bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMAA: an R/CRAN package to accomplish NomInal data Mining AnAlysis
Authors: Jafari Mohieddin , Chen Cheng , Mirzaie Mehdi , Tang Jing 
Published: January 2022

AbstractSummaryNominal data is data that has been “labeled” and can be designated into a number of non-overlapping unordered groups. The analysis of this type of data is often trivial because it is not feasible to conduct extensive numerical methods on this type of data. Graphs or networks, on the other hand, are comprised of sets of nodes and edges that can also be considered as nominal variables. By integrating graph theory and data mining approaches, we offer the R package NIMAA to define a nominal data-mining pipeline to explore more information. Using nominal variables in a dataset, NIMAA provides functions for constructing weighted and unweighted bipartite graphs, analysing the similarity of labels in nominal variables, clustering labels or categories to super-labels, validating clustering results, predicting bipartite edges by missing weight imputation, and providing a variety of visualization tools. Here, we also indicated the application of nominal data mining in a biological dataset with well-riched nominal variables.AvailabilityNIMAA’s official release and the beta update are available on CRAN and Github, respectively. URLs: https://CRAN.R-project.org/package=NIMAA and https://github.com/jafarilab/NIMAAContactmohieddin.jafari@helsinki.fi; jing.tang@helisnki.fiContributionsMJ conceived the study and developed the models, MJ and CC adopted and implemented the methods, MM improved the methods, JT provided the funding, MJ, CC, MM and JT wrote the paper.
Generation of novel SARS-CoV-2 variants on B.1.1.7 lineage in three patients with advanced HIV disease
Authors: Riddell Anna C. , Kele Beatrix , Harris Kathryn , Bible Jon , Murphy Maurice , Dakshina Subathira , Storey Nathaniel , Owoyemi Dola , Pade Corinna , Gibbons Joseph M. , Harrington David , Alexander Eliza , McKnight Áine , Cutino-Moguel Teresa 
Published: January 2022

ABSTRACTThe emergence of new SARS-COV-2 variants is of public health concern in case of vaccine escape. Described are three patients with advanced HIV-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations which are associated with increased transmissibility and immune escape.
A survey assessing antimicrobial prescribing at UNRWA primary health care centers in Jordan
Authors: Orubu ESF , Albeik S , Ching C , Hussein R , Mousa A , Horino M , Naqa R , Elayyan M , Saadeh R , Zaman MH 
Published: January 2022

AbstractAntimicrobial resistance (AMR) is a public health emergency. There is insufficient information on AMR in the context of humanitarian settings. An understanding of behavioural and institutional level factors can strengthen antimicrobial stewardship. This study used a semi-structured questionnaire to assess both knowledge, attitudes and practices (KAP) on antimicrobial use, resistance and stewardship, and options to improving prescribing, among prescribers at the Primary Healthcare facilities of the UNRWA Jordan field office. Responses to the KAP questions were evaluated using the Capability, Opportunity, Motivation, Behaviour (COM-B) framework and Bloom’s cutoffs. For each framework component, Blooms cutoffs and interpretations were: >80%, “good”; 60-79%, “moderate”; and <60%’ “poor”. Fourteen options to improve prescribing were each assessed using 5-point Likert scales from very unhelpful to very helpful, aggregated by helpful and very helpful and ranked as: >90%, best/most acceptable; >80-90%, as acceptable; and, 70-80% as maybe acceptable/good. The questionnaire response rate was 59% (37/63) with a completion rate of 92% (34/37). Aggregate scores for real knowledge on AMR was 97%; opportunity to improve prescribing 88%; and motivation 16% - participants did not believe that there was a connection between their prescribing and AMR or that they had a key role in helping control AMR. Good options (74% aggregate score) to improving prescribing were the availability of guidelines and resistance data. There was good knowledge of AMR and good opportunities, but poor motivation for rational prescribing or behavioral change. There is a clinical need for antimicrobial resistance data to promote rational antibiotic prescribing.
Data-driven extraction of human kinase-substrate relationships from omics datasets
Authors: Maier Benjamin Dominik , Petursson Borgthor , Lussana Alessandro , Petsalaki Evangelia 
Published: January 2022

