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

JourneyFormer: Encoding Airbnb Guest Journey with Sequence Modeling

arXiv:2606.19108v1 Announce Type: new Abstract: Sequence modeling has become increasingly popular in recommendation and ranking algorithms, owing to its capacity to model users' historical behaviors and infer user intentions. Despite its theoretical simplicity, the practical deployment of a sequence model in production is non-trivial due to complexity of the sequence and sparse labels. For example, in Airbnb, guest sequences are often long, exploratory and complex, and we focus on booking labels, which are sparse. As such, we are often required to make various design decisions regarding data and modeling to strike a balance between effectiveness and scalability. This work delved into these production challenges and deployed JourneyFormer, a sequence modeling solution for search ranking at Airbnb. We detail crucial design considerations, covering aspects such as guest event selection, ID embeddings, model architecture, and label attribution. Additionally, we describe several tailored strategies to accelerate model training and inference. JourneyFormer has been successfully deployed within Airbnb's production, where its effectiveness and impact have been evidenced not only by improved offline ranking metrics but also by significant gains in key business metrics through online A/B testing across 2 production surfaces.

02.
arXiv (CS.CL) 2026-06-24

CN-NewsTTS Bench: a target-level automatic benchmark for raw-input Chinese news TTS pronunciation

Authors:

Chinese news text contains dense written forms such as scores, hyphenated model names, ranges, unit symbols, percentages, English abbreviations, and mixed Chinese-Latin-digit names. These forms are frequent in real listening workflows, and a text-to-speech (TTS) system can preserve the written string while changing the spoken meaning. We introduce CN-NewsTTS Bench v0.1, an open target-level benchmark for evaluating whether Chinese news TTS products pronounce such targets correctly from raw text, without user-side rules, LLM rewriting, SSML hints, or manual edits. The release contains a 200-record development set, an 800-record public test set, 992 public auto-evaluable targets, fixed transcripts from a three-ASR ensemble, an automatic target scorer, and initial results for seven product TTS systems. We additionally report ASR-route diagnostics, ASR-subset ablations, category-level results, confidence intervals, and provider configuration metadata. The best system reaches 0.879 strict accuracy, while several systems remain below 0.60.

03.
arXiv (CS.AI) 2026-06-15

COGNITION: From Evaluation to Defense against Multimodal LLM CAPTCHA Solvers

arXiv:2512.02318v4 Announce Type: replace-cross Abstract: This paper studies how multimodal large language models (MLLMs) undermine the security guarantees of visual CAPTCHA. We identify the attack surface where an adversary can cheaply automate CAPTCHA solving using off-the-shelf models. We evaluate 7 representative MLLMs on 18 real-world CAPTCHA task types, measuring single-shot accuracy, success under limited retries, end-to-end latency, and per-solve cost. We further validate our findings through a supplemental external dataset and an adaptive-attacker setting with session memory, while also analyzing the impact of task-specific prompt engineering and few-shot demonstrations on solver effectiveness. We reveal that MLLMs can reliably solve recognition-oriented and low-interaction CAPTCHA tasks at human-like cost and latency, whereas tasks requiring fine-grained localization, multi-step spatial reasoning, or cross-frame consistency remain significantly harder for current models. By examining the reasoning traces of such MLLMs, we investigate the underlying mechanisms of why models succeed/fail on specific CAPTCHA puzzles and use these insights to derive defense-oriented guidelines for selecting and strengthening CAPTCHA tasks. To validate these principles, we present a proof-of-concept by hardening a vulnerable CAPTCHA type using our guidelines. We demonstrate that incorporating fine-grained localization and implicit counting reduces the success rate of state-of-the-art MLLMs from over 95\% to 0\%, confirming that structural changes can effectively mitigate the threat. We conclude by emphasizing the urgent need for CAPTCHA redesign as MLLM capabilities increasingly threaten existing defenses. Code Availability (https://doi.org/10.5281/zenodo.20406852).

