bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbidities, Behaviors, and Socioeconomic Factors and Mortality from Diseases of the Heart in New Jersey
Authors: Guariglia Matthew , Poos Stephen , Gawash Ahmed , Lo David F. 
Published: January 2023

AbstractMortality from diseases of the heart claimed the lives of 186,074 New Jerseyans from 2010 to 2019. This study aims to establish correlations between each of health-related risk factors and death from heart disease in each of the six New Jersey counties. Each of the counties ranked by age-adjusted mortality per 100,000 from diseases of the heart. The six counties were divided by the least (Hunterdon, Somerset, Bergen) and greatest (Cape May, Salem, and Cumberland) mortality rates from heart disease. Additionally, this data was broken down into three main categories that include comorbidities, socioeconomic status, and behavior patterns. Each main category is further broken down into subcategories that provide further evidence of how mortality from heart disease impacts the garden state. The main outcome of death in adults over 25 from heart disease from 2010 to 2019 was correlated to 28 health factors including comorbidities, behaviors, and socioeconomic factors. An R squared value was calculated to evaluate the strength of the correlation between each factor and the outcome of mortality from disease of the heart.
Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution
Authors: Bartos Laura M , Kirchleitner Sabrina V , Kolabas Zeynep Ilgin , Quach Stefanie , Blobner Jens , Mueller Stephan A , Ulukaya Selin , Hoeher Luciano , Horvath Izabela , Wind-Mark Karin , Holzgreve Adrien , Ruf Viktoria C , Gold Lukas , Kunze Lea H , Kunte Sebastian T , Beumers Philipp , Antons Melissa , Zatcepin Artem , Briel Nils , Hoermann Leonie , Messerer Denise , Bartenstein Peter , Riemenschneider Markus J , Lindner Simon , Ziegler Sibylle , Herms Jochen , Lichtenthaler Stefan F , Ertürk Ali , Tonn Joerg C , Baumgarten Louisa von , Albert Nathalie L , Brendel Matthias 
Published: January 2023

AbstractVarious cellular sources hamper interpretation of positron-emission-tomography (PET) biomarkers in the tumor microenvironment (TME). We developed immunomagnetic cell sorting afterin vivoradiotracer injection (scRadiotracing) in combination with 3D-histology via tissue clearing to dissect the cellular allocation of PET signals in the TME. In SB28 glioblastoma mice, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs). Cellular radiotracer uptake was validated by proteomics and confirmed forin vitrosamples of patients with glioblastoma. Regional agreement between PET signals and single cell tracer uptake predicted the individual cell distribution in 3D-histology. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma, however proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D-histology facilitates precise allocation of complex PET signal sources and will serve to validate novel TAM-specific radioligands.
Multi-omics data integration approach identifies potential biomarkers for Prostate cancer
Authors: Chikwambi Zedias , Hidjo Marie , Chikondowa Pageneck , Jayeoba Glory , Aketch Vincent , Afolabi Lawrence , Awe Olaitan I. , Enoma David 
Published: January 2023

AbstractProstate cancer (PCa) is one of the most common malignancies, and many studies have shown that PCa has a poor prognosis, which varies across different ethnicities. This variability is caused by genetic diversity. High-throughput omics technologies have identified and shed some light on the mechanisms of its progression and finding new biomarkers. Still, a systems biology approach is needed for a holistic molecular perspective. In this study, we applied a multi-omics approach to data analysis using different publicly available omics data sets from diverse populations to better understand the PCa disease etiology. Our study used multiple omic datasets, which included genomic, transcriptomic and metabolomic datasets, to identify drivers for PCa better. Individual omics datasets were analysed separately based on the standard pipeline for each dataset. Furthermore, we applied a novel multi-omics pathways algorithm to integrate all the individual omics datasets. This algorithm applies the p-values of enriched pathways from unique omics data types, which are then combined using the MiniMax statistic of the PathwayMultiomics tool to prioritise pathways dysregulated in the omics datasets. The single omics result indicated an association between up-regulated genes in RNA-Seq data and the metabolomics data. Glucose and pyruvate are the primary metabolites, and the associated pathways are glycolysis, gluconeogenesis, pyruvate kinase deficiency, and the Warburg effect pathway. From the interim result, the identified genes in RNA-Seq single omics analysis are linked with the significant pathways from the metabolomics analysis. The multi-omics pathway analysis will eventually enable the identification of biomarkers shared amongst these different omics datasets to ease prostate cancer prognosis.
Heparan sulfates regulate axonal excitability and context generalization through Ca2+/calmodulin-dependent protein kinase II
Authors: Song Inseon , Kuznetsova Tatiana , Baidoe-Ansah David , Mirzapourdelavar Hadi , Senkov Oleg , Hayani Hussam , Mironov Andrey , Kaushik Rahul , Druzin Michael , Johansson Staffan , Dityatev Alexander 
Published: January 2023

