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

UniT: Unified Multimodal Chain-of-Thought Test-time Scaling

Unified models can handle both multimodal understanding and generation within a single architecture, yet they typically operate in a single pass without iteratively refining their outputs. Many multimodal tasks, especially those involving complex spatial compositions, multiple interacting objects, or evolving instructions, require decomposing instructions, verifying intermediate results, and making iterative corrections. While test-time scaling (TTS) has demonstrated that allocating additional inference compute for iterative reasoning substantially improves language model performance, extending this paradigm to unified multimodal models remains an open challenge. We introduce UniT, a framework for multimodal chain-of-thought test-time scaling that enables a single unified model to reason, verify, and refine across multiple rounds. UniT combines agentic data synthesis, unified model training, and flexible test-time inference to elicit cognitive behaviors including verification, subgoal decomposition, and content memory. Our key findings are: (1) unified models trained on short reasoning trajectories generalize to longer inference chains at test time; (2) sequential chain-of-thought reasoning provides a more scalable and compute-efficient TTS strategy than parallel sampling; (3) training on generation and editing trajectories improves out-of-distribution visual reasoning. These results establish multimodal test-time scaling as an effective paradigm for advancing both generation and understanding in unified models.

02.
medRxiv (Medicine) 2026-06-16

Comparative Effectiveness and Safety of Prophylactic Vasopressors for Preventing Post-induction Hypotension in the Elderly: A Systematic Review and Network Meta-analysis

Background: Post-induction hypotension is a predictable haemodynamic hazard in older adults undergoing general anaesthesia. Prevention remains divided among volume optimisation, anaesthetic dose reduction, rescue treatment after hypotension occurs and proactive vasoactive support. Methods: We searched PubMed, Embase, Web of Science, CENTRAL, CNKI, Wanfang and VIP from inception to 30 March 2026. Eligible studies were randomised trials of prophylactic vasoactive drugs given before, during or immediately after induction in older adults. The primary outcome was post-induction hypotension. Secondary outcomes were post-induction mean arterial pressure (MAP), systolic arterial pressure (SBP), heart rate (HR) and reported haemodynamic adverse events. Random-effects network meta-analysis was used, and confidence in network estimates was assessed using CINeMA principles. Results: Thirty-one trials including 2,821 participants were included in the revised network. Compared with placebo/control, all active agents favoured lower post-induction hypotension. The most favourable point estimates were observed for phenylephrine (odds ratio [OR] 0.17, 95% confidence interval [CI] 0.01 to 2.16) and metaraminol (OR 0.19, 95% CI 0.02 to 1.53), although both were imprecise. More precise reductions were observed for methoxamine (OR 0.23, 95% CI 0.13 to 0.43), norepinephrine (OR 0.25, 95% CI 0.13 to 0.47) and ephedrine (OR 0.34, 95% CI 0.19 to 0.63). Phenylephrine ranked highest for MAP support, norepinephrine ranked highest for SBP support, and ephedrine ranked highest for HR preservation. Global inconsistency was detected for SBP but not for hypotension incidence, MAP or HR, supporting cautious profile-based interpretation. Conclusions: Prophylactic vasopressor choice during induction should be guided by haemodynamic phenotype rather than ranking alone. In the revised network, active prophylaxis consistently favoured lower hypotension, but sparse nodes produced uncertainty. Norepinephrine retained a comparatively balanced profile when vasodilatory post-induction hypotension is anticipated, phenylephrine and related alpha-agonists provided stronger pressure support when HR and cardiac-output reserve are preserved, and ephedrine was most relevant when chronotropic support is desired. Keywords: general anaesthesia; induction; hypotension; norepinephrine; phenylephrine; ephedrine; network meta-analysis; older adults.

