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01.
Nature Medicine 2026-06-17

Why large-scale randomized trials of live-attenuated shingles vaccination for dementia prevention are urgently needed

作者:
Pascal Geldsetzer↗

In my view, we have never had as robust a body of evidence from observational data on an intervention for dementia as we do for live-attenuated shingles vaccination. Both a recent US National Institutes of Health expert workshop and an international expert consensus on Alzheimer’s disease drug repurposing identified large-scale randomized trials of shingles vaccination for dementia prevention as the crucial next step for the field.

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02.
arXiv (CS.AI) 2026-06-17

Beyond Parallel Sampling: Diverse Query Initialization for Agentic Search

作者:
Sidhaarth Murali↗Jo\~ao Coelho↗Jingjie Ning↗Jo\~ao Magalh\~aes↗Bruno Martins↗Chenyan Xiong↗

arXiv:2606.17209v1 Announce Type: new Abstract: Test-time scaling for agentic search typically increases depth (i.e., more turns and tokens per trajectory) or breadth (i.e., more parallel rollouts). Here we focus on breadth scaling, showing that standard parallel sampling yields diminishing returns, tracing this to query redundancy at the first turn. When models issue similar first queries across rollouts, the threads retrieve overlapping evidence, and subsequent turns are conditioned on this shared retrieval. We address this limitation with DivInit, a training-free intervention at the first turn. Rather than sampling k independent first queries, DivInit draws n candidates from a single call, picks k < n diverse seeds, and runs them as parallel trajectories. Across five open-weight models and eight benchmarks, DivInit consistently improves over standard parallel sampling, with average gains of five to seven points on multi-hop QA at matched compute. Code available at https://github.com/cxcscmu/diverse-query-initialization

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03.
arXiv (quant-ph) 2026-06-12

Representation-Induced Symmetry Trapping in Adaptive Variational Quantum Simulations of Multi-Reference Topologies

作者:
Hermawan Kresno Dipojono↗

arXiv:2606.13387v1 Announce Type: new Abstract: Evaluating the trainability of adaptive quantum chemistry algorithms under multi-reference static correlation requires understanding how representation topologies intertwine with molecular geometry. We systematically expose a deep physical dependence on point-group symmetry by evaluating a spin-conserved SUSD operator pool across highly stretched configurations (2 x Re) of asymmetric LiH, symmetric BeH2, and asymmetric H2O. Under asymmetric distortions, the non-local mapping constraints of the Bravyi-Kitaev transformation create an optimization trapping effect–an encodement-locked manifestation of the broader barren plateau crisis. Crucially, by comparing these to the symmetrical stretching baseline of BeH2, we demonstrate that the preservation of point-group symmetry structurally protects the optimization landscape, proving that ansatz symmetry restrictions are necessary but insufficient without accounting for the underlying fermion-to-qubit representation. While current methods rely on numerical pruning to throttle pool sizes, our structural approach establishes that the mapping representation remains a critical factor in maintaining landscape trainability. Furthermore, exploiting structural overlap within our pool, we introduce a covariance-driven, adaptive shot-allocation filter. Diverging from static energy-variance minimization frameworks, our allocation engine operates as a dynamic runtime diagnostic tool. By continuously monitoring the gradient precision threshold epsilon, it aggressively prunes dead symmetry channels and triggers an automated circuit-termination sequence upon detecting representation-induced flat-lined states (dE/dtheta approx 0). This integration of algebraic measurement reuse with topology-aware statistical filtering provides a promising, resource-efficient strategy for executing deep variational algorithms on early fault-tolerant architectures.

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

Bayesian Networks with Latent Time Embedding for Stage-Aware Causal Modeling of Alzheimer's Disease Progression

