Predictive modeling in biology and medicine: Digital twins and multi-scale modeling
by Mark Alber, Amber Smith, Reinhard Laubenbacher, Roeland M. H. Merks
Academic Intelligence · Curated Daily
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by Mark Alber, Amber Smith, Reinhard Laubenbacher, Roeland M. H. Merks
Person re-identification via 3D skeletons is an important emerging research area that attracts increasing attention within the pattern recognition community. With distinctive advantages across various application scenarios, numerous 3D skeleton based person re-identification (SRID) methods with diverse skeleton modeling and learning paradigms have been proposed in recent years. In this paper, we provide a comprehensive review and analysis of recent SRID advances. First of all, we define the SRID task and provide an overview of its origin and major advancements. Secondly, we formulate a systematic taxonomy that organizes existing methods into three categories centered on hand-crafted, sequence-based, and graph-based modeling. Then, we elaborate on the representative models along these three types with an illustration of foundational mechanisms. Meanwhile, we provide an overview of mainstream supervised, self-supervised, and unsupervised SRID learning paradigms and corresponding common methods. A thorough evaluation of state-of-the-art SRID methods is further conducted over various types of benchmarks and protocols to compare their effectiveness, efficiency, and key properties. Finally, we present the key challenges and prospects to advance future research, and highlight interdisciplinary applications of SRID with a case study.
The increasing availability of large-scale textual corpora has opened new possibilities for data-driven, quantitative approaches to historical analysis using Natural Language Processing (NLP). However, diachronic corpora with historical relevance from the pre-digital era remain scarce and often incomplete. We present a quantitative approach to historical analysis based on the reconstruction and exploration of a diachronic corpus of around 600,000 articles from the Italian newspaper "La Repubblica", covering all the articles published from the 1st of January 1985 to the 31st of December 2000 - a period of major political, social, and geopolitical change in Italy and globally. Using NLP techniques, we analyze the text at both lexical and semantic levels; we then apply tools from complex systems and statistical physics to trace shifts in media discourse over time. This allows us to detect key transition periods, such as the transition from the First Republic to the Second Republic in Italy, or major international conflicts like the Gulf War or the Kosovo War, without relying on prior labeling. The results show how combining computational linguistics with ideas from complex systems can offer new quantitative insight into historical changes, opening up new paths for studying the dynamics of media and society through large-scale textual data.
Climate adaptation products have traditionally been developed using a supply-driven model reliant on available climate information, leading to usability gaps1–4. To better meet user needs, the climate services field has recognized a need to shift towards a demand-driven model emphasizing co-production, that is, user-driven, scientifically informed products created through shared knowledge practices1–5. However, co-production can be challenging, especially for researchers unfamiliar with the approach or for digital and software-based products with complex user needs2,5–8. User-centred design, from the human–computer interaction field, offers a process that could complement co-production approaches to product development, yet its potential remains underexplored2. Here we show how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products. Through a systematic review of the co-production and user-centred design literature, we identify key processes, mechanisms and best practices for both approaches. Our findings offer practical guidance for researchers and propose an integrated approach for developing climate adaptation products that are useful, usable and used. A systematic review and analysis shows how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products.
Modern pretrained self-supervised automatic speech recognition models are trained on large-scale audio data to encode speech into contextualized representations. However, their training data are heavily skewed toward high-resource languages with little data from low-resource languages, raising concerns about the potential underrepresentation of typologically uncommon speech sounds such as click consonants primarily found in Khoisan languages. This leads to our central research question: Can these models recognize click consonants as accurately as other speech sounds? To address this question, we fine-tune and compare pretrained self-supervised speech models (Wav2Vec2 and HuBERT) on data from two click-rich Khoisan languages (G|ui and West !Xoon). Our results reveal that the fine-tuned models consistently recognize clicks more accurately than non-clicks, suggesting that self-supervision enables generalization across human speech sounds including rare phonemes.
