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01.
arXiv (quant-ph) 2026-06-16

A complexity theory for non-local quantum computation

arXiv:2505.23893v2 Announce Type: replace Abstract: Non-local quantum computation (NLQC) replaces a local interaction between two systems with a single round of communication and shared entanglement. Despite many partial results, it is known that a characterization of entanglement cost in at least certain NLQC tasks would imply significant breakthroughs in complexity theory. Here, we avoid these obstructions and take an indirect approach to understanding resource requirements in NLQC, which mimics the approach used by complexity theorists: we study the relative hardness of different NLQC tasks by identifying resource efficient reductions between them. Most significantly, we prove that $f$-measure and $f$-route, the two best studied NLQC tasks, are in fact equivalent under $O(1)$ overhead reductions. This result simplifies many existing proofs in the literature and extends several new properties to $f$-measure. For instance, we obtain sub-exponential upper bounds on $f$-measure for all functions, and efficient protocols for functions in the complexity class $\mathsf{Mod}_k\mathsf{L}$. Beyond this, we study a number of other examples of NLQC tasks and their relationships.

02.
arXiv (CS.AI) 2026-06-19

Reinforcement-aware Knowledge Distillation for LLM Reasoning

arXiv:2602.22495v3 Announce Type: replace-cross Abstract: Reinforcement learning (RL) post-training has recently driven major gains in long chain-of-thought reasoning large language models (LLMs), but the high inference cost of such models motivates distillation into smaller students. Most existing knowledge distillation (KD) methods are designed for supervised fine-tuning (SFT), relying on fixed teacher traces or teacher-student Kullback-Leibler (KL) divergence-based regularization. When combined with RL, these approaches often suffer from distribution mismatch and objective interference: teacher supervision may not align with the student's evolving rollout distribution, and the KL regularizer can compete with reward maximization and require careful loss balancing. To address these issues, we propose RL-aware distillation (RLAD), which performs selective imitation during RL – guiding the student toward the teacher only when it improves the current policy update. Our core component, Trust Region Ratio Distillation (TRRD), replaces the teacher-student KL regularizer with a PPO/GRPO-style likelihood-ratio objective anchored to a teacher–old-policy mixture, yielding advantage-aware, trust-region-bounded distillation on student rollouts and naturally balancing exploration, exploitation, and imitation. Across diverse logic reasoning and math benchmarks, RLAD consistently outperforms offline distillation, standard GRPO, and KL-based on-policy teacher-student knowledge distillation.

03.
arXiv (CS.LG) 2026-06-16

Imbalanced Classification under Capacity Constraints

arXiv:2605.03289v2 Announce Type: replace-cross Abstract: Detecting observations from a minority class under severe class imbalance is a central challenge in applications such as fraud detection, medical screening, and industrial quality control. In these settings, each positive prediction triggers a costly follow-up action, an MRI scan, a transaction audit, whose execution is subject to real operational constraints. This paper proposes a formal classification framework under capacity constraints: given a user-defined bound limit $b$ on the proportion of observations that can be labeled as belonging to the minority class, the goal is to find the classifier that maximizes sensitivity on that class. We characterize the optimal classifier under this constraint and establish its equivalence with the classical Bayes classifier under a reweighting of the prior probabilities. We also introduce a capacity-adjusted performance metric $M$ that accounts for the effective detection rate when the capacity constraint is binding. The framework is implemented on top of standard learning methods, k-NN, SVM, random forests, and neural networks, and statistical consistency is established for each. We further show that these methods reduce to post-hoc thresholding when no hyperparameters are oriented toward the capacity-constrained objective, and introduce a capacity-aware support vector machine that exploits the constraint during training and achieves the strongest empirical performance. Experiments on the Taiwanese credit card default dataset confirm that capacity-constrained classifiers substantially outperform both classical approaches and SMOTE under high imbalance regimes. The framework extends naturally to multiclass settings and online environments.

