bluuebunny/crossref_metadata_2025_split huggingface dataset:
A robust core architecture of functional brain networks supports topological resilience and cognitive performance in aging
Authors: Stanford William , Mucha Peter J. , Dayan Eran 
Published: February 2022

AbstractAging is associated with gradual changes in cognition, yet some individuals exhibit protection against aging-related cognitive decline. The topological characteristics of brain networks that support protection against cognitive decline in aging are unknown. Here, we investigated whether the robustness of brain networks, queried via the delineation of the brain’s core network structure, supports superior cognitive performance in healthy aging individuals (n=320, ages 60-90). First, we decomposed each subject’s functional brain networks using k-shell decomposition, finding that cognitive function is associated with more robust connectivity of core nodes, primarily within the frontoparietal control network (FPCN). Next, we find that the resilience of core brain network nodes, within the FPCN in particular, relates to cognition. Finally, we show that the degree of segregation in functional networks mediates relationships between network resilience and cognition. Together, these findings suggest that brain networks balance between robust core connectivity and segregation to facilitate high cognitive performance in aging.
Distal gene regulation mediated by non-coding RNAs contributes to germline risk for breast and prostate cancer
Authors: Cole Nolan , Lee Paige , Schwarz Tommer , Zhang Pan , Freedman Matthew L. , Gusev Alexander , Lindström Sara , Gandal Michael J. , Pasaniuc Bogdan , Bhattacharya Arjun 
Published: February 2022

ABSTRACTGenome-wide association studies (GWAS) have identified numerous genetic loci associated with breast and prostate cancer risk, suggesting that germline genetic dysregulation influences tumorigenesis. However, the biological function underlying many genetic associations is not well-understood. Previous efforts to annotate loci focused on protein-coding genes (pcGenes) largely ignore non-coding RNAs (ncRNAs) which account for most transcriptional output in human cells and can regulate transcription of both pcGenes and other ncRNAs. Though the biological roles of most ncRNAs are not well-defined, many ncRNAs are involved in cancer development. Here, we explore one regulatory hypothesis: ncRNAs astrans-acting mediators of gene expression regulation in non-cancerous and tumor breast and prostate tissue. Using germline genetics as a causal anchor, we categorize distal (>1 Megabase) expression quantitative trait loci (eQTLs) of pcGenes significantly mediated by local-eQTLs of ncRNAs (within 1 Megabase). We find over 300 mediating ncRNAs and show the linked pcGenes are enriched for immunoregulatory and cellular organization pathways. By integrating eQTL and cancer GWAS results through colocalization and genetically-regulated expression analyses, we detect overlapping signals in nine known breast cancer loci and one known prostate cancer locus, and multiple novel genetic associations. Our results suggest a strong transcriptional impact of ncRNAs in breast and prostate tissue with implications for cancer etiology. More broadly, our framework can be systematically applied to functional genomic features to characterize genetic variants distally regulating transcription throughtrans-mechanisms.SIGNIFICANCEThis study identifies non-coding RNAs that potentially regulate gene expression intrans-pathways and overlap with genetic signals for breast and prostate cancer susceptibility, with implications for interpretation of cancer genome-wide association studies.
Step forward in epidemiological modeling: Introducing the indicator function to capture waves
Authors: Atangana Abdon , Araz Seda İğret 
Published: February 2022

AbstractIn the last century mathematical modelled have been used to depict the dynamic spread of infectious. The aim is to determine the total numbers of infectious, recovered and susceptible classes, however the classes only represent accumulative. Having these classes one will be unable to predict waves, to determine a day to day numbers of newly infected cases some additional calculations are required. Collected data from real world situations are represented as day to day newly infections, from these data help to determine numbers of waves. The current existing mathematical models cannot be used to predict waves, while having known the predicted numbers of waves one can take several measures to control the situation. To solve this problem, we questioned the fact that the rates of infection and recovery are constant and suggested an indicator function, the function is obtained using experimental data. The indicator function is used as rate and introduced into the mathematical model. We considered a simple SIR model with different types of differential operators including classical and fractional derivatives. The models were solved numerically using well-known numerical schemes. The numerical solutions were plotted for different theoretical parameters, the obtained results depict real-world behaviours. To test the efficiency of this new approach, we collected data from South Afrıca and compared with experimental data. Not only our model waves but also it fit experimental data very accurately. This new approach will open new doors of investigation toward revolution to epidemiological modelling.
Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico
Authors: Ponce-de-León Samuel , Torres Martha , Soto-Ramírez Luis Enrique , José Calva Juan , Santillán-Doherty Patricio , Carranza-Salazar Dora Eugenia , Carreño Juan Manuel , Carranza Claudia , Juárez Esmeralda , Carreto-Binaghi Laura E. , Ramírez-Martínez Luis , Rosa Georgina Paz-De la , Vigueras-Moreno Rosalía , Ortiz-Stern Alejandro , López-Vidal Yolanda , Macías Alejandro E. , Torres-Flores Jesús , Rojas-Martínez Oscar , Suárez-Martínez Alejandro , Peralta-Sánchez Gustavo , Kawabata Hisaaki , González-Domínguez Irene , Martínez-Guevara José Luis , Sun Weina , Sarfati-Mizrahi David , Soto-Priante Ernesto , Chagoya-Cortés Héctor Elías , López-Macías Constantino , Castro-Peralta Felipa , Palese Peter , García-Sastre Adolfo , Krammer Florian , Lozano-Dubernard Bernardo 
Published: February 2022

