bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gardenin A improves cognitive and motor function in A53T-α-syn mice
Authors: Hack Wyatt , Gladen-Kolarsky Noah , Chatterjee Swarnali , Liang Qiaoli , Maitra Urmila , Ciesla Lukasz , Gray Nora E 
Published: November 2023

AbstractOxidative stress and neuroinflammation are widespread in the Parkinson’s disease (PD) brain and contribute to the synaptic degradation and dopaminergic cell loss that result in cognitive impairment and motor dysfunction. The polymethoxyflavone Gardenin A (GA) has been shown to activate the NRF2-regulated antioxidant pathway and inhibit the NFkB-dependent pro-inflammatory pathway in aDrosophilamodel of PD. Here, we evaluate the effects of GA on A53T alpha-synuclein overexpressing (A53TSyn) mice.A53TSyn mice were treated orally for 4 weeks with 0, 25, or 100 mg/kg GA. In the fourth week, mice underwent behavioral testing and tissue was harvested for immunohistochemical analysis of tyrosine hydroxylase (TH) and phosphorylated alpha synuclein (pSyn) expression, and quantification of synaptic, antioxidant and inflammatory gene expression. Results were compared to vehicle-treated C57BL6 mice.Treatment with 100 mg/kg GA improved associative memory and decreased abnormalities in mobility and gait in A53TSyn mice. GA treatment also reduced cortical and hippocampal levels of pSyn and attenuated the reduction in TH expression in the striatum. Additionally, GA increased cortical expression of NRF2-regulated antioxidant genes and decreased expression of NFkB-dependent pro-inflammatory genes. GA was readily detectable in the brains of treated mice and modulated the lipid profile in the deep gray brain tissue of those animals.While the beneficial effects of GA on cognitive deficits, motor dysfunction and PD pathology are promising, future studies are needed to further fully elucidate the mechanism of action of GA, optimizing dosing and confirm these effects in other PD models.Significance StatementThe polymethoxyflavone Gardenin A can improve cognitive and motor function and attenuate both increases in phosphorylated alpha synuclein and reductions in tyrosine hydroxylase expression in A53T alpha synuclein overexpressing mice. These effects may be related to activation of the NRF2-regulated antioxidant response and downregulation of NFkB-dependent inflammatory response by Gardenin A in treated animals. The study also showed excellent brain bioavailability of Gardenin A and modifications of the lipid profile, possibly through interactions between Gardenin A with the lipid bilayer, following oral administration. The study confirms neuroprotective activity of Gardenin A previously reported in toxin inducedDrosophilamodel of Parkinson’s disease.
Transdiagnostic brain module dysfunctions across sub-types of frontotemporal dementia: a connectome-based investigation
Authors: Xinglin Zeng , Jiangshan He , Kaixi Zhang , Xiaoluan Xia , Shiyang Xu , Yuan Zhen 
Published: November 2023

