bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
Authors: Stojanović Stevan D. , Fuchs Maximilian , Liang Chunguang , Schmidt Kevin , Xiao Ke , Just Annette , Pfanne Angelika , Pich Andreas , Warnecke Gregor , Braubach Peter , Petzold Christina , Jonigk Danny , Distler Jörg H. W. , Fiedler Jan , Thum Thomas , Kunz Meik 
Published: June 2021

AbstractThe family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.
Social-ecological filters drive the functional diversity of beetles in homegardens of campesinos and migrants in the southern Andes
Authors: Ibarra José Tomás , Caviedes Julián , Altamirano Tomás A. , Urra Romina , Barreau Antonia , Santana Francisca 
Published: June 2021

AbstractHomegardens are coupled social-ecological systems that act as biodiversity reservoirs while contributing to local food sovereignty. These systems are characterized by their structural complexity, while involving management practices according to gardener’s cultural origin. Social–ecological processes in homegardens may act as filters of species’ functional traits, and thus influence the species richness-functional diversity relationship of critical agroecosystem components like beetles (Coleoptera). We tested the species richness-functional diversity relationship of beetle communities and examined whether habitat structure across different levels, sociodemographic profiles, and management practices act as filters in homegardens in a Global Biodiversity Hotspot, Chile. For 100 homegardens (50 campesino and 50 migrant), we sampled beetles and habitat attributes, and surveyed gardeners’ sociodemographic profiles and management practices. We recorded 85 beetle species and found a positive relationship between species richness and functional richness that saturated when functionally similar species co-occur more often than expected by chance, indicating functional redundancy in species-rich homegardens. Gardener origin (campesino/migrant), homegarden area (m2), structural complexity (index), and pest control strategy (natural, chemical, or none) were the most influential social–ecological filters that selectively remove beetle species according to their functional traits. We discuss opportunities in homegarden management for strengthening local functional diversity and resilience under social-environmental changes.
Peptide profiling in cow urine reveals molecular signature of physiology-driven pathways and in-silico predicted bioactive properties
Authors: Kumar Rohit , Ali Syed Azmal , Singh Sumit Kumar , Bhushan Vanya , Kaushik Jai Kumar , Mohanty Ashok Kumar , Kumar Sudarshan 
Published: June 2021

AbstractPeptidomics allows the identification of peptides that are derived from proteins. Urinary peptidomics has revolutionized the field of diagnostics as the samples represent complete systemic changes happening in the body. Moreover, it can be collected in a non-invasive manner. We profiled the peptides in urine collected from different physiological states (heifer, pregnancy, and lactation) of Sahiwal cows. Endogenous peptides were extracted from 30 individual cows belonging to three groups, each group comprising of ten animals (biological replicates n = 10). Nano Liquid chromatography Mass spectrometry (nLC-MS/MS) experiments revealed 5239, 4774, and 5466 peptides in the heifer, pregnant and lactating animals respectively. Urinary peptides of <10 kDa size were considered for the study. Peptides were extracted by 10 kDa MWCO filter. Sequences were identified by scanning the MS spectra ranging from 200 to 2200 m/z. The peptides exhibited diversity in sequences across different physiological states and in-silico experiments were conducted to classify the bioactive peptides into anti-microbial, anti-inflammatory, anti-hypertensive, and anti-cancerous groups. We have validated the antimicrobial effect of urinary peptides on Staphylococcus aureus and Escherichia coli under an in-vitro experimental set up. The origin of these peptides was traced back to certain proteases viz. MMPs, KLKs, CASPs, ADAMs etc. which were found responsible for the physiology-specific peptide signature of urine. Proteins involved in extracellular matrix structural constituent (GO:0005201) were found significant during pregnancy and lactation in which tissue remodeling is extensive. Collagen trimers were prominent molecules under cellular component category during lactation. Homophilic cell adhesion was found to be an important biological process involved in embryo attachment during pregnancy. The in-silico study also highlighted the enrichment of progenitor proteins on specific chromosomes and their relative expression in context to specific physiology. The urinary peptides, precursor proteins, and proteases identified in the study offers a base line information in healthy cows which can be utilized in biomarker discovery research for several pathophysiological studies.
Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
Authors: Mannar Dhiraj , Leopold Karoline , Subramaniam Sriram 
Published: June 2021