AbstractPhosphorylation forms an important part of the signalling system that cells use for decision making and regulation of processes such as cell division and differentiation. To date, a large portion of identified phosphosites are not known to be targeted by any kinase. At the same time around 30% of kinases have no known target. This knowledge gap stresses the need to make large scale, data-driven computational predictions.In this study, we have created a machine learning-based model to derive a probabilistic kinase-substrate network from omics datasets. Our methodology displays improved performance compared to other state-of-the-art kinase-substrate prediction methods, and provides predictions for more kinases. Importantly, it better captures new experimentally-identified kinase-substrate relationships. It can therefore allow the improved prioritisation of kinase-substrate pairs for illuminating the dark human cell signalling space.Our model is integrated into a web server, SELPHI2.0, to allow unbiased analysis of phosphoproteomics data, facilitating the design of downstream experiments to uncover mechanisms of signal transduction across conditions and cellular contexts.
CNAViz: An interactive webtool for user-guided segmentation of tumor DNA sequencing data
Authors: Lalani Zubair , Chu Gillian , Hsu Silas , Kagawa Shaw , Xiang Michael , Zaccaria Simone , El-Kebir Mohammed 
Published: January 2022

AbstractCopy-number aberrations (CNAs) are genetic alterations that amplify or delete the number of copies of large genomic segments. Although they are ubiquitous in cancer and, thus, a critical area of current cancer research, CNA identification from DNA sequencing data is challenging because it requires partitioning of the genome into complex segments with the same copy-number states that may not be contiguous. Existing segmentation algorithms address these challenges either by leveraging the local information among neighboring genomic regions, or by globally grouping genomic regions that are affected by similar CNAs across the entire genome. However, both approaches have limitations: overclustering in the case of local segmentation, or the omission of clusters corresponding to focal CNAs in the case of global segmentation. Importantly, inaccurate segmentation will lead to inaccurate identification of important CNAs. For this reason, most pan-cancer research studies rely on manual procedures of quality control and anomaly correction. To improve copy-number segmentation and their control, we introduce CNAViz, a web-based tool that enables the user to simultaneously perform local and global segmentation, thus overcoming the limitations of each approach. Using simulated data, we demonstrate that by several metrics, CNAViz allows the user to obtain more accurate segmentation relative to existing local and global segmentation methods. Moreover, we analyze six bulk DNA sequencing samples from three breast cancer patients. By validating with parallel singlecell DNA sequencing data from the same samples, we show that by using CNAViz, our user was able to obtain more accurate segmentation and improved accuracy in downstream copy-number calling. CNAViz is available at https://github.com/elkebir-group/cnaviz.
Sero-Prevalence of Covid-19 among workers in Malaysia
Authors: Noordin Noorliza Mohamad , Omar Aziyati binti , Isharudin Ishmah Hana , Idris Riasah , Chem Yukie , Mat Sahat Intan Surianne , Sengol Selvanesan , Aziz Zirwatul Adilah , Lim Zhuo-zhi , Lim Teck-Onn 
Published: January 2022

AbstractFrom the beginning of the pandemic in Feb 2020, Malaysia has been through 4 waves of outbreak, the magnitude of each wave is several orders larger than the preceding one. By the end of the fourth wave in October 2021, Malaysia has among the highest death toll in Asia, cumulative incidence of confirmed cases has reached 7.0% (>30% in Klang Valley). However it remains uncertain what is the true proportion of the population infected.We conducted a sero-survey on 1078 workers from 17 worksites in Klang Valley and Perak between July and September 2021. We tested them for SARS-CoV-2–specific antibodies using Ecotest, a lateral flow immunoassay (LFIA). The ability of antibody testing to detect prior infection depends on the assay and sero-reversion. We therefore adjusted the prevalence estimates to correct for potential misclassification bias due to the use of LFIA and sero-reversion using test sensitivity and specificity results estimated from an independent validation study.The mean age of the workers was 32 years, 89% were male and migrant workers comprised 81% of all subjects, 59% the subjects were from Klang valley. 33% of workers had prior RT-PCR confirmed Covid-19 infections. We estimated 82.2 percent of workers had been infected by Covid-19 by July-September 2021. Prevalence was 99.9% among migrant workers and 12.1% among local workers. Klang Valley, the most industrialized region in Malaysia where most migrant workers are found, had 100% prevalence, giving an infection-to-case ratio (ICF) of ∼3.Our sero-prevalence results show that the incidence of Covid19 is extremely high among migrant workers in Malaysia, consistent with findings from other countries such as Kuwait and Singapore which also hosted large number of migrant workers.
Pooled RNA: extraction free testing of saliva for SARS-CoV-2 detection
Authors: Allicock Orchid M. , Yolda-Carr Devyn , Todd John A. , Wyllie Anne L. 
Published: January 2022

