bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust enhancer-gene regulation identified by single-cell transcriptomes and epigenomes
Authors: Xie Fangming , Armand Ethan J. , Yao Zizhen , Liu Hanqing , Bartlett Anna , Behrens M. Margarita , Li Yang Eric , Lucero Jacinta D. , Luo Chongyuan , Nery Joseph R. , Pinto-Duarte Antonio , Poirion Olivier , Preissl Sebastian , Rivkin Angeline C. , Tasic Bosiljka , Zeng Hongkui , Ren Bing , Ecker Joseph R. , Mukamel Eran A. 
Published: October 2021

AbstractIntegrating single-cell transcriptomes and epigenomes across diverse cell types can link genes with the cis-regulatory elements (CREs) that control expression. Gene co-expression across cell types confounds simple correlation-based analysis and results in high false prediction rates. We developed a procedure that controls for co-expression between genes and integrates multiple molecular modalities, and used it to identify >10,000 gene-CRE pairs that contribute to gene expression programs in different cell types in the mouse brain.
PREPRINT: Mechanisms of Motoric Cognitive Risk – hypotheses based on a systematic review and meta-analysis of longitudinal cohort studies of older adults
Authors: Mullin Donncha S. , Cockburn Alastair , Welstead Miles , Luciano Michelle , Russ Tom C. , Muniz-Terrera Graciela 
Published: October 2021

AbstractWe aimed to refine the hypothesis that Motoric Cognitive Risk (MCR), a syndrome combining measured slow gait speed and self-reported cognitive complaints, is prognostic of incident dementia and other major causes of morbidity in older age. We propose mechanisms on the relationship between motor and cognitive function and describe a roadmap to validate these hypotheses. We systematically searched major electronic databases from inception to August 2021 for original longitudinal cohort studies of adults aged ≥60 years that compared an MCR group to a non-MCR group with any health outcome. Fifteen cohorts were combined by meta-analysis. Participants with MCR were at an increased risk of cognitive impairment (adjusted hazard ratio [aHR] 1.76, 95%CI 1.49-2.08; I2=24.9%), dementia (aHR 2.12, 1.85-2.42; 33.1%), falls (adjusted Relative Risk 1.38, 1.15-1.66; 62.1%), and mortality (aHR 1.49, 1.16-1.91; 79.2%). The prognostic value of MCR is considerable and mechanisms underlying the syndrome are proposed.Systematic review registrationPROSPERO CRD42020225183.
Protocol for 18F-PSMA PET imaging in staging and management of prostate cancer – a retrospective cohort study
Authors: Byrne Matthew H V , Ranasinha Nithesh , Bryant Richard J , Hamdy Freddie C , Leslie Tom , Miah Saiful , Gleeson Fergus , MacPherson Ruth , Tuthill Mark , Protheroe Andy , Camilleri Philip , Turner Phil , Sabharwal Ami , Andrade Gerard , Lamb Alastair D 
Published: October 2021

ABSTRACTBackgroundMRI, bone scan, and CT staging is recommended in the staging of prostate cancer. However, prostate-specific membrane antigen positron emission tomography (PSMA PET) could be superior in detection of local and distant prostate cancer cells. Most PSMA PET scans for prostate cancer are performed with a Gallium-68 ligand, with the Fluorine-18 (18F) ligand being introduced more recently. Methods: We will conduct a retrospective review of electronic patient records for all consecutive patients who underwent preoperative 18F-PSMA PET scan for prostate cancer from its introduction at our centre in 2019. We will compare PET scans with other imaging modalities and evaluate its use in diagnosis and management decisions for prostate cancer.ConclusionsUnderstanding the role of 18F-PSMA PET in diagnosis and management could influence the diagnostic pathway of primary and secondary prostate cancer.Trial registrationNot applicable.
White matter microstructure in Parkinson’s disease with and without elevated REM sleep muscle tone
Authors: Patriat Rémi , Pisharady Pramod K. , Amundsen-Huffmaster Sommer , Linn-Evans Maria , Howell Michael , Chung Jae Woo , Petrucci Matthew N. , Videnovic Aleksandar , Holker Erin , De Kam Joshua , Tuite Paul , Lenglet Christophe , Harel Noam , MacKinnon Colum D. 
Published: October 2021

