound regimes. We present EfficientRollout, a system-aware self-SD framework designed to address this gap for RL rollouts. EfficientRollout induces a quantized drafter from the target model (i.e. self-speculative decoding), keeping it coupled to the evolving policy without separate drafter pretraining or online adaptation. It further coordinates a system-aware SD toggle policy with acceptance-aware draft-length adaptation, enabling speculation only in beneficial regimes while matching the drafting budget to evolving drafter quality. EfficientRollout reduces rollout and end-to-end latency by up to 19.6% and 12.7%, respectively, over an accelerated AR rollout baseline, while preserving final model quality.

04.
medRxiv (Medicine) 2026-06-10

Longitudinal brain structural changes during clozapine treatment: associations with neuroreceptor architecture and clinical response

In treatment-resistant schizophrenia, clozapine treatment has been associated with longitudinal reductions in subcortical volumes, ventricular enlargement, and widespread cortical thinning. However, it is unknown how these structural changes relate to clozapines pharmacological profile and clinical efficacy. We combined five longitudinal datasets with MRI acquired before and on average 5 months after clozapine initiation in 143 individuals to quantify brain structural changes and their association with normative maps relating to neuroreceptor architecture and physiological systems, and improvement in symptom severity. Clozapine treatment was associated with grey matter volume reductions across multiple subcortical regions (including the amygdala, hippocampus, thalamus, caudate, putamen and nucleus accumbens), increases in pallidal volume, ventricular enlargement, and widespread cortical thinning. Cortical regions showing the greatest magnitude of thinning corresponded to areas with higher normative densities of serotonergic 5-HT1A, 5-HT2A and 5-HT4 receptors. Changes in subcortical volume or cortical thickness during clozapine treatment were not associated with changes in total or positive symptom severity. In addition, baseline subcortical volume, cortical thickness, or gyrification prior to starting clozapine did not predict subsequent symptom improvement. Cortical thinning may partly reflect clozapines activity at serotonergic receptors, which have been implicated in cortical network stabilisation and neuroplasticity, however structural remodelling during clozapine treatment may reflect a process independent from its clinical efficacy in improving core symptoms of psychosis.

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

Grounded Inference: Principles for Deterministically Encapsulated Generative Models

Authors:

arXiv:2606.19753v1 Announce Type: new Abstract: The incorporation of generative models into traditional computational systems presents both enormous opportunity and tremendous peril. Although many early adopters have realized these perils at great expense, the field still requires foundational frameworks to de-risk incorporation of AI into traditional systems. This manuscript establishes this foundation through the definition of four specific primitives of AI blended architecture, designed to enable deterministic encapsulation of probabilistic models. It further establishes two overarching anti-patterns broadly represented across industry to serve as warnings for engineers in this field. This framework was designed to enable successful integration of AI into traditional systems while providing a foundation upon which generative model providers could build the next generation of generative model interfaces.

07.
arXiv (math.PR) 2026-06-15

Limiting partition function for the Mallows model: a conjecture and partial evidence

Authors:

arXiv:2406.18855v2 Announce Type: replace Abstract: Let $S_n$ denote the set of permutations of $n$ labels. We consider a class of Gibbs probability models on $S_n$ that is a subfamily of the so-called Mallows model of random permutations. The Gibbs energy is given by a class of right invariant divergences on $S_n$ that includes common choices such as the Spearman foot rule and the Spearman rank correlation. Mukherjee in 2016 computed the limit of the (scaled) log partition function (i.e. normalizing factor) of such models as $n\rightarrow \infty$. Our objective is to compute the exact limit, as $n\rightarrow \infty$, without the log. We conjecture that this limit is given by the Fredholm determinant of an integral operator related to the so-called Schrödinger bridge probability distributions from optimal transport theory. We provide partial evidence for this conjecture, although the argument lacks a final error bound that is needed for it to become a complete proof.

