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02.
medRxiv (Medicine) 2026-06-15

Repurposing cardiovascular disease risk models to predict incident and co-occurring cardiovascular, cardiometabolic and neurocognitive outcomes.

Authors:
Quill↗Chaturvedi↗van Vugt↗Hingorani↗A. D↗Schmidt↗A. F↗

Background: Cardiovascular disease (CVD), cardiometabolic and neurocognitive conditions share risk factors and frequently co-occur. We evaluated whether four established CVD risk prediction models (QRISK3, PCE, SCORE2, SCORE2-OP) can be repurposed to predict 10-year risk of these conditions and their co-occurrence with CVD. Methods: The models were recalibrated using 20% of the UK Biobank (UKB) and evaluated in the remaining 80%. We performed external validation using data from Clinical Practice Research Datalink (CPRD) Aurum, assessing model discrimination (c-statistics) and calibration (intercept and slope). We used permuted feature importance to determine the influence of each individual predictor in the models. Results: Depending on the model, the c-statistics for incident CVD ranged from 0.71 to 0.74 in the UKB test set (16,137 events). Discrimination was equal to or higher than CVD when evaluated against non-traditional CVD outcomes: 0.74 to 0.77 for heart failure (3,471 events), 0.72 to 0.73 for atrial fibrillation (9,213 events), 0.73 to 0.75 for peripheral arterial disease (1,927 events) and 0.80 to 0.82 for abdominal aortic aneurysm (595 events). For the multimorbidity endpoints, model discrimination ranged from 0.74 for the composite of CVD and T2DM (SCORE2-OP) to 0.83 for the composite of CVD and dementia or Parkinson's disease (QRISK3). When considering the onset of any cardiovascular, cardiometabolic, or neurocognitive outcome discrimination ranged from 0.71 to 0.72. The repurposed models slightly underestimated the predicted risk in the CPRD compared to the UKB: average difference in calibration intercept was at most -0.64. After age and sex, smoking status and systolic blood pressure contributed most to model predictions. Conclusions: Repurposed CVD models can be used to identify 10-year risk of many CVD-related conditions and their multimorbidity. These may be used to support risk-based approaches to prevention and screening. The repurposed models have been made available at: https://repurposed-cvd-risk-models.shinyapps.io/cvd_cmd_dementia_app/ Keywords: Risk prediction; cardiovascular disease; cardiometabolic disease; dementia; disease prevention.

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

Critically Engaged Pragmatism: Scientific Norm and Social, Pragmatist Epistemology for AI Science Evaluation Tools

Authors:
Carole J. Lee↗

arXiv:2601.09753v2 Announce Type: replace-cross Abstract: AI science evaluation tools aim to assess research credibility. As with traditional metrics such as impact factors, their edicts can be decontextualised and repurposed in problematic ways. To address this, I propose Critically-Engaged Pragmatism as a scientific norm enjoining scientific communities to scrutinise the purposes and purpose-specific reliability of AI science evaluation tools. To foster Critically Engaged Pragmatism, creators of AI science evaluation tools should transparently and fully report design, training, and benchmarking details to facilitate assessments of purpose-specific reliability, liability to different types of error, and bias. What count as best practices for the transparent reporting of AI science evaluation tools should be updated as new forms of error, bias, and gamesmanship are discovered. Under this framework, AI science evaluation tools are not objective arbiters of scientific credibility. Rather, they are the object of critical discursive practices that ultimately ground the credibility of scientific communities.

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04.
medRxiv (Medicine) 2026-06-22

''Circumstantial Determinants'': An Efficient Approach to Reaching People in Need of HIV Prevention?

