bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Tear-Based Approach for Rapid Identification of Bacterial Pathogens in Corneal Ulcers Using Nanopore Sequencing
Authors: Dibbs Mark , Matesva Mitchelle , Theotoka Despoina , Jayaraj Christina , Metiku Beruk , Demkowicz Patrick , Heng Jacob S. , Wang Yvonne , Bakhoum Christine Y. , Chow Jessica , Bakhoum Mathieu F. 
Published: September 2024

AbstractPurposeCorneal ulcers pose a significant threat to vision, with the need for prompt and precise pathogen identification being critical to effective treatment. This study assesses the efficacy of using next-generation portable sequencing (Nanopore Technology) to detect and identify bacterial pathogens directly from tear samples, providing a non-invasive alternative to traditional corneal scraping and culture, which are limited by high false-negative rates.DesignProspective observational study.ParticipantsTen participants diagnosed with corneal ulcers.MethodsTear samples were collected from the ocular surface using Schirmer strips. Corneal scrapings and cultures were performed as medically indicated. The 16S rRNA gene was amplified directly from the tear samples using polymerase chain reaction (PCR), and Nanopore sequencing was used for bacterial species identification and taxonomic classification. Comparative analysis was conducted to evaluate the concordance between Nanopore sequencing results and traditional culture methods.Main Outcome MeasuresComparison of bacterial species detected via Nanopore sequencing with those identified through traditional culture methods.ResultsBacterial DNA was identified in 8 of the 10 samples analyzed using the tear-based sequencing method. Notably, Nanopore sequencing accurately identified the causative bacteria in all 4 samples that exhibited bacterial growth on culture. Additionally, it detected bacterial pathogens in 2 of the 4 ulcers that did not show bacterial growth on culture. In 2 cases where cultures could not be obtained due to the small size of the ulcer, tear sequencing successfully identified bacterial species, highlighting potentially overlooked pathogens in corneal ulcers.ConclusionsPCR amplification of 16S RNA directly from tears followed by Nanopore sequencing is an effective, non-invasive method to identify bacterial pathogens in corneal ulcers, offering non-inferior results to traditional culture methods. This technique not only allows for the detection of traditionally hard-to-culture organisms, providing immediate diagnostic value to guide treatment, but also enhances our understanding of the microbiological landscape of corneal ulcers, thereby informing more effective treatment strategies.
Stakeholder Perspectives on an Adult Cerebral Palsy Community Registry: A Qualitative Study
Authors: Sarmiento Cristina A. , Hurvitz Edward , Cohen Jocelyn , Gannotti Mary 
Published: September 2024

AbstractBackgroundThe Cerebral Palsy Research Network (CPRN) community registry has yielded valuable information about changes in function and pain in adults with cerebral palsy (CP) through a patient-reported outcomes registry. However, it requires increased enrollment and diversity of participants to produce more generalizable conclusions.ObjectiveTo identify stakeholder perspectives about the barriers and facilitators to enrollment in the CPRN Community Registry, strategies to enhance recruitment efforts, and important questions for the registry.MethodsQualitative descriptive study using iterative focus groups, followed by inductive thematic analysis. Participants included adults with CP and caregivers, clinical investigators, and community leaders in the CP and disability spaces. We explored perspectives about motivations for registry participation, barriers and facilitators to participation, and strategies for increasing and enhancing diversity of enrollment.ResultsWe conducted four focus groups (20 participants with lived experience; 10 clinical investigators; 9 community leaders). All participants valued the information provided by the registry and felt that ongoing data collection was important. Barriers and related facilitators to participation include benefits of participation, awareness, accessibility, and collaboration with community and clinical partners. Adults with lived experience seek more precisely defined health and function outcomes for adults with CP.ConclusionsAdults with lived experience, clinical investigators, and community leaders identified barriers and facilitators to participation in a patient-reported registry and important questions. Our study revealed that communicating a direct benefit to the participant, improved visibility and accessibility, leveraging collaboration with clinical and community partners and answering more precise research questions could promote enrollment.
Predictive Time Series Modeling of Malaria Incidence in India: A 20-Year Retrospective and 5-Year Forecast
Authors: Soni Ami 
Published: September 2024