AbstractThere is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.
“Half the truth is often a great lie:” testing for tick-borne diseases and implications for surveillance
Authors: Marusiak Amanda Brown , Hollingsworth Brandon D. , Abernathy Haley , Alejo Aidin , Arahirwa Victor , Mansour Odai , Giandomenico Dana , Schmitz John , Williams Carl , Barbarin Alexis , Boyce Ross M. 
Published: February 2022

ABSTRACTImportanceTick-borne diseases (TBD) including Spotted Fever Group Rickettsiosis (SFGR), ehrlichiosis, and increasingly Lyme disease represent a substantial public health concern throughout much of the Southeastern United States. Yet, there is uncertainty about the epidemiology of these diseases due to pitfalls in existing diagnostic test methodologies.ObjectiveTo examine patterns of diagnostic testing and incidence of TBD in a large, academic healthcare system.DesignCross-sectional study of diagnostic test results from UNC Health for the period January 1st, 2017 to November 30th, 2020.SettingLarge, academic healthcare system in central North Carolina including inpatient and outpatient facilities.ParticipantsAll Individuals seeking routine care at UNC Health facilities who had testing for SFGR, ehrlichiosis or Lyme disease performed during the study periodMeasurementsRates of test positivity, testing completeness, and incidence of TBDResultsAmong the 20,528 diagnostic tests performed, we identified 47 laboratory-confirmed, incident cases of SFGR, 27 of ehrlichiosis, and 76 of Lyme, representing incidence rates of 4.7%, 7.1%, and 0.7% respectively. However, 79.3% of SFGR tests and 74.3% Ehrlichia tests lacked a paired convalescent sample. The total number of tests for Lyme disease was more than SFGR and ehrlichiosis combined, despite the relatively low incidence of disease in region. Most striking, testing for ehrlichiosis was performed in only half of patients in whom SFGR was ordered, suggesting that this disease remains underrecognized. Overall, we estimate that there were 187 incident cases of SFGR and 309 of ehrlichiosis that were not identified due to incomplete testing; a number that would drastically increase – and in the case of ehrlichiosis, nearly double – the total number of cases reported.Conclusions and RelevanceA majority of patients suspected of having TBD did not have testing performed in accordance with established guidelines, substantially limiting our understanding of TBD epidemiology. Furthermore, there appears to be a large discrepancy between the local burden of disease and the testing that is performed. These findings underscore the need to pursue more robust, active surveillance strategies to estimate the burden of TBDs and distribution of causative pathogens.
Resistance bioassays and allele characterisation inform analysis ofSpodoptera frugiperda(Lepidoptera: Noctuidae) introduction pathways in Asia and Australia
Authors: Tay W. T. , Rane R. V. , James W. , Gordon K. H. J. , Downes S. , Kim J. , Kuniata L. , Walsh TK T. K. 
Published: February 2022

AbstractThe fall armyworm (FAW)Spodoptera frugiperdais present in over 70 countries in Africa, Asia, and Oceania. Its rapid dispersal since 2016 when it was first reported in western Africa, and associated devastation to agricultural productivity, highlight the challenges posed by this pest. Currently, its management largely relies on insecticide sprays and transgenicBacillus thuringiensistoxins, therefore understanding their responses to these agents and characteristics of any resistance genes enables adaptive strategies. In Australia,S. frugiperdawas reported at the end of January 2020 in northern Queensland and by March 2020, also in northern Western Australia. As an urgent first response we undertook bioassays on two Australian populations, one each from these initial points of establishment. To assist with preliminary sensitivity assessment, two endemic noctuid pest species,Helicoverpa armigeraandSpodoptera litura, were concurrently screened to obtain larval LC50 estimates against various insecticides. We characterised known resistance alleles from the VGSC, ACE-1, RyR, and ABCC2 genes to compare with published allele frequencies and bioassay responses from native and invasiveS. frugiperdapopulations. An approximately 10x LC50 difference for indoxacarb was detected between Australian populations, which was approximately 28x higher than that reported from an Indian population. Characterisation of ACE-1 and VGSC alleles provided further evidence of multiple introductions in Asia, and multiple pathways involving genetically distinct individuals into Australia. The preliminary bioassay results and resistance allele patterns from invasiveS. frugiperdapopulations suggest multiple introductions have contributed to the pest’s spread and challenge the axiom of its rapid ‘west-to-east’ spread.
Immunomodulatory actions of a kynurenine-derived endogenous electrophile
Authors: Carreño Mara , Pires Maria F. , Woodcock Steven R. , Brzoska Tomasz , Ghosh Samit , Salvatore Sonia R. , Dunn Matthew , Connors Nora , Yuan Shuai , Straub Adam C. , Wendell Stacy G. , Kato Gregory J. , Freeman Bruce A. , Ofori-Acquah Solomon , Sundd Prithu , Schopfer Francisco J. , Vitturi Dario A. 
Published: February 2022

