bluuebunny/crossref_metadata_2025_split huggingface dataset:
Motor Cortex Excitability in Chronic Low Back Pain
Authors: Corti E.J , Marinovic W , Nguyen A.T , Gasson N , Loftus A.M 
Published: March 2022

AbstractIntroductionChronic pain is associated with dysfunctional cortical excitability. Research has identified altered intracortical motor cortex excitability in Chronic Lower Back Pain (CLBP). However, research identifying the specific intracortical changes underlying CLBP has been met with inconsistent findings. In the present case-control study, we examined intracortical excitability of the primary motor cortex using transcranial magnetic stimulation (TMS) in individuals with CLBP.MethodsTwenty participants with CLBP (Mage = 54.45 years, SDage = 15.89 years) and 18 age- and gender-matched, pain-free controls (M = 53.83, SD = 16.72) were included in this study. TMS was applied to the hand motor area of the right hemisphere and motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle of the contralateral hand. Resting motor threshold (rMT) and MEP amplitude were measured using single-pulse stimulation. Short intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed using paired-pulse stimulation.ResultsIndividuals with CLBP had significantly higher rMT (decreased corticospinal excitability) and reduced ICF compared to controls. No significant differences were found in MEP amplitude and SICI.ConclusionThese findings add to the growing body of evidence that CLBP is associated with deficits in intracortical modulation involving glutamatergic mechanisms.SignificanceThis article reports chronic lower back pain is associated with changes in intracortical excitability, specifically reduced intracortical facilitation. Furthermore, the imbalance between facilitation and inhibition may be related to pain intensity. These findings may help clinicians in the treatment of chronic pain with an increased focus on using neuromodulation techniques, targeting maladaptive intracortical facilitation, as a potential therapeutic tool in chronic pain.
Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure
Authors: Gavriilidis Efstratios , Antoniadou Christina , Chrysanthopoulou Akrivi , Ntinopoulou Maria , Smyrlis Andreas , Fotiadou Iliana , Zioga Nikoleta , Kogias Dionysios , Natsi Anastasia-Maria , Pelekoudas Christos , Satiridou Evangelia , Bakola Stefania-Aspasia , Papagoras Charalampos , Mitroulis Ioannis , Peichamperis Paschalis , Mikroulis Dimitrios , Papadopoulos Vasileios , Skendros Panagiotis , Ritis Konstantinos 
Published: March 2022

AbstractCOVID-19-related severe respiratory failure (SRF) leads to mechanical ventilation increasing the in-hospital mortality substantially. Abundancy of lung fibroblasts (LFs) in injured lung tissue has been associated with the progression of respiratory failure in COVID-19. Aiming to reduce mortality in patients with SRF (PaO2/FiO2<100 mmHg) and considering the multi-mechanistic nature of severe COVID-19 pathogenesis, we applied a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone and heparin) comprised inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, such as anti-IL-6 receptor tocilizumab and selective JAK1/2 inhibitor baricitinib. COMBI (n=22) was compared with SOC (n= 26), and with two previously and consecutively used therapeutic approaches, including either IL-1 receptor antagonist anakinra (ANA, n=19), or tocilizumab (TOCI, n=11), on top of SOC. In parallel, evaluation of immunothrombosis was assessed in vitro in human LFs, treated with the applied therapeutic agents upon stimulation with COVID-19 plasma. COMBI was associated with lower in-hospital mortality (p=0.014) and intubation rate (p=0.013), shorter duration of hospitalization (p=0.019), and prolonged overall survival after a median follow-up of 110±4 days (p=0.003). In vitro, COVID-19 plasma markedly induced tissue factor/thrombin pathway in LFs, while this effect was inhibited by the immunomodulatory agents of COMBI providing a mechanistic explanation for the clinical observations. These results suggest the design of randomized trials using combined immunomodulatory therapies in COVID-19-associated SRF targeting multiple interconnected pathways of immunothrombosis.
METHYLATION BIOMARKERS ASSOCIATED WITH DRUG-RESISTANT EPILEPSY
Authors: Sánchez Jiménez Patricia , Elizalde-Horcada Marcos , Sanz-García Ancor , Granero-Cremades Inmaculada , De Toledo María , Pulido Paloma , Navas Marta , Gago-Veiga Ana Beatriz , Alonso-Guirado Lola , Alonso-Cerezo María Concepción , Nava-Cedeño Desirée , Abad-Santos Francisco , Torres-Díaz Cristina Virginia , Ovejero-Benito María Carmen 
Published: March 2022