04.
arXiv (CS.AI) 2026-06-16

AlignCoder: Aligning Retrieval with Target Intent for Repository-Level Code Completion

arXiv:2601.19697v2 Announce Type: replace-cross Abstract: Repository-level code completion remains a challenging task for existing code large language models (code LLMs) due to their limited understanding of repository-specific context and domain knowledge. While retrieval-augmented generation (RAG) approaches have shown promise by retrieving relevant code snippets as cross-file context, they suffer from two fundamental problems: misalignment between the query and the target code in the retrieval process, and the inability of existing retrieval methods to effectively utilize the inference information. To address these challenges, we propose AlignCoder, a repository-level code completion framework that introduces a query enhancement mechanism and a reinforcement learning based retriever training method. Our approach generates multiple candidate completions to construct an enhanced query that bridges the semantic gap between the initial query and the target code. Additionally, we employ reinforcement learning to train an AlignRetriever that learns to leverage inference information in the enhanced query for more accurate retrieval. We evaluate AlignCoder on two widely-used benchmarks (CrossCodeEval and RepoEval) across five backbone code LLMs, demonstrating an 18.1% improvement in EM score compared to baselines on the CrossCodeEval benchmark. The results show that our framework achieves superior performance and exhibits high generalizability across various code LLMs and programming languages.

05.
arXiv (CS.LG) 2026-06-18

Robust and Interpretable Adaptation of Equivariant Materials Foundation Models via Sparsity-promoting Fine-tuning

arXiv:2606.18691v1 Announce Type: new Abstract: Pre-trained materials foundation models, or machine learning interatomic potentials, leverage general physicochemical knowledge to effectively approximate potential energy surfaces. However, they often require domain-specific calibration due to physicochemical diversity as well as mismatches between practical computational settings and those used in constructing the pre-training data. To address this, we propose a sparsity-promoting fine-tuning method that selectively updates model parameters by exploiting the structural properties of E(3)-equivariant materials foundation models. On energy and force prediction tasks across molecular and crystalline benchmarks, our method matches or surpasses full fine-tuning and equivariant low-rank adaptation while updating only $\sim$3~\% of parameters, and in some cases as little as $\sim$0.5~\%. Beyond energy and force calibration, we further demonstrate task generalizability by applying our method to magnetic moment prediction and magnetism-aware total energy modeling. Finally, analysis of sparsity patterns reveals physically interpretable signatures, such as enhanced $d$-orbital contributions in transition metal systems. Overall, our results establish sparsity-promoting fine-tuning as a flexible and interpretable method for domain specialization of equivariant materials foundation models.

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

Adapting Prithvi-EO for Fallow Detection for Food-Water Nexus: ViT-Adapter Necks and Parameter-Efficient Backbone tuning of Geospatial Foundation Model

Understanding spatial distribution of fallow land is important for optimizing the food-water (FW) nexus, given fallowing's role in crop rotation and water conservation. Fallow is a low accuracy class in USDA Cropland Data Layer (CDL). Geospatial foundation model (GFM), Prithvi-EO has shown strong transferability across computer vision tasks. However, its Vision Transformer (ViT) backbone produces features at a single spatial scale that are ill-suited for the multi-scale features required by object detection heads. Existing approaches synthesise multi-scale pyramids through scaling of single stride tokens, sacrificing spatial heterogeneity, and full backbone fine-tuning is computationally prohibitive for GFMs. We evaluate a fallow detection pipeline combining two parameter-efficient fine tuning (PEFT) schemes: Low-Rank Adaptation (LoRA) and a hybrid PEFT, with three neck designs: pseudo multi-scale, Lite ViT-Adapter, and Full ViT-Adapter. Our best configuration, Lite ViT-Adapter with a one-stage head, achieves a mAP@50 of 0.9479 with the Diou loss, suggesting the effectiveness of center-aware localization for irregular fallow field detection. ViT-Adapter free one-stage detection under LoRA improves the adapter-free anchor-based approach by 6.42%, and the best configuration improves baseline adapter-free anchor-based approach by 25.70%. These results demonstrate that lightweight spatial prior fusion and selective backbone unfreezing enable Prithvi-EO to capture local fallow patterns more effectively, outperforming approaches that rely on reshaped single-stride ViT tokens.

