julilili42/papers huggingface dataset:
Bone Marrow Mesenchymal Stem-Cell-Derived Exosomes Ameliorate Deoxynivalenol-Induced Mice Liver Damage
2023-02-27

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. DON is mainly metabolized and detoxified by the liver. When the concentration of DON exceeds the metabolic capacity of the liver, it will trigger acute or chronic damage to the liver tissue. Previous studies demonstrated that bone marrow mesenchymal stem-cell-secreted exosomes (BMSC-exos) reduce liver injury. Therefore, we issue a hypothesis that in vitro-cultured rat BMSC-secreted exos could ameliorate liver damage after 2 mg/kg bw/day of DON exposure. In total, 144 lipids were identified in BMEC-exos, including high polyunsaturated fatty acid (PUFA) levels. BMSC-exos treatment alleviated liver pathological changes and decreased levels of alanine aminotransferase, aspartate aminotransferase, inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and lipid peroxidation. Otherwise, low or high BMSC-exos treatment obviously changes DON-induced hepatic oxylipin patterns. According to the results from our correlation network analysis, Pearson correlation coefficient analysis, and hierarchical clustering analysis, the top 10% oxidized lipids can be classified into two categories: one that was positively correlated with copper–zinc superoxide dismutase (Cu/Zn SOD) and another that was positively correlated with liver injury indicators. Altogether, BMSC-exos administration maintained normal liver function and reduced oxidative damage in liver tissue. Moreover, it could also significantly change the oxylipin profiles under DON conditions.
Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer's Disease
2023-02-27

Objective Identifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR‐tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes. We examined the cerebrospinal fluid (CSF) MTBR‐tau species in dominantly inherited Alzheimer's disease (DIAD) mutation carriers to assess the association with Alzheimer's disease (AD) biomarkers and clinical symptoms. Methods Cross‐sectional and longitudinal CSF from 229 DIAD mutation carriers and 130 mutation non‐carriers had sequential characterization of N‐terminal/mid‐domain phosphorylated tau (p‐tau) followed by MTBR‐tau species and tau positron emission tomography (tau PET), other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy. Results CSF MTBR‐tau species located within the putative “border” region and one species corresponding to the “core” region of aggregates in neurofibrillary tangles (NFTs) increased during the presymptomatic stage and decreased during the symptomatic stage. The “border” MTBR‐tau species were associated with amyloid pathology and CSF p‐tau; whereas the “core” MTBR‐tau species were associated stronger with tau PET and CSF measures of neurodegeneration. The ratio of the border to the core species provided a continuous measure of increasing amounts that tracked clinical progression and NFTs. Interpretation Changes in CSF soluble MTBR‐tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R‐specific MTBR‐tau (border) to the NFT (core) MTBR‐tau species corresponds to the pathology of NFTs in DIAD and change with disease progression. The dynamics between different MTBR‐tau species in the CSF may serve as a marker of tau‐related disease progression and target engagement of anti‐tau therapeutics. ANN NEUROL 2023;93:1158–1172
Preferential production and secretion of the complement regulator factor H-like protein 1 (FHL-1) by human myeloid cells
2023-02-27

Factor H is a pivotal complement regulatory protein that is preferentially produced by the liver and circulates in high concentrations in serum. There has been an increasing interest in the extrahepatic production of complement factors, including by cells of the immune system, since this contributes to non-canonical functions of local complement activation and regulation. Here we investigated the production and regulation of factor H and its splice variant factor H-like protein 1 (FHL-1) by human myeloid cells. As validation, we confirmed the predominant presence of intact factor H in serum, despite a strong but comparable mRNA expression of CFH and FHL1 in liver. Comparable levels of CFH and FHL1 were also observed in renal tissue, although a dominant staining for FHL-1 was shown within the proximal tubules. Human in vitro generated pro- and anti-inflammatory macrophages both expressed and produced factor H/FHL-1, but this was strongest in pro-inflammatory macrophages. Production was not affected by LPS activation, but was increased upon stimulation with IFN-γ or CD40L. Importantly, in both macrophage subsets mRNA expression of FHL1 was significantly higher than CFH. Moreover, production of FHL-1 protein could be confirmed using precipitation and immunoblotting of culture supernatants. These data identify macrophages as producers of factor H and FHL-1, thereby potentially contributing to local complement regulation at sites of inflammation.
Effects of flexibility in coarse-grained models for bovine serum albumin and immunoglobulin G
2023-02-27

