bluuebunny/crossref_metadata_2025_split huggingface dataset:
Directionality of neural activity in and out of the seizure onset zone in focal epilepsy
Authors: Karimi-Rouzbahani Hamid , McGonigal Aileen 
Published: August 2024

AbstractEpilepsy affects over 50 million people worldwide, with approximately 30% experiencing drug- resistant forms that may require surgical intervention. Accurate localisation of the epileptogenic zone (EZ) is crucial for effective treatment, but how best to use intracranial EEG data to delineate the EZ remains unclear. Previous studies have used the directionality of neural activities across the brain to investigate seizure dynamics and localise the EZ. However, the different connectivity measures used across studies have often provided inconsistent insights about the direction and the localisation power of signal flow as a biomarker for EZ localisation. In a data-driven approach, this study employs a large set of 13 distinct directed connectivity measures to evaluate neural activity flow in and out the seizure onset zone (SOZ) during interictal and ictal periods. These measures test the hypotheses of “sink SOZ” (SOZ dominantly receiving neural activities during interictal periods) and “source SOZ” (SOZ dominantly transmitting activities during ictal periods). While the results were different across connectivity measures, several measures consistently supported higher connectivity directed towards the SOZ in interictal periods and higher connectivity directed away during ictal period. Comparing six distinct metrics of node behaviour in the network, we found that SOZ separates itself from the rest of the network allowing for the metric of “eccentricity”to localise the SOZ more accurately than any other metrics including “in strength”and “out strength”. This introduced a novel biomarker for localising the SOZ, leveraging the discriminative power of directed connectivity measures in an explainable machine learning pipeline. By using a comprehensive, objective and data-driven approach, this study addresses previously unresolved questions on the direction of neural activities in seizure organisation, and sheds light on dynamics of interictal and ictal activity in focal epilepsy.
Faster amylin aggregation on fibrillar collagen hastens diabetic progression through β cell death and loss of function
Authors: Hazari Md Asrafuddoza , Kannan Gautam , Jha Akash Kumar , Pavan Musale Krushna , Dasgupta Subrata , Sultana Farhin , Pujahari Soumya Ranjan , Singh Simran , Dutta Sarbajeet , Pydi Sai Prasad , Dutta Sankhadeep , Bhaumik Prasenjit , Zafar Hamim , Kumar Ashutosh , Sen Shamik 
Published: August 2024

AbstractAmyloid deposition of the neuroendocrine peptide amylin in islet tissues is a hallmark of type 2 diabetes (T2DM), leading to β-cell toxicity through nutrient deprivation, membrane rupture and apoptosis. Though accumulation of toxic amylin aggregates in islet matrices is well documented, the role of the islet extracellular matrix in mediating amylin aggregation and its pathological consequences remains elusive. Here, we address this question by probing amylin interaction with collagen I (Col I)—whose expression in the islet tissue increases during diabetes progression. By combining multiple biophysical techniques, we show that hydrophobic, hydrophilic & cation-π interactions regulate amylin binding to Col I, with fibrillar collagen driving faster amylin aggregation. Amylin-entangled Col I matrices containing high amounts of amylin induce death and loss of function of INS1E β-cells. Together, our results illustrate how amylin incorporation in islet matrices through amylin-Col interactions drives T2DM progression by impacting β-cell viability and insulin secretion.
PPARγ activation by lipolysis-generated ligands is required for cAMP dependentUCP1induction in human thermogenic adipocytes
Authors: Desai Anand , Yang Loureiro Zinger , DeSouza Tiffany , Yang Qin , Solivan-Rivera Javier , Corvera Silvia 
Published: August 2024

