Miracle-dz/UniFAR-FTUs huggingface dataset:
Spinosin ameliorates insulin resistance by suppressing reactive oxygen species-associated inflammation

Objective(s): Spinosin is the predominant C-glycoside flavonoid derived from the seeds of Zizyphus jujuba var. Spinosa (Rhamnaceae). The present study aimed to investigate the effects of spinosin on insulin resistance (IR) in vascular endothelium. Materials and Methods: The anti-IR effect of spinosin was evaluated in a high-fat diet (HFD) treated mice model. The effects of spinosin pretreatment on reactive oxygen species (ROS)-associated inflammation in Human umbilical vein endothelial cells (HUVEC) were evaluated by western blot analysis and reverse transcription-polymerase chain reaction. The effect of spinosin on insulin-mediated endothelium-dependent vasodilation of rat aortae was further evaluated. Results: Spinosin at 20 mg/kg alleviates increased mice’s body weight, fasting serum glucose, oral glucose tolerance, serum insulin, insulin resistance index, and serum lipid of HFD-treated mice. Spinosin at 20 μM suppressed ROS overproduction, and inhibited ROS-related HUVEC inflammation by inhibiting mRNA expression of tumor necrosis factor-α and interleukin-6. In addition, spinosin at 0.1 μM showed a vasodilation effect of isoprenaline-pretreated rat aortae and increased insulin-mediated NO production in endothelial cells. These effects were shown to be related to the spinosin regulating serine/tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) facilitated/phosphoinositide 3-kinase (PI3K) signaling. Conclusion: Spinosin may ameliorate IR and ROS-associated inflammation, and increase endothelial NO production by mediating IRS-1/PI3K/endothelial nitric oxide synthase (eNOS) pathway.
Gadolinium-based contrast agents for imaging of the central nervous system: A multicenter European prospective study

Contrast-enhanced MR (CE-MR) imaging is required to improve lesion detection and characterization and to increase diagnostic confidence. This study aims to evaluate the safety, effectiveness, and usage patterns of recently introduced ClariscanTM (gadoterate meglumine) and other macrocyclic gadolinium-based contrast agents (GBCAs) used for magnetic resonance imaging (MRI) of the central nervous system (CNS). Data was obtained from a European multicenter, prospective, observational postmarketing study that included pediatric and adult patients undergoing contrast-enhanced MRI with a GBCA used in routine clinical practice. Safety data was collected by spontaneous patient adverse event (AE) reporting. Effectiveness was assessed via changes in radiological diagnosis, diagnostic confidence, and image quality. 766 patients with CNS-related indications were included from 8 centers across 5 European countries between December 2018 and November 2019. Clariscan (gadoterate meglumine) was used in 66% (503) of exams, Dotarem® (gadoterate meglumine) in 20% (160), Gadovist® (gadobutrol) in 13% (97), and ProHance® (gadoteridol) in 1%. GBCA use increased the diagnostic confidence in 95% (724/766) of patients and a change in radiological diagnosis in 65% (501/766) of patients. The Clariscan-specific data revealed an increase in diagnostic confidence in 94% (472/503) of patients and resulted in a change in radiological diagnosis in 58% (293/503) of patients. Image quality was considered excellent or good in 95% of patients across all GBCAs and in 94% of patients who received Clariscan. No AEs were reported in this cohort including Clariscan. This data demonstrates the excellent safety and efficacy profile of Clariscan and other GBCAs used in MRI examination of the CNS.
TNFAIP3 is anti-inflammatory in the retinal vasculature

