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01.
medRxiv (Medicine) 2026-06-17

Sao Tome and Principe on the verge of eliminating lymphatic filariasis as a public health problem: evidence from IDA impact assessment surveys

Background Accelerated efforts to eliminate lymphatic filariasis (LF) as a public health problem have been supported by the introduction of the triple-drug regimen of ivermectin, diethylcarbamazine and albendazole (IDA) in endemic settings. In Sao Tome and Principe, nationwide mass drug administration (MDA) with diethylcarbamazine and albendazole was implemented in 2018, followed by IDA in 2019 and 2020. This study assesses progress towards elimination using post-MDA impact assessment surveys conducted after cessation of treatment. Methods Cross-sectional surveys were conducted among adults aged 20 years and older in 2022 and again between December 2024 and January 2025. Circulating filarial antigen (CFA) was detected using the filarial test strip (FTS). Individuals who tested positive were examined for microfilaremia using nocturnal calibrated thick blood smear microscopy. Additionally, programme data on MDA coverage and morbidity were obtained from national surveillance records. Results Three rounds of nationwide MDA achieved high epidemiological coverage (86.4% in 2018, 74.2% in 2019 and 80.0% in 2020). The impact assessment surveys conducted in 2022 evaluated 14 132 adults, with 21 individuals (0.15%) testing positive for CFA, while the follow-up survey conducted between December 2024 and January 2025 assessed 14 653 adults and detected seven positive cases (0.05%). No microfilariae were detected among the 28 antigen-positive individuals examined using nocturnal calibrated thick blood smears. National morbidity records documented 190 cases of lymphoedema and nine cases of hydrocoele. Conclusions Infection indicators remain well below WHO decision thresholds, suggesting that LF transmission is unlikely to be sustained. Sao Tome and Principe appears to be close to eliminating LF as a public health problem. However, strengthening morbidity management services will be essential to support the preparation of the national elimination dossier.

02.
medRxiv (Medicine) 2026-06-10

Prediction of immunotherapy response using live tumor fragments from routine clinical biopsies

Functional ex vivo assays using live tumor tissues have demonstrated strong predictive accuracy for response to immune checkpoint inhibitors (ICIs) but are not scalable, requiring manual processing of large resections collected at academic centers. Here, an ex vivo live tumor fragment (LTF) platform was developed using standard-of-care biopsies from 228 patients with suspected malignancy collected across prospective, multicenter observational trials and biobanks. Hierarchical clustering of ICI-mediated changes in cytokine production identified two groups: responders and nonresponders. A binary classifier (elive index) using 8 cytokines achieved an AUC of 0.99 for cluster prediction. elive index correctly predicted clinical benefit in 93% (26/28) of patients (P = 3.2x10-5) and accurately identified 83% (10/12) of objective responders. Critically, elive responders were identified among biomarker-negative patients, highlighting the platform as a scalable approach that complements existing companion diagnostics and expands the population of patients identified to benefit from ICI therapy.

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

Learning Hybrid Biophysical Neuron Models with Neural ODEs

arXiv:2606.16693v1 Announce Type: cross Abstract: Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications – omitting channels or reducing morphological detail – introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.

04.
bioRxiv (Bioinfo) 2026-06-17

Posterior-calibrated multimodal motor states reveal longitudinal and imaging-associated heterogeneity in Parkinson's disease

Parkinson's disease (PD) motor heterogeneity is commonly summarized by hard subtype labels, although clinical states vary longitudinally, severity can dominate unsupervised structure, and model uncertainty is rarely calibrated. We developed a posterior and refit-stability calibrated multimodal motor state framework that assigns probabilistic MDS-UPDRS-III motor states, aggregates them at the patient level, separates global burden from residual tremor-axial profile, and tests whether imaging can recover the resulting posterior distribution. In 29,366 aligned PPMI motor-posterior visits spanning 4,773 participant identifiers, patient-level state families were stable on average (modal-family fraction 0.925; 95% CI 0.921 - 0.930), but 25.5% of patients transitioned state over follow-up (95% CI 24.1 - 26.7%). PD-only cohort definitions produced smaller denominators and are reported as sensitivity cohorts with rerun calibration and imaging-posterior checks. Severity and covariates explained substantial motor-domain variance, especially bradykinesia (rsecond=0.850), but residual profile modeling retained five active components across total-severity, principal-component, leave-one-domain, non-target-burden, and clinical-only severity axes. Refit-stability calibration with 250 patient-blocked bootstrap refits showed high nominal posterior confidence (0.989) but lower empirical label consistency (0.849), quantifying overconfidence rather than hiding it. Patient-held-out temporal modeling predicted future axial burden (best XGBoost rsecond=0.605) and future state transition (XGBoost AUC=0.830; 95% CI 0.822 - 0.837). DaTSCAN plus FreeSurfer ROI features predicted patient-level soft motor posterior vectors (RF jsd=0.209; 95% CI 0.199 - 0.220; macro-AUROC=0.692), while severity/demographic-adjusted imaging features further improved soft posterior recovery (jsd=0.188). BioFIND transfer reproduced clinically meaningful endpoint gradients after state assignment in 225 external patients, supporting external face validity rather than definitive transportability. These results support PD motor phenotypic states as calibrated, dynamic, clinically interpretable profiles with convergent imaging associations, not as definitive biological subtypes.