08.
bioRxiv (Bioinfo) 2026-06-13

ADMETron: An AI-driven SaaS platform for comprehensive ADMET prediction and compound prioritisation

ONTOSIGHT(R) ADMETron is an AI-driven platform designed for rapid prediction and visualization of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties to support modern drug discovery. The platform integrates an interactive web interface with a scalable predictive engine, enabling high-throughput virtual screening and batch analysis of chemical compounds. Its core architecture combines recurrent neural network (RNN)-derived molecular embeddings from SMILES representations with physicochemical descriptors, which are subsequently modeled using gradient boosting machines (GBMs). This framework provides predictions across 34 ADMET endpoints, including physicochemical properties, absorption, CYP450 interactions, hERG liability, and mutagenicity. The predictive performance of ADMETron was evaluated using benchmark datasets from the Therapeutics Data Commons (TDC), demonstrating strong performance and generalizability across both classification and regression tasks. Beyond predictive modeling, the platform introduces an interactive radar graph-based structure-activity relationship (SAR) visualization framework that enables real-time comparison of multiple compounds and reference drugs across selected ADMET parameters. This feature facilitates intuitive interpretation of multidimensional molecular profiles and supports lead optimization and compound prioritization. Comparative assessment against widely used online ADMET tools further demonstrated broad endpoint coverage spanning pharmacokinetic, physicochemical, toxicity, and medicinal chemistry properties within a unified environment. Together, these capabilities establish ADMETron as a comprehensive platform for ADMET assessment and data-driven decision-making in drug discovery. (https://admetron.partex.ai/).

09.
arXiv (CS.AI) 2026-06-15

Selective Agentic Recovery for UAV Autonomy with a Persistent Mission Runtime

arXiv:2606.14219v1 Announce Type: cross Abstract: Agentic AI can support unmanned aerial vehicle (UAV) autonomy by providing high-level recovery reasoning when local waypoint- or setpoint-based execution encounters blocked passages, repeated no-progress behavior, or mission-level ambiguity. On physical UAVs, however, remote reasoning is most useful when it is invoked selectively, since each call introduces latency, resource cost, backend uncertainty, and a need to validate the returned decision. This paper presents Persistent Mission Runtime (PMR), a UAV recovery framework that keeps the mission loop and safety-critical execution local while using an external agentic reasoner only as an on-demand recovery module. The reasoner selects from predefined recovery skills, and each returned decision is parsed, verified, safety-filtered, and mapped to local executor actions before it can affect flight. PMR introduces learned Cognitive Value of Invocation (learned-CVI), a compact admission gate that estimates when remote agentic reasoning is likely to improve near-term mission progress enough to justify its operational cost. Across a fixed 400-run Gazebo/PX4 benchmark with eight scenarios, learned-CVI raises hard/ambiguous-regime success from 5.0% under local-only autonomy to 95.0%, outperforms one-shot and periodic reasoning baselines by 20.0 and 32.5 percentage points, and reduces remote-agent calls by 16.7% and logged tokens by 29.2% relative to a manually tuned rule-based invocation baseline.

10.
Nature (Science) 2026-06-22

Daily briefing: First-ever ‘nuclear’ clocks put atomic clocks in the shade

Authors:

Two research teams have created a new, long-awaited type of timekeeper. Plus, how backlash has saved an ocean-monitoring network targeted by Trump and how our cultural heritage is put at risk by climate change. Two research teams have created a new, long-awaited type of timekeeper. Plus, how backlash has saved an ocean-monitoring network targeted by Trump and how our cultural heritage is put at risk by climate change.

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

Judging Against the Reference: Uncovering Knowledge-Driven Failures in LLM-Judges on QA Evaluation

While large language models (LLMs) are increasingly used as automatic judges for question answering (QA) and other reference-conditioned evaluation tasks, little is known about their ability to adhere to a provided reference. We identify a critical failure mode of such reference-based LLM QA evaluation: when the provided reference conflicts with the judge model's parametric knowledge, the resulting scores become unreliable, substantially degrading evaluation fidelity. To study this phenomenon systematically, we introduce a controlled swapped-reference QA framework that induces reference-belief conflicts. Specifically, we replace the reference answer with an incorrect entity and construct diverse pairings of original and swapped references with correspondingly aligned candidate answers. Surprisingly, grading reliability drops sharply under swapped references across a broad set of judge models. We empirically show that this vulnerability is driven by judges' over-reliance on parametric knowledge, leading judges to disregard the given reference under conflict. Finally, we find that this failure persists under common prompt-based mitigation strategies, highlighting a fundamental limitation of LLM-as-a-judge evaluation and motivating reference-based protocols that enforce stronger adherence to the provided reference.

