bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early emergence phase of SARS-CoV-2 Delta variant in Florida
Authors: Cella Eleonora , Ali Sobur , Schmedes Sarah E. , Rife Brittany , Marini Simone , Salemi Marco , Blanton Jason , Azarian Taj 
Published: February 2022

AbstractSARS-CoV-2, the causative agent of COVID-19, emerged in late 2020. The highly contagious B.1.617.2 (Delta) Variant of Concern (VOC) was first identified in October 2020 in India and subsequently disseminated worldwide, later becoming the dominant lineage in the U.S. Despite considerable genomic analysis of SARS-CoV-2 in the U.S., several gaps in the understanding of the local dynamics during early introductions remain, which when elucidated could translate the results of viral genomic epidemiology to actionable mitigation efforts. Here, we explore the early emergence of the Delta variant in Florida, U.S. using phylogenetic analysis of representative Florida and globally sampled genomes. We find multiple independent introductions into Florida primarily from North America and Europe, with a minority originating from Asia. These introductions lead to three distinct clades that demonstrated varying relative rates of transmission and possessed five distinct substitutions that were 3-21 times more prevalent in the Florida sample as compared to the global sample. Our results underscore the benefits of routine viral genomic surveillance to monitor epidemic spread and support the need for more comprehensive genomic epidemiology studies of emerging variants. In addition, we provide a model of epidemic spread of newly emerging VOCs that can inform future public health responses.
Assessment and Optimization of the Interpretability of Machine Learning Models Applied to Transcriptomic Data
Authors: Zhao Yongbing , Shao Jinfeng , Asmann Yan W 
Published: February 2022

AbstractExplainable artificial intelligence aims to interpret how the machine learning models make decisions, and many model explainers have been developed in the computer vision field. However, the understandings of the applicability of these model explainers to biological data are still lacking. In this study, we comprehensively evaluated multiple explainers by interpreting pretrained models of predicting tissue types from transcriptomic data, and by identifying top contributing genes from each sample with the greatest impacts on model prediction. To improve the reproducibility and interpretability of results generated by model explainers, we proposed a series of optimization strategies for each explainer on two different model architectures of Multilayer Perceptron (MLP) and Convolutional Neural Network (CNN). We observed three groups of explainer and model architecture combinations with high reproducibility. Group II, which contains three model explainers on aggregated MLP models, identified top contributing genes in different tissues that exhibited tissue-specific manifestation and were potential cancer biomarkers. In summary, our work provides novel insights and guidance for exploring biological mechanisms using explainable machine learning models.
Automated detection of speech timing alterations in autopsy-confirmed non-fluent/agrammatic variant primary progressive aphasia
Authors: García Adolfo M. , Welch Ariane E. , Mandelli Maria Luisa , Henry Maya L. , Lukic Sladjana , Torres-Prioris María José , Deleon Jessica , Ratnasiri Buddhika M. , Lorca Puls Diego L. , Miller Bruce L. , Seeley William W. , Vogel Adam P. , Gorno-Tempini Maria Luisa 
Published: February 2022