Background: Hyperbolic tapering is an increasingly recognized approach for discontinuing serotonin reuptake inhibitor (SRI) antidepressants that involves non-linear dose reductions with equal stepwise reductions in serotonin transporter (SERT) occupancy to mitigate withdrawal symptoms. Its theoretical basis is the hyperbolic relationship between SRI dose and SERT occupancy reported in radioligand imaging studies. Hyperbolic tapering implicitly assumes that changes in SERT occupancy approximate changes in biologic effect and withdrawal risk. Because SERT occupancy plateaus across the therapeutic dose range of SRIs, this framework predicts relatively small biologic effects and withdrawal risk within this range. However, SERT occupancy influences serotonergic activity only indirectly via its effects on extracellular serotonin concentrations, and the relationship between these two variables is poorly characterized. Methods: We developed a two-pathway clearance model derived from mass-action kinetics to evaluate the steady-state relationship between SERT occupancy and extracellular serotonin concentrations under chronic SRI treatment. Results: Our analysis indicates that serotonin concentrations increase hyperbolically as transporter occupancy increases, suggesting that biologically meaningful differences in serotonergic signaling persist across the therapeutic dose range of SRIs despite plateauing occupancy. Conclusions: Our model predicts a hyperbolic relationship between SERT occupancy and extracellular serotonin concentrations, suggesting that changes in occupancy may not map proportionally onto serotonergic effect. These findings provide a potential mechanistic explanation for dose-dependent clinical effects of SRIs despite plateauing transporter occupancy and generate testable hypotheses regarding antidepressant tapering strategies. Empirical validation is warranted.
arXiv:2606.19741v1 Announce Type: new Abstract: Neural Combinatorial Optimization (NCO) achieves strong performance, yet its black-box nature remains a key roadblock to deployment and scientific diagnosis. Standard interpretability tools, such as Concept Bottleneck Models (CBMs), are ill-equipped for NCO, whose decisions are dynamic, state-dependent, and lack proper concept vocabulary definition. To close this gap, we introduce Evolving Programmatic Bottlenecks (EPB), to our knowledge, the first framework for interpreting NCO policies by distilling black-box NCO models into human-readable program portfolios. EPB employs an LLM to autonomously evolve a bank of programs, where each program's per-step action distribution serves as the bottleneck. EPB works through an iterative framework: Block I fixes program bank capacity and introduces a hybrid textual-numerical gradient descent scheme that couples numerical gradients for student router updates and textual gradients for LLM-based program revision; Block II dynamically adapts bank capacity via fault-targeted expansion and redundancy pruning. Extensive experiments demonstrate EPB's effectiveness and broad applicability, where the distilled program portfolios largely match original performance. EPB also reveals that NCO behavior shifts across optimization stages and can be approximated as a composition of classic heuristic variants. Our work advances interpretable NCO and establishes EPB as a promising tool for interpreting sequential decision-making models.
Introduction: The overlap between chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health challenge. We investigated the impact of MASLD and metabolic comorbidity in a diverse London viral hepatitis clinic. Methods: This retrospective cross-sectional study (May 2018-Feb 2024) included adults with CHB having controlled attenuation parameter (CAP) measurements. MASLD was defined as CAP >264 dB/m plus [≥]1 cardiometabolic factor (CMF). We used univariable and multivariable models to examine MASLD's relationship with liver stiffness and hepatitis B viral load (HBV VL). Results: Among 323 individuals (67% male, median age 36), most were from Black (35%) or non-white British/Irish (29%) backgrounds. Overall, 64% had [≥]1 CMF, and 20% had MASLD. The CHB/MASLD group was significantly older (median 43 vs 35 years, p
Purpose To determine the frequency of echocardiographic abnormalities in women with preeclampsia with severe features. To describe the spectrum and types of echocardiographic abnormalities associated with preeclampsia with severe features. Method This is a Prospective observational study conducted in Vani Vilas hospital attached to Bangalore Medical College and Research Institute, Bangalore from January 2023 to December 2025. 560 pregnant women diagnosed with severe preeclampsia(SPE) were included in the study. Chronic hypertension without superimposed preeclampsia, underlying cardiac diseases and previous history of peripartum cardiomyopathy were excluded from the study. Transthoracic echocardiography-TTE (2D ECHO) was done to evaluate cardiac structure and function. Echocardiographic abnormalities identified during the study were documented and analysed using descriptive statistical methods. Results Abnormalities in ECHO was noted in 23.03%. A unique finding was the documentation of elevated pulmonary artery systolic pressures (PASP) suggestive of Pulmonary Hypertension (PH) (PASP >35 mm HG) among 20.25% of the participants. It was also the commonest abnormality on ECHO. Mild PH was the commonest (15.71%), moderate PH was seen in 3.92% and severe PH in 0.71% of cases. Next most frequent abnormality was moderate to severe valvular regurgitation (10%), followed by left ventricular hypertrophy (5.53%). Diastolic dysfunction (DD) was seen in 3.92%, systolic dysfunction(SD) in 3.57%, chamber dilatation in 3.57% and LV global hypokinesia in 3.03% cases of SPE Conclusion Preeclampsia with severe features (SPE) is associated with 23.03% abnormalities on echocardiography. SPE is associated with systolic dysfunction, diastolic dysfunction, chamber dilatation, valvular regurgitation, left ventricular hypertrophy and pulmonary hypertension.
