Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Toll-Like Receptors Differentially Modulates Inflammation in the Human Reproductive Tract: Preliminary Findings

The female reproductive tract (FRT) is the main site of entry of sexually transmitted infections (STIs). Toll-like receptors (TLRs) that recognize pathogenic motifs are widely expressed in the FRT. TLR stimulation induces immune activation and local production of inflammatory mediators. In the FRT, this response should also be compatible with reproductive functions and symbiosis with host microbiota. With a view to develop efficient mucosal vaccines to prevent STI acquisition, the role of TLR ligands in the FRT needs to be explored. We have therefore investigated the cytokine profiles of the different compartments of the FRT (vagina, endocervix, ectocervix, and uterus) before and after stimulation of mononuclear cells from human tissue specimens. The comparison with PBMCs allowed us to highlight the FRT specificities. We first characterized the main immune cell populations in each compartment and observed that their distribution was different through the compartments. The CD45+ cells represented a maximum of 11% in the FRT in contrast to 96% in PBMCs. We identified two main populations among the CD45+ cells in the four compartments of the FRT: CD3+ T cells (CD4+ and CD8+) and CD14+ APCs. B cell populations (CD19+) were much less frequent than T cells in all the FRT regions and were equally distributed. NK CD56+ cells were detected in all compartments and were more abundant in the uterus. Stimulation of the mononuclear cells was then performed with TLR agonists: R848 for TLR7/8, Poly I:C for TLR3, LPS for TLR4 and ODN CpG for TLR9. Cytokine levels in unstimulated cultures of cells isolated from all FRT compartments were higher than in cultures of unstimulated PBMCs. In contrast, after stimulation with TLR agonists, cytokine responses induced by TLR agonists were moderate in the FRT and significantly lower than in PBMCs. These responses were varied with different TLR ligands and FRT compartments. The cytokine profile induced by TLR activation in the FRT supports the role of these tissues in genital anti-microbial immunity and in the control of inflammation while allowing maintenance of its reproductive function.
Trajectories of Physical Activity Among Adolescents in the Transition From Primary to Secondary School

Research on physical activity (PA) behavior reveals an overall decrease worldwide from early childhood and throughout adulthood. The ability to illuminate which factors promote activity for whom and in which phase of life, therefore, becomes a key concept in extending our understanding of individuals' physical activity trajectories. Accordingly, this study investigates latent trajectories of objectively measured PA in adolescents (n = 306) over 3 years from ages 13 to 15. Further, it was tested whether eagerness for physical activity, perceived athletic competence, and parental support were associated with the different trajectories of PA. Latent class growth analysis revealed two PA trajectories (trajectory 1: “decrease from very high” and trajectory 2: “steeper decrease from high”). Trajectory 1 had a higher PA level at baseline and less PA decline than trajectory 2. Trajectory 1, “decrease from very high,” was associated with higher levels of eagerness for physical activity and perception of competence at all three time points. Furthermore, the effect size of differences between trajectory 1, “decrease from very high,” and trajectory 2, “steeper decrease from high,” increased from baseline (age 13, seventh grade) to posttest (age 15, ninth grade). This finding indicates a stronger experience of PA as enjoyable, personally relevant, and self-confirming behavior (i.e., “I regard myself as a person who exercises”) within the most active adolescents and even stronger as they get older. Consistent with previous research, the PA level declined from seventh to ninth grade. Being more eager for PA and perceiving oneself more as athletically competent is related to higher levels of PA. This highlights the importance of optimizing environmental factors that increase adolescents' experience of eagerness for physical activity and physical athletic competence.
The Postbiotic Activity of Lactobacillus paracasei 28.4 Against Candida auris

