julilili42/papers huggingface dataset:
Diversity of Neurotransmitter-Producing Human Skin Commensals
2024-11-17

Recent findings indicate that human microbiota can excrete trace amines, dopamine, and serotonin. These neurotransmitters (NTs) can either affect classical neurotransmitter signaling or directly trigger trace amine-associated receptors (TAARs), with still unclear consequences for host physiology. Compared to gut microbiota, less information is available on the role of skin microbiota in NT production. To explore this, 1909 skin isolates, mainly from the genera Staphylococcus, Bacillus, and Corynebacterium, were tested for NT production. Only 6.7% of the isolates were capable of producing NTs, all of which belonged to the Staphylococcus genus. Based on substrate specificity, we identified two distinct profiles among the NT producers. One group primarily produced tryptamine (TRY) and phenylethylamine (PEA), while the other mainly produced tyramine (TYM) and dopamine (Dopa). These differing production profiles could be attributed to the activity of two distinct aromatic amino acid decarboxylase enzymes, SadA and TDC, responsible for generating the TRY/PEA and TYM/Dopa product spectra, respectively. SadA and TDC orthologues differ in structure and size; SadA has approximately 475 amino acids, whereas the TDC type consists of about 620 amino acids. The genomic localization of the respective genes also varies: tdc genes are typically found in small, conserved gene clusters, while sadA genes are not. The heterologous expression of sadA and tdc in Escherichia coli yielded the same product spectrum as the parent strains. The possible effects of skin microbiota-derived NTs on neuroreceptor signaling in the human host remain to be investigated.
Frequency and clinical associations of common mental disorders in adults with high‐grade glioma—A multicenter study
2024-11-17

Abstract Background One third of adults with cancer suffer from common mental disorders in addition to their malignant disease. However, it is unknown whether this proportion is the same in patients who have brain tumors and which factors modulate the risk for psychiatric comorbidity. Methods In a multicenter study, patients with high‐grade glioma at 13 neurooncology clinics were enrolled consecutively and interviewed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID) to diagnose common mental disorders. Predictors of psychiatric comorbidity were investigated using binary logistic regression. Results Six hundred ninety‐one patients were interviewed. The proportion of patients who had mental disorders was 31% (95% confidence interval [CI], 28%–35%). There was evidence for an association of psychiatric comorbidity with the following factors: younger age (odds ratio [OR], 1.9; 95% CI, 1.1–3.4; p = .04), stable disease versus complete remission (OR, 1.7; 95% CI, 1.1–2.8; p = .04), lower income (OR, 1.7; 95% CI, 1.0–2.8; p = .04), living alone (OR, 1.6; 95% CI, 1.0–2.6; p = .05), fatigue (OR, 1.6; 95% CI, 1.1–2.4; p = .03), and impaired cognitive functioning (OR, 2.3; 95% CI, 1.5–3.6; p &lt; .01). There was no evidence for independent effects of gender, histology, affected lobe, time since diagnosis, or employment status. Conclusions Approximately one third of adult patients with high‐grade glioma may suffer from a clinically relevant common mental disorder, without notable disparity between the genders. In particular, clinicians should pay attention to possible comorbidities for cases in which patients exhibit compromised subjective cognitive function, are younger than 50 years, maintain a state of stable disease, or live alone.
Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer’s disease
2024-11-18

Abstract Disease-modifying therapies for Alzheimer’s disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating mutation carriers from non-carrier controls 10-20 years before the estimated onset of clinical symptoms, depending on the statistical model used. However, after symptom onset the rate of change in CSF NfL continued to increase steadily, whereas the rate of change in plasma NfL leveled off. Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration. These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients.
Machine Learning Enhances Soil Aggregate Stability Mapping for Effective Land Management in a Semi-Arid Region
2024-11-18

Soil aggregate stability (SAS) is needed to evaluate the soil’s resistance to degradation and erosion, especially in semi-arid regions. Traditional laboratory methods for assessing SAS are labor-intensive and costly, limiting timely and cost-effective monitoring. Thus, we developed cost-efficient wall-to-wall spatial prediction maps for two fundamental SAS proxies [mean weight diameter (MWD) and geometric mean diameter (GMD)], across a 5000-hectare area in Southwest Iran. Machine learning algorithms coupled with environmental and soil covariates were used. Our results showed that topographic covariates were the most influential covariates in predicting these SAS proxies. Overall, our SAS maps are valuable tools for sustainable soil and natural resource management, enabling decision-making for addressing potential soil degradation and promoting sustainable land use in semi-arid regions.
Covalent Fragments Acting as Tyrosine Mimics for Mutant p53-Y220C Rescue by Nucleophilic Aromatic Substitution
2024-11-18