ABSTRACTEpilepsy is a disabling neurological disease that affects 2% of the population. Drug-resistant epilepsy (DRE) affects 25-30% of epilepsy patients. Understanding its underlying mechanisms is key to adequately manage this condition. To analyze the main epigenetic marks of DRE an epigenome-wide association study was carried out including samples from different regions of DRE patients’ brain and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array including cortex, hippocampus, amygdala, and peripheral blood from DRE subjected to neurosurgical resection of the epileptogenic zone was used. Overall, 32, 59, 3210, and 6 differentially methylated probes (DMPs) associated with DRE were found in the hippocampus, amygdala, cortex, and peripheral blood, respectively. These DMPs harbored 19, 28, 1574, and 7 genes, respectively, which play different roles in processes such as neurotrophic or calcium signaling. Three of the top DMPs observed in cortex were validated with methylation specific qPCR. Moreover, 163 DMPs associated with neurosurgery response at 6 months were found in the hippocampus. Genes located on these DMPs were involved in diverse processes such as synaptic signaling and central nervous system development. Besides 3 DMPs in blood samples were associated with response to neurosurgery at 12 months. In conclusion, the present study reports genome-wide DNA methylation changes across different regions of the DRE brain. These changes could be useful for further studies to disentangle the bases of DRE to search for therapeutic alternatives for this disease. Furthermore, they could also help identify patients likely to respond to neurosurgery.
Pan-cancer Analyses reveal functional similarities of three lncRNAs across multiple tumors
Authors: Khazaal Abir , Zandavi Seid Miad , Smolnikov Andrei , Fatima Shadma , Vafaee Fatemeh 
Published: March 2022

AbstractLong non-coding RNAs (lncRNAs) are emerging as key regulators in many biological processes. The dysregulation of lncRNA expression has been associated with many diseases, including cancer. Mounting evidence suggests that lncRNAs are involved in cancer initiation, progression, and metastasis. Thus, understanding the functional implications of lncRNAs in tumorigenesis can aid in developing novel biomarkers and therapeutic targets. Rich cancer datasets, documenting genomic and transcriptomic alterations together with advancement in bioinformatics tools, have presented an opportunity to perform pan-cancer analyses across different cancer types. This study is aimed at conducting a pan-cancer analysis of lncRNAs by performing differential expression and functional analyses between tumor and normal adjacent samples across eight cancer types. Among dysregulated lncRNAs, seven were shared across all cancer types. We focused on three lncRNAs, found to be consistently dysregulated among tumors. It has been observed that these three lncRNAs of interest are interacting with a wide range of genes across different tissues, yet enriching substantially similar biological processes, found to be implicated in cancer progression and proliferation.
A modality independent proto-organization of human multisensory areas
Authors: Setti Francesca , Handjaras Giacomo , Bottari Davide , Leo Andrea , Diano Matteo , Bruno Valentina , Tinti Carla , Cecchetti Luca , Garbarini Francesca , Pietrini Pietro , Ricciardi Emiliano 
Published: March 2022

