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

AQ4SViT: An Automated Quantization Framework with Search Gating Policy for Compressing Spiking Vision Transformers

arXiv:2606.15523v1 Announce Type: cross Abstract: Spiking Vision Transformers (SViTs) have emerged as alternative low-power ViT models, but their large sizes hinder their deployments on resource-constrained embedded AI systems. To address this, state-of-the-art works proposed quantization techniques to compress SViT models, but their manual, human-guided approach needs a huge design time and power/energy consumption to find the appropriate quantization setting for each given network, making this approach not scalable for quantizing multiple networks. Toward this, we propose AQ4SViT, a novel automated quantization framework for SViTs that can provide quick quantization settings with good trade-offs between accuracy and memory. To achieve this, AQ4SViT employs the following key ideas: quantization search strategy that evaluates the quantization setting candidates while considering the accuracy constraint; and search gating policy that quickly evaluates and selects promising quantization candidates by leveraging membrane potential drift as a performance proxy. In the search gating policy, AQSViT employs two search algorithm variants to provide trade-off options: Greedy search, which performs fast but may lead to local optima; and Beam search, which performs slower but has better performance in finding global optima selection due to a wider search space. Experimental results show that AQ4SViT-Greedy quickly finds the appropriate quantization settings, achieving up to 6.6x faster search time and up to 82.5% memory saving compared to the state-of-the-art; while AQ4SViT-Beam further reduces the memory footprint by up to 90% compared to the state-of-the-art, but with 4.5x longer search time; all these results are obtained while maintaining high accuracy within 1.5% from the original/non-quantized models on the ImageNet dataset. These results highlight that AQ4SViT framework offers advancements toward SViT deployments on embedded AI systems.

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

An Empirical Study on Learning Latent Representations for Emotional Speech Synthesis

For the last couple of years, the field of speech synthesis has improved dramatically thanks to deep learning. There are more and more deep learning-based TTS systems developed to make it possible to produce voices with high intelligibility and naturalness. Meanwhile, controlling the expressiveness is yet a big deal, generating speech in different styles or manners has received a lot of attention from community recently. This paper aims to give our solutions to deal with the task emotional speech synthesis (ESS) at VLSP 2022 which allows to generate humanlike natural-sounding voice from a given input text with desired emotional expression. By integrating speaker embedding, prosody bottleneck into FastSpeech 2, our systems can promisingly generate emotional speech of a single speaker (Sub-task 1), transfer speaking styles from another speaker to the target speaker with neutral non-expressive data while retaining the target speaker's identity (Sub-task 2).

03.
medRxiv (Medicine) 2026-06-15

Routine use of oral iron for people with heart failure and iron deficiency in primary care; retrospective cohort study

Aims: Iron deficiency is common among people with heart failure and associated with morbidity and mortality. While intravenous iron improves clinical outcomes, oral iron continues to be prescribed in routine practice despite limited evidence of benefit. Methods: We completed a retrospective primary care cohort study (2016 to 2021) to investigate the proportion of people with an incident diagnosis of heart failure who had iron deficiency identified (defined as ferritin

04.
bioRxiv (Bioinfo) 2026-06-16

MetaPilot: genome-aware adaptive search-space refinement for unified DDA and DIA metaproteomics

Metaproteomic peptide identification is constrained by the structure and size of the protein search space. Pooled gene catalogues provide coverage but obscure genome-level evidence, and current workflows for data-dependent (DDA) and data-independent (DIA) acquisition diverge in their database strategies. We present MetaPilot, a genome-aware workflow that uses conserved marker-protein evidence to rank candidate genomes from MGnify catalogues and construct adaptive, sample-specific search spaces. Applied to paired DDA/DIA datasets of defined mixtures and fecal samples, MetaPilot adapted genome selection to community complexity and reproduced published peptide evidence while expanding the detectable peptide space. In DDA-independent reanalysis of Orbitrap human gut DIA data, MetaPilot identified 24.4% more peptides than the published DDA-derived library and 2.06-fold more than the matched DDA-assisted DIA search. On timsTOF DIA-PASEF mouse intestinal data, it outperformed uMetaP by 41.8~119.7%, enabling genome-resolved functional interpretation without DDA-PASEF input.