Authors:
Bagnay↗S. H↗Gregson↗Skovdal↗Maswera↗Moorhouse↗L. R↗Ncube↗Tsenesa↗Mandizvidza↗Pickles↗Garnett↗…

HIV prevention and testing programmes primarily reach people who self-refer or attend routine health services. Higher-risk individuals are missed if they are healthy, under-estimate their risk of infection or under-report sexual risk-behaviours. We assess a new approach to address limitations in existing programmes by targeting HIV services on ''Circumstantial Determinants'' (CDs) of HIV risk - the social circumstances, settings, and norms associated with behaviours that increase risk of HIV acquisition. Data on potential CDs and sexual behaviour were collected in a population survey in Zimbabwe in 2018/19 (N=9141). HIV-negative individuals reporting [≥] 1 sexual risk-behaviours were defined as the 'priority population' for HIV prevention. For each sex, six circumstantial determinants were associated with being in the priority population (aOR [≥] 1.30; p [≤] 0.01). Reach and efficiency of CDs (and combinations) were calculated; ROC curve algorithms evaluated their ability to identify priority population membership; and HIV prevention condom cascades were compared between CD-defined priority population subgroups. Example findings include that targeting men at bars and beerhalls could reach 48.5% of the priority population and 25.1% of lower-risk men. These percentages increase to 77.1% and 53.7% if men with poor mental health, no religious affiliation, negative social capital, or living on agricultural estates are also targeted. Targeting women with poor mental health could reach 32.0% of the priority population and 21.3% of lower-risk women. Targeting additional circumstantial determinants increases these percentages to 54.1% and 37.5%, respectively. Cascade barriers to condom use differed between CD-defined subgroups. The Circumstantial Determinants approach demonstrates proof-of-concept potential to strengthen HIV prevention services.

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

CacheWeaver: Cache-Aware Evidence Ordering for Efficient Grounded RAG Inference

Authors:
Kaizhen Tan↗Rong Gu↗Mingyuan Li↗

Retrieval-Augmented Generation (RAG) improves factual grounding, but it also lengthens prompts and raises prefill cost. Prefix caching in serving engines such as vLLM reduces this cost only when requests share the same token prefix. In grounded generation, however, adjacent queries may retrieve overlapping evidence in different orders, so set overlap does not become reusable prefix overlap. We present CacheWeaver, a lightweight prompt-layer method for cache-aware evidence ordering. The method keeps a prefix tree over recently served evidence sequences and uses a greedy walk to place the most reusable prefix first, while leaving the serving engine and retrieved evidence set unchanged. Across three vLLM configurations, the method lowers median time-to-first-token (TTFT) by about 20-33 percent relative to retrieval-order prefix caching, without hurting answer quality in our QA tests. The greedy policy reaches 97.5 percent of the median TTFT gain from oracle ordering, indicating that most reusable prefix locality can be recovered by a simple scheduling layer between retrieval and inference.

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

Tensor Methods: A Unified and Interpretable Approach for Material Design

Authors:
Shaan Pakala↗Aldair E. Gongora↗Brian Giera↗Evangelos E. Papalexakis↗

arXiv:2602.10392v2 Announce Type: replace Abstract: When designing new materials, it is often necessary to tailor the material design to have some desired properties. As the set of design parameters grow, the search space grows exponentially, making the actual synthesis and evaluation of all material combinations virtually impossible. Even using traditional computational methods such as Finite Element Analysis becomes too computationally heavy to search the design space. Recent methods use machine learning (ML) surrogate models to more efficiently determine optimal material designs; unfortunately, these methods often (i) are notoriously difficult to interpret and (ii) under perform when the training data comes from a non-uniform sampling of the design space. We suggest the use of tensor completion methods as an all-in-one approach for interpretability and predictions. We observe classical tensor methods are able to compete with traditional ML in predictions, with the added benefit of their interpretable tensor factors (which are given completely for free, as a result of the prediction). In our experiments, we are able to rediscover physical phenomena via the tensor factors, indicating that our predictions are aligned with the true underlying physics of the problem. This also means these tensor factors could be used by experimentalists to identify potentially novel patterns, given we are able to rediscover existing ones. We also study the effects of both types of surrogate models when we encounter training data from a non-uniform sampling of the design space. We observe more specialized tensor methods that can give better generalization in these non-uniforms sampling scenarios. We find the best generalization comes from a tensor model, which is able to improve upon the baseline ML methods by up to 5% on aggregate $R^2$, and halve the error in some out of distribution regions.

