Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders

Evidence from multiple laboratories has accumulated to show that mosaic neuronal aneuploidy and consequent apoptosis characterizes and may underlie neuronal loss in many neurodegenerative diseases, particularly Alzheimer’s disease and frontotemporal dementia. Furthermore, several neurodevelopmental disorders, including Seckel syndrome, ataxia telangiectasia, Nijmegen breakage syndrome, Niemann–Pick type C, and Down syndrome, have been shown to also exhibit mosaic aneuploidy in neurons in the brain and in other cells throughout the body. Together, these results indicate that both neurodegenerative and neurodevelopmental disorders with apparently different pathogenic causes share a cell cycle defect that leads to mosaic aneuploidy in many cell types. When such mosaic aneuploidy arises in neurons in the brain, it promotes apoptosis and may at least partly underlie the cognitive deficits that characterize the neurological symptoms of these disorders. These findings have implications for both diagnosis and treatment/prevention.
Evaluating Cortical Alterations in Patients With Chronic Back Pain Using Neuroimaging Techniques: Recent Advances and Perspectives

Chronic back pain (CBP) is a leading cause of disability and results in considerable socio-economic burdens worldwide. Although CBP patients are commonly diagnosed and treated with a focus on the “end organ dysfunction” (i.e., peripheral nerve injuries or diseases), the evaluation of CBP remains flawed and problematic with great challenges. Given that the peripheral nerve injuries or diseases are insufficient to define the etiology of CBP in some cases, the evaluation of alterations in the central nervous system becomes particularly necessary and important. With the development of advanced neuroimaging techniques, extensive studies have been carried out to identify the cortical abnormalities in CBP patients. Here, we provide a comprehensive overview on a series of novel findings from these neuroimaging studies to improve our understanding of the cortical abnormalities originated in the disease. First, CBP patients normally exhibit central sensitization to external painful stimuli, which is indexed by increased pain sensitivity and brain activations in pain-related brain regions. Second, long-term suffering from chronic pain leads to emotional disorders, cognitive impairments, and the abnormalities of the relevant brain networks among CBP patients. Third, CBP is associated with massive cortical reorganization, including structural, functional, and metabolic brain changes. Overall, a deep insight into the neural mechanisms underlying the development and outcome of CBP through more sophisticated neuroimaging investigations could not only improve our current understanding of the etiology of CBP but also facilitate the diagnosis and treatment of CBP based on precision medicine.
Association of rs4680 COMT, rs6280 DRD3, and rs7322347 5HT2A With Clinical Features of Youth-Onset Schizophrenia

We investigated the associations of rs4680 COMT, rs6280 DRD3, and rs7322347 5HT2A with youth-onset schizophrenia in the Russian population in a case–control study, and the role of the genotype in the severity of clinical features. The association between rs7322347 and schizophrenia (p = 0.0001) is described for the first time. Furthermore, we found a link with rs6280 and rs4680 in females (p = 0.001 and p = 0.02 respectively) and with rs7322347 in males (p = 0.002). Clinical symptoms were assessed on three scales: the Clinician-Rated Dimensions of Psychosis Symptom Severity scale, Positive and Negative Syndrome Scale, and Frontal Assessment Battery. Gender differences in clinical features are of particular interest. In our study we found gender differences in the severity of clinical features—higher scores for delusions (Positive and Negative Syndrome Scale and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) in males and higher scores for depression, delusions, somatic concern, motor retardation, poor attention were found in females.
Anthropogenic Disturbances Eroding the Genetic Diversity of a Threatened Palm Tree: A Multiscale Approach

Habitat loss and the illegal exploitation of natural resources are among the main drivers of species extinction around the world. These disturbances act at different scales, once changes in the landscape composition and configuration operate at large scales and exploitation of natural resources at local scales. Evidence suggests that both scales are capable of triggering genetic erosion in the remaining populations. However, most of the studies so far did not evaluate simultaneously the effects of these disturbances on genetic diversity and structure of plants. In this study, we used a multiple scale approach to empirically evaluate the impacts caused by local and landscape scale disturbances in the genetic diversity and structure of an endangered palm tree, Euterpe edulis. We sampled and genotyped with microsatellite markers 544 juveniles of E. edulis in 17 fragments of Atlantic Forest in Brazil. In addition, we estimated the local logging rate and the forest cover and isolation at landscape scale. We found that the palm populations have not undergone any recent bottleneck events and that only logging intensification had affected the fixation index and the number of private alleles. Additionally, we did not detect any evidence of spatial genetic structure or genetic divergence associated with environmental disturbance variables at different scales. However, we identified distinct genetic clusters, which may indicate a reduction of gene flow between fragments that were previously a continuous habitat. Our results show that local disturbances, which act directly on population size reduction, such as logging, modified the genetic diversity more rapidly, whereas genetic structure is probably more influenced by large-scale modifications. In this way, to maximize the conservation efforts of economically exploited species, we recommend to increase the inspection to reduce the illegal exploitation, and reforestation of degraded areas, in order to increase the gene flow in Atlantic Forest fragments.
Research on the Physio-Biochemical Mechanism of Non-Thermal Plasma-Regulated Seed Germination and Early Seedling Development in Arabidopsis