AbstractBackgroundFrontotemporal dementia (FTD) is a complex neurodegenerative disorder encompassing heterogeneous subtypes, including behavioral variant frontotemporal dementia (BV-FTD), semantic variant frontotemporal dementia (SV-FTD), and progressive non-fluent aphasia frontotemporal dementia (PNFA-FTD). Unraveling the shared and distinctive brain module organizations among these subtypes is critical for unraveling the underlying neural basis of the disease. This study aims to explore brain module organization in FTD subtypes, seeking potential biomarkers and insights into their pathophysiology.MethodsResting-state functional magnetic resonance imaging data were obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative, comprising 41 BV-FTD, 32 SV-FTD, 28 PNFA-FTD, and 94 healthy controls, following exclusion of participants with excessive head motion. Individual functional brain networks were constructed at the voxel level of gray matter and binarized with a 1% density threshold. Using predefined brain modules, we computed the modular segregation index (MSI) for each module, analyzed intermodular and intramodular connections to identify driving modular connections, and calculated the participation coefficient (PC) to detect regions with altered nodal properties associated with module integrity. A machine learning algorithm was employed for FTD subtype classification based on these matrices. Correlations between modular measures and clinical scores in each FTD subtype were examined.ResultsDistinct brain module organizations were observed across FTD subtypes, with lower MSI in the subcortical module (SUB), default mode network (DMN), and ventral attention network (VAN) in both BV-FTD and SV-FTD. Specifically, only BV-FTD exhibited disruption in the frontoparietal network (FPN). Notably, the bilateral fusional gyrus, left orbitofrontal cortex, left precuneus, and right insular thalamus showed significant group effects on PC, indicating altered nodal properties associated with module integrity. Our machine learning achieved a multiple classification accuracy of 85%. Correlations between specific network alterations and clinical variables in each FTD subtype were also identified.ConclusionsThese findings illuminate the diverse brain module organization in different FTD subtypes, offering insights into potential neurobiological differences that underlie the clinical heterogeneity of the disease. Regions with altered modular properties may serve as valuable biomarkers for early diagnosis and disease monitoring. Furthermore, understanding disruptions in modular connectivity provides valuable insights into the neuropathological mechanisms of FTD subtypes, paving the way for targeted therapeutic interventions.
Sarand: Exploring Antimicrobial Resistance Gene Neighborhoods in Complex Metagenomic Assembly Graphs
Authors: Kafaie Somayeh , Beiko Robert G. , Maguire Finlay 
Published: November 2023

ABSTRACTAntimicrobial resistance (AMR) is a major global challenge to human and animal health. The genomic element (e.g., chromosome, plasmid, and genomic islands) and neighbouring genes associated with an AMR gene play a major role in its function, regulation, evolution, and propensity to undergo lateral gene transfer. Therefore, characterising these genomic contexts is vital to effective AMR surveillance, risk assessment, and stewardship. Metagenomic sequencing is widely used to identify AMR genes in microbial communities, but analysis of short-read data offers fragmentary information that lacks this critical contextual information. Alternatively, metagenomic assembly, in which a complex assembly graph is generated and condensed into contigs, provides some contextual information but systematically fails to recover many mobile genetic elements. Here we introduce Sarand, a method that combines the sensitivity of read-based methods with the genomic context offered by assemblies by extracting AMR genes and their associated context directly from metagenomic assembly graphs. Sarand combines BLAST-based homology searches with coverage statistics to sensitively identify and visualise AMR gene contexts while minimising inference of chimeric contexts. Using both real and simulated metagenomic data, we show that Sarand outperforms metagenomic assembly and recently developed graph-based tools in terms of precision and sensitivity for this problem. Sarand (https://github.com/beiko-lab/sarand) enables effective extraction of metagenomic AMR gene contexts to better characterize AMR evolutionary dynamics within complex microbial communities.
A Neanderthal Origin of Genetic Variants Associated with Asthma
Authors: Day Andrew S. H. , Gaulton Kyle J. 
Published: November 2023

SUMMARYWhile genome-wide association studies have implicated a number asthma-associated genes, whether the disease-linked variants originate from ancient genomes has not been explored. Here we show that of the 51 asthma-associated loci that we surveyed, 39 carry variants that were derived in the Neanderthal lineage. The shared sequences suggest that some asthma variants may have originated from the Neanderthal genome after admixture and subsequent introgression into the Eurasian population. Of note, one variant, rs4742170, previously linked to asthma and childhood wheezing, was shown in a recent study to disrupt glucocorticoid receptor binding to a putativeIL33enhancer, and elevate enhancer activity of this key asthma gene. Further analysis of theIL33-associated variant in publicly available single nucleus ATACseq data of the human lung addressed its localization in open chromatin, providing an additional approach to screen for variants that may impact the expression of asthma-associated genes. Together, these findings suggest a possible Neanderthal origin of genetic variants associated with asthma.
High-throughput, label-free detection of DNA origami in single-cell suspensions using origamiFISH-Flow
Authors: Alexander Shana , Wang Wendy Xueyi , Tseng Chung-Yi , Douglas Travis R. , Chou Leo Y.T. 
Published: November 2023

