julilili42/papers huggingface dataset:
Resistance Training Reshapes the Gut Microbiome for Better Health
2025-08-13

ABSTRACT Objectives The gut microbiome plays a critical role in metabolism, immunity, and aging. While endurance training has been shown to beneficially modulate the microbiome, the effects of resistance training remain less clear, with some studies reporting minimal changes. This project aims to investigate whether structured resistance training elicits significant changes in gut microbiome composition and diversity in sedentary, healthy adults. Methods 150 participants completed an 8-week supervised resistance training program. Session-level training data, including weights and repetitions, were recorded alongside metrics like load and compliance. Fecal samples were collected throughout the study period at designated timepoints for 16S rRNA gene amplicon sequencing to assess microbiome composition and for metabolomics analyses to evaluate microbial metabolic activity. Results No differences in microbial diversity were observed, and there were no significant changes in microbial community composition or fecal metabolomics across all participants post-training. However, within-individual microbial community changes significantly correlated with strength improvement, and significantly stronger shifts in beta diversity were observed in participants with high average strength gains compared to those with smaller gains. In these high responders, differential abundance analysis revealed time-dependent microbial changes, with more taxa enriched or depleted by week 8 of training. Notably, Faecalibacterium and Roseburia hominis —both associated with a healthier, anti-inflammatory microbiome—were significantly enriched. Many differentially abundant taxa belonged to the Lachnospiraceae family. Conclusion Resistance training drives significant, time-dependent gut microbiome changes, particularly in those demonstrating greater improvements in strength. These shifts mirror endurance training effects and may reflect improved overall health. Summary While endurance training has been consistently shown to enhance gut microbiome composition, the effects of resistance training remain less well defined, with findings to date being variable. Our results indicate that resistance training can induce meaningful, time-dependent shifts in the gut microbiome, particularly among sedentary individuals who experience substantial strength gains. Notably, we observed enrichment of key health-associated taxa, including Faecalibacterium and Roseburia hominis , both linked to anti-inflammatory effects and improved gut function. These findings suggest that resistance training may contribute to gut health in conjunction with physical fitness, supporting its broader application in health promotion strategies and future microbiome-focused research.
Pharmacological and pupillary evidence for the noradrenergic contribution to reinforcement learning in Parkinson’s disease
2025-08-14

Abstract Noradrenaline plays an integral role in learning by optimising behavioural strategies and facilitating choice execution. Testing the noradrenergic framework of learning in the context of human diseases offers a test bed for current normative neuroscience theories and may also indicate therapeutic potential. Parkinson’s disease is often considered as a model of dopamine deficits, including dopamine’s role in reinforcement learning. However, noradrenergic function is also severely impaired by Parkinson’s disease, contributing to cognitive deficits. Using a single dose of the noradrenaline reuptake inhibitor atomoxetine in people with Parkinson’s disease (in a randomised double-blind placebo-controlled crossover design), we show improvements in learning compared to placebo. Computational cognitive modelling confirmed a substantial shift in the decision noise parameter, indicative of more exploitative choices. This response pattern closely resembled that of age-matched controls and simulations of optimal response strategies. Pupillometry revealed increased baseline pupil diameter under atomoxetine, which correlated with behavioural improvements, and a heightened phasic pupillary response to feedback. Our findings confirm the noradrenergic contribution to reinforcement learning, and in doing so they challenge the simple interpretation of tonic-phasic locus coeruleus firing patterns based on pupillometry. Noradrenergic modulation is a potential treatment strategy for cognitive symptoms in Parkinson’s disease and related disorders.
Relevant answers to polar questions.
2025-08-14