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

Implicit Neural Representations of Individual Behavior

arXiv:2606.12200v1 Announce Type: cross Abstract: We study policy representation learning from unlabeled multi-policy behavioral data. Each episode is generated by a fixed policy, but policy labels are unavailable. This setting appears in robotics play, demonstrations, games, racing, and other datasets where heterogeneous behaviors are mixed without annotations. We introduce Behavioral INR, a self-supervised generative model that adapts implicit neural representations (INRs) from vision to behavior. Instead of mapping coordinates to RGB values, Behavioral INR represents a policy as a state-action function mapping states to subsequent actions. An episode-level latent modulates this function through FiLM layers, yielding a generative prior over policies and allowing policy identity to be inferred without supervision. Because INRs treat each datapoint as samples from an underlying function, the same model naturally accommodates variable episode lengths and different sampling granularities, as in vision INRs with different image resolutions. We also define policy-level out-of-distribution (OOD) shifts along state-distribution and action-distribution axes, which arise when policies overlap in states or actions but are not captured by standard behavioral OOD settings based only on new agents or environments. We evaluate on synthetic Gaussian random field data, MuJoCo demonstrations with controlled OOD splits, and real-world chess, Formula 1 racing, robotics, and Seek-Avoid datasets. Behavioral INR most consistently improves policy identifiability in the hardest continuous state-action settings, especially when longer episodes, more policies, and OOD splits reduce the usefulness of marginal shortcuts; amortized history encoders remain competitive when policy identity can be recovered from symbolic repetition or low-dimensional action statistics. We release code and checkpoints.

05.
arXiv (quant-ph) 2026-06-19

Computing noise-canceling observables via Pauli propagation

arXiv:2606.20441v1 Announce Type: new Abstract: The pursuit of quantum advantage is driving the co-evolution of quantum processors and classical simulation methods. Despite advances in scale and quality, the accuracy of quantum simulation is ultimately limited by error rates and sampling overheads. Similarly, while classical simulation methods such as Pauli propagation have made remarkable progress, their accuracy is ultimately limited by the exponential growth of operator paths and the truncations needed to control memory and runtime. Here we show that these complementary limitations can be mitigated by embedding Pauli propagation within a hybrid error-mitigation framework that reduces quantum sampling overhead while achieving lower truncation errors with fewer classical resources than traditional Pauli propagation alone. In this framework, a target observable is classically propagated through noise-canceling inverse channels, producing a modified observable that is measured directly on a quantum processor. We prototype two implementations and benchmark their performance numerically on canonical models that challenge traditional Pauli propagation. We also perform experiments on a quantum processor using 56 superconducting qubits, revealing the tradeoffs of their respective truncation strategies. These results illustrate how classical and quantum resources can be orchestrated to extend observable estimation beyond the limits of either approach alone, providing a foundation for quantum-centric supercomputing and future demonstrations of quantum advantage.

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

ChiKhaPo: A Large-Scale Multilingual Benchmark for Evaluating Lexical Comprehension and Generation in Large Language Models

Existing benchmarks for large language models (LLMs) are largely restricted to high- or mid-resource languages, and often evaluate performance on higher-order tasks in reasoning and generation. However, plenty of evidence points to the fact that LLMs lack basic linguistic competence in the vast majority of the world's 3800+ written languages. We introduce ChiKhaPo, consisting of 8 subtasks of varying difficulty designed to evaluate the lexical comprehension and generation abilities of generative models. ChiKhaPo draws on existing lexicons, monolingual data, and bitext, and provides coverage for 2700+ languages for 2 subtasks, surpassing any existing benchmark in terms of language coverage. We further show that 6 SOTA models struggle on our benchmark, and discuss the factors contributing to performance scores, including language family, language resourcedness, task, and comprehension versus generation directions. With ChiKhaPo, we hope to enable and encourage the massively multilingual benchmarking of LLMs.

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

Pix2Pix-Hybrid: Structure-Guided Conditional Synthesis of Hajj Crowd Images with Multi-Channel Conditioning and Weak Attribute Supervision