AbstractThe inflammatory upregulation of kynurenine metabolism induces immunomodulatory responses via incompletely understood mechanisms. We report that increases in cellular and systemic kynurenine levels yield the electrophilic derivative kynurenine-carboxyketoalkene (Kyn-CKA), as evidenced by the accumulation of thiol-conjugates and saturated metabolites. Under physiological conditions, Kyn-CKA induces Nrf2-regulated genes and inhibits NF-κB and NLRP3-dependent pro-inflammatory signaling. Sickle Cell Disease (SCD) is a hereditary hemolytic condition characterized by basal inflammation and recurrent vaso-occlusive crises. Both a transgenic SCD murine model and SCD patients exhibit increased kynurenine synthesis and elevated Kyn-CKA metabolite levels. Plasma hemin and kynurenine concentrations are positively correlated, indicating that Kyn-CKA synthesis in SCD is upregulated during pathogenic vascular stress. Remarkably, exogenous administration of Kyn-CKA abrogated pulmonary microvasculature occlusion in SCD mice, an important factor in the development of lung injury. These findings demonstrate that the upregulation of kynurenine synthesis and its metabolism to Kyn-CKA is an adaptive response that attenuates inflammation and protects tissues.One-Sentence SummaryKyn-CKA is a kynurenine-derived signaling mediator that transduces its immunomodulatory protective actions and attenuates vaso-occlusion in sickle cell disease.
DNA barcoding of fungal specimens using long-read high-throughput sequencing
Authors: Runnel Kadri , Abarenkov Kessy , Copoț Ovidiu , Mikryukov Vladimir , Kõljalg Urmas , Saar Irja , Tedersoo Leho 
Published: February 2022

AbstractMolecular methods are increasingly used to identify species that lack conspicuous macro- or micromorphological characters. Taxonomic and ecological research teams barcode large numbers of collected voucher specimens annually. In this study we assessed the efficiency of long-read high throughput sequencing (HTS) as opposed to the traditionally used Sanger method for taxonomic identification of multiple vouchered fungal specimens, and providing reference information about intra-individual allele polymorphism. We developed a workflow based on a test-set of 423 fungal specimens (representing 205 species), PacBio HTS method, and ribosomal rRNA operon internal transcribed spacer (ITS) and 28S rRNA gene (LSU) markers. PacBio HTS had a higher success rate than Sanger sequencing at a comparable cost. Species identification based on PacBio reads was usually straightforward, because the dominant operational taxonomic unit (OTU) typically represented the targeted organism. Unlike the Sanger method, PacBio HTS enabled detecting widespread allele polymorphism within the ITS marker in the studied specimens. We conclude that multiplex DNA barcoding of the fungal ITS and LSU markers using a PacBio HTS is a useful tool for taxonomic identification of large amounts of collected voucher specimens at competitive price. Furthermore, PacBio HTS accurately recovers various alleles, which can provide crucial information for species delimitation and population-level studies.
Chimeric Inheritance and Crown-Group Acquisitions of Carbon Fixation Genes within Chlorobiales
Authors: Paoletti Madeline M. , Fournier Gregory P. 
Published: February 2022

