Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational Assessment of Chito-Oligosaccharides Interactions with Plasma Proteins

It is widely rec ognized that chitin and chitosan are potential sources of bioactive materials and that their oligosaccharides reveal various biological activities (including antimicrobial) that are correlated with their structures and physicochemical properties. This study uses the molecular docking approach to assess the interactions of small chito-oligosaccharides (MW< 1500 Da) with plasma proteins in order to obtain information regarding their fate of distribution in the human organism. There are favorable interactions of small chito-oligomers with plasma proteins, the interactions with human serum albumin being stronger than those with α-1-acid glycoprotein. The interaction energies increase with increasing the molecular weight, decrease with increasing deacetylation degrees and are reliant on the deacetylation pattern. This study could inform the application of chito-oligosaccharides with varying molecular weights, degrees, and patterns of deacetylation in human health.
Shaping Ability and Debris Extrusion of New Rotary Nickel-Titanium Root Canal Instruments

The aim was to evaluate the canal straightening and the amount of apically extruded debris associated with five rotary nickel-titanium when preparing curved root canals. A total of 100 root canals in extracted human teeth (angles of curvatures 20°–30°; radii 5.9–13.5 mm) were divided into five groups (n = 20/group). The groups were balanced with respect to the angle and the radius of canal curvature. The root canals were prepared using conventional austenite 55-NiTi alloy instruments F360, F6 SkyTaper (both Komet, Lemgo, Germany), and the heat-treated NiTi Jizai, Silk-Complex and Silk-Standard instruments (all Mani, Tochigi, Japan) to an apical size 25. The amount of extruded debris was assessed with a micro balance. Statistical analysis was performed using Kruskal–Wallis test with Bonferroni correction at a significance level of p < 0.05. During canal preparation, neither instrument fractures nor procedural preparation errors were noticed. Regarding canal straightening, the use of Jizai instruments resulted in the significantly lowest straightening (p < 0.05), while no significant differences were obtained between all other groups (p > 0.05). Regarding the amount of apically extruded debris, no significant differences between all groups were obtained (p > 0.05). Within the limitations of this study, all instruments performed well, and especially the Jizai instruments showed an excellent shaping ability.
Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone

ABSTRACT Background Environmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified. Objectives The objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes. Methods In a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations. Results The 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L: M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (β: –0.08; 95% CI: –0.14, –0.02) and WLZ (β: –0.03; 95% CI: –0.06, –0.01) were negatively associated with GI score. A high GD score (β: 0.36; 95% CI: 0.08, 0.64) and low AAT (β: –1.35; 95% CI: –2.35, –0.36) were associated with recovery from MAM. Conclusions Scores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.
Functional genomic analyses highlight a shift in Gpr17‐regulated cellular processes in oligodendrocyte progenitor cells and underlying myelin dysregulation in the aged mouse cerebrum

Brain ageing is characterised by a decline in neuronal function and associated cognitive deficits. There is increasing evidence that myelin disruption is an important factor that contributes to the age‐related loss of brain plasticity and repair responses. In the brain, myelin is produced by oligodendrocytes, which are generated throughout life by oligodendrocyte progenitor cells (OPCs). Currently, a leading hypothesis points to ageing as a major reason for the ultimate breakdown of remyelination in Multiple Sclerosis (MS). However, an incomplete understanding of the cellular and molecular processes underlying brain ageing hinders the development of regenerative strategies. Here, our combined systems biology and neurobiological approach demonstrate that oligodendroglial and myelin genes are amongst the most altered in the ageing mouse cerebrum. This was underscored by the identification of causal links between signalling pathways and their downstream transcriptional networks that define oligodendroglial disruption in ageing. The results highlighted that the G‐protein coupled receptor Gpr17 is central to the disruption of OPCs in ageing and this was confirmed by genetic fate‐mapping and cellular analyses. Finally, we used systems biology strategies to identify therapeutic agents that rejuvenate OPCs and restore myelination in age‐related neuropathological contexts.
Impact of age on survival in radioiodine refractory differentiated thyroid cancer patients.

