bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire
Authors: Melani Rafael D. , Soye Benjamin J. Des , Kafader Jared O. , Forte Eleonora , Hollas Michael , Blagojevic Voislav , Negrão Fernanda , McGee John P. , Drown Bryon , Lloyd-Jones Cameron , Seckler Henrique S. , Camarillo Jeannie M. , Compton Philip D. , LeDuc Richard D. , Early Bryan , Fellers Ryan T. , Cho Byoung-Kyu , Mattamana Basil Baby , Goo Young Ah , Thomas Paul M. , Ash Michelle K. , Bhimalli Pavan P. , Al-Harthi Lena , Sha Beverly E. , Schneider Jeffrey R. , Kelleher Neil L. 
Published: July 2021

AbstractMethods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we presentIg-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multi-parametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We apply Ig-MS to plasma from subjects with severe & mild COVID-19, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, with compatibility to any recombinant antigen to gauge our immune responses to vaccination, pathogens, or autoimmune disorders.
A cross-sectional study investigating the prevalence and causes of vision impairment in Northwest Portugal using capture-recapture
Authors: Ramos Pedro Lima , Santana Rui , Marques Ana Patrícia , Sousa Inês , Rocha-Sousa Amândio , Macedo Antonio Filipe 
Published: July 2021

AbstractObjectivesThe aim of this study was to estimate the prevalence and causes of vision impairment (VI) in Portugal.SettingInformation about people with VI was obtained from Primary Care Centres, blind association (ACAPO) and from hospitals (the PCVIP-study) in the Northwest of Portugal during a period spanning years 2014-2015. Causes of VI were obtained from hospitals.ParticipantsAdministrative and medical records of people with visual acuity in the better seeing eye of 0.5 decimal (0.30logMAR) or worse and/or visual field less than 20 degrees were investigated. Capture-recapture with log-linear models was applied to estimate the number of individuals missing from lists of cases obtained from available sources.Primary and secondary outcome measuresLog-linear models were used to estimate the crude prevalence and the category specific prevalence of VI.ResultsCrude prevalence of VI was 1.97% (95%CI=1.56-2.54), and standardized prevalence was 1% (95%CI=0.78-1.27). The age-specific prevalence was 3.27% (95% CI=2.36-4.90), older than 64 years, 0.64% (95%CI=0.49-0.88), aged 25-64 years, and 0.07% (95%CI=0.045-0.13), aged less than 25 years. The female-to-male ratio was1.3, that is, higher prevalence amongst females. The five leading causes of VI were Diabetic Retinopathy, Cataract, Age-related Macular Degeneration, Glaucoma and Disorders of the Globe.ConclusionsThe prevalence of VI in Portugal was within the expected range and in line with other European countries. A significant number of cases of VI might be due to preventable cases and, therefore, a reduction of the prevalence of VI in Portugal seems possible. Women and old people were more likely to have VI and, therefore, these groups require extra attention. Future studies are necessary to characterize temporal changes in prevalence of VI in Portugal.Strengths and limitations of this studyMedical records and registers of people with vision impairment were used to determine the number of cases in these sources.Data from 3 sources (lists) with records about people with vision impairment were combined using log-linear models to determine the number of “uncaptured” cases.Capture-recapture methods were used to determine the prevalence of vision impairment in the Northwest Portugal.Capture-recapture methods to compute prevalence are more accurate than pure case counting from lists and more affordable than cross-sectional studies.A limitation of the current study was the low completeness, that is, the number of cases captured compared with the number of uncaptured cases.
Mental Illness Self-Stigma in Young People: A Scoping Review Protocol
Authors: Taylor Rachel , Cogan Nicola , Jenkins Pamela , Liu Xi , Flowers Paul , Hunter Simon C. , Corrigan Patrick 
Published: July 2021

AbstractBackgroundSelf-stigma (the internalisation of negative stereotypes) is known to reduce help-seeking behaviours and treatment adherence in people who have a mental illness, resulting in worsening health outcomes. Moreover, self-stigma diminishes self-esteem and self-efficacy, and leads to higher levels of depression. Half of all lifetime cases of mental illness have manifested by the age of 14, and therefore young people are vulnerable to the negative impact of suffering mental illness self-stigma. While literature in this field has been flourishing in recent years, mental illness self-stigma remains poorly understood in youth. It is important that we seek to understand what is currently known about mental illness self-stigma in young people, and subsequently use this information to guide future research to advance knowledge of this topic. To date, a scoping review which maps the available literature on mental illness self-stigma in young people has yet to be conducted. Here, we outline the protocol for a scoping review on mental illness self-stigma in young people.MethodsThis protocol outlines the process of conducting a scoping review of primary research concerning mental illness self-stigma in young people. The Joanna Briggs Institute guidance on best practice for conducting a scoping review will utilised throughout. A systematic search of appropriate databases will be conducted which will allow for a two-step screening process and data charting. Inclusion criteria for this review dictates that eligible studies will i) include a population within the age range of 10-35 (or mean age within this range), ii) include the term ‘self-stigma’ or ‘internalised stigma’ relating to mental health/illness/disorder, iii) be primary research, iv) be published post-2009 (following the seminal study by Moses, 2009) and v) be published in English.DiscussionThe findings of the scoping review outlined in this protocol will be used to inform future research which aims to explore self-stigmatising attitudes and beliefs of young people experiencing mental illness. This research will result in co-produced, impactful resources for young people on the topic of mental illness self-stigma with the aim of raising awareness and stigma reduction.
Impairment Of Aversive Episodic Memories During COVID-19 Pandemic: The Impact Of Emotional Context On Memory Processes
Authors: Sofía León Candela , Matías Bonilla , Benítez Facundo Urreta , Ignacio Brusco Luis , Jingyi Wang , Cecilia Forcato 
Published: July 2021

