Scientific Reports

In this study, we investigate the individuality and information content of infrared molecular profiles derived from blood samples in a large, longitudinal health-profiling cohort and compare them to a standard clinical laboratory panel. Using Fourier-transform infrared spectroscopy, we obtained comprehensive molecular fingerprints from 4,704 self-reported healthy individuals over five visits spanning 1.5 years, alongside routine clinical laboratory measurements. We show that infrared profiles are highly individual-specific and remarkably stable over time, with intra-individual variability significantly lower than inter-individual differences--paralleling the characteristics observed in clinical laboratory data. To quantify and compare the information content of these molecular datasets, we employ individual identification as a proxy for Shannon entropy. In this framework, higher identification accuracy reflects a higher amount of information. Infrared profiles outperform the clinical laboratory panel in identifying individuals at scale, suggesting higher intrinsic information content. Furthermore, combining infrared and clinical laboratory data substantially improves identification performance (the identification of less than 3000 individuals by the clinical laboratory panel is boosted to more than 4000 by incorporating the infrared spectroscopic markers), highlighting the value of integrating complementary data modalities. These findings suggest a practical framework, rooted in information theory, for comparing molecular profiling approaches and emphasize the potential of infrared spectroscopy as a complementary tool in personalized medicine.

Zebrafish have been used a prominent model for high-throughput phenotypic screens of candidate risk gene mutations for several disorders. This also includes models for attention deficit/hyperactivity disorder (ADHD). Traditional behavioural tests, such as the forced light/dark assay, concentrate on basic locomotion measures. However, recently developed visually-driven locomotion assays, for example closed-loop systems using virtual reality, have allowed extraction of richer data on animal locomotion and decision-making under different sensory stimuli. Here, we have used such a system to assess the behaviour in adgrl3.1 mutant fish, an established model for ADHD. Our results show that mutants exhibit a higher baseline excitability and a lower threshold for initiating motor events, demonstrating that collecting behavioural responses in an interactive environment enables a more precise characterisation of ADHD-relevant phenotypes associated with adgrl3.1 disruption. More generally, we establish a scalable translational platform to screen gene-function relationships and possible therapeutic interventions, not only for ADHD but multiple neurodevelopmental disorders.

This study examines the temporal dynamics of expressive piano performance by means of a quantitative analysis of motor timing in an elite pianist, with particular reference to stylistic contrasts between Baroque and Romantic repertoire. In line with kinematic models of expressive timing, which describe musical performance as reflecting principles of biological motion, we examined whether a common temporal structure underlies stylistically divergent executions. Despite marked differences in structural complexity and gesture density, both performances exhibited a shared low-frequency oscillatory pattern ([~]0.36 Hz) in beat-level timing variability. This infra-delta rhythmic modulation is consistent with the presence of an underlying motor timing scaffold and suggests a common temporal organization across expressive behaviors. These findings support the hypothesis that musical performance relies on a rhythmically structured control architecture, potentially shared with other complex motor activities such as speech and locomotion.

Balancing exploration and exploitation is a fundamental challenge for adaptive behavior, yet it remains unclear whether visual sampling and spatial locomotion reflect a single cross-domain trait or operate independently. We addressed this question by recording head-mounted eye-tracking and full-body motion tracking while 26 participants freely navigated "Westbrook", a large-scale virtual city for a total of 150 min across five sessions. From the movement trajectories we derived three spatial descriptors: median walking speed, occupancy entropy, and the proportion of explorative route choices. From the gaze data, we computed 38 robust visual descriptors encompassing fixation dynamics, pupil size, saccadic amplitude, gaze-head alignment, and transition entropy. Principal-component analysis reduced the visual descriptors to three components that captured 58 % of variance, with the first component (PC1) reflecting "gaze dynamism" (frequent shifts, larger saccades, higher transition entropy). Canonical correlation analysis revealed a strong coupling between spatial and visual behaviours: the first pair of canonical variates correlated at r = 0.68 (cross-validated r = 0.45), driven primarily by the association of high walking speed and occupancy entropy with elevated gaze dynamism. In contrast, the proportion of explorative route choices contributed little to this coupling. These findings demonstrate that individual differences in low-level locomotor speed and spatial coverage co-vary with an exploratory visual style, supporting the existence of a domain-general "exploration" factor that shapes both how people move through, and attend to, complex environments.