Developing accurate crowd-counting models for Hajj pilgrimage scenes remains challenging because domain-specific annotated images are scarce and data collection during large gatherings raises privacy concerns. To address these limitations, this paper proposes Pix2Pix-Hybrid (P2P-H), a hybrid conditional GAN for structure-guided Hajj crowd-image synthesis and data augmentation. P2P-H builds on Pix2Pix and employs a U-Net generator conditioned on eight input channels that jointly encode structural cues (edges and grayscale) and contextual attributes (crowd density and time of day). To capture detailed textures in dense scenes, the framework integrates two multi-scale PatchGAN discriminators operating at different resolutions. The training procedure combines adversarial, perceptual, and feature-matching objectives with adaptive data augmentation and stabilization strategies. The model was trained on 993 real Hajj frames collected from 60 publicly available video sources, with conditioning attributes derived automatically to reduce manual labeling effort. Using this framework, we constructed CrowdH, a synthetic dataset of 10,000 high-resolution Hajj crowd images. Experimental results show that P2P-H improves structure-preserving conditional synthesis quality compared with Pix2Pix and StyleGAN2-ADA baselines and shows favorable transfer to other crowd datasets. To assess downstream utility, we further constructed CrowdH-Mix-469, an annotated mixed real-synthetic dataset comprising 384 real Hajj images and 85 selected synthetic images,and evaluated five crowd-counting models under real-only and real-plus-synthetic training. The selected synthetic data reduced MAE across all five models, with the strongest gain observed for CSRNet.

08.
arXiv (quant-ph) 2026-06-12

Diffusive Dynamics of Nonstabilizerness

arXiv:2606.13606v1 Announce Type: new Abstract: Symmetries shape the quantum-information dynamics of many-body systems, but their effect on nonstabilizerness, the resource complementary to entanglement, is less understood. We compute the stabilizer Rényi entropy, a measure of nonstabilizerness, in $\mathrm{U}(1)$-symmetric one-dimensional random circuits. The disorder-averaged dynamics is captured by a four-replica tensor network, which we evaluate by $S_4$-adapted infinite time-evolving block decimation (iTEBD) directly in the thermodynamic limit. Together with a hydrodynamic argument, our results identify a diffusive universality class for the late-time approach of nonstabilizerness to its random-state value, with the stabilizer Rényi entropy gap closing as $1/t$. The same scaling is verified in an energy-conserving nonintegrable Ising chain. More broadly, our framework provides a hydrodynamic perspective on nonstabilizerness generation and offers insight into the design of approximate Haar-random states in Hamiltonian dynamics.

09.
arXiv (math.PR) 2026-06-17

Moment generating function of the tacnode process

Authors:

arXiv:2606.17771v1 Announce Type: cross Abstract: The tacnode process is a universal determinantal point process arising in non-intersecting particle systems and random tiling models. In this paper, we study the generating function for the counting functions of the tacnode process on a union of $m$ intervals, $m\in\mathbb{N}^{+}$. Our first result provides an integral representation for the $m$-point generating function in terms of the Hamiltonian governing a system of $8m+4$ coupled differential equations. Combined with several differential identities for this Hamiltonian, the representation yields the large gap asymptotics, up to and including the constant term. As further applications, we obtain asymptotic formulae for the expectations, variances, and covariances of the counting functions, and establish a central limit theorem for their joint fluctuations. These results extend the previously known $1$-point theory for the tacnode process to the multi-interval setting with multiple discontinuities.

11.
PLOS Medicine 2026-06-24

Cardiovascular outcomes and safety associated with statin therapy for primary prevention in older adults with type 2 diabetes: A target trial emulation study

Authors:

by Linda Chan, Wanchun Xu, Esther W. Y. Chan, Eric Yuk Fai Wan Background There is limited evidence on the use of statins for primary prevention of cardiovascular disease (CVD) in older adults with type 2 diabetes due to underrepresentation of this population in randomized controlled trials (RCTs). We aimed to determine the effectiveness and safety of statin therapy for primary CVD prevention among type 2 diabetes patients aged ≥75 years. Methods and findings In this cohort study, territory-wide electronic health records (EHRs) from the Hospital Authority Clinical Management System in Hong Kong were used to emulate a sequence of nested target trials. Eligible patients were included in a rolling basis in each calendar month from January 2009 to December 2015, and thus we emulated 84 ‘nested monthly trials’. In each monthly trial, all type 2 diabetes patients aged ≥60 years with elevated low-density lipoprotein cholesterol (≥2.6 mmol/L) in the baseline calendar month were included; patients with a history of type 1 diabetes, CVDs, cancers, muscle-related disorders, or liver dysfunction were excluded from analysis. Eligible individuals were classified into statin initiators or noninitiators based on whether they initiated statin therapy at the time of enrollment. They were categorized into various age groups (60–74, 75–84, ≥85 years) for analysis, with those aged 60–74 years forming a benchmark group to test the validity of the emulated target trial. Patients were followed up until the outcome of interest, death, or the administrative end (December 2018), whichever occurred first. We estimated hazard ratios (HRs) comparing statin use versus nonuse for CVDs, all-cause mortality, muscle-related adverse events (AEs), and liver dysfunction using pooled logistic models, with inverse probability weighting to adjust for time-varying confounders related to treatment adherence, under the assumption of no unmeasured confounding. Propensity score matching was performed on eligible person-trials at baseline, incorporating demographic characteristics, clinical and laboratory parameters, comorbidities, medication history, and healthcare utilization as matching variables. Among 30,804 matched person-trials aged 75–84 years, a significant reduction in the incidence of CVDs (HR 0.69 (95% CI [0.65, 0.75]; p 

