bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE FIRST COMPREHENSIVE FORENSIC GENETIC STUDY OF A MEMBER OF CHRISTOPHER COLUMBUS’ FAMILY: HIS GREAT-GREAT-GRANDSON
Authors: Navarro-Vera I , Yravedra Saez de los Terreros J , Bonilla A , Tirapu M , Albert M , Jímenez P , Herránz D , García C 
Published: October 2024

ABSTRACTThe present study has successfully obtained genetic information that allow the identification from direct descendants of Christopher Columbus, dating from 1526 to 1734. This represents the first achievement of this unique objective. The results obtained from the analysed samples, characterized by their significant antiquity, yield exceptional insights into forensic genetics and its newest protocols and methodologies applied to the study of ancient skeletal remains. This work presents the preliminary results of the whole family study using massive parallel sequencing, focusing on the autosomal Single Nucleotide Polymorphism (SNP) and Short Tandem Repeats (STR) markers, including their flanking region sequences, as well as ancestry informative markers (AIMS) of the great-great-grandson of the discoverer.The results of this project pave the way towards the application of new sequencing technologies for the study of genetic evolution, biogeographical origins and forensic identification of historical characters.
General purpose genotypes and evolution of higher plasticity in clonality underlie knotweed invasion
Authors: Wang Shengyu , Liao Zhiyong , Cao Peipei , Schmid Marc W. , Zhang Lei , Bi Jingwen , Endriss Stacy B. , Zhao Yujie , Parepa Madalin , Hu Wenyi , Akamine Hikaru , Wu Jihua , Ju Ruiting , Bossdorf Oliver , Richards Christina L. , Li Bo 
Published: October 2024

AbstractMany widespread invasive plant species express high phenotypic variation across novel environments, providing a unique opportunity to examine ecological and evolutionary dynamics under global change. However, biogeographical studies often lack information about the origin of introduced populations, limiting our understanding of post-introduction evolution of introduced species in the new range. Here, we assessed the responses ofReynoutria japonicafrom 128 populations spanning three latitudinal transects in the native ranges of China and Japan, and the introduced ranges of North America and Europe. When grown in two common gardens in the native range, plants from introduced populations in North America and Europe differed in almost all traits from those from native Chinese populations, but were similar to plants from native Japanese populations. Compared to Chinese populations, North American, European and Japanese populations expressed lower trait values and plasticity in most traits. However, plants from both introduced ranges and from Japanese populations expressed higher clonality and plasticity in clonality than plants from Chinese populations. In addition, introduced populations expressed higher plasticity in clonality but lower plasticity in basal diameter compared to Japanese populations. Our study showed heritable differences in phenotypes between plants from the native ranges of Japan and China, and those from the introduced ranges were similar to the putative source of origin in Japan. However, we found that introduced populations may have evolved higher plasticity in clonal growth. Our findings emphasize the critical role of clonality and plasticity in invasion success, demonstrating the importance of discriminating between source and non-source native populations to identify ecological and evolutionary responses of invasive plants to novel environments.
The impact of a fairytale-like story on the food choices of preschool children
Authors: Zahedi Anoushiravan , Katembu Stephen , Sind Sharon Michelle , Sommer Undine , Kimamo Charles , Sommer Werner 
Published: October 2024

AbstractThe ongoing obesity epidemic is an indicator that traditional efforts towards diet change are insufficient, and interventions focusing mainly on restrictions of unhealthy food are of limited success. Therefore, approaches targeting food preferences should be integral in counteracting the current epidemic. However, food preferences are affected by a multitude of factors and are usually resistant to changes later in life. Hence, we tested whether the food choices of preschool children can be changed by a child-appropriate, interactive, fairytale-like narrative. We used two interactive stories: the first (experimental) story was about how two protagonists of similar age as the participants saved their hometown from being drained of color with the help of magic fruits or vegetables, while the second (control) story consisted of a similar plot that did not mention food. In Experiment 1, we used a crossover design with a one-week baseline measurement. After the experimental stories, healthy food choices (i.e., pieces of fruit vs. cookies, sweets, or cake) increased significantly relative to the one-week baseline, whereas no change was observed after the control story. In preregistered Experiment 2, we replicated these results with vegetables as healthy options using a random control design and investigated the longevity of the effects. The food-story effect on vegetable choices was similar to fruits (Exp. 1) and lasted for two weeks. These findings demonstrate that appropriate narratives about food can have a strong and lasting effect on the healthy food choices of preschool children and might promote healthy food consumption if incorporated into nutrition education.
National Patterns of Remote Patient Monitoring Service Availability at US Hospitals and their Readmission Performance for Cardiovascular Conditions
Authors: Pedroso Aline F. , Lin Zhenqiu , Ross Joseph S. , Khera Rohan 
Published: October 2024