arXiv:2605.18909v2 Announce Type: replace Abstract: Any system that models the world under finite representational capacity must compress; any compression entails a prior; and the prior is the system's bias. What has not been established is whether uncertainty participates in the dynamics governing future behavior, or merely describes the output distribution without consequence. We introduce a structural distinction between descriptive uncertainty, which does not recursively modulate the system's policy, and regulatory uncertainty, which directly enters the optimization landscape and drives persistent adaptive restructuring. We prove formally that current transformer architectures are confined to descriptive uncertainty at inference. We ground this in thermodynamics via Landauer's principle: for uncertainty to be regulatory, epistemic error must cost real energy; in a decoupled system, hallucinations and correct derivations dissipate identical energy. We test this empirically across three locally-deployed language models (3B, 8B, 70B parameters). Token-level Shannon entropy is statistically invariant across tasks spanning pattern retrieval, causal operator application, and out-of-distribution causal generalization in all three models (all pairwise p >= 0.568; within-model ranges 0.011-0.028 nats), while task accuracy varies substantially across the same conditions (0%-100%). Entropy and accuracy are orthogonal. The decoupling is scale-invariant: larger models achieve higher accuracy but identical entropy flatness. This structural incapacity is not resolvable by additional parameters or training data. Genuine epistemic grounding requires physical coupling between thermodynamic substrate state and information processing cost.
arXiv:2606.11469v1 Announce Type: cross Abstract: We study the task of density estimation, where we hope to accurately estimate a probability density from $n$ samples. A textbook method for density estimation in total variation distance is the minimum-distance estimator approach, where we conclude both the algorithm and the analysis merely from bounding the VC dimension of a particular concept class (the so-called Yatracos class). While this technique has originally yielded sharp guarantees primarily for total variation distance, in this work we extend the minimum-distance estimator approach for learning within Hellinger distance. Our main observation is that we may produce an analogous recipe for Hellinger (where we only require bounding the VC dimension of a related concept class) by drawing connections to recent results yielding reverse data processing inequalities. This recipe is flexible enough to accommodate fast algorithms originally designed for total variation distance; by modifying the approach of Acharya et al. (2017) we conclude the first near-linear time algorithm for learning classes including univariate mixtures of log-concave densities and mixtures of Gaussians (with arbitrary variances), with near-optimal sample complexity.
Large Language Models (LLMs) struggle to incorporate new knowledge without forgetting or costly retraining. We propose DYNA, a lightweight framework that augments a frozen LLM with a temporal knowledge graph where events are nodes and temporal relations are directed, timestamped edges. The graph serves as an external, updatable memory. At query time, DYNA retrieves relevant nodes via random walks and centrality measures, then augments the LLM's response. Evaluated on three temporal recall tasks, DYNA reduces catastrophic forgetting by ~7% compared to fine-tuning and improves temporal ordering by ~5% over standard RAG. Higher graph clustering coefficients correlate with better retrieval, showing that graph structure matters. Contributions: (1) episodic memory as temporal KG, (2) retraining-free LLM augmentation, (3) graph properties as predictors of retrieval performance.