AbstractThe processing of multisensory information is based upon the capacity of brain regions, such as the superior temporal cortex, to combine information across modalities. However, it is still unclear whether the representation of coherent auditory and visual events does require any prior audiovisual experience to develop and function. In three fMRI experiments, intersubject correlation analysis measured brain synchronization during the presentation of an audiovisual, audio-only or video-only versions of the same narrative in distinct groups of sensory-deprived (congenitally blind and deaf) and typically-developed individuals. The superior temporal cortex synchronized across auditory and visual conditions, even in sensory-deprived individuals who lack any audiovisual experience. This synchronization was primarily mediated by low-level perceptual features and relied on a similar modality-independent topographical organization of temporal dynamics. The human superior temporal cortex is naturally endowed with a functional scaffolding to yield a common representation across multisensory events.
MODEL PREDICTIVE CONTROL OF CANCER CELLULAR DYNAMICS: A NEW STRATEGY FOR THERAPY DESIGN
Authors: Smart Benjamin , de Cesare Irene , Renson Ludovic , Marucci Lucia 
Published: March 2022

AbstractRecent advancements in Cybergenetics have led to the development of new computational and experimental platforms that enable to robustly steer cellular dynamics by applying external feedback control. Such technologies have never been applied to regulate intracellular dynamics of cancer cells. Here, we show in silico that adaptive model predictive control (MPC) can effectively be used to steer signalling dynamics in Non-Small Cell Lung Cancer (NSCLC) cells to resemble those of wild-type cells, and to support the design of combination therapies. Our optimisation-based control algorithm enables tailoring the cost function to force the controller to alternate different drugs and/or reduce drug exposure, minimising both drug-induced toxicity and resistance to treatment. Our results pave the way for new cybergenetics experiments in cancer cells for drug combination therapy design.
Genetic engineering of Acidithiobacillus ferridurans with CRISPR-Cas9/dCas9 systems
Authors: Chen Jinjin , Liu Yilan , Mahadevan Radhakrishnan 
Published: March 2022

AbstractGenus Acidithiobacillus includes a group of Gram-negative Fe/S-oxidizing acidophilic chemolithotrophic bacteria that are extensively studied and used for biomining processes. Synthetic biology approaches are key means to study and improve their biomining performance. However, efficient genetic manipulations in Acidithiobacillus are still major bottlenecks. In this study, we report a simple and efficient pAFi system (CRISPR-dCas9) and a scarless pAF system (CRISPR-Cas9) for genetic manipulations in A. ferridurans JAGS. The pAFi system harboring both dCas9 and sgRNA was constructed based on pBBR1MCS-2 to knockdown HdrA and TusA genes, separately, of which the transcription levels were significantly downregulated by 48% and 93%, separately. The pAF system carrying pCas9-sgRNA-homology arms was constructed based on pJRD215 to delete HdrB3 gene and overexpress Rus gene. Our results demonstrated that the pAF system is a fast and efficient genome editing method with an average rate of 15-20% per transconjugant in one recombination event, compared to 10-3 and then 10-2 in two recombination events by traditional markerless engineering strategy. Moreover, with these two systems, we successfully regulated iron and sulfur metabolisms in A. ferridurans JAGS: the deletion of HdrB3 reduced 48% of sulfate production, and substitution overexpression of Rus promoter showed 8.82-fold of mRNA level and enhanced iron oxidation rate. With these high-efficient genetic tools for A. ferridurans, we will be able to study gene functions and create useful recombinants for biomining applications. Moreover, these systems could be extended to other Acidithiobacillus strains and promote the development of synthetic biology-assisted biomining.HighlightsTwo shuttle vectors were constructed for Acidithiobacillus ferriduransAll-in-one pAFi (CRISPR-dCas9) and pAF (CRISPR-Cas9) systems were built up for gene knockdown and genome editing, separatelyThe transcription levels of HdrA and TusA were reduced 48% and 93% using pAFi system and thus suppressed sulfur oxidationHdrB3 deletion and Rus overexpression were achieved using pAF system and showed significant effects on sulfur and iron oxidation respectivelyOur pAF system facilitated genome editing in Acidithiobacillus ferridurans with high efficiency (15-20%) in less than 4 weeks
Detecting patterns of accessory genome coevolution in bacterial species using data from thousands of bacterial genomes
Authors: Mehta Rohan S , Petit Robert A , Read Timothy D , Weissman Daniel B 
Published: March 2022

