bluuebunny/crossref_metadata_2025_split huggingface dataset:
Web and social media searches highlight menstrual irregularities as a global concern in COVID-19 vaccinations
Authors: Katz Ariel , Tepper Yoav , Birk Ohad , Eran Alal 
Published: February 2022

AbstractBackgroundDelineation of public concerns that prevent vaccine compliance is a major step in generating assurances and enhancing the success of COVID-19 prevention programs. We therefore sought to identify public concerns associated with COVID-19 vaccines, as reflected by web and social media searches, with a focus on menstrual irregularities.MethodsWe used trajectory analyses of web and social media search data in combination with global COVID-19 data to reveal time-dependent correlations between vaccination rates and the relative volume of vaccine and period related searches.ResultsA surge of period and vaccine related Google searches followed the introduction of Covid vaccines around the world, and the commencement of vaccination programs in English speaking countries and across the United States. The relative volume of searches such as “Covid vaccine menstrual irregularities”, “Covid vaccine menstrual period”, “Pfizer vaccine menstruation”, and “Moderna vaccine menstruation” was each significantly correlated with vaccination rates (Spearman r = 0.42-0.88, P = 4.33 × 10−34-1.55 × 10−5), and significantly different before and after the introduction of COVID vaccines (Mann-Whitney P = 2.00 × 10−21-7.10 × 10−20). TikTok users were more engaged in period problems in 2021 than ever before.ConclusionsInternational, national, and state-level correlations between COVID-19 vaccinations and online activity demonstrate a global major concern of vaccine-related menstrual irregularities. Whether it is a potential side effect or an unfounded worry, monitoring of web and social media activity could reveal the public perception of COVID-19 prevention efforts, which could then be directly addressed and translated into insightful public health strategies.
The effects of sequencing depth on the assembly of coding and noncoding transcripts in the human genome
Authors: Babarinde Isaac Adeyemi , Hutchins Andrew Paul 
Published: January 2022

AbstractBackgroundInvestigating the functions and activities of genes requires proper annotation of the transcribed units. However, transcript assembly efforts have produced a surprisingly large variation in the number of transcripts, and especially so for noncoding transcripts. The heterogeneity of the assembled transcript sets might be partially explained by sequencing depth.ResultsHere, we used real and simulated short-read sequencing data as well as long-read data to systematically investigate the impact of sequencing depths on the accuracy of assembled transcripts. We assembled and analyzed transcripts from 671 human short-read data sets and four long-read data sets. At the first level, there is a positive correlation between the number of reads and the number of recovered transcripts. However, the effect of the sequencing depth varied based on cell or tissue type, the type of read considered and the nature and expression levels of the transcripts. The detection of coding transcripts saturated rapidly for both short-read and long-reads, however, there was no sign of saturation for noncoding transcripts at any sequencing depth. Increasing long-read sequencing depth specifically benefited transcripts containing transposable elements. Finally, we show how single-cell RNA-seq can be guided by transcripts assembled from bulk long-read samples, and demonstrate that noncoding transcripts are expressed at similar levels to coding transcripts but are expressed in fewer cells.ConclusionsThis study shows the impact of sequencing depth on transcript assembly. Sequencing read depth has a relatively minor impact on coding transcript assembly, but a major effect on the assembly of noncoding transcripts. This study highlights important factors to consider when deciding the sequencing read depths to be used for transcript assembly.
HiC-LDNet: A general and robust deep learning framework for accurate chromatin loop detection in genome-wide contact maps
Authors: Chen Siyuan , Wang Jiuming , Gao Xin , Li Yu 
Published: February 2022