AbstractOur previous studies demonstrated that enzymatic removal of highly sulfated heparan sulfates with heparinase 1 impaired axonal excitability and reduced expression of ankyrin G at the axon initial segments in the CA1 region of the hippocampus ex vivo, impaired context discrimination in vivo, and elevated Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity in vitro. Here, we show that in vivo delivery of heparinase 1 in the CA1 region of the hippocampus elevated autophosphorylation of CaMKII 24 hours after injection in mice. Patch-clamp recording in CA1 neurons revealed no significant heparinase effects on the amplitude or frequency of miniature excitatory and inhibitory postsynaptic currents, while the threshold for action potential generation was increased and fewer spikes were generated in response to current injection. Delivery of heparinase on the next day after contextual fear conditioning induced context overgeneralization 24 hours after injection. Co-administration of heparinase with the CaMKII inhibitor (autocamtide-2-related inhibitory peptide) rescued neuronal excitability and expression of ankyrin G at the axon initial segment. It also restored context discrimination, suggesting a key role of CaMKII in neuronal signaling downstream of heparan sulfate proteoglycans and highlighting a link between impaired CA1 pyramidal cell excitability and context generalization during recall of contextual memories.
The Hidradenitis Suppurativa ‘Omics Database (HS-OmicsDB)
Authors: Dimitrion Peter , Loveless Ian , Zhou Li , Mi Qing-Sheng , Adrianto Indra 
Published: January 2023

AbstractLarge scale meta-analyses of genomics and genetics have spurred research in a number of fields, such as cancer, genetics and immunology. Publicly available ‘omics databases provide valuable hypothesis generating and validation tools. To date, no such initiative has been undertaken for Hidradenitis Suppurativa (HS), an inflammatory skin disease of unknown etiology. We present here, a longitudinal initiative seeking to aggregate publicly available ‘omics data to enhance research efforts in HS. In its first iteration, we include bulk and single-cell RNA sequencing data from untreated HS patients. Our data, aggregated from publicly available GEO datasets provides a tool to profile gene expression in specific tissue types (i.e. lesional, perilesional, nonlesional and healthy skin) as well as map cell-specific gene expression on single-cell data from HS lesions.
Spatial Multimodal Analysis of Transcriptomes and Metabolomes in Tissues
Authors: Vicari Marco , Mirzazadeh Reza , Nilsson Anna , Shariatgorji Reza , Bjärterot Patrik , Larsson Ludvig , Lee Hower , Nilsson Mats , Foyer Julia , Ekvall Markus , Czarnewski Paulo , Zhang Xiaoqun , Svenningsson Per , Andrén Per E. , Lundeberg Joakim 
Published: January 2023

AbstractWe present a spatial omics approach that merges and expands the capabilities of independently performedin situassays on a single tissue section. Our spatial multimodal analysis combines histology, mass spectrometry imaging, and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular weight metabolites across tissue regions. We demonstrate the potential of our method using murine and human brain samples in the context of dopamine and Parkinson’s disease.
Behavioural individuality determines infection risk in clonal ant colonies
Authors: Li Z. , Frank E.T. , Oliveira-Honorato T. , Azuma F. , Bachmann V. , Parker D. J. , Schmitt T. , Economo E. , Ulrich Y. 
Published: January 2023