Purpose To determine whether tumor necrosis factor alpha-induced protein 3 (TNFAIP3) regulates inflammatory and permeability proteins in the retinal vasculature. Methods We used retinal lysates from type 1 diabetic mice and endothelial cell-specific exchange protein for cAMP 1 (Epac1) knockout mice to determine the protein levels of TNFAIP3. We also treated retinal endothelial cells (RECs) in normal (5 mM) and high (25 mM) glucose with an Epac1 agonist or with TNFAIP3 siRNA. We performed western blotting for TNFAIP3 and inflammatory and permeability proteins after treatment. TNFAIP3 siRNA was used only in cells grown in high glucose. Immunostaining was performed for localization of ZO-1 and tight junction protein 1. Results TNFAIP3 was reduced in the diabetic retinas and the retinas of the Epac1 conditional knockout mice. The Epac1 agonist increased TNFAIP3 levels in RECs grown in high glucose. Reduction of TNFAIP3 with siRNA led to increased levels of tumor necrosis factor alpha (TNFα) and phosphorylation of nuclear factor kappa beta (NF-kB), while decreasing occludin and zonula occludens 1 (ZO-1) protein levels and inhibitory kappa beta kinase (IkB) phosphorylation. Tumor receptor-associated factor 6 (TRAF6) levels were increased above high glucose levels. Conclusions TNFAIP3 serves as an anti-inflammatory factor in the retinal vasculature. Epac1 regulates TNFAIP3. TNFAIP3 may offer a new mechanism for regulating inflammation and permeability in the retinal vasculature.
Interaction of saffron and its constituents with Nrf2 signaling pathway: A review

Saffron (Crocus sativus) is a natural compound and its constituents such as crocin, crocetin, and safranal have many pharmacological properties such as anti-oxidant, anti-inflammatory, antitumor, antigenotoxic, anti-depressant, hepatoprotective, cardioprotective, and neuroprotective. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays an important role against inflammation, oxidative stress, and carcinogenesis. In the regulation of the Nrf2 signaling pathway, kelch-like ECH-associated protein 1 (keap1) is the most studied pathway. In this review, we gathered various studies and describe the pharmacological effects of saffron and its constituents with their related mechanisms of action, particularly the Nrf2 signaling pathway. In this review, we used search engines or electronic databases including Scopus, Web of Science, and Pubmed, without time limitation. The search keywords contained saffron, “Crocus sativus”, crocetin, crocin, safranal, picrocrocin, “nuclear factor erythroid 2-related factor 2“, and Nrf2. Saffron and its constituents could have protective properties through various mechanisms particularly the Nrf2/HO-1/Keap1 signaling pathway in different tissues such as the liver, heart, brain, pancreas, lung, joints, colon, etc. The vast majority of studies discussed in this review indicate that saffron and its constituents could induce the Nrf2 signaling pathway leading to its anti-oxidant and therapeutic effects.
Effects of wasp venom on venous thrombosis in rats

Objective(s): This study aimed to investigate the potential effects of wasp venom (WV) from Vespa magnifica on antithrombosis in rats with inferior vena cava (IVC) thrombosis. Materials and Methods: The thrombosis rat model was established by improving the IVC stenosis, in which rats were subjected to IVC ligation for 75 min. Rats were administered argatroban (IP) or WV (s.c.) for 4 hr after IVC thrombosis. The weight, inhibition rate, and pathological morphology of the thrombosis induced by IVC ligation and the variation in four coagulation parameters, coagulation factors, and CD61+CD62P+ were simultaneously determined in IVC rats. Results: The thrombus formed as a result of IVC ligation was stable. Compared with the control group, the weight of the thrombus was significantly reduced in the argatroban group. Thrombus weight was reduced by treatment with 0.6, 0.2, and 0.05 mg/kg WV, with inhibition rates of 52.19%, 35.32%, and 28.98%, respectively. Inflammatory cells adhered to and infiltrated the vessel wall in the IVC group more than in the sham group. However, the pathological morphology and CD61+CD62P+ of the WV treatment groups tended to be normal. Conclusion: We improved the model of IVC thrombosis to be suitable for evaluation of antithrombotic drugs. Our findings demonstrated that WV could inhibit IVC thrombosis associated with reducing coagulation factors V and CD61+CD62p expression in rats.
Palisade Cartilage Tympanoplasty, an Alternative Surgical Approach for CSOM