AbstractBackgroundMalaria poses a significant health challenge in India, with notable contributions to the global malaria burden. This study aims to analyze trends in malaria incidence in India over the past two decades, evaluating the effectiveness of public health interventions.ObjectiveThe objective of this study is to analyze trends in malaria incidence in India over the past decades, evaluate the effectiveness of public health interventions, and project future trends in order to support the country’s goal of malaria elimination by 2030.MethodsA comprehensive 20-year dataset was utilized to conduct time series analyses, including linear regression and ARIMA modeling. The linear regression model assessed the trend in malaria incidence per 1,000 population at risk, while the ARIMA model was used for forecasting future trends. Residuals were evaluated for adequacy to ensure model reliability.ResultsThe linear regression analysis revealed a significant annual decrease in malaria incidence by approximately 0.92 units (p < 0.001), explaining 90.77% of the variability in the data. The ARIMA model forecasts indicate a continued decline, projecting negative incidence values by 2026 and 2027, despite some residual autocorrelation suggesting further model refinement may be necessary.DiscussionThese findings highlight the effectiveness of current public health strategies and the importance of ongoing monitoring to address remaining challenges. The projected downward trend aligns with India’s goal of malaria elimination by 2030, reinforcing the need for sustained interventions in high-burden areas.ConclusionThis study underscores the positive impact of public health initiatives on malaria incidence in India, while emphasizing the necessity for continuous research and adaptive strategies to achieve the ambitious target of malaria eradication by 2030.
Human Glycolysis Isomerases are Inhibited by Weak Metabolite Modulators
Authors: Jónatansdóttir Yiming Yang , Rolfsson Óttar , Hjörleifsson Jens G. 
Published: September 2024

AbstractModulation of enzyme activity by metabolites represents the most efficient and rapid way of controlling metabolism. Investigating enzyme-metabolite interactions can deepen our understanding of metabolic control and aid in identifying enzyme modulators with potential therapeutic applications. These interactions vary in strength, with dissociation constants (Kd) ranging from strong (nM) to weak (µM-mM). However, weak interactions are often overlooked due to the challenges in studying them. Despite this, weak modulators can reveal novel binding modes and serve as starting points for compound optimization. In this study, we aim to identify metabolites that weakly modulate the activity of human glucose-6-phosphate isomerase (GPI) and triosephosphate isomerase (TPI), which are potential therapeutic targets in tumor glycolysis. Through a combination of activity and binding assays, the screening revealed multiple weak inhibitors for the two targets, causing partial attenuation of their activity, with Kdand Kiin the low mM range. X-ray crystallography revealed six orthosteric ligands binding to the active sites – four inhibitors of GPI and two of TPI. Our findings underscore the role of weak interactions in enzyme regulation and may provide structural insights that could guide the design of inhibitors targeting human GPI and TPI in cancer intervention.Abstract Figure
Transcripts with high distal heritability mediate genetic effects on complex metabolic traits
Authors: Tyler Anna L. , Mahoney J. Matthew , Keller Mark P. , Baker Candice N. , Gaca Margaret , Srivastava Anuj , Gerdes Gyuricza Isabela , Braun Madeleine J. , Rosenthal Nadia A. , Attie Alan D. , Churchill Gary A. , Carter Gregory W. 
Published: September 2024