AbstractBackground and ObjectivesMotor speech function, including speech timing, is a key domain for diagnosing non-fluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments employ subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically-confirmed diagnoses. This study overcomes such caveats via automated speech timing analyses in a unique cohort of autopsy-proven cases.MethodsIn a cross-sectional study, we administered an overt reading task and quantified articulation rate, mean syllable and pause duration, and syllable and pause duration variability. Neuroanatomical disruptions were assessed via cortical thickness and white matter atrophy analysis.ResultsWe evaluated 22 persons with nfvPPA (mean age: 67.3; 13 females) and confirmed underlying four-repeat tauopathy, 15 persons with semantic variant primary progressive aphasia (svPPA; mean age: 66.5; 8 females), and 10 healthy controls (HCs; 70 years; 5 females). All five speech timing measures revealed alterations in persons with nfvPPA relative to both the HC and svPPA groups, controlling for dementia severity. Articulation rate robustly discriminated individuals with nfvPPA from HCs (AUC = .95), outperforming specialist-dependent perceptual measures of dysarthria and apraxia of speech severity. Patients with nfvPPA exhibited structural abnormalities in left precentral and middle frontal as well as bilateral superior frontal regions, including their underlying white matter. Articulation rate was associated with atrophy of the left pars opercularis and supplementary/presupplementary motor areas. Secondary analyses showed that, controlling for dementia severity, all measures yielded greater deficits in patients with nfvPPA and corticobasal degeneration (nfvPPA-CBD, n = 12) than in those with progressive supranuclear palsy pathology (nfvPPA-PSP, n = 10). Articulation rate robustly discriminated between individuals in each subgroup (AUC = .82). More widespread cortical thinning was observed for the nfvPPA-CBD than the nfvPPA-PSP group across frontal regions.DiscussionAutomated speech timing analyses can capture specific markers of nfvPPA while potentially discriminating between patients with different tauopathies. Thanks to its objectivity and scalability, this approach could support standard speech assessments.
Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules
Authors: Nersisyan Stepan , Zhiyanov Anton , Zakharova Maria , Ishina Irina , Kurbatskaia Inna , Mamedov Azad , Galatenko Alexey , Shkurnikov Maxim , Gabibov Alexander , Tonevitsky Alexander 
Published: February 2022

AbstractThe T-cell immune response is a major determinant of effective SARS-CoV-2 clearance. Here, using the recently developed T-CoV bioinformatics pipeline (https://t-cov.hse.ru) we analyzed the peculiarities of the viral peptide presentation for the Omicron, Delta and Wuhan variants of SARS-CoV-2. First, we showed the absence of significant differences in the presentation of SARS-CoV-2-derived peptides by the most frequent HLA class I/II alleles and the corresponding HLA haplotypes. Then, the analysis was limited to the set of peptides originating from the Spike proteins of the considered SARS-CoV-2 variants. The major finding was the destructive effect of the Omicron mutations on PINLVRDLPQGFSAL peptide, which was the only tight binder from the Spike protein for HLA-DRB1*03:01 allele and some associated haplotypes. Specifically, we predicted a dramatical decline in binding affinity of HLA-DRB1*03:01 and this peptide after N211 deletion, L212I substitution and EPE 212-214 insertion. The computational prediction was experimentally validated by ELISA with the use of corresponding thioredoxin-fused peptides and recombinant HLA-DR molecules. Another finding was the significant reduction in the number of tightly binding Spike peptides for HLA-B*07:02 HLA class I allele (both for Omicron and Delta variants). Overall, the majority of HLA alleles and haplotypes was not significantly affected by the mutations, suggesting the maintenance of effective T-cell immunity against the Omicron and Delta variants. Finally, we introduced the Omicron variant to T-CoV portal and added the functionality of haplotype-level analysis to it.
A novel intranasal administration adenoviral vector-based platform for rapid COVID-19 vaccine development
Authors: Yuan Yifei , Gao Xing , Ni Fengfeng , Xie Wenbo , Fu Wenbin , Zhang Gaoxia , Hu Huimin , Li Yuncheng , Hu Qinxue , Huang Chuanmengyuan , Liu Bo , Liu Yalan , Shen Qiong , Liang Min 
Published: February 2022

AbstractThe coronavirus SARS-CoV-2 has a severe impact on global public health, and the emerging variants threaten the efficacy of the circulating vaccines. Here, we report that a single vaccination with a non-replicating chimpanzee adenovirus-based vaccine against the SARS-CoV-2 Delta variant (JS1-delta) elicits potent humoral, cellular and mucosal immunity in mice. Additionally, a single intranasal administration of JS1-delta provides effective protection against the Delta (B.1.617.2) variant challenge in mice. This study indicates that chimpanzee adenovirus type 3 (ChAd3) derived vector represents a promising platform for antiviral vaccine development against respiratory infections and JS1-delta is worth further investigation in human clinical trials.HighlightsA new chimpanzee adenoviral vaccine against the SARS-CoV-2 Delta variant was developed.The vaccine elicited potent humoral, cellular and mucosal immunity in mice.The vaccine protected mice from the Delta variant challenge.
Cadmium-induced endocytosis of the broad spectrum root metal transporter of Arabidopsis
Authors: Spielmann Julien , Cointry Virginia , Neveu Julie , Vert Grégory 
Published: February 2022

