bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Pharmaceutical Interventions and COVID-19 Burden in the United States
Authors: Ahlers Michael J. , Aralis Hilary J. , Tang Wilson L. , Sussman Jeremy B. , Fonarow Gregg C. , Ziaeian Boback 
Published: September 2021

ABSTRACTBackgroundNon-pharmaceutical interventions (NPIs) are mitigation strategies used to reduce the spread of transmissible diseases. The relative effectiveness of specific NPIs remains uncertain.MethodsWe used state-level Coronavirus disease 2019 (COVID-19) case and mortality data between January 19, 2020 and March 7, 2021 to model NPI policy effectiveness. Empirically derived breakpoints in case and mortality velocities were used to identify periods of stable, decreasing, or increasing COVID-19 burden. The associations between NPI adoption and subsequent decreases in case or death velocities were estimated using generalized linear models accounting for weekly variability shared across states. State-level NPI policies included: stay at home order, indoor public gathering ban (mild >10 or severe ≤10), indoor restaurant dining ban, and public mask mandate.Results28,602,830 cases and 511,899 deaths were recorded. The odds of a decrease in COVID-19 case velocity were significantly elevated for stay at home (OR 2.02, 95% CI 1.63-2.52), indoor dining ban (OR 1.62, 95% CI 1.25-2.10), public mask mandate (OR 2.18, 95% CI 1.47-3.23), and severe gathering ban (OR 1.68, 95% CI 1.31-2.16). In mutually adjusted models, odds remained elevated for stay at home (AOR 1.47, 95% CI 1.04-2.07) and public mask mandate (AOR = 2.27, 95% CI 1.51-3.41). Stay at home (OR 2.00, 95% CI 1.53-2.62; AOR 1.89, 95% CI 1.25-2.87) was also associated with greater likelihood of decrease in death velocity in unadjusted and adjusted models.ConclusionsNPIs employed in the U.S. during the COVID-19 pandemic, most significantly stay at home orders, were associated with decreased COVID-19 burden.
Changes in dispensing of medicines proposed for re-purposing in the first year of the COVID-19 pandemic in Australia
Authors: Schaffer Andrea L , Henry David , Zoega Helga , Elliott Julian H , Pearson Sallie-Anne 
Published: September 2021

AbstractObjectiveWe quantified changes in dispensing of common medicines proposed for “re-purposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia, a country with relatively low COVID-19 incidence in the first year of the pandemic.MethodsWe performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidised medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analogue). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models (ARIMA) and compared characteristics of initiators in 2020 and 2019.ResultsIn March 2020, we observed a 99% (95%CI 96%-103%) increase in hydroxychloroquine dispensing (of which approximately 22% attributable to new use), and a 199% increase (95%CI 184%-213%) in initiation, with a shift towards prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing to relevant specialties. There was a small but sustained increase in ivermectin dispensing over multiple months, with a 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no increases in initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin remained lower than expected in April through November 2020.ConclusionsWhile most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we did observed increases in initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harms.
Systematic Transmission Electron Microscopy-Based Identification and 3D Reconstruction of Cellular Degradation Machinery
Authors: Neikirk Kit , Vue Zer , Katti Prasanna , Rodriguez Ben I. , Omer Salem A. , Shao Jianqiang , Christensen Trace , Lopez Edgar Garza , Marshall Andrea , Palavicino-Maggio Caroline B. , Ponce Jessica , Alghanem Ahmad , Vang Larry , Barongan Taylor , Beasley Heather K. , Rodman Taylor , Mungai Margaret , Correia Marcelo , Exil Vernat , Murray Sandra A. , Salisbury Jeffrey L. , Glancy Brian , Pereira Renata O. , Abel E. Dale , Hinton Antentor O. 
Published: September 2021