12.
arXiv (CS.AI) 2026-06-11

Internet of Everything in the 6G Era: Paradigms, Enablers, Potentials and Future Directions

arXiv:2604.25018v2 Announce Type: replace-cross Abstract: The Internet of Everything (IoE) represents an evolution of the Internet of Things (IoT) by integrating people, data, processes, and things into a unified intelligent ecosystem. IoE aims to enhance automation, decision-making, and service efficiency across multiple application domains such as smart cities, healthcare, industry, and next-generation wireless networks. This paper provides a structured overview of the IoE concept, its core components, architectural foundations, enabling technologies, and major research challenges. Finally, open research directions toward 6G-enabled intelligent IoE systems are discussed, with emphasis on scalability, security, privacy, and energy efficiency.

13.
bioRxiv (Bioinfo) 2026-06-23

Systematic benchmarking of zero-shot utility and robustness in single-cell transcriptomic foundation models

Single-cell foundation models (scFMs) have been proposed as reusable representations for transcriptomic analysis, yet their practical utility and robustness when applied without task-specific fine-tuning remain incompletely characterized. Here, we systematically evaluated single-cell transcriptomic representations in zero-shot settings across 20 methods, 6 downstream tasks and 1,607 datasets comprising nearly 21.8 million cells. We characterized model behavior along three complementary dimensions: baseline utility, structural robustness, and dataset-level drivers of performance variability. Our large-scale analysis reveals a decoupling between utility and robustness: methods ranking highly on standard benchmarks often show marked instability under shifts in dataset structure. Furthermore, no single model performs uniformly well across tasks. In several tasks, classical statistical representations based on highly variable genes remain competitive under zero-shot conditions. Together, these results define the practical boundaries of zero-shot use in scFMs and provide a large-scale benchmark and decision framework for representation selection in single-cell genomics.

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

MVEB: Massive Video Embedding Benchmark

We introduce the Massive Video Embedding Benchmark (MVEB), a 23-task benchmark for video embeddings spanning classification, zero-shot classification, clustering, pair classification, retrieval, and video-centric question answering. We evaluate 33 models and find that no single model dominates: MLLM-based embeddings lead on classification, clustering, pair classification, and QA; multimodal binding leads on retrieval and zero-shot classification; generative MLLMs without contrastive adaptation collapse on cross-modal tasks. Paired video-only vs. audio+video evaluations show that audio's contribution depends on dataset annotation provenance: audio helps when labels were produced from both modalities and hurts when they were produced from visuals alone, a six-point gap consistent across model families. MVEB is derived from MVEB+, a 184-task pool, and is designed to maintain task diversity while reducing evaluation cost. It integrates into the MTEB ecosystem for unified evaluation across text, image, audio, and video. We release MVEB and all 184 tasks along with code and a leaderboard at https://github.com/embeddings-benchmark/mteb.

