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

MADAR: An Address-Free Processor

arXiv:2606.15535v1 Announce Type: cross Abstract: In a modern processor, computing is the cheap part. Most of its area and energy go to addressing – moving operands to and from a register file and cache, and running the tags, ports, miss queues, and bypass networks that find a value where it was left. MADAR deletes that machinery by abolishing the address. All state circulates in rings of slots that advance one position per clock; instructions and data ride in the same slots; a value is named by its place in an orbit – a \rp{} coordinate – not by an address; a fixed station computes when a circulating instruction sweeps past its operands, on a schedule set at compile time; and a hierarchy of rings of increasing period replaces the cache hierarchy, movement between them scheduled rather than triggered by a miss. No prior circulating-store, dataflow, or statically scheduled machine combines all four of these. We define the execution model, validate it in a cycle-accurate register-transfer-level implementation, show it compilable – a constructive scheduler emits programs cross-checked against the implementation – and price it with a first-order energy model. The payoff is clearest for AI acceleration: the multiply-accumulate at the heart of every matmul and convolution compiles to a streaming form whose energy per operation stays flat as the reduction grows, and the operand reuse that makes matrix multiplication efficient is carried by the ring-period hierarchy – the memory hierarchy doing by rotation what a cache does by tags. MADAR is a new design point for any computation whose data movement is known before the program runs.

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

Automated 3D Kinematic Monitoring for Circadian Activity and Anomaly Detection in Juvenile Fish

Precision aquaculture faces a "phenotyping bottleneck" in tracking high-resolution behavioral traits, as conventional methods cannot quantify instantaneous three-dimensional (3D) physical exertion. To address this, we present a high-throughput 3D behavioral phenotyping framework integrating deep learning object detection with binocular stereo vision for real-time monitoring of juvenile tilapia in high-density environments. The system automates non-contact body length estimation and reconstructs 3D swimming trajectories from absolute spatial coordinates. By eliminating 2D perspective distortions, this approach precisely quantifies 3D velocity and acceleration, marking the first estimation of true physical swimming speeds in free-roaming juveniles. Results show the framework successfully establishes circadian locomotor baselines, serving as an early warning system for physiological stress and providing an objective metric for fish vitality.

03.
arXiv (CS.LG) 2026-06-19

Physics-Informed Neural Network with Squeeze-Excitation-like Attention

arXiv:2606.19853v1 Announce Type: new Abstract: We introduce SEA-PINN, a novel architecture that incorporates a Squeeze-Excitation-like attention mechanism into physics-informed neural networks to dynamically recalibrate the importance of neurons across layers. A key feature of SEA-PINN is its highly stable initialization. On 17 out of 20 benchmark problems, SEA-PINN exhibit nearly negligible variance and significantly reduced initial loss, establishing a quasi-deterministic and favorable starting point for optimization. Notably, without employing Fourier feature embeddings or periodic activation functions, SEA-PINN attained competitive accuracy (83\% vs. 90\% improvement relative to FNN-PINN on the high-frequency case 7) as compared with TSA-PINN-a model specifically engineered for high-frequency problems via learnable frequencies in sinusoidal activations. Furthermore, integrating SEA-PINN into TSA-PINN boosted performance by 42.49\%. These results underscore SEA-PINN as a lightweight plug-in module that enhances nonlinear representation power, promotes more robust and efficient convergence, and strengthens the overall reliability of physics-informed learning.