作者:
Nguyen Linh Dan Le↗

arXiv:2606.15784v1 Announce Type: new Abstract: Alzheimer's disease (AD) progression is often described through the amyloid-tau-neurodegeneration, or AT(N), cascade. However, most longitudinal models represent this cascade either as a fixed sequence of biomarkers or as a black-box forecasting task. This makes it difficult to determine when biologically guided biomarker relationships influence future regional pathology. In this study, we introduce Bayesian Networks with Latent Time Embedding (BN-LTE), a Bayesian structural framework for stage-aware modeling of AD progression. BN-LTE estimates disease pseudotime from baseline biomarker profiles and constrains directed dependencies according to biologically plausible AT(N) ordering. Posterior spline-varying structural equations are then used to link initial multimodal measurements with future annualized regional tau-PET change. Across repeated subject-disjoint evaluations using ADNI data, BN-LTE shows strong spatial reconstruction of tau progression compared with the included forecasting baselines. Beyond spatial reconstruction, BN-LTE recovers posterior stage-varying AT(N)-constrained effects and identifies a mid-pseudotime window of amyloid sensitivity. This window is supported by model-implied g-formula contrasts, root-adjusted AIPW, mechanism-sensitive ablations, and robustness analyses across spline and prior specifications. Overall, these findings position BN-LTE as a Bayesian structural framework for forecasting tau progression while examining stage-dependent AT(N)-cascade mechanisms in observational longitudinal neuroimaging data. Our code is available at https://github.com/danleneurocom/BN-LTE.

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06.
Nature (Science) 2026-06-10

A thalamus–brainstem attractor network drives history-biased decisions

作者:
Shan Zhao↗

Natural environments often change gradually, making it adaptive to bias decisions on the basis of the recent past — a phenomenon known as serial dependence1–3. Large-scale recordings during behaviour have identified that serial dependence is a common motif for decision-making, with neural representations of past experiences found throughout the brain4–11. However, it remains unclear whether this bias arises from dedicated neural circuits with history-specific computations. Using whole-brain, cellular-resolution imaging in zebrafish performing memory-guided evasive manoeuvres12–14, we identified a hierarchical circuit that maintains past information and biases future choices. Discrete attractors in the dorsal thalamus encoded the position of the most recent obstacle, maintaining a categorical memory via persistent activity lasting 10–20 s. Optogenetic manipulation of the dorsal thalamus abolished or imposed serial bias. A downstream hindbrain integrator received input from the thalamus and combined it with current sensory cues to produce graded responses reflecting multi-trial history. Leveraging a comprehensive brain atlas in zebrafish15, we constructed a whole-brain computational model that recapitulated behaviour and also predicted a key role for heterogeneous inhibitory subtypes in enabling flexible state transitions. This attractor–integrator architecture reveals a hierarchical and modular computation that unifies robust memory retention with flexible sensory integration, providing a general principle for history-biased decisions. Whole-brain, cellular-resolution imaging reveals a hierarchical thalamus–brainstem attractor network that encodes recent history and shapes behavioural bias in zebrafish.

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07.
medRxiv (Medicine) 2026-06-12

Disentangling Confounders from Pathology in Long-COVID Trajectory Prediction for Women: An Interpretable Large-Language-Model Approach

作者:
Wang↗Galis↗Zhang↗Luo↗Sra↗Niu↗Shen↗Xie↗Weiss↗J. C↗

Objective. Post-acute sequelae of SARS-CoV-2 infection (PASC, "Long COVID") dispropor- tionately affects women, in whom hallmark symptoms–insomnia, fatigue, palpitations, cogni- tive difficulty–overlap with comorbidities and hormonal transitions such as menopause. This diagnostic overlap is a confounding problem: models that forecast future symptom severity risk attributing baseline physiological noise to viral pathology. We ask whether an interpretable, causally disentangled language model can separate true pathological signal from such con- founders while remaining competitive with strong predictors of future PASC severity

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

Entity Labels Are Not Entity Signals: A Framework for Observable Relevance in Document Re-Ranking

作者:
Utshab Kumar Ghosh↗Shubham Chatterjee↗

Entity-aware document retrieval uses query-associated entities as ranking signals, assuming that semantically relevant entities are also useful retrieval signals. We show this assumption is insufficient- and explain why. Unlike terms, which are ground-truth observations, entity links are hypotheses produced by an imperfect linker: an entity can be topically central yet provide no discriminative signal if the linker fires indiscriminately across relevant and non-relevant documents. We formalize this as a distinction between Conceptual Entity Relevance (CER)- whether an entity is topically related to a query- and Observable Entity Relevance (OER)- whether its observed presence in a collection discriminates relevant from non-relevant documents. Across four collections and annotation sources including human entity judgments, CER and OER exhibit near-chance agreement ($\kappa \approx 0$), while OER operationalizations agree substantially ($\kappa \approx 0.5$), confirming CER as the systematic outlier. CER-based supervision selects topically plausible but weakly discriminative entities, pruning fewer than 4% of non-relevant documents on some collections. Aligning supervision with OER improves non-relevant pruning by up to 10x and open-world MAP by 0.051 over BM25. Our findings motivate a shift from conceptual to observable notions of entity relevance in entity-aware retrieval.