Introduction: The hearing outcome and graft take in patients of CSOM with sclerotic mastoids were studied using the novel technique of palisade cartilage tympanoplasty. Besides, it was compared with tympanoplasty type-1 above and over the cortical mastoidectomy in both groups. Materials and Methods: Out of 313 patients of CSOM, 125 had sclerotic mastoid and were included in the study. Palisade cartilage group patients were subjected to palisade cartilage tympanoplasty type-1. While as in the Temporalis fascia group patients, type-1 tympanoplasty was done using temporalis fascia as graft material. These procedures were performed in addition to cortical mastoidectomy done in all cases. Results: Statistically significant (P<0.001) mean postoperative hearing gain was achieved (> 20 dB) in both the groups with a reduction of AB gap to 13.3 & 11.79 dB, respectively. However, the post-surgery hearing outcomes achieved were similar in both groups (P=0.09). The overall graft take rate of 86% was seen in the Palisade cartilage group. The remaining 14% had graft take failure. The primary graft failure rate was 10% (5/50), and the secondary failure rate within six months of follow-up was 4% (2/50). The Temporalis fascia group graft take rate was higher (92%) than the Palisade cartilage group, with only 4 % (3/75) of cases having a primary graft failure rate. However, these findings (92% vs. 86%) were not statistically significant (P=0.2830). Conclusions: As the hearing outcomes and graft take rates were comparable in the two groups, the present study highlighted the use of palisade cartilage tympanoplasty in patients of CSOM with sclerotic mastoids as an alternative method to tympanoplasty.
Spatial Navigation and Its Association With Biomarkers and Future Dementia in Memory Clinic Patients Without Dementia

Background and Objectives Impaired spatial navigation is considered an early sign in many neurodegenerative diseases. We aimed to determine whether spatial navigation was associated with future dementia in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) and to explore associations between spatial navigation and biomarkers of Alzheimer disease (AD) and neurodegeneration. Methods This study included memory clinic patients without dementia in the longitudinal BioFINDER cohort. The Floor Maze Test (FMT) was used to assess spatial navigation at baseline. Conversion to dementia was evaluated at 2-year and 4-year follow-ups. At baseline, amyloid-β 42/40 ratio, phosphorylated-tau (P-tau), and neurofilament light (NfL) were analyzed in CSF. Cortical thickness and volume of regions relevant for navigation and white matter lesion volume were quantified from MRI. The predictive role of the FMT for conversion to all-cause dementia was analyzed using logistic regression analyses in 2 models: (1) controlled for age, sex, and education and (2) adding baseline cognitive status and MMSE. Associations between FMT and biomarkers were adjusted for age, sex, and cognitive status (SCD or MCI). Results One hundred fifty-six patients with SCD and 176 patients with MCI were included. FMT total time was associated with progression to all-cause dementia in model 2 at 2-year (OR 1.10, 95% CI 1.04–1.16) and at 4-year follow-up (OR 1.10, 95% CI 1.04–1.16), i.e., a 10% increase in odds of developing dementia per every 10 seconds increase in FMT. In the adjusted analyses, P-tau and NfL were associated with FMT total time, as well as hippocampal volume, parahippocampal, and inferior parietal cortical thickness. Amyloid-β 42/40 ratio was not associated with FMT total time. Discussion Impaired spatial navigation was associated with conversion to dementia within 2 and 4 years and with key CSF and MRI biomarkers for AD and neurodegeneration in patients with SCD and MCI. This supports its use in early cognitive assessments, but the predictive accuracy should be validated in other cohorts. Classification of Evidence This is a Class I prospective cohort study demonstrating association of baseline markers of spatial recognition with development of dementia in patients with SCD or MCI at baseline.
Valproic acid determination by liquid chromatography coupled to mass spectrometry (LC–MS/MS) in whole blood for forensic purposes

Abstract Valproic acid (VPA) is a well‐known drug prescribed as anti‐epileptic. It has a narrow therapeutic range and shows great individual differences in pharmacodynamics and pharmacokinetics. Consequently, the therapeutical drug monitoring (TDM) in patient's plasma is of crucial importance. Liquid chromatography coupled to mass spectrometry (LC–MS/MS) has gained importance in TDM applications for its features of sensitivity, selectivity and rapidity. However, in case of VPA, the LC–MS/MS selectivity could be hampered by the lack of a sufficient number of multiple reaction monitoring (MRM) transitions describing the molecule. In fact, the product ion scan of deprotonated molecules of VPA does not produce any ion and thus most LC–MS/MS methods are based on the detection of the unique MRM transition m/z 143➔143. In this way, the advantages of selectivity in LC–MS cannot be effectively exploited. In the present method, stable analyte adducts were exploited for the determination of VPA in blood. An Acquity HSS C18 column and mobile phases consisting of 5‐mM ammonium formate and acetonitrile both added 0.1% formic acid were used. Source worked in negative acquisition mode and parameters were optimized to increase the adduct (m/z 189) and dimer (m/z 287) stability, and their fragmentation were used to increase the selectivity of MRM detection. The method has been validated according to the toxicological forensic guidelines and successfully applied to 10 real blood samples. Finally, the present method showed suitable for the rapid LC–MS/MS detection of VPA in whole blood, demonstrating the possibility to increase specificity by exploiting stable in‐source adducts. This should be considered of utmost importance in the case of forensic applications.
Acute Effects of High-Intensity Interval Running on Lower-Body and Upper-Body Explosive Strength and Throwing Velocity in Handball Players

