bluuebunny/crossref_metadata_2025_split huggingface dataset:
TOMOMAN: a software package for large scale cryo-electron tomography data preprocessing, community data sharing, and collaborative computing
Authors: Khavnekar Sagar , Erdmann Philipp S. , Wan William 
Published: May 2024

AbstractCryo-electron tomography (cryo-ET) and subtomogram averaging (STA) are becoming the preferred methodologies for investigating subcellular and macromolecular structures in native or near-native environments. While cryo-ET is amenable to a wide range of biological problems, these problems often have data processing requirements that need to be individually optimized, precluding the notion of a one-size-fits-all processing pipeline. Cryo-ET data processing is also becoming progressively more complex due to an increasing number of packages for each processing step. Though each package has its own strengths and weaknesses, independent development and different data formats makes them difficult to interface with one another. TOMOMAN (TOMOgram MANager) is an extensible package for streamlining the interoperability of packages, enabling users to develop project-specific processing workflows. TOMOMAN does this by maintaining an internal metadata format and wrapping external packages to manage and perform preprocessing, from raw tilt-series data to reconstructed tomograms. TOMOMAN can also export this metadata between various STA packages. TOMOMAN also includes tools for archiving projects to data repositories; allowing subsequent users to download TOMOMAN projects and directly resume processing where it was previously left off. By tracking essential metadata, TOMOMAN streamlines data sharing, which improves reproducibility of published results, reduces computational costs by minimizing reprocessing, and enables distributed cryo-ET projects between multiple groups and institutions. TOMOMAN provides a way for users to test different software packages to develop processing workflows that meet the specific needs of their biological questions and to distribute their results with the broader scientific community.
Elucidating the Impact ofHypericum alpestreExtract and L-NAME on the PI3K/Akt Signaling Pathway in A549 Lung Adenocarcinoma Cells
Authors: Javrushyan Hayarpi , Ginovyan Mikayel , Petrosyan Gayane , Qocharyan Mery , Harutyunyan Tigran , Gevorgyan Smbat , Karabekian Zaruhi , Maloyan Alina , Avtandilyan Nikolay 
Published: May 2024

AbstractPlants within theHypericaceaefamily have been traditionally used for their medicinal properties, showcasing a wide range of effects such as antibacterial, antiviral, and antioxidant qualities.Hypericum alpestre(HA) extracts have exhibited significant cytotoxicity against various cancer cell lines. The phenolic compounds found in HA extracts have attracted attention for their potential in cancer prevention. L-NAME, known for its ability to inhibit nitric oxide synthase (NOS) activity, has emerged as a promising approach in cancer therapy. However, the precise molecular mechanisms underlying the anticancer effects of HA and L-NAME remain unclear. This study aims to clarify the impact of HA and L-NAME on the PI3K/Akt signaling pathway in A549 lung adenocarcinoma cells, with a specific focus on TNFa/COX-2 and VEGFa/MMP-2 pathways.In silicoanalysis, they identified the compounds with the highest affinity for PI3K/Akt, a finding validated by subsequentin vitroexperiments. Furthermore, the combination of herbs and L-NAME exhibited superior efficacy compared to the herb and 5-FU combination, as evidenced by the promotion of apoptosis. Both the herb alone and the combination of the herb with L-NAME demonstrated inhibitory effects on the TNFa/COX-2 and VEGFa/MMP-2 pathways. This therapeutic approach is hypothesized to operate through the PI3k/Akt cell signaling pathway. A better understanding of the interaction between HA polyphenols and PI3K/Akt signaling could pave the way for novel therapeutic strategies against cancer, including drug-resistant tumors.
parafac4microbiome: Exploratory analysis of longitudinal microbiome data using Parallel Factor Analysis
Authors: van der Ploeg G.R. , Westerhuis J.A. , Heintz-Buschart A. , Smilde A.K. 
Published: May 2024