AbstractMany interconnected degradation machineries including autophagosomes, lysosomes, and endosomes work in tandem to conduct autophagy, an intracellular degradation system that is crucial for cellular homeostasis. Altered autophagy contributes to the pathophysiology of various diseases, including cancers and metabolic diseases. Although many studies have investigated autophagy to elucidate disease pathogenesis, identification of specific components of the autophagy machinery has been challenging. The goal of this paper is to describe an approach to reproducibly identify and distinguish subcellular structures involved in macro autophagy. We provide methods that help avoid common pitfalls, including a detailed explanation for distinguishing lysosomes and lipid droplets and discuss differences between autophagosomes and inclusion bodies. These methods are based on using transmission electron microscopy (TEM), capable of generating nanometer-scale micrographs of cellular degradation components in a fixed sample. We also utilize serial block face-scanning electron microscopy (SBF-SEM) to offer a protocol for visualizing 3D morphology of degradation machinery. In addition to TEM and 3D reconstruction, we discuss other imaging techniques, such as immunofluorescence and immunogold labeling that can be utilized to reliably and accurately classify cellular organelles. Our results show how these methods may be used to accurately quantify the cellular degradation machinery under various conditions, such as treatment with the endoplasmic reticulum stressor thapsigargin or ablation of the dynamin-related protein 1.
CDK1 and HSP90AA1 appears as novel regulatory gene in Non-Small Cell Lung Cancer: A Bioinformatics Approach
Authors: Bhattacharyya Nirjhar , Gupta Samriddhi , Sharma Shubham , Soni Aman , Bhattacharyya Malini , Mukherjee Atreyee , Ray Ashwini kumar , Malik Md. Zubbair 
Published: September 2021

AbstractLung cancer is one of the most invasive cancer affecting over a million of population. Non-small cell lung cancer constitutes up to 85% of all lung cancer cases. Therefore, it is important to identify prognostic biomarkers of NSCLC for therapeutic purpose. The complex behaviour of the NSCLC gene-regulatory network interaction is investigated using a network theoretical approach. We used eight NSCLC microarray datasets GSE19188, GSE118370, GSE10072, GSE101929, GSE7670, GSE33532, GSE31547, GSE31210 and meta analyse them to find differentially expressed genes (DEGs), construct protein-protein interaction (PPI) network, analysed its topological properties, significant modules using network analyser with MCODE, construct a PPI-MCODE network using the genes of the significant modules. We used topological properties such as Maximal Clique Centrality (MCC) and bottleneck from the PPI-MCODE network. We compare them with hub genes (those with highest degrees) to find key regulator (KR) gene. This result is also validated by finding of common genes among top twenty hub genes, genes with highest betweenness, closeness centrality and eigenvector values. It was found that two genes, CDK1 and HSP90AA1 were common in PPI-MCODE combined analysis, and it was also found that CDK1, HSP90AA1 and HSPA8 were common among hub and bottle neck properties and suggesting significant regulatory role of CDK1 in non-small cell lung cancer. After validation, the common genes among top twenty hubs and centrality values like Betweenness Centrality, Closeness Centrality and eigen vector properties, CDK1 again appeared as the common gene. Our study as a summary suggested CDK1 as key regulator gene in complex NSCLC network interaction using network theoretical approach and described the complex topological properties of the network.
IsMycobacterium aviumsubspeciesparatuberculosis(MAP) associated with Crohn’s Disease?
Authors: Patterson Joshua M. , Winstead Cherese , Milligan Kimberly 
Published: September 2021

AbstractObjectiveThis retroactive meta-analysis assesses the relationship betweenMycobacterium aviumsubspeciesparatuberculosis(MAP) and Crohn’s Disease (CD).MethodsA meta-analysis of PCR– and culture–based studies was conducted to determine if there is a relationship between MAP and Crohn’s Disease. The chi-squared test of independence was also conducted to determine if MAP infection and Crohn’s disease onset are independent events.ResultsThe studies analyzed were able to provide evidence thatMycobacterium aviumsubspeciesparatuberculosisis highly associated with Crohn’s disease. It is also shown that, regardless of detection method, MAP can effectively be detected in Crohn’s patients.ConclusionMAP is strongly connected with Crohn’s Disease.SummaryThis paper examines the incidence of MAP in the tissue of Crohn’s disease patients. We found evidence to support MAP being strongly associated with Crohn’s disease.
Sub-Saharan African Countries’ COVID-19 Research: An analysis of the External and Internal Contributions, Collaboration Patterns and Funding Sources
Authors: Asubiaro Toluwase Victor , Shaik Hafsah 
Published: September 2021