07.
arXiv (CS.AI) 2026-06-18

As You Wish: Mission Planning with Formal Verification using LLMs in Precision Agriculture

arXiv:2606.18519v1 Announce Type: cross Abstract: Though robotic systems are now being commercialized and deployed in various industries, many of these systems are highly specialized and often require an advanced skill set to operate and ensure they perform as instructed. To mitigate this problem, we recently introduced a mission planner leveraging LLMs to synthesize mission plans in precision agriculture based on mission descriptions provided in natural language. While the system demonstrates impressive performance, it also suffers from the inherent ambiguities of natural language. In this paper, we extend our system to address this issue by introducing multiple feedback loops in the planning architecture that leverage linear temporal logic (LTL) to ensure the mission planning system meets the specifications formulated by the user while still using natural language. To mitigate potential bias, this is achieved by using two different commercial LLMs in charge of the specification and verification subtasks. Through extensive experiments, we highlight the strengths and limitations of integrating mission verification into a fully autonomous pipeline, particularly regarding an LLM's ability to generate valuable LTL formulas, and show how our proposed implementation addresses and solves these challenges.

08.
Nature (Science) 2026-06-10

Building user-driven climate adaptation products

Climate adaptation products have traditionally been developed using a supply-driven model reliant on available climate information, leading to usability gaps1–4. To better meet user needs, the climate services field has recognized a need to shift towards a demand-driven model emphasizing co-production, that is, user-driven, scientifically informed products created through shared knowledge practices1–5. However, co-production can be challenging, especially for researchers unfamiliar with the approach or for digital and software-based products with complex user needs2,5–8. User-centred design, from the human–computer interaction field, offers a process that could complement co-production approaches to product development, yet its potential remains underexplored2. Here we show how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products. Through a systematic review of the co-production and user-centred design literature, we identify key processes, mechanisms and best practices for both approaches. Our findings offer practical guidance for researchers and propose an integrated approach for developing climate adaptation products that are useful, usable and used. A systematic review and analysis shows how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products.

09.
arXiv (CS.CL) 2026-06-19

Generative Engine Optimization at Scale: Measuring Brand Visibility Across AI Search Engines

People increasingly get answers straight from AI search engines like ChatGPT, Claude, Perplexity, and Gemini rather than scrolling search results. Brands that once focused on search engine optimization (SEO) must now optimize for how these engines represent, cite, and recommend them – a shift variously called Generative Engine Optimization (GEO), Answer Engine Optimization (AEO), and AI Search Visibility. We treat AEO and AI Visibility as part of GEO, and study how to measure brand visibility across AI engines: what they value when they cite a brand, which sources they rely on, and what content large language models surface. The hard case is everyone outside the already-authoritative top brands – SMEs, D2C brands, creators, and early-stage startups. We analyze 100K+ prompt responses across 100+ brands tracked on Ranqo between March and May 2026. First visibility runs form a clear three-tier brand-stature ladder: global household names (e.g., Stripe, Nike) appear in 73% of relevant AI answers on their first run; established mid-market and regional brands (e.g., Olipop, Klaviyo) in 44%; niche and small brands in just 11% – about 30 percentage points per step. When engines cite sources, about 78% go to corporate websites; among non-corporate sources YouTube leads, ahead of Reddit, editorial media, and Wikipedia. The highest-leverage page is the ranked "best-of" listicle, the most-cited content format at about 21% of all citations. Sentiment is the unstable signal: whether a brand is framed positively or negatively flips about 6.7 times more often than whether it is mentioned at all. These findings provide a first large-scale baseline for measuring GEO: AI brand visibility can be measured, differs by platform, and varies strongly by brand maturity. We close by proposing seven v1.1 protocols to test whether specific recommendations can causally improve AI visibility.