ABSTRACTObjectiveThe uncoupling protein 1 (UCP1) is induced in brown or “beige” adipocytes through catecholamine-induced cAMP signaling, which activates diverse transcription factors. UCP1 expression can also be enhanced by PPARγ agonists such as rosiglitazone (Rsg). However, it is unclear whether this upregulation results from de-novo differentiation of beige adipocytes from progenitor cells, or from the induction of UCP1 in pre-existing adipocytes. To explore this, we employed human adipocytes differentiated from progenitor cells and examined their acute response to Rsg, to the adenylate-cyclase activator forskolin (Fsk), or to both simultaneously.MethodsAdipocytes generated from primary human progenitor cells were differentiated without exposure to PPARγ agonists, and treated for 3, 6 or 78 hours to Fsk, to Rsg, or to both simultaneously. Bulk RNASeq, RNAScope, RT-PCR, CRISPR-Cas9 mediated knockout, oxygen consumption and western blotting were used to assess cellular responses.ResultsUCP1mRNA expression was induced within 3 hours of exposure to either Rsg or Fsk, indicating that Rsg’s effect is independent on additional adipocyte differentiation. Although Rsg and Fsk induced distinct overall transcriptional responses, both induced genes associated with calcium metabolism, lipid droplet assembly, and mitochondrial remodeling, denoting core features of human adipocyte beiging. Unexpectedly, we found that Fsk-inducedUCP1expression was reduced by approximately 80% following CRISPR-Cas9-mediated knockout ofPNPLA2, the gene encoding the triglyceride lipase ATGL. As anticipated, ATGL knockout suppressed lipolysis; however, the associated suppression of UCP1 induction indicates that maximal cAMP-mediatedUCP1induction requires products of ATGL-catalyzed lipolysis. Supporting this, we observed that the reduction in Fsk-stimulated UCP1 induction caused by ATGL knockout was reversed by Rsg, implying that the role of lipolysis in this process is to generate natural PPARγ agonists.ConclusionUCP1transcription is known to be stimulated by transcription factors activated downstream of cAMP-dependent protein kinases. Here we demonstrate thatUCP1transcription can also be acutely induced through PPARγ-activation. Moreover, both pathways are activated in human adipocytes in response to cAMP, synergistically inducing UCP1 expression. The stimulation of PPARγ in response to cAMP occurs as a result of the production of natural PPARγ activating ligands through ATGL-mediated lipolysis.GRAPHICAL ABSTRACT
3D printed microtissue cassettes enabling high throughput proton radiobiological assays
Authors: Yang Chih-Tsung , Cho I-Chun , Yu Ching-Fang , Cheah Edward , Liu Tesi , Lin Yi-Ping , Hu Sing-Yu , Jheng Jyun-Wei , Kempson Ivan , Chao Tsi-Chian , Lee Sen-Hao , Bezak Eva , Thierry Benjamin 
Published: August 2024

AbstractUncertainties on proton relative biological effectiveness (RBE) across the spread out of Bragg peak (SOBP) (typically assumed to be 1.1) may lead to suboptimal treatment plan and unwarranted toxicity to organs-at-risk. Herein, we report a reliable analytical method to determine the proton RBE along the SOBP and distal fall-off region. The 3D microtissue cassette enables the high throughput assessment of biological assays including clonogenic assay and γ-H2AX assay following a single proton irradiation. Clonogenic assay shows the RBE of 1.6 (10% cellular survival) which is consistent with the deter-mined RBE of 1.58 using the γ-H2AX assay. Besides, we also show that the high spatial resolution of the cassette can distinguish the minute but significant foci changes (number, area) in response to small proton radiation dose fraction. The results validate the reliability of our setup in addressing critical proton radiobiological questions.
Use of Biochemical Biomarkers to Evaluate the Role of Oxidative Stress in the Progression of COVID-19 Severity
Authors: Marcano-Marcano Luis , Salazar-Lugo Raquel 
Published: August 2024