We construct a coarse-grained, structure-based, low-resolution, 6-bead flexible model of bovine serum albumin (BSA, PDB: 4F5S), which is a popular example of a globular protein in biophysical research. The model is obtained via direct Boltzmann inversion using all-atom simulations of a single molecule, and its particular form is selected from a large pool of 6-bead coarse-grained models using two suitable metrics that quantify the agreement in the distribution of collective coordinates between all-atom and coarse-grained Brownian dynamics simulations of solutions in the dilute limit. For immunoglobulin G (IgG), a similar structure-based 12-bead model has been introduced in the literature [Chaudhri et al., J. Phys. Chem. B 116, 8045 (2012)] and is employed here to compare findings for the compact BSA molecule and the more anisotropic IgG molecule. We define several modified coarse-grained models of BSA and IgG, which differ in their internal constraints and thus account for a variation of flexibility. We study denser solutions of the coarse-grained models with purely repulsive molecules (achievable by suitable salt conditions) and address the effect of packing and flexibility on dynamic and static behavior. Translational and rotational self-diffusivity is enhanced for more elastic models. Finally, we discuss a number of effective sphere sizes for the BSA molecule, which can be defined from its static and dynamic properties. Here, it is found that the effective sphere diameters lie between 4.9 and 6.1 nm, corresponding to a relative spread of about ±10% around a mean of 5.5 nm.
Plants cultivated for ecosystem restoration can evolve towards a domestication syndrome
2023-02-27

Abstract The UN Decade on Ecosystem Restoration calls for upscaling restoration efforts, but many terrestrial restoration projects are constrained by seed availability. To overcome these constraints, wild plants are increasingly propagated on farms to produce seeds for restoration projects. During on-farm propagation, the plants face non-natural conditions with different selection pressures, and they might evolve adaptations to cultivation that parallel those of agricultural crops, which could be detrimental to restoration efforts. To test this, we compared traits of 19 species grown from wild-collected seeds to those from their farm-propagated offspring of up to four cultivation generations, produced by two European seed growers, in a common garden experiment. We found that some plants rapidly evolved across cultivated generations towards increased size and reproduction, lower within-species variability, and more synchronized flowering. In one species, we found evolution towards less seed shattering. These trait changes are typical signs of the crop domestication syndrome, and our study demonstrates that it can also occur during cultivation of wild plants, within only few cultivated generations. However, there was large variability between cultivation lineages, and the observed effect sizes were generally rather moderate, which suggests that the detected evolutionary changes are unlikely to compromise farm-propagated seeds for ecosystem restoration. To mitigate the potential negative effects of unintended selection, we recommend to limit the maximum number of generations the plants can be cultivated without replenishing the seed stock from new wild collections. Significance Statement Globally upscaling demands for native seeds for ecosystem restoration can be covered by agricultural seed propagation. Yet, agricultural practice can unintentionally select for specific traits and reduce adaptive variability, which could affect plant performance once sown back to the wild. We show, across 19 wild species, two seed producers and up to four consecutive cultivated generations, that some plants under cultivation evolved higher vigor, reduced adaptive variability, synchronized flowering and in one case, reduced seed shattering. Yet, there were substantial differences among cultivation lineages, with negligible changes in most, and large changes only in a few cases. Substantial unintended evolution in cultivation is thus rather an exception than the rule.
Mobilfunk ja – aber Masten und Antennen bitte nicht hier! Diskursive Aushandlungsprozesse um die Standortwahl von Sendeanlagen in Deutschland
2023-02-27

A stable and nationwide mobile network coverage is increasingly regarded as essential. This requires an expansion of mobile networks throughout the country. However, the installation of masts and antennas has often been the subject of conflict in Germany, especially due to fears about potential health effects of electromagnetic fields. Transmitters become both a trigger and a target of social protests. From a discourse-theoretical perspective, we identify central lines of argumentation in the German cellular network conflicts. A triangulation of quantitatively oriented and qualitative analysis components forms the methodological basis. Regional case studies provide an opportunity to identify local differences. A comparison of past and recent conflicts reveals discursive shifts over time. Debates about the possible health effects of mobile radio were particularly contentious in the context of UMTS mobile phone expansion at the turn of the millennium. The (planned) installation of transmitters at the local level often sparked this discussion. During the expansion of the 5G network, in addition to the debate about the health risks of the technology, questions are now being raised about whether and to whom the expansion is necessary. Compared to the previous period of investigation, local conflicts about transmitters now appear to be less virulent and can be found primarily in southern and southwestern Germany.
Ready-to-use nanopore platform for ethanolamine quantification using an aptamer-based strand displacement assay
2023-02-27

Abstract In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance because small molecules are difficult or expensive to detect using available methods such as HPLC or LC-MS. Moreover, DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Here, we describe a method for the quantification of ethanolamine using Oxford Nanopore’s ready-to-use sequencing platform. To this end, we have developed a strand displacement assay using a binding ethanolamine aptamer and magnetic beads. The displaced aptamer can be detected using the MinION® nanopores and analysed/quantified using our in-house developed analysis software.
Freshwater Landscape Reconstruction from the Bronze Age Site of Borsodivánka (North-Eastern Hungary)
2023-02-27