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

DiT-JSCC: Rethinking Deep JSCC with Diffusion Transformers and Semantic Representations

Generative joint source-channel coding (GJSCC) has emerged as a new Deep JSCC paradigm for achieving high-fidelity and robust image transmission under extreme wireless channel conditions, such as ultra-low bandwidth and low signal-to-noise ratio. Recent studies commonly adopt diffusion models as generative decoders, but they frequently produce visually realistic results with limited semantic consistency. This limitation stems from a fundamental mismatch between reconstruction-oriented JSCC encoders and generative decoders, as the former lack explicit semantic discriminability and fail to provide reliable conditional cues. In this paper, we propose DiT-JSCC, a novel GJSCC backbone that can jointly learn a semantics-prioritized representation encoder and a diffusion transformer (DiT) based generative decoder, our open-source project aims to promote the future research in GJSCC. Specifically, we design a semantics-detail dual-branch encoder that aligns naturally with a coarse-to-fine conditional DiT decoder, prioritizing semantic consistency under extreme channel conditions. Moreover, a training-free adaptive bandwidth allocation strategy inspired by Kolmogorov complexity is introduced to further improve the transmission efficiency, thereby indeed redefining the notion of information value in the era of generative decoding. Extensive experiments demonstrate that DiT-JSCC consistently outperforms existing JSCC methods in both semantic consistency and visual quality, particularly in extreme regimes.

06.
medRxiv (Medicine) 2026-06-10

Gendered pathways to adolescent mental health: An empirical assessment of a new conceptual framework

Introduction Gender norms and roles are important determinants of physical and mental health in the key period of adolescence. Yet, the gendered pathways to mental health in adolescents are not fully understood. Using a conceptual framework for global adolescent mental health that we developed based on a Delphi process, we empirically investigated the associations between six gender-related constructs and adolescent mental health. Methods We used cross-sectional Gender and Adolescence: Global Evidence (GAGE) data from Ethiopia (2020) to explore the associations between sex, gender norms, psychological competencies, gender attitudes, gender roles, with the latter two also serving as mediators, and psychological distress (GHQ-12), using Structural Equation Modelling (SEM). Results The SEM model contained measurements from 1,584 adolescents, including 843 girls and 741 boys, with a median age of 13 years. Out of 14 pathways tested, we found statistically significant associations between psychological competencies and psychological distress; sex and gender attitudes; and between gender norms and psychological competencies, gender attitudes, and gender roles. Hence, the gender-related constructs were mostly associated with each other, rather than with psychological distress. Conclusion The gender-related constructs are strongly interrelated, thereby attenuating their individual effects on psychological distress. The interplay of gender-related constructs should be considered when developing interventions to promote mental health in adolescents.

07.
arXiv (CS.CL) 2026-06-16

Depth-Attention: Cross-Layer Value Mixing for Language Models

Self-attention selects information freely across the sequence, but across depth, Transformers merely add each layer's output to the residual stream, so later layers cannot selectively reuse earlier-layer representations. Recent cross-layer methods improve this flow but operate on hidden states outside attention, adding state beyond the key-value cache at inference–a cost that becomes increasingly salient as modern LLMs compress the cache with grouped-query and multi-head latent attention. We introduce Depth-Attention, which performs this selection inside the attention module itself: before a layer attends over the sequence, its query attends over the keys of earlier layers at the same token position and mixes their values into the value that self-attention then reads. Because Depth-Attention reuses the standard attention queries, keys, and value-cache slots, storing depth-mixed values in place of the original values, it adds no parameters and introduces no persistent inference state beyond the standard key-value cache–the same cache size as a vanilla decoder and less than hidden-state-based cross-layer methods. On Qwen3-style decoders at 1.5B and 3B parameters, Depth-Attention attains the lowest perplexity and the highest average downstream accuracy, improving over the vanilla Transformer by up to 2.3 accuracy points and surpassing strong cross-layer baselines in perplexity and average accuracy, while adding under 0.01% extra arithmetic FLOPs and no additional persistent inference state. The gains hold from 360M to 3B parameters and extend to looped Transformers.