Previous investigations have explored the effects of hypermagnetic fields, that is, fields in excess of the Earths background geomagnetic field strength of approximately 50 {micro}T, on Escherichia coli (E. coli). Conversely, this study investigates the effects of hypomagnetic field conditions, that is, fields below the geomagnetic background intensity, on the growth of E. coli K12 by using a hypomagnetic chamber to shield cultures, with a measured residual magnetic field inside the chamber of 19 nT. When grown in rich media from a semi-anaerobic, stationary-phase starting culture under geomagnetic and hypomagnetic conditions, the lag phases of E. coli were approximately 86 minutes and 132 minutes, respectively. Despite this increase in lag phase, exceeding two E. coli doubling times, the log-phase growth rate of E. coli was identical under both geomagnetic and hypomagnetic conditions. In addition to demonstrating a biologically relevant sensitivity to magnetic field parameters in the hypomagnetic direction, this represents a much greater absolute magnetosensitivity, with a deviation of only 50 {micro}T between the hypomagnetic and geomagnetic conditions, than has previously been demonstrated for E. coli.

OBJECTIVES: Compare results of the Pediatric Outcomes Data Collection Instrument (PODCI) in children ages 2-18 years with cerebral palsy (CP) across all severity levels of the Gross Motor Function Classification System (GMFCS) with children in the General Population, confirming discriminant validity as a performance assessment tool and health-related quality of life (HRQOL) measure. METHODS: Cross-sectional study: single response PODCI proxy survey databases of 5238 children ages 2-18 years in GP and 2470 in the Population with CP were analyzed. Statistical methods included Analysis of Variance (ANOVA), Analysis of Covariance (ANCOVA), Linear Trend Test, and Standard Error Assessment. RESULTS: A statistically significant difference exists between PODCI subscales in General Population and Population with CP across age groups and GMFCS levels. Motor scales and Global Functioning increase with age in both populations and are inversely proportional to GMFCS level in the Population with CP. HRQOL measures decrease with age in both populations with Happiness decreasing more in the General Population than those with CP as age increases. CONCLUSIONS: PODCI demonstrates a statistically significant difference in motor performance and HRQOL in children ages 2-18, between the General Population and the population with CP. PODCI is a valid performance assessment tool for use in CP ages 2-18 across all GMFCS levels. KEYWORDS: Cerebral Palsy, General Population, PODCI, ICF, Performance

A substantial body of evidence demonstrates that measures from mammograms are predictive of breast cancer risk. In this matched case-control study, mammograms acquired near the time of diagnosis were analyzed to investigate bilateral breast asymmetry as measure of short-term risk prediction. Specifically, contralateral breast images were compared with measures derived in the Fourier domain (FD); this technique summarizes power in concentric radial bands that cover the Fourier plane. Equivalently, this approach can be described as a multiscale characterization of the image. The summarized power difference between respective contralateral bands produces an asymmetry measure. Full field digital mammography (FFDM) and synthetic two-dimensional images from digital breast tomosynthesis (DBT) were investigated for women that had both types of mammograms acquired at the same time. Odds ratios (ORs) and the area under the receiver operating curves (Azs) were generated from conditional logistic regression modeling with 95% confidence intervals. Raw unprocessed FFDM images produced significant findings: OR = 1.90 (1.58, 2.29) and Az = 1.72 (0.67, 0.76) per one standard deviation unit. Associations were significant but attenuated for both clinical FFDM and DBT images: OR = 1.31 (1.11, 1.54) and Az = 0.63 (0.58, 0.67); and OR = 1.48 (1.25, 1.76) and Az = 0.65 (0.60, 0.70), respectively. Results suggest that clinical FFDM and DBT images are inferior to raw FFDM images in capturing breast asymmetry with information loss for breast cancer risk prediction. Moreover, these DBT images have lower spatial resolution but produced stronger associations than the clinical FFDM images.