AbstractBacterial genomes exhibit widespread horizontal gene transfer, resulting in highly variable genome content that complicates the inference of genetic interactions. In this study, we develop a method for detecting coevolving genes from large datasets of bacterial genomes that we call a “coevolution score”. The method is based on pairwise comparisons of closely related individuals, analogous to a pedigree study in eukaryotic populations. This approach avoids the need for an accurate phylogenetic tree and allows very large datasets to be analyzed for signatures of recent coevolution. We apply our method to all of the more than 3 million pairs of genes from the entire annotated Staphylococcus aureus accessory genome of 2,756 annotated genes using a database of over 40,000 whole genomes. We find many pairs of genes that that appear to be gained or lost in a coordinated manner, as well as pairs where the gain of one gene is associated with the loss of the other. These pairs form networks of dozens of rapidly coevolving genes, primarily consisting of genes involved in metal resistance, virulence, mechanisms of horizontal gene transfer, and antibiotic resistance, particularly the SCCmec complex. Our results reflect the fact that the evolution of many bacterial pathogens since the middle of the twentieth century has largely been driven by antibiotic resistance gene gain, and in the case of S. aureus the SCCmec complex is the most prominent of these elements driving the evolution of resistance. The frequent coincidence of these gene gain or loss events suggests that S. aureus switch between antibiotic-resistant niches and antibiotic-susceptible ones. While we focus on gene gain and loss, our method can also detect genes which tend to acquire substitutions in tandem or, in datasets that include phenotypic information, genotype-phenotype or phenotype-phenotype coevolution.
Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation
Authors: Currant Hannah , Fitzgerald Tomas W , Patel Praveen J , Khawaja Anthony P ,   UK Biobank Eye and Vision Consortium, Webster Andrew R , Mahroo Omar A , Birney Ewan 
Published: March 2022

AbstractPhotoreceptor cells (PRCs) are the light-detecting cells of the retina. Such cells can be non-invasively imaged using optical coherence tomography (OCT) which is used in clinical settings to diagnose and monitor ocular diseases. Here we present the largest genome-wide association study of PRC morphology to date utilising quantitative phenotypes extracted from OCT images within the UK Biobank. We discovered 111 loci associated with the thickness of one or more of the PRC layers, many of which had prior associations to ocular phenotypes and pathologies. We further identified 10 genes associated with PRC thickness through gene burden testing using exome data. In both cases there was a significant enrichment for genes involved in rare eye pathologies, in particular retinitis pigmentosa. There was evidence for an interaction effect between common genetic variants, VSX2 involved in eye development and PRPH2 known to be involved in retinal dystrophies. We further identified a number of genetic variants with a differential effect across the macular spatial field. Our results suggest a continuum between normal and rare variation which impacts retinal structure, sometimes leading to disease.
Identifying the genes impacted by cell proliferation in proteomics and transcriptomics studies
Authors: Locard-Paulet Marie , Palasca Oana , Jensen Lars Juhl 
Published: March 2022

ABSTRACTToday, hypothesis-free high-throughput profiling allows relative quantification of thousands of proteins or transcripts across samples and thereby identification of differentially expressed genes. It is used in many biological contexts to characterize differences between cell lines and tissues, identify drug mode of action or drivers of drug resistance, among others. Genes can also be differentially regulated because of confounding factors that were not accounted for in the experimental plan, such as change in cell proliferation. Here, we identified genes for which expression consistently correlates with cell proliferation rates in proteomics and transcriptomics high-throughput data sets to determine the overall impact of cell growth rate on these data. We combined the analysis of 449 cell lines and 1,040 cell lines in five proteomics and three transcriptomics data sets to generate a refined list of 223 confounding genes that correlate with cell proliferation rates. These include many actors in DNA replication and mitosis, and genes periodically expressed during the cell cycle. It constitutes a valuable resource when analyzing high-throughput datasets showing changes in proliferation across conditions. We show how to use this resource to analyze in vitro drug screens and tumor samples. By disregarding the proliferation confounders, one can instead focus on the experiment-specific regulation events otherwise buried in the statistical analysis.
Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation
Authors: Singh Alok K. , Wang Rulin , Lombardo Kara A. , Praharaj Monali , Bullen C. Korin , Um Peter , Davis Stephanie , Komm Oliver , Illei Peter B. , Ordonez Alvaro A. , Bahr Melissa , Huang Joy , Gupta Anuj , Psoter Kevin J. , Jain Sanjay K. , Bivalacqua Trinity J. , Yegnasubramanian Srinivasan , Bishai William R. 
Published: March 2022