AbstractPeople with Parkinson’s disease who have elevated muscle activity during rapid eye movement sleep (REM sleep without atonia) typically have worse motor and cognitive impairment compared to those with normal muscle atonia during REM sleep. This study used tract-based spatial statistics to compare diffusion MRI measures of fractional anisotropy, radial, mean and axial diffusivity (measures of axonal microstructure based on the directionality of water diffusion) in white matter tracts between people with Parkinson’s disease with and without REM sleep without atonia and controls and their relationship to measures of motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson’s disease and twenty-one matched control subjects underwent ultra-high-field MRI (7Tesla), quantitative motor assessments of gait and bradykinesia, and neuropsychological testing. The Parkinson’s disease cohort was separated post-hoc into those with and without elevated chin or leg muscle activity during REM sleep based on polysomnography findings. Fractional anisotropy was significantly higher, and diffusivity significantly lower, in regions of the corpus callosum, projection, and association white matter pathways in the Parkinson’s group with normal REM sleep muscle tone compared to controls, and in a subset of pathways relative to the Parkinson’s disease group with REM sleep without atonia. The Parkinson’s disease group with elevated REM sleep muscle tone showed significant impairments in gait and upper arm speed compared to controls and significantly worse scores in specific cognitive domains (executive function, visuospatial memory) compared to the Parkinson’s disease group with normal REM sleep muscle tone. Regression analyses showed that gait speed and step length in the Parkinson’s disease cohort were predicted by measures of fractional anisotropy of the anterior corona radiata, whereas elbow flexion velocity was predicted by fractional anisotropy of the superior corona radiata. Visuospatial memory task performance was predicted by the radial diffusivity of the posterior corona radiata. These findings show that people with mild-to-moderate severity of Parkinson’s disease who have normal muscle tone during REM sleep demonstrate compensatory-like adaptations in axonal microstructure that are associated with preserved motor and cognitive function, but these adaptations are reduced or absent in those with increased REM sleep motor tone.
An increase in surface hydrophobicity mediates chaperone activity in N-chlorinated proteins
Authors: Varatnitskaya Marharyta , Fasel Julia , Müller Alexandra , Lupilov Natalie , Shi Yunlong , Fuchs Kristin , Krewing Marco , Jung Christoph , Jakob Timo , Sitek Barbara , Bandow Julia E. , Carroll Kate S. , Hoffmann Eckhard , Leichert Lars I. 
Published: October 2021

ABSTRACTUnder physiological conditions, Escherichia coli RidA is an enamine/imine deaminase, which promotes the release of ammonia from reactive enamine/imine intermediates. However, when modified by hypochlorous acid (HOCl), as produced by the host defense, RidAHOCl turns into a potent chaperone-like holdase that can effectively protect the proteome of E. coli during oxidative stress. We previously reported that the activation of RidA’s chaperone-like function coincides with the addition of at least seven and up to ten chlorine atoms. These atoms are reversibly added to basic amino acids in RidAHOCl and removal by reducing agents leads to inactivation. Nevertheless, it remains unclear, which residues in particular need to be chlorinated for activation. Here, we employ a combination of LC-MS/MS analysis, a chemo-proteomic approach, and a mutagenesis study to identify residues responsible for RidA’s chaperone-like function. Through LC-MS/MS of digested RidAHOCl, we obtained direct evidence of the chlorination of one arginine residue (and, coincidentally, two tyrosine residues), while other N- chlorinated residues could not be detected, presumably due to the instability of the modification and its potential interference with a proteolytic digest. Therefore, we established a chemoproteomic approach using 5-(dimethylamino) naphthalene-1-sulfinic acid (DANSO2H) as a probe to label N-chlorinated lysines. Using this probe, we were able to detect the N-chlorination of six additional lysine residues. Moreover, using a mutagenesis study to genetically probe the role of single arginine and lysine residues, we found that the removal of arginines R105 and R128 leads to a substantial reduction of RidAHOCl’s chaperone activity. These results, together with structural analysis, confirm that the chaperone activity of RidA is concomitant with the loss of positive charges on the protein surface, leading to an increased overall protein hydrophobicity. Molecular modelling of RidAHOCl and the rational design of a RidA variant that shows chaperone activity even in the absence of HOCl further supports our hypothesis. Our data provide a molecular mechanism for HOCl-mediated chaperone activity found in RidA and a growing number of other HOCl-activated chaperones.
DEAD-box RNA helicase 18 disrupts IRF3-binding to the interferon-β promoter
Authors: Xiao Xun , Wang Mohan , Zhao Wenkai , Fang Puxian , Zhou Yanrong , Wang Dang , Fang Liurong , Xiao Shaobo 
Published: October 2021