AbstractAlthough many genes are subject to local regulation, recent evidence suggests that complex distal regulation may be more important in mediating phenotypic variability. To assess the role of distal gene regulation in complex traits, we combined multi-tissue transcriptomes with physiological outcomes to model diet-induced obesity and metabolic disease in a population of Diversity Outbred mice. Using a novel high-dimensional mediation analysis, we identified a composite transcriptome signature that summarized genetic effects on gene expression and explained 30% of the variation across all metabolic traits. The signature was heritable, interpretable in biological terms, and predicted obesity status from gene expression in an independently derived mouse cohort and multiple human studies. Transcripts contributing most strongly to this composite mediator frequently had complex, distal regulation distributed throughout the genome. These results suggest that trait-relevant variation in transcription is largely distally regulated, but is nonetheless identifiable, interpretable, and translatable across species.
Asymptomatic infection and antibody prevalence to co-occurring avian influenza viruses vary substantially between sympatric seabird species following H5N1 outbreaks
Authors: Greco Fiona , Ravenswater Hannah M. , Ruiz-Raya Francisco , D’Avino Chiara , Newell Mark A. , Hewitt Josie , Taylor Erin , Benninghaus Ella , Daunt Francis , Goodman Gidona , Steel David , Park Jenny , Philip Emma , Thomas Saumya , Slomka Marek J. , Falchieri Marco , Reid Scott M. , James Joe , Banyard Ashley C. , Burthe Sarah J. , Cunningham Emma J.A. 
Published: September 2024

AbstractEmerging infectious diseases are of major concern to animal and human health. Recent emergence of high pathogenicity avian influenza virus (HPAIV) (H5N1 clade 2.3.4.4b) led to substantial global mortality across a range of host species. Co-occurring species showed marked differences in mortality, generating an urgent need for better epidemiological understanding within affected populations. We therefore tested for antibodies, indicative of previous exposure and recovery, and for active viral infection in apparently healthy individuals (n=350) across five co-occurring seabird species on the Isle of May, Scotland, during 2023, following H5N1 HPAIV associated mortality in the preceding summer. Antibody prevalence to AIV subtypes varied substantially between species, ranging from 1.1% in European shags (Gulosus aristotelis) (to H5) to 78.7% in black-legged kittiwakes (Rissa tridactyla) (to H16 or both H13 and H16), and between 31-41% for three auk species (H5, H16 or both). At least 20.4% of auks had antibodies to an as yet unidentified subtype, suggesting further subtypes circulating in the population. We found low levels of active, but asymptomatic, AIV infection in individuals (1.6-4.5%), but excluded this as H5N1. Our results emphasise the importance of testing healthy individuals to understand the prevalence of co-circulating AIV subtypes in wild populations, and the potential for future reassortment events which could alter virus behaviour and impact.
A long-term ecological research data set from the marine genetic monitoring programme ARMS-MBON 2018-2020
Authors: Daraghmeh Nauras , Exter Katrina , Pagnier Justine , Bałazy Piotr , Cancio Ibon , Chatzigeorgiou Giorgos , Chatzinikolaou Eva , Chełchowski Maciej , Chrismas Nathan Alexis Mitchell , Comtet Thierry , Dailianis Thanos , Deneudt Klaas , Diaz de Cerio Oihane , Digenis Markos , Gerovasileiou Vasilis , González José , Kauppi Laura , Kristoffersen Jon Bent , Kukliński Piotr , Lasota Rafał , Levy Liraz , Małachowicz Magdalena , Mavrič Borut , Mortelmans Jonas , Paredes Estefania , Poćwierz-Kotus Anita , Reiss Henning , Santi Ioulia , Sarafidou Georgia , Skouradakis Grigorios , Solbakken Jostein , Staehr Peter A.U. , Tajadura Javier , Thyrring Jakob , Troncoso Jesus S. , Vernadou Emmanouela , Viard Frederique , Zafeiropoulos Haris , Zbawicka Małgorzata , Pavloudi Christina , Obst Matthias 
Published: September 2024