03.
arXiv (CS.AI) 2026-06-17

A Gradient-based Causal Discovery Framework with Applications to Complex Industrial Processes

arXiv:2507.11178v3 Announce Type: replace-cross Abstract: With the advancement of deep learning technologies, various neural network-based Granger causality models have been proposed. Although these models have demonstrated notable improvements, several limitations remain. Most existing approaches adopt the component-wise architecture, necessitating the construction of a separate model for each time series, which results in substantial computational costs. In addition, imposing the sparsity-inducing penalty on the first-layer weights of the neural network to extract causal relationships weakens the model's ability to capture complex interactions. To address these limitations, we propose Gradient Regularization-based Neural Granger Causality (GRNGC), which requires only one time series prediction model and applies $L_{1}$ regularization to the gradient between model's input and output to infer Granger causality. Moreover, GRNGC is not tied to a specific time series forecasting model and can be implemented with diverse architectures such as KAN, MLP, and LSTM, offering enhanced flexibility. Numerical simulations on DREAM, Lorenz-96, fMRI BOLD, and CausalTime show that GRNGC outperforms existing baselines and significantly reduces computational overhead. Meanwhile, experiments on real-world DNA, Yeast, HeLa, and bladder urothelial carcinoma datasets further validate the model's effectiveness in reconstructing gene regulatory networks.

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

DEEPRUBRIC: Evidence-Tree Rubric Supervision for Efficient Reinforcement Learning of Deep Research Agents

Deep research agents synthesize long-form reports by searching and reasoning over retrieved evidence. Reinforcement learning with rubric-based rewards improves these agents by optimizing them against checkable criteria that translate report quality into reward signals, but its efficiency depends on whether those criteria reliably capture the task scope and evidence needs. Most existing studies ask an LLM to generate rubrics for a given query, but when the model fails to infer the underlying information needs, the generated rubrics may be incomplete and reduce RL efficiency. To obtain more reliable query–rubric supervision, we introduce DeepRubric, a data construction framework that reverses this process: instead of inferring evaluation criteria for a given query, it first determines what an evidence-backed report should be evaluated on and then synthesizes aligned query–rubric pairs from those evaluation targets. Starting from a sampled seed topic, DeepRubric builds an evidence tree by recursively expanding evidence-backed sub-questions, whose leaves serve as atomic and verifiable evaluation targets. It then uses the evidence tree to synthesize the training query and rubrics, ensuring that the reward evaluates exactly the information requested by the query. Using DeepRubric, we construct 9K query–rubric supervision examples and train DeepRubric-8B with rubric-based GRPO, achieving comparable performance to prior open state-of-the-art deep research models across three benchmarks with roughly 13x fewer RL GPU-hours.

05.
arXiv (CS.LG) 2026-06-15

Learning the Context of Errors: Black-Box Online Adaptation of Time Series Foundation Models

arXiv:2606.14222v1 Announce Type: new Abstract: The rapid evolution of Time Series Foundation Models (TSFMs) has advanced zero-shot forecasting across diverse domains. Inspired by the current form of Large Language Models, future TSFMs may be offered as commercialized, closed-source API services. However, many existing online adaptation methods still rely on white-box access for parameter fine-tuning or gradient backpropagation. This paradigm mismatch raises a question: In black-box online adaptation for TSFMs, what should we learn? We answer this with an insight: the predictive errors of the base model are conditioned on both the input and output of the base model (i.e., the context of errors). To validate this insight, we propose ORCA (Online Residual Contextual Adaptation). We conduct extensive experiments across 5 state-of-the-art TSFMs and 8 datasets to demonstrate the effectiveness of our approach. Furthermore, through ablation studies, we quantitatively analyze the impact of different adapter learning hypotheses on the final adaptation performance in black-box online adaptation. Code available at https://github.com/Fifthky/ORCA.

06.
PLOS Medicine 2026-05-26

Requiring code sharing to strengthen transparency and trust in research

by Helen Lumbard, Lauren Cadwallader, Devin Soper, on behalf of the PLOS Medicine Staff Editors PLOS Medicine has always championed open science and data transparency. Now, recognizing that code is as essential a research artifact as the data it analyzes, we are strengthening our code sharing policy to further ensure reproducibility and trust in the scientific record. Recognizing that code is as essential a research artifact as the data it analyzes, this Editorial outlines how PLOS Medicine is strengthening its code sharing policy to further ensure reproducibility and trust in the scientific record.