AbstractIn social groups, disease risk is not distributed evenly across group members. Individual behaviour is a key source of variation in infection risk, yet its effects are difficult to separate from those of other factors. Here, we combine long-term epidemiological experiments and automated tracking in clonal raider ant colonies, where behavioural individuality emerges among identical workers. We find that: 1) division of labour determines the distribution of parasitic nematodes (Diploscapter) among hosts, showing that differences in infection can emerge from behavioural variation alone, 2) infections affect colony social organisation by causing infected workers to stay in the nest. By disproportionally infecting some workers and shifting their spatial distribution, infections reduce division of labour and increase spatial overlap between hosts, which is expected to facilitate parasite transmission. Thus, division of labour, a defining feature of many societies, not only shapes infection risk and distribution but can also be modified by parasites.
decOM: Similarity-based microbial source tracking of ancient oral samples using k-mer-based methods
Authors: González Camila Duitama , Vicedomini Riccardo , Lemane Téo , Rascovan Nicolas , Richard Hugues , Chikhi Rayan 
Published: January 2023

AbstractBackgroundThe analysis of ancient oral metagenomes from archaeological human and animal samples is largely confounded by contaminant DNA sequences from modern and environmental sources. Existing methods for Microbial Source Tracking (MST) estimate the proportions of environmental sources, but do not perform well on ancient metagenomes. We developed a novel method called decOM for Microbial Source Tracking and classification of ancient and modern metagenomic samples using k-mer matrices.ResultsWe analysed a collection of 360 ancient oral, modern oral, sediment/soil and skin metagenomes, using stratified five-fold cross-validation. decOM estimates the contributions of these source environments in ancient oral metagenomic samples with high accuracy, outperforming two state-of-the-art methods for source tracking, FEAST and mSourceTracker.ConclusionsdecOM is a high-accuracy microbial source tracking method, suitable for ancient oral metagenomic data sets. The decOM method is generic and could also be adapted for MST of other ancient and modern types of metagenomes. We anticipate that decOM will be a valuable tool for MST of ancient metagenomic studies.
Niche conservatism in a generalist felid: low differentiation of the climatic niche among subspecies of the leopard(Panthera pardus)
Authors: Leedham Sidney , Paijmans Johanna L. A. , Manica Andrea , Leonardi Michela 
Published: January 2023

AbstractAimSpecies distribution modelling can be used to reveal if the ecology of a species varies across its range, to investigate if range expansions entailed niche shifts, and to help assess ecological differentiation: the answers to such questions are vital for effective conservation. The leopard (Panthera pardus spp.) is a generalist species composed of one African and eight Asian subspecies, reflecting dispersal from an ancestral African range. This study uses species distribution models to compare the niches of leopard subspecies, to investigate if they conserved their niches when moving into new territories or adapted to local conditions and shifted niche.LocationAfrica and EurasiaMethodsWe assembled a database ofP. pardus spp. presences. We then associated them with bioclimatic variables to identify which are relevant in predicting the distribution of the leopard. We then constructed a species distribution model and compared the distribution predicted from models based on presences from all subspecies versus the ones built only using African leopards. Finally, we used multivariate analysis to visualise the niche occupied by each subspecies in the climate space, and to compare niche overlaps to assess ecological differentiation.ResultsNiche comparisons and model predictions suggest a general lack of niche separation between all subspecies. Most Asian subspecies have overlapping niches and occupy subsets of the niche of the African leopard. Nevertheless, we found the Persian leopardPanthera pardus saxicolorto have the most distinct niche, giving some evidence for niche expansion in more Northern Asian subspecies.Main conclusionsThese results suggest little ecological differentiation among leopard subspecies and a lack of adaptation to novel climates after dispersal from Africa. This finding complements recent genetic studies in implying that the taxonomy of Asian leopards may not reflect biological differentiation, an issue that is important to resolve due to its relevance for the conservation of the species.
N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy
Authors: Griffin Matthew E. , Tsukidate Taku , Hang Howard C. 
Published: January 2023