The tumor suppressor p53 is frequently mutated in human cancers. The Y220C mutant is the ninth most common p53 cancer mutant and is classified as a structural mutant, as it leads to strong thermal destabilization and degradation by creating a solvent-accessible hydrophobic cleft. To identify small molecules that thermally stabilize p53, we employed DSF to screen S<sub>N</sub>Ar-type electrophiles from our covalent fragment library (CovLib) for binding to different structural (Y220C, R282W) and DNA contact (R273H) mutants of p53. The reactive fragments SN001, SN006, and SN007 were detected to specifically stabilize Y220C, indicating the arylation of Cys220 in the mutational cleft, as confirmed by X-ray crystallography. The fragments occupy the central cavity and mimic the ring system of the WT tyrosine lost by the mutation. Surpassing previously reported noncovalent ligands, SN001 stabilized T-p53C-Y220C concentration-dependently up to 4.45 °C and, due to its small size, represents a promising starting point for optimization.
How people (fail to) control the influence of affective stimuli on attitudes.
2024-11-18

People's attitudes toward almost any stimulus (e.g., brands, people, food items) can change in line with the valence of co-occurring stimuli (e.g., images, messages, other people), a phenomenon known as the evaluative conditioning (EC) effect. Recent research has shown that EC effects are not always controlled, which is problematic in many circumstances (e.g., advertising, misinformation). We examined conditions under which uncontrolled EC effects are more likely to reflect retrieval failures or uncontrolled encoding processes. To provide an experimental test of this question, we propose that people can either integrate or add validity information to the stimulus valence. Specifically, we propose that controlled processes can integrate validity information into the stored valence representations mostly when validity information is provided at the time of exposure to the evaluative information. Control attempts taking place later are more likely to add than to integrate the validity information to the stored representation. Moreover, if validity information is merely added to the stimulus valence as compared to integrated, forgetting this information potentially inflates indices of uncontrolled processes. Our findings demonstrate important boundary conditions for the interpretation of measures of uncontrolled encoding processes. Nevertheless, they provide further evidence that uncontrolled encoding processes can contribute to EC effects. We discuss implications for theories of attitude change and for protection from misinformation. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
Constraints on self-interaction cross-sections of dark matter in universal bound states from direct detection
2024-11-18

Abstract <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>Λ</mml:mi> </mml:math> -Cold Dark Matter ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>Λ</mml:mi> </mml:math> CDM) has been successful at explaining the large-scale structures in the universe but faces severe issues on smaller scales when compared to observations. Introducing self-interactions between dark matter particles claims to provide a solution to the small-scale issues in the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>Λ</mml:mi> </mml:math> CDM simulations while being consistent with the observations at large scales. The existence of the energy region in which these self-interactions between dark matter particles come close to saturating the S-wave unitarity bound can result in the formation of dark matter bound states called darkonium. In this scenario, all the low energy scattering properties are determined by a single parameter, the inverse scattering length <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>γ</mml:mi> </mml:math> . In this work, we set bounds on <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>γ</mml:mi> </mml:math> by studying the impact of darkonium on the observations at direct detection experiments using data from CRESST-III and XENON1T. The exclusion limits on <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>γ</mml:mi> </mml:math> are then subsequently converted to exclusion limits on the self-interaction cross-section and compared with the constraints from astrophysics and N-body simulations.
Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and its Variants Displaying Potent Antiviral Activity
2024-11-18

The main protease (Mpro) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 Mpro inhibitors, including compounds 8n (IC50 = 0.0752 μM), 8p (IC50 = 0.0887 μM), 8r (IC50 = 0.0199 μM), 10a (IC50 = 0.0376 μM), 10c (IC50 = 0.0177 μM), and 10f (IC50 = 0.0130 μM). Most of them additionally inhibited cathepsin L and were also active against SARS-CoV-1 and MERS-CoV Mpro. In Calu-3 cells, several inhibitors, including 8r, 10a, and 10c, displayed high antiviral activity in the nanomolar range without showing cellular toxicity. The co-crystal structure of SARS-CoV-2 Mpro in complex with 8p revealed covalent binding to the enzyme’s catalytic residue Cys145 and showed specific, unprecedented interactions within the substrate binding pocket. Compounds 8n and 10c, especially 8n, were effective against a panel of naturally occurring nirmatrelvir-resistant mutants, particularly E166V, and showed metabolic stability and additional favorable pharmacokinetic properties, making it a suitable candidate for further preclinical development.
Gaussian Opacity Fields: Efficient Adaptive Surface Reconstruction in Unbounded Scenes
2024-11-19