08.
arXiv (CS.CV) 2026-06-15

OmniVideo-100K: A Dataset for Audio-Visual Reasoning through Structured Scripts and Evidence Chains

Current automated pipelines for audio-visual Question Answering (QA) generally adopt a ``video-caption-QA'' paradigm. However, these methods typically segment videos into short clips and generate separate descriptions for audio and visual modalities. This decoupled processing severs inherent associations between sounds and their visual sources, while independent clip processing often causes inconsistent descriptions of the same entity across segments. Furthermore, coupling long-text comprehension and QA synthesis into a single step often restricts models to localized events, yielding questions lacking long-term temporal connections and deep cross-modal reasoning. To address these issues, we propose an automated data engine featuring two mechanisms: (1) Entity-Anchored Video Scripting transforms videos into structured scripts, comprising summaries, main entity lists, and segment-wise audio-visual descriptions. The entity list serves as a global prior to ensure cross-segment referential consistency and reconstruct audio-visual associations. (2) Clue-Guided QA Generation prompts models to first mine cross-segment, multimodal clues from the script, and subsequently generate QA pairs based on these high-value clues. Leveraging this pipeline, we construct the instruction-tuning dataset OmniVideo-100K and a human-verified test set, OmniVideo-Test. Fine-tuning VITA-1.5, Qwen2.5-Omni-7B and Qwen3-Omni-30B on OmniVideo-100K yields performance gains of up to 20.59% on OmniVideo-Test, demonstrating strong generalization (up to 12.64% improvements) across established benchmarks like Daily-Omni and JointAVBench.

09.
arXiv (quant-ph) 2026-06-16

Diagonal-Budgeted Trotterization for Efficient Quantum Hamiltonian Simulation

arXiv:2606.16959v1 Announce Type: new Abstract: Efficient classical simulation of quantum Hamiltonian dynamics is often bottlenecked by exponential state growth and the overhead of generic sparse linear algebra. We introduce diagonal-budgeted Trotterization, a structure-aware strategy that decomposes Hamiltonians into factors preserving diagonal sparsity while tightly controlling fidelity loss. Our implementation, HamSim, utilizes a compact diagonal-sparse data layout and specialized C++/CUDA kernels to bypass the overheads of generic formats like CSR. By leveraging SIMD vectorization, multithreading, and GPU acceleration, HamSim achieves high performance across heterogeneous architectures. Benchmarks on the HamLib suite show that HamSim significantly outperforms Qiskit-Aer. On CPUs, HamSim attains speedups of $182$–$1,269\times$ on optimization instances (TSP, MaxCut) and $4.8$–$841\times$ on physical models (TFIM, Heisenberg). On GPUs, it achieves up to $178\times$ speedup for $12$–$16$ qubit problems. Unlike traditional Trotterization, HamSim maintains near-perfect fidelity without requiring exponential steps. This demonstrates that diagonal-aware numerical kernels provide a scalable foundation for high-fidelity classical Hamiltonian simulation.

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

Fodor and Pylyshyn's Systematicity Challenge Still Stands

The recent successes of neural networks producing human-like language have caused significant stir in cognitive science, with many researchers arguing that classical puzzles about human cognition and challenges to artificial intelligence are being solved by neural networks. A notable case is the argument from systematicity due to Jerry Fodor and Zenon Pylyshyn, argues that humans display systematic biconditional dependencies. For example, someone can understand the sentence "John saw Mary" just in case that they understand the sentence "Mary saw John." Symbolic systems explain this systematicity of language and thought, while neural networks offer no immediate explanation. Several recent articles argue that this challenge has now been met by neural networks. In particular, Brenden Lake and Marco Baroni argue that their meta-learning for compositionality protocol matches and perhaps explains human systematicity. We demonstrate that these conclusions are premature. Among other results, we found that their model struggles to learn rules that are even slightly out of distribution compared to their training data. Furthermore, the model behaves unsystematically even on many within-distribution problems. We conclude that Fodor and Pylyshyn's challenge to neural networks remains unmet.