arXiv:2606.15441v1 Announce Type: cross Abstract: Indirect prompt injection attacks hijack LLM-based agents by embedding malicious instructions in third-party data that the agent retrieves during task execution. Existing defenses report near-zero attack success rate on static benchmarks, yet recent adaptive evaluations show that these results collapse once the attacker is allowed to optimize against the deployed defense. In this work, we trace this collapse to two failure modes. First, existing defense methods are confined to recognizing specific attack patterns, rather than assessing whether the intent of every embedded instruction is relevant to the user task. Second, training-based defenses, which otherwise offer the strongest safety-utility trade-off, assemble their adversarial examples from a handful of hand-crafted templates, and the resulting defender fails to generalize outside that narrow strategy distribution. To address these gaps, we propose RETA, a training-based method that grounds defense decisions on the user tasks rather than attacker-controlled data. At each tool-output step, the defender undertakes chain-of-thought reasoning verifying that its actions are consistent with the user task. Leveraging red-teaming, a simulated attacker synthesizes adversarial training data and receives a dictionary-learning diversity reward, achieving broad coverage of injection-reformulation strategies. Together, these allow the defender to be optimized via multi-objective reinforcement learning and achieve better safety-utility trade-off. Across six black-box adaptive attacks, RETA keeps every per-attack ASR below 10%, with average ASR of 2.92% and 3.75% on the two target models, while preserving most utility under attack and on clean inputs.
Objective: A questionnaire on the knowledge, attitude and practice of ICU nurses regarding the management of blood oxygen saturation in patients with mechanical ventilation was compiled, and its reliability and validity were tested. Method: Drawing upon the knowledge-attitude-practice theory, the initial questionnaire draft was developed through literature review and consultation with Delphi experts. Employing convenience sampling, 32 nurses from the General ICU of Wuxi Second People's Hospital were surveyed between 1 August 2025 and 27 September 2025, enabling item screening and assessment of reliability and validity.The full version of the developed questionnaire is provided as Supporting Information (S1 File). All items are published under a CC BY 4.0 license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Result: A questionnaire on the knowledge, attitude and practice of ICU nurses regarding the management of blood oxygen saturation in mechanically ventilated patients was finalised, comprising 26 items: 11 in the knowledge dimension, 6 in the attitude dimension and 9 in the behaviour dimension. The overall Cronbach's coefficient for the questionnaire was 0.88, with dimension-specific coefficients of 0.787, 0.722, and 0.781 respectively. The Spearman-Brown coefficient for the entire questionnaire was 0.967, while dimension-specific coefficients were 0.796, 0.666, and 0.728 respectively. The content validity index at the questionnaire level (S-CVI) was 0.886, and the item-level content validity index (I-CVI) ranged from 0.913 to 0.967. 0.728. The questionnaire's level content validity index (S-CVI) was 0.886, and the item level content validity index (I-CVI) ranged from 0.913 to 1.00. Conclusion: The questionnaire on knowledge, attitude and practice of blood oxygen saturation management in mechanically ventilated patients demonstrates good reliability and validity. It may serve as an assessment tool for intensive care unit nurses regarding their knowledge, attitude, and practices concerning blood oxygen saturation management in mechanically ventilated patients, thereby establishing a foundation for developing targeted intervention strategies in future practice.
Short pretraining runs can reduce experimental cost, but they can also over-promote configurations that only look strong at tiny budgets. We study an auditable staged-promotion protocol for a fixed micro-pretraining runner on two heterogeneous host blocks: Windows A100 and Linux L40S. Starting from twelve prior-screened configurations, we use staged budgets of 2 minutes, 5 minutes, 10 minutes, 60 minutes, and 12 hours, with frozen promotion rules before expensive continuations. The early screens are intentionally treated as unstable: the 5- and 10-minute rankings are host-sensitive, and the eventual 12-hour top-ranked condition is not the mean-best condition at the replicated 10-minute gate. Because seed ranges differ across stages, these changes are operational promotion evidence, not within-seed curves. A replicated 60-minute gate keeps the Staged Factorial Screening bridge reference in the promoted set, where it ranks first in all four 60-minute host-seed cells. In the final 12-hour confirmation package, the bridge condition ranks first in all four host-seed cells across two seeds; the greedy comparator does not meet the frozen 0.010 val_bpb near-equivalence rule; and the cheaper d8/ar48 (depth-8, aspect-48) sentinel does not meet the frozen 0.020 mean-gap rule. The executed 12-hour branch spends 144 GPU-hours, and the full staged protocol records 169.2 training GPU-hours including screening stages. Continuing all four 60-minute candidates would spend 192 GPU-hours, while continuing all nine replicated 10-minute candidates would spend 432 GPU-hours. The latter numbers are accounting counterfactuals for unrun continuations, not evidence that skipped candidates could not have overtaken the reference. The result is a bounded cost-allocation finding, not a claim of global optimality, capacity-normalized superiority, or superiority over adaptive hyperparameter optimization methods.