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

GridVQA-X: A Framework for Evaluating Multimodal Explainability Methods

With the increasing development of Vision-Language Models, it becomes imperative that their predictions are readily explainable to relevant stakeholders. However, the field of explainability has not kept pace with the multimodal surge. While recent Multimodal Explainable AI (MxAI) methods generate explanations to attribute the interaction between different modalities, current evaluation protocols lack the ground truth required to distinguish between true cross-modal reasoning (e.g., spatial composition) and shallow cross-modal shortcuts (e.g., Bag-of-Words attribute matching). It remains unknown whether MxAI methods faithfully capture synergistic interactions or merely hallucinate reasoning on models acting as simple feature detectors. In this paper, we introduce GridVQA-X, the first diagnostic framework specifically designed to evaluate cross-modal explainability. Unlike natural datasets, GridVQA-X leverages a closed-world synthesis logic to generate unique, mathematically guaranteed explanations. We utilize this controlled environment to train paired ground-truth models on identical architectures: $M_{pure}$, which learns robust spatial-relational reasoning and $M_{spur}$, which is structurally forced to rely on cross-modal shortcuts. This behavioral divergence creates a rigorous testbed: a faithful explainer must report distinct reasoning pathways for each model. Our findings reveal that widely used methods fail to distinguish between models relying on genuine spatial-relational reasoning and those exploiting cross-modal shortcuts, highlighting a critical gap in capturing true cross-modal synergy and misrepresenting how multimodal models actually make decisions.

16.
arXiv (math.PR) 2026-06-15

Laws of Large Numbers for Non-Independent Random Variables on Hyperspaces with respect to the Hausdorff Metric

arXiv:2011.07199v5 Announce Type: replace Abstract: This paper investigates the limit behavior of the Minkowski sums for sequences of set-valued random variables. When the underlying space is finite dimensional, by using the support function, we establish the weak and strong laws of large numbers for non-independent random variables in the hyperspace with respect to the Hausdorff metric $d_H$.

17.
arXiv (CS.CV) 2026-06-19

Abstraction in Style: Beyond Texture and Color

Artistic styles often embed abstraction beyond surface appearance, involving deliberate reinterpretation of structure rather than mere changes in texture or color. Conventional style transfer methods typically preserve the input geometry and therefore struggle to capture this deeper abstraction behavior, especially for illustrative and nonphotorealistic styles. In this work, we introduce Abstraction in Style (AiS), a generative framework that separates structural abstraction from visual stylization. Given a target image and a small set of style exemplars, AiS first derives an intermediate abstraction proxy that reinterprets the target's structure in accordance with the abstraction logic exhibited by the style. The proxy captures semantic structure while relaxing geometric fidelity, enabling subsequent stylization to operate on an abstracted representation rather than the original image. In a second stage, the abstraction proxy is rendered to produce the final stylized output, preserving visual coherence with the reference style. Both stages are implemented using a shared image space analogy, enabling transformations to be learned from visual exemplars without explicit geometric supervision. By decoupling abstraction from appearance and treating abstraction as an explicit, transferable process, AiS supports a wider range of stylistic transformations, improves controllability, and enables more expressive stylization.

18.
bioRxiv (Bioinfo) 2026-06-24

SEMFA: A General Framework for Inferring Statistical Significance of Mahalanobis Similarity between Multi-Omics Profiled Samples Built on Multiple Factor Analysis

Motivation: With rapid advances in sequencing technologies, many heterogeneous omics datasets have been generated, as seen in the Encyclopedia of DNA Elements (ENCODE) and many single-cell multi-omics sequencing projects, bringing substantial challenges to existing integrative methods. In this article, we report a novel multi-omics fusion and analysis software SEMFA which performs general parametric tests for the Mahalanobis Similarity of samples based on the factor scores generated by an Extended version of conventional Multiple Factor Analysis. Results: Our developed method is effective and robust under both Gaussian and non-Gaussian assumptions. The mean F1 scores are over 0.8 when the column similarity level is 0.9 and the noise level ranges between 0.1 and 0.2, using simulation studies based on ENCODE count data. It was also efficient and effective at handling large-scale single-cell multi-omics data, as demonstrated in colon cancer cases as it unveiled signature network organization patterns of cells for stages III and IV.

19.
arXiv (CS.CV) 2026-06-16

Interpolation between Convolution and Attention via K-Nearest Neighbors

Authors:

The shift from Convolutional Neural Networks to Transformers has reshaped computer vision, yet these two architectural families are typically viewed as fundamentally distinct. Convolutional Neural Networks are defined by spatially local convolution operations, while Transformers rely on global self-attention. We argue that convolution and self-attention, despite their apparent differences, can be unified within a single k-nearest neighbor aggregation framework. The critical insight is that both operations are special cases of neighbor selection and weighted aggregation. Convolution selects neighbors by spatial proximity while self-attention selects by feature similarity, revealing that they lie on a continuous spectrum rather than representing categorically different computations. We introduce Convolutional Nearest Neighbors (ConvNN), a unified framework that formalizes this connection. ConvNN exactly recovers standard and depthwise convolution by restricting neighbor selection to normalized spatial coordinates, and exactly recovers self-attention and its sparse variants, including KVT-attention, by replacing spatial proximity with scaled dot-product similarity. Beyond these special cases, ConvNN serves as a drop-in replacement for both convolution and attention layers, enabling systematic exploration of the intermediate spectrum between local and global aggregation through configurable similarity functions, neighbor selection strategies, positional encodings, and aggregation kernels.