ABSTRACTThe characterization of microbiota mechanisms in health and disease has reinvigorated pattern recognition receptors as prominent targets for immunotherapy. Notably, our recent studies onEnterococcusspecies revealed peptidoglycan remodeling and activation of NOD2 as key mechanisms for microbiota enhancement of immune checkpoint inhibitor therapy. Inspired by this work and other studies of NOD2 activation, we performedin silicoligand screening and developedN-arylpyrazole dipeptides as novel NOD2 agonists. Importantly, ourN-arylpyrazole NOD2 agonist is enantiomer-specific, effective at promoting immune checkpoint inhibitor therapy and requires NOD2 for activityin vivo. Given the significant functions of NOD2 in innate and adaptive immunity, these next-generation agonists afford new therapeutic leads and adjuvants for a variety of NOD2-responsive diseases.
The nanoscale organization of reticulon 4 shapes local endoplasmic reticulum structurein situ
Authors: Fuentes Lukas A. , Marin Zach , Tyson Jonathan , Baddeley David , Bewersdorf Joerg 
Published: January 2023

AbstractThe endoplasmic reticulum’s (ER) structure is directly linked to the many functions of the ER but its formation is not fully understood. We investigate how the ER-membrane curving protein reticulon 4 (Rtn4) localizes to and organizes in the membrane and how that affects local ER structure. We show a strong correlation between the local Rtn4 density and the local ER membrane curvature. Our data further reveal that the typical ER tubule possesses an elliptical cross-section with Rtn4 enriched at either end of the major axis. Rtn4 oligomers are linear-shaped, contain about five copies of the protein, and preferentially orient parallel to the tubule axis. Our observations support a mechanism in which oligomerization leads to an increase of the local Rtn4 concentration with each molecule increasing membrane curvature through a hairpin wedging mechanism. This quantitative analysis of Rtn4 and its effects on the ER membrane result in a new model of tubule shape as it relates to Rtn4.SummaryRtn4 forms linear-shaped oligomers that contain an average of five Rtn4 proteins, localize to the sides of elliptical tubules, prefer orientations near parallel to the tubule axis, and increase local curvature of the ER membrane by increasing local Rtn4 density.
Structure of human NaV1.6 channel reveals Na+selectivity and pore blockade by 4,9-anhydro-tetrodotoxin
Authors: Li Yue , Yuan Tian , Huang Bo , Zhou Feng , Peng Chao , Li Xiaojing , Qiu Yunlong , Yang Bei , Zhao Yan , Huang Zhuo , Jiang Daohua 
Published: January 2023

AbstractThe sodium channel NaV1.6 is widely expressed in neurons of the central and peripheral nervous systems, which plays a critical role in regulating neuronal excitability. Dysfunction of NaV1.6 has been linked to epileptic encephalopathy, intellectual disability and movement disorders. Here we present cryo-EM structures of human NaV1.6/β1/β2 alone and complexed with a guanidinium neurotoxin 4,9-anhydro-tetrodotoxin (4,9-ah-TTX), revealing molecular mechanism of NaV1.6 inhibition by the blocker. In the apo-form structure, two potential Na+binding sites were revealed in the selectivity filter, suggesting a possible mechanism for Na+selectivity and conductance. In the 4,9-ah-TTX-bound structure, 4,9-ah-TTX binds to a pocket similar to the tetrodotoxin (TTX) binding site, which occupies the Na+binding sites and completely blocks the channel. Molecular dynamics simulation results show that subtle conformational differences in the selectivity filter affect the affinity of TTX analogues. Taken together, our results provide important insights into NaV1.6 structure, ion conductance, and inhibition.
SeqPanther: Sequence manipulation and mutation statistics toolset
Authors: San James Emmanuel , Van Wyk Stephanie , Tegally Houriiyah , Eche Simeon , Wilkinson Eduan , Kanzi Aquillah M. , de Oliveira Tulio , Kiran Anmol M. 
Published: January 2023

