Miracle-dz/UniFAR-FTUs huggingface dataset:
Descriptive Study of Gut Microbiota in Infected and Colonized Subjects by Clostridiodes difficile

Clostridiodes difficile can lead to a range of situations from the absence of symptoms (colonization) to severe diarrhea (infection). Disruption of gut microbiota provides an ideal environment for infection to occur. Comparison of gut microbiota of infected and colonized subjects could provide relevant information on susceptible groups or protectors to the development of infection, since the presence of certain genera could be related to the inhibition of transition from a state of colonization to infection. Through high-throughput sequencing of 16S rDNA gene, we performed alpha and beta diversity and composition studies on 15 infected patients (Group CDI), 15 colonized subjects (Group P), and 15 healthy controls (Group CTLR). A loss of alpha diversity and richness and a different structure have been evidenced in the CDI and P groups with respect to the CTRL group, but without significant differences between the first two. In CDI and P groups, there was a strong decrease in phylum Firmicutes and an expansion of potential pathogens. Likewise, there was a loss of inhibitory genus of C. difficile germination in infected patients that were partially conserved in colonized subjects. Therefore, infected and colonized subjects presented a gut microbiota that was completely different from that of healthy controls, although similar to each other. It is in composition where we found that colonized subjects, especially in minority genera, presented differences with respect to those infected.
Isolation of High Molecular Weight DNA from the Model Beetle Tribolium for Nanopore Sequencing

The long-read Nanopore sequencing has been recently applied for assembly of complex genomes and analysis of linear genome organization. The most critical factor for successful long-read sequencing is extraction of high molecular weight (HMW) DNA of sufficient purity and quantity. The challenges associated with input DNA quality are further amplified when working with extremely small insects with hard exoskeletons. Here, we optimized the isolation of HMW DNA from the model beetle Tribolium and tested for use in Nanopore sequencing. We succeeded in overcoming all the difficulties in HMW handling and library preparation that were encountered when using published protocols and commercial kits. Isolation of nuclei and subsequent purification of DNA on an anion-exchange chromatography column resulted in genomic HMW DNA that was efficiently relaxed, of optimal quality and in sufficient quantity for Nanopore MinION sequencing. DNA shearing increased average N50 read values up to 26 kb and allowed us to use a single flow cell in multiple library loads for a total output of more than 13 Gb. Although our focus was on T. castaneum and closely related species, we expect that this protocol, with appropriate modifications, could be extended to other insects, particularly beetles.
Synthesis and Antiplasmodial Activity of Bisindolylcyclobutenediones

Malaria is one of the most dangerous infectious diseases. Because the causative Plasmodium parasites have developed resistances against virtually all established antimalarial drugs, novel antiplasmodial agents are required. In order to target plasmodial kinases, novel N-unsubstituted bisindolylcyclobutenediones were designed as analogs to the kinase inhibitory bisindolylmaleimides. Molecular docking experiments produced favorable poses of the unsubstituted bisindolylcyclobutenedione in the ATP binding pocket of various plasmodial protein kinases. The synthesis of the title compounds was accomplished by sequential Friedel-Crafts acylation procedures. In vitro screening of the new compounds against transgenic NF54-luc P. falciparum parasites revealed a set of derivatives with submicromolar activity, of which some displayed a reasonable selectivity profile against a human cell line. Although the molecular docking studies suggested the plasmodial protein kinase PfGSK-3 as the putative biological target, the title compounds failed to inhibit the isolated enzyme in vitro. As selective submicromolar antiplasmodial agents, the N-unsubstituted bisindolylcyclobutenediones are promising starting structures in the search for antimalarial drugs, albeit for a rational development, the biological target addressed by these compounds has yet to be identified.
Mercury and Antibiotic Resistance Co-Selection in Bacillus sp. Isolates from the Almadén Mining District

