Miracle-dz/UniFAR-FTUs huggingface dataset:
The Transverse Infrapatellar View: A New Ultrasound Technique to Measure Distal Femoral Cartilage Thickness

To examine the reliability and face validity of ultrasound (US) measurements of distal femoral cartilage thickness (CT) using the infrapatellar view (IPV) with knee extension compared to the traditional suprapatellar view (SPV) with knee hyperflexion in young asymptomatic participants and patients with painful knee osteoarthritis (KOA).
Duration of Efficacy Increases with the Repetition of Botulinum Toxin A Injections in Primary Axillary Hyperhidrosis: A 15-year Study in 117 Patients.

Changes in the duration of efficacy of botulinum toxin A injections for primary axillary hyperhidrosis have not been studied in depth. The aim of this study was to assess such changes. In a retrospective cohort of 220 patients, seen over a 17-year period, duration of efficacy was recorded, including duration of efficacy of first and last injections. Of 220 patients, 117 fulfilled the study criteria (79 females and 38 males, age 17-79 years, mean age 38.3 years). Patients received 3-24 injections (mean 5.5). The duration of efficacy of the first injections was 3 weeks to 30 months (median 6 months), and the duration of efficacy of the final injections was 3 weeks to 66 months (median 8 months) (p < 0.001). An increase in duration of efficacy occurred in 62% of patients. Of the 20 patients with a follow up ≥10 years, the mean number of treatments was 8.25/patient; in 18 of these patients the duration of efficacy increased by > 50%. In conclusion, repeated botulinum toxin A injections lead to an increase in duration of efficacy without secondary decrease.
Combinatorial ixazomib and belinostat therapy induces NFE2L2‐dependent apoptosis in Hodgkin and T‐cell lymphoma

Ixazomib activity and transcriptomic analyses previously established in T cell (TCL) and Hodgkin (HL) lymphoma models predicted synergistic activity for histone deacetylase (HDAC) inhibitory combination. In this present study, we determined the mechanistic basis for ixazomib combination with the HDAC inhibitor, belinostat, in HL and TCL cells lines (ixazomib‐sensitive/resistant clones) and primary tumour cells. In ixazomib‐treated TCL and HL cells, transient inhibition followed by full recovery of proteasomal activity observed was accompanied by induction of proteasomal gene expression with NFE2L2 (also termed NRF2) as a prominent upstream regulator. Downregulation of both NFE2L2 and proteasomal gene expression (validated by quantitative real time polymerase chain reaction) occurred with belinostat treatment in Jurkat and L428 cells. In addition, CRISPR/Cas9 mediated knockdown of NFE2L2 in Jurkat cells resulted in a significant decrease in cell viability with ixazomib compared with untreated control cells. Using transcriptomic and proteasomal activity evaluation of ixazomib, belinostat, or ixazomib + belinostat treated cells, we observed that NFE2L2, proteasome gene expression and functional recovery were abrogated by ixazomib + belinostat combination, resulting in synergistic drug activity in ixazomib‐sensitive and ‐resistant cell lines and primary cells. Altogether, these results suggest that the synergistic activity of ixazomib + belinostat is mediated via inhibition NFE2L2‐dependent proteasomal recovery and extended proteasomal inhibition culminating in increased cell death.
Docosahexaenoic acid and hydroxytyrosol co-administration fully prevents liver steatosis and related parameters in mice subjected to high-fat diet: A molecular approach.