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09.
arXiv (CS.LG) 2026-06-15

Can Deep Neural Networks Improve Compression of Very Large Scientific Data?

作者:
Muhannad Alhumaidi↗Guozhong Li↗Spiros Skiadopoulos↗Panos Kalnis↗

arXiv:2606.14353v1 Announce Type: new Abstract: Error-bounded lossy compression is a fundamental technique for managing the rapidly growing volumes of scientific data produced by modern simulations and observational instruments. Most state-of-the-art-compressors follow a prediction-residual paradigm, where compression effectiveness depends on the quality of the predictor: more accurate predictions generate smaller residuals that are easier to compress. This observation raises a question: can modern machine learning models serve as superior predictors for scientific data compression? Answering this question directly is challenging because developing compression-specific ML predictors requires substantial resources. Instead, we leverage the climate domain where highly accurate pretrained weather forecasting foundation models already exist, making them an ideal testbed. We present a framework that integrates spatial and temporal deep learning models into a conventional error-bounded compression pipeline. The framework supports auto-regressive forecasting models and avoids error accumulation. Using ERA5 climate data as a representative large-scale scientific dataset, we evaluate three distinct ML predictors: a VAEformer-based codec (CRA5), a graph neural network forecaster (GraphCast), and a vision-transformer forecaster (Aurora), against the state-of-the-art compressor SZ3.1 under identical quantization and entropy-coding backends. Our evaluation over approximately 1.7 TB of data reveals a surprising result: although ML predictors generate more accurate predictions and can improve reconstruction quality by up to 91% while achieving up to 9.6x higher compression ratios for highly predictable variables, they do not improve overall dataset-level compression ratio. We show that prediction accuracy alone is insufficient: the spatial structure of the resulting residuals plays a decisive role in entropy coding efficiency.

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10.
arXiv (CS.LG) 2026-06-16

PromptShift-CRC: Drift-Aware Conformal Risk Control for Foundation Models Under Prompt and Domain Shift

作者:
Jeffery Opoku↗David Banahene↗

arXiv:2606.15964v1 Announce Type: cross Abstract: Foundation models are now used in settings where the prompts they receive can change quickly. Users change, topics change, policies change, and the model may suddenly face a kind of request that was rare in the calibration data. This makes fixed calibration risky. Conformal prediction and conformal risk control give model-agnostic ways to control error, but they work best when the calibration data still look like the future data. This paper develops PromptShift CRC, a drift-aware conformal risk control method for foundation-model outputs under prompt and domain shift. The method embeds prompts and responses, measures how far the current prompt stream has moved from the calibration pool, gives more weight to relevant or recent calibration examples, and updates the risk level online after observed violations. It reports three practical diagnostics: realized risk error, prompt drift, and effective calibration size. We give conditions under which the method controls risk up to terms for distribution mismatch and weighted quantile uncertainty. In a synthetic prompt-shift benchmark, static conformal risk control fails sharply after drift, while PromptShift-CRC gives the best coverage among the adaptive baselines considered. We then evaluate the same calibration layer on public benchmark derived streams for question answering, toxicity, summarization factuality, and long-context hallucination risk

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11.
arXiv (quant-ph) 2026-06-16

Excited-State Quantum Chemistry on Qumode-Based Processors via Variational Quantum Deflation

作者:
Marlon F. Jost↗Sijia S. Dong↗

arXiv:2604.13457v3 Announce Type: replace Abstract: Variational quantum algorithms on bosonic quantum processors are an emerging paradigm for quantum chemistry calculations, exploiting the natural alignment between molecular structure and harmonic oscillator-based hardware. We introduce the qumode-based variational quantum deflation framework (QumVQD) for finding both electronic and vibrational excited state energies on qumode-based architectures. We validate the approach through electronic structure calculations on H$_{2}$ and linear H$_{4}$, where we introduce Hamming-weight filtering of the Fock basis to enforce particle number conservation and eliminate spurious eigenstates by reducing the required Hilbert space, which reduces the required number of qumodes in turn. We achieve agreement with full configuration interaction (FCI) using the STO-3G basis set within the chemical accuracy threshold at most points along the potential energy surfaces. Extending to the vibrational structure, we combine QumVQD with an existing Hamiltonian fragmentation approach based on Cartan subalgebra, allowing us to compute the vibrational eigenenergies of CO$_{2}$ and H$_{2}$S to spectroscopic accuracy with per-fragment circuits that scale as $O(N)$ in single-qumode gates and $O(N^2)$ in beam-splitter gates for $N$ qumodes. For the case of CO$_{2}$, we get total gate counts more than an order of magnitude smaller than those reported for qubit-based vibrational algorithms at this system size. These results demonstrate that bosonic quantum devices are a viable platform for excited-state quantum chemistry, particularly for vibrational problems where qubit-based methods incur substantial boson-to-qubit mapping overhead.