Non-thermal plasma holds great potentials as an efficient, economical, and eco-friendly seed pretreatment method for improving the seed germination and seedling growth, but the mechanisms are still unclear. Therefore, a plant model organism Arabidopsis thaliana was used to investigate the physio-biochemical responses of seeds to non-thermal plasma at different treatment times by measuring the plant growth parameters, redox-related parameters, calcium (Ca2+) level and physicochemical modification of seed surface. The results showed that short-time plasma treatment (0.5, 1, and 3 min) promoted seed germination and seedling growth, whereas long-time plasma treatment (5 and 10 min) exhibited inhibitory effects. The level of superoxide anion (O2•−) and nitric oxide (NO) and the intensity of infrared absorption of the hydroxyl group were significantly higher in short-time plasma treated Arabidopsis seeds, and the level of hydrogen peroxide (H2O2) was remarkably increased in long-time plasma treated seeds, indicating that O2•−, ·OH, and NO induced by plasma may contribute to breaking seed dormancy and advancing seed germination in Arabidopsis, while plasma-induced H2O2 may inhibit the seed germination. The intensity of hydroxyl group and the contents of H2O2, malondialdehyde, and Ca2+ in Arabidopsis seedlings were obviously increased with the plasma treatment time. Catalase, superoxide dismutase, and peroxidase activities as well as proline level in short-time treated seedlings were apparently higher than in control. The etching effects of plasma on seed surface were dose-dependent, spanning from slight shrinkages to detached epidermis, which also significantly increased the oxidation degree of seed surface. Therefore, the improved activities of antioxidant systems, moderate ·OH, H2O2, and Ca2+ accumulation and seed surface modification induced by plasma all contribute to the enhanced seedling growth of Arabidopsis after short-time plasma treatment.
Understanding Ciprofloxacin Failure in Pseudomonas aeruginosa Biofilm: Persister Cells Survive Matrix Disruption

Biofilms are commonly recalcitrant to antibiotics, through incompletely elucidated mechanisms such as tolerance and persistence. We aimed at investigating how a Pseudomonas aeruginosa biofilm escapes ciprofloxacin treatment. P. aeruginosa PA14 in vitro mature biofilms were challenged with supra-MIC ciprofloxacin concentrations. Cell viability was quantified by fluorescein diacetate assay. Population dynamics were determined by counts of surviving culturable cells. Biofilms were analyzed using confocal laser scanning microscopy (CLSM), and the expression of genes involved in stringent response, toxin-antitoxin HigB/HigA, and type 3 secretion system (T3SS) was quantified by RT-qPCR in untreated and treated biofilms. Ciprofloxacin exposure resulted in an initial reduction of bacterial counts following a biphasic time-kill curve. After 24 h of treatment, the overall cell activity and the density of culturable cells significantly decreased as compared to untreated biofilm. No resistant mutant was isolated among the <1% surviving cells. Phenotypic adaptation toward persistence appeared to start after only 1 h of antibiotic exposure, by an overexpression of the genes involved in stringent response and in the toxin-antitoxin system, whereas the expression of genes encoding for the T3SS remained unchanged. After 4 h of ciprofloxacin exposure, stringent response genes returned to their basal level of expression. After a prolonged ciprofloxacin exposure, a deep alteration in the matrix structure that became thinner and lost mushroom-like aggregates was observed, in relation with reduced biovolumes of exopolysaccharides and extracellular DNA. These results support that ciprofloxacin might first induce the bacterial killing of most bacterial cells, but simultaneously activate stringent response mechanisms contributing to the switch of a subpopulation toward a persister phenotype. Once the persister phenotype is expressed, and despite an unexpected alteration of the biofilm matrix, ciprofloxacin fails to eradicate biofilm.
Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr. & Gray)

Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality. Therefore, the identification of genes that play a role in xylogenesis is extremely important for understanding the mechanisms shaping the plant phenotype. Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development. The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems. Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems. While hemicellulose degradation was typical for stems, possibly due to the intensive level of cell wall lignification. Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support. Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
Epigenetic Regulation in the Pathogenesis of Sjögren Syndrome and Rheumatoid Arthritis

Autoimmune rheumatic diseases, such as Sjögren syndrome (SS) and rheumatoid arthritis (RA), are characterized by chronic inflammation and autoimmunity, which cause joint tissue damage and destruction by triggering reduced mobility and debilitation in patients with these diseases. Initiation and maintenance of chronic inflammatory stages account for several mechanisms that involve immune cells as key players and the interaction of the immune cells with other tissues. Indeed, the overlapping of certain clinical and serologic manifestations between SS and RA may indicate that numerous immunologic-related mechanisms are involved in the physiopathology of both these diseases. It is widely accepted that epigenetic pathways play an essential role in the development and function of the immune system. Although many published studies have attempted to elucidate the relation between epigenetic modifications (e.g. DNA methylation, histone post-translational modifications, miRNAs) and autoimmune disorders, the contribution of epigenetic regulation to the pathogenesis of SS and RA is at present poorly understood. This review attempts to shed light from a critical point of view on the identification of the most relevant epigenetic mechanisms related to RA and SS by explaining intricate regulatory processes and phenotypic features of both autoimmune diseases. Moreover, we point out some epigenetic markers which can be used to monitor the inflammation status and the dysregulated immunity in SS and RA. Finally, we discuss the inconvenience of using epigenetic data obtained from bulk immune cell populations instead specific immune cell subpopulations.
Cryptotanshinone Attenuates Airway Remodeling by Inhibiting Crosstalk Between Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Transforming Growth Factor Beta 1 Signaling Pathways in Asthma

The study is to investigate the effect of cryptotanshinone (CTS) on airway remodeling and the possible mechanism. Male BALB/c mice were pretreated with CTS or dexamethasone 30 min before nebulized inhalation of ovalbumin (OVA). CTS significantly inhibited OVA-induced increases of eosinophils and neutrophils infiltration of bronchoalveolar lavage fluids (BALFs), reduced airway resistance in asthmatic mice, decreased the accumulation of inflammatory cells, the hyperplasia of goblet cells and the deposition of collagen in asthmatic mice lung tissue, as well as markedly attenuated the leakage of inflammatory cells and the level of OVA-specific immunoglobulin E in BALFs. CTS also inhibited the expressions of alpha-smooth muscle actin, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), Fn14, transforming growth factor (TGF)-β1, Smad4, and phosphorylation of Smad2/3 and STAT3 (Tyr705). In comparison to TWEAK inhibitor or TWEAK small interfering RNA (siRNA), which were used to inhibit TWEAK/STAT3 signaling pathways, CTS caused a similar effect as them on airway remodeling. Additionally, CTS also played a similar role as the TGF-β1 inhibitor or TGF-β1 siRNA in TGF-β1/STAT3 signaling pathways in airway remodeling. The anti-inflammatory effects of CTS against OVA-induced airway remodeling may be through inhibiting STAT3, which further suppresses TWEAK and TGF-β1 signaling cross talk in asthma. CTS may be a promising therapeutic reagent for asthma treatment.
Zinc Supplementation Promotes a Th1 Response and Improves Clinical Symptoms in Fewer Hours in Children With Pneumonia Younger Than 5 Years Old. A Randomized Controlled Clinical Trial

Background: Pneumonia caused 704,000 deaths in children younger than 5 years in 2015. Zinc is an important micronutrient due to its role in immune function. Since 2004, WHO recommends zinc supplementation for children with diarrhea to shorten the duration and decrease severity. Zinc supplementation for children with pneumonia is controversial. Methods: A randomized controlled clinical trial was conducted, and 103 children 1 month to 5 years old with pneumonia were included. Zinc or placebo was given during hospitalization. Clinical symptoms were recorded, and a blood draw was obtained to determine serum zinc levels, lymphoproliferation, and cytokines at hospitalization and at discharge of the patient; a nasal wash was obtained to detect viral or bacterial pathogens by multiplex RT-PCR. Results: Zinc supplementation improved in fewer hours the clinical status (76 ± 7 vs. 105 ± 8, p = 0.01), the respiratory rate (37 ± 6 vs. 57 ± 7, p = 0.04), and the oxygen saturation (53 ± 7 vs. 87 ± 9, p = 0.007) compared to the placebo group. An increase in IFNγ and IL-2 after treatment in the zinc group was observed. Conclusions: Zinc supplementation improved some clinical symptoms in children with pneumonia in fewer hours and induced a cellular immune response. Clinical Trial Registration: The trial was retrospectively registered in ClinicalTrials.gov, identifier NCT03690583, URL https://clinicaltrials.gov/ct2/show/NCT03690583? term=zinc+children&cond=Pneumonia&draw=2&rank=1.
Literacies and the Development of Social, Critical, and Creative Thought in Textbook Activities for Primary Education in Social Sciences and the Spanish Language