AbstractStructural DNA nanotechnology enables custom fabrication of nanoscale devices and promises diverse biological applications. However, the effects of design on DNA nanostructure (DN)-cell interactions in vitro and in vivo are not yet well-characterized. origamiFISH is a recently developed technique for imaging DNs in cells and tissues. Compared to the use of fluorescent tags, origamiFISH offers label-free and structure-agnostic detection of DNs with significantly improved sensitivity. Here, we extend the origamiFISH technique to quantifying DNs in single-cell suspensions, including nonadherent cells such as subsets of immune cells, via readout by flow cytometry. This method, referred to as origamiFISH-Flow, is high-throughput (e.g., 10,000 cells per second) and compatible with immunostaining for concurrent cell-type and -state characterization. We demonstrate that origamiFISH-Flow enhances signal-to-noise ratio by up to 20-fold compared to dye labeling approaches, leading to the capture of >25-fold more DN+cells at low, single-picomolar DN uptake concentrations. We additionally show the use of origamiFISH-Flow to profile cell-type and shape-specific DN uptake patterns across cell lines and splenocytes and quantify in vivo DN accumulation in lymphoid organs. Together, origamiFISH-Flow offers a new tool to interrogate DN interactions with cells and tissues, while providing insights for tailoring their designs in bio-applications.
pathCLIP: Detection of Genes and Gene Relations from Biological Pathway Figures through Image-Text Contrastive Learning
Authors: He Fei , Liu Kai , Yang Zhiyuan , Chen Yibo , Hammer Richard D. , Xu Dong , Popescu Mihail 
Published: November 2023

AbstractIn biomedical literature, biological pathways are commonly described through a combination of images and text. These pathways contain valuable information, including genes and their relationships, which provide insight into biological mechanisms and precision medicine. Curating pathway information across the literature enables the integration of this information to build a comprehensive knowledge base. While some studies have extracted pathway information from images and text independently, they often overlook the correspondence between the two modalities. In this paper, we present a pathway figure curation system named pathCLIP for identifying genes and gene relations from pathway figures. Our key innovation is the use of an image-text contrastive learning model to learn coordinated embeddings of image snippets and text descriptions of genes and gene relations, thereby improving curation. Our validation results, using pathway figures from PubMed, showed that our multimodal model outperforms models using only a single modality. Additionally, our system effectively curates genes and gene relations from multiple literature sources. A case study on extracting pathway information from non-small cell lung cancer literature further demonstrates the usefulness of our curated pathway information in enhancing related pathways in the KEGG database.
N1-methylation of adenosine (m1A) in ND5 mRNA leads to complex I dysfunction in Alzheimer’s disease
Authors: Jörg Marko , Plehn Johanna E. , Kristen Marco , Lander Marc , Walz Lukas , Lietz Christine , Wijns Julie , Pichot Florian , Rojas-Charry Liliana , Wirtz Martin Katja M. , Ruffini Nicolas , Kreim Nastasja , Gerber Susanne , Motorin Yuri , Endres Kristina , Rossmanith Walter , Methner Axel , Helm Mark , Friedland Kristina 
Published: November 2023