Recently, 3D Gaussian Splatting (3DGS) has demonstrated impressive novel view synthesis results, while allowing the rendering of high-resolution images in real-time. However, leveraging 3D Gaussians for surface reconstruction poses significant challenges due to the explicit and disconnected nature of 3D Gaussians. In this work, we present Gaussian Opacity Fields (GOF), a novel approach for efficient, high-quality, and adaptive surface reconstruction in unbounded scenes. Our GOF is derived from ray-tracing-based volume rendering of 3D Gaussians, enabling direct geometry extraction from 3D Gaussians by identifying its levelset, without resorting to Poisson reconstruction or TSDF fusion as in previous work. We approximate the surface normal of Gaussians as the normal of the ray-Gaussian intersection plane, enabling the application of regularization that significantly enhances geometry. Furthermore, we develop an efficient geometry extraction method utilizing Marching Tetrahedra, where the tetrahedral grids are induced from 3D Gaussians and thus adapt to the scene's complexity. Our evaluations reveal that GOF surpasses existing 3DGS-based methods in surface reconstruction and novel view synthesis. Further, it compares favorably to or even outperforms, neural implicit methods in both quality and speed.
Exploring the cognitive underpinnings of early hominin stone tool use through an experimental EEG approach
2024-11-19

Abstract Technological innovation has been crucial in the evolution of our lineage, with tool use and production linked to complex cognitive processes. While previous research has examined the cognitive demands of early stone toolmaking, the neurocognitive aspects of early hominin tool use remain largely underexplored. This study relies on electroencephalography to investigate brain activation patterns associated with two distinct early hominin tool-using behaviors: forceful hammerstone percussion, practiced by both humans and non-human primates and linked to the earliest proposed stone tool industries, and precise flake cutting, an exclusive hominin behavior typically associated with the Oldowan. Our results show increased engagement of the frontoparietal regions during both tasks. Furthermore, we observed significantly increased beta power in the frontal and centroparietal areas when manipulating a cutting flake compared to a hammerstone, and increased beta activity over contralateral frontal areas during the aiming (planning) stage of the tool-using process. This original empirical evidence suggests that certain fundamental brain changes during early hominin evolution may be linked to precise stone tool use. These results offer new insights into the complex interplay between technology and human brain evolution and encourage further research on the neurocognitive underpinnings of hominin tool use.
Vertebrate vision is ancestrally based on competing cone circuits
2024-11-19

Vision first evolved in the water, where light becomes increasingly monochromatic with viewing distance. The presence of spectrally broad (′white′) light is therefore the exclusive remit of the visual foreground. However, if and how aquatic visual systems exploit this ′white effect′ as an inductive bias, for example to judge distance, remains unknown. By combining two-photon imaging with hyperspectral stimulation, genetic cone-type ablation, and behaviour, we here show that zebrafish suppress neural responses to the visual background by contrasting ′greyscale′ and ′colour′ circuits that emerge at the first synapse of vision. To do so, zebrafish use an early retinal architecture that fundamentally differs from that of mammals: Rather than combining cone signals to drive the retinal output leading to behaviour, zebrafish vision is built around competing ancestral cone systems: Red/UV versus green/blue. Of these, the non-opponent red and UV cones, which are retained in mammals, are necessary and sufficient for vision. By contrast, the colour opponent green and blue cones, which are lost in mammals, form a net-suppressive ′auxiliary′ system that shape the ′core′ drive from red and UV cones. Our insights challenge the long–held notions that cones act in concert to drive visual behaviour, and that their spectral diversity primarily serves colour vision. Instead, we posit that vertebrate vision is ancestrally built upon opposing cone systems that emerged to exploit the strong spectral interactions of light with water. This alternative view points at terrestrialisation, not nocturnalisation, as the leading driver for visual circuit reorganisation in mammals.
Solid-State Nanopores for Spatially Resolved Chemical Neuromodulation
2024-11-19

Most neural prosthetic devices are based on electrical stimulation, although the modulation of neuronal activity by a localized chemical delivery would better mimic physiological synaptic machinery. In the past decade, various drug delivery approaches attempted to emulate synaptic transmission, although they were hampered by poor retention of their cargo while reaching the target destination, low spatial resolution, and poor biocompatibility and stability of the materials involved. Here, we propose a planar solid-state device for multisite neurotransmitter translocation at the nanoscale consisting of a nanopatterned ceramic membrane connected to a reservoir designed to store neurotransmitters. We achieved diffusion-mediated glutamate stimulation of primary neurons, while we showed the feasibility to translocate other molecules through the pores by either pressure or diffusion, proving the versatility of the proposed technology. Finally, the system proved to be a promising neuronal stimulation interface in mice and nonhuman primates <i>ex vivo</i>, paving the way toward a biomimetic chemical stimulation in neural prosthetics and brain machine interfaces.
Deep learning reconstruction for accelerated high-resolution upper abdominal MRI improves lesion detection without time penalty
2024-11-19