Attenuation of high-fat diet (HFD)-induced liver steatosis is accomplished by different nutritional interventions. Considering that the n-3 PUFA docosahexaenoic acid (DHA) modulates lipid metabolism and the antioxidant hydroxytyrosol (HT) diminishes oxidative stress underlying fatty liver, it is hypothesized that HFD-induced steatosis is suppressed by DHA and HT co-administration. Male C57BL/6J mice were fed a control diet (CD; 10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks, without and with supplementation of DHA (50 mg/kg/day), HT (5 mg/kg/day) or both. The combined DHA + HT protocol fully prevented liver steatosis and the concomitant pro-inflammatory state induced by HFD, with suppression of lipogenic and oxidative stress signaling, recovery of fatty acid oxidation capacity and enhancement in resolvin availability affording higher inflammation resolution capability. Abrogation of HFD-induced hepatic steatosis by DHA and HT co-administration represents a crucial therapeutic strategy eluding disease progression into stages lacking efficacious handling at present time.
The miRFIB-Score: A Serological miRNA-Based Scoring Algorithm for the Diagnosis of Significant Liver Fibrosis

Background: The current diagnosis of early-stage liver fibrosis often relies on a serological or imaging-based evaluation of the stage of fibrosis, sometimes followed by an invasive liver biopsy procedure. Novel non-invasive experimental diagnostic tools are often based on markers of hepatocyte damage, or changes in liver stiffness and architecture, which are late-stage characteristics of fibrosis progression, making them unsuitable for the diagnosis of early-stage liver fibrosis. miRNAs control hepatic stellate cell (HSC) activation and are proposed as relevant diagnostic markers. Methods: We investigated the possibility of circulating miRNAs, which we found to be dysregulated upon HSC activation, to mark the presence of significant liver fibrosis (F ≥ 2) in patients with chronic alcohol abuse, chronic viral infection (HBV/HCV), and non-alcoholic fatty liver disease (NAFLD). Results: miRNA-profiling identified miRNA-451a, miRNA-142-5p, Let-7f-5p, and miRNA-378a-3p to be significantly dysregulated upon in vitro HSC activation, and to be highly enriched in their extracellular vesicles, suggesting their potential use as biomarkers. Analysis of the plasma of patients with significant liver fibrosis (F ≥ 2) and no or mild fibrosis (F = 0–1), using miRNA-122-5p and miRNA-29a-3p as positive control, found miRNA-451a, miRNA-142-5p, and Let-7f-5p, but not miRNA-378a-3p, able to distinguish between the two patient populations. Using logistic regression analysis, combining all five dysregulated circulating miRNAs, we created the miRFIB-score with a predictive value superior to the clinical scores Fibrosis-4 (Fib-4), aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and AST to platelet ratio index (APRI). The combination of the miRFIB-score with circulating PDGFRβ-levels further increased the predictive capacity for the diagnosis of significant liver fibrosis. Conclusions: The miRFIB- and miRFIBp-scores are accurate tools for the diagnosis of significant liver fibrosis in a heterogeneous patient population.
Why now? Examining antecedents for substance use initiation among African American adolescents

Abstract Current adolescent substance use risk models have inadequately predicted use for African Americans, offering limited knowledge about differential predictability as a function of developmental period. Among a sample of 500 African American youth (ages 11–21), four risk indices (i.e., social risk, attitudinal risk, intrapersonal risk, and racial discrimination risk) were examined in the prediction of alcohol, marijuana, and cigarette initiation during early (ages 11–13), mid (ages 16–18), and late (ages 19–21) adolescence. Results showed that when developmental periods were combined, racial discrimination was the only index that predicted initiation for all three substances. However, when risk models were stratified based on developmental period, variation was found within and across substance types. Results highlight the importance of racial discrimination in understanding substance use initiation among African American youth and the need for tailored interventions based on developmental stage.
Cellular pharmacokinetics and pharmacodynamics mechanisms of ginkgo diterpene lactone and its modulation of P-glycoprotein expression in human SH- SY5Y cells.