OBJECTIVE The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age. METHODS This single centre, retrospective study enrolled 155 patients diagnosed with RAIR-DTC. The primary end point was overall survival (OS) according to different cut-off (45,55,65,75 years). Secondary endpoints were progression free survival (PFS) and prognostic factors in patients under and over 65 years. RESULTS Median OS after RAIR diagnosis was 8.2 years (95% IC: 5.3-9.6). There was no difference according to age with a 65 (p=0.47) and 55 years old cut-off (p=0.28). Median OS was significantly improved before 45 years old (p=0,0043). After 75 years old, median OS significantly decrease (p= 0,0008). Median PFS was 2.1 years (95% CI: 0.8-3) in patients < 65 years, and 1 year in patients ≥ 65 years (95% CI: 0.8-1.55) with no statistical difference (p=0.22). There was no impact of age on PFS with any cut-off. In both groups, progressive disease despite 131I treatment reduced OS. In patients < 65, an interval of less than 3 years between the initial diagnosis and the diagnosis of RAIR metastatic disease was predictive of poor survival. In patients > 65, the presence of a mediastinum metastasis was a significant factor for mortality (HR: 4.55, 95% CI: 2.27-9.09). CONCLUSION In RAIR-DTC patients, a cut-off age of 65 years old was not a significant predictive factor of survival. 45 and 75 years old cut off were predictive for OS, but not PFS.
Human Papillomavirus and Cellular Pathways: Hits and Targets

The Human Papillomavirus (HPV) is the causative agent of different kinds of tumors, including cervical cancers, non-melanoma skin cancers, anogenital cancers, and head and neck cancers. Despite the vaccination campaigns implemented over the last decades, we are far from eradicating HPV-driven malignancies. Moreover, the lack of targeted therapies to tackle HPV-related tumors exacerbates this problem. Biomarkers for early detection of the pathology and more tailored therapeutic approaches are needed, and a complete understanding of HPV-driven tumorigenesis is essential to reach this goal. In this review, we overview the molecular pathways implicated in HPV infection and carcinogenesis, emphasizing the potential targets for new therapeutic strategies as well as new biomarkers.
In Vitro Evaluation of Desensitizing Agents Containing Bioactive Scaffolds of Nanofibers on Dentin Remineralization

This study evaluated the effect of the incorporation of bioactive nanofibers in desensitizing agents on dentin permeability. Sixty disks of dentin were randomly distributed in four groups (n = 15). Distribution was based on the desensitizing agents, fluoride varnish and self-etching adhesive, and the presence of nanofibers: C (self-etching adhesive Clearfil SE Bond), CN (Clearfil SE Bond with 1% nanofiber), D (Duraphat varnish), and DN (Duraphat varnish with 1% nanofiber). Dentin permeability was determined using hydraulic conductivity. For a qualitative analysis, confocal laser microscopy and scanning electron microscopy were performed. The C group showed the lowest hydraulic conductance (Lp%) (89.33), while the DN group showed the highest Lp% (116.06). No statistical significance was observed in the Lp% values in all groups after the treatment and 6% citric acid challenge (p > 0.239). In the images, the CN group presented a higher superficial and intratubular deposition. In addition, this group presented a more homogeneous dentin surface and wide occlusion of dentinal tubules than the other treatments. Despite there being no statistical differences among the treatments employed, the images showed that the CN group presented a higher surface and intratubular deposition compared to the other treatments, even after the acid challenge.
Novel Template Plasmids pCyaA’-Kan and pCyaA’-Cam for Generation of Unmarked Chromosomal cyaA’ Translational Fusion to T3SS Effectors in Salmonella