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

EvoMemBench: Benchmarking Agent Memory from a Self-Evolving Perspective

Recent benchmarks for Large Language Model (LLM) agents mainly evaluate reasoning, planning, and execution. However, memory is also essential for agents, as it enables them to store, update, and retrieve information over time. This ability remains under-evaluated, largely because existing benchmarks do not provide a systematic way to assess memory mechanisms. In this paper, we study agent memory from a self-evolving perspective and introduce EvoMemBench, a unified benchmark organized along two axes: memory scope (in-episode vs. cross-episode) and memory content (knowledge-oriented vs. execution-oriented). We compare 15 representative memory methods with strong long-context baselines under a standardized protocol. Results show that current memory systems are still far from a general solution: long-context baselines remain highly competitive, memory helps most when the current context is insufficient or tasks are difficult, and no single memory form works consistently across all settings. Retrieval-based methods remain strong for knowledge-intensive settings, whereas procedural and long-term memory methods are more effective for execution-oriented tasks when their stored experience matches the task structure. We hope EvoMemBench facilitates future research on more effective memory systems for LLM-based agents. Our code is available at https://github.com/DSAIL-Memory/EvoMemBench.

21.
arXiv (quant-ph) 2026-06-16

Adiabatic preparation of a fractional quantum Hall fluid by coherently pumping atoms from a Bose-Einstein condensate

arXiv:2606.15951v1 Announce Type: cross Abstract: We propose a protocol to adiabatically prepare a many-particle fractional quantum Hall fluid of bosonic ultracold atoms exploiting a time-dependent coherent coupling of a strongly interacting atomic state with a large dilute Bose-Einstein condensate. Starting from an empty cloud, atoms with well-defined angular momentum are coherently pumped into the fluid by Raman beams with a Laguerre-Gauss profile. Compared to number-conserving schemes which rely on finite-size-induced topological gaps, we identify an adiabatic path in the Fock space which avoids crossing topological phase transitions and thus maintains a sizable adiabatic gap open at all times. The efficiency of our preparation protocol is numerically assessed for typical experimental parameters up to particle numbers that largely exceed the experimental state-of-the-art. The crucial advantage of including an anharmonic confinement is finally highlighted.

22.
arXiv (CS.AI) 2026-06-16

SkillsBench: Benchmarking How Well Agent Skills Work Across Diverse Tasks

arXiv:2602.12670v4 Announce Type: replace Abstract: Agent Skills are structured packages of procedural knowledge that augment large language model (LLM) agents at inference time. Despite rapid adoption, there is no standard way to measure whether they actually help. We present SkillsBench, a benchmark whose current inventory contains 87 tasks across 8 domains paired with curated Skills and deterministic verifiers. Our latest aggregate evaluation runs the 87-task benchmark under matched no-Skills and curated-Skills conditions for 18 model-harness configurations. Curated Skills raise the average pass rate from 33.9% to 50.5% (+16.6 percentage points; 25.5% normalized gain), with configuration-level gains ranging from +4.1 to +25.7 pp. Focused Skills with at most three modules outperform larger or exhaustive bundles, and smaller models with Skills can match larger models without them. SkillsBench establishes paired evaluation as the foundation for rigorous measurement of Skill efficacy on agentic, expertise-heavy work.