Ginkgo diterpene lactone (GDL) is the raw material for ginkgo diterpene lactone meglumine injection (GDLI), which is used for treating cerebral ischemia. The aims of this study were to explore cellular pharmacokinetic (PK) of GDL in whole cell and subcellular fractions, detect cellular pharmacodynamic (PD) on the human SH-SY5Y cells induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Firstly, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the amount of ginkgolide A (GA), B (GB) and K (GK) in cellular/subcellular samples. Then, phosphatidylserine (PS) and mitochondria membrane potential (MMP) were assayed to evaluate the extent of apoptosis effect. The study showed that the cellular/subcellular accumulation of GA and GB were increased in a concentration dependent manner, GA, GB in cytosol was the highest among these subcellular organelles. Meanwhile, GDL also attenuated the OGD/R-induced increases in the percentage of apoptotic and MMP. In addition, verapamil increased the rate and amount of GA and GB entering cellular/subcellular compartments through inhibition of P-glycoprotein (P-gp) activity, and promoted the protective effect of GDL. The present study reported the cellular pharmacokinetics profiles of GA and GB in normal and OGD/R-induced SH-SY5Y cells in vitro for the first time, which provided valuable information for clinical safety application.
Bangor Business School Working Paper ( C 24 ) BBSWP / 11 / 011 ‘ Too Systemically Important to Fail ’ in Banking By

The recent financial turmoil and bailouts of a large number of banks have raised substantial policy concerns regarding banks that are considered ‘Too-systemicallyimportant-to-fail’ (TSITF). In this paper, we exploit a sample of bank mergers and acquisitions (M&As) between 1997 and 2008 in nine EU economies and use an innovative setup derived from the frontier literature to capture safety net subsidy effects and evaluate their ramifications for systemic risk. We focus on three closely related phenomena: First, we use frontier methods to extract information on whether banks deliberately pay premiums for being considered TSITF. Second, we incorporate the safety net subsidies derived from the frontier methods in a probit model to assess whether they affect the probability of a bank being rescued during the recent crisis. We find that safety net benefits derived from M&A activity have a significantly positive association with the rescue probability, suggesting the moral hazard issue in banking systems pre-crisis. Third, we do not find that gaining safety net subsidies leads to TSITF bank’s increased interdependence on its peer banks. From a policy perspective, the findings help understand whether banks exploit national safety nets and increase instability in the financial system.
Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort

Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.
Cyclin–CDK Complexes are Key Controllers of Capacitation-Dependent Actin Dynamics in Mammalian Spermatozoa

Mammalian spermatozoa are infertile immediately after ejaculation and need to undergo a functional maturation process to acquire the competence to fertilize the female egg. During this process, called capacitation, the actin cytoskeleton dramatically changes its organization. First, actin fibers polymerize, forming a network over the anterior part of the sperm cells head, and then it rapidly depolymerizes and disappears during the exocytosis of the acrosome content (the acrosome reaction (AR)). Here, we developed a computational model representing the actin dynamics (AD) process on mature spermatozoa. In particular, we represented all the molecular events known to be involved in AD as a network of nodes linked by edges (the interactions). After the network enrichment, using an online resource (STRING), we carried out the statistical analysis on its topology, identifying the controllers of the system and validating them in an experiment of targeted versus random attack to the network. Interestingly, among them, we found that cyclin-dependent kinase (cyclin–CDK) complexes are acting as stronger controllers. This finding is of great interest since it suggests the key role that cyclin–CDK complexes could play in controlling AD during sperm capacitation, leading us to propose a new and interesting non-genomic role for these molecules.
Fire cues trigger germination and stimulate seedling growth of grass species from Brazilian savannas.