This multiproxy work presents the archeozoological analysis of fish and microvertebrate remains from the Middle Bronze Age tell site of Borsodivánka (Borsod Plain, North-eastern Hungary). The fish faunal assemblage provides valuable data on the choice of exploited consumption patterns, taphonomy, and aquatic paleoenvironmental conditions at the site during the Bronze Age. Only freshwater taxa are present in the assemblage, for example, northern pike (Esox lucius); cyprinids: roach (Rutilus rutilus), common carp (Cyprinus carpio), common chub (Squalius cephalus) and common nase (Chondrostoma nasus); and percids: European perch (Perca fluviatilis) and pikeperch (Sander lucioperca). Herpetofaunal and micromammal remains are also part of this study, improving our knowledge of the site’s freshwater ecosystem. The grass snake (Natrix cf. natrix) and the European pond terrapin (Emys orbicularis), typical of aquatic ecosystems, are associated with the Aesculapian ratsnake (Zamenis longissimus), more typical of forest, shrubland, and grassland. The presence of amphibians such as toads (Bufo/Bufotes sp.) and frogs (Rana sp.) complete the herpetofaunal list. The microvertebrates also support a mature fluvial system, as represented by taxa like the European water vole (Arvicola amphibius). Other micromammals are present, such as the wood mouse (Apodemus sylvaticus), the group of the common/field vole (Microtus arvalis/agrestis), the European mole (Talpa europaea), and the house mouse (Mus musculus). All of them are common in forests, shrubland, and grassland. However, the commensal house mouse is more commonly associated with anthropogenic areas. In conclusion, Borsodivánka is characterized by a diverse landscape mosaic, displayed by the co-existence of a well-developed forest and a freshwater inland ecosystem with agricultural land in the wider area. Finally, the Tisza River and its flood plain represented the main water source close to the site, distinguished by the dominance of fish species from deep and slow-flowing waters.
Chatbots for future docs: exploring medical students’ attitudes and knowledge towards artificial intelligence and medical chatbots
2023-02-28

Artificial intelligence (AI) in medicine and digital assistance systems such as chatbots will play an increasingly important role in future doctor - patient communication. To benefit from the potential of this technical innovation and ensure optimal patient care, future physicians should be equipped with the appropriate skills. Accordingly, a suitable place for the management and adaptation of digital assistance systems must be found in the medical education curriculum. To determine the existing levels of knowledge of medical students about AI chatbots in particular in the healthcare setting, this study surveyed medical students of the University of Luebeck and the University Hospital of Tuebingen. Using standardized quantitative questionnaires and qualitative analysis of group discussions, the attitudes of medical students toward AI and chatbots in medicine were investigated. From this, relevant requirements for the future integration of AI into the medical curriculum could be identified. The aim was to establish a basic understanding of the opportunities, limitations, and risks, as well as potential areas of application of the technology. The participants (<i>N</i> = 12) were able to develop an understanding of how AI and chatbots will affect their future daily work. Although basic attitudes toward the use of AI were positive, the students also expressed concerns. There were high levels of agreement regarding the use of AI in administrative settings (83.3%) and research with health-related data (91.7%). However, participants expressed concerns that data protection may be insufficiently guaranteed (33.3%) and that they might be increasingly monitored at work in the future (58.3%). The evaluations indicated that future physicians want to engage more intensively with AI in medicine. In view of future developments, AI and data competencies should be taught in a structured way during the medical curriculum and integrated into curricular teaching.
Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial
2023-02-28

PURPOSE Patients with relapsed high-risk neuroblastoma (rHR-NB) have a poor prognosis. We hypothesized that graft-versus-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells (haplo-SCT) exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta (DB). This phase I/II trial assessed safety, feasibility, and outcomes of immunotherapy with DB plus subcutaneous interleukin-2 (scIL2) after haplo-SCT in patients with rHR-NB. METHODS Patients age 1-21 years underwent T-/B-cell–depleted haplo-SCT followed by DB and scIL2. The primary end point ‘success of treatment’ encompassed patients receiving six cycles, being alive 180 days after end of trial treatment without progressive disease, unacceptable toxicity, acute graft-versus-host-disease (GvHD) ≥grade 3, or extensive chronic GvHD. RESULTS Seventy patients were screened, and 68 were eligible for immunotherapy. Median number of DB cycles was 6 (range, 1-9). Median number of scIL2 cycles was 3 (1−6). The primary end point was met by 37 patients (54.4%). Median observation time was 7.8 years. Five-year event-free survival (EFS) and overall survival from start of trial treatment were 43% (95% CI, 31 to 55) and 53% (95% CI, 41 to 65), respectively. Five-year EFS among patients in complete remission (CR; 52%; 95% CI, 31 to 69) or partial remission (44%; 95% CI, 27 to 60) before immunotherapy were significantly better compared with patients with nonresponse/mixed response/progressive disease (13%; 95% CI, 1 to 42; P = .026). Overall response rate in 43 patients with evidence of disease after haplo-SCT was 51% (22 patients), with 15 achieving CR (35%). Two patients developed GvHD grade 2 and 3 each. No unexpected adverse events occurred. CONCLUSION DB therapy after haplo-SCT in patients with rHR-NB is feasible, with low risk of inducing GvHD, and results in long-term remissions likely attributable to increased antineuroblastoma activity by donor-derived effector cells.
Role of bioavailability and protein binding of four anionic perfluoroalkyl substances in cell-based bioassays for quantitative in vitro to in vivo extrapolations
2023-02-28