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

Dialogue SWE-Bench: A Benchmark for Dialogue-Driven Coding Agents

Authors:
Brendan King↗Jeffrey Flanigan↗

AI coding agents have rapidly transformed software engineering, powering widely used interactive coding assistants. Despite their interactive real-world use, existing benchmarks evaluate them as fully-autonomous systems. In this work, we introduce Dialogue SWE-Bench, an automatic benchmark dataset for evaluating the ability of coding agents to resolve real-world software engineering problems through dialogue with a user. We design a novel, persona-grounded user simulator to support our task evaluation, and augment our task evaluation with automatic evaluations of dialogue quality. We also propose a new schema-guided agent, aimed at improving the dialogue capabilities of off-the-shelf coding agents, which improves over strong baselines by 3-14%. Our results indicate that better coding models do not always correspond to better dialogue models, suggesting that dialogue capability is a distinct and currently understudied dimension of coding agent performance.

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08.
arXiv (CS.LG) 2026-06-17

Non-negative Matrix Factorisation with Topological Regularisation

Authors:
Matias de Jong van Lier↗Shizuo Kaji↗Keunsu Kim↗

arXiv:2606.17531v1 Announce Type: new Abstract: We investigate the learning of interpretable bases in non-negative matrix factorisation (NMF) by regularising the topology of the learned basis functions. Our approach is motivated by the observation that many data modalities can be viewed as non-negative functions on a structured domain, where the quality of a basis is intrinsically linked to its topology. However, naive methods for incorporating the topology of the support are often hindered by discreteness and threshold dependence, rendering them unsuitable for continuous optimisation. We address these challenges by employing persistent homology as a stable, threshold-free topological quantifier and by designing topological scores that integrate into the NMF objective as regularisers. The resulting framework encompasses spatially coherent image components, periodic time-series structures, and clique-like graph signals within a unified modelling language.

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

Geometry-Preserving in 3D Gaussian Splatting for LiDAR-Camera Extrinsic Calibration

Authors:
Kyoleen Kwak↗Daeho Kim↗Jeong Woon Lee↗Hyoseok Hwang↗

Accurate LiDAR-camera calibration is essential for robust multi-modal perception. Targetless approaches avoid manual setup but remain limited by the scarcity of discriminative cross-modal features. Recent methods address this by reconstructing the scene within a differentiable model, enabling extrinsic optimization through dense photometric supervision. Among these, 3D Gaussian Splatting (3DGS) has been widely adopted as a geometric proxy that bridges LiDAR and camera within a single differentiable framework. However, since 3DGS was originally designed for novel view synthesis, existing methods tend to prioritize rendering quality, causing the proxy geometry to drift from the true LiDAR structure. We propose a framework that preserves the metric geometry of the Gaussian proxy by aggregating multi-view LiDAR observations for dense depth supervision and blocking photometric gradients from updating the Gaussian spatial parameters. We validate our method on public driving datasets, where it consistently outperforms existing targetless methods in calibration accuracy.

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

CRC-Screen: Certified DNA-Synthesis Hazard Screening Under Taxonomic Shift

Authors:
Najmul Hasan↗

arXiv:2605.00074v2 Announce Type: replace-cross Abstract: DNA-synthesis providers screen incoming orders by searching the requested sequence against curated hazard lists. We show that this baseline collapses to a 100% false-flag rate when the hazardous sequence comes from a taxonomic family absent from the reference set: under Conformal Risk Control's certified miss-rate constraint, a low-discrimination signal forces the threshold below the entire test-benign mass. We compose three signals derived from a synthesis order's public annotation: $k$-mer Jaccard similarity to known toxins, the trimmed-mean score of a five-LLM judge panel, and cosine similarity to clustered embedding centroids. Fused under a monotone logistic aggregator and calibrated by Conformal Risk Control, the resulting screener certifies $\mathbb{E}[\mathrm{FNR}] \le \alpha + \mathrm{TV}$, where the additive term is the calibration-to-test distribution shift under family holdout (a certified ceiling of 24-49% across folds). Across ten leave-one-taxonomic-family-out folds at $\alpha=0.05$ on UniProt KW-0800 reviewed toxins, the calibrated screener achieves 0% empirical test miss rate on every fold and 0% test false-flag rate on nine of ten folds. The bound's finite-sample slack $1/(n_{\mathrm{cal}}+1)$ caps the certifiable miss rate at 1.77% on our 200-hazard subsample; reaching procurement-grade $\alpha=10^{-3}$ requires an $18\times$ larger calibration set, which the full reviewed UniProt KW-0800 corpus is large enough to deliver. The binding constraint on certifiable DNA-synthesis screening is calibration data, not algorithms. Code: https://github.com/najmulhasan-code/crc-screen