AbstractThe production of type I interferons (IFN-α/β) requires strict control to avoid excessive activation during viral infections. The binding of interferon regulatory factor 3 (IRF3) to the IFN-β promoter region in the nucleus is essential for IFN-β transcription; however, whether nuclear factors have important negative-regulatory roles in this process is largely unknown. By screening for IRF3-interacting partners in the nucleus, we identified DEAD-box RNA helicase 18 (DDX18) as an important negative regulator of intranuclear IRF3. Overexpression of DDX18 suppressed virus- and IRF3-induced IFN-β production, whereas knockdown of DDX18 expression or knockout of the DDX18 gene had opposite effects. Mechanistically, DDX18 interacts with IRF3 and decreases the binding of IRF3 to the IFN-β promoter after viral infection. DDX18 knockdown mice (Ddx18+/-) further demonstrated that DDX18 suppressed antiviral innate immunity in vivo. Thus, despite many members of the DDX family act as important positive regulators in the cytoplasm, DDX18 plays a unique “braking” role in balancing virus-induced type I IFN production.
Event-triggered STED imaging
Authors: Alvelid Jonatan , Damenti Martina , Testa Ilaria 
Published: October 2021

AbstractThe observation of protein organization during cellular signalling calls for imaging methods with increased spatial and temporal resolution. STED nanoscopy can access dynamics of nanoscale structures in living cells. However, the available number of recordable frames is often limited by photo-bleaching. Here, we present an automated method, event-triggered STED, which instantly (< 40 ms) images synaptic proteins with high spatial and temporal resolution (~30 nm, 2.5 Hz) in small regions upon and at the site of local calcium sensing.
Extensive sequence divergence of non-coding regions between Aspergillus fumigatus, a major fungal pathogen of humans, and its relatives
Authors: Brown Alec , Mead Matthew E. , Steenwyk Jacob L. , Goldman Gustavo H. , Rokas Antonis 
Published: October 2021

AbstractInvasive aspergillosis is a deadly fungal disease; more than 400,000 patients are infected worldwide each year and the mortality rate can be as high as 50-95%. Of the ∼450 species in the genus Aspergillus only a few are known to be clinically relevant, with the major pathogen Aspergillus fumigatus being responsible for ∼50% of all invasive mold infections. Genomic comparisons of A. fumigatus to other Aspergillus species have historically focused on protein-coding regions. However, most A. fumigatus genes, including those that modulate its virulence, are also present in non-pathogenic close relatives of A. fumigatus. Our hypothesis is that differential gene regulation – mediated through the non-coding regions upstream of genes’ transcription start sites – contributes to A. fumigatus pathogenicity. To begin testing this, we compared non-coding regions up to 500 base pairs upstream of the first codon of single-copy orthologous genes from the two A. fumigatus reference strains Af293 and A1163 and eight closely related Aspergillus section Fumigati species. We found that non-coding regions showed extensive sequence variation and lack of homology across species. By examining the evolutionary rates of both protein-coding and non-coding regions in a subset of orthologous genes with highly conserved non-coding regions across the phylogeny, we identified 418 genes, including 25 genes known to modulate A. fumigatus virulence, whose non-coding regions exhibit a different rate of evolution in A. fumigatus. Examination of sequence alignments of these non-coding regions revealed numerous instances of insertions, deletions, and other types of mutations of at least a few nucleotides in A. fumigatus compared to its close relatives. These results show that closely related Aspergillus species that vary greatly in their pathogenicity exhibit extensive non-coding sequence variation and identify numerous changes in non-coding regions of A. fumigatus genes known to contribute to virulence.
SCS313 Serrano, a big trefoil selected for flowering ability and seed production
Authors: Rocha Dediel A. , Cordova Ulisses A. , Flaresso Jefferson , Stradiotto Joseli , Dalla-Costa Murilo 
Published: October 2021