AbstractStudies investigating microbial temporal dynamics are increasingly common, leveraging longitudinal designs that collect microbial abundance data across multiple time points from the same subjects. Traditional exploratory approaches like Principal Component Analysis (PCA) fail to fully utilize this structure. By organizing data as a three-way array—subjects as rows, microbial abundances as columns, and time points as the third dimension—multi-way methods such as Parallel Factor Analysis (PARAFAC) can better capture temporal and structural patterns. This study demonstrates Parallel Factor Analysis (PARAFAC) as a method to explore longitudinal microbiome data using three exemplary studies.In the first example, a long time series of in vitro microbiomes, PARAFAC identifies primary time-resolved variations. The second example, a longitudinal infant gut microbiome study, shows that PARAFAC can distinguish subject groups and enhance comparative analysis, even with moderate missing data. In the third example, a gingivitis intervention study of the oral microbiome, PARAFAC enables the identification of microbial subcommunities of interest through post-hoc clustering.These examples highlight PARAFAC’s broad applicability for analyzing longitudinal microbiome data across diverse environments. The approach is implemented in the R packageparafac4microbiome, available on CRAN, providing researchers with accessible tools for similar analyses.ImportanceUnderstanding how microbiomes change over time can give us valuable insights into their role in health and disease. Many traditional methods like Principal Component Analysis (PCA) miss important patterns in data collected over time, but Parallel Factor Analysis (PARAFAC) helps uncover these trends in a much clearer way. Using this approach, we were able to identify key changes in microbiomes across different settings, like lab experiments, the infant gut, and the mouth. PARAFAC also works well even when some data is missing, which is a common issue. To make this tool accessible, we’ve included it in a user-friendly R package, enabling other researchers to analyze microbiome dynamics in their own studies and explore how these changes might influence health and treatments.
Genetic modification of the shikimate pathway to reduce lignin content in switchgrass (Panicum virgatumL.) significantly impacts plant microbiomes
Authors: Liu Shuang , Chou Ming-Yi , Benucci Gian Maria Niccolò , Eudes Aymerick , Bonito Gregory 
Published: May 2024

AbstractSwitchgrass (Panicum virgatumL.) is considered a sustainable biofuel feedstock, given its fast-growth, low input requirements, and high biomass yields. Improvements in bioenergy conversion efficiency of switchgrass could be made by reducing its lignin content. Engineered switchgrass that expresses a bacterial 3-dehydroshikimate dehydratase (QsuB) has reduced lignin content and improved biomass saccharification due to the rerouting of the shikimate pathway towards the simple aromatic protocatechuate at the expense of lignin biosynthesis. However, the impacts of this QsuB trait on switchgrass microbiome structure and function remains unclear. To address this, wildtype and QsuB engineered switchgrass were grown in switchgrass field soils and samples were collected from inflorescences, leaves, roots, rhizospheres, and bulk soils for microbiome analysis. We investigated how QsuB expression influenced switchgrass-associated fungal and bacterial communities using high-throughput Illumina MiSeq amplicon sequencing of ITS and 16S rDNA. Compared to wildtype, QsuB engineered switchgrass hosted different microbial communities in roots, rhizosphere, and leaves. Specifically, QsuB engineered plants had a lower abundance of arbuscular mycorrhizal fungi (AMF). Additionally, QsuB engineered plants had fewerActinobacteriotain root and rhizosphere samples. These findings may indicate that changes in the plant metabolism impact both organismal groups similarly, or potential interactions between AMF and the bacterial community. This study enhances understanding of plant-microbiome interactions by providing baseline microbial data for developing beneficial bioengineering strategies and by assessing non-target impacts of engineered plant traits on the plant microbiome.
Discovering Intron Gain Events in Humans through Large-Scale Evolutionary Comparisons
Authors: Hoh Celine , Salzberg Steven L 
Published: May 2024

ABSTRACTThe rapid growth in the number of sequenced genomes makes it possible to search for the appearance of entirely new introns in the human lineage. In this study, we compared the genomic sequences for 19,120 human protein-coding genes to a collection of 3493 vertebrate genomes, mapping the patterns of intron alignments onto a phylogenetic tree. This mapping allowed us to trace many intron gain events to precise locations in the tree, corresponding to distinct points in evolutionary history. We discovered 584 intron gain events, all of them relatively recent, in 514 distinct human genes. Among these events, we explored the hypothesis that intronization was the mechanism responsible for intron gain. Intronization events were identified by locating instances where human introns correspond to exonic sequences in homologous vertebrate genes. Although apparently rare, we found three compelling cases of intronization, and for each of those we compared the human protein sequence and structure to homologous genes that lack the introns.
Dark exposure reduces high-frequency hearing loss in C57BL/6J mice
Authors: Jendrichovsky Peter , Lee Hey-Kyoung , Kanold Patrick O. 
Published: May 2024