SummaryIron is an essential micronutrient for plant growth and development. Under low iron conditions, Arabidopsis plants take up soil iron using the root iron transporter IRT1. In addition to iron, IRT1 also transports others divalent metals including cadmium that consequently accumulates into plant tissues and enters the food chain. IRT1 expression was shown to be regulated at the transcriptional and post-translational levels by its essential metal substrates to maximize iron uptake while limiting the accumulation of zinc, manganese or cobalt. Here, we characterized the regulation of IRT1 by cadmium and uncovered a cadmium-mediated downregulation of IRT1 protein by endocytosis. A short term exposure to cadmium indeed decreased the celle surface levels of IRT1 through endocytosis and degradation. This is mediated through the direct binding of cadmium to histidine residues within the regulatory loop of IRT1. Moreover, we demonstrated that cadmium-induced IRT1 degradation uses ubiquitin-mediated endocytosis driven by the IDF1 E3 ligase. Altogether, this work sheds light on the mechanisms of cadmium-mediated downregulation of IRT1 and offers a unique opportunity to boost plant cadmium uptake in phytoremediation/phytoextraction strategies.
Checks and balances of the RTG pathway under arginine deprivation and canavanine exposure in Saccharomyces cerevisiae
Authors: Druseikis Marina E. , Covo Shay 
Published: February 2022

AbstractDecades of research in Saccharomyces cerevisiae underlie the current dogma of mitochondrial retrograde (RTG) signaling: Rtg2-dependent translocation of the heterodimer Rtg1/Rtg3 from the cytoplasm to the nucleus induces the transcription of RTG-target genes under glutamate starvation or loss of respiration. We previously found that RTG mutants show severe growth inhibition from arginine deprivation and are highly sensitive to canavanine when grown on glucose. Here, we show that on solid media, RTG mutants are also sensitive to thialysine, a toxic lysine analog, although lysine deprivation causes a milder growth defect. Growth on an alternative carbon source restores RTG mutants’ ability to grow without arginine or lysine and improves their tolerance of toxic analogs; deletion of MIG1 affords a similar rescue on glucose and improves canavanine tolerance, except for in rtg2Δ. It is well known that the target of rapamycin (TOR) signaling pathway inhibits the RTG pathway. Batch growth experiments with or without TOR inhibition reveal phenotypic and regulatory differences between RTG mutants. rtg1Δ can sustain simultaneous canavanine exposure and TOR inhibition via rapamycin, but rtg2Δ and rtg3Δ cannot. Surprisingly, our data show that under fermentative lifestyle and arginine deprivation, both RTG signaling and TOR activity are required. This expands the universe of TOR and RTG signaling, suggesting bilateral communication rather than unidirectional RTG regulation by TOR. To the best of our knowledge, this work shows for the first time that Rtg3 activity can be separate from its role as a heterodimer with Rtg1. This work also strongly suggests a specific role for Rtg2 in canavanine tolerance.
LazyPair: scalable prediction of protein-protein interactions and interaction types
Authors: Lim Chun Shen , Bhandari Bikash K. , Gardner Paul P. 
Published: February 2022