Radiation-induced intestinal injury is a widely used model for studying mechanisms regulating tissue injury and regeneration. Traditionally, Cesium (137Cs) radiation has been used in research applications, but over the past decade, X-ray irradiation has become increasingly favored due to its improved safety and non-radioactive profile. Since each type of radiation has distinct physical characteristics that drive its performance, we sought to systematically compare the effects of the X-ray and 137Cs irradiators on intestinal epithelial injury and regeneration. Using established in vitro models, including colorectal cancer cell lines such as HCT116, RKO, and DLD-1, and mouse intestinal organoids, alongside an in vivo model, Bmi1-CreER;Rosa26eYFP, we evaluated differences in transcriptional, protein, and histopathological responses to irradiation. Our results demonstrate that X-ray produced intestinal injury and regenerative responses comparable to those induced by 137Cs, supporting its reliability as an alternative modality for studying intestinal radiation.

The Mediterranean Sea harbors a rich diversity of macroalgae with pharmacological potential. In this study, metabolite composition, antioxidant and antifungal activities of methanol and ethyl acetate extracts from Rugulopteryx okamurae, Dictyota fasciola, Batophora sp., Codium fragile, and Palisada tenerrima from the southeastern coast of Spain were evaluated. R. okamurae, Batophora sp. and C. fragile are non-native. All extracts exhibited antioxidant activity, particularly those obtained with methanol. R. okamurae and Batophora sp. showed the highest activity, inhibiting the DPPH{middle dot}radical by more than 40% at 1 mg/ml. All extracts contained phenolics and flavonoids, which may contribute to the observed antioxidant activity. Moreover, the methanolic extracts of R. okamurae and P. tenerrima exhibited in vitro fungistatic activity against the wilt pathogen Fusarium oxysporum f. sp. cubense tropical race 4. R. okamurae extracts showed the strongest antifungal activity against F. oxysporum f. sp. cubense TR4, with inhibition values of 23.3% and 30.5% at doses of 10 and 20 mg/well, respectively. The methanolic P. tenerrima also showed notable activity (19.8% and 20.7% inhibition), whereas other extracts displayed lower effect. LC-MS/MS analysis of R. okamurae extract revealed a diverse metabolite profile including oxylipin-type metabolites, terpenoid-like compounds and carotenoids. Our findings highlight coastal macroalgae from SE Spain as sources of bioactive compounds and support the valorization of biomass from invaders such as R. okamurae.

Purpose: To quantify whether fundus tracking in microperimetry improves psychometric parameter estimation (in vivo demonstration of improved stimulus-delivery precision), and to derive a psychometrically grounded criterion intensity for suprathreshold (defect-mapping) microperimetry. Methods: Twenty-five healthy volunteers underwent MAIA2-microperimetry at five loci: three outside and two inside the blind spot. Frequency-of-seeing (FoS) functions were measured in four blocks (2 tracking on; 2 tracking off). FoS-data were fit using cumulative-Gaussian psychometric functions estimating sensitivity parameters. Mixed-effect models assessed tracking effects, and posterior simulations defined the optimal criterion intensity for separating 'seeing' from 'non-seeing' loci. Results: Tracking had little effect on threshold estimates at loci outside the blind spot, but lowered threshold estimates within the blind spot (posterior median difference PMD [95% CrI] of -1.46 dB [-2.30, -0.62] at locus 4, and -1.02 dB [-1.94, -0.08] at locus 5). Tracking was associated with steeper psychometric slope parameters at loci 1-3 (PMD of -0.14 dB [-0.29, 0.01], -0.27 dB [-0.43, -0.12], and -0.22 dB [-0.40, -0.04]). Without tracking, false-positive responses were more frequent when fixation shifts displaced stimuli toward the 'seeing' retina. Simulation-based analysis identified 13 dB as nominally optimal criterion for suprathreshold microperimetry (Youden index: 0.76 [0.74, 0.79], comparable to 10 dB (0.74 [0.72, 0.76]). Conclusions: Even in healthy volunteers with stable fixation, fundus tracking measurably reduced sensitivity estimates at 'non-seeing' loci and sharpened FoS curves in the 'seeing' retina. A criterion intensity of 10 to 13 dB is a defensible choice for separating 'seeing' and 'non-seeing' retina in suprathreshold (defect-mapping) perimetry paradigms.