10.
arXiv (CS.LG) 2026-06-15

PepALD: Macrocyclic Peptide Generation via Autoregressive Latent Diffusion

arXiv:2606.14510v1 Announce Type: new Abstract: Macrocyclic peptides are promising therapeutic candidates for intracellular targets, but their design requires simultaneous control over non-natural monomer chemistry, ring topology, membrane permeability, and target binding. Existing SMILES- or HELM-string generative models either operate in long atom-level sequence spaces or treat monomers as symbolic tokens with limited chemical grounding. We introduce PepALD, an Autoregressive Latent Diffusion (ALD) foundation model for de novo macrocyclic peptide generation. The model represents HELM monomers with structured chemical embeddings, generates each residue through context-conditioned diffusion in chemically informed latent space, predicts R-group-aware ring closures during autoregressive generation, and aligns the denoiser to affinity rewards using winner-protected diffusion-adapted preference optimization. In silico experiments demonstrate PepALD's generation quality and reward-optimization performance against representative peptide generation baselines.

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

DecompSR: A dataset for decomposed analyses of compositional multihop spatial reasoning

arXiv:2511.02627v3 Announce Type: replace Abstract: We introduce DecompSR, decomposed spatial reasoning, a large benchmark dataset (over 5m datapoints) and generation framework designed to analyse compositional spatial reasoning ability. The generation of DecompSR allows users to independently vary several aspects of compositionality, namely: productivity (reasoning depth), substitutivity (entity and linguistic variability), overgeneralisation (input order, distractors) and systematicity (novel linguistic elements). DecompSR is built procedurally in a manner which makes it is correct by construction, which is independently verified using a symbolic solver to guarantee the correctness of the dataset. DecompSR is comprehensively benchmarked across a host of Large Language Models (LLMs) where we show that LLMs struggle with productive and systematic generalisation in spatial reasoning tasks whereas they are more robust to linguistic variation. DecompSR provides a provably correct and rigorous benchmarking dataset with a novel ability to independently vary the degrees of several key aspects of compositionality, allowing for robust and fine-grained probing of the compositional reasoning abilities of LLMs.

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

HeatKV: Head-tuned KV-cache Compression for Visual Autoregressive Modeling

Visual Autoregressive (VAR) models have recently demonstrated impressive image generation quality while maintaining low latency. However, they suffer from severe KV-cache memory constraints, often requiring gigabytes of memory per generated image. We introduce HeatKV, a novel compression method that adapts cache allocation in each head based on its attention to previously generated scales. Using a small offline calibration set, the attention heads are ranked according to their attention scores over prior scales. Based on this ranking, we construct a static pruning schedule tailored to a given memory budget. Applied to the Infinity-2B model, HeatKV achieves $2 \times$ higher compression ratio in memory allocation for KV cache compared to existing methods, while maintaining similar or better image fidelity, prompt alignment and human perception score. Our method achieves a new state-of-the-art (SOTA) for VAR model KV-cache compression, showcasing the effectiveness of fine-grained, head-specific cache allocation. Code and calibration script available at https://github.com/arm-research/heatkv.