People often provide answers that go beyond what a question literally asks, but it has been difficult to pin down what makes some answers more relevant than others. Here, we introduce Pragmatic Reasoning In Overinformative Responses to Polar Questions (PRIOR-PQ), a probabilistic cognitive model formalizing how people use theory of mind (ToM) to produce and interpret relevantly overinformative answers to yes-no questions. Specifically, PRIOR-PQ grounds the pragmatics of question answering in inferences about the underlying <i>goal</i> that motivated the questioner to ask the given question as opposed to a different question. We evaluate our probabilistic model against human answering behaviour elicited in three case studies of increasing complexity, demonstrating its ability to predict nuanced patterns of relevance better than existing models, including state-of-the-art large language models. We also show how the goal-sensitive reasoning instantiated in our probabilistic model motivates a novel chain-of-thought prompting method allowing language models to approach more human-like performance. This work illuminates the mechanistic role of ToM in the pragmatics of question-answer exchanges, bridging formal semantics, cognitive science and artificial intelligence. Our findings have implications for developing more socially grounded dialogue systems and highlight the importance of integrating explanatory cognitive models with machine learning approaches.This article is part of the theme issue 'At the heart of human communication: new views on the complex relationship between pragmatics and Theory of Mind'.
He sees the forest, I see the trees: Narrative perspective shifts how abstractly people construe a text.
2025-08-14

Humans tell stories to share information, evoke emotions, and change opinions. An inherent dimension of these stories is the narrative perspective from which they are told: Sometimes stories are told from a person's first-person narrative perspective (e.g., using I/me pronouns), whereas other times, they are told about the person using a third-person narrative perspective (e.g., using he/him, she/her, etc., pronouns). The current work tests the hypothesis that the first-person (vs. third-person) narrative perspective causes people to construe information more concretely (vs. abstractly), with downstream effects on how readers interpret and are influenced by a text. Experiments 1a/1b support this claim by showing that participants construe others' actions more concretely (vs. abstractly) when those actions are written from the first-person (vs. third-person) narrative perspective. Experiments 2a/2b build on this finding to show that people prefer concrete (vs. abstract) summary descriptions of short narrative stories that are written from the first-person (vs. third-person) narrative perspective. Experiment 3 tests the implications of this effect for persuasion, showing people were more motivated to donate blood when first-person (vs. third-person) donation testimonials were paired with concrete (vs. abstract) arguments for donating. Finally, Experiment 4 shows that narrative perspective influences identification with a character depending on the relatability of the character's experience. First-person (vs. third-person) narratives increase identification with characters, unless their experiences are too difficult to relate to. These findings provide insight into how narrative perspective influences people's understanding of a written text, as well as its subsequent influence on attitudes and behaviors. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
Logarithmic Concavity of Bimatroids
2025-08-14

Abstract A bimatroid is a matroid-like generalization of the collection of regular minors of a matrix. In this article, we use the theory of Lorentzian polynomials to study the logarithmic concavity of natural sequences associated with bimatroids. Bimatroids can be used to characterize morphisms of matroids and this observation (originally due to Kung) allows us to prove a weak version of logarithmic concavity of the number of bases of a morphism of matroids. This is weaker than the original result by Eur and Huh; it nevertheless provides us with a new perspective on Mason’s log-concavity conjecture for independent sets of matroids. We finally show that for realizable bimatroids, the regular minor polynomial is a volume polynomial. Applied to morphisms of matroids, this shows that the weak basis generating polynomial of a morphism is a volume polynomial; this confirms a conjecture of Eur–Huh for morphisms of nullity <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mo>≤</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> </mml:math> and gives an algebro-geometric explanation for Mason’s log-concavity conjecture in the realizable case.
AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects
2025-08-15