Candida auris has emerged as a medically important pathogen with considerable resistance to antifungal agents. The ability to produce biofilms is an important pathogenicity feature of this species that aids escape of host immune responses and antimicrobial agents. The objective of this study was to verify antifungal action using in vitro and in vivo models of the Lactobacillus paracasei 28.4 probiotic cells and postbiotic activity of crude extract (LPCE) and fraction 1 (LPF1), derived from L. paracasei 28.4 supernatant. Both live cells and cells free supernatant of L. paracasei 28.4 inhibited C. auris suggesting probiotic and postbiotic effects. The minimum inhibitory concentration (MIC) for LPCE was 15 mg/mL and ranges from 3.75 to 7.5 mg/mL for LPF1. Killing kinetics determined that after 24 h treatment with LPCE or LPF1 there was a complete reduction of viable C. auris cells compared to fluconazole, which decreased the initial inoculum by 1-logCFU during the same time period. LPCE and LPF1 significantly reduced the biomass (p = 0.0001) and the metabolic activity (p = 0.0001) of C. auris biofilm. There was also a total reduction (~108 CFU/mL) in viability of persister C. auris cells after treatment with postbiotic elements (p < 0.0001). In an in vivo study, injection of LPCE and LPF1 into G. mellonella larvae infected with C. auris prolonged survival of these insects compared to a control group (p < 0.05) and elicited immune responses by increasing the number of circulating hemocytes and gene expression of antimicrobial peptide galiomicin. We concluded that the L. paracasei 28.4 cells and postbiotic elements (LPCE and LPF1) have antifungal activity against planktonic cells, biofilms, and persister cells of C. auris. Postbiotic supplementation derived from L. paracasei 28.4 protected G. mellonella infected with C. auris and enhanced its immune status indicating a dual function in modulating a host immune response.
Evaluation of the Heterogeneous Spatial Distribution of Population and Stores/Facilities by Multifractal Analysis

The spatial distribution of a population is not homogeneous—some areas attract many residents, while others do not. The spatial distribution of stores and facilities that have been coevolving with that of the population is also heterogeneous. Previous studies have shown that multifractality is a characteristic of the spatial distribution of a population, as well as other quantities associated with the urban system. We found that stores/facilities belonging to some categories also exhibit multifractality in spatial distribution. We quantified the spatial distributions of the population and stores/facilities in each category by multifractal analysis and compared their multifractal properties. Multifractal measures that reflect the heterogeneity of the densities in each location were able to capture additional features that cannot be seen when only the box-counting dimension was observed. Further, high concentrations of stores/facilities in categories relating to professional or commercial businesses were observed, consistent with previous studies on the scaling law, another pattern observed in urban morphology. We discuss the implications of the multifractal properties on the arrangement of locations where stores/facilities are concentrated. We believe that multifractal analysis is a powerful tool for the quantification of spatial distributions and expect that our interpretation of multifractal measures will stimulate further investigations into urban morphology.
Updates and Comparative Analysis of the Mitochondrial Genomes of Paracoccidioides spp. Using Oxford Nanopore MinION Sequencing

The mitochondrial genome of the Paracoccidioides brasiliensis reference isolate Pb18 was first sequenced and described by Cardoso et al. (2007), as a circular genome with a size of 71.3 kb and containing 14 protein coding genes, 25 tRNAs, and the large and small subunits of ribosomal RNA. Later in 2011, Desjardins et al. (2011) obtained partial assemblies of mitochondrial genomes of P. lutzii (Pb01), P. americana (Pb03), and P. brasiliensis sensu stricto (Pb18), although with a size of only 43.1 kb for Pb18. Sequencing errors or other limitations resulting from earlier technologies, and the advantages of NGS (short and long reads), prompted us to improve and update the mtDNA sequences and annotations of two Paracoccidioides species. Using Oxford Nanopore and Illumina read sequencing, we generated high-quality complete de novo mitochondrial genome assemblies and annotations for P. brasiliensis (Pb18) and P. americana (Pb03). Both assemblies were characterized by an unusually long spacer or intron region (>50 kb) between exons 2 and 3 of the nad5 gene, which was moderately conserved between Pb03 and Pb18 but not similar to other reported sequences, except for an unassigned contig in the 2011 assembly of Pb03. The reliability of the insert missing from previous mtDNA genome assemblies was confirmed by inspection of the individual Nanopore read sequences containing nad5 coding DNA, and experimentally by PCR for Pb18. We propose that the insert may aid replication initiation and may be excised to produce a smaller structural variant. The updated mtDNA genomes should enable more accurate SNP and other comparative or evolutionary analyses and primer/probe designs. A comparative analysis of the mtDNA from 32 isolates of Paracoccidioides spp. , using the SNPs of the aligned mitochondrial genomes, showed groupings within the brasiliensis species complex that were largely consistent with previous findings from only five mitochondrial loci.
A cross-sectional study of cutaneous changes in patients with acquired thyroid disorders