ABSTRACTBackgroundDigital remote patient monitoring (RPM) enables longitudinal care outside traditional healthcare settings, especially in the vulnerable period after hospitalizations, with broad coverage of the service by payers. We sought to evaluate patterns of RPM service availability at US hospitals and the association of these services with 30-day readmissions for two key cardiovascular conditions, heart failure (HF) and acute myocardial infarction (AMI).MethodsWe used contemporary national data from the American Hospital Association (AHA) Annual Survey to ascertain US hospitals offering RPM services for post-discharge or chronic care and used census-based county-level data to define the characteristics of the communities they serve. We linked these with hospitals’ benchmarked risk-standardized relative performance on readmissions (excess readmission ratio [ERR]) from CMS Hospital Quality Reports (2018-2022). We used mixed-effects multivariable regression to examine the association between RPM services at hospitals and hospital characteristics-adjusted ERR for HF and AMI.ResultsThere were 2,754 hospitals with CMS quality report data. Over five years of the study, there was a 38.3% increase in the number of hospitals offering RPM services, rising from 952 (42.0%) hospitals in 2018 to 1,237 (58.1%) in 2022. However, the availability of RPM services varied across different hospital groups with smaller, non-teaching hospitals, particularly those serving rural, low-income communities, and those located in the South, were less likely to offer RPM services. There was a consistent association between the availability of RPM services and better risk-standardized readmission performance for HF, with lower ERR for hospitals offering RPM compared with those not offering RPM (absolute difference, -0.016 [-0.023, -0.009], standardized difference, 24.6%, p<0.001). However, no such association was observed for AMI (-0.007 [-0.016, 0.002], standardized difference, 10.3%, p=0.19).ConclusionsIn this national study of US hospitals, there has been a large increase in the availability of RPM services but with large variation among hospitals, with lower availability in hospitals serving low-income and rural communities. RPM services were associated with lower hospital readmission rates for HF but not AMI.
Predicting uptake and elimination kinetics of chemicals in invertebrates: a technical note on residual variance modeling
Authors: van Lingen Henk J. , Saccenti Edoardo , Suarez-Diez Maria , Baccaro Marta , van den Brink Nico W. 
Published: October 2024

AbstractToxicokinetic models for predicting contents of nanomaterials and other toxic chemicals are often fitted without evaluation of the residual variance structure. The aim of the present study was to evaluate various residual variance structures, assuming either homoscedasticity or heteroscedasticity, when fitting non-linear toxicokinetic one-compartment models for predicting uptake, bioaccumulation and elimination of chemicals in invertebrate organisms. Data describing the exposure of several aquatic and terrestrial invertebrates to specific metal nanomaterials and other chemicals were available from real experiments for evaluating the residual variance functions for toxicokinetic models. As proof of concept, datasets of truly homoscedastic and heteroscedastic nature were simulated. Depending the dataset, applying models with different residuals variance assumption largely affected the residual plots and the error margins of parameters or the predicted content of a chemical. Consequently, selecting the most accurate residual variance functions for toxicokinetic modeling, either homoscedastic or heteroscedastic, improves the prediction of chemical contents in invertebrate organisms and the estimation of the associated uptake and elimination rates.HighlightsResidual plots indicate if an accurate model was fitted to the toxicological dataChoice of residual variance function affects the error margins of predicted chemicalsSelecting proper residual variance models may prevent false positives and negatives
PPARα-ERRα crosstalk mitigates metabolic dysfunction-associated steatotic liver disease progression
Authors: Antwi Milton Boaheng , Lefere Sander , Clarisse Dorien , Koorneef Lisa , Heldens Anneleen , Onghena Louis , Decroix Kylian , Fijalkowska Daria , Thommis Jonathan , Hellemans Madeleine , Hoorens Anne , Geerts Anja , Devisscher Lindsey , De Bosscher Karolien 
Published: October 2024