HR-VIBE<sub>DL</sub> images of the upper abdomen result in superior image quality, better lesion conspicuity, and improved lesion detection without time penalty by comparsion with conventional VIBE images.
Perisaccadic perceptual mislocalization strength depends on the visual appearance of saccade targets
2024-11-19

Brief visual probes are grossly mislocalized when presented in the temporal vicinity of saccades. Although the mechanisms of such mislocalization are still under investigation, one component of them could derive from corollary discharge signals associated with saccade movement commands. Here, we were motivated by the observation that superior colliculus movement bursts, one source of corollary discharge, vary with saccade target image appearance. If so, then perisaccadic mislocalization should also do so, which we confirmed.
Feasibility of Non-Invasive Sentinel Lymph Node Identification in Early-Stage NSCLC Through Ultrasound Guided Intra-Tumoral Injection of 99mTc-Nanocolloid and Iodinated Contrast Agent During Navigation Bronchoscopy
2024-11-19

Background: As the first sentinel lymph nodes (SLN) in lung cancer are most likely to harbor metastasis, their non-invasive identification could have a significant role in future treatments. We investigated the feasibility of adding an SLN procedure to a diagnostic navigation bronchoscopy. Methods: Thirty-one patients were included for injection of 99mTc-nanocolloid and an iodinated contrast agent intra-/peritumorally and assessment of tracer dissipation via SPECT and CBCT imaging. Injections were performed endobronchially using a multi-modal catheter (Pioneer Plus), combining radial ultrasound and an angulated retractable needle to place injections under fluoroscopy and real-time ultrasound. Results: The injection of an imaging tracer was feasible in all cases using the catheter. Ultrasound visualized 29/30 tumors, and tracer injection was performed in 100% of patients. An SLN was subsequently identified in 10 out of 31 cases (32.3%) via SPECT/CT imaging. Iodinated contrast agent injection under CBCT imaging prior to 99mTc nanocolloid injection visualized dissipation pathways and enabled needle relocation for subsequent 99mTc-nanocolloid injection. Conclusions: Performing imaging tracer injections with a multi-modal catheter provided safe and local depot placement immediately following diagnostic navigation bronchoscopy. SPECT/CT imaging using 99mTc-nanocolloid showed inconsistent results for SLN identification.
Uncertainty mapping and probabilistic tractography using Simulation-based Inference in diffusion MRI: A comparison with classical Bayes
2024-11-19

Abstract Simulation-Based Inference (SBI) has recently emerged as a powerful framework for Bayesian inference: Neural networks are trained on simulations from a forward model, and learn to rapidly estimate posterior distributions. We here present an SBI framework for parametric spherical deconvolution of diffusion MRI data of the brain. We demonstrate its utility for estimating white matter fibre orientations, mapping uncertainty of voxel-based estimates and performing probabilistic tractography by spatially propagating fibre orientation uncertainty. We conduct an extensive comparison against established Bayesian methods based on Markov-Chain Monte-Carlo (MCMC) and find that: a) in-silico training can lead to calibrated SBI networks with accurate parameter estimates and uncertainty mapping for both single- and multi-shell diffusion MRI, b) SBI allows amortised inference of the posterior distribution of model parameters given unseen observations, which is orders of magnitude faster than MCMC, c) SBI-based tractography yields reconstructions that have a high level of agreement with their MCMC-based counterparts, equal to or higher than scan-rescan reproducibility of estimates. We further demonstrate how SBI design considerations (such as dealing with noise, defining priors and handling model selection) can affect performance, allowing us to identify optimal practices. Taken together, our results show that SBI provides a powerful alternative to classical Bayesian inference approaches for fast and accurate model estimation and uncertainty mapping in MRI.
The German Bible from Martin Luther to Johann Eck
2024-11-19

Abstract The Middle Ages provided German-speaking readers with a good number of vernacular translations. All of them followed the Vulgate with the exception of Luther’s which took Erasmus’s Greek New Testament as a basis for what would become his tremendously successful translation of the New Testament. The Scripture principle and the idea of the priesthood of all baptized together formed the Reformation’s impulse in translating the Bible. Even Catholic authors could not ignore joining in the success of the Bible in the vernacular. Jerome Emser edited a translation of the New Testament in 1527 meant to replace Luther’s version with a Catholic one, which nonetheless followed Luther’s translation almost completely, even as Emser raised some issues about alleged dogmatic prejudices staining Luther’s efforts. In the end, the history of German Bible translations in the Reformation era is a story that revolves around the Luther Bible.