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11.
arXiv (quant-ph) 2026-06-15

Dissipation-induced superradiance in matter coupled to a self-interacting cavity

Authors:
Sebastian Schmid↗Matteo Soriente↗Oded Zilberberg↗Javier del Pino↗

arXiv:2606.14526v1 Announce Type: new Abstract: Light-matter interactions are often modeled via the Dicke model, namely, by two-level systems coupled to a cavity mode. Alas, the threshold for superradiance is often experimentally inaccessible or hindered by light's diamagnetic term. Here, within the Dicke setting, we consider self-interacting light in a cavity, modeled by a photonic Kerr nonlinearity. We show that negative Kerr nonlinearity gives rise to a low-threshold superradiant phase with spin inversion. While unstable in a closed system, cavity dissipation stabilizes this lit phase, opening avenues for lasing and bath-engineered phases.

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12.
arXiv (quant-ph) 2026-06-17

Coupled-Mode Equations with Arbitrary Mode Combinations for Kinetic-Inductance Superconducting Traveling-Wave Parametric Devices: Theory and Experimental Validation

Authors:
F. Patricio Mena↗Camilo Espinoza↗Ryan O. Berriel↗Ricardo Finger↗David J. Thoen↗

arXiv:2606.17264v1 Announce Type: cross Abstract: The coupled-mode equations (CMEs) have proven very successful in describing parametric processes in nonlinear optics. More recently, the same formulation has been used to model microwave superconducting parametric amplifiers and frequency multipliers. However, when applied to the microwave regime, not all assumptions remain valid and losses play a more dramatic role. Here, we revisit the CMEs applied to traveling-wave superconducting amplifiers to include losses and provide a formulation that enables their systematic derivation for any combination of traveling waves. As examples, we discuss the impact of unwanted harmonics and intermodulation products on parametric amplification, as well as harmonic generation. We verify that, if not properly accounted for, device performance can deviate considerably from the ideal case. Furthermore, using a superconducting CPW-based artificial transmission line and combining an independent experimental determination of its nonlinear parameter $I'_*$ with simulations of its linear properties, we obtain a parameter-free validation of this formulation. The nonlinear parameter was determined to be $I'_* \approx 27$ mA which, surprisingly, scales with the theoretical depairing current and not with the much smaller critical current of the device. For the validation, we measured multiple-harmonic generation and found excellent agreement between theory and experiment. The fact that $I'_* \gg I_C$ has direct implications for device design.

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13.
PLOS Computational Biology 2026-06-18

scMagnifier: Resolving fine-grained cell subtypes via GRN-informed perturbations and consensus clustering

Authors:
Zhenhui He↗

by Zhenhui He, Dong Kangning Resolving fine-grained cell subtypes in single-cell RNA sequencing (scRNA-seq) data remains challenging, as their subtle transcriptional differences are often obscured by technical noise and data sparsity. Here, we present scMagnifier, a consensus clustering framework that leverages gene regulatory network (GRN)-informed in silico perturbations to amplify subtle transcriptional differences and uncover latent cell subpopulations. scMagnifier perturbs candidate transcription factors (TFs), propagates perturbation effects through cluster-specific GRNs to simulate post-perturbation expression profiles, and integrates clustering results across multiple perturbations into stable subtype assignments. Additionally, scMagnifier introduces regulatory perturbation consensus UMAP (rpcUMAP), a perturbation-aware visualization that provides clearer separation between cell subtypes and guides the selection of the optimal number of clusters. In both single-batch and multi-batch benchmarks, scMagnifier consistently improves the resolution and accuracy of fine-grained cell type identification. Notably, when integrated with spatial clustering methods such as STAGATE, scMagnifier is compatible with spatial transcriptomics workflows and effectively reveals tumor cell subtypes and their spatial organization in ovarian cancer.