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

RooseBERT: A New Deal For Political Language Modelling

The increasing amount of political debates and politics-related discussions calls for the definition of novel computational methods to automatically analyse such content with the final goal of lightening up political deliberation to citizens. However, the specificity of the political language and the argumentative form of these debates (employing hidden communication strategies and leveraging implicit arguments) make this task very challenging, even for current general-purpose pre-trained Language Models (LMs). To address this, we introduce a novel pre-trained LM for political discourse language called RooseBERT. Pre-training a LM on a specialised domain presents different technical and linguistic challenges, requiring extensive computational resources and large-scale data. RooseBERT has been trained on large political debate and speech corpora (11GB) in English. To evaluate its performances, we fine-tuned it on multiple downstream tasks related to political debate analysis, i.e., stance detection, sentiment analysis, argument component detection and classification, argument relation prediction and classification, policy classification, named entity recognition (NER). Our results show improvements over general-purpose LMs on the majority of these tasks, highlighting how domain-specific pre-training enhances performance in political debate analysis. We release RooseBERT for the research community.

13.
Nature (Science) 2026-06-17

Molecular basis of polyadenylated RNA fate determination in the nucleus

Authors:

Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs1,2, which are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, including protein-coding RNPs, are exported to the cytoplasm, whereas transcripts within non-functional pA+ RNPs are degraded in the nucleus1–4. How cells distinguish these opposing fates remains unknown. The DExD-box ATPase UAP56 (also known as DDX39B) is a central component of functional pA+ RNPs, and promotes their docking to the nuclear pore complex-anchored TREX-25,6, which triggers transcript release from UAP56 to facilitate export7. Here we reveal that the poly(A) tail exosome targeting (PAXT) connection8 binds a TREX-2-like module, which releases pA+ RNAs from UAP56 for decay by the nuclear exosome. The core of this module consists of a LENG8–PCID2–SEM1 trimer, which we show is structurally and biochemically equivalent to the central GANP–PCID2–SEM1 trimer of TREX-2. Mutagenesis and transcriptomic data demonstrate that the nuclear fate of pA+ RNPs is governed by the contending actions of nucleoplasmic PAXT and nuclear pore complex-associated TREX-2, which interpret RNA-bound UAP56 as a signal for RNA decay or export, respectively. As RNA targets of PAXT are generally short and intron-poor, we propose an overall model for pA+ RNP fate determination whereby the distinct sub-nuclear localizations of PAXT and TREX-2 govern the degradation of short non-functional pA+ RNAs while allowing export of their longer and functional counterparts. Biochemical, structural and cell biological analyses reveal that UAP56 (DDX39B) assembles with a TREX-2–like module that redirects non-functional polyadenylated RNAs from export to degradation.

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

Multi-view feature High-order Fusion for Space Weak Object Detection and Segmentation

Weak objects are common in images and videos of space applications. However, it is hard to learn proper representations from their limited appearance information. Inspired by multi-view learning, we develop simple multi-view attentions, treating their outputs as multi-view features. We also propose a multi-view feature high-order fusion method (MHF) to aggregate more accurate and richer features of weak objects. Our MHF extends the commonly used low-order feature fusion method to higher orders. It enhances the model's capacity to capture relevant and complementary information about weak objects. This is achieved by introducing high-order multi-view features perception and a recursive task-contribution gated selection of multi-view features. The new operation is highly flexible and customizable. It is compatible with various variants of multi-view feature representations. We conduct extensive experiments on two newly constructed space science datasets and an open, large-scale satellite video dataset. Our MHF serves as a plug-and-play module and significantly improves various vision transformers and convolution-based detection and segmentation models. We achieve all state-of-the-art accuracies on both tasks across three datasets. Our MHF can be a new basic module for visual modeling that effectively represents weak objects in terms of multi-view learning. The code will be available at https://github.com/Kingdroper/MHF.

15.
arXiv (CS.CL) 2026-06-16

Uncertainty Is Not a Safety Net for Clinical VQA, but Can It Anticipate Model Failure?