AbstractOne mechanism of particular interest to regulate mRNA fate post-transcriptionally is mRNA modification. Especially the extent of m1A mRNA methylation is highly discussed due to methodological differences. However, one single m1A site in mitochondrial ND5 mRNA was unanimously reported by different groups. ND5 is a subunit of complex I of the respiratory chain. It is considered essential for the coupling of oxidation and proton transport. Here we demonstrate that this m1A site might be involved in the pathophysiology of Alzheimer’s disease (AD). One of the pathological hallmarks of this neurodegenerative disease is mitochondrial dysfunction, mainly induced by Amyloid β (Aβ). Aβ mainly disturbs functions of complex I and IV of the respiratory chain. However, the molecular mechanism of complex I dysfunction is still not fully understood. We found enhanced m1A methylation of ND5 mRNA in an AD cell model as well as in AD patients. Formation of this m1A methylation is catalyzed by increased TRMT10C protein levels, leading to translation repression of ND5. As a consequence, here demonstrated for the first time, TRMT10C induced m1A methylation of ND5 mRNA leads to mitochondrial dysfunction. Our findings suggest that this newly identified mechanism might be involved in Aβ-induced mitochondrial dysfunction.
Three-dimensional visualization of blood vessels in human gliomas based on tissue clearing and deep learning
Authors: Wang Xinyue , Yang Xiaodu , He Dian , Luo Yunhao , Huang Qiyuan , Li Ting , Ye Zhaoyu , Ye Chun , Zhang Minglin , Lai Hei Ming , Xu Yingying , Sun Haitao 
Published: November 2023

AbstractGliomas, with their intricate and aggressive nature, call for a detailed visualization of their vasculature. While many studies lean towards 2D imaging of thin sections, this method often overlooks the full spatial heterogeneity inherent to tumors. To overcome this limitation, our study melded state-of-the-art techniques, encompassing tissue clearing technology, 3D confocal microscopy imaging, and deep learning-aided vessel extraction, resulting in a comprehensive 3D visualization of glioma vasculature in intact human tissue. Specifically, we treated formalin-fixed thick human glioma tissue sections (500 μ m) with OPTIClear for transparency and subsequently performed immunofluorescent labeling using CD31. Using confocal microscopy, we obtained 3D images of the glioma vasculature. For vessel extraction, we employed a specialized 3D U-Net, enriched with image preprocessing and post-processing methods, and benchmarked its performance against the Imaris software. Our findings indicated that OPTIClear-enabled tissue clearing yielded a holistic 3D representation of immunolabeled vessels in clinical human glioma samples. Impressively, our deep learning technique outshined the traditional Imaris approach in terms of accuracy and efficiency in vessel extraction. Further, discernible variations in vascular metrics, such as mean diameter, branching point count, and volume ratio, were observed between low-grade and high-grade gliomas. In essence, our innovative blend of tissue clearing and deep learning not only enables enhanced 3D visualization of human glioma vasculature but also underscores morphological disparities across glioma grades, potentially influencing pathological grading, therapeutic strategies, and prognostic evaluations.
Gods Lockdown: the effect of the April 2022 Colorado low blizzard on SARS-Cov-2 transmission in the midwest United States
Authors: Strobel Stephenson , Daly Michael 
Published: November 2023

AbstractBackgroundLockdowns have been used as a primary non-pharmaceutical intervention to stop transmission of COVID19. There are many issues with interpreting the causal effects of most of these intentional, policy driven interventions. We leverage a natural experiment to avoid many of these issues to better understand the direct effects of lockdown like conditions on COVID19 transmission.MethodsWe exploit a blizzard that interrupted activity across several midwestern states in April 2022. This blizzard broke records for snowfall and caused economic disruption. We leverage this to create control and treatment counties that were more or less affected by the snowfall. We demonstrate effects using event studies comparing these treatment and control counties.ResultsWe find that mobility within treatment counties was severely curtailed as a result of the blizzard relative to control counties. We find cumulative declines in the number of COVID19 cases per country by 400 and cumulative declines in COVID19 deaths by 1 per county over the 30 days after the storm. We find declines in by one per hospitalization due to COVID19.ConclusionsThe April 2022 blizzard caused disruption in activity across the midwest United States akin to a lockdown. It reduced the number of COVID19 cases, deaths, and hospitalizations in treatment counties relative to control counties suggesting that similar policies do limit transmissions of SARS-Cov-2.
Learning goal orientation as a background to project efficiency: the mediating role of impact on the team
Authors: Chies Tawnee , Mazieri Marcos 
Published: November 2023

Purpose
The emphasis on short-term by project-based firms (PBFs) implies the adoption of project efficiency and impact on the team as project success drivers in PBFs context. Good performance by employees, as individuals in a team, can be explained by their behaviors, associated with goal orientation theory. Learning and performance orientations are associated with teams’ effectiveness and overall project performance. The purpose of this paper is to analyze the relationships between the dimensions of goal orientation, especially learning orientation, and project efficiency and impact on the team, in PBFs context.