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

Boosting Knowledge Graph Foundation Models via Enhanced Negative Sampling

arXiv:2605.27023v2 Announce Type: replace Abstract: Knowledge graphs (KGs) have become the core backbone of numerous downstream tasks such as question answering and recommender systems. However, despite all this, KGs are often very incomplete. To perform zero-shot knowledge graph completion in unseen KGs, which have different relational vocabularies from those used for pre-training, KG foundation models (KGFMs) receive a wide range of attention. Existing KGFMs often perform training using random negative triples, which are constructed by replacing the head or tail entity of a positive triple with a random entity. However, these negative triples are often constructed with limited quality, providing weak supervision for KGFM training. In this paper, we propose a simple yet effective adaptive negative sampling approach, KMAS, to enhance existing KGFMs. KMAS constructs hard negative triples through the updated relation embeddings generated from the existing KGFM's relation encoder. To further adaptively align with the evolving capability of the KGFM during the training process, KMAS adjusts the ratio of hard negative triples dynamically throughout the whole training process: after a warmup phrase, it increases the ratio linearly and then decreases linearly. Extensive experiments are conducted over 44 data sets. Experimental results demonstrate that our proposed negative sampling method can enhance many SOTA KGFMs without requiring excessive additional time or memory consumption.

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

Quantum Otto engine powered by an anisotropic Heisenberg XYZ model under independent local magnetic fields

arXiv:2606.12877v1 Announce Type: new Abstract: We study a quantum Otto heat engine whose working substance is an anisotropic two-qubit Heisenberg XYZ model. Independent local magnetic fields are used to control each spin individually. The influence of the longitudinal coupling, anisotropy, transverse coupling, and local fields on the net work output and efficiency is systematically examined. Reducing the longitudinal coupling is found to markedly improve both the maximum work and the peak efficiency. The engine performance reaches an optimum at a particular value of the anisotropy parameter. A local work analysis clarifies how work is produced during the cycle. Because of the asymmetric local fields and the intrinsic spin-spin interaction, the two qubits play markedly different thermodynamic roles; the interaction term itself contributes crucially to the total work. We further analyze the variation of quantum entanglement, quantified by concurrence, along the cycle. The results indicate that a pronounced change in entanglement between the hot and cold isomagnetic strokes is closely correlated with the efficiency enhancement. This work offers new insight into the operating principles and control of quantum Otto heat engines.

07.
arXiv (CS.AI) 2026-06-11

DiffCold: A Diffusion-based Generative Model for Cold-Start Item Recommendation

arXiv:2606.12245v1 Announce Type: cross Abstract: Cold-start item recommendation remains a persistent challenge in real-world systems due to the absence of interaction histories. While prior models attempt to bridge this gap using item content features, they universally suffer from the seesaw dilemma: enhancing performance for cold items inevitably degrades performance for warm items, and vice versa. We identify that this dilemma stems from a fundamental distributional disparity: warm item embeddings occupy a complex ``behavioral manifold" shaped by rich interaction signals, whereas cold item embeddings are constrained to a ``semantic manifold" derived solely from auxiliary content. Existing methods often force a rigid mapping between these inconsistent spaces, causing the model to sacrifice the precision of warm representations to accommodate cold ones. To address this, we propose DiffCold, a diffusion-based generative model that unifies warm and cold representations. Unlike GANs or VAEs, DiffCold leverages conditional diffusion to reconstruct warm item embeddings from content, preserving the underlying manifold structure without degradation. We further tailor this paradigm with two specific designs: a Retrieval-enhanced Aggregator that initializes generation using semantically similar warm items to bypass inefficient noise, and a Simulation-based Representation Alignment module that enforces distribution consistency between generated and real embeddings via contrastive learning. Experiments on three benchmarks confirm that DiffCold resolves the seesaw dilemma, consistently outperforming state-of-the-art methods across all metrics.