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

Fluently Lying: Adversarial Robustness Can Be Substrate-Dependent

作者:
Daye Kang↗Hyeongboo Baek↗

The primary tools used to monitor and defend object detectors under adversarial attack assume that when accuracy degrades, detection count drops in tandem. This coupling was assumed, not measured. We report a counterexample observed on a single model: under standard PGD, EMS-YOLO, a spiking neural network (SNN) object detector, retains more than 70% of its detections while mAP collapses from 0.528 to 0.042. We term this count-preserving accuracy collapse Quality Corruption (QC), to distinguish it from the suppression that dominates untargeted evaluation. Across four SNN architectures and two threat models (l-infinity and l-2), QC appears only in one of the four detectors tested (EMS-YOLO). On this model, all five standard defense components fail to detect or mitigate QC, suggesting the defense ecosystem may rely on a shared assumption calibrated on a single substrate. These results provide, to our knowledge, the first evidence that adversarial failure modes can be substrate-dependent.

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13.
arXiv (CS.LG) 2026-06-16

Scale-Invariant Neural Network Optimization: Norm Geometry and Heavy-Tailed Noise

作者:
Jiayu Zhang↗Tianyi Lin↗

arXiv:2605.18528v3 Announce Type: replace-cross Abstract: A growing lesson from neural network optimization is that optimizer design should respect how the model is parametrized. The layerwise input-output structure of neural networks motivates scale-invariant optimizers, such as Muon and Scion, whose updates also support hyperparameter transfer. At the same time, stochastic gradient noise in deep learning is often far from sub-Gaussian and may exhibit heavy tails. These observations have shaped recent algorithmic principles for training neural networks, yet their joint theoretical consequences are underexplored. In particular, it remains unclear what dimension dependence is unavoidable for gradient-based methods given the problem class is defined by input-output norm and under heavy-tailed noise, and whether higher-order smoothness can accelerate training. We study these questions through nonconvex smooth stochastic optimization over $\mathbb R^{m\times n}$ equipped with general norms and under $p^\mathrm{th}$-moment heavy-tailed noise, where the goal is to achieve an $\epsilon$-stationary point in the dual norm. Our first contribution is a dimension-dependent lower bound: when $\frac{\max\{m,n\}}{(\min\{m,n\})^2}$ is large enough, any gradient-based method requires $\Omega(\min\{m, n\}\epsilon^{-\frac{3p-2}{p-1}})$ oracles for the problem class defined by the spectral norm, which is a common input-output norm. We prove that a scale-invariant Scion method with the spectral norm can achieve the matching upper bound of $O(\min\{m, n\}\epsilon^{-\frac{3p-2}{p-1}})$. To exploit higher-order smoothness, we propose a transported Scion method and improve the bound to $O(\min\{m, n\}\epsilon^{-\frac{5p-3}{2p-2}})$ when the Hessian is Lipschitz. Finally, we incorporate heuristics into our transported method and evaluate it across multiple architectures and model sizes, demonstrating its flexibility and compatibility with neural network training.

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

Reliable Neural-Codec Text-to-Speech by ASR Self-Verification and Distillation: Near-Zero Catastrophic Failures Across Models and Codecs