arXiv:2606.19457v1 Announce Type: new Abstract: Quantum computers promise to solve the electronic structure problem for a large class of molecules. However, the performance of relevant quantum algorithms hinges on preparing initial states with substantial overlap with the target eigenvector. For classically challenging molecules with strong electron correlation, starting from multi-reference states, such as complete active space (CAS) wavefunctions is necessary. Unfortunately, the most advanced state preparation protocols applied to such states result in a gate complexity that scales exponentially with the active space size $d$. In fact, even encoding a CAS state classically is traditionally believed to be intractable for chemically relevant systems. Here, we draw insights from the recently introduced Quantum Paldus Transform (QPT) to show that there exists an efficient classical representation of CAS states and to design a new state preparation routine outperforming previous ones. The QPT represents a transformation from the Fock basis to a friendlier symmetry-adapted basis. Our main contribution consists in showing that CAS states expanded in this basis can efficiently be represented as a matrix product state (MPS) with a bond dimension scaling as $O(d^2)$. One can then efficiently load the MPS on a quantum computer and use the inverse QPT to transform the state to the Fock basis. Moreover, our method can easily be extended to the efficient preparation of CAS states in first quantisation with similar complexity. Crucially, we demonstrate that the complexity of both state preparation protocols only grows polynomially as $O(d^3)$ , which constitutes to the best of our knowledge an exponential improvement over the state of the art.
Bioethical debates increasingly unfold on social media, yet stance detection research lacks large-scale, domain-specific resources for modeling such context-dependent discourse. We present BioStance, a context-aware dataset of 39,600 annotated Post-Comment pairs from Reddit bioethical discussions. BioStance covers six controversial targets across three dimensions of bioethical controversy: fundamental value conflicts, individual liberty versus collective responsibility, and technological uncertainty. Each instance preserves hierarchical conversational context and is labeled by three independent annotators using a three-class stance scheme: Favor, Against, and None. The annotations achieve a mean Krippendorff's $\alpha$ of 0.82, indicating substantial reliability. By combining thematic diversity, conversational structure, and high-quality human annotation, BioStance supports research on context-aware stance detection, argument mining, and computational analysis of bioethical discourse.
arXiv:2606.13133v1 Announce Type: cross Abstract: Recently, Antoniadis et al. (ICLR 2025) proposed a framework for incorporating predictions to approximate NP-hard selection problems. Despite its simplicity, this approach tightly matches theoretical lower bounds, making its generalization highly compelling. We address an open question raised in the work of Antoniadis et al., concerning the extension of this approach to other important problems outside the class of selection problems, such as scheduling. We develop a learning-augmented algorithm for the makespan minimization problem on unrelated machines, denoted by $R\|C_{\max}$. By using predictions of heavy job assignments, we achieve a polynomial-time $(1+\varepsilon)$-approximation for accurate predictions that smoothly degrades to a worst-case 2-approximation as the error increases. We conclude our work with an empirical analysis of our method.