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

On the Study of Biometric Spoofing Detection using Deep Learning

Biometric systems are increasingly deployed in security applications; however, they remain vulnerable to spoofing attacks, in which attackers exploit counterfeit biometric data to gain unauthorized access. This research evaluates the effectiveness of state-of-the-art machine learning models, MobileNetV2, DenseNet-121, Inception-v3, and Spoof Trace Disentanglement (STD) in detecting spoofing attacks within facial recognition systems. Using the CelebA-Spoof dataset, the study evaluates model effectiveness using metrics such as accuracy, precision, recall, and F1 Score. Cross-dataset validation is carried out on the MSU-MFSD dataset to assess generalizability. The results show MobileNetV2 as the most efficient model, achieving 92% accuracy while balancing computational effectiveness, making it appropriate for real-life applications. Inception-v3 shows moderate robustness, while DenseNet-121 and STD struggle with generalization. The findings highlight the need for advances in domain adaptation and hybrid architectures to enhance biometric security systems.

12.
arXiv (CS.CL) 2026-06-16

MemBoost: A Memory-Boosted Framework for Cost-Aware LLM Inference

Large Language Models (LLMs) deliver strong performance but incur high inference cost in real-world services, especially under workloads with repeated or near-duplicate queries across users and sessions. In this work, we propose MemBoost, a memory-boosted LLM serving framework that enables a lightweight model to reuse previously generated answers and retrieve relevant supporting information for cheap inference, while selectively escalating difficult or uncertain queries to a stronger model. Unlike standard retrieval-augmented generation, which primarily grounds a single response, MemBoost is designed for interactive settings by supporting answer reuse, continual memory growth, and cost-aware routing. Experiments across multiple models under simulated workloads show that MemBoost substantially reduces expensive large-model invocations and overall inference cost, while maintaining high answer quality comparable to the strong model baseline.

13.
arXiv (quant-ph) 2026-06-19

Quantum Kernels are Spectral Tensor Networks

arXiv:2606.20402v1 Announce Type: new Abstract: Quantum kernels admit Fourier representations whose frequencies are determined by the data-encoding gates of the underlying feature map. We show that entangling tensor kernels are matrix product operator factorizations of the corresponding Fourier coefficient tensors, thereby identifying quantum kernels as spectral tensor networks. By grouping gate-level frequency configurations that yield the same feature-wise frequency, we obtain a grouped Fourier form that induces a more compact spectral tensor network representation of the kernel. We further show that kernel target alignment serves as a bridge between the Fourier and tensor network views. On a grid that resolves the accessible Fourier modes, it becomes the Frobenius cosine similarity between Fourier coefficient tensors. Our numerical experiments show that layered quantum kernels admit accurate representations with small bond dimension, revealing a compressibility governed by correlations between Fourier modes. This compressibility provides a diagnostic of classical representability and of whether kernel evaluation is likely to remain classically tractable.

14.
arXiv (quant-ph) 2026-06-11

Optimizing Encoder Circuits of Entanglement-Assisted Quantum LDPC Codes via Beam Search

arXiv:2606.11468v1 Announce Type: new Abstract: Entanglement-assisted (EA) quantum QC-LDPC codes offer strong error-correction capabilities with structured parity-check matrices, but their practical use depends on efficient encoder circuits and the availability of pre-shared Bell pairs (ebits). In all encoder implementations based on the stabilizer formalism, the dominant contribution to this complexity comes from the use of controlled gates. In this paper, we adopt the Sharma-Kumar-Garani (SKG) encoder construction. We formulate the encoder optimization as a search over GF(2) row operations that decompose the binary matrix derived from its CNOT sub-sequence. We solve this problem using a beam search algorithm guided by a Hamming-distance heuristic. For the tested EA quantum QC-LDPC code families, the proposed method achieves CNOT-count reductions of 7.3-34.0% relative to the SKG baseline encoder. The optimized circuits also yield lower CNOT counts than Patel-Markov-Hayes synthesis on all tested instances and are verified by stabilizer-tableau simulation. These results show that substantial encoder simplification is possible for structured EA QC-LDPC codes.