08.
medRxiv (Medicine) 2026-06-18

Cardiac rhythm development: A wearable device index of risk for physical and mental illness in adolescence

Objective. The autonomic nervous system, which regulates cardiac rhythm, undergoes pronounced maturation across adolescence. How cardiac rhythm develops over this period, however, and whether individual differences in its development forecast mental and physical illness, remain open questions. We used three waves of Fitbit data from the Adolescent Brain Cognitive Development (ABCD) Study to characterize the developmental trajectory of the cardiac rhythm and to test whether variation in that trajectory predicts onset of psychopathology and cardiometabolic disease. Methods. 8,301 adolescents contributed 242,811 valid Fitbit wear days across Waves 2 (Mage=12), 4 (Mage=14), and 6 (Mage=16). Cosinor mixed-effects models yielded three rhythm parameters per session: mesor (24-hour mean), amplitude (diurnal swing), and acrophase (peak timing). We first characterized age- and sex-specific trajectories, cross-wave stability, and factors shaping the rhythm. We then used parallel-process latent growth models to test whether within-person changes in rhythm tracked symptom trajectories, and hierarchical logistic models to test whether rhythm parameters predicted the first clinical onset of psychopathology and of obesity and hypertension. Results. The cardiac rhythm changed substantially across adolescence: mesor decreased, amplitude flattened, and acrophase shifted later. Within-person change in the rhythm tracked change in blood pressure, BMI, and trajectories of depression and ADHD symptoms. Higher mesor predicted incident onset of all five outcomes controlling for demographics, baseline symptoms, and behavior (ORs 1.36-1.54); amplitude, acrophase, and rhythm instability conferred additional risk. Conclusions. The 24-hour cardiac rhythm is a passively measurable substrate of adolescent autonomic development that indexes transdiagnostic risk for psychiatric and cardiometabolic illness.

09.
arXiv (CS.LG) 2026-06-16

If These Walls Could Talk: Critical Play with Large Language Models in Museums

arXiv:2606.15565v1 Announce Type: cross Abstract: Large Language Models (LLMs) are increasingly being used in museums to as role playing chatbots which let visitors talk to simulated versions of people and artefacts from the past. While such installations can be playful and engaging, they are also problematic because LLMs cannot be trusted to speak truthfully. I identify a fundamental dilemma for the use of LLMs in museum chatbots: LLMs cannot be trusted to tell the truth, and efforts to make them more reliable may ruin that which is attractive about the bots in the first place - their ability to engage in life-like conversation. In response, I propose designing for critical play with LLM-based bots: Designing for playful interactions with bots that are unreliable but still able to represent the past in an adequate and engaging manner - as fictional characters representing historical narratives, styles of discourse, diverse perspectives, humor and satire.

10.
arXiv (quant-ph) 2026-06-19

Phase locking nuclear spins in silicon with spin-orbit coupling

arXiv:2606.20340v1 Announce Type: new Abstract: Because they have such long coherence times, nuclear spins have extraordinary potential for use in quantum information processing devices. However, coherent nuclear spin control generally requires external phase references, such as microwave control fields. Here, we phase-lock a $^{29}$Si nuclear spin ensemble in a silicon quantum dot using only the internal electronic spin-orbit coupling as a phase reference. When driven with the quantum-dot electrons, the nuclear spins align themselves to a phase determined by the electronic spin-orbit coupling and the timing of the drive protocol. This enables us to measure the coherent precession and inhomogeneous dephasing of the nuclear spins. We corroborate our results with detailed numerical simulations of the many-body electron nuclear system. Our work opens new routes for coherently controlling solid-state nuclear spin ensembles.

11.
Nature (Science) 2026-06-17

Cortical development dynamics across autism spectrum disorder mouse models

Despite the functional diversity of over 100 causal genes1–3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD. Using single-nucleus multi-omic sequencing, diverse autism spectrum disorder-linked gene mutations converge on transient, stage-specific disruptions in early brain development, and highlight sex-specific gene expression alterations.