Abstract Seipp, D, Feuerbacher, JF, Jacobs, MW, Dragutinovic, B, and Schumann, M. Acute effects of high-intensity interval running on lower-body and upper-body explosive strength and throwing velocity in handball players. J Strength Cond Res 36(11): 3167–3172, 2022—The purpose of this study was to determine the acute effects of handball-specific high-intensity interval training (HIIT) on explosive strength and throwing velocity, after varying periods of recovery. Fourteen highly trained male handball players (age: 25.4 (26.2 ± 4.2) performed HIIT consisting of repeated 15-second shuttle runs at 90% of final running speed (VIFT) to exhaustion. Upper-body and lower-body explosive strength and throwing velocities were measured before and immediately after HIIT, as well as after 6 hours. These tests included 3 repetitions of both bench press and squat exercise at 60% of the 1 repetition maximum (1RM) as well as 3 repetitions of the set shot without run up and jump shot, respectively. Explosive squat performance was significantly reduced at post (−5.48%, p = 0.026) but not at 6 h (−0.24%, p = 1.000). Explosive bench press performance remained statistically unaltered at post (0.32%, p = 1.000) and at 6 hour (1.96%, p = 1.000). This was also observed in the subsequent throws both immediately after (−0.60%, p = 1.000) (−0.31%, p = 1.000) and at 6 h (−1.58%, p = 1.000) (1.51%, p = 0.647). Our data show a reduction in explosive strength of the lower but not upper extremities when preceded by running HIIT. Since throwing velocity was not affected by intense lower-body exercise, combining lower-body HIIT and throwing practice may be of no concern in highly trained handball players.
Soluble guanylate cyclase activator BAY 54–6544 improves vasomotor function and survival in an accelerated ageing mouse model

DNA damage is a causative factor in ageing of the vasculature and other organs. One of the most important vascular ageing features is reduced nitric oxide (NO)soluble guanylate cyclase (sGC)—cyclic guanosine monophosphate (cGMP) signaling. We hypothesized that the restoration of NO‐sGC‐cGMP signaling with an sGC activator (BAY 54–6544) may have beneficial effects on vascular ageing and premature death in DNA repair‐defective mice undergoing accelerated ageing. Eight weeks of treatment with a non‐pressor dosage of BAY 54–6544 restored the decreased in vivo microvascular cutaneous perfusion in progeroid Ercc1∆/− mice to the level of wild‐type mice. In addition, BAY 54–6544 increased survival of Ercc1∆/− mice. In isolated Ercc1∆/− aorta, the decreased endothelium‐independent vasodilation was restored after chronic BAY 54–6544 treatment. Senescence markers p16 and p21, and markers of inflammation, including Ccl2, Il6 in aorta and liver, and circulating IL‐6 and TNF‐α were increased in Ercc1∆/−, which was lowered by the treatment. Expression of antioxidant genes, including Cyb5r3 and Nqo1, was favorably changed by chronic BAY 54–6544 treatment. In summary, BAY 54–6544 treatment improved the vascular function and survival rates in mice with accelerated ageing, which may have implication in prolonging health span in progeria and normal ageing.
Can Prolongate Use of Social Media Immediately Before Training Worsen High Level Male Volleyball Players’ Visuomotor Skills?