AbstractThe SARS-CoV-2 spike glycoprotein is a focal point for vaccine immunogen and therapeutic antibody design, and also serves as a critical antigen in the evaluation of immune responses to COVID-19. A common feature amongst enveloped viruses such as SARS-CoV-2 and HIV-1 is the propensity for displaying host-derived glycans on entry spike proteins. Similarly displayed glycosylation motifs can serve as the basis for glyco-epitope mediated cross-reactivity by antibodies, which can have important implications on virus neutralization, antibody-dependent enhancement (ADE) of infection, and the interpretation of antibody titers in serological assays. From a panel of nine anti-HIV-1 gp120 reactive antibodies, we selected two (PGT126 and PGT128) that displayed high levels of cross-reactivity with the SARS-CoV-2 spike. We report that these antibodies are incapable of neutralizing pseudoviruses expressing SARS-CoV-2 spike proteins and are unlikely to mediate ADE via FcγRII receptor engagement. Nevertheless, ELISA and other immunoreactivity experiments demonstrate these antibodies are capable of binding the SARS-CoV-2 spike in a glycan-dependent manner. These results contribute to the growing literature surrounding SARS-CoV-2 S cross-reactivity, as we demonstrate the ability for cross-reactive antibodies to interfere in immunoassays.
A novel bone-thinning technique for transcranial stimulation motor-evoked potentials in rats
Authors: Maeda Yuyo , Otsuka Takashi , Mitsuhara Takafumi , Okazaki Takahito , Yuge Louis , Takeda Masaaki 
Published: June 2021

AbstractTranscranial electrical stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans, and even in animal studies, tcMEPs are used to evaluate neurological dysfunction. However, there is a dearth of reports on extended tcMEP recordings in both animal models and humans. Therefore, this study examined a new technique for stably recording tcMEPs over several weeks in six healthy female Sprague–Dawley rats. We thinned the skull bone using the skull base and spinal surgery technique to reduce electrical resistance for electrical stimulation. tcMEPs were recorded on days 1, 7, 14, 21, and 28 after surgery. The onset latency and amplitude of tcMEPs from the hindlimbs were recorded and evaluated, and histological analysis was performed. Stable amplitude and onset latency could be recorded over several weeks, and histological analysis indicated no complications attributable to the procedure. Thus, our novel technique allows for less invasive, safer, easier, and more stable extended tcMEP recordings than previously reported techniques. The presently reported technique may be applied to the study of various nerve injury models in rats: specifically, to evaluate the degree of nerve dysfunction and recovery in spinal cord injury, cerebral infarction, and brain contusion models.
Life-course trajectories of weight and their impact on the incidence of type 2 diabetes
Authors: Yacamán-Méndez Diego , Trolle-Lagerros Ylva , Zhou Minhao , Monteiro Ponce de Leon Antonio , Gudjonsdottir Hrafnhildur , Tynelius Per , Lager Anton 
Published: June 2021

AbstractAlthough exposure to overweight and obesity at different ages is associated to a higher risk of type 2 diabetes, the effect of different patterns of exposure through life remains unclear. We aimed to characterize life-course trajectories of weight categories and estimate their impact on the incidence of type 2 diabetes. We categorized the weight of 7203 participants as lean, normal or overweight at five time-points from ages 7–55 using retrospective data. Participants were followed for an average of 19 years for the development of type 2 diabetes. We used latent class analysis to describe distinctive trajectories and estimated the risk ratio, absolute risk difference and population attributable fraction (PAF) associated to different trajectories using Poisson regression. We found five distinctive life-course trajectories. Using the stable-normal weight trajectory as reference, the stable overweight, lean increasing weight, overweight from early adulthood and overweight from late adulthood trajectories were associated to higher risk of type 2 diabetes. The estimated risk ratios and absolute risk differences were statistically significant for all trajectories, except for the risk ratio of the lean increasing trajectory group among men. Of the 981 incident cases of type 2 diabetes, 47.4% among women and 42.9% among men were attributable to exposure to any life-course trajectory different from stable normal weight. Most of the risk was attributable to trajectories including overweight or obesity at any point of life (36.8% of the cases among women and 36.7% among men). The overweight from early adulthood trajectory had the highest impact (PAF: 23.2% for woman and 28.5% for men). We described five distinctive life-course trajectories of weight that were associated to increased risk of type 2 diabetes over 19 years of follow-up. The variability of the effect of exposure to overweight and obesity on the risk of developing type 2 diabetes was largely explained by exposure to the different life-course trajectories of weight.
Metastable states in plateaus and multi-wave epidemic dynamics of Covid-19 spreading in Italy
Authors: Campi Gaetano , Mazziotti Maria Vittoria , Valletta Antonio , Ravagnan Giampietro , Marcelli Augusto , Perali Andrea , Bianconi Antonio 
Published: June 2021