AbstractThe geological record of microbial metabolisms and ecologies primarily consists of stable isotope fractionations and the diagenetic products of biogenic lipids. Carotenoid lipid biomarkers are particularly useful proxies for reconstructing this record, providing information on microbial phototroph primary productivity, redox couples, and oxygenation. The biomarkers okenane, chlorobactane, and isorenieratene are generally considered to be evidence of anoxygenic phototrophs, and provide a record that extends to ∼1.64 Ga. The utility of the carotenoid biomarker record may be enhanced by examining the carbon isotopic ratios in these products, which are diagnostic for specific pathways of biological carbon fixation found today within different microbial groups. However, this joint inference assumes that microbes have conserved these pathways across the duration of the preserved biomarker record. Testing this hypothesis, we performed phylogenetic analyses of the enzymes constituting the reductive tricarboxylic acid (rTCA) cycle in Chlorobiales, the group of anoxygenic phototrophic bacteria usually implicated in the deposition of chlorobactane and isorenieretane. We find phylogenetically incongruent patterns of inheritance across all enzymes, indicative of horizontal gene transfers to both stem and crown Chlorobiales from multiple potential donor lineages. This indicates that a complete rTCA cycle was independently acquired at least twice within Chlorobiales and was not present in the last common ancestor. When combined with recent molecular clock analyses, these results predict that the Mesoproterzoic lipid biomarker record diagnostic for Chlorobiales should not preserve isotopic fractionations indicative of a full rTCA cycle. Furthermore, we conclude that coupling isotopic and biomarker records is insufficient for reliably reconstructing microbial paleoecologies in the absence of a complementary and consistent phylogenomic narrative.
A simulation study of the ecological speciation conditions in the Galician marine snailLittorina saxatilis
Authors: Fernández-Meirama M. , Rolán-Alvarez E. , Carvajal-Rodríguez A. 
Published: February 2022

AbstractIn the last years the interest on evolutionary divergence at small spatial scales has increased and so did the study of speciation caused by ecologically-based divergent natural selection. The evolutionary interplay between gene flow and local adaptation can lead to low-dispersal locally adapted specialists. When this occurs the evolutionary interplay between gene flow and local adaptation could eventually lead to speciation.TheL. saxatilissystem consists of two ecotypes displaying a microhabitat-associated intraspecific dimorphism along the wave-exposed rocky shores of Galicia. In spite of being a well-known system, the dynamics of the ecotype formation remains unclear and cannot be studied from empirical evidence alone. In this study, individual-based simulations were used to incorporate relevant ecological, spatial and genetic information, to check different evolutionary scenarios that could evolve non-random mating preferences and finally may facilitate speciation.As main results, we observed the evolution of intermediate values of choice which matches estimates from empirical data ofL. saxatilisin Galician shores and coincides with previous theoretical outcomes. Also, the use of the mating correlation as a proxy for assortative mating led to spuriously inferring greater reproductive isolation in the middle habitat than in the others, which does not happen when directly considering the choice values from the simulations. We also corroborate the well-known fact that the occurrence of speciation is influenced by the strength of selection. Taken together, this means, also according to otherL. saxatilissystems, that speciation is not an immediate consequence of local divergent selection and mating preferences, but a fine tuning among several factors including the ecological conditions in the shore levels, the selection strength, the mate choice stringency and cost to choosiness. TheL. saxatilissystem could correspond to a case of incomplete reproductive isolation, where choice intensity is intermediate and local adaptation within the habitat is strong. These results support previous interpretations of theL. saxatilismodel system and indicate that further empirical studies would be interesting to test whether the mate choice mechanism functions as a similarity-like mechanism as has been shown in other littorinids.
The addition of FAIMS Increases Targeted Proteomics Sensitivity from FFPE Tumor Biopsies
Authors: Sweet Steve , Chain David , Yu Wen , Martin Philip , Rebelatto Marlon , Chambers Andrew , Cecchi Fabiola , Kim Yeoun Jin 
Published: February 2022

ABSTRACTMass spectrometry-based targeted proteomics allows objective protein quantitation of clinical biomarkers from a single section of formalin-fixed, paraffin-embedded (FFPE) tumor tissue biopsies. We combined high-field asymmetric waveform ion mobility spectrometry (FAIMS) and parallel reaction monitoring (PRM) to increase assay sensitivity. The modular nature of the FAIMS source allowed direct comparison of the performance of FAIMS-PRM to PRM. Limits of quantitation were determined by spiking synthetic peptides into a human spleen matrix. In addition, 20 clinical samples were analyzed using FAIMS-PRM and the quantitation of HER2 was compared with that obtained with the Ventana immunohistochemistry assay. FAIMS-PRM improved the overall signal-to-noise ratio over that from PRM and increased assay sensitivity in FFPE tissue analysis for four (HER2, EGFR, cMET, and KRAS) of five proteins of clinical interest. FAIMS-PRM enabled sensitive quantitation of basal HER2 expression in breast cancer samples classified as HER2 negative by immunohistochemistry. Furthermore, we determined the degree of FAIMS-dependent background reduction and showed that this correlated with an improved lower limit of quantitation with FAIMS. FAIMS-PRM is anticipated to benefit clinical trials in which multiple biomarker questions must be addressed and the availability of tumor biopsy samples is limited.
Growing Phylogenetic Trees Using Hierarchical Clustering
Authors: Eberhard Onno 
Published: February 2022

AbstractWe compare mitochondrial DNA of different species to build a phylogenetic tree. The main challenge is that the calculation of the Levenshtein distance is very slow for large sequences. We introduce an approximate scheme which uses Levenshtein for lower-level details and a fast distance based on sequence length for high-level attributes. The tree is built using average linkage hierarchical clustering.