12.
arXiv (CS.LG) 2026-06-18

BLADE: Scalable Bi-level Adaptive Data Selection for LLM Training

arXiv:2606.18650v1 Announce Type: new Abstract: As Large Language Model (LLM) datasets scale to trillions of tokens, data selection has emerged as a critical frontier to filter out uninformative noise and construct adaptive learning trajectories. Beyond static heuristic filtering, advanced data selection methods for LLM training largely follow two paradigms, each with fundamental limitations. Influence-based methods provide principled bi-level objectives but require intractable inverse-Hessian computations, while excess-loss methods are computationally efficient but rely on a static reference model that becomes misaligned with the evolving proxy model during training. We propose BLADE (Bi-Level Adaptive Data sElection), a Hessian-free framework for data selection. BLADE reformulates the bi-level optimization problem underlying influence-based methods as a penalized single-level objective via Lagrange multipliers, avoiding inverse-Hessian computation while revealing a principled connection to excess-loss based data selection. The resulting objective recovers an excess-loss form but replaces the static reference model with a dynamic one that stays synchronized with training. Theoretically, we prove that this penalized formulation guarantees first-order convergence. For efficient online batch selection, we instantiate BLADE as a memoryless randomized block-coordinate Frank-Wolfe algorithm. Extensive experiments show that BLADE consistently outperforms state-of-the-art data selection baselines, providing a practical recipe for LLM training.

13.
arXiv (CS.CL) 2026-06-11

MA-DLE: Speech-based Automatic Depression Level Estimation via Memory Augmentation

Speech-based automatic estimation of depression levels is essential for enabling early detection and timely intervention, particularly in resource-constrained mental health settings. In recent years, deep learning has demonstrated impressive success across various domains, including affective computing and mental health assessment. Most existing approaches rely on RNN-based architectures (such as LSTM and GRU) to model temporal information for depression estimation. However, the extracted features often emphasize only a few adjacent speech segments, limiting their ability to capture long-range dependencies. To overcome this limitation, we introduce a memory-based feature augmentation method that enhances the representational capacity of GRU-extracted features. Rather than indiscriminately incorporating historical data, our memory bank is designed to selectively integrate two types of components in order to reduce redundancy and irrelevance: (1) historical temporal features that closely resemble the current GRU output, offering complementary contextual information; and (2) dynamic memory features identified based on feature variability, which capture behavioral and emotional fluctuations indicative of depressive symptoms. To effectively fuse the memory-augmented features with GRU outputs, we further design a Hierarchical Attention Fusion (HAF) module. Our method is evaluated on the widely used DAIC-WOZ and E-DAIC datasets, achieving state-of-the-art performance.

14.
arXiv (CS.CV) 2026-06-12

GeoCFNet: Geometry-Aware Confidence Field Network for Robot-Assisted Endoscopic Submucosal Dissection

Advanced surgical robotics has made robot-assisted endoscopic submucosal dissection (ESD) a promising approach for the en-bloc resection of large lesions, with the potential to reduce recurrence and improve long-term outcomes. However, the technical complexity and risk of complications in ESD demand stable and precise visual guidance to maintain an accurate dissection corridor and a safe tissue margin. Dense confidence fields provide an effective representation for this purpose by describing both the preferred dissection region and its spatial transition to surrounding tissue. However, reliable confidence field estimation remains challenging in dynamic endoscopic scenes due to smoke, specular highlights, tissue deformation, weak texture, and the thin geometric structure of the target region. To address these challenges, we formulate dissection guidance as a geometry-aware confidence field estimation problem and propose GeoCFNet, a geometry-aware confidence field network built on a pretrained DINOv3 backbone. GeoCFNet integrates a Token-Differentiated Fusion module to aggregate class-token context with dense patch representations, a SegFormer decoder for confidence regression, and Geometry-Aware Spatial Regularization (GASR) to preserve spatial coherence and local geometric transitions. Experimental results show that GeoCFNet achieves RMSE 0.0480, PSNR 27.1995, SSIM 0.3397, and CC 0.2466, indicating accurate and geometrically stable confidence field estimation for robot-assisted ESD guidance.

15.
arXiv (CS.CL) 2026-06-11

Neural FOXP2 – Language Specific Neuron Steering for Targeted Language Improvement in LLMs

LLMs are multilingual by training, yet their lingua franca is often English, reflecting English language dominance in pretraining. Other languages remain in parametric memory but are systematically suppressed. We argue that language defaultness is governed by a sparse, low-rank control circuit, language neurons, that can be mechanistically isolated and safely steered. We introduce Neural FOXP2, that makes a chosen language (Hindi or Spanish) primary in a model by steering language-specific neurons. Neural FOXP2 proceeds in three stages: (i) Localize: We train per-layer SAEs so each activation decomposes into a small set of active feature components. For every feature, we quantify English vs. Hindi/Spanish selectivity overall logit-mass lift toward the target-language token set. Tracing the top-ranked features back to their strongest contributing units yields a compact language-neuron set. (ii) Steering directions: We localize controllable language-shift geometry via a spectral low-rank analysis. For each layer, we build English to target activation-difference matrices and perform layerwise SVD to extract the dominant singular directions governing language change. The eigengap and effective-rank spectra identify a compact steering subspace and an empirically chosen intervention window (where these directions are strongest and most stable). (iii) Steer: We apply a signed, sparse activation shift targeted to the language neurons. Concretely, within low to mid layers we add a positive steering along the target-language dominant directions and a compensating negative shift toward the null space for the English neurons, yielding controllable target-language defaultness.