13.
arXiv (CS.LG) 2026-06-12

A Privacy-Preserving Framework Using Remote Data Science for Inter-Institutional Student Retention Prediction

arXiv:2606.12845v1 Announce Type: cross Abstract: This study explores privacy-preserving machine learning (PPML) techniques using the PySyft platform to enable collaborative prediction of student retention between institutions. We developed a remote data science (RDS) framework with a semi-air-gapped architecture consisting of high-side and low-side servers, allowing researchers from three universities to build predictive models on sensitive student data without direct data access. Using historical data from a small private university (N=720), we evaluated three synthetic data generation approaches and validated the framework through inter-institutional collaboration. The results demonstrate consistent classification performance across institutions (Macro F1: 0.690–0.695) while maintaining strict Family Educational Rights and Privacy Act (FERPA) compliance. We also propose Data-Type-Aware Templates, a novel synthetic data method that prioritizes privacy over distributional fidelity. Our findings confirm that RDS-based PPML is technically feasible for educational settings and offers a practical alternative to federated learning for small-scale inter-institutional collaborations. The code is available at https://github.com/jtfields/NAIRR240195-Privacy-Preserving-Machine-Learning.

14.
arXiv (CS.AI) 2026-06-18

Explaining Attention with Program Synthesis

arXiv:2606.19317v1 Announce Type: cross Abstract: A longstanding goal of research on interpretable deep learning is to replace opaque neural computations with human-meaningful symbolic descriptions. In this paper, we propose an approach for approximating the behavior of components of deep networks with executable programs. We focus on attention heads in transformer language models. For a given head, we first compute its associated attention matrices on a collection of randomly selected training examples. Next, we prompt a pre-trained language model with a summary of these matrices, and instruct it to generate a set of Python programs that can reproduce the associated attention patterns given only text from the input sentence. Finally, we re-rank programs according to how well our final set of programs predict behavior on held-out inputs. We demonstrate that a set of fewer than 1,000 such generated programs can reproduce the attention patterns of heads in GPT-2, TinyLlama-1.1B, and Llama-3B, achieving an average Intersection-over-Union similarity above 75% on TinyStories. Moreover, the best-fit programs can replace neural attention heads without substantially affecting model behavior: replacing 25% of attention heads with programmatic surrogates across the three models incurs only a 16% average perplexity increase, while maintaining performance on a variety of downstream question answering benchmarks. This work contributes a scalable pipeline for reverse-engineering attention heads in transformer models using human-readable, executable code, advancing a path toward symbolic transparency in neural models.

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

OTCHA: Optimal Transport-driven Confidence-aware Latent Hub Alignment for Multi-View Medical Image Classification

Multi-view imaging, such as mammography and chest radiography, is a standard component of clinical practice. However, medical images are often unregistered and contain view-specific artifacts or irrelevant background cues that can obscure diagnostically relevant findings. Many existing methods directly fuse per-view representations, allowing such irrelevant content to contaminate the fused embedding and reducing robustness under varying view configurations. We propose OTCHA, a confidence-aware latent hub token alignment module based on optimal transport (OT) that refines patch tokens before fusion for multi-view classification. OTCHA introduces a set of learnable latent hub tokens shared across views. For each view, we compute an OT plan between patch tokens and hub tokens that jointly considers feature similarity and geometry, and augment the OT formulation with token-conditional dustbins to enable partial matching and discard irrelevant tokens. The resulting transport plan provides token-wise matching confidence, which gates hub-mediated message passing and weights a novel optimal-transport-based representation alignment loss to stabilize refinement. Experiments on three multi-view medical image datasets demonstrate consistent improvements over competing baselines across diverse anatomies and view configurations. Our code is available at https://github.com/labhai/OTCHA.

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

Self-Preference Is Weak or Absent in Verifiable Instruction-Following Revision: A Four-Model Test Under Genuine Authorship

Large language models (LLMs) increasingly review and revise text, including their own. A documented self-preference bias (models favoring their own generations when acting as judges) raises the question of whether models also resist valid corrections to their own writing. We test this in a setting where "valid" is decided not by another model but by a deterministic verifier: instruction-following revision on IFEval. A model writes a draft; the official IFEval checker confirms the draft violates a constraint and that a candidate edit fixes it; the model then accepts or rejects that edit either as the genuine in-context author or as a fresh model that sees the draft neutrally. Across four mid-tier model families and 85 author-versus-fresh comparisons, we find no detectable self-preference: authors reject verified-good fixes to their own drafts at essentially the same rate as fresh models judging the same drafts (gap -5.1 pp, 95% CI [-12.9, +2.7]). A self-skepticism hint from a smaller pilot did not replicate at scale. The one robust observation is qualitative: when authors do reject a verified-good fix, 97% of their stated reasons are flaw-catching rather than preference, that is, about the character of rejections, not an elevated rate. Effects smaller than ~13 pp cannot be excluded at this sample size.