Antibiotic resistance (AR) in the environment is of great global concern and a threat to public health. Soil bacteria, including Bacillus spp. , could act as recipients and reservoirs of AR genes of clinical, livestock, or agricultural origin. These genes can be shared between bacteria, some of which could be potentially human pathogens. This process can be favored in conditions of abiotic stress, such as heavy metal contamination. The Almadén mining district (Ciudad Real, Spain) is one of the environments with the highest mercury (Hg) contamination worldwide. The link between heavy metal contamination and increased AR in environmental bacteria seems clear, due to co-resistance and co-selection phenomena. In the present study, 53 strains were isolated from rhizospheric and bulk soil samples in Almadén. AR was tested using Vitek® 2 and minimum inhibitory concentration (MIC) values were obtained and interpreted based on the criteria of the Clinical and Laboratory Standards Institute (CLSI) guidelines. Based on the resistance profiles, five different antibiotypes were established. The Hg minimum bactericidal concentration (MBC) of each strain was obtained using the plating method with increasing concentrations of HgCl2. A total of 72% of Bacillus spp. showed resistance to two or more commonly used antibiotics. A total of 38 isolates expressed AR to cephalosporins. Finally, the environmental co-selection of AR to cephalosporins and tetracyclines by selective pressure of Hg has been statistically demonstrated.
Fused Filament Fabrication of NiTi Components and Hybridization with Laser Powder Bed Fusion for Filigree Structures

The present study introduces an approach to the powder metallurgical shaping of a pseudo-elastic nickel–titanium (NiTi 44 alloy) combining two different Additive Manufacturing (AM) processes, namely fused filament fabrication (FFF) and Laser Powder Bed Fusion (LPBF), by manufacturing filigree structures on top of sintered FFF parts. Both processes start with commercial gas atomized NiTi powder, which is fractionated into two classes. Using the fine fraction with particle sizes <15 µm, robust thermoplastic filaments based on a non-commercial binder system were produced and processed to different auxetic and non-auxetic geometries employing a commercial standard printer. FTIR analysis for thermal decomposition products was used to develop a debinding regime. After sintering, the phase transformation austenite/martensite was characterized by DSC in as sintered and annealed state. Precipitates resulting from residual impurities were detected by micrographs and XRD. They led to an increased transformation temperature. Adjusting the oxygen and carbon content in the alloy remains a challenging issue for powder metallurgical processed NiTi alloys. Filigree lattice structures were built onto the surfaces of the sintered FFF parts by LPBF using the coarser powder fraction (15–45 µm). A good material bond was formed, resulting in the first known NiTi hybrid, which introduces new production and design options for future applications.
School-Based Prevention of Screen-Related Risk Behaviors during the Long-Term Distant Schooling Caused by COVID-19 Outbreak

The COVID-19 outbreak and related restrictions meant a higher incidence of screen-related risk behaviors in both children and adolescents. Our goal was to assess the perceived importance and extent of school-based preventions related to these risks during the long-term, nation-wide distant schooling period in the Czech Republic. The online survey was responded to by the school-based prevention specialists (N = 1698). For the analysis, within-subject analysis of variance (ANOVA) and binominal logistic regression were used. At-risk internet use and cyber-bullying were perceived as pressing, but other risks, for example, excessive internet use or the use of cyberpornography, received substantially less priority. The differences in all grades were significant and moderate to large (η2G between 0.156 and 0.288). The proportion of schools which conducted prevention interventions of screen-related risks was low (between 0.7% and 27.8%, depending on the grade and the type of the risk). The probability of delivering prevention intervention was in all grades significantly predicted by the presence of screen-related problems in pupils (OR 3.76–4.88) and the perceived importance of the screen-related risks (OR 1.55–1.97). The limited capacity of schools to deliver prevention interventions during distant schooling as well as the low awareness and impaired ability to recognize the importance of some screen-related risks should be addressed.
In Utero Fetal Weight in Pigs Is Regulated by microRNAs and Their Target Genes