The skills of thinking, reading conceptions and reading practice (literacy levels) found in textbook activities for the sixth year of Primary Education in Social Sciences and Spanish Language in Spain are analyzed in this paper. A mixed methodology is used to triangulate the data, integrating the critical analysis of discourse and two types of statistical analysis: descriptive (frequencies and percentages) and inferential (χ2, ANOVA, and the Mann-Whitney U Test). The results inform us of both the permanence and the strengthening of the design of an activity oriented toward the development of traditional conceptions of linguistic-cognitive reading. In the framework of education for global citizenship, the conclusion is the need for student reading practices that begin with the principles of critical literacy directed at the acquisition of social, critical, and creative thinking skills.
Antireflux valve metal stent versus conventional self-expandable metal stent in distal malignant biliary obstruction: a systematic review and meta-analysis

Background: In patients with distal malignant biliary obstruction (MBO), endoscopic biliary drainage using the conventional self-expandable metal stent (SEMS) is the gold standard method for palliative treatment. However, there are limited data on the role of the antireflux valve metal stent (ARVMS). The aim of this study was to compare the safety and efficacy of ARVMS and SEMS in patients with distal MBO. Methods: We searched PubMed, Ovid, Embase and the Cochrane Library from inception until April 2019 for relevant randomized controlled trials (RCTs). The selected studies provided data regarding technical and clinical success rates, adverse events, and stent dysfunction. Data were meta-analyzed using RevMan software. Results: Three RCTs were selected, enrolling 293 patients (147 ARVMS and 146 SEMS). The rates of technical success were 95.23% and 99.31% for ARVMS and SEMS groups, respectively (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.01-1.06; P=0.06). The clinical success rates were 91.57% and 89.36% for ARVMS and SEMS groups, respectively (OR 1.30, 95%CI 0.48-3.51; P=0.61). There was no significant difference between the ARVMS and SEMS groups in terms of adverse events (OR 0.61, 95%CI 0.35-1.05; P=0.07) or stent dysfunction (OR 0.77, 95%CI 0.31-1.95; P=0.58), while the incidence of stent occlusion was significantly lower in the ARVMS group (OR 0.44, 95%CI 0.26-0.76; P=0.003). Conclusion: Our study showed that ARVMS and SEMS had similar technical and clinical success rates. Adverse events were comparable between the 2 arms; however, ARVMS was associated with a lower risk of stent occlusion. Larger RCTs are required to verify the benefit of ARVMS in distal MBO patients.
Electroskip auditory biofeedback in a patient with Parkinson disease: a case report

The purpose of this case study was to observe the effects of a rehabilitation program with an audio-biofeedback technology device called Electroskip in a patient with Parkinson disease. The patient was a 61-year-old man with moderate Parkinson disease (Hoehn and Yahr Parkinson’s scale stage III) and dementia who had progressive episodes of freezing of gait. The patient also had a history of recent falls. The patient completed a 6-week rehabilitation program focused on functional tasks, balance and gait training while using Electroskip technology, which is a wireless, wearable device that sends a discrete real-time generative audio-biofeedback signal when the user steps on either the heel or toe force sensors positioned under the innersoles. The outcome measures included the Timed Up and Go test, the modified Gait Abnormality Rating Scale, the modified Parkinson’s Activity Scale, and the Freezing of Gait Questionnaire. The patient completed 17 of the 18 scheduled training sessions and all testing sessions; no adverse events occurred during the rehabilitation program and high satisfaction levels were reported by the patient and family after completion of the 6-week rehabilitation program. Clinically significant improvements were seen in all measures at 6 weeks. The results of this report suggest that a rehabilitation program focused on functional tasks, balance, and gait training using the Electroskip technology may be beneficial for improving gait and balance in a patient with moderate Parkinson disease. Future work is needed to determine the effectiveness of Electroskip technology by means of randomized controlled trials.