The type III secretion systems (T3SS) encoded in pathogenicity islands SPI-1 and SPI-2 are key virulence factors of Salmonella. These systems translocate proteins known as effectors into eukaryotic cells during infection. To characterize the functionality of T3SS effectors, gene fusions to the CyaA’ reporter of Bordetella pertussis are often used. CyaA’ is a calmodulin-dependent adenylate cyclase that is only active within eukaryotic cells. Thus, the translocation of an effector fused to CyaA’ can be evaluated by measuring cAMP levels in infected cells. Here, we report the construction of plasmids pCyaA’-Kan and pCyaA’-Cam, which contain the ORF encoding CyaA’ adjacent to a cassette that confers resistance to kanamycin or chloramphenicol, respectively, flanked by Flp recombinase target (FRT) sites. A PCR product from pCyaA’-Kan or pCyaA’-Cam containing these genetic elements can be introduced into the bacterial chromosome to generate gene fusions by homologous recombination using the Red recombination system from bacteriophage λ. Subsequently, the resistance cassette can be removed by recombination between the FRT sites using the Flp recombinase. As a proof of concept, the plasmids pCyaA’-Kan and pCyaA’-Cam were used to generate unmarked chromosomal fusions of 10 T3SS effectors to CyaA’ in S. Typhimurium. Each fusion protein was detected by Western blot using an anti-CyaA’ monoclonal antibody when the corresponding mutant strain was grown under conditions that induce the expression of the native gene. In addition, T3SS-1-dependent secretion of fusion protein SipA-CyaA’ during in vitro growth was verified by Western blot analysis of culture supernatants. Finally, efficient translocation of SipA-CyaA’ into HeLa cells was evidenced by increased intracellular cAMP levels at different times of infection. Therefore, the plasmids pCyaA’-Kan and pCyaA’-Cam can be used to generate unmarked chromosomal cyaA’ translational fusion to study regulated expression, secretion and translocation of Salmonella T3SS effectors into eukaryotic cells.
A systematic review and meta‐analysis of perforator flaps in plantar defects: Risk analysis of complications

The purpose of this study was to identify the risk factors for complications of perforator flaps in plantar reconstruction. A systematic review was performed by searching the PubMed, Cochrane Library, MEDLINE, and EMBASE databases from their inception date up to October 2020. Only studies on reconstructing plantar defects with perforator flaps were included, and specific data were required for each patient in the included studies. A total of 14 studies involving 111 flaps were identified and included in the meta‐analysis. Our meta‐analysis identified two risk factors for postoperative complications: flap size over 50 cm2 (risk ratio [RR] = 3.12; P = .02), diabetes mellitus foot (RR = 3.26; P = .03). No significant differences were found regarding heel defects (P = .34), single perforator (P = .57), age older than 60 years (P = .19), chronic aetiology (P = .13), trauma (P = .33), tumour resection (P = .60), ulcer (P = .84), and burn (P = .76). Although more high‐quality studies with adequate sample sizes are needed, this meta‐analysis indicated that flap size over 50 cm2 and diabetes mellitus foot were significant risk factors for postoperative complications of perforator flaps in plantar reconstruction.
Synthesis of New Aryl-substituted Tandospirone and Epiboxidine Analogues and Isoxazoline Derivatives

Synthesis of New Aryl-substituted Tandospirone and Epiboxidine Analogues and Isoxazoline Derivatives Irem Kulu a , Gokce Goksu a , Bilgesu Onur Sucu a , Asli Kopruceli a , Nuket Ocal a & Dieter E. Kaufmann b a Yildiz Technical University, Faculty of Science and Arts, Department of Chemistry, Davutpasa Campus, 34220, Esenler, Istanbul, Turkey b Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstr. 6, D-38678, Clausthal-Zellerfeld, Germany
A review of functionalised bacterial cellulose for targeted biomedical fields