Impaired skeletal muscle growth in utero can result in reduced birth weight and poor carcass quality in pigs. Recently, we showed the role of microRNAs (miRNAs) and their target genes in prenatal skeletal muscle development and pathogenesis of intrauterine growth restriction (IUGR). In this study, we performed an integrative miRNA-mRNA transcriptomic analysis in longissimus dorsi muscle (LDM) of pig fetuses at 63 days post conception (dpc) to identify miRNAs and genes correlated to fetal weight. We found 13 miRNAs in LDM significantly correlated to fetal weight, including miR-140, miR-186, miR-101, miR-15, miR-24, miR-29, miR-449, miR-27, miR-142, miR-99, miR-181, miR-199, and miR-210. The expression of these miRNAs decreased with an increase in fetal weight. We also identified 1315 genes significantly correlated to fetal weight at 63 dpc, of which 135 genes were negatively correlated as well as identified as potential targets of the above-listed 13 miRNAs. These miRNAs and their target genes enriched pathways and biological processes important for fetal growth, development, and metabolism. These results indicate that the transcriptomic profile of skeletal muscle can be used to predict fetal weight, and miRNAs correlated to fetal weight can serve as potential biomarkers of prenatal fetal health and growth.
Comparison of Nutritional Compositions and Essential Oil Profiles of Different Parts of a Dill and Two Fennel Cultivars

Fennel and dill are widely used as food additives owing to their various biological activities, such as antioxidants, antimicrobials, food-preservatives, and seasoning capacities. Herein, the nutritional composition and essential oil (EO) chemical profiles of fruits, umbels, stalks, and roots from one dill and two fennel cultivars were evaluated. The fruits had the highest content of crude protein (≥15%), crude fat (≥8%), and phosphorus (≥0.5%), and exhibited the highest total energy (≥20 MJ/kg) and EO yield (≥2%). Moreover, estragole (86.56% in Fdf), anethole (71.17% in Fhf), fenchone (16.74% in Fhf), limonene (50.19% in Agf), and carvone (42.41% in Agf) were the main components of the EOs generated from the fruits. The chemical profiles of EOs in the roots were significantly different from those of the aerial parts of the fennel and dill; thus, the roots and aerial parts could be distinguished based on myristicin (Variable Importance in Projection (VIP) = 1.90399) and apiol (VIP = 1.85922). The EO components of the aerial parts varied remarkably, and the chemical markers for differentiating these three cultivars were anethole (VIP = 1.36571), estragole (VIP = 1.30292), and carvone (VIP = 1.11947). Overall, our results provide a noteworthy chemical basis for further development of fennel and dill, especially as food additives.
Bone Response to Conventional Titanium Implants and New Zirconia Implants Produced by Additive Manufacturing

The aim of the present study was to evaluate the in vivo bone response to an additively manufactured zirconia surface compared to osseointegration into titanium (Ti) surfaces. Scanning electron microscopy, confocal laser scanning microscopy, and electron spectroscopy for chemical analysis were performed to assess the surface characteristics of implant specimens. For the in vivo evaluation, eight Ti implants and eight 3D-printed zirconia implants were used. The surface of four Ti implants was sandblasted, large-grit, and acid-etched (Ti-SLA group), while those of the other four Ti implants were left untreated (Ti-turned group). The zirconia implants had no further surface modification. Implants were placed into the tibiae of four rabbits; two received the Ti-SLA and zirconia implants and the other two received Ti-turned and zirconia implants. The experimental animals were sacrificed after four weeks of surgery, and the undecalcified microscopic slides were prepared. The bone–implant interface was analyzed by histomorphometry to evaluate the bone response. The degree of surface roughness showed that Ti-SLA was the highest, followed by zirconia and Ti-turned surfaces. The 3D-printed zirconia surface showed similar bone-to-implant contact to the Ti-turned surface, and Ti-SLA had the most bone-to-implant contact. The additively manufactured zirconia implant surface is biocompatible with respect to osseointegration compared to the commercially pure Ti surface.
Value of Left Ventricular Feature Tracking Strain Analysis for Detection of Early Cardiac Involvement in Fabry Disease (FD)