Safe deployment of clinical vision-language models (VLMs) requires reliable uncertainty estimation (UE): a signal indicating when predictions should be trusted or escalated to a clinician. We test whether current UE methods actually deliver this signal. Benchmarking 8 methods across 12 VLMs on clinical visual question-answering (VQA), we find that UE quality is not an intrinsic property of the UE method: it tracks model accuracy, degrading precisely where the model performance is weakest, and therefore where reliability is most needed. When we stress-test models by hiding the correct option among the multiple-choice answers (NOTA perturbations), accuracy collapses while uncertainty barely changes, leaving models systematically miscalibrated. Yet, we find that uncertainty on the unperturbed input reliably anticipates which predictions will collapse under NOTA, indicating that UE in current VLMs carries diagnostic information about model fragility. Our results position UE as a diagnostic tool for identifying fragile predictions and motivate perturbation-based evaluation as a path toward safe clinical deployment.

16.
arXiv (CS.CL) 2026-06-11

Mapping Scientific Literature with Large Language Models and Topic Modeling

Scientific literature is increasingly fragmented by disciplinary boundaries, specialized terminology, and potentially sparse keyword systems, making it difficult to capture the evolving structure of modern science. This study introduces a large language model (LLM)-driven framework for mapping scientific literature from a topic modeling perspective. The approach is demonstrated on a 20-year corpus of more than 1,500 engineering-related articles published in the Proceedings of the National Academy of Sciences (PNAS). A two-stage classification pipeline first assigns a primary thematic category to each article based on its abstract, followed by full-text analysis to identify secondary classifications that reveal latent cross-topic connections within the corpus. Unlike conventional topic models, the LLM-based framework produces semantically interpretable topics while maintaining strong quantitative performance. Comparative evaluation against established topic modeling methods shows higher topic diversity and lower overlap with competitive coherence metrics. Manual validation on a randomly sampled subset of abstracts yields an accuracy of 75.9%. Additional traditional natural language processing analyses confirm that the generated topics correspond to meaningful linguistic patterns in the corpus. A bipartite network linking primary and secondary classifications further reveals implicit thematic relationships that are not readily observable through abstracts or keyword systems alone. The findings indicate that the framework independently recovers much of the journal's editorial dual-classification structure without prior knowledge of its schema. Overall, the proposed approach offers a powerful tool for mapping science and identifying emerging cross-topic connections in research.

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

Geometrical fairness in graph neural networks

arXiv:2606.17684v1 Announce Type: cross Abstract: Graph-based learning methods have become increasingly prominent due to their strong performance across diverse applications. Among these, recent frameworks grounded in diffusion processes provide a unifying perspective that extends traditional graph neural network formulations while addressing limitations of standard message-passing mechanisms. Despite these advances, concerns remain regarding the fairness of such models, as they may propagate or amplify biases present in the data. In this work, we introduce a fairness-aware adaptation of graph-based diffusion by modifying the underlying Laplacian operator. Our approach incorporates multiple complementary transformations, including subspace projections, spectral adjustments, and frequency-based filtering, to mitigate bias-related components. Leveraging the intrinsic smoothing properties of graph diffusion, we provide a principled analysis of the resulting behavior and establish theoretical insights into fairness properties. We evaluate the proposed framework on both synthetic and real-world datasets, demonstrating that it achieves competitive performance while improving fairness metrics with limited additional computational cost.

18.
arXiv (CS.AI) 2026-06-17

Counterfactual Optimization of Baseball Pitch Sequences and Estimation of Its Impact on Season-Level Statistics

arXiv:2606.17345v1 Announce Type: cross Abstract: Although pitch sequencing is a central topic in baseball analytics, previous studies have primarily focused on optimizing the final pitch within a single plate appearance, leaving the role of preceding setup pitches and their impact on long-term season-level performance insufficiently examined. To address these issues, this study conducted counterfactual analyses using MLB Statcast data. A Transformer-based machine-learning model was trained to predict whether a target pitch would result in an in-play outcome or swing-out. Counterfactual pitch sequences were then generated by replacing either the final pitch or the preceding setup pitch with alternative pitch types and locations while keeping the surrounding contextual information fixed. Optimal counterfactual selections were defined as those that minimized the predicted in-play probability, and their expected effects on pitchers' seasonal statistics were estimated using regression models linking model outputs to season statistics. The results suggest that the optimization of both final and setup pitches may substantially influence season-level performance, including improvements of more than 1.0 in K/9. The analyses also provided several practical insights, including velocity-band-specific effective locations, the importance of pitch commands, and the expansion of pitch-selection options through middle-velocity pitches. These findings quantitatively support the strategic importance of pitch sequencing in baseball.