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14.
arXiv (CS.LG) 2026-06-11

Renewable Lasso without Batch-Number Constraints: A Gradient-Enhanced Approach

Authors:
Junzhuo Gao↗Ling Peng↗Xu Guo↗Heng Lian↗

arXiv:2606.11738v1 Announce Type: cross Abstract: We study online estimation for high-dimensional generalized linear models with streaming data. First, for the non-distributed setting, we propose a gradient-enhanced surrogate loss that approximates the cumulative loss using only historical summaries, which modifies and improves upon the existing renewable estimation approach for the same model in the high-dimensional setting, and removes the batch-number constraint in previous studies. We then extend the method to distributed streaming data under the master-client architecture, where batches are partitioned across sites and only summaries (gradient vectors) are exchanged. Instead of directing applying the popular method of Jordan et al. (2019) to the surrogate quadratic loss, our adjusted approach does not require the clients to compute the full surrogate loss. We derive non-asymptotic error bounds under the high-dimensional scaling, without the stringent constraint on the number of batches in the previous studies. Simulation results under linear and logistic models, together with a real-data application, show improved accuracy over existing renewable estimators.

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

When the Same Musical Knowledge Forgets Differently: A Clean Probe of Pathway-Dependent Forgetting

Authors:
Yu Liu↗Zhiwei Yang↗Wenxiao Zhang↗Cong Cao↗Fangfang Yuan↗Kun Peng↗Haimei Qin↗Lei Jiang↗Jin B. Hong↗Hao Peng↗Yanbing Liu↗

A model can learn that the piano piece Für Elise is calm and reflective by listening to the audio or by reading a text description, but does it matter which route that knowledge took when it is later at risk of being forgotten? Forgetting research in multimodal models measures what knowledge is lost under adaptation, yet has not asked whether acquisition route affects how easily that knowledge is forgotten. We call this untested premise the Pathway-Invariant Assumption. Music understanding enables a clean test because a music clip and a canonical text description can be aligned to the same perceptual content, allowing the same knowledge unit to enter a model through listening or reading while the target remains fixed. Across multiple architecturally distinct audio-language models, we observe a consistent asymmetry: text-pathway knowledge is forgotten more than matched audio-pathway knowledge under identical adaptation pressure. To attribute this effect to route rather than confounds, we introduce the Paired Pathway Controlled Protocol (PPCP), a three-phase design that establishes matched pathway baselines, activates both pathways under symmetric supervision on the same knowledge pool, and applies identical forgetting pressure to both pathways. The gap is stable across models and gain-controlled analyses, persists when contradictory overwrite is replaced by correct-label cross-domain learning, remains under single-modality pressure, and is not removed by lightweight replay. Two independent routing-depth controls confirm that the effect is not explained by architectural depth, pointing to input representation as the dominant factor. Under PPCP, our results demonstrate that forgetting is highly route-dependent, establishing acquisition route as a new analytical dimension for forgetting research and multimodal system design.

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17.
medRxiv (Medicine) 2026-06-18

MOSAIC: Methylation-Oriented Site Analysis and Information Classifier for Robust Epigenomic Classification of Acute Leukemia in Clinical Cohorts with Variable Tumor Purity

Authors:
Shah↗Green↗Wainmann↗Karrs↗

DNA methylation-based classification offers a rapid diagnostic complement to conventional molecular workflows in acute leukemia. Existing classifiers are trained on array-derived reference cohorts whose construction favors specimens with adequate tumor content, leaving clinically relevant low-purity specimens underrepresented and classifier robustness in this regime uncharacterized. On held-out low-purity specimens, existing classifiers were concordant with expert pathology in only 7 of 10 (MARLIN) and 5 of 10 (ALMA) cases, motivating a classifier built to maintain accuracy at low tumor purity. We developed MOSAIC (Methylation-Oriented Site Analysis and Information Classifier), a neural network classifier built to maintain accuracy across the full range of tumor purities encountered in clinical practice. MOSAIC is a neural network trained on publicly available array-based methylation data augmented with native methylation calls from Oxford Nanopore sequencing. MOSAIC was evaluated on low-purity specimens held out entirely from training. On these held-out low-blast leukemia specimens, all below 25% blasts and including a case at 1.4%, MOSAIC was concordant with expert pathology in every case, recovering the correct subtype where diluted disease signal would otherwise be mistaken for normal or unrelated tissue. Gradient-based saliency analysis showed that the network relies on a partially distinct set of discriminative CpG probes when classifying low-blast specimens. MOSAIC demonstrates that augmenting training with clinically representative clinical specimens yields methylation-based leukemia classification that maintains effectiveness under the variable tumor purity of real clinical cohorts.