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

MLLP-VRAIN UPV system for the IWSLT 2026 Simultaneous Speech Translation task

This work describes the participation of the MLLP-VRAIN research group in the shared task of the IWSLT 2026 Simultaneous Speech Translation track. Our submission utilizes the recently released Parakeet and Qwen 3.5 models to create a robust, cascaded solution for long-form SimulST through the use of adaptive "black-box" policies. We explore relaxations of these policies to achieve better quality-latency trade-offs. Compared to last year, we participate on all language directions. In addition to this, for the En$\rightarrow${De, It, Zh} directions we also participate in this year's new context track employing a combination of ASR word-boosting and a RAG mechanism of offline pre-translated exemplars to guide generation and enrich our system with domain-specific context. Finally, we provide a detailed latency analysis of our system. Compared to last year, results on the MCIF En$\rightarrow$De test set shows a substantial quality improvement of +5.82 XCOMET-XL. Our context track processing further improves performance by +1.03.

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

NaturalFlow: Reducing Disruptive Pauses for Natural Speech Flow in Simultaneous Speech-to-Speech Translation

Simultaneous speech-to-speech translation aims to enable near-real-time communication by minimizing latency, offering a compelling, real-time alternative to the high latency of consecutive translation. However, the excessive pursuit of low latency often results in fragmented chunk-wise speech. Consequently, listeners are subjected to an unnatural acoustic flow punctuated by frequent pauses, which could increase their cognitive load. To bridge this gap, we introduce a fluency-aware optimization framework designed to discover the sweet spot between the low-latency benefits of simultaneous translation and the natural flow of consecutive translation. Our framework minimizes inter-chunk silences by leveraging model-internal signals, including linguistic diversity and induced temporal variability in speech durations. Experiments on short- and long-form benchmarks show that our framework produces natural speech flow while maintaining competitive latency and translation quality.

19.
arXiv (CS.CV) 2026-06-11

Periodic-MAE: Periodic Video Masked Autoencoder for rPPG Estimation

In this paper, we propose Periodic-MAE, a self-supervised framework for learning generalizable spatio-temporal representations of periodic physiological signals from unlabeled facial videos. The proposed method leverages a masked autoencoder (MAE), which learns high-dimensional facial representations by reconstructing masked video tokens without relying on remote photoplethysmography (rPPG) specific supervision. To explicitly align representation learning with the characteristics of rPPG, we introduce a periodicity-aware frame masking strategy based on video resampling, enabling the encoder to learn representations that capture quasi-periodic temporal patterns relevant to pulse signal estimation. In addition, physiological bandlimit constraints are integrated into the MAE pre-training framework, exploiting the sparsity of pulse signals in the frequency domain to guide the learned representations toward physiologically meaningful patterns. After pre-training, the learned representations are transferred to downstream rPPG estimation, where the encoder serves as a generic feature extractor for recovering pulse-related signals from facial videos. We conduct extensive experiments on four benchmark datasets, including PURE, UBFC-rPPG, MMPD, and V4V. Moreover, we evaluate the proposed approach on a real-world rPPG dataset collected under unconstrained lighting conditions and subject motion. Experimental results demonstrate that Periodic-MAE consistently improves rPPG estimation performance, particularly in challenging cross-dataset and real-world evaluation settings. Our code is available at https://github.com/ziiho08/Periodic-MAE.