AbstractThe threatening context of the COVID-19 pandemic provided a unique setting to study the effects of negative psychological symptoms on memory processes. Episodic memory is an essential function of the human being related to the ability to store and remember experiences and anticipate possible events in the future. Studying this function in this context is crucial to help understand what effects the pandemic will have on the formation of episodic memories. To study this, the formation of episodic memories was evaluated by free recall, recognition, and episode order tasks for an aversive and neutral content. The results indicated that aversive episodic memory is impaired both in the free recall task and in the recognition task. Even the beneficial effect that emotional memory usually has for the episodic order was undermined as there were no differences between the neutral and aversive condition. The present work adds to the evidence that indicates that the level of activation does not modify memory processes in a linear way, which also depends on the type of evocation that people are asked and the characteristics of the content to be encoded.
Global Effects of a PD Risk-SNP at the Alpha-Synuclein Locus
Authors: Prahl Jordan , Pierce Steven E. , van der Schans Edwin JC , Coetzee Gerhard A. , Tyson Trevor 
Published: July 2021

SUMMARYOne of the most significant Parkinson’s disease (PD) risk variants, rs356182, is located at the PD-associated locus near the alpha-synuclein encoding gene, SNCA. SNCA-proximal variants, including rs356182, are thought to function in PD via allele-specific regulatory effects on SNCA expression. However, this interpretation discounts the complex activity of genetic enhancers and possible nonconical effects of alpha-synuclein. Here we investigate a novel risk mechanism for rs356182. We use CRISPR-Cas9 in LUHMES cells, a model for dopaminergic neurons, to generate precise hemizygous lesions at rs356182. The PD-protective (A/-), PD-risk (G/-), and WT (A/G) strains are differentiated into dopaminergic neurons then compared transcriptionally and morphologically. We observe effects not typically ascribed to SNCA; hundreds of differentially expressed genes associated with neuronal differentiation and axonogenesis. Together, the data implicate a risk mechanism for rs356182 in which the risk-allele (G) is associated with abnormal neuronal differentiation. We speculate the disease-relevant effect originates as a diminished population of DA neurons leading to the predisposition for PD later in life.
Identification of the functions of 4-coumarate-CoA ligase/ acyl-CoA synthetase paralogs in potato
Authors: Valiñas Matías Ariel , Have Arjen ten , Andreu Adriana Balbina 
Published: July 2021

ABSTRACTBackgroundThe 4CL/ ACS protein family is well known for its 4-coumarate-CoA ligase (4CL) enzymes but there are many aspects of this family that are still unclear or generally known. Cytosolic class I and class II 4CL enzymes control the biosynthesis of lignin/ suberin and flavonoids, respectively. Many 4CL homologs have broad substrate permissiveness in vitro and have no clear cut function. However, it has been demonstrated unequivocally that a peroxisomal 4CL-like homolog from Arabidopsis efficiently uses p-coumarate for ubiquinone biosynthesis. Another homolog has been shown to act as a fatty acyl-CoA synthetase and yet another as OPDA-CoA ligase. Hence, despite this knowledge, most homologs remain annotated as “4CL-like” whereas other researches study the ACS protein family.ResultsWe set out identify the specific functions of 4CL/ ACS homologs, specifically in order to study the 4CL family in Solanum tuberosum. An in depth phylogenetic analysis was done. Using clustering techniques, functional annotation and taxonomic signals, three major clades were depicted. Clade 1 is composed of class I from monocotyledons, class I from dicotyledons and class II canonical 4CL enzymes subclades. Specificity determining positions and 3D structure analysis shows that clade 2 cytosolic 4CL-like enzymes show a rather different binding cleft and presumably use medium- to long-chain fatty acids. Clade 3 is composed of five subclades, four of which have a broad taxonomic contribution and a similar binding cleft as 4CLs whereas a fifth, specific for dicotyledons shows a significantly different binding pocket. The potato 4CL family comprises four class I (St4CL-I(A-D)) and one class II (St4CL-II) members. Transcript levels of St4CLs and of marker genes of the flavonoid (chalcone synthase, CHS) and suberin (feruloyl-CoA transferase, FHT) pathways were determined by qRT-PCR in flesh and skin from Andean varieties. St4CL-IA was barely detected in the skin of some varieties whereas St4CL-IB did not show a clear pattern. St4CL-IC and St4CL-ID could not be detected. St4CL-II expression pattern was similar to CHS. St4CL-IA and St4CL-IB were induced by wounding as did FHT whereas St4CL-II and CHS expression was repressed. Constitutive and wound-induced expression suggests that St4CL-IA and St4CL-IB isoforms are likely involved in soluble and/ or suberin-bound phenolic compounds while St4CL-II appears to be involved in flavonoid biosynthesis.
Rapid speciation and karyotype evolution in Orthoptera
Authors: Palacios-Gimenez Octavio M. 
Published: July 2021