ABSTRACTMotivationAlmost all cellular processes require protein-protein interactions. Common interaction types include binding, post-translational modifications, and catalysis. However, existing prediction tools do not take these interaction types into account and do not scale well on proteome-wide prediction.ResultsHere we show that a random forest classifier trained on per-residue physicochemical and biochemical properties is useful for predicting protein-protein interactions. Counterintuitively, we find that training random forests by individual interaction types improves accuracy. Furthermore, a combination of these specialised classifiers improves generalisability. We call our protein-protein interaction prediction tool LazyPair. More importantly, LazyPair outperforms the state-of-the-art in accuracy, generalisability and scalability.Availability and implementationLazyPair and the source code and data for reproducing our analysis are freely available at https://github.com/Gardner-BinfLab/PPI_Analysis_2022 and https://doi.org/10.5281/zenodo.6071630. The web server version and the source code are freely available at https://tisigner.com/lazypair/ and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS, respectively.
Application of the Weight Self-Stigma Questionnaire (WSSQ) in Subjects with Overweight and Obesity living in Italy
Authors: Livia Quintiliani , Antonella Sisto , Flavia Vicinanza , Ilaria Bertoncini , Pasquarelli Valentina , Silvia Manfrini , Mikiko Watanabe , Dario Tuccinardi , Giuseppe Curcio 
Published: February 2022

AbstractAimsAlthough weight-based stigmatization is widespread in everyday life, a suitable measure of weight self-stigma is currently unavailable for those with overweight/obesity whose primary language is Italian. The purpose of this study was to translate and test the psychometric properties of the Italian version of the Weight Self-stigma Questionnaire (I-WSSQ) to administer it to adults with overweight/obesity.Materials and MethodsA cross-sectional study was conducted on 214 adults with overweight or obesity. Data including Body Mass Index (BMI), I-WSSQ, and Body Uneasiness Test (BUT) scores were collected from April the 2ndto July the 6th, 2021.ResultsReliability was assessed through internal consistency: the Cronbach α of the I-WSSQ was α =.814, indicating good reliability. The exploratory factor analysis revealed a two-factor structure of I-WSSQ (self-devaluation and fear of enacted stigma, respectively) that explained 49,25% of the total variance. In addition, the I-WSSQ score directly correlated with BMI and BUT score, indicating an acceptable criterion-related validity.ConclusionThe I-WSSQ shows adequate reliability and validity. Health professionals may use the I-WSSQ to assess the weight self-stigma of adults with overweight/obesity whose primary language is Italian.
Multi-ancestry Genome-wide Association Study of Varicose Veins Reveals Polygenic Architecture, Genetic Overlap with Arterial and Venous Disease, and Novel Therapeutic Opportunities
Authors: Levin Michael G. , Huffman Jennifer E. , Verma Anurag , Sullivan Kyle A. , Rodriguez Alexis A. , Kainer David , Garvin Michael R. , Lane Matthew , Won Hyejung , Li Binglan , Luo Yuan , Jarvik Gail P. , Hakonarson Hakon , Jasper Elizabeth A. , Bick Alexander G. , Ritchie Marylyn D. , Jacobson Daniel A. , Madduri Ravi K. , Damrauer Scott M. 
Published: February 2022

ABSTRACTBackgroundVaricose veins represent a common cause of cardiovascular morbidity, with limited available medical therapies. Although varicose veins are heritable and epidemiologic studies have identified several candidate varicose veins risk factors, the molecular and genetic basis remains uncertain. Here, we analyzed the contribution of common genetic variants to varicose veins using data from the VA Million Veteran Program and other large multi-ancestry biobanks. Among 49,765 individuals with varicose veins and 1,334,301 disease-free controls, we identified 139 risk loci. We identified genetic overlap between varicose veins, other vascular diseases, and dozens of anthropometric factors. Using Mendelian randomization, we prioritized novel therapeutic targets via integration of proteomic and transcriptomic data. Finally, topological enrichment analyses confirmed the biologic roles of endothelial shear flow disruption, inflammation, vascular remodeling, and angiogenesis. These findings may facilitate future efforts to develop non-surgical therapies for varicose veins.
Associative memory of structured knowledge
Authors: Steinberg Julia , Sompolinsky Haim 
Published: February 2022