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

NanoQuant: Efficient Sub-1-Bit Quantization of Large Language Models

arXiv:2602.06694v3 Announce Type: replace Abstract: Weight-only quantization has become a standard approach for efficiently serving large language models (LLMs). However, existing methods fail to efficiently compress models to binary (1-bit) levels, as they either require large amounts of data and compute or incur additional storage. In this work, we propose NanoQuant, the first post-training quantization (PTQ) method to compress LLMs to both binary and sub-1-bit levels. NanoQuant formulates quantization as a low-rank binary factorization problem, and compresses full-precision weights to low-rank binary matrices and scales. Specifically, it utilizes an efficient alternating direction method of multipliers (ADMM) solver to precisely initialize latent binary matrices and scales, and then tunes the initialized parameters through a block and model reconstruction process. Consequently, NanoQuant establishes a new Pareto frontier in low-memory post-training quantization, and enables sub-1-bit compression. NanoQuant makes large-scale deployment feasible on consumer hardware. For example, it compresses Llama2-70B by 25.8$\times$ in just 13 hours on a single H100, enabling a 70B model to operate on a consumer 8 GB GPU. Code is available at https://github.com/SamsungLabs/NanoQuant.

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

DataMagic: Transforming Tabular Data into Data Insight Video

arXiv:2606.20388v1 Announce Type: cross Abstract: Data videos integrate dynamic charts, voice narration, and synchronized animations to communicate data insights as temporal narratives, making them an effective medium for improving data consumption efficiency in the data management lifecycle. However, producing high-quality data videos requires expertise spanning data analysis, narrative design, and video production. Existing approaches fall short: static visualization tools (e.g., BI dashboards) lack narrative logic and animation; authoring tools require users to pre-prepare visualizations rather than working from raw data; pixel-level video generation models cannot guarantee data fidelity or provenance. We demonstrate DataMagic, an end-to-end interactive system that transforms raw tabular data and natural language queries into narrative data-insight videos. To ensure data fidelity, DataMagic introduces the declarative specification DVSpec, which binds visual and animation elements to underlying data fields through data-driven semantic references. To address the combinatorial explosion of the design space, DataMagic adopts a Generate-then-Orchestrate multi-agent architecture that generates candidate scenes in parallel and then optimizes narrative coherence through global orchestration. Leveraging DVSpec's decoupling of logic and rendering, the system further supports three interaction modes and structured provenance-based data Q&A, transforming one-way videos into explorable interactive data interfaces. Evaluation on 109 real-world samples validates the effectiveness of the DataMagic. Homepage: https://datamagic-home.github.io/

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

RoboSSM: Scalable In-context Imitation Learning via State-Space Models

arXiv:2509.19658v2 Announce Type: replace-cross Abstract: In-context imitation learning (ICIL) enables robots to learn tasks from prompts consisting of just a handful of demonstrations. By eliminating the need for parameter updates at deployment time, this paradigm supports few-shot adaptation to novel tasks. However, recent ICIL methods rely on Transformers, which have computational limitations and tend to underperform when handling longer prompts than those seen during training. In this work, we introduce RoboSSM, a scalable recipe for in-context imitation learning based on state-space models (SSM). Specifically, RoboSSM replaces Transformers with Longhorn – a state-of-the-art SSM that provides linear-time inference and strong extrapolation capabilities, making it well-suited for long-context prompts. Through diverse experiments on the LIBERO benchmark, we demonstrate the effectiveness of applying SSMs to ICIL, achieving improved generalization to both unseen and long-horizon tasks than Transformer-based ICIL methods by handling longer contexts at test-time. These results show for the first time that SSMs are an efficient and scalable backbone for ICIL. Our code is available at https://github.com/youngjuY/RoboSSM.