AbstractThe role of oxidative stress and the use of biochemical biomarkers in the severity of COVID-19 was evaluated through a literature review (2020–2021) using scientific search engines such as PubMed, Science Direct, and Google Scholar. The search was limited to articles published in Spanish or English that reported on COVID-19 and its relationship with oxidative stress, following PRISMA-2020 guidelines. The search terms included oxidative stress, COVID-19, SARS-CoV-2, oxidative biomarkers, and oxidative damage. 93.5% of the selected studies were from the year 2021. These studies evaluated both oxidative stress biomarkers and oxidative damage biomarkers in COVID-19 patients. The reviewed studies reinforce the strong association of SARS-CoV-2 with oxidative stress and demonstrate how SARS-CoV-2-induced ROS production and disruption of the antioxidant defense system trigger a pro-inflammatory environment and cause severe tissue damage. In 64.7% of the studies, a combination of oxidative stress biomarkers (antioxidant and oxidative damage biomarkers) was used to assess COVID-19 severity. The most commonly used antioxidant biomarkers were thiols and total antioxidant capacity, followed by glutathione. The most commonly used oxidative damage biomarkers were malondialdehyde and peroxides, followed by advanced oxidation protein products. COVID-19 leads to a decrease in the antioxidant defense system, reflected by a decrease in antioxidant biomarkers and an increase in oxidative damage biomarkers.
Study Protocol: A Scoping Review on Costing Methodologies in Robotic Ventral Hernia Repair
Authors: Nielsen Kristian Als , Kaiser Karsten , Helligsø Per , Nielsen Michael Festersen , Valorenzos Alexandros 
Published: August 2024

AbstractBackgroundHealthcare expenditure is increasing at a rate that surpasses the growth of the gross domestic product in most Western nations, emphasizing the need for precise hospital accounting practices. In resource-constrained environments, accurately estimating the costs of hospital services, such as robotic ventral hernia repair, is essential for achieving efficiency and transparency. Despite the existence of several studies reporting on the cost of robotic ventral hernia repair, there is a lack of systematic mapping of current knowledge on the methodological designs used in studies reporting on the costs and resource use.MethodsThis study protocol outlines the methodology for a scoping review aimed at systematically mapping the existing literature on costing methodologies in robotic ventral hernia repair. The scoping review will follow the framework outlined by Arksey and O’Malley and adhere to the PRISMA-ScR guidelines. A systematic search will be conducted in Embase, Medline and Cochrane Library. Studies will be included if they involve patients undergoing robotic ventral hernia repair and report on cost/costing methodologies. The review will extract data on study characteristics, intervention specifics, and detailed costing methodologies. Two independent reviewers will conduct the data extraction, with discrepancies resolved through discussion or by a third reviewer.DiscussionThe review will identify significant variations in costing methodologies, including differences in perspectives (hospital vs. societal), time horizons, and cost components. It aims to highlight gaps and inconsistencies in the current literature, providing a foundation for future research to standardize costing methodologies and improve the accuracy of economic evaluations in robotic surgery. By systematically mapping the existing literature, this scoping review will provide valuable insights into the current state of costing methodologies in robotic ventral hernia repair. It will serve as a foundational reference for researchers, policymakers, and healthcare providers, offering recommendations to enhance the economic evaluation of robotic surgical technologies.
Assessing Population-level Accessibility to Medical College Hospitals in India: A Geospatial Modeling Study
Authors: Thakkar Harsh , Reddy Chaitanya , Passi Varun Raj , Miyajiwala Aamir , Kale Sahil , Raj Ankit , Zadey Siddhesh 
Published: August 2024