AbstractBackground and aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common liver disease worldwide. This study investigates how targeting two key nuclear receptors involved in hepatic energy metabolism, peroxisome proliferator-activated receptor alpha (PPARα) and estrogen-related receptor alpha (ERRα), impacts MASLD.MethodsThe PPARα agonist pemafibrate and/or ERRα inverse agonist C29 were administered in a short- and long-term Western diet plus fructose model, and a diabetic-background streptozotocin-Western diet model (STZ-WD). Liver morphology, histological samples, serum metabolites, RNA and protein levels were analysed and scanning electron microscopy was performed. In addition, we performed cell-based assays and immunohistochemistry and immunofluorescence stainings with light and super-resolution confocal microscopy of healthy, MASLD and MASH human livers.ResultsThe ligand combinations’ efficacy was underscored by reduced liver steatosis in all the mouse models. Both long-term models showed improvements in body weight and liver morphology, alongside reductions in inflammation and fibrosis. Additionally, tumor formation was prevented in the STZ-WD mice model. Cell-based assays demonstrated that ERRα inhibits PPARα’s activity, likely explaining why ERRα blockage improves inflammatory and lipid metabolism gene profiles and enhances lipid-lowering effects. Complementary RNA sequencing and shotgun proteomics, combined with enrichment analysis, jointly identified downregulated serum amyloid A1/A2 as an essential component underlying the combination treatment’s effectiveness. MASLD/MASH patient livers showed reduced PPARα and increased ERRα levels supporting disrupted NR crosstalk in the hepatocyte nucleus.ConclusionOur study comprehensively supports that dual nuclear receptor targeting by simultaneously increasing PPARα and diminishing ERRα activity may represent a viable novel strategy against MASLD.Lay summaryOur study using three distinct MASLD mouse models shows that a simultaneous targeting of PPARα and ERRα reduces liver fat, fibrosis, inflammation, and tumor formation. The combination treatment modifies lipid metabolism pathways, and uniquely lowers levels of serum amyloid A1/A2 in the liver.Impact and implicationsOur research introduces a novel therapeutic strategy against MASLD by simultaneously increasing PPARα activity while diminishing ERRα activity. With PPARα agonists already tested in phase III clinical trials, ERRα ligands/modulators need further (clinical) development to make our findings applicable to both MASLD patients and physicians.
Network mechanisms in rapid-onset dystonia-parkinsonism
Authors: Möller Meret , Nieweler Johanna A. , Nikulin Vadim V. , van Riesen Christoph 
Published: October 2024

AbstractBackgroundRapid-onset dystonia-parkinsonism (RDP) is a rare neurological disorder caused by mutations in the ATP1A3 gene. Symptoms are characterized by a dystonia-parkinsonism. Recently, experimental studies have shown that the pathophysiology of the disease is based on a combined dysfunction of the cerebellum (CB) and basal ganglia (BG) and that blocking their interaction can alleviate the symptoms. The underlying network mechanisms have not been studied so far.ObjectiveOur aim was to characterize neuronal network activity in the BG and CB and motor cortex in the ouabain model of RDP by site-specific infusion of ouabain.MethodsRats were chronically infused with ouabain either in the CB, striatum (STR) or at both places simultaneously. Motor behavior was scored using published rating systems. Parallel in vivo recordings of local field potentials (LFP) from M1, deep cerebellar nuclei (DCN) and substantia nigra reticulata (SNr) were performed. Data were compared to untreated controls.ResultsOuabain infusion into the cerebellum produced severe dystonia that was associated with increased high-frequency gamma oscillations in the DCNs, which were subsequently transmitted to the BG and M1. Striatal infusion led to parkinsonism and elevated beta- oscillations in SNr that were transmitted to the CB and M1. The simultaneous application of STRs and CB with ouabain resulted in dystonia-parkinsonism and increased beta oscillations in BG, CB, and M1.ConclusionWe demonstrate that symptom-specific beta and gamma oscillations can be transmitted between the BG and CB, which is likely to be very important for the understanding of disease mechanisms.
From movements to words: action monitoring in the medial frontal cortex along a caudal to rostral prediction error gradient
Authors: Lydia Dorokhova , Shiqing Shen , Morgane Peirolo , Jean-Luc Anton , Bruno Nazarian , Julien Sein , Valérie Chanoine , Pascal Belin , Kee Loh Kep , Elin Runnqvist 
Published: October 2024