Woody breast (WB) is a myopathy in modern broiler chickens that causes the breast muscle to become unusually stiff and fibrous, leading to decreased meat quality and significant economic losses. State-of-the-art automated WB detection relies on a side-view imaging system to analyze the bending behavior of a single fillet as it falls off a conveyor belt. While highly accurate, this approach is constrained by its single-fillet field of view, creating throughput bottlenecks on commercial processing lines. In this paper, we address this limitation via a novel multi-fillet detection architecture utilizing a top-down camera configuration. To validate our approach, we first develop a high-fidelity digital twin of an industrial conveyor system. Next, we synthesize a diverse dataset of 3D fillet meshes and model their viscoelastic bending dynamics using a physics-based simulation engine. Lastly, a continuous 2D shape deformation score is extracted from the top-down perspective as the simulated fillets traverse the roller precipice. Experimental results demonstrate that the top-down shape score effectively captures the contour changes of the fillets as it bends, providing a robust and scalable alternative to a side-view imaging system for simultaneous multi-fillet WB evaluation.
How much meaning does a text carry? Shannon's theory measures uncertainty over symbols and is intentionally indifferent to meaning, while pairwise metrics such as BERTScore compare two texts rather than characterizing one. We develop a geometric framework that measures semantic content from the structure of a text's sentence embeddings. The framework has three parts. First, within a fixed embedding and baseline, six natural axioms uniquely determine a scalar measure up to scale, a frame-conditional uniqueness theorem. The resulting scalar is empirically too coarse, motivating a richer representation. Second, we propose a three-coordinate semantic profile capturing novelty (displacement from generic discourse), breadth (diversity of distinct ideas), and integration (connectedness among them), together with a discrete minimal unit (the semantic quantum) whose resolution is fixed by a clustering threshold $\tau$. Third, we prove a no-go theorem: no scalar summary of the profile can simultaneously satisfy analytic stability under paraphrase and concatenation, ordinal robustness across text scales, and cross-representation comparability. We exhibit two practical scalars, $S_{\mathrm{minmax}}$ and $S_{\mathrm{rank}}$, each occupying a distinct corner of this trade-off triangle. Validation across 23 synthetic categories, 5 Project Gutenberg novels, and 3 embedding models confirms the trade-off. The recommended rank-normalized configuration passes 25 of 28 ordinal checks as point estimates (21 of 28 after Benjamini-Hochberg correction), outperforming seven baselines including unigram entropy and a BERTScore-based novelty signal. A separate variational result connects the breadth coordinate to the log-determinant of a determinantal point process (Spearman $\rho = 0.985$ over 507 Gutenberg chapters), giving an optimization-theoretic foundation for breadth.
Data-independent acquisition (DIA) mass spectrometry has become increasingly prevalent in proteomics as advances in instrumentation, chromatography, and computational analysis have enabled robust proteome identification across complex biological samples. However, analytical depth achieved with fast chromatographic gradients remains lower than that obtained using long-gradients, reflecting a throughput-depth trade-off. Here, we present PeptiDIA, a machine learning framework that enhances peptide identification in fast-gradient DIA data by leveraging paired fast and long-gradient acquisitions from identical samples. PeptiDIA processes DIA-NN outputs generated at relaxed false discovery rate thresholds to obtain expanded candidate peptide pools and trains gradient-boosted decision tree models using long-gradient identifications as reference labels. The model integrates DIA-NN features with engineered peptide descriptors and applies isotonic regression to calibrate probabilities, enabling controlled peptide recovery relative to the long-gradient reference. Applied to human and murine datasets spanning six tissues acquired on an Orbitrap Exploris 480, PeptiDIA increased peptide identifications by 25-34% at 1% target reference-discordance rate (RDR) and increased the number of protein groups containing at least one rescued peptide by 15-17%. Overall, PeptiDIA improves the identification depth of fast-gradient DIA-NN workflows without altering acquisition strategies. The framework is available as a web application and command-line tool at https://github.com/Jordano700/PeptiDIA.