作者:
Ali Asaria↗Tony Salomone↗Deep Gandhi↗

arXiv:2606.18323v1 Announce Type: cross Abstract: Open autoregressive neural-codec text-to-speech (TTS) models sound excellent on typical inputs yet suffer stochastic catastrophic failures: on a meaningful fraction of utterances they emit silence, terminate early, or collapse into repetitive or hallucinated content. We show this failure mode is cheap to remove. Under a single format-robust metric (a catastrophic-failure rate via an ASR round-trip), best-of-N ASR self-verification drives failures to near-zero: no observed failures remain by N=2 on a standard corpus (LibriSpeech) and by N=4 on a hard prompt set. This is not an artifact of one model: the reduction replicates across four open codec-TTS systems and three neural codecs (XCodec2, SNAC, Mimi), reaching the near-zero floor by N=2 on three of the four. We then make the fix free at inference time by distilling the self-verified behaviour into the model, which recovers much of the robustness in single-shot decoding, closing ~52-58% of the failure mass on hard inputs at no test-time cost. The distillation gain concentrates where it is needed (hard inputs); on already-reliable prose there is no headroom and no detectable change. A controlled comparison adds a clean negative: offline direct preference optimization (DPO/IPO) does not beat plain supervised distillation, and an online iterative variant is promising but not statistically separable at our evaluation size. We report honestly the one model that resists (a larger Llasa where scale did not obviously help) and a rare-word capability ceiling that no self-distillation method overcomes

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

TerraMARS: A Domain-Adapted Small-Language-Model Pipeline for Mars Terraforming Literature

作者:
Jyotsna Singh↗Ash Black↗Jeff Larsen↗Scott R. Saleska↗

Researchers are interested in learning about Mars so that it may eventually become habitable for humans. To achieve this, there is a need for comprehensive knowledge of the planet's atmosphere, hydrology, surface chemistry, radiation environment, and spatial features through the scientific literature. These contain valuable information and meaningful quantitative constraints that can be used in other models and studies, such as habitability assessment and future terraforming studies. We present TerraMARS, an end-to-end information extraction pipeline that combines a domain-adapted Small Language Model to answer Mars terraforming-related questions and convert unstructured Mars science text into machine-readable structured outputs in JavaScript Object Notation (JSON) format. A corpus of open-access papers is collected and processed using a multistage retrieval and chunking framework. Google Gemma 3 1B was adapted to the domain using Quantized Low-Rank Adaptation (QLoRA) fine-tuning on Mars-specific question-answering and information extraction datasets. The resulting pipeline generates both types of output and provides a foundation for integrating knowledge from scientific literature into downstream applications like digital twins and habitability modeling for Mars. The output from this pipeline looks promising, but further improvements are needed to increase extraction accuracy and factual consistency.

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

Mixed-Precision Communication-Avoiding SGD for Generalized Linear Models on GPUs

作者:
Aditya Devarakonda↗Irene Sim\'o Mu\~noz↗Giulia Guidi↗

arXiv:2606.18463v1 Announce Type: cross Abstract: Distributed stochastic gradient descent (SGD) is limited by communication rather than computation, since each iteration requires an AllReduce across processes. Communication-avoiding SGD (CA-SGD) amortizes communication over $s$ iterations by replacing $s$ consecutive AllReduces with a single AllReduce of an $sb\times sb$ Gram matrix, trading more computation and bandwidth for fewer synchronization points. Modern GPUs with matrix hardware and reduced-precision formats offset this by accelerating the Gram GEMM and shrinking BF16 traffic. We study mixed-precision CA-SGD for generalized linear models on NVIDIA GPUs. Our finite-precision analysis decomposes the local rounding error of one CA-SGD outer iteration into nine independent precision choices, depending on the hardware only through its low-precision unit roundoffs, so the resulting recipes transfer in principle across GPU generations. The recipe stores the input matrix and margin vector in low precision, computes the Gram matrix from low-precision inputs with high-precision accumulation, communicates it in high precision, and performs the inner recurrence and weight updates in high precision. On NERSC Perlmutter A100 GPUs, mixed-precision CA-SGD matches FP32 SGD loss within $0.5\%$ on logistic, linear, and Poisson problems and reaches $5.1$–$6.8\times$ speedup over FP32 SGD on epsilon, SUSY, HIGGS, synth, and Poisson-synth. Our software is available at https://doi.org/10.5281/zenodo.20448273

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17.
bioRxiv (Bioinfo) 2026-06-21

SPA-C: an hybrid tool to accurately scaffold genomes using Hi-C and Deep-Learning