AbstractCOVID-19 continues to exact a toll on human health despite the availability of several vaccines. Bacillus Calmette Guérin (BCG) has been shown to confer heterologous immune protection against viral infections including COVID-19 and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model together with immune profiling and single cell RNA sequencing (scRNAseq). We observed that BCG reduced both lung SCV2 viral load and bronchopneumonia. This was accompanied by an increase in lung alveolar macrophages, a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. Single cell transcriptome profiling showed that BCG uniquely recruits immunoglobulin-producing plasma cells to the lung suggesting accelerated antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, and differentially expressed gene (DEG) analysis showed a transcriptional shift away from exhaustion markers and towards antigen presentation and repair. Similarly, BCG enhanced lung recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, with both cell-types also showing reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.
miR319-targeted TCP4/LANCEOLATE directly regulates OVATE and auxin responses to modulate tomato gynoecium patterning and fruit morphology
Authors: Carvalho Airton , Vicente Mateus H. , Ferigolo Leticia F. , Silva Eder M. , Levy Matan , Peres Lazaro E.P. , Sablowski Robert , Schommer Carla , Ori Naomi , Nogueira Fabio T.S. 
Published: March 2022

SUMMARYDiversity in fruit morphology is one of the hallmarks of varietal differences among modern cultivars of fruit-bearing crops. As evolutionarily related organs, fruits and leaves share developmental processes, but there are surprisingly few connections between regulatory pathways for fruit and leaf development. Here, we show the regulation of the leaf development-associated TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) TCP4/LANCEOLATE (TCP4/LA) transcription factor by the microRNA319 (miR319) is crucial for gynoecium patterning and establishment of fruit morphology. Loss of miR319 regulation leads to a premature, ectopic TCP4/LA expression during gynoecium patterning, which results in elongated fruits, resembling ovate mutants. TCP4/LA modulates tomato fruit development and morphology partially by directly repressing OVATE expression as early as 5-8 days post-inflorescence (dpi) flower buds. Furthermore, miR319-targeted CINCINNATA-like TCP4/LANCEOLATE controls auxin responses in developing flower buds by directly binding to the SlYUCCA4 promoter. Modulation of auxin biosynthesis by TCP4/LA is shared with other CINCINNATA-like TCPs during Arabidopsis gynoecium patterning. Our study defines a novel miRNA-based molecular link between OVATE, a fundamental gene associated with tomato domestication, and auxin responses in the control of fruit development and morphology. Given the striking variation in fruit shape among members of the Solanaceae family, fine-tuning regulation of gene expression by miRNA coupled with modulation of hormone dynamics may be a common driver in the evolution of fruit-shape diversity.
Using relative brain size as predictor variable: serious pitfalls and solutions
Authors: Smeele Simeon Q. 
Published: March 2022

AbstractThere is a long-standing interest in the effect of relative brain size on other life history variables in a comparative context. Historically, residuals have been used to calculate these effects, but more recently it has been recognised that regression on residuals is not good practice. Instead, absolute brain size and body size are included in a multiple regression, with the idea that this controls for allometry.I use a simple simulation to illustrate how a case in which brain size is a response variable differs from a case in which relative brain size is a predictor variable. I use the simulated data to test which modelling approach can estimate the underlying causal effects for each case.The results show that a multiple regression model with both body size and another variable as predictor variable and brain size as response variable work well. However, if relative brain size is a predictor variable, a multiple regression fails to correctly estimate the effect of body size.I propose the use of structural equation models to simultaneously estimate relative brain size and its effect on the third variable and discuss other potential methods.