AbstractSCS313 Serrano is a tetraploid cultivar of Lotus uliginosus developed by the Research and Rural Extension Company of Santa Catarina, Brazil, to improve flowering ability and seed production in low-latitude regions. SCS313 Serrano was developed from the selection of individual plants of the cultivar Grasslands Maku. Seeds from the initial breeding population was bulked and used to establish a field trial with spaced plants. The plants were selected and classified as late or early, regarding the beginning of flowering, through visual evaluations based on the time for the beginning of flowering. Selected plants were transplanted to crossing blocks and seed harvested on individual plants; a progeny test was conducted, with four replications, through the establishment of approximately 100 genotypes in a field. This process was repeated for three consecutive cycles of recurrent selection. Considering the mean time for the beginning of flowering and vigor performance, the best five genotypes were selected as parental lines for the synthetic cultivar SCS313 Serrano. A morphological difference between SCS313 Serrano and Grasslands Maku is that SCS313 Serrano has absence of hairs in stems whereas Grasslands Maku has a medium stem hair density. In addition, SCS313 Serrano exhibits profuse flowering ability while Grasslands Maku exhibits very sparse seedhead formation. SCS313 Serrano exhibited good persistence under wet conditions and similar forage yields compared to other lotus commercial cultivars. Thus, SCS313 Serrano is recommended to be used as pasture in mixtures with grass in livestock systems, mainly on wet soils.
Text Mining Drug-Protein Interactions using an Ensemble of BERT, Sentence BERT and T5 models
Authors: Sui Xin , Wang Wanjing , Zhang Jinfeng 
Published: October 2021

AbstractIn this work, we trained an ensemble model for predicting drug-protein interactions within a sentence based on only its semantics. Our ensembled model was built using three separate models: 1) a classification model using a fine-tuned BERT model; 2) a fine-tuned sentence BERT model that embeds every sentence into a vector; and 3) another classification model using a fine-tuned T5 model. In all models, we further improved performance using data augmentation. For model 2, we predicted the label of a sentence using k-nearest neighbors with its embedded vector. We also explored ways to ensemble these 3 models: a) we used the majority vote method to ensemble these 3 models; and b) based on the HDBSCAN clustering algorithm, we trained another ensemble model using features from all the models to make decisions. Our best model achieved an F-1 score of 0.753 on the BioCreative VII Track 1 test dataset.
Geo-epidemiology of Malaria in Burkina Faso, 2013-2018: a recent re-increase
Authors: Bationo Cédric S. , Lokossou Virgil , Landier Jordi , Sylla Bry , Tougri Gauthier , Ouedraogo Boukary , Cissoko Mady , Moiroux Nicolas , Gaudart Jean 
Published: October 2021