Design/methodology/approach
A quantitative approach was adopted, based on data from a survey of 714 respondents, representing project managers, that turned into a valid sample of 315 composed only by PBFs respondents. The results were analyzed through multiple linear regression and, mainly, mediation analysis methods.

Findings
Performance-avoid orientation is a predictor of project efficiency; performance-prove orientation, a predictor of impact on the team. Learning orientation relates positively to both project success criteria. Project managers should balance/induce the proper orientation within the team, favoring learning orientation according to the results, to have short-term project success in PBFs.

Originality/value
There is a direct relationship between learning orientation and project efficiency, but it is fully mediated by impact on the team, which it was not found in previous studies. This study argues that they are not parallel constructs, constituent parts of equal weight in project success, but that impact on the team precedes project efficiency when learning orientation is considered.
Enablers and impact of social innovation in higher education institutes: a futuristic perspective
Authors: Afsar Bilal , AlGhazali Basheer M. 
Published: November 2023

Purpose
Social innovation is a nascent field. Within research on social innovation, the context of higher education has largely been ignored. To better understand social innovation, it is important to explore factors that facilitate social innovation in universities’ context. There is little research on enablers of social innovation in universities and the impacts of social innovation. Therefore, the purpose of this study is to understand the enablers of social innovation in the Saudi Arabian context. Moreover, the impacts of social innovation projects are also explored.

Design/methodology/approach
A qualitative approach was used to carry out this study. Data were collected through semistructured interviews, and content analysis was performed.

Findings
Data revealed that institutional commitment, mission, active collaborations, curriculum, support, training, community university engagement offices, university social impact offices and reward and evaluation were among critical enablers. The impact of social innovation in terms of social, institutional, economic and community specific was also reported.

Originality/value
Research on the enablers and outcomes of social innovation in the higher education context is limited. This study adds to the innovation literature by investigating what processes and factors (enablers) can help universities to engage in social innovation initiatives and what are the outcomes (impact) of engaging in social innovation. Findings of the study have important policy implications.
Interpersonal conflict and psychological well-being at work: the beneficial effects of teleworking and emotional intelligence
Authors: Parent-Lamarche Annick , Saade Sabine 
Published: November 2023

Purpose
This cross-sectional study had several objectives. This paper aims to study the direct effect of teleworking on interpersonal conflict, the mediating role that interpersonal conflict can play between teleworking and psychological well-being, the moderating role emotional intelligence (EI) can play between teleworking and interpersonal conflict and whether this moderation effect can, in turn, be associated with psychological well-being (moderated mediation effect).

Design/methodology/approach
Path analyses using Mplus software were performed on a sample of 264 employees from 19 small- and medium-sized organizations.

Findings
While teleworking was associated with lower interpersonal conflict, it was not associated with enhanced psychological well-being. Interestingly, workload seemed to be associated with higher interpersonal conflict, while decision authority and support garnered from one’s supervisor seemed to be associated with lower interpersonal conflict. Teleworking was indirectly associated with higher psychological well-being via interpersonal conflict. Finally, EI played a moderating role between teleworking and lower interpersonal conflict. This was, in turn, associated with higher psychological well-being.

Practical implications
EI is an essential skill to develop in the workplace.

Originality/value
A deepened understanding of the role played by EI at work could help organizations to provide positive work environments, both in person and online. This is especially relevant today, with the continued increase in teleworking practices and the resulting rapidly changing interpersonal relationships.