08.
arXiv (CS.AI) 2026-06-16

VGPT-RSI for RH-Adjacent Formal Progress: Boundary Certificates, Verified Finite Lagarias Inequalities, and Explicit Failure Localization

arXiv:2606.15096v1 Announce Type: new Abstract: The Riemann Hypothesis remains one of the central unsolved problems in mathematics. Rather than claiming proof, we investigate whether a verifiable AI-assisted reasoning system can produce reliable, formally checked partial progress while explicitly identifying the remaining mathematical obstructions. We apply the Verifiable Growing Physical Transformer with Recursive Self-Improvement (VGPT-RSI) to two RH-adjacent certification tasks. First, we construct and verify a finite RH-boundary certificate for inequality on a parameterized safe lower curve over a region. The numerical boundary curve is converted into a certificate-backed lower curve, audited using outward-rounded interval arithmetic and Arb/FLINT ball arithmetic, and then checked in Rocq/CoqInterval for the parameterized theorem. Second, we initiate a formal Lagarias-route certificate. Lagarias criterion states that RH is equivalent to the global inequality. We formalize the finite quantity and produce a Coq-checked finite certificate. The final system identifies the exact unresolved mathematical bottlenecks: formalizing the Lagarias equivalence, proving the global tail theorem beyond any finite cutoff, and potentially reducing counterexamples to colossally abundant or related extremal integers. These results demonstrate that VGPT-RSI can produce certified RH-adjacent formal progress, organize proof dependencies, and avoid overclaiming when the remaining obstruction is genuinely mathematical.

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

Attention is Just Another Name for Coupling?: A Fast-Slow ODE Perspective on Hierarchical Pretraining

arXiv:2606.16730v1 Announce Type: cross Abstract: Causal self-attention is a coupling mechanism: each token's hidden state is updated by a learned mixture of preceding tokens at the same timescale. This paper asks whether a second, temporally slower coupling-a slow sub-system operating on a temporally-downsampled view of the sequence and fed back into the fast path through a zero-initialised gate-complements it. The question is framed in the language of singularly perturbed ordinary differential equations (ODEs), where the fast variable $x$ evolves at the token rate, the slow variable $y$ evolves at one update per $P$ tokens, and the timescale ratio $\varepsilon = 1/P$ is enforced structurally by causal block-mean pooling. The paper instantiates the fast-slow ODE formalism as a concrete neural network: a fast path of standard causal attention over $T$ tokens, a slow path of full attention over $T/P$ pooled tokens ($P^2 \times$ cheaper per layer), and a zero-initialised additive gate. In addition, under a linear-generator assumption on the fast dynamics, we prove that the equilibrium manifold $x = \phi(y)$ is exactly the master-equation (ME) stationary distribution $p_{\mathrm{st}}(y)$; in that regime a learned MLP $\phi_\theta(y)$ is a variational approximation of it (the trained block is not a generator, so this identity is the structured limit, not a claim about the network as trained). Empirically, at $500$k tokens the coupling is neutral – the gate stays closed and the coupled and frozen ablations are within run-to-run noise – at a wall-clock cost comparable to a dense baseline. The contribution is the precise, gap-marked mapping itself, not a performance gain.

10.
arXiv (quant-ph) 2026-06-12

Improving Variational Counterdiabatic Driving with Weighted Actions and Computer Algebra

arXiv:2505.18367v4 Announce Type: replace Abstract: Variational counterdiabatic (CD) driving is a disciplined and widely used method to robustly control quantum many-body systems by mimicking adiabatic processes with high fidelity and reduced duration. Central to this technique is a universal structure of the adiabatic gauge potential (AGP) over a parameterized Hamiltonian. Here, we reveal that introducing a new degree of freedom into the theory of the AGP can significantly improve variational CD driving. Specifically, we find that the algebraic characterization of the AGP is not unique, and we exploit this nonuniqueness to develop the weighted variational method for deriving a refined driving protocol. This approach extends the conventional method in two aspects: it assigns customized weights to matrix elements relevant to specific problems, and it effectively incorporates nonlocal information into local driving coefficients. We also develop an efficient numerical algorithm to compute the refined driving protocol using computer algebra. Our framework is broadly applicable and, in principle, it can replace any previous use of variational CD driving. We demonstrate its practicality by applying it to adiabatic evolution along the ground state of a parameterized Hamiltonian. This proposal outperforms the conventional method in terms of fidelity, as confirmed by extensive numerical simulations on quantum Ising models.