05.
medRxiv (Medicine) 2026-06-18

Rare Coding Variants Reveal Distinct Genetic Architectures Across Multidimensional Sleep Phenotypes

Sleep and circadian traits have been widely studied using common variants, but the contribution of rare coding variation remains unclear. We analyzed rare coding variants in 397,065 whole-exome sequenced UK Biobank participants across 36 sleep phenotypes from self-report, diagnoses, sleep medication use and accelerometry, and meta-analyzed results with 171,536 whole-genome sequenced All of Us participants of diverse ancestries, with replication in the Mass General Brigham Biobank (N = 31,275). We identified 260 genes associated with sleep phenotypes, including novel associations with sleep medication use in 29 genes and 24 out of 29 have not previously been reported with any sleep phenotypes. We observed modest but significant rare variant heritability and strong genetic correlations between sleep medication use, insomnia and fatigue. Temporal gene expression trajectory analyses indicate that genes associated with self-reported sleep traits show constant high prenatal expression, whereas genes linked to sleep medication phenotypes exhibit peak expression in the late prenatal period. These findings highlight distinct biological mechanisms captured by different measurement sources of sleep phenotypes and reveal rare-variant-informed targets for therapeutic discovery.

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

Bound State Solutions of the Relativistic Finite-difference Equation for the Ring-shaped Quesne Oscillator Potential

arXiv:2606.12082v1 Announce Type: new Abstract: We solve exactly the relativistic finite-difference equation for the quantum three-dimensional ring-shaped Quesne oscillator potential. Our investigation is based on a finite-difference version of relativistic quantum mechanics. So-called relativistic configurational r-space is a key concept here. We show that the radial wavefunctions and angular wavefunctions are expressed through the continuous dual Hahn polynomials and Jacobi polynomials, respectively. A discrete energy spectrum has been found. The radial wave functions and energy spectrum have the correct nonrelativistic limit. We also build a dynamical symmetry group SU (1, 1) for the radial part of the equation of motion, which allows us to find the energy spectrum purely algebraically.

07.
arXiv (CS.CV) 2026-06-17

DiffAttn: Diffusion-Based Drivers' Visual Attention Prediction with LLM-Enhanced Semantic Reasoning

Drivers' visual attention provides critical cues for anticipating latent hazards and directly shapes decision-making and control maneuvers, where its absence can compromise traffic safety. To emulate drivers' perception patterns and advance visual attention prediction for intelligent vehicles, we propose DiffAttn, a diffusion-based framework that formulates this task as a conditional diffusion-denoising process, enabling more accurate modeling of drivers' attention. To capture both local and global scene features, we adopt Swin Transformer as encoder and design a decoder that combines a Feature Fusion Pyramid for cross-layer interaction with dense, multi-scale conditional diffusion to jointly enhance denoising learning and model fine-grained local and global scene contexts. Additionally, a large language model (LLM) layer is incorporated to enhance top-down semantic reasoning and improve sensitivity to safety-critical cues. Extensive experiments on four public datasets demonstrate that DiffAttn achieves state-of-the-art (SoTA) performance, surpassing most video-based, top-down-feature-driven, and LLM-enhanced baselines. Our framework further supports interpretable driver-centric scene understanding and has the potential to improve in-cabin human-machine interaction, risk perception, and drivers' state measurement in intelligent vehicles.

08.
arXiv (quant-ph) 2026-06-15

On-site interactions in quantum thermal machines: efficiency, rectification and entanglement beyond local and global master equations

arXiv:2606.14593v1 Announce Type: new Abstract: Advances in experimental techniques have opened new routes for harnessing non-equilibrium dynamics in mesoscopic quantum systems. In this context, we study the impact of on-site interactions on the transport properties of a continuous quantum thermal machine composed of two coupled oscillators connected to two thermal reservoirs. In the weak system-reservoir coupling regime, where a long-standing debate concerns which reduced description should be preferred, we first show that the Redfield master equation (RME) provides an accurate and unifying framework that interpolates between two well-known limits: the local and global master equations. By relying on the Hierarchy of Pure States (HOPS), a numerically exact stochastic method, we then explore the full parameter space and show that interactions can be leveraged to tune the efficiency of the thermal machine at high temperatures (while leaving it essentially unchanged at low temperatures), induce non-reciprocal transport under asymmetric reservoir couplings, and generate steady-state entanglement within the junction. We derive expressions for system-bath correlators, such as heat and particle currents, consistently across different frameworks. Our work features on-site interactions to enhance the versatility of quantum thermodynamic junctions and clarifies the role of non-Markovianity and non-linearities in quantum transport.

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

Improving Code-Switching ASR with Code-Mixing Guided Synthetic Speech

arXiv:2606.19381v1 Announce Type: cross Abstract: Code-switch (CS) Automatic Speech Recognition (ASR) remains challenging due to limited availability of high quality CS text-speech pairs for training. Although synthetic data augmentation via Text-to-speech (TTS) has been explored, existing CS TTS approaches primarily optimise reconstruction fidelity and do not explicitly enforce language-boundary consistency, thereby limiting their effectiveness for CS ASR augmentation. This paper proposes a code-mixing guided preference-learning framework that steers synthetic speech generation toward improved code-switching fidelity using the Code Mixing Index (CMI). Experiments on the SEAME Mandarin-English conversational corpus demonstrate that the proposed method enhances the utility of synthetic data for ASR fine-tuning. Specifically, when fine-tuning Whisper Large, the proposed approach reduces Mixed Error Rate (MER) from 12.1%/17.8% to 8.9%/14.2% on the DevMAN and DevSGE sets, respectively.