AbstractThis study aims at providing some evidence-based insight into Sub-Saharan Africa’s first eighteen months of COVID-19 research by evaluating its research contributions, patterns of collaboration, and funding sources. Eighteen months (2020 January 1-2021 June 30) COVID-19 publication data of 46 Sub-Saharan African countries was collected from Scopus for analysis. Country of affiliation of the authors and funding agencies data was analyzed to understand country contributions, collaboration pattern and funding sources. USA (23.08%) and the UK (19.63%), the top two external contributors, collaborated with Sub-Saharan African countries about three times more than other countries. Collaborative papers between Sub-Saharan African countries - without contributions from outside the region-made up less than five percent of the sample, whereas over 50% of the papers were written in collaboration with researchers from outside the region. Organizations that are in USA and the UK funded 45% of all the COVID-19 research from Sub-Saharan Africa. 53.44% of all the funding from Sub-Saharan African countries came from South African organizations. This study provides evidence that pan-African COVID-19 research collaboration is low, perhaps due to poor funding and lack of institutional support within Sub-Saharan Africa. This mirrors the collaborative features of science in Sub-Saharan Africa before the COVID-19 pandemic. The high volume of international collaboration during the pandemic is a good development. There is also a strong need to forge more robust pan-African research collaboration networks, through funding from Africa’s national and regional government organizations, with the specific objective of meeting local COVID-19 and other healthcare needs.
Single cell Iso-Sequencing enables rapid genome annotation for scRNAseq analysis
Authors: Healey Hope M. , Bassham Susan , Cresko William A. 
Published: September 2021

ABSTRACTSingle cell RNA sequencing (scRNAseq) is a powerful technique that continues to expand across various biological applications. However, incomplete 3′ UTR annotations in less developed or non-model systems can impede single cell analysis resulting in genes that are partially or completely uncounted. Performing scRNAseq with incomplete 3′ UTR annotations can impede the identification of cell identities and gene expression patterns and lead to erroneous biological inferences. We demonstrate that performing single cell isoform sequencing (ScISOr-Seq) in tandem with scRNAseq can rapidly improve 3′ UTR annotations. Using threespine stickleback fish (Gasterosteus aculeatus), we show that gene models resulting from a minimal embryonic ScISOr-Seq dataset retained 26.1% greater scRNAseq reads than gene models from Ensembl alone. Furthermore, pooling our ScISOr-Seq isoforms with a previously published adult bulk Iso-Seq dataset from stickleback, and merging the annotation with the Ensembl gene models, resulted in a marginal improvement (+0.8%) over the ScISOr-Seq only dataset. In addition, isoforms identified by ScISOr-Seq included thousands of new splicing variants. The improved gene models obtained using ScISOr-Seq lead to successful identification of cell types and increased the reads identified of many genes in our scRNAseq stickleback dataset. Our work illuminates ScISOr-Seq as a cost-effective and efficient mechanism to rapidly annotate genomes for scRNAseq.
Tasselyzer, a machine learning method to quantify maize anther exertion, based on PlantCV
Authors: Teng Chong , Fahlgren Noah , Meyers Blake C. 
Published: September 2021

SummaryMale fertility in maize involves complex genetic programming affected by environmental factors. Evaluating the presence and proportion of fertile anthers is crucial for agronomic purposes. Anthers in maize emerge from male-only florets, and quantifying anther exertion is a key indicator of male fertility; however, traditional manual scoring methods are subjective. To address this limitation, we developed an automated method,Tasselyzer, for large-scale analysis. This image-based program uses the PlantCV platform to provide a quantitative assessment of anther exertion, capturing regional differences within the tassel based on the distinct color of anthers. We successfully applied this method to diverse maize lines to demonstrate its utility for research and breeding programs.Significance StatementTasselyzer is a novel image-based segmentation tool for automated, large-scale measurement of anther exertion and the impact of genetic and environmental variation on male fertility in maize.
Involvement of non-LTR retrotransposons in mammal cancer incidence and ageing
Authors: Ricci Marco , Peona Valentina , Taccioli Cristian 
Published: September 2021