11.
arXiv (quant-ph) 2026-06-12

Toward Entanglement Bootstrap for Conformal Field Theory in Any Dimension

arXiv:2606.12540v1 Announce Type: cross Abstract: Given a quantum critical wavefunction in any dimension, we propose a reconstructed Hamiltonian, analogous to the ones previously found for 1+1d CFT and for 2+1d bosonic liquid topologically-ordered states. We test numerically that, for known regularized approximate CFT groundstates (on the icosahedron and the fuzzy sphere), (1) they are close to the groundstate of their reconstructed Hamiltonian, and (2) the spectrum of their reconstructed Hamiltonian on the unit sphere has CFT properties (integer spacing of descendants) and matches known low-lying energies. We show that this provides an automated method to improve the finite-size effects in a fixed Hilbert space.

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

ThousandWorlds: A benchmark for climate emulation of potentially habitable exoplanets

arXiv:2606.18338v1 Announce Type: new Abstract: The search for life beyond Earth will depend on detecting faint signatures in the atmospheres of potentially habitable exoplanets. Interpreting those signatures requires understanding the host planet's climate: the same molecule may signal life on one planet and abiotic chemistry on another. Global climate models (GCMs) provide this understanding, but individual runs can require up to millions of core-hours and substantial domain expert time. Machine-learning emulators could remove this bottleneck, but progress has been limited by the absence of a curated, multi-model exoclimate dataset. We introduce ThousandWorlds, an ML-ready benchmark for exoclimate emulation and for the broader regime of low-data, multi-simulator, parameter-to-field regression. The dataset contains approximately 1800 simulations from five GCMs, mapping eight planet parameters to 3D atmospheric fields including temperature, humidity, winds, clouds, and radiation. Three nested subsets define progressively harder challenges: single-simulator regression, multi-simulator regression with complete observations, and multi-simulator regression with structured missingness. We propose two evaluation protocols: one for ranking methods, and one that measures performance relative to the disagreement between GCMs themselves. We evaluate seven baselines spanning simple methods, deep learning, and Gaussian processes. GP-based methods perform best, suggesting that ThousandWorlds exposes a regime where off-the-shelf deep learning does not yet succeed. Data: https://doi.org/10.57967/hf/8695. Code: https://github.com/edstevenson/ThousandWorlds.

13.
arXiv (CS.CV) 2026-06-19

TriFlow: Generating Artist-Like 3D Mesh Topology via Nearest-Vertex Vector Fields

We present TriFlow, a new generative approach for producing compact 3D meshes with artist-like triangle topology directly from input geometry conditions such as signed distance fields. Our key insight is to represent mesh topology as a nearest-vertex vector field (NVF) defined over the surface, where each point encodes its association to the nearest triangle vertex in the local barycentric frame. We train a latent flow-matching model to synthesize this field, enabling topology generation conditioned on the input geometry. To extract a coherent mesh, we cluster surface regions using the generated NVF and guide a constrained quadric error metric (QEM) mesh simplification with topology-aware optimization. This yields output meshes that closely match the input geometry while exhibiting structured, artist-like connectivity. Experiments demonstrate that TriFlow achieves stronger generalization and significantly improved topology quality compared to state-of-the-art learning-based approaches, alongside 90% lower Chamfer Distance and an 8x speedup.

14.
arXiv (CS.CV) 2026-06-17

Beyond Visual Cues: CoT-Enhanced Reasoning for Semi-supervised Medical Image Segmentation