Glioma grading and survival prediction require the integration of heterogeneous information collected at different spatial and biological scales. Histopathology describes tissue morphology, mRNA expression captures molecular activity, and magnetic resonance imaging provides a non-invasive view of tumor extent and radiological heterogeneity. Existing glioma prognosis models often combine only two of these sources, while their alignment objectives remain mostly pairwise. This paper introduces GLORIA, a novel trimodal framework for GLioma Omics - Radiology - hIstopathology Alignment. GLORIA processes whole-slide image regions, gene-expression profiles, and 3D MRI volumes through modality-specific encoders, projects them into a shared latent space, and aligns them with a Gramian contrastive loss that measures the volume spanned by the three modality embeddings. The aligned representations are fused through a cross-modal gating module and optimized jointly for three-class glioma grading and overall survival prediction. We evaluate GLORIA on a matched TCGA-GBM/LGG and BraTS21 cohort, comprising 132 patients with all three modalities. On the shared trimodal test set, GLORIA improves over the bimodal WSI-mRNA baseline in all the metrics considered.
arXiv:2606.07482v2 Announce Type: replace Abstract: We address two open questions in the rough volatility literature. First, we prove finite positive moments for the rough Bergomi price process, and for a wider class of Gaussian Volterra Bergomi models, in the whole subcritical range under negative correlation. More precisely, if \(\rho\in[-1,0)\), then \(\E[S_T^p]
arXiv:2606.17767v1 Announce Type: cross Abstract: Personal health data from wearables are typically presented through dashboards of charts and summary statistics, requiring users to actively interpret patterns and implications. We explore an alternative interaction paradigm: engaging with personal health data through an embodied conversational agent that facilitates objective data reflection in dialogue with the user. We present a system that combines lightweight preprocessing of wearable data with a Unity-based embodied character. Internally, the system follows a dual-agent design in which an Observer agent extracts descriptive statistics and temporal trends, and a Presenter agent communicates these findings through "spoken statistics," intentionally refraining from clinical advice to isolate the impact of the interaction modality. We evaluate this approach through a simulated-self user study (N=5) using a within-subject design. Participants adopted health personas and goals derived from the LifeSnaps dataset to compare traditional dashboard exploration with embodied conversational reflection. Our evaluation focuses on perceived understanding, the specificity of generated actions, and the cognitive shift from passive viewing to active sensemaking. The paper contributes a functional prototype, a design pattern for objective health data narrative generation, and early empirical insights into how embodiment affects the interpretation of personal health metrics.
Abstract Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex and incompletely understood molecular mechanisms. Understanding circulating proteins associated with RA may improve understanding of disease biology and clarify its pathological links with cardiometabolic comorbidities. Methods A proteome-wide two-sample Mendelian randomisation (MR) drug target analysis was conducted using plasma proteins measured in 54,219 participants from the UK Biobank Pharma Proteomics Project as exposures and RA and cardiometabolic diseases as the outcomes. Summary statistics for RA included 53,663 cases and 1,070,200 controls. Colocalisation analysis was performed to confirm shared single causal variants and prioritise RA proteins supported by both MR and colocalisation. The prioritised proteins were then evaluated in the Accelerating Medicines Partnership RA Phase II synovial single-cell dataset for cell-type expression patterns. Druggability was then assessed followed by analysis of genetic overlap between RA-associated proteins and cardiometabolic diseases. Results 37 plasma proteins had a causal effect on RA risk, supported by combined evidence from MR and conditional colocalisation. In synovial tissue, TPPP3, RARRES2, AKAP12, and GGT5 were predominantly expressed in stromal and endothelial cell clusters. Druggability assessment identified IFNGR2, IL6R, CD40, and FCGR2B as Tier 1 targets. However, several biologically relevant proteins, including RARRES2, AKAP12, TPPP3, and SNX2, had limited available druggability data. Genetic overlap analysis demonstrated shared protein signals between RA and cardiovascular diseases, including overlap of RARRES2 and TPPP3 with coronary artery disease (CAD) and FCGR2B with atrial fibrillation (AF). To approximate the therapeutic effect of target inhibition, the direction of effect estimates for proteins showing overlap between RA-CAD and RA-AF was reversed. Conclusion This study identified circulating proteins involved in RA pathogenesis and reveals shared mechanisms between RA and cardiovascular diseases. While some proteins showed clear translational potential targets, several prioritised proteins had limited available druggability information and could not be confidently classified. Addressing these gaps may help identify new targets relevant to RA management. Future work should also use phenome-wide MR studies to evaluate potential on-target adverse effects of protein inhibition across RA-CAD and RA-AF.