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

Rel-Zero: Harnessing Patch-Pair Invariance for Robust Zero-Watermarking Against AI Editing

Recent advancements in diffusion-based image editing pose a significant threat to the authenticity of digital visual content. Traditional embedding-based watermarking methods often introduce perceptible perturbations to maintain robustness, inevitably compromising visual fidelity. Meanwhile, existing zero-watermarking approaches, typically relying on global image features, struggle to withstand sophisticated manipulations. In this work, we uncover a key observation: while individual image patches undergo substantial alterations during AI-based editing, the relational distance between patch pairs remains relatively invariant. Leveraging this property, we propose Relational Zero-Watermarking (Rel-Zero), a novel framework that requires no modification to the original image but derives a unique zero-watermark from these editing-invariant patch relations. By grounding the watermark in intrinsic structural consistency rather than absolute appearance, Rel-Zero provides a non-invasive yet resilient mechanism for content authentication. Extensive experiments demonstrate that Rel-Zero achieves substantially improved robustness across diverse editing models and manipulations compared to prior zero-watermarking approaches.

17.
arXiv (quant-ph) 2026-06-16

Quantum Algorithm for Open-System Battery Cathodes by Modeling Multiple Strongly Coupled Holstein Polarons with Chain-Mapped Caldeira-Leggett Dynamics

arXiv:2606.16017v1 Announce Type: new Abstract: Cathode lithiation occupies a chemical regime of tightly localized orbitals, narrow bandwidths, and strong electron-lattice coupling. The defining electrochemical observables (open-circuit voltage and differential capacity) are open-system, reservoir-equilibration quantities that closed-Hamiltonian quantum simulation cannot produce, set by exchange with electron, Li$^+$, and phonon baths. We present a fault-tolerant quantum algorithm that recovers them through a unitary chain-mapped Caldeira-Leggett embedding, rendering the baths Trotterizable. The resulting fourth-order Trotter step has a T-gate count polynomial in system size, validating its open-system dynamics against hierarchical equations of motion (HEOM) at strong coupling and the Lindblad limit at weak coupling. For single-carrier olivine LiFePO$_4$, a single voltage anchor on an otherwise DFT-fixed Hamiltonian places the differential-capacity peak within the $\pm5$ mV reproducibility of the experimental plateau. For multi-carrier spinel LiMn$_2$O$_4$, whose $1{:}1$ Mn$^{3+}$/Mn$^{4+}$ filling makes the inter-site Coulomb repulsion dynamically active, the same kernel yields a two-plateau voltage curve with a $125$ mV split, within $17\%$ of the observed $150$ mV. We deliver an end-to-end fault-tolerant resource estimate for such a multi-carrier, three-reservoir observable: $368$ logical qubits and $\sim3\times10^5$ T-gates per step, or $\sim1.7\times10^{12}$ T-gates for a full voltage curve (parallelizable over $\sim10^3$ trajectories), leaving the production-scale dynamical run as a milestone for future hardware. The same kernel reproduces macroscopic quantum coherence, two-band superconductivity, and the Mikheyev-Smirnov-Wolfenstein resonance without modification, placing dynamical battery chemistry and similar Hamiltonians within scope for fault-tolerant quantum simulation.