AbstractBackgroundAfter a global decline, malaria cases re-increases have been shown recently.The aim of this analysis was to update the epidemiological facies of malaria in Burkina Faso (around 4% of malaria cases worldwide) by estimating weekly malaria incidences at health district levels, from 2013 to 2018, associated to environmental and meteorological factors.MethodsMalaria cases and deaths weekly reports were extracted from the National Malaria Control Program for each health district from 2013 to 2018. Population data were extracted from the reports of the national statistics council. Environmental data were collected through remote sensing.After estimating incidence through time and space, trend was assessed by an additive decomposition of the incidence and malaria seasons of transmission was estimated by change point analysis (PELT algorithm).Incidence maps for each year of the study period were assessed to highlight spatial variability through years. Maps of rainfall, temperature, and vegetation (NDVI) were produced to characterize the health district environmental variability.ResultsIn 2013, 775 cases /100,000 inhab.week were observed in average, and remain roughly constant until 2015. Malaria re-increased from 2016, reaching 2428 cases /100,000 inhab.week in 2018.From 2013 to 2016, two transmission periods were observed: low from January to July (included) and high from August to December (included).From 2017 to 2018, an intermediate transmission period from mid-November to early January intercalated between the low transmission period from mid-February to early June and the high transmission period from July to late DecemberFrom 2013 to 2015, the most affected districts were located in the center and central-eastern part of the country. From 2016 to 2018 all health districts, except those in the Sahel region, were affected with at least 45,000 cases per 100,000 persons/year. This south-to-north gradient was also observed with rainfall, temperature and NDVI.ConclusionMalaria incidences re-increased through years and across the country since 2016. But no modification of the environmental factor variability was observed during the same period, in time or space. The re-increase of malaria in Burkina Faso could be due to a real increase of the disease, or to a better access to diagnostic and cure, together with the development of the epidemiological information system.
The Effect of Bilingual Exposure on Language and Cognitive Development in Children Following Ischemic Stroke
Authors: Leung Kai Ian , Dlamini Nomazulu , Westmacott Robyn , Molnar Monika 
Published: October 2021

AbstractAIMWhile many children who experience ischemic stroke come from bilingual backgrounds, it is unclear whether bilingual exposure affects post-stroke development. Our research evaluates the effects of bilingual vs. monolingual exposure on linguistic/cognitive development post-stroke.METHODAn institutional stroke registry and medical charts were used to gather data on 237 children across 3 stroke-onset groups: neonatal - <28 days, first-year - 28 days to 12 months and childhood - 13 months to 18 years. The Pediatric Stroke Outcome Measure (PSOM) was administered at several times post-stroke, to evaluate cognition and linguistic development.RESULTSBilingual children had better post-stroke performance on the language subscales, compared to monolinguals. An interaction with stroke-onset group was also observed, with monolinguals in the first-year group having worse outcomes.INTERPRETATIONOverall, no detrimental effects of bilingualism were found on children’s post-stroke cognition and linguistic development. Our study suggests that a bilingual environment may facilitate language development in children post-stroke.
COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication from the COVID and Cognition Study
Authors: Guo Panyuan , Ballesteros Alvaro Benito , Yeung Sabine P , Liu Ruby , Saha Arka , Curtis Lyn , Kaser Muzaffer , Haggard Mark P , Cheke Lucy G 
Published: October 2021

AbstractCoronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions particularly in the left hemisphere. There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those suffering from Long COVID—the chronic illness following COVID-19 infection that affects between 10–25% of sufferers. However, there is as yet little research testing cognition in Long COVID. The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had suffered COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits. In this second paper from the study, we assess this sample on tests of memory, language and executive function. We hypothesize that performance on “objective” cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information as to mechanism. We found a consistent pattern of memory deficits in those that had suffered COVID-19 infection, with deficit increasing with severity of self-reported ongoing symptoms. Fatigue/Systemic symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.
An evolutionarily conserved stop codon enrichment at the 5’ ends of mammalian piRNAs
Authors: Bornelöv Susanne , Czech Benjamin , Hannon Gregory J 
Published: October 2021

SUMMARYPIWI-interacting RNAs (piRNAs) are small RNAs required to recognize and silence transposable elements. The 5’ ends of mature piRNAs are defined through cleavage of long precursor transcripts, primarily by Zucchini (Zuc). Zuc-dependent cleavage typically occurs immediately upstream of a uridine. However, Zuc lacks sequence preference in vitro, pointing towards additional unknown specificity factors. We examined murine piRNAs and revealed a strong and specific enrichment of three sequences (UAA, UAG, UGA)— corresponding to stop codons—at piRNA 5’ ends. Stop codon sequences were also enriched immediately after piRNA processing intermediates, reflecting their Zuc-dependent tail-to-head arrangement. Further analyses revealed that a Zuc in vivo cleavage preference at four sequences (UAA, UAG, UGA, UAC) promotes 5’ end stop codons. This observation was conserved across mammals and possibly further. Our work provides new insights into Zuc-dependent cleavage and may point to a previously unrecognized connection between piRNA biogenesis and the translational machinery.