Background: Thyroid disorders are quite common in India. Thyroid hormone affects the skin and its appendages, and the cutaneous manifestations are more notable during deficiency or excess state. Apart from this, thyroid diseases are accompanied by various autoimmune dermatoses. Aim: The present study was designed to assess the dermatological manifestations in patients with thyroid disease. Materials and Methods: This was a hospital-based, cross-sectional, descriptive study conducted in a tertiary care center in Northern India over a period of 1 year. A total of 126 newly diagnosed patients with acquired thyroid disorders were enrolled in the study. All the patients were assessed for cutaneous, hair, nail changes, and associated autoimmune dermatological diseases. Results: Out of 126 patients, 113 had hypothyroidism and 13 had hyperthyroidism. Females outnumbered males in both the study groups. Some patients had more than one dermatological manifestation. The most common dermatological manifestation in hypothyroid patients was generalized xerosis (67.25%), followed by diffuse hair loss (47.78%) and coarse hair (44.24%). In hyperthyroid patients, the most common manifestation was thin soft hair (61.53%), followed by warm skin (53.84%) and Jellinek's sign (38.46%). Chronic urticaria was the most common associated autoimmune dermatological disease in both the study groups. Conclusion: In some instances, the initial and the most prominent complaint of the patient is related to alterations in the skin, and therefore, the dermatologist is at times being the first physician consulted. Identifying the endocrinopathy is very important so that the patients might receive corrective rather than symptomatic treatment.
Comparison of Graph-based Model Transformation Rules

With model transformations arising to primary development artifacts in Model-Driven Engineering, dedicated tools supporting transformation developers in the development and maintenance of model transformations are strongly required. In this paper, we address the versioning of model transformations, which essentially relies on a basic service for comparing diﬀerent versions of model transformations, e.g., a local workspace version and the latest version of a repository. Focusing on rule-based model transformations based on graph transformation concepts, we pro-pose to compare such transformation rules using a maximum common subgraph (MCS) algorithm as the underlying matching engine. Although the MCS problem is known as a non-polynomial optimization problem, our research hypothesis is that using an MCS algorithm as a basis for comparing graph-based transformation rules is feasible for real-world model transformations and increases the quality of comparison results compared to standard model comparison algorithms. Experimental results obtained on a benchmark set for model transformation conﬁrm this hypothesis.
CYP2D6 Genotype-Based Dose Recommendations for Risperidone in Asian People

The aim of this study was to provide dose recommendations for risperidone in Asian people based on cytochrome P450 enzyme CYP2D6 genotype. First, we investigated the influence of CYP2D6 polymorphism on the pharmacokinetics of risperidone in Chinese patients with schizophrenia. Then, we performed a search for studies covering the relationship between pharmacokinetic parameters of risperidone and CYP2D6 genotype. Pooled pharmacokinetic parameters were meta-analyzed using a random-effects model. Lastly, we calculated the dose adjustment for risperidone based on CYP2D6 genotype for white and Asian people. Significant differences between the extensive metabolizer and intermediate metabolizer groups were observed for dose-adjusted risperidone level, 9-hydroxyrisperidone level, and risperidone/9-hydroxyrisperidone ratio, but not for the total active moiety. Meta-analysis showed that significant differences were observed among the four phenotype groups, including steady state concentration, peak risperidone concentration, and the area under the curve, using the Kruskal-Wallis test. No differences were found in oral clearance. For risperidone, dose recommendations for poor and ultrarapid metabolizers of CYP2D6 for Asians were different compared to that for white people for poor metabolizers (dose adjustment around 45% for white people, while for Asians the risperidone dose should be reduced by 26%). For ultrarapid metabolizers, risperidone dose should be increased by about 33% for white people and 30% for Asians. This was a first attempt to apply pharmacogenetics to suggest dose-regimens for Asian people; further research to replicate and extend these findings is recommended.
Catalog of Lung Cancer Gene Mutations Among Chinese Patients