Bacterial cellulose (BC), which can be produced by microorganisms, is an ideal biomaterial especially for tissue engineering and drug delivery systems thanks to its properties of high purity, biocompatibility, high mechanical strength, high crystallinity, 3 D nanofiber structure, porosity and high-water holding capacity. Therefore, wide ranges of researches have been done on the BC production process and its structural and physical modifications to make it more suitable for certain targeted biomedical applications thoroughly. BC’s properties such as mechanical strength, pore diameter and porosity can be tuned in situ or ex situ processes by using various polymer and compounds. Besides, different organic or inorganic compounds that support cell attachment, proliferation and differentiation or provide functions such as antimicrobial effectiveness can be gained to its structure for targeted application. These processes not only increase the usage options of BC but also provide success for mimicking the natural tissue microenvironment, especially in tissue engineering applications. In this review article, the studies on optimisation of BC production in the last decade and the BC modification and functionalisation studies conducted for the three main perspectives as tissue engineering, drug delivery and wound dressing with diverse approaches are summarized.
Proteomics Approach of Rapamycin Anti-Tumoral Effect on Primary and Metastatic Canine Mammary Tumor Cells In Vitro

Rapamycin is an antifungal drug with antitumor activity and acts inhibiting the mTOR complex. Due to drug antitumor potential, the aim of this study was to evaluate its effect on a preclinical model of primary mammary gland tumors and their metastases from female dogs. Four cell lines from our cell bank, two from primary canine mammary tumors (UNESP-CM1, UNESP-CM60) and two metastases (UNESP-MM1, and UNESP-MM4) were cultured in vitro and investigated for rapamycin IC50. Then, cell lines were treated with rapamycin IC50 dose and mRNA and protein were extracted in treated and non-treated cells to perform AKT, mTOR, PTEN and 4EBP1 gene expression and global proteomics by mass spectrometry. MTT assay demonstrated rapamycin IC50 dose for all different tumor cells between 2 and 10 μM. RT-qPCR from cultured cells, control versus treated group and primary tumor cells versus metastatic tumor cells, did not shown statistical differences. In proteomics were found 273 proteins in all groups, and after data normalization 49 and 92 proteins were used for statistical analysis for comparisons between control versus rapamycin treatment groups, and metastasis versus primary tumor versus metastasis rapamycin versus primary tumor rapamycin, respectively. Considering the two statistical analysis, four proteins, phosphoglycerate mutase, malate dehydrogenase, l-lactate dehydrogenase and nucleolin were found in decreased abundance in the rapamycin group and they are related with cellular metabolic processes and enhanced tumor malignant behavior. Two proteins, dihydrolipoamide dehydrogenase and superoxide dismutase, also related with metabolic processes, were found in higher abundance in rapamycin group and are associated with apoptosis. The results suggested that rapamycin was able to inhibit cell growth of mammary gland tumor and metastatic tumors cells in vitro, however, concentrations needed to reach the IC50 were higher when compared to other studies.
2.4 GHz GaN HEMT Class-F Synchronous Rectifier Using an Independent Second Harmonic Tuning Circuit

This paper proposes a class-F synchronous rectifier using an independent second harmonic tuning circuit for the power receiver of 2.4 GHz wireless power transmission systems. The synchronous rectifier can be designed by inverting the RF output port to the RF input port of the pre-designed class-F power amplifier based on time reversal duality. The design of the class-F power amplifier deploys an independent second harmonic tuning circuit in the matching networks to individually optimize the impedances of the fundamental and the second harmonic. The synchronous rectifier at the 2.4 GHz frequency is designed and implemented using a 6 W gallium nitride high electron mobility transistor (GaN HEMT). Peak RF-dc conversion efficiency of the rectifier of 69.6% is achieved with a dc output power of about 7.8 W, while the peak drain efficiency of the class-F power amplifier is 72.8%.
Pest Activity and Protection Practices: Four Decades of Transformation in Quebec Apple Orchards