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

DAL: A Practical Prior-Free Black-Box Framework for Piecewise Stationary Bandits

Authors:
Argyrios Gerogiannis↗Yu-Han Huang↗Subhonmesh Bose↗Venugopal V. Veeravalli↗

arXiv:2501.19401v5 Announce Type: replace Abstract: We introduce a practical, black-box framework termed Detection Augmented Learning (DAL) for the problem of piecewise stationary bandits without knowledge of the underlying non-stationarity. DAL accepts any stationary bandit algorithm with order-optimal regret as input and augments it with a change detector, enabling applicability to all common bandit variants. Extensive experimentation demonstrates that DAL consistently surpasses all state-of-the-art methods across diverse non-stationary scenarios, including synthetic benchmarks and real-world datasets, underscoring its versatility and scalability. We provide theoretical insights into DAL's strong empirical performance, complemented by thorough empirical validation.

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

Who Flips? Self- and Cross-Model Counterarguments Reveal Answer Instability in LLMs

Authors:
Nafiseh Nikeghbal↗Amir Hossein Kargaran↗Shaghayegh Kolli↗Jana Diesner↗

Standard accuracy benchmarks are designed to test how closely large language models (LLMs) approach correct answers, but are not suitable for testing whether LLMs stick with a correct answer when that answer is challenged by a plausible counter-argument. We introduce a controlled protocol for evaluating answer stability: after a model answers a multiple-choice question correctly, we challenge the model's answer with a coherent argument for an incorrect option and measure whether the model flips. The setup a) isolates argumentative content from overt social pressure and b) varies argument length, self-attribution, and cross-model source. Across seven frontier models and 57 MMLU subjects, flip rates range from 17.5% to 97.3%, revealing large differences in stability that are not captured by accuracy metrics alone. We find that self-attribution consistently increases flip rates (mean +7.1pp, up to +18.7pp). Also, pooling wrong-answer arguments across models and selecting the most effective one per question yields stronger adversarial challenges than relying on any single source model. We further construct MaxFlip, a curated challenge set that amplifies flips by up to +23.6pp over standard self-generated challenges. We release the protocol, challenge records, and MaxFlip to support stability evaluation alongside standard accuracy benchmarks. Materials are available at https://github.com/nafisenik/WhoFlips and https://hf.co/datasets/nafisehNik/WhoFlips.

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20.
arXiv (CS.CL) 2026-06-15

MoDiCoL: A Modular Diagnostic Continual Learning Dataset for Robust Speech Recognition

Authors:
Theresa Pekarek Rosin↗Matthias Kerzel↗Stefan Wermter↗

Modern Automatic Speech Recognition (ASR) systems have made remarkable progress on standard benchmarks, yet performance gaps have emerged under real-world distribution shifts, caused by recording conditions, accents, speech impairments, and noise. Existing datasets and benchmarks typically isolate these factors, which overlooks their co-occurrence in real-world applications. In this paper, we argue that model robustness can be treated as a dynamic capability that continually develops, and we introduce MoDiCoL, a Modular Diagnostic Continual Learning dataset designed for controlled analysis of linguistic content, speaker characteristics, and acoustic environments. Furthermore, we propose a real-world-inspired continual learning curriculum to simulate incremental updates and study how robustness is acquired, transferred, and forgotten. We evaluate three continual learning strategies and provide detailed insights into robustness under evolving conditions.