AbstractThe key to limiting SARS-CoV-2 spread is to identify virus-infected individuals (both symptomatic and asymptomatic) and isolate them from the general population. Hence, routine weekly testing for SARS-CoV-2 in all asymptomatic (capturing both infected and non-infected) individuals is considered critical in situations where a large number of individuals congregate such as schools, prisons, aged care facilities and industrial workplaces. Such testing is hampered by operational issues such as cost, test availability, access to healthcare workers and throughput. We developed the SalivaDirect RT-qPCR assay to increase access to SARS-CoV-2 testing via a low-cost, streamlined protocol using self-collected saliva. To expand the single sample testing protocol, we explored multiple extraction-free pooled saliva testing workflows prior to testing with the SalivaDirect assay. A pool size of five, with or without heat inactivation at 65°C for 15 minutes prior to testing resulted in a positive agreement of 98% and 89%, respectively, and an increased Ct value shift of 1.37 and 1.99 as compared to individual testing of the positive clinical saliva specimens. Applying this shift in Ct value to 316 individual, sequentially collected, SARS-CoV-2 positive saliva specimen results reported from six clinical laboratories using the original SalivaDirect assay, 100% of the samples would have been detected (Ct value >45) had they been tested in the 1:5 pool strategy. The availability of multiple pooled testing workflows for laboratories can increase test turnaround time, permitting results in a more actionable time frame while minimizing testing costs and changes to laboratory operational flow.
Evolution of a novel left-right asymmetry involving tissue remodelling and MyoID
Authors: Lefèvre Bénédicte M. , Delvigne Marine , Vidal Josué , Courtier-Orgogozo Virginie , Lang Michael 
Published: January 2022

AbstractLeft-right asymmetries recurrently evolve in animals but the underlying developmental mechanisms are unknown. In mostDrosophilaspecies, the male genitalia is symmetric and undergoes a clockwise 360° rotation during development. InD. melanogaster, this tissue remodeling process is directed by class I myosins: in MyoID mutants the rotation is reversed and the genitalia remains symmetric. Males ofDrosophila pacheahave evolved unique left-right asymmetric genital organs and a characteristic right-sided copulation posture in the past 3-6 million years. To test if these asymmetries in morphology and behavior evolved via the recruitment of pre-existing directional cues controlled by MyoID, we used CRISPR to knockout MyoID inD. pachea. Strikingly, mutant males undergo a reverse genitalia rotation and develop mirror-image asymmetric genitalia, indicating that MyoID controls both the direction of genitalia rotation direction and morphological asymmetry. Although genital asymmetry is reversed, MyoID mutants still adopt a wild-type right-sided copulation posture. Our results show that MyoID and its asymmetry guidance role were recruited for the evolution of a novel left-right asymmetry inD. pacheaand that lateralized copulation behavior is determined by other mechanisms. The evolution of a new left-right organ size asymmetry inD. pacheainvolved recruitment of existing directional cues.
Topological supramolecular network enabled highly conductive and stretchable organic bioelectronics
Authors: Jiang Yuanwen , Zhang Zhitao , Wang Yi-Xuan , Li Deling , Coen Charles-Théophile , Hwaun Ernie , Chen Gan , Wu Hung-Chin , Zhong Donglai , Niu Simiao , Wang Weichen , Saberi Aref , Lai Jian-Cheng , Wang Yang , Trotsyuk Artem A. , Loh Kang Yong , Shih Chien-Chung , Xu Wenhui , Liang Kui , Zhang Kailiang , Hu Wenping , Jia Wang , Cheng Zhen , Dauskardt Reinhold H. , Gurtner Geoffrey C. , Tok Jeffery B.-H. , Deisseroth Karl , Soltesz Ivan , Bao Zhenan 
Published: January 2022

AbstractIntrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. However, the grand challenge remains for the conducting polymer to possess both high mechanical ductility and good electrical conduction at cellular level feature sizes. This longstanding material limitation in organic bioelectronics has impeded the full exploitation of its unique benefits. Here, we introduce a new molecular engineering strategy based on rationally designed topological supramolecular networks, which allows effective decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We achieve two orders of magnitude improvement in the conductivity under 100% strain in physiological environment, along with the capability for direct photopatterning down to 2 μm. These unprecedented capabilities allow us to realize previously inaccessible bioelectronic applications including high-resolution monitoring of ‘soft and malleable’ creatures, e.g., octopus, and localized neuromodulation down to single nucleus precision for controlling organ-specific activities through delicate tissues, e.g., brainstem.
Crystal Structure of Caskin1/CASK complex reveals the molecular basis of the binding specificity of CASK_CAMK domain and its binding partners
Authors: Wang Yue , Chen Qiangou , Jiang Riting , Ye Xiaoyang , Wan Jun , Li Jianchao , Liu Wei 
Published: January 2022

AbstractCASK is a unique scaffold protein in the synapse system. It links numerous proteins to the pre- or post-synaptic region and is critical to the homeostasis of synaptic vesicles. The N-terminus of CASK is a calcium/calmodulin-dependent protein kinase (CAMK) domain, which has diverse functions and interacts with downstream proteins to form a scaffold platform. Caskin1 is one of the brain-specific adaptor proteins of CASK. Previous studies showed that CASK_CAMK domain interacts with Caskin1 CID domain with relatively low affinity. In this study, we re-visit this interaction by remapping the interaction boundary and solving their complex structure. Based on the structure, we systematically compared the interactions between CASK_CAMK and other binding partners. Our results showed that CAMK domain occupies the CID peptide by using its C-lobe groove (between the α1 and α2) and there is a highly conserved signature motif (ζ-x-ψ-W-ψ-x-R) in the CID domain, where ζ is acidic side chain containing residues, x is any amino acid residue, ψ is hydrophobic residues, W is for tryptophan, and R is arginine. These findings allowed us to identify several new potential cytoplasmic binding partners for CASK_CAMK.
Divergent age-related methylation patterns in long and short-lived mammals
Authors: Haghani Amin , Wang Nan , Lu Ake T. , Mozhui Khyobeni ,   Mammalian Methylation Consortium, Raj Ken , Yang X. William , Horvath Steve 
Published: January 2022

ABSTRACTAge-related changes to cytosine methylation have been extensively characterized across the mammalian family. Some cytosines that are conserved across mammals exhibit age-related methylation changes that are so consistent that they were used to successfully develop cross-species age predictors. In a similar vein, methylation levels of some conserved cytosines correlate highly with species lifespan, leading to the development of highly accurate lifespan predictors. Surprisingly, little to no commonality is found between these two sets of cytosines even though the relationship between aging and lifespan is by most measures linked. We ventured to address this conundrum by first identifying age-related cytosines whose methylation levels change in opposite directions between short and long-lived species. We hypothesized that age-related CpGs that are also associated with species lifespan would tap into biological processes that simultaneously impact aging and lifespan. To this end, we analyzed age-related cytosine methylation patterns in 82 mammalian species. For each CpG, we correlated the intra-species age correlation with maximum lifespan across mammalian species. We refer to this correlation of correlations as Lifespan Uber Correlation (LUC). This approach is unique in incorporating age and species lifespan in a single analysis. We identified 629 CpGs with opposing methylation aging patterns in long and short-lived species. Many of these are found to be near BCL11B, NPTN, and HOXC4 loci. Methylation and transcription analyses of Bcl11b knockout mice indicate that this gene partially regulates the methylation state of LUC CpGs. We developed DNAm age estimators (epigenetic clocks) based on LUC CpGs. These LUC clocks exhibited the expected behavior in benchmark aging interventions such as caloric restriction, growth hormone receptor knockout and high-fat diet. Furthermore, we found that Bcl11b heterozygous knockout mice exhibited an increased epigenetic age in the striatum. Overall, we present a bioinformatics approach that identified CpGs and their associated genes implicated both in aging and lifespan. These cytosines lend themselves to developing epigenetic clocks that are sensitive to perturbations that impact both age and lifespan.
Entamoeba histolytica EHD1 is involved in mitosome-endosome contact
Authors: Santos Herbert J. , Hanadate Yuki , Imai Kenichiro , Watanabe Haruo , Nozaki Tomoyoshi 
Published: January 2022