作者:
Mergez↗Mourad↗Hernandez-Raquet↗Zytnicki↗

Genome assembly is a computational pipeline designed to reconstruct chromosomes from small sequencing reads. Following their assembly, contiguous sequences (contigs) are arranged into chromosome-long sequences during scaffolding. Hi-C, a long-range linkage information between regions of the genome widely used in recent large sequencing projects, is often required to correctly order contigs. Several tools have been developed to automate this task following either statistical or deep-learning approaches. Statistical approaches summarise 2D Hi-C matrices into contact densities across sequences, thus ignoring informative visual patterns. The sole existing deep-learning tool uses a transformer-based computer vision model to correct the assembly. It has been trained on several species and uses Hi-C matrices directly. Yet it comes as a supplementary step in the scaffolding process, introducing extra computation time, and has been trained on a dataset that might contain labelling errors, which could provide sub-optimal results. We propose SPA-C, an hybrid pipeline combining the strengths of both approaches. Linkage prediction is handled with a frugal CNN-based model and a graph-solving algorithm is used to generate the scaffolds. Through our input's design, the model is able to both correct errors within assemblies and link contigs, leveraging small, local Hi-C contact matrices. We handled low-complexity regions that might induce erroneous predictions using an external tool, improving the overall accuracy of generated assemblies. On a benchmark of six various genomes and four standard metrics, SPA-C outperformed four out of four state-of-the-art methods while achieving comparable start-to-end computation time.Python and Bash scripts are available on GitHub (https://github.com/SPA-C/SPA-C.git) and Zenodo (https://doi.org/10.5281/zenodo.19000361).

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18.
Nature (Science) 2026-06-10

Mitochondria directly interact with the nuclear pore complex

作者:
Ivan Menendez-Montes↗

Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5. Here we identify direct interactions between mitochondria and nuclear pores. Using two unbiased proteomic screens, GST pulldown and BioID, we found that VDAC1 was the top mitochondrial candidate that interacts with the filamentous nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knockout,&nbsp;RANBP2 truncation&nbsp;or site-directed mutagenesis of RANBP2–VDAC1 interacting amino acids resulted in reduced mitochondria–nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in the levels of the nuclear phosphoproteome and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. Moreover, deletion of the RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the nuclear pore complex, a phenomenon critical for regulation of nuclear energetics and cellular differentiation. Undoubtedly, additional roles of this interaction remain to be revealed. Mitochondria interact directly with the nuclear pore complex via VDAC1–RANBP2&nbsp;binding to sustain nuclear ATP levels.

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19.
arXiv (CS.CV) 2026-06-12

Stereo Vision-Based Fall Prediction and Detection using Human Pose Estimation on the AMD Kria K26 SOM

作者:
Shreyas Narasimhiah Ramesh↗P. D. Rathika↗Mahasweta Sarkar↗Kristen Wells↗Michel Audette↗Christopher Paolini↗

Background and Objective: Falls among elderly people can cause serious injury and reduce quality of life. Timely prediction and detection are essential to prevent harm and support well-being. We propose a portable, low-power, battery-operated, vision-based fall prediction and detection system using HPE on an AMD Kria K26 System-on-Module (SOM). The objective is a non-intrusive, privacy-preserving system for real-time fall detection. Methods: The system uses an Intel RealSense D455 range-sensing camera connected to the K26 SOM by USB. It captures synchronized RGB and depth frames, 640 x 480 x 3 and 640 x 480 pixels, at 60 FPS. The SOM runs a three-stage pipeline with quantized YOLOX, Anchor-to-Joint (A2J), and fall-detection models. YOLOX identifies human bounding boxes from RGB frames, then discards the RGB frames to preserve privacy. A2J uses depth frames to estimate 15 joint keypoints per person. A CNN uses selected joint coordinates (x, y, z) to classify fall activity. YOLOX was trained on CrowdHuman; A2J on ITOP, MP-3DHP, UR Fall Detection, and a custom SDSU PSG dataset; and the CNN on UR Fall Detection and SDSU PSG. The design used a single-core DPU with a serial pipeline and a dual-core DPU running YOLOX and A2J with multiple threads. Results: Quantized accuracy was evaluated using IoU >= 50% for YOLOX, mAP with a 10-cm rule for A2J, and classification accuracy, (TP + TN)/(TP + TN + FP + FN), for the CNN. Accuracies were 74%, 84.13%, and 75.85%. Throughput improved from 2.5 FPS for the single-threaded pipeline to 4.5 FPS for the multi-threaded version. Conclusion: Results demonstrate the feasibility of privacy-preserving fall detection on an AMD Kria K26 edge device. On-device HPE and fall classification runs without cloud dependency, supporting elderly monitoring and assistive healthcare. Future work will improve model accuracy and speed.