AbstractMotivationIdentifying chromatin loops from genome-wide interaction matrices like Hi-C data is notoriously difficult. Such kinds of patterns can span through the genome from a hundred kilobases to thousands of kilobases. Most loop patterns are frequently related to biological functions, such as providing contacts between regulatory regions and promoters. They can also affect the cell-specific biological functions of different regulatory regions of DNA, thus leading to disease and tumorigenesis. While most statistical methods failed in the generalization to multiple cell types, recently proposed machine learning-based methods struggled when tested on sparse single-cell Hi-C (scHi-C) contact maps. We notice that there is an urgent need for an algorithm that can handle sparse scHi-C maps, and at the same time, can generate confident loop calls on regular cell lines.ResultsTherefore, we propose a novel deep learning-based framework for Hi-C chromatin loop detection (HiC-LDNet) and provide corresponding downstream analysis. HiC-LDNet can give relatively more accurate predictions in multiple tissue types and contact technologies. Compared to other loop calling algorithms, such as HiCCUPS, Peakachu, and Chromosight, HiC-LDNet recovers a higher number of loop calls in multiple experimental platforms (Hi-C, ChIA-PET, DNA-SPRITE, and HiChIP), and achieves higher confidence scores in multiple cell types (Human GM12878, K562, HAP1, and H1-hESC). For example, in genome-wide loop detection on the human GM12878 cell line, HiC-LDNet successfully recovered 82.5% of loops within only 5 pixels of 10k bp resolution. Furthermore, in the sparse scHi-C ODC tissue, HiC-LDNet achieves superior performance by recovering 93.5% of ground truth loops with high confidence scores, compared with that of Peakachu (31.5%), Chromosight(69.6%), and HiCCUPS(9.5%). Therefore, our method is a robust and general pipeline for genome-wide chromatin loop detection for both bulk Hi-C and scHi-C data.Availabilityhttps://github.com/frankchen121212/HiC-LDNetContactliyu@cse.cuhk.edu.hk and xin.gao@kaust.edu.sa
Do place cells dream of deceptive moves in a signaling game?
Authors: Fenton André A. , Hurtado José R. , Broek Jantine A.C. , Park EunHye , Mishra Bud 
Published: February 2022

ABSTRACTWe consider the possibility of applying game theory to analysis and modeling of neurobiological systems. Specifically, the basic properties and features of information asymmetric signaling games are considered and discussed as having potential to explain diverse neurobiological phenomena at levels of biological function that include gene regulation, molecular and biochemical signaling, cellular and metabolic function, as well as the neuronal action potential discharge that can represent cognitive variables such as memory and purposeful behavior. We begin by arguing that there is a pressing need for conceptual frameworks that can permit analysis and integration of information and explanations across the many scales of diverse levels of biological function. Developing such integrative frameworks is crucial if we are to understand cognitive functions like learning, memory, and perception. The present work focuses on systems level neuroscience organized around the connected brain regions of the entorhinal cortex and hippocampus. These areas are intensely studied in rodent subjects as model neuronal systems that undergo activity-dependent synaptic plasticity to form and represent memories and spatial knowledge used for purposeful navigation. Examples of cognition-related spatial information in the observed neuronal discharge of hippocampal place cell populations and medial entorhinal head-direction cell populations are used to illustrate possible challenges to information maximization concepts. It may be natural to explain these observations using the ideas and features of information asymmetric signaling games.
The occurrence and characteristics of severe pain in patients with axial spondyloarthritis
Authors: Jones Gareth T , Rotariu Ovidiu , Dean Linda E , MacDonald Alan G , Macfarlane Gary J 
Published: February 2022