AbstractInter-organellar crosstalk is often mediated by membrane contact sites (MCSs), which are zones where participating membranes come within a proximity of 30 nm. MCSs have been found in organelles including the endoplasmic reticulum, Golgi bodies, endosomes, and mitochondria. Despite its seeming ubiquity, reports of MCS involving mitochondrion-related organelles (MROs) present in a few anaerobic parasitic protozoa remain lacking. Entamoeba histolytica, the etiological agent of amoebiasis, possesses an MRO called mitosome. We previously discovered several Entamoeba-specific transmembrane mitosomal proteins (ETMPs) from in silico and cell biological analyses. One of them, ETMP1 (EHI_175060), was predicted to have one transmembrane domain and two coiled-coil regions, and was demonstrated to be mitosome membrane-integrated based on carbonate fractionation and immunoelectron microscopy (IEM) data. Immunoprecipitation analysis detected a candidate interacting partner, EH-domain containing protein (EHD1, EHI_105270). We expressed HA-tagged EHD1 in E. histolytica and subsequent immunofluorescence and IEM data indicated an unprecedented MCS between the mitosome and the endosome. Live imaging of GFP-EHD1 expressing strain demonstrated that EHD1 is involved in early endosome formation, and is observed in MCS between endosomes of various sizes. In vitro assay using recombinant His-EHD1 demonstrated ATPase activity. MCSs are involved in lipid transfer, ion homeostasis, and organelle dynamics. The serendipitous discovery of the ETMP1 interacting partner EHD1, led to the observation of the mitosome-endosome contact site in E. histolytica. It opened a new view of how the relic mitochondria of Entamoeba may likewise be involved in organelle crosstalk, a conserved feature of mitochondria and other organelles in general.
An efficient simplified method for the generation of corneal epithelial cells from human pluripotent stem cells
Authors: Abdalkader Rodi , Kamei Ken-ichiro 
Published: January 2022

AbstractCorneal epithelial cells derived from human pluripotent stem cells (hPSCs) are an important cell source for preclinical models to test ophthalmic drugs. However, current differentiation protocols lack instructions regarding optimal culturing conditions, which hinders the quality of cells and limits scale-up. Here, we introduce a simplified small molecule-based corneal induction method (SSM-CI) to generate corneal epithelial cells from hPSCs. SSM-CI provides the advantage of minimizing cell culturing time using two defined culturing media containing TGF-β, and Wnt/β-catenin pathway inhibitors, and bFGF growth factor over 25 days. Compared to the conventional human corneal epithelial cell line (HCE-T) and human primary corneal epithelial cells (hPCEpCs), corneal epithelial cells generated by SSM-CI are well-differentiated and express relevant maturation markers, including PAX6 and CK12. RNA-seq analysis indicated the faithful differentiation of hPSCs into corneal epithelia, with significant upregulation of corneal progenitor and adult corneal epithelial phenotypes. Furthermore, despite the initial inhibition of TGF-β and Wnt/β-catenin, upregulation of these pathway-related transcripts was observed in the later stages, indicating their necessity in the generation of mature corneal epithelial cells. Moreover, we observed a shift in gene signatures associated with the metabolic characteristics of mature corneal epithelial cells, involving a decrease in glycolysis- and an increase in fatty acid oxidation. This was also attributed to the overexpression of metabolic enzymes and transporter-related transcripts responsible for fatty acid metabolism. Thus, SSM-CI provides a comprehensive method for the generation of functional corneal epithelial cells for use in preclinical models.