Background: Detailed catalog of lung cancer-associated gene mutations provides valuable information for lung cancer diagnosis and treatment. In China, there has never been a wide-ranging study cataloging lung cancer-associated gene mutations. This study aims to reveal a comprehensive catalog of lung cancer gene mutations in china, focusing on EGFR, ALK, KRAS, HER2, PIK3CA, MET, BRAF, HRAS, and CTNNB1 as major targets. Additionally, we also aim to correlate smoking history, gender, and age distribution and pathological types with various types of gene mutations. Patients and Methods: A retrospective data acquisition was conducted spanning 6 years (2013–2018) among all patients who underwent lung cancer surgeries not bronchial or percutaneous lung biopsy at three major tertiary hospitals. Finally, we identified 1,729 patients who matched our inclusion criteria. Results: 1081 patients (62.49%) harbored EGFR mutation. ALK (n = 42, 2.43%), KRAS (n = 201, 11.62%), CTNNB1 (n = 28, 1.62%), BRAF (n = 31, 1.79%), PIK3CA (n = 51, 2.95%), MET (n = 14, 0.81%), HER2 (n = 47, 2.72%), HRAS (n = 3, 0.17%), and other genes(n = 232, 13.4%). Females expressed 55.38% vs. males 44.62% mutations. Among subjects with known smoking histories, 32.82% smokers, 67.15% non-smokers were observed. Generally, 51.80% patients were above 60 years vs. 48.20% in younger patients. Pathological types found includes LUADs 71.11%, SQCCs 1.68%, ASC 0.75%, LCC 0.58%, SCC 0.35%, ACC 0.17%, and SC 0.06%, unclear 25.19%. Conclusion: We offer a detailed catalog of the distribution of lung cancer mutations. Showing how gender, smoking history, age, and pathological types are significantly related to the prevalence of lung cancer in China.
Paradoxical Case Fatality Rate dichotomy of Covid-19 among rich and poor nations points to the hygiene hypothesis.

In the first six months of its deadly spread across the world, the Covid-19 incidence has exhibited interesting dichotomy between the rich and the poor countries. Surprisingly, the incidence and the Case Fatality Rate has been much higher in the richer countries compared with the poorer countries. However, the reasons behind this dichotomy have not been explained based on data or evidence, although some of the factors for the susceptibility of populations to SARS-CoV-2 infections have been proposed. We have taken into consideration all publicly available data and mined for the possible explanations in order to understand the reasons for this phenomenon. The data included many parameters including demography of nations, prevalence of communicable and non-communicable diseases, sanitation parameters etc. Results of our analyses suggest that demography, improved sanitation and hygiene, and higher incidence of autoimmune disorders as the most plausible factors to explain higher death rates in the richer countries Thus, the much debated hygiene hypothesis appears to lend credence to the Case Fatality Rate dichotomy between the rich and the poor countries.
Hand Movement detection Using Empirical Mode Decomposition And Higher Order Spectra

With the industrialization of societies, the number of disabilities is increasing, and one of these disabilities can occur and severely affect the lives of individuals and society. There are several ways to control an artificial prosthesis, one of which is to use an electromyography signal. For this purpose, we use the dataset set available at the UCI database, which has 6 different hand movements in the form of free access. In this study, each signal is first decomposed into intrinsic mode, and each signal is converted to 8 IMF, and then, using high-order spectrum to show the changes. The results show that from the third IMF onwards, HOS patterns are repeated. The first and second IMFs are used as an input signal to artificial prosthesis and the feature of kurtosis, skewness and variance are extracted. The results have shown the accuracy of classification with the first IMF and SVM classifier is 98.26%.
oprC Impairs Host Defense by Increasing the Quorum-Sensing-Mediated Virulence of Pseudomonas aeruginosa