ABSTRACTMolecular methods such as DNA/eDNA metabarcoding have emerged as useful tools to document biodiversity of complex communities over large spatio-temporal scales. We established an international Marine Biodiversity Observation Network (ARMS-MBON) combining standardised sampling using autonomous reef monitoring structures (ARMS) with metabarcoding for genetic monitoring of marine hard-bottom benthic communities. Here, we present the data of our first sampling campaign comprising 56 ARMS units deployed in 2018-2019 and retrieved in 2018-2020 across 15 observatories along the coasts of Europe and adjacent regions. We describe the open-access data set (image, genetic, and metadata) and explore the genetic data to show its potential for marine biodiversity monitoring and ecological research. Our analysis shows that ARMS recovered more than 60 eukaryotic phyla capturing diversity of up to ∼5,500 amplicon sequence variants and ∼1,800 operational taxonomic units, and up to ∼250 and ∼50 species per observatory using the cytochromecoxidase subunit I (COI) and 18S rRNA marker genes, respectively. Further, ARMS detected threatened, vulnerable and non-indigenous species often targeted in biological monitoring. We show that while deployment duration does not drive diversity estimates, sampling effort and sequencing depth across observatories do. We recommend that ARMS should be deployed for at least three to six months during the main growth season to use resources as efficiently as possible and that post-sequencing curation is applied to enable statistical comparison of spatio-temporal entities. We suggest that ARMS should be used in biological monitoring programmes and long-term ecological research and encourage the adoption of our ARMS-MBON protocols.
Twist is the key to the gating of mechanosensitive ion channel NOMPC
Authors: Duan Jingze , Song Chen 
Published: September 2024

AbstractNOMPC, a tethered mechanosensitive ion channel from the transient receptor potential (TRP) family, can convert mechanical stimuli to ionic electric signals to excite neuron cells. Previous investigations revealed that a pushing force exerted on the linker helix domain or the compression of NOMPC’s ankyrin repeat (AR) domain triggers channel opening. In this study, we explored the direct mechanical cause for NOMPC channel opening as well as the torsional properties of the AR domain using all-atom molecular dynamics simulations. Our results demonstrate that a torque pointing toward the extracellular side, exerted on the amphipathic TRP domain, serves as the direct cause of driving the channel open. The coupling between the compression and twisting of the AR domain ensures that both types of deformations can open the channel. Therefore, we propose a twist-to-open model, facilitated by the compression-twist coupling property of the AR domain, to further elucidate the gating mechanism of the NOMPC channel.
WITHDRAWN: New neural-inspired controller generalises modularity over lower limb tasks through internal models
Authors: Muñoz David , Holland Donal , Severini Giacomo 
Published: September 2024

Withdraw statementThe authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2023/569887. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2023.12.04.569887
A qualitative review of Oxford Nanopore Sequencing datasets for RNA modifications
Authors: Pahar Madhurananda , Liu Qian 
Published: September 2024

AbstractThere are many oxford nanopore datasets available to study methylations. Methylations and modifications occur at nucleotides such as adenine (A), cytosine (C), guanine (G) and theanine (T) or uracil (U). Among all these provided datasets, some have the most common m6A methylation and others have m5C etc. using various real organism reference sequences such as human, mouse and artificial reference sequences which are prepared in the laboratory such as curlcake and IVT. These datasets are required to be organized by the methylation types to research ONT datasets. Here we provide a summary of the read qualities, base mapping success rates etc. for these methylation types and reference genomes. We have used minimap2 base mapping and longreadsum results. We find that methylated data have lower success rates than non-methylated data and mapping quality is lower for the real reference genomes such as human and mice. This could be because they contain more than 100,000 transcriptomes whereas artificial reference sequences contain only a few transcriptomes. Datasets which contain artificially created reference sequences have a higher quality than the others, thus they are recommended to be used for methylation or modification classification tasks in the future.DatasetAll datasets used in this study are the publicly available.Dataset LicenseAll datasets used in this study are the publicly available.
Small eukaryotic phytoplankton can play an outsized role in carbon export in iron-limited regions
Authors: Meyer Meredith G. , White Vincent J. , Torano Olivia , Hannoush Heidi , Marchetti Adrian 
Published: September 2024