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

DiffAttn: Diffusion-Based Drivers' Visual Attention Prediction with LLM-Enhanced Semantic Reasoning

Drivers' visual attention provides critical cues for anticipating latent hazards and directly shapes decision-making and control maneuvers, where its absence can compromise traffic safety. To emulate drivers' perception patterns and advance visual attention prediction for intelligent vehicles, we propose DiffAttn, a diffusion-based framework that formulates this task as a conditional diffusion-denoising process, enabling more accurate modeling of drivers' attention. To capture both local and global scene features, we adopt Swin Transformer as encoder and design a decoder that combines a Feature Fusion Pyramid for cross-layer interaction with dense, multi-scale conditional diffusion to jointly enhance denoising learning and model fine-grained local and global scene contexts. Additionally, a large language model (LLM) layer is incorporated to enhance top-down semantic reasoning and improve sensitivity to safety-critical cues. Extensive experiments on four public datasets demonstrate that DiffAttn achieves state-of-the-art (SoTA) performance, surpassing most video-based, top-down-feature-driven, and LLM-enhanced baselines. Our framework further supports interpretable driver-centric scene understanding and has the potential to improve in-cabin human-machine interaction, risk perception, and drivers' state measurement in intelligent vehicles.

19.
bioRxiv (Bioinfo) 2026-06-11

OMIO: A policy-driven Python library for reproducible microscopy image I/O

Modern fluorescence and multiphoton microscopy workflows operate within a heterogeneous ecosystem of file formats, partially overlapping metadata standards, and reader-specific conventions. In practice, this frequently leads to silent axis misinterpretations, loss or corruption of physical voxel size information, and laboratory-specific glue code that is fragile, poorly documented, and difficult to reproduce. OMIO, short for Open Microscopy Image I/O, addresses these issues by providing a lightweight, policy-driven image I/O layer for Python that enforces a canonical, OME-compatible data representation at the API boundary. The central contribution of OMIO is the explicit separation of low-level format access from semantic normalization. Existing reader libraries are used as interchangeable backends for extracting pixel data and available metadata, while OMIO enforces axis conventions, metadata interpretation, and fallback decisions in a centralized and auditable policy layer. This design allows heterogeneous microscopy inputs to be converted into a stable representation without propagating backend-specific assumptions into downstream analysis code. The core design principles of OMIO include canonical axis semantics (TZCYX), robust metadata normalization with explicit and auditable fallbacks, memory-aware operation via optional Zarr-based backends, and workflow-level semantics that extend beyond individual files to folder stacks and BIDS-like project structures. This architecture allows OMIO to orchestrate existing reader libraries into a coherent and reproducible I/O pipeline without replacing or duplicating their functionality. OMIO is implemented as an open-source and community-oriented system in which support for additional file formats and metadata conventions can be added incrementally through modular reader backends. By encouraging the contribution of example datasets, backend extensions, and feature requests, OMIO is designed to evolve alongside emerging acquisition systems while preserving strict semantic guarantees at the interface level. The resulting standardized OME-TIFF outputs are immediately suitable for downstream quantitative analysis and interactive inspection in scientific Python workflows, including workflows based on ImageJ and Napari.

20.
bioRxiv (Bioinfo) 2026-06-13

Testing the reliability of AI-generated protein structures

Although AlphaFold2 and its competitors have demonstrated remarkable abilities to predict protein structure, more work is needed to explore the limitations of these methods. Here we investigated the reliability of AlphaFold2 and ColabFold by creating a set of realistic but false protein sequences, using ColabFold to predict their structure, and then asking how often the program produces a high-scoring structure for a sequence that does not represent a protein. We determined that AlphaFold2 has a very small but non-zero false positive rate, estimated here at approximately 1 in 435 if one uses a threshold pLDDT score of 70 to define positive predictions. We also discovered, serendipitously, that some high-scoring sequences in the human genome were not false positives, but instead were previously unknown and un-annotated pseudogenes. These latter findings indicate that some well-established human annotations of protein-coding genes may have incorrectly extended the 5-prime untranslated regions too far. They also suggest that the false positive rate of AlphaFold2 is low enough that almost any high-scoring structure, even in a noncoding region, is worthy of further investigation.