Purpose: Detection of cardiac involvement in Fabry disease (FD) is of high importance for treatment management. Native T1 mapping especially showed great potential for detection of early cardiac manifestations. Echocardiographic studies showed strain abnormalities in FD patients, but data on MRI feature tracking strain analysis (FT-SA) is limited. Therefore, the aim of our study was to evaluate the potential of FT-SA compared to native T1 and the FD specific biomarker Globotriaosylsphingosine (LysoGb3). Methods: 28 consecutive FD patients (18 female; 47.8 years ± 17.4 standard deviation (SD)) and 28 control subjects (18 female; 46.6 years ± 18.2 SD) underwent cardiac MRI at 1.5 Tesla. Global native T1 times and left ventricular FT-SA were evaluated. Results were correlated to serum Lyso-Gb3-levels. Results: Native T1 times, global longitudinal (GLS) and global radial strain (GRS) were significantly reduced in FD patients (p < 0.0064, p = 0.0009 and p = 0.0184, respectively). Moreover, native T1 times and GLS were significantly lower in Lyso-Gb3 positive FD patients (p < 0.005 and p = 0.03). GLS, native T1 times showed significant moderate correlations to LysoGb3 (p = 0.002 and p < 0.001). Furthermore, GLS and native T1 times reduce when LysoGb3 was elevated and increasingly with presence of left ventricular hypertrophy (LVH) or late gadolinium enhancement (LGE). Conclusions: Native T1 times and strain values differ significantly between FD patients and control subjects and showed promising correlations to the FD specific biomarker LysoGb3. We therefore conclude that strain abnormalities occur early beside native T1 reductions in cardiac FD involvement. Large scale trials are needed to verify our findings.
Inter-Rater Reliability of Magnetic Resonance Imaging in Comparison to Computed Tomography and Wrist Arthroscopy in SLAC and SNAC Wrist

The aim of the study was to assess the inter-rater reliability of magnetic resonance imaging (MRI) in comparison to computed tomography (CT) and wrist arthroscopy in patients with scapholunate (SLAC) or scaphoid non-union advanced collapse (SNAC) as well as to evaluate a grading score of cartilage lesions. A total of 42 patients (36 male, 6 female) at a mean age of 45 years (range: 19–65 years) with a SLAC or SNAC wrist who had a preoperative MRI and CT scan as well as underwent arthroscopy of the wrist between 2013 and 2018 were included in this study. Cartilage lesions, as assessed by MRI, CT and wrist arthroscopy, were classified by two hand surgeons in three stages. Inter-rater reliability was evaluated using the Kendall Tau-b test as well as the chi-square test to analyze for trend. The correlation between cartilage lesions, classified by arthroscopy and MRI, was low. A moderate correlation between CT and arthroscopy staging was shown. The highest inter-rater correlation was found between MRI and CT staging. An additionally performed logistic regression showed that progression of cartilage lesions as shown in MRI scans correlates with a restriction of range of motion (ROM). The level of cartilage lesion may be more severely classified in an MRI than during arthroscopy. Arthroscopy remains the gold standard in detecting cartilage lesions and thus in the decision-making process of the definitive treatment in carpal collapse.
Network-Based Integration of Multi-Omics Data Identifies the Determinants of miR-491-5p Effects

Simple Summary The re-introduction of miRNAs with tumor-suppressor activity in cancer cells has not yet been implemented in clinical practice yet. However, the identification of miRNAs’ targets and associated regulatory networks might allow the definition of new strategies using drugs whose association mimics a given miRNA’s effects. We devised a multi-omics approach to precisely characterize the effects of miR-491-5p, a cytotoxic miRNA in ovarian cancer cells, and performed an integrated network analysis. We identified the already known EGFR and BCL2L1 but also EP300, CTNNB1 and several small-GTPases—either direct or indirect targets of miR-491-5p—as regulatory hubs for miR-491-5p-mediated effects. Targeting different combinations of these hubs with specific inhibitors mimic miR-491-5p-induced cytotoxicity. Pharmacological inhibitors of these targets are available for clinical use or in clinical trials; thus, this study might enable innovative therapeutic options for ovarian cancer, the leading cause of death from gynecological malignancies in developed countries. Abstract The identification of miRNAs’ targets and associated regulatory networks might allow the definition of new strategies using drugs whose association mimics a given miRNA’s effects. Based on this assumption we devised a multi-omics approach to precisely characterize miRNAs’ effects. We combined miR-491-5p target affinity purification, RNA microarray, and mass spectrometry to perform an integrated analysis in ovarian cancer cell lines. We thus constructed an interaction network that highlighted highly connected hubs being either direct or indirect targets of miR-491-5p effects: the already known EGFR and BCL2L1 but also EP300, CTNNB1 and several small-GTPases. By using different combinations of specific inhibitors of these hubs, we could greatly enhance their respective cytotoxicity and mimic the miR-491-5p-induced phenotype. Our methodology thus constitutes an interesting strategy to comprehensively study the effects of a given miRNA. Moreover, we identified targets for which pharmacological inhibitors are already available for a clinical use or in clinical trials. This study might thus enable innovative therapeutic options for ovarian cancer, which remains the leading cause of death from gynecological malignancies in developed countries.
Molecular Dynamics-Derived Pharmacophore Model Explaining the Nonselective Aspect of KV10.1 Pore Blockers