20.
arXiv (quant-ph) 2026-06-16

On-chip semi-device-independent quantum random number generator exploiting contextuality

arXiv:2601.08392v2 Announce Type: replace Abstract: We present a semi-device-independent quantum random number generator (QRNG) based on the violation of a contextuality inequality, implemented by the integration of two silicon photonic chips. Our system combines a heralded single-photon source with a reconfigurable interferometric mesh to implement qutrit state preparation, transformations, and measurements suitable for testing a KCBS contextuality inequality. This architecture enables the generation of random numbers from the intrinsic randomness of single-photon interference in a complex optical network, while simultaneously allowing a quantitative certification of their security without requiring entanglement. We observe a contextuality violation exceeding the classical bound by more than 10{\sigma}, unambiguously confirming non-classical behavior. From this violation, we certify a conditional min-entropy per experimental round of Hmin = 0.077 +- 0.002, derived via a tailored semidefinite-programming-based security analysis. Each measurement outcome therefore contains at least 0.077 +- 0.002 bits of extractable genuine randomness, corresponding to an asymptotic generation rate of 21.7 +- 0.5 bits/s. These results establish a viable route towards general-purpose, untrusted quantum random number generators compatible with practical integrated photonic quantum networks.

21.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

22.
medRxiv (Medicine) 2026-06-11

Impact of Out-Migration and Remittances on Food Consumption Outcomes among Rural Households in Tigray, Ethiopia

作者:

This study examines the effects of rural out-migration and remittance inflows on food consumption outcomes among rural households in the Tigray region of Ethiopia. Utilizing household survey data collected from 521 rural households across three distinct Weredas (districts) (Tahtay Maichew, Kola Tembien, and Kilte-awlaelo). A Binary Probit model was employed to identify factors influencing migration decisions, while an Endogenous Switching Regression (ESR) model was used to estimate the impact of migration on food consumption outcomes while controlling for selection bias and unobserved heterogeneity. Food security was measured using the Food Consumption Score (FCS) and dietary diversity indicators. The empirical results reveal that severe food insecurity is widespread, with over 60% of all surveyed households falling into the "Poor" food consumption category. Descriptive baseline comparisons show that migration and remittance transfers marginally shift the raw average FCS upward from 23.86 to 25.48. However, this impact is profoundly nuanced: remittances serve as an immediate consumption-smoothing safety net but run parallel to a "labor-lost" constraint that reduces own-production capacities, forcing households to rely increasingly on market purchases for staple foods. The findings reveal that migration creates short-term labor shortages in agricultural production; however, remittance inflows substantially improve household food consumption frequencies, particularly for pulses, vegetables, and other nutrient-rich foods. After accounting for self-selection bias and unobserved traits, the rigorous ESR estimates indicate that migration increases the Food Consumption Score of participating households by an average Treatment Effect on the Treated (ATT) of 10.75 points, shifting them into more secure dietary tiers. Moreover, remittances help households mitigate the adverse effects of drought and other shocks by relaxing liquidity constraints and supporting both food purchases and agricultural investments. The study recommends establishing target food security safety nets for non-remittance households, promoting scale-appropriate labor-saving agricultural technologies, expanding traditional communal labor-sharing innovations, and boosting irrigation and agricultural input support programs to enhance rural food security and livelihood resilience.

23.
arXiv (math.PR) 2026-06-18

Functions of Bounded Variation and Point Processes

arXiv:2606.08304v2 Announce Type: replace-cross Abstract: We investigate the relationship between the analytical properties of functions of bounded variation and the statistical behavior of hyperuniform point processes. We establish several characterization formulas for the jump part of the gradient of a bounded variation function, extending and unifying previous results by Beretti–Gennaioli and Dávila. In particular, we provide new expressions for the $L^2$-jump of the gradient using both difference quotients and Fourier transform methods. Furthermore, we connect these analytic structures to the theory of hyperuniform point processes. By analyzing the variance of linear statistics associated with bounded variation functions, we provide asymptotic estimates that depend on the specific classification of the hyperuniformity of the point process. The results show how the regularity and jump discontinuities of a function dictate the growth rate of fluctuations in point processes. Finally, we introduce an averaged quadratic BMO-type oscillation functional over translated and rotated cube partitions, similar to the one recently studied by Ambrosio et al., and prove, using results from point process, that it converges to an explicit dimensional constant times the $L^2-$jump, giving in particular a further new characterization of the perimeter of a set.