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

Temporal Self-Imitation Learning

arXiv:2606.19752v1 Announce Type: cross Abstract: Long-horizon robot manipulation policies trained with reward shaping can still exploit dense rewards through inefficient interaction, while rare efficient behaviors may be forgotten during training. We argue that temporal efficiency itself provides a powerful and underutilized source of self-supervision for reinforcement learning. We introduce Temporal Self-Imitation Learning (TSIL), a reinforcement learning framework that mines temporally efficient successful trajectories generated during learning and converts them into reusable supervision for future policy improvement. TSIL progressively refines learning using configuration-conditioned adaptive temporal targets derived from fast successful trajectories, while preserving and replaying efficient behaviors through efficiency-weighted self-imitation learning. Across 15 distinct long-horizon manipulation tasks, TSIL consistently improves learning efficiency, task-completion efficiency, revisitation of fast successful behaviors, and robustness to unstable training conditions. More broadly, our results suggest that the temporal structure of successful behavior itself provides a scalable self-supervisory signal for reinforcement learning beyond manually engineered reward shaping alone.

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

CaReTS: A Multi-Task Framework Unifying Classification and Regression for Time Series Forecasting

arXiv:2511.09789v2 Announce Type: replace Abstract: Recent advances in deep forecasting models have achieved remarkable performance, yet most approaches still struggle to provide both accurate predictions and interpretable insights into temporal dynamics. This paper proposes CaReTS, a novel multi-task learning framework that combines classification and regression tasks for multi-step time series forecasting problems. The framework adopts a dual-stream architecture, where a classification branch learns the stepwise trend into the future, while a regression branch estimates the corresponding deviations from the latest observation of the target variable. The dual-stream design provides more interpretable predictions by disentangling macro-level trends from micro-level deviations in the target variable. To enable effective learning in output prediction, deviation estimation, and trend classification, we design a multi-task loss with uncertainty-aware weighting to adaptively balance the contribution of each task. Furthermore, four variants (CaReTS1–4) are instantiated under this framework to incorporate mainstream temporal modelling encoders, including convolutional neural networks (CNNs), long short-term memory networks (LSTMs), and Transformers. Experiments on real-world datasets demonstrate that CaReTS outperforms state-of-the-art (SOTA) algorithms in forecasting accuracy, while achieving higher trend classification performance.

21.
arXiv (math.PR) 2026-06-19

Power-law hypothesis and (un)fairness of PageRank on undirected multi-type PAMs

arXiv:2606.19583v1 Announce Type: new Abstract: The preferential attachment model (PAM) describes the sequential growth of a network based on the "rich-get-richer" principle. Several versions of it have become established for modeling, e.g., citation networks, capturing a power-law degree distribution. Directed versions of the preferential attachment model where the edges are directed from the new to the old vertices have been the subject of extensive research. They have been shown to exhibit remarkable properties such as heavier tails for the limiting graph-normalized PageRank than for the in-degrees. By contrast, for the undirected version, we recently showed that PageRank has similar tails as the degree. In the present paper, we discuss the PageRank asymptotics for a multi-type version of the undirected PAM (here vertices have different colors), complementing previous results of Antunes, Bhamidi, Banerjee and Pipiras on the asymptotics of PageRank on similar directed multi-type or colored PAMs. Our studies are motivated by the aim to go beyond the rigid rule of edge orientation in directed preferential attachment models. As the main result, for the case of a finite set of colors, we show that the power-law hypothesis for PageRank is fulfilled also for the colored undirected PAM, where, by contrast to the directed case, the power-law exponent is color-dependent for some choices of the initial color distribution and the attractiveness function. For the specific case of a two-type model, we discuss implications of our results on fairness in sampling underrepresented nodes from the network.