Abstract Duchenne muscular dystrophy (DMD) is caused by pathogenic sequence variants occurring in the DMD gene which lead to the loss of the dystrophin protein, a molecular ‘shock absorber’ that protects muscle from contraction-induced injury. The large size of the dystrophin open reading frame precludes delivery of the full-length protein using a single adeno-associated virus (AAV) vector, which led to the development of internally-deleted dystrophin minigenes encoding partially-functional dystrophin. Indeed, five such microdystrophin therapies have been assessed in various clinical programmes. In 2023, Elevidys (Sarepta Therapeutics) received accelerated approval based on levels of dystrophin as a surrogate biomarker. In 2024, it received full approval despite unclear efficacy (i.e. not meeting primary or secondary outcomes in a phase 3 trial). Additionally, in 2025, two DMD individuals treated with Elevidys died after acute liver failure. A separate microdystrophin therapy, PF-06939926 (Pfizer) was discontinued for both efficacy and safety reasons (including the deaths of two clinical trial participants). Solid Biosciences, Genethon, REGENXBIO, and Insmed continue to develop microdystrophin therapies differing in transgene structure, promoter sequences, and AAV serotype. Here we describe recent progress in AAV-microdystrophin therapeutics development, and discuss the challenges facing such approaches, including pre-existing anti-capsid immunity, anti-transgene immunity, the unknown functionality of microdystrophin transgenes, transduction of muscle stem cells, and long-term transgene persistence.
Constraints on axion-like particles from active galactic nuclei seen through galaxy clusters
2025-08-15

Abstract Hypothetical axion-like particles (ALPs) are of interest because of their potential to act as dark matter or to reveal information about yet undiscovered fundamental constituents of matter. Such particles may be created when photons traverse regions of magnetic fields. The conversion probability depends on both the magnetic field parameters and the photon energy, leading to several spectral absorption features as light passes through magnetized regions. Traditionally, astrophysical searches have focused on detecting such features in individual objects. However, our limited understanding of the properties of cosmic magnetic fields has hindered progress. Here we introduce a new approach based on analysing the stacked (rather than individual) spectra of active galactic nuclei behind galaxy clusters, which are gigantic magnetic field reservoirs. Stacking efficiently averages over the uncertainties in magnetic fields, predicting a distinct step-like spectral signature of photon-to-ALP conversion. With this approach, we advance into previously inaccessible regions of the ALP parameter space for nano-electronvolt masses. Adopting this method using data from different telescopes and increasing the size of the stacked datasets will significantly improve existing bounds across a wide range of masses. The Cherenkov Telescope Array Observatory will enable this method to probe a broad region of parameter space where ALPs could serve as dark matter.
Latent Representations of Early Brain Development: A Multivariate Normative Model of Brain Structure and Behaviour
2025-08-15

Abstract Individual variation in neurodevelopment plays a central role in shaping cognitive abilities and behavioural profiles, influencing both typical functioning and risk for neurodevelopmental conditions. While much research has focused on characterising trajectories of brain structure changes during development, this typically entails assessing brain regions individually, overlooking the multivariate nature of neuroimaging data. In this study, we trained an autoencoder to map latent representations of children’s brain development using T1-weighted MRI scans from a paediatric cohort (n = 564, 55% male, mean age 4.90 years, age range [0.11,15.38]). This approach enabled us to establish multivariate normative models of brain structure, providing a more comprehensive framework for understanding neurodevelopmental variation. The latent space representation from this model effectively captured demographic variables (age and sex), while preserving both global and local structural features. The model accurately reconstructed the data, having mean reconstruction of 0.04 ± 0.01, whilst also capturing demographic features with classification accuracy for sex of 84% ± 4% , and a mean absolute error of 0.79 ± 0.06 years for age prediction, highlighting its sensitivity to developmental changes. Further, we validated the approach using correlation analysis to show that deviations from the latent norms were significantly associated with multiple cognitive and behavioural measures, suggesting that variations in brain structure may reflect individual differences in neurodevelopment. Finally, we generated reference brain images that represent typical development and used them to visualise structural differences in individuals who deviate from this normative pattern. Our findings demonstrate that semi-supervised autoencoders, combined with multivariate normative modelling, offer a framework for characterizing neurodevelopmental trajectories. This approach can identify meaningful deviations associated with cognition and behaviour and has potential future applications across the lifespan.
The Elusive Chemistry of Pyrroloquinoline Quinone Dimethyl Ester Lanthanide Complexes in Biomimetic Alcohol Oxidation
2025-08-15