AbstractTo test the hypothesis that high speciation rate in groups is coupled with high rate of karyotype evolution but also that younger groups having a higher rate of karyotypic diversity, I estimated rates of speciation and rates of karyotype evolution in 1,177 species belonging to 26 families in the insect order Orthoptera. Rates of karyotype evolution were estimated using the diploid number and the number of chromosome arms (fundamental number) from published karyotypes of Orthoptera. Rates of speciation were quantified considering the number of species examined karyotypically in each family, the most recent common ancestor of each family and the information about extinction rate. The rate of speciation was strongly correlated with rate of karyotype evolution and the average rates of speciation was nearly ~177 times higher than the background rate estimated for Orthoptera based on acoustic communication using phylogenomic data, as well as 8.4 and 35.6 times higher than the estimated speciation rate in vertebrates and bivalve mollusks respectively, indicating that Orthoptera has evolved very fast at chromosomal level. The findings supported the hypothesis of a high speciation rate in lineages with high rate of chromosomal evolution but there were not evidences that younger groups tended to have higher rate of karyotypic diversity. Furthermore, rates of karyotype evolution most closely fitted the punctuational evolutionary model indicating the existence of long periods of stasis of karyotype change with most karyotype change occurring quickly over short evolutionary times. I discussed genetic drift, divergent selection and meiotic drive as potential biological mechanisms to explain karyotype evolution allowing or impeding for the fixation of chromosomal rearrangements and in turn speciation in orthopterans lineages.
Approximation of the age distribution of cancer incidence using a mutational model
Authors: Tetearing Alexandr N. 
Published: July 2021

AbstractThe approximation of the age distributions of cancers was carried out using a complex mutational model presented in our work [1]. Datasets from the American National Cancer Institute (SEER program) were used.We approximated the datasets for the age distributions of lung, stomach, colon and breast cancer in women; cancer of the lung, stomach, colon and prostate in men.The average number of mutations (required for cancer formation) averaged over the four types of cancer is 5 mutations per cell in women and in men. The average (over the four types of cancer) mutation rate is estimated as 1.0 · 10 −1 mutations per year per cell for women and 3.8 · 10 −1 mutations per year per cell for men.This article is a continuation of work [1].
KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data
Authors: Crowl Sam , Jordan Benjamin , Ahmed Hamza , Ma Cynthia , Naegle Kristen M. 
Published: July 2021

AbstractKinase inhibitors are one of the largest classes of FDA-approved drugs and are major targets in oncology. Although kinase inhibitors have played an important role in improving cancer outcomes, major challenges still exist, including the development of resistance and failure to respond to treatments. Improvements for tumor profiling of kinase activity would be an important step in improving treatment outcomes and identifying effective kinase targets. Here, we present a graph- and statistics-based algorithm, called KSTAR, which harnesses the phosphoproteomic profiling of human cells and tissues by predicting kinase activity profiles from the observed phosphorylation of kinase substrates. The algorithm is based on the hypothesis that the more active a kinase is, the more of its substrates will be observed in a phosphoproteomic experiment. This method is error- and bias-aware in its approach, overcoming challenges presented by the variability of phosphoproteomic pipelines, limited information about kinase-substrate relationships, and limitations of global kinase-substrate predictions, such as training set bias and high overlap between predicted kinase networks. We demonstrate that the predicted kinase activities: 1) reproduce physiologically-relevant expectations and generates novel hypotheses within cell-specific experiments, 2) improve the ability to compare phosphoproteomic samples on the same tissues from different labs, and 3) identify tissue-specific kinase profiles. Global benchmarking and comparison to other algorithms demonstrates that KSTAR is particularly superior for predicting tyrosine kinase activities and, given its focus on utilizing more of the available phosphoproteomic data, significantly less sensitive to study bias. Finally, we apply the approach to complex human tissue biopsies in breast cancer, where we find that KSTAR activity predictions complement current clinical standards for identifying HER2-status – KSTAR can identify clinical false positives, patients who will fail to respond to inhibitor therapy, and clinically defined HER2-negative patients that might benefit from HER2-targeted therapy. KSTAR will be useful for both basic biological understanding of signaling networks and for improving clinical outcomes through improved clinical trial design, identification of new and/or combination therapies, and for identifying the failure to respond to targeted kinase therapies.
Straintables: An application that extracts sequences from genome assemblies and generates dissimilarity matrices
Authors: Araujo Gabriel Nogueira , Francis Richard W , Ferreira Cristina dos Santos , Rangel Alba Lucínia Peixoto 
Published: July 2021