Semi-supervised medical image segmentation has emerged as a dominant research problem in medical image analysis, mitigating annotation scarcity by leveraging consistency regularization on unlabeled data. However, existing approaches operate predominantly via visual pattern matching, relying heavily on pixel-level similarities. This visual-centric dependency often falters in clinical scenarios characterized by the visual-semantic mismatch, where visually similar lesions warrant distinct diagnostic conclusions, thus failing to capture the underlying diagnostic logic used by experts. To address this, we move beyond visual cues and propose CERS (CoT-Enhanced Reasoning Segmentation), a framework that integrates Chain-of-Thought (CoT) reasoning to distinguish pathologically distinct cases. Specifically, we construct a knowledge pool enriched with linguistic reasoning descriptions generated by large language models (LLMs). A semantic-aware reference selection strategy is introduced to identify historical evidence, filtering candidates first by morphology, and then refining them via CoT consistency to eliminate hard negatives. Furthermore, a multi-scale coordinate attention module (MCAM) is designed to effectively fuse this reasoning-derived context into the decoding process. Extensive experiments demonstrate the superiority of CERS against state-of-the-art approaches, particularly in resolving boundary ambiguities and semantic inconsistencies. The code is available at https://github.com/cymasuna/CERS.

15.
arXiv (CS.AI) 2026-06-12

Democracy in the Era of Artificial Intelligence

arXiv:2606.13026v1 Announce Type: cross Abstract: Interfacing Artificial Intelligence (AI) with democracy is one of the most profound challenges of our times. On the one hand, AI comes with opportunities to overcome long-standing challenges in democracy, such as low participation in deliberative and voting processes with poor representation of people. On the other hand, new risks arise from AI algorithms that are privacy-intrusive, biased, manipulative, spread misinformation and influence election results. Moving beyond the over-simplistic question of whether AI is good or bad for democracy, the Handbook on Democracy in the Era of Artificial Intelligence asks instead: how to upgrade democracies and the principles they are built on, using AI? How to engage with AI and on what terms? Which new values and design principles are required to build democratic resilience? In 34 chapters by 59 authors across the world from different disciplines, we explore how AI can empower collective intelligence for democracy (Part 1) and what is the future of deliberative democracy using large language models and social media (Part 2). We also illustrate the role of AI for building resilient self-governance systems (Part 3) and the challenges of transforming democracy in the age of AI (Part 4). We conclude with broader perspectives (Part 5) that re-imagine the interplay of democracy and AI.

16.
bioRxiv (Bioinfo) 2026-06-21

OracleScreen-LILRB4: Machine Learning-Guided Discovery of Myeloid Immune Checkpoint Binders Validated in Patient-Derived Cells

The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit rates observed in conventional high-throughput screening campaigns. Here we report OracleScreen-LILRB4, an ensemble machine learning framework trained on quantitative biophysical screening data from two structurally diverse compound libraries (19,800 compounds total) screened against the myeloid immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3). By formulating binding prediction as a regression task targeting continuous {Delta}Fnorm values rather than binary hit classifications, OracleScreen-LILRB4 achieved a mean Spearman R of 0.61 and ROC-AUC of 0.86 under scaffold-aware cross-validation. Prospective virtual screening of a 45,760-member compound library and experimental validation of the top 200 predictions yielded a 28.5% hit rate, representing a 15.0-fold enrichment over baseline, with 16 compounds demonstrating nanomolar-affinity LILRB4 (ILT3) engagement. Lead compounds ORS-22 and ORS-14 restored anti-tumor immune activity across patient-derived colorectal cancer and acute myeloid leukemia co-culture systems, reversing SCG2-mediated immunosuppression and recovering cytotoxic T-cell function. These findings establish OracleScreen-LILRB4 as an effective computational framework for accelerating small molecule discovery against non-enzymatic immune checkpoint targets.

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

Decentralized Autoregressive Generation

arXiv:2601.03184v3 Announce Type: replace-cross Abstract: The decentralization of autoregressive generation has attracted considerable attention in recent years as a solution to scaling bottlenecks. However, despite promising empirical results, this paradigm currently lacks rigorous theoretical justification. In this work, we formally establish the theoretical equivalence between decentralized and centralized training. To achieve this, we adapt the Discrete Flow Matching framework for autoregressive generation, leveraging its inherent properties to demonstrate that global models naturally decompose into independent experts. Finally, we conduct extensive experiments across diverse multimodal benchmarks, empirically validating that decentralized training maintains competitive parity with standard centralized architectures.