23.
medRxiv (Medicine) 2026-06-17

Frequency-dependent cognitive effects of Deep Brain Stimulation in Parkinson's Disease: A Systematic Review and Meta-Analysis

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves levodopa-induced motor complications and cardinal motor symptoms of Parkinson's disease (PD), but stimulation frequency may differentially shape outcomes. This is evident for axial and gait symptoms, which may respond differently to lower-frequency stimulation. Whether frequency-dependent effects extend to cognition remains unclear. Objective: To investigate the cognitive effects of DBS at distinct frequencies in PD. Methods: We conducted a systematic review and meta-analysis (PROSPERO - CRD42024618253). PubMed, Web of Science, and EMBASE were searched for studies assessing cognitive outcomes under different stimulation frequencies. Eight cognitive domains were defined: verbal fluency, cognitive flexibility, executive control, working memory, attention, processing speed, episodic memory, and time processing. Multilevel random-effects meta-analyses were performed, with effect sizes expressed as Hedges' g. Results: Forty-three studies met the inclusion criteria, the majority (n = 31) involving STN-DBS. Twenty-one STN-DBS studies, including 355 patients, were included in the meta-analysis. Compared with HFS ([≥] 130 Hz), lower frequencies (4-80 Hz) were associated with better verbal fluency (g = 0.27) and cognitive flexibility (g = 0.38), with consistent effects across sensitivity and leave-one-out analyses. Accuracy-based executive control measures also favored lower-frequency stimulation. OFF-stimulation comparisons showed a concordant pattern. Evidence for other targets (PPN and NBM) was limited. Conclusions: Lower-frequency STN-DBS was associated with modest benefits in specific cognitive domains compared with HFS. These findings highlight the need for future research to determine how frequency interacts with stimulation location and symptom-specific networks to shape cognitive and cognitive-motor outcomes in PD.

24.
PLOS Computational Biology 2026-06-12

Stage-dependent role of NEK7 in the inactive-to-active conformational transition of NLRP3 monomer

Authors:

by Jin Peng, Wenjian Li, Hao Wang, Xiaohui Chen, Manjie Zhang, Bin Sun The NLRP3 inflammasome is a multiprotein complex that primes cytokine production in the innate immune system. The inflammasome activation involves the cage-to-disk transition of NLRP3 oligomers, facilitated by the co-factor NEK7 protein. While NEK7’s role in promoting cage disassembly has been reported, its involvement in the large conformational changes of the NLRP3 monomer during activation remains elusive. Here, by using multi-scale simulations, we uncovered a stage-dependent role of NEK7 in the inactive-to-active transition. In the early stage, NEK7 reshapes the dynamics of the highly unstable inactive NLRP3 monomer to resemble active state, priming the conformational transition. In the middle stage, NEK7 impedes progression by populating an intermediate state farther from the active conformation than the NEK7-free counterpart, and structures in this state exhibit reduced allosteric potential toward activation. In the late stage, NEK7 has negligible impact, as the active conformation remains inherently isolated by a high energy barrier regardless of NEK7 presence. This highlights the critical role of oligomeric assembly in enabling monomeric NLRP3 to complete its conformational transition, in agreement with experiment observations. Our work suggests a multilayered activation mechanism where oligomer-level assembly and monomeric conformational changes are coupled, providing new mechanistic insights into this physiologically essential macromolecular process.

25.
arXiv (CS.LG) 2026-06-18

Ensuring Trustworthy Online A/B Testing: Addressing Five Key Questions on CUPED

arXiv:2606.18750v1 Announce Type: cross Abstract: A/B testing has become the gold standard for data-driven decision-making in large-scale online experimentation, providing critical guidance for feature launch, pricing optimization, and user experience enhancement. To maximize statistical sensitivity, many technology companies routinely employ Controlled-experiment Using Pre-Experiment Data (CUPED), a technique that achieves substantial variance reduction while preserving the unbiasedness of estimating the average treatment effect. Despite its widespread adoption, several critical methodological and practical nuances of CUPED remain underexplored. This paper systematically addresses five frequently encountered yet overlooked questions regarding the application of CUPED. First, we provide a comparative analysis of various post-CUPED estimators to identify the optimal adjustment specification. Second, we evaluate the validity of regression-based adjustments and delineate robust variance estimation methods tailored for such frameworks. Finally, we extend our investigation to complex but common scenarios, including multi-arm experiments and two-stage sampling designs. Our findings reveal that in these settings, naive reliance on standard variance estimators can lead to severely misleading inferences. By offering rigorous theoretical insights and extensive experimental validation, this work deepens the conceptual understanding of CUPED. Notably, the recommended methodologies have been successfully deployed and integrated into ByteDance's experimentation platform.