AbstractBackground and ObjectivesThe dissimilarity matrix (DM) is an important component of phylogenetic analysis, and many software packages exist to build and show DMs. However, as the common input for this type of software are sequences in FASTA file format, the process of extracting and aligning each set of sequences to produce a big number of matrices can be laborious. Additionally, existing software do not facilitate the comparison of clusters of similarity across several DMs built for the same group of individuals, using different genomic regions. To address our requirements of such a tool, we designed Straintables to extract specific genomic region sequences from a group of intraspecies genomic assemblies, using extracted sequences to build dissimilarity matrices.MethodsA Python module with executable scripts was developed for a study on genetic diversity across strains of Toxoplasma gondii, being a general purpose system for DM calculation and visualization for preliminary phylogenetic studies. For automatic region sequence extraction from genomic assemblies we assembled a system that designs virtual primers using reference sequences located at genomic annotations, then matches those primers on genome files by using regex patterns. Extracted sequences are then aligned using Clustal Omega and compared to generate matrices.ResultsUsing this software saves the user from manual preparation and alignment of the sequences, a process that can be laborious when a large number of assemblies or regions are involved. The automatic sequence extraction process can be checked against BLAST results using extracted sequence as queries, where correct results were observed for same-species pools for various organisms. The package also contains a matrix visualization tool focused on cluster visualization, capable of drawing matrices into image files with custom settings, and features methods of reordering matrices to facilitate the comparison of clustering patterns across two or more matrices.ConclusionStraintables may replace and extend the functionality of existing matrix-oriented phylogenetic software, featuring automatic region extraction from genomic assemblies and enhanced matrix visualization capabilities emphasizing cluster identification. This module is open source, available at GitHub (https://github.com/Gab0/straintables) under a MIT license and also as a PIPY package.HighlightsSimple in-silico protocol for generation, visualization and comparison of dissimilarity matrices.Accurate automatic sequence extraction from multiple genomic assemblies by using virtual primers built from reference sequences in an annotation file.Draws matrices as images, with enhanced cluster visualization and customized options.Supports reordering of matrix indices to better visualize clustering pattern conservation across multiple regions.
Harmonic Passive Motion Paradigm
Authors: Tiseo Carlo , Charitos Sydney Rebecca , Mistry Michael 
Published: July 2021

AbstractHow humans robustly interact with external dynamics is not yet fully understood. This work presents a hierarchical architecture of semi-autonomous controllers that can control the redundant kinematics of the limbs during dynamic interaction, even with delays comparable to the nervous system. The postural optimisation is performed via a non-linear mapping of the system kineto-static properties, and it allows independent control of the end-effector trajectories and the arms stiffness. The proposed architecture is tested in a physical simulator in the absence of gravity, presence of gravity, and with gravity plus a viscous force field. The data indicate that the architecture can generalise motor strategies to different environmental conditions. The experiments also verify the existence of a deterministic solution to the task-separation principle. The architecture is also compatible with Optimal Feedback Control and the Passive Motion Paradigm. The existence of a deterministic mapping implies that this task could be encoded in neural networks capable of generalisation of motion strategies to affine tasks.
Rapid extraction and kinetic analysis of protein complexes from single cells
Authors: Sarıkaya Sena , Dickinson Daniel J. 
Published: July 2021

AbstractProteins contribute to cell biology by forming dynamic, regulated interactions, and measuring these interactions is a foundational approach in biochemistry. We present a rapid, quantitativein vivoassay for protein-protein interactions, based on optical cell lysis followed by time-resolved single-molecule analysis of protein complex binding to an antibody-coated substrate. We show that our approach has better reproducibility, higher dynamic range, and lower background than previous single-molecule pull-down assays. Furthermore, we demonstrate that by monitoring cellular protein complexes over time after cell lysis, we can measure the dissociation rate constant of a cellular protein complex, providing information about binding affinity and kinetics. Our dynamic single-cell, single-molecule pull-down method thus approaches the biochemical precision that is often sought fromin vitroassays, while being applicable to native protein complexes isolated from single cellsin vivo.