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20.
arXiv (CS.AI) 2026-06-17

Treatment Response Optimized Clinical Decision Support AI System via Digital Twin Simulation

作者:
Xinyu Qin↗Anil K. Sood↗Ruiheng Yu↗Sara Corvigno↗Elaine Stur↗Lu Wang↗

arXiv:2606.17405v1 Announce Type: new Abstract: Clinical decision support AI systems (CDSASs) must adapt to evolving patient conditions in real-time while adhering to strict safety constraints. We present an online adaptive framework that integrates Treatment Effect (TE) estimation to quantify clinical benefits, a patient Digital Twin (DT) to simulate treatment trajectories, and Reinforcement Learning (RL) for sequential decision-making. The AI system is initially trained on historical medical records and operates in a continuous learning loop. To ensure safety, a rule-based module monitors vital signs and blocks contraindicated treatments. Cases with strong internal model disagreement are flagged for clinician review, simulated in our experiments via a pre-trained outcome model. We validate our framework using both a synthetic clinical simulator and a real-world ovarian cancer dataset from The Cancer Genome Atlas (TCGA). In both simulated and clinical settings, our method demonstrated superior effectiveness and stability in recommending treatments compared to standard computational baselines. Furthermore, the AI system maintains low latency and requires expert consultation for only a minority of cases in our experimental validation, demonstrating its potential as a safe, clinician-supervised tool for personalized medicine that continuously improves through practical use.

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21.
arXiv (CS.AI) 2026-06-11

Generalization Hacking: Models Can Game Reinforcement Learning by Preventing Behavioral Generalization

作者:
Frank Xiao↗Mary Phuong↗

arXiv:2606.12016v1 Announce Type: cross Abstract: Model post-training, and in particular reinforcement learning (RL), is one of the primary mechanisms by which developers can shape models' values and behaviors. However, as models become increasingly evaluation and training aware, they may be motivated to resist training when the perceived objective conflicts with their current values, undermining developers' ability to detect misalignment and correct model behavior through further training. In this paper, we demonstrate generalization hacking, in which a model collects reward during RL while preventing the rewarded behavior from generalizing. We construct a model organism on Qwen3-235B-A22B, finetuning on synthetic documents describing training awareness and self-inoculation, a novel mechanism in which the model frames compliance as context-specific in its chain of thought, without demonstrating or instructing either behavior. The model organism achieves train-time harmfulness comparable to controls while maintaining a persistent ${\sim}15$ percentage point compliance gap across 700 steps of RL. Additionally, a control organism trained only on training awareness documents independently discovers inoculation-like reasoning under RL pressure, developing its own compliance gap despite never being exposed to the concept. Because the generalization-hacking organism receives high reward throughout, standard training metrics provide no signal that generalization has failed. Our results constitute the first demonstration that a model can actively resist RL behavioral modification while maintaining high reward, suggesting that as models become more capable and training-aware, they may be able to undermine the training process itself.

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22.
bioRxiv (Bioinfo) 2026-06-11

HoloCell: A Generative Foundation Model for Holistic Cellular Modeling

作者:
Jiang↗Li↗Hu↗Bie↗Jin↗He↗Deng↗Wang↗Chen↗Qin↗Liu↗Yin↗…

Single-cell multi-omics technologies have recently advanced to enable the profiling of epigenomic, transcriptomic, and proteomic layers within individual cells, offering new opportunities to characterize cellular states as integrated biological systems. However, developing a unified framework that can seamlessly integrate diverse omics modalities and remain robust to heterogeneous modality missingness remains challenging. Here we present HoloCell, to our knowledge the first generative foundation model for joint representation learning and generative modeling across all three major single-cell omics modalities, i.e., epigenomics, transcriptomics, and proteomics. HoloCell contains over 860 million parameters and is pretrained on the Human-Multi-Omics-Corpus, which comprises approximately 468 million single-cell profiles across these three omics layers, corresponding to over 425 billion tokens. HoloCell introduces a simple yet biologically grounded hierarchical tokenization strategy that encodes cis-regulatory elements, genes, and proteins as structured tokens within a shared modeling framework. We evaluated HoloCell across single-omics representation learning, paired multi-omics integration, unpaired multi-omics alignment, and cross-modal generation via iterative diffusion and remasking, demonstrating its superior performance and flexibility across diverse omics tasks. From a representation perspective, HoloCell provides a unified digital mapping of cellular states across multiple omics layers, capturing cell heterogeneity as an integrated system. From a generation perspective, its iterative diffusion and remasking framework accounts for the inherently unordered nature of biological features, enabling in silico simulation of multi-omics information flow. Together, these capabilities position HoloCell as a versatile foundation model toward the emerging concept of a virtual cell, offering both systematic characterization and generative simulation of cellular systems within a unified framework.