We completed a video-based, four-night, in-home, level 3 sleep apnea study of healthy, low-risk pregnant participants and their bed partners in order to characterize sleep physiology in the third trimester of pregnancy. Demographic, anthropometric, and baseline sleep health characteristics were recorded, and the NightOwl home sleep apnea test device was used to measure sleep breathing, posture, and architecture parameters. Symptoms of restless legs syndrome were elicited in the exit interview. Forty-one pregnant participants and 36 bed partners completed the study. Bed partners had a significantly higher prevalence of sleep apnea than their pregnant co-sleepers (31% vs. 5.9%). Bed partners also had more severe sleep apnea than their pregnant co-sleepers, and this persisted on an adjusted analysis for baseline differences in factors known to increase risk of sleep apnea. In pregnant participants, increasing gestational age was found to be protective against mild respiratory events but not more severe events. While the correlation between STOP-Bang score and measures of sleep apnea severity was weak, an affirmative response to the witnessed apneas item on the STOP-Bang questionnaire was a strong predictor of more severe sleep apnea for all participants. Smoking history also increased sleep apnea risk. Pregnant participants had lower sleep efficiency and longer self-reported sleep onset latency. Restless legs syndrome was experienced by 39.5% of the pregnant participants but no bed partners. From a sleep breathing perspective, people with healthy, low-risk pregnancies have better sleep than their bed partners despite lower sleep efficiency and higher rates of restless legs syndrome.

Magnetoreception, the ability to perceive the geomagnetic field, is widespread across animals. The underlying sensory mechanism remains elusive, but a long-standing hypothesis proposes single-domain magnetite linked to mechanosensitive ion channels. The Ansells mole-rat (Fukomys anselli) is a subterranean rodent with a magnetic sense, and published behavioral and histological data are consistent with magnetite-based magnetoreceptors in the cornea or retina. Here, we systematically screened for magnetite in the mole-rat eye, combining iron detection via enhanced Prussian blue staining and synchrotron X-ray fluorescence microscopy (XFM) with magnetic detection via MRI quantitative susceptibility mapping (MRI-QSM) and quantum-diamond microscopy (QDM). This revealed only a few iron particles in the retina and cornea, which predominantly overlapped with titanium or chromium, indicating a non-biogenic origin. XFM showed iron-enriched lines in the cornea, but these did not show ferrimagnetic signals. Focusing on other ocular tissues, MRI-QSM revealed the highest susceptibility in the ciliary body, where iron-rich pigmented cells were identified. A TEM-screen, however, failed to detect single-domain magnetite particles in these cells. We conclude that our high-sensitivity multimodal screen provides no evidence for magnetite-based magnetoreceptors in the mole-rat eye, suggesting that mole-rat magnetoreceptors either do not reside in the eye or are based on different physical principles.

We investigated whether multimodal sensing that combines functional near-infrared spectroscopy (fNIRS) with peripheral physiological signals can improve subject-independent classification of arousal and valence, the fundamental affective dimensions in Russells circumplex model. We developed Japanese emotion-inducing music-video stimuli (60 seconds each) and recorded subjects central nervous system activity using fNIRS, alongside peripheral physiological measures, specifically electrodermal activity (EDA) and photoplethysmography (PPG), during video viewing. To prioritize reproducibility and methodological transparency, we extracted simple, easily computed features from each modality and performed binary (high vs. low) classification separately for arousal and valence using a support vector machine. The combination of fNIRS and EDA yielded the highest performance, with a macro-averaged F1 score of 0.73 for arousal and 0.64 for valence. These findings underscore the utility of integrating fNIRS with peripheral physiological signals for subject-independent emotion classification.

Childhood socioeconomic position (SEP) can have lifelong effects on health. Many studies have used adult height as a surrogate marker for early-life conditions. In this study, we derived the non-genetic component of height, calculated as the residual from sex-specific standardized height regressed on genetically predicted height, as a surrogate for childhood SEP, using data from the Hispanic Community Healthy Study/Study of Latinos (2008-2011). A positive residual would indicate favorable early-life conditions promoting growth, while a negative residual indicates early-life adversity that may stunt the development. The height residual was associated with early-life variables such as parental education, year of birth, US nativity and age at first migration to the US (50 states/DC), supporting the validity of height residual as a surrogate for early-life conditions. Furthermore, a height residual was positively associated with better cardiovascular health (CVH) and cognitive function among middle-aged and older adults. Interestingly, among <35 years old, the height residual was negatively associated with the "Lifes Essential 8" clinical CVH scores. These results suggest the non-genetic component of height as a surrogate for childhood environment, with predictive value for CVH and cognitive function.