Since its discovery, pyrroloquinoline quinone (PQQ) has been under constant investigation regarding its efficiency in biomimetic complexes for alcohol dehydrogenation. The discovery of lanthanide (Ln) dependent methanol dehydrogenases has led to the use of lanthanide complexes bearing PQQ derivatives to oxidize alcohols. However, the mechanism of these oxidations is still a subject of debate. Herein, La 3+ and Lu 3+ complexes of PQQ dimethyl ester (PQQDME), that are able to stoichiometrically oxidize an alcohol substrate, are reported. In the presence of air, some catalytic turnover is observed, but less than with other, more heavily modified PQQ biomimetics known in the literature. To investigate the reason for this low turnover, the reduced counterpart, PQQDMEH 2 , is synthesized. It is shown that in the presence of atmospheric oxygen, the complexes of the reduced form undergo oxidation and can then also convert alcohol to aldehyde. Additionally, the involvement of radicals in the alcohol oxidation reaction and the origin and nature of these radicals is investigated.
Biallelic variants in the non-coding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes
2025-08-16

ABSTRACT Genetic variants in RNU4-2 , which encodes U4, a key non-coding small nuclear RNA (snRNA) component of the major spliceosome, were recently shown to cause a prevalent neurodevelopmental disorder (NDD) called ReNU syndrome. These variants, which almost exclusively arise de novo , act in a dominant fashion and are clustered within 18 nucleotides (nt) in the centre of RNU4-2 . Here we describe a novel recessive NDD associated with homozygous and compound heterozygous variants in RNU4-2 . We identified 32 individuals with biallelic variants outside of the 18 nt ReNU syndrome region, that cluster within other functionally important elements of U4, including the Stem II region, the k-turn motif, and the Sm protein binding site. We characterise the clinical phenotype in 27 of these individuals, demonstrating that the recessive disorder is clinically distinct from dominant ReNU syndrome and is associated with distinctive white matter abnormalities, including enlarged perivascular spaces. Together, these findings expand the genotypic and phenotypic spectrum of RNU4-2 -associated NDDs.
Beyond Estrogenicity: A Comparative Assessment of Bisphenol A and Its Alternatives in In Vitro Assays Questions Safety of Replacements
2025-08-16

Bisphenol A (BPA) is a well-known endocrine disruptor linked to numerous adverse health outcomes and was, therefore, banned in food-contact materials in the European Union. Numerous alternatives are now in commerce, but their health hazards are often inadequately addressed. This study compared BPA and 26 alternatives in six in vitro bioassays for cytotoxicity, endocrine disruption, xenobiotic metabolism, adaptive stress responses, mitochondrial toxicity, and neurotoxicity. We developed a cumulative specificity ratio score that integrates the degree of specific activation and overall toxicological activity across a test battery, enabling direct comparison of BPA with its alternatives. Several alternatives with close structural resemblance showed similar or stronger activation of the estrogen receptor α (ERα) than BPA. The lack of estrogenicity for several BPA alternatives, e.g., 4-(4-phenylmethoxyphenyl)sulfonylphenol (BPS-MPE), was accompanied by a shift toward peroxisome proliferator-activated receptor γ (PPARγ) activation, a receptor that is not relevant for BPA itself. Some alternatives additionally inhibited mitochondrial functions and caused neurotoxicity. Simulated phase I metabolism reduced the cytotoxicity of all alternatives except for methyl bis(4-hydroxyphenyl)acetate (Bz) and 4-[[4-(allyloxy)phenyl]sulfonyl]phenol (BPS-MAE), while estrogenic activity remained unchanged or decreased. This study demonstrates the utility of bioassays for rapid hazard assessment and comparative evaluation, suggesting that many BPA alternatives are regrettable substitutes, although 2,2,4,4-tetramethyl-1,3-cyclobutanediol (TMCD) is a potentially more benign alternative.
Test–Retest Reliability and Inter-Scanner Reproducibility of Improved Spinal Diffusion Tensor Imaging
2025-08-16