ABSTRACTBackgroundWhile studies have investigated the availability of Medical College Hospitals (MCHs) in India, data on geographical accessibility is limited. Our study looks at the current geographical accessibility to these MCHs across 36 states and union territories (UTs) and 735 districts.Methods and FindingsWe provided and validated the MCH data acquired from the National Health Profile Report 2022. We took motorized and walking travel-time friction surface rasters from the Malaria Atlas Project 2019 and high-resolution population estimates from WorldPop 2020. Using these, we examined the density of MCHs per million population and the median travel time to the nearest MCH. We assessed the Access Population Coverage (APC), defined as the proportion of the population within 30, 60, 90, and 120 minutes by motorized transport and within 30 and 60 minutes from the nearest MCH by walking.In 2022, India had an average density of 0.47 MCHs per million. The median travel time to the nearest MCH was 67.94 minutes by motorized transport and 589.82 minutes by walking. 71.76% of the population could access the nearest MCH by motorized transport within 60 minutes (range across districts: 0-100%). 4.22% of the population could access the nearest MCH by walking within 30 minutes (range across districts: 0-71.86%). The APC was 62.20% within 60 minutes by motorized transport in rural vs. 92.34% in urban areas. The APC within 60 minutes by motorized transport for public MCHs was 63.62%, while that for private was 45.95%. These estimates do not account for resource availability at the hospitals or vehicular ownership in the population.ConclusionsMedian travel time and APC are useful for assessing geographical accessibility. Our study found a wide disparity in MCH access across Indian states and rural vs. urban areas. These analyses can guide the optimal placement of new MCHs.
OzWheat: a genome-to-phenome platform to resolve complex traits for wheat pre-breeding and research
Authors: Hyles Jessica E. , Eagles Howard A. , Ramm Kerrie , Sherman Bjorg , Gock Andrew , Stops Sandra , Phongkham Tanya , Leyne Emmett , Rathjen Tina , Suchecki Radoslaw , Stevens Lauren , Ord Louise , Fradgley Nick S. , McNeil Meredith D. , Marquardt Annelie , Andrew Samuel C. , Forrest Kerrie , Eastwood Russell F. , Norman Adam , Tredrea Annette , Trethowan Richard , Trevaskis Ben , Dillon Shannon K. 
Published: August 2024

AbstractFor over a century, Australian wheat breeders have successfully adapted wheat to a broad range of climatic conditions and crop management practices. The OzWheat genome-to-phenome (G2P) platform was established to capture this breeding history and explore traits, genes, and their interactions with the environment to enable ongoing research and deliver targets for wheat improvement. A panel of 285 cultivars and landraces were chosen through knowledge of breeding pedigrees to represent both global diversity and the historic flow of genetic variation over more than 100 years of selective breeding in Australia. Genetic characterisation of the panel included identification of genome-wide sequence variants and gene expression profiling across environments. Important traits for adaptation (flowering time and plant height) were assayed in controlled environments and at multiple field sites and years, with genome-wide association analyses (GWAS) using linear mixed models detecting both known and novel loci. Here, we report establishment of the OzWheat G2P platform as a powerful tool to integrate wheat genomes and phenomes and demonstrate its use to identify candidate genes and understand gene by environment interactions. This provides the wheat research and breeding community a new resource to support future cultivar development.
Neural Sequences Underlying Directed Turning inC. elegans
Authors: Kramer Talya S. , Wan Flossie K. , Pugliese Sarah M. , Atanas Adam A. , Hiser Alex W. , Luo Jinyue , Bueno Eric , Flavell Steven W. 
Published: August 2024

AbstractComplex behaviors like navigation rely on sequenced motor outputs that combine to generate effective movement. The brain-wide organization of the circuits that integrate sensory signals to select and execute appropriate motor sequences is not well understood. Here, we characterize the architecture of neural circuits that controlC. elegansolfactory navigation. We identify error-correcting turns during navigation and use whole-brain calcium imaging and cell-specific perturbations to determine their neural underpinnings. These turns occur as motor sequences accompanied by neural sequences, in which defined neurons activate in a stereotyped order during each turn. Distinct neurons in this sequence respond to sensory cues, anticipate upcoming turn directions, and drive movement, linking key features of this sensorimotor behavior across time. The neuromodulator tyramine coordinates these sequential brain dynamics. Our results illustrate how neuromodulation can act on a defined neural architecture to generate sequential patterns of activity that link sensory cues to motor actions.
Interpretable improving prediction performance of general protein language model by domain-adaptive pretraining on DNA-binding protein
Authors: Zeng Wenwu , Dou Yutao , Pan Liangrui , Xu Liwen , Peng Shaoliang 
Published: August 2024