ABSTRACTObjectivesPharmacological management of axial spondylarthritis (axSpA) seek to control inflammation. Even if successful, available evidence suggests that many patients continue to experience pain. The aim of the current study was to determine the prevalence and characteristics of severe pain, among persons with axSpA.MethodsThe Scotland Registry for Ankylosing Spondylitis (SIRAS) collected clinical and patient-reported data from adults seen in secondary care in Scotland with a clinical diagnosis of ankylosing spondylitis. Questionnaires asked about severe pain (high pain intensity; high pain interference; and extreme/unbearable pain), lifestyle, and various aspects of health. The relationship between severe pain and clinical/patient-reported factors was assessed using logistic regression.Results929 participants had pain data available (73% male; median symptom duration 20yrs). High pain intensity and pain interference were more common (57% and 42%) than extreme/unbearable pain (11%). Prevalence did not differ with age, although women were less likely to report severe pain than men (Odds Ratios (ORs) 0.56-0.61) as were those with longer duration of education, and those from more affluent areas. The odds of severe pain increased with every 1 unit increase in BASFI (ORs 1.44-1.56). Strong associations were also seen with disease activity, spinal mobility, fatigue, poor sleep, and worse quality of life.ConclusionIn axSpA, severe pain is common, with a clear socio-economic gradient and major impact on quality of life. Rheumatologists need to be aware of the large unmet need in terms of pain management in this patient group with around 1 in 9 patients reporting extreme/unbearable pain.KEY MESSAGESWhat is already known about this subject?Axial spondyloarthritis is a painful inflammatory arthritis, although the epidemiology of specific pain phenotypes – and ‘severe’ pain in particular – is unknown.What does this study add?Severe pain (extreme/unbearable pain, pain of high intensity, or with a high level of interference) is commonly reported among people with axial spondyloarthritis.Three-quarters of individuals reporting severe pain still report severe pain two years later.Patients with severe pain are characterised by certain demographic characteristics, higher disease activity, poorer function, and a number of other clinical and lifestyle factors.How might this impact on clinical practice or future developments?Rheumatologists should be aware of the large unmet need in terms of pain management in this patient group. Specific pain management strategies should be considered to complement therapies aimed at reducing inflammation.
Omicron-specific mRNA vaccine induced potent neutralizing antibody against Omicron but not other SARS-CoV-2 variants
Authors: Lee I-Jung , Sun Cheng-Pu , Wu Ping-Yi , Lan Yu-Hua , Wang I-Hsuan , Liu Wen-Chun , Tseng Sheng-Che , Tsung Szu-I , Chou Yu-Chi , Kumari Monika , Chang Yu-Wei , Chen Hui-Feng , Lin Yin-Shiou , Chen Tsung-Yen , Chiu Chi-Wen , Hsieh Chung-Hsuan , Chuang Cheng-Ying , Lin Chih-Chao , Cheng Chao-Min , Lin Hsiu-Ting , Chen Wan-Yu , Chiang Po-Cheng , Lee Chong-Chou , Liao James C. , Wu Han-Chung , Tao Mi-Hua 
Published: February 2022

AbstractThe emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals receiving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a “Hybrid” vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specific RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.
Intervertebral disc cell chondroptosis elicits neutrophil response inStaphylococcus aureusspondylodiscitis
Authors: Schweizer Tiziano A. , Andreoni Federica , Acevedo Claudio , Scheier Thomas C. , Heggli Irina , Maggio Ewerton Marques , Eberhard Nadia , Brugger Silvio D. , Dudli Stefan , Zinkernagel Annelies S. 
Published: February 2022

AbstractObjectiveTo understand the pathophysiology of spondylodiscitis due toStaphylococcus aureus, an emerging infectious disease of the intervertebral disc (IVD) and vertebral body with a high complication rate, by combining clinical insights and experimental approaches.DesignClinical data and histological material of nine patients suffering fromS. aureusspondylodiscitis were retrospectively collected at a single center. To mirror the clinical findings experimentally, we developed a novel porcineex vivomodel mimicking acuteS. aureusspondylodiscitis and assessed the interaction betweenS. aureusand IVD cells within their native environment. In addition, the inflammatory features underlying this interaction were assessed in primary human IVD cells. Finally, mirroring the clinical findings, we assessed primary human neutrophils for their ability to respond to secreted inflammatory modulators of IVD cells uponS. aureuschallenge.ResultsAcuteS. aureusspondylodiscitis in patients was characterized by tissue necrosis and neutrophil infiltration. Additionally, the presence of empty IVD cells’ lacunae was observed. This was mirrored in the ex vivo porcine model, whereS. aureusinduced extensive IVD cell death, leading to empty lacunae. Concomitant engagement of the apoptotic and pyroptotic cell death pathways was observed in primary human IVD cells, resulting in cytokine release. Among the released cytokines, functionally intact neutrophil-priming as well as broad pro- and anti-inflammatory cytokines known for their involvement in IVD degeneration were found.ConclusionsIn patients as well asex vivoin a novel porcine model,S. aureusspondylodiscitis infection caused IVD cell death, resulting in empty lacunae, which was accompanied by release of inflammation markers and recruitment of neutrophils. These findings offer valuable insights into the important role of inflammatory IVD cell death during the onset of spondylodiscitis and potential future therapeutic approaches.
HOW CONCERNING IS A SARS-COV-2 VARIANT OF CONCERN? COMPUTATIONAL PREDICTIONS AND THE VARIANTS LABELING SYSTEM
Authors: Ashoor Dana , Marzouq Maryam , Trabelsi Khaled , Chlif Sadok , Abotalib Nasser , Ben Khalaf Noureddine , Ramadan Ahmed R. , Fathallah M-Dahmani 
Published: February 2022