ABSTRACTA long standing challenge in biological and artificial intelligence is to understand how new knowledge can be constructed from known building blocks in a way that is amenable for computation by neuronal circuits. Here we focus on the task of storage and recall of structured knowledge in long-term memory. Specifically, we ask how recurrent neuronal networks can store and retrievemultipleknowledge structures. We modeleachstructure as a set of binary relations between events and attributes (attributes may represent e.g., temporal order, spatial location, role in semantic structure), and map each structure to a distributed neuronal activity pattern using a vector symbolic architecture (VSA) scheme.We then use associative memory plasticity rules to store the binarized patterns as fixed points in a recurrent network. By a combination of signal-to-noise analysis and numerical simulations, we demonstrate that our model allows for efficient storage of these knowledge structures, such that the memorized structures as well as their individual building blocks (e.g., events and attributes) can be subsequently retrieved from partial retrieving cues. We show that long-term memory of structured knowledge relies on a new principle of computation beyond the memory basins. Finally, we show that our model can be extended to store sequences of memories as single attractors.
Antimicrobial resistance in dairy slurry tanks: a critical point for measurement and control
Authors: Baker Michelle , Williams Alexander D , Hooton Steven P.T. , Helliwell Richard , King Elizabeth , Dodsworth Thomas , Baena-Nogueras Rosa María , Warry Andrew , Ortori Catherine A. , Todman Henry , Gray-Hammerton Charlotte J. , Pritchard Alexander C. W. , Iles Ethan , Cook Ryan , Emes Richard D. , Jones Michael A , Kypraios Theodore , West Helen , Barrett David A , Ramsden Stephen J , Gomes Rachel L , Hudson Chris , Millard Andrew D , Raman Sujatha , Morris Carol , Dodd Christine E R , Kreft Jan-Ulrich , Hobman Jon L , Stekel Dov J 
Published: February 2022

AbstractWaste from dairy production is one of the world’s largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs). However, studies to date do not provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with >99% reduction in cephalosporin resistantEscherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for prevalence and control of AMR, and that measures to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.
Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus
Authors: Somaiya Rachana Deven , Stebbins Katelyn , Gingrich Ellen C. , Xie Hehuang , Campbell John N. , Garcia A. Denise R. , Fox Michael A. 
Published: February 2022

AbstractAxons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate Fgf15 and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in Fgf15 expression, as well as in the percentage of interneurons recruited into visual thalamus. Thus, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.
Exploring blockchain in the accounting domain: a bibliometric analysis
Authors: Lardo Alessandra , Corsi Katia , Varma Ashish , Mancini Daniela 
Published: February 2022

PurposeConsidering the growing interests in managerial and accounting issues related to blockchain technology (BT), the study aims at identifying the main research venues in this specific field. In particular, the purpose is to understand the spatial and temporal production and distribution of research documents, highlighting the most relevant topics, the most influential authors and research.Design/methodology/approachThis research carries out a bibliometric analysis of 189 research documents in the business, management and accounting areas. Data collection and refining is carried out from the Scopus database. The data analysis is based on a hybrid literature review approach using a descriptive bibliometric method, data analysis visualization (through VOSViewer software) and thematic analysis.FindingsResults indicate that research studies focused on BT and accounting have been growing exponentially over the last three years, with authors who previously focused on generalist themes, and are now facing more specific issues. Through cluster analysis, the authors propose the framework of accounting domain and blockchain technology (ADOB) to systematize and visualize the map of current studies about the BT in the accounting domain.Research limitations/implicationsThe analysis highlights some aspects less investigated at the first research stage in the field of BT and accounting, such as the growing need of new accounting and control processes to address the practical issues of BT implementation and the need for education and training to stimulate a proper use of BT by accountants and practitioners.Originality/valueThis study is the first to adopt a bibliometric and thematic analysis to investigate BT in the accounting domain. The authors provide significant insights that could guide and foster the use of BT for accountants and practitioners, defining future research lines and a research agenda for academic researchers.