18.
arXiv (CS.AI) 2026-06-16

MASCOT-Android: A Curated Dataset and Automated Collection Pipeline for Android Malware Source Code Specimens

arXiv:2606.16072v1 Announce Type: cross Abstract: Compared with binaries and decompiled code, malware source code more directly reflects the attackers' original intent. However, the scarcity of source code and the high cost of manual review make such datasets difficult to build and maintain. We propose MASCOT-Android, a curated dataset of Android malware source code and an automated collection framework for scalable malware source code discovery on GitHub. A key finding of our work is that repository-level documentation alone provides a strong signal for malware source code collection. Our model extracts character-level TF-IDF features from 8,772 malware and 25,747 benign README documents and trains a LinearSVC classifier to distinguish malware repositories. This README-only model achieves an accuracy of 96.28\% and an FPR of 1.06\% in local evaluation. In addition, the model outputs confidence scores, allowing users to adjust the decision threshold to balance FPR and coverage, which is practical in real-world malware source code collection.

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

A nonparametric two-sample test using a parametric integral probability metric

arXiv:2606.16941v1 Announce Type: cross Abstract: Detecting distributional differences between two independent samples is a fundamental problem in statistics and machine learning. Nonparametric two-sample testing provides a principled framework for determining whether two samples are drawn from the same underlying distribution, without assuming any specific parametric form for the distribution. In this study, we propose a new two-sample test statistic based on a newly introduced integral probability metric (IPM), using a specially designed parametric discriminator class with a single node of a neural network. We show that the resulting test statistic, called PReLU-IPM, is nonparametric and establish theoretical guarantees for the associated two-sample testing procedure, PReLU-TST, including its consistency and asymptotical equivalence to nonparametric IPM-based tests under regularity conditions. By analyzing multiple simulated and real benchmark datasets, we demonstrate that PReLU-TST achieves higher power across a range of alternatives or performs comparably to its competitors, for finite samples.

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

StarOR: Synergizing Tree Search and Test-Time Reinforcement Learning for Optimization Modeling

arXiv:2606.15197v1 Announce Type: cross Abstract: Optimization modeling is inherently hierarchical, requiring a precise sequence of symbolic commitments. Traditional learning-based automated optimization modeling methods improve modeling policies through large-scale annotated or curated training data, but are costly to adapt to new problem distributions. Meanwhile, one-shot generation remains brittle in hierarchical modeling, where early symbolic errors can propagate into invalid formulations. Test-time scaling offers a promising alternative by enabling structural exploration with additional instance-level computation; however, existing search-based methods typically rely on a fixed policy, causing repeated rollouts to inherit similar modeling biases and providing limited credit assignment for intermediate decisions. To address these limitations, we propose StarOR, a synergistic search-and-adaptation framework that couples MCTS with Test-Time Reinforcement Learning for optimization modeling. StarOR decomposes the modeling process into four stages and updates a transient LoRA adapter via GRPO at each non-terminal node. By using MCTS-generated siblings as local comparison sets, StarOR transforms search-time exploration into instance-specific policy refinement. Moreover, an unsupervised multi-faceted reward system provides fine-grained feedback for intermediate formulation decisions without ground-truth labels. Experiments across five optimization benchmarks show that StarOR achieves state-of-the-art performance even with a 4B backbone, outperforming existing methods and the frontier LLMs.

21.
arXiv (math.PR) 2026-06-11

Second-order PACF asymptotics and discrimination between fractional Gaussian noise and $\operatorname{FARIMA}(0,d,0)$

作者:

arXiv:2605.31416v2 Announce Type: replace-cross Abstract: Fractional Gaussian noise and $\operatorname{FARIMA}(0,d,0)$ have the same long-memory pole $|\theta|^{-2d}$ and hence the same leading PACF law $\alpha(n)\sim d/n$. We show that this agreement breaks at the first non-universal order. For $0

22.
Nature (Science) 2026-06-17

Towards Conversational AI for Disease Management

While large language models (LLMs) have shown promise in diagnostic dialogue1, their capabilities for effective management reasoning—including disease progression, therapeutic response, and safe medication prescription—remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE)1−3 through a new LLM-based agentic system optimized for multi-visit clinical management and dialogue. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini’s long-context capabilities4, combining in-context retrieval with structured reasoning to align its output with up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialists and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. Though AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE’s strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management.