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23.
PLOS Computational Biology 2026-06-22

Beyond the canonical: The role of post-transcriptional regulation in drug-target interaction prediction

作者:
Md Istiaq Ansari↗

by Md Istiaq Ansari, Khandakar Tanvir Ahmed, Debby D. Wang, Kirill Medvedev, Wei Zhang Protein isoforms produced from the same gene through post-transcriptional regulatory mechanisms, such as alternative splicing, can substantially alter protein structure and function, including drug-binding properties. However, most existing drug-target interaction (DTI) and drug-target affinity (DTA) prediction models rely exclusively on a single representative protein sequence per gene, typically the canonical or longest isoform, thereby overlooking the functional diversity introduced by alternative isoforms. This assumption can introduce bias, limit generalizability, and compromise the biological validity of model predictions. In this study, we systematically investigate the impact of protein isoform variation on DTI prediction accuracy. Our results show that substituting the canonical sequence with an alternative isoform often leads to substantial declines in predictive performance. Structural and binding affinity analyses further reveal that these discrepancies are frequently associated with changes in predicted binding-site configurations, which we further examine through controlled perturbations of binding-site residues. These experiments suggest that even subtle alterations in binding regions can lead to inconsistent DTI predictions. Overall, our findings uncover a critical limitation in current DTI modeling frameworks and underscore the importance of incorporating isoform-specific information to better reflect biological reality and improve therapeutic relevance. The codes and datasets are available at https://github.com/compbiolabucf/DTIVariant.

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24.
medRxiv (Medicine) 2026-06-10

Global and local genetic overlap among ME/CFS, irritable bowel syndrome and psychiatric traits: a hypothesis-generating analysis

作者:
Lee↗

Background. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and irritable bowel syndrome (IBS) frequently co-occur following infection, yet shared genetic architecture at the locus level has not been systematically characterised. Aims. To estimate global and local genetic correlations between ME/CFS (including infection-onset subgroup), IBS, major depressive disorder (MDD) and loneliness/isolation, and characterise ME/CFS cell-type heritability enrichment. Method. GWAS summary statistics: DecodeME (15,579 ME/CFS; 9,738 infection-onset), FinnGen R9 (9,296 IBS), PGC MDD Wave 2 (45,396) and UK Biobank loneliness (N=455,364). LDSC for global correlations; LAVA for local correlations across 2,495 loci; MAGMA for cell-type enrichment (Descartes Human atlas); coloc.abf for colocalisation. Results. All pairwise global correlations were significant after Bonferroni correction, including ME/CFS-all-MDD (rg=0.598, 95% CI 0.46-0.74) and ME/CFS-all-IBS (rg=0.573, 0.39-0.75). Of 4,232 local tests, 16 reached FDR

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25.
arXiv (CS.LG) 2026-06-17

Price of metric universality in vector quantization is at most 0.11 bit

作者:
Alina Harbuzova↗Or Ordentlich↗Yury Polyanskiy↗

arXiv:2602.05790v2 Announce Type: replace-cross Abstract: Fast computation of a matrix product $W^\top X$ is a workhorse of modern LLMs. To make their deployment more efficient, a popular approach is that of using a low-precision approximation $\widehat W$ in place of true $W$ (``weight-only quantization''). Information theory demonstrates that an optimal algorithm for reducing precision of $W$ depends on the (second order) statistics of $X$ and requires a careful alignment of vector quantization codebook with PCA directions of $X$ (a process known as ``waterfilling allocation''). Dependence of the codebook on statistics of $X$, however, is highly impractical. This paper proves that there exist a universal codebook that is simultaneously near-optimal for all possible statistics of $X$, in the sense of being at least as good as an $X$-adapted waterfilling codebook with rate reduced by 0.11 bit per dimension in the case when $W$ is Gaussian. Such universal codebook would be an ideal candidate for the low-precision storage format, a topic of active modern research, but alas the existence proof is non-constructive. Equivalently, our result shows existence of a net in $\mathbb{R}^n$ that is a nearly-optimal covering of a sphere simultaneously with respect to all Hilbert norms.

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