Objective: Skin sympathetic nerve activity (SKNA) has emerged as a promising non-invasive surrogate measure of sympathetic drive, but its relevant physiological characteristics remain ill-defined. This observational study aims to investigate its regulatory patterns during rest and Valsalva maneuver (VM) in healthy participants. Method: Using a two-layer strategy integrating signal analysis and physiological modelling, we analyzed data recorded from 41 subjects performing repeated VMs. The observational layer includes time-domain feature comparisons using linear mixed-effect models, and time-varying spectral coherence analysis. The mechanistic layer proposes a mathematical model to investigate whether baroreflex and respiratory modulation are sufficient to reproduce the observed HR and average SKNA (aSKNA) dynamics. Main Results: Mean integrated SKNA (iSKNA) showed more significant change than HRV for VM induced effects. We also found mean iSKNA increase during VM varies with BMI and sex. The coherence analysis indicated that iSKNA strongly synchronized with EDR under resting conditions. The proposed model successfully reproduced main characteristics of aSKNA dynamics, yielding a high median Pearson correlation coefficient of 0.80 ([Q1, Q3] = [0.60, 0.91]). In contrast, HR dynamics were only partially captured, with a median PCC of 0.37 ([Q1, Q3] = [0.16, 0.55]). These results likely suggest SKNA provides a more direct representation of sympathetic burst dynamics during VM in healthy subjects. Significance: This study provides convergent evidence that SKNA reflects known autonomic regulatory influences in healthy subjects. These findings strengthen the physiological interpretability of SKNA while clarifying its appropriate use as a practical biomarker of sympathetic function.

Autism spectrum disorder (ASD) is a neurodevelopmental condition for which timely and accurate detection remains a major clinical priority. Early and reliable identification is important because it can facilitate access to assessment, diagnosis, and appropriate support; however, current diagnostic pathways still rely largely on behavioural evaluation and clinical judgement. In this context, machine-learning (ML) approaches have attracted growing interest because they can identify subtle and complex patterns in speech data that may not be easily captured through conventional methods. The current study capitalizes on this potential by developing and evaluating ML models for distinguishing autistic individuals from neurotypical individuals based on speech features. More specifically, acoustic features of vowels, including fundamental frequency (F0), first three formants (F1, F2, F3), duration, jitter, shimmer, harmonics-to-noise ratio (HNR), and intensity, were elicited from 18 autistic adults and 18 neurotypical adults through a controlled production task. Then, four supervised ML models were trained and evaluated on these features: LightGBM, Random Forest, Support Vector Machine, and XGBoost. All models demonstrated good classification performance, with the best-performing model achieving a strong discriminability of 89%. The explainability analysis identified F0 as the most influential predictor by a substantial margin, followed by intensity, F3, and F1, while duration, shimmer, HNR, jitter, and F2 contributed more modestly. These findings demonstrate that vowel acoustics contain clinically relevant information for distinguishing autistic from neurotypical adult speech and highlight the potential of interpretable, speech-based ML as a transparent and scalable aid for ASD screening and assessment.

PurposeTo determine whether circadian timing defines critical molecular windows in myopia development and to assess the transferability of circadian gene programs across ocular tissues, disease stages, and species. MethodsPublicly available retinal and choroidal RNA-seq datasets from chick models of form-deprivation myopia were analyzed using unsupervised transcriptomic profiling and multistage machine-learning classification. Circadian windows were defined based on Zeitgeber time, and samples were grouped accordingly for downstream analyses. Classification model robustness was evaluated through cross-tissue and cross-stage validation and further assessed using external validation in an independent dataset. Functional translation to humans was examined using ortholog-based Gene Ontology enrichment analysis to identify conserved biological processes and higher-order regulatory pathways. ResultsA circadian critical window at ZT8-ZT12 exhibited the strongest transcriptional divergence during both myopia onset and progression. Gene signatures derived from this window generalized across retina and choroid and remained predictive across disease stages, supporting coordinated molecular regulation between ocular tissues. External validation confirmed the reproducibility of these signatures despite differences in experimental design and gene coverage. Functional mapping revealed that conserved molecular components in chicks are reorganized into more complex neuroendocrine and regulatory networks in humans, indicating cross-species conservation with increased functional complexity. ConclusionsCircadian timing strongly shapes myopia-related gene expression and underlies coordinated retina-choroid signaling. These findings highlight circadian biology as a key factor of refractive development and suggest that time-dependent mechanisms may influence myopia susceptibility, progression, and response to treatment.