23.
arXiv (CS.LG) 2026-06-15

The Risk Shadow of Principal Component Analysis: When 99.9999% Variance Preservation Causes Catastrophic Decision Errors

arXiv:2606.14533v1 Announce Type: new Abstract: Principal Component Analysis (PCA) preserves variance, not the information needed to detect rare catastrophic events. This paper proves the existence of a {\it Risk Shadow}: PCA can retain over 99.9999 percent of total variance while completely erasing all signal about rare, high-impact failures. When this happens, even the best possible classifier operating on the PCA representation reduces to a constant predictor. The root cause is a fundamental mismatch between variance maximization and tail risk awareness. To break the shadow, we introduce Expectile PCA (ExPCA) and Tail-Preserving PCA (TP-PCA), two methods that reweight the data covariance toward high-impact events. We prove theoretically that ExPCA strictly outperforms PCA in retaining rare-event information, and we validate our claims on synthetic data and a real-world credit card fraud detection benchmark. Our results call for a fundamental rethinking of variance-based dimensionality reduction in high-stakes decisions.

24.
medRxiv (Medicine) 2026-06-16

Efficacy of Ergothioneine Supplementation on Postpartum Fatigue, Sleep Quality, and Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Postpartum asthenia, characterized by severe fatigue, sleep disturbances, and physiological stress, lacks effective targeted interventions. Ergothioneine (EGT) is a unique, naturally occurring antioxidant that actively accumulates in mitochondria, offering a compelling therapeutic rationale for systemic recovery. This study aimed to evaluate the efficacy of EGT in accelerating postpartum functional restoration and alleviating fatigue. Methods: This single-center, randomized, double-blind, placebo-controlled trial enrolled 40 postpartum women (SF-36 total score [≤] 70) who had ceased breastfeeding. Participants were randomized (1:1) to receive either 120 mg/day of EGT or a matched placebo for 30 days. Efficacy was assessed using the SF-36, Pittsburgh Sleep Quality Index (PSQI), Fatigue Scale-14 (FS-14), and Traditional Chinese Medicine (TCM) asthenia scale. To rigorously evaluate the treatment effects, advanced statistical modeling, including Linear Mixed-Effects Models (LMM) and Analysis of Covariance (ANCOVA) adjusted for baseline covariates, was employed. Results: All 40 participants completed the trial. The EGT group demonstrated robust and accelerated functional recovery. Notably, significant improvements in sleep quality (p = 0.0361) and systemic fatigue (p = 0.0059) were observed as early as Day 15. Importantly, EGT yielded a statistically significant between-group superiority in alleviating mental fatigue compared to placebo at Day 15 (p = 0.0313). By Day 30, the EGT cohort exhibited substantial within-group improvements across all primary metrics, including SF-36 (+35.94%, p = 0.0006) and FS-14 (-27.78%, p = 0.0011). Furthermore, as an additional physiological benefit, EGT induced a selective and significant reduction in hepatic transaminases (ALT: -30.42%; AST: -17.44%) within normal limits, a trend not observed in the placebo group. EGT was exceptionally well-tolerated with no treatment-related adverse events. Conclusions: EGT supplementation (120 mg/day) safely accelerates postpartum functional recovery, offering rapid relief from mental fatigue and sleep disturbances within 15 days, while concurrently optimizing hepatic physiological status. These preliminary clinical signals warrant confirmation in larger, adequately powered cohorts. Trial Registration: ChiCTR2500114171; Prospectively registered on 2025-12-08.

25.
medRxiv (Medicine) 2026-06-17

Investigating shared genetic overlap of immune-mediated inflammatory diseases and cardiometabolic diseases

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.