AbstractPathogen genomes harbor critical information necessary to support genomic investigations that inform public health interventions such as treatment, control, and eradication. To extract this information, their sequences are analysed to identify structural variations such as single nucleotide polymorphisms (SNPs) and insertions and deletions (indels) that may be associated with phenotypes of interest. Typically, this involves generating a consensus sequence from raw reads, aligning it to a reference and identifying positions where variations occur. Several pipelines exist to map raw reads and assemble whole genomes for downstream analysis. However, there is no easy to use, freely available bioinformatics quality control (QC) tool to explore mappings for both positional codons and nucleotide distributions in mapped short reads of microbial genomes. To address this problem, we have developed a fast and accurate tool to summarise read counts associated with codons, nucleotides, and indels in mapped next-generation sequencing (NGS) short reads. The tool, developed in Python, also provides a visualization of the genome sequencing depth and coverage. Furthermore, the tool can be run in single or batch mode, where several genomes need to be analysed. Our tool produces a text-based report that enables quick review or can be imported into any analytical tool for upstream analysis. Additionally, the tool also provides functionality to modify the consensus sequences by adding, masking, or restoring to wild type mutations specified by the user.AvailabilitySeqPanther is available athttps://github.com/codemeleon/seqPanther, along with the necessary documentation for installation and usage.
The intrinsic clock of the hippocampal subfield CA3 rescues limbic seizures in a biohybrid graft-host interaction in vitro
Authors: Caron Davide , Buccelli Stefano , Canal-Alonso Ángel , Hernández Marco , Pruzzo Giacomo , Corchado Juan Manuel , Chiappalone Michela , Panuccio Gabriella 
Published: January 2023

ABSTRACTHippocampal dysfunction is the hallmark of mesial temporal lobe epilepsy (MTLE), the most common epileptic syndrome in adults and the most often refractory to medical therapy. Deep brain stimulation (DBS) may ameliorate drug-refractory MTLE, but it still cannot guarantee a seizure-free life. One major drawback is that the stimulation policy is informed by trial-and-error rather than by the operating mode of the brain. Thus, optimizing DBS parameters is still an unmet clinical need.Here, we propose the deployment of hippocampal interictal activity in a biohybrid approach to control limbic ictogenesis. Specifically, an electronic bridge establishes a graft-host interaction between the hippocampal subfield CA3 (graft) and the parahippocampal cortex (CTX – host) of distinct rodent brain slices, both treated with 4-aminopyridine; the electronic bridge relays the graft interictal events to the host via electrical pulses. We show that interictal activity generated by the graft CA3 controls limbic ictogenesis in the host CTX even in the absence of feedback from it, thus likely reflecting an intrinsic anti-ictogenic clock of this brain region.This work opens a translational perspective for MTLE treatment via biohybrid neuroprostheses relying on the intrinsic clock of incorporated hippocampal cells.
Mechanistic basis of staphylococcal interspecies competition for skin colonization
Authors: Maciag Joseph J. , Chantraine Constance , Mills Krista B. , Yadav Rahul , Yarawsky Alexander E. , Chaton Catherine T. , Vinod Divya , Fitzkee Nicholas C. , Mathelié-Guinlet Marion , Dufrêne Yves F. , Fey Paul D. , Horswill Alexander R. , Herr Andrew B. 
Published: January 2023

AbstractStaphylococci, whether beneficial commensals or pathogens, often colonize human skin, potentially leading to competition for the same niche. In this multidisciplinary study we investigate the structure, binding specificity, and mechanism of adhesion of the Aap lectin domain required forStaphylococcus epidermidisskin colonization and compare its characteristics to the lectin domain from the orthologousStaphylococcus aureusadhesin SasG. The Aap structure reveals a legume lectin-like fold with atypical architecture, showing specificity for N-acetyllactosamine and sialyllactosamine. Bacterial adhesion assays using human corneocytes confirmed the biological relevance of these Aap-glycan interactions. Single-cell force spectroscopy experiments measured individual binding events between Aap and corneocytes, revealing an extraordinarily tight adhesion force of nearly 900 nN and a high density of receptors at the corneocyte surface. The SasG lectin domain shares similar structural features, glycan specificity, and corneocyte adhesion behavior. We observe cross-inhibition of Aap- and SasG-mediated staphylococcal adhesion to corneocytes. Together, these data provide insights into staphylococcal interspecies competition for skin colonization and suggest potential avenues for inhibition ofS. aureuscolonization.