ABSTRACTWe herein report a study to evaluate the use of computational prediction of SARS-CoV-2 genetic variations in improving the current variants labeling system. First, we reviewed the basis of the system developed by the World Health Organization (WHO) for the labeling of SARS-CoV-2 genetic variants and the adaptations made to it by the United States Center of Diseases Control (CDC). We observed that the labeling system is based upon the virus’ major attributes. However, we found that the labeling criteria of the SARS-CoV-2 variants derived from these attributes are not accurately defined and are used differently by the two health management agencies. Consequently, discrepancies exist between the labels given by WHO and CDC to same variants. Our observations suggest that giving the VOC label to a new variant is premature and might not be appropriate. Therefore, we carried out a comparative computational study to predict the effects of the mutations on the virus structure and functions of five VOCs. By linking these data to the criteria used by WHO and the CDC for variant labeling, we ascertained that comparative computational predictions of the impact of genetic variations are a better ground for rapid and more accurate labelling of SARS-CoV-2 variants. We propose to label all emergent variants VUM or VBM and to carry out computational predictive studies and thorough variants comparison, upon which more appropriate and informative labels can be attributed. Furthermore, harmonization of the variants labeling system would be globally beneficial to communicate about and fight COVID-19 pandemic.
A novel role of 3’,5’-cAMP in the regulation of actin cytoskeleton in Arabidopsis
Authors: Chodasiewicz Monika , Figueroa Nicolás E. , Franz Peter , Luzarowski Marcin , Moreno Juan C. , Childs Dorothee , Masiuk Aleksandra , Saluja Manny , Sampathkumar Arun , Tsiavaliaris Georgios , Skirycz Aleksandra 
Published: February 2022

AbstractThe role of cyclic adenosine monophosphate (3’,5’-cAMP) in plants is not well understood, and here, we report a novel role of 3’,5’-cAMP in regulating the actin cytoskeleton. The 3’,5’-cAMP treatment affects the thermal stability of 51 proteins, including a vegetative actin isoform, ACTIN2. Consistent with the above results, the increase in 3’,5’-cAMP levels, obtained either by feeding or by chemical modulation of 3’,5’-cAMP metabolism, is sufficient to partially rescue the short hypocotyl phenotype of the actin2 actin7 mutant, severely compromised in actin level. No such complementation was measured for a positional isomer of 3’,5’-cAMP, 2’,3’-cAMP, attesting to the specificity of 3’,5’-cAMP treatment. Moreover, supplementation of 3’,5’-cAMP partly counters the activity of an actin-depolymerizing drug latrunculin B. In vitro characterization of the 3’,5’-cAMP – actin interaction argues against the direct binding. Instead, based on the proteomics characterization of the act2act7 mutant supplemented with 3’,5’-cAMP, we hypothesize that 3’,5’-cAMP affects cytoskeleton dynamic by modulation of calcium signaling, and actin binding proteins.
Peptide location fingerprinting identifies species- and tissue-conserved structural remodelling of proteins as a consequence of ageing and disease
Authors: Eckersley Alexander , Ozols Matiss , Chen Peikai , Tam Vivian , Ward Liam J. , Hoyland Judith A. , Trafford Andrew , Yuan Xi-Ming , Schiller Herbert B. , Chan Danny , Sherratt Michael J. 
Published: February 2022