ABSTRACTDNA-protein interactions exert the fundamental structure of many pivotal biological processes, such as DNA replication, transcription, and gene regulation. However, accurate and efficient computational methods for identifying these interactions are still lacking. In this study, we propose a novel method ESM-DBP through refining the DNA-binding protein (DBP) sequence repertory and domain-adaptive pretraining based the protein language model (PLM). Our method considers the lack of exploration of general PLM for DBP domain-specific knowledge, so we screened out 170,264 DBPs from the UniProtKB database to construct the model that more suitable for learning crucial characteristics of DBP. The evaluation of ESM-DBP is systematically performed in four different DBP-related downstream prediction tasks, i.e., DNA-binding protein, DNA-binding residue, transcription factor, and DNA-binding Cys2His2 zinc-finger predictions. Experimental results show that ESM-DBP provides a better feature representation of DBP compared to the original PLM, resulting in improved prediction performance and outperforming other state-of-the-art prediction methods. In addition, ESM-DBP incorporates the integrated gradient algorithm for interpretable analysis, which usually ignored in the previous methods. It reveals that ESM-DBP possesses high sensitivity to the key decisive DNA-binding domains. Moreover, we find that ESM-DBP can still perform well even for those DBPs with only a few similar homologous sequences, and this generalization performs better than the original PLM. The data and standalone program of ESM-DBP are freely accessible athttps://github.com/pengsl-lab/ESM-DBP.
Characterization of a marine bacteria through a novel metabologenomics approach
Authors: Arini Gabriel Santos , Borelli Tiago Cabral , Ferreira Elthon Góis , de Felício Rafael , Teixeira Paula Rezende , Pedrino Matheus , Rabiço Franciene , de Siqueira Guilherme Marcelino Viana , Mencucini Luiz Gabriel , Tsuji Henrique , Andrade Lucas Sousa Neves , Garrido Leandro Maza , Padilla Gabriel , Gil-de-la-Fuente Alberto , Wang Mingxun , Lopes Norberto Peporine , Trivella Daniela Barretto Barbosa , Costa Lotufo Leticia Veras , Guazzaroni María-Eugenia , da Silva Ricardo Roberto 
Published: August 2024

AbstractExploiting microbial natural products is a key pursuit of the bioactive compound discovery field. Recent advances in modern analytical techniques have increased the volume of microbial genomes and their encoded biosynthetic products measured by mass spectrometry-based metabolomics. However, connecting multi-omics data to uncover metabolic processes of interest is still challenging. This results in a large portion of genes and metabolites remaining unannotated. Further exacerbating the annotation challenge, databases and tools for annotation and omics integration are scattered, requiring complex computations to annotate and integrate omics datasets. Here we performed a two-way integrative analysis combining genomics and metabolomics data to describe a new approach to characterize the marine bacterial isolate BRA006 and to explore its biosynthetic gene cluster (BGC) content as well as the bioactive compounds detected by metabolomics. We described BRA006 genomic content and structure by comparing Illumina and Oxford Nanopore MinION sequencing approaches. Digital DNA:DNA hybridization (dDDH) taxonomically assigned BRA006 as a potential new species of theMicromonosporagenus. Starting from LC-ESI(+)-HRMS/MS data, and mapping the annotated enzymes and metabolites belonging to the same pathways, our integrative analysis allowed us to correlate the compound Brevianamide F to a new BGC, previously assigned to other function.
Environmental DNA Surveys of Invertebrate Community on Forest Canopies Using Rainwater Analysis
Authors: Miwa Takumaru , Miyashita Naoya , Numa Chisato , Doi Hideyuki 
Published: August 2024

AbstractForest canopies, known for their high biodiversity, are essential for understanding forest ecosystems. Traditional methods for canopy surveys, such as tree climbing and canopy walkways, face challenges related to safety, cost, and time constraints. Environmental DNA (eDNA) analysis, which involves examining DNA from environmental samples, offers a promising alternative for these surveys. This study investigates the feasibility of using rainwater to collect eDNA from forest canopies, utilizing rain’s natural ability to wash away DNA from hard-to-reach areas. By comparing DNA analysis results from rainwater with conventional records obtained through visual and capture surveys, this research aims to validate the effectiveness and reliability of this method. Preliminary findings suggest that eDNA analysis from rainwater could provide an efficient approach to canopy biodiversity surveys, though further validation is required. This study marks an important first step towards developing eDNA analysis as a complementary tool for forest canopy research.