Drug-related UVA-induced photoreactions have been reported for several therapeutic compounds, including fluoroquinolones. CX5461 is a clinically relevant quinolone-derived anti-cancer small molecule with documented UVA-sensitising activity. Here we compared, by bulk and clonal whole genome sequencing (WGS) under light-protected conditions, the mutational signatures in human retinal pigment epithelial cells (RPE1) exposed to UVA, CX5461, or co-exposed to UVA and CX5461. Treatment with CX5461 or UVA alone resulted in a low SNV burden and background-like mutational profiles. In contrast, bulk sequencing of human cells co-exposed to UVA and CX5461 had a markedly higher SNV burden characterized by T>A and T>C substitutions. Furthermore, single-cell clonal expansion and sequencing of CX5461 alone, UVA alone or CX5461+UVA treatments confirmed that the pattern was only observed when cells were exposed to both UVA and CX5461. The CX5461+UVA-associated SNV signature we report arises only when CX5461-treated cells are exposed to UVA, and is not observed when CX5461-treated cells are shielded from light. We do not observe strong single base mutagenic activity of CX5461 alone, under light protected conditions. Our data emphasise the need for appropriate controls and light-exposure precautions when studying base mutagenesis activity of known photosensitiser molecules.

Irritable Bowel Syndrome (IBS) affects a substantial proportion of university students, yet its factors remain incompletely characterised in South Asian populations. We reanalysed a publicly available dataset of 550 Bangladeshi students from Hasan et al. (2025), conducting a data audit that identified implausible records, including males reporting menstrual symptoms, and reduced the analytic sample to 506 observations. Using Explainable Boosting Machines (EBMs), which capture non-linear effects and pairwise interactions without sacrificing interpretability, we found that psychological distress, elevated BMI and academic dissatisfaction were the strongest predictors of IBS (mean AUC = 0.852 across 100 stratified train-test splits). Critically, several findings diverged from the original logistic regression analysis. Physical activity showed a non-linear risk pattern only at high intensity, the association with gender was substantially weaker when we accounted for metabolic and psychological factors as well and malnourishment does not have a strong an impact as in the original study. These divergences likely arise because the machine-learning model captures non-linear effects and interactions that were not represented in the original regression specification. Our findings underscore the value of reanalysing existing datasets with methods suited to capturing complexity and highlight data quality verification as a necessary step in the secondary analysis.

Background: Increasing evidence suggests that blood pressure variability (BPV) may offer prognostic value beyond average blood pressure levels. However, data on the association between BPV of ambulatory blood pressure monitoring and mortality in patients aged 80 and older are limited. This study aimed to investigate the relationship between BPV and all-cause mortality in this population. Methods: A total of 5,838 ABPM records from the Geriatrics Department of Beijing Friendship Hospital, collected between October 12, 2018, and June 9, 2025, were analyzed. Patients were divided into death and non-death groups. Subgroup analyses were performed based on the number of completed ABPM sessions. Cox proportional hazards models assessed the associations between BPV and mortality. Kaplan?Meier analysis and log-rank tests were used to compare survival across groups. Results: A median follow-up of 32.0 months included 727 hypertensive patients aged ?80 years. Multivariable cox regression and kaplan?meier analyses showed that the reverse-dipper blood pressure pattern was significantly associated with increased mortality. While short-term BPV was not linked to mortality, greater long-term variability in nighttime SBP and daytime DBP was significantly associated with higher mortality. Conclusion: Among individuals aged 80 and older, those with a reverse-dipper pattern and higher long-term BPV had a significantly higher mortality risk, despite achieving recommended blood pressure targets. Key words: blood pressure variability, ABPM, reverse-dipper pattern, elderly hypertension, mortality