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21.
medRxiv (Medicine) 2026-06-12

The Clinical Characteristics and mortality outcomes of Atrial fibrillation complicating Heart failure with reduced ejection fraction: A prospective study from South Africa

Authors:
Mboweni↗N. N↗Maseko↗Tsabedze↗N. I↗Toman↗Nel↗Kagodora↗B. S↗

Background: A growing burden of cardiovascular risk factors has raised cardiovascular disease-related mortality in Sub-Saharan Africa (SSA), driving higher prevalence of heart failure with reduced ejection fraction (HFrEF) and its complication with atrial fibrillation (AF). No prospective study has examined AF's clinical impact on HFrEF in SSA. Aim: To determine AF prevalence in HFrEF, describe HFrEF-AF clinical characteristics, and determine AF's impact on mortality. Methods: In this prospective observational study at a tertiary hospital in Johannesburg, 136 HFrEF patients were enrolled and categorised as HFrEF- SR (sinus rhythm) or HFrEF-AF. Baseline clinical characteristics and biochemistry were recorded. Comprehensive echocardiography including left atrial strain by 2D speckle-tracking was performed. Median follow-up was 30.6 months. Results: AF was present in 28 patients (21%). The mean age was 58.7 {+/-} 14.9 years (52.9% male) and differed between groups (p < 0.001). Hypertensive heart disease was the leading cause of HFrEF (36%). Compared with SR, HFrEF-AF patients had poorer health status (KCCQ 27 [16-43] vs 45 [32-60], p < 0.001) and lower left atrial strain (26.2 {+/-} 11.3%, p < 0.001). Guideline-directed medical therapy was suboptimal in the AF group: anticoagulation use was higher than SR (60% vs 9.5%, p < 0.001) but overall inadequate; HFrEF-AF patients received lower median doses of carvedilol (15.6 mg vs 25 mg, p = 0.002) and enalapril (10 mg vs 20 mg, p = 0.004), and fewer received spironolactone (50% vs 75.3%, p = 0.013). Survival was significantly lower in HFrEF-AF (0.41 [0.22-0.61]) versus SR (0.73 [0.61-0.82], p < 0.001). Independent predictors of mortality included prior stroke, lower TAPSE and KCCQ, and higher E/e' and heart rate. Conclusion: AF is common among HFrEF patients in this SSA cohort (though lower than in high-income countries) and associates with worse clinical status, suboptimal therapy, and higher mortality.

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

Beyond Classification: A Cough Regression Benchmark for Respiratory Acoustic Foundation Models

Authors:
Mayur Sanap↗Prasanna Desikan↗Edgar Lobaton↗

arXiv:2606.15436v1 Announce Type: cross Abstract: Respiratory acoustic foundation models (FMs) excel at cough classification, yet their ability to predict continuous health quantities from cough audio remains largely unexplored, despite the clinical value of passive age, BMI, and disease probability estimation in settings where physical measurements are unavailable. We introduce the multi-model, multi-target cough regression benchmark evaluating five FMs (OPERA-CT, OPERA-CE, OPERA-GT, HeAR, M2D+Resp) across six targets on three datasets under subject-disjoint protocols, comparing linear, MLP-small, and full MLP regression heads. MLP-small beats the mean-predictor baseline on all tasks and linear probing in 23 of 30 model x task cases, with full MLP overfitting on small clinical data but recovering on larger sets, revealing a dataset size x head-capacity trade-off. HeAR leads within-dataset age regression on Coswara (9.12 yr MAE); its CIDRZ result is excluded from headline claims owing to possible HeAR-CIDRZ pretraining overlap. OPERA-GT is favored over OPERA-CT on age in all three datasets, with the CIDRZ margin within seed variance, extending a generative-pretraining advantage from breath to cough. HeAR and M2D+Resp reach near-full performance at N = 50 samples while OPERA models require N = 400. Cross-dataset transfer is strongly asymmetric as large diverse data generalises to small clinical populations (CoughVID to CIDRZ: -0.17 yr) but not vice versa (CIDRZ to Coswara: +2.43 yr, +26.6%).