SummaryPlastic changes in the brain are primarily limited to early postnatal periods. Recovery of adult brain plasticity is critical for the effective development of therapies. A brief (1-2 week) duration of visual deprivation (dark exposure, DE) in adult mice can trigger functional plasticity of thalamocortical and intracortical circuits in the primary auditory cortex suggesting improved sound processing. We tested if DE enhances the ability of adult mice to detect sounds. We trained and continuously evaluated the behavioral performance of mice in control and DE conditions using automated home-cage training. Consistent with age-related peripheral hearing loss present in C57BL/6J mice, we observed decreased performance for high-frequency sounds with age, which was reduced by DE. In CBA mice with preserved peripheral hearing, we also found that DE enhanced auditory performance in low and mid frequencies over time compared to the control.
Design of a genetically programmable and customizable protein scaffolding system for the hierarchical assembly of robust, functional macroscale materials
Authors: Zhang Ruijie , Kang Sun-Young , Gaascht Francois , Pena Eliana L. , Dannert Claudia Schmidt- 
Published: May 2024

ABSTRACTInspired by the properties of natural protein-based biomaterials, protein nanomaterials are increasingly designed with natural or engineered peptides, or with protein building blocks. Very few examples describe the design of functional protein-based materials for biotechnological applications that can be readily manufactured, are amenable to functionalization, and exhibit robust assembly properties for macroscale material formation. Here, we designed a protein-scaffolding system that self-assembles into robust, macroscale materials suitable for cell-free applications. By controlling the co-expression inE. coliof self-assembling scaffold building blocks with and without modifications for covalent attachment of cross-linking cargo proteins, hybrid scaffolds with spatially organized conjugation sites are overproduced that can be readily isolated. Cargo proteins, including enzymes, are rapidly cross-linked onto scaffolds for the formation of functional materials. We show that these materials can be used for the cell-free operation of a co-immobilized two-enzyme reaction and that the protein material can be recovered and reused. We believe that this work will provide a versatile platform for the design and scalable production of functional materials with customizable properties and the robustness required for biotechnological applications.
Unravelling undiagnosed rare disease cases by HiFi long-read genome sequencing
Authors: Steyaert Wouter , Sagath Lydia , Demidov German , Yépez Vicente A. , Esteve-Codina Anna , Gagneur Julien , Ellwanger Kornelia , Derks Ronny , Weiss Marjan , den Ouden Amber , van den Heuvel Simone , Swinkels Hilde , Zomer Nick , Steehouwer Marloes , O’Gorman Luke , Astuti Galuh , Neveling Kornelia , Schüle Rebecca , Xu Jishu , Synofzik Matthis , Beijer Danique , Hengel Holger , Schöls Ludger , Claeys Kristl G , Baets Jonathan , Van de Vondel Liedewei , Ferlini Alessandra , Selvatici Rita , Morsy Heba , Saeed Abd Elmaksoud Marwa , Straub Volker , Müller Juliane , Pini Veronica , Perry Luke , Sarkozy Anna , Zaharieva Irina , Muntoni Francesco , Bugiardini Enrico , Polavarapu Kiran , Horvath Rita , Reid Evan , Lochmüller Hanns , Spinazzi Marco , Savarese Marco ,   Solve-RD DITF-ITHACA,   Solve-RD DITF-Euro-NMD,   Solve-RD DITF-RND,   Solve-RD DITF-EpiCARE, Matalonga Leslie , Laurie Steven , Brunner Han G. , Graessner Holm , Beltran Sergi , Ossowski Stephan , Vissers Lisenka E.L.M. , Gilissen Christian , Hoischen Alexander 
Published: May 2024