Background/Objectives: Spinal diffusion tensor imaging (sDTI) remains a challenging method for the selective evaluation of key anatomical structures, like pyramidal tracts (PTs) and dorsal columns (DCs), and for reliably quantifying diffusion metrics such as fractional anisotropy (FA), radial diffusivity (RD), mean diffusivity (MD), and axial diffusivity (AD). This prospective, single-center study aimed to assess the reproducibility, robustness, and reliability of an optimized axial sDTI protocol, specifically intended for long fiber tracts. Methods: We developed an optimized Stejskal–Tanner sequence for high-resolution, axial sDTI of the cervical spinal cord at 3.0 T. Using advanced standardized evaluation and post-processing methods, we estimated DTI values for PTs, DCs, and AHs at the level of the second cervical vertebra. Reliability was evaluated through repeated measurements in 16 healthy volunteers and by comparing results from two 3.0 T scanners (Magnetom Skyra and Magnetom Prisma, Siemens Healthineers, Erlangen, Germany). Reproducibility was assessed using paired t-tests, intraclass correlation coefficients (ICCs), Bland–Altman analysis, and coefficients of variation (CVs). Results: The optimized sDTI protocol demonstrated high consistency for FA between test–retest sessions and across scanners. For the Skyra, the DC region showed the highest reliability (average ICC = 0.858) followed by the PT region (average ICC = 0.789). On the Prisma, the PT region reached an average ICC of 0.854, with the DC region at 0.758. Pooled inter-scanner data indicated good-to-excellent agreement, particularly in the PT region (average ICC = 0.860). FA CVs remained low (&lt;10%) across all regions and scanners. RD showed good-to-excellent ICC values for PTs and DCs (average ICC for Skyra 0.642 and 0.769 and 0.926 and 0.830 for Prisma, respectively) but showed a higher CV between 14.6 and 19.4% for these two scanners. Conclusions: Improved sDTI offers highly reproducible FA measurements for all metrics with scanner independence, supporting its potential as a robust tool for detecting and monitoring spinal cord pathologies.
Influence of compression stockings with different compression classes on lower leg edema and perceived discomfort during a two-hour static standing exposure – a pilot study
2025-08-18

Lower leg edema (LLE) is considered a surrogate-parameter for stress on the venous system in situations with venous hypertension such as standing at work. Therapy with medical compression stockings (MCS) is well-established in chronic venous insufficiency (CVI) patients for reducing venous pressure. It remains unclear though to what extent increased levels of LLE related to prolonged standing can be diminished by MCS in healthy individuals as well as CVI patients. This paper investigated to what extent wearing MCS class I (CCL I) and II (CCL II) reduces LLE and rating of perceived discomfort (RPD) during prolonged standing among both healthy subjects (n = 32) and CVI patients (n = 12) and how wearing comfort differs between classes. This randomized cross-over trial had three conditions: two-hour standing without MCS, with CCL I (18-21 mmHg), with CCL II (23-32 mmHg). LLE was quantified using waterplethysmography and bioelectrical impedance. RPD was assessed using an 11-point Likert scale. Wearing comfort was assessed using a self-developed questionnaire. Wearing MCS statistically significantly reduced LLE in healthy subjects and CVI patients, with least edema development after wearing CCL II. RPD was reported mainly in the lower-back after two hours (mean 0.9). Wearing comfort was rated slightly better for CCL I. Healthy subjects and CVI patients who spend large parts of the day standing can decrease LLE by wearing MCS, of which CCL I may lead to better long-term compliance.