AbstractThe control of Covid 19 epidemics by public health policy in Italy during the first and the second epidemic waves has been driven by using reproductive number Rt(t) to identify the supercritical (percolative), the subcritical (arrested), separated by the critical regime. Here we show that to quantify the Covid-19 spreading rate with containment measures there is a need of a 3D expanded parameter space phase diagram built by the combination of Rt(t) and doubling time Td(t). In this space we identify the Covid-19 dynamics in Italy and its administrative Regions. The supercritical regime is mathematically characterized by (i) the power law of Td vs. [Rt(t) − 1] and (ii) the exponential behaviour of Td vs. time, either in the first and in the second wave. The novel 3D phase diagram shows clearly metastable states appearing before and after the second wave critical regime. for loosening quarantine and tracing of actives cases. The metastable states are precursors of the abrupt onset of a next nascent wave supercritical regime. This dynamic description allows epidemics predictions needed by policymakers interested to point to the target "zero infections" with the elimination of SARS-CoV-2, using the Finding mobile Tracing policy joint with vaccination-campaign, in order to avoid the emergence of recurrent new variants of SARS-CoV-2 virus, accompined by recurrent long lockdowns, with large economical losses, and large number of fatalities.
Drug–drug interactions between treatment specific pharmacotherapy and concomitant medication in patients with COVID-19 in the first wave in Spain
Authors: Cantudo-Cuenca M. D. , Gutiérrez-Pizarraya Antonio , Pinilla-Fernández Ana , Contreras-Macías Enrique , Fernández‑Fuertes M. , Lao‑Domínguez F. A , Rincón Pilar , Pineda Juan Antonio , Macías Juan , Morillo-Verdugo Ramón 
Published: June 2021

AbstractPrimary aim was to assess prevalence and severity of potential and real drug–drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) (‘potential interactions’) and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02–1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12–1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.
Pre-transplant donor-reactive IL-21 producing T cells as a tool to identify an increased risk for acute rejection
Authors: Mendoza Rojas Aleixandra , van Gelder Teun , de Kuiper Ronella , Reijerkerk Derek , Clahsen-van Groningen Marian C. , Hesselink Dennis A. , Baan Carla C. , van Besouw Nicole M. 
Published: June 2021

AbstractPre-transplant screening focuses on the detection of anti-HLA alloantibodies. Previous studies have shown that IFN-γ and IL-21 producing T cells are associated with the development of acute rejection (AR). The aim of this study, was to assess whether pre-transplant donor-reactive T cells and/or B cells are associated with increased rejection risk. Samples from 114 kidney transplant recipients (transplanted between 2010 and 2013) were obtained pre-transplantation. The number of donor-reactive IFN-γ and IL-21 producing cells was analyzed by ELISPOT assay. The presence of donor specific antibodies (DSA) was also determined before transplantation. Numbers of donor-reactive IFN-γ producing cells were similar in patients with or without AR whereas those of IL-21 producing cells were higher in patients with AR (p = 0.03). Significantly more patients with AR [6/30(20%)] had detectable DSA compared to patients without AR [5/84(5.9%), p = 0.03]. Multivariate logistic regression showed that donor age (OR 1.06), pre-transplant DSA (OR 5.61) and positive IL-21 ELISPOT assay (OR 2.77) were independent predictors of an increased risk for the development of AR. Aside from an advanced donor-age and pre-transplant DSA, also pre-transplant donor-reactive IL-21 producing cells are associated with the development of AR after transplantation.
A multi-method approach to modeling COVID-19 disease dynamics in the United States
Authors: Mokhtari Amir , Mineo Cameron , Kriseman Jeffrey , Kremer Pedro , Neal Lauren , Larson John 
Published: June 2021