AbstractThe presence in nature of closely related species showing drastic differences in lifespan and cancer incidence has recently increased the interest of the scientific community on these topics. In particular, the adaptations and genomic characteristics underlying the evolution of cancer-resistant and long-lived species have recently focused on the presence of alterations in the number of non-coding RNAs, on epigenetic regulation and, finally, on the activity of transposable elements (TEs). In this study, we compared the content and dynamics of TE activity in the genomes of four rodent and six bat species exhibiting different lifespans and cancer susceptibility. Mouse, rat and guinea pig (short-lived and cancer-prone organisms) were compared with the naked mole rat (Heterocephalus glaber) which is the rodent with the longest lifespan. The long-lived and cancer-resistant bats of the genera Myotis, Rhinolophus, Pteropus and Rousettus were instead compared with the Molossus, which is instead a short-lived and cancer-resistant organism. Analyzing the patterns of recent accumulations of TEs in the genome in these species, we found a strong suppression or negative selection to accumulation, of non-LTR retrotransposons in long-lived and cancer-resistant organisms. On the other hand, all short-lived and cancer-prone species have shown recent accumulation of this class of TEs. Among bats, the Molossus molossus turned out to be a very particular species and, at the same time, an important model because, despite being susceptible to rapid ageing, it is resistant to cancer. In particular, we found that its genome has the highest density of SINE (non-LTR retrotransposons), but, on the other hand, a total lack of active LINE retrotransposons. Our hypothesis is that the lack of LINEs presumably makes the Molossus cancer resistant due to lack of retrotransposition but, at the same time, the high presence of SINE, may be related to their short life span due to “sterile inflammation” and high mutation load. We suggest that research on ageing and cancer evolution should put particular attention to the involvement of non-LTR retrotransposons in these phenomena.
AlphaFold2: A role for disordered protein prediction?
Authors: Wilson Carter J. , Choy Wing-Yiu , Karttunen Mikko 
Published: September 2021

AbstractThe development of AlphaFold2 was a paradigm-shift in the structural biology community; herein we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that a näaive use of Dictionary of Secondary Structure of Proteins (DSSP) to separate ordered from disordered regions leads to a dramatic overestimation in disorder content, and that the predicted Local Distance Difference Test (pLDDT) provides a much more rigorous metric. In addition, we show that even when used for disorder prediction, conventional predictors can outperform the pLDDT in disorder identification, and note an interesting relationship between the pLDDT and secondary structure, that may explain our observations, and hints at a broader application of the pLDDT to IDP dynamics.
The Open Field test as a tool for behavior analysis in pigs - is a standardization of setup necessary? A systematic review
Authors: Schulz M. , Zieglowski L. , Kopaczka M. , Tolba R.H. 
Published: September 2021

AbstractThe Open Field test is a common tool to measure anxiety and behavioral changes in rodents. However, scientific findings of rodent experiments may not translate adequately to humans and it has been shown that larger animal models might perform better in that regard. As a result, the number of published studies involving the Open Field test in domestic pig models is increasing. The aim of our review was to investigate the Open Field set-ups in published studies as well as similarity between performance and parameters published. Following the PRISMA guidelines for reviews we selected 69 studies for data extraction in this systematic review. We were able to determine specific set-up conditions such as size, duration and daytime for most of the included studies and found a high variability within these test specifiers. Results indicate a non-uniform performance of set-up including size, timing, parameters and additional combined tests such as the novel object test. We would like to point out the need for standardization of Open Field test for pigs in order to improve result, comparability and reduce inconsistencies.
Distinct neural representations for prosocial and self-benefitting effort
Authors: Lockwood Patricia L. , Wittmann Marco , Nili Hamed , Matsumoto-Ryan Mona , Abdurahman Ayat , Cutler Jo , Husain Masud , Apps Matthew A. J. 
Published: September 2021