The KV10.1 voltage-gated potassium channel is highly expressed in 70% of tumors, and thus represents a promising target for anticancer drug discovery. However, only a few ligands are known to inhibit KV10.1, and almost all also inhibit the very similar cardiac hERG channel, which can lead to undesirable side-effects. In the absence of the structure of the KV10.1–inhibitor complex, there remains the need for new strategies to identify selective KV10.1 inhibitors and to understand the binding modes of the known KV10.1 inhibitors. To investigate these binding modes in the central cavity of KV10.1, a unique approach was used that allows derivation and analysis of ligand–protein interactions from molecular dynamics trajectories through pharmacophore modeling. The final molecular dynamics-derived structure-based pharmacophore model for the simulated KV10.1–ligand complexes describes the necessary pharmacophore features for KV10.1 inhibition and is highly similar to the previously reported ligand-based hERG pharmacophore model used to explain the nonselectivity of KV10.1 pore blockers. Moreover, analysis of the molecular dynamics trajectories revealed disruption of the π–π network of aromatic residues F359, Y464, and F468 of KV10.1, which has been reported to be important for binding of various ligands for both KV10.1 and hERG channels. These data indicate that targeting the KV10.1 channel pore is also likely to result in undesired hERG inhibition, and other potential binding sites should be explored to develop true KV10.1-selective inhibitors as new anticancer agents.
Different Modes of Low-Frequency Focused Ultrasound-Mediated Attenuation of Epilepsy Based on the Topological Theory

Epilepsy is common brain dysfunction, where abnormal synchronized activities can be observed across multiple brain regions. Low-frequency focused pulsed ultrasound has been proven to modulate the epileptic brain network. In this study, we used two modes of low-intensity focused ultrasound (pulsed-wave and continuous-wave) to sonicate the brains of KA-induced epileptic rats, analyzed the EEG functional brain connections to explore their respective effect on the epileptic brain network, and discuss the mechanism of ultrasound neuromodulation. By comparing the brain network characteristics before and after sonication, we found that two modes of ultrasound both significantly affected the functional brain network, especially in the low-frequency band below 12 Hz. After two modes of sonication, the power spectral density of the EEG signals and the connection strength of the brain network were significantly reduced, but there was no significant difference between the two modes. Our results indicated that the ultrasound neuromodulation could effectively regulate the epileptic brain connections. The ultrasound-mediated attenuation of epilepsy was independent of modes of ultrasound.
Detection of Enteric Viruses and Core Microbiome Analysis in Artisanal Colonial Salami-Type Dry-Fermented Sausages from Santa Catarina, Brazil

Microbial fermentation plays an important role in the manufacturing of artisanal sausages and can have major effects on product quality and safety. We used metagenomics and culture-dependent methods to study the presence of Hepatitis E virus (HEV) and Rotavirus-A (RV-A), and fungal and bacterial communities, in artisanal Colonial salami-type dry-fermented sausages in Santa Catarina state, Brazil. Lactic acid bacteria (LAB) and yeast dominated the microbiome. Latilactobacillus sakei and Debaryomyces hansenii were ubiquitous and the most abundant species. The DNA of some foodborne pathogens was found in very low concentrations although viable cells of most of these species were undetectable by cultivation methods. The characteristics of the raw material and hygiene of the artisanal sausage manufacturing process resulted in high loads of beneficial microorganisms and the absence of HEV and RV-A viruses as determined by RT-qPCR assays. In conclusion, high LAB load in sausages was more relevant to preventing pathogen growth than the ripening time and/or physicochemical characteristics. However, the presence of Clostridium spp. and other pathogens in some samples must be taken into account for the development of future preservation methods; appropriate LAB starter cultures and health surveillance are required in the production process to prevent foodborne outbreaks.