Simple Summary Commercial orchards from Quebec (Canada) were followed for over 40 years to track patterns of activity of major fruit pests, fruit damage and impacts (environmental and financial) of pesticide applications. Some insects (as expected) were more prevalent in the insecticide-free orchard than in commercial orchards, while others were (surprisingly) more prevalent in commercial orchards or as prevalent in both orchard types. Annual fruit damage in the insecticide-free orchard was extremely high (as much as 98% for a single pest) and mostly from the apple maggot, the plum curculio and the codling moth. In commercial orchards, fruit damage was ten times less important and mostly from the plum curculio, the tarnished plant bug and the oblique-banded leafroller. The number of registered pesticides, the number of applications and the total cost of pesticides gradually increased from 1977 to 2019, while the environmental and health risks followed a downward trend for most pesticide categories. The historical trends presented here were likely modulated by external factors such as the pesticide regulatory framework, the arrival of non-native insects and climate change. Abstract A group of commercial orchards from Quebec (Canada) was followed from 1977 to 2019 as part of a project to implement Integrated Pest Management (IPM) practices. Collected data comprised activity of major fruit pests (from monitoring traps), fruit damage at harvest and pesticide applications, from which the annual costs and impacts of protection programs over 42 years were calculated. Activity and fruit damage in commercial orchards were compared to patterns observed in a reference insecticide-free orchard. Some insects (European apple sawfly, codling moth, apple maggot) were more prevalent in the insecticide-free orchard than in commercial orchards, while others were more prevalent in commercial orchards (oblique-banded leafroller) or as prevalent in both orchard types (tarnished plant bug). Annual fruit damage in the insecticide-free orchard was mostly from the apple maggot (up to 98%), the plum curculio (up to 90%) and the codling moth (up to 58%). The average situation was different in commercial orchards, whose damage was mostly from the plum curculio (up to 7.6%), the tarnished plant bug (up to 7.5%) and the oblique-banded leafroller (up to 1.7%). While the number of registered pesticides, the number of applications and the total cost of pesticides gradually increased from 2002 to 2019, the risks incurred, as measured by indicators of environmental and health impacts, followed a downward trend for insecticides and acaricides and varied slightly for fungicides.
Sonographic Features Differentiating Follicular Thyroid Cancer from Follicular Adenoma–A Meta-Analysis

Simple Summary The risk of thyroid malignancy assessment may include certain ultrasound features. The analysis is lacking for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). Our meta-analysis aimed to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. Based on twenty studies describing sonographic features of 10,215 nodules, we found that the most crucial feature associated with an increased risk of FTC were tumor protrusion (odds ratios—OR = 10.19), microcalcifications or mixed type of calcifications: 6.09, irregular margins: 5.11, marked hypoechogenicity: 4.59, and irregular shape: 3.6. Abstract Certain ultrasound features are associated with an increased risk of thyroid malignancy. However, they were studied mainly in papillary thyroid cancers (PTCs); these results cannot be simply extrapolated for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). The aim of our study was to perform a meta-analysis to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. We searched thirteen databases from January 2006 to December 2020 to find all relevant, full-text journal articles written in English. Analyses assessed the accuracy of malignancy detection in case of follicular lesions, potentially differentiating FTA and FTC included the odds ratio (OR), sensitivity, specificity, positive and negative predictive values. A random-effects model was used to summarize collected data. Twenty studies describing sonographic features of 10,215 nodules met the inclusion criteria. The highest overall ORs to increase the risk of malignancy were calculated for tumor protrusion (OR = 10.19; 95% confidence interval: 2.62–39.71), microcalcifications or mixed type of calcifications (coexisting micro and macrocalcifications): 6.09 (3.22–11.50), irregular margins: 5.11 (2.90–8.99), marked hypoechogenicity: 4.59 (3.23–6.54), and irregular shape: 3.6 (1.19–10.92). The most crucial feature associated with an increased risk of FTC is capsule protrusion, followed by the presence of calcifications, irrespectively of their type.