22.
bioRxiv (Bioinfo) 2026-06-16

Accelerating String Comparison in RLZ Compressed Sequences via LCE Jumps

Relative Lempel-Ziv (RLZ) is an effective compression method for large, repetitive collections; however, the fundamental primitives required to elevate it from a passive archival format to a tractable representation for compressed construction have yet to be fully established. In this paper, we introduce an algorithmic framework for structurally comparing and lexicographically sorting sequences of RLZ factors. We characterize when direct factor comparisons are necessary and when they can be bypassed using RLZ specific shortcuts. We further introduce a method for extending truncated factors into right-maximal matches, enabling the recovery of matching statistics from the RLZ parse. Experimentally, RLZ sorting achieved speedups of up to 3.93x over character-based sorting. Together, these results advance the use of the RLZ format as a foundation for compressed construction.

23.
medRxiv (Medicine) 2026-06-16

MRMU: A New Paradigm for Mendelian Randomization by Accounting for Measured Covariates and Unmeasured Confounders

Mendelian randomization (MR) is a powerful approach for causal inference, however, its reliability is frequently compromised by unadjusted covariates and unmeasured confounders, such as unmeasured pleiotropy and sample structure. To address these challenges, we introduce MRMU, a novel paradigm for the MR framework. Unlike traditional single-variable or multivariable MR methods, MRMU selects instrumental variables only from the exposure of interest and estimates one exposure effect at a time, while jointly accounting for measured covariates and unmeasured confounders. This design improves the reliability of MR analyses. In simulations and real data, MRMU achieved better type I error control, higher statistical power, and more accurate effect estimation than existing MR methods. Applying to coronary artery disease (CAD), MRMU identified robust cardiometabolic risk factors, including LDL-C, APOB, systolic blood pressure, body mass index, and smoking initiation, with consistent evidence across multiple CAD datasets. In contrast, traits such as HDL-C, height, and educational attainment, which were found to be significant by existing MR methods, were no longer supported by MRMU. MRMU further supported blood pressure-related traits, rather than lipid traits, as the more relevant pathway linking urate to CAD. Finally, by integrating large-scale plasma proteomics data, MRMU identified candidate CAD drug targets beyond established HMGCR- and PCSK9-related pathways, highlighting its utility for therapeutic target prioritization.

24.
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.

25.
medRxiv (Medicine) 2026-06-23

Systemic and Mucosal Antibody Correlates of Protection Against Bordetella pertussis in a Controlled Human Infection Model

Abstract Background Despite high vaccination coverage, pertussis has resurged globally. Whole-cell (wP) and acellular (aP) pertussis vaccines induce distinct immune profiles, yet immune correlates of protection against infection and symptomatic disease remain incompletely defined. We leveraged a controlled human infection model (CHIM) to identify systemic and mucosal humoral signatures associated with resistance to Bordetella pertussis. Methods Adults with documented history of vaccination had previously been enrolled in a CHIM study and challenged intranasally with B. pertussis D420. For the present work, longitudinal serum and nasal wash samples were analyzed using systems serology to comprehensively profile antibody features. Multivariate modeling and network analyses were performed to define discriminatory immune features. Findings Baseline aP vaccine antigen-specific antibodies did not distinguish infection outcomes. In wP-primed individuals, protection from B. pertussis infection was associated with broad, high-magnitude, polyfunctional antibody responses targeting non-canonical antigens, including BrkA, TcfA, OmpP, OmlA, FauA, and Pal. Protective signatures associated with resistance to symptomatic disease in both vaccine groups were characterized by enhanced Fc-receptor-engaging antibody profiles with distinct antigenic patterns shaped by vaccine history. Importantly, while conventional aP vaccine antigens failed to reliably distinguish individuals susceptible to infection or symptom development, correlates generated by integrated serum and mucosal models based on select non-canonical antigens achieved near-perfect discrimination of infection and symptom outcomes, outperforming models restricted to aP-vaccine. antigens only. Interpretation Resistance to infection was largely restricted to wP-primed individuals and was associated with integrated systemic and mucosal antibody responses directed against antigens beyond those included in acellular vaccines. Protection from symptomatic disease in both vaccine groups was linked to distinct antibody response signatures, shaped by prior vaccination history. These findings indicate that immune mechanisms preventing infection differ from those limiting clinical disease and provide a framework for redesign of next-generation pertussis vaccines aimed at blocking infection and symptomatic disease.