Perfluoroalkyl substances (PFAS) are persistent and pose a risk to human health. High throughput screening (HTS) cell-based bioassays may inform risk assessment of PFAS provided that quantitative in vitro to in vivo extrapolation (QIVIVE) can be developed. The QIVIVE ratio is the ratio of nominal (C<sub>nom</sub>) or freely dissolved concentration (C<sub>free</sub>) in human blood to C<sub>nom</sub> or C<sub>free</sub> in the bioassays. Considering that the concentrations of PFAS in human plasma and in vitro bioassays may vary by orders of magnitude, we tested the hypothesis that anionic PFAS bind to proteins concentration-dependently and therefore the binding differs substantially between human plasma and bioassays, which has an impact on QIVIVE. Solid phase microextraction (SPME) with C18-coated fibers served to quantify the C<sub>free</sub> of four anionic PFAS (perfluorobutanoate (PFBA), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS)) in the presence of proteins and lipid, medium components, cells and human plasma over five orders of magnitude in concentrations. The C18-SPME method was used to quantify the non-linear binding to proteins, human plasma and medium, and the partition constants to cells. These binding parameters were used to predict C<sub>free</sub> of PFAS in cell bioassays and human plasma by a concentration-dependent mass balance model (MBM). The approach was illustrated with a reporter gene assay indicating activation of the peroxisome proliferator-activated receptor gamma (PPARγ-GeneBLAzer). Blood plasma levels were collected from literature for occupational exposure and the general population. The QIVIVE<sub>nom</sub> ratios were higher than the QIVIVE<sub>free</sub> ratios due to the strong affinity to proteins and large differences in protein contents between human blood and bioassays. For human health risk assessment, the QIVIVE<sub>free</sub> ratios of many in vitro assays need to be combined to cover all health relevant endpoints. If C<sub>free</sub> cannot be measured, they can be estimated with the MBM and concentration-dependent distribution ratios.
HESS J1809−193: A halo of escaped electrons around a pulsar wind nebula?
2023-02-28

Context. HESS J1809−193 is an unassociated very-high-energy γ -ray source located on the Galactic plane. While it has been connected to the nebula of the energetic pulsar PSR J1809−1917, supernova remnants and molecular clouds present in the vicinity also constitute possible associations. Recently, the detection of γ -ray emission up to energies of ∼100 TeV with the HAWC observatory has led to renewed interest in HESS J1809−193. Aims. We aim to understand the origin of the γ -ray emission of HESS J1809−193. Methods. We analysed 93.2 h of data taken on HESS J1809−193 above 0.27 TeV with the High Energy Stereoscopic System (H.E.S.S.), using a multi-component, three-dimensional likelihood analysis. In addition, we provide a new analysis of 12.5 yr of Fermi -LAT data above 1 GeV within the region of HESS J1809−193. The obtained results are interpreted in a time-dependent modelling framework. Results. For the first time, we were able to resolve the emission detected with H.E.S.S. into two components: an extended component (modelled as an elongated Gaussian with a 1- σ semi-major and semi-minor axis of ∼0.62° and ∼0.35°, respectively) that exhibits a spectral cutoff at ∼13 TeV, and a compact component (modelled as a symmetric Gaussian with a 1- σ radius of ∼0.1°) that is located close to PSR J1809−1917 and shows no clear spectral cutoff. The Fermi -LAT analysis also revealed extended γ -ray emission, on scales similar to that of the extended H.E.S.S. component. Conclusions. Our modelling indicates that based on its spectrum and spatial extent, the extended H.E.S.S. component is likely caused by inverse Compton emission from old electrons that form a halo around the pulsar wind nebula. The compact component could be connected to either the pulsar wind nebula or the supernova remnant and molecular clouds. Due to its comparatively steep spectrum, modelling the Fermi -LAT emission together with the H.E.S.S. components is not straightforward.