AbstractProsocial behaviours – actions that benefit others – are central to individual and societal well-being. Most prosocial acts are effortful. Yet, how the brain encodes effort costs when actions benefit others is unknown. Here, using a combination of multivariate representational similarity analysis and model-based univariate analysis during fMRI, we reveal how the costs of prosocial efforts are processed. Strikingly, we identified a unique neural signature of effort in the anterior cingulate gyrus for prosocial acts both when choosing to help others and when exerting force for their benefit. This pattern was absent for similar self-benefitting behaviour and correlated with individual levels of empathy. In contrast, the ventral tegmental area and the ventral insula signalled subjective value preferentially when choosing whether to exert effort to benefit oneself. These findings demonstrate partially distinct brain areas guide the evaluation and exertion of effort costs when acts are prosocial or self-benefitting.
Overcoming the effect of ASH1L haploinsufficiency on stem cells amenability to genome editing and differentiation into the neuronal lineage – a technical report
Authors: Cheon Seon Hye , Ritchie Foster D. , Vacharasin Janay M. , Marinelli Nicholas , Cheatle Collin , McCord Mikayla M. , Cox Kaitlin , Lizarraga Sofia B. 
Published: September 2021

ABSTRACTGenome editing and neuronal differentiation protocols have proliferated in the last decade. Mutations in genes that control pluripotency could lead to a potential obstacle with regards to the survival and differentiation potential of the genome-edited cell lines. Here we describe a protocol for the generation, and differentiation, of cell lines containing CRISPR/Cas9 induced mutations in the histone methyl transferase ASH1L. This chromatin modifier was previously implicated in hematopoietic stem cell pluripotency and is a major genetic risk factor for autism spectrum disorders (ASD). We find that haploinsufficiency of ASH1L leads to decreased NANOG gene expression leading to reduce cell survival and increased spontaneous differentiation. We report a method that provides improved single-cell survival with higher colony formation efficiency in ASH1L mutant stem cells. Additionally, we describe a modified dual-SMAD inhibition neuronal induction methodology that permits the successful generation of human neurons with mutations in ASH1L, in a smaller scale than previously reported methods. With our modified CRISPR-genome editing and neuronal differentiation protocols, it is possible to generate genome-edited stem cells containing mutations in genes that impact pluripotency and could affect subsequent cell lineage specific differentiation. Our detailed technical report presents cost-effective strategies that will benefit researchers focusing on both translational and basic science using stem cell experimental systems.
Intraspecific variation stabilizes classic predator-prey dynamics
Authors: Allesina Stefano , Miller Zachary R. , Serván Carlos A. 
Published: September 2021

ABSTRACTIn 1920, Alfred J. Lotka found that, to his “considerable surprise”, the dynamics of a simple predatorprey model he had devised led “to undamped, and hence indefinitely continued, oscillations”1,2— which he thought epitomized the “rhythm of Nature” dear to the Victorians. In 1926, the same model was proposed independently by mathematician Vito Volterra3,4, who was inspired by the work of his son-in-law, fish biologist Umberto D’Ancona5. For over a century, the equations that now bear their names have served as a template for the development of sophisticated models for population dynamics6–10. Coexistence in this classic predator-prey model is fragile—stochasticity or temporal variability in parameter values result in extinctions. The dynamics can be stabilized by intraspecific competition or other forms of self-regulation, but the prevalence of these processes in large food webs has been questioned11,12. Here we show that when we consider populations characterized by intraspecific variability, dynamics are stable—despite the absence of any direct self-regulation. Our results can be generalized further, defining a new class of consumer-resource models8,13. By accounting for intraspecific variation, which is manifest in all biological populations, we obtain dynamics that differ qualitatively and quantitatively from those found for homogeneous populations—challenging a central assumption of many ecological models.