AbstractSolve-RD is a pan-European rare disease (RD) research program that aims to identify disease-causing genetic variants in previously undiagnosed RD families. We utilised 10-fold coverage HiFi long-read sequencing (LRS) for detecting causative structural variants (SVs), single nucleotide variants (SNVs), insertion-deletions (InDels), and short tandem repeat (STR) expansions in extensively studied RD families without clear molecular diagnoses. Our cohort includes 293 individuals from 114 genetically undiagnosed RD families selected by European Rare Disease Network (ERN) experts. Of these, 21 families were affected by so-called ‘unsolvable’ syndromes for which genetic causes remain unknown, and 93 families with at least one individual affected by a rare neurological, neuromuscular, or epilepsy disorder without genetic diagnosis despite extensive prior testing.Clinical interpretation and orthogonal validation of variants in known disease genes yielded thirteen novel genetic diagnoses due tode novoand rare inherited SNVs, InDels, SVs, and STR expansions. In an additional four families, we identified a candidate disease-causing SV affecting several genes including anMCF2/FGF13fusion andPSMA3deletion. However, no common genetic cause was identified in any of the ‘unsolvable’ syndromes. Taken together, we found (likely) disease-causing genetic variants in 13.0% of previously unsolved families and additional candidate disease-causing SVs in another 4.3% of these families.In conclusion, our results demonstrate the added value of HiFi long-read genome sequencing in undiagnosed rare diseases.
BRCA-DIRECT digital pathway for diagnostic germline genetic testing within a UK breast oncology setting: a randomised, non-inferiority trial
Authors: Torr B. , Jones C. , Kavanaugh G. , Hamill M. , Allen S. , Choi S. , Garrett A. , Valganon-Petrizan M. , MacMahon S. , Yuan L. , Way R. , Harder H. , Gold R. , Taylor A. , Gabe R. , Lucassen A. , Manchanda R. , Fallowfield L. , Jenkins V. , Gandhi A. , Evans D.G. , George A. , Hubank M. , Kemp Z. , Bremner S. , Turnbull C. 
Published: May 2024

ABSTRACTBACKGROUNDGenetic testing to identify germline high-risk pathogenic variants in breast cancer susceptibility genes is an important step in the breast cancer diagnostic pathway. To expand capacity and reduce turnaround time, testing is increasingly offered within ‘mainstream’ oncology services, rather than via referral to clinical genetics. However, mainstream capacity is also stretched, as testing is offered to greater proportions of patients. Novel patient-centred pathways may offer opportunity for improved access.PATIENTS AND METHODSWe recruited 1,140 women with unselected breast cancer to undergo germline genetic testing through the BRCA-DIRECT digital pathway; compromising at-home saliva sampling and consenting, with access to a digital dashboard to complete tasks and a genetic counselling telephone hotline.Ahead of consenting to the test, participants were randomised to receive information about genetic testing digitally (569/1140, 49.9%) or via a pre-test genetic counselling consultation (571/1140, 50.1%). The primary outcome was uptake of genetic testing. We also measured patient knowledge, anxiety, and satisfaction, and conducted a healthcare professional survey.RESULTS1,001 (87.8%) participants progressed to receive their pre-test information and consented to testing. Uptake was higher within participants randomised to receive digital information compared with those randomised to a pre-test genetic counselling consultation (90.8% (95% CI: 88.5% to 93.1%) vs 84.7% (95% CI: 81.8% to 87.6%), p=0.002, adjusted for participant age and site). Non-inferiority was observed in relation to all other outcomes evaluated. Usage of the telephone hotline was modest (<20% of participants; 1,441 total minutes, 344 clinical minutes recorded) and, of 37 healthcare professionals surveyed, there was majority agreement that all elements of the pathway were equivalent to current standard-of-care.CONCLUSIONFindings demonstrate that standardised, digital information offers a non-inferior alternative to conventional genetic counselling consultation, and that an end-to-end patient-centred, digital pathway (supported by genetic counselling hotline) could feasibly be implemented into mainstream breast oncology settings.
Demonstration of a Decongestant Effect of “Coldamaris Akut” Compared to Saline Nasal Spray in Participants Suffering from Seasonal Allergic Rhinitis
Authors: Unger-Manhart Nicole , Morokutti-Kurz Martina , Zieglmayer Petra , Lemell Patrick , Savli Markus , Zieglmayer René , Dellago Hanna , Prieschl-Grassauer Eva 
Published: May 2024