Our aim was to analyze the effect of mental fatigue caused by prolonged social media use on high-level volleyball players' visuomotor skills. Eighteen high-level male young volleyball players participated in this randomized, counterbalanced, crossover design. All participants underwent a 2-week experiment in which we measured their response times when performing a visuomotor task with and without mental fatigue inducement through repeated use of social media immediately before training sessions. In the control condition, participants watched TV for 30-minutes, and in the social media condition, they used a social media app (Instagram®) on smartphones for 30-minutes. We found a significant Condition x Time interaction on visuomotor task response time (p = 0.03), but there was no significant main effect of either Time or Condition. Mental fatigue, induced by repeated app-based social media use for 30-minutes immediately before training sessions, affected elite male volleyball players’ visuomotor skills.
Mask-related skin changes among healthcare workers in a community-based hospital

Abstract Context During the COVID-19 pandemic, dermatologists within the Beaumont Farmington Hills’ Dermatology program noticed an increase in conditions associated with mask wearing, such as “maskne” (acne in a mask distribution, thought to be caused by mask wearing), as well as worsening of previously diagnosed dermatologic conditions. Objectives The goal of our study was to explore various factors that impacted mask-related skin changes and how these skin changes affected quality of life. Methods A cross-sectional study was performed. The primary 10-item survey instrument administered was the Dermatology Life Quality Index (DLQI). Respondents were asked a series of 10 additional questions concerning the degree to which abnormal mask-related skin conditions affect their skin symptoms, possible embarrassment/self-consciousness, and perceived impact of mask-related skin changes. A series of descriptive statistics, cross-tabulation charts, and graphical examinations of data was utilized to evaluate sample subgroup and outcome distributional patterns. Pearson r bivariate correlation coefficients between possible collinear predictive measures on the primary study outcome were calculated. A series of simple inferential chi-squared (Χ2) tests of independence were also conducted. Results A total of 370 out of 430 (86.0%) Beaumont Health employees noticed some degree of skin changes since the work-hours face mask requirement was instituted, while 378 out of 430 (87.9%) felt that their skin was better when not wearing a mask. The majority of respondents, 283 (65.8%), reported having at least a little symptomatic skin (i.e., itchy, painful, sore, stinging) during the prior week. Furthermore, 72.3% reported that they were at least a little embarrassed or self-conscious of their skin. Chi-squared analysis of composite DLQI score categories by the number of types of masks utilized (Pearson X2=19.0, df=8, p=0.015), and some degree of symptomatic skin (Pearson X2=156.4, df=4, p<0.001) were found to be statistically significant. Conclusions A large number of healthcare workers are affected by mask-related skin changes. Further research should be directed at better understanding how skin changes associated with mask wearing impact one’s quality of life and mental health.
Gaussian process based model predictive control : a thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Engineering, School of Engineering and Advanced Technology, Massey University, New Zealand

The performance of using Model Predictive Control (MPC) techniques is highly dependent on a model that is able to accurately represent the dynamical system. The datadriven modelling techniques are usually used as an alternative approach to obtain such a model when first principle techniques are not applicable. However, it is not easy to assess the quality of learnt models when using the traditional data-driven models, such as Artificial Neural Network (ANN) and Fuzzy Model (FM). This issue is addressed in this thesis by using probabilistic Gaussian Process (GP) models. One key issue of using the GP models is accurately learning the hyperparameters. The Conjugate Gradient (CG) algorithms are conventionally used in the problem of maximizing the Log-Likelihood (LL) function to obtain these hyperparameters. In this thesis, we proposed a hybrid Particle Swarm Optimization (PSO) algorithm to cope with the problem of learning hyperparameters. In addition, we also explored using the Mean Squared Error (MSE) of outputs as the fitness function in the optimization problem. This will provide us a quality indication of intermediate solutions. The GP based MPC approaches for unknown systems have been studied in the past decade. However, most of them are not generally formulated. In addition, the optimization solutions in existing GP based MPC algorithms are not clearly given or are computationally demanding. In this thesis, we first study the use of GP based MPC approaches in the unconstrained problems. Compared to the existing works, the proposed approach is generally formulated and the corresponding optimization problem is eff- ciently solved by using the analytical gradients of GP models w.r. t. outputs and control inputs. The GPMPC1 and GPMPC2 algorithms are subsequently proposed to handle the general constrained problems. In addition, through using the proposed basic and extended GP based local dynamical models, the constrained MPC problem is effectively solved in the GPMPC1 and GPMPC2 algorithms. The proposed algorithms are verified in the trajectory tracking problem of the quadrotor. The issue of closed-loop stability in the proposed GPMPC algorithm is addressed by means of the terminal cost and constraint technique in this thesis. The stability guaranteed GPMPC algorithm is subsequently proposed for the constrained problem. By using the extended GP based local dynamical model, the corresponding MPC problem is effectively solved.