21.
medRxiv (Medicine) 2026-06-22

Associations of Chemical Exposures with Psychological Distress and Depression Diagnosis among Waste Pickers in Brasilia, Brazil: A Cross-Sectional Study

Introduction: Waste pickers face chemical exposures. We evaluated whether chemical exposure is associated with psychological distress and depression. Methods: A 2017 cross-sectional survey included 1,141 waste pickers working in the Estrutural open dump in Brasilia, Brazil. Participants self-reported occupational exposure to 11 chemical categories, 17 psychological distress symptoms, and depression diagnoses. Associations of chemical exposure with mean psychological distress scores and depression prevalence were assessed, adjusted for age, sex, marital status, and income. Results: Mean psychological distress score was higher among those exposed to any chemical (mean of 8.1 vs 6.1; adjusted mean difference [aMD]: 1.8 [0.9, 2.7]) and higher among those exposed to each of 11 chemical categories, for example, smoke (aMD: 1.2 [0.6, 1.7]), batteries (aMD: 1.5 [1.0, 1.9], and oils (aMD: 1.3 [0.9, 1.8]). Depression was more prevalent among those exposed to oils (16.6% vs 10.6%; adjusted prevalence difference [aPD]: 6.3% [95% CI: 2.3, 10.2]), cleaning products (aPD: 5.4% [1.2, 9.5]), medications (aPD: 4.7% [0.6, 8.8]), and aerosols (aPD: 5.3% [1.3, 9.3]) but, not smoke, batteries, greases, insecticides, solvents, paints, chemical containers, or any chemical. Conclusion: These associations highlight the need to consider policy level protections for waste pickers to reduce chemical exposure and guard against psychological distress. Further research is necessary to explore which specific chemicals, within broad chemical categories, are associated with psychological distress and depression.

22.
Nature Medicine 2026-06-15

Blood signatures of cell type-specific aging forecast disease risk and resilience

作者: 未知作者

By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular ‘clocks’ to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.

23.
medRxiv (Medicine) 2026-06-18

Intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion (MeVO-TNK): Study rationale and design

Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

24.
arXiv (CS.LG) 2026-06-18

Toward Simultaneously Optimal Regret in U-Calibration

arXiv:2606.18527v1 Announce Type: cross Abstract: U-calibration studies online forecasting algorithms whose predictions can be consumed by any unknown downstream agent, guaranteeing sublinear regret simultaneously for all proper loss functions. Existing U-calibration algorithms achieve worst-case optimal $O(\sqrt{T})$ regret for every bounded proper loss, but they fail to adapt to easier losses: as we show, even for smooth losses such as squared loss, they incur $\Omega(\sqrt{T})$ regret instead of the optimal $O(\log T)$ regret. In this work, we show that this limitation is not inherent. Specifically, we design a single forecast algorithm that simultaneously achieves $\tilde O(\sqrt{T})$ regret for every bounded proper loss and $O(\log T)$ regret for every bounded smooth proper loss. More generally, our algorithm also attains logarithmic regret for losses that are smooth relative to the log-barrier, which include several non-Lipschitz examples. Our approach is based on a novel variant of Follow-the-Perturbed-Leader (FTPL) in which perturbations are applied directly in the prediction space using self-concordant noise. The resulting analysis also departs substantially from prior FTPL analyses due to the complex nature of this noise and may be of independent interest.

25.
arXiv (CS.CL) 2026-06-16

Building Customer Support AI Agents at 100M-User Scale: An Evaluation-Driven Framework

The rapid rise in LLM capabilities has made AI agents increasingly viable across a broad range of tasks. Among the most promising applications is building production-ready customer-facing agents, a challenge that demands coordinated excellence in evaluation methodology, context engineering, training, and online measurement. Yet these critical pillars are typically developed in isolation, creating blind spots that only surface after deployment. In this paper, we present a unified framework that bridges offline development with online impact for customer support AI agents at Nubank, a company with 100M+ users. Our approach integrates several key components: (1) structured context engineering tailored to customer support agents, (2) systematic human-in-the-loop prompt iteration, (3) rigorous LLM judge evaluation with measured inter-rater agreement and GEPA optimization for consistency, and (4) ideation-to-production validation. A central insight is that evaluation-pipeline quality directly determines iteration velocity. We present results from five production deployments spanning distinct domains: card delivery, debt management, credit-limit support, card management, and product explanation. These deployments deliver consistent customer-satisfaction gains while substantially accelerating iteration. In our card-delivery deployment, large-scale A/B testing yields a 37 percentage-point improvement in AI transactional Net Promoter Score and a 29 percentage-point gain in self-service rate over prior agent variants, alongside a strong correlation between offline simulation metrics and online outcomes, demonstrating that eval-driven development reliably predicts production impact. On most use cases, AI satisfaction reaches within a few percentage points of expert human agents.