AbstractPurposeCarrageenan-containing nasal sprays are known to alleviate symptoms of common cold and allergic symptoms by building a barrier against airborne intruders. The objective of this study was to develop a hyperosmolar nasal spray with barrier-forming properties and to demonstrate its decongestant effect in the context of allergic rhinitis.MethodsThe efficacy of the nasal spray components was first demonstratedin vitroby a virus replication inhibition, water absorption, and barrier assay. Clinical efficacy was assessed in a randomized, controlled, crossover trial, where adults with a history of severe seasonal allergic rhinitis were exposed to grass pollen allergens under controlled conditions for a total of 6 hours. Participants received either the carrageenan- and sorbitol containing nasal spray (CS) or saline solution (SS) after 1h45min of allergen exposure. After one week, participants repeated the exposure, receiving the treatment (CS or SS) they had not received before. The primary efficacy endpoint was the mean change in ’Nasal Congestion Symptom Score’ (NCSS) during the allergen exposure. Secondary efficacy endpoints were nasal airflow, nasal secretion, total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total respiratory symptom score (TRSS).ResultsPreclinical assays showed virus-blocking, barrier building and water withdrawing properties of the CS components. In the clinical study, a total of 46 participants were screened, 41 were randomized and 39 completed the study. There was no significant difference in mean NCSS change from pre- to post-treatment between CS and SS (mean difference of 0.02 [95% CI -0.19; 0.24] during the first 2 hours after treatment) when analyzed by intention-to-treat. However, nasal airflow increased over time after treatment with CS, while it declined after SS, leading to a growing difference in airflow between CS- and SS-treated participants (p=0.039 at 6:00h). The anterior nasal airflow increased after treatment in 23/38 (61%) of the CS treated participants, compared to only 13/38 (34%) of the SS treated participants (p=0.024). The mean nasal secretion over 2-6 h was reduced by 1.00 g or -25% after CS (p=0.003) compared to pre-treatment, while it was reduced by only -0.50 g after SS (p=0.137). No significant differences in TNSS, TOSS and TRSS were observed between CS and SS treatments.ConclusionCS builds a barrier at the mucosa against viruses and dust and is safe and effective in alleviating nasal congestion, nasal airflow and nasal secretion in adults with grass pollen allergy.Trial registrationNCT04532762
High-resolution vector-borne disease infection risk mapping with Area-to-Point Poisson Kriging and Species Distribution Modeling
Authors: Moliński Szymon 
Published: May 2024

AbstractBackgroundDisease infection data is usually aggregated and shared as a sum of infections in a given area over time. This data is presented as choropleth maps. The aggregation process protects privacy and simplifies decision-making but introduces visual bias for large areas and sparsely populated places. Moreover, aggregated areas of varying sizes cannot be simply used as the input for complex ecological models, which are based on data retrieved at higher resolution on regular grids. The issue is especially painful for vector-borne diseases, e.g. Lyme Disease, where infection risk is closely related to vector species and their ecological niche.MethodsThe paper presents the method of obtaining high-resolution risk maps using a pipeline with two components: (1) spatial disaggregation component, which transforms incidence rate aggregates into the point-support model using Area-to-Point Poisson Kriging, and (2) species distribution modeling component, which detects areas where ticks bite is more likely using MaxEnt model. The first component disaggregates Lyme Disease incidence rates summed over counties in Poland, Central Europe, in 2015. The second component uses ticks occurrence maps, Leaf Area Index, Normalized Difference Vegetation Index, Land Surface Temperature derived from Earth Observation satellites, and Digital Elevation Model.The final weighted population-at-risk map is a product of both components outputs. The pipeline is built upon open source and open science projects, and it is reusable.ResultsThe presented pipeline creates high-resolution risk maps: vector occurrence probability map, population-at-risk map, and weighted population-at-risk map which includes information about local infections and about vector species. The final maps have much better resolution than aggregated incidence rates. Visual bias for population-at-risk maps is removed, and unpopulated areas are not presented on the map.ConclusionsThe pipeline might be used for other vector-borne diseases. The final weighted population-at-risk map might be used as an input for another analytical model requiring high-resolution data placed over a regular grid. The pipeline removes visual bias and transforms aggregated data into a high-resolution point-support layer.