PREMISE Although fire cues (high temperatures and smoke) influence seed germination in numerous species from fire-prone environments, their effects on seed germination of species from neotropical savannas are poorly understood. METHODS We exposed seeds of eight grass species from the Cerrado, the Brazilian savanna to heat-shock (80°C or 110°C for 5 min) and/or smoke water, and then set them to germinate in light or dark, at either summer (28°C/18°C) or winter (27°C/14°C) temperature regimes in an incubator. In addition, we evaluated the effects of smoke water on seedling root and shoot growth for four of the species. RESULTS Smoke interacted with the dark treatment to increase germination from 28% to 93% in Aristida recurvata and 77% to 95% in Aristida riparia. Smoke had no effect on germination of either of these species in the light. Heat-shock alone also promoted seed germination in A. recurvata. For Digitaria lehmanniana, smoke interacted with heat-shock to improve germination from 5% to 16%. In contrast, the fire treatments did not have any effect on the seed germination of the remaining five species. Smoke water stimulated root growth for A. riparia, A. recurvata, and Ctenium cirrosum but had no effect on their shoot growth. CONCLUSIONS The strong promotive effect of smoke on Aristida germination suggests that these species are fire-adapted. Aristida species have an active awn system, which facilitates seed burial, and the smoke and dark interaction would ensure buried seeds germinated post-fire. The species that showed no response to fire cues may either have adapted via alternative strategies or require different concentrations of smoke or levels of heat. This study is one of very few examples showing a positive germination and seedling growth response to smoke for species from neotropical savannas.
Effect of Transformational Leadership on Organizational Citizenship Behavior in Physical Education Teachers in Mashhad

This study aimed to investigate the effect of transformational leadership and organizational citizenship behavior. This study was a descriptive correlational study and in terms of purpose is applied research. The study population comprised of the physical education teachers in Mashhad that their number was 1,300 and table 386 were selected as statistical samples of research. Data collection tools included two questionnaires leadership style Bass and Avolio (2004) and organizational citizenship behavior Podsakoff et al (1990), and the validity of which has been approved by ten sports management and reliability to the test Cronbach's alpha of 0/88 to 0/79 questionnaire leadership style and organizational citizenship behavior was calculated. To analyze the data from the test Kolmogorov Smirnov, Pearson correlation and structural equations were used. The results showed that among all the components of transformational leadership and organizational citizenship behavior and there was a positive correlation. According to the research findings suggest that school administrators and experts responsible for education efforts in the development of transformational leadership style and develop physical exercise and training in community and increased sport participation to students.
The Complex Phosphorylation Patterns That Regulate the Activity of Hsp70 and Its Cochaperones

Proteins must fold into their native structure and maintain it during their lifespan to display the desired activity. To ensure proper folding and stability, and avoid generation of misfolded conformations that can be potentially cytotoxic, cells synthesize a wide variety of molecular chaperones that assist folding of other proteins and avoid their aggregation, which unfortunately is unavoidable under acute stress conditions. A protein machinery in metazoa, composed of representatives of the Hsp70, Hsp40, and Hsp110 chaperone families, can reactivate protein aggregates. We revised herein the phosphorylation sites found so far in members of these chaperone families and the functional consequences associated with some of them. We also discuss how phosphorylation might regulate the chaperone activity and the interaction of human Hsp70 with its accessory and client proteins. Finally, we present the information that would be necessary to decrypt the effect that post-translational modifications, and especially phosphorylation, could have on the biological activity of the Hsp70 system, known as the “chaperone code”.
Behavioral and Neural Pathways Supporting the Development of Prosocial and Risk‐Taking Behavior Across Adolescence

This study tested the pathways supporting adolescent development of prosocial and rebellious behavior. Self‐report and structural brain development data were obtained in a three‐wave, longitudinal neuroimaging study (8–29 years, N = 210 at Wave 3). First, prosocial and rebellious behavior assessed at Wave 3 were positively correlated. Perspective taking and intention to comfort uniquely predicted prosocial behavior, whereas fun seeking (current levels and longitudinal changes) predicted both prosocial and rebellious behaviors. These changes were accompanied by developmental declines in nucleus accumbens and medial prefrontal cortex (MPFC) volumes, but only faster decline of MPFC (faster maturity) related to less rebellious behavior. These findings point toward a possible differential susceptibility marker, fun seeking, as a predictor of both prosocial and rebellious developmental outcomes.
Complicating effects of obstructive sleep apnea syndrome on the severity of adult asthma