AbstractSmall eukaryotic phytoplankton can account for considerable amounts of biomass and primary production in high nutrient, low chlorophyll (HNLC) regions of the ocean where iron-limitation is pronounced. However, the strategies these cells invoke to cope under low iron conditions and the extent to which they are responsible for new production (i.e., the fraction of primary production supported by nutrients from outside of the euphotic zone) is unclear. Here, we examine how a representative picoeukaryote, the chlorophyteBathycoccus sp., recently isolated from the iron-limited subarctic North Pacific Ocean, responds to iron-limitation and quantify its potential contribution to carbon export. Iron-limitedBathycoccusexhibits reductions in cellular growth rate, volume, and carbon and nitrogen quotas along with a restructuring of cellular metabolism. Gene expression and pathway analyses show evidence of cellular strategies to mitigate iron limitation but constitutive expression of genes related to nitrogen uptake and utilization. Additionally, when grown on nitrate, cellular carbon and nitrogen quotas ranged from 0.02 – 0.17 pmol C cell-1and 3.3 x 10-3– 2.2 x 10-2pmol N cell-1, respectively, as a function of iron status. Based on the measured cellular quotas, we estimate that representative picoeukaryotes, such asBathycoccus,in HNLC North Pacific waters can account for a majority of new production under ambient iron-limited conditions, supporting the need for a paradigm shift in our thinking of the role small eukaryotic phytoplankton play in the global carbon cycle.
Laser Speckle Particle Sizer (SPARSE) Informs the Size Distribution of Tissue Granularities
Authors: Hajjarian Zeinab , Zeng Ziqian , Leartprapun Nichaluk , Nadkarni Seemantini K. 
Published: September 2024

AbstractParticle sizing of biomaterials and tissues holds profound implications across diverse industrial and clinical disciplines. Conventional approaches such as dynamic light scattering (DLS) are restricted to dilute liquids, and unable to assess particle size distribution in intact, untampered biomaterials and tissues in their native state. Here, we introduce the laser Speckle PARticle SizEr (SPARSE), which leverages the size-dependent attributes of polarized back-scattered laser speckle to characterize the average radius of a continuum of endogenous scattering particles, in the 10nm-10μm range, in biological fluids and soft tissues in their native state. The SPARSE approach exploits cross- and co-polarized attributes of spatial and temporal laser speckle intensity fluctuations to quantify the average particle size in various specimens, including polystyrene microspheres, milk, whole blood specimens, and intact soft tissues, without prior knowledge or explicit account of refractive index and scattering concentrations. Through scanning the laser beam across the tissue surface, we establish the capability of SPARSE to evaluate a spatial map of heterogenous scattering particle sizes with a resolution of a few 10s ofμm that closely mirrors histopathological microstructures in benign and carcinoma breast tissue specimens. By enabling the size characterization of intact tissues and biomaterials across a continuum of granularities, non-destructively in native specimens, SPARSE opens substantial opportunities for quality control in industrial applications, drug development, and advanced clinical diagnostics.
Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown
Authors: Dargan Rachael , Mikheenko Alla , Johnson Nicholas L. , Packer Benjamin , Li Ziyi , Craig Emma J. , Sarbanes Stephanie L. , Bereda Colleen , Mehta Puja R. , Keuss Matthew , Nalls Mike A. , Qi Yue A. , Weller Cory A. , Fratta Pietro , Ryan Veronica H. 
Published: September 2024

AbstractNeurons rely on mRNA transport and local translation to facilitate rapid protein synthesis in processes far from the cell body. These processes allow precise spatial and temporal control of translation and are mediated by RNA binding proteins (RBPs), including those known to be associated with neurodegenerative diseases. Here, we use proteomics, transcriptomics, and microscopy to investigate the impact of RBP knockdown on mRNA transport and local translation in iPSC-derived neurons. We find thousands of transcripts enriched in neurites and that many of these transcripts are locally translated, possibly due to the shorter length of transcripts in neurites. Loss of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS)-associated RBPs TDP- 43 and hnRNPA1 lead to distinct alterations in the neuritic proteome and transcriptome. TDP-43 knockdown (KD) leads to increased neuritic mRNA and translation. In contrast, hnRNPA1 leads to increased neuritic mRNA, but not translation, and more moderate effects on local mRNA profiles, possibly due to compensation by hnRNPA3. These results highlight the crucial role of FTD/ALS-associated RBPs in mRNA transport and local translation in neurons and the importance of these processes in neuron health and disease.