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

CropTrack: A Tracking with Re-Identification Framework for Precision Agriculture

Multiple-object tracking (MOT) in agricultural environments presents major challenges due to repetitive patterns, similar object appearances, sudden illumination changes, and frequent occlusions. Contemporary trackers in this domain rely on the motion of objects rather than appearance for association. Nevertheless, they struggle to maintain object identities when targets undergo frequent and strong occlusions. The high similarity of object appearances makes integrating appearance-based association nontrivial for agricultural scenarios. To solve this problem we propose CropTrack, a novel MOT framework based on the combination of appearance and motion information. CropTrack integrates a reranking-enhanced appearance association, a one-to-many association with appearance-based conflict resolution strategy, and an exponential moving average prototype feature bank to improve appearance-based association. Evaluated on publicly available agricultural MOT datasets, CropTrack demonstrates consistent identity preservation, outperforming traditional motion-based tracking methods. Compared to the state of the art, CropTrack achieves significant gains in association accuracy and identification precision scores with a lower number of identity switches.

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

Calibration Drift Under Reasoning: How Chain-of-Thought Budgets Induce Overconfidence in Large Language Models

The ability of large language models (LLMs) to express calibrated uncertainty is important for safe deployment. Chain-of-thought (CoT) reasoning is widely used to improve accuracy and reliability, but its effect on calibration is not fully understood. We show that this picture is incomplete: in some settings, increasing the reasoning budget beyond a task-specific threshold can cause models to become systematically overconfident, assigning high confidence to incorrect answers. We call this phenomenon Calibration Drift Under Reasoning (CDUR) and study it both theoretically and empirically. We define reasoning budget B and analyze conditions under which Expected Calibration Error ECE(B) follows a non-monotonic pattern: it first decreases as reasoning corrects errors, then increases as longer reasoning produces internally consistent but incorrect explanations. We propose a Hypothesis Lock-In model based on autoregressive generation to explain this behavior. We evaluate Llama-3.1-8B and Llama-3.3-70B on 47 reasoning-trap questions across four reasoning budgets and three seeds (1,368 API calls; 574 valid responses). The 8B model shows non-monotonic calibration behavior, while results for the 70B model are limited to baseline evaluation and are inconclusive for budget-dependent effects. We introduce CABStop, a calibration-aware stopping rule that halts reasoning when confidence diverges from an auxiliary accuracy estimate. These results suggest that increasing reasoning depth does not always improve reliability and should be monitored carefully.

21.
arXiv (CS.LG) 2026-06-19

Federated Bilevel Performative Prediction

arXiv:2606.19734v1 Announce Type: new Abstract: Federated bilevel optimization is widely used for nested learning problems across distributed clients, such as federated hyperparameter tuning and meta-learning under privacy and communication constraints. Most existing formulations assume fixed client data distributions, which can be violated by performativity, where deployed decisions reshape client behavior and data collection, inducing client-specific, decision-dependent distribution shift. We study federated bilevel performative prediction, where both upper-level (UL) and lower-level (LL) objectives are evaluated under client-dependent, decision-dependent distributions. We formalize the federated bilevel performatively stable (FBPS) point under a decoupled-risk perspective and provide sufficient conditions for its existence and uniqueness. We then develop two federated methods to compute the FBPS solution: FBi-RRM, which converges linearly under a contraction condition, and FBi-SGD, a communication-efficient stochastic method based on federated hypergradient estimation with convergence guarantees under diminishing step sizes when sensitivities are sufficiently small. Experiments on strategic regression and meta strategic classification validate the predicted stability thresholds and demonstrate improved meta-generalization over non-performative baselines, and CNN-based classification further demonstrates the practical effectiveness of the proposed methods in nonconvex neural network settings.