Abstract Introduction: Bronchial asthma (BA) and obstructive sleep apnea syndrome (OSAS) are common causes of respiratory disturbance. Many cases of patients with both conditions have been reported, and BA and OSAS may exacerbate each other, but information remains sparse. Methods:We retrospectively evaluated 60 patients under treatment for BA in our department between April 2016 and March 2018 who also underwent portable polysomnography (PSG) for suspected OSAS to assess potential association between PSG results and asthma treatment or respiratory function. BA was diagnosed and treated according to the Asthma Prevention and Management Guideline 2015. Results: We found that BA treatment intensity step was significantly higher for patients with BA who had concurrent moderate or severe OSAS (p = 0.0016). However, neither respiratory function, fraction of exhaled nitric oxide (FeNO), nor forced oscillation technique (FOT) differed significantly between patients with and without OSAS, and apnea hypopnea index was not significantly correlated with respiratory function, FeNO or FOT parameters. Conclusion:We conclude that even though BA patients with OSAS had good respiratory function, their BA was more severe than that of patients without OSAS, suggesting that OSAS may exacerbate BA. Background factors and asthma parameters were not predictive of PSG results, and patients with suspected OSAS should be evaluated proactively by using PSG.
Stochastic Finite Element Analysis Framework for Modelling Mechanical Properties of Particulate Modified Polymer Composites

Polymers have become indispensable in many engineering applications because of their attractive properties, including low volumetric mass density and excellent resistance to corrosion. However, polymers typically lack in mechanical, thermal, and electrical properties that may be required for certain engineering applications. Therefore, researchers have been seeking to improve properties by modifying polymers with particulate fillers. In the research presented herein, a numerical modeling framework was employed that is capable of predicting the properties of binary or higher order composites with randomly distributed fillers in a polymer matrix. Specifically, mechanical properties, i.e., elastic modulus, Poisson’s ratio, and thermal expansion coefficient, were herein explored for the case of size-distributed spherical filler particles. The modeling framework, employing stochastic finite element analysis, reduces efforts for assessing material properties compared to experimental work, while increasing the level of accuracy compared to other available approaches, such as analytical methods. Results from the modeling framework are presented and contrasted with findings from experimental works available in the technical literature. Numerical predictions agree well with the non-linear trends observed in the experiments, i.e., elastic modulus predictions are within the experimental data scatter, while numerical data deviate from experimental Poisson’s ratio data for filler volume fractions greater than 0.15. The latter may be the result of morphology changes in specimens at higher filler volume fractions that do not comply with modelling assumptions.
Requirement of IFT-B–BBSome complex interaction in export of GPR161 from cilia

ABSTRACT The intraflagellar transport (IFT) machinery, which includes the IFT-A and IFT-B complexes, mediates bidirectional trafficking of ciliary proteins. In addition to these complexes, the BBSome, which is composed of eight subunits that are encoded by the causative genes of Bardet-Biedl syndrome (BBS), has been proposed to connect the IFT machinery to ciliary membrane proteins, such as G protein-coupled receptors, to mediate their export from cilia. However, little is known about the connection between the IFT machinery and the BBSome. Using the visible immunoprecipitation assay, we here identified the interaction between IFT38 from the IFT-B complex and BBS1, BBS2 and BBS9 from the BBSome. Furthermore, by analyzing phenotypes of IFT38-knockout cells exogenously expressing wild-type IFT38 or its mutant lacking the ability to interact with BBS1+BBS2+BBS9, we showed that knockout cells expressing the IFT38 mutant have restored ciliogenesis; however, similar to BBS1-knockout cells, they demonstrated significant accumulation of GPR161 within cilia upon stimulation of Hedgehog signaling. These results indicate that the IFT-B–BBSome interaction is required for the export of GPR161 across the ciliary gate. Summary: We here determine an interface between the IFT-B complex and the BBSome involving IFT38 and BBS1+BBS2+BBS9, and show that the interaction is crucial for GPR161 export from cilia.