AbstractSpeech error monitoring recruits the medial frontal cortex (MFC) region in the human brain. Error monitoring-related activity in the MFC has been interpreted both in terms of conflict monitoring and feedback-driven control, but as similar regions of the MFC are implicated in various levels of behavioral control ranging from basic motor movement control to high-level cognitive control functions, a more comprehensive account is needed. Moreover, as speech errors and other actions that involve varying control demands engage a widespread yet partially overlapping set of regions of the MFC, such an account should ideally explain the anatomical distribution of error-related functional activations within the MFC. Here we wanted to assess the hypothesis that the MFC has a similar role in the evaluation of action outcomes for motor and mental actions, operating along a rostral-caudal gradient of higher-lower level control demands involving prediction errors from both sensory and epistemic sources. To this end, we conducted an individual-specific annotation of task-fMRI BOLD activation peaks related to speech errors versus correct productions (i.e. that involve the largest cognitive control demands, Study I and II), tongue movement monitoring (i.e. that involve an intermediate level of cognitive and motor control demands) and tongue movement (i.e. that involve only motor control demands, Study II) in the MFC region. Results revealed overlapping clusters across the three contrasts across the MFC, but importantly both the number of peaks and their relative position along the rostral caudal axis were consistent with a hierarchical rostral caudal processing gradient in the MFC. While tongue movement showed more caudal activation in the MFC, speech errors showed more rostral activation, and tongue movement monitoring patterned in between. Furthermore, the combined results of both studies suggested that activation peaks were located more dorsally for participants that had a paracingulate gyrus, replicating a previously documented effect for movement and further supporting a common functional role of the MFC across very distinct actions.
Development and Validation of a Comprehensive Tumor Treating Fields System for Glioblastoma Therapy: From Prototype Design to Preclinical Evaluation
Authors: Wang Xindong , Lv Han , Wang Zhiyong , Wang Xian 
Published: October 2024

AbstractGlioblastoma (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Tumor Treating Fields (TTF) therapy, which uses alternating electric fields to disrupt cancer cell division, has emerged as a promising non-invasive treatment. However, the development and optimization of TTF systems remain challenging, with limited studies detailing the design and practical application of such systems. In this study, we developed a novel TTF prototype, focusing on the design and fabrication of key components such as the electrical signal regulation, transmission and corresponding therapeutic effects. We evaluated the system’s efficacy through a series ofin vitroandin vivoexperiments.In vitro, we demonstrated significant inhibition of GBM cell proliferation under varying electric field intensities, with stronger fields showing greater efficacy.In vivostudies using a rat glioblastoma model revealed reduced tumor growth, increased apoptosis, and enhanced immune infiltration in the TTF-treated group compared to controls. This comprehensive study provides a valuable reference for TTF system development, offering insights into both the technical design and biological application of TTF therapy, and highlighting its potential for improving GBM treatment outcomes.
Zymoseptoria triticieffectors structurally related to killer proteins UmV-KP4 and UmV-KP6 are toxic to fungi, and define extended protein families in fungi
Authors: de Guillen Karine , Mammri Léa , Gracy Jérôme , Padilla André , Barthe Philippe , Hoh François , Lahfa Mounia , Rouffet Justine , Petit-Houdenot Yohann , Kroj Thomas , Lebrun Marc-Henri 
Published: October 2024