24.
medRxiv (Medicine) 2026-06-17

Non-Medical COVID-19 Impacts and Hearing Status: A Global Study of Differential Health Impact Among Deaf, Hard of Hearing, and Hearing Populations

Background: Deaf and hard of hearing (HoH) experienced complex challenges during the COVID19 pandemic, including obscured visual communication from mask mandates, inaccessible public health messaging, and inadequate interpreter availability. We examined whether hearing status predicted nonmedical COVID19 impact on a global level. Methods: We conducted a nested cross-sectional analysis within a global study collecting data across two waves (April to May 2020 and July to August 2022) from 184 countries. Participants (N=7,998) were categorized as Deaf (n=304), Hard of Hearing (HoH; n=951), or Hearing (n=6,743). The primary outcome was a composite COVID-related non-medical Personal Impact TScore derived from 14 items across employment, resource access, and healthcare domains. Multinomial logistic regression models progressively adjusted for demographic, structural, and psychosocial variables. Results: Deaf participants reported substantially higher rates of pandemic-related job loss (28.9% vs. 9.6% hearing), healthcare cancellations (39.9% vs. 24.6%), and inability to obtain basic supplies. Over half (55.9%) of Deaf participants scored above the median composite impact index, compared to 39.2% of hearing participants. In the fully adjusted model, Deaf status remained an independent predictor of high non-medical impact (aOR=1.6, 95% CI: 1.1 to 2.4). HoH status showed no statistically significant difference from hearing participants in any model. Conclusions: People identifying as Deaf experienced significant disparities during COVID19 when compared with HoH or hearing people, driven by language access barriers and institutional exclusion rather than hearing loss per se. These experiences underscore the importance for systemic interventions centering on accessible communication, Deaf-centered needs, and reducing audism in Deaf-hearing interaction.

25.
medRxiv (Medicine) 2026-06-11

Large-scale proteomics and timing of hypertensive disorders of pregnancy

Background: Hypertensive disorders of pregnancy (HDP) may first be diagnosed antepartum, during labor, or postpartum. We utilized untargeted large-scale proteomics to identify pathways associated with HDP based on timing of onset. Methods: We performed a nested case-control study comparing differential protein expression, from the SomaScan 7K platform, based on timing of onset of HDP versus controls (referent) using first-trimester samples from the NuMoM2b-Heart Health Study, a multi-site cohort that followed nulliparous individuals from the first trimester. Associations of proteins with timing of onset of HDP, adjusted for co-variates, were assessed using logistic regression q value-based false discovery rates and pathway enrichment and differential expression analysis were conducted. Results: Of 1628 individuals included, 678 had HDP, of which 67% manifested antepartum (AP), 29% intrapartum (IP), and 3% postpartum (PP). After adjusting for co-variates, compared to controls, 698 proteins, 39 proteins, and 144 proteins were differentially expressed in those with HDP according to AP, IP, PP onset, respectively. There was little overlap in individual protein expression based on timing of HDP. Pathway enrichment and graphical summary analyses suggested distinct processes. Specifically, there was downregulation of angiogenic proteins in AP HDP, downregulation of immune-related proteins in IP HDP, and upregulation of complement activation promoting fibrotic changes leading to cardiac dysfunction in PP HDP. Conclusion: There are differences in first-trimester protein expression based on whether HDP first manifests AP, IP or PP. This raises the possibility that there may be distinct mechanistic phenotypes that could uniquely inform diagnostic and therapeutic targets for HDP.