AbstractExtracellular matrix (ECM) in the intervertebral disc (IVD), lung and artery are thought to undergo the age-dependant accumulation of damage by chronic exposure to mechanisms such as reactive oxygen species, proteases and glycation. It is unknown whether this damage accumulation is species-dependant (via differing lifespans and hence cumulative exposures) or whether it can influence the progression of age-related diseases such as atherosclerosis. Peptide location fingerprinting (PLF) is a new proteomic analysis method, capable of the non-targeted identification of structure-associated changes within proteins. Here we applied PLF to publicly available ageing human IVD (outer annulus fibrosus), ageing mouse lung and human arterial atherosclerosis datasets and identified novel target proteins alongside common age-associated differences within protein structures which were conserved between tissue regions, organs, sexes and species and in age-related disease. We identify peptide yield differences across protein structures which coincide with biological regions, potentially reflecting the functional consequences of ageing or atherosclerosis for macromolecular assemblies (collagen VI and fibrin), enzyme/inhibitor activity (cathepsin B and alpha-2 macroglobulin), activation states (complement C3 and thrombin) and interaction states (laminins, perlecan, fibronectin, filamin-A, collagen XIV and apolipoprotein-B). Furthermore, we show that alpha-2 macroglobulin, prothrombin, collagen XIV and apolipoprotein-B all exhibit possible shared structural consequences in IVD ageing and arterial atherosclerosis, providing novel links between an age-related disease and intrinsic ageing. Crucially, we also demonstrate that fibronectin, laminin beta chains and filamin-A all exhibit conserved age-associated structural differences between mouse lung and human IVD, providing evidence that ECM, and their associating proteins, may be subjected to potentially similar mechanisms or consequences of ageing across species, irrespective of differences in lifespan and tissue function.
Spatial Venomics - Cobra Venom System Reveals Spatial Differentiation of Snake Toxins by Mass Spectrometry Imaging
Authors: Hempel Benjamin-Florian , Damm Maik , Petras Daniel , Kazandjian Taline D. , Szentiks Claudia A. , Fritsch Guido , Nebrich Grit , Casewell Nicholas R. , Klein Oliver , Süssmuth Roderich D. 
Published: February 2022

AbstractAmong venomous animals, toxic secretions have evolved as biochemical weapons associated with various highly specialized delivery systems on many occasions. Despite extensive research, there is still limited knowledge of the functional biology of most animal toxins, including their venom production and storage, as well as the morphological structures within sophisticated venom producing tissues that might underpin venom modulation. Here we report on the spatial exploration of a snake venom gland system by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), in combination with standard proteotranscriptomic approaches, to enable in situ toxin mapping in spatial intensity maps across a venom gland sourced from the Egyptian cobra (Naja haje). MALDI-MSI toxin visualization on the elapid venom gland reveals high spatial heterogeneity of different toxin classes at the proteoform level, which may be the result of physiological constraints on venom production and/or storage that reflects the potential for venom modulation under diverse stimuli.
Chromatin-associated microprocessor assembly is regulated by PRP40, the U1 snRNP auxiliary protein
Authors: Stepien Agata , Dolata Jakub , Gulanicz Tomasz , Bielewicz Dawid , Bajczyk Mateusz , Smolinski Dariusz J. , Szweykowska-Kulinska Zofia , Jarmolowski Artur 
Published: February 2022

AbstractCotranscriptional processing of RNA polymerase II-generated primary transcripts is a well-documented phenomenon. We recently showed that in plants, miRNA biogenesis is also a cotranscriptional event. Here, we report that Arabidopsis PRP40, the U1 snRNP auxiliary protein, positively regulates the recruitment of SE, the core component of the plant microprocessor, to miRNA genes. The association of DCL1, the microprocessor endoribonuclease, with chromatin was altered in prp40ab mutant plants. Impaired cotranscriptional microprocessor assembly was accompanied by RNA polymerase II accumulation at miRNA genes and retention of miRNA precursors at their transcription sites in the prp40ab mutant plants. We show that cotranscriptional microprocessor assembly, regulated by AtPRP40, positively affects RNAPII transcription of miRNA genes and is important to reach the correct levels of produced miRNAs.