AbstractFungal effectors play crucial roles in plant infection. Despite low sequence identity, effectors were recently classified into structural families. In this study, we have elucidated the structures of Zt-NIP1 and Mycgr3-91409 effectors of the wheat fungal pathogenZymoseptoria tritici,using X-ray crystallography and NMR. These effectors displayed a structural homology with, respectively, KP4 and KP6α killer toxins, from UmV dsRNA viruses infecting the corn fungal pathogenUstilago maydis. Consequently, Zt-NIP1 and Mycgr3-91409 were renamed Zt-KP4-1 and Zt-KP6-1. Orthologs and paralogs of Zt-KP4-1 and Zt-KP6-1 were identified inZymoseptoria, but not in other fungi, except Ecp2 effectors related to Zt-KP4-1. Assessment of the biological activities of Zt-KP6-1 and Zt-KP4-1 revealed their toxicity to fungi such asBotrytis cinereaandZ. tritici, but not to wheat. A novel pipeline relying on Foldseek and cysteine-pattern constrained HMM searches of AlphaFold2 predicted structures from Uniprot generated a comprehensive inventory of KP4 and KP6 proteins in fungi and plants. A structure-based classification of these proteins revealed four KP4 and three KP6 structural super families. This classification provided far-reaching hypotheses on their biological function and evolution. This unifying structural framework highlights the power of structure determination for the classification of effectors, and their functional investigation.
Data- and knowledge-derived functional landscape of human solute carriers
Authors: Goldmann Ulrich , Wiedmer Tabea , Garofoli Andrea , Sedlyarov Vitaly , Bichler Manuel , Wolf Gernot , Christodoulaki Eirini , Ingles-Prieto Alvaro , Ferrada Evandro , Frommelt Fabian , Teoh Shao Thing , Leippe Philipp , Haladik Ben , Onea Gabriel , Pfeifer Martin , Kohlbrenner Mariah , Chang Lena , Selzer Paul , Reinhardt Jürgen , Digles Daniela , Ecker Gerhard F. , Osthushenrich Tanja , MacNamara Aidan , Malarstig Anders , Hepworth David , Superti-Furga Giulio 
Published: October 2024

AbstractResearch on the understudied solute carrier (SLC) superfamily of membrane transporters would greatly profit from a comprehensive knowledgebase, synthesizing data and knowledge on different aspects of SLC function. We consolidated multi-omics data sets with selected curated information from the public domain, such as structure prediction, substrate annotation, disease association and subcellular localization. This SLC-centric knowledge is made accessible to the scientific community via a web portal, featuring interactive dashboards and a tool for family-wide, tree-based visualization of SLC properties. Making use of the systematically collected and curated data sets, we selected eight feature-dimensions to compute an integrated functional landscape of human SLCs. This landscape represents various functional aspects, harmonizing local and global features of the underlying data sets, as demonstrated by inspecting structural folds and subcellular locations of selected transporters. Based on all available data sets and their integration, we assigned a biochemical/biological function to each SLC, making it one of the largest systematic annotations of human gene function and likely acting as a blueprint for future endeavours.
Behavioral and neural alterations of the ventral tegmental area by Cafeteria diet exposure in rats
Authors: Lalanza Jaume F. , Oyem John C. , Huijgens Patty T. , McCutcheon James E. , Heijkoop Roy , Snoeren Eelke MS 
Published: October 2024

SummaryThe brain reward system is essential for regulating appetitive and consummatory behaviors in response to various incentive stimuli. Junk food, known for its high palatability, is particularly associated with the potential for excessive consumption. While previous studies have shown that excessive junk food intake can impact reward circuitry, the precise mechanisms remain unclear. Additionally, it is unknown whether the functionality of this brain system is similarly altered in response to other natural rewards. In this study, we used fiber photometry combined with a behavioral reward test to investigate how six weeks of excessive cafeteria (CAF) diet consumption affects VTA neural activity and behavioral responses to food and sexual rewards in sexually experienced female rats. For the first time, we demonstrate that prolonged exposure to a CAF diet decreases interest in a food reward, resulting in reduced consumption. These behavioral changes were accompanied by diminished neural activity in the VTA. Similarly, but to a lesser extent, reductions in VTA activity responses were observed in response to a sexual partner, although no significant behavioral differences were detected during sexual interactions. Furthermore, a two-week reversal diet of standard chow was insufficient to restore VTA neural activity in CAF-exposed animals, which continued to show decreased VTA responses to both food rewards and sexual partners. Our findings suggest that prolonged junk food exposure leads to desensitization of the VTA, a key node in the brain’s reward circuitry, resulting in reduced responsiveness to natural rewards.