Pseudomonas aeruginosa, found widely in the wild, causes infections in the lungs and several other organs in healthy people but more often in immunocompromised individuals. P. aeruginosa infection leads to inflammasome assembly, pyroptosis, and cytokine release in the host. OprC is one of the bacterial porins abundant in the outer membrane vesicles responsible for channel-forming and copper binding. Recent research has revealed that OprC transports copper, an essential trace element involved in various physiological processes, into bacteria during copper deficiency. Here, we found that oprC deletion severely impaired bacterial motility and quorum-sensing systems, as well as lowered levels of lipopolysaccharide and pyocyanin in P. aeruginosa. In addition, oprC deficiency impeded the stimulation of TLR2 and TLR4 and inflammasome activation, resulting in decreases in proinflammatory cytokines and improved disease phenotypes, such as attenuated bacterial loads, lowered lung barrier damage, and longer mouse survival. Moreover, oprC deficiency significantly alleviated pyroptosis in macrophages. Mechanistically, oprC gene may impact quorum-sensing systems in P. aeruginosa to alter pyroptosis and inflammatory responses in cells and mice through the STAT3/NF-κB signaling pathway. Our findings characterize OprC as a critical virulence regulator, providing the groundwork for further dissection of the pathogenic mechanism of OprC as a potential therapeutic target of P. aeruginosa.
Context-dependent effects of predator removal from experimental microcosm communities

The loss of a predator from an ecological community can cause large changes in community structure and ecosystem processes, or have very little consequence for the remaining species and ecosystem. Understanding when and why the loss of a predator causes large changes in community structure and ecosystem processes is critical for understanding the functional consequences of biodiversity loss. We used experimental microbial communities to investigate how the removal of a large generalist predator affected the extinction frequency, population abundance and total biomass of its prey. We removed this predator in the presence or absence of an alternative, more specialist, predator in order to determine whether the specialist predator affected the outcome of the initial species removal. Removal of the large generalist predator altered some species’ populations but many were unaffected and no secondary extinctions were observed. The specialist predator, though rare, altered the response of the prey community to the removal of the large generalist predator. In the absence of the specialist predator, the effects of the removal were only measurable at the level of individual species. However, when the specialist predator was present, the removal of the large generalist predator affected the total biomass of prey species. The results demonstrate that the effect of species loss from high trophic levels may be very context-dependent, as rare species can have disproportionately large effects in food webs.
Ranolazine-Mediated Attenuation of Mechanoelectric Feedback in Atrial Myocyte Monolayers

Background Mechanical stretch increases Na+ inflow into myocytes, related to mechanisms including stretch-activated channels or Na+/H+ exchanger activation, involving Ca2+ increase that leads to changes in electrophysiological properties favoring arrhythmia induction. Ranolazine is an antianginal drug with confirmed beneficial effects against cardiac arrhythmias associated with the augmentation of INaL current and Ca2+ overload. Objective This study investigates the effects of mechanical stretch on activation patterns in atrial cell monolayers and its pharmacological response to ranolazine. Methods Confluent HL-1 cells were cultured in silicone membrane plates and were stretched to 110% of original length. The characteristics of in vitro fibrillation (dominant frequency, regularity index, density of phase singularities, rotor meandering, and rotor curvature) were analyzed using optical mapping in order to study the mechanoelectric response to stretch under control conditions and ranolazine action. Results HL-1 cell stretch increased fibrillatory dominant frequency (3.65 ± 0.69 vs. 4.35 ± 0.74 Hz, p < 0.01) and activation complexity (1.97 ± 0.45 vs. 2.66 ± 0.58 PS/cm2, p < 0.01) under control conditions. These effects were related to stretch-induced changes affecting the reentrant patterns, comprising a decrease in rotor meandering (0.72 ± 0.12 vs. 0.62 ± 0.12 cm/s, p < 0.001) and an increase in wavefront curvature (4.90 ± 0.42 vs. 5.68 ± 0.40 rad/cm, p < 0.001). Ranolazine reduced stretch-induced effects, attenuating the activation rate increment (12.8% vs. 19.7%, p < 0.01) and maintaining activation complexity—both parameters being lower during stretch than under control conditions. Moreover, under baseline conditions, ranolazine slowed and regularized the activation patterns (3.04 ± 0.61 vs. 3.65 ± 0.69 Hz, p < 0.01). Conclusion Ranolazine attenuates the modifications of activation patterns induced by mechanical stretch in atrial myocyte monolayers.