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23.
PLOS Medicine 2026-06-02

Proteomic signatures of early retinal neurodegeneration in type 2 diabetes mellitus

Authors:
Huangdong Li↗

by Huangdong Li, Ziyu Zhu, Shaopeng Yang, Weijing Cheng, Shaoying Tan, Zhuoyao Xin, Lei Zhang, Zhuoting Zhu, Shida Chen, Wenyong Huang, Wei Wang Background Retinal neurodegeneration is an early and independent feature of diabetic retinal disease and has been proposed as a window into the systemic neural consequences of diabetes, yet accessible molecular biomarkers and individualized prediction tools remain scarce. We aimed to identify circulating plasma protein signatures of diabetic retinal neurodegeneration (DRN) and to translate them into a clinically usable risk prediction system. Methods and findings In this multi-cohort prospective observational study, we integrated high-throughput plasma proteomics with longitudinal optical coherence tomography (OCT) in two independent populations. The discovery cohort comprised 1,492 participants had baseline plasma proteomics and OCT, and 1,218 were followed with repeated OCT over 6 years in Guangzhou Diabetic Eye Study (GDES). DRN was quantified by the annualized OCT-derived retinal nerve fiber layer thinning rate. In multivariable analyses adjusted for age, sex, smoking, systolic blood pressure, HbA1c, and diabetes duration, we identified 71 plasma proteins associated with development and progression of DRN. These proteins mapped onto pathways governing inflammatory immune recruitment, extracellular matrix remodeling, and microvascular homeostasis, providing a plausible biological basis for DRN. We developed a proteomics-based DRN model (Pro-DRN) using eight machine learning (ML) algorithms, including XGBoost and LightGBM. In the independent test set, Pro-DRN achieved a C-index of 0.860, rising to 0.908 when integrated with clinical variables. Compared with six conventional models, Pro-DRN improved discrimination (ΔC-index 0.137 to 0.159; all P 

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24.
arXiv (CS.AI) 2026-06-16

Architectural Wisdom: A Framework for Governing Optimization in AI Systems

Authors:
Edward Y. Chang↗

arXiv:2606.16319v1 Announce Type: new Abstract: Modern AI systems exhibit structural failures that capability scaling alone does not reliably fix: they optimize under-specified objectives with no architectural mechanism to question whether the objective should be optimized at all. Engagement maximization can amplify harmful pathways; tool-using agents can commit irreversible actions; preference-trained language models can become sycophantic. We argue that this failure is a wisdom problem, not an intelligence problem. We use "wisdom" in a deliberately architectural sense, not as a claim about virtue, consciousness, or moral omniscience. Intelligence accepts a goal and optimizes within it; wisdom interrogates whether the goal should be optimized at all. The two are separable architectural properties. We propose architectural wisdom as a corrigible objective-governance layer above the optimization substrate. The layer makes three structural commitments explicit and nondegenerate before any action: temporal horizon, relational boundary, and irreversibility. It is realized by four components (Structural Utility Transform, Moral Admissibility Interface, Arbitration and Escalation Controller, Value Revision Channel) that compute a six-coordinate wisdom tuple over horizon, relational coverage, irreversibility, admissibility, value revision, and auditability. We motivate the architecture by eight cases drawn from contemporary AI failures, secular wisdom traditions, and hard ethical situations, and defend the distinction against the intelligence-completeness thesis using goal-questioning over goal-taking, Bostrom's orthogonality, structural separation in our exemplar cases, and persistent failure modes despite capability scaling. The framework is the conceptual contract for a larger architecture whose formal specifications and empirical validation are developed in subsequent work.

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25.
PLOS Computational Biology 2026-06-01

Challenges and progress in RNA velocity: Comparative analysis across multiple biological contexts

Authors:
Sarah Ancheta↗

by Sarah Ancheta, Leah Dorman, Guillaume Le Treut, Abel Gurung, Greg Huber, Loïc A. Royer, Alejandro Granados, Merlin Lange Single-cell RNA sequencing is revolutionizing our understanding of cell state dynamics, allowing researchers to capture and quantify the transcriptomic profile of a single cell at a specific timepoint. Among the computational techniques used to predict cellular trajectories, RNA velocity has emerged as a predominant tool for modeling transcriptional dynamics. RNA velocity leverages the mRNA maturation process to generate velocity vectors that predict the likely future state of a cell, offering insights into cellular differentiation, aging, and disease progression. Although this technique has shown promise across biological fields, the performance accuracy varies depending on the RNA velocity method and dataset. We established a comparative pipeline and analyzed the performance of five RNA velocity methods on three datasets based on local consistency, method agreement, identification of driver genes, and robustness to sequencing depth. This benchmark provides a resource for scientists to understand the strengths and limitations of different RNA velocity methods.

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