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

Interactor: Agentic RL oriented Iterative Creation for Ad Description Generation in Sponsored Search

This paper focuses on automatically generating informative ad descriptions in sponsored search. Unlike ad titles which are usually optimized to attract user click feedbacks, ad descriptions have a longer text span and possess the potential of incorporating world knowledge to address user search intents while presenting the fine-grained selling points of the ads. We propose Interactor, a multi-turn iterative creation framework optimized with agentic RL for ad description generation. The generation model acts as a policy that interacts with a customized environment consisting of multiple generative reward models. Given initial generations by the policy, the customized GenRMs evaluate multi-dimensional qualities including knowledge capacity and landing page consistency, providing both binary signals and reasoning feedbacks. The policy then iteratively refines the descriptions based on such feedbacks to ensure continuous improvement. Experiments on industrial datasets show that the Interactor framework significantly outperforms state-of-the-art approaches in generating knowledge-rich and faithful ad descriptions. Since May 2026, it has been deployed online in a leading search ads system, contributing to both ad revenue and user experience.

23.
arXiv (quant-ph) 2026-06-11

Gate-tunable spin-valley transport via carrier velocity in monolayer WSe$_2$

arXiv:2606.12353v1 Announce Type: cross Abstract: We theoretically investigate spin- and valley-resolved quantum transport in monolayer tungsten diselenide (WSe$_2$) described by an effective massive Dirac Hamiltonian. Particular attention is devoted to a finite barrier region characterized by simultaneously modulated Fermi velocity and scalar potential. The barrier velocity $v_2$ is related to the external velocity $v_1$ through a velocity ratio $\xi=v_2/v_1$, motivated by an optical analogy with the Snell-Descartes law. The exact refraction condition depends on the full spin- and valley-resolved dispersion, and the simple ratio $\xi=v_2/v_1$ is recovered only in the massless, symmetric limit. The interplay of intrinsic spin-orbit coupling in the conduction and valence bands, quantified by $\lambda_c$ and $\lambda_v$, with spin- and valley-dependent Zeeman fields, $M_s$ and $M_v$, gives rise to substantial changes in the quasiparticle dispersion, leading to pronounced modifications of the transport characteristics. By solving the Dirac equation and enforcing current-conserving matching conditions at the interfaces, we compute the spin- and valley-dependent transmission probability and conductance. Our results demonstrate that the barrier velocity, scalar potential, incidence angle, incident energy, and barrier width serve as effective control parameters for transport, giving rise to strong anisotropy and resonant tunneling features. Furthermore, we show that both the magnitude and orientation of spin- and valley-polarized currents can be continuously tuned via velocity and potential modulation. These findings establish combined velocity and potential engineering as a powerful theoretical framework for controlling spin-valley physics in two-dimensional transition-metal dichalcogenides.

24.
bioRxiv (Bioinfo) 2026-06-14

Systematic AI-Driven Drug Repurposing via Clinical Trial Data Mining: A Framework and Six Cross-Therapeutic Case Studies.

作者:

Drug repurposing, the application of approved or shelved compounds to new therapeutic indications, offers a cost- and time-efficient alternative to de novo drug discovery. However, the systematic identification of repurposing candidates from the rapidly expanding body of clinical trial data remains a significant challenge. Here we present a publicly accessible AI-powered tool that mines the ClinicalTrials.gov registry to identify approved drugs with under-explored therapeutic potential in high-value disease areas. The tool integrates natural language processing, mechanism-of-action pathway analysis, and trial density scoring to surface candidates where biological plausibility is high and clinical trial coverage is sparse. We demonstrate the tool's utility across six cross-therapeutic case studies spanning oncology, cardiology, neurology, rare diseases, immunology, and infectious disease. Key findings include: the identification of Zonisamide as an under-explored combination candidate for obesity alongside GLP-1 receptor agonists; mechanistic validation of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF); and a novel cross-domain mapping of anti-TNF biologics to early-stage neurodegeneration via shared neuroinflammatory pathways. The tool is freely accessible and designed to lower the barrier for academic and industry researchers to systematically pursue repurposing opportunities.

25.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.