AbstractIn this paper, we proposed a multi-method modeling approach to community-level spreading of COVID-19 disease. Our methodology was composed of interconnected age-stratified system dynamics models in an agent-based modeling framework that allowed for a granular examination of the scale and severity of disease spread, including metrics such as infection cases, deaths, hospitalizations, and ICU usage. Model parameters were calibrated using an optimization technique with an objective function to minimize error associated with the cumulative cases of COVID-19 during a training period between March 15 and October 31, 2020. We outlined several case studies to demonstrate the model’s state- and local-level projection capabilities. We further demonstrated how model outcomes could be used to evaluate perceived levels of COVID-19 risk across different localities using a multi-criteria decision analysis framework. The model’s two, three, and four week out-of-sample projection errors varied on a state-by-state basis, and generally increased as the out-of-sample projection period was extended. Additionally, the prediction error in the state-level projections was generally due to an underestimation of cases and an overestimation of deaths. The proposed modeling approach can be used as a virtual laboratory to investigate a wide range of what-if scenarios and easily adapted to future high-consequence public health threats.
Changes in electromyographic activity, mechanical power, and relaxation rates following inspiratory ribcage muscle fatigue
Authors: Sarmento Antonio , Fregonezi Guilherme , Lira Maria , Marques Layana , Pennati Francesca , Resqueti Vanessa , Aliverti Andrea 
Published: June 2021

AbstractMuscle fatigue is a complex phenomenon enclosing various mechanisms. Despite technological advances, these mechanisms are still not fully understood in vivo. Here, simultaneous measurements of pressure, volume, and ribcage inspiratory muscle activity were performed non-invasively during fatigue (inspiratory threshold valve set at 70% of maximal inspiratory pressure) and recovery to verify if inspiratory ribcage muscle fatigue (1) leads to slowing of contraction and relaxation properties of ribcage muscles and (2) alters median frequency and high-to-low frequency ratio (H/L). During the fatigue protocol, sternocleidomastoid showed the fastest decrease in median frequency and slowest decrease in H/L. Fatigue was also characterized by a reduction in the relative power of the high-frequency and increase of the low-frequency. During recovery, changes in mechanical power were due to changes in shortening velocity with long-lasting reduction in pressure generation, and slowing of relaxation [i.e., tau (τ), half-relaxation time (½RT), and maximum relaxation rate (MRR)] was observed with no significant changes in contractile properties. Recovery of median frequency was faster than H/L, and relaxation rates correlated with shortening velocity and mechanical power of inspiratory ribcage muscles; however, with different time courses. Time constant of the inspiratory ribcage muscles during fatigue and recovery is not uniform (i.e., different inspiratory muscles may have different underlying mechanisms of fatigue), and MRR, ½RT, and τ are not only useful predictors of inspiratory ribcage muscle recovery but may also share common underlying mechanisms with shortening velocity.
The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysis
Authors: Kunkel Amber , Jeon Seonghye , Joseph Haim C. , Dilius Pierre , Crowdis Kelly , Meltzer Martin I. , Wallace Ryan 
Published: June 2021

AbstractDog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the last nation-wide dog vaccination campaign occurred in 2018. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios. We modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005 to 2025, with varying assumptions about when dog vaccinations resume. We compared model outputs to surveillance data on human rabies deaths from 2005 to 2020 and animal rabies cases from 2018 to 2020. Model predictions and surveillance data both suggest a 5- to 8-fold increase in animal rabies cases occurred in Haiti’s capital city between Fall 2019 and Fall 2020. Restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6541 human rabies exposures over a five-year period. It may also decrease program costs due to reduced need for human post-exposure prophylaxis. These results show that interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.
A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome
Authors: Kawatani Keiji , Nambara Toshihiko , Nawa Nobutoshi , Yoshimatsu Hidetaka , Kusakabe Haruna , Hirata Katsuya , Tanave Akira , Sumiyama Kenta , Banno Kimihiko , Taniguchi Hidetoshi , Arahori Hitomi , Ozono Keiichi , Kitabatake Yasuji 
Published: June 2021

AbstractAstrocytes exert adverse effects on the brains of individuals with Down syndrome (DS). Although a neurogenic-to-gliogenic shift in the fate-specification step has been reported, the mechanisms and key regulators underlying the accelerated proliferation of astrocyte precursor cells (APCs) in DS remain elusive. Here, we established a human isogenic cell line panel based on DS-specific induced pluripotent stem cells, the XIST-mediated transcriptional silencing system in trisomic chromosome 21, and genome/chromosome-editing technologies to eliminate phenotypic fluctuations caused by genetic variation. The transcriptional responses of genes observed upon XIST induction and/or downregulation are not uniform, and only a small subset of genes show a characteristic expression pattern, which is consistent with the proliferative phenotypes of DS APCs. Comparative analysis and experimental verification using gene modification reveal dose-dependent proliferation-promoting activity of DYRK1A and PIGP on DS APCs. Our collection of human isogenic cell lines provides a comprehensive set of cellular models for further DS investigations.