Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnosing Autism Spectrum Disorders in Deaf Children Using Two Standardised Assessment Instruments: The ADIR-Deaf Adaptation and the ADOS-2 Deaf Adaptation

The aim was to investigate the agreement between the ADI-R Deaf adaptation and ADOS-2 Deaf adaptation overall diagnostic categorisation for autism (AUT) and a wider threshold to include autism spectrum (ASD) in a cohort of deaf children with and without ASD. We compared results of the instruments used on their own and when combined and propose standard criteria for the combined use of the ADI-R Deaf adaptation and ADOS-2 Deaf adaptation for use with deaf children. In total, 116 deaf children had a Gold standard NICE guideline assessment; 58 diagnosed with ASD and 58 without ASD, and for both groups a blinded informant based ADI-R Deaf adaptation and direct assessment using the ADOS-2 Deaf adaptation were separately completed. There was moderate agreement between the ADI-R Deaf adaptation and ADOS-2 Deaf adaptation for the wider threshold of ASD (Kappa, 0.433). To achieve the lowest number of false negatives, the most successful assessment tool approach is using the wider threshold of ASD with either ADI-R Deaf adaptation or ADOS-2-Deaf adaptation (95% sensitivity). This compares with 88% for the ADI-R Deaf adaptation alone and 74% for the ADOS-2-Deaf adaptation alone (wider threshold of ASD). To achieve a low number of false positives, the most successful assessment tool approach is a combination of ADI-R Deaf adaptation and ADOS-2- Deaf adaptation (using the narrow threshold of autism for both) (95% specificity). This compares with 83% for the ADI-R Deaf adaptation alone and 81% for the ADOS-2-Deaf adaptation (narrow threshold) alone. This combination is therefore recommended in specialist clinics for diagnostic assessment in deaf children.
Prevalence of Psychological Distress and Associated Factors in Nursing Students during the COVID-19 Pandemic: A Cross-Sectional Study

Little is known about psychological distress and its associated factors during the COVID-19 pandemic among nursing students, especially during the initial spread. The present study aimed to investigate the prevalence of psychological distress among Japanese nursing students after the first semester of 2020 with shifted classes and practice online. Furthermore, we examined whether factors such as health issues and resilience were associated with psychological distress. The data were obtained from a cross-sectional, self-administered questionnaire survey at a Japanese nursing college from September to November 2020 (n = 289). We collected data such as sociodemographic variables, medical history, insomnia, and resilience (Bidimensional Resilience Scale). Psychological distress was measured using the K6 scale (scores ≥ 5). The prevalence of psychological distress was 58.5%. The multivariate Poisson regression analysis found a negative association between innate resilience factors, and positive associations between medical history, insomnia, and psychological distress. The present study showed that more than half of the study participants experienced high levels of psychological distress. Our results suggest the importance of monitoring mental health among nursing students, focusing not only on health issues, but also personality components such as innate resilience during the prolonged COVID-19 pandemic.
Physicochemical Characteristics of Chitosan-Based Hydrogels Containing Albumin Particles and Aloe vera Juice as Transdermal Systems Functionalized in the Viewpoint of Potential Biomedical Applications

In recent years, many investigations on the development of innovative dressing materials with potential applications, e.g., for cytostatics delivery, have been performed. One of the most promising carriers is albumin, which tends to accumulate near cancer cells. Here, chitosan-based hydrogels containing albumin spheres and Aloe vera juice, designed for the treatment of skin cancers or burn wounds resulting from radiotherapy, were developed. The presence of albumin in hydrogel matrices was confirmed via Fourier transform infrared (FT-IR) and Raman spectroscopy. Albumin spheres were clearly visible in microscopic images. It was proved that the introduction of albumin into hydrogels resulted in their increased resistance to the tensile load, i.e., approximately 30% more force was needed to break such materials. Modified hydrogels showed approximately 10% more swelling ability. All hydrogels were characterized by hydrophilicity (contact angles were <90°) which may support the regeneration of epithelial cells and non-cytotoxicity towards murine fibroblasts L929 and released Aloe vera juice more effectively in an acidic environment than in a neutral one wherein spheres introduced into the hydrogel matrix extended the release time. Thus, the developed materials, due to their chemical composition and physicochemical properties, constitute promising materials with great application potential for biomedical purposes.
Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies

In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (1–4) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC50) and SARS-CoV-2 inhibitory concentrations (IC50). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2, gallic acid 3, and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC50 values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.
The Phenoxyalkyltriazine Antagonists for 5-HT6 Receptor with Promising Procognitive and Pharmacokinetic Properties In Vivo in Search for a Novel Therapeutic Approach to Dementia Diseases

Among the serotonin receptors, one of the most recently discovered 5-HT6 subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. However, none of its selective ligands have reached the pharmaceutical market yet. Recently, a new chemical class of potent 5-HT6 receptor agents, the 1,3,5-triazine-piperazine derivatives, has been synthesized. Three members, the ortho and meta dichloro- (1,2) and the unsubstituted phenyl (3) derivatives, proved to be of special interest due to their high affinities (1,2) and selectivity (3) toward 5-HT6 receptor. Thus, a broader pharmacological profile for 1–3, including comprehensive screening of the receptor selectivity and drug-like parameters in vitro as well as both, pharmacokinetic and pharmacodynamic properties in vivo, have been investigated within this study. A comprehensive analysis of the obtained results indicated significant procognitive-like activity together with beneficial drug-likeness in vitro and pharmacokinetics in vivo profiles for both, (RS)-4-[1-(2,3-dichlorophenoxy)propyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (2) and (RS)-4-(4-methylpiperazin-1-yl)-6-(1-phenoxypropyl)-1,3,5-triazin-2-amine (3), but insensibly predominant for compound 2. Nevertheless, both compounds (2 and 3) seem to be good Central Nervous System drug candidates in search for novel therapeutic approach to dementia diseases, based on the 5-HT6 receptor target.
Butyrylcholinesterase–Protein Interactions in Human Serum

Measuring various biochemical and cellular components in the blood is a routine procedure in clinical practice. Human serum contains hundreds of diverse proteins secreted from all cells and tissues in healthy and diseased states. Moreover, some serum proteins have specific strong interactions with other blood components, but most interactions are probably weak and transient. One of the serum proteins is butyrylcholinesterase (BChE), an enzyme existing mainly as a glycosylated soluble tetramer that plays an important role in the metabolism of many drugs. Our results suggest that BChE interacts with plasma proteins and forms much larger complexes than predicted from the molecular weight of the BChE tetramer. To investigate and isolate such complexes, we developed a two-step strategy to find specific protein–protein interactions by combining native size-exclusion chromatography (SEC) with affinity chromatography with the resin that specifically binds BChE. Second, to confirm protein complexes′ specificity, we fractionated blood serum proteins by density gradient ultracentrifugation followed by co-immunoprecipitation with anti-BChE monoclonal antibodies. The proteins coisolated in complexes with BChE were identified by mass spectroscopy. These binding studies revealed that BChE interacts with a number of proteins in the human serum. Some of these interactions seem to be more stable than transient. BChE copurification with ApoA-I and the density of some fractions containing BChE corresponding to high-density lipoprotein cholesterol (HDL) during ultracentrifugation suggest its interactions with HDL. Moreover, we observed lower BChE plasma activity in individuals with severely reduced HDL levels (≤20 mg/dL). The presented two-step methodology for determination of the BChE interactions can facilitate further analysis of such complexes, especially from the brain tissue, where BChE could be involved in the pathogenesis and progression of AD.
Secondary Metabolites with Anti-Inflammatory Activities from One Actinobacteria Amycolatopsis taiwanensis

Phytochemical investigation and chromatographic separation of extracts from one new actinobacteria strain Amycolatopsis taiwanensis that was isolated from soil of Yilan township, in the north of Taiwan, led to the isolation of nine new compounds, amycolataiwanensins A–I (1–9, resp.), and one new natural product, namely amycolataiwanensin J (10). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic-data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3, 5, 7 and 8 exhibited potent anti-NO production activity, with IC50 values of 17.52, 12.31, 17.81 and 13.32 μM, respectively, compared to that of quercetin, an iNOS inhibitor with an IC50 value of 35.94 μM. This is the first report on indole metabolite from the genus Amycolatopsis.
Individual bacteria in structured environments rely on phenotypic resistance to phage

Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic resistance to phages remains a concern. In vitro, bacteria evolve genetic resistance, preventing phage adsorption or degrading phage DNA. In natural environments, evolved resistance is lower possibly because the spatial heterogeneity within biofilms, microcolonies, or wall populations favours phenotypic survival to lytic phages. However, it is also possible that the persistence of genetically sensitive bacteria is due to less efficient phage amplification in natural environments, the existence of refuges where bacteria can hide, and a reduced spread of resistant genotypes. Here, we monitor the interactions between individual planktonic bacteria in isolation in ephemeral refuges and bacteriophage by tracking the survival of individual cells. We find that in these transient spatial refuges, phenotypic resistance due to reduced expression of the phage receptor is a key determinant of bacterial survival. This survival strategy is in contrast with the emergence of genetic resistance in the absence of ephemeral refuges in well-mixed environments. Predictions generated via a mathematical modelling framework to track bacterial response to phages reveal that the presence of spatial refuges leads to fundamentally different population dynamics that should be considered in order to predict and manipulate the evolutionary and ecological dynamics of bacteria–phage interactions in naturally structured environments.
Fluorescein Hydrazide-Appended Metal–Organic Framework as a Chromogenic and Fluorogenic Chemosensor for Mercury Ions

In this work, we prepared a fluorescein hydrazide-appended Ni(MOF) (Metal–Organic Framework) [Ni3(BTC)2(H2O)3]·(DMF)3(H2O)3 composite, FH@Ni(MOF). This composite was well-characterized by PXRD (powder X-ray diffraction), FT-IR (Fourier transform infrared spectroscopy), N2 adsorption isotherm, TGA (thermogravimetric analysis), XPS (X-ray photoelectron spectroscopy), and FESEM (field emission scanning electron microscopy). This composite was then tested with different heavy metals and was found to act as a highly selective and sensitive optical sensor for the Hg2+ ion. It was found that the aqueous emulsion of this composite produces a new peak in absorption at 583 nm, with a chromogenic change to a pink color visible to the naked eye upon binding with Hg2+ ions. In emission, it enhances fluorescence with a fluorogenic change to green fluorescence upon complexation with the Hg2+ ion. The binding constant was found to be 9.4 × 105 M−1, with a detection limit of 0.02 μM or 5 ppb. This sensor was also found to be reversible and could be used for seven consecutive cycles. It was also tested for Hg2+ ion detection in practical water samples from ground water, tap water, and drinking water.
Effects of Probiotics, Prebiotics, and Synbiotics on Uremic Toxins, Inflammation, and Oxidative Stress in Hemodialysis Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The dysbiosis of gut microbiota may cause many complications in patients with end-stage renal disease, which may be alleviated by probiotic, prebiotic, and synbiotic supplementation. The aim of this systematic review and meta-analysis was to assess the effects of these supplementations on circulatory uremic toxins, biomarkers of inflammation, and oxidative stress in hemodialysis patients. We searched the EMBASE, MEDLINE, Web of Science, and Cochrane Library databases until 8 August 2021. Randomized controlled trials evaluating adult patients receiving hemodialysis were included. The pooled results from 23 studies with 931 hemodialysis patients indicated that interventions significantly decreased the circulating levels of p-cresyl sulfate (standardized mean difference (SMD): 0.38; 95% CI: −0.61, −0.15; p = 0.001), endotoxins (SMD: −0.58; 95% CI: −0.99, −0.18; p = 0.005), malondialdehyde (SMD: −1.16; 95% CI: −1.81, −0.52; p = 0.0004), C-reactive proteins (CRP) (SMD: −0.61; 95% CI: −0.99, −0.23; p = 0.002), and interleukin 6 (SMD: −0.92; 95% CI: −1.51, −0.33; p = 0.002), and improved the total antioxidant capacity (SMD: 0.89; 95% CI: 0.49, 1.30; p < 0.0001) and glutathione (SMD: 0.40; 95% CI: 0.14, 0.66; p = 0.003) when compared to the placebo group. Our results suggest that treatment with probiotics, prebiotics, and synbiotics may help alleviate uremic toxin levels, oxidative stress, and the inflammatory status in hemodialysis patients.
Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

Simple Summary Vimentin is an important filamentous protein providing structural and functional support to the cell. During initial stages of cancer development, vimentin concentration is very low, however, it increases when cancer starts to invade the surrounding areas. This review highlights the varied roles of vimentin in cancer growth and its spread to distant areas of the body. We have tried to explore the potential new areas of research related to the role of vimentin in cancer progression. We have also highlighted the reported damage to the vimentin gene in cancers, although how the damaged vimentin helps in cancer growth and spread is not known. We propose that latest technologies should be employed to medicinally target vimentin to reduce the cancer growth and its spread thereby helping to increase treatment outcomes and patients’ survival. Abstract Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity.
Civil Liability of Regional Health Services: The Case of the Piedmont Region

Civil liability represents one of the main responsibilities for healthcare facilities; it is the legal responsibility of paying money for damage to a person’s health. Even though this responsibility plays a key role in the economic sustainability of healthcare facilities, the literature does not enough investigate this responsibility in regional health services. The paper aims to define the evolution of compensation models for health civil liability adopted by regional health services. Through a longitudinal case study, the paper investigates the compensation model by a leading regional health service. The finding highlights the evolution of the compensation model for health civil liability adopted by a leading Regional Health Service from 1990 to 2021. It describes a transition from an insurance model to a mixed model based on self-coverage up to a set economic level, an insurance policy with self-insurance retention and deductible for all claims. The research contributes to the literature and practice throughout the definition of a compensation model for damages based on self-insurance of regional health service and insurance policies. The research promotes a compensation model used by a leading regional health service.
Analysis of Flavonoid Metabolites in Watercress (Nasturtium officinale R. Br.) and the Non-Heading Chinese Cabbage (Brassica rapa ssp. chinensis cv. Aijiaohuang) Using UHPLC-ESI-MS/MS

Flavonoids from plants play an important role in our diet. Watercress is a special plant that is rich in flavonoids. In this study, four important watercress varieties were compared with non-heading Chinese cabbage by ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS). A total of 132 flavonoid metabolites (including 8 anthocyanins, 2 dihydroflavone, 3 dihydroflavonol, 1 flavanols, 22 flavones, 11 flavonoid carbonosides, 82 flavonols, and 3 isoflavones) were detected. Flavonoid metabolites varied widely in different samples. Both the non-heading Chinese cabbage and the variety of watercress from Guangdong, China, had their own unique metabolites. This work is helpful to better understand flavonoid metabolites between the non-heading Chinese cabbage and the other four watercress varieties, and to provide a reliable reference value for further research.
Evaluation of Stress Distribution and Force in External Hexagonal Implant: A 3-D Finite Element Analysis

Purpose: To analyze the stress distribution and the direction of force in external hexagonal implant with crown in three different angulations. Materials and Methods: A total of 60 samples of geometric models were used to analyze von Mises stress and direction of force with 0-, 5-, and 10-degree lingual tilt. Von Mises stress and force distribution were evaluated at nodes of hard bone, and finite element analysis was performed using ANSYS 12.1 software. For calculating stress distribution and force, we categorized and labeled the groups as Implant A1, Implant A2, and Implant A3, and Implant B1, Implant B2, and Implant B3 with 0-, 5-, and 10-degree lingual inclinations, respectively. Inter- and intra-group comparisons were performed using ANOVA test. A p-value of ≤0.05 was considered statistically significant. Results: In all the three models, overall maximum stress was found in implant model A3 on the implant surface (86.61), and minimum was found on model A1 in hard bone (26.21). In all the three models, the direction of force along three planes was maximum in DX (0.01025) and minimum along DZ (0.002) direction with model B1. Conclusion: Maximum von Mises stress and the direction of force in axial direction was found at the maximum with the implant of 10 degrees angulation